\\n\\n
More than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
\\n\\nOur breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
\\n\\n“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
\\n\\nAdditionally, each book published by IntechOpen contains original content and research findings.
\\n\\nWe are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
\\n\\n\\n\\n
\\n"}]',published:!0,mainMedia:null},components:[{type:"htmlEditorComponent",content:'
Simba Information has released its Open Access Book Publishing 2020 - 2024 report and has again identified IntechOpen as the world’s largest Open Access book publisher by title count.
\n\nSimba Information is a leading provider for market intelligence and forecasts in the media and publishing industry. The report, published every year, provides an overview and financial outlook for the global professional e-book publishing market.
\n\nIntechOpen, De Gruyter, and Frontiers are the largest OA book publishers by title count, with IntechOpen coming in at first place with 5,101 OA books published, a good 1,782 titles ahead of the nearest competitor.
\n\nSince the first Open Access Book Publishing report published in 2016, IntechOpen has held the top stop each year.
\n\n\n\nMore than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
\n\nOur breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
\n\n“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
\n\nAdditionally, each book published by IntechOpen contains original content and research findings.
\n\nWe are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
\n\n\n\n
\n'}],latestNews:[{slug:"intechopen-maintains-position-as-the-world-s-largest-oa-book-publisher-20201218",title:"IntechOpen Maintains Position as the World’s Largest OA Book Publisher"},{slug:"all-intechopen-books-available-on-perlego-20201215",title:"All IntechOpen Books Available on Perlego"},{slug:"oiv-awards-recognizes-intechopen-s-editors-20201127",title:"OIV Awards Recognizes IntechOpen's Editors"},{slug:"intechopen-joins-crossref-s-initiative-for-open-abstracts-i4oa-to-boost-the-discovery-of-research-20201005",title:"IntechOpen joins Crossref's Initiative for Open Abstracts (I4OA) to Boost the Discovery of Research"},{slug:"intechopen-hits-milestone-5-000-open-access-books-published-20200908",title:"IntechOpen hits milestone: 5,000 Open Access books published!"},{slug:"intechopen-books-hosted-on-the-mathworks-book-program-20200819",title:"IntechOpen Books Hosted on the MathWorks Book Program"},{slug:"intechopen-s-chapter-awarded-the-guenther-von-pannewitz-preis-2020-20200715",title:"IntechOpen's Chapter Awarded the Günther-von-Pannewitz-Preis 2020"},{slug:"suf-and-intechopen-announce-collaboration-20200331",title:"SUF and IntechOpen Announce Collaboration"}]},book:{item:{type:"book",id:"556",leadTitle:null,fullTitle:"Advanced Bariatric and Metabolic Surgery",title:"Advanced Bariatric and Metabolic Surgery",subtitle:null,reviewType:"peer-reviewed",abstract:"Bariatric surgery has gained importance in the last 20 years because of the high prevalence of global obesity, and the vast understating of the physiological and pathological aspects of obesity and associated metabolic syndromes. This book has been written by a number of highly outstanding authors and pioneering bariatric surgeons from all over the world. The intended audience for this book includes all medical professionals involved in caring for bariatric patients. The chapters cover the choice of operation, preoperative preparation including psychological aspect, postoperative care and management of complication. It also extends to concept and result of metabolic surgery and scarless bariatric surgery.",isbn:null,printIsbn:"978-953-307-926-4",pdfIsbn:"978-953-51-6764-8",doi:"10.5772/1066",price:139,priceEur:155,priceUsd:179,slug:"advanced-bariatric-and-metabolic-surgery",numberOfPages:338,isOpenForSubmission:!1,isInWos:1,hash:"a95bc3c431019e91cf7293e157ad9fd4",bookSignature:"Chih-Kun Huang",publishedDate:"February 29th 2012",coverURL:"https://cdn.intechopen.com/books/images_new/556.jpg",numberOfDownloads:42674,numberOfWosCitations:6,numberOfCrossrefCitations:7,numberOfDimensionsCitations:17,hasAltmetrics:0,numberOfTotalCitations:30,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"April 6th 2011",dateEndSecondStepPublish:"May 4th 2011",dateEndThirdStepPublish:"September 8th 2011",dateEndFourthStepPublish:"October 8th 2011",dateEndFifthStepPublish:"February 7th 2012",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,editors:[{id:"90031",title:"Dr.",name:"Chih-Kun",middleName:null,surname:"Huang",slug:"chih-kun-huang",fullName:"Chih-Kun Huang",profilePictureURL:"https://mts.intechopen.com/storage/users/90031/images/2105_n.jpg",biography:"Dr. Huang, Chih-Kun is the director of B.M.I Surgery center and also International Minimally Invasive Surgery Training Center of E-Da hospital in Kaohsiung, Taiwan. He is also the president of Taiwan Obesity Support Association (T.O.S.A) and also the founding Chairman of International Excellence Federation for Bariatric & Metabolic Surgery(I.E.F). Dr Huang has been devoted to minimally invasive surgery and bariatric surgery for 10 years. And he finished 1st single incision trans-umbilical laparoscopic Roux-en-Y gastric bypass in 2008 and 1st laparoscopic adjustable gastric banded plication in 2009 in the world. His center was also designated as 1st International Center of Excellence for Bariatric Surgery (I.C.E) in Asia-Pacific area in 2009. Because of the contribution and devotion, he was awarded of Endos Award in Medical Science & Technology in 2010 and International Award of ASMBS in 2011.He is also the founding Chairman of International Excellence Federation for Bariatric & Metabolic Surgery.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"4",totalChapterViews:"0",totalEditedBooks:"2",institution:{name:"China Medical University",institutionURL:null,country:{name:"Taiwan"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1140",title:"Bariatric Surgery",slug:"bariatric-surgery"}],chapters:[{id:"29482",title:"Surgical Procedures to Achieve Weight Loss",doi:"10.5772/32044",slug:"surgical-procedures-to-achieve-weight-loss",totalDownloads:2031,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Roman Grinberg, John N. Afthinos and Karen E. Gibbs",downloadPdfUrl:"/chapter/pdf-download/29482",previewPdfUrl:"/chapter/pdf-preview/29482",authors:[{id:"89919",title:"Dr.",name:"Karen E.",surname:"Gibbs",slug:"karen-e.-gibbs",fullName:"Karen E. Gibbs"},{id:"135375",title:"Dr.",name:"Roman",surname:"Grinberg",slug:"roman-grinberg",fullName:"Roman Grinberg"},{id:"135377",title:"Dr.",name:"John N.",surname:"Afthinos",slug:"john-n.-afthinos",fullName:"John N. Afthinos"}],corrections:null},{id:"29483",title:"Effect of Obesity on Circulating Adipokines and Their Expression in Omental Adipose Tissue of Female Bariatric Surgery Patients",doi:"10.5772/36059",slug:"effect-of-obesity-on-circulating-adipokines-and-their-expression-in-omental-adipose-tissue-of-female",totalDownloads:2011,totalCrossrefCites:0,totalDimensionsCites:1,signatures:"John N. Fain",downloadPdfUrl:"/chapter/pdf-download/29483",previewPdfUrl:"/chapter/pdf-preview/29483",authors:[{id:"106948",title:"Prof.",name:"John",surname:"Fain",slug:"john-fain",fullName:"John Fain"}],corrections:null},{id:"29484",title:"The Economic Impact of Bariatric Surgery",doi:"10.5772/33003",slug:"the-economic-impact-of-bariatric-surgery",totalDownloads:3872,totalCrossrefCites:1,totalDimensionsCites:2,signatures:"Anke-Peggy Holtorf, Harald Rinde, Frederic Rupprecht, Henry Alder and Diana Brixner",downloadPdfUrl:"/chapter/pdf-download/29484",previewPdfUrl:"/chapter/pdf-preview/29484",authors:[{id:"93567",title:"Dr",name:"Diana",surname:"Brixner",slug:"diana-brixner",fullName:"Diana Brixner"},{id:"100230",title:"Dr.",name:"Anke-Peggy",surname:"Holtorf",slug:"anke-peggy-holtorf",fullName:"Anke-Peggy Holtorf"},{id:"100708",title:"Dr.",name:"Harald",surname:"Rinde",slug:"harald-rinde",fullName:"Harald Rinde"},{id:"100709",title:"Dr.",name:"Frederic",surname:"Rupprecht",slug:"frederic-rupprecht",fullName:"Frederic Rupprecht"},{id:"128560",title:"Mr.",name:"Henry",surname:"Alder",slug:"henry-alder",fullName:"Henry Alder"}],corrections:null},{id:"29485",title:"Medical Assessment and Preparation of Patients Undergoing Bariatric Surgery",doi:"10.5772/32798",slug:"medical-assessment-and-preparation-of-patients-undergoing-bariatric-surgery",totalDownloads:2870,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Wen Bun Leong and Shahrad Taheri",downloadPdfUrl:"/chapter/pdf-download/29485",previewPdfUrl:"/chapter/pdf-preview/29485",authors:[{id:"92742",title:"Dr.",name:"Shahrad",surname:"Taheri",slug:"shahrad-taheri",fullName:"Shahrad Taheri"},{id:"104649",title:"Dr.",name:"Wen Bun",surname:"Leong",slug:"wen-bun-leong",fullName:"Wen Bun Leong"}],corrections:null},{id:"29486",title:"Rethinking the Preoperative Psychological Evaluation – A New Paradigm for Improved Outcomes and Predictive Power",doi:"10.5772/32174",slug:"rethinking-the-preoperative-psychological-evaluation-a-new-paradigm-for-improved-outcomes-and-predic",totalDownloads:3044,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Susan F. Franks and Kathryn A. Kaiser",downloadPdfUrl:"/chapter/pdf-download/29486",previewPdfUrl:"/chapter/pdf-preview/29486",authors:[{id:"90457",title:"Dr.",name:"Susan",surname:"Franks",slug:"susan-franks",fullName:"Susan Franks"},{id:"100881",title:"Dr.",name:"Kathryn",surname:"Kaiser",slug:"kathryn-kaiser",fullName:"Kathryn Kaiser"}],corrections:null},{id:"29487",title:"Bariatric Surgery – Anesthesiologic Concerns",doi:"10.5772/34386",slug:"anesthesiologic-concerns",totalDownloads:2778,totalCrossrefCites:1,totalDimensionsCites:1,signatures:"Johan Raeder",downloadPdfUrl:"/chapter/pdf-download/29487",previewPdfUrl:"/chapter/pdf-preview/29487",authors:[{id:"99922",title:"Prof.",name:"Johan",surname:"Raeder",slug:"johan-raeder",fullName:"Johan Raeder"}],corrections:null},{id:"29488",title:"Gastric Banding and Bypass for Morbid Obesity – Preoperative Assessment, Operative Techniques and Postoperative Monitoring",doi:"10.5772/32896",slug:"gastric-banding-and-bypass-for-morbid-obesity-preoperative-assessment-operative-techniques-and-posto",totalDownloads:1667,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Brane Breznikar, Dejan Dinevski and Milan Zorman",downloadPdfUrl:"/chapter/pdf-download/29488",previewPdfUrl:"/chapter/pdf-preview/29488",authors:[{id:"11260",title:"Dr.",name:"Milan",surname:"Zorman",slug:"milan-zorman",fullName:"Milan Zorman"},{id:"15129",title:"Prof.",name:"Dejan",surname:"Dinevski",slug:"dejan-dinevski",fullName:"Dejan Dinevski"},{id:"93108",title:"Dr.",name:"Brane",surname:"Breznikar",slug:"brane-breznikar",fullName:"Brane Breznikar"}],corrections:null},{id:"29489",title:"BPD and BPD-DS Concerns and Results",doi:"10.5772/32041",slug:"bpd-and-bpd-ds-concerns-and-results",totalDownloads:3776,totalCrossrefCites:1,totalDimensionsCites:3,signatures:"Francesco Saverio Papadia, Hosam Elghadban, Andrea Weiss, Corrado Parodi and Francesca Pagliardi",downloadPdfUrl:"/chapter/pdf-download/29489",previewPdfUrl:"/chapter/pdf-preview/29489",authors:[{id:"89911",title:"Dr.",name:"Francesco Saverio",surname:"Papadia",slug:"francesco-saverio-papadia",fullName:"Francesco Saverio Papadia"},{id:"90995",title:"Dr.",name:"Hosam",surname:"Elghadban",slug:"hosam-elghadban",fullName:"Hosam Elghadban"},{id:"95247",title:"Dr.",name:"Corrado",surname:"Parodi",slug:"corrado-parodi",fullName:"Corrado Parodi"},{id:"128949",title:"Dr.",name:"Andrea",surname:"Weiss",slug:"andrea-weiss",fullName:"Andrea Weiss"},{id:"128951",title:"Dr.",name:"Francesca",surname:"Pagliardi",slug:"francesca-pagliardi",fullName:"Francesca Pagliardi"}],corrections:null},{id:"29490",title:"Body Weight and Energy Intake and Expenditure in Bariatric Surgery",doi:"10.5772/32240",slug:"body-weight-and-energy-balance-after-bariatric-surgery",totalDownloads:4001,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Maria Rita Marques de Oliveira, Patrícia Fátima Sousa Novais, Karina Rodrigues Quesada, Carolina Leandro de Souza, Irineu Rasera Junior and Celso Vieira de Souza Leite",downloadPdfUrl:"/chapter/pdf-download/29490",previewPdfUrl:"/chapter/pdf-preview/29490",authors:[{id:"90684",title:"Dr.",name:"Maria Rita Marques",surname:"De Oliveira",slug:"maria-rita-marques-de-oliveira",fullName:"Maria Rita Marques De Oliveira"},{id:"100486",title:"MSc.",name:"Patrícia Fátima",surname:"Souza Novais",slug:"patricia-fatima-souza-novais",fullName:"Patrícia Fátima Souza Novais"},{id:"100487",title:"BSc.",name:"Karina",surname:"Rodrigues Quesada",slug:"karina-rodrigues-quesada",fullName:"Karina Rodrigues Quesada"},{id:"100489",title:"Prof.",name:"Irineu",surname:"Rasera Junior",slug:"irineu-rasera-junior",fullName:"Irineu Rasera Junior"},{id:"100493",title:"Dr.",name:"Celso",surname:"Vieira De Souza Leite",slug:"celso-vieira-de-souza-leite",fullName:"Celso Vieira De Souza Leite"}],corrections:null},{id:"29491",title:"Origins for Micronutrient Deficiencies",doi:"10.5772/32689",slug:"origins-for-micronutrient-deficiencies",totalDownloads:2883,totalCrossrefCites:2,totalDimensionsCites:3,signatures:"Anyea S. Lovette, Timothy R. Shope and Timothy R. Koch",downloadPdfUrl:"/chapter/pdf-download/29491",previewPdfUrl:"/chapter/pdf-preview/29491",authors:[{id:"92342",title:"Dr.",name:"Timothy",surname:"Koch",slug:"timothy-koch",fullName:"Timothy Koch"},{id:"92706",title:"Ms.",name:"Anyea",surname:"Lovette",slug:"anyea-lovette",fullName:"Anyea Lovette"},{id:"99989",title:"Dr.",name:"Timothy",surname:"Shope",slug:"timothy-shope",fullName:"Timothy Shope"}],corrections:null},{id:"29492",title:"Foot Drop as a Complication of Weight Loss After Bariatric Surgery – Is It Preventable?",doi:"10.5772/34082",slug:"foot-drop-after-excessive-weight-loss",totalDownloads:2508,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Frank J. M. Weyns, Frauke Beckers, Linda Vanormelingen, Marjan Vandersteen and Erik Niville",downloadPdfUrl:"/chapter/pdf-download/29492",previewPdfUrl:"/chapter/pdf-preview/29492",authors:[{id:"98602",title:"Dr.",name:"Frank",surname:"Weyns",slug:"frank-weyns",fullName:"Frank Weyns"}],corrections:null},{id:"29493",title:"Diabetes Improvement Following Bariatric and Metabolic Surgery",doi:"10.5772/33188",slug:"diabetes-improvement-following-bariatric-and-metabolic-surgery",totalDownloads:1461,totalCrossrefCites:1,totalDimensionsCites:2,signatures:"Rodolfo Lahsen, Marcos Berry and Patricio Lamoza",downloadPdfUrl:"/chapter/pdf-download/29493",previewPdfUrl:"/chapter/pdf-preview/29493",authors:[{id:"94395",title:"Dr.",name:"Rodolfo",surname:"Lahsen",slug:"rodolfo-lahsen",fullName:"Rodolfo Lahsen"},{id:"101529",title:"Dr.",name:"Marcos",surname:"Berry",slug:"marcos-berry",fullName:"Marcos Berry"},{id:"128658",title:"Dr.",name:"Patricio",surname:"Lamoza",slug:"patricio-lamoza",fullName:"Patricio Lamoza"}],corrections:null},{id:"29494",title:"Bariatric Surgery on Obese Type 2 Diabetes Patients",doi:"10.5772/33002",slug:"bariatric-surgery-on-obese-type-2-diabetes-patients-",totalDownloads:1442,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Junichirou Mori, Yoshihiko Sato and Mitsuhisa Komatsu",downloadPdfUrl:"/chapter/pdf-download/29494",previewPdfUrl:"/chapter/pdf-preview/29494",authors:[{id:"93549",title:"Prof.",name:"Mitsuhisa",surname:"Komatsu",slug:"mitsuhisa-komatsu",fullName:"Mitsuhisa Komatsu"},{id:"101127",title:"Dr.",name:"Junichirou",surname:"Mori",slug:"junichirou-mori",fullName:"Junichirou Mori"},{id:"101129",title:"Dr.",name:"Yoshihiko",surname:"Sato",slug:"yoshihiko-sato",fullName:"Yoshihiko Sato"}],corrections:null},{id:"29495",title:"Bariatric and Metabolic Surgery for Asians",doi:"10.5772/33891",slug:"bariatric-and-metabolic-surgery-for-asians",totalDownloads:3407,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Kazunori Kasama, Yosuke Seki and Tsuyoshi Yamaguchi",downloadPdfUrl:"/chapter/pdf-download/29495",previewPdfUrl:"/chapter/pdf-preview/29495",authors:[{id:"97626",title:"Dr.",name:"Kazunori",surname:"Kasama",slug:"kazunori-kasama",fullName:"Kazunori Kasama"},{id:"100519",title:"Dr.",name:"Yosuke",surname:"Seki",slug:"yosuke-seki",fullName:"Yosuke Seki"},{id:"135555",title:"Dr.",name:"Tsuyoshi",surname:"Yamaguchi",slug:"tsuyoshi-yamaguchi",fullName:"Tsuyoshi Yamaguchi"}],corrections:null},{id:"29496",title:"Robotic-Assisted Bariatric Surgery",doi:"10.5772/34993",slug:"robotic-assisted-bariatric-surgery",totalDownloads:3182,totalCrossrefCites:1,totalDimensionsCites:5,signatures:"Ulises Garza, Angela Echeverria and Carlos Galvani",downloadPdfUrl:"/chapter/pdf-download/29496",previewPdfUrl:"/chapter/pdf-preview/29496",authors:[{id:"102528",title:"Dr.",name:"Carlos",surname:"Galvani",slug:"carlos-galvani",fullName:"Carlos Galvani"},{id:"102530",title:"Dr.",name:"Angela",surname:"Echeverria",slug:"angela-echeverria",fullName:"Angela Echeverria"},{id:"129703",title:"Dr.",name:"Ulises",surname:"Garza",slug:"ulises-garza",fullName:"Ulises Garza"}],corrections:null},{id:"29497",title:"Scarless Bariatric Surgery",doi:"10.5772/32070",slug:"scarless-bariatric-surgery",totalDownloads:1742,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Chih-Kun Huang, Rajat Goel and Satish Pattanshetti",downloadPdfUrl:"/chapter/pdf-download/29497",previewPdfUrl:"/chapter/pdf-preview/29497",authors:[{id:"90031",title:"Dr.",name:"Chih-Kun",surname:"Huang",slug:"chih-kun-huang",fullName:"Chih-Kun Huang"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},relatedBooks:[{type:"book",id:"3814",title:"Essentials and Controversies in Bariatric Surgery",subtitle:null,isOpenForSubmission:!1,hash:"f696074cc097179739dd92721fcded2b",slug:"essentials-and-controversies-in-bariatric-surgery",bookSignature:"Chih-Kun Huang",coverURL:"https://cdn.intechopen.com/books/images_new/3814.jpg",editedByType:"Edited by",editors:[{id:"90031",title:"Dr.",name:"Chih-Kun",surname:"Huang",slug:"chih-kun-huang",fullName:"Chih-Kun Huang"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5346",title:"Body Contouring and Sculpting",subtitle:null,isOpenForSubmission:!1,hash:"79bcaa74382f64066fe10bf59e89be6d",slug:"body-contouring-and-sculpting",bookSignature:"Nikolay P. Serdev",coverURL:"https://cdn.intechopen.com/books/images_new/5346.jpg",editedByType:"Edited by",editors:[{id:"32585",title:"Dr.",name:"Nikolay",surname:"Serdev",slug:"nikolay-serdev",fullName:"Nikolay Serdev"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1591",title:"Infrared Spectroscopy",subtitle:"Materials Science, Engineering and Technology",isOpenForSubmission:!1,hash:"99b4b7b71a8caeb693ed762b40b017f4",slug:"infrared-spectroscopy-materials-science-engineering-and-technology",bookSignature:"Theophile Theophanides",coverURL:"https://cdn.intechopen.com/books/images_new/1591.jpg",editedByType:"Edited by",editors:[{id:"37194",title:"Dr.",name:"Theophanides",surname:"Theophile",slug:"theophanides-theophile",fullName:"Theophanides Theophile"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3092",title:"Anopheles mosquitoes",subtitle:"New insights into malaria vectors",isOpenForSubmission:!1,hash:"c9e622485316d5e296288bf24d2b0d64",slug:"anopheles-mosquitoes-new-insights-into-malaria-vectors",bookSignature:"Sylvie Manguin",coverURL:"https://cdn.intechopen.com/books/images_new/3092.jpg",editedByType:"Edited by",editors:[{id:"50017",title:"Prof.",name:"Sylvie",surname:"Manguin",slug:"sylvie-manguin",fullName:"Sylvie Manguin"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3161",title:"Frontiers in Guided Wave Optics and Optoelectronics",subtitle:null,isOpenForSubmission:!1,hash:"deb44e9c99f82bbce1083abea743146c",slug:"frontiers-in-guided-wave-optics-and-optoelectronics",bookSignature:"Bishnu Pal",coverURL:"https://cdn.intechopen.com/books/images_new/3161.jpg",editedByType:"Edited by",editors:[{id:"4782",title:"Prof.",name:"Bishnu",surname:"Pal",slug:"bishnu-pal",fullName:"Bishnu Pal"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"72",title:"Ionic Liquids",subtitle:"Theory, Properties, New Approaches",isOpenForSubmission:!1,hash:"d94ffa3cfa10505e3b1d676d46fcd3f5",slug:"ionic-liquids-theory-properties-new-approaches",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/72.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1373",title:"Ionic Liquids",subtitle:"Applications and Perspectives",isOpenForSubmission:!1,hash:"5e9ae5ae9167cde4b344e499a792c41c",slug:"ionic-liquids-applications-and-perspectives",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/1373.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"57",title:"Physics and Applications of Graphene",subtitle:"Experiments",isOpenForSubmission:!1,hash:"0e6622a71cf4f02f45bfdd5691e1189a",slug:"physics-and-applications-of-graphene-experiments",bookSignature:"Sergey Mikhailov",coverURL:"https://cdn.intechopen.com/books/images_new/57.jpg",editedByType:"Edited by",editors:[{id:"16042",title:"Dr.",name:"Sergey",surname:"Mikhailov",slug:"sergey-mikhailov",fullName:"Sergey Mikhailov"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"371",title:"Abiotic Stress in Plants",subtitle:"Mechanisms and Adaptations",isOpenForSubmission:!1,hash:"588466f487e307619849d72389178a74",slug:"abiotic-stress-in-plants-mechanisms-and-adaptations",bookSignature:"Arun Shanker and B. Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"878",title:"Phytochemicals",subtitle:"A Global Perspective of Their Role in Nutrition and Health",isOpenForSubmission:!1,hash:"ec77671f63975ef2d16192897deb6835",slug:"phytochemicals-a-global-perspective-of-their-role-in-nutrition-and-health",bookSignature:"Venketeshwer Rao",coverURL:"https://cdn.intechopen.com/books/images_new/878.jpg",editedByType:"Edited by",editors:[{id:"82663",title:"Dr.",name:"Venketeshwer",surname:"Rao",slug:"venketeshwer-rao",fullName:"Venketeshwer Rao"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],ofsBooks:[]},correction:{item:{id:"66301",slug:"corrigendum-to-denim-fabrics-woven-with-dual-core-spun-yarns",title:"Corrigendum to: Denim Fabrics Woven with Dual Core-Spun Yarns",doi:null,correctionPDFUrl:"https://cdn.intechopen.com/pdfs/66301.pdf",downloadPdfUrl:"/chapter/pdf-download/66301",previewPdfUrl:"/chapter/pdf-preview/66301",totalDownloads:null,totalCrossrefCites:null,bibtexUrl:"/chapter/bibtex/66301",risUrl:"/chapter/ris/66301",chapter:{id:"63209",slug:"denim-fabrics-woven-with-dual-core-spun-yarns",signatures:"Osman Babaarslan, Esin Sarioğlu, Halil İbrahim Çelik and Münevver\nArtek Avci",dateSubmitted:"February 5th 2018",dateReviewed:"July 12th 2018",datePrePublished:"November 5th 2018",datePublished:"February 13th 2019",book:{id:"7242",title:"Engineered Fabrics",subtitle:null,fullTitle:"Engineered Fabrics",slug:"engineered-fabrics",publishedDate:"February 13th 2019",bookSignature:"Mukesh Kumar Singh",coverURL:"https://cdn.intechopen.com/books/images_new/7242.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"36895",title:"Dr.",name:"Mukesh Kumar",middleName:null,surname:"Singh",slug:"mukesh-kumar-singh",fullName:"Mukesh Kumar Singh"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"119775",title:"Prof.",name:"Osman",middleName:null,surname:"Babaarslan",fullName:"Osman Babaarslan",slug:"osman-babaarslan",email:"teksob@cu.edu.tr",position:null,institution:{name:"Cukurova University",institutionURL:null,country:{name:"Turkey"}}},{id:"178353",title:"Dr.",name:"Halil",middleName:"İbrahim",surname:"Çelik",fullName:"Halil Çelik",slug:"halil-celik",email:"hcelik@gantep.edu.tr",position:null,institution:{name:"Gaziantep University",institutionURL:null,country:{name:"Turkey"}}},{id:"216179",title:"Dr.",name:"Esin",middleName:null,surname:"Sarıoğlu",fullName:"Esin Sarıoğlu",slug:"esin-sarioglu",email:"sarioglu@gantep.edu.tr",position:null,institution:{name:"Gaziantep University",institutionURL:null,country:{name:"Turkey"}}},{id:"245674",title:"Mrs.",name:"Münevver",middleName:null,surname:"Ertek Avci",fullName:"Münevver Ertek Avci",slug:"munevver-ertek-avci",email:"Munevver.ErtekAvci@calikdenim.com",position:null,institution:null}]}},chapter:{id:"63209",slug:"denim-fabrics-woven-with-dual-core-spun-yarns",signatures:"Osman Babaarslan, Esin Sarioğlu, Halil İbrahim Çelik and Münevver\nArtek Avci",dateSubmitted:"February 5th 2018",dateReviewed:"July 12th 2018",datePrePublished:"November 5th 2018",datePublished:"February 13th 2019",book:{id:"7242",title:"Engineered Fabrics",subtitle:null,fullTitle:"Engineered Fabrics",slug:"engineered-fabrics",publishedDate:"February 13th 2019",bookSignature:"Mukesh Kumar Singh",coverURL:"https://cdn.intechopen.com/books/images_new/7242.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"36895",title:"Dr.",name:"Mukesh Kumar",middleName:null,surname:"Singh",slug:"mukesh-kumar-singh",fullName:"Mukesh Kumar Singh"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"119775",title:"Prof.",name:"Osman",middleName:null,surname:"Babaarslan",fullName:"Osman Babaarslan",slug:"osman-babaarslan",email:"teksob@cu.edu.tr",position:null,institution:{name:"Cukurova University",institutionURL:null,country:{name:"Turkey"}}},{id:"178353",title:"Dr.",name:"Halil",middleName:"İbrahim",surname:"Çelik",fullName:"Halil Çelik",slug:"halil-celik",email:"hcelik@gantep.edu.tr",position:null,institution:{name:"Gaziantep University",institutionURL:null,country:{name:"Turkey"}}},{id:"216179",title:"Dr.",name:"Esin",middleName:null,surname:"Sarıoğlu",fullName:"Esin Sarıoğlu",slug:"esin-sarioglu",email:"sarioglu@gantep.edu.tr",position:null,institution:{name:"Gaziantep University",institutionURL:null,country:{name:"Turkey"}}},{id:"245674",title:"Mrs.",name:"Münevver",middleName:null,surname:"Ertek Avci",fullName:"Münevver Ertek Avci",slug:"munevver-ertek-avci",email:"Munevver.ErtekAvci@calikdenim.com",position:null,institution:null}]},book:{id:"7242",title:"Engineered Fabrics",subtitle:null,fullTitle:"Engineered Fabrics",slug:"engineered-fabrics",publishedDate:"February 13th 2019",bookSignature:"Mukesh Kumar Singh",coverURL:"https://cdn.intechopen.com/books/images_new/7242.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"36895",title:"Dr.",name:"Mukesh Kumar",middleName:null,surname:"Singh",slug:"mukesh-kumar-singh",fullName:"Mukesh Kumar Singh"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}}},ofsBook:{item:{type:"book",id:"6679",leadTitle:null,title:"Serotonin",subtitle:null,reviewType:"peer-reviewed",abstract:"My scientific journey brought me from Lanzhou in China, Leuven in Belgium, Bethesda in the USA, all the way to San Diego. Sometimes I pick up an assortment of scattered seashells while walking along the beautiful Torrey Pines Beach in San Diego. Likewise, this book contains an assortment of discussions of different aspects of serotonin to enrich our knowledge and understanding of this neurochemical. The book contains four different chapters: 1. Introductory chapter: From Measuring Serotonin Neurotransmission to Evaluating Serotonin Post-Receptor Signaling Transduction; 2. Serotonin Reuptake Inhibitors and Their Role in Chronic Pain Management; 3. Serotonin and Emotional Decision-Making; and 4. Clinical Aspects Related to Plasma Serotonin in the Horse.",isbn:"978-1-78985-236-3",printIsbn:"978-1-78985-235-6",pdfIsbn:"978-1-83962-026-3",doi:"10.5772/intechopen.72010",price:100,priceEur:109,priceUsd:129,slug:"serotonin",numberOfPages:74,isOpenForSubmission:!1,hash:"9c833c86546ec9d3c38fb24a1072dbd0",bookSignature:"Ying Qu",publishedDate:"February 13th 2019",coverURL:"https://cdn.intechopen.com/books/images_new/6679.jpg",keywords:null,numberOfDownloads:2038,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfDimensionsCitations:4,numberOfTotalCitations:4,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"November 20th 2017",dateEndSecondStepPublish:"December 11th 2017",dateEndThirdStepPublish:"February 9th 2018",dateEndFourthStepPublish:"April 30th 2018",dateEndFifthStepPublish:"June 29th 2018",remainingDaysToSecondStep:"3 years",secondStepPassed:!0,currentStepOfPublishingProcess:5,editedByType:"Edited by",kuFlag:!1,biosketch:null,coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"94028",title:"Dr.",name:"Ying",middleName:null,surname:"Qu",slug:"ying-qu",fullName:"Ying Qu",profilePictureURL:"https://mts.intechopen.com/storage/users/94028/images/5914_n.jpg",biography:"Dr. Ying Qu is a multi-disciplinary scientist, currently working in Leulan Bioscience, USA. She received her BS and MS in Chemistry from Lanzhou University, China and her PhD in Neuroscience from the Catholic University of Leuven, Belgium. Dr. Qu has spent part of her career at the National Institutes of Health, USA, studying depression mechanisms underlying serotonin post-receptor regulated signaling transduction. She is also involved in a drug discovery program at Johnson and Johnson in the USA developing novel dual-acting antidepressants with selective serotonin reuptake inhibitors. In 2002, she received a Sevier Young Investigator Award from the Serotonin Club at the International Union of Basic and Clinical Pharmacology (IUPHAR) Satellite Meeting on Serotonin. She has published over 30 peer-reviewed papers, 40 abstracts and two book chapters in the fields of neuropsychopharmacology and bioanalysis.",institutionString:"Leulan Bioscience",position:"Senior Scientist",outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"1",institution:null}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1115",title:"Neuropharmacology",slug:"neuropharmacology"}],chapters:[{id:"65286",title:"Introductory Chapter: From Measuring Serotonin Neurotransmission to Evaluating Serotonin Post-Receptor Signaling Transduction",slug:"introductory-chapter-from-measuring-serotonin-neurotransmission-to-evaluating-serotonin-post-recepto",totalDownloads:487,totalCrossrefCites:0,authors:[{id:"94028",title:"Dr.",name:"Ying",surname:"Qu",slug:"ying-qu",fullName:"Ying Qu"}]},{id:"63750",title:"Serotonin Reuptake Inhibitors and Their Role in Chronic Pain Management",slug:"serotonin-reuptake-inhibitors-and-their-role-in-chronic-pain-management",totalDownloads:647,totalCrossrefCites:0,authors:[null]},{id:"64092",title:"Serotonin and Emotional Decision-Making",slug:"serotonin-and-emotional-decision-making",totalDownloads:472,totalCrossrefCites:0,authors:[null]},{id:"61898",title:"Clinical Aspects Related to Plasma Serotonin in the Horse",slug:"clinical-aspects-related-to-plasma-serotonin-in-the-horse",totalDownloads:433,totalCrossrefCites:0,authors:[{id:"125292",title:"Dr.",name:"Katy",surname:"Satué Ambrojo",slug:"katy-satue-ambrojo",fullName:"Katy Satué Ambrojo"}]}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"185543",firstName:"Maja",lastName:"Bozicevic",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/185543/images/4748_n.jpeg",email:"maja.b@intechopen.com",biography:"As an Author Service Manager my responsibilities include monitoring and facilitating all publishing activities for authors and editors. From chapter submission and review, to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. Whether that be identifying an exceptional author and proposing an editorship collaboration, or contacting researchers who would like the opportunity to work with IntechOpen, I establish and help manage author and editor acquisition and contact."}},relatedBooks:[{type:"book",id:"7256",title:"Dopamine",subtitle:"Health and Disease",isOpenForSubmission:!1,hash:"e46d08f526c35d787be15bcb17126fb8",slug:"dopamine-health-and-disease",bookSignature:"Sarat Chandra Yenisetti",coverURL:"https://cdn.intechopen.com/books/images_new/7256.jpg",editedByType:"Edited by",editors:[{id:"181774",title:"Prof.",name:"Sarat Chandra",surname:"Yenisetti",slug:"sarat-chandra-yenisetti",fullName:"Sarat Chandra Yenisetti"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6404",title:"Drug Addiction",subtitle:null,isOpenForSubmission:!1,hash:"f432d0ab93a06628d3592b4c0fea44ae",slug:"drug-addiction",bookSignature:"Fang Zhao and Meng Li",coverURL:"https://cdn.intechopen.com/books/images_new/6404.jpg",editedByType:"Edited by",editors:[{id:"207525",title:"Dr.",name:"Fang",surname:"Zhao",slug:"fang-zhao",fullName:"Fang Zhao"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5894",title:"Neurotoxins",subtitle:null,isOpenForSubmission:!1,hash:"4ed24b0789b6d0bf230c24637f2f7575",slug:"neurotoxins",bookSignature:"J. Eric McDuffie",coverURL:"https://cdn.intechopen.com/books/images_new/5894.jpg",editedByType:"Edited by",editors:[{id:"161246",title:"Dr.",name:"J. Eric",surname:"McDuffie",slug:"j.-eric-mcduffie",fullName:"J. Eric McDuffie"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8166",title:"Receptors P1 and P2 as Targets for Drug Therapy in Humans",subtitle:null,isOpenForSubmission:!1,hash:"546c9abc8145b3a3ecf13557a03f7590",slug:"receptors-p1-and-p2-as-targets-for-drug-therapy-in-humans",bookSignature:"Robson Faria",coverURL:"https://cdn.intechopen.com/books/images_new/8166.jpg",editedByType:"Edited by",editors:[{id:"79615",title:"Dr.",name:"Robson",surname:"Faria",slug:"robson-faria",fullName:"Robson Faria"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7116",title:"Antidepressants",subtitle:"Preclinical, Clinical and Translational Aspects",isOpenForSubmission:!1,hash:"1bd4340dfebb60697e12fc04a461d9ac",slug:"antidepressants-preclinical-clinical-and-translational-aspects",bookSignature:"Olivier Berend",coverURL:"https://cdn.intechopen.com/books/images_new/7116.jpg",editedByType:"Edited by",editors:[{id:"71579",title:"Prof.",name:"Berend",surname:"Olivier",slug:"berend-olivier",fullName:"Berend Olivier"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1591",title:"Infrared Spectroscopy",subtitle:"Materials Science, Engineering and Technology",isOpenForSubmission:!1,hash:"99b4b7b71a8caeb693ed762b40b017f4",slug:"infrared-spectroscopy-materials-science-engineering-and-technology",bookSignature:"Theophile Theophanides",coverURL:"https://cdn.intechopen.com/books/images_new/1591.jpg",editedByType:"Edited by",editors:[{id:"37194",title:"Dr.",name:"Theophanides",surname:"Theophile",slug:"theophanides-theophile",fullName:"Theophanides Theophile"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3092",title:"Anopheles mosquitoes",subtitle:"New insights into malaria vectors",isOpenForSubmission:!1,hash:"c9e622485316d5e296288bf24d2b0d64",slug:"anopheles-mosquitoes-new-insights-into-malaria-vectors",bookSignature:"Sylvie Manguin",coverURL:"https://cdn.intechopen.com/books/images_new/3092.jpg",editedByType:"Edited by",editors:[{id:"50017",title:"Prof.",name:"Sylvie",surname:"Manguin",slug:"sylvie-manguin",fullName:"Sylvie Manguin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3161",title:"Frontiers in Guided Wave Optics and Optoelectronics",subtitle:null,isOpenForSubmission:!1,hash:"deb44e9c99f82bbce1083abea743146c",slug:"frontiers-in-guided-wave-optics-and-optoelectronics",bookSignature:"Bishnu Pal",coverURL:"https://cdn.intechopen.com/books/images_new/3161.jpg",editedByType:"Edited by",editors:[{id:"4782",title:"Prof.",name:"Bishnu",surname:"Pal",slug:"bishnu-pal",fullName:"Bishnu Pal"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"72",title:"Ionic Liquids",subtitle:"Theory, Properties, New Approaches",isOpenForSubmission:!1,hash:"d94ffa3cfa10505e3b1d676d46fcd3f5",slug:"ionic-liquids-theory-properties-new-approaches",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/72.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1373",title:"Ionic Liquids",subtitle:"Applications and Perspectives",isOpenForSubmission:!1,hash:"5e9ae5ae9167cde4b344e499a792c41c",slug:"ionic-liquids-applications-and-perspectives",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/1373.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"64798",title:"Osteoarthritis as a Chronic Inflammatory Disease: A Review of the Inflammatory Markers",doi:"10.5772/intechopen.82565",slug:"osteoarthritis-as-a-chronic-inflammatory-disease-a-review-of-the-inflammatory-markers",body:'
Osteoarthritis (OA) is a common disease that can affect joints from any part of the body, and it represents a major cause of disability and joint pain worldwide [1, 2]. OA most commonly affects the knee, hip, and shoulder, and it was estimated that more than 25 million people in the USA were affected by some form of OA in the last decade [3]. In addition, OA presents a high susceptibility to affect female gender, elderly people, and obese individuals [4].
The progression of OA leads to cartilage degradation with subchondral bone remodeling, hypertrophy of the joint capsule, and osteophytes formation, causing pain [1, 5, 6]. Although the development of OA is considered a heterogeneous process, which comprises a number of genetic and environmental causes, the presence of local causes, such as trauma and hypermobility of the joint, may worsen OA [2, 7].
The accurate identification of osteoarthritic features has been studied in order to radiographically grade the stages of OA. The Kellgren-Lawrence classification is the most widely used, especially in clinical researches. This classification evaluates the appearance of osteophytes and cysts, joint space loss, and sclerosis, and it grades the severity from 0 to 5 points. The radiological features found in OA joints were graded as follows: (1) formation of osteophytes on joint margins or on tibia spines for knee OA; (2) periarticular ossicles in relation to distal and proximal interphalangeal joints; (3) narrowing of joint cartilage and sclerosis of subchondral bone; (4) pseudocystic areas with sclerotic walls in the subchondral bone; and (5) altered shape of the bone ends [8]. Some of these criteria were adopted by the World Health Organization (WHO) as the standard for studies on OA.
Current options for the treatment of OA focus on reducing pain (non-steroidal anti-inflammatory drugs—NSAIDs) and joint viscosupplementation (intra-articular injections of hyaluronic acid) [1]. Besides presenting a short-term effect, the chronic use of some of these medications, especially NSAIDs, may cause serious adverse events, including toxicity and risk of thromboembolism [9, 10]. In severe cases, surgical procedures, mostly joint replacement, are suggested [1]. Novel alternative therapies, called orthobiologics, have emerged from the need of tissue regeneration. Clinical trials using orthobiologics, which comprise platelet-rich plasma (PRP), bone marrow aspirate concentrate (BMAC), fat graft (Biofat), and expanded mesenchymal stem cells, have shown promising results for the treatments of OA from any origin [11, 12, 13, 14].
Moreover, monoclonal antibody (mAb) therapy represents one of the alternative treatments that aim to control inflammation and slow structural progression [15]. This approach focuses on blocking specific molecules responsible for the maintenance of OA. Preclinical studies with ADAMTS mAbs reported a significant decrease in histological scores after 3 months of treatment [16]. Adalimumab is an anti-TNF-α therapy used in diverse immune-mediated diseases, and it presents a protective role for OA as it reduces the severity of the cartilage lesion and improves the structure of subchondral bone [17]. Since IL-1 family may induces the production of metalloproteinases (MMP), it has also become a target for mAb therapy, and, in a randomized controlled trial with patients who presented knee OA, it was reported great improvement on pain relief [18].
In addition to macroscopic features, several cellular and molecular alterations are present in OA, such as catabolism and anabolism events; hypertrophy and, consequently, death of chondrocytes; and impaired autophagy process [19]. Also, a chronic low-grade inflammation interplayed with immune system has been considered to present a crucial role in the maintenance of OA [1]. This fact is supported by recent progress, which has considerably improved the knowledge regarding factors involved in the OA development and the mechanisms responsible for its progression.
The inflammation observed in OA is believed to involve innate immune response prior to a mild degree of adaptive immunity [20]. During tissue damage, a group of endogenous molecules, called damage-associated molecular pattern (DAMP), signals the immune cells to induce a protective response against the tissue, causing tissue repair. However, a prolonged signaling of DAMP to immune cells leads to an exacerbated cytokine release, which can be destructive to the tissue [21, 22].
Innate immune cells activated by DAMP include macrophages and mast cells, which have shown to present (displayed or demonstrated) a key role in the pathogenesis of OA. Mast cells are considered regulators of vascular permeability, and they may play a crucial role in OA joint inflammation as they facilitate leukocyte infiltration [23].
Macrophages exhibit a functional plasticity based on the environment in which they are located or present [22]. However, their chronic activation can lead to the production of proinflammatory cytokines, which worsen the osteoarthritic joints [24]. In vitro studies of human OA synovium-derived cells showed that macrophage depletion results in diminishing of inflammatory response by decrease of proteolytic enzyme expression, such as metalloproteinases (MMP) This fact is supported by in vitro studies with cell culture suspension of human OA synovium, which reported that, after macrophage depletion, there was a decrease in the production of inflammatory response by less activity of proteolytic enzymes, such as metalloproteinases (MMP) [25]. Although macrophages may also present a protective role, as they are known to secrete transforming growth factor β (TGF-β), which would enhance cartilage repair, intra-articular injection of TGF-β in mice knee led to osteophyte formation and fibrosis [26].
In addition, natural killer (NK) infiltrates are commonly found in synovial tissue from patients who underwent joint replacement surgeries, and a subset of NK cells (CD56bright) was found to be greatly expanded in patients with inflammatory arthritis who have not undergone joint replacement surgeries. However, the effect of these cells on the development of OA has not been elucidated yet [27, 28, 29]. NK cells secrete protease enzymes called granzyme type A and B, which correlate to cytolytic potency. Granzymes can be released during degranulation of cytotoxic cells and, when delivered intracellularly to the target cells, they induce apoptosis. Granzyme A also stimulates the production of tumor necrosis factor (TNF-α), IL-6, and IL-8, while granzyme B may intensify the degradation of extracellular matrix [30, 31]. Tak et al. identified both types of granzymes in synovia from OA and rheumatoid arthritis. However, another study later showed that NK cells within OA synovia were granzyme negative with potential to produce the interferon-γ (IFN-γ) when expanded with IL-2 and stimulated with cytokines known to trigger IFN-γ production in blood NK cells, such as IL-12 and IL-18 [27, 32].
The presence of IFN-γ has a role in the bone resorption and consequently in the osteoclastogenesis process, but the studies have shown controversial results in this regard: in vitro evidence reported that IFN-γ, via TRANCE pathway, strongly suppresses osteoclastogenesis in culture of mononuclear phagocyte cells, which are the osteoclast precursors [33], whereas in culture of peripheral blood it may enhance osteoclast production as IFN-γ increases superoxide generation by neutrophils [34]. In addition, experimental studies in which IFN-γ receptor was silenced suggested a more rapid onset of collagen-induced arthritis [35]. Although IFN-γ plays a key role in angiogenesis, there is no evidence that this cytokine is able to promote angiogenesis in OA.
Proteins from complement system have been found to play a role in OA, especially in early stages, as they were upregulated in both synovial membrane and fluid [23, 36]. Additionally, the deposition of the membrane attack complex (MAC, C5b-9) is correlated with the presence of inflammation on histology of synovial membrane, and it was present in chondrocytes in late OA [36]. MAC can lead to chondrocyte destruction as it stimulates catabolic events through the increase of leukocytes and, consequently, the production of MMP [23]. Also in the studies with experimental knockout models for C5 and C6, the joint damages were attenuated [36].
Cellular infiltrates from adaptive immune response have also been observed in synovial fluid from OA joints. Although the main cell type present in this infiltrate is CD3+ T cells, both CD4+ and CD8+ cells have also been found in OA [37]. Th1 cells, and consequently their secretory cytokines, such as IL-2 and INF-γ, appear to be expressed five times greater than Th2 in most of OA patients [37]. Based on lymphocyte aggregates, there is a suggestion of an active cell-mediated immune response since T-cells in lymphocytic aggregates in OA synovium were shown to bear early (CD69), intermediate (CD25 and CD38), and late (CD45RO) activation markers [38].
Inflammatory mediators observed in OA joints are thought to be the downstream effectors of the pathogenesis of the disease. Cytokines are among the most extensively studied mediators of inflammation. Several cytokines have been reported to play a role in the progression of OA, such as TNF, IL-1β, IL-6, IL-15, IL-17, IL-18, IL-4, and IL-10. Although their precise mechanism of action has not been completely elucidated yet, it has been proposed that their presence influences cartilage homeostasis as they induce catabolic events as well as inhibit anabolic processes [21, 39, 40].
Interleukin (IL)-1β and tumor necrosis factor (TNF) are considered the major mediators in the pathophysiology of OA. They both are secreted not only by immune cells, especially mononuclear cells, but also by chondrocytes and osteoblasts. In OA joints, these cytokines are increased in both synovial fluid and membrane. They are known to drive the inflammatory cascade, and their increased expression induces catabolic events as they enhance MMP [39]. IL-1β and TNF downregulate the synthesis of major extracellular matrix (ECM) components by inhibiting anabolic activities of chondrocytes [40] and reducing type II collagen production [41].
IL-1β is activated through the binding of its specific receptor type I (IL-1RI). Overexpression of IL-1RI in cartilage proximal to the macroscopic injury in OA joints resulting in increased binding of IL-1β was observed [42]. IL-1β has also been reported to be responsible for the catabolic events present in OA: its expression combined with TNF induces the production of MMP-1, -3, and -13 and stimulates the production of aggrecanases (ADAMTS)-4 and -5 in human and bovine chondrocytes [43, 44]. TNF receptor type I (TNFRI) is overexpressed in OA chondrocytes [45]. High levels of TNF-α in cartilage explants seem to inhibit the synthesis of proteoglycan and stimulate resorption [40].
In OA joint, IL-1β and TNF amplify the arthritic condition by inducing the production of proinflammatory cytokines, such as IL-6, IL-8, and monocyte chemoattractant protein 1. In addition, chondrocytes treated with IL-1β and TNF increase the production of nitric oxide (NO), cyclooxygenase 2 (COX-2), and prostaglandin E2 (PGE2), which contribute to articular inflammation and cartilage destruction as they enhance MMP activity, inhibit the production of anabolic products such as collagen and proteoglycan, and induce chondrocyte apoptosis [39].
The catabolic events observed (the catabolic events that occur due to the presence of…) in the presence of IL-1β and TNF are mediated through the activation of signaling pathways, including nuclear factor-κB (NF-κB) signaling. NF-κB pathway induces the expression of the genes related to the inflammatory mediators cited above and also contributes to the induction of MMP-1 and -13 and ADAMTS-4 [46]. However, some signaling pathways are involved in the downregulation of the IL-1β and TNF effects in OA, such as peroxisome proliferator-activated receptor-γ (PPAR-γ). The activation of PPAR-γ seems to reduce the progression of cartilage lesion in experimental models of OA as it assists the downregulation of inflammatory and catabolic responses mediated by IL-1β and TNF [47, 48].
IL-6 is a proinflammatory cytokine, whose signaling pathway involves the activation of receptors, such as membrane-bound IL-6 receptor (IL6R), soluble IL-6R (sIL-6R), and gp130, followed by the activation of STAT1 and STAT3 pathways [39]. In physiological conditions, the production of IL-6 by chondrocytes is considerably low. However, the exact mechanism of IL-6 action in OA is unknown, but its production can be stimulated by the number of cytokines and growth factors present in OA, including IL-1β, TGF-β, and PGE2 [25, 49].
Increased levels of IL-6 in synovial fluid and serum have been correlated with the severity of lesions in X-ray imaging [50]. In vitro studies have shown that IL-6, in combination with IL-1β and TNF, upregulates the production of MMP-1 and -13 in human and bovine chondrocytes and induces proteoglycan and type II collagen degradation [51, 52]. The effect of IL-6 in studies with animal models has shown uncertain results. IL-6 knockout mice revealed more advanced degenerative changes compared to wild-type animals [53]. However, when IL-6 was injected in the joint cavity of IL-6-deficient mice, the reduction in the loss of proteoglycans in the acute phase of inflammation was observed [54].
One of the most considered active components in OA is the change in subchondral bone tissue, and IL-6 has been a critical mediator in this regard. Its effect, together with IL-1β and TNF, is based on promoting osteoclast formation and, consequently, bone resorption [55]. In response to IL-6, osteoblasts stimulate the production of receptor activator of NF-κB ligand, IL-1β, and PGE2, which activate osteoclasts [56]. In addition, osteoblasts activated by these cytokines produce MMPs, which adversely affect the surrounding cartilage [57].
Despite a better documented involvement in rheumatoid arthritis [58], the knowledge regarding IL-15 and its action in OA is still poor. It acts based on the stimulation and proliferation of T cells and NK cells, and it may also induce the production of MMP [59]. IL-15 levels are elevated in synovial fluid in early stages of OA, and this concentration correlates with pain and severity of lesions seen on X-ray imaging [60, 61].
Due to its inflammatory effects, IL-17 family has been implied to play a role in OA [62]. IL-17 is mainly stimulated by CD4+ T cells and mast cells, which are present in the cellular infiltrates observed in OA joints [63]. Within the joints, IL-17 primarily targets chondrocytes and fibroblast-like synoviocytes, which express IL-17 receptor (IL-17R) on their surface [64]. It was reported that IL-17 is able to inhibit proteoglycan synthesis by chondrocytes and increase the production of MMPs [65]. Also, high levels of IL-17 in both serum and synovial fluid were correlated with radiographic lesions in OA [66].
The genetic correlation between IL-17 and OA was suggested: a polymorphism in the gene IL-17A G-197A could be associated with the susceptibility to the development of OA [67]. In addition, IL-17 is produced by a specific T cell lineage called T helper 17, and it is able to cause hypertrophy of synovial membrane as its presence influences the secretion of vascular endothelial growth factor (VEGF), which leads to excessive blood vessel formation [68]. It can also indirectly affect cartilage by inducing the production of cytokines responsible for tissue degradation, such as IL-1β, TNF, IL-6, NO, and PGE2 [64].
The active form of IL-18 results from the activation of caspase-1, which has been reported to be elevated in articular cartilage and synovium of OA, leading to great promotion of IL-18 and IL-1β. The production of IL-18 in joints is mainly determined by chondrocytes, osteoblasts, and macrophages [69]. IL-18 affects cartilage by upregulating the production of IL-18Rα on chondrocyte surface and stimulates excessive production of MMP-1, -3, and -13 [70]. Also, IL-18 negatively influences the production of proteoglycans, aggrecan, and type II collagen and may cause morphological changes typically observed in apoptotic processes [71, 72].
The increased concentration of IL-18 observed in synovial fluid, synovium, cartilage, and even blood serum from patients with OA has been correlated with the severity of lesions seen in radiographic imaging [73]. Also, studies have correlated the development of OA and lumbar disc degeneration with polymorphisms in the gene encoding IL-18 and its receptor (IL-18R) [74, 75].
Anti-inflammatory cytokines also present a role in the maintenance of OA. IL-4 is associated with chondroprotective effects as it is shown to reduce MMP production and, consequently, inhibit the degradation of proteoglycans in the articular cartilage [76]. However, chondrocytes from OA joints have shown a decreased susceptibility to this IL-4 protective effect, leaving the cartilage unprotected, quickening the degeneration via the action of the proinflammatory cytokines cited above [77]. In addition, a polymorphism in the gene encoding IL-4 and its main receptor (IL-4Rα) could predetermine the development of OA in hand and knee joints [78, 79]. It was also further reported that, when compared with healthy patients, OA patients present an elevated level of soluble IL-4Rα (sIL-4Rα) [80].
The activation of IL-4 depends on intracellular signal transduction by gradual phosphorylation of IL-4Rα, which leads to the expression of several proinflammatory genes [81]. IL-4 production is mainly determined by T cells, especially Th2, which are present in the cellular infiltrates observed in OA [37]. It was reported that IL-4 alone or in combination with IL-10 is able to reduce the production of diverse proinflammatory mediators, such as IL-1β, TNF-α receptors, IL-6, PGE2, and COX-2 [82, 83, 84].
Due to its anti-inflammatory features, IL-10 is another cytokine that presents chondroprotective effects, and it is linked to the release of IFN [62]. In vitro studies have shown increased proteoglycan and type II collagen syntheses after the administration of IL-10 in chondrocytes [62]. The protective effects that IL-10 exhibits are likely due to a stimulation of the synthesis of IL-1β antagonist and a tissue inhibition of MMP-1 (TIMP-1) [85]. Also, IL-10, as well as IL-4, reduces apoptotic events in chondrocytes and production of MMP [86, 87].
IL-10 induces the expression of bone morphogenetic protein-2 and -6 (BMP2 and BMP6), which are related to chondrogenesis as they belong to TGF-β family [88]. Together with BMP production, IL-10 activates signaling pathways, such as NKX-3.2/SOX9, that induce the differentiation of mesenchymal stem cells into chondrocytes [89]. Also, by reducing the expression of TNF-α receptors, IL-10 is able to attenuate the effect of TNF-α on synovial fibroblasts. A decrease in COX-2 production was also noted in the same study [90].
The secretion of IL-10 can be influenced by physical exercises. Patients with and without OA had synovial fluid and periarticular tissue harvested from their knee before, during, and after they underwent exercise practice for 3 hours. A significant increase in IL-10 levels was observed in these patients after the exercise. Although it is not clear what exact mechanism led to this result, this observation is likely attributed to an increase in intra-articular pressure and subsequent effects on cellular secretion [91, 92].
Chemokines comprise small proteins that act as chemoattractants to assist cells to migrate to injured tissue. Diverse chemokines have gained attention in the development of OA. Some of them including their receptors, such as IL-8, CCL5, CCL19, CCR1, CCR2, CCR3, and CCR5, may induce the production of MMP-3 by chondrocytes and increase the breakdown of cartilage matrix components, which trigger the onset of OA [60, 93]. However, some chemokines might present a protective role in OA, such as stromal cell-derived factor-1 (also called CXCL12), whose main function is to recruit mesenchymal stem cells to the injured area in order to promote tissue repair [94].
Several chemokines were reported to be overexpressed in OA, such as IL-8/CXCL-8, GROα/CXCL-1, MCP-1/CCL-2, RANTES/CCL-5, MIP-1α/CCL-3, and MIP-1β/CCL-4. Some of these chemokines are stimulated by IL-1β, which is upregulated in OA, and they induce MMP production upon binding to their ligands, causing tissue degradation [93]. Levels of INF-γ-inducible protein 10 (IP-10), also called as CXCL-10, in plasma and synovial fluid have been correlated with radiographic knee OA. CX3CL1, a serum fractalkine, has also been reported to be significantly elevated in severe knee OA in a study that compared OA patients with healthy patients [95].
To support the role of macrophage in the inflammatory response observed in OA, MCP-1, also known as chemokine ligand-2 (CCL2), has been reported to recruit macrophages into adipose tissue and atherosclerotic lesions [96]. Also, MCP-1 levels in both serum and synovial fluid has been associated with self-reported pain and disability in patients who present knee OA [97]. In addition, it was observed that, in severe knee OA, the levels of macrophage-derived chemokine (MDC) and IP-10 in synovial fluid were elevated, while eotaxin levels, an eosinophil chemotactic protein, were lower when compared with healthy patients [98].
Adipokines have been associated with the incidence and severity of OA [99]. In vitro studies reported that the presence of adipokines, such as leptin, adiponectin, visfatin, and resistin, increases the production of inflammatory mediators and also induces chondrolysis [99]. Although the exact mechanism of how these cytokines derived from adipose tissue act on arthritic joints has not yet been elucidated, researchers have studied the role of fat pad as a local inflammation mediator in OA, particularly in knee OA due to the infrapatellar fat pad, which has proven to be infiltrated with macrophages, lymphocytes, and granulocytes [100]. These findings support the thought that obesity supports the development of OA more through biochemical pathways rather than biomechanical overload risks on a weight-bearing joint.
The COX-2 enzyme is responsible for the production of lipid mediators, including PGE2 and leukotrienes, and it is also upregulated in OA joints. In addition, the overexpression of COX-2 in OA has been associated with the increased production of IL-1β, TNF, and IL-6 via toll-like receptor-4 (TLR-4) [101]. Besides assisting the production of MMPs and other functions already cited above, PGE2 is also involved in apoptosis and structural changes that characterize arthritic disease [102].
Leukotrienes have also been investigated for their role in OA. These mediators are converted from arachidonic acid, which also produces PGE2 via the activity of the enzyme phospholipase A2 [21]. Leukotrienes, mainly leukotriene B4 (LTB4), are present, to a lesser extent, in OA synovium, bone, and cartilage. Also, LTB4 has been reported to stimulate the production of IL-1β and TNF in arthritic synovium [103].
The cumulative evidences over the years have shown that increased expression of proinflammatory cytokines, in particular IL-1β, TNF, and IL-6, in cartilage as well as synovial fluid and membrane, has played a key role in the pathogenesis of OA. Inflammatory processes linked with immune responses have characterized OA as a complex disease and not as a simple age-related cartilage degeneration as it is thought to be. The understanding of individual roles of inflammatory mediators and their compounds is of utmost importance to target new therapies for OA, since the current options are elusive and may be noneffective, invasive, or even capable of presenting serious side effects. Due to advancements in molecular tools, the overall aim would be to dissect the role of each cytokine in the pathophysiology of OA and, together with drug delivery systems, to develop specific anticytokine therapy, given that inflammatory responses contribute substantially to OA maintenance.
The authors have no conflict of interest to declare.
Osteoarthritis (OA) is a common disease that can affect joints from any part of the body, and it represents a major cause of disability and joint pain worldwide [1, 2]. OA most commonly affects the knee, hip, and shoulder, and it was estimated that more than 25 million people in the USA were affected by some form of OA in the last decade [3]. In addition, OA presents a high susceptibility to affect female gender, elderly people, and obese individuals [4].
The progression of OA leads to cartilage degradation with subchondral bone remodeling, hypertrophy of the joint capsule, and osteophytes formation, causing pain [1, 5, 6]. Although the development of OA is considered a heterogeneous process, which comprises a number of genetic and environmental causes, the presence of local causes, such as trauma and hypermobility of the joint, may worsen OA [2, 7].
The accurate identification of osteoarthritic features has been studied in order to radiographically grade the stages of OA. The Kellgren-Lawrence classification is the most widely used, especially in clinical researches. This classification evaluates the appearance of osteophytes and cysts, joint space loss, and sclerosis, and it grades the severity from 0 to 5 points. The radiological features found in OA joints were graded as follows: (1) formation of osteophytes on joint margins or on tibia spines for knee OA; (2) periarticular ossicles in relation to distal and proximal interphalangeal joints; (3) narrowing of joint cartilage and sclerosis of subchondral bone; (4) pseudocystic areas with sclerotic walls in the subchondral bone; and (5) altered shape of the bone ends [8]. Some of these criteria were adopted by the World Health Organization (WHO) as the standard for studies on OA.
Current options for the treatment of OA focus on reducing pain (non-steroidal anti-inflammatory drugs—NSAIDs) and joint viscosupplementation (intra-articular injections of hyaluronic acid) [1]. Besides presenting a short-term effect, the chronic use of some of these medications, especially NSAIDs, may cause serious adverse events, including toxicity and risk of thromboembolism [9, 10]. In severe cases, surgical procedures, mostly joint replacement, are suggested [1]. Novel alternative therapies, called orthobiologics, have emerged from the need of tissue regeneration. Clinical trials using orthobiologics, which comprise platelet-rich plasma (PRP), bone marrow aspirate concentrate (BMAC), fat graft (Biofat), and expanded mesenchymal stem cells, have shown promising results for the treatments of OA from any origin [11, 12, 13, 14].
Moreover, monoclonal antibody (mAb) therapy represents one of the alternative treatments that aim to control inflammation and slow structural progression [15]. This approach focuses on blocking specific molecules responsible for the maintenance of OA. Preclinical studies with ADAMTS mAbs reported a significant decrease in histological scores after 3 months of treatment [16]. Adalimumab is an anti-TNF-α therapy used in diverse immune-mediated diseases, and it presents a protective role for OA as it reduces the severity of the cartilage lesion and improves the structure of subchondral bone [17]. Since IL-1 family may induces the production of metalloproteinases (MMP), it has also become a target for mAb therapy, and, in a randomized controlled trial with patients who presented knee OA, it was reported great improvement on pain relief [18].
In addition to macroscopic features, several cellular and molecular alterations are present in OA, such as catabolism and anabolism events; hypertrophy and, consequently, death of chondrocytes; and impaired autophagy process [19]. Also, a chronic low-grade inflammation interplayed with immune system has been considered to present a crucial role in the maintenance of OA [1]. This fact is supported by recent progress, which has considerably improved the knowledge regarding factors involved in the OA development and the mechanisms responsible for its progression.
The inflammation observed in OA is believed to involve innate immune response prior to a mild degree of adaptive immunity [20]. During tissue damage, a group of endogenous molecules, called damage-associated molecular pattern (DAMP), signals the immune cells to induce a protective response against the tissue, causing tissue repair. However, a prolonged signaling of DAMP to immune cells leads to an exacerbated cytokine release, which can be destructive to the tissue [21, 22].
Innate immune cells activated by DAMP include macrophages and mast cells, which have shown to present (displayed or demonstrated) a key role in the pathogenesis of OA. Mast cells are considered regulators of vascular permeability, and they may play a crucial role in OA joint inflammation as they facilitate leukocyte infiltration [23].
Macrophages exhibit a functional plasticity based on the environment in which they are located or present [22]. However, their chronic activation can lead to the production of proinflammatory cytokines, which worsen the osteoarthritic joints [24]. In vitro studies of human OA synovium-derived cells showed that macrophage depletion results in diminishing of inflammatory response by decrease of proteolytic enzyme expression, such as metalloproteinases (MMP) This fact is supported by in vitro studies with cell culture suspension of human OA synovium, which reported that, after macrophage depletion, there was a decrease in the production of inflammatory response by less activity of proteolytic enzymes, such as metalloproteinases (MMP) [25]. Although macrophages may also present a protective role, as they are known to secrete transforming growth factor β (TGF-β), which would enhance cartilage repair, intra-articular injection of TGF-β in mice knee led to osteophyte formation and fibrosis [26].
In addition, natural killer (NK) infiltrates are commonly found in synovial tissue from patients who underwent joint replacement surgeries, and a subset of NK cells (CD56bright) was found to be greatly expanded in patients with inflammatory arthritis who have not undergone joint replacement surgeries. However, the effect of these cells on the development of OA has not been elucidated yet [27, 28, 29]. NK cells secrete protease enzymes called granzyme type A and B, which correlate to cytolytic potency. Granzymes can be released during degranulation of cytotoxic cells and, when delivered intracellularly to the target cells, they induce apoptosis. Granzyme A also stimulates the production of tumor necrosis factor (TNF-α), IL-6, and IL-8, while granzyme B may intensify the degradation of extracellular matrix [30, 31]. Tak et al. identified both types of granzymes in synovia from OA and rheumatoid arthritis. However, another study later showed that NK cells within OA synovia were granzyme negative with potential to produce the interferon-γ (IFN-γ) when expanded with IL-2 and stimulated with cytokines known to trigger IFN-γ production in blood NK cells, such as IL-12 and IL-18 [27, 32].
The presence of IFN-γ has a role in the bone resorption and consequently in the osteoclastogenesis process, but the studies have shown controversial results in this regard: in vitro evidence reported that IFN-γ, via TRANCE pathway, strongly suppresses osteoclastogenesis in culture of mononuclear phagocyte cells, which are the osteoclast precursors [33], whereas in culture of peripheral blood it may enhance osteoclast production as IFN-γ increases superoxide generation by neutrophils [34]. In addition, experimental studies in which IFN-γ receptor was silenced suggested a more rapid onset of collagen-induced arthritis [35]. Although IFN-γ plays a key role in angiogenesis, there is no evidence that this cytokine is able to promote angiogenesis in OA.
Proteins from complement system have been found to play a role in OA, especially in early stages, as they were upregulated in both synovial membrane and fluid [23, 36]. Additionally, the deposition of the membrane attack complex (MAC, C5b-9) is correlated with the presence of inflammation on histology of synovial membrane, and it was present in chondrocytes in late OA [36]. MAC can lead to chondrocyte destruction as it stimulates catabolic events through the increase of leukocytes and, consequently, the production of MMP [23]. Also in the studies with experimental knockout models for C5 and C6, the joint damages were attenuated [36].
Cellular infiltrates from adaptive immune response have also been observed in synovial fluid from OA joints. Although the main cell type present in this infiltrate is CD3+ T cells, both CD4+ and CD8+ cells have also been found in OA [37]. Th1 cells, and consequently their secretory cytokines, such as IL-2 and INF-γ, appear to be expressed five times greater than Th2 in most of OA patients [37]. Based on lymphocyte aggregates, there is a suggestion of an active cell-mediated immune response since T-cells in lymphocytic aggregates in OA synovium were shown to bear early (CD69), intermediate (CD25 and CD38), and late (CD45RO) activation markers [38].
Inflammatory mediators observed in OA joints are thought to be the downstream effectors of the pathogenesis of the disease. Cytokines are among the most extensively studied mediators of inflammation. Several cytokines have been reported to play a role in the progression of OA, such as TNF, IL-1β, IL-6, IL-15, IL-17, IL-18, IL-4, and IL-10. Although their precise mechanism of action has not been completely elucidated yet, it has been proposed that their presence influences cartilage homeostasis as they induce catabolic events as well as inhibit anabolic processes [21, 39, 40].
Interleukin (IL)-1β and tumor necrosis factor (TNF) are considered the major mediators in the pathophysiology of OA. They both are secreted not only by immune cells, especially mononuclear cells, but also by chondrocytes and osteoblasts. In OA joints, these cytokines are increased in both synovial fluid and membrane. They are known to drive the inflammatory cascade, and their increased expression induces catabolic events as they enhance MMP [39]. IL-1β and TNF downregulate the synthesis of major extracellular matrix (ECM) components by inhibiting anabolic activities of chondrocytes [40] and reducing type II collagen production [41].
IL-1β is activated through the binding of its specific receptor type I (IL-1RI). Overexpression of IL-1RI in cartilage proximal to the macroscopic injury in OA joints resulting in increased binding of IL-1β was observed [42]. IL-1β has also been reported to be responsible for the catabolic events present in OA: its expression combined with TNF induces the production of MMP-1, -3, and -13 and stimulates the production of aggrecanases (ADAMTS)-4 and -5 in human and bovine chondrocytes [43, 44]. TNF receptor type I (TNFRI) is overexpressed in OA chondrocytes [45]. High levels of TNF-α in cartilage explants seem to inhibit the synthesis of proteoglycan and stimulate resorption [40].
In OA joint, IL-1β and TNF amplify the arthritic condition by inducing the production of proinflammatory cytokines, such as IL-6, IL-8, and monocyte chemoattractant protein 1. In addition, chondrocytes treated with IL-1β and TNF increase the production of nitric oxide (NO), cyclooxygenase 2 (COX-2), and prostaglandin E2 (PGE2), which contribute to articular inflammation and cartilage destruction as they enhance MMP activity, inhibit the production of anabolic products such as collagen and proteoglycan, and induce chondrocyte apoptosis [39].
The catabolic events observed (the catabolic events that occur due to the presence of…) in the presence of IL-1β and TNF are mediated through the activation of signaling pathways, including nuclear factor-κB (NF-κB) signaling. NF-κB pathway induces the expression of the genes related to the inflammatory mediators cited above and also contributes to the induction of MMP-1 and -13 and ADAMTS-4 [46]. However, some signaling pathways are involved in the downregulation of the IL-1β and TNF effects in OA, such as peroxisome proliferator-activated receptor-γ (PPAR-γ). The activation of PPAR-γ seems to reduce the progression of cartilage lesion in experimental models of OA as it assists the downregulation of inflammatory and catabolic responses mediated by IL-1β and TNF [47, 48].
IL-6 is a proinflammatory cytokine, whose signaling pathway involves the activation of receptors, such as membrane-bound IL-6 receptor (IL6R), soluble IL-6R (sIL-6R), and gp130, followed by the activation of STAT1 and STAT3 pathways [39]. In physiological conditions, the production of IL-6 by chondrocytes is considerably low. However, the exact mechanism of IL-6 action in OA is unknown, but its production can be stimulated by the number of cytokines and growth factors present in OA, including IL-1β, TGF-β, and PGE2 [25, 49].
Increased levels of IL-6 in synovial fluid and serum have been correlated with the severity of lesions in X-ray imaging [50]. In vitro studies have shown that IL-6, in combination with IL-1β and TNF, upregulates the production of MMP-1 and -13 in human and bovine chondrocytes and induces proteoglycan and type II collagen degradation [51, 52]. The effect of IL-6 in studies with animal models has shown uncertain results. IL-6 knockout mice revealed more advanced degenerative changes compared to wild-type animals [53]. However, when IL-6 was injected in the joint cavity of IL-6-deficient mice, the reduction in the loss of proteoglycans in the acute phase of inflammation was observed [54].
One of the most considered active components in OA is the change in subchondral bone tissue, and IL-6 has been a critical mediator in this regard. Its effect, together with IL-1β and TNF, is based on promoting osteoclast formation and, consequently, bone resorption [55]. In response to IL-6, osteoblasts stimulate the production of receptor activator of NF-κB ligand, IL-1β, and PGE2, which activate osteoclasts [56]. In addition, osteoblasts activated by these cytokines produce MMPs, which adversely affect the surrounding cartilage [57].
Despite a better documented involvement in rheumatoid arthritis [58], the knowledge regarding IL-15 and its action in OA is still poor. It acts based on the stimulation and proliferation of T cells and NK cells, and it may also induce the production of MMP [59]. IL-15 levels are elevated in synovial fluid in early stages of OA, and this concentration correlates with pain and severity of lesions seen on X-ray imaging [60, 61].
Due to its inflammatory effects, IL-17 family has been implied to play a role in OA [62]. IL-17 is mainly stimulated by CD4+ T cells and mast cells, which are present in the cellular infiltrates observed in OA joints [63]. Within the joints, IL-17 primarily targets chondrocytes and fibroblast-like synoviocytes, which express IL-17 receptor (IL-17R) on their surface [64]. It was reported that IL-17 is able to inhibit proteoglycan synthesis by chondrocytes and increase the production of MMPs [65]. Also, high levels of IL-17 in both serum and synovial fluid were correlated with radiographic lesions in OA [66].
The genetic correlation between IL-17 and OA was suggested: a polymorphism in the gene IL-17A G-197A could be associated with the susceptibility to the development of OA [67]. In addition, IL-17 is produced by a specific T cell lineage called T helper 17, and it is able to cause hypertrophy of synovial membrane as its presence influences the secretion of vascular endothelial growth factor (VEGF), which leads to excessive blood vessel formation [68]. It can also indirectly affect cartilage by inducing the production of cytokines responsible for tissue degradation, such as IL-1β, TNF, IL-6, NO, and PGE2 [64].
The active form of IL-18 results from the activation of caspase-1, which has been reported to be elevated in articular cartilage and synovium of OA, leading to great promotion of IL-18 and IL-1β. The production of IL-18 in joints is mainly determined by chondrocytes, osteoblasts, and macrophages [69]. IL-18 affects cartilage by upregulating the production of IL-18Rα on chondrocyte surface and stimulates excessive production of MMP-1, -3, and -13 [70]. Also, IL-18 negatively influences the production of proteoglycans, aggrecan, and type II collagen and may cause morphological changes typically observed in apoptotic processes [71, 72].
The increased concentration of IL-18 observed in synovial fluid, synovium, cartilage, and even blood serum from patients with OA has been correlated with the severity of lesions seen in radiographic imaging [73]. Also, studies have correlated the development of OA and lumbar disc degeneration with polymorphisms in the gene encoding IL-18 and its receptor (IL-18R) [74, 75].
Anti-inflammatory cytokines also present a role in the maintenance of OA. IL-4 is associated with chondroprotective effects as it is shown to reduce MMP production and, consequently, inhibit the degradation of proteoglycans in the articular cartilage [76]. However, chondrocytes from OA joints have shown a decreased susceptibility to this IL-4 protective effect, leaving the cartilage unprotected, quickening the degeneration via the action of the proinflammatory cytokines cited above [77]. In addition, a polymorphism in the gene encoding IL-4 and its main receptor (IL-4Rα) could predetermine the development of OA in hand and knee joints [78, 79]. It was also further reported that, when compared with healthy patients, OA patients present an elevated level of soluble IL-4Rα (sIL-4Rα) [80].
The activation of IL-4 depends on intracellular signal transduction by gradual phosphorylation of IL-4Rα, which leads to the expression of several proinflammatory genes [81]. IL-4 production is mainly determined by T cells, especially Th2, which are present in the cellular infiltrates observed in OA [37]. It was reported that IL-4 alone or in combination with IL-10 is able to reduce the production of diverse proinflammatory mediators, such as IL-1β, TNF-α receptors, IL-6, PGE2, and COX-2 [82, 83, 84].
Due to its anti-inflammatory features, IL-10 is another cytokine that presents chondroprotective effects, and it is linked to the release of IFN [62]. In vitro studies have shown increased proteoglycan and type II collagen syntheses after the administration of IL-10 in chondrocytes [62]. The protective effects that IL-10 exhibits are likely due to a stimulation of the synthesis of IL-1β antagonist and a tissue inhibition of MMP-1 (TIMP-1) [85]. Also, IL-10, as well as IL-4, reduces apoptotic events in chondrocytes and production of MMP [86, 87].
IL-10 induces the expression of bone morphogenetic protein-2 and -6 (BMP2 and BMP6), which are related to chondrogenesis as they belong to TGF-β family [88]. Together with BMP production, IL-10 activates signaling pathways, such as NKX-3.2/SOX9, that induce the differentiation of mesenchymal stem cells into chondrocytes [89]. Also, by reducing the expression of TNF-α receptors, IL-10 is able to attenuate the effect of TNF-α on synovial fibroblasts. A decrease in COX-2 production was also noted in the same study [90].
The secretion of IL-10 can be influenced by physical exercises. Patients with and without OA had synovial fluid and periarticular tissue harvested from their knee before, during, and after they underwent exercise practice for 3 hours. A significant increase in IL-10 levels was observed in these patients after the exercise. Although it is not clear what exact mechanism led to this result, this observation is likely attributed to an increase in intra-articular pressure and subsequent effects on cellular secretion [91, 92].
Chemokines comprise small proteins that act as chemoattractants to assist cells to migrate to injured tissue. Diverse chemokines have gained attention in the development of OA. Some of them including their receptors, such as IL-8, CCL5, CCL19, CCR1, CCR2, CCR3, and CCR5, may induce the production of MMP-3 by chondrocytes and increase the breakdown of cartilage matrix components, which trigger the onset of OA [60, 93]. However, some chemokines might present a protective role in OA, such as stromal cell-derived factor-1 (also called CXCL12), whose main function is to recruit mesenchymal stem cells to the injured area in order to promote tissue repair [94].
Several chemokines were reported to be overexpressed in OA, such as IL-8/CXCL-8, GROα/CXCL-1, MCP-1/CCL-2, RANTES/CCL-5, MIP-1α/CCL-3, and MIP-1β/CCL-4. Some of these chemokines are stimulated by IL-1β, which is upregulated in OA, and they induce MMP production upon binding to their ligands, causing tissue degradation [93]. Levels of INF-γ-inducible protein 10 (IP-10), also called as CXCL-10, in plasma and synovial fluid have been correlated with radiographic knee OA. CX3CL1, a serum fractalkine, has also been reported to be significantly elevated in severe knee OA in a study that compared OA patients with healthy patients [95].
To support the role of macrophage in the inflammatory response observed in OA, MCP-1, also known as chemokine ligand-2 (CCL2), has been reported to recruit macrophages into adipose tissue and atherosclerotic lesions [96]. Also, MCP-1 levels in both serum and synovial fluid has been associated with self-reported pain and disability in patients who present knee OA [97]. In addition, it was observed that, in severe knee OA, the levels of macrophage-derived chemokine (MDC) and IP-10 in synovial fluid were elevated, while eotaxin levels, an eosinophil chemotactic protein, were lower when compared with healthy patients [98].
Adipokines have been associated with the incidence and severity of OA [99]. In vitro studies reported that the presence of adipokines, such as leptin, adiponectin, visfatin, and resistin, increases the production of inflammatory mediators and also induces chondrolysis [99]. Although the exact mechanism of how these cytokines derived from adipose tissue act on arthritic joints has not yet been elucidated, researchers have studied the role of fat pad as a local inflammation mediator in OA, particularly in knee OA due to the infrapatellar fat pad, which has proven to be infiltrated with macrophages, lymphocytes, and granulocytes [100]. These findings support the thought that obesity supports the development of OA more through biochemical pathways rather than biomechanical overload risks on a weight-bearing joint.
The COX-2 enzyme is responsible for the production of lipid mediators, including PGE2 and leukotrienes, and it is also upregulated in OA joints. In addition, the overexpression of COX-2 in OA has been associated with the increased production of IL-1β, TNF, and IL-6 via toll-like receptor-4 (TLR-4) [101]. Besides assisting the production of MMPs and other functions already cited above, PGE2 is also involved in apoptosis and structural changes that characterize arthritic disease [102].
Leukotrienes have also been investigated for their role in OA. These mediators are converted from arachidonic acid, which also produces PGE2 via the activity of the enzyme phospholipase A2 [21]. Leukotrienes, mainly leukotriene B4 (LTB4), are present, to a lesser extent, in OA synovium, bone, and cartilage. Also, LTB4 has been reported to stimulate the production of IL-1β and TNF in arthritic synovium [103].
The cumulative evidences over the years have shown that increased expression of proinflammatory cytokines, in particular IL-1β, TNF, and IL-6, in cartilage as well as synovial fluid and membrane, has played a key role in the pathogenesis of OA. Inflammatory processes linked with immune responses have characterized OA as a complex disease and not as a simple age-related cartilage degeneration as it is thought to be. The understanding of individual roles of inflammatory mediators and their compounds is of utmost importance to target new therapies for OA, since the current options are elusive and may be noneffective, invasive, or even capable of presenting serious side effects. Due to advancements in molecular tools, the overall aim would be to dissect the role of each cytokine in the pathophysiology of OA and, together with drug delivery systems, to develop specific anticytokine therapy, given that inflammatory responses contribute substantially to OA maintenance.
The authors have no conflict of interest to declare.
General requirements for Open Access to Horizon 2020 research project outputs are found within Guidelines on Open Access to Scientific Publication and Research Data in Horizon 2020. The guidelines, in their simplest form, state that if you are a Horizon 2020 recipient, you must ensure open access to your scientific publications by enabling them to be downloaded, printed and read online. Additionally, said publications must be peer reviewed.
',metaTitle:"Horizon 2020 Compliance",metaDescription:"General requirements for Open Access to Horizon 2020 research project outputs are found within Guidelines on Open Access to Scientific Publication and Research Data in Horizon 2020. The guidelines, in their simplest form, state that if you are a Horizon 2020 recipient, you must ensure open access to your scientific publications by enabling them to be downloaded, printed and read online. Additionally, said publications must be peer reviewed. ",metaKeywords:null,canonicalURL:null,contentRaw:'[{"type":"htmlEditorComponent","content":"Publishing with IntechOpen means that your scientific publications already meet these basic requirements. It also means that through our utilization of open licensing, our publications are also able to be copied, shared, searched, linked, crawled, and mined for text and data, optimizing our authors' compliance as suggested by the European Commission.
\\n\\nMetadata for all publications is also automatically deposited in IntechOpen's OAI repository, making them available through the Open Access Infrastructure for Research in Europe's (OpenAIRE) search interface further establishing our compliance.
\\n\\nIn other words, publishing with IntechOpen guarantees compliance.
\\n\\nRead more about Open Access in Horizon 2020 here.
\\n\\nWhich scientific publication to choose?
\\n\\nWhen choosing a publication, Horizon 2020 grant recipients are encouraged to provide open access to various types of scientific publications including monographs, edited books and conference proceedings.
\\n\\nIntechOpen publishes all of the aforementioned formats in compliance with the requirements and criteria established by the European Commission for the Horizon 2020 Program.
\\n\\nAuthors requiring additional information are welcome to send their inquiries to funders@intechopen.com
\\n"}]'},components:[{type:"htmlEditorComponent",content:'Publishing with IntechOpen means that your scientific publications already meet these basic requirements. It also means that through our utilization of open licensing, our publications are also able to be copied, shared, searched, linked, crawled, and mined for text and data, optimizing our authors' compliance as suggested by the European Commission.
\n\nMetadata for all publications is also automatically deposited in IntechOpen's OAI repository, making them available through the Open Access Infrastructure for Research in Europe's (OpenAIRE) search interface further establishing our compliance.
\n\nIn other words, publishing with IntechOpen guarantees compliance.
\n\nRead more about Open Access in Horizon 2020 here.
\n\nWhich scientific publication to choose?
\n\nWhen choosing a publication, Horizon 2020 grant recipients are encouraged to provide open access to various types of scientific publications including monographs, edited books and conference proceedings.
\n\nIntechOpen publishes all of the aforementioned formats in compliance with the requirements and criteria established by the European Commission for the Horizon 2020 Program.
\n\nAuthors requiring additional information are welcome to send their inquiries to funders@intechopen.com
\n'}]},successStories:{items:[]},authorsAndEditors:{filterParams:{sort:"featured,name"},profiles:[{id:"6700",title:"Dr.",name:"Abbass A.",middleName:null,surname:"Hashim",slug:"abbass-a.-hashim",fullName:"Abbass A. Hashim",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/6700/images/1864_n.jpg",biography:"Currently I am carrying out research in several areas of interest, mainly covering work on chemical and bio-sensors, semiconductor thin film device fabrication and characterisation.\nAt the moment I have very strong interest in radiation environmental pollution and bacteriology treatment. The teams of researchers are working very hard to bring novel results in this field. I am also a member of the team in charge for the supervision of Ph.D. students in the fields of development of silicon based planar waveguide sensor devices, study of inelastic electron tunnelling in planar tunnelling nanostructures for sensing applications and development of organotellurium(IV) compounds for semiconductor applications. I am a specialist in data analysis techniques and nanosurface structure. I have served as the editor for many books, been a member of the editorial board in science journals, have published many papers and hold many patents.",institutionString:null,institution:{name:"Sheffield Hallam University",country:{name:"United Kingdom"}}},{id:"54525",title:"Prof.",name:"Abdul Latif",middleName:null,surname:"Ahmad",slug:"abdul-latif-ahmad",fullName:"Abdul Latif Ahmad",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"20567",title:"Prof.",name:"Ado",middleName:null,surname:"Jorio",slug:"ado-jorio",fullName:"Ado Jorio",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Universidade Federal de Minas Gerais",country:{name:"Brazil"}}},{id:"47940",title:"Dr.",name:"Alberto",middleName:null,surname:"Mantovani",slug:"alberto-mantovani",fullName:"Alberto Mantovani",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"12392",title:"Mr.",name:"Alex",middleName:null,surname:"Lazinica",slug:"alex-lazinica",fullName:"Alex Lazinica",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/12392/images/7282_n.png",biography:"Alex Lazinica is the founder and CEO of IntechOpen. After obtaining a Master's degree in Mechanical Engineering, he continued his PhD studies in Robotics at the Vienna University of Technology. Here he worked as a robotic researcher with the university's Intelligent Manufacturing Systems Group as well as a guest researcher at various European universities, including the Swiss Federal Institute of Technology Lausanne (EPFL). During this time he published more than 20 scientific papers, gave presentations, served as a reviewer for major robotic journals and conferences and most importantly he co-founded and built the International Journal of Advanced Robotic Systems- world's first Open Access journal in the field of robotics. Starting this journal was a pivotal point in his career, since it was a pathway to founding IntechOpen - Open Access publisher focused on addressing academic researchers needs. Alex is a personification of IntechOpen key values being trusted, open and entrepreneurial. Today his focus is on defining the growth and development strategy for the company.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"19816",title:"Prof.",name:"Alexander",middleName:null,surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/19816/images/1607_n.jpg",biography:"Alexander I. Kokorin: born: 1947, Moscow; DSc., PhD; Principal Research Fellow (Research Professor) of Department of Kinetics and Catalysis, N. Semenov Institute of Chemical Physics, Russian Academy of Sciences, Moscow.\r\nArea of research interests: physical chemistry of complex-organized molecular and nanosized systems, including polymer-metal complexes; the surface of doped oxide semiconductors. He is an expert in structural, absorptive, catalytic and photocatalytic properties, in structural organization and dynamic features of ionic liquids, in magnetic interactions between paramagnetic centers. The author or co-author of 3 books, over 200 articles and reviews in scientific journals and books. He is an actual member of the International EPR/ESR Society, European Society on Quantum Solar Energy Conversion, Moscow House of Scientists, of the Board of Moscow Physical Society.",institutionString:null,institution:{name:"Semenov Institute of Chemical Physics",country:{name:"Russia"}}},{id:"62389",title:"PhD.",name:"Ali Demir",middleName:null,surname:"Sezer",slug:"ali-demir-sezer",fullName:"Ali Demir Sezer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62389/images/3413_n.jpg",biography:"Dr. Ali Demir Sezer has a Ph.D. from Pharmaceutical Biotechnology at the Faculty of Pharmacy, University of Marmara (Turkey). He is the member of many Pharmaceutical Associations and acts as a reviewer of scientific journals and European projects under different research areas such as: drug delivery systems, nanotechnology and pharmaceutical biotechnology. Dr. Sezer is the author of many scientific publications in peer-reviewed journals and poster communications. Focus of his research activity is drug delivery, physico-chemical characterization and biological evaluation of biopolymers micro and nanoparticles as modified drug delivery system, and colloidal drug carriers (liposomes, nanoparticles etc.).",institutionString:null,institution:{name:"Marmara University",country:{name:"Turkey"}}},{id:"61051",title:"Prof.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"100762",title:"Prof.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"St David's Medical Center",country:{name:"United States of America"}}},{id:"107416",title:"Dr.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Texas Cardiac Arrhythmia",country:{name:"United States of America"}}},{id:"64434",title:"Dr.",name:"Angkoon",middleName:null,surname:"Phinyomark",slug:"angkoon-phinyomark",fullName:"Angkoon Phinyomark",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/64434/images/2619_n.jpg",biography:"My name is Angkoon Phinyomark. I received a B.Eng. degree in Computer Engineering with First Class Honors in 2008 from Prince of Songkla University, Songkhla, Thailand, where I received a Ph.D. degree in Electrical Engineering. My research interests are primarily in the area of biomedical signal processing and classification notably EMG (electromyography signal), EOG (electrooculography signal), and EEG (electroencephalography signal), image analysis notably breast cancer analysis and optical coherence tomography, and rehabilitation engineering. I became a student member of IEEE in 2008. During October 2011-March 2012, I had worked at School of Computer Science and Electronic Engineering, University of Essex, Colchester, Essex, United Kingdom. In addition, during a B.Eng. I had been a visiting research student at Faculty of Computer Science, University of Murcia, Murcia, Spain for three months.\n\nI have published over 40 papers during 5 years in refereed journals, books, and conference proceedings in the areas of electro-physiological signals processing and classification, notably EMG and EOG signals, fractal analysis, wavelet analysis, texture analysis, feature extraction and machine learning algorithms, and assistive and rehabilitative devices. I have several computer programming language certificates, i.e. Sun Certified Programmer for the Java 2 Platform 1.4 (SCJP), Microsoft Certified Professional Developer, Web Developer (MCPD), Microsoft Certified Technology Specialist, .NET Framework 2.0 Web (MCTS). I am a Reviewer for several refereed journals and international conferences, such as IEEE Transactions on Biomedical Engineering, IEEE Transactions on Industrial Electronics, Optic Letters, Measurement Science Review, and also a member of the International Advisory Committee for 2012 IEEE Business Engineering and Industrial Applications and 2012 IEEE Symposium on Business, Engineering and Industrial Applications.",institutionString:null,institution:{name:"Joseph Fourier University",country:{name:"France"}}},{id:"55578",title:"Dr.",name:"Antonio",middleName:null,surname:"Jurado-Navas",slug:"antonio-jurado-navas",fullName:"Antonio Jurado-Navas",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/55578/images/4574_n.png",biography:"Antonio Jurado-Navas received the M.S. degree (2002) and the Ph.D. degree (2009) in Telecommunication Engineering, both from the University of Málaga (Spain). He first worked as a consultant at Vodafone-Spain. From 2004 to 2011, he was a Research Assistant with the Communications Engineering Department at the University of Málaga. In 2011, he became an Assistant Professor in the same department. From 2012 to 2015, he was with Ericsson Spain, where he was working on geo-location\ntools for third generation mobile networks. Since 2015, he is a Marie-Curie fellow at the Denmark Technical University. His current research interests include the areas of mobile communication systems and channel modeling in addition to atmospheric optical communications, adaptive optics and statistics",institutionString:null,institution:{name:"University of Malaga",country:{name:"Spain"}}}],filtersByRegion:[{group:"region",caption:"North America",value:1,count:5681},{group:"region",caption:"Middle and South America",value:2,count:5161},{group:"region",caption:"Africa",value:3,count:1683},{group:"region",caption:"Asia",value:4,count:10200},{group:"region",caption:"Australia and Oceania",value:5,count:886},{group:"region",caption:"Europe",value:6,count:15610}],offset:12,limit:12,total:117095},chapterEmbeded:{data:{}},editorApplication:{success:null,errors:{}},ofsBooks:{filterParams:{sort:"dateEndThirdStepPublish",topicId:"25"},books:[{type:"book",id:"8737",title:"Rabies Virus",subtitle:null,isOpenForSubmission:!0,hash:"49cce3f548da548c718c865feb343509",slug:null,bookSignature:"Dr. Sergey Tkachev",coverURL:"https://cdn.intechopen.com/books/images_new/8737.jpg",editedByType:null,editors:[{id:"61139",title:"Dr.",name:"Sergey",surname:"Tkachev",slug:"sergey-tkachev",fullName:"Sergey Tkachev"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10830",title:"Animal Feed Science",subtitle:null,isOpenForSubmission:!0,hash:"b6091426454b1c484f4d38efc722d6dd",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/10830.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10496",title:"Feed Additives in Animal Nutrition",subtitle:null,isOpenForSubmission:!0,hash:"8ffe43a82ac48b309abc3632bbf3efd0",slug:null,bookSignature:"Prof. László Babinszky",coverURL:"https://cdn.intechopen.com/books/images_new/10496.jpg",editedByType:null,editors:[{id:"53998",title:"Prof.",name:"László",surname:"Babinszky",slug:"laszlo-babinszky",fullName:"László Babinszky"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],filtersByTopic:[{group:"topic",caption:"Agricultural and Biological Sciences",value:5,count:9},{group:"topic",caption:"Biochemistry, Genetics and Molecular Biology",value:6,count:17},{group:"topic",caption:"Business, Management and Economics",value:7,count:2},{group:"topic",caption:"Chemistry",value:8,count:7},{group:"topic",caption:"Computer and Information Science",value:9,count:10},{group:"topic",caption:"Earth and Planetary Sciences",value:10,count:5},{group:"topic",caption:"Engineering",value:11,count:15},{group:"topic",caption:"Environmental Sciences",value:12,count:2},{group:"topic",caption:"Immunology and Microbiology",value:13,count:5},{group:"topic",caption:"Materials Science",value:14,count:4},{group:"topic",caption:"Mathematics",value:15,count:1},{group:"topic",caption:"Medicine",value:16,count:60},{group:"topic",caption:"Nanotechnology and Nanomaterials",value:17,count:1},{group:"topic",caption:"Neuroscience",value:18,count:1},{group:"topic",caption:"Pharmacology, Toxicology and Pharmaceutical Science",value:19,count:6},{group:"topic",caption:"Physics",value:20,count:2},{group:"topic",caption:"Psychology",value:21,count:3},{group:"topic",caption:"Robotics",value:22,count:1},{group:"topic",caption:"Social Sciences",value:23,count:3},{group:"topic",caption:"Technology",value:24,count:1},{group:"topic",caption:"Veterinary Medicine and Science",value:25,count:2}],offset:12,limit:12,total:3},popularBooks:{featuredBooks:[{type:"book",id:"9343",title:"Trace Metals in the Environment",subtitle:"New Approaches and Recent Advances",isOpenForSubmission:!1,hash:"ae07e345bc2ce1ebbda9f70c5cd12141",slug:"trace-metals-in-the-environment-new-approaches-and-recent-advances",bookSignature:"Mario Alfonso Murillo-Tovar, Hugo Saldarriaga-Noreña and Agnieszka Saeid",coverURL:"https://cdn.intechopen.com/books/images_new/9343.jpg",editors:[{id:"255959",title:"Dr.",name:"Mario Alfonso",middleName:null,surname:"Murillo-Tovar",slug:"mario-alfonso-murillo-tovar",fullName:"Mario Alfonso Murillo-Tovar"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7769",title:"Medical Isotopes",subtitle:null,isOpenForSubmission:!1,hash:"f8d3c5a6c9a42398e56b4e82264753f7",slug:"medical-isotopes",bookSignature:"Syed Ali Raza Naqvi and Muhammad Babar Imrani",coverURL:"https://cdn.intechopen.com/books/images_new/7769.jpg",editors:[{id:"259190",title:"Dr.",name:"Syed Ali Raza",middleName:null,surname:"Naqvi",slug:"syed-ali-raza-naqvi",fullName:"Syed Ali Raza Naqvi"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9376",title:"Contemporary Developments and Perspectives in International Health Security",subtitle:"Volume 1",isOpenForSubmission:!1,hash:"b9a00b84cd04aae458fb1d6c65795601",slug:"contemporary-developments-and-perspectives-in-international-health-security-volume-1",bookSignature:"Stanislaw P. Stawicki, Michael S. Firstenberg, Sagar C. Galwankar, Ricardo Izurieta and Thomas Papadimos",coverURL:"https://cdn.intechopen.com/books/images_new/9376.jpg",editors:[{id:"181694",title:"Dr.",name:"Stanislaw P.",middleName:null,surname:"Stawicki",slug:"stanislaw-p.-stawicki",fullName:"Stanislaw P. Stawicki"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7831",title:"Sustainability in Urban Planning and Design",subtitle:null,isOpenForSubmission:!1,hash:"c924420492c8c2c9751e178d025f4066",slug:"sustainability-in-urban-planning-and-design",bookSignature:"Amjad Almusaed, Asaad Almssad and Linh Truong - Hong",coverURL:"https://cdn.intechopen.com/books/images_new/7831.jpg",editors:[{id:"110471",title:"Dr.",name:"Amjad",middleName:"Zaki",surname:"Almusaed",slug:"amjad-almusaed",fullName:"Amjad Almusaed"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9279",title:"Concepts, Applications and Emerging Opportunities in Industrial Engineering",subtitle:null,isOpenForSubmission:!1,hash:"9bfa87f9b627a5468b7c1e30b0eea07a",slug:"concepts-applications-and-emerging-opportunities-in-industrial-engineering",bookSignature:"Gary Moynihan",coverURL:"https://cdn.intechopen.com/books/images_new/9279.jpg",editors:[{id:"16974",title:"Dr.",name:"Gary",middleName:null,surname:"Moynihan",slug:"gary-moynihan",fullName:"Gary Moynihan"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7807",title:"A Closer Look at Organizational Culture in Action",subtitle:null,isOpenForSubmission:!1,hash:"05c608b9271cc2bc711f4b28748b247b",slug:"a-closer-look-at-organizational-culture-in-action",bookSignature:"Süleyman Davut Göker",coverURL:"https://cdn.intechopen.com/books/images_new/7807.jpg",editors:[{id:"190035",title:"Associate Prof.",name:"Süleyman Davut",middleName:null,surname:"Göker",slug:"suleyman-davut-goker",fullName:"Süleyman Davut Göker"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7796",title:"Human 4.0",subtitle:"From Biology to Cybernetic",isOpenForSubmission:!1,hash:"5ac5c052d3a593d5c4f4df66d005e5af",slug:"human-4-0-from-biology-to-cybernetic",bookSignature:"Yves Rybarczyk",coverURL:"https://cdn.intechopen.com/books/images_new/7796.jpg",editors:[{id:"72920",title:"Prof.",name:"Yves",middleName:"Philippe",surname:"Rybarczyk",slug:"yves-rybarczyk",fullName:"Yves Rybarczyk"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9711",title:"Pests, Weeds and Diseases in Agricultural Crop and Animal Husbandry Production",subtitle:null,isOpenForSubmission:!1,hash:"12cf675f1e433135dd5bf5df7cec124f",slug:"pests-weeds-and-diseases-in-agricultural-crop-and-animal-husbandry-production",bookSignature:"Dimitrios Kontogiannatos, Anna Kourti and Kassio Ferreira Mendes",coverURL:"https://cdn.intechopen.com/books/images_new/9711.jpg",editors:[{id:"196691",title:"Dr.",name:"Dimitrios",middleName:null,surname:"Kontogiannatos",slug:"dimitrios-kontogiannatos",fullName:"Dimitrios Kontogiannatos"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10178",title:"Environmental Emissions",subtitle:null,isOpenForSubmission:!1,hash:"febf21ec717bfe20ae25a9dab9b5d438",slug:"environmental-emissions",bookSignature:"Richard Viskup",coverURL:"https://cdn.intechopen.com/books/images_new/10178.jpg",editors:[{id:"103742",title:"Dr.",name:"Richard",middleName:null,surname:"Viskup",slug:"richard-viskup",fullName:"Richard Viskup"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8511",title:"Cyberspace",subtitle:null,isOpenForSubmission:!1,hash:"8c1cdeb133dbe6cc1151367061c1bba6",slug:"cyberspace",bookSignature:"Evon Abu-Taieh, Abdelkrim El Mouatasim and Issam H. Al Hadid",coverURL:"https://cdn.intechopen.com/books/images_new/8511.jpg",editors:[{id:"223522",title:"Dr.",name:"Evon",middleName:"M.O.",surname:"Abu-Taieh",slug:"evon-abu-taieh",fullName:"Evon Abu-Taieh"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9534",title:"Banking and Finance",subtitle:null,isOpenForSubmission:!1,hash:"af14229738af402c3b595d7e124dce82",slug:"banking-and-finance",bookSignature:"Razali Haron, Maizaitulaidawati Md Husin and Michael Murg",coverURL:"https://cdn.intechopen.com/books/images_new/9534.jpg",editors:[{id:"206517",title:"Prof.",name:"Razali",middleName:null,surname:"Haron",slug:"razali-haron",fullName:"Razali Haron"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"2160",title:"MATLAB",subtitle:"A Fundamental Tool for Scientific Computing and Engineering Applications - Volume 1",isOpenForSubmission:!1,hash:"dd9c658341fbd264ed4f8d9e6aa8ca29",slug:"matlab-a-fundamental-tool-for-scientific-computing-and-engineering-applications-volume-1",bookSignature:"Vasilios N. Katsikis",coverURL:"https://cdn.intechopen.com/books/images_new/2160.jpg",editors:[{id:"12289",title:"Prof.",name:"Vasilios",middleName:"N.",surname:"Katsikis",slug:"vasilios-katsikis",fullName:"Vasilios Katsikis"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],offset:12,limit:12,total:5126},hotBookTopics:{hotBooks:[],offset:0,limit:12,total:null},publish:{},publishingProposal:{success:null,errors:{}},books:{featuredBooks:[{type:"book",id:"9343",title:"Trace Metals in the Environment",subtitle:"New Approaches and Recent Advances",isOpenForSubmission:!1,hash:"ae07e345bc2ce1ebbda9f70c5cd12141",slug:"trace-metals-in-the-environment-new-approaches-and-recent-advances",bookSignature:"Mario Alfonso Murillo-Tovar, Hugo Saldarriaga-Noreña and Agnieszka Saeid",coverURL:"https://cdn.intechopen.com/books/images_new/9343.jpg",editors:[{id:"255959",title:"Dr.",name:"Mario Alfonso",middleName:null,surname:"Murillo-Tovar",slug:"mario-alfonso-murillo-tovar",fullName:"Mario Alfonso Murillo-Tovar"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7769",title:"Medical Isotopes",subtitle:null,isOpenForSubmission:!1,hash:"f8d3c5a6c9a42398e56b4e82264753f7",slug:"medical-isotopes",bookSignature:"Syed Ali Raza Naqvi and Muhammad Babar Imrani",coverURL:"https://cdn.intechopen.com/books/images_new/7769.jpg",editors:[{id:"259190",title:"Dr.",name:"Syed Ali Raza",middleName:null,surname:"Naqvi",slug:"syed-ali-raza-naqvi",fullName:"Syed Ali Raza Naqvi"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9376",title:"Contemporary Developments and Perspectives in International Health Security",subtitle:"Volume 1",isOpenForSubmission:!1,hash:"b9a00b84cd04aae458fb1d6c65795601",slug:"contemporary-developments-and-perspectives-in-international-health-security-volume-1",bookSignature:"Stanislaw P. Stawicki, Michael S. Firstenberg, Sagar C. Galwankar, Ricardo Izurieta and Thomas Papadimos",coverURL:"https://cdn.intechopen.com/books/images_new/9376.jpg",editors:[{id:"181694",title:"Dr.",name:"Stanislaw P.",middleName:null,surname:"Stawicki",slug:"stanislaw-p.-stawicki",fullName:"Stanislaw P. Stawicki"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7831",title:"Sustainability in Urban Planning and Design",subtitle:null,isOpenForSubmission:!1,hash:"c924420492c8c2c9751e178d025f4066",slug:"sustainability-in-urban-planning-and-design",bookSignature:"Amjad Almusaed, Asaad Almssad and Linh Truong - Hong",coverURL:"https://cdn.intechopen.com/books/images_new/7831.jpg",editors:[{id:"110471",title:"Dr.",name:"Amjad",middleName:"Zaki",surname:"Almusaed",slug:"amjad-almusaed",fullName:"Amjad Almusaed"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9279",title:"Concepts, Applications and Emerging Opportunities in Industrial Engineering",subtitle:null,isOpenForSubmission:!1,hash:"9bfa87f9b627a5468b7c1e30b0eea07a",slug:"concepts-applications-and-emerging-opportunities-in-industrial-engineering",bookSignature:"Gary Moynihan",coverURL:"https://cdn.intechopen.com/books/images_new/9279.jpg",editors:[{id:"16974",title:"Dr.",name:"Gary",middleName:null,surname:"Moynihan",slug:"gary-moynihan",fullName:"Gary Moynihan"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7807",title:"A Closer Look at Organizational Culture in Action",subtitle:null,isOpenForSubmission:!1,hash:"05c608b9271cc2bc711f4b28748b247b",slug:"a-closer-look-at-organizational-culture-in-action",bookSignature:"Süleyman Davut Göker",coverURL:"https://cdn.intechopen.com/books/images_new/7807.jpg",editors:[{id:"190035",title:"Associate Prof.",name:"Süleyman Davut",middleName:null,surname:"Göker",slug:"suleyman-davut-goker",fullName:"Süleyman Davut Göker"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7796",title:"Human 4.0",subtitle:"From Biology to Cybernetic",isOpenForSubmission:!1,hash:"5ac5c052d3a593d5c4f4df66d005e5af",slug:"human-4-0-from-biology-to-cybernetic",bookSignature:"Yves Rybarczyk",coverURL:"https://cdn.intechopen.com/books/images_new/7796.jpg",editors:[{id:"72920",title:"Prof.",name:"Yves",middleName:"Philippe",surname:"Rybarczyk",slug:"yves-rybarczyk",fullName:"Yves Rybarczyk"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9711",title:"Pests, Weeds and Diseases in Agricultural Crop and Animal Husbandry Production",subtitle:null,isOpenForSubmission:!1,hash:"12cf675f1e433135dd5bf5df7cec124f",slug:"pests-weeds-and-diseases-in-agricultural-crop-and-animal-husbandry-production",bookSignature:"Dimitrios Kontogiannatos, Anna Kourti and Kassio Ferreira Mendes",coverURL:"https://cdn.intechopen.com/books/images_new/9711.jpg",editors:[{id:"196691",title:"Dr.",name:"Dimitrios",middleName:null,surname:"Kontogiannatos",slug:"dimitrios-kontogiannatos",fullName:"Dimitrios Kontogiannatos"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10178",title:"Environmental Emissions",subtitle:null,isOpenForSubmission:!1,hash:"febf21ec717bfe20ae25a9dab9b5d438",slug:"environmental-emissions",bookSignature:"Richard Viskup",coverURL:"https://cdn.intechopen.com/books/images_new/10178.jpg",editors:[{id:"103742",title:"Dr.",name:"Richard",middleName:null,surname:"Viskup",slug:"richard-viskup",fullName:"Richard Viskup"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8511",title:"Cyberspace",subtitle:null,isOpenForSubmission:!1,hash:"8c1cdeb133dbe6cc1151367061c1bba6",slug:"cyberspace",bookSignature:"Evon Abu-Taieh, Abdelkrim El Mouatasim and Issam H. Al Hadid",coverURL:"https://cdn.intechopen.com/books/images_new/8511.jpg",editors:[{id:"223522",title:"Dr.",name:"Evon",middleName:"M.O.",surname:"Abu-Taieh",slug:"evon-abu-taieh",fullName:"Evon Abu-Taieh"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],latestBooks:[{type:"book",id:"8468",title:"Sheep Farming",subtitle:"An Approach to Feed, Growth and Sanity",isOpenForSubmission:!1,hash:"838f08594850bc04aa14ec873ed1b96f",slug:"sheep-farming-an-approach-to-feed-growth-and-sanity",bookSignature:"António Monteiro",coverURL:"https://cdn.intechopen.com/books/images_new/8468.jpg",editedByType:"Edited by",editors:[{id:"190314",title:"Prof.",name:"António",middleName:"Cardoso",surname:"Monteiro",slug:"antonio-monteiro",fullName:"António Monteiro"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9523",title:"Oral and Maxillofacial Surgery",subtitle:null,isOpenForSubmission:!1,hash:"5eb6ec2db961a6c8965d11180a58d5c1",slug:"oral-and-maxillofacial-surgery",bookSignature:"Gokul Sridharan",coverURL:"https://cdn.intechopen.com/books/images_new/9523.jpg",editedByType:"Edited by",editors:[{id:"82453",title:"Dr.",name:"Gokul",middleName:null,surname:"Sridharan",slug:"gokul-sridharan",fullName:"Gokul Sridharan"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9785",title:"Endometriosis",subtitle:null,isOpenForSubmission:!1,hash:"f457ca61f29cf7e8bc191732c50bb0ce",slug:"endometriosis",bookSignature:"Courtney Marsh",coverURL:"https://cdn.intechopen.com/books/images_new/9785.jpg",editedByType:"Edited by",editors:[{id:"255491",title:"Dr.",name:"Courtney",middleName:null,surname:"Marsh",slug:"courtney-marsh",fullName:"Courtney Marsh"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9018",title:"Some RNA Viruses",subtitle:null,isOpenForSubmission:!1,hash:"a5cae846dbe3692495fc4add2f60fd84",slug:"some-rna-viruses",bookSignature:"Yogendra Shah and Eltayb Abuelzein",coverURL:"https://cdn.intechopen.com/books/images_new/9018.jpg",editedByType:"Edited by",editors:[{id:"278914",title:"Ph.D.",name:"Yogendra",middleName:null,surname:"Shah",slug:"yogendra-shah",fullName:"Yogendra Shah"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8816",title:"Financial Crises",subtitle:"A Selection of Readings",isOpenForSubmission:!1,hash:"6f2f49fb903656e4e54280c79fabd10c",slug:"financial-crises-a-selection-of-readings",bookSignature:"Stelios Markoulis",coverURL:"https://cdn.intechopen.com/books/images_new/8816.jpg",editedByType:"Edited by",editors:[{id:"237863",title:"Dr.",name:"Stelios",middleName:null,surname:"Markoulis",slug:"stelios-markoulis",fullName:"Stelios Markoulis"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9585",title:"Advances in Complex Valvular Disease",subtitle:null,isOpenForSubmission:!1,hash:"ef64f11e211621ecfe69c46e60e7ca3d",slug:"advances-in-complex-valvular-disease",bookSignature:"Michael S. Firstenberg and Imran Khan",coverURL:"https://cdn.intechopen.com/books/images_new/9585.jpg",editedByType:"Edited by",editors:[{id:"64343",title:null,name:"Michael S.",middleName:"S",surname:"Firstenberg",slug:"michael-s.-firstenberg",fullName:"Michael S. Firstenberg"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10150",title:"Smart Manufacturing",subtitle:"When Artificial Intelligence Meets the Internet of Things",isOpenForSubmission:!1,hash:"87004a19de13702d042f8ff96d454698",slug:"smart-manufacturing-when-artificial-intelligence-meets-the-internet-of-things",bookSignature:"Tan Yen Kheng",coverURL:"https://cdn.intechopen.com/books/images_new/10150.jpg",editedByType:"Edited by",editors:[{id:"78857",title:"Dr.",name:"Tan Yen",middleName:null,surname:"Kheng",slug:"tan-yen-kheng",fullName:"Tan Yen Kheng"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9386",title:"Direct Numerical Simulations",subtitle:"An Introduction and Applications",isOpenForSubmission:!1,hash:"158a3a0fdba295d21ff23326f5a072d5",slug:"direct-numerical-simulations-an-introduction-and-applications",bookSignature:"Srinivasa Rao",coverURL:"https://cdn.intechopen.com/books/images_new/9386.jpg",editedByType:"Edited by",editors:[{id:"6897",title:"Dr.",name:"Srinivasa",middleName:"P",surname:"Rao",slug:"srinivasa-rao",fullName:"Srinivasa Rao"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9139",title:"Topics in Primary Care Medicine",subtitle:null,isOpenForSubmission:!1,hash:"ea774a4d4c1179da92a782e0ae9cde92",slug:"topics-in-primary-care-medicine",bookSignature:"Thomas F. Heston",coverURL:"https://cdn.intechopen.com/books/images_new/9139.jpg",editedByType:"Edited by",editors:[{id:"217926",title:"Dr.",name:"Thomas F.",middleName:null,surname:"Heston",slug:"thomas-f.-heston",fullName:"Thomas F. Heston"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9208",title:"Welding",subtitle:"Modern Topics",isOpenForSubmission:!1,hash:"7d6be076ccf3a3f8bd2ca52d86d4506b",slug:"welding-modern-topics",bookSignature:"Sadek Crisóstomo Absi Alfaro, Wojciech Borek and Błażej Tomiczek",coverURL:"https://cdn.intechopen.com/books/images_new/9208.jpg",editedByType:"Edited by",editors:[{id:"65292",title:"Prof.",name:"Sadek Crisostomo Absi",middleName:"C. Absi",surname:"Alfaro",slug:"sadek-crisostomo-absi-alfaro",fullName:"Sadek Crisostomo Absi Alfaro"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},subject:{topic:{id:"1182",title:"Clinical Pharmacology",slug:"clinical-pharmacology",parent:{title:"Drug Discovery",slug:"drug-discovery"},numberOfBooks:3,numberOfAuthorsAndEditors:123,numberOfWosCitations:4,numberOfCrossrefCitations:48,numberOfDimensionsCitations:100,videoUrl:null,fallbackUrl:null,description:null},booksByTopicFilter:{topicSlug:"clinical-pharmacology",sort:"-publishedDate",limit:12,offset:0},booksByTopicCollection:[{type:"book",id:"8008",title:"Antioxidants",subtitle:null,isOpenForSubmission:!1,hash:"76361b4061e830906267933c1c670027",slug:"antioxidants",bookSignature:"Emad Shalaby",coverURL:"https://cdn.intechopen.com/books/images_new/8008.jpg",editedByType:"Edited by",editors:[{id:"63600",title:"Prof.",name:"Emad",middleName:null,surname:"Shalaby",slug:"emad-shalaby",fullName:"Emad Shalaby"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7258",title:"Resveratrol",subtitle:"Adding Life to Years, Not Adding Years to Life",isOpenForSubmission:!1,hash:"b02655d4c4df83b50688fa1a22661d49",slug:"resveratrol-adding-life-to-years-not-adding-years-to-life",bookSignature:"Farid A. Badria",coverURL:"https://cdn.intechopen.com/books/images_new/7258.jpg",editedByType:"Edited by",editors:[{id:"41865",title:"Prof.",name:"Farid A.",middleName:null,surname:"Badria",slug:"farid-a.-badria",fullName:"Farid A. Badria"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"716",title:"Clinical Use of Local Anesthetics",subtitle:null,isOpenForSubmission:!1,hash:"e8e4b699b914aa5fa2cf49f0ce8c42b9",slug:"clinical-use-of-local-anesthetics",bookSignature:"Asadolah Saadatniaki",coverURL:"https://cdn.intechopen.com/books/images_new/716.jpg",editedByType:"Edited by",editors:[{id:"88079",title:"Associate Prof.",name:"Asadoliah",middleName:null,surname:"Saadatniaki",slug:"asadoliah-saadatniaki",fullName:"Asadoliah Saadatniaki"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],booksByTopicTotal:3,mostCitedChapters:[{id:"66259",doi:"10.5772/intechopen.85270",title:"Antioxidant Compounds and Their Antioxidant Mechanism",slug:"antioxidant-compounds-and-their-antioxidant-mechanism",totalDownloads:4740,totalCrossrefCites:16,totalDimensionsCites:39,book:{slug:"antioxidants",title:"Antioxidants",fullTitle:"Antioxidants"},signatures:"Norma Francenia Santos-Sánchez, Raúl Salas-Coronado, Claudia Villanueva-Cañongo and Beatriz Hernández-Carlos",authors:[{id:"143354",title:"Dr.",name:"Raúl",middleName:null,surname:"Salas-Coronado",slug:"raul-salas-coronado",fullName:"Raúl Salas-Coronado"},{id:"148546",title:"Dr.",name:"Norma Francenia",middleName:null,surname:"Santos-Sánchez",slug:"norma-francenia-santos-sanchez",fullName:"Norma Francenia Santos-Sánchez"},{id:"193718",title:"Dr.",name:"Beatriz",middleName:null,surname:"Hernández-Carlos",slug:"beatriz-hernandez-carlos",fullName:"Beatriz Hernández-Carlos"},{id:"278133",title:"Dr.",name:"Claudia",middleName:null,surname:"Villanueva-Cañongo",slug:"claudia-villanueva-canongo",fullName:"Claudia Villanueva-Cañongo"}]},{id:"65331",doi:"10.5772/intechopen.83731",title:"Flavonoids and Phenolic Acids as Potential Natural Antioxidants",slug:"flavonoids-and-phenolic-acids-as-potential-natural-antioxidants",totalDownloads:1743,totalCrossrefCites:14,totalDimensionsCites:25,book:{slug:"antioxidants",title:"Antioxidants",fullTitle:"Antioxidants"},signatures:"Biljana Kaurinovic and Djendji Vastag",authors:[{id:"142369",title:"Prof.",name:"Biljana",middleName:null,surname:"Kaurinovic",slug:"biljana-kaurinovic",fullName:"Biljana Kaurinovic"},{id:"286918",title:"Prof.",name:"Djendji",middleName:null,surname:"Vastag",slug:"djendji-vastag",fullName:"Djendji Vastag"}]},{id:"62084",doi:"10.5772/intechopen.78977",title:"Resveratrol and SIRT1 Activators for the Treatment of Aging and Age-Related Diseases",slug:"resveratrol-and-sirt1-activators-for-the-treatment-of-aging-and-age-related-diseases",totalDownloads:1569,totalCrossrefCites:2,totalDimensionsCites:5,book:{slug:"resveratrol-adding-life-to-years-not-adding-years-to-life",title:"Resveratrol",fullTitle:"Resveratrol - Adding Life to Years, Not Adding Years to Life"},signatures:"Alessandra Stacchiotti, Gaia Favero and Rita Rezzani",authors:[{id:"175171",title:"Prof.",name:"Rita",middleName:null,surname:"Rezzani",slug:"rita-rezzani",fullName:"Rita Rezzani"},{id:"238047",title:"Dr.",name:"Gaia",middleName:null,surname:"Favero",slug:"gaia-favero",fullName:"Gaia Favero"},{id:"245898",title:"Dr.",name:"Alessandra",middleName:null,surname:"Stacchiotti",slug:"alessandra-stacchiotti",fullName:"Alessandra Stacchiotti"}]}],mostDownloadedChaptersLast30Days:[{id:"66259",title:"Antioxidant Compounds and Their Antioxidant Mechanism",slug:"antioxidant-compounds-and-their-antioxidant-mechanism",totalDownloads:4740,totalCrossrefCites:16,totalDimensionsCites:39,book:{slug:"antioxidants",title:"Antioxidants",fullTitle:"Antioxidants"},signatures:"Norma Francenia Santos-Sánchez, Raúl Salas-Coronado, Claudia Villanueva-Cañongo and Beatriz Hernández-Carlos",authors:[{id:"143354",title:"Dr.",name:"Raúl",middleName:null,surname:"Salas-Coronado",slug:"raul-salas-coronado",fullName:"Raúl Salas-Coronado"},{id:"148546",title:"Dr.",name:"Norma Francenia",middleName:null,surname:"Santos-Sánchez",slug:"norma-francenia-santos-sanchez",fullName:"Norma Francenia Santos-Sánchez"},{id:"193718",title:"Dr.",name:"Beatriz",middleName:null,surname:"Hernández-Carlos",slug:"beatriz-hernandez-carlos",fullName:"Beatriz Hernández-Carlos"},{id:"278133",title:"Dr.",name:"Claudia",middleName:null,surname:"Villanueva-Cañongo",slug:"claudia-villanueva-canongo",fullName:"Claudia Villanueva-Cañongo"}]},{id:"65067",title:"Diseases Related to Types of Free Radicals",slug:"diseases-related-to-types-of-free-radicals",totalDownloads:872,totalCrossrefCites:0,totalDimensionsCites:1,book:{slug:"antioxidants",title:"Antioxidants",fullTitle:"Antioxidants"},signatures:"Narendra Maddu",authors:[{id:"272889",title:"Dr.",name:"Narendra",middleName:null,surname:"Maddu",slug:"narendra-maddu",fullName:"Narendra Maddu"}]},{id:"62579",title:"Where and How in the mTOR Pathway Inhibitors Fight Aging: Rapamycin, Resveratrol, and Metformin",slug:"where-and-how-in-the-mtor-pathway-inhibitors-fight-aging-rapamycin-resveratrol-and-metformin",totalDownloads:1603,totalCrossrefCites:1,totalDimensionsCites:1,book:{slug:"resveratrol-adding-life-to-years-not-adding-years-to-life",title:"Resveratrol",fullTitle:"Resveratrol - Adding Life to Years, Not Adding Years to Life"},signatures:"Sage Arbor",authors:[{id:"245319",title:"Ph.D.",name:"Sage",middleName:null,surname:"Arbor",slug:"sage-arbor",fullName:"Sage Arbor"}]},{id:"62084",title:"Resveratrol and SIRT1 Activators for the Treatment of Aging and Age-Related Diseases",slug:"resveratrol-and-sirt1-activators-for-the-treatment-of-aging-and-age-related-diseases",totalDownloads:1569,totalCrossrefCites:2,totalDimensionsCites:5,book:{slug:"resveratrol-adding-life-to-years-not-adding-years-to-life",title:"Resveratrol",fullTitle:"Resveratrol - Adding Life to Years, Not Adding Years to Life"},signatures:"Alessandra Stacchiotti, Gaia Favero and Rita Rezzani",authors:[{id:"175171",title:"Prof.",name:"Rita",middleName:null,surname:"Rezzani",slug:"rita-rezzani",fullName:"Rita Rezzani"},{id:"238047",title:"Dr.",name:"Gaia",middleName:null,surname:"Favero",slug:"gaia-favero",fullName:"Gaia Favero"},{id:"245898",title:"Dr.",name:"Alessandra",middleName:null,surname:"Stacchiotti",slug:"alessandra-stacchiotti",fullName:"Alessandra Stacchiotti"}]},{id:"66504",title:"Antioxidants as a Double-Edged Sword in the Treatment of Cancer",slug:"antioxidants-as-a-double-edged-sword-in-the-treatment-of-cancer",totalDownloads:873,totalCrossrefCites:4,totalDimensionsCites:2,book:{slug:"antioxidants",title:"Antioxidants",fullTitle:"Antioxidants"},signatures:"Majid Asadi-Samani, Najmeh Kaffash Farkhad, Mohammad Reza Mahmoudian-Sani and Hedayatollah Shirzad",authors:[{id:"237542",title:"Dr.",name:"Majid",middleName:null,surname:"Asadi-Samani",slug:"majid-asadi-samani",fullName:"Majid Asadi-Samani"},{id:"275475",title:"Dr.",name:"Mohammad",middleName:null,surname:"Reza Mahmoudian-Sani",slug:"mohammad-reza-mahmoudian-sani",fullName:"Mohammad Reza Mahmoudian-Sani"},{id:"295230",title:"Dr.",name:"Najmeh",middleName:null,surname:"Kafash Farkhad",slug:"najmeh-kafash-farkhad",fullName:"Najmeh Kafash Farkhad"},{id:"295231",title:"Dr.",name:"Hedayatollah",middleName:null,surname:"Shirzad",slug:"hedayatollah-shirzad",fullName:"Hedayatollah Shirzad"}]},{id:"65331",title:"Flavonoids and Phenolic Acids as Potential Natural Antioxidants",slug:"flavonoids-and-phenolic-acids-as-potential-natural-antioxidants",totalDownloads:1743,totalCrossrefCites:14,totalDimensionsCites:25,book:{slug:"antioxidants",title:"Antioxidants",fullTitle:"Antioxidants"},signatures:"Biljana Kaurinovic and Djendji Vastag",authors:[{id:"142369",title:"Prof.",name:"Biljana",middleName:null,surname:"Kaurinovic",slug:"biljana-kaurinovic",fullName:"Biljana Kaurinovic"},{id:"286918",title:"Prof.",name:"Djendji",middleName:null,surname:"Vastag",slug:"djendji-vastag",fullName:"Djendji Vastag"}]},{id:"65225",title:"Antioxidant Categories and Mode of Action",slug:"antioxidant-categories-and-mode-of-action",totalDownloads:967,totalCrossrefCites:0,totalDimensionsCites:3,book:{slug:"antioxidants",title:"Antioxidants",fullTitle:"Antioxidants"},signatures:"Manal Azat Aziz, Abdulkareem Shehab Diab and Abeer Abdulrazak Mohammed",authors:[{id:"276717",title:"Associate Prof.",name:"Manal",middleName:null,surname:"Azat Aziz",slug:"manal-azat-aziz",fullName:"Manal Azat Aziz"},{id:"286369",title:"Dr.",name:"Abdulkareem",middleName:null,surname:"Shehab Diab",slug:"abdulkareem-shehab-diab",fullName:"Abdulkareem Shehab Diab"},{id:"312155",title:"Dr.",name:"Abeer Abdulrazak",middleName:null,surname:"Mohammed",slug:"abeer-abdulrazak-mohammed",fullName:"Abeer Abdulrazak Mohammed"}]},{id:"62439",title:"Protective Activity of Resveratrol in Cardio- and Cerebrovascular Diseases",slug:"protective-activity-of-resveratrol-in-cardio-and-cerebrovascular-diseases",totalDownloads:689,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"resveratrol-adding-life-to-years-not-adding-years-to-life",title:"Resveratrol",fullTitle:"Resveratrol - Adding Life to Years, Not Adding Years to Life"},signatures:"Albino Carrizzo, Carmine Izzo and Carmine Vecchione",authors:[{id:"209420",title:"Prof.",name:"Carmine",middleName:null,surname:"Vecchione",slug:"carmine-vecchione",fullName:"Carmine Vecchione"},{id:"210626",title:"MSc.",name:"Albino",middleName:null,surname:"Carrizzo",slug:"albino-carrizzo",fullName:"Albino Carrizzo"},{id:"219305",title:"Mr.",name:"Carmine",middleName:null,surname:"Izzo",slug:"carmine-izzo",fullName:"Carmine Izzo"}]},{id:"66809",title:"Dietary Antioxidants in the Chemoprevention of Prostate Cancer",slug:"dietary-antioxidants-in-the-chemoprevention-of-prostate-cancer",totalDownloads:465,totalCrossrefCites:1,totalDimensionsCites:2,book:{slug:"antioxidants",title:"Antioxidants",fullTitle:"Antioxidants"},signatures:"Dwayne Tucker, Melisa Anderson, Fabian Miller, Kurt Vaz, Lennox Anderson-Jackson and Donovan McGrowder",authors:[{id:"155804",title:"Dr.",name:"Donovan",middleName:null,surname:"McGrowder",slug:"donovan-mcgrowder",fullName:"Donovan McGrowder"},{id:"158092",title:"Mr.",name:"Lennox",middleName:null,surname:"Anderson-Jackson",slug:"lennox-anderson-jackson",fullName:"Lennox Anderson-Jackson"},{id:"280661",title:"Mr.",name:"Dwayne",middleName:null,surname:"Tucker",slug:"dwayne-tucker",fullName:"Dwayne Tucker"},{id:"280662",title:"Ms.",name:"Melisa",middleName:null,surname:"Anderson",slug:"melisa-anderson",fullName:"Melisa Anderson"},{id:"280664",title:"Mr.",name:"Fabian",middleName:null,surname:"Miller",slug:"fabian-miller",fullName:"Fabian Miller"},{id:"291987",title:"Ph.D. Student",name:"Kurt",middleName:null,surname:"Vaz",slug:"kurt-vaz",fullName:"Kurt Vaz"}]},{id:"65762",title:"Antioxidants in Date Fruits and the Extent of the Variability of the Total Phenolic Content: Review and Analysis",slug:"antioxidants-in-date-fruits-and-the-extent-of-the-variability-of-the-total-phenolic-content-review-a",totalDownloads:627,totalCrossrefCites:2,totalDimensionsCites:4,book:{slug:"antioxidants",title:"Antioxidants",fullTitle:"Antioxidants"},signatures:"Abdulameer Allaith",authors:[{id:"277441",title:"Associate Prof.",name:"Abdulameer",middleName:null,surname:"Allaith",slug:"abdulameer-allaith",fullName:"Abdulameer Allaith"}]}],onlineFirstChaptersFilter:{topicSlug:"clinical-pharmacology",limit:3,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[{type:"book",id:"10176",title:"Microgrids and Local Energy Systems",subtitle:null,isOpenForSubmission:!0,hash:"c32b4a5351a88f263074b0d0ca813a9c",slug:null,bookSignature:"Prof. Nick Jenkins",coverURL:"https://cdn.intechopen.com/books/images_new/10176.jpg",editedByType:null,editors:[{id:"55219",title:"Prof.",name:"Nick",middleName:null,surname:"Jenkins",slug:"nick-jenkins",fullName:"Nick Jenkins"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],offset:8,limit:8,total:1},route:{name:"profile.detail",path:"/profiles/169828/victor-manuel-hernandez-guzman",hash:"",query:{},params:{id:"169828",slug:"victor-manuel-hernandez-guzman"},fullPath:"/profiles/169828/victor-manuel-hernandez-guzman",meta:{},from:{name:null,path:"/",hash:"",query:{},params:{},fullPath:"/",meta:{}}}},function(){var e;(e=document.currentScript||document.scripts[document.scripts.length-1]).parentNode.removeChild(e)}()