\\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:"8896",leadTitle:null,fullTitle:"Sustainable Mobility",title:"Sustainable Mobility",subtitle:null,reviewType:"peer-reviewed",abstract:"The concept of sustainability is already applied in all industrial sectors. The fight against climate change therefore forces us to look for alternatives in the way we move. Different alternative fuels are discussed in this book: from liquid and gaseous biofuels to electricity. Moreover, waste to fuel processes are another option to produce a significant amount of fuels. In the spirit of this book, there is not only collecting different alternatives, but creativity is also promoted in the readers of this book, so that they take an active part of the solution necessary to reduce greenhouse gas emissions.",isbn:"978-1-78984-563-1",printIsbn:"978-1-78984-562-4",pdfIsbn:"978-1-78984-620-1",doi:"10.5772/intechopen.82169",price:119,priceEur:129,priceUsd:155,slug:"sustainable-mobility",numberOfPages:186,isOpenForSubmission:!1,isInWos:null,hash:"c5b28b438521dcd383df9b6e797ec462",bookSignature:"Bernardo Llamas, Marcelo F. Ortega Romero and Eugenia Sillero",publishedDate:"April 22nd 2020",coverURL:"https://cdn.intechopen.com/books/images_new/8896.jpg",numberOfDownloads:2201,numberOfWosCitations:0,numberOfCrossrefCitations:1,numberOfDimensionsCitations:2,hasAltmetrics:0,numberOfTotalCitations:3,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"October 30th 2018",dateEndSecondStepPublish:"March 20th 2019",dateEndThirdStepPublish:"September 27th 2019",dateEndFourthStepPublish:"October 4th 2019",dateEndFifthStepPublish:"November 27th 2019",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!0,editors:[{id:"169368",title:"Dr.",name:"Bernardo",middleName:null,surname:"Llamas",slug:"bernardo-llamas",fullName:"Bernardo Llamas",profilePictureURL:"https://mts.intechopen.com/storage/users/169368/images/system/169368.jpeg",biography:"Dr. Llamas is a professor in the area of project management at the Polytechnic University of Madrid. His specialization and participation in research projects has been related to the energy and resources of the subsoil. Specifically, in the area of production of microalgae for energy purposes, the geological storage of CO2 and, recently in the production of biomethane. There are several scientific articles and international patents that relate the indicated research.",institutionString:"Universidad Politécnica de Madrid",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"4",institution:{name:"Technical University of Madrid",institutionURL:null,country:{name:"Spain"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:{id:"281674",title:"Dr.",name:"Marcelo",middleName:null,surname:"F. Ortega Romero",slug:"marcelo-f.-ortega-romero",fullName:"Marcelo F. Ortega Romero",profilePictureURL:"https://mts.intechopen.com/storage/users/281674/images/system/281674.jpg",biography:"Marcelo F. Ortega has been a professor at the Technical University of Madrid for 7 year. He is the coordinator and professor of process engineering in Department of Energy and Fuels and the author of 22 scientific publications indexed with relative quality index in the Journal of Citation Report (more than half are located in the first quartile) and researcher in some projects. His specialization and participation in research projects has been related to the energy, biofuels and environmental pollution.",institutionString:"Universidad Politécnica de Madrid",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Technical University of Madrid",institutionURL:null,country:{name:"Spain"}}},coeditorTwo:{id:"281672",title:"Dr.",name:"Eugenia",middleName:null,surname:"Sillero",slug:"eugenia-sillero",fullName:"Eugenia Sillero",profilePictureURL:"https://mts.intechopen.com/storage/users/281672/images/system/281672.jpeg",biography:"Eugenia Sillero holds a master\\'s degree in fuel and energy engineering from the Polytechnic University of Madrid, she has done business studies in IESE business school (Navarra University), and she holds a PhD in journalism and communication from the CEU San Pablo University.\r\nNowadays she is the general secretary of Gasnam, the Spanish and Portuguese association that promotes the use of natural and renewable gas as fuel in maritime and road mobility. Gasnam has 125 members from different sectors: energy, automotive, shipping, universities.\r\nHer professional career started in the automotive components industry, at Grupo Antolín. For more than ten years, until she joined Gasnam, she held various responsibilities in the maritime administration (ministry of transport)",institutionString:"Asociación Ibérica de Gas Natural para la Movilidad, GASNAM",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:null},coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"770",title:"Renewable Energy",slug:"engineering-energy-engineering-renewable-energy"}],chapters:[{id:"70589",title:"The Pathway to Sustainable Transport",doi:"10.5772/intechopen.90219",slug:"the-pathway-to-sustainable-transport",totalDownloads:234,totalCrossrefCites:0,totalDimensionsCites:1,signatures:"Pedro Cotera and Manuel Arias",downloadPdfUrl:"/chapter/pdf-download/70589",previewPdfUrl:"/chapter/pdf-preview/70589",authors:[{id:"310308",title:"Mr.",name:"Pedro",surname:"Cotera",slug:"pedro-cotera",fullName:"Pedro Cotera"},{id:"310511",title:"Dr.",name:"Manuel",surname:"Arias",slug:"manuel-arias",fullName:"Manuel Arias"}],corrections:null},{id:"70092",title:"Evolution towards a Sustainable Public Transport in the City of Madrid",doi:"10.5772/intechopen.90102",slug:"evolution-towards-a-sustainable-public-transport-in-the-city-of-madrid",totalDownloads:190,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Gonzalo Fernández-Sánchez, Juan Ángel Terrón and Álvaro Fernández-Heredia",downloadPdfUrl:"/chapter/pdf-download/70092",previewPdfUrl:"/chapter/pdf-preview/70092",authors:[{id:"297996",title:"Dr.",name:"Gonzalo",surname:"Fernandez-Sanchez",slug:"gonzalo-fernandez-sanchez",fullName:"Gonzalo Fernandez-Sanchez"}],corrections:null},{id:"70860",title:"Feedstocks for Advanced Biofuels",doi:"10.5772/intechopen.91006",slug:"feedstocks-for-advanced-biofuels",totalDownloads:266,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Enrique Espí, Íñigo Ribas, Carlos Díaz and Óscar Sastrón",downloadPdfUrl:"/chapter/pdf-download/70860",previewPdfUrl:"/chapter/pdf-preview/70860",authors:[{id:"292559",title:"Ph.D.",name:"Enrique",surname:"Espi",slug:"enrique-espi",fullName:"Enrique Espi"},{id:"314951",title:"Mr.",name:"Iñigo",surname:"Ribas",slug:"inigo-ribas",fullName:"Iñigo Ribas"},{id:"314952",title:"Mr.",name:"Carlos",surname:"Diaz",slug:"carlos-diaz",fullName:"Carlos Diaz"},{id:"314953",title:"Dr.",name:"Oscar",surname:"Sastron",slug:"oscar-sastron",fullName:"Oscar Sastron"}],corrections:null},{id:"69792",title:"Valorization of Microalgae and Energy Resources",doi:"10.5772/intechopen.90072",slug:"valorization-of-microalgae-and-energy-resources",totalDownloads:166,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Cynthia V. González-López, Francisco García-Cuadra, Natalia Jawiarczyk, José M. Fernández-Sevilla and Francisco G. Acién-Fernández",downloadPdfUrl:"/chapter/pdf-download/69792",previewPdfUrl:"/chapter/pdf-preview/69792",authors:[{id:"196375",title:"Prof.",name:"Francisco G.",surname:"Acién-Fernández",slug:"francisco-g.-acien-fernandez",fullName:"Francisco G. Acién-Fernández"},{id:"304584",title:"Dr.",name:"Cynthia V.",surname:"González-López",slug:"cynthia-v.-gonzalez-lopez",fullName:"Cynthia V. González-López"},{id:"305109",title:"Dr.",name:"Jose M.",surname:"Fernández-Sevilla",slug:"jose-m.-fernandez-sevilla",fullName:"Jose M. Fernández-Sevilla"},{id:"305110",title:"Dr.",name:"Natalia",surname:"Jawiarczyk",slug:"natalia-jawiarczyk",fullName:"Natalia Jawiarczyk"},{id:"305111",title:"Dr.",name:"Francisco",surname:"García Cuadra",slug:"francisco-garcia-cuadra",fullName:"Francisco García Cuadra"}],corrections:null},{id:"70583",title:"Recycling of Waste Plastics into Pyrolytic Fuels and Their Use in IC Engines",doi:"10.5772/intechopen.90639",slug:"recycling-of-waste-plastics-into-pyrolytic-fuels-and-their-use-in-ic-engines",totalDownloads:597,totalCrossrefCites:1,totalDimensionsCites:1,signatures:"Sinan Erdogan",downloadPdfUrl:"/chapter/pdf-download/70583",previewPdfUrl:"/chapter/pdf-preview/70583",authors:[{id:"298608",title:"Dr.",name:"Sinan",surname:"Erdogan",slug:"sinan-erdogan",fullName:"Sinan Erdogan"}],corrections:null},{id:"71008",title:"Gaseous Biofuels to Sustainable Mobility",doi:"10.5772/intechopen.90944",slug:"gaseous-biofuels-to-sustainable-mobility",totalDownloads:163,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Carlos Repáraz Martín, Ignacio de Godos Crespo, Marcelo F. Ortega Romero and Bernardo Llamas Moya",downloadPdfUrl:"/chapter/pdf-download/71008",previewPdfUrl:"/chapter/pdf-preview/71008",authors:[{id:"295707",title:"Mr.",name:"Carlos",surname:"Repáraz",slug:"carlos-reparaz",fullName:"Carlos Repáraz"}],corrections:null},{id:"71242",title:"Natural Gas as a Gateway for Renewable Gas in Transport",doi:"10.5772/intechopen.91344",slug:"natural-gas-as-a-gateway-for-renewable-gas-in-transport",totalDownloads:199,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Eugenia Sillero Maté, Carla García, Paloma Martínez Ramos and Elena Martínez Calvo",downloadPdfUrl:"/chapter/pdf-download/71242",previewPdfUrl:"/chapter/pdf-preview/71242",authors:[{id:"281672",title:"Dr.",name:"Eugenia",surname:"Sillero",slug:"eugenia-sillero",fullName:"Eugenia Sillero"},{id:"303764",title:"Dr.",name:"Paloma",surname:"Martinez",slug:"paloma-martinez",fullName:"Paloma Martinez"},{id:"303765",title:"Dr.",name:"Carla",surname:"Garcia",slug:"carla-garcia",fullName:"Carla Garcia"},{id:"314230",title:"Dr.",name:"Elena",surname:"Martínez",slug:"elena-martinez",fullName:"Elena Martínez"}],corrections:null},{id:"70641",title:"Sustainability Analyses for Hydrogen Fuel Cell Electric Vehicles",doi:"10.5772/intechopen.90675",slug:"sustainability-analyses-for-hydrogen-fuel-cell-electric-vehicles",totalDownloads:230,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Hüseyin Turan Arat, Bahattin Tanç and Nevzat Özaslan",downloadPdfUrl:"/chapter/pdf-download/70641",previewPdfUrl:"/chapter/pdf-preview/70641",authors:[{id:"201245",title:"Dr.",name:"Hüseyin Turan",surname:"Arat",slug:"huseyin-turan-arat",fullName:"Hüseyin Turan Arat"},{id:"202901",title:"Dr.",name:"Bahattin",surname:"Tanç",slug:"bahattin-tanc",fullName:"Bahattin Tanç"},{id:"313014",title:"Mr.",name:"Nevzat",surname:"Özaslan",slug:"nevzat-ozaslan",fullName:"Nevzat Özaslan"}],corrections:null},{id:"70648",title:"Management of Innovation Performance on the Example of the Automotive Supply Chains",doi:"10.5772/intechopen.90638",slug:"management-of-innovation-performance-on-the-example-of-the-automotive-supply-chains",totalDownloads:156,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Ewa Stawiarska",downloadPdfUrl:"/chapter/pdf-download/70648",previewPdfUrl:"/chapter/pdf-preview/70648",authors:[{id:"296907",title:"Dr.",name:"Ewa",surname:"Stawiarska",slug:"ewa-stawiarska",fullName:"Ewa Stawiarska"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},relatedBooks:[{type:"book",id:"4697",title:"Greenhouse Gases",subtitle:null,isOpenForSubmission:!1,hash:"a571ed811b623e82680d1ade5b4feb98",slug:"greenhouse-gases",bookSignature:"Bernardo Llamas Moya and Juan Pous",coverURL:"https://cdn.intechopen.com/books/images_new/4697.jpg",editedByType:"Edited by",editors:[{id:"169368",title:"Dr.",name:"Bernardo",surname:"Llamas",slug:"bernardo-llamas",fullName:"Bernardo Llamas"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6027",title:"Case Study of Innovative Projects",subtitle:"Successful Real Cases",isOpenForSubmission:!1,hash:"3121d02b853882157d8762e04b3b82b3",slug:"case-study-of-innovative-projects-successful-real-cases",bookSignature:"Bernardo Llamas Moya, M. Dolores Storch de Gracia and Luis F. Mazadiego",coverURL:"https://cdn.intechopen.com/books/images_new/6027.jpg",editedByType:"Edited by",editors:[{id:"169368",title:"Dr.",name:"Bernardo",surname:"Llamas",slug:"bernardo-llamas",fullName:"Bernardo Llamas"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5697",title:"Key Issues for Management of Innovative Projects",subtitle:null,isOpenForSubmission:!1,hash:"c8366c1e85a2b1c300ec46aba34a3aaa",slug:"key-issues-for-management-of-innovative-projects",bookSignature:"Bernardo Llamas Moya, M. Dolores Storch de Gracia and Luis F. Mazadiego",coverURL:"https://cdn.intechopen.com/books/images_new/5697.jpg",editedByType:"Edited by",editors:[{id:"169368",title:"Dr.",name:"Bernardo",surname:"Llamas",slug:"bernardo-llamas",fullName:"Bernardo Llamas"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3633",title:"Solar Energy",subtitle:null,isOpenForSubmission:!1,hash:null,slug:"solar-energy",bookSignature:"Radu D Rugescu",coverURL:"https://cdn.intechopen.com/books/images_new/3633.jpg",editedByType:"Edited by",editors:[{id:"8615",title:"Prof.",name:"Radu",surname:"Rugescu",slug:"radu-rugescu",fullName:"Radu Rugescu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1288",title:"Solar Cells",subtitle:"Dye-Sensitized Devices",isOpenForSubmission:!1,hash:"05a255471069664ecf5fbf8778b92076",slug:"solar-cells-dye-sensitized-devices",bookSignature:"Leonid A. Kosyachenko",coverURL:"https://cdn.intechopen.com/books/images_new/1288.jpg",editedByType:"Edited by",editors:[{id:"6262",title:"Prof.",name:"Leonid A.",surname:"Kosyachenko",slug:"leonid-a.-kosyachenko",fullName:"Leonid A. Kosyachenko"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3118",title:"Solar Cells",subtitle:"Research and Application Perspectives",isOpenForSubmission:!1,hash:"5502d7fd7559d60419f2615615ae4cf5",slug:"solar-cells-research-and-application-perspectives",bookSignature:"Arturo Morales-Acevedo",coverURL:"https://cdn.intechopen.com/books/images_new/3118.jpg",editedByType:"Edited by",editors:[{id:"90486",title:"Prof.",name:"Arturo",surname:"Morales-Acevedo",slug:"arturo-morales-acevedo",fullName:"Arturo Morales-Acevedo"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"877",title:"Third Generation Photovoltaics",subtitle:null,isOpenForSubmission:!1,hash:"c3bdfaebac38dab83a69c488bcda219d",slug:"third-generation-photovoltaics",bookSignature:"Vasilis Fthenakis",coverURL:"https://cdn.intechopen.com/books/images_new/877.jpg",editedByType:"Edited by",editors:[{id:"68723",title:"Dr.",name:"Vasilis",surname:"Fthenakis",slug:"vasilis-fthenakis",fullName:"Vasilis Fthenakis"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"4479",title:"Solar Cells",subtitle:"New Approaches and Reviews",isOpenForSubmission:!1,hash:"f6907a79a7d35f34d0c719d6297a2667",slug:"solar-cells-new-approaches-and-reviews",bookSignature:"Leonid A. Kosyachenko",coverURL:"https://cdn.intechopen.com/books/images_new/4479.jpg",editedByType:"Edited by",editors:[{id:"6262",title:"Prof.",name:"Leonid A.",surname:"Kosyachenko",slug:"leonid-a.-kosyachenko",fullName:"Leonid A. Kosyachenko"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1290",title:"Solar Cells",subtitle:"New Aspects and Solutions",isOpenForSubmission:!1,hash:"52415367e48e5b68d47325bdfc81cdce",slug:"solar-cells-new-aspects-and-solutions",bookSignature:"Leonid A. Kosyachenko",coverURL:"https://cdn.intechopen.com/books/images_new/1290.jpg",editedByType:"Edited by",editors:[{id:"6262",title:"Prof.",name:"Leonid A.",surname:"Kosyachenko",slug:"leonid-a.-kosyachenko",fullName:"Leonid A. Kosyachenko"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3676",title:"Solar Collectors and Panels",subtitle:"Theory and Applications",isOpenForSubmission:!1,hash:null,slug:"solar-collectors-and-panels--theory-and-applications",bookSignature:"Reccab Manyala",coverURL:"https://cdn.intechopen.com/books/images_new/3676.jpg",editedByType:"Edited by",editors:[{id:"12002",title:"Associate Prof.",name:"Reccab",surname:"Manyala",slug:"reccab-manyala",fullName:"Reccab Manyala"}],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:"8807",leadTitle:null,title:"Organic Synthesis",subtitle:null,reviewType:"peer-reviewed",abstract:"
\r\n\tOrganic synthesis has always been one of the central topics of research for the scientific community in the academic laboratories and industrial world. Many striking journal articles and remarkable reviews and books have been published in the past year describing the practicability and applications of the subject demonstrating the importance of organic synthesis. In the present book, we will be putting together the topics in organic synthesis which may include but not limited to, (1) the basic terms and concepts, (2) various organic reactions including reduction, oxidation, addition, elimination, rearrangements, and cycloadditions, (3) Total Synthesis of Natural products, (4) transition metal catalysts, organocatalysts, enzymes and biotransformations, (5) applications in medicinal chemistry and drug design and development, (6) purification methods and characterization techniques, etc. To set a limit and to increase the scope of the book, author(s) are encouraged to send the chapters that include selected examples with practical applications and good yielding reactions reported within the past decade. Older topics with significant findings or their essence to prepare the foundation may be included in the chapter are welcomed as well.
",isbn:null,printIsbn:"979-953-307-X-X",pdfIsbn:null,doi:null,price:0,priceEur:null,priceUsd:null,slug:null,numberOfPages:0,isOpenForSubmission:!1,hash:"f3bbbd989d0896f142d317ccb8abcc35",bookSignature:"Dr. Prashant S Deore",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/8807.jpg",keywords:"Natural Product Synthesis, Organic Reaction Mechanism, Stereoselective synthesis, Chirality, C-H Functionalization, Cross-Coupling Reactions, Heterogeneous Catalysis, Homogeneous Catalysis, Green Synthesis, Green Solvents and Reagents, Bioorganic synthesis, Click Chemistry",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"December 10th 2018",dateEndSecondStepPublish:"January 14th 2019",dateEndThirdStepPublish:"March 15th 2019",dateEndFourthStepPublish:"May 20th 2019",dateEndFifthStepPublish:"July 19th 2019",remainingDaysToSecondStep:"2 years",secondStepPassed:!0,currentStepOfPublishingProcess:5,editedByType:null,kuFlag:!1,biosketch:null,coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"251769",title:"Dr.",name:"Prashant",middleName:"S",surname:"Deore",slug:"prashant-deore",fullName:"Prashant Deore",profilePictureURL:"https://mts.intechopen.com/storage/users/251769/images/system/251769.png",biography:"Dr. Prashant S. Deore was born in India. He received a Master’s degree in organic chemistry from Pune University in 2007. In the same year, he qualified with the SET and CSIR-NET (JRF) and joined in the group of Prof. Narshinha P. Argade for the doctoral studies in National Chemical Laboratory, India. In 2014, he awarded with a Ph. D. in Chemistry and was a recipient of the 2nd prize in “2014 Eli Lilly and Company Asia Outstanding Thesis Awards”. In July 2014 he moved to Canada and joined as a postdoctoral researcher in the group of Prof. Richard Manderville at the University of Guelph, Canada. Presently, Dr. Deore is working on the collaborative project between the University of Guelph and Aterica health Inc., and providing consulting to the company. His research interest includes organic synthesis, fluorescent probes development, nucleic acid synthesis and modifications, and aptasensor development for proteins and food toxins.",institutionString:"University of Guelph",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:null}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"8",title:"Chemistry",slug:"chemistry"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"270935",firstName:"Rozmari",lastName:"Marijan",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/270935/images/7974_n.png",email:"rozmari@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:"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"}},{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"}],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"}],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"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"4816",title:"Face Recognition",subtitle:null,isOpenForSubmission:!1,hash:"146063b5359146b7718ea86bad47c8eb",slug:"face_recognition",bookSignature:"Kresimir Delac and Mislav Grgic",coverURL:"https://cdn.intechopen.com/books/images_new/4816.jpg",editedByType:"Edited by",editors:[{id:"528",title:"Dr.",name:"Kresimir",surname:"Delac",slug:"kresimir-delac",fullName:"Kresimir Delac"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3621",title:"Silver Nanoparticles",subtitle:null,isOpenForSubmission:!1,hash:null,slug:"silver-nanoparticles",bookSignature:"David Pozo Perez",coverURL:"https://cdn.intechopen.com/books/images_new/3621.jpg",editedByType:"Edited by",editors:[{id:"6667",title:"Dr.",name:"David",surname:"Pozo",slug:"david-pozo",fullName:"David Pozo"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"59154",title:"The Role of Mesenteric Adipose Tissue in Crohn’s Disease",doi:"10.5772/intechopen.73872",slug:"the-role-of-mesenteric-adipose-tissue-in-crohn-s-disease",body:'Adipose tissue was initially described as an energy storehouse. However, in the last decades, it has also come to be recognized as an endocrine organ with multiple functions. Adipose tissue is composed of adipocytes, connective and nerve tissue, fibroblasts, chondrocytes, osteocytes, myocytes, and immune system cells, which constitute the stromal vascular fraction [1, 2, 3].
Adipose tissue is very dynamic, and it is able to secrete a diverse spectrum of biologically active substances designated as adipocytokines, such as cytokines, and hormone-like proteins, such as leptin, adiponectin, and resistin. These substances exhibit endocrine or paracrine functions, and they are important in maintaining energy homeostasis [1, 3, 4, 5, 6].
Recent studies have shown that abnormal adipose tissue expansion associated with inflammation predisposes, in turn, to obesity, cardiovascular disease, chronic kidney disease, and inflammatory bowel disease [5, 7, 8, 9].
This chapter deals with adipose tissue in general, the morphological and functional differences among its compartments, and presents the main characteristics of mesenteric adipose tissue (MAT) in Crohn’s disease (CD), in addition to its possible role in the etiopathology of the disease.
Adipose tissue can be classified into white adipose tissue (WAT), brown adipose tissue (BAT), and the recently discovered beige adipose tissue (BAT) [2, 10].
WAT comprises the vast majority of adipose tissue in the human body. WAT presents an energy-storing property and a secretory function [3, 4, 5]. WAT is anatomically divided into distinct depots: subcutaneous and visceral fat [2, 9].
Several studies have reported morphological and functional differences between these adipose tissue compartments. Obese patients have visceral adiposity and are more prone to develop insulin resistance, which strongly correlates with metabolic syndrome. Moreover, the pattern of adipokines secreted by visceral and subcutaneous adipose tissue is different [2, 9, 11].
The importance of anatomical parameters in the regulation of WAT biology is highlighted by the fact that in obese subjects abdominal deep subcutaneous WAT expands much more than superficial subcutaneous WAT [1, 9, 12]. A further instance of this can be seen in that subcutaneous and visceral WAT contribute to cardiovascular disease, whereas femoral WAT may have an overall protective effect. Therefore, changes in biological characteristics of different depots of adipose tissue give rise to different cardiometabolic conditions [9, 13].
Indeed, the heterogeneity among different anatomical depots also appears to stem from their intrinsic diversity, including cellular developmental origin, proliferative capacity, glucose and lipid metabolism, insulin sensitivity, cytokine pattern, thermogenic ability, and vascularization [1, 2, 5].
The features of obesity lie not only in WAT expansion but also in WAT dysfunction associated with qualitative changes in its biological characteristics. In an obese condition, the ingestion of excess nutrients and energy results in hypertrophy, consequent rupturing of adipocytes, and increased local inflammatory cell accumulation, including macrophages, T cells, and altered production of adipokines. These adipose tissue changes and their systemic consequences lead to the concept of obesity as a chronic inflammatory state, and they increase the risk for multiple chronic diseases, such as type 2 diabetes, cardiovascular disease, several types of cancer, and inflammatory bowel disease (IBD) [1, 3, 5, 9].
At a molecular level, BAT is distinguished from WAT by its expression of uncoupling protein 1 (UCP1), which is crucial to mitochondrial heat production and is involved in the maintenance of body temperature [10, 14, 15]. Neonates exhibit a considerable amount of BAT and a larger fraction of total adipose tissue mass. The thermogenic function of BAT in human neonates has not been yet well assessed due to the absence of safe experimental protocols. Probably, neonates activate a non-shivering thermogenesis (NST) in order to prevent hypothermia [14, 16]. Adult humans exhibit another mechanism to produce heat, and BAT mass seems reduced when compared with neonates. Currently, the activity of BAT in humans shows an inverse correlation to age, body mass index, and the glucose level. Adult humans possess functional BAT in the neck, supraclavicular, and axillary regions, as well as around major vessels, such as the aorta [15, 16].
Thermogenesis is a major function of BAT in rodent and adult humans. Recent advances showed that this tissue may also regulate glucose and lipid metabolism and that it plays a role in regulating energy homeostasis in humans. However, little is still known about secreted adipocytokines in vivo and their role in the regulation of energy metabolism. Studies have shown that transplanted BAT from a healthy mouse into obese-induced and leptin-deficient (ob/ob) mice improves whole-body energy metabolism, increasing insulin sensitivity and reversing preexisting obesity. These effects were accompanied by modulation in the secretion of interleukin (IL)-6, adiponectin, and others cytokines [14, 15].
Recently, another type of adipose tissue, described as beige, has been described. Exposure to cold or to β3-adrenoceptor agonist treatment stimulates WAT. This tissue expresses large amount of UCP1, which can perform a thermoregulatory function. Besides that, beige adipose tissue exists within WAT, mainly in the supraclavicular region, and may be revealed by potent exposure to cold under experimental conditions [10, 14, 15].
Classical brown adipocytes and beige cells play a critical role in the maintenance of body temperature in a cold environment. Therefore, brown and beige adipocytes are promising targets for the treatment of obesity and its related metabolic disorders [10, 14, 15].
Progress in understanding the morphological characteristics of adipocytes, as well as understanding how immune cells contribute to the control of the immunometabolism can provide new potential targets of intervention. The formation of heat-producing beige adipocytes in WAT and the polarization of macrophages transitioning from an inflammatory phenotype toward an anti-inflammatory one are examples of potential targets to explore [5, 10, 14, 15].
Several studies have come out recently concerning the typically increased mesentery in CD (named “creeping fat”) near the affected intestinal area. Histological characteristics of the MAT in CD with reduced adipocyte size independent of the weight body have also been reported [17, 18]. However, humoral and cellular changes in this adipose tissue are specific and differ from those observed in hypertrophied fat tissue of obese patients. The functional impact of MAT on CD development and progression is not clear yet and has been studied intensively in recent years.
IBD has become an increasingly widespread chronic health problem throughout the last few decades, particularly in developing countries. In young adults, one of the most common forms of IBD is CD. CD is a multifactorial genetic disease characterized by transmural granulomatous inflammation, which affects mainly the terminal ileum and the colon. Defective inflammatory pathways, immune adaptive complex, and environmental factors are involved in CD. This disease presents periods of remission and recurrence followed by diarrhea, abdominal pain, and malnutrition, which often lead to lumen bowel stenosis associated to multiple fistulas [19].
Evidence linking the development of mesenteric and intestinal alterations in CD is increasing. It has been suggested that increased visceral adiposity (of which mesenteric fat is the main component) is pathognomonic of CD. The involvement of MAT is increasingly thought to provide a mechanistic contribution to CD progression. In addition, the increased MAT near the affected intestinal area is considered a hallmark of an active and more aggressive CD [20, 21, 22].
For over a century, mesenteric anatomy has been universally depicted in an inaccurate manner. Recent observations confirm a simpler and continuous structure from the duodenojejunal flexure to the mesorectum [23, 24]. In a prospective observational study of a cohort submitted to total excisional surgery of the mesocolon, it was demonstrated that the mesentery binds in all intestinal segments [25, 26]. The mesentery is located between the intestines and the abdominal wall, although the greatest mass of MAT is present in the ileocecal region [23].
This ectopic inflamed tissue in CD patients, also referred as “creeping fat,” was already identified by Crohn and collaborators in 1932 [27]. He described its thickening and suggested its possible involvement in CD, even though direct evidence was still lacking. MAT from CD patients presents a large phenotypic variation according to what is observed in surgical specimens, with notorious thickening of adipose tissue near the affected intestinal area when compared to patients who do not present CD. Therefore, surgeons are familiar with the phenotypic variation of the creeping fat, and it is used as an anatomical marker to delineate the extent of active disease in CD patients (see Figure 1) [28, 29].
Surgical aspects of creeping fat (mesenteric adipose tissue) in the ileum affected by Crohn’s disease. The arrows in (A) indicate the inflamed small bowel surrounded by the creeping fat. The blue line in (B) shows contiguous longitudinal ulcer in the intestinal mucosa localized in the mesenteric face of the bowel (source: Archives of Colorectal Surgery Unit—UNICAMP).
Considering the microscopic appearance of the MAT in CD, the histopathology shows immune cell infiltration, and the adipocytes are smaller (lower mean area and perimeter) than the controls, displaying an intriguing feature [17]. To investigate this morphological feature, apoptosis was studied in these tissues. Analysis by TUNEL assay showed a significantly lower number of apoptotic cells in the MAT of CD when compared to MAT of control group [18]. There was a strong positive correlation between the adipocyte size and the apoptotic index (accessed by TUNEL). In addition, immunohistochemistry for Ki-67 was performed on all MAT samples to access the proliferation rate of the adipocytes. However, no evidence of proliferation was verified in MAT from both groups [18]. In fact, proliferation of adipocytes occurs only in severe obesity, which produces an increased adipocyte count. Surprisingly, we have an interesting situation in CD, in which the tissue looks like a MAT from a severely obese patient, but the proliferation rate is zero. Whether adipocytes migrate to the affected area or mesenchymal cells differentiate to adipocytes/fibroblasts has to be further investigated.
Another microscopic feature is the adipocyte hyperplasia in the submucosa of CD creating a similar histologic feature seen in the mesentery [30]. However, only colonic specimens were evaluated. This characteristic was not verified in samples from ileal CD [31]. For this reason, further investigation is needed, but fibrocytes may play a role in this, for they are increased in the mesentery of CD [32].
Indeed, MAT may present a role in the etiopathology of CD. As it has been demonstrated with other fat deposits, MAT is able to propagate both metabolic and inflammatory signals systemically, potentially modulating clinical features of CD. Its location allows MAT to respond to environmental stimuli and to coordinate intestinal responses locally and systemically [33, 34, 35].
The importance of various mesenteric components in the development and maintenance of CD, such as blood vessels, lymph nodes, and nerves, is reported [24, 26, 36, 37]. Although this relationship has not been completely elucidated, some studies provide evidence for the MAT component role in CD, as will be highlighted in the following paragraphs.
A recent study showed the presence of fibrosis, inflamed perivascular, thickened lymphatic vessels, infiltration of stromal cell, perineuronal chronic inflammation, engorgement of vasa recta, and small-sized adipocytes of MAT in patients with active CD [38]. MAT is divided into avascular and vascular regions. Within the vascularized segments, the fibro-adipose tissue involves large vessels and their ramifications [24, 39]. In healthy individuals, the mesentery is soft, and it can be easily separated from the vascularized area. However, when affected by CD, the mesentery thickens, and it interferes in the surgical dissection [28, 29].
Besides these features, histopathological findings, such as vascular lesions, focal arteritis, fibrin deposition, arterial occlusion, and granulomatous vasculitis, are observed in CD patients. These alterations demonstrate the role of mesenteric blood vessels in chronic intestinal inflammation [38, 40, 41]. Changes in vascular endothelium and abnormal leukocyte recruitment were also verified in CD [42]. Moreover, increase in the microvascular density and dysregulated angiogenic activities are other morphological and functional findings in the gut of CD patients [43].
Concerning immune cells, Kredel and collaborators identified an increase of regulatory M2 macrophages in the mesentery of CD, which suggests a protective role of the mesentery in this disease [44].
Zuo and collaborators demonstrated that the function and morphology of the normal MAT in CD patients were similar to control tissues [45]. However, increased MAT adjacent to involved ileum in CD was dysfunctional, exhibiting higher expression of hypoxia-inducible factor 1α when compared to controls, which suggests hypoxia in this tissue.
Moreover, the mesenteric nerves may also influence the pathogenesis, behavior, and prognosis of CD. In an experimental study, functional and structural alterations were observed in the mesenteric nerves of animals with colitis. Mice with colitis induced by trinitrobenzene sulfonic acid or acetic acid presented hyperexcitability of visceromotor neurons causing changes in the lower mesenteric ganglia during the intestinal inflammatory process [38, 46].
Recently, studies have highlighted a new function for MAT as an immune organ [47]. MAT’s basic cellular components comprise adipocytes, preadipocytes, fibroblasts, mesenchymal stem cells, and endothelial cells. However, when the inflammatory process is initiated, an increase of immune effector cells occurs, including T cells, natural killer cells, and macrophages, as well as innate immune cells [48]. These cells are responsible for the production of several pro- and anti-inflammatory cytokines, such as TNF-α, IL-6, IL-8, IL-23, and IL-10 [49]. Given the potential therapeutic effect of their blockade, a large number of these inflammatory mediators present in MAT and their role in the development of CD have been closely investigated [31].
One of the main pro-inflammatory cytokines in CD is TNF-α. TNF-α has a fundamental role in CD due to the discovery of the therapeutic effect of its blockage [50]. The complete mechanism by which TNF-α regulates MAT inflammation in CD patients has not yet been elucidated, but it is likely a complex and multifactorial process. However, it is known that TNF-α inhibits the proliferation of new adipocytes, which leads to an increased amount of free fatty acids [51].
Another important molecule in the inflammatory process is the peroxisome proliferator-activated receptor (PPAR) transcription factor, which plays an essential role in the regulation of cellular differentiation, development, and metabolism. In CD, it has some specific functions related to the maintenance of the process, such as cytokine production, adipocyte differentiation, fibrocytes differentiation inhibition, and IκB/NF-κB activation [33, 52, 53]. On the one hand, studies have shown a decrease of the PPAR-γ in MAT from CD patients [53, 54]. On the other hand, Desreumaux and collaborators showed that significant accumulation of intra-abdominal fat is associated with overexpression of PPARY and TNF-α in the MAT of the small bowel mesentery in CD patients, which suggests adipocytes as one of the sources of TNF-α production [55].
Although adipose tissue is able to increase TNF-α secretion via leptin, a hormone produced by adipocytes [56], some studies in the literature did not find high levels of TNF-α in the MAT of CD, neither higher levels of IL-1B, IL6, IL8, IL23, and NF-KB activation [21, 31, 38, 57]. Again, on the one hand, a decrease NF-kB pathway activation (decreased pIKB/IKB ratio) and increased IL-10 expression in MAT of CD patients have been demonstrated, which suggest a possible anti-inflammatory role of MAT [21, 31]. On the other hand, STAT-1 transcription factor is activated in the MAT of CD patients, suggesting a potential role in the inflammatory process [31]. This topic needs further investigation due these conflicting findings. Figure 2 summarizes this differential expression of molecular pathways in the MAT and the intestinal mucosa of CD.
Molecular pathways in the mesenteric adipose tissue and intestinal mucosa of Crohn’s disease patients (source: By Support Didactic from the School of Medical Sciences—UNICAMP).
In another study, adiponectin, an anti-inflammatory adipokine, was produced and released by adipose tissue that inhibited NF-κB activation in endothelial cells in MAT of CD patients [58]. However, Rodrigues and collaborators obtained low levels of serum and mesenteric adiponectin in MAT of CD, which suggests a defect in this anti-inflammatory pathway, which could in turn help to perpetuate a state of chronic inflammation [17]. Interestingly, all patients had the same BMI, below 25, and this alteration was independent of this parameter and of the presence of metabolic disorders. Resistin, another adipokine, was also studied and was verified to be increased in MAT of CD. Resistin may have a pro-inflammatory role in the MAT and is correlated with increased systemic C-reactive protein in CD patients [59].
Moreover, the autophagy pathways have been addressed in the last few years; for this process, it is crucial for mucosal immunity, and there is a growing number of autophagy-related genes associated with the development of CD [60, 61, 62]. Leal and collaborators demonstrated a reduction in autophagy markers in MAT of CD patients, which may maintain the inflammatory response in the affected intestine [63]. In this study, LC3-II protein, which is indispensable for the formation of autophagosome, was lower in the MAT of CD, suggesting an impairment of the autophagy process in this tissue. The altered autophagy could lead to unprocessed unnecessary protein accumulation, which activates pro-inflammatory pathways implicated in the pathogenesis of CD.
MAT may have an important role in CD inflammation, for it was possible to observe an altered balance between pro-inflammatory and anti-inflammatory factors in this tissue, decreased apoptosis, as well as defective autophagy. Available data indicate that mesenteric changes are primarily anti-inflammatory but can ultimately cause inflammation in CD. Currently, the mesenteric events in the chronology of CD are under discussion. MAT may be involved in the maintenance of inflammation in the late stages of the disease and in the mechanism that leads to relapses during the course of the disease. Moreover, the interaction between cytokines, adipokines, transcription factors, adipose stem cells, vascular endothelia, and adipocyte plasticity may imply in MAT remodeling, which certainly influences CD physiopathology.
We thank Prof. Tristan Torriani for revising the English version of our text.
The authors declare that they have no conflict of interest.
Ever since Davis [1] first used human amniotic membrane (Figure 1) (AM) for skin transplantation, people have been exploring this remarkable biomaterial. AM is located in the innermost layer of the fetal membranes [2]. It is 0.02–0.05 mm thick, lightweight, elastic, almost transparent, and avascular membrane classically composed of three layers: the epithelium, the basement membrane and the stroma layer [2]. There are two types of cells with stemness properties in AM: amniotic epithelial cells (AECs) and amniotic mesenchymal cells (AMSCs) [3], which are responsible for its unique biological properties including anti-inflammatory, anti-scarring, anti-microbial, angio-modulating, immunomodulatory, and anti-cancer effects [4, 5, 6, 7, 8, 9, 10]. Due to these properties, AM has become an ideal material for ocular reconstruction including the treatment of persistent epithelial defects and non-healing corneal ulcers, corneal perforations and descemetoceles, bullous keratopathy, as well as corneal disorders with associated limbal stem cell deficiency, pterygium, conjunctival reconstruction, corneoscleral melts and perforations, and glaucoma surgeries. However, its use span is short and many viruses (such as HIV-1/2, hepatitis B, hepatitis C, human T-cell lymphotropic virus, syphilis, and cytomegalovirus) can be in their “window period” and escape detection, further limiting the use of fresh AM. To overcome these concerns, different preservation methods have emerged, such as freezing, lyophilization, and cryopreservation. However, most methods result in the destruction of endogenous cells and cause varying degrees of extracellular matrix (ECM) damage, which can affect the functionality of AM and its clinical benefits for wound treatment [11, 12]. Cryopreservation was first introduced by Lee and Tseng and has been proven to achieve high success rate in AM transplantation, which has been distinguished from many methods for its attractive advantages of prolonging use span, optimally retaining tissue structure, and minimizing infection risk [13, 14].
Amniotic membrane (AM).
In this part, we classify the cryopreservation methods applied to amnion by commonly used cryoprotectant and analyze the influence of cryopreservation on AM combined with specific clinical trials.
The AM is normally washed using balanced saline solution containing antibiotics such as streptomycin, penicillin, neomycin, and amphotericin prior to storage. Pieces of AM resting on a carrier are placed in a vial containing cryoprotectant solution at a controlled cooling rate. Storage temperatures of −80°C are often utilized, with the maximum storage times ranging between 1 and 2 years [1, 11, 12].
The main disadvantage of cryopreservation is the requirement of a deep-freezing facility, which is expensive, cumbersome, and frequently unavailable, especially in underdeveloped countries. In addition, maintaining stable storage temperatures during transportation is also relatively difficult.
Glycerol storage was first introduced in the Netherlands in 1984 to preserve donor skin for transplantation [13]. Positive results over subsequent decades have led to its clinical acceptance, including in the preservation of AM. Glycerol has led to higher cell viability and higher bFGF secretion for up to three months of AM storage [14]. After strict preservation and sterilization processes, pieces of AM resting on a carrier are placed in a vial containing storage solution. Tseng’s laboratory introduced a methodology of glycerol (86%) in Dulbecco’s Modified Eagle Medium at a ratio of 1:1 [15, 16]. The most common cryopreservation protocol reported in the literature involves the use of 50% glycerol and storage at −80°C [17, 18, 19, 20, 21]. Undiluted and 98% glycerol have also been reported to be clinically effective [15].
In 2011, Thomasen et al. [21] showed that long-term storage of 50% glycerol cryopreserved AM for durations up to 24 months at −80°C did not significantly impair the histology of AM. Wagner et al. [14] used 85% glycerol for cryopreserved AM, and their histological examinations had no significant alterations following cryopreservation, either for straight cryopreservation or with glycerol. They also demonstrated that neither tensile strength nor Young’s modulus was significantly influenced by the storage method. In addition, they also detected a significant increase in tensile strength over storage time, independent of the storage method.
Some groups have found that storage of AM in 50% glycerol at −80°C decellularizes the AM and results in low viability [17, 18, 19, 20]. Interestingly, the results from Wagner et al. [14] research showed that epithelial cells were not significantly reduced during freezing in comparison to stromal cells, possibly indicating a higher sensitivity of stromal AM cells to freezing damage than epithelial cells (Figure 2). Through repeated measurement analysis, storage time showed a significant effect on cell viability. Prabhasawat et al. [22, 23] reported that the use of a highly concentrated glycerol solution abolishes AM cell viability. The possible toxic effect of glycerol is responsible for that.
Pathways of cellular injury during freeing.
To summarize, glycerol-cryopreserved AM retains the histological characteristics of fresh AM independent of an increase in glycerol concentration. Tensile strength and elasticity can also be better preserved, with tensile strength increasing with storage time. However, the cell viability of cryopreserved AM was significantly affected by storage time and glycerol concentration. In particular, the stromal cells were more sensitive. A previous study [24] showed that this method had little effect on the growth factors of AM. More research is needed to confirm the effect of glycerol cryopreservation on AMs.
DMSO has been used as an alternative for AM in glycerol-cryopreservation. An increasing concentration of DMSO is used instead of washing the AM with an antibiotic-saline solution after placenta collection [12]. Azuara-Blanco et al. [25] used 4%, 8%, and 10% DMSO, while Kubo et al. [26] used 0.5 M, 0.1 M, and 0.15 M DMSO for washing. AMs can be stored in 10% or 0.15 M DMSO at −80°C for several months without significant damage. In general, solutions containing DMSO are used less often for AM cryopreservation compared to glycerol, due to high toxicity [12]. However, AM storage solutions containing DMSO have been studied a lot regarding its ability to increase cell viability in AM under experimental conditions [2].
A cryopreservation method with DMSO from Duan-Arnold’s group [24] showed a retained cell viability of over 80%. Cryopreserved AM tested after three months of storage showed no changes in the tissue architecture and collagen IV, which exists in the basement membrane, compared with fresh AM. However, in 2015, Yazdanpanah et al. [8] showed that the viability of epithelial cells in fresh AMs was estimated at 97% after staining with trypan blue, decreasing to about 50% in DMSO cryopreserved tissues after six months. They evaluated the effects of cryopreservation on AM angiogenesis modulation activity compared to fresh tissue in an animal model, showing that cryopreserved AM has the same effect on angiogenesis as fresh AM. The epithelial surface of cryopreserved AM inhibited angiogenesis, and the mesenchymal surface augmented vessel sprouting and length. In 2013, Tehrani et al. [27] used 10% DMSO as a cryoprotectant to evaluate the antibacterial properties of AM after preservation in vitro. The results of this study showed that the antibacterial property of AM was maintained after cryopreservation, but was dependent on bacterial genus and strain.
To sum up, the literature we collected on DMSO-cryopreserved AM showed no significant differences in tissue integrity and biological properties (antibacterial and angiogenesis modulation) compared with fresh AM. However, although many research groups use DMSO as a cryoprotectant, the data related to cell viability vary. These conflicting results can be attributed to several factors, including differing cryopreservation procedures and storage times.
In 2000, Kruse et al. [18] believed that devitalized AM exhibited therapeutic effects, and their data showed that the preservation of viable cells in AM provided no additional benefits. This conclusion led to the development of cryopreservation methods including AM devitalization steps. One of them, known as the CRYOTEK® process, includes a freezing step before cryopreservation, resulting in devitalized tissue [28]. However, Yan et al. [29] demonstrated that the combination of exogenous cells and acellular AM resulted in faster wound closure compared with acellular AM alone. Duan-Arnold et al. [24] demonstrated that endogenous viable cells allow cryopreserved AM with higher angiogenic, anti-inflammatory, antioxidant, fibroblast, and keratinocyte chemo-attractive activities when compared with AM in devitalization. Before 2001, most studies reported that cell viability of 50% or less at cryopreserved post-thaw with cells failing to survive after 18 months of storage at −80°C [26, 30]. Since then, scientists have been attempting to improve the cryopreservation method, for improved cell viability retention. For example, the cryopreservation protocol invented by the group of Duan Arnold et al. [24] can maintain 70% or greater cell viability after 24 months of storage at −80°C. AM storage solutions containing dimethyl sulfoxide (DMSO) have been studied, mostly under experimental conditions, and shown the ability to increase AM cell viability [2]. Although the survival of amniotic cells is related to storage time, different cryopreservation steps can also affect cell viability, thus exerting different clinical effects.
The best storage temperature (−196°C or − 80°C) is also a controversial issue for cryopreservation. AMs stored at −196°C have showed morphology similar to fresh AM in both preservation media, and AM stored at −80°C showed disruption of the stromal matrix [2, 31]. However, −80°C is still widely used by international scientists.
To sum up, cryopreservation protocols are not standardized. Preparation and sterilization before cryopreservation, as well as the selection of cryoprotectant during cryopreservation, will lead to high variability in cell viability [2, 32]. Different storage temperature and storage time also affects the structure and function of amniotic membrane. It is important to establish adaptable protocols for the clinical banking of AM that include verification of graft quality and viability before its release for transplantation, whether in the trial or clinical stage.
PROKERA®Slim (PKS) (Bio-Tissue, Inc., Miami, FL, USA) is a Class II medical device approved by the Food and Drug Administration in 2003 to be used as a temporary AM patch for delivering the biological actions of AM to a corneal surface without using sutures. It contains a piece of cryopreserved AM clipped into a concave poly-carbonate dual-ring system, like a symblepharon ring, that conforms to the corneal and limbal surface like a contact lens. The ring system has an inner diameter of 15 or 16 mm.
It has become the most common commercially available cryopreserved AM product in ophthalmology and is applied to various ocular surface and orbital disorders. It is a safe and effective method that makes AM transplantation sutureless and adhesiveless, contributing to healing and reconstruction of the ocular surface and orbit with minimal side effects [33]. However, PROKERA is not recommended for eyes with functioning blebs or glaucoma drainage implants because of the oppositional positioning of the retaining ring [34].
Corneal disease is one of the world’s leading causes of blindness. Corneal scarring and haze due to various factors can affect vision, making corneal transplantation an important means of treatment for corneal diseases [35, 36, 37]. Advances in corneal preservation techniques have improved the survival rate of corneal grafts [38] and have largely contributed to the development of modern corneal transplant surgery [39]. With the flourishing of corneal preservation technology, breakthroughs have been made in preservation times and corneal activity. Nevertheless, cryopreservation is the only current method that can virtually preserve tissue structure for a long time.
Meanwhile, the development of modern eye banks have been accompanied by the advancement of corneal preservation technology. The establishment of an eye bank provides favorable conditions for corneal transplantation [40, 41].
The idea of replacing the turbid cornea with transparent tissue was first proposed by Pellier de Quengsy in 1789 [42, 43]. In 1824, Reisinger exploited animal corneas in surgery [44], which was named keratoplasty. Later in the nineteenth century, a large number of animal experiments helped doctors realize that inter-species transplantation was a necessary condition to avoid corneal opacity after transplantation [45, 46, 47]. In view of this, researchers began to experiment with human corneal transplantation. Early corneal transplantation relied on living donor tissues due to fears relating to transplanting dead tissue. The first successful full-thickness corneal transplantation (including all corneal layers) was completed in 1905 [48]. It was not until the 1930s that the cornea of the deceased donor was used and the entire eye was kept in a glass jug (wet room) for several days [49].
In 1912, Magitot reported that excised corneal grafts could be preserved in red blood cells at 5°C for eight days [50, 51, 52]. The grafts were successfully used for corneal lamellar transplantation [53]. At first, the freshness of the cornea was considered key to corneal transplantation [54, 55]. However, Ukrainian doctor Filatov systematically reported the application of corpus corneal tissue to clinical practice [56], which possessed an inter-generational meaning. It opened a new era of corneal preservation and transplantation [57, 58, 59]. These developments led to the establishment of the world’s first ophthalmology bank in New York in the 1940s. The preservation technique of the original eye bank was very simple [60, 61]: eyeballs were kept in a small glass bottle in a humid and cool environment [62]. Immediate removal of the eyeball after donor death was the only way to ensure the quality of the corneal grafts [63, 64, 65]. Eye banks were established in major cities, such as London, to guarantee that eyeballs were promptly forwarded [66, 67]. In the early 1950s, the activity of CECs was first considered as an important factor affecting transplantation [68, 69, 70]. The emphasis on preservation techniques was transferred to maintain the activity and integrity of CECs [71, 72]. Since then, corneal preservation techniques have been increasingly successful, resulting in approximately 40,000 corneal transplants per year in the United States, 20,000 per year in Europe, and thousands per year in other countries, such as India.
Corneal preservation is divided into two categories according to the survival of CECs: inactive and active preservation [73, 74, 75]. The former method includes dry preservation and cryopreservation [76, 77, 78] and operates under the principle of removing corneal moisture while inhibiting enzyme activity and autolysis in cells for long-term preservation [79, 80]. Common preservatives are glycerin, molecular sieves, and silica gel [81, 82, 83], which can preserve intact lamellar collagen structure [84]. Active preservation comprises short-term (hours to two days), medium-long term (7 to 30 days) and long-term (months to years) preservation. In terms of storage conditions, it utilizes normal (34~37°C), low (usually 4°C) and deep low (subzero) temperatures [85, 86, 87, 88].
Short-term corneal storage mainly refers to the preservation of wet rooms, the simplest and most convenient of all corneal storage technologies. For this reason, it is still the basic technology for preserving cornea in the eye banks of developing countries. As for medium-term corneal preservation, corneal preservation solution is stored at 4°C for 4 to 14 days [89].
The prolongation of corneal preservation allows more preparation for patients and flexible adjusting of operation times, while also satisfying blood test and corneal transportation times. With the improvement of preservation techniques, the composition of the corneal preservation solution has been constantly changing. A certain concentration of chondroitin sulfate is added to modify M-K solution, which can alleviate the swelling state during preservation. Optisol corneal medium preservation solution was proposed by Lindstrom and has become the most common preservation solution in US eye banks, which is mainly a mixture of K-liquid and Dexsol solution [90]. Long-term corneal preservation refers to organ culture storage and cryopreservation. Organ culture is to simulate the presence of a normal human cornea environment with medium at 30–37°C [91].
At present, there are several corneal preservation methods applied in global eye banks, but none of those is perfect. Each preservation method has its own advantages and disadvantages, which differ from the preservation temperature, the composition of the preservation solution, and the penetrant preventing matrix edema.
After donor death, the sudden stop of the aqueous humor causes nutrient and oxygen shortages, leading to final depletion at room temperature, which can, in turn, lead to autolysis of the corneal cells and initial damage to the cornea [92]. During the period from donor death to corneal removal and storage, the donor’s corpse is exposed to room temperatures, necessitating minimal time delays to ensure that the initial donor cornea is healthy and intact along with functional endothelial cells.
The acceptable short storage time, as well as organ damage, poses a logistical challenge to organ storage and ultimately affects grafts and patient survival. Prolonged storage times can cause many transplantable organs, further exacerbating the growing imbalance between organ supply and demand. Organ cryopreservation is used to preserve long-lived cells and tissues. Theoretically, the storage of biological materials, including cells, tissues, and organs for transplantation at a low temperature (i.e., in liquid nitrogen at −160°C) is uncertain [93, 94]. Such a technique would have the potential to alter the way in which organs are recovered, distributed, and utilized for transplantation. However, ice is the biggest enemy in the cryopreservation of organs and tissues. Ice crystals, especially intracellular ice, can cause significant cellular damage and destroy the complex macroscopic tissues of intact organs. In this field, current developments are used to avoid the formation of ice, or mitigate it, during cryogenic storage. Any successful organ cryopreservation strategy requires a delicate balance between the relative needs of cryopreservation and toxicity in these situations.
In 1954, Eastcott first adopted a cryopreserved human cornea for transplantation successfully [95, 96], pretreating the keratin tissue in glycerol before freezing it in a mixture of alcohol and carbon dioxide for cryopreservation of the full-thickness cornea [97]. This method generally removes the cornea under the protection of a cryogen to −80°C, and stores it in liquid nitrogen at −196°C. Therefore, the CECs are in a dormant state. The state can completely inhibit the metabolism of cells, eliminate the toxic effects caused by the accumulation of metabolites, and avoid the need to change the liquid during organ culture. In addition, it also restrains microorganisms during cryopreservation, protecting the cornea from microbial invasion.
The components currently contained in corneal cryoprotectants include DMSO, propylene glycol, ChS, and sucrose. DMSO is a relatively stable protective agent to maintain the integrity of corneal cells, while sucrose molecules act as buffers in corneal protection, and ChS improves CEC activity in cryopreservation [98]. DMSO began to be treated as a tissue preservative to preserve cultured rabbit CECs by Smith [99]. Shortly thereafter, Mueller injected a preservation solution containing DMSO into the anterior chamber of an eyeball, placing the eyeball in a preservation solution containing glycerol. The cornea was removed before surgery for full-thickness transplantation [100, 101]. In 1965, Capella [102] used DMSO as an antifreeze to improve a cryopreservation method, ensuring corneal graft activity. According to another report [103], the clinical application of cryopreservation techniques has little differences in techniques. The corneal tissue must be preserved eight hours after death. By increasing the level of DMSO, it eventually reaches a concentration of 7.5%. The classic four-step cooling is to initiate a cooling rate at 1.5~2°C/min, drop the temperature to −30°C, change to 5–7°C/min, and ultimately maintain −80°C [104, 105].
It is still essential to further explore the rate of cooling to keep CEC activity and reduce cell loss [106, 107]. Temperature-controlled thawing before transplantation is a key step in protecting the corneal endothelium. At present, the prevalent view is that rapid rewarming could decrease the contact of cells with high concentrations of electrolytes and reduce cell damage [108]. The thawing process of the cryopreserved cornea must be strictly controlled, as the solute containing DMSO has endotoxicity once the temperature exceeds 37°C [109]. Cryopreservation would impair the morphology and function of the corneal endothelium. During the thawing process, an ascending solute concentration, the formation of crystals, changes in pH, and osmotic pressure will reduce the survival rate of CECs [110]. Glycerol, polyvinylpyrrolidone, and DMSO can all be used as cryopreservatives, but DMSO is currently the most widely used [111, 112].
The ultra-low temperature preservation method overcomes the drawbacks of most other corneal preservation methods, significantly prolonging corneal preservation time, reducing pollution, and avoiding the toxic effects of its own metabolic substances. Electron microscopy can observe changes in the subcellular morphology of CECs caused by cryopreservation, some of which are considered irreversible [113]. Studies have shown that, after cryopreservation, the barrier function of endothelial cells is impaired. Compared with wet room preservation and MK solution preservation, cryopreserved corneal grafts have been completely transparent for a long time after surgery. For one-year cryopreservation, 55% of endothelial cells were deactivated, while the rate of CECs preserved by MK solution was only 21–22% [114]. There are barely significant structural differences in microbiological, histological, and ultrastructural features when comparing long-term cryopreservation of tissue (>7 years) and short-term cryopreserved cat corneal sclera (<1 year) [115]. As such, tissues cryopreserved for up to 10 years could be used for tectonic support without structural or microbial barriers.
Under suitable conditions, no crystal solidification occurs during the freezing process, called vitrification [116]. Vitrification requires a high concentration of cryoprotectant, yet theoretically, tissue could be stored in a very low temperature environment without forming intracellular or extracellular crystals, and corneal endothelium damage could be avoided significantly [117]. Glycerol, 1,2-propanetriol, and 2,3-butanediol are all considered as eligible cryopreservation agents for corneal vitrification [118, 119].
Studies have found that an effective concentration of a single cryopreservative is toxic to CECs, yet the mixture of preservatives or the addition of preservatives at low temperatures seems to reduce toxicity [120]. As a means of corneal preservation, further study is warranted to investigate whether vitrification would achieve good results. In 1981, Sperling used corneal grafts in a corneal preservation solution at the early stage and carried out a cryopreservation operation later. After rewarming, the cornea was transferred to a preservation solution, identifying corneal activity. The following studies indicated that the corneal grafts maintained transparency 71% of the time after 1 year and 58% of the time after 12 years [121].
In our previous study, we performed lamellar keratoplasty combined with keratopigmentation in 22 corneal leukoma eyes using glycerol-cryopreserved corneal tissues, and no graft-rejection occurred during the 3 years of follow-up. Moreover, the outcome of a low graft rejection rate in glycerol-cryopreserved corneal tissues was also confirmed by our preceding study in treating Terrien marginal degeneration. In the subsequent study, for patients with refractive herpes simplex keratitis, 3 eyes of 27 eyes (11.1%) suffered allograft stromal rejection, all eyes reversed after prompt medication. Meanwhile, only 2 eyes (7.41%) exhibited refractive herpes simplex keratitis recurrence and the main site was located at the margin of the graft and the recipient bed. This result is consistent with the theory that grafts survive better when compared with reports clarifying that up to 33% of patients have suffered recurrence using fresh grafts. The recurrence rate in fresh grafts may be partially related to the long-term usage of topical steroid eye drops; however, it may be much more closely correlated with fewer keratocytes in the cryopreserved donor tissue to reactivate immune-inflammatory responses [122, 123, 124]. Based on the above information, glycerol-cryopreserved corneal tissues can be effectively and biosafely used with a low rejection and recurrence rate in corneal transplantation, especially in developing countries where good donor corneas are difficult to get.
The cryopreservation method can preserve the activity of the AM and cornea for extended periods up to several years, solving the problem of preservation time and activity deterioration. However, equipment complications, expensive technical support, and transport difficulties have become impediments to widespread use. The functional status of AM, endothelial cells, and corneal transparency have been of vital importance in the development of cryopreservation. As researchers become more aware of the function and properties of CECs, attempts to find a more conducive method and media for the preservation of AMs and corneas will continue.
We declare that we have no conflicts of interest.
The National Nature Science Foundation of China (81470028).
The Municipal Human Resources Development Program for Outstanding Leaders in Medical Disciplines in Shanghai (2017BR060).
Shanghai Shenkang Hospital Development Project: A Three- Year Action Plan (16CR3027A).
IntechOpen implements a robust policy to minimize and deal with instances of fraud or misconduct. As part of our general commitment to transparency and openness, and in order to maintain high scientific standards, we have a well-defined editorial policy regarding Retractions and Corrections.
",metaTitle:"Retraction and Correction Policy",metaDescription:"Retraction and Correction Policy",metaKeywords:null,canonicalURL:"/page/retraction-and-correction-policy",contentRaw:'[{"type":"htmlEditorComponent","content":"IntechOpen’s Retraction and Correction Policy has been developed in accordance with the Committee on Publication Ethics (COPE) publication guidelines relating to scientific misconduct and research ethics:
\\n\\n1. RETRACTIONS
\\n\\nA Retraction of a Chapter will be issued by the Academic Editor, either following an Author’s request to do so or when there is a 3rd party report of scientific misconduct. Upon receipt of a report by a 3rd party, the Academic Editor will investigate any allegations of scientific misconduct, working in cooperation with the Author(s) and their institution(s).
\\n\\nA formal Retraction will be issued when there is clear and conclusive evidence of any of the following:
\\n\\nPublishing of a Retraction Notice will adhere to the following guidelines:
\\n\\n1.2. REMOVALS AND CANCELLATIONS
\\n\\n2. STATEMENTS OF CONCERN
\\n\\nA Statement of Concern detailing alleged misconduct will be issued by the Academic Editor or publisher following a 3rd party report of scientific misconduct when:
\\n\\nIntechOpen believes that the number of occasions on which a Statement of Concern is issued will be very few in number. In all cases when such a decision has been taken by the Academic Editor the decision will be reviewed by another editor to whom the author can make representations.
\\n\\n3. CORRECTIONS
\\n\\nA Correction will be issued by the Academic Editor when:
\\n\\n3.1. ERRATUM
\\n\\nAn Erratum will be issued by the Academic Editor when it is determined that a mistake in a Chapter originates from the production process handled by the publisher.
\\n\\nA published Erratum will adhere to the Retraction Notice publishing guidelines outlined above.
\\n\\n3.2. CORRIGENDUM
\\n\\nA Corrigendum will be issued by the Academic Editor when it is determined that a mistake in a Chapter is a result of an Author’s miscalculation or oversight. A published Corrigendum will adhere to the Retraction Notice publishing guidelines outlined above.
\\n\\n4. FINAL REMARKS
\\n\\nIntechOpen wishes to emphasize that the final decision on whether a Retraction, Statement of Concern, or a Correction will be issued rests with the Academic Editor. The publisher is obliged to act upon any reports of scientific misconduct in its publications and to make a reasonable effort to facilitate any subsequent investigation of such claims.
\\n\\nIn the case of Retraction or removal of the Work, the publisher will be under no obligation to refund the APC.
\\n\\nThe general principles set out above apply to Retractions and Corrections issued in all IntechOpen publications.
\\n\\nAny suggestions or comments on this Policy are welcome and may be sent to permissions@intechopen.com.
\\n\\nPolicy last updated: 2017-09-11
\\n"}]'},components:[{type:"htmlEditorComponent",content:'IntechOpen’s Retraction and Correction Policy has been developed in accordance with the Committee on Publication Ethics (COPE) publication guidelines relating to scientific misconduct and research ethics:
\n\n1. RETRACTIONS
\n\nA Retraction of a Chapter will be issued by the Academic Editor, either following an Author’s request to do so or when there is a 3rd party report of scientific misconduct. Upon receipt of a report by a 3rd party, the Academic Editor will investigate any allegations of scientific misconduct, working in cooperation with the Author(s) and their institution(s).
\n\nA formal Retraction will be issued when there is clear and conclusive evidence of any of the following:
\n\nPublishing of a Retraction Notice will adhere to the following guidelines:
\n\n1.2. REMOVALS AND CANCELLATIONS
\n\n2. STATEMENTS OF CONCERN
\n\nA Statement of Concern detailing alleged misconduct will be issued by the Academic Editor or publisher following a 3rd party report of scientific misconduct when:
\n\nIntechOpen believes that the number of occasions on which a Statement of Concern is issued will be very few in number. In all cases when such a decision has been taken by the Academic Editor the decision will be reviewed by another editor to whom the author can make representations.
\n\n3. CORRECTIONS
\n\nA Correction will be issued by the Academic Editor when:
\n\n3.1. ERRATUM
\n\nAn Erratum will be issued by the Academic Editor when it is determined that a mistake in a Chapter originates from the production process handled by the publisher.
\n\nA published Erratum will adhere to the Retraction Notice publishing guidelines outlined above.
\n\n3.2. CORRIGENDUM
\n\nA Corrigendum will be issued by the Academic Editor when it is determined that a mistake in a Chapter is a result of an Author’s miscalculation or oversight. A published Corrigendum will adhere to the Retraction Notice publishing guidelines outlined above.
\n\n4. FINAL REMARKS
\n\nIntechOpen wishes to emphasize that the final decision on whether a Retraction, Statement of Concern, or a Correction will be issued rests with the Academic Editor. The publisher is obliged to act upon any reports of scientific misconduct in its publications and to make a reasonable effort to facilitate any subsequent investigation of such claims.
\n\nIn the case of Retraction or removal of the Work, the publisher will be under no obligation to refund the APC.
\n\nThe general principles set out above apply to Retractions and Corrections issued in all IntechOpen publications.
\n\nAny suggestions or comments on this Policy are welcome and may be sent to permissions@intechopen.com.
\n\nPolicy last updated: 2017-09-11
\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:"193",title:"Pathology",slug:"medicine-pathology",parent:{title:"Medicine",slug:"medicine"},numberOfBooks:12,numberOfAuthorsAndEditors:366,numberOfWosCitations:78,numberOfCrossrefCitations:80,numberOfDimensionsCitations:177,videoUrl:null,fallbackUrl:null,description:null},booksByTopicFilter:{topicSlug:"medicine-pathology",sort:"-publishedDate",limit:12,offset:0},booksByTopicCollection:[{type:"book",id:"9135",title:"Rare Diseases",subtitle:null,isOpenForSubmission:!1,hash:"607a44edc1c494df4d5d126af71ca89c",slug:"rare-diseases",bookSignature:"Zhan He Wu",coverURL:"https://cdn.intechopen.com/books/images_new/9135.jpg",editedByType:"Edited by",editors:[{id:"226446",title:"Dr.",name:"Zhan He",middleName:null,surname:"Wu",slug:"zhan-he-wu",fullName:"Zhan He Wu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6790",title:"Fluid and Electrolyte Disorders",subtitle:null,isOpenForSubmission:!1,hash:"5f74d43da90463b17a26bbf2fb7a09ed",slug:"fluid-and-electrolyte-disorders",bookSignature:"Usman Mahmood",coverURL:"https://cdn.intechopen.com/books/images_new/6790.jpg",editedByType:"Edited by",editors:[{id:"183337",title:"Dr.",name:"Usman",middleName:null,surname:"Mahmood",slug:"usman-mahmood",fullName:"Usman Mahmood"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7009",title:"Hypoxia and Anoxia",subtitle:null,isOpenForSubmission:!1,hash:"80148bd84e86e5fe1c7527637e8e3be8",slug:"hypoxia-and-anoxia",bookSignature:"Kusal K. Das and Mallanagouda Shivanagouda Biradar",coverURL:"https://cdn.intechopen.com/books/images_new/7009.jpg",editedByType:"Edited by",editors:[{id:"187859",title:"Prof.",name:"Kusal",middleName:"K.",surname:"Das",slug:"kusal-das",fullName:"Kusal Das"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6297",title:"Histopathology",subtitle:"An Update",isOpenForSubmission:!1,hash:"395c889b2d2cc4f452fe7e1ad8226fe4",slug:"histopathology-an-update",bookSignature:"Supriya Srivastava",coverURL:"https://cdn.intechopen.com/books/images_new/6297.jpg",editedByType:"Edited by",editors:[{id:"85273",title:"Dr.",name:"Supriya",middleName:null,surname:"Srivastava",slug:"supriya-srivastava",fullName:"Supriya Srivastava"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5906",title:"Pathophysiology",subtitle:"Altered Physiological States",isOpenForSubmission:!1,hash:"b277409ee570d9c47798ff5b42638603",slug:"pathophysiology-altered-physiological-states",bookSignature:"David C. Gaze",coverURL:"https://cdn.intechopen.com/books/images_new/5906.jpg",editedByType:"Edited by",editors:[{id:"71983",title:"Dr.",name:"David C.",middleName:null,surname:"Gaze",slug:"david-c.-gaze",fullName:"David C. Gaze"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6025",title:"Temporomandibular Joint Pathology",subtitle:"Current Approaches and Understanding",isOpenForSubmission:!1,hash:"6663d492aea23855b9fdcf753089981e",slug:"temporomandibular-joint-pathology-current-approaches-and-understanding",bookSignature:"Yusuf Emes, Buket Aybar and Gühan Dergin",coverURL:"https://cdn.intechopen.com/books/images_new/6025.jpg",editedByType:"Edited by",editors:[{id:"178414",title:"Prof.",name:"Yusuf",middleName:null,surname:"Emes",slug:"yusuf-emes",fullName:"Yusuf Emes"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5955",title:"Chronic Kidney Disease",subtitle:"from Pathophysiology to Clinical Improvements",isOpenForSubmission:!1,hash:"b371e3b8f0d78aa871934011fa0860c7",slug:"chronic-kidney-disease-from-pathophysiology-to-clinical-improvements",bookSignature:"Thomas Rath",coverURL:"https://cdn.intechopen.com/books/images_new/5955.jpg",editedByType:"Edited by",editors:[{id:"67436",title:"Dr.",name:"Thomas",middleName:null,surname:"Rath",slug:"thomas-rath",fullName:"Thomas Rath"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"2619",title:"Histopathology",subtitle:"Reviews and Recent Advances",isOpenForSubmission:!1,hash:"fe380d20a204de277654d4d89459cfc4",slug:"histopathology-reviews-and-recent-advances",bookSignature:"Enrique Poblet Martinez",coverURL:"https://cdn.intechopen.com/books/images_new/2619.jpg",editedByType:"Edited by",editors:[{id:"157748",title:"Dr.",name:"Enrique",middleName:null,surname:"Poblet",slug:"enrique-poblet",fullName:"Enrique Poblet"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"788",title:"Topics in Renal Biopsy and Pathology",subtitle:null,isOpenForSubmission:!1,hash:"ff37da307f4471516e16d5801fbb9164",slug:"topics-in-renal-biopsy-and-pathology",bookSignature:"Muhammed Mubarak and Javed I. Kazi",coverURL:"https://cdn.intechopen.com/books/images_new/788.jpg",editedByType:"Edited by",editors:[{id:"119854",title:"Dr.",name:"Muhammed",middleName:null,surname:"Mubarak",slug:"muhammed-mubarak",fullName:"Muhammed Mubarak"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"733",title:"Muscle Biopsy",subtitle:null,isOpenForSubmission:!1,hash:"6d793e898675e9191a913e63cfebab37",slug:"muscle-biopsy",bookSignature:"Challa Sundaram",coverURL:"https://cdn.intechopen.com/books/images_new/733.jpg",editedByType:"Edited by",editors:[{id:"75812",title:"Dr.",name:"Challa",middleName:null,surname:"Sundaram",slug:"challa-sundaram",fullName:"Challa Sundaram"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"985",title:"Prostate Biopsy",subtitle:null,isOpenForSubmission:!1,hash:"2d821ee10598f9f1022eda0fe588f035",slug:"prostate-biopsy",bookSignature:"Nabil Kaddis Bissada",coverURL:"https://cdn.intechopen.com/books/images_new/985.jpg",editedByType:"Edited by",editors:[{id:"92564",title:"Dr.",name:"Nabil K.",middleName:null,surname:"Bissada",slug:"nabil-k.-bissada",fullName:"Nabil K. Bissada"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"287",title:"Liver Biopsy",subtitle:null,isOpenForSubmission:!1,hash:"9856c3e2c382494e27f34c5264f50fd4",slug:"liver-biopsy",bookSignature:"Hirokazu Takahashi",coverURL:"https://cdn.intechopen.com/books/images_new/287.jpg",editedByType:"Edited by",editors:[{id:"40534",title:"Dr",name:"Hirokazu",middleName:null,surname:"Takahashi",slug:"hirokazu-takahashi",fullName:"Hirokazu Takahashi"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],booksByTopicTotal:12,mostCitedChapters:[{id:"18773",doi:"10.5772/20110",title:"Ishak versus METAVIR: Terminology, Convertibility and Correlation with Laboratory Changes in Chronic Hepatitis C",slug:"ishak-versus-metavir-terminology-convertibility-and-correlation-with-laboratory-changes-in-chronic-h",totalDownloads:33114,totalCrossrefCites:9,totalDimensionsCites:18,book:{slug:"liver-biopsy",title:"Liver Biopsy",fullTitle:"Liver Biopsy"},signatures:"Gamal Shiha and Khaled Zalata",authors:[{id:"37453",title:"Prof.",name:"Gamal",middleName:null,surname:"Shiha",slug:"gamal-shiha",fullName:"Gamal Shiha"}]},{id:"18781",doi:"10.5772/19224",title:"Transient Elastography for Assessment of Non-Alcoholic Fatty Liver Disease",slug:"transient-elastography-for-assessment-of-non-alcoholic-fatty-liver-disease",totalDownloads:2559,totalCrossrefCites:0,totalDimensionsCites:9,book:{slug:"liver-biopsy",title:"Liver Biopsy",fullTitle:"Liver Biopsy"},signatures:"Ludovico Abenavoli",authors:[{id:"34117",title:"Prof.",name:"Ludovico",middleName:null,surname:"Abenavoli",slug:"ludovico-abenavoli",fullName:"Ludovico Abenavoli"}]},{id:"25595",doi:"10.5772/33534",title:"Generation and Use of Cultured Human Primary Myotubes",slug:"generation-and-use-of-cultured-human-primary-myotubes",totalDownloads:2954,totalCrossrefCites:5,totalDimensionsCites:9,book:{slug:"muscle-biopsy",title:"Muscle Biopsy",fullTitle:"Muscle Biopsy"},signatures:"Lauren Cornall, Deanne Hryciw, Michael Mathai and Andrew McAinch",authors:[{id:"96027",title:"Dr.",name:"Andrew",middleName:null,surname:"McAinch",slug:"andrew-mcainch",fullName:"Andrew McAinch"}]}],mostDownloadedChaptersLast30Days:[{id:"59286",title:"Surgical Approaches to the Temporomandibular Joint",slug:"surgical-approaches-to-the-temporomandibular-joint",totalDownloads:5359,totalCrossrefCites:1,totalDimensionsCites:1,book:{slug:"temporomandibular-joint-pathology-current-approaches-and-understanding",title:"Temporomandibular Joint Pathology",fullTitle:"Temporomandibular Joint Pathology - Current Approaches and Understanding"},signatures:"Mohammad Esmaeelinejad and Maryam Sohrabi",authors:[{id:"172188",title:"Dr.",name:"Mohammad",middleName:null,surname:"Esmaeelinejad",slug:"mohammad-esmaeelinejad",fullName:"Mohammad Esmaeelinejad"},{id:"240723",title:"Dr.",name:"Maryam",middleName:null,surname:"Sohrabi",slug:"maryam-sohrabi",fullName:"Maryam Sohrabi"}]},{id:"41363",title:"Molecular Histopathology",slug:"molecular-histopathology",totalDownloads:6047,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"histopathology-reviews-and-recent-advances",title:"Histopathology",fullTitle:"Histopathology - Reviews and Recent Advances"},signatures:"Hussein A. Kaoud",authors:[{id:"265070",title:"Dr.",name:"Hussein Abdelhay",middleName:null,surname:"Essayed Kaoud",slug:"hussein-abdelhay-essayed-kaoud",fullName:"Hussein Abdelhay Essayed Kaoud"}]},{id:"58358",title:"Internal Derangements of the Temporomandibular Joint: Diagnosis and Management",slug:"internal-derangements-of-the-temporomandibular-joint-diagnosis-and-management",totalDownloads:2059,totalCrossrefCites:1,totalDimensionsCites:3,book:{slug:"temporomandibular-joint-pathology-current-approaches-and-understanding",title:"Temporomandibular Joint Pathology",fullTitle:"Temporomandibular Joint Pathology - Current Approaches and Understanding"},signatures:"Ufuk Tatli and Vladimir Machon",authors:[{id:"203864",title:"Associate Prof.",name:"Ufuk",middleName:null,surname:"Tatli",slug:"ufuk-tatli",fullName:"Ufuk Tatli"},{id:"204401",title:"Dr.",name:"Vladimir",middleName:null,surname:"Machon",slug:"vladimir-machon",fullName:"Vladimir Machon"}]},{id:"58425",title:"Inflammation and Chronic Kidney Disease: Current Approaches and Recent Advances",slug:"inflammation-and-chronic-kidney-disease-current-approaches-and-recent-advances",totalDownloads:1503,totalCrossrefCites:0,totalDimensionsCites:2,book:{slug:"chronic-kidney-disease-from-pathophysiology-to-clinical-improvements",title:"Chronic Kidney Disease",fullTitle:"Chronic Kidney Disease - from Pathophysiology to Clinical Improvements"},signatures:"Simona Mihai, Elena Codrici, Ionela Daniela Popescu, Ana-Maria\nEnciu, Laura Georgiana Necula, Gabriela Anton and Cristiana\nTanase",authors:[{id:"76152",title:"Dr.",name:"Cristiana",middleName:null,surname:"Pistol-Tanase",slug:"cristiana-pistol-tanase",fullName:"Cristiana Pistol-Tanase"},{id:"80114",title:"Dr.",name:"Gabriela",middleName:null,surname:"Anton",slug:"gabriela-anton",fullName:"Gabriela Anton"},{id:"215418",title:"Dr.",name:"Ana-Maria",middleName:null,surname:"Enciu",slug:"ana-maria-enciu",fullName:"Ana-Maria Enciu"},{id:"216223",title:"Dr.",name:"Elena",middleName:null,surname:"Codrici",slug:"elena-codrici",fullName:"Elena Codrici"},{id:"216226",title:"Dr.",name:"Ionela Daniela",middleName:null,surname:"Popescu",slug:"ionela-daniela-popescu",fullName:"Ionela Daniela Popescu"},{id:"216227",title:"Dr.",name:"Simona",middleName:null,surname:"Mihai",slug:"simona-mihai",fullName:"Simona Mihai"},{id:"223988",title:"Dr.",name:"Laura Georgiana",middleName:null,surname:"Necula",slug:"laura-georgiana-necula",fullName:"Laura Georgiana Necula"}]},{id:"41355",title:"Ossifying Fibromas of the Craniofacial Skeleton",slug:"ossifying-fibromas-of-the-craniofacial-skeleton",totalDownloads:3180,totalCrossrefCites:5,totalDimensionsCites:6,book:{slug:"histopathology-reviews-and-recent-advances",title:"Histopathology",fullTitle:"Histopathology - Reviews and Recent Advances"},signatures:"Bruno Carvalho, Manuel Pontes, Helena Garcia, Paulo Linhares and Rui Vaz",authors:[{id:"140061",title:"Dr.",name:"Bruno",middleName:null,surname:"Carvalho",slug:"bruno-carvalho",fullName:"Bruno Carvalho"},{id:"142266",title:"Dr.",name:"Manuel",middleName:null,surname:"Pontes",slug:"manuel-pontes",fullName:"Manuel Pontes"},{id:"142267",title:"Dr.",name:"Paulo",middleName:null,surname:"Linhares",slug:"paulo-linhares",fullName:"Paulo Linhares"},{id:"142268",title:"Prof.",name:"Rui",middleName:null,surname:"Vaz",slug:"rui-vaz",fullName:"Rui Vaz"},{id:"142958",title:"Dr.",name:"Helena",middleName:null,surname:"Garcia",slug:"helena-garcia",fullName:"Helena Garcia"}]},{id:"62184",title:"Hyponatremia and Psychotropic Drugs",slug:"hyponatremia-and-psychotropic-drugs",totalDownloads:1011,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"fluid-and-electrolyte-disorders",title:"Fluid and Electrolyte Disorders",fullTitle:"Fluid and Electrolyte Disorders"},signatures:"Mireia Martínez Cortés and Pedro Gurillo Muñoz",authors:null},{id:"18778",title:"The Current Status of Non-Invasive Assessment of Liver Fibrosis: Real Time Tissue Elastography",slug:"the-current-status-of-non-invasive-assessment-of-liver-fibrosis-real-time-tissue-elastography",totalDownloads:3115,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"liver-biopsy",title:"Liver Biopsy",fullTitle:"Liver Biopsy"},signatures:"Hiroyasu Morikawa and Norifumi Kawada",authors:[{id:"34696",title:"Prof.",name:"Norifumi",middleName:null,surname:"Kawada",slug:"norifumi-kawada",fullName:"Norifumi Kawada"},{id:"53289",title:"Dr.",name:"Hiroyasu",middleName:null,surname:"Morikawa",slug:"hiroyasu-morikawa",fullName:"Hiroyasu Morikawa"}]},{id:"62764",title:"Thyroid Nodules in Diagnostic Pathology: From Classic Concepts to Innovations",slug:"thyroid-nodules-in-diagnostic-pathology-from-classic-concepts-to-innovations",totalDownloads:841,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"histopathology-an-update",title:"Histopathology",fullTitle:"Histopathology - An Update"},signatures:"Ilze Fridrihsone, Ilze Strumfa, Boriss Strumfs, Andrejs Vanags, Dainis\nBalodis, Arvids Jakovlevs, Arnis Abolins and Janis Gardovskis",authors:[{id:"54021",title:"Prof.",name:"Ilze",middleName:null,surname:"Strumfa",slug:"ilze-strumfa",fullName:"Ilze Strumfa"},{id:"159998",title:"Dr.",name:"Arnis",middleName:null,surname:"Abolins",slug:"arnis-abolins",fullName:"Arnis Abolins"},{id:"160000",title:"Prof.",name:"Janis",middleName:null,surname:"Gardovskis",slug:"janis-gardovskis",fullName:"Janis Gardovskis"},{id:"174929",title:"Dr.",name:"Andrejs",middleName:null,surname:"Vanags",slug:"andrejs-vanags",fullName:"Andrejs Vanags"},{id:"202252",title:"Dr.",name:"Arvids",middleName:null,surname:"Jakovlevs",slug:"arvids-jakovlevs",fullName:"Arvids Jakovlevs"},{id:"202253",title:"Dr.",name:"Dainis",middleName:null,surname:"Balodis",slug:"dainis-balodis",fullName:"Dainis Balodis"},{id:"203012",title:"Dr.",name:"Ilze",middleName:null,surname:"Fridrihsone",slug:"ilze-fridrihsone",fullName:"Ilze Fridrihsone"},{id:"205692",title:"MSc.",name:"Boriss",middleName:null,surname:"Strumfs",slug:"boriss-strumfs",fullName:"Boriss Strumfs"}]},{id:"55576",title:"The Roles of Indoxyl Sulphate and p-Cresyl Sulphate in Patients with Chronic Kidney Disease: A Review of Therapeutic Options",slug:"the-roles-of-indoxyl-sulphate-and-p-cresyl-sulphate-in-patients-with-chronic-kidney-disease-a-review",totalDownloads:782,totalCrossrefCites:1,totalDimensionsCites:3,book:{slug:"chronic-kidney-disease-from-pathophysiology-to-clinical-improvements",title:"Chronic Kidney Disease",fullTitle:"Chronic Kidney Disease - from Pathophysiology to Clinical Improvements"},signatures:"Melissa Nataatmadja, Yeoungjee Cho, Katrina Campbell and David\nW. Johnson",authors:[{id:"50425",title:"Prof.",name:"David",middleName:null,surname:"Johnson",slug:"david-johnson",fullName:"David Johnson"},{id:"183338",title:"Dr.",name:"Yeoungjee",middleName:null,surname:"Cho",slug:"yeoungjee-cho",fullName:"Yeoungjee Cho"},{id:"205845",title:"Dr.",name:"Melissa",middleName:null,surname:"Nataatmadja",slug:"melissa-nataatmadja",fullName:"Melissa Nataatmadja"},{id:"205846",title:"Dr.",name:"Katrina",middleName:null,surname:"Campbell",slug:"katrina-campbell",fullName:"Katrina Campbell"}]},{id:"41354",title:"Neuronal and Mixed Neuronal-Glial Tumors of the Central Nervous System",slug:"neuronal-and-mixed-neuronal-glial-tumors-of-the-central-nervous-system",totalDownloads:3810,totalCrossrefCites:1,totalDimensionsCites:1,book:{slug:"histopathology-reviews-and-recent-advances",title:"Histopathology",fullTitle:"Histopathology - Reviews and Recent Advances"},signatures:"Mohammed M.A. Al Barbarawi, Mohammed Z. Allouh and Suhair M.A. Qudsieh",authors:[{id:"139562",title:"Dr.",name:"Mohammed",middleName:null,surname:"Barbarawi",slug:"mohammed-barbarawi",fullName:"Mohammed Barbarawi"},{id:"141645",title:"Dr.",name:"Suhair",middleName:null,surname:"Qudsieh",slug:"suhair-qudsieh",fullName:"Suhair Qudsieh"},{id:"154721",title:"Dr.",name:"Mohammed",middleName:null,surname:"Allouh",slug:"mohammed-allouh",fullName:"Mohammed Allouh"}]}],onlineFirstChaptersFilter:{topicSlug:"medicine-pathology",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/95898/elizabeth-troncoso",hash:"",query:{},params:{id:"95898",slug:"elizabeth-troncoso"},fullPath:"/profiles/95898/elizabeth-troncoso",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)}()