Physical properties and lipid compositions of lipoprotein classes
\\n\\n
Dr. Pletser’s experience includes 30 years of working with the European Space Agency as a Senior Physicist/Engineer and coordinating their parabolic flight campaigns, and he is the Guinness World Record holder for the most number of aircraft flown (12) in parabolas, personally logging more than 7,300 parabolas.
\\n\\nSeeing the 5,000th book published makes us at the same time proud, happy, humble, and grateful. This is a great opportunity to stop and celebrate what we have done so far, but is also an opportunity to engage even more, grow, and succeed. It wouldn't be possible to get here without the synergy of team members’ hard work and authors and editors who devote time and their expertise into Open Access book publishing with us.
\\n\\nOver these years, we have gone from pioneering the scientific Open Access book publishing field to being the world’s largest Open Access book publisher. Nonetheless, our vision has remained the same: to meet the challenges of making relevant knowledge available to the worldwide community under the Open Access model.
\\n\\nWe are excited about the present, and we look forward to sharing many more successes in the future.
\\n\\nThank you all for being part of the journey. 5,000 times thank you!
\\n\\nNow with 5,000 titles available Open Access, which one will you read next?
\\n\\nRead, share and download for free: https://www.intechopen.com/books
\\n\\n\\n\\n
\\n"}]',published:!0,mainMedia:null},components:[{type:"htmlEditorComponent",content:'
Preparation of Space Experiments edited by international leading expert Dr. Vladimir Pletser, Director of Space Training Operations at Blue Abyss is the 5,000th Open Access book published by IntechOpen and our milestone publication!
\n\n"This book presents some of the current trends in space microgravity research. The eleven chapters introduce various facets of space research in physical sciences, human physiology and technology developed using the microgravity environment not only to improve our fundamental understanding in these domains but also to adapt this new knowledge for application on earth." says the editor. Listen what else Dr. Pletser has to say...
\n\n\n\nDr. Pletser’s experience includes 30 years of working with the European Space Agency as a Senior Physicist/Engineer and coordinating their parabolic flight campaigns, and he is the Guinness World Record holder for the most number of aircraft flown (12) in parabolas, personally logging more than 7,300 parabolas.
\n\nSeeing the 5,000th book published makes us at the same time proud, happy, humble, and grateful. This is a great opportunity to stop and celebrate what we have done so far, but is also an opportunity to engage even more, grow, and succeed. It wouldn't be possible to get here without the synergy of team members’ hard work and authors and editors who devote time and their expertise into Open Access book publishing with us.
\n\nOver these years, we have gone from pioneering the scientific Open Access book publishing field to being the world’s largest Open Access book publisher. Nonetheless, our vision has remained the same: to meet the challenges of making relevant knowledge available to the worldwide community under the Open Access model.
\n\nWe are excited about the present, and we look forward to sharing many more successes in the future.
\n\nThank you all for being part of the journey. 5,000 times thank you!
\n\nNow with 5,000 titles available Open Access, which one will you read next?
\n\nRead, share and download for free: https://www.intechopen.com/books
\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:"5500",leadTitle:null,fullTitle:"Genetic Diversity",title:"Genetic Diversity",subtitle:null,reviewType:"peer-reviewed",abstract:"Genetic diversity is the entire amount of genes and genotypes in a group of organisms and is of vital importance for their adaptation to different living conditions. If, for example, all humans were identical, the extinction of the entire kind could happen very fast. Let us care and nourish differences! The goal of this book is to present some of the contemporary thoughts on understandings of the genetic diversity patterns and their altering in a changing world. The book is aimed to the ones inspired to study and contemplate genetic diversity and to the audience beyond any frames.",isbn:"978-953-51-2950-9",printIsbn:"978-953-51-2949-3",pdfIsbn:"978-953-51-5470-9",doi:"10.5772/63174",price:119,priceEur:129,priceUsd:155,slug:"genetic-diversity",numberOfPages:150,isOpenForSubmission:!1,isInWos:1,hash:"ce1bd13553d444bb950f6c4462f98584",bookSignature:"Lidija Bitz",publishedDate:"March 1st 2017",coverURL:"https://cdn.intechopen.com/books/images_new/5500.jpg",numberOfDownloads:6944,numberOfWosCitations:5,numberOfCrossrefCitations:10,numberOfDimensionsCitations:20,hasAltmetrics:0,numberOfTotalCitations:35,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"May 2nd 2016",dateEndSecondStepPublish:"May 23rd 2016",dateEndThirdStepPublish:"August 27th 2016",dateEndFourthStepPublish:"November 25th 2016",dateEndFifthStepPublish:"December 25th 2016",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,editors:[{id:"153375",title:"Dr.",name:"Lidija",middleName:null,surname:"Bitz",slug:"lidija-bitz",fullName:"Lidija Bitz",profilePictureURL:"https://mts.intechopen.com/storage/users/153375/images/3846_n.jpg",biography:"Lidija Bitz is a principle research scientist of plant genomics at the Natural Resources Institute Finland (Luke). She has a decade of working experience and research exchange from Bosnia and Herzegovina, Denmark, Germany, Netherlands, Sweden and Switzerland. Lidija obtained a MSc degree and defended a PhD thesis at the University of Ljubljana, Slovenia. During those times she was very active in inventory, collection and genetic diversity evaluations within different germplasm. She is active in the dissemination of achieved results through the authorship and editing of monographs, scientific papers, book chapters and professional articles. She has also been successful in implementing international and regional scientific and developmental projects, starting from her student days.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Natural Resources Institute Finland",institutionURL:null,country:{name:"Finland"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"419",title:"Microbial Genetics",slug:"biochemistry-genetics-and-molecular-biology-microbiology-microbial-genetics"}],chapters:[{id:"53510",title:"Diversity of Plant Virus Populations: A Valuable Tool for Epidemiological Studies",doi:"10.5772/66820",slug:"diversity-of-plant-virus-populations-a-valuable-tool-for-epidemiological-studies",totalDownloads:1433,totalCrossrefCites:1,totalDimensionsCites:2,signatures:"Fernando Escriu",downloadPdfUrl:"/chapter/pdf-download/53510",previewPdfUrl:"/chapter/pdf-preview/53510",authors:[{id:"191603",title:"Dr.",name:"Fernando",surname:"Escriu",slug:"fernando-escriu",fullName:"Fernando Escriu"}],corrections:null},{id:"53974",title:"Local Scale Genetic Diversity and its Role in Coping with Changing Climate",doi:"10.5772/67166",slug:"local-scale-genetic-diversity-and-its-role-in-coping-with-changing-climate",totalDownloads:1095,totalCrossrefCites:6,totalDimensionsCites:7,signatures:"Andrés J. Cortés",downloadPdfUrl:"/chapter/pdf-download/53974",previewPdfUrl:"/chapter/pdf-preview/53974",authors:[{id:"190729",title:"Dr.",name:"Andrés",surname:"Cortés",slug:"andres-cortes",fullName:"Andrés Cortés"}],corrections:null},{id:"53953",title:"Genetic Diversity within Chemokine Receptor 5 (CCR5) for Better Understanding of AIDS",doi:"10.5772/67256",slug:"genetic-diversity-within-chemokine-receptor-5-ccr5-for-better-understanding-of-aids",totalDownloads:953,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Ali A. Al-Jabri and Sidgi S. Hasson",downloadPdfUrl:"/chapter/pdf-download/53953",previewPdfUrl:"/chapter/pdf-preview/53953",authors:[{id:"34571",title:"Prof.",name:"Ali",surname:"Al-Jabri",slug:"ali-al-jabri",fullName:"Ali Al-Jabri"}],corrections:null},{id:"53724",title:"From the Gene Sequence to the Phylogeography through the Population Structure: The Cases of Yersinia ruckeri and Vibrio tapetis",doi:"10.5772/67182",slug:"from-the-gene-sequence-to-the-phylogeography-through-the-population-structure-the-cases-of-yersinia-",totalDownloads:663,totalCrossrefCites:0,totalDimensionsCites:1,signatures:"Asmine Bastardo, Sabela Balboa and Jesús L. Romalde",downloadPdfUrl:"/chapter/pdf-download/53724",previewPdfUrl:"/chapter/pdf-preview/53724",authors:[{id:"192422",title:"Dr.",name:"Jesus",surname:"Romalde",slug:"jesus-romalde",fullName:"Jesus Romalde"},{id:"194373",title:"Dr.",name:"Asmine",surname:"Bastardo",slug:"asmine-bastardo",fullName:"Asmine Bastardo"},{id:"194374",title:"Dr.",name:"Sabela",surname:"Balboa",slug:"sabela-balboa",fullName:"Sabela Balboa"}],corrections:null},{id:"53527",title:"Biodiversity Studies in Key Species from the African Mopane and Miombo Woodlands",doi:"10.5772/66845",slug:"biodiversity-studies-in-key-species-from-the-african-mopane-and-miombo-woodlands",totalDownloads:1622,totalCrossrefCites:3,totalDimensionsCites:8,signatures:"Isabel Moura, Ivete Maquia, Alfan A. Rija, Natasha Ribeiro and\nAna Isabel Ribeiro-Barros",downloadPdfUrl:"/chapter/pdf-download/53527",previewPdfUrl:"/chapter/pdf-preview/53527",authors:[{id:"171036",title:"Dr.",name:"Ana",surname:"Ribeiro De Barros",slug:"ana-ribeiro-de-barros",fullName:"Ana Ribeiro De Barros"}],corrections:null},{id:"53443",title:"National and International Conservation of Biological Diversity in Terms of Administrative Law “Sample of Turkey”",doi:"10.5772/66846",slug:"national-and-international-conservation-of-biological-diversity-in-terms-of-administrative-law-sampl",totalDownloads:1180,totalCrossrefCites:0,totalDimensionsCites:2,signatures:"Yavuz Guloglu",downloadPdfUrl:"/chapter/pdf-download/53443",previewPdfUrl:"/chapter/pdf-preview/53443",authors:[{id:"184806",title:"Dr.",name:"Yavuz",surname:"Guloglu",slug:"yavuz-guloglu",fullName:"Yavuz Guloglu"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},relatedBooks:[{type:"book",id:"1446",title:"Senescence",subtitle:null,isOpenForSubmission:!1,hash:"7aa2772cf0b5653b6c599dba90f4c709",slug:"senescence",bookSignature:"Tetsuji Nagata",coverURL:"https://cdn.intechopen.com/books/images_new/1446.jpg",editedByType:"Edited by",editors:[{id:"93967",title:"Dr.",name:"Tetsuji",surname:"Nagata",slug:"tetsuji-nagata",fullName:"Tetsuji Nagata"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1406",title:"Antimicrobial Agents",subtitle:null,isOpenForSubmission:!1,hash:"716194563847e4c8e0f4a7c07ff858ed",slug:"antimicrobial-agents",bookSignature:"Varaprasad Bobbarala",coverURL:"https://cdn.intechopen.com/books/images_new/1406.jpg",editedByType:"Edited by",editors:[{id:"90574",title:"Dr.",name:"Varaprasad",surname:"Bobbarala",slug:"varaprasad-bobbarala",fullName:"Varaprasad Bobbarala"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3509",title:"Gene Therapy",subtitle:"Tools and Potential Applications",isOpenForSubmission:!1,hash:"0fd8b4898c201b4a9f8e597cbcf4d968",slug:"gene-therapy-tools-and-potential-applications",bookSignature:"Francisco Martin Molina",coverURL:"https://cdn.intechopen.com/books/images_new/3509.jpg",editedByType:"Edited by",editors:[{id:"32294",title:"Dr.",name:"Francisco",surname:"Martin",slug:"francisco-martin",fullName:"Francisco Martin"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"364",title:"Gene Duplication",subtitle:null,isOpenForSubmission:!1,hash:"79e1de88c46f703c92c157b80d886221",slug:"gene-duplication",bookSignature:"Felix Friedberg",coverURL:"https://cdn.intechopen.com/books/images_new/364.jpg",editedByType:"Edited by",editors:[{id:"62782",title:"Prof.",name:"Felix",surname:"Friedberg",slug:"felix-friedberg",fullName:"Felix Friedberg"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5090",title:"RNA Interference",subtitle:null,isOpenForSubmission:!1,hash:"9edcfa43c752e926f9e51ecb610e34db",slug:"rna-interference",bookSignature:"Ibrokhim Y. Abdurakhmonov",coverURL:"https://cdn.intechopen.com/books/images_new/5090.jpg",editedByType:"Edited by",editors:[{id:"213344",title:"Dr.",name:"Ibrokhim Y.",surname:"Abdurakhmonov",slug:"ibrokhim-y.-abdurakhmonov",fullName:"Ibrokhim Y. Abdurakhmonov"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3429",title:"Senescence and Senescence-Related Disorders",subtitle:null,isOpenForSubmission:!1,hash:"2dc962eff773b82b389299073279b4c8",slug:"senescence-and-senescence-related-disorders",bookSignature:"Zhiwei Wang and Hiroyuki Inuzuka",coverURL:"https://cdn.intechopen.com/books/images_new/3429.jpg",editedByType:"Edited by",editors:[{id:"164282",title:"Dr.",name:"Wang",surname:"Zhiwei",slug:"wang-zhiwei",fullName:"Wang Zhiwei"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"4558",title:"Advances in DNA Repair",subtitle:null,isOpenForSubmission:!1,hash:"768283d24cc5f9e965ce14d737aa0313",slug:"advances-in-dna-repair",bookSignature:"Clark C. Chen",coverURL:"https://cdn.intechopen.com/books/images_new/4558.jpg",editedByType:"Edited by",editors:[{id:"62462",title:"Prof.",name:"Clark",surname:"Chen",slug:"clark-chen",fullName:"Clark Chen"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3428",title:"Meiosis",subtitle:null,isOpenForSubmission:!1,hash:"5be852a0afc01de31a5dd7164bcd025e",slug:"meiosis",bookSignature:"Carol Bernstein and Harris Bernstein",coverURL:"https://cdn.intechopen.com/books/images_new/3428.jpg",editedByType:"Edited by",editors:[{id:"61946",title:"Dr.",name:"Carol",surname:"Bernstein",slug:"carol-bernstein",fullName:"Carol Bernstein"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5944",title:"Applications of RNA-Seq and Omics Strategies",subtitle:"From Microorganisms to Human Health",isOpenForSubmission:!1,hash:"3be741447e351b9cb9dc96a133302c6b",slug:"applications-of-rna-seq-and-omics-strategies-from-microorganisms-to-human-health",bookSignature:"Fabio A. Marchi, Priscila D.R. Cirillo and Elvis C. Mateo",coverURL:"https://cdn.intechopen.com/books/images_new/5944.jpg",editedByType:"Edited by",editors:[{id:"206664",title:"Dr.",name:"Fabio",surname:"Marchi",slug:"fabio-marchi",fullName:"Fabio Marchi"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5354",title:"Microsatellite Markers",subtitle:null,isOpenForSubmission:!1,hash:"a53f044725f885fbb6a4f36bde2c9d65",slug:"microsatellite-markers",bookSignature:"Ibrokhim Y. Abdurakhmonov",coverURL:"https://cdn.intechopen.com/books/images_new/5354.jpg",editedByType:"Edited by",editors:[{id:"213344",title:"Dr.",name:"Ibrokhim Y.",surname:"Abdurakhmonov",slug:"ibrokhim-y.-abdurakhmonov",fullName:"Ibrokhim Y. Abdurakhmonov"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],ofsBooks:[]},correction:{item:{id:"65667",slug:"erratum-the-roll-of-the-entrepreneur-in-the-establishment-of-economic-equilibria",title:"Erratum - The Roll of the Entrepreneur in the Establishment of Economic Equilibria",doi:null,correctionPDFUrl:"https://cdn.intechopen.com/pdfs/65667.pdf",downloadPdfUrl:"/chapter/pdf-download/65667",previewPdfUrl:"/chapter/pdf-preview/65667",totalDownloads:null,totalCrossrefCites:null,bibtexUrl:"/chapter/bibtex/65667",risUrl:"/chapter/ris/65667",chapter:{id:"57461",slug:"the-roll-of-the-entrepreneur-in-the-establishment-of-economic-equilibria",signatures:"Er’el Granot",dateSubmitted:"April 7th 2017",dateReviewed:"August 22nd 2017",datePrePublished:"December 20th 2017",datePublished:"January 24th 2018",book:{id:"6165",title:"Entrepreneurship",subtitle:"Development Tendencies and Empirical Approach",fullTitle:"Entrepreneurship - Development Tendencies and Empirical Approach",slug:"entrepreneurship-development-tendencies-and-empirical-approach",publishedDate:"January 24th 2018",bookSignature:"Ladislav Mura",coverURL:"https://cdn.intechopen.com/books/images_new/6165.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"85474",title:"Associate Prof.",name:"Ladislav",middleName:null,surname:"Mura",slug:"ladislav-mura",fullName:"Ladislav Mura"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"181601",title:"Prof.",name:"Er'El",middleName:null,surname:"Granot",fullName:"Er'El Granot",slug:"er'el-granot",email:"erelgranot@gmail.com",position:null,institution:{name:"Ariel University",institutionURL:null,country:{name:"Israel"}}}]}},chapter:{id:"57461",slug:"the-roll-of-the-entrepreneur-in-the-establishment-of-economic-equilibria",signatures:"Er’el Granot",dateSubmitted:"April 7th 2017",dateReviewed:"August 22nd 2017",datePrePublished:"December 20th 2017",datePublished:"January 24th 2018",book:{id:"6165",title:"Entrepreneurship",subtitle:"Development Tendencies and Empirical Approach",fullTitle:"Entrepreneurship - Development Tendencies and Empirical Approach",slug:"entrepreneurship-development-tendencies-and-empirical-approach",publishedDate:"January 24th 2018",bookSignature:"Ladislav Mura",coverURL:"https://cdn.intechopen.com/books/images_new/6165.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"85474",title:"Associate Prof.",name:"Ladislav",middleName:null,surname:"Mura",slug:"ladislav-mura",fullName:"Ladislav Mura"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"181601",title:"Prof.",name:"Er'El",middleName:null,surname:"Granot",fullName:"Er'El Granot",slug:"er'el-granot",email:"erelgranot@gmail.com",position:null,institution:{name:"Ariel University",institutionURL:null,country:{name:"Israel"}}}]},book:{id:"6165",title:"Entrepreneurship",subtitle:"Development Tendencies and Empirical Approach",fullTitle:"Entrepreneurship - Development Tendencies and Empirical Approach",slug:"entrepreneurship-development-tendencies-and-empirical-approach",publishedDate:"January 24th 2018",bookSignature:"Ladislav Mura",coverURL:"https://cdn.intechopen.com/books/images_new/6165.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"85474",title:"Associate Prof.",name:"Ladislav",middleName:null,surname:"Mura",slug:"ladislav-mura",fullName:"Ladislav Mura"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}}},ofsBook:{item:{type:"book",id:"9878",leadTitle:null,title:"Electromagnetic Wave Propagation for Industry and Biomedical Applications",subtitle:null,reviewType:"peer-reviewed",abstract:"
\r\n\tElectromagnetic imaging is an emerging biomedical imaging modality, which when matured, might present an effective supplement to current imaging technologies for non-invasive assessment of functional and pathological conditions of tissues. This book aims to provide a state-of-art for the most relevant advancements in the development of electromagnetic sensing and imaging for non-invasive detection, by covering all aspects related to the design, modeling, and experimentation. The authors are welcome to submit original research and review articles reporting recent advances in the application of electromagnetic waves technologies in industry and bioengineering.
\r\n\r\n\tThe scope of this book will be the collection of new and/or review results exploring the use of electromagnetic waves for industrial and biomedical applications with particular focus on inclusion detection and medical treatment as well as a diagnostic tool for disease detection. Potential topics include but are not limited to the following: Electromagnetic sensing and imaging for industry applications, Electromagnetic sensing and imaging for biomedical applications, Microwave sensing and imaging , Non-invasive electromagnetic diagnostic tools, Usage of electromagnetic waves for probing organs and advanced MRI techniques, Theoretical modeling of electromagnetic wave propagation, Application of electromagnetic waves in advanced MRI techniques, RF sensors and coils, Biomaterials for wearable sensors, In vitro and in vivo testing.
",isbn:"978-1-83968-582-8",printIsbn:"978-1-83968-581-1",pdfIsbn:"978-1-83968-583-5",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,hash:"e57ef4b5bada0d966637cd303d76278f",bookSignature:"Distinguished Prof. Lulu Wang",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/9878.jpg",keywords:"Electromagnetic Sensing, Imaging, Biomedical Applications, Electromagnetic Measurements, Conductivity, Electromagnetic Induction Tomography, Electric Impedance Imaging, Microwave Imaging, Biomaterials, RF Coils, Electromagnetic Scattering Problems, Integral Equations",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"August 26th 2020",dateEndSecondStepPublish:"November 3rd 2020",dateEndThirdStepPublish:"January 2nd 2021",dateEndFourthStepPublish:"March 23rd 2021",dateEndFifthStepPublish:"May 22nd 2021",remainingDaysToSecondStep:"3 months",secondStepPassed:!0,currentStepOfPublishingProcess:4,editedByType:null,kuFlag:!1,biosketch:"With an M.E. (Hons.) and a Ph.D. degree from the Auckland University of Technology, New Zealand, Dr. Wang is the first author of over 60 peer-reviewed publications, received multiple national and international awards from various professional societies and organizations she is a member of (ASME, IEEE, AAAS, PSNZ, and IPENZ ).",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"257388",title:"Distinguished Prof.",name:"Lulu",middleName:null,surname:"Wang",slug:"lulu-wang",fullName:"Lulu Wang",profilePictureURL:"https://mts.intechopen.com/storage/users/257388/images/system/257388.jpg",biography:"Lulu Wang is a Full Professor of Biomedical Engineering at Shenzhen Technology University in China. She received the M.E. (First class Hons.) and Ph.D. degrees from the Auckland University of Technology, New Zealand, in 2009 and 2013, respectively. From 2013 to 2015, she was a Research Fellow with the Institute of Biomedical Technologies, Auckland University of Technology, New Zealand. In 2015, Dr. Wang became an Associate Professor of biomedical engineering with the Hefei University of Technology. In 2019, she became a Full Professor of biomedical engineering with the College of Health Science and Environmental Engineering, Shenzhen Technology University. Her research interests include medical devices, electromagnetic sensing and imaging, and computational mechanics. Over the past five years, Dr. Wang is the first author of 60 peer-reviewed publications, 2 ASME books, 7 book chapters, and 12 innovation patents. She has edited three books and two special issues of international journals. Dr. Wang is a member of ASME, IEEE, AAAS, PSNZ, and IPENZ. She has been an active scientific reviewer for numerous journals and international conferences. She received multiple National and International Awards from various professional societies and organizations.",institutionString:"Shenzhen Technology University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"2",institution:{name:"Shenzhen Technology University",institutionURL:null,country:{name:"China"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"20",title:"Physics",slug:"physics"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"259492",firstName:"Sara",lastName:"Gojević-Zrnić",middleName:null,title:"Mrs.",imageUrl:"https://mts.intechopen.com/storage/users/259492/images/7469_n.png",email:"sara.p@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:"6835",title:"Computer Methods and Programs in Biomedical Signal and Image Processing",subtitle:null,isOpenForSubmission:!1,hash:"19f08ef15d97900c94dc8fb04f9afb5f",slug:"computer-methods-and-programs-in-biomedical-signal-and-image-processing",bookSignature:"Lulu Wang",coverURL:"https://cdn.intechopen.com/books/images_new/6835.jpg",editedByType:"Edited by",editors:[{id:"257388",title:"Distinguished Prof.",name:"Lulu",surname:"Wang",slug:"lulu-wang",fullName:"Lulu Wang"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8347",title:"Computer Architecture in Industrial, Biomechanical and Biomedical Engineering",subtitle:null,isOpenForSubmission:!1,hash:"3d7024a8d7d8afed093c9c79ec31f15a",slug:"computer-architecture-in-industrial-biomechanical-and-biomedical-engineering",bookSignature:"Lulu Wang and Liandong Yu",coverURL:"https://cdn.intechopen.com/books/images_new/8347.jpg",editedByType:"Edited by",editors:[{id:"257388",title:"Distinguished Prof.",name:"Lulu",surname:"Wang",slug:"lulu-wang",fullName:"Lulu Wang"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8356",title:"Metastable, Spintronics Materials and Mechanics of Deformable Bodies",subtitle:"Recent Progress",isOpenForSubmission:!1,hash:"1550f1986ce9bcc0db87d407a8b47078",slug:"solid-state-physics-metastable-spintronics-materials-and-mechanics-of-deformable-bodies-recent-progress",bookSignature:"Subbarayan Sivasankaran, Pramoda Kumar Nayak and Ezgi Günay",coverURL:"https://cdn.intechopen.com/books/images_new/8356.jpg",editedByType:"Edited by",editors:[{id:"190989",title:"Dr.",name:"Subbarayan",surname:"Sivasankaran",slug:"subbarayan-sivasankaran",fullName:"Subbarayan Sivasankaran"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1591",title:"Infrared Spectroscopy",subtitle:"Materials Science, Engineering and Technology",isOpenForSubmission:!1,hash:"99b4b7b71a8caeb693ed762b40b017f4",slug:"infrared-spectroscopy-materials-science-engineering-and-technology",bookSignature:"Theophile Theophanides",coverURL:"https://cdn.intechopen.com/books/images_new/1591.jpg",editedByType:"Edited by",editors:[{id:"37194",title:"Dr.",name:"Theophanides",surname:"Theophile",slug:"theophanides-theophile",fullName:"Theophanides Theophile"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3092",title:"Anopheles mosquitoes",subtitle:"New insights into malaria vectors",isOpenForSubmission:!1,hash:"c9e622485316d5e296288bf24d2b0d64",slug:"anopheles-mosquitoes-new-insights-into-malaria-vectors",bookSignature:"Sylvie Manguin",coverURL:"https://cdn.intechopen.com/books/images_new/3092.jpg",editedByType:"Edited by",editors:[{id:"50017",title:"Prof.",name:"Sylvie",surname:"Manguin",slug:"sylvie-manguin",fullName:"Sylvie Manguin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3161",title:"Frontiers in Guided Wave Optics and Optoelectronics",subtitle:null,isOpenForSubmission:!1,hash:"deb44e9c99f82bbce1083abea743146c",slug:"frontiers-in-guided-wave-optics-and-optoelectronics",bookSignature:"Bishnu Pal",coverURL:"https://cdn.intechopen.com/books/images_new/3161.jpg",editedByType:"Edited by",editors:[{id:"4782",title:"Prof.",name:"Bishnu",surname:"Pal",slug:"bishnu-pal",fullName:"Bishnu Pal"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"72",title:"Ionic Liquids",subtitle:"Theory, Properties, New Approaches",isOpenForSubmission:!1,hash:"d94ffa3cfa10505e3b1d676d46fcd3f5",slug:"ionic-liquids-theory-properties-new-approaches",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/72.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1373",title:"Ionic Liquids",subtitle:"Applications and Perspectives",isOpenForSubmission:!1,hash:"5e9ae5ae9167cde4b344e499a792c41c",slug:"ionic-liquids-applications-and-perspectives",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/1373.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{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"}}]},chapter:{item:{type:"chapter",id:"39538",title:"Lipoproteins and Cardiovascular Diseases",doi:"10.5772/48132",slug:"lipoproteins-and-cardiovascular-diseases",body:'Lipids consists of a broad group of naturally occurring molecules that include fats, waxes, sterols including cholesterol, fat-soluble vitamins (such as vitamins A, D, E, and K), monoglycerides, diglycerides, triglycerides, phospholipids, and others. Lipids were previously known as sources of energy storage and the building blocks for cell membrane. Lipids are now known to play several key roles in intracellular signalling, membrane trafficking, hormonal regulation, blood clotting (Muller-Roeber and Pical, 2002; Vance and Vance, 2002; Fahy et al., 2009). All lipids may be defined as hydrophobic or amphiphilic small molecules. The amphiphilic nature of some lipids allows them to form structures such as vesicles, liposomes, or membranes in an aqueous environment. Biological lipids originate entirely or in part from two distinct types of biochemical subunits, which are ketoacyl and isoprene groups (Fahy et al., 2009).
Lipids typically do not travel alone in the blood. Instead, it binds to a protein that transports it to its destination in the body. The complex formed by the binding of lipid to protein i.e. lipoprotein, makes lipids water soluble, which enables its transportation in blood. The lipoprotein particle is composed of an outer shell of phospholipids, which renders the particle soluble in water; a core of fats called lipid, including cholesterol and a surface apoprotein (apolipoprotein). Ideally, the lipoprotein aggregates should be described in terms of the different protein components (apolipoprotein) because this determines the overall structures and metabolism of the lipoprotein, and the interactions with receptor molecules in liver and peripheral tissues. The apolipoprotein molecule enables tissues to recognize and take up the lipoprotein particle. However, lipoproteins are classified based on their characteristic density on ultracentrifugation, which has been used to segregate the different lipoprotein classes. Lipoproteins are broadly classified as high density lipoprotein (HDL), low density lipoprotein (LDL), intermediate density lipoprotein (IDL), very low density lipoprotein (VLDL) and chylomicrons (CM). Each of these particles perform different functions and can be detrimental (VLDL, IDL, LDL) or beneficial (HDL) to the cardiovascular system.
Structure of Lipoprotein available from http://www.campbell.edu
CM | VLDL | IDL | HDL | |
Density (g/ml) | < 0.94 | 0.94 – 1.006 | 1.006 – 1.063 | 1.063 -1.210 |
Diameter (Á) | 6000 - 2000 | 600 | 250 | 70-120 |
Total lipid (wt %) * | 99 | 91 | 80 | 44 |
Triacylglycerols | 85 | 55 | 10 | 6 |
Cholesterol esters | 3 | 18 | 50 | 40 |
Cholesterol | 2 | 7 | 11 | 7 |
Phospholipids | 8 | 20 | 29 | 46 |
Physical properties and lipid compositions of lipoprotein classes
It is relevant to establish the important of cholesterol in the body to be able to relate the various metabolic events associated with cholesterol and its homeostasis. Mammalian cell membranes contain varying proportions of cholesterol depending on organelle and cell type. These levels are tightly controlled by lipid transfer, through both vesicular and protein-bound pathways. With its rigid sterol backbone, cholesterol preferentially locates among saturated membrane lipids that have straight, elongated hydrocarbon chains rather than among kinked, unsaturated species. The presence of cholesterol in the membrane increases lateral ordering of lipids, reducing permeability and fluidity and potentially restricting diffusion of membrane proteins. Its distribution is not uniform within a membrane: regions of high cholesterol and corresponding low fluidity are termed lipid rafts. These areas act as platforms for the assembly of signalling complexes within the membrane and have been implicated in the development of numerous disease processes, notably arteriosclerosis and cancer (Di Vizio et al., 2008; Ikonen, 2008).
Elevated plasma levels of low density lipoprotein (LDL) and low levels of high density lipoprotein (HDL) poses a major risk of development of cardiovascular diseases (Grundy et al., 1999). A dietary intake of saturated fat and a sedentary lifestyle has been associated with about 31% of coronary heart disease and 11% of stroke in humans. According to the Framingham Heart Study and other studies (Wilson et al., 1998), the major and independent risk factors for coronary heart disease (CHD) are cigarette smoking of any amount, elevated blood pressure, elevated serum total cholesterol and low-density lipoprotein cholesterol (LDL-C), low serum high-density lipoprotein cholesterol (HDL-C), diabetes mellitus, and advancing age. More recently, a review by Patrick and Uzick (2001) documented new risk factors for CHD which included levels of circulating homocysteine, fibrinogen, C-reactive protein (CRP), endogenous tissue plasminogen-activator, plasminogen-activator inhibitor type I, lipoprotein(a), factor VII and certain infections such as Chlamydia pneumonia. These studies showed that the total risk of an individual is the summation of all major risk factors.
Other factors contributing to the total risk for CHD are categorized as conditional risk factors and predisposing risk factors. The conditional risk factors are associated with increased risk for CHD, although their causative, independent, and quantitative contributions to CHD have not been well documented. The predisposing risk factors are those that worsen the independent risk factors. Two of these risk factors; obesity and physical inactivity, are designated major risk factors by the American Heart Association (AHA) (Fletcher et al., 1996; Eckel, 1997). The adverse effects of obesity are worsened when it is expressed as abdominal obesity, an indicator of insulin resistance. These risk factors apply before clinical manifestation of coronary atherosclerotic diseases. The clinical significance of these risk assessment is to identify high-risk patients who require attention, motivate patients to adhere to risk-reduction therapies and modify the intensity of risk reduction effort required in potential patients (Grundy et al., 1999).
Cholesterol is a building block of the outer layer of cell membranes. Cholesterol is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals (Leah, 2009). As an essential structural component of mammalian cell membranes, it is required to establish proper membrane permeability and fluidity. In addition, cholesterol is an important component for the manufacture of bile acids, steroid hormones, and vitamin D. Cholesterol is the principal sterol synthesized by animals; however, small quantities can be synthesized in other eukaryotes such as plants and fungi. It is almost completely absent among prokaryotes including bacteria (Pearson et al., 2003).
Owing to its limited solubility in water, cholesterol is transported in blood in lipoproteins. The lipoprotein outer layer is formed of amphiphilic cholesterol and phospholipid molecules, studded with proteins, surrounding a hydrophobic core of triglycerides and cholesterol esters. Lipoproteins are specifically targeted to cells by distinct apolipoproteins on their surface that bind to specific receptors. Low density lipoprotein (LDL) contains the highest level of cholesterol. LDL receptors in peripheral tissues bind LDL, triggering its endocytosis, lysosomal targeting and hydrolysis. When cells have abundant cholesterol, LDL receptor synthesis is inhibited by the sterol regulatory element binding proteins (SREBP) pathway (Wang et al., 1993; Yokoyama et al., 1993; Brown and Goldstein, 2009).
The biosynthesis of cholesterol is intensely regulated in the body with negative feedback of plasma cholesterol levels. The molecular basis of this regulation was set out by Michael Brown and Joseph Goldstein, earning them the Nobel Prize in Physiology and Medicine in 1985 (Leah, 2009). A key irreversible step of cholesterol synthesis is catalyzed by HMG-CoA reductase. Transcription of the HMG gene is controlled by SREBPs, transcription factors that bind sterol regulatory elements. SREBPs are only able to enter the nucleus when cholesterol levels fall. At other times they are tied up in a complex that includes Scap (SREBP-cleavage activating protein), an escort protein with a cholesterol-binding motif that senses cellular cholesterol levels. The SREBP pathway is now implicated in multiple regulatory aspects of lipid formation and metabolism (Brown and Goldstein, 2009).
The first stages of cholesterol build up in the blood vessels (atherosclerosis) occur when LDL particles circulating in the blood penetrate through the inner lining of blood vessels and become trapped in the artery wall. The normal function of LDL is to deliver cholesterol to cells, where it is used in membranes or for the synthesis of steroid hormones. Cells take up cholesterol by receptor-mediated endocytosis. LDL binds to a specific LDL receptor and is internalized in an endocytic vesicle. Receptors are recycled to the cell surface, while hydrolysis in an endolysosome releases cholesterol for use in the cell. The liver removes LDL and other lipoproteins from the circulation by receptor-mediated endocytosis.
Deregulation of cholesterol levels results in the existence of more LDL in the blood than can be taken up by LDL receptors. Excess LDL is oxidized and taken up by macrophages, forming foam cells that can become trapped in the walls of blood vessels along with cells of inflammation (Zioncheck et al., 1991; Young and McEneny, 2001). Fatty streaks, consisting of subendothelial collection of foam cells are initially formed in blood vessels. Small, dense LDL particles are more atherogenic than large, buoyant LDL particles, and oxidation of LDL also increases its atherogenicity. In addition, LDL belongs to the group of lipoproteins that contain apolipoprotein (apo) B-100. Some of the particles in this highly heterogeneous group contain other apolipoproteins, such as apo C-II, apo C-III, and apo E. Furthermore, some particles are larger and rich in triglycerides (large VLDL), whereas others are smaller and rich in cholesteryl esters (small VLDL, IDL). It is now known that remnant lipoproteins containing apo C-III are highly atherogenic and may be more specific measures of coronary heart disease (CHD) risk assessment than plasma triglycerides (Carmena et al., 2004).
The end result is the formation of an atherosclerotic plaque which occludes the endothelial lumen and impedes blood flow, leading to myocardial infarction, the major cause of heart attacks and strokes. Although LDL levels correlate with heart attack risk, high density lipoprotein (HDL) has an inverse ratio of risk because HDL particles transport cholesterol to the liver for excretion. Modern cholesterol tests distinguish the LDL/HDL ratio as well as the overall level (Barter et al., 2007). Other sub-fractions of lipoproteins such as chylomicrons, IDL and VLDL may enter the endothelial spaces due to their sizes, thus contribute substantially to development of atherosclerotic plaques. They may also increase prothrombotic factors, triggering cardiovascular diseases (Brunzell et al., 2008).
Sizes of Lipoproteins available at http://www.sigmaaldrich.com/european-export.html
Triglyceride-rich lipoproteins comprise a great variety of nascent and metabolically modified lipoprotein particles differing in size, density, and lipid and apolipoprotein composition. Studies have shown an inverse relationship between the size of lipoproteins and their ability to cross the endothelial barrier to enter the arterial intima. Chylomicrons and large VLDLs are probably not capable of entering the arterial wall. On the other hand, small VLDL and IDL can enter the arterial intima. Therefore, certain triglyceride rich lipoproteins are atherogenic, whereas others are not. A large body of evidence suggests that small VLDLs and IDLs are independently associated with atherosclerosis (Carmena et al., 2004).
Apolipoproteins are the carrier proteins for lipoproteins and they consist of a single polypeptide chain often with relatively little tertiary structure. They are required to solubilise the non-polar lipids in the circulation and in some instances to recognise specific receptors. They are classified as Apo A1, A2, A4, A5, B48, B100, C1, C2, C3, D, E, H, J, L, M and Apo (a). Most apolipoproteins are synthesised by the liver and intestine.
Apolipoprotein | Molecular weight | Lipoprotein | Function |
Apo AI | 29,100 | HDL | Lecithin: cholesterol acyltransferase (LCAT) activation. Main structural protein. Binds ABCA1 on macrophages |
Apo AII | 17,400 | HDL | Enhances hepatic lipase activity |
Apo AIII | 46,000 | CM | |
Apo AIV | 46,000 | HDL, CM | Inhibits food intake in CNS |
Apo AV | 39,000 | HDL | Enhances triacylglycerol uptake |
Apo B48 | 241,000 | CM | Derived from Apo B100 gene by RNA editing, lacks the LDL receptor binding site |
Apo B100 | 512,000 | LDL, IDL, VLDL | Binds to LDL receptor |
Apo CI | 7,600 | VLDL, CM | Activates LCAT |
Apo CII | 8,900 | VLDL, CM | Activates lipoprotein lipase |
Apo CIII | 8,750 | VLDL, CM | Inhibits lipoprotein lipase |
Apo D | 33,000 | HDL | Closely associated with LCAT, progesterone binding |
Apo E | 34,000 | HDL | At least 3 forms. Binds to LDL receptor |
Apo(a) | 300,000 – 800,000 | LDL, Lp(a) | Linked by disulfide bonds to apo B100 and similar to plasminogen, associated with premature coronary artery disease and stroke |
Apo H | 50,000 | Chylomicrons | Involved with triacylglycerol metabolism |
Apo M | HDL | Transports sphingosine-1- phosphate |
Classes of apolipoproteins, their molecular weight and functions
Apo A are subdivided into apo AI, AII, AIII, AIV and AV. Apo AI and AII are the major apolipoproteins in the HDL particle. HDL is primarily saddled with the responsibility of removing excess cholesterol from peripheral tissues and delivering it to the liver for excretion in bile as bile acids in a process known as reverse cholesterol transport. Apo AI is synthesised mainly by the liver and also by the intestine. The protein consists of 243 amino acids arranged as eight α-helical segments of 22 amino acids which have 11 –mer repeats, no disulfide bonds or glycosylations. The helices are believed to be amphipathic in nature with both hydrophobic and hydrophilic faces. This nature enhances its interaction with the lipid and aqueous phases. Apo AII on the other hand is found as a twin chain of 77 amino acids each, linked by disulfide bonds. It enhances the activity of hepatic lipase, thus increasing lipoprotein metabolism. Apo III is found in chylomicrons.
Three isoforms of this apolipoprotein exist and they are all synthesised mainly by the liver and also by several tissues such as arterial wall, brain and adipose tissue. They are important for homeostasis of lipid and lipoproteins in blood circulation as well as their metabolism in these tissues. Apo E is required for the clearance of VLDL remnant (IDL) from circulation in the liver. Other suggestions on its involvement with immune response and inflammation have also been put forward.
Two types of apolipoprotein B are synthesised from the intestine and liver as apo B100 which has the full length of 4536 amino acid residues and a truncated form with 48% of the full length known as apo B48. These proteins which are synthesised on ribosomes, an organelle located on the surface of rough endoplasmic reticulum are translocated through the reticular membrane into the lumen of endoplasmic reticulum. Assembly of VLDL occurs here by accretion of lipids to the core of apo B particle. This occurs in three distinct stages as the apo B grows bigger, forming the pre-VLDL to VLDL 2 which eventually grows to become the triacylglycerol-rich VLDL 1 or chylomicrons, the most energy dense substances in the body. VLDL 2 is a triacylglycerol-poor version of VLDL and its assembly occurs in golgi bodies. This is transported to basolateral membrane of the intestinal cells where final assembly of VLDL 1 or chylomicrons occur and these are secreted into the lamina propria of the intestinal cells by reverse exocytosis.
Apo B100 and B48 are large and water-insoluble, and are the only non-exchangeable apolipoproteins. They are major components of chylomicrons and VLDL, and usually remain with their lipid aggregates throughout their passage in plasma and several metabolic changes occurring during their circulation in plasma. Chylomicrons are usually transported through the intestinal lymphatic system and flow into blood circulation via the left subclavian vein. As apo B carries the VLDL or chylomicrons through the blood stream, their triacylglycerol content are removed by peripheral tissues via enzymatic activity of lipoprotein lipase, located in the endothelial wall. This makes free fatty acids available for energy production in muscle and some are stored in adipose tissue. Apo B48 remains with the remnant of the lipoprotein particle, along with dietary cholesterol and apo E. the lipoprotein remnant is eventually cleared from circulation in the liver by an apo E dependent receptor-mediated reaction.
ApoB-100 is one of the largest monomeric proteins known and it is the major apolipoprotein component common to the atherogenic lipoproteins [VLDL, LDL, IDL and Lp(a)] (Boerwinkle et al., 1992; Carmena et al., 2004). Apo B100 differs from apo B48 by the presence of LDL receptor site on the apo B100 molecule. Apo B-100 is encoded for by the Apo B gene and mutations in this gene cause familial hypercholesterolemia, an autosomal hereditary metabolic disorder. The level of apo B-100 is a stronger predictor of risk than LDL in humans. Apo B-100 is speculated to mediate delivery of the cholesterol content of lipoproteins to cells via an unknown mechanism. It is well established that Apo B-100 is associated with atherogenic lipoproteins, thus the number of Apo B-100 can be used to determine the risk of atherosclerosis and CHD in individuals. Apo B-100/apo A-I ratio are strongly and positively related to increased risk of fatal myocardial infarction. Apolipoprotein A-I (apo A-I) is the major apolipoprotein in the HDL structure. The Apo B-100/apo A-I ratio is especially valuable in patients with normal or low LDL concentrations, a frequent observation in type 2 diabetes mellitus which may present with hypertriglyceridemia and hyper-apo B concentrations (Carmena et al., 2004).
Apolipoprotein C is subdivided into three and each has its own distinct function. Apo CI is involved with activation of Lecithin: cholesterol acyltransferase (LCAT) along with apo AI. This enzyme converts free cholesterol into cholesterol ester, which enhances the incorporation of cholesterol into the lipid core of a lipoprotein particle, particularly in assembly of HDL particle. The enzyme is mainly bound to HDL and LDL in plasma. Apo CII and CIII have antagonistic activity to each other which are required in regulation of lipoprotein lipase activity. Apo CII is required for activation of lipoprotein lipase, while CIII inhibits lipoprotein lipase activity. Apo CII is believed to open a lid-like region of the enzyme which allows the active site to hydrolyse the fatty acid ester bonds of triacylglycerols. In addition to inhibition of lipoprotein lipase, apo CIII also inhibits the binding of lipoproteins to receptors at the cell surface, thereby decreasing hydrolysis of triacylglycerols. High levels of apo CIII have been associated with elevated serum levels of triacylglycerols (hypertriglyceridemia).
Lipids enter blood circulation bound to apolipoproteins as chylomicrons or VLDL which as secreted into the blood stream from the intestines. Chylomicrons or VLDL consist mainly of apo B100 and B48, but also consist of some apo AI, along with other apolipoprotein which will be discussed. These lipoproteins carry triacylglycerol-rich cholesterols to the peripheral tissues to provide sources of energy and for storage, while HDL carries excess cholesterol from peripheral tissue to the liver for excretion in bile acids. Immediately chylomicrons enter blood circulation, an exchange of apolipoproteins occurs between chylomicrons and HDL. The apo AI content of chylomicrons is exchanged for the apo C and E content of HDL. Apo C content is required for activation and inhibition of lipoprotein lipase which hydrolyses the triacylglycerol content of chylomicrons and VLDL, while apo E is needed for the receptor mediated clearance from circulation. Circulation of VLDL and chylomicrons in the blood stream exposes the particles to enzymatic release of triacylglycerols from the lipoprotein core and excess cholesterol is removed from cells. The triacylglycerol- poor and cholesterol rich LDL remnant produced is potentially toxic to the body and needed to be safely cleared from blood circulation. The main concern for this lipoprotein is its toxic effect on the cardiovascular system. The liver scavenges and disposes chylomicrons remnant more effectively than the LDL particles, a mechanism put in place by the body to get rid of the more atherogenic particle of the two; chylomicrons remnant. LDL particles are mostly removed by other mechanisms involving HDL.
Apolipoprotein(a) itself is a large glycoprotein that exhibits size heterogeneity among individuals with isoforms that range between 180 – 700kDa in size. Apo(a) genotypes were determined using a newly developed pulsed-field gel electrophoresis method which distinguished 19 different genotypes at the apo(a) locus. The apo(a) gene itself was found to account for virtually all the genetic variability in plasma Lp(a) levels (Boerwinkle et al., 1992). The apo(a) cDNA contains multiple tandem copies of a sequence that encodes a cysteine-rich protein motif called a kringle. The particular repeated kringle in apo(a) is designated kringle 4 because it closely resembles the fourth kringle in plasminogen, with the protease domain of apo(a) containing 88% amino-acid identity to plasminogen. McLean et al. (1992) proposed that the apo(a) isoforms are of different sizes because of variations in the numbers of kringle 4-encoding repeats in the apo(a) gene. The molecular mass of apo(a) protein varies from 187 kDa for an apo(a) that contains 12 kringle 4 domains, to 662 kDa for an apo(a) that contains 50 kringle 4 domains (Carmena et al., 2004).
Lipoprotein [Lp(a)] is a variant of LDL with an additional apolipoprotein in the structure. Lp(a) is essentially an LDL particle with a large glycoprotein, apolipoprotein (a) [apo(a)] attached to it (McLean et al., 1987; Loscalzo et al., 1990; Boerwinkle et al., 1992; Palabrica et al., 1995). Lp(a) resembles low density lipoprotein (LDL) in lipid composition, but it is distinguished by the presence of apo(a) which is bound by a disulfide linkage to apolipoprotein B-100, a ligand in the LDL molecule by which LDL binds to its receptor. Lp(a) levels has been demonstrated to have a clear association with development of atherosclerosis and other cardiovascular diseases (Zenker et al., 1986; Danesh et al., 2000; Berglund and Anuurad, 2008; Danik et al., 2008). The postulated atherogenicity of Lp(a) is probably due to the presence of apo(a) component of the Lp(a) molecule. A study showed that the removal of apo(a) from Lp(a) particles result in a lipoprotein with greatly enhanced affinity for the LDL receptor (Armstrong et al., 1985).
Apo(a) is expressed by liver cells (hepatocytes), and the assembly of apo(a) and LDL particles seems to take place at the outer hepatocyte surface. The half-life of Lp(a) in the circulation is about 3 to 4 days (Rader et al., 1993) and this particle varies in blood concentration from one individual to another from <0.2 - >200 mg/dL. Ethnicity is a factor, with those of Asian and African origin averaging the highest concentrations. Within ethnic groups, individual elevation of Lp(a) is directly associated with increased risk of cardiovascular diseases (Sandholzer et al., 1991; Chien et al., 2008). Lp(a) is usually unaffected by factors like age, blood pressure, and total cholesterol.
The structure of Lp(a) is similar to plasminogen, a naturally occurring glycoprotein that participates in dissolving of clots that form in the bloodstream, and tissue plasminogen activator (tPA). Lp(a) competes with plasminogen for its binding site, leading to reduced fibrinolysis (Loscalzo et al., 1990; Palabrica et al., 1995). Also because Lp(a) stimulates secretion of PAI-1 it leads to thrombogenesis. In addition, because of LDL cholesterol content, Lp(a) contributes to atherosclerosis (Schreiner et al., 1993; Sotiriou et al., 2006) and ultimately a cardiovascular risk factor (Berglund and Ramakrishnan, 2004).
There is a general inverse correlation between the size of the apo(a) isoform and the Lp(a) plasma concentration (Bowden et al., 1994; Kraft et al., 1996) which is caused by a variable rate of degradation before the apo(a) protein has matured for Lp(a) assembly (White et al., 1994). The plasma concentration of Lp(a) is unaffected by many physiological, pharmacological, and environmental factors that affect the levels of other plasma lipoproteins (Albers et al., 1977). A genetic determination of plasma Lp(a) levels was strongly suggested due to this lack of environmental and physiological influences. Consistent with this formulation, early genetic studies suggested that the presence of Lp(a) in plasma was inherited as a single autosomal dominant trait (Berg and Mohr, 1963; Iselius et al., 1981), with an estimated heritability level ranging from 0.75 to 0.98 (Boerwinkle et al., 1992).
Plasma Lp(a) concentrations vary 1000-fold between individuals and represent a continuous quantitative genetic trait with a skewed distribution in Caucasian populations (Utermann, 1989). A study was conducted by Lackner et al. (1991) in which the apo(a) gene of members of 12 Caucasian families were segregated. It was found that within a given family, sibling pairs with identical apo(a) genotypes tended to have very similar plasma Lp(a) levels (Lackner et al., 1991). However, individuals with the same apo(a) genotypes who were members of different families often had significantly different plasma concentrations of Lp(a). Taken together, these observations suggest that the apo(a) gene is the major determinant of plasma Lp(a) levels and that cis-acting DNA sequences at or near the apo(a) locus, other than the number of kringle 4 repeats, contribute importantly to plasma Lp(a) concentrations (Boerwinkle et al., 1992). Variation in the hypervariable apo(a) gene on chromosome 6q2.6-q2.7 and interaction of apo(a) alleles with defective LDL-receptor genes explain a large fraction of the variability of plasma Lp(a) concentrations (Utermann, 1989).
Furthermore, the size of the apo(a) glycoprotein varies in individuals and this size is inversely correlated with the plasma level of Lp(a). The reason for the inverse correlation between the size of the apo(a) gene and level of plasma Lp(a) is not known, but a variation of length within the kringle 4-encoding region of the apo(a) gene may account for a greater proportion of the inter-individual variation in plasma Lp(a) concentrations. Also, the number of kringle 4 repeats in the gene may not have a direct effect on plasma Lp(a) concentration (Boerwinkle et al., 1992; Brunner et al., 1996). A study conducted on apo(a) gene of mamorset monkeys showed a plasma Lp(a) concentration of a very wide range of over a 100-fold, but only one apo(a) isoform (Guo et al., 1991). This may be explained by the differences in the composition of kringle 4 sequence of apo(a) genes in which individuals may have same sizes of apo(a) alleles but different plasma Lp(a) concentrations. The frequency of recombination activity in this locus may be responsible for the variation in their kringle 4 composition and number which may have marked effect on synthesis and /or degradation of Lp(a) (Boerwinkle et al., 1992).
Oxidative stress, especially LDL oxidation has been suggested for almost three decades as the most probable aetiology of atherosclerosis (Steinbrecher et al., 1984). Markers of LDL oxidation in plasma, particularly circulating oxidized LDL and auto-antibodies against oxidized LDL, could be used to assess the development of atherosclerosis in patients (Carmena et al., 2004). Circulating oxidized LDL is additive to the global risk score based on age, sex, total and HDL cholesterol, diabetes mellitus, hypertension, and smoking as a useful marker for identifying persons at risk for CAD (Holvoet et al., 2001; Toshima et al., 2000).
A study has associated circulating oxidized LDL with both subclinical atherosclerosis (clinically silent ultrasound assessed atherosclerotic changes in the carotid and femoral arteries) and inflammatory variables (C-reactive protein and the inflammatory cytokines interleukin-6 and tumor necrosis factor-α). This conclusion supports the concept that oxidatively modified LDL may play a major role in development of atherosclerosis (Hulthe and Fagerberg, 2002). It has been proposed that, because of the antigenic properties of oxidized LDL, the anti-oxidized LDL antibody titer could represent a useful index of in vivo LDL oxidation. Autoantibodies against oxidized LDL have been reported to be associated with atherosclerosis, but existing reports are still conflicting. Some studies have reported a positive relationship between autoantibodies against oxidized LDL and CHD (Sherer et al., 2001) whereas another did not (Leinonen et al., 1998). There is a strong cross-reactivity between autoantibodies against oxidized LDL and anticardiolipin antibodies, which have been positively associated with CHD (Erkkila et al., 2000).
Cardiovascular heart disease risk is usually significantly increased when elevated levels of small, dense LDL accompanied by hypertriglyceridemia, reduced HDL-cholesterol levels, abdominal obesity, and insulin resistance. Results from the Que´bec Cardiovascular Study have indicated that persons displaying elevated plasma concentrations of insulin and apo B together with small, dense LDL particles showed a remarkable increase in CHD risk (Lamarche et al., 1999).
Sensitivity to insulin in diabetic and non-diabetic individuals was assessed using nuclear magnetic resonance (NMR) spectroscopy. Insulin resistance had profound effects on lipoprotein size and an increase in serum triglycerides. The lipid profile revealed a 2- to 3-fold increase in concentrations of large VLDL particles with no change in medium or small VLDL, increase in overall LDL particle concentration with more small LDL particle size and reduced large LDL. In type 2 diabetes, these alterations could be attributed primarily to the underlying insulin resistance. These changes in the NMR lipoprotein subclass profile predictably increased the risk of cardiovascular disease but were not fully apparent in the conventional lipid profile (Garvey et al., 2003). The Diabetes Atherosclerosis Intervention Study (DAIS) (Vakkilainen et al., 2003) showed that lipid-modifying treatment decreased the angiographic progression of coronary atherosclerosis in subjects with type 2 diabetes. This effect was related in part to the correction of lipoprotein abnormalities. Compared with placebo, fenofibrate treatment significantly increased LDL particle size and HDL cholesterol and decreased plasma total cholesterol, LDL cholesterol, and triglyceride concentrations. The final LDL particle size was inversely correlated with the increase in percentage diameter stenosis (Vakkilainen et al., 2003).
The Pittsburgh Epidemiology of Diabetes Complications Study on whether NMR lipoprotein spectroscopy improves the prediction of coronary artery disease (CAD) in patients with childhood-onset type 1 diabetes, independently of conventional lipid and other risk factors showed that both lipid mass and particle concentrations (NMR spectroscopy) of all VLDL subclasses, small LDL, medium LDL, and medium HDL were increased in CAD cases compared with controls, whereas large HDL was decreased. Mean LDL and HDL particle sizes were also less in CAD cases (Soedamah-Muthu et al., 2003; Carmena et al., 2004).
Dyslipoproteinaemia is a term broadly used for derangement in lipid and lipoprotein metabolism, which may either be hyperlipoproteinaemia or hypolipoproteinaemia. Dyslipoproteinaemias are generally classified as familial (primary) or acquired (secondary). This chapter discusses hyperlipoproteinaemia with its close relevance to development of cardiovascular diseases. Primary hyperlipoproteinaemias are of genetic origin and may be due to a mutation in a receptor protein which presents as inborn errors of lipid metabolism, and includes common hypercholesterolemia, combined familiar hyperlipidemia, familiar hypercholesterolemia, familiar hypertriglyceridemia, VLDL remnants hyperlipidemia and primary chylomicronaemia (Garmendia, 2003). Primary hyperlipoproteinaemia was first classified by Fredrickson and Lees (1965) and this classification was adopted by World Health Organization (WHO). They divided primary hyperlipoproteinaemias into four types and details are show in Table 3 below.
The secondary hyperlipoproteinemias also mimic primary types and may present with similar symptoms. Secondary dyslipoproteinaemias are usually due to other underlying causes that lead to alterations in plasma lipid and lipoprotein metabolism, including hypothyroidism, diabetes mellitus, nephrotic syndrome, chronic biliary obstruction, renal insufficiency. Some drugs modify lipid metabolism and these include alcohol, beta-adrenergic blockers, diuretics, progestagens, corticosteroids (Garmendia, 2003). Treatment of the underlying cause or discontinuation of offending drug may resolve the dyslipoproteinaemia. Lipid and lipoprotein abnormalities are common observations and are regarded as modifiable risk factors for development of cardiovascular diseases.
Hyperlipo-proteinaemia | Sub-type | Classification | Defect | Lipoprotein increased | Treatment |
Type I | a, c | Familial hyperchylo-micronemia | ↓ Lipoprotein lipase (LpL) | Chylomicrons | Diet control |
b | apoprotein CII deficiency | Altered Apo CII | |||
Type II | a | Familial hypercholesterolemia | LDL receptor deficiency | LDL | Bile acid sequestrants, statins,niacin |
b | Familial combined hyperlipidemia | ↓ LDL receptor or and ↑Apo B | LDL and VLDL | Statins, niacin,fibrate | |
Type III | Familial dysbetalipo-proteinaemia | Apo E2 synthesis | IDL | Fibrate, statins | |
Type IV | Familial hypertriglyce-ridaemia | ↑VLDL and ↓LpL | VLDL | Fibrate, niacin, statin | |
Type V | ↑VLDL and ↓LpL | VLDL and chylomicrons | Niacin, fibrate |
Arteries are blood vessels that carry oxygenated blood from the heart to all tissues of the body. The arterial wall is composed of three layers, namely the intima (inner lining), media and adventitia. A single layer of endothelial cells line the inner surface of the intima, forming a barrier to blood cells and plasma flowing within the blood vessel. Atherosclerosis is characterized by lesions in the intima of arteries, seen as raised fibrous plagues ranging in colour from pearly gray to yellowish gray. The cellular components of the plaque include a cell similar to the adjacent endothelial cell, macrophages, fibrinogen from which fibrin is formed and white blood cells intersparsed between dense connective tissue which consist majorly of collagen fibers. The cells within and around the plaque are usually lipid ladened. Atherosclerosis poses a high risk not just because it can close up an artery, slowing down or entirely restricting blood flow, but may also lead to thrombus formation. A thrombus is a complex aggregation of platelets, red and white blood cells in a fibrin network. Several theories have emanated, suggesting the actual pathogenesis of atherosclerosis.
Schoenhagen (2006) documented the different theories that have been postulated in the course of history. In 1851, a scientist, Rokitansky suggested the encrustation theory or thrombogenesis in which it is said that atherosclerosis began in the intima of arteries with the deposition of thrombus. This is followed by the organisation of the thrombus through infiltration of fibroblast, secondarily followed by deposition of lipid. The German pathologist, Rudolf Virchow postulated the insudation or inflammation theory in 1856, a different initiation of atherosclerosis. It was suggested that infiltration of fatty substances from the blood stream into the arterial wall leads to deposition of cholesterol which acts as an irritant, causing inflammation and the proliferation of cells. The cholesterol deposits act as irritant in the arterial intima, initiating inflammatory process as macrophages are incriminated as key role players in the phases of the disease. This theory was further supported by the work of N.N. Anitschkow in 1933 where he discovered that a disease resembling human atherosclerosis could be reproduced in rabbits with high serum cholesterol or LDL levels. He thus stated this occurrence may be as a result of defects in metabolism of lipids and lipids Schoenhagen, 2006).
The flow theory relates the circulation of blood in vessels to its effect on arterial wall. It stated that lesions occurred more often at curved, branching, or bifurcated sites, generally at regions of perturbed blood flow. Other hypotheses that arose from the flow theory include the stagnation point hypothesis by Fox and Hugh (1966), high wall shear stress hypothesis proposed by Fry (1968), low wall shear stress hypothesis by Caro et al. (1969), diminished lateral pressure hypothesis by Texon (1980) and the convection-diffusion hypothesis.
All the theories above were established based on three methods. Atherosclerotic plaques from autopsy findings from individuals of both sexes, various ages and race with different diseases which included hyperlipidaemia, diabetes and hypertension were considered. Epidemiological studies of factors which promote or prevent development of atherosclerosis, and finally experimental pathology which established the sequence of lesion development or regression were considered. None of these theories entirely explains the pathogenesis of atherosclerosis, but each has explained an aspect of this process.
The contributing factors to development of cardiovascular diseases are numerous as mentioned in the risk factors above. Lowering of plasma cholesterol levels is usually the first line of intervention for prevention and treatment of cardiovascular diseases. Dramatic successes have been recorded with cholesterol-lowering therapy which may suggest that maintenance of low cholesterol levels is sufficient to prevent development of atherosclerosis or reversing an established disease condition (Brunzell et al., 2008). Different approaches have been used for prevention and treatment of this condition, some are enumerated below.
High density lipoprotein-cholesterol (HDL-C) is the smallest of the lipoprotein sub-fractions. It is however, the most complicated and diverse of the lipoproteins. It is the major lipoprotein which transports excess cholesterol from the plasma to the liver for excretion or utilization in the liver and other hormone producing regions of the body. Excess cholesterol is eliminated from the body via the liver, which secretes cholesterol in bile or converts it to bile salts (Toth, 2005; Tall, 2008). Also, its anti-inflammatory property protects LDL from oxidation and limits the concentrations of oxidized components, which may pose as atherogenic treats. HDL-C have been associated with reduced risk of cardiovascular events (Duffy and Rader, 2009; Khera et al., 2011). HDL-C plays a key role in the reverse transportation of cholesterol by accepting cholesterol from lipid-laden macrophages (Lehrke et al., 2007). In the study conducted by Khera et al. (2011), the ability of HDL to promote cholesterol efflux from macrophages was strongly and inversely associated with both subclinical atherosclerosis and obstructive coronary artery disease. It was also discovered that the associations persisted after adjustment for traditional cardiovascular risk factors, including the levels of HDL cholesterol and apolipoprotein A-I. HDL has several protein constituents which are exchangeable with other lipoproteins, and it acquires different apolipoproteins in the process of maturation such as apo AII, AIV, AV, CI, CII, CIII and E which results in generation of diverse HDL particles with various metabolic functions. In addition to being carrier proteins for the HDL particle, these proteins have protective roles which they play against cardiovascular diseases, such as by acting as anti-inflammatory regulators to limit the activity of pro-inflammatory cytokines.
Nascent HDL is synthesised and secreted by the liver and small intestine. It travels in the circulation where it gathers cholesterol to form mature HDL, which then returns the cholesterol to the liver via various pathways. Apolipoprotein A-I (ApoA-I) is the major protein component of high density lipoprotein (HDL) in plasma. The protein is encoded for by APOAI gene (Breslow et al., 1982, Arinami et al., 1990). Defects in this gene have been associated with HDL deficiencies (HUGO Gene Nomenclature Committee, 2011). This protein increases the efflux of cholesterol from tissue to liver where it is excreted. A few individuals were reported to produce a HDL ApoA-I protein variant called ApoA-I Milano, an abnormal and apparently more efficient apolipoprotein. It has low measured HDL-C levels yet very low rates of cardiovascular events even with high blood cholesterol values (Franceschini et al., 1981). Apo CI, CII and apo E also accumulate in the nascent HDL particle, which serves as a store for these apolipoproteins in circulation.
Phospholipids are transferred from macrophages by a specific transporter molecule known as ATP-binding cassette transport protein A1 (ABCA-1) into the core of the lipoprotein, and cholesterols are extracted from the cells by a transporter protein derived from macrophages in the sub-endothelial spaces of tissues; ABCG-1 transporter. The eventual maturation of the HDL particle is dependent on the lecithin: cholesterol acyltransferase (LCAT), an enzyme activated by apoAI, which catalyses the formation of cholesterol esters from cholesterol. Mobilization of free cholesterol and phospholipids from IDL and LDL continues until a matured, spherical HDL particle is formed. Endocytosis of the matured HDL into hepatocytes occurs and the cholesterol and cholesterol esters are transported via a facilitated transfer to distinct pools within the cell. The modified HDL particles are secreted back into circulation where they can further acquire cholesterol before they re-circulate to the liver. The complete reverse cholesterol transport occurs with the addition of apo E to the HDL particle which facilitates their uptake and catabolism.
Activation of lipoprotein lipase (LpL) activity has been reported to have anti-atherogenic activity. Lipoprotein lipase (LpL) is a rate-limiting enzyme found on the surface of endothelial cells. It is polypeptide with 839 amino acids and an extracellular domain which binds to apo B100 and apo E. LpL catalyses the hydrolysis of the triacylglycerol (TAG) component of circulating chylomicrons and very low density lipoproteins (VLDL). The enzyme digests the TAG to fatty acids and monoglycerides. This provides non-esterified fatty acids and 2-monoacylglycerol which can be utilised immediately by cells for energy production or synthesis of other lipids. Unutilized fatty acids may be bound to circulating albumin and released slowly to meet future cellular requirements. Glycerol produced from LpL activity is transported back to the liver and kidneys, where it is converted to dihydroxyacetone phosphate in the alternative glycolytic pathway. The fatty acids from LpL activity in the muscle may diffuse into cells to be oxidized to two-carbon units or used to re-synthesis TAG which are stored in adipose cells (Clee et al., 2000; Tsutsumi, 2003). Significant LpL activity occurs in muscle, adipose tissue and lactating mammary glands. Accumulation of VLDL remnants (IDL with apo B100 and apo E are converted to LDL with further loss of triacylglycerols. Both carrier proteins are necessary for recognition of IDL and LDL by the LDL receptors in the liver, after which they are taken up into hepatocytes by endocytosis and catabolized.
Research carried out over the past two decades have not only established a central role for LpL in the overall lipid metabolism and transport but have also identified additional, non-catalytic functions of the enzyme. Furthermore, abnormalities in LpL function have been found to be associated with a number of pathophysiological conditions, including atherosclerosis, chylomicronaemia, obesity, Alzheimer\'s disease, and dyslipidaemia associated with diabetes, insulin resistance, and infection (Mead et al., 2002).
Summary of the fate of Lipoprotein sub-fractions (Adapted from http://courses.washington.edu/conj/bess/cholesterol/liver.html)
LpL encodes lipoprotein lipase, which is expressed in heart, muscle, and adipose tissue. LpL functions as a homodimer, and has the dual functions of triglyceride hydrolysis and ligand/bridging factor for receptor-mediated lipoprotein uptake. Through catalysis, VLDL is converted to IDL and then to LDL. Severe mutations that cause LpL deficiency result in type I hyperlipoproteinemia, while less extreme mutations in LpL are linked to many disorders of lipoprotein metabolism.
LpL isozymes are regulated differently depending on the tissue. For example, insulin is known to activate LpL in adipocytes and its placement in the capillary endothelium. By contrast, insulin has been shown to decrease expression of muscle LpL (Kiens et al., 1989). The form that is in adipocytes is activated by insulin, whereas that in muscle and myocardium is activated by glucagon and epinepherine. This helps to explain why during fasting, LpL activity increases in muscle tissue and decreases in adipose tissue. After feasting, the opposite occurs (Braun and Severson, 1992; Mead et al., 2002).
The concentration of LpL displayed on endothelial cell surface cannot be regulated by endothelial cells, as they neither synthesize nor degrade LpL. Instead, this regulation occurs by managing the flux of LpL arriving at the lipolytic site and being released into circulation attached to lipoproteins (Braun and Severson, 1992; Goldberg, 1996). The typical concentration of LpL in plasma is in the nanomolar range. Lipoprotein lipase deficiency leads to hypertriglyceridemia (elevated levels of triglycerides in the bloodstream) and decreased high density lipoprotein activity (Clee et al., 2000; Tsutsumi, 2003; Okubo et al., 2007). Diets high in refined carbohydrates have been shown to cause tissue-specific overexpression of LpL. This has been implicated in tissue-specific insulin resistance and consequent development of type 2 diabetes mellitus & obesity.
Several studies have reported conflicting reports on the effect of hormonal replacement therapy on plasma LDL-C and Lp(a) levels (Taskinen et al., 1996; Shlipak et al., 2000; Vigna et al., 2002). In a cohort study conducted by Danik et al. (2008), the effect of hormone replacement therapy (HT) on Lp(a) and cardiovascular risk was investigated. It was reported that the relationship of high Lp(a) levels with increased cardiovascular disease is modified by hormonal therapy. These data suggest that the predictive utility of Lp(a) is markedly attenuated among women taking HT and may inform clinicians\' interpretation of Lp(a) values in such patients. It was noteworthy that the effect of hormonal therapy was observed only in women with high LDL cholesterol levels, in agreement with previous studies suggesting an interaction between Lp(a) and LDL cholesterol (Berglung and Anuurad, 2008).
Elevated serum LDL-C and low levels of HDL-C are known as major and independent risk factors for CHD. Small, dense lipoprotein sub-fractions have been reported to have atherogenic potentials, with particular reference to Lipoprotein(a) [Lp(a)], a variant of low density lipoprotein (LDL). Other atherogenic sub-fractions of lipoproteins are VLDL, LDL, and IDL. These sub-fractions are characterized by the presence of apolipoprotein B-100, with an additional apolipoprotein known as apo(a) in the Lp(a) structure. Apo(a) is structurally and functionally similar to plasminogen and it accounts for virtually all the genetic variability in plasma Lp(a) levels. Variation of length within the kringle 4-encoding region of the apo(a) gene may account for a greater proportion of the inter-individual variation in plasma Lp(a) concentrations, with a strong genetic involvement inherited as a single autosomal dominant trait.
In the course of the pathogenesis of atherosclerosis, oxidized LDL is taken up by macrophages and into endothelial cells. This leads to formation of atherosclerotic plaques which precedes development of CHD. Oxidized LDL is antigenic and titres of auto-antibodies against oxidized LDL in plasma can be used as indicator of a positive association with CHD. A positive association has also been established between plasma level of LDL, specifically oxidized LDL and other risk factors contributing to development of CHD. Such risk factors were identified as hypertriglyceridemia, reduced HDL-C levels, abdominal obesity and insulin resistance. Treatment of CHD can be achieved by lowering of plasma cholesterol levels which has been achieved by cholesterol-lowering therapy, suggesting that maintenance of low cholesterol levels may sufficiently prevent or reverse an established atherosclerosis. Increasing plasma levels of HDL-C has been reported to also be of benefit. HDL-C has anti-inflammatory activity which may prevent oxidation of LDL and it plays a key role in reverse transportation of cholesterol from lipid-laden macrophages.
The enzyme Lipoprotein lipase (LpL) may be useful in chemotherapy or prophylaxis of CHD. LpL has anti-atherogenic activity by its dual functions of triglyceride hydrolysis and ligand/brigding factor for receptor-mediated lipoprotein uptake. Activation of the enzyme is dependent on the tissue, resulting in variability of its activity. Hormonal replacement therapy may also be of benefit to patients with CHD and related diseases, but reported on current findings are conflicting.
The concept of biomarkers has existed from the time of the inception of ayurvedic medicine, just around the seventh century when the sweetness of urine was linked to diabetes even though the terminology had not been developed then [1]. The perspective of what constitutes the definition of a biomarker is somewhat diverse. Biomarkers (biological markers) are generally biomolecules whose qualitative and quantitative presence provides an indication of the state of a biological system. A more exhaustive definition as provided by the World Health Organization (WHO) led joint venture on chemical safety that describes a biomarker as any substance, structure, or process that can be measured in the body or its products that can influence or predict the incidence of outcome or disease [2]. The application of biomarkers has attained a vital and grounded position in clinical research, usually as predictors of the clinical outcomes for a varied number of disease conditions and their management [3].
\nExtensive scientific investigation into the mechanism of wound healing has revealed that the traditional guides in the determination of the wound healing potential, i.e., erythrocyte sedimentation rate (ESR) and C-reactive protein, do not yield enough positive and negative predictive values [4]. In lieu of the scientific evidence available, the focus has shifted to cytokines, chemokines, and proteases which hold the greatest potential as biomarkers [4].
\nCytokines are proteins of relatively low molecular weight that are secreted to influence or modulate the behavior of immune cells and also other cells [5]. Crucial among them include interleukins, lymphokines, and other signaling molecules such as interferons and tissue necrosis factor (TNF-α). It has been long considered and corroborated by scientific evidence that pro-inflammatory cytokines such as interleukins 1α (IL-1α), 1β (IL-1β), and 6 (IL-6) and TNF-α play essential roles in wound healing process such as the stimulation of keratinocyte and fibroblast proliferation, modulation of immune response, synthesis and breakdown of extracellular matrix proteins, and the chemotaxis of fibroblast to the wound site [6].
\nGrellner et al. [7, 8] in their work to quantitatively analyze pro-inflammatory cytokines in human skin wounds realized an upregulation of the expression of IL-1α, IL-1β, IL-6, and TNF-α in the inflammatory phase of the wound healing process. The levels of these pro-inflammatory cytokines (TNF-α, IL-1, and IL-6) were higher in nonhealing wounds than healing wounds owing to the fact that nonhealing wounds stay in the inflammatory phase of wound healing process [4]. Bilder et al. [9] also report an increase in the levels of IL-8 in chronic nonhealing wounds as opposed to those with a healing potential. Ligi et al. [10] upon the assessment of several studies which evaluated the level expression of cytokines and chemokines in the microenvironment of a chronic ulcer alluded to a heightened pro-inflammatory condition in a nonhealing wound, thus corroborating other studies. It was however noted that the level of cytokines detectable does not necessarily correlate to its bioactivity due to anti-inflammatory cytokines whose presence counteracts the activity of these pro-inflammatory cytokines [10]. There are also specific cytokine inhibitors and proteolytic enzymes that also act on these cytokines to mask their bioavailability [10]. Patel et al. [4] also report the inconsistency in wound and serum levels of cytokines which poses a challenge in its use as reliable biomarkers of nonhealing wounds.
\nThe IL-1 family of cytokines is made up of two pro-inflammatory cytokines, namely, IL-α and IL-β. Interleukin 1 is primarily sourced from macrophages in the event of injury, infection, and antigenic challenge although the epidermal, epithelial, lymphoid, and vascular tissues also serve as reservoirs for the polypeptide [11]. The actions of IL-1 span from systemic changes in the neurological, hematologic, endocrinologic, and metabolic systems to some local effects that are particularly relevant in wound healing [12]. By influencing both destructive and repair processes, it contributes the mesenchymal tissue remodeling, and it does so by influencing quite a number of cells. First of all, it stimulates capillary endothelial cells to produce chemokines such as MCP-1 and also cause an upregulation of the synthesis of vascular adhesion molecules such as ICAM-1, VCAM-1, and E-selectin [13, 14]. The combined effect of these two actions is to cause the infiltration of the injury site with mononuclear cells, thus setting the stage for inflammatory response. The expression of matrix metalloproteases (MMPs) from resident fibroblasts is also under the control of IL-1. The call of MMPs to play results in the degradation of the extracellular matrix to allow for enhanced monocyte migration. It also leads to a down-modulation of the inflammatory response as MMPs degrade IL-1. Inhibiting the IL-1 pathway through the use of recombinant antibodies and macrophages from IL-1 receptor knockout mice appeared to turn the tables around as far as the wound microenvironment is concerned by inducing a switch from pro-inflammatory to healing-associated macrophage phenotypes and growth factors [14]. Therefore, there is a negative implication for wound healing in the absence of high expression of IL-1.
\nInterleukin 6 is described as the chief contributor to the stimulation of a majority of the acute-phase proteins during inflammation. IL-6-deficient transgenic mice (IL-6 KO) therefore showed a substantial delayed cutaneous wound healing relative to the wild-type control animals by about threefold, the time required for healing [15].
\nBased on similar animal model studies on IL-6 knockout mice and the administration of recombinant murine IL-6 protein, IL-6 was found to be essential in stimulating the mitogenic activity of keratinocytes, an action that has been linked to scar formation as well as exerting a chemo-attractive action on neutrophils [6]. These effects seek to kick-start the wound healing process. However, a study conducted to determine the indicators of inflammation in the pathogenesis of diabetic foot ulcers identified a positive correlation between high serum IL-6 levels in diabetic patients with foot ulcers and low serum IL-6 levels in those without foot ulcers. This implicates its effect on poor wound healing [16].
\nThis is not surprising as IL-6 has a reputation for dictating the transition from acute to chronic inflammation systemically by its stimulatory effects on T and B cells.
\nTumor necrosis factor alpha (TNF-α) is a key pro-inflammatory cytokine involved in the early phase of most inflammatory events in the body. Employing mouse models, the expression of TNF-α at detectable levels was discovered to happen just after wound creation and sees an increase in the first several hours until it reaches a peak within 24 hours after which it returns to the basal level [17]. Vascular endothelial cells, keratinocytes, and fibroblasts are the major sources of TNF-α which cause an initiation of the inflammatory phase of the wound healing by promoting the recruitment of inflammatory leukocytes. TNF-α is also involved in the regulation of the activity of fibroblasts, keratinocytes, and vascular endothelial cells as well as in modulating synthesis of extracellular matrix proteins and matrix metalloproteinase [17, 18]. Based on diabetic models, an increase in TNF-α level coupled with decrease in IL-10 that has anti-inflammatory properties results in sustained expression of chemokines CXCL2 and CCL2 and leads to continuous infiltration of leucocytes to the injury site. This ultimately prolongs the inflammation and reduces the wound healing potential [19].
\nTransforming growth factor describes the superfamily for pluripotent cytokines which have very important functions to perform during disease, homeostasis, development, and repair. These sets of proteins are structurally related, but functionally distinguishable and relevant among them for wound healing are the isoforms TGF-β 1–3 [20]. The roles of these isoforms in the wound healing process can be both distinct and overlapping. However, the overall nature of their contribution to the wound healing has generated some controversy and thus is among the most studied molecules involved in the process [6]. Transforming growth factor β1 (TNF-β1) however has the widest spectrum of actions, affecting all manners of cell types that are involved in all stages of wound healing. These effects have been reported to be both positive and negative [21]. Historically, the synthesis of TNF-β1 from keratinocytes, platelets, and macrophages is upregulated right after injury, and this is crucial for initiating inflammation and granulation tissue formation. In addition, TNF-β1 contributes to the chemotactic migration of cells during wound repair. Some proteases such as MMP-1, MMP-2, MMP-3, and MMP-9 are also under the control of TNF-β1 [6, 22]. Based on human studies, TNF-β1 was found to stimulate the production of extracellular matrix molecules, including collagens and fibronectin, which strengthen the repaired wound. In spite of this knowledge, available evidence goes to raise questions about the true effects of TNF-β1 levels on wound healing [23]. Wound healing in Smad knockout mice, which have the signaling pathway of TNF-β1 blocked, was rather accelerated to the surprise of the investigators. In similar fashion, TNF-β1 knockout mice showed demonstrated reepithelialization during incisional wound repair, in comparison with wild-type mice. The consensus in the face of current evidence is that the selective inhibition of TNF-β1 in some cells may prove beneficial [24].
\nThe growth factors are essentially responsible for the initiation of the proliferation stage of the wound healing process. The platelet-derived growth factor (PDGF), transforming growth factors (TGF-𝛼, TGF-𝛽), insulin growth factor (IGF-1), fibroblast growth factor (FGF), and granulocyte-macrophage colony-stimulating factors (GM-CSF) are examples of growth factors whose roles in wound healing as well as their possible use as biomarkers have been studied extensively based on their expressed levels [25]. In spite of the fact that insight about ideal levels and the spatiotemporal distribution of growth factors is far from complete, available data points to no local growth factor deficiency in chronic leg ulcers with the possible exception of TGF [6]. Trengove et al. [26] after studying wound fluids from both healing and nonhealing wounds arrive at similar conclusion that poor wound healing may be due to inflammatory mediators rather than a deficiency of growth factors.
\nPlatelet-derived growth factors (PDGFs) are made up of a family of homodimeric or heterodimeric growth factors, including PDGF-AA, PDGF-AB, PDGF-BB, PDGF-CC, and PDGF-DD [27]. PDGF has been established to have chemotactic role for cells that migrate to the healing wound site such as fibroblasts, neutrophils, and monocytes. It was actually the very first growth factor shown to have this function [28]. It additionally stimulates the proliferation of fibroblast and the deposition of extracellular matrix. In vitro studies have also revealed that it stimulates insulin growth factor (IGF) release in fibroblasts which is vital to the initiation of the repair process [28]. Lastly, it stimulates fibroblasts to contract collagen matrices and induces the myofibroblast phenotype in the implicated cells. It has thus been established to be a major player in the wound healing and has formed the basis for studies into its clinical application in the treatment of wound healing disorders.
\nOwing to the close proximity of the expression sites of the PDGF, which is predominantly in the epidermis, and its receptors which are also in the dermis and granulating tissue, a paracrine mechanism has been suggested for its action [6, 29]. However, unlike other growth factors like fibroblast growth factor (FGF) and vascular epithelial growth factor (VEGF) that see an overexpression in the microenvironment or at the site of a healing wound or one in a granulation phase, the increase in the expression of PDGF-BB is without this spatial limitation as its levels in plasma also increases. It does make it potentially useful as the biomarker in wound healing [10].
\nThe action of proteases and their inhibitors goes a long way to influence the equilibrium between extracellular matrix (ECM) degradation and deposition which is responsible for the coordinated and timely healing of wounds [30]. There is an overwhelming wealth of evidence to suggest that nonhealing wounds are characterized by an increase in the levels of proteases and an imbalance in the protease/protease inhibitor levels [30, 31]. This manifests as a persistence of proteolysis and degradation of the extracellular matrix causing wound healing to delay. Significant among these proteases are the matrix metalloproteases (MMPs) [32]. MMPs are part of a family of zinc endopeptidase which essentially help in the degradation of provisional extracellular matrix, facilitate the migration of inflammatory cells to the wound site, remodel the granulation tissue, and modulate angiogenesis [28]. MMP activity as measured using Azocoll assay was found to be significantly elevated in chronic wounds as compared to acute wounds, thus implicating it poor wound healing [26].
\nProteases as biomarkers for wound healing hold the key to transform clinical approach to the management of wounds. For example, the appropriateness of using protease-modulating dressing and tissue-engineered products, scaffolds, and skin grafts for the treatment can be made by the determination of the levels of proteases [33].
\nMatrix metalloproteinases (MMPs) are a group of endopeptidase that are zinc and calcium dependent and are usually divided into six groups depending on the substrate they act on. These MMPs consist of collagenases (MMP-1, MMP-3, MMP-8); gelatinases (MMP-2, MMP-9); stromelysins (MMP-3, MMP-10); matrilysins (MMP-7, MMP-26); membrane-type MMPs (MT-MMP) like MMP-14, MMP-15, MMP-16, and MMP-24; and other MMPs (MMP-11, MMP-12, MMP-19, MMP-20, MMP-22, MMP-23, MMP-28) [34].
\nVarious MMPs are relevant to the wound healing process at varied points, and the tight control of their proteolytic activity is also essential to conduct the different events of wound healing [36]. MMPs are however generally involved in the inflammatory, proliferative, and remodeling phases of the wound healing process by modulating cytokine/chemokine activity by activating them enzymatically or influencing their availability by cleaving them from cell surface. Additionally, the actions of MMPs involve the breakdown of proteins part of the cell-cell and cell-extracellular matrix interaction [35, 36].
\nIn terms of the predictive roles of MMPs’ level for the wound healing process, some studies have focused on the MMP-1 to tissue inhibitor of metalloproteinase (TIMP-1) ratio. In one study, for instance, a significant correlation was found between a high ratio of MMP-1/TIMP-1 and good healing (r = 0.65, p = 0.008) with receiver operator curve (ROC) analysis showing an MMP-1/TIMP-1 ratio of 0.39 being the best predictive value for wound healing. High levels of MMP-8 and MMP-9 also appear to have negative predictive value for the process of wound healing [32].
\nWith the growing research into the therapeutic benefits of biomarkers comes the challenge of identifying biomarkers that satisfy the required characteristics for use clinically. It is prudent to validate new biomarkers affecting the wound healing process by employing innovative, simple, and cost-effective molecular approaches to determine the type, level, and activity of all potential biomarkers. With the advent of trendsetting technical knowhow in defining diseases and other biological processes, it has become increasingly possible to identify and characterize novel biomarkers of the wound healing process. Continuing the research into identification of new biomarkers affecting the wound healing process is imperative since it will eventually have weighty health benefits on patients and offer a relevant guide to wound management. This will significantly lower the risks of microbial colonization and invasion of wounds and loss of structural function as a result of chronic wounds.
\nIntechOpen 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:"105746",title:"Dr.",name:"A.W.M.M.",middleName:null,surname:"Koopman-van Gemert",slug:"a.w.m.m.-koopman-van-gemert",fullName:"A.W.M.M. Koopman-van Gemert",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/105746/images/5803_n.jpg",biography:"Dr. Anna Wilhelmina Margaretha Maria Koopman-van Gemert MD, PhD, became anaesthesiologist-intensivist from the Radboud University Nijmegen (the Netherlands) in 1987. She worked for a couple of years also as a blood bank director in Nijmegen and introduced in the Netherlands the Cell Saver and blood transfusion alternatives. She performed research in perioperative autotransfusion and obtained the degree of PhD in 1993 publishing Peri-operative autotransfusion by means of a blood cell separator.\nBlood transfusion had her special interest being the president of the Haemovigilance Chamber TRIP and performing several tasks in local and national blood bank and anticoagulant-blood transfusion guidelines committees. Currently, she is working as an associate professor and up till recently was the dean at the Albert Schweitzer Hospital Dordrecht. She performed (inter)national tasks as vice-president of the Concilium Anaesthesia and related committees. \nShe performed research in several fields, with over 100 publications in (inter)national journals and numerous papers on scientific conferences. \nShe received several awards and is a member of Honour of the Dutch Society of Anaesthesia.",institutionString:null,institution:{name:"Albert Schweitzer Hospital",country:{name:"Gabon"}}},{id:"83089",title:"Prof.",name:"Aaron",middleName:null,surname:"Ojule",slug:"aaron-ojule",fullName:"Aaron Ojule",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Port Harcourt",country:{name:"Nigeria"}}},{id:"295748",title:"Mr.",name:"Abayomi",middleName:null,surname:"Modupe",slug:"abayomi-modupe",fullName:"Abayomi Modupe",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/no_image.jpg",biography:null,institutionString:null,institution:{name:"Landmark University",country:{name:"Nigeria"}}},{id:"94191",title:"Prof.",name:"Abbas",middleName:null,surname:"Moustafa",slug:"abbas-moustafa",fullName:"Abbas Moustafa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94191/images/96_n.jpg",biography:"Prof. Moustafa got his doctoral degree in earthquake engineering and structural safety from Indian Institute of Science in 2002. He is currently an associate professor at Department of Civil Engineering, Minia University, Egypt and the chairman of Department of Civil Engineering, High Institute of Engineering and Technology, Giza, Egypt. He is also a consultant engineer and head of structural group at Hamza Associates, Giza, Egypt. Dr. Moustafa was a senior research associate at Vanderbilt University and a JSPS fellow at Kyoto and Nagasaki Universities. He has more than 40 research papers published in international journals and conferences. He acts as an editorial board member and a reviewer for several regional and international journals. His research interest includes earthquake engineering, seismic design, nonlinear dynamics, random vibration, structural reliability, structural health monitoring and uncertainty modeling.",institutionString:null,institution:{name:"Minia University",country:{name:"Egypt"}}},{id:"84562",title:"Dr.",name:"Abbyssinia",middleName:null,surname:"Mushunje",slug:"abbyssinia-mushunje",fullName:"Abbyssinia Mushunje",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Fort Hare",country:{name:"South Africa"}}},{id:"202206",title:"Associate Prof.",name:"Abd Elmoniem",middleName:"Ahmed",surname:"Elzain",slug:"abd-elmoniem-elzain",fullName:"Abd Elmoniem Elzain",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Kassala University",country:{name:"Sudan"}}},{id:"98127",title:"Dr.",name:"Abdallah",middleName:null,surname:"Handoura",slug:"abdallah-handoura",fullName:"Abdallah Handoura",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"École Supérieure des Télécommunications",country:{name:"Morocco"}}},{id:"91404",title:"Prof.",name:"Abdecharif",middleName:null,surname:"Boumaza",slug:"abdecharif-boumaza",fullName:"Abdecharif Boumaza",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Abbès Laghrour University of Khenchela",country:{name:"Algeria"}}},{id:"105795",title:"Prof.",name:"Abdel Ghani",middleName:null,surname:"Aissaoui",slug:"abdel-ghani-aissaoui",fullName:"Abdel Ghani Aissaoui",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/105795/images/system/105795.jpeg",biography:"Abdel Ghani AISSAOUI is a Full Professor of electrical engineering at University of Bechar (ALGERIA). He was born in 1969 in Naama, Algeria. He received his BS degree in 1993, the MS degree in 1997, the PhD degree in 2007 from the Electrical Engineering Institute of Djilali Liabes University of Sidi Bel Abbes (ALGERIA). He is an active member of IRECOM (Interaction Réseaux Electriques - COnvertisseurs Machines) Laboratory and IEEE senior member. He is an editor member for many international journals (IJET, RSE, MER, IJECE, etc.), he serves as a reviewer in international journals (IJAC, ECPS, COMPEL, etc.). He serves as member in technical committee (TPC) and reviewer in international conferences (CHUSER 2011, SHUSER 2012, PECON 2012, SAI 2013, SCSE2013, SDM2014, SEB2014, PEMC2014, PEAM2014, SEB (2014, 2015), ICRERA (2015, 2016, 2017, 2018,-2019), etc.). His current research interest includes power electronics, control of electrical machines, artificial intelligence and Renewable energies.",institutionString:"University of Béchar",institution:{name:"University of Béchar",country:{name:"Algeria"}}},{id:"99749",title:"Dr.",name:"Abdel Hafid",middleName:null,surname:"Essadki",slug:"abdel-hafid-essadki",fullName:"Abdel Hafid Essadki",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"École Nationale Supérieure de Technologie",country:{name:"Algeria"}}},{id:"101208",title:"Prof.",name:"Abdel Karim",middleName:"Mohamad",surname:"El Hemaly",slug:"abdel-karim-el-hemaly",fullName:"Abdel Karim El Hemaly",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/101208/images/733_n.jpg",biography:"OBGYN.net Editorial Advisor Urogynecology.\nAbdel Karim M. A. El-Hemaly, MRCOG, FRCS � Egypt.\n \nAbdel Karim M. A. El-Hemaly\nProfessor OB/GYN & Urogynecology\nFaculty of medicine, Al-Azhar University \nPersonal Information: \nMarried with two children\nWife: Professor Laila A. Moussa MD.\nSons: Mohamad A. M. El-Hemaly Jr. MD. Died March 25-2007\nMostafa A. M. El-Hemaly, Computer Scientist working at Microsoft Seatle, USA. \nQualifications: \n1.\tM.B.-Bch Cairo Univ. June 1963. \n2.\tDiploma Ob./Gyn. Cairo Univ. April 1966. \n3.\tDiploma Surgery Cairo Univ. Oct. 1966. \n4.\tMRCOG London Feb. 1975. \n5.\tF.R.C.S. Glasgow June 1976. \n6.\tPopulation Study Johns Hopkins 1981. \n7.\tGyn. Oncology Johns Hopkins 1983. \n8.\tAdvanced Laparoscopic Surgery, with Prof. Paulson, Alexandria, Virginia USA 1993. \nSocieties & Associations: \n1.\t Member of the Royal College of Ob./Gyn. London. \n2.\tFellow of the Royal College of Surgeons Glasgow UK. \n3.\tMember of the advisory board on urogyn. FIGO. \n4.\tMember of the New York Academy of Sciences. \n5.\tMember of the American Association for the Advancement of Science. \n6.\tFeatured in �Who is Who in the World� from the 16th edition to the 20th edition. \n7.\tFeatured in �Who is Who in Science and Engineering� in the 7th edition. \n8.\tMember of the Egyptian Fertility & Sterility Society. \n9.\tMember of the Egyptian Society of Ob./Gyn. \n10.\tMember of the Egyptian Society of Urogyn. \n\nScientific Publications & Communications:\n1- Abdel Karim M. El Hemaly*, Ibrahim M. Kandil, Asim Kurjak, Ahmad G. Serour, Laila A. S. Mousa, Amr M. Zaied, Khalid Z. El Sheikha. \nImaging the Internal Urethral Sphincter and the Vagina in Normal Women and Women Suffering from Stress Urinary Incontinence and Vaginal Prolapse. Gynaecologia Et Perinatologia, Vol18, No 4; 169-286 October-December 2009.\n2- Abdel Karim M. El Hemaly*, Laila A. S. Mousa Ibrahim M. Kandil, Fatma S. El Sokkary, Ahmad G. Serour, Hossam Hussein.\nFecal Incontinence, A Novel Concept: The Role of the internal Anal sphincter (IAS) in defecation and fecal incontinence. Gynaecologia Et Perinatologia, Vol19, No 2; 79-85 April -June 2010.\n3- Abdel Karim M. El Hemaly*, Laila A. S. Mousa Ibrahim M. Kandil, Fatma S. El Sokkary, Ahmad G. Serour, Hossam Hussein.\nSurgical Treatment of Stress Urinary Incontinence, Fecal Incontinence and Vaginal Prolapse By A Novel Operation \n"Urethro-Ano-Vaginoplasty"\n Gynaecologia Et Perinatologia, Vol19, No 3; 129-188 July-September 2010.\n4- Abdel Karim M. El Hemaly*, Ibrahim M. Kandil, Laila A. S. Mousa and Mohamad A.K.M.El Hemaly.\nUrethro-vaginoplasty, an innovated operation for the treatment of: Stress Urinary Incontinence (SUI), Detursor Overactivity (DO), Mixed Urinary Incontinence and Anterior Vaginal Wall Descent. \nhttp://www.obgyn.net/urogyn/urogyn.asp?page=/urogyn/articles/ urethro-vaginoplasty_01\n\n5- Abdel Karim M. El Hemaly, Ibrahim M Kandil, Mohamed M. Radwan.\n Urethro-raphy a new technique for surgical management of Stress Urinary Incontinence.\nhttp://www.obgyn.net/urogyn/urogyn.asp?page=/urogyn/articles/\nnew-tech-urethro\n\n6- Abdel Karim M. El Hemaly, Ibrahim M Kandil, Mohamad A. Rizk, Nabil Abdel Maksoud H., Mohamad M. Radwan, Khalid Z. El Shieka, Mohamad A. K. M. El Hemaly, and Ahmad T. El Saban.\nUrethro-raphy The New Operation for the treatment of stress urinary incontinence, SUI, detrusor instability, DI, and mixed-type of urinary incontinence; short and long term results. \nhttp://www.obgyn.net/urogyn/urogyn.asp?page=urogyn/articles/\nurethroraphy-09280\n\n7-Abdel Karim M. El Hemaly, Ibrahim M Kandil, and Bahaa E. El Mohamady. Menopause, and Voiding troubles. \nhttp://www.obgyn.net/displayppt.asp?page=/English/pubs/features/presentations/El-Hemaly03/el-hemaly03-ss\n\n8-El Hemaly AKMA, Mousa L.A. Micturition and Urinary\tContinence. Int J Gynecol Obstet 1996; 42: 291-2. \n\n9-Abdel Karim M. El Hemaly.\n Urinary incontinence in gynecology, a review article.\nhttp://www.obgyn.net/urogyn/urogyn.asp?page=/urogyn/articles/abs-urinary_incotinence_gyn_ehemaly \n\n10-El Hemaly AKMA. Nocturnal Enuresis: Pathogenesis and Treatment. \nInt Urogynecol J Pelvic Floor Dysfunct 1998;9: 129-31.\n \n11-El Hemaly AKMA, Mousa L.A.E. Stress Urinary Incontinence, a New Concept. Eur J Obstet Gynecol Reprod Biol 1996; 68: 129-35. \n\n12- El Hemaly AKMA, Kandil I. M. Stress Urinary Incontinence SUI facts and fiction. Is SUI a puzzle?! http://www.obgyn.net/displayppt.asp?page=/English/pubs/features/presentations/El-Hemaly/el-hemaly-ss\n\n13-Abdel Karim El Hemaly, Nabil Abdel Maksoud, Laila A. Mousa, Ibrahim M. Kandil, Asem Anwar, M.A.K El Hemaly and Bahaa E. El Mohamady. \nEvidence based Facts on the Pathogenesis and Management of SUI. http://www.obgyn.net/displayppt.asp?page=/English/pubs/features/presentations/El-Hemaly02/el-hemaly02-ss\n\n14- Abdel Karim M. El Hemaly*, Ibrahim M. Kandil, Mohamad A. Rizk and Mohamad A.K.M.El Hemaly.\n Urethro-plasty, a Novel Operation based on a New Concept, for the Treatment of Stress Urinary Incontinence, S.U.I., Detrusor Instability, D.I., and Mixed-type of Urinary Incontinence.\nhttp://www.obgyn.net/urogyn/urogyn.asp?page=/urogyn/articles/urethro-plasty_01\n\n15-Ibrahim M. Kandil, Abdel Karim M. El Hemaly, Mohamad M. Radwan: Ultrasonic Assessment of the Internal Urethral Sphincter in Stress Urinary Incontinence. The Internet Journal of Gynecology and Obstetrics. 2003. Volume 2 Number 1. \n\n\n16-Abdel Karim M. El Hemaly. Nocturnal Enureses: A Novel Concept on its pathogenesis and Treatment.\nhttp://www.obgyn.net/urogynecolgy/?page=articles/nocturnal_enuresis\n\n17- Abdel Karim M. El Hemaly. Nocturnal Enureses: An Update on the pathogenesis and Treatment.\nhttp://www.obgyn.net/urogynecology/?page=/ENHLIDH/PUBD/FEATURES/\nPresentations/ Nocturnal_Enuresis/nocturnal_enuresis\n\n18-Maternal Mortality in Egypt, a cry for help and attention. The Second International Conference of the African Society of Organization & Gestosis, 1998, 3rd Annual International Conference of Ob/Gyn Department � Sohag Faculty of Medicine University. Feb. 11-13. Luxor, Egypt. \n19-Postmenopausal Osteprosis. The 2nd annual conference of Health Insurance Organization on Family Planning and its role in primary health care. Zagaziz, Egypt, February 26-27, 1997, Center of Complementary Services for Maternity and childhood care. \n20-Laparoscopic Assisted vaginal hysterectomy. 10th International Annual Congress Modern Trends in Reproductive Techniques 23-24 March 1995. Alexandria, Egypt. \n21-Immunological Studies in Pre-eclamptic Toxaemia. Proceedings of 10th Annual Ain Shams Medical Congress. Cairo, Egypt, March 6-10, 1987. \n22-Socio-demographic factorse affecting acceptability of the long-acting contraceptive injections in a rural Egyptian community. Journal of Biosocial Science 29:305, 1987. \n23-Plasma fibronectin levels hypertension during pregnancy. The Journal of the Egypt. Soc. of Ob./Gyn. 13:1, 17-21, Jan. 1987. \n24-Effect of smoking on pregnancy. Journal of Egypt. Soc. of Ob./Gyn. 12:3, 111-121, Sept 1986. \n25-Socio-demographic aspects of nausea and vomiting in early pregnancy. Journal of the Egypt. Soc. of Ob./Gyn. 12:3, 35-42, Sept. 1986. \n26-Effect of intrapartum oxygen inhalation on maternofetal blood gases and pH. Journal of the Egypt. Soc. of Ob./Gyn. 12:3, 57-64, Sept. 1986. \n27-The effect of severe pre-eclampsia on serum transaminases. The Egypt. J. Med. Sci. 7(2): 479-485, 1986. \n28-A study of placental immunoreceptors in pre-eclampsia. The Egypt. J. Med. Sci. 7(2): 211-216, 1986. \n29-Serum human placental lactogen (hpl) in normal, toxaemic and diabetic pregnant women, during pregnancy and its relation to the outcome of pregnancy. Journal of the Egypt. Soc. of Ob./Gyn. 12:2, 11-23, May 1986. \n30-Pregnancy specific B1 Glycoprotein and free estriol in the serum of normal, toxaemic and diabetic pregnant women during pregnancy and after delivery. Journal of the Egypt. Soc. of Ob./Gyn. 12:1, 63-70, Jan. 1986. Also was accepted and presented at Xith World Congress of Gynecology and Obstetrics, Berlin (West), September 15-20, 1985. \n31-Pregnancy and labor in women over the age of forty years. Accepted and presented at Al-Azhar International Medical Conference, Cairo 28-31 Dec. 1985. \n32-Effect of Copper T intra-uterine device on cervico-vaginal flora. Int. J. Gynaecol. Obstet. 23:2, 153-156, April 1985. \n33-Factors affecting the occurrence of post-Caesarean section febrile morbidity. Population Sciences, 6, 139-149, 1985. \n34-Pre-eclamptic toxaemia and its relation to H.L.A. system. Population Sciences, 6, 131-139, 1985. \n35-The menstrual pattern and occurrence of pregnancy one year after discontinuation of Depo-medroxy progesterone acetate as a postpartum contraceptive. Population Sciences, 6, 105-111, 1985. \n36-The menstrual pattern and side effects of Depo-medroxy progesterone acetate as postpartum contraceptive. Population Sciences, 6, 97-105, 1985. \n37-Actinomyces in the vaginas of women with and without intrauterine contraceptive devices. Population Sciences, 6, 77-85, 1985. \n38-Comparative efficacy of ibuprofen and etamsylate in the treatment of I.U.D. menorrhagia. Population Sciences, 6, 63-77, 1985. \n39-Changes in cervical mucus copper and zinc in women using I.U.D.�s. Population Sciences, 6, 35-41, 1985. \n40-Histochemical study of the endometrium of infertile women. Egypt. J. Histol. 8(1) 63-66, 1985. \n41-Genital flora in pre- and post-menopausal women. Egypt. J. Med. Sci. 4(2), 165-172, 1983. \n42-Evaluation of the vaginal rugae and thickness in 8 different groups. Journal of the Egypt. Soc. of Ob./Gyn. 9:2, 101-114, May 1983. \n43-The effect of menopausal status and conjugated oestrogen therapy on serum cholesterol, triglycerides and electrophoretic lipoprotein patterns. Al-Azhar Medical Journal, 12:2, 113-119, April 1983. \n44-Laparoscopic ventrosuspension: A New Technique. Int. J. Gynaecol. Obstet., 20, 129-31, 1982. \n45-The laparoscope: A useful diagnostic tool in general surgery. Al-Azhar Medical Journal, 11:4, 397-401, Oct. 1982. \n46-The value of the laparoscope in the diagnosis of polycystic ovary. Al-Azhar Medical Journal, 11:2, 153-159, April 1982. \n47-An anaesthetic approach to the management of eclampsia. Ain Shams Medical Journal, accepted for publication 1981. \n48-Laparoscopy on patients with previous lower abdominal surgery. Fertility management edited by E. Osman and M. Wahba 1981. \n49-Heart diseases with pregnancy. Population Sciences, 11, 121-130, 1981. \n50-A study of the biosocial factors affecting perinatal mortality in an Egyptian maternity hospital. Population Sciences, 6, 71-90, 1981. \n51-Pregnancy Wastage. Journal of the Egypt. Soc. of Ob./Gyn. 11:3, 57-67, Sept. 1980. \n52-Analysis of maternal deaths in Egyptian maternity hospitals. Population Sciences, 1, 59-65, 1979. \nArticles published on OBGYN.net: \n1- Abdel Karim M. El Hemaly*, Ibrahim M. Kandil, Laila A. S. Mousa and Mohamad A.K.M.El Hemaly.\nUrethro-vaginoplasty, an innovated operation for the treatment of: Stress Urinary Incontinence (SUI), Detursor Overactivity (DO), Mixed Urinary Incontinence and Anterior Vaginal Wall Descent. \nhttp://www.obgyn.net/urogyn/urogyn.asp?page=/urogyn/articles/ urethro-vaginoplasty_01\n\n2- Abdel Karim M. El Hemaly, Ibrahim M Kandil, Mohamed M. Radwan.\n Urethro-raphy a new technique for surgical management of Stress Urinary Incontinence.\nhttp://www.obgyn.net/urogyn/urogyn.asp?page=/urogyn/articles/\nnew-tech-urethro\n\n3- Abdel Karim M. El Hemaly, Ibrahim M Kandil, Mohamad A. Rizk, Nabil Abdel Maksoud H., Mohamad M. Radwan, Khalid Z. El Shieka, Mohamad A. K. M. El Hemaly, and Ahmad T. El Saban.\nUrethro-raphy The New Operation for the treatment of stress urinary incontinence, SUI, detrusor instability, DI, and mixed-type of urinary incontinence; short and long term results. \nhttp://www.obgyn.net/urogyn/urogyn.asp?page=urogyn/articles/\nurethroraphy-09280\n\n4-Abdel Karim M. El Hemaly, Ibrahim M Kandil, and Bahaa E. El Mohamady. Menopause, and Voiding troubles. \nhttp://www.obgyn.net/displayppt.asp?page=/English/pubs/features/presentations/El-Hemaly03/el-hemaly03-ss\n\n5-El Hemaly AKMA, Mousa L.A. Micturition and Urinary\tContinence. Int J Gynecol Obstet 1996; 42: 291-2. \n\n6-Abdel Karim M. El Hemaly.\n Urinary incontinence in gynecology, a review article.\nhttp://www.obgyn.net/urogyn/urogyn.asp?page=/urogyn/articles/abs-urinary_incotinence_gyn_ehemaly \n\n7-El Hemaly AKMA. Nocturnal Enuresis: Pathogenesis and Treatment. \nInt Urogynecol J Pelvic Floor Dysfunct 1998;9: 129-31.\n \n8-El Hemaly AKMA, Mousa L.A.E. Stress Urinary Incontinence, a New Concept. Eur J Obstet Gynecol Reprod Biol 1996; 68: 129-35. \n\n9- El Hemaly AKMA, Kandil I. M. Stress Urinary Incontinence SUI facts and fiction. Is SUI a puzzle?! http://www.obgyn.net/displayppt.asp?page=/English/pubs/features/presentations/El-Hemaly/el-hemaly-ss\n\n10-Abdel Karim El Hemaly, Nabil Abdel Maksoud, Laila A. Mousa, Ibrahim M. Kandil, Asem Anwar, M.A.K El Hemaly and Bahaa E. El Mohamady. \nEvidence based Facts on the Pathogenesis and Management of SUI. http://www.obgyn.net/displayppt.asp?page=/English/pubs/features/presentations/El-Hemaly02/el-hemaly02-ss\n\n11- Abdel Karim M. El Hemaly*, Ibrahim M. Kandil, Mohamad A. Rizk and Mohamad A.K.M.El Hemaly.\n Urethro-plasty, a Novel Operation based on a New Concept, for the Treatment of Stress Urinary Incontinence, S.U.I., Detrusor Instability, D.I., and Mixed-type of Urinary Incontinence.\nhttp://www.obgyn.net/urogyn/urogyn.asp?page=/urogyn/articles/urethro-plasty_01\n\n12-Ibrahim M. Kandil, Abdel Karim M. El Hemaly, Mohamad M. Radwan: Ultrasonic Assessment of the Internal Urethral Sphincter in Stress Urinary Incontinence. The Internet Journal of Gynecology and Obstetrics. 2003. Volume 2 Number 1. \n\n13-Abdel Karim M. El Hemaly. Nocturnal Enureses: A Novel Concept on its pathogenesis and Treatment.\nhttp://www.obgyn.net/urogynecolgy/?page=articles/nocturnal_enuresis\n\n14- Abdel Karim M. El Hemaly. Nocturnal Enureses: An Update on the pathogenesis and Treatment.\nhttp://www.obgyn.net/urogynecology/?page=/ENHLIDH/PUBD/FEATURES/\nPresentations/ Nocturnal_Enuresis/nocturnal_enuresis",institutionString:null,institution:{name:"Al Azhar University",country:{name:"Egypt"}}},{id:"113313",title:"Dr.",name:"Abdel-Aal",middleName:null,surname:"Mantawy",slug:"abdel-aal-mantawy",fullName:"Abdel-Aal Mantawy",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Ain Shams University",country:{name:"Egypt"}}}],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:1683},chapterEmbeded:{data:{}},editorApplication:{success:null,errors:{}},ofsBooks:{filterParams:{sort:"qngrRaqGuveqFgrcChoyvfu"},books:[],filtersByTopic:[{group:"topic",caption:"Agricultural and Biological Sciences",value:5,count:9},{group:"topic",caption:"Biochemistry, Genetics and Molecular Biology",value:6,count:18},{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:14},{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:63},{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:0,limit:12,total:null},popularBooks:{featuredBooks:[{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",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"}},{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",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"}},{type:"book",id:"8697",title:"Virtual Reality and Its Application in Education",subtitle:null,isOpenForSubmission:!1,hash:"ee01b5e387ba0062c6b0d1e9227bda05",slug:"virtual-reality-and-its-application-in-education",bookSignature:"Dragan Cvetković",coverURL:"https://cdn.intechopen.com/books/images_new/8697.jpg",editors:[{id:"101330",title:"Dr.",name:"Dragan",middleName:"Mladen",surname:"Cvetković",slug:"dragan-cvetkovic",fullName:"Dragan Cvetković"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{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",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"}},{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:"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:"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",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"}},{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",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"}},{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:"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:"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"}}],offset:12,limit:12,total:5126},hotBookTopics:{hotBooks:[],offset:0,limit:12,total:null},publish:{},publishingProposal:{success:null,errors:{}},books:{featuredBooks:[{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",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"}},{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",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"}},{type:"book",id:"8697",title:"Virtual Reality and Its Application in Education",subtitle:null,isOpenForSubmission:!1,hash:"ee01b5e387ba0062c6b0d1e9227bda05",slug:"virtual-reality-and-its-application-in-education",bookSignature:"Dragan Cvetković",coverURL:"https://cdn.intechopen.com/books/images_new/8697.jpg",editors:[{id:"101330",title:"Dr.",name:"Dragan",middleName:"Mladen",surname:"Cvetković",slug:"dragan-cvetkovic",fullName:"Dragan Cvetković"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{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",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"}},{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:"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",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"}},{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",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"}},{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:"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:"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"}}],latestBooks:[{type:"book",id:"8468",title:"Sheep Farming",subtitle:"An Approach to Feed, Growth and Health",isOpenForSubmission:!1,hash:"838f08594850bc04aa14ec873ed1b96f",slug:"sheep-farming-an-approach-to-feed-growth-and-health",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:"1306",title:"Machine Intelligence",slug:"machine-intelligence",parent:{title:"Robotic Surgery",slug:"robotic-surgery"},numberOfBooks:1,numberOfAuthorsAndEditors:1,numberOfWosCitations:27,numberOfCrossrefCitations:18,numberOfDimensionsCitations:37,videoUrl:null,fallbackUrl:null,description:null},booksByTopicFilter:{topicSlug:"machine-intelligence",sort:"-publishedDate",limit:12,offset:0},booksByTopicCollection:[{type:"book",id:"3709",title:"Robot Surgery",subtitle:null,isOpenForSubmission:!1,hash:null,slug:"robot-surgery",bookSignature:"Seung Hyuk Baik",coverURL:"https://cdn.intechopen.com/books/images_new/3709.jpg",editedByType:"Edited by",editors:[{id:"6560",title:"Prof.",name:"Seung Hyuk",middleName:null,surname:"Baik",slug:"seung-hyuk-baik",fullName:"Seung Hyuk Baik"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],booksByTopicTotal:1,mostCitedChapters:[{id:"6510",doi:"10.5772/6893",title:"Classification, Design and Evaluation of Endoscope Robots",slug:"classification-design-and-evaluation-of-endoscope-robots",totalDownloads:4096,totalCrossrefCites:8,totalDimensionsCites:13,book:{slug:"robot-surgery",title:"Robot Surgery",fullTitle:"Robot Surgery"},signatures:"Kazuhiro Taniguchi, Atsushi Nishikawa, Mitsugu Sekimoto, Takeharu Kobayashi, Kouhei Kazuhara, Takaharu Ichihara, Naoto Kurashita, Shuji Takiguchi, Yuichiro Doki, Masaki Mori, and Fumio Miyazaki",authors:null},{id:"6511",doi:"10.5772/6894",title:"Extreme Telesurgery",slug:"extreme-telesurgery",totalDownloads:4662,totalCrossrefCites:6,totalDimensionsCites:7,book:{slug:"robot-surgery",title:"Robot Surgery",fullTitle:"Robot Surgery"},signatures:"Tamás Haidegger and Zoltán Benyó",authors:null},{id:"6519",doi:"10.5772/6902",title:"Robotic Surgery in Ophthalmology",slug:"robotic-surgery-in-ophthalmology",totalDownloads:4568,totalCrossrefCites:3,totalDimensionsCites:5,book:{slug:"robot-surgery",title:"Robot Surgery",fullTitle:"Robot Surgery"},signatures:"Irena Tsui, Angelo Tsirbas, Charles W. Mango, Steven D. Schwartz and Jean-Pierre Hubschman",authors:null}],mostDownloadedChaptersLast30Days:[{id:"6511",title:"Extreme Telesurgery",slug:"extreme-telesurgery",totalDownloads:4662,totalCrossrefCites:6,totalDimensionsCites:7,book:{slug:"robot-surgery",title:"Robot Surgery",fullTitle:"Robot Surgery"},signatures:"Tamás Haidegger and Zoltán Benyó",authors:null},{id:"6519",title:"Robotic Surgery in Ophthalmology",slug:"robotic-surgery-in-ophthalmology",totalDownloads:4568,totalCrossrefCites:3,totalDimensionsCites:5,book:{slug:"robot-surgery",title:"Robot Surgery",fullTitle:"Robot Surgery"},signatures:"Irena Tsui, Angelo Tsirbas, Charles W. Mango, Steven D. Schwartz and Jean-Pierre Hubschman",authors:null},{id:"6513",title:"Simulation Model for the Dynamics Analysis of a Surgical Assistance Robot",slug:"simulation-model-for-the-dynamics-analysis-of-a-surgical-assistance-robot",totalDownloads:3003,totalCrossrefCites:0,totalDimensionsCites:2,book:{slug:"robot-surgery",title:"Robot Surgery",fullTitle:"Robot Surgery"},signatures:"Hans-Christian Schneider and Juergen Wahrburg",authors:null},{id:"6520",title:"Robot-Assisted Laparoscopic Central Pancreatectomy with Pancreaticogastrostomy (Transgastric Approach)",slug:"robot-assisted-laparoscopic-central-pancreatectomy-with-pancreaticogastrostomy-transgastric-approach",totalDownloads:3449,totalCrossrefCites:0,totalDimensionsCites:2,book:{slug:"robot-surgery",title:"Robot Surgery",fullTitle:"Robot Surgery"},signatures:"Chang Moo Kang and M.D.",authors:null},{id:"6517",title:"Robotic Assisted Laparoscopic Hysterectomy",slug:"robotic-assisted-laparoscopic-hysterectomy",totalDownloads:9236,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"robot-surgery",title:"Robot Surgery",fullTitle:"Robot Surgery"},signatures:"Khaled Sakhel",authors:null},{id:"6515",title:"Robotic Surgery of the Colon: The Peoria Experience",slug:"robotic-surgery-of-the-colon-the-peoria-experience",totalDownloads:2889,totalCrossrefCites:0,totalDimensionsCites:4,book:{slug:"robot-surgery",title:"Robot Surgery",fullTitle:"Robot Surgery"},signatures:"Steven S Tsoraides, M.D., M.P.H., Franziska Huettner, M.D., P.h.D., Arthur L Rawlings M.D., M.Div. and David L Crawford, M.D.",authors:null},{id:"6516",title:"Robotic Sacrocolpopexy and Sacrocervicopexy for the Correction of Pelvic Organ Prolapse",slug:"robotic-sacrocolpopexy-and-sacrocervicopexy-for-the-correction-of-pelvic-organ-prolapse",totalDownloads:3833,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"robot-surgery",title:"Robot Surgery",fullTitle:"Robot Surgery"},signatures:"James C Brien, Michael D Fabrizio and James C Lukban",authors:null},{id:"6518",title:"Robotic Surgery for Lung Cancer",slug:"robotic-surgery-for-lung-cancer",totalDownloads:3183,totalCrossrefCites:1,totalDimensionsCites:1,book:{slug:"robot-surgery",title:"Robot Surgery",fullTitle:"Robot Surgery"},signatures:"Joao-Carlos Das-Neves-Pereira, Marc Riquet, Françoise Le-Pimpec-Barthes, Paulo-Manuel Pego-Fernandes and Fabio Biscegli Jatene",authors:null},{id:"6510",title:"Classification, Design and Evaluation of Endoscope Robots",slug:"classification-design-and-evaluation-of-endoscope-robots",totalDownloads:4096,totalCrossrefCites:8,totalDimensionsCites:13,book:{slug:"robot-surgery",title:"Robot Surgery",fullTitle:"Robot Surgery"},signatures:"Kazuhiro Taniguchi, Atsushi Nishikawa, Mitsugu Sekimoto, Takeharu Kobayashi, Kouhei Kazuhara, Takaharu Ichihara, Naoto Kurashita, Shuji Takiguchi, Yuichiro Doki, Masaki Mori, and Fumio Miyazaki",authors:null},{id:"6514",title:"Robotic Assisted Colorectal Surgery",slug:"robotic-assisted-colorectal-surgery",totalDownloads:4285,totalCrossrefCites:0,totalDimensionsCites:1,book:{slug:"robot-surgery",title:"Robot Surgery",fullTitle:"Robot Surgery"},signatures:"Seung Hyuk Baik and M.D.",authors:null}],onlineFirstChaptersFilter:{topicSlug:"machine-intelligence",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/97808/julia-vainonen",hash:"",query:{},params:{id:"97808",slug:"julia-vainonen"},fullPath:"/profiles/97808/julia-vainonen",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)}()