More than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
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Our breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
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“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
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Additionally, each book published by IntechOpen contains original content and research findings.
\\n\\n
We are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
Simba Information has released its Open Access Book Publishing 2020 - 2024 report and has again identified IntechOpen as the world’s largest Open Access book publisher by title count.
\n\n
Simba Information is a leading provider for market intelligence and forecasts in the media and publishing industry. The report, published every year, provides an overview and financial outlook for the global professional e-book publishing market.
\n\n
IntechOpen, De Gruyter, and Frontiers are the largest OA book publishers by title count, with IntechOpen coming in at first place with 5,101 OA books published, a good 1,782 titles ahead of the nearest competitor.
\n\n
Since the first Open Access Book Publishing report published in 2016, IntechOpen has held the top stop each year.
\n\n\n\n
More than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
\n\n
Our breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
\n\n
“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
\n\n
Additionally, each book published by IntechOpen contains original content and research findings.
\n\n
We are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
\n\n
\n\n
\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"3372",leadTitle:null,fullTitle:"Humanoid Robots, Human-like Machines",title:"Humanoid Robots",subtitle:"Human-like Machines",reviewType:"peer-reviewed",abstract:'In this book the variety of humanoid robotic research can be obtained. This book is divided in four parts: Hardware Development: Components and Systems, Biped Motion: Walking, Running and Self-orientation, Sensing the Environment: Acquisition, Data Processing and Control and Mind Organisation: Learning and Interaction.\r\nThe first part of the book deals with remarkable hardware developments, whereby complete humanoid robotic systems are as well described as partial solutions.\r\nIn the second part diverse results around the biped motion of humanoid robots are presented. The autonomous, efficient and adaptive two-legged walking is one of the main challenge in humanoid robotics. The two-legged walking will enable humanoid robots to enter our environment without rearrangement.\r\nDevelopments in the field of visual sensors, data acquisition, processing and control are to be observed in third part of the book.\r\nIn the fourth part some "mind building" and communication technologies are presented.',isbn:null,printIsbn:"978-3-902613-07-3",pdfIsbn:"978-953-51-5805-9",doi:"10.5772/37",price:159,priceEur:175,priceUsd:205,slug:"humanoid_robots_human_like_machines",numberOfPages:652,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"581c6d2ca6e91bebee1a1679c857a0c4",bookSignature:"Matthias Hackel",publishedDate:"June 1st 2007",coverURL:"https://cdn.intechopen.com/books/images_new/3372.jpg",numberOfDownloads:120865,numberOfWosCitations:112,numberOfCrossrefCitations:68,numberOfCrossrefCitationsByBook:6,numberOfDimensionsCitations:202,numberOfDimensionsCitationsByBook:6,hasAltmetrics:1,numberOfTotalCitations:382,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"April 26th 2012",dateEndSecondStepPublish:"May 17th 2012",dateEndThirdStepPublish:"August 21st 2012",dateEndFourthStepPublish:"November 19th 2012",dateEndFifthStepPublish:"December 19th 2012",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"144263",title:"Dr.",name:"Matthias",middleName:null,surname:"Hackel",slug:"matthias-hackel",fullName:"Matthias Hackel",profilePictureURL:"https://mts.intechopen.com/storage/users/144263/images/system/144263.jpg",biography:"Matthias Hackel received his Master’s degree in physics in 1997 from RWTH Aachen, Germany. 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\r\n\tThe primary aim of this book is to integrate the knowledge of dairy product manufacturing with the chemistry of ingredients, along with the chemistry of several reactions which appear during the preparation of these products. Therefore, understanding the basic composition of milk and the chemistry of various constituents is of utmost importance. This will be the first topic that will be covered in this book, along with the advance and updated knowledge on the ingredients/ milk constituents. Over the years, the processing and manufacturing of several dairy products have witnessed upgraded processing equipment and hence the protocols of manufacturing. We also hope to cover the advanced processing methods for the production of dairy products. \r\n\tFurthermore, during the preparation of high-quality dairy products, several physical, chemical, enzymatic, and microbial transformations take place. We will consciously focus on this interaction of different constituents of milk under different processing conditions for the development of the products.
",isbn:"978-1-83768-093-1",printIsbn:"978-1-83768-092-4",pdfIsbn:"978-1-83768-094-8",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,isNomenclature:!1,hash:"420e687768b56ca7b3238d77f63f1302",bookSignature:"Dr. Neelam Upadhyay and Dr. Veena Nagaraj",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/12173.jpg",keywords:"Protein, Fat, Lactose, Carbohydrates, Milk Processing, Milk Products, Milk Constituents, Acid Coagulated, Enzyme Treated, Heat Treated, Dairy Products, Protocols of Manufacturing",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"May 18th 2022",dateEndSecondStepPublish:"July 19th 2022",dateEndThirdStepPublish:"September 17th 2022",dateEndFourthStepPublish:"December 6th 2022",dateEndFifthStepPublish:"February 4th 2023",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"13 days",secondStepPassed:!1,areRegistrationsClosed:!1,currentStepOfPublishingProcess:2,editedByType:null,kuFlag:!1,biosketch:"Dr. Upadhyay has received many awards most notable being the Young Woman Scientist Award 2020 from the Agro-Environmental Development Society and the Best Poster Award 2021 from the National Conference on Moringa Food Conclave 2021. She is a dedicated researcher in food and dairy processing and has published many research articles and papers in both national and international journals and publications.",coeditorOneBiosketch:"Dr. N. Veena has been involved in different research projects such as Milkfed (Punjab), ICAR, DST, and RKVY as PI and Co-PI. She has published 17 research papers in peer-reviewed journals, edited 2 books, and authored 13 book chapters, 15 popular articles, and 7 practical manuals. She is a member of various professional bodies such as the SASNET-Fermented Foods, the Indian Dairy Association, the Association of Food Scientists and Technologists (India), and the Dairy Technology Society of India.",coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"269538",title:"Dr.",name:"Neelam",middleName:null,surname:"Upadhyay",slug:"neelam-upadhyay",fullName:"Neelam Upadhyay",profilePictureURL:"https://mts.intechopen.com/storage/users/269538/images/system/269538.jpg",biography:"BRIEF BIODATA\n1.\tName in full: Neelam Upadhyay \n2.\tDate & Place of Birth: 29th December, 1987 at Delhi\n3.\tField of specialization: Food Technology\n4.\tPresent Position/ Designation: Scientist- Senior Scale\n5.\tAddress:\t(a)\tOfficial:\tTel. No.:0184-2259258\n\t\t\t\tE-mail: \ticar.neelam@gmail.com; neelam.upadhyay@icar.gov.in \n\t\t\t\tAddress: \tLaboratory No. 146, Dairy Technology Division, ICAR- \n\t\t\t\t\t\tNational Dairy Research Institute, Karnal \n\t\t\t(b)\tResidential: Tel. No.: +91-9255772587\n\tAddress (Permanent): 41-D, MIG DDA Flats, Shivam Enclave, Delhi-110032\n6.\t(a) Academic career and (b) professional attainments\n(a) Examination\tClass/ Percentage\tYear of Passing\tSubjects Taken\tName of University / Board\nXth \t1st/83\n(415/500)\t2003\tMathematics, Social Science, Science, English, Hindi\tK.V., Mumbai (CBSE)\nXIIth\t1st/78.2 \n(391/500)\t2005\tPhysics, Mathematics, Chemistry, Biology, English\tK.V., Delhi (CBSE)\nB.A.Sc. (Hons.)\t1st/83.43 (2044/2450)\n(3rd position)\t2008\tFood Technology\tSRCASW, University of Delhi, Delhi\nM.Sc.\t1st/8.62\n(1st position)\t2010\tFood Science & Technology\tCCS Har. Agri. Uni., Hisar, Haryana\nTitle of Research:\tDevelopment of flavoured whey-soya milk beverage\nMajor Advisor:\tDr. R. S. Dabur (Professor and Head)\nPh.D.\t1st/8.0\n(1st position)\t2014\tDairy Chemistry\tNational Dairy Research Institute, Karnal, Haryana\nTitle of Research: \tDetection of vegetable oil and animal body fat adulteration in ghee using solvent fractionation technique\nMajor Advisor:\tDr. Darshan Lal (Principal Scientist and Ex-Head)\nDistinctions during Academics\nDegree\tDistinctions\nBachelor of Applied Science (Hons.)\ti.\tY.K. Kapoor Memorial Scholarship 2006 by All India Food Processor’s Association \nii.\t3rd position in university\niii.\tReceived highest attendance award\niv.\tReceived trophy for ‘Most Disciplined Student’ for the graduation period 2005-2008\nv.\tCertificate of Honor from Honb’le Mr. Justice K.G. Balakrishnan, Chief Justice of India\nMaster of Science\ti.\t1st position in discipline and 2nd position in college\nii.\tReceived recognition for academic excellence from Jawaharlal Nehru Memorial Fund; \niii.\tQualified GATE\niv.\t2nd in inter-college yoga competition\nv.\tParticipated in various events of All India Youth Festival organized at UAS, Bangalore.\nDoctor of Philosophy\ti.\tReceived Merit Certificate for Academic Excellence in PhD course work\nii.\tReceived Certificate of Appreciation for outstanding work in the field of Dairy Processing during PhD\niii.\tQualified ICAR’s National Eligibility Test in 2010; Qualified the ICAR’s All India Examination, ICAR-SRF (PGS_-2011-2012 for award of ICAR-SRF (PGS) with 2nd rank (both in first attempt) \niv.\tQualified Agricultural Research Service Examination-2013 conducted by Agricultural Scientist Recruitment Board against the single vacancy (for UR) in the discipline of Food Technology\nv.\tStage Management Secretary of student’s council 2010-11\nvi.\tLiterary secretary of Student’s Council 2011-12\nvii.\tCompleted certificate e-course on “Publishing a Journal Manuscript - the Groundwork” directed by Springer in 2013\nviii.\tHave successfully completed certificate e-course – “Peer Review Academy” directed by Springer in 2013\nix.\tReceived a certificate on accomplishment IRIS 4-2 Information Literacy Plagiarism Quiz (on-line) in 2013 developed by Distance Learning Council of Washington, USA \n (b) Position Held\tInstitution \tPeriod of Appointment\tNature of Appointment\nScientist (Food Technology)\tICAR- National Academy of Agricultural Research Management, Hyderabad\t3 months\n(1st January, 2015 till 31st March, 2015)\tPermanent\n(Received ‘A’ grade for FOCARS)\nScientist \n(Food Technology)\tICAR- National Dairy Research Institute, Karnal\t10th March, 2015 till 31st December, 2018\n(after availing 10 days of transfer period)\tPermanent\nScientist-Senior Scale\n(Food Technology)\tICAR- National Dairy Research Institute, Karnal\t1st January, 2019 till date\tPermanent\n\n7. Special attainments in Research\n(https://scholar.google.co.in/citations?hl=en&user=PRz0Tz4AAAAJ&view_op=list_works&sortby=pubdate)\nPublications\tNumbers\tRemarks \nResearch Articles\t35\n(24 Intl, 9 National, 2 others)\tTotal Impact: 72.302\n\nBook Chapters\t7\t5 APA/CRC Press; 1 InTech Open; \n1 National\nReview Articles\t2\tTotal Impact:8.327\nTechnical Articles\t7\tCompendium of trainings, seminars, etc\nInstitute publication\t1\t\nPopular Article\t12\t6 in English; 5 in hindi\nCitations \t1066\t(as per googlescholar)\nH-index/ i10-index\t15/ 17\t\n.\n.\nJournal\tNumber of publications\tImpact factor\nResearch Articles\t35\t72.302\nInternational\t24 (15 as either corresponding or first author)\t72.302\nNational\t9 (3 as first or corresponding author)\tNAAS score\nOthers\t2\t\nReview article (International)\t2\t8.327\nInternational\t2\t8.327\n.\n \n\n\n\nRESEARCH ARTICLES\nInternational Journals \n1.\tTiwari, S., Upadhyay, N.*, Singh, A. K. (2022). Stability assessment of emulsion of carotenoids extracted from carrot bio-waste in flaxseed oil and its application in food model system. Food Bioscience, 47, 101631. https://doi.org/10.1016/j.fbio.2022.101631.\n2.\tPatil, A. T., Meena, G. S., Upadhyay, N., Khetra, Y., Singh, A. K., & Borad, S. G. (2021). Buffalo milk protein concentrate 60: Effect of skim milk heat treatment on its reconstitutability and functionality. Food Science & Technology – Lebensmittel -Wissenschaft & Tech, 148, 111638. \n3.\tUttamrao, H. J., Meena, G. S., Khetra, Y., Upadhyay, N., Singh, A. K., Arora, S., & Borad, S. G. (2022). Homogenization and sodium hydrogen phosphate induced effect on physical and rheological properties of ultrafilterd concentrated milk. Journal of Food Science and Technology, 59(3), 956-967. \n4.\tTiwari, S., Upadhyay, N.*, Malhotra, R. (2021). Three way ANOVA for emulsion of carotenoids extracted in flaxseed oil from carrot bio-waste. Waste Management, 121, 67-76. \n5.\tRanvir, S., Sharma, R., Gandhi, K., Upadhyay, N., Mann, B. (2020). Assessment of proteolysis in ultra-high temperature milk using attenuated total reflectance–Fourier transform infrared spectroscopy. International Journal of Dairy Technology. 73(2): 366-375. doi: 10.1111/1471-0307.12683. \n6.\tPonbhagavathi, T.R., Singh, A.K., Raju, P.N., Upadhyay, N. (2020). High performance liquid chromatographic (HPLC) determination of available lysine in milk protein-maize composite extrudates and its stability during storage. Journal of the Indian Chemical Society, 97(11a), 2344-2350\n7.\tTiwari, S., Upadhyay, N.*, Singh, A. K., Meena, G. S., & Arora, S. (2019). Organic solvent-free extraction of carotenoids from carrot bio-waste and its physico-chemical properties. Journal of Food Science and Technology, 1-10. 10.1007/s13197-019-03920-5\n8.\tBaria, B., Upadhyay, N.*, Singh, A. K., & Malhotra, R. K. (2019). Optimization of ‘green’extraction of carotenoids from mango pulp using split plot design and its characterization. Food Science & Technology – Lebensmittel -Wissenschaft & Tech, 104, 186-194. \n9.\tPatil, A. T., Meena, G. S., Upadhyay, N., Khetra, Y., Borad, S. G., & Singh, A. K. (2019). Effect of change in pH, heat treatment and diafiltration on properties of medium protein buffalo milk protein concentrate. Journal of Food Science and Technology, 56(3), 1462-1472. \n10.\tUttamrao, H. J., Meena, G. S., Borad, S. G., Punjaram, S. A., Khetra, Y., Upadhyay, N., & Singh, A. K. (2019). Effect of disodium phosphate and homogenization on physico-chemical and rheological properties of buffalo skim milk based ultrafiltered retentate. Journal of food science and technology, 56(5), 2426-2435. \n11.\tMeena, G.S., Dewan, A., Upadhyay, N., Barapatre, R., Kumar, N., Singh, A.K., & Rana, J.S. (2019). Fuzzy Analysis of Sensory Attributes of Gluten Free Pasta Prepared From Brown Rice, Amaranth, Flaxseed Flours and Whey Protein Concentrates. Journal of Food Science and Nutrition Research, 2(1), 022-037. DOI: 10.26502/jfsnr.2642-1100006\n12.\tPatil, A. T., Meena, G. S., Upadhyay, N.*, Khetra, Y., Borad, S., & Singh, A. K. (2018). Production and characterization of milk protein concentrates 60 (MPC60) from buffalo milk. Food Science & Technology – Lebensmittel -Wissenschaft & Tech, 91, 368-374. https://doi.org/10.1016/j.lwt.2018.01.028 \n13.\tUpadhyay, N.*, Jaiswal, P., & Jha, S. N. (2018). Application of attenuated total reflectance Fourier Transform Infrared spectroscopy (ATR–FTIR) in MIR range coupled with chemometrics for detection of pig body fat in pure ghee (heat clarified milk fat). Journal of Molecular Structure, 1153, 275-281. \n14.\tUpadhyay, N.*, Kumar A., Goyal A. and Lal, D. (2017). Complete liquification time test coupled with solvent fractionation technique to detect adulteration of foreign fats in ghee (heat-clarified milk fat). International Journal of Dairy Technology. 70(1): 110-118. doi: 10.1111/1471-0307.12323. \n15.\tUpadhyay, N.*, Goyal A., Kumar A. and Lal, D. (2017). Detection of adulteration of caprine body fat and mixture of caprine body fat and groundnut oil in bovine and buffalo ghee using Differential Scanning Calorimetry. International Journal of Dairy Technology. 70(2): 297-303. May 2017.doi:10.1111/1471-0307.12336. \n16.\tKumar, A., Upadhyay, N.*, Ghai, D.L., Kumar, A. Gandhi, K. and Sharma, V. (2016). Effect of preparation and storage of khoa on physico-chemical properties of milk fat. International Journal of Dairy Technology. 69(2): 294-300. doi: 10.1111/1471-0307.12266. \n17.\tUpadhyay, N.*, Jaiswal, P. & Jha, S.N. (2016). Detection of goat body fat adulteration in pure ghee using ATR-FTIR spectroscopy coupled with chemometric strategy. Journal of Food Science and Technology. 53 (10): 3752-3760. doi:10.1007/s13197-016-2353-2 ISSN 0022-1155\n18.\tRathi, M., Upadhyay, N.*, Dabur, R.S. and Goyal A. (2015). Formulation and physic-chemical analysis of whey –soymilk dahi. Journal of Food Science and Technology. 52(2): 968-975. doi 10.1007/s13197-013-1074-z. ISSN: 0022-1155. \n19.\tKanthale, P., Kumar, A. Upadhyay, N.*, Lal, D., Rathod G. and Sharma, V. (2015). Qualitative test for the detection of extraneous Thiocyanate in Milk. Journal of Food Science and Technology. 52(3): 1698-1704. DOI: 10.1007/s13197-013-1174-9. ISSN: 0022-1155.\n20.\tGoyal, A., Sharma, V., Upadhyay, N., Singh, A.K., Arora, S. and Ghai, D.L. (2015). Development of stable flaxseed oil emulsions as a potential delivery system of ω-3 fatty acids. Journal of Food Science and Technology. 52(7):4256-4265. \n21.\tUpadhyay, N.*, Kumar, A., Rathod, G., Goyal, A. and Lal, D. (2015). Development of a method employing reversed-phase thin-layer chromatography for establishing milk fat purity with respect to adulteration with vegetable oils. International Journal of Dairy Technology. 68(2): 207-217. doi. 10.1111/1471-0307.12178. \n22.\tGoyal, A., Siddiqui, S. Upadhyay, N., Soni, J. (2014). Effects of ultraviolet irradiation, pulsed electric field, hot water and ethanol vapours treatment on functional properties of mung bean sprouts. Journal of Food Science and Technology. 51(4): 708-714. doi 10.1007/s13197-011-0538-2. Publisher Springer. ISSN (electronic version): 0975-8402. \n23.\tKundu, H., Grewal, R.B., Goyal, A., Upadhyay, N.*, and Prakash S. (2014). Effect of incorporation of pumpkin (Cucurbita moshchata) powder and guar gum on the rheological properties of wheat flour. Journal of Food Science and Technology. 51(10):2600-2607. DOI: 10.1007/s13197-012-0777-x. ISSN: 0022-1155. \n24.\tUpadhyay, N.*, Kumar, A., Goyal, A. and Lal, D. (2014). A planar chromatographic method to detect adulteration of vegetable oils in ghee. JPC-Journal of Planar Chromatography-Modern TLC. 27 (6): 431-437. DOI: 10.1556/JPC.27.2014.6.5 \nNational Journals\n1.\tPonbhagavathi, T. R., Singh, A. K., Raju, P. N., Upadhyay, N. (2021). Textural and Sensory Characteristics of Milk Protein-Maize Flour-based Extrudates. Journal of Agricultural Engineering, 58(2), 124-136. 10.52151/jae2021581.1740\n2.\tPonbhagavathi, T.R., Singh, A.K., Raju, P.N., Upadhyay, N. (2020). Effect of Rennet Casein and Whey Protein Concentrate on Extrusion Behavior of Maize Flour. Current Journal of Applied Science and Technology. 39(33), 16-27, Article no.CJAST.57830.\n3.\tUpadhyay, N.*, Kumar, A., Lal, D., Kant, R., & Goyal, A. (2018). Detection of groundnut oil and goat body fat adulteration in ghee using principal component analysis on fatty acid profile. Indian Journal of Dairy Science. 71(5):464-472. \n4.\tUpadhyay, N.*, Kumar, A., Gandhi, K., Goyal, A. and Lal, D. (2014). Standardization of solvent fractionation technique for detection of adulteration in ghee by enriching animal body fat and vegetable oil in different fractions. Indian Journal of Dairy Science. 67 (4):323-327.\n5.\tGandhi. K., Upadhyay, N., Aghav, A.D., Sharma, V., and Lal, D. (2014). Detection of adulteration of ghee (clarified milk fat) with palmolein and sheep body fat using Reichert-Meissl (RM) value coupled with solvent fractionation technique. Indian Journal of Dairy Science. 67(5): 387-393. Received Second Best Paper Award during 44th Dairy Industry Conference organized by ICAR-NDRI, Karnal and Indian Dairy Association from 18-20, February 2016.\n6.\tAghav, A.D., Gandhi, K., Upadhyay, N., Kumar, A. and Lal, D. (2014). A study on the physico-chemical changes occurring in the milk fat during preparation of Paneer. Indian Journal of Dairy Science. 67 (5): 398-404.\n7.\tKumar, A., Upadhyay, N., Gandhi, K., Lal, D. and Sharma, V. (2013). Detection of soybean oil and buffalo depot fat in ghee using Normal-Phase Thin Layer Chromatography. Indian Journal of Dairy Science. 66(4): 294-99. ISSN: 0019-5146.\n8.\tKumar, A., Upadhyay, N., Gandhi, K., Kumar, A., Lal, D. and Sharma, V. (2013). Reverse-Phase Thin Layer Chromatography of Unsaponifiable Matter of ghee for detecting adulteration with soybean oil and buffalo depot fat. Indian Journal of Dairy Science. 66(6): 496-501. ISSN: 0019-5146.\n9.\tUpadhyay, N.*, Dabur R.S. and Rathi, M. (2011). Development and Shelf life Study of Flavoured Whey-soya milk beverage. Indian Journal of Dairy Science. 64(2): 92-101. ISSN: 0019-5146.\nOther Journals\n1.\tDewan, A., Meena, G.S., Upadhyay, N., Barapatre, R. Singh, A.K., Rana, J.S. (2017). Formulation of non-Gluten Pasta from the Optimized levels of Dairy and Non-Dairy ingredients. Madridge Journal of Food Technology. 2(2): 92–98. \n2.\tGalmessa, U., Prasad, S., Kumaresan, A., Oberoi, P. S., Baithalu, R. K., Upadhyay, N., and Dang, A. K. (2015). Modulation of Milk Fatty acid profile milk yield and composition through supplementation of omega-3 fatty acid in transition cow’s diet. Journal of Science and Sustainable Development. 3(1): 25-38. ISSN: 2070-1748\nREVIEW ARTICLES\n1.\tUpadhyay, N.*, Goyal, A. Kumar, A., Lal, D. and Singh, D. (2014). Preservation of milk and milk products for analytical purposes: A review. Food Reviews International. 30(3):203-224. DOI 10.1080/87559129.2014.913292. ISSN: 1525-6103\n2.\tGoyal, A., Sharma, V., Upadhyay, N., Gill, S. and Sihag, M. (2014). Flax and flaxseed oil: an ancient medicine & modern functional food. Journal of Food Science and Technology. 51(9): 1633-1653. DOI 10.1007/s13197-013-1247-9. ISSN: 0975-8402. \nBOOK CHAPTERS\n1.\tKumari, L., Sharma, M., & Upadhyay, N. (2021). Three-Dimensional Printing of Food Products: Printing Techniques, Novel Applications, and Printable Food Materials. Handbook of Research on Food Processing and Preservation Technologies: Volume 3: Computer-Aided Food Processing and Quality Evaluation Techniques, 55. Boca Raton, CRC Press\n2.\tUpadhyay, N.*, Harshitha, C. G., Pathak, N. K., & Sharma, R. (2021). Fourier Transform Infrared (FTIR) Spectroscopy with Chemometrics: Evaluation of Food Quality and Safety. Handbook of Research on Food Processing and Preservation Technologies: Volume 5: Emerging Techniques for Food Processing, Quality, and Safety Assurance, 271.\n3.\tNagarajappa, V., Upadhyay, N., Chawla, R., Mishra, S.K., & Nath, S. (2019). Functional Properties of Milk Proteins. In: Engineering Practices for milk products- Dairyceuticals, Novel Technologies, and Quality (pp 3-26). Apple Academic Press.\n4.\tUpadhyay, N., Kumar, M. C. T., Sharma, H., Borad, S., & Singh, A. K. (2019). Pulse Electric Field Processing of Milk and Milk Products. In: Non-thermal Processing of Foods (pp.129-144). Boca Raton, CRC Press\n5.\tUpadhyay, N., Nagaraj, V., & Singh, A. K. (2019). Advances in Fractionation of Milk Lipids: Analysis and Applications of fractions In: Recent Technologies in Dairy Science (pp. 325-344). Today and Tomorrow’s Printers and Publishers.\n6.\tNagaraj, V., Upadhyay, N.*, Nath, B. S., & Singh, A. K. (2018). Advances in Fractionation and Analysis of Milk Carbohydrates. In Technological Approaches for Novel Applications in Dairy Processing (pp. 127-147). IntechOpen. http://dx.doi.org/10.5772/intechopen.76312\n7.\tUpadhyay, N.*, Veena, N., Borad, S., & Singh, A. K. (2017). Application of Natural Antioxidants in Dairy Foods. In Natural Antioxidants (pp. 281-318). London: Apple Academic Press.\nINSTITUTE PUBLICATION\n1.\tDr. T. K. Datta, Dr. Meena Malik and Dr. Neelam Upadhyay (2017). Foundation Programme for Freshers at ICAR-NDRI 2017.\nPOPULAR AND LEAD ARTICLES\n1.\tPatil, A. T., Meena, G. S., Upadhyay, N., & Singh, A.K. (2017). Milk protein concentrates- Their Applications. Indian Dairyman, 69(9), 44-48.\n2.\tUpadhyay, N.* and R.K. Malik (2015). Nutritive Value of Milk. In: In Touch, Heinz Nutrition Foundation of India. Volume 17, Number 2&3, 2-11. (Lead Article). \n3.\tGoyal, A., Sharma, V., Upadhyay, N., Sihag, M. and Kaushik, R. (2013). High Pressure Processing and its impact on milk proteins: A Review. Research and Reviews: Journal of Dairy Science and Technology. 2 (1): 1-9. ISSN: 2319-3409.\n4.\tKumar, A., Upadhyay, N., and Naagar, S. (2012). Allergenicity of Milk Proteins, and its Management. Indian Food Industry. 31 (5&6): 45-50. ISSN: 0972-2610.\n5.\tGoyal, A. and Upadhyay, N. (2012). Nuclear Magnetic Resonance Spectroscopy in Dairy Science. Indian Food Industry. 31(1): 39-45. ISSN: 0972-2610.\n6.\tUpadhyay, N.*, Goyal, A. and Rathod, G. (2011). Microwave Spectroscopy and its applications in online processing. Indian Food Industry. 30(5&6): 63-73. ISSN: 0972-2610.\n7.\tउपाध्याय, नी*. (२०१८) भारत में कुपोषण: स्थिति और इससे निपटने के लिए रणनीतियाँ. दुग्ध—गंगा (आठवाँ अंक). अप्रैल-सितम्बर. २४-२९. \n8.\tउपाध्याय, नी.*, सिंह, आ.कु., गांगुली, स., सबिखी, ल. (२०१८) खाध्य और डेयरी क्षेत्र मे महिला उद्यमिता: कारण, समस्याए एवम उपलब्ध मंच. दुग्ध—गंगा (आठवाँ अंक). अप्रैल-सितम्बर. ६४-६९.\n9.\tउपाध्याय, नी*. (२०१९) ek¡ dk nw/k % f'k'kqvksa ds ekufld] 'kkjhfjd ,oa lkekftd mRFkku gsrq ve`r. दुग्ध—गंगा (नवाँ अंक). अकटूबर –मार्च १०२-१०४.\n10.\tउपाध्याय, नी*, fç;k ;koys (२०१९) [kk| inkFkksaZ esa —f=e ds cnys çk—frd jax o.kZd ds mi;ksx dh vko';drk दुग्ध—गंगा (दसवाँ अंक). अकटूबर –मार्च १०२-१०५.\n11.\tuhye mikè;k;, fuys'k dqekj ikBd (२०१९) d`f\"k] [kk| ,oa Ms;jh m|ksx ds Hkfo\"; eas lkSj ÅtkZ dk egRo दुग्ध—गंगा (दसवाँ अंक). अकटूबर –मार्च १२६-१३०. \n12.\tवैज्ञानिक और तकनीकी विषय के मूल हिंदी लेख जोकि गेहूँ एवम् जौ स्वर्णिमा में प्रकाशित हुए: उपाध्याय, नी*, राकेश कुमार (2020) महिला उद्यमिता के माध्यम से महिला सशक्तिकरण. गेहूँ एवम् जौ स्वर्णिमा (बारहवााँ अंक), पृष्ठ सं. 55-58; भाकृअनुप- भारतीय गेहूँ एवम् जौ अनुसंधान संस्थान, करनाल- १३२००१ द्वारा प्रकाशित\n\n8. Concepts/Processes/Products/Technologies/Patents/Others\n(i)\tConcepts \nCurrently, I am working on the integrated approach of application of green technology for the development of functional foods by utilizing under-utilized/ indigenous fruits and vegetables and/ or bio-waste. In the research projects, I am also keenly working on food chemistry and instrumental food analysis and applications of technologies/ products in dairy and non-dairy products. \nBesides this, I am working on development of functional food for addressing menopausal symptoms in osteopenic mice model. \n(ii)\tProducts/ Technologies ready for commercialization- 5\n1. Production of Milk Protein Concentrate 60 (MPC60), a high protein low lactose powder from buffalo milk (Co-Inventor)\n2. Technology for omega-3 rich mixed fat table spread (Inventor)\n3. Lipid and water soluble yellow natural colouring ingredient from bio-waste (Inventor)\n4. Technology for preparation of encapsulated flaxseed oil for its applications in foods (Inventor)\n5. Production of buffalo milk based Milk Protein Concentrate 60 (MPC60) powder with improved solubility (Co-Inventor)\n(iii) Expertise on\n1.Gas Liquid Chromatography\t5.Thin Layer Chromatography\n2.Fourier Transform Infra-red Spectroscopy\t6. Spectrophotometry\n3.Differential Scanning Calorimetry\t7.Chemical analysis including titration, distillation, etc.\n4.High Pressure Liquid Chromatography\t\n\n\n9. List of completed, on-going and submitted projects\nTitle of Project\tDuration\tRole\tFunding\tStatus\tRemarks\nEffect of storage on Baudouin test, sesamin test and RP-TLC test to detect adulteration of vanaspati and vegetable oils in ghee\t2015-2017\tCo-PI\tICAR-NDRI\n\tCompleted\tTwo research articles on RP-TLC\nPreparation and Characterization of Micro/nano delivery systems for “green” carotenoids\t2016-2019\tPI\t-Do-\t\t3 research articles+ 3 products/ technologies\nTechnology Development for the Production of Milk Protein Concentrate (MPC60) From Buffalo Milk\t2016-2019\tCo-PI\t-Do-\t\t4 research articles+ 2 products/ technologies\nTechnology of Goat Milk based Functional Beverage\t2017-2020\tCo-PI\t-Do-\t\tOne oral presentation\nTechnology for Moringa oleifera enriched cheese spread\t2020-2023\tPI\t-Do-\tOn-going\tCharacterization and incorporation of M. oleifera- pods in cheese spread is complete; shelf life study and animal trial is in progress\nDevelopment of flaxseed-rich probiotic dairy foods to address menopause symptoms\t2020-2023\tCo-PI\tDST\t\tDeveloped method -estimation of phytoestrogen; validation -in progress\nNutritional and therapeutic validation of chhachh and ghee prepared from indigenous cows by traditional method\tThree years (proposed)\tPI\tSEED Division, DST\tSubmitted \n \t\nCharacterization of Moringa oleifera leaves for functional bioactives and its application in table spread as model food system\tThree years (proposed)\tPI\tSYST, DST\t\t\nOther research work: \nDetection of adulteration of goat body fat and pig body fat in ghee using ATR-FTIR coupled with chemometrics; carried out during Professional Attachment Training at ICAR-CIPHET, Ludhiana\n\n\n\n10. Awards & honours \nName of Award\tYear\tAwarding Agency\nBest Paper Award\t2022\tGSAT (Gender Advancement for Transforming Institutions Self-Assessment Team), NDRI\nBest Poster Award\t2021\tNational Conference on Moringa Food Conclave-2021\nYoung Woman Scientist Award\t2020\tAgro Environmental Development Society during International Web-conference \nSecond Best Poster Award\t2020\tIndian Dairy Association\nCommendation certificate for Institute’s Magazine in which I am co-Editor\t2020\tTown Official Language Implementation Committee, Karnal\nLetter of Appreciation to editorial board of Institute’s magazine for receiving ICAR’s Second Prize and Trophy under Ganesh Shankar Vidyarthi Hindi Patrika Puraskar (2018-19)\t2020\tICAR- National Dairy Research Institute, Karnal\nAssociate Fellowship\t2019\tNational Academy of Dairy Science India\nFirst Prize in E-poster \t2018\tIndian Dairy Association\nOne Best oral Presentation\t2018\tHome Science Association of India\nBest Oral Presentation to my Master’s student\t2018\tICMR- National Institute of Nutrition\nBest Poster Award\t2016\tIndian Dairy Association\nSecond Best Paper Award\t2016\tIndian Dairy Association\nICAR-SRF (PGS) with 2nd rank\t2011-12\tICAR\nGATE (Engg Sciences: Food Tech; Thermodynamics)\t2010\tMHRD, GoI\nInstitution level awards\nThird prize in poster presentation \t2021\tICAR- National Dairy Research Institute, Karnal\nInstitute’s Rajbhasha Gaurav Certificate\t2020\t\nFirst prize in Scientific and Technical writing\t2019\t\nConsolation prize in Scientific and Technical writing \t2020, 2019 \t\nFirst prize in Poster Presentation- 2020, 2018, 2017\t\t\nThird prize in poster presentation\t2019\t\nFirst Prize in hindi extempore\t2017\t\nThird, first and second prize in hindi essay writing in consecutive years – 2020, 2019, 2018\t\t\n\n\n11. Teaching Assignments \n(a) Teaching: Actively involved either as course in-charge or associate \nClass\tB.Tech (DT)\tMSc/ MTech\n(FT) (till 2021)\tM.Tech (DT)\tPhD (DT/ DC/ FSQA)\nNo. of courses\t1-2\t2-3\t0-1\t2-3\nDT- Dairy Technology, DC- Dairy Chemistry, FT- Food Technology, FSQA- Food Safety Quality Assurance\n(b) Student’s guided\nDegree\tMajor Advisor \tCo-Advisory\tStatus/ Remarks\nM. Tech (DT)\t8\t2\tCompleted\n\t1\t0\tOn going\nM. Tech/ M Sc (FT/ FSN)\t2\t1\tCompleted\nM. Tech (DC)\t0\t3\tCompleted\nM. Tech (DM)\t0\t1\tCompleted\nPhD (DT)\t2 \t0\tOngoing \n\t0\t2\tCompleted\nPhD (DC)\t0\t1 \tCompleted\n\t\t1\tOn going\ni.\tThree students under my guidance as major advisor and one student as co-advisory member nominated for Best thesis award; \nii.\tOne represented NDRI at zonal-level student research convention ANVESHAN-2018\n\n12. Lectures/ member/convener of committees: \ni.\tLectures: \na.\tEntrepreneurship Development Programme (EDP) (conducted by SINED-TBI/BPD unit, ICAR-NDRI) and Online Training of Master Trainers on Fat and Oilseed processing conducted by SINED-TBI/BPD unit (ICAR-CIPHET); \nb.\tStudent’s Counselling session at SRCASW, University of Delhi, \nc.\tWorkshop conducted at DAV college, Karnal, etc\nd.\tDelivered talks at various villages on the importance of mother’s milk, nutrition in first 1000 days of an infant’s life, nutri-thali, etc\nii.\tTraining Organized: \na.\tTwenty one days Training at Centre for Advanced Faculty Training (DT Division) on ‘R & D strategies and interventions for effective agribusiness and entrepreneurship development in dairy and food sector’; \nb.\tone/two months or shorter duration trainings for students and others under BPD unit and KVK, NDRI, Karnal\nc.\tFive days training on the aspects of dairy processing to the farmers of Karnal district. \niii.\tGeneral Secretary, Staff Club, NDRI, Karnal\niv.\tMember: Student Empowerment Unit, Conferences organized from 2015 till 2018, convocation, credit seminar evaluation committees; Mera Gaon Mera Gaurav program, Farmer’s First Door programme, Swatchh Bharat Abhiyan, coordinator and mentor of different groups for organizing Foundation Program-2017, 2018, Nodal officer of Poshan Maah-2020 etc\nv.\tConvener/ Rapporteur of sessions: Conference, Dr. K. K. Iya Memorial oration; International conference of Proteomics Society of India\nvi.\tOther responsibilities: Management Representative of QMS-IS/ISO 9001:2008 and HACCP- IS 15000:2013 of Experimental Dairy (essential part of institute) until Jan 2019; one of the editors of Institute hindi magazine Dudgh Ganga which also received coveted award from ICAR (until 2019).\nvii.\tResource Generation on account of consultancy provided in field of dairy processing and by conducting sponsored trainings \nMore than ₹ 2 50 000/- (Two lakhs fifty thousand only)\nviii.\tBesides research, teaching and extension activities, I am also involved in promotion of Hindi language and have won several prizes during competitions (like extempore, essay, e-mail writing) organized by Official Language Units.\nix.\tLifetime Member of three scientific bodies: Indian Dairy Association- RE/NZ/LM/10852/HR; Association of Food Scientists & Technologists (INDIA)- AFST/LM/9-2018/KRN/2444; Lifetime member of Home Science Association of India; Membership number: HSAI-2017-HR-127-LF\nx.\tReviewed research papers of Journal of Ayurveda and Integrative Medicine (Elsevier), LWT, International Journal of Food Properties, Indian Journal of Dairy Science, Indian Journal of Natural Products and Resources, United Scientific Group, etc. \n\n\n\n\n\n\n\n\nDated: 12-04-2022\t \nNeelam Upadhyay",institutionString:"National Dairy Research Institute",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"National Dairy Research Institute",institutionURL:null,country:{name:"India"}}}],coeditorOne:{id:"207452",title:"Dr.",name:"Veena",middleName:null,surname:"Nagaraj",slug:"veena-nagaraj",fullName:"Veena Nagaraj",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRLB5QAO/Profile_Picture_2022-06-29T10:37:56.jpg",biography:"N. Veena, Ph.D., is working as an Assistant Professor in the Department of Dairy Chemistry, College of Dairy Science and Technology, Guru Angad Dev Veterinary and Animal Sciences University, Ludhiana, Punjab. She received her B.Tech degree in Dairy Technology from Karnataka Veterinary, Animal and Fisheries Sciences University, Bidar, Karnataka, India, and her M.Tech and Ph.D. degrees in Dairy Chemistry from ICAR-National Dairy Research Institute, Karnal, Haryana, India. Her expertise includes fortification of milk, development, characterization of functional dairy foods, and nanoencapsulation of nutraceuticals and their delivery. She is the recipient of junior research and institutional fellowships during her master's and doctoral programs from the ICAR-National Dairy Research Institute, Karnal, Haryana, India. She has been involved in different institutional and externally funded research projects such as Milkfed (Punjab), ICAR, DST, and RKVY as PI and Co-PI. \r\nShe has published 17 research papers in peer-reviewed journals, 2 edited books, 13 book chapters, 15 popular articles, and 7 practical manuals. She has developed the e-learning content for post-graduate dairy chemistry courses under the NAHEP project. She has presented her research work at various national and international seminars and conferences and received several awards for best oral and poster presentations. She is a member of various professional bodies such as life member of SASNET-Fermented Foods, Indian Dairy Association, Association of Food Scientists and Technologists (India), and Dairy Technology Society of India, among others.",institutionString:"Guru Angad Dev Veterinary and Animal Sciences University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Guru Angad Dev Veterinary and Animal Sciences University",institutionURL:null,country:{name:"India"}}},coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"5",title:"Agricultural and Biological Sciences",slug:"agricultural-and-biological-sciences"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"444312",firstName:"Sara",lastName:"Tikel",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/444312/images/20015_n.jpg",email:"sara.t@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. 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1. Introduction
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1.1. LeFort osteotomies
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Midface osteotomies have been used to correct maxillary‐zygomatic deformities, and historically have been classified anatomically based on the Guerin‐LeFort fracture classification [1]. The first total LeFort I osteotomy was performed by Wassmund in 1927 for correction of the skeletal open bite [2]. In spite of all the advancements made in the field of orthognathic surgery, a variety of complications are documented [3]. These include maxillary sinusitis, loss of tooth vitality, sensory nerve morbidity, aseptic necrosis, vascular complications (i.e., arteriovenous fistulae or hemorrhage) nasal septum deviation, unfavorable fractures of the skull base and pterygoid plates, ophthalmic complications (including blindness) malpositioning, nonunion, maxilla instability, and relapse [4].
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1.2. Hemorrhage
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Excessive bleeding has been reported as a common complication of LeFort osteotomies. The incidence of life‐threatening hemorrhage in maxillary osteotomies is reported in approximately 1% [5]. The descending palatine artery is the most common source for mild to moderate bleeding during LeFort I osteotomy and delayed bleeding afterward. The descending palatine artery damage may occur during the medial wall osteotomy. Injury to the descending palatine artery during LeFort I osteotomy can be minimized by limiting the osteotomy to 30 mm posterior to the piriform rim in females and to 35 mm in males[6]. In maxillary superior repositioning, bone removal around the descending palatine artery is a common cause of vascular injury. If the surgeon encounters the descending palatine artery, it should be cauterized. The internal maxillary artery is the most frequently cited source of massive hemorrhage [7]. Meticulous placement of the curved osteotome in the pterygomaxillary junction is important to avoid injury to the internal maxillary artery and its branches. Turvey and Fonseca reported that the main trunk of the maxillary artery was most vulnerable to the damage within the pterygopalatine fossa in the lateral position and they recommended angling the posterior lateral maxillary osteotomy downward to avoid damaging the artery [8]. Packing is suggested as the first attempt to tamponade the hemorrhage. In delayed bleeding after LeFort I osteotomy, the surgeon should reopen surgical site and move the maxilla downward to find the bleeding source (Figure 1). In many cases, direct visualization of the bleeding source and cauterization of injured vessels stops the hemorrhage (Figure 2). Several techniques have been suggested to control bleeding from the internal maxillary artery such as ligation of the external carotid artery and angiographic embolization. Emergency access to vascular embolization is crucial. If a patient has severe bleeding, the surgeon should not waste time and intervene immediately. The collateral arteries and the anastomoses between circulations lead to the limited success of surgical ligation of the external carotid artery [9]. A recent study recommended use of tranexamic acid irrigation in obviating perioperative blood loss during orthognathic surgery [10].
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Figure 1.
Possible bleeding sources during LeFort I osteotomy.
Figure 2.
Relationship of osteotomy sites and major hemorrhage sources during LeFort I osteotomy.
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1.3. Neurosensory deficit
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The infraorbital nerve may be compressed, retracted or transected inadvertently during subperiosteal dissection.
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Infraorbital nerve injury may have resulted from incorrect separation during disimpaction.
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As are the cases with bilateral sagittal ramus osteotomy, nerve sensitivity may return within 6–12 months [11].
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The absence of post‐operatory sensitivity after a LeFort I procedure was documented in a study that applied both objective and subjective tests. The results showed a greater incidence of insensitivity in the region above the upper lip, followed by the lower lip and the chin, as was observed in bimaxillary procedures [12]. Neurosensory alterations are normally immediately perceived in the post‐operatory period. They are the result of traction of the infraorbital nerve and direct trauma to the anterior, medial, and posterior superior alveolar nerves, as well as to the nasopalatine nerve and the descending palatal nerve [13]. A study performed at the University of North Carolina on patients undergoing bilateral Sagittal split ramus osteotomy (SSRO) reported that 98% of the patients presented altered sensitivity of the chin 1 month after the operation; with 81% of these patients still presenting with this alteration 6 months after the operation [14]. It is recommended that the patient be advised of possible neurosensory alterations in pre‐operatory visits, thus reducing the patient\'s post‐operatory anxiety [15]. Many studies confirm the return of neurosensory function up to 1 year after surgery [11].
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1.4. Tooth sensitivity
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An osteotomy closer than 5 mm of the apices of the teeth has risk of root injuries[16]. In superior repositioning of the maxilla by more than 6 mm, saving of 5 mm margin is not always possible because of the infraorbital foramen position [4]. After orthognathic surgery, loss of vascularity of the dentition is rare, but initial loss of response to pulpal stimulation is common. Long‐term suppressed response to stimulation can occur, but does not necessarily mean a tooth requires endodontic therapy. Although some teeth may eventually become necrotic and require endodontic treatment, many teeth recover without treatment and return to normal coloration and respond to pulp testing [17]. De Jongh et al. studied electric and thermal pulp testing of 10 patients after LeFort I osteotomy in compared to 10 control patients without osteotomy. Their study showed that 71% of 128 teeth were responsive to electric and thermal pulp stimulation and 93% of 136 teeth in the controls [18].
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1.5. Maxillary sinusitis
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Sinusitis after LeFort I osteotomy is uncommon, with a reported incidence of septic complications of 0.5–4.8% [19]. Possible explanations for postoperative maxillary sinusitis following LeFort I osteotomy were pre‐existing sinus disease or non‐viable bone fragments left in the maxillary sinus (Figure 3) [20]. A recent study by Valestar et al. showed LeFort I procedure did not influence already existing physical or mental complaints, and nasal ventilation was not negatively affected. However, evaluation of sino‐nasal pathology should be emphasized in the preoperative work‐up [19]. A recent study by Nocini et al. suggested that LeFort I osteotomies can affect the maxillary sinus. The postoperative radiologic views of the maxillary sinus showed inflammation and rhinosinusitis symptoms after LeFort osteotomies. Larger long‐term studies are warranted to clarify the postoperative outcomes and complications (Figure 4) [21].
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Figure 3.
Maxillary sinusitis after LeFort I osteotomy.
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Figure 4.
Radiologic findings: postoperative computed tomography scan displaying interruption of the medial walls [21].
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1.6. Nose deformity
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Septal malposition may occur during LeFort osteotomy and cause nasal deviation. A possible reason for a cartilagenous septum deviation after a maxillary osteotomy is dislocation by a partially deflated cuff during extubation. Manual inspection of the nares after extubation is important, yet often forgotten [22]. Nasal ventilation generally improves after orthognathic surgery [19]. The most common reason for postoperative nasal‐septal deviation is compression or displacement from inadequate bone removal of the nasal crest of the maxilla or inadequate trimming of the cartilagenous septum (Figure 5) [9].
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Figure 5.
Severe nasal deviation after LeFort I osteotomy.
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1.7. Aseptic necrosis
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Avascular necrosis of the maxilla after LeFort I osteotomy has been reported [23]. Usually, these complications relate to the degree of vascular compromise and occur in less than 1% of cases. Rupture of the descending palatine artery during surgery, postoperative vascular thrombosis, perforation of palatal mucosa when splitting the maxilla into segments, or partial stripping of palatal soft tissues to increase maxillary expansion may impair blood supply to the maxillary segments. Sequelae of compromised vasculature include loss of tooth vitality, development of periodontal defects, tooth loss, or loss of major segments of alveolar bone or the entire maxilla (Figure 6) [24]. The risk is increased in patients with anatomical irregularities, such as craniofacial dysplasia\'s, orofacial clefts, or vascular anomalies [5]. The treatment of avascular necrosis of the maxilla is not easily manageable [25]. Regarding no treatment protocol has been established, aseptic necrosis of the maxilla should be treated by maintenance of optimal hygiene, antibiotic therapy to prevent secondary infection, heparinization, and hyperbaric oxygenation [24]. In such cases, it is evident that there is a serious problem with the tissue perfusion immediately postoperatively and the patient must be taken back to the theatre immediately to reposition the segment; delay only makes it worse [26].
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Figure 6.
Initial aspect of the aseptic maxillary necrosis on the seventh postoperative day [24].
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1.8. Unfavorable fractures
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Unfavorable fractures may consist of pterygoid plate, sphenoid bone, and middle cranial fossa fractures. Lanigan and Guest demonstrated pterygomaxillary dysjunction using a curved osteotome and described high‐level fractures of the pterygoid plates with disruption of the pterygopalatine fossa which could extend to the skull base [27]. Unfavorable pterygoid plate fracture is well studied and documented (Figure 7) [28]. Postoperative CT scans indicated that the prevalence of unfavorable fractures of the pterygomaxillary region may be more than previous expectations. Many of these unfavorable fractures are unobserved as there was no CSF leak because of a local soft tissue seal [29]. Renicke et al. reported the incidence of pterygoid plate fracture was 58% following LeFort I osteotomy using postoperative CT scans [30].
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Figure 7.
Possible lines of bad split during LeFort I osteotomy.
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1.9. Improper maxillary repositioning
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Figure 8.
Over‐correction after maxillary superior repositioning.
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Several factors are responsible for improper maxillary repositioning such as missing a centric relation‐centric occlusion discrepancy preoperatively; failure to achieve the desired maxillary position during isolated maxillary surgery, failure to seat the condyle because of inadequate removal of posterior bony interference and inaccurate vertical positioning [9]. Improper maxillary positioning may occur in correction of vertical maxillary excess. In a study by the first author, the incidence of under‐correction (25%) was more than over‐correction (7.5%) (Figure 8). Five millimeter was considered as a cutoff point for tooth shows at rest and 15 mm at the maximum smile. When tooth show at rest was more than 5 mm presurgically, 50.5% of clinical predictions did not follow the clinical results, and 75% of clinical predictions revealed the same results when the tooth show was less than 5 mm. When the amount of tooth shown in the maximum smile was more than 15 mm presurgically, 75% of clinical predictions did not follow clinical results, and 25% of the predictions met the same results in the maximum smile was less than. Clinical predictions based on the tooth show at rest and at the maximum smile did not have a reliable correlation with clinical results in maxillary superior repositioning. The risk of errors in predictions raised when the amount of superior repositioning of the maxilla increased. Generally, surgeons had a tendency to under‐correct rather than over‐correct. Also clinical prediction is used as a guideline by many surgeons, and it may be associated with variable clinical results [31].
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1.10. Trigemino‐cardiac reflex
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Trigemino‐cardiac reflex (TCR) is characterized by cardiac arrhythmia, ectopic beats, atrioventricular block, bradycardia, syncope, vomiting, and asystole. This life‐threatening condition has been documented during simple zygomatic arch elevations, repositioning of blowout and maxillary fractures, orthognathic surgery, and nasoethmoidal fractures [32]. Besides evaluation of at‐risk patients (e.g., children and patients with a medical history of cardiac disease) and high‐risk surgeries (e.g., strabismus), some authors suggested using ketamine for anesthetic induction to decrease the oculocardiac reflex in children undergoing strabismus surgery [32]. Predisposing factors besides cardiac disease are hypoxia and hypercarbia, and use of opioids and β‐blockers. TCR has been identified with a sudden onset of parasympathetic hypotension, apnea, or gastric hypermotility during stimulation of any of the sensory branches of the trigeminal nerve. In some cases, stopping the surgery has resulted in recovery of a normal rhythm; in other cases, anticholinergic drugs and cardiac massage have been mentioned. It is recommended that the anesthesiology team be informed that they may be prepared for mobilization in case of adverse effects. In every high‐risk case presented in the classification, prophylactic administration of, for example, 0.5 mg atropine IV, right before any surgical manipulation known to be risky for TCR is mandatory [32].
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1.11. Ophthalmic complications
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Potential ophthalmic complications following LeFort I osteotomy includes decrease in visual acuity, extraocular muscle dysfunction, neuroparalytic keratitis, and lacrimal apparatus problems including epiphora [33]. Visual impairment after LeFort I osteotomy may be due to inappropriate separation of the pterygomaxillary junction and resulting fractures extending to the pterygoid plates, sphenoid bone, orbital floor, optic canal, or the skull base. It may damage the optic nerve or its vascular supply. Hemorrhage from the descending palatine artery or sphenopalatine artery in LeFort I osteotomy may be considered as a reason for systemic hypotension. Hemorrhage from the pterygopalatine fossa may leak the orbital cavity through the inferior orbital fissure and increase intraocular pressure (IOP). Hypotensive anesthesia is useful during a maxillofacial operation for blood loss control and enhancing the visibility in the surgical field. The blood flow to the globes may be changed by elevated IOP or dropped systemic blood pressure. Hypotensive anesthesia may potentially reduce the blood supply to the retina and choroid and may cause embolism of the vessels or infarction of the optic nerve. The effect of hypotensive anesthesia on visual impairment has not been clarified yet [34].
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1.12. Nasolacrimal duct obstruction
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Nasolacrimal duct obstruction (NLDO) after maxillary orthognathic surgery is rare. The absence of an NLDO after LeFort I osteotomy is reasonable because the distance from the nasal opening of the NLD to the levels of osteotomy should be at least 5 mm. The normal distance between the NLD nasal opening and the nasal floor is 11–17 mm. LeFort I osteotomy should be performed 5 mm above the nasal floor. The distal to the proximal part of the NLD is vulnerable to be obstructed after maxillary osteotomy. Secondary inflammatory changes associated with an indirect injury of the NLD lead to obstruction. So surgeons should be aware of the risk of NLDO after orthognathic surgery (Figures 9–11); this can be managed by dacryocystorhinostomy with high success rate [35].
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Figure 9.
Representative dacryocystograms showing obstruction of the nasolacrimal duct in a patient who underwent orthognathic surgery and complained of permanent epiphora [35].
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Figure 10.
(A) Bad split occurred on the right side. (B) Fixation of bone fragment was done and replaced.
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Figure 11.
Complete destruction of condyle in a patient, who had undergone orthognathic surgery, was re‐treated with the aid of temporomandibular joint prostheses. Before surgery (A), 3D image of the mandible showing bilateral absence of condyles (B), and after surgery (C) [53].
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1.13. Nonunion of segments
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Nonunion of segments in conventional LeFort I osteotomy is rare. In segmental osteotomy the risk of nonunion is higher. A good vascular pedicle and bone grafts are crucial. Additional stability of the maxillary segments after fixation with miniplates was suggested by the use of palatal dressing plates. Use of split with intermaxillary fixation may be useful. Three‐dimensional fixation or immobilization can therefore be gained by using miniplates superiorly on the bony aspect, a dressing plate on the palatal aspect, and a wired‐in final surgical wafer on the occlusal aspect of the dentoalveolar segments [36]. If nonunion occurs the surgical site should be reopened, fibrous tissue removed and proper rigid fixation be used for predictable union of segments.
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1.14. Tooth damage
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Tooth damage in segmental osteotomy is not uncommon. In LeFort I, the risk of damage to the teeth roots increases when the horizontal osteotomy line is 5 mm or less. Close proximity to interdental osteotomy cuts or to screws may cause tooth damage, and pulp necrosis [36]. The pulpal blood flow of teeth adjacent to vertical osteotomies of LeFort I segmental maxillary osteotomies has been reported to be decreased significantly at 4 days after surgeries for lateral incisors, canines, and premolars. However, recovery was seen 56 days after operations. The central incisors and teeth that are distant from the vertical osteotomy have blood flow without significant change [37]. It is advocated that presurgical orthodontic separation of the roots by at least 2 mm at the cementoenamel junction and 4 mm at the apical third be maintained to avoid vascular compromise or damage to the roots adjacent to interdental osteotomies [36].
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2. Sagittal split osteotomy
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Sagittal split osteotomy (SSO) is a conventional technique to correct mandibular excess or retrognathia. Since its introduction by Trauner and Obwegeser, SSO has undergone numerous modifications and improvements [38].
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2.1. Neurosensory disturbance
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In SSO, the inferior alveolar nerve (IAN) may be injured and cause neurosensory disturbance (NSD) in the lower lip. The NSD caused by damage to the IAN is reportedly 9–84.6% [39, 40]. Even with careful surgery, injury to the IAN appears unpredictable. Multiple factors are considered responsible for the development of NSD after SSO, including fixation methods, patient age and surgical procedures, improper splinting, magnitude of mandibular movement, experience of the surgeon, and timing of the postoperative neurosensory evaluation [40]. Injury to the IAN may happen with direct and indirect intraoperative trauma and results in change of sensibility or altered sensation of the lower lip and/or mental region. It may lead the negative effect on patients’ normal functions such as eating, drinking, speech, and social interaction. NSD may affect patients’ everyday lives and can have social or psychological problems [41]. The position of the canal is important in NSD following SSO because the canal position is impacted by osteotomy design and fixation techniques. Nowadays, technologies and software help to evaluate the canal by using CBCT data. An increased distance between the canal and cortical bone presurgically decreased the incidence of postoperative NSD, and high bone density increased of the risk of postoperative NSD. A short post‐operation assessment comparing monocortical and bicortical fixation in a monkey model, showed that IAN function was better with plate fixation than screw fixation [42].
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2.2. Unfavorable split
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An unfavorable fracture, called a “bad split” although infrequent in the hands of an experienced operator, occasionally develop and can lead to intraoperative difficulties as well as postoperative relapse [43]. Frequently cited reasons for bad split include incomplete osteotomies, using osteotomes that are too large, attempting to split the segments too rapidly presence of impacted third molars, misdirecting the medial osteotomy upward toward the condyle and placement of the medial osteotomy too far superior to the lingula [44].
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Synonyms used for bad split include “buccal cortical plate fracture” (proximal segment) and “lingual cortical plate fracture” (distal segment) [45]. A bad split can occur during SSO of the mandible regarding precautions. The incidence of bad split is low (0.7% of all SSOs) and patients sometimes have uneventful healing. A significant decrease in incidence did not report during the 20‐year period, and neither technical progress nor the surgeon\'s experience further decreased the frequency of bad splits [45]. It was reported that older patients experienced more bad splits than younger patients [46]. The length of the medial osteotomy line—short or long—did not alter the prevalence of a bad split. The bone thickness of the ramus may affect the type of fracture pattern on the medial side of the ramus [47]. It is clear that certain mandibular anatomic differences can increase the risk of a bad split during SSO [44]. Use of splitters and separators instead of chisels does not increase the risk of a bad split and is therefore safe with predictable results [48].
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2.3. Infection
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Postoperative infection was reported in studies of patients undergoing bilateral sagittal ramus osteotomy in a period ranging from 5 days to up to a year after surgery. Infections required antibiotic therapy, and in some cases, the patients underwent surgical drainage. osteomyelitis in bilateral sagittal ramus osteotomy was reported [11]. The rate of infection after SSO is up to 11.3%. Infection after SSO is within normal range for a clean‐contaminated procedure. Rigid fixation of the osteotomy may decrease the need for hardware removal [49].
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2.4. Excessive bleeding
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In the literature, there were no uniform criteria defining bleeding complications. Incidence varied between 0.39 and 38% ranging from slight to a life‐threatening hemorrhage.
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Minor bleeding in SSOs can usually be easily managed by using local anesthetics containing 1:100,000 adrenalines injected before the operation, electrocautery or compression. Excessive blood loss may due to surgical injury of larger vessels. It was reported that excessive blood loss happen mainly to maxillary surgery and the need for blood transfusion in mandibular operations is rarely necessary [50].
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2.5. Condylar resorption
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Condylar resorption (CR) or condylysis can be defined as progressive change of condylar shape with a reduction in mass. Most patients have a decrease in posterior face height, retrognathism, and progressive anterior open bite with clockwise rotation of the mandible. CR may be defined as osteoarthrosis and can be categorized as primary (idiopathic) and secondary. Current evidence on CR is not clear but seen more in female with mandibular deficiency and high mandibular plane angle after bimaxillary surgery; a change in occlusal plane (counterclockwise rotation) may be associated with condylar resorption after orthognathic surgery [51]. It was hypothesized that condylar remodeling is due to an imbalance between mechanical stress applied to the temporomandibular joints (TMJ) and patient’ adaptive capacities. It mainly occurs in 14 to 50‐years‐old women with pre‐existing TMJ dysfunction, estrogen deficiency, and class II malocclusion with a high mandibular plane angle, a diminished posterior facial height and posteriorly inclined condylar neck. Mandibular advancement superior to 10 mm, counterclockwise rotation of the mandible, and posterior condylar repositioning were associated with an increased risk of CROS. Treatment consists of re‐operation in case of degradation after an inactivity period of at least 6 months [52].
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2.6. Temporomandibular dysfunction
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The effect of orthognathic surgeries on temporomandibular dysfunction(TMD) is controversial. Some studies support degrees of improvement of TMD [5, 54]. Patients with preexisting TMJ dysfunction undergoing orthognathic surgery, particularly mandibular advancement, are likely to have significant worsening of the TMJ dysfunction postsurgery. TMJ dysfunction must be closely evaluated, treated if necessary and monitored in the orthognathic surgery patients [55]. Use of lag screws, improper control of the proximal segments, and advancement more than 10 mm increases the risk of post‐orthognathic TMD. Orthognathic surgery should not be used solely for management of TMD; patients having orthognathic treatment for correction of their dentofacial deformities with TMD problem had more improvement in their signs and symptoms than deterioration [56].
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2.7. Postoperative airway problem
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It is clear that mandibular set back can affect upper airway patency [57]. The amount of narrowing of the pharyngeal airway is smaller in patients undergoing bimaxillary surgery than in patients undergoing mandibular setback surgery [58]. Bimaxillary orthognathic surgery for correction of Class III malocclusion caused an increase of the total airway volume and improvement of polysomnography parameters [59]. Bimaxillary surgery rather than mandibular setback surgery should be used to correct a class III deformity and reduce the risk of obstructive sleep apnea; in fact, bimaxillary surgery may have less effect on the pharyngeal airway patency than mandibular setback surgery alone [60]. A recent study suggested that BSSO presents less change in the pharyngeal airway space after mandibular setback surgery compared to intraoral vertical ramus osteotomy. Furthermore, bimaxillary surgery is superior to mandibular setback surgery alone for the correction of the prognathic mandible, particularly in patients with factors predisposing them to the development of breathing problems [61].
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3. Intraoral vertical ramus osteotomy
\n
Intraoral vertical ramus osteotomy (IVRO) is another approach for the correction of mandibular prognathism. It is very simple and rapid. The inherent anatomic architecture of the mandible poses little interference on the cut surface of the IVRO osteotomy site during mandibular setback, even in cases of severe asymmetry. In addition, because the segments are not fixed, no stress occurs while the distal segment is positioned with the condylar head during and after the osteotomy procedure. Moreover, IVRO has less chance of nerve damage during the osteotomy procedure than SSRO. In addition to advantages provided during the operation, this procedure has various postoperative advantages. It seems to have curable effects on most patients with preoperative TMD [9].
\n
Figure 12.
Classification of the shape of the osteotomy line [62].
\n
During IVRO, inferior alveolar nerve (IAN) damage may occur due to the proximity of the vertical osteotomy to the IAN. Preoperatively, the surgeon should evaluate the lingula on radiographic views. The antilingular eminence on the lateral surface of the ramus should be detected. This small protuberance is located at the posterior one third from the posterior border of the ramus and about 10 mm above the occlusal plane of the lower molars in the vertical aspect, which corresponds to the opposite side of the mandibular foramen. The cut should begin 6–7 mm from the posterior border of the ramus. Kawase‐Koga et al. classified the osteotomy line into three types, namely vertical, C‐shaped, and oblique. The most complications occurred in the vertical type cases, and no complications were found in oblique type cases. Condylar luxation was found mainly in unilateral IVRO cases, and bony interference was found in bilateral IVRO cases. These results suggest that the oblique type of osteotomy line has the advantage of avoiding complications (Figure 12) [62].
\n
Figure 13.
Condylar sagging at the (left side) after IVRO.
\n
Condylar luxation and bony interference are major complications of IVRO [62]. The most troublesome sequelae are skeletal instability and antero‐inferior condylar displacement (sag), with resultant unpredictability of postoperative mandibular position [63]. Condylar luxation is considered to be related to condylar sag, which occurs with the antero‐inferior postoperative displacement of the proximal segment [62]. When the attachments of the masseter and medial pterygoid muscles to the proximal segment are removed extensively, large condylar sag occurs as a complication of IVRO. Condylar luxation is also related to forward force on the condyle from the lateral pterygoid muscle. Normally, the condyle is located in the anterior and inferior position within the glenoid fossa immediately after IVRO. It is gradually reseated into the original position after surgery with the application of intermaxillary elastics [64]. Several techniques have been reported to avoid condylar luxation and interference of the proximal segment. Suturing the periosteum of the segments around the incision with3–0 Vicryl to prevent sagging against the mandibular fossa has been suggested [64]. Rigid fixation is not recommended in IVRO and increases risk of post‐operation open bite. Elastic therapy after osteotomy effectively decreases open bite due to the muscle tension (Figure 13).
\n
\n\n',keywords:"osteotomies, complications",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/51365.pdf",chapterXML:"https://mts.intechopen.com/source/xml/51365.xml",downloadPdfUrl:"/chapter/pdf-download/51365",previewPdfUrl:"/chapter/pdf-preview/51365",totalDownloads:2528,totalViews:1543,totalCrossrefCites:2,totalDimensionsCites:3,totalAltmetricsMentions:0,impactScore:2,impactScorePercentile:82,impactScoreQuartile:4,hasAltmetrics:0,dateSubmitted:"July 16th 2015",dateReviewed:"May 2nd 2016",datePrePublished:null,datePublished:"August 31st 2016",dateFinished:"June 27th 2016",readingETA:"0",abstract:"Orthognathic surgery is a common approach for treatment of maxillofacial deformities. Sagittal split ramus osteotomy (SSRO) is one of the most common techniques used to treat various mandibular deformities. A LeFort I osteotomy is suggested in deformities of the maxilla and can be used along with SSRO or intra‐oral vertical ramus osteotomy (IVRO).The aim of orthognathic surgery is to improve function and facial appearance; this benefits the patient psychologically and socially. Common complications which may occur in orthognathic surgery include vascular disease, temporomandibular joints (TMJ) problems, nerve damage, infection, bone necrosis, periodontal disease, vision impairment, hearing problems, hair loss, and neuropsychiatric problems. Rarely complications could be fatal. Because of the wide range of complications the surgeon should keep prevention protocols in mind and be prepared to treat them should they occur. In this chapter, common complications of various osteotomies in the mandible and maxilla are discussed.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/51365",risUrl:"/chapter/ris/51365",book:{id:"5112",slug:"a-textbook-of-advanced-oral-and-maxillofacial-surgery-volume-3"},signatures:"Reza Tabrizi and Hassan Mir Mohammad Sadeghi",authors:[{id:"171716",title:"Dr.",name:"Reza",middleName:null,surname:"Tabrizi",fullName:"Reza Tabrizi",slug:"reza-tabrizi",email:"tabmed@gmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Shahid Beheshti University of Medical Sciences",institutionURL:null,country:{name:"Iran"}}}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_1_2",title:"1.1. LeFort osteotomies",level:"2"},{id:"sec_2_2",title:"1.2. Hemorrhage",level:"2"},{id:"sec_3_2",title:"1.3. Neurosensory deficit",level:"2"},{id:"sec_4_2",title:"1.4. Tooth sensitivity",level:"2"},{id:"sec_5_2",title:"1.5. Maxillary sinusitis",level:"2"},{id:"sec_6_2",title:"1.6. Nose deformity",level:"2"},{id:"sec_7_2",title:"1.7. Aseptic necrosis",level:"2"},{id:"sec_8_2",title:"1.8. Unfavorable fractures",level:"2"},{id:"sec_9_2",title:"1.9. Improper maxillary repositioning",level:"2"},{id:"sec_10_2",title:"1.10. Trigemino‐cardiac reflex",level:"2"},{id:"sec_11_2",title:"1.11. Ophthalmic complications",level:"2"},{id:"sec_12_2",title:"1.12. Nasolacrimal duct obstruction",level:"2"},{id:"sec_13_2",title:"1.13. Nonunion of segments",level:"2"},{id:"sec_14_2",title:"1.14. Tooth damage",level:"2"},{id:"sec_16",title:"2. Sagittal split osteotomy",level:"1"},{id:"sec_16_2",title:"2.1. Neurosensory disturbance",level:"2"},{id:"sec_17_2",title:"2.2. Unfavorable split",level:"2"},{id:"sec_18_2",title:"2.3. Infection",level:"2"},{id:"sec_19_2",title:"2.4. Excessive bleeding",level:"2"},{id:"sec_20_2",title:"2.5. Condylar resorption",level:"2"},{id:"sec_21_2",title:"2.6. Temporomandibular dysfunction",level:"2"},{id:"sec_22_2",title:"2.7. Postoperative airway problem",level:"2"},{id:"sec_24",title:"3. Intraoral vertical ramus osteotomy",level:"1"}],chapterReferences:[{id:"B1",body:'\nKim, S.‐G., and S.‐S. Park, Incidence of complications and problems related to orthognathic surgery. Journal of Oral and Maxillofacial Surgery, 2007. 65(12): p. 2438–2444.\n'},{id:"B2",body:'\nTabrizi, R., H. Pakshir, and B. Nasehi, Does the type of maxillomandibular deformity influence complication rate in orthognathic surgery? Journal of Craniofacial Surgery, 2015. 26(7): p. e643–e647.\n'},{id:"B3",body:'Wassmund, M., Leipzig: H. Meußer Lehrbuch der praktischen Chirurgie des Mundes und der Kiefer. Vol. 1. 1935: H. Meusser.\n'},{id:"B4",body:'\nGarg, S., and S. Kaur, Evaluation of post‐operative complication rate of Le Fort I osteotomy: a retrospective and prospective study. Journal of Maxillofacial and Oral Surgery, 2014. 13(2): p. 120–127.\n'},{id:"B5",body:'\nKramer, F.J., et al., Intra‐ and perioperative complications of the LeFort I osteotomy: a prospective evaluation of 1000 patients. Journal of Craniofacial Surgery, 2004. 15(6): p. 971–977; discussion 978–979.\n'},{id:"B6",body:'\nLi, K.K., J.G. Meara, and A. Alexander, Jr., Location of the descending palatine artery in relation to the Le Fort I osteotomy.Journal of Oral and Maxillofacial Surgery, 1996.54(7): p. 822–825; discussion 826–827.\n'},{id:"B7",body:'\nKhanna, S., and A.B. Dagum, A critical review of the literature and an evidence‐based approach for life‐threatening hemorrhage in maxillofacial surgery. Annals of Plastic Surgery, 2012. 69(4): p. 474–478.\n'},{id:"B8",body:'\nTurvey, T., and R. Fonseca, The anatomy of the internal maxillary artery in the pterygopalatine fossa: its relationship to maxillary surgery. Journal of Oral Surgery (American Dental Association: 1965), 1980. 38(2): p. 92.\n'},{id:"B9",body:'\nFelice O\'Rayan, A.S., Complications with Orthognathic Surgery, in Oral and maxillofacial surgery, M. Fonseca, Turvey, Editor. 2009, Saunders Elsevier. p. 419–489.\n'},{id:"B10",body:'\nEftekharian, H., et al., Effect of tranexamic acid irrigation on perioperative blood loss during orthognathic surgery: a double‐blind, randomized controlled clinical trial. Journal of Oral Maxillofacial Surgery, 2015. 73(1): p. 129–133.\n'},{id:"B11",body:'\nSousa, C.S., and R.N.T. Turrini, Complications in orthognathic surgery: a comprehensive review. Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology, 2012. 24(2): p. 67–74.\n'},{id:"B12",body:'\nEssick, G., et al., Short‐term sensory impairment after orthognathic surgery. Oral and Maxillofacial Surgery Clinics of North America, 2001. 13(2): p. 295–314.\n'},{id:"B13",body:'Hummes, B., et al., Complicações no tratamento cirúrgico da deficiência transversa do osso maxilar. Stomatos, 2008. 14(27):p. 63–73.\n'},{id:"B14",body:'\nEssick, G.K., et al., Facial altered sensation and sensory impairment after orthognathic surgery. International Journal of Oral and Maxillofacial Surgery, 2007. 36(7): p. 577–582.\n'},{id:"B15",body:'\nPanula, K., K. Finne, and K. Oikarinen, Incidence of complications and problems related to orthognathic surgery: a review of 655 patients. Journal of Oral and Maxillofacial Surgery, 2001. 59(10): p. 1128–1136.\n'},{id:"B16",body:'\nKahnberg, K., and H. Engström, Recovery of maxillary sinus and tooth sensibility after Le Fort I osteotomy. British Journal of Oral and Maxillofacial Surgery, 1987. 25(1): p. 68–73.\n'},{id:"B17",body:'\nRobl, M.T., B.B. Farrell, and M.R. Tucker, Complications in orthognathic surgery: a report of 1000 cases. Oral and Maxillofacial Surgery Clinics of North America, 2014. 26(4): p. 599–609.\n'},{id:"B18",body:'\nde Jongh, M., D. Barnard, and D. Birnie, Sensory nerve morbidity following Le Fort I osteotomy. Journal of Maxillofacial Surgery, 1986. 14: p. 10–13.\n'},{id:"B19",body:'\nValstar, M.H., et al., Maxillary sinus recovery and nasal ventilation after Le Fort I osteotomy: a prospective clinical, endoscopic, functional and radiographic evaluation. International Journal of Oral Maxillofacial Surgery, 2013. 42(11): p. 1431–1436.\n'},{id:"B20",body:'\nBell, C.S., W.J. Thrash, and M.K. Zysset, Incidence of maxillary sinusitis following Le Fort I maxillary osteotomy. Journal of Oral and Maxillofacial Surgery, 1986. 44(2): p. 100–103.\n'},{id:"B21",body:'\nNocini, P.F., et al., Is Le Fort I osteotomy associated with maxillary sinusitis? Journal of Oral and Maxillofacial Surgery, 2016. 74(2): p. 400. e1–400. e12.\n'},{id:"B22",body:'\nAcebal‐Bianco, F., et al., Perioperative complications in corrective facial orthopedic surgery: a 5‐year retrospective study. Journal of Oral and Maxillofacial Surgery, 2000. 58(7): p. 754–760.\n'},{id:"B23",body:'\nLanigan, D.T., J.H. Hey, and R.A. West, Aseptic necrosis following maxillary osteotomies: report of 36 cases. Journal of Oral and Maxillofacial Surgery, 1990. 48(2): p. 142–156.\n'},{id:"B24",body:'\nPereira, F.L., et al., Maxillary aseptic necrosis after Le Fort I osteotomy: a case report and literature review. Journal of Oral and Maxillofacial Surgery, 2010. 68(6): p. 1402–1407.\n'},{id:"B25",body:'\nKahnberg, K.E., and C. Hagberg, The approach to dentofacial skeletal deformities using a multisegmentation technique. Clinics in Plastic Surgery, 2007. 34(3): p. 477–484.\n'},{id:"B26",body:'\nSingh, J., et al., Reconstruction of post‐orthognathic aseptic necrosis of the maxilla. British Journal of Oral Maxillofacial Surgery, 2008. 46(5): p. 408–410.\n'},{id:"B27",body:'\nLanigan, D.T., and P. Guest, Alternative approaches to pterygomaxillary separation. International Journal of Oral Maxillofacial Surgery, 1993. 22(3): p. 131–138.\n'},{id:"B28",body:'\nPrecious, D.S., et al., Pterygoid plate fracture in Le Fort I osteotomy with and without pterygoid chisel: a computed tomography scan evaluation of 58 patients. Journal of Oral Maxillofacial Surgery, 1993. 51(2): p. 151–153.\n'},{id:"B29",body:'\nBhaskaran, A., et al., A complication of Le Fort I osteotomy. International Journal of Oral and Maxillofacial Surgery, 2010. 39(3): p. 292–294.\n'},{id:"B30",body:'\nRenick, B.M., and J.M. Symington, Postoperative computed tomography study of pterygomaxillary separation during the Le Fort I osteotomy. Journal of Oral Maxillofacial Surgery, 1991. 49(10): p. 1061–1065; discussion 1065–1066.\n'},{id:"B31",body:'\nTabrizi, R., B. Zamiri, and H. Kazemi, Correlation of clinical predictions and surgical results in maxillary superior repositioning. Journal of Craniofacial Surgery, 2014. 25(3): p. e220–e223.\n'},{id:"B32",body:'\nLübbers, H.‐T., et al., Classification of potential risk factors for trigeminocardiac reflex in craniomaxillofacial surgery. Journal of Oral and Maxillofacial Surgery, 2010. 68(6): p. 1317–1321.\n'},{id:"B33",body:'\nLanigan, D.T., K. Romanchuk, and C.K. Olson, Ophthalmic complications associated with orthognathic surgery. Journal of Oral and Maxillofacial Surgery, 1993. 51(5): p. 480–494.\n'},{id:"B34",body:'\nCheng, H.C., et al., Blindness and basal ganglia hypoxia as a complication of Le Fort I osteotomy attributable to hypoplasia of the internal carotid artery: a case report. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology and Endodontology, 2007. 104(1): p. e27–e33.\n'},{id:"B35",body:'\nJang, S.Y., et al., Nasolacrimal duct obstruction after maxillary orthognathic surgery. Journal of Oral and Maxillofacial Surgery, 2013. 71(6): p. 1085–1098.\n'},{id:"B36",body:'\nHo, M., et al., Surgical complications of segmental Le Fort I osteotomy. British Journal of Oral and Maxillofacial Surgery, 2011. 49(7): p. 562–566.\n'},{id:"B37",body:'\nEmshoff, R., et al., Effect of segmental Le Fort I osteotomy on maxillary tooth type‐related pulpal blood‐flow characteristics. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology and Endodontology, 2000. 89(6): p. 749–752.\n'},{id:"B38",body:'\nTrauner, R., and H. Obwegeser, The surgical correction of mandibular prognathism and retrognathia with consideration of genioplasty. I. Surgical procedures to correct mandibular prognathism and reshaping of the chin. Oral Surgery, Oral Medicine, Oral Pathology , 1957. 10(7): p. 677–689; contd.\n'},{id:"B39",body:'\nAl‐Bishri, A., et al., Neurosensory disturbance after sagittal split and intraoral vertical ramus osteotomy: as reported in questionnaires and patients’ records. International Journal of Oral and Maxillofacial Surgery, 2005. 34(3): p. 247–251.\n'},{id:"B40",body:'\nKuroyanagi, N., et al., Prediction of neurosensory alterations after sagittal split ramus osteotomy. International Journal of Oral and Maxillofacial Surgery, 2013. 42(7): p. 814–822.\n'},{id:"B41",body:'\nBruckmoser, E., et al., Factors influencing neurosensory disturbance after bilateral sagittal split osteotomy: retrospective analysis after 6 and 12 months. Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, 2013. 115(4): p. 473–482.\n'},{id:"B42",body:'\nRich, J., B.A. Golden, and C. Phillips, Systematic review of preoperative mandibular canal position as it relates to postoperative neurosensory disturbance following the sagittal split ramus osteotomy. International Journal of Oral and Maxillofacial Surgery, 2014. 43(9): p. 1076–1081.\n'},{id:"B43",body:'\nSmith, B.R., et al., Mandibular ramus anatomy as it relates to the medial osteotomy of the sagittal split ramus osteotomy. Journal of Oral and Maxillofacial Surgery, 1991. 49(2): p. 112–116.\n'},{id:"B44",body:'\nAarabi, M., et al., Relationship between mandibular anatomy and the occurrence of a bad split upon sagittal split osteotomy. Journal of Oral and Maxillofacial Surgery, 2014. 72(12): p. 2508–2513.\n'},{id:"B45",body:'\nFalter, B., et al., Occurrence of bad splits during sagittal split osteotomy. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology, 2010. 110(4): p. 430–435.\n'},{id:"B46",body:'\nKriwalsky, M.S., et al., Risk factors for a bad split during sagittal split osteotomy. British Journal of Oral and Maxillofacial Surgery, 2008. 46(3): p. 177–179.\n'},{id:"B47",body:'Zamiri, B., et al., Medial cortex fracture patterns after sagittal split osteotomy using short versus long medial cuts: can we obviate bad splits? International Journal of Oral and Maxillofacial Surgery, 2015.44(7): p. 809–15\n'},{id:"B48",body:'\nMensink, G., et al., Bad split during bilateral sagittal split osteotomy of the mandible with separators: a retrospective study of 427 patients. British Journal of Oral and Maxillofacial Surgery, 2013. 51(6): p. 525–529.\n'},{id:"B49",body:'\nBouchard, C. and M. Lalancette, Infections after sagittal split osteotomy: a retrospective analysis of 336 patients. Journal of Oral and Maxillofacial Surgery, 2015. 73(1): p. 158–161.\n'},{id:"B50",body:'\nTeltzrow, T., et al., Perioperative complications following sagittal split osteotomy of the mandible. Journal of Craniomaxillofacial Surgery, 2005. 33(5): p. 307–313.\n'},{id:"B51",body:'\nde Cirugía Ortognática, R.C.D. and U.R. Sistemática, Condylar resorption after orthognathic surgery: a systematic review. International Journal of Morphology, 2012. 30(3): p. 1023–1028.\n'},{id:"B52",body:'\nCatherine, Z., P. Breton, and P. Bouletreau, Condylar resorption after orthognathic surgery: a systematic review. Revue de stomatologie, de chirurgie maxillo‐faciale et de chirurgie orale, 2015.\n'},{id:"B53",body:'\nValladares‐Neto, J., et al., TMJ response to mandibular advancement surgery: an overview of risk factors. Journal of Applied Oral Science, 2014. 22(1): p. 2–14.\n'},{id:"B54",body:'\nPanula, K., et al., Effects of orthognathic surgery on temporomandibular joint dysfunction. International Journal of Oral & Maxillofacial Surgery, 2000. 29(3): p. 183–187.\n'},{id:"B55",body:'\nWolford, L.M., O. Reiche‐Fischel, and P. Mehra, Changes in temporomandibular joint dysfunction after orthognathic surgery. Journal of Oral and Maxillofacial Surgery, 2003. 61(6): p. 655–660; discussion 661.\n'},{id:"B56",body:'\nAl‐Riyami, S., S.J. Cunningham, and D.R. Moles, Orthognathic treatment and temporomandibular disorders: a systematic review. Part 2. Signs and symptoms and meta‐analyses. American Journal of Orthodontics and Dentofacial Orthopedics, 2009. 136(5): p. 626.e1–16, discussion 626–627.\n'},{id:"B57",body:'\nFernandez‐Ferrer, L., et al., Effects of mandibular setback surgery on upper airway dimensions and their influence on obstructive sleep apnoea—a systematic review. Journal of Craniomaxillofacial Surgery, 2015. 43(2): p. 248–253.\n'},{id:"B58",body:'\nHong, J.S., et al., Three‐dimensional changes in pharyngeal airway in skeletal class III patients undergoing orthognathic surgery. Journal of Craniomaxillofacial Surgery, 2011. 69(11): p. e401–e408.\n'},{id:"B59",body:'\nGokce, S.M., et al., Evaluation of pharyngeal airway space changes after bimaxillary orthognathic surgery with a 3‐dimensional simulation and modeling program. American Journal of Orthodontics and Dentofacial Orthopedics, 2014. 146(4): p. 477–492.\n'},{id:"B60",body:'\nSantagata, M., et al., Effect of orthognathic surgery on the posterior airway space in patients affected by skeletal class III malocclusion. Journal of Craniomaxillofacial Surgery, 2015. 14(3): p. 682–686.\n'},{id:"B61",body:'\nAl‐Moraissi, E.A., et al., Impact on the pharyngeal airway space of different orthognathic procedures for the prognathic mandible. International Journal of Oral and Maxillofacial Surgery, 2015. 44(9): p. 1110–1118.\n'},{id:"B62",body:'\nKawase‐Koga, Y., et al., Complications after intraoral vertical ramus osteotomy: relationship to the shape of the osteotomy line. International Journal of Oral and Maxillofacial Surgery, 2016. 45(2): p. 200–204.\n'},{id:"B63",body:'\nUeki, K., et al., The effects of changing position and angle of the proximal segment after intraoral vertical ramus osteotomy. International Journal of Oral and Maxillofacial Surgery, 2009. 38(10): p. 1041–1047.\n'},{id:"B64",body:'\nYamauchi, K., T. Takenobu, and T. Takahashi, Condylar luxation following bilateral intraoral vertical ramus osteotomy. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology, 2007. 104(6): p. 747–751.\n'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Reza Tabrizi",address:"tabmed@gmail.com",affiliation:'
Department of Oral and Maxillofacial Surgery, Shahid Beheshti University of Medical Sciences, Tehran, Iran
'},{corresp:null,contributorFullName:"Hassan Mir Mohammad Sadeghi",address:null,affiliation:'
Department of Oral and Maxillofacial Surgery, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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1. Introduction
At the time this chapter is being written, the world is still experiencing the Severe Acute Respiratory Syndrome Coronavirus −2 (SARS-CoV-2)/COVID-19 pandemic. The dominant circulating strain of the virus has gone under multiple changes during the pandemic. The initial ancestral strain gave way to the alpha strain which gave way to the delta and omicron strain, which are currently the dominating circulating strains [1]. In addition, there have been emergence of other variants of interests (VOIs) or variants of concern (VOC) such as beta, gamma, P1, P2, lambda, and mu which could be a threat to international health security [1]. The emergence of these variants suggests virus adaptations to various determinants, responsible for the selection of these mutated variants.
This perspective chapter considers different biological determinants capable to contribute to viral mutations and thereby, emergence of new variants and the potential impact of this on the tools (vaccines and antibody therapy) against the SARS-CoV-2. However, it is important to note the determinants mentioned here may not be an exhaustive list of potential mechanisms to induce mutations. This chapter is based on theoretical and fundamental scientific concepts known to be involved from past outbreaks or current case reports from the ongoing pandemic. It is known that biological and environmental, among other determinants may drive viral mutations by different processes or mechanisms. Furthermore, by considering the roles these potential determinants may or already contribute to future SARS-CoV-2 variants we can improve global pandemic responses, saves lives, and contribute to the international health security.
2. Methods
A scoping literature review in search for current topics associated with SARS-CoV-2 or COVID-19 viral replication, adaptations, and biological determinants known to cause variant emergence (e.g., molecular factors, animal reservoirs, immunological factors, etc.) was conducted in biomedical databases such as PubMed, MEDLINE, and Google search engine. Additionally, World Health Organization (WHO), Centers for Disease Control and Prevention (CDC), and Food and Drug Administration (FDA) websites were relied upon to get the most recent information related to content of the chapter. Papers related to the biological determinants commonly associated with viral replication, recombination, adaptation, and immunological seletion were chosen based on the scope of the chapter. Biological determinants of variant emergence and their possible or current implications on the COVID-19 pandemic are presented below.
3. Biological determinants of SARS-CoV-2 variants emergence
3.1 Molecular determinants
3.1.1 Viral replication/recombination
SARS-CoV-2, a beta coronavirus, is a RNA virus using an error-prone RNA-dependent RNA polymerase for replication [2]. The virus encodes a proofreading 3′ exonuclease (nsp140) but despite this activity, it accumulates genomic changes having a potential to create heterogenous mixture of antigenic proteins resulting in emergence of new variants [2]. The genomic mutation rate of SARS-CoV-2 in humans is estimated at 0.8–2.38 x 10−3 nucleotide substitutions per site per year with experimental data suggesting the virus capable of mutating and accumulating changes when it encounters new cell types [3, 4]. Thus, high viral load means high viral replication and thus higher potential for genomic errors due to replication. Along with the replication associated changes, dramatic changes in the virus phenotype can be observed due to genomic recombination in a cell infected with more than one coronavirus [2, 5]. Till now eight recombination events have been observed in SARS-CoV-2 but the frequency of such events is not known [6]. Random errors accumulated during replication/recombination along with population level natural and vaccine induced immunity, play an important role in Darwinian selection of these variants [2].
3.2 Zoonotic determinants
Although the exact precursor of SARS-CoV-2 is unknown, it is established it is of wild origin. The initial December 2019 outbreak in Wuhan, China was linked to the seafood and live animal city market [7]. This market was reported to trade poultry, snakes, hedgehogs, and other wild animals [8].
The different SARS-CoV-2 variants detected in animals including dogs, cats, tigers, lions, minks, and gorillas all had genomes related to the human variant yet had additional mutations. The presence and infection of these animal reservoirs with SARS-CoV-2 virus also increases the possibility of viral mutations/recombinations and emergence of variants. Zoonotic reservoirs capable of carrying and providing an environment for viral multiplication are listed below.
3.2.1 Bats and pangolins
At the beginning of the pandemic bats were declared as the possible SARS-CoV-2 reservoir because of the genomic similarities with other coronaviruses infecting bats [9]. During the initial molecular epidemiological investigations, it was found the SARS-CoV-2 genome had similarities with coronaviruses isolated in Rhinolophus bats [10]. In Cambodia, a coronavirus with 93% genomic similarities was detected in horseshoe bats Rhinolophus shameli, but this specific bat species does not reside at the location of original SARS-CoV-2 outbreak [11, 12]. Similarly, 200 novel coronaviruses have been identified among bats worldwide [13]. Furthermore, bats are reservoirs for other emerging pathogens like Ebola, Nipah, rabies, Hendra, and rotaviruses [14]. Nevertheless, there are three events contradicting the hypothesis that bats were the initial reservoir from which SARS-CoV-2 jumped into other species: 1) during the beginning of the pandemic bats were hibernating; 2) bats were not sold at the animal market during the initial outbreak; and 3) although other bat coronaviruses have up to 96% genomic similarities, SARS-CoV-2 has not been detected among bat species [15].
The fist isolated variant of SARS-CoV-2 was identified as pangolin-CoV because of similarities with coronaviruses isolated in the carcasses of Malayan pangolins Manis javanica [16]. SARS-CoV-2 has 89% nucleotide and 98% amino acid similarities with the pangolin coronavirus genome [17]. Moreover, recent investigations done in other pangolin species conclude the pangolin coronavirus can be the precursor of SARS-CoV-2 because of their high genetic variation and given no coronaviruses were found in pre-COVID-19 pangolin samples [18].
3.2.2 SARS-CoV-2 variants in domestic and wild animals
The virus has been detected in domestic cats and dogs [14]. Therefore, the transmission from humans to domestic animals is plausible. Specifically, the B.1.1.7 (Alpha) variant has been identified in domestic cats as well as in domestic dogs [19]. In contrast it appears that cattle, goats, and sheep are not infected by the virus [20].
Among animals kept in zoos the virus has been detected in gorillas, tigers, pumas, cougars, Asian small-clawed otters, and snow leopards. The genetic variability of SARS-CoV-2 is evident from the 9 genomes identified in tigers, lions, and their keepers [21]. The B.1.1.7 (Alpha) variant has been detected in gorillas, lions, leopards, and tigers [20, 22]. In another study the B.1.617.2 (Delta) variant was reported in Asiatic lions from India [23]. Farmed wild animals have been diagnosed with SARS-CoV-2. Specifically, SARS-CoV-2 has been identified in American minks (Neovison vison) and in ferrets (Musteal furo) [20].
Therefore, this possibility of emergence of new variants is ever present due to SARS-CoV-2 spread to different ecological environments and newer animal reservoirs resulting in a subsequent risk for spillover into humans and other species.
3.3 Immunological determinants
3.3.1 Herd immunity
Lately, the phrase “Herd Immunity” is constantly brought up in news outlets, in commentaries, opinion pieces, and peer-reviewed articles. First introduced almost 100 years ago, it only recently gained popularity [24]. Although Herd Immunity is now a widely accepted concept, it may take on multiple meanings, each slightly different than the next. Some researchers consider Herd Immunity a threshold of the proportion of immune individuals that leads to a decline in infections or outbreaks [25, 26]. While others may use it to describe the proportion immune to a specific infection among a population or refer to it as a protective immunity pattern [25]. Herd Immunity is most referred to as the reduction of risk, of an infection, to susceptible individuals by the proximity and presence of immune individuals [25]. Herd Immunity may be used interchangeably as “indirect protection” or “herd effect”. Regardless of the definition variations, Herd Immunity leads to one outcome – the reduction of infection incidence. This concept, in conjunction with vaccines, has contributed to some of the most important public health achievements in the 20th and 21st century such as the smallpox eradication, polio elimination, and other vaccine-preventable diseases. This section explores the concepts behind Herd Immunity and current and future implications during the COVID-19 pandemic.
3.3.1.1 Theories which constructed herd immunity
Topley and Wilson (1923) were the first to coin the term “Herd Immunity” and specifically look at host resistance in comparison with mass infection. After first mention of Herd Immunity, the term and overall concept started appearing and developing soon after [27, 28, 29]. Dudley [27] explored the idea of a “herd” or community and how it could be defined. He defined the idea of “infection pressure” (i.e., fundamental parasite factor) which may be determined by the infectious agent distribution frequency rates which is in the members of the herd [27]. He claimed, infectious pressure reacts with Herd Immunity, the increase of one increases the other and then decreases it to zero. This introduced the idea of needing a minimum amount of Herd Immunity, a threshold, in order to keep the infectious pressure at zero. Furthermore, he mentioned those two factors contributed to the type, quantity, infection speed (i.e., now known as R0) and the frequency and distribution of cases and their severity [27].
Yet Herd Immunity had one large limitation—to provide protection, a high proportion of the population must be immune to the pathogen. Before immunizations individuals had to survive and pass the pathogen to become immune; depending on the pathogen, likelihood of survival and being left with life-altering morbidities varied. However, as concepts behind Herd Immunity were evolving, vaccinations were becoming a staple of public health practice, allowing a large proportion of the population to be safely immunized against specific pathogens. Vaccination allowed for the fulfillment of Herd Immunity at a much faster rate and safer manner. This allowed for the concepts to be turned into mathematical possibilities.
Before vaccination and Herd Immunity there were two main hypotheses as to why outbreaks would end even though not all susceptible were affected: (1) the agent naturally loses virulence (2) the dynamics between susceptible, infected, and immune [26]. The later hypothesis, prevailed with its mathematical idea of “mass action principle” (MAP) [26]. This principle was based on a simple logical argument in favor of indirect protection given by Herd Immunity and became an epidemiological theoretical cornerstone. Eventually three theories converged into one general theory driving Herd Immunity: MAP, case reproduction rates (later called base reproductive rates [BRR]), and the Reed-Frost heterogenous population simulation approach [26]. The current formula used for Herd Immunity is H = 1–1/R0 = (R0–1)/R0, where R0 is the BRR. H is the Herd Immunity threshold, the proportion of immunes needed in order to reduce incidence and R0 is derived from the duration of contagiousness of an infected individual, the likelihood of infection per contact between a susceptible person and an infectious person or vector, and the contact rate [30]. The BRR serves as an indicator of the contagiousness of an infectious agent—the higher the R0, the more transmissible. An R0 > 1 indicates an outbreak will continue, while a R0 < 1 indicates the end of an outbreak, if R0 = 1 then the outbreak is stable [30]. In novel outbreaks, where everyone is susceptible the R0 defines the infectiousness of a pathogen. However, as individuals pass the infection or become immunized, the number of susceptible decreases and immune increases, and although this does not technically reduce the BRR, because the definition of R0 assumes a completely susceptible population, one can use the effective reproduction number (R) in lieu, which is similar to R0 but does not assume complete population susceptibility and, thus, can be estimated with populations with immune members [30]. Efforts aimed at reducing the number of susceptible persons through vaccination would result in a reduction of the R value, rather than R0 value.
3.3.1.2 Herd immunity in the context of COVID-19
Currently there are multiple vaccines approved internationally for human use and immunization campaigns are urging communities to get vaccinated, therefore reducing the number of susceptible in hopes to achieve herd immunity. However, there are multiple factors to consider in achieving herd immunity from the SARS-CoV-2 virus.
Originally, with an estimated BRR of 2–3, researchers estimated the proportion of the population needed to be immunized to induce Herd Immunity around 50–67% [31, 32, 33]. Since then, the emergence of new SARS-CoV-2 variants, most famously the Delta variant, studies suggest a higher BRR (>5) [34, 35] than the alpha variant (2–3) [31, 32, 33, 36, 37, 38, 39] increasing the vaccination/immune threshold needed in order to achieve a protective effect. An increase in the necessary number of individuals vaccinated propose additional hurdles in reaching Herd Immunity, with the ever-increasing anti-vax movement or individuals acting as “freeloaders” (i.e., individuals who are not vaccinated, yet expect to be protected by the rest of the community being vaccinated).
Secondly, future SARS-CoV-2 variants may mutate enough where the protection offered by the currently available vaccines or natural immunity may no longer suffice. The emergence of the Delta variant showed a reduced vaccine effectiveness compared to the previous variants, which the vaccines were developed from [40, 41]. While currently approved vaccines still provide significant protection from the Delta variant for reduced risk of infection and disease severity, the reduction in vaccine effectiveness is alarming. If emerging variants significantly or completely evade the protection offered by current vaccines or natural immunity, individuals may no longer fall under the immune proportion of the population. An example of this possible situation was reported in Manaus, Brazil, where by December 2020 the population was estimated to have naturally achieved the herd immunity threshold (i.e., before vaccinations were approved and available), estimated at 67%, yet experienced a wave of hospitalizations in January 2021 [42]. This case study further highlighted the limitations with calculating Herd Immunity. Possible reasons for the Manaus outbreak were an overestimation of the immune population, a possible waning immune response, mutants capable of evading responses from previous natural infection, and mutants may have higher transmissibility than previously circulating lineages [42]. Future scenarios where Herd Immunity may not be achievable or severely reduced would be staggering in relation to vaccination campaigns and reaching herd immunity—a grave threat to international health security.
3.3.2 Artificial immunization/natural infection
All COVID-19 vaccines authorized or have received emergency use authorization (EUA) by FDA, EU/EEA, or WHO require a two-dose schedule except for the Janssen vaccines. All these vaccines require a period of 21 days to 12 weeks spacing between the primary and secondary dose [43]. In the early phase of the pandemic to reduce widespread community transmission, logistical issues, and shortages, many countries (e.g., UK, Canada) elected to delay the second dose in the population, thereby increasing the number of individuals with at least one dose. Policies such as the aforementioned in conjunction with waning of immunity after SARS-CoV-2 natural infection may result in large groups of people with only partial immunity against SARS-CoV-2 [43].
The Darwinian selection of variants with mutations for immune escape and its transmission in the community will depend on substantial selection pressure [44]. The greatest potential for the emergence of these immune escape mutations will be in those hosts with highest viral loads (increased mutations) while the greatest selection pressure will be in those with strongest immunological response [2, 44]. The level of immunological protection conferred after first dosage is dependent on the type of vaccine product in addition to the individual characteristics and variant [43]. In individuals with poor immunological response after first dose, there is potential for greater infection burden [44]. These individuals will have higher assumed rates of evolutionary adaptation because of higher viral load and replication. In those individuals with strong but partial immunological response, the infection rates would be lower but evolutionary selection pressure would be large, resulting in high rates of viral adaptations. Previous phylogenic research done on influenza viruses suggested the viral evolution and emergence of immune escape variants is maximum in those individuals with partial immunity (i.e., intermediate levels of selection and viral replication) [45]. Thus, having partially immunized individuals could lead to short-term benefits such as reduced peak of disease but in long term can result in higher infection burden and substantially higher risk of viral evolution to immune escape variants [44].
3.3.2.1 Chemical and biological therapy
Several monoclonal antibodies were developed against the spike protein of SARS-CoV-2 to block the transmission of the virus inside the cells [46]. A single (Bamlanivimab) or combination monoclonal antibodies (Bamlanivimab/Etsevimab or Casirivimab/Imdevimab) received EUA for therapeutic management of SARS-CoV-2 and post-exposure prophylaxis [47, 48]. In theory, administration of monoclonal antibody therapy can alter the immunological selective pressure resulting in viral adaptation for the emergence of variants resistant to one or more monoclonal antibodies [49, 50]. This potential for the emergence of monoclonal antibody resistance has been observed in immunocompromised patients [51, 52, 53]. In trials for monoclonal antibodies, mutations resistant to antibodies were detected by next generation sequencing (NGS) assay in 10% of the patients receiving therapy with its transmissibility not determined [54]. Recently, a Wisconsin (WI) study using Bamlanivimab described the emergence of new resistant mutation E484K with further transmission to nearby contacts [55]. The emergence of variants with reduced susceptibility to neutralizing antibodies after polyclonal convalescent plasma therapy provides further proof of the effect of immunological selective pressure on emergence of new variants [49, 56]. It is conceivable, the widespread use of monoclonal or polyclonal antibody therapy may reduce barriers for the emergence of resistant variants to these antibodies which can further transmit to wider communities, potentially becoming a variant of concern. A widespread genomic surveillance is warranted to identify and control the spread of these antibody resistant variants [55].
3.3.3 Immunosuppressed individuals
During evaluation of the efficacy of vaccines, subjects with inhered or acquired immunodeficiencies are excluded from clinical trials. Therefore, there are limited information about the immunogenicity of SARS-CoV-2 vaccines among these patients. Field studies evaluating the effectiveness of COVID-19 vaccines demonstrate that immunocompromised subjects mount a lower antibody response when compared with immunocompetent subjects [57].
Viruses are highly sophisticated molecular machines that can go into an adaptive evolution in the human host establishing a latent reservoir, integrating into the human genome, or causing a chronic infection. Viruses such as hepatitis B virus, hepatitis C virus, and human immunodeficiency virus go into latent stage evading the host immune response while other viruses like Ebola can persist in immune sanctuaries [58]. Considering COVID-19 is an infection of pandemic proportions, it is plausible to think human host immune pressure can contribute to SARS-CoV-2 genetic diversity and selection with phenotypic changes [59]. Consequently, it is necessary to address the relationship between viral persistence in the immunosuppressed host. As a matter of fact, one of the hallmarks of SARS-CoV-2 is its capacity to co-opt various cellular factors and machineries damping the immune response [60]. Although not yet demonstrated, it is plausible to suggest SARS-CoV-2 may establish a latent infection or remain in immune sanctuary. However, SARS-CoV-2 persistence in the immunocompromised patient is well documented [61, 62], with viral persistence reported among cancer patients and transplant recipients [61, 63, 64, 65, 66, 67]. Viral coronavirus RNA has been detected up to ~60 days in cancer patients that developed respiratory symptoms. Moreover, the longest persistence of coronavirus RNA is recorded at 151 days in a patient with anti-phospholipid syndrome, which suggest these pathogens are of the opportunistic characteristic [68, 69, 70]. In the aforementioned patient, there were 31 substitutions and 3 deletions identified in the genome sequencies from the isolated agent. There were 12 mutations in the spike protein including 7 in the receptor-binding domain segment. Due to severe pulmonary complication the patient died [71]. Increased viral changes were also detected in another immunocompromised patient, whose disease prolonged for 101 days, where viral changes were limited during the first 60 days but increased after receiving plasma form a convalescent patient at days 63 and 65. Moreover, rapid shifts were observed in the spike area during the last days of the monitoring [71]. In another case-series, three patients receiving chimeric antigen receptor (CAR) T cells because of B-cell acute lymphocytic leukemia, showed multiple escape SARS-CoV-2 variants [71]. Consequently, like SARS-CoV-2 longer persistence in immunosuppressed patients, immunosusceptible elderly patients may also harbor the virus for prolonged periods compared to immunocompetent patients. Gaspar-Rodriguez et al. enunciated in 2021 that SARS-CoV-2 and other coronaviruses potentially establish a long-term, non-productive persistent infection in epithelial, myeloid, and neural host cells until viral clearance is achieved [62]. Prolonged COVID-19 in the immunosuppressed patient can be a determinant of the development of SARS-CoV-2 variants which can be spread among the general population [71]. This persistence of the virus in different types of immunosuppression are listed below.
3.3.3.1 SARS-CoV-2 in Cancer patients
Cancer patients are in immunodepression conditions because of the malignancy and oncological treatments like chemotherapy, radiotherapy, transplants, and immunotherapy. Patients with lung, blood, and bone marrow carcinomas are at a higher risk of harboring the virus for prolonged periods when compared with other cancer patients [72]. Patients with chronic lymphocytic leukemia (CLL) have shown inadequate levels of antibodies as well as cellular immune response [73]. These inadequate immune responses in CLL patients correlates with severe and prolonged forms of COVID-19 and has been supported by late conversion to negative PCR monitoring tests and longer hospitalizations [74]. The impaired humoral and cellular immune response in the CLL patients make these patients long term shedders of SARS-CoV-2 until infection is passed. One case study showed a COVID-19 positive CLL patient having persistent positive PCR test for 105 days after diagnosis [63]. Moreover, during this period a continuous variability in predominant viral variants was observed [63]. This delay in viral clearance in COVID-19 patients has been observed in patients receiving intravenous immunoglobulins as well as in those with hypertension [75].
3.3.3.2 SARS-CoV-2 in organ transplant patients
Organ transplant recipients are patients with long-lasting immunosuppression; therefore, organ transplant recipients have been declared subjects with high risk for severe COVID-19. When COVID-19 positive liver transplant patients were compared with COVID-19 immunocompetent patients, the transplant recipients showed lower prevalence of antibodies against SARS-CoV-2, as well as a faster antibody decline [57]. Regarding viral shedding, immunocompetent asymptomatic COVID-19 infection subjects experience a faster viral clearance when compared with symptomatic individuals [76]. Kidney transplant patients with immunosuppression showed a longer shedding of the virus, of more than 28 days, which was correlated with a prolongation of symptoms [77].
3.3.3.3 SARS-CoV-2 in elderly patients
It is demonstrated SARS-CoV-2 causes highest mortality among elderly populations. Also, viral shedding is increased, enhancing the spread of the virus as it was observed in the increased transmission in nursing homes. An explanation for these complications may be due to the elderly immune system being less competent than in young populations. In the elderly, it appears the production of cytokine and T-cells production worsen the inflammation process especially among those with comorbidities [78]. The increased shedding of SARS-CoV-2 is associated with a more severe clinical presentation and higher viral load peaks [79, 80, 81]. The delayed viral clearance in elderly patients’ airways can be explained by a decreased respiratory muscle function and diminished mucociliary function [79, 82].
3.3.3.4 SARS-CoV-2 in patients with corticosteroid treatment
Although corticosteroid therapy is being used to ameliorate the inflammation process, the use of corticosteroids at an early stage can suppress the immune cells which can prolong the clearance of the virus as well as its shedding. In a randomized study in the patients without respiratory failure, the methylprednisolone group showed a median viral shedding of 10 days vs. 6 days in the control group [83].
4. Discussion
The molecular mechanisms of viral replication, multiple animal reservoirs, and immunological selection methods have the possibility for viral evolution to immune escape variants (Figure 1). Such epidemiological and evolutionary mechanisms are already seen in the emergence of different VOC worldwide [44].
Figure 1.
Biological determinants of emergence of SARS-CoV-2 variants. An infection of SARS-CoV-2 in humans results in viral replication. In born errors of viral replication or genomic recombination can result in viral mutations. People with natural/artificial immunity will neutralize the non-mutated virus but has non-neutralizing immune response against mutated variant. Mutated SARS-CoV-2 thus undergoes this immunological selection for emergence of SARS-CoV-2 variant. Infection in animals with different host cell machinery led to mutated SARS-CoV-2 with potential for species jump and spillover into humans and emergence of SARS-CoV-2 variant.
4.1 Impact of emergence of new variants on vaccine
Since the beginning of the pandemic, VOC having selective advantage of more transmissibility and resistance to natural or vaccine induced immunity have been evolving and supplanting previously circulating strains [43, 84]. The emergence of these VOC affects the effectiveness of vaccines in both partially and fully immunized individuals [43]. In vitro studies demonstrated lower neutralization capacity against all VOC compared to ancestral strains [41, 85, 86]. Based on evidence available for all vaccine types, partially immunized individuals have a lower degree of protection against symptomatic infection, moderate disease, and probable transmission with Delta VOC than Alpha VOC. In general, the vaccine effectiveness for all variants against symptomatic disease was much lower than those reported against severe diseases. The fully immunized individuals confer nearly equivalent protection for all outcomes against Alpha to that of Delta variants [43]. Table 1 summarizes the results of vaccine effectiveness by type of vaccine, outcome, and VOC.
Variant
Original
Original
Alpha
Beta
Gamma
Delta
Delta
Vaccine
SI
SD
SI
SI
SI
SI
SD
Comirnaty (Pfizer/BioNTech)
95%
100%
89.5%
75%
61%
87.9%
96%
SpikeVax (Moderna)
94.1%
100%
↓ Ant Neu
↓ Ant Neu
↓ Ant Neu
↓ Ant Neu
Vaxzeria (AstraZeneca)
70.4%
81.3%
66.1%
10.4%
↓ Ant Neu
59.8%
92%
Johnson & Johnson
74.2%
85.4%
64%
↓ Ant Neu
Cansino
90–95%
Sputnik V
91.6%
100%
No difference
↓ Ant Neu
Sinovac
78.1%
100%
↓ Ant Neu
↓ Ant Neu
↓ Ant Neu
Soberana (Cuba)
62%
Table 1.
Vaccine effectiveness of two dose of vaccines against symptomatic infection and severe disease caused by non-VOCs, alpha, and Delta VOCs.
SI, symptomatic disease; SD, Severe disease.
The emergence of new vaccine-resistant variants may necessitate the development of modified vaccines based on new sequences to prevent the prolonged circulation of vaccine-resistant variants [84]. It is important to conduct studies of these modified vaccines to determine its efficacy in developing a neutralizing immunological response against vaccine-resistant variants. This research is important despite the deployment of these newer vaccines not required until there is evidence of failure of current vaccines. Once the modified vaccines are introduced the molecular and immunological determinants of viral adaptation will necessitate to repeat the cycle of monitoring for even newer variants that might require further modifications in the antigenic sequence in vaccines.
4.2 Impact of emergence of new variants antibody therapy
Like vaccines, the viral adaptations seen against the monoclonal antibody therapy can complicate the deployment of these treatments at large scale in the general population [55]. The initial widespread use of Bamlanivimab as a single therapy and later removal due to epidemiologic trend further provides evidence for judicious use of monoclonal antibody therapy [87]. The usage of cocktail of antibodies should in theory reduce the probability of random selection of resistant variants however it does not totally remove this possibility [55]. This combined with monoclonal antibodies not preventing transmission, not providing immediate cure, lacking durable immunity, and potentially leading to antibody strains with some cross-resistance against vaccine or natural-acquired immunity suggests the need for caution before widespread usage of monoclonal antibody therapy [41, 55]. Increasing the scale of surveillance for mutations along with research into monoclonal antibodies against newer antigens should be adopted if the scale of use of monoclonal antibody has to be expanded [55].
Thus, the determinants of emergence of SARS-CoV-2 variants necessitates the inclusion of epidemiological, evolutionary, clinical, animal, and in vitro data related to changing antigenic sequences, vaccine and monoclonal antibody efficacy in the decision making of which antigens to be included in vaccines or targeted for therapy [84]. Lastly, it is important to recognize the limitations of the concepts presented in this chapter. This is a prospective chapter piece using concepts and theoretical ideologies commonly attributed to variant emergence. The inclusion of the determinants presented are a combination of expert knowledge on behalf of the authors and a scoping literature review conducted on SARS-CoV-2 and its current variants, therefore, this chapter is not meant to replace a systematic review.
5. Conclusion
This chapter presents theoretical and current determinants for variant emergence, specifically for SAR-CoV-2. The emergence of different VOC through the evolutionary cycle of the SARS-CoV-2 virus during the current pandemic (2019- ongoing) makes it important to understand the biological determinants of new emerging variants. The inherent errors in viral replication in humans and animal reservoirs combined with immunological selective pressure result in the Darwinian selection of variants of SARS-CoV-2 with potential for higher transmissibility and resistance to vaccine-based immunity or monoclonal antibodies. The different types of vaccines and associated immune response, partial immunization, waning of immunity, and heterogenicity in worldwide immunity results in wide differences in immunological selective pressure based on regions and virus evolutions. The global inequality in vaccine distribution further complicates this immunological selection pressure. The epidemiological and evolutionary cycle can result in viral adaptations with potential for selection of variants with higher transmissibility and immune escape properties. The emergence of these dangerous new variants can influence vaccine and antibody therapy effectiveness necessitating modifications in antigenic sequences used in production. This emergence of novel variants thus is a concern for international health security with a potential for furthering the COVID-19 pandemic and its associated negative health, economic, and social effects.
\n',keywords:"SARS-CoV-2, COVID-19, variants, determinants",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/81865.pdf",chapterXML:"https://mts.intechopen.com/source/xml/81865.xml",downloadPdfUrl:"/chapter/pdf-download/81865",previewPdfUrl:"/chapter/pdf-preview/81865",totalDownloads:10,totalViews:0,totalCrossrefCites:0,dateSubmitted:"November 8th 2021",dateReviewed:"March 31st 2022",datePrePublished:"May 19th 2022",datePublished:null,dateFinished:"May 19th 2022",readingETA:"0",abstract:"In epidemic and pandemic circumstances, mutant RNA viruses go into a Darwinian selection of species with the predominance of the most transmissible, pathogenic, and virulent variants. Nevertheless, our current knowledge about the determinants of emergence of the new mutants is limited. The perspective chapter presents theoretical concepts related to biological determinants responsible for viral mutations or potential variant emergence. A scoping literature review was done in biomedical databases (PubMed, Medline) and google search engine with papers selected based about the book chapter. Public health and governmental agency websites were utilized for most recent information. Molecular determinants, the heterogenic herd immunity achieved by world populations, partial induced natural immunity by the disease, partial artificial immunity caused by incomplete immunization schedules, animal reservoirs, immunosuppression and chemical and biological antiviral therapies can result in genomic mutations combined with immunological selective pressure resulting in emergence of variants of concern. These variants could be resistant to current vaccines and monoclonal antibodies and can influence the future directions of the COVID-19 pandemic. This can be a threat to international health security and thus it is important to increase the genomic surveillance for mutations and research into modified vaccines and monoclonal antibodies against newer antigens to prevent the prolongation of the pandemic.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/81865",risUrl:"/chapter/ris/81865",signatures:"Ricardo Izurieta, Tatiana Gardellini, Adriana Campos and Jeegan Parikh",book:{id:"11113",type:"book",title:"Contemporary Developments and Perspectives in International Health Security - Volume 3",subtitle:null,fullTitle:"Contemporary Developments and Perspectives in International Health Security - Volume 3",slug:null,publishedDate:null,bookSignature:"Dr. Stanislaw P. Stawicki and Prof. Ricardo Izurieta",coverURL:"https://cdn.intechopen.com/books/images_new/11113.jpg",licenceType:"CC BY 3.0",editedByType:null,isbn:"978-1-83969-837-8",printIsbn:"978-1-83969-836-1",pdfIsbn:"978-1-83969-838-5",isAvailableForWebshopOrdering:!0,editors:[{id:"181694",title:"Dr.",name:"Stanislaw P.",middleName:null,surname:"Stawicki",slug:"stanislaw-p.-stawicki",fullName:"Stanislaw P. 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Introduction",level:"1"},{id:"sec_2",title:"2. Methods",level:"1"},{id:"sec_3",title:"3. Biological determinants of SARS-CoV-2 variants emergence",level:"1"},{id:"sec_3_2",title:"3.1 Molecular determinants",level:"2"},{id:"sec_3_3",title:"3.1.1 Viral replication/recombination",level:"3"},{id:"sec_5_2",title:"3.2 Zoonotic determinants",level:"2"},{id:"sec_5_3",title:"3.2.1 Bats and pangolins",level:"3"},{id:"sec_6_3",title:"3.2.2 SARS-CoV-2 variants in domestic and wild animals",level:"3"},{id:"sec_8_2",title:"3.3 Immunological determinants",level:"2"},{id:"sec_8_3",title:"3.3.1 Herd immunity",level:"3"},{id:"sec_8_4",title:"3.3.1.1 Theories which constructed herd immunity",level:"4"},{id:"sec_9_4",title:"3.3.1.2 Herd immunity in the context of COVID-19",level:"4"},{id:"sec_11_3",title:"3.3.2 Artificial immunization/natural infection",level:"3"},{id:"sec_11_4",title:"3.3.2.1 Chemical and biological therapy",level:"4"},{id:"sec_13_3",title:"3.3.3 Immunosuppressed individuals",level:"3"},{id:"sec_13_4",title:"3.3.3.1 SARS-CoV-2 in Cancer patients",level:"4"},{id:"sec_14_4",title:"3.3.3.2 SARS-CoV-2 in organ transplant patients",level:"4"},{id:"sec_15_4",title:"3.3.3.3 SARS-CoV-2 in elderly patients",level:"4"},{id:"sec_16_4",title:"3.3.3.4 SARS-CoV-2 in patients with corticosteroid treatment",level:"4"},{id:"sec_20",title:"4. Discussion",level:"1"},{id:"sec_20_2",title:"4.1 Impact of emergence of new variants on vaccine",level:"2"},{id:"sec_21_2",title:"4.2 Impact of emergence of new variants antibody therapy",level:"2"},{id:"sec_23",title:"5. Conclusion",level:"1"}],chapterReferences:[{id:"B1",body:'World Health Organization. Tracking SARS-CoV-2 variants. 2021. Available from: https://www.who.int/en/activities/tracking-SARS-CoV-2-variants/ [Accessed 31-10-2021]'},{id:"B2",body:'Banerjee A, Mossman K, Grandvaux N. Molecular determinants of SARS-CoV-2 variants. Trends in Microbiology. 2021;29(10):871-873'},{id:"B3",body:'Massimo A.et al. Mutation rate of SARS-CoV-2 and emergence of mutators during experimental evolution, Evolution, Medicine, and Public Health. 2022;10(1):142-155'},{id:"B4",body:'De Maio N et al. Mutation rates and selection on synonymous mutations in SARS-CoV-2. Genome Biology and Evolution. 2021;13(5):1-14'},{id:"B5",body:'Lai MM et al. 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The European Respiratory Journal. 2005;26(4):609-615'},{id:"B83",body:'Tang X et al. Early use of corticosteroid may prolong SARS-CoV-2 shedding in non-intensive care unit patients with COVID-19 pneumonia: A Multicenter, single-blind, randomized control trial. Respiration. 2021;100(2):116-126'},{id:"B84",body:'Krause PR et al. SARS-CoV-2 variants and vaccines. New England Journal of Medicine. 2021;385(2):179-186'},{id:"B85",body:'Liu C et al. Reduced neutralization of SARS-CoV-2 B.1.617 by vaccine and convalescent serum. Cell. 2021;184(16):4220-4236.e13'},{id:"B86",body:'Yadav PD et al. Neutralization of Beta and Delta variant with sera of COVID-19 recovered cases and vaccinees of inactivated COVID-19 vaccine BBV152/Covaxin. Journal of Travel Medicine. 2021;28(7):1-3'},{id:"B87",body:'U.S. Food and Drug Administration, FDA Revokes Emergency Use Authorization for Monoclonal Antibody Bamlanivimab. U.S. FDA: Silver Spring, MD,U.S.; 2021'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Ricardo Izurieta",address:"ricardoi@usf.edu",affiliation:'
College of Public Health, University of South Florida, Tampa, Florida, United States
College of Public Health, University of South Florida, Tampa, Florida, United States
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For Authors who are still unable to obtain funding from their institutions or research funding bodies for individual projects, IntechOpen does offer the possibility of applying for a Waiver to offset some or all processing feed. Details regarding our Waiver Policy can be found here.
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Indexing and listing across major repositories, see details ...
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The forearc basin type and tectonic history are characteristic for each forearc territory, reflecting the differences in plate tectonic processes. Several major unconformity events seem to be synchronous for a forearc territory or whole forearc territories around Japan, suggesting that these events originated from more or less wider scale plate tectonic events. In the NE Japan forearc territory, the Oligocene unconformity can be the largest events, which transformed the forearc basin styles from the trench slope break-uplifted, fluvial system-dominated type to the tensional, deeper marine sloped type. In the SW Japan and Ryukyu forearc territories, the latest Oligocene to Middle Miocene gap was the transformation phase from the Palaeogene Shimanto-type forearc and accretionary complex, to the Neogene compressive, sloped to ridged forearc basins, developments of which have been interrupted by several unconformity events possibly related to changes in plate tectonic condition. 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\r\n\tTransforming our World: the 2030 Agenda for Sustainable Development endorsed by United Nations and 193 Member States, came into effect on Jan 1, 2016, to guide decision making and actions to the year 2030 and beyond. Central to this Agenda are 17 Goals, 169 associated targets and over 230 indicators that are reviewed annually. The vision envisaged in the implementation of the SDGs is centered on the five Ps: People, Planet, Prosperity, Peace and Partnership. This call for renewed focused efforts ensure we have a safe and healthy planet for current and future generations.
\r\n
\r\n\t
\r\n
\r\n\tThis Series focuses on covering research and applied research involving the five Ps through the following topics:
\r\n
\r\n\t
\r\n
\r\n\t1. Sustainable Economy and Fair Society that relates to SDG 1 on No Poverty, SDG 2 on Zero Hunger, SDG 8 on Decent Work and Economic Growth, SDG 10 on Reduced Inequalities, SDG 12 on Responsible Consumption and Production, and SDG 17 Partnership for the Goals
\r\n
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\r\n\t2. Health and Wellbeing focusing on SDG 3 on Good Health and Wellbeing and SDG 6 on Clean Water and Sanitation
\r\n
\r\n\t
\r\n
\r\n\t3. Inclusivity and Social Equality involving SDG 4 on Quality Education, SDG 5 on Gender Equality, and SDG 16 on Peace, Justice and Strong Institutions
\r\n
\r\n\t
\r\n
\r\n\t4. Climate Change and Environmental Sustainability comprising SDG 13 on Climate Action, SDG 14 on Life Below Water, and SDG 15 on Life on Land
\r\n
\r\n\t
\r\n
\r\n\t5. Urban Planning and Environmental Management embracing SDG 7 on Affordable Clean Energy, SDG 9 on Industry, Innovation and Infrastructure, and SDG 11 on Sustainable Cities and Communities.
\r\n
\r\n\t
\r\n
\r\n\tThe series also seeks to support the use of cross cutting SDGs, as many of the goals listed above, targets and indicators are all interconnected to impact our lives and the decisions we make on a daily basis, making them impossible to tie to a single topic.
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Currently, he is a professor of Orthodontics. He holds a Certificate of Advanced Study type A in Technology of Biomaterials used in Dentistry (1995); Certificate of Advanced Study type B in Dento-Facial Orthopaedics (1997) from the Faculty of Dental Surgery, University Denis Diderot-Paris VII, France; Diploma of Advanced Study (DESA) in Biocompatibility of Biomaterials from the Faculty of Medicine and Pharmacy of Casablanca (2002); Certificate of Clinical Occlusodontics from the Faculty of Dentistry of Casablanca (2004); University Diploma of Biostatistics and Perceptual Health Measurement from the Faculty of Medicine and Pharmacy of Casablanca (2011); and a University Diploma of Pedagogy of Odontological Sciences from the Faculty of Dentistry of Casablanca (2013). 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Radiotherapy and Nuclear Medicine Technology has always been my aspiration and my life. As years passed I accumulated a tremendous amount of skills and knowledge in Radiotherapy and Nuclear Medicine, Conventional Radiology, Radiation Protection, Bioinformatics Technology, PACS, Image processing, clinically and lecturing that will enable me to provide a valuable service to the community as a Researcher and Consultant in this field. My method of translating this into day to day in clinical practice is non-exhaustible and my habit of exchanging knowledge and expertise with others in those fields is the code and secret of success.",institutionString:null,institution:{name:"Majmaah University",country:{name:"Saudi Arabia"}}},{id:"313277",title:"Dr.",name:"Bartłomiej",middleName:null,surname:"Płaczek",slug:"bartlomiej-placzek",fullName:"Bartłomiej Płaczek",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/313277/images/system/313277.jpg",biography:"Bartłomiej Płaczek, MSc (2002), Ph.D. (2005), Habilitation (2016), is a professor at the University of Silesia, Institute of Computer Science, Poland, and an expert from the National Centre for Research and Development. His research interests include sensor networks, smart sensors, intelligent systems, and image processing with applications in healthcare and medicine. He is the author or co-author of more than seventy papers in peer-reviewed journals and conferences as well as the co-author of several books. He serves as a reviewer for many scientific journals, international conferences, and research foundations. Since 2010, Dr. Placzek has been a reviewer of grants and projects (including EU projects) in the field of information technologies.",institutionString:"University of Silesia",institution:{name:"University of Silesia",country:{name:"Poland"}}},{id:"35000",title:"Prof.",name:"Ulrich H.P",middleName:"H.P.",surname:"Fischer",slug:"ulrich-h.p-fischer",fullName:"Ulrich H.P Fischer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/35000/images/3052_n.jpg",biography:"Academic and Professional Background\nUlrich H. P. has Diploma and PhD degrees in Physics from the Free University Berlin, Germany. He has been working on research positions in the Heinrich-Hertz-Institute in Germany. Several international research projects has been performed with European partners from France, Netherlands, Norway and the UK. He is currently Professor of Communications Systems at the Harz University of Applied Sciences, Germany.\n\nPublications and Publishing\nHe has edited one book, a special interest book about ‘Optoelectronic Packaging’ (VDE, Berlin, Germany), and has published over 100 papers and is owner of several international patents for WDM over POF key elements.\n\nKey Research and Consulting Interests\nUlrich’s research activity has always been related to Spectroscopy and Optical Communications Technology. Specific current interests include the validation of complex instruments, and the application of VR technology to the development and testing of measurement systems. He has been reviewer for several publications of the Optical Society of America\\'s including Photonics Technology Letters and Applied Optics.\n\nPersonal Interests\nThese include motor cycling in a very relaxed manner and performing martial arts.",institutionString:null,institution:{name:"Charité",country:{name:"Germany"}}},{id:"341622",title:"Ph.D.",name:"Eduardo",middleName:null,surname:"Rojas Alvarez",slug:"eduardo-rojas-alvarez",fullName:"Eduardo Rojas Alvarez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/341622/images/15892_n.jpg",biography:null,institutionString:null,institution:{name:"University of Cuenca",country:{name:"Ecuador"}}},{id:"215610",title:"Prof.",name:"Muhammad",middleName:null,surname:"Sarfraz",slug:"muhammad-sarfraz",fullName:"Muhammad Sarfraz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/215610/images/system/215610.jpeg",biography:"Muhammad Sarfraz is a professor in the Department of Information Science, Kuwait University. His research interests include computer graphics, computer vision, image processing, machine learning, pattern recognition, soft computing, data science, intelligent systems, information technology, and information systems. Prof. Sarfraz has been a keynote/invited speaker on various platforms around the globe. He has advised various students for their MSc and Ph.D. theses. He has published more than 400 publications as books, journal articles, and conference papers. He is a member of various professional societies and a chair and member of the International Advisory Committees and Organizing Committees of various international conferences. Prof. Sarfraz is also an editor-in-chief and editor of various international journals.",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"32650",title:"Prof.",name:"Lukas",middleName:"Willem",surname:"Snyman",slug:"lukas-snyman",fullName:"Lukas Snyman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/32650/images/4136_n.jpg",biography:"Lukas Willem Snyman received his basic education at primary and high schools in South Africa, Eastern Cape. He enrolled at today's Nelson Metropolitan University and graduated from this university with a BSc in Physics and Mathematics, B.Sc Honors in Physics, MSc in Semiconductor Physics, and a Ph.D. in Semiconductor Physics in 1987. After his studies, he chose an academic career and devoted his energy to the teaching of physics to first, second, and third-year students. After positions as a lecturer at the University of Port Elizabeth, he accepted a position as Associate Professor at the University of Pretoria, South Africa.\r\n\r\nIn 1992, he motivates the concept of 'television and computer-based education” as means to reach large student numbers with only the best of teaching expertise and publishes an article on the concept in the SA Journal of Higher Education of 1993 (and later in 2003). The University of Pretoria subsequently approved a series of test projects on the concept with outreach to Mamelodi and Eerste Rust in 1993. In 1994, the University established a 'Unit for Telematic Education ' as a support section for multiple faculties at the University of Pretoria. In subsequent years, the concept of 'telematic education” subsequently becomes well established in academic circles in South Africa, grew in popularity, and is adopted by many universities and colleges throughout South Africa as a medium of enhancing education and training, as a method to reaching out to far out communities, and as a means to enhance study from the home environment.\r\n\r\nProfessor Snyman in subsequent years pursued research in semiconductor physics, semiconductor devices, microelectronics, and optoelectronics.\r\n\r\nIn 2000 he joined the TUT as a full professor. Here served for a period as head of the Department of Electronic Engineering. Here he makes contributions to solar energy development, microwave and optoelectronic device development, silicon photonics, as well as contributions to new mobile telecommunication systems and network planning in SA.\r\n\r\nCurrently, he teaches electronics and telecommunications at the TUT to audiences ranging from first-year students to Ph.D. level.\r\n\r\nFor his research in the field of 'Silicon Photonics” since 1990, he has published (as author and co-author) about thirty internationally reviewed articles in scientific journals, contributed to more than forty international conferences, about 25 South African provisional patents (as inventor and co-inventor), 8 PCT international patent applications until now. Of these, two USA patents applications, two European Patents, two Korean patents, and ten SA patents have been granted. A further 4 USA patents, 5 European patents, 3 Korean patents, 3 Chinese patents, and 3 Japanese patents are currently under consideration.\r\n\r\nRecently he has also published an extensive scholarly chapter in an internet open access book on 'Integrating Microphotonic Systems and MOEMS into standard Silicon CMOS Integrated circuitry”.\r\n\r\nFurthermore, Professor Snyman recently steered a new initiative at the TUT by introducing a 'Laboratory for Innovative Electronic Systems ' at the Department of Electrical Engineering. The model of this laboratory or center is to primarily combine outputs as achieved by high-level research with lower-level system development and entrepreneurship in a technical university environment. Students are allocated to projects at different levels with PhDs and Master students allocated to the generation of new knowledge and new technologies, while students at the diploma and Baccalaureus level are allocated to electronic systems development with a direct and a near application for application in industry or the commercial and public sectors in South Africa.\r\n\r\nProfessor Snyman received the WIRSAM Award of 1983 and the WIRSAM Award in 1985 in South Africa for best research papers by a young scientist at two international conferences on electron microscopy in South Africa. He subsequently received the SA Microelectronics Award for the best dissertation emanating from studies executed at a South African university in the field of Physics and Microelectronics in South Africa in 1987. In October of 2011, Professor Snyman received the prestigious Institutional Award for 'Innovator of the Year” for 2010 at the Tshwane University of Technology, South Africa. This award was based on the number of patents recognized and granted by local and international institutions as well as for his contributions concerning innovation at the TUT.",institutionString:null,institution:{name:"University of South Africa",country:{name:"South Africa"}}},{id:"317279",title:"Mr.",name:"Ali",middleName:"Usama",surname:"Syed",slug:"ali-syed",fullName:"Ali Syed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/317279/images/16024_n.png",biography:"A creative, talented, and innovative young professional who is dedicated, well organized, and capable research fellow with two years of experience in graduate-level research, published in engineering journals and book, with related expertise in Bio-robotics, equally passionate about the aesthetics of the mechanical and electronic system, obtained expertise in the use of MS Office, MATLAB, SolidWorks, LabVIEW, Proteus, Fusion 360, having a grasp on python, C++ and assembly language, possess proven ability in acquiring research grants, previous appointments with social and educational societies with experience in administration, current affiliations with IEEE and Web of Science, a confident presenter at conferences and teacher in classrooms, able to explain complex information to audiences of all levels.",institutionString:null,institution:{name:"Air University",country:{name:"Pakistan"}}},{id:"75526",title:"Ph.D.",name:"Zihni Onur",middleName:null,surname:"Uygun",slug:"zihni-onur-uygun",fullName:"Zihni Onur Uygun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/75526/images/12_n.jpg",biography:"My undergraduate education and my Master of Science educations at Ege University and at Çanakkale Onsekiz Mart University have given me a firm foundation in Biochemistry, Analytical Chemistry, Biosensors, Bioelectronics, Physical Chemistry and Medicine. After obtaining my degree as a MSc in analytical chemistry, I started working as a research assistant in Ege University Medical Faculty in 2014. In parallel, I enrolled to the MSc program at the Department of Medical Biochemistry at Ege University to gain deeper knowledge on medical and biochemical sciences as well as clinical chemistry in 2014. In my PhD I deeply researched on biosensors and bioelectronics and finished in 2020. Now I have eleven SCI-Expanded Index published papers, 6 international book chapters, referee assignments for different SCIE journals, one international patent pending, several international awards, projects and bursaries. In parallel to my research assistant position at Ege University Medical Faculty, Department of Medical Biochemistry, in April 2016, I also founded a Start-Up Company (Denosens Biotechnology LTD) by the support of The Scientific and Technological Research Council of Turkey. Currently, I am also working as a CEO in Denosens Biotechnology. The main purposes of the company, which carries out R&D as a research center, are to develop new generation biosensors and sensors for both point-of-care diagnostics; such as glucose, lactate, cholesterol and cancer biomarker detections. My specific experimental and instrumental skills are Biochemistry, Biosensor, Analytical Chemistry, Electrochemistry, Mobile phone based point-of-care diagnostic device, POCTs and Patient interface designs, HPLC, Tandem Mass Spectrometry, Spectrophotometry, ELISA.",institutionString:null,institution:{name:"Ege University",country:{name:"Turkey"}}},{id:"267434",title:"Dr.",name:"Rohit",middleName:null,surname:"Raja",slug:"rohit-raja",fullName:"Rohit Raja",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/267434/images/system/267434.jpg",biography:"Dr. Rohit Raja received Ph.D. in Computer Science and Engineering from Dr. CVRAMAN University in 2016. His main research interest includes Face recognition and Identification, Digital Image Processing, Signal Processing, and Networking. Presently he is working as Associate Professor in IT Department, Guru Ghasidas Vishwavidyalaya (A Central University), Bilaspur (CG), India. He has authored several Journal and Conference Papers. He has good Academics & Research experience in various areas of CSE and IT. He has filed and successfully published 27 Patents. He has received many time invitations to be a Guest at IEEE Conferences. He has published 100 research papers in various International/National Journals (including IEEE, Springer, etc.) and Proceedings of the reputed International/ National Conferences (including Springer and IEEE). He has been nominated to the board of editors/reviewers of many peer-reviewed and refereed Journals (including IEEE, Springer).",institutionString:"Guru Ghasidas Vishwavidyalaya",institution:{name:"Guru Ghasidas Vishwavidyalaya",country:{name:"India"}}},{id:"246502",title:"Dr.",name:"Jaya T.",middleName:"T",surname:"Varkey",slug:"jaya-t.-varkey",fullName:"Jaya T. Varkey",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/246502/images/11160_n.jpg",biography:"Jaya T. Varkey, PhD, graduated with a degree in Chemistry from Cochin University of Science and Technology, Kerala, India. She obtained a PhD in Chemistry from the School of Chemical Sciences, Mahatma Gandhi University, Kerala, India, and completed a post-doctoral fellowship at the University of Minnesota, USA. She is a research guide at Mahatma Gandhi University and Associate Professor in Chemistry, St. Teresa’s College, Kochi, Kerala, India.\nDr. Varkey received a National Young Scientist award from the Indian Science Congress (1995), a UGC Research award (2016–2018), an Indian National Science Academy (INSA) Visiting Scientist award (2018–2019), and a Best Innovative Faculty award from the All India Association for Christian Higher Education (AIACHE) (2019). She Hashas received the Sr. Mary Cecil prize for best research paper three times. She was also awarded a start-up to develop a tea bag water filter. \nDr. Varkey has published two international books and twenty-seven international journal publications. She is an editorial board member for five international journals.",institutionString:"St. Teresa’s College",institution:null},{id:"250668",title:"Dr.",name:"Ali",middleName:null,surname:"Nabipour Chakoli",slug:"ali-nabipour-chakoli",fullName:"Ali Nabipour Chakoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/250668/images/system/250668.jpg",biography:"Academic Qualification:\r\n•\tPhD in Materials Physics and Chemistry, From: Sep. 2006, to: Sep. 2010, School of Materials Science and Engineering, Harbin Institute of Technology, Thesis: Structure and Shape Memory Effect of Functionalized MWCNTs/poly (L-lactide-co-ε-caprolactone) Nanocomposites. Supervisor: Prof. Wei Cai,\r\n•\tM.Sc in Applied Physics, From: 1996, to: 1998, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Determination of Boron in Micro alloy Steels with solid state nuclear track detectors by neutron induced auto radiography, Supervisors: Dr. M. Hosseini Ashrafi and Dr. A. Hosseini.\r\n•\tB.Sc. in Applied Physics, From: 1991, to: 1996, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Design of shielding for Am-Be neutron sources for In Vivo neutron activation analysis, Supervisor: Dr. M. Hosseini Ashrafi.\r\n\r\nResearch Experiences:\r\n1.\tNanomaterials, Carbon Nanotubes, Graphene: Synthesis, Functionalization and Characterization,\r\n2.\tMWCNTs/Polymer Composites: Fabrication and Characterization, \r\n3.\tShape Memory Polymers, Biodegradable Polymers, ORC, Collagen,\r\n4.\tMaterials Analysis and Characterizations: TEM, SEM, XPS, FT-IR, Raman, DSC, DMA, TGA, XRD, GPC, Fluoroscopy, \r\n5.\tInteraction of Radiation with Mater, Nuclear Safety and Security, NDT(RT),\r\n6.\tRadiation Detectors, Calibration (SSDL),\r\n7.\tCompleted IAEA e-learning Courses:\r\nNuclear Security (15 Modules),\r\nNuclear Safety:\r\nTSA 2: Regulatory Protection in Occupational Exposure,\r\nTips & Tricks: Radiation Protection in Radiography,\r\nSafety and Quality in Radiotherapy,\r\nCourse on Sealed Radioactive Sources,\r\nCourse on Fundamentals of Environmental Remediation,\r\nCourse on Planning for Environmental Remediation,\r\nKnowledge Management Orientation Course,\r\nFood Irradiation - Technology, Applications and Good Practices,\r\nEmployment:\r\nFrom 2010 to now: Academic staff, Nuclear Science and Technology Research Institute, Kargar Shomali, Tehran, Iran, P.O. Box: 14395-836.\r\nFrom 1997 to 2006: Expert of Materials Analysis and Characterization. Research Center of Agriculture and Medicine. Rajaeeshahr, Karaj, Iran, P. O. Box: 31585-498.",institutionString:"Atomic Energy Organization of Iran",institution:{name:"Atomic Energy Organization of Iran",country:{name:"Iran"}}},{id:"248279",title:"Dr.",name:"Monika",middleName:"Elzbieta",surname:"Machoy",slug:"monika-machoy",fullName:"Monika Machoy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248279/images/system/248279.jpeg",biography:"Monika Elżbieta Machoy, MD, graduated with distinction from the Faculty of Medicine and Dentistry at the Pomeranian Medical University in 2009, defended her PhD thesis with summa cum laude in 2016 and is currently employed as a researcher at the Department of Orthodontics of the Pomeranian Medical University. She expanded her professional knowledge during a one-year scholarship program at the Ernst Moritz Arndt University in Greifswald, Germany and during a three-year internship at the Technical University in Dresden, Germany. She has been a speaker at numerous orthodontic conferences, among others, American Association of Orthodontics, European Orthodontic Symposium and numerous conferences of the Polish Orthodontic Society. She conducts research focusing on the effect of orthodontic treatment on dental and periodontal tissues and the causes of pain in orthodontic patients.",institutionString:"Pomeranian Medical University",institution:{name:"Pomeranian Medical University",country:{name:"Poland"}}},{id:"252743",title:"Prof.",name:"Aswini",middleName:"Kumar",surname:"Kar",slug:"aswini-kar",fullName:"Aswini Kar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252743/images/10381_n.jpg",biography:"uploaded in cv",institutionString:null,institution:{name:"KIIT University",country:{name:"India"}}},{id:"204256",title:"Dr.",name:"Anil",middleName:"Kumar",surname:"Kumar Sahu",slug:"anil-kumar-sahu",fullName:"Anil Kumar Sahu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204256/images/14201_n.jpg",biography:"I have nearly 11 years of research and teaching experience. I have done my master degree from University Institute of Pharmacy, Pt. Ravi Shankar Shukla University, Raipur, Chhattisgarh India. I have published 16 review and research articles in international and national journals and published 4 chapters in IntechOpen, the world’s leading publisher of Open access books. I have presented many papers at national and international conferences. I have received research award from Indian Drug Manufacturers Association in year 2015. My research interest extends from novel lymphatic drug delivery systems, oral delivery system for herbal bioactive to formulation optimization.",institutionString:null,institution:{name:"Chhattisgarh Swami Vivekanand Technical University",country:{name:"India"}}},{id:"253468",title:"Dr.",name:"Mariusz",middleName:null,surname:"Marzec",slug:"mariusz-marzec",fullName:"Mariusz Marzec",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/253468/images/system/253468.png",biography:"An assistant professor at Department of Biomedical Computer Systems, at Institute of Computer Science, Silesian University in Katowice. Scientific interests: computer analysis and processing of images, biomedical images, databases and programming languages. He is an author and co-author of scientific publications covering analysis and processing of biomedical images and development of database systems.",institutionString:"University of Silesia",institution:null},{id:"212432",title:"Prof.",name:"Hadi",middleName:null,surname:"Mohammadi",slug:"hadi-mohammadi",fullName:"Hadi Mohammadi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/212432/images/system/212432.jpeg",biography:"Dr. Hadi Mohammadi is a biomedical engineer with hands-on experience in the design and development of many engineering structures and medical devices through various projects that he has been involved in over the past twenty years. Dr. Mohammadi received his BSc. and MSc. degrees in Mechanical Engineering from Sharif University of Technology, Tehran, Iran, and his PhD. degree in Biomedical Engineering (biomaterials) from the University of Western Ontario. He was a postdoctoral trainee for almost four years at University of Calgary and Harvard Medical School. He is an industry innovator having created the technology to produce lifelike synthetic platforms that can be used for the simulation of almost all cardiovascular reconstructive surgeries. He’s been heavily involved in the design and development of cardiovascular devices and technology for the past 10 years. He is currently an Assistant Professor with the University of British Colombia, Canada.",institutionString:"University of British Columbia",institution:{name:"University of British Columbia",country:{name:"Canada"}}},{id:"254463",title:"Prof.",name:"Haisheng",middleName:null,surname:"Yang",slug:"haisheng-yang",fullName:"Haisheng Yang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/254463/images/system/254463.jpeg",biography:"Haisheng Yang, Ph.D., Professor and Director of the Department of Biomedical Engineering, College of Life Science and Bioengineering, Beijing University of Technology. He received his Ph.D. degree in Mechanics/Biomechanics from Harbin Institute of Technology (jointly with University of California, Berkeley). Afterwards, he worked as a Postdoctoral Research Associate in the Purdue Musculoskeletal Biology and Mechanics Lab at the Department of Basic Medical Sciences, Purdue University, USA. He also conducted research in the Research Centre of Shriners Hospitals for Children-Canada at McGill University, Canada. Dr. Yang has over 10 years research experience in orthopaedic biomechanics and mechanobiology of bone adaptation and regeneration. He earned an award from Beijing Overseas Talents Aggregation program in 2017 and serves as Beijing Distinguished Professor.",institutionString:null,institution:{name:"Beijing University of Technology",country:{name:"China"}}},{id:"89721",title:"Dr.",name:"Mehmet",middleName:"Cuneyt",surname:"Ozmen",slug:"mehmet-ozmen",fullName:"Mehmet Ozmen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/89721/images/7289_n.jpg",biography:null,institutionString:null,institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"242893",title:"Ph.D. Student",name:"Joaquim",middleName:null,surname:"De Moura",slug:"joaquim-de-moura",fullName:"Joaquim De Moura",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/242893/images/7133_n.jpg",biography:"Joaquim de Moura received his degree in Computer Engineering in 2014 from the University of A Coruña (Spain). In 2016, he received his M.Sc degree in Computer Engineering from the same university. He is currently pursuing his Ph.D degree in Computer Science in a collaborative project between ophthalmology centers in Galicia and the University of A Coruña. His research interests include computer vision, machine learning algorithms and analysis and medical imaging processing of various kinds.",institutionString:null,institution:{name:"University of A Coruña",country:{name:"Spain"}}},{id:"294334",title:"B.Sc.",name:"Marc",middleName:null,surname:"Bruggeman",slug:"marc-bruggeman",fullName:"Marc Bruggeman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/294334/images/8242_n.jpg",biography:"Chemical engineer graduate, with a passion for material science and specific interest in polymers - their near infinite applications intrigue me. \n\nI plan to continue my scientific career in the field of polymeric biomaterials as I am fascinated by intelligent, bioactive and biomimetic materials for use in both consumer and medical applications.",institutionString:null,institution:null},{id:"255757",title:"Dr.",name:"Igor",middleName:"Victorovich",surname:"Lakhno",slug:"igor-lakhno",fullName:"Igor Lakhno",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255757/images/system/255757.jpg",biography:"Igor Victorovich Lakhno was born in 1971 in Kharkiv (Ukraine). \nMD – 1994, Kharkiv National Medical Univesity.\nOb&Gyn; – 1997, master courses in Kharkiv Medical Academy of Postgraduate Education.\nPh.D. – 1999, Kharkiv National Medical Univesity.\nDSC – 2019, PL Shupik National Academy of Postgraduate Education \nProfessor – 2021, Department of Obstetrics and Gynecology of VN Karazin Kharkiv National University\nHead of Department – 2021, Department of Perinatology, Obstetrics and gynecology of Kharkiv Medical Academy of Postgraduate Education\nIgor Lakhno has been graduated from international training courses on reproductive medicine and family planning held at Debrecen University (Hungary) in 1997. Since 1998 Lakhno Igor has worked as an associate professor in the department of obstetrics and gynecology of VN Karazin National University and an associate professor of the perinatology, obstetrics, and gynecology department of Kharkiv Medical Academy of Postgraduate Education. Since June 2019 he’s been a professor in the department of obstetrics and gynecology of VN Karazin National University and a professor of the perinatology, obstetrics, and gynecology department. He’s affiliated with Kharkiv Medical Academy of Postgraduate Education as a Head of Department from November 2021. Igor Lakhno has participated in several international projects on fetal non-invasive electrocardiography (with Dr. J. A. Behar (Technion), Prof. D. Hoyer (Jena University), and José Alejandro Díaz Méndez (National Institute of Astrophysics, Optics, and Electronics, Mexico). He’s an author of about 200 printed works and there are 31 of them in Scopus or Web of Science databases. Igor Lakhno is a member of the Editorial Board of Reproductive Health of Woman, Emergency Medicine, and Technology Transfer Innovative Solutions in Medicine (Estonia). He is a medical Editor of “Z turbotoyu pro zhinku”. Igor Lakhno is a reviewer of the Journal of Obstetrics and Gynaecology (Taylor and Francis), British Journal of Obstetrics and Gynecology (Wiley), Informatics in Medicine Unlocked (Elsevier), The Journal of Obstetrics and Gynecology Research (Wiley), Endocrine, Metabolic & Immune Disorders-Drug Targets (Bentham Open), The Open Biomedical Engineering Journal (Bentham Open), etc. He’s defended a dissertation for a DSc degree “Pre-eclampsia: prediction, prevention, and treatment”. Three years ago Igor Lakhno has participated in a training course on innovative technologies in medical education at Lublin Medical University (Poland). Lakhno Igor has participated as a speaker in several international conferences and congresses (International Conference on Biological Oscillations April 10th-14th 2016, Lancaster, UK, The 9th conference of the European Study Group on Cardiovascular Oscillations). His main scientific interests: are obstetrics, women’s health, fetal medicine, and cardiovascular medicine. \nIgor Lakhno is a consultant at Kharkiv municipal perinatal center. He’s graduated from training courses on endoscopy in gynecology. He has 28 years of practical experience in the field.",institutionString:null,institution:null},{id:"244950",title:"Dr.",name:"Salvatore",middleName:null,surname:"Di Lauro",slug:"salvatore-di-lauro",fullName:"Salvatore Di Lauro",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0030O00002bSF1HQAW/ProfilePicture%202021-12-20%2014%3A54%3A14.482",biography:"Name:\n\tSALVATORE DI LAURO\nAddress:\n\tHospital Clínico Universitario Valladolid\nAvda Ramón y Cajal 3\n47005, Valladolid\nSpain\nPhone number: \nFax\nE-mail:\n\t+34 983420000 ext 292\n+34 983420084\nsadilauro@live.it\nDate and place of Birth:\nID Number\nMedical Licence \nLanguages\t09-05-1985. Villaricca (Italy)\n\nY1281863H\n474707061\nItalian (native language)\nSpanish (read, written, spoken)\nEnglish (read, written, spoken)\nPortuguese (read, spoken)\nFrench (read)\n\t\t\nCurrent position (title and company)\tDate (Year)\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. Private practise.\t2017-today\n\n2019-today\n\t\n\t\nEducation (High school, university and postgraduate training > 3 months)\tDate (Year)\nDegree in Medicine and Surgery. University of Neaples 'Federico II”\nResident in Opthalmology. Hospital Clinico Universitario Valladolid\nMaster in Vitreo-Retina. IOBA. University of Valladolid\nFellow of the European Board of Ophthalmology. Paris\nMaster in Research in Ophthalmology. University of Valladolid\t2003-2009\n2012-2016\n2016-2017\n2016\n2012-2013\n\t\nEmployments (company and positions)\tDate (Year)\nResident in Ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl.\nFellow in Vitreo-Retina. IOBA. University of Valladolid\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. \n\t2012-2016\n2016-2017\n2017-today\n\n2019-Today\n\n\n\t\nClinical Research Experience (tasks and role)\tDate (Year)\nAssociated investigator\n\n' FIS PI20/00740: DESARROLLO DE UNA CALCULADORA DE RIESGO DE\nAPARICION DE RETINOPATIA DIABETICA BASADA EN TECNICAS DE IMAGEN MULTIMODAL EN PACIENTES DIABETICOS TIPO 1. Grant by: Ministerio de Ciencia e Innovacion \n\n' (BIO/VA23/14) Estudio clínico multicéntrico y prospectivo para validar dos\nbiomarcadores ubicados en los genes p53 y MDM2 en la predicción de los resultados funcionales de la cirugía del desprendimiento de retina regmatógeno. Grant by: Gerencia Regional de Salud de la Junta de Castilla y León.\n' Estudio multicéntrico, aleatorizado, con enmascaramiento doble, en 2 grupos\nparalelos y de 52 semanas de duración para comparar la eficacia, seguridad e inmunogenicidad de SOK583A1 respecto a Eylea® en pacientes con degeneración macular neovascular asociada a la edad' (CSOK583A12301; N.EUDRA: 2019-004838-41; FASE III). Grant by Hexal AG\n\n' Estudio de fase III, aleatorizado, doble ciego, con grupos paralelos, multicéntrico para comparar la eficacia y la seguridad de QL1205 frente a Lucentis® en pacientes con degeneración macular neovascular asociada a la edad. (EUDRACT: 2018-004486-13). Grant by Qilu Pharmaceutical Co\n\n' Estudio NEUTON: Ensayo clinico en fase IV para evaluar la eficacia de aflibercept en pacientes Naive con Edema MacUlar secundario a Oclusion de Vena CenTral de la Retina (OVCR) en regimen de tratamientO iNdividualizado Treat and Extend (TAE)”, (2014-000975-21). Grant by Fundacion Retinaplus\n\n' Evaluación de la seguridad y bioactividad de anillos de tensión capsular en conejo. Proyecto Procusens. Grant by AJL, S.A.\n\n'Estudio epidemiológico, prospectivo, multicéntrico y abierto\\npara valorar la frecuencia de la conjuntivitis adenovírica diagnosticada mediante el test AdenoPlus®\\nTest en pacientes enfermos de conjuntivitis aguda”\\n. National, multicenter study. Grant by: NICOX.\n\nEuropean multicentric trial: 'Evaluation of clinical outcomes following the use of Systane Hydration in patients with dry eye”. Study Phase 4. Grant by: Alcon Labs'\n\nVLPs Injection and Activation in a Rabbit Model of Uveal Melanoma. Grant by Aura Bioscience\n\nUpdating and characterization of a rabbit model of uveal melanoma. Grant by Aura Bioscience\n\nEnsayo clínico en fase IV para evaluar las variantes genéticas de la vía del VEGF como biomarcadores de eficacia del tratamiento con aflibercept en pacientes con degeneración macular asociada a la edad (DMAE) neovascular. Estudio BIOIMAGE. IMO-AFLI-2013-01\n\nEstudio In-Eye:Ensayo clínico en fase IV, abierto, aleatorizado, de 2 brazos,\nmulticçentrico y de 12 meses de duración, para evaluar la eficacia y seguridad de un régimen de PRN flexible individualizado de 'esperar y extender' versus un régimen PRN según criterios de estabilización mediante evaluaciones mensuales de inyecciones intravítreas de ranibizumab 0,5 mg en pacientes naive con neovascularización coriodea secunaria a la degeneración macular relacionada con la edad. CP: CRFB002AES03T\n\nTREND: Estudio Fase IIIb multicéntrico, randomizado, de 12 meses de\nseguimiento con evaluador de la agudeza visual enmascarado, para evaluar la eficacia y la seguridad de ranibizumab 0.5mg en un régimen de tratar y extender comparado con un régimen mensual, en pacientes con degeneración macular neovascular asociada a la edad. CP: CRFB002A2411 Código Eudra CT:\n2013-002626-23\n\n\n\nPublications\t\n\n2021\n\n\n\n\n2015\n\n\n\n\n2021\n\n\n\n\n\n2021\n\n\n\n\n2015\n\n\n\n\n2015\n\n\n2014\n\n\n\n\n2015-16\n\n\n\n2015\n\n\n2014\n\n\n2014\n\n\n\n\n2014\n\n\n\n\n\n\n\n2014\n\nJose Carlos Pastor; Jimena Rojas; Salvador Pastor-Idoate; Salvatore Di Lauro; Lucia Gonzalez-Buendia; Santiago Delgado-Tirado. Proliferative vitreoretinopathy: A new concept of disease pathogenesis and practical\nconsequences. Progress in Retinal and Eye Research. 51, pp. 125 - 155. 03/2016. DOI: 10.1016/j.preteyeres.2015.07.005\n\n\nLabrador-Velandia S; Alonso-Alonso ML; Di Lauro S; García-Gutierrez MT; Srivastava GK; Pastor JC; Fernandez-Bueno I. Mesenchymal stem cells provide paracrine neuroprotective resources that delay degeneration of co-cultured organotypic neuroretinal cultures.Experimental Eye Research. 185, 17/05/2019. DOI: 10.1016/j.exer.2019.05.011\n\nSalvatore Di Lauro; Maria Teresa Garcia Gutierrez; Ivan Fernandez Bueno. Quantification of pigment epithelium-derived factor (PEDF) in an ex vivo coculture of retinal pigment epithelium cells and neuroretina.\nJournal of Allbiosolution. 2019. ISSN 2605-3535\n\nSonia Labrador Velandia; Salvatore Di Lauro; Alonso-Alonso ML; Tabera Bartolomé S; Srivastava GK; Pastor JC; Fernandez-Bueno I. Biocompatibility of intravitreal injection of human mesenchymal stem cells in immunocompetent rabbits. Graefe's archive for clinical and experimental ophthalmology. 256 - 1, pp. 125 - 134. 01/2018. DOI: 10.1007/s00417-017-3842-3\n\n\nSalvatore Di Lauro, David Rodriguez-Crespo, Manuel J Gayoso, Maria T Garcia-Gutierrez, J Carlos Pastor, Girish K Srivastava, Ivan Fernandez-Bueno. A novel coculture model of porcine central neuroretina explants and retinal pigment epithelium cells. Molecular Vision. 2016 - 22, pp. 243 - 253. 01/2016.\n\nSalvatore Di Lauro. Classifications for Proliferative Vitreoretinopathy ({PVR}): An Analysis of Their Use in Publications over the Last 15 Years. Journal of Ophthalmology. 2016, pp. 1 - 6. 01/2016. DOI: 10.1155/2016/7807596\n\nSalvatore Di Lauro; Rosa Maria Coco; Rosa Maria Sanabria; Enrique Rodriguez de la Rua; Jose Carlos Pastor. Loss of Visual Acuity after Successful Surgery for Macula-On Rhegmatogenous Retinal Detachment in a Prospective Multicentre Study. Journal of Ophthalmology. 2015:821864, 2015. DOI: 10.1155/2015/821864\n\nIvan Fernandez-Bueno; Salvatore Di Lauro; Ivan Alvarez; Jose Carlos Lopez; Maria Teresa Garcia-Gutierrez; Itziar Fernandez; Eva Larra; Jose Carlos Pastor. Safety and Biocompatibility of a New High-Density Polyethylene-Based\nSpherical Integrated Porous Orbital Implant: An Experimental Study in Rabbits. Journal of Ophthalmology. 2015:904096, 2015. DOI: 10.1155/2015/904096\n\nPastor JC; Pastor-Idoate S; Rodríguez-Hernandez I; Rojas J; Fernandez I; Gonzalez-Buendia L; Di Lauro S; Gonzalez-Sarmiento R. Genetics of PVR and RD. Ophthalmologica. 232 - Suppl 1, pp. 28 - 29. 2014\n\nRodriguez-Crespo D; Di Lauro S; Singh AK; Garcia-Gutierrez MT; Garrosa M; Pastor JC; Fernandez-Bueno I; Srivastava GK. Triple-layered mixed co-culture model of RPE cells with neuroretina for evaluating the neuroprotective effects of adipose-MSCs. Cell Tissue Res. 358 - 3, pp. 705 - 716. 2014.\nDOI: 10.1007/s00441-014-1987-5\n\nCarlo De Werra; Salvatore Condurro; Salvatore Tramontano; Mario Perone; Ivana Donzelli; Salvatore Di Lauro; Massimo Di Giuseppe; Rosa Di Micco; Annalisa Pascariello; Antonio Pastore; Giorgio Diamantis; Giuseppe Galloro. Hydatid disease of the liver: thirty years of surgical experience.Chirurgia italiana. 59 - 5, pp. 611 - 636.\n(Italia): 2007. ISSN 0009-4773\n\nChapters in books\n\t\n' Salvador Pastor Idoate; Salvatore Di Lauro; Jose Carlos Pastor Jimeno. PVR: Pathogenesis, Histopathology and Classification. Proliferative Vitreoretinopathy with Small Gauge Vitrectomy. Springer, 2018. ISBN 978-3-319-78445-8\nDOI: 10.1007/978-3-319-78446-5_2. \n\n' Salvatore Di Lauro; Maria Isabel Lopez Galvez. Quistes vítreos en una mujer joven. Problemas diagnósticos en patología retinocoroidea. Sociedad Española de Retina-Vitreo. 2018.\n\n' Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor Jimeno. iOCT in PVR management. OCT Applications in Opthalmology. pp. 1 - 8. INTECH, 2018. DOI: 10.5772/intechopen.78774.\n\n' Rosa Coco Martin; Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor. amponadores, manipuladores y tinciones en la cirugía del traumatismo ocular.Trauma Ocular. Ponencia de la SEO 2018..\n\n' LOPEZ GALVEZ; DI LAURO; CRESPO. OCT angiografia y complicaciones retinianas de la diabetes. PONENCIA SEO 2021, CAPITULO 20. (España): 2021.\n\n' Múltiples desprendimientos neurosensoriales bilaterales en paciente joven. Enfermedades Degenerativas De Retina Y Coroides. SERV 04/2016. \n' González-Buendía L; Di Lauro S; Pastor-Idoate S; Pastor Jimeno JC. Vitreorretinopatía proliferante (VRP) e inflamación: LA INFLAMACIÓN in «INMUNOMODULADORES Y ANTIINFLAMATORIOS: MÁS ALLÁ DE LOS CORTICOIDES. RELACION DE PONENCIAS DE LA SOCIEDAD ESPAÑOLA DE OFTALMOLOGIA. 10/2014.",institutionString:null,institution:null},{id:"265335",title:"Mr.",name:"Stefan",middleName:"Radnev",surname:"Stefanov",slug:"stefan-stefanov",fullName:"Stefan Stefanov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/265335/images/7562_n.jpg",biography:null,institutionString:null,institution:null},{id:"243698",title:"Dr.",name:"Xiaogang",middleName:null,surname:"Wang",slug:"xiaogang-wang",fullName:"Xiaogang Wang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243698/images/system/243698.png",biography:"Dr. Xiaogang Wang, a faculty member of Shanxi Eye Hospital specializing in the treatment of cataract and retinal disease and a tutor for postgraduate students of Shanxi Medical University, worked in the COOL Lab as an international visiting scholar under the supervision of Dr. David Huang and Yali Jia from October 2012 through November 2013. Dr. Wang earned an MD from Shanxi Medical University and a Ph.D. from Shanghai Jiao Tong University. Dr. Wang was awarded two research project grants focused on multimodal optical coherence tomography imaging and deep learning in cataract and retinal disease, from the National Natural Science Foundation of China. 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Many parasitic diseases are classified as neglected tropical diseases because they have received minimal funding over recent years and, in many cases, are under-reported despite the critical role they play in morbidity and mortality among human and animal hosts. The current topic, Parasitic Infectious Diseases, in the Infectious Diseases Series aims to publish studies on the systematics, epidemiology, molecular biology, genomics, pathogenesis, genetics, and clinical significance of parasitic diseases from blood borne to intestinal parasites as well as zoonotic parasites. We hope to cover all aspects of parasitic diseases to provide current and relevant research data on these very important diseases. In the current atmosphere of the Coronavirus pandemic, communities around the world, particularly those in different underdeveloped areas, are faced with the growing challenges of the high burden of parasitic diseases. At the same time, they are faced with the Covid-19 pandemic leading to what some authors have called potential syndemics that might worsen the outcome of such infections. Therefore, it is important to conduct studies that examine parasitic infections in the context of the coronavirus pandemic for the benefit of all communities to help foster more informed decisions for the betterment of human and animal health.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/5.jpg",keywords:"Blood Borne Parasites, Intestinal Parasites, Protozoa, Helminths, Arthropods, Water Born Parasites, Epidemiology, Molecular Biology, Systematics, Genomics, Proteomics, Ecology"},{id:"6",title:"Viral Infectious Diseases",scope:"The Viral Infectious Diseases Book Series aims to provide a comprehensive overview of recent research trends and discoveries in various viral infectious diseases emerging around the globe. The emergence of any viral disease is hard to anticipate, which often contributes to death. A viral disease can be defined as an infectious disease that has recently appeared within a population or exists in nature with the rapid expansion of incident or geographic range. This series will focus on various crucial factors related to emerging viral infectious diseases, including epidemiology, pathogenesis, host immune response, clinical manifestations, diagnosis, treatment, and clinical recommendations for managing viral infectious diseases, highlighting the recent issues with future directions for effective therapeutic strategies.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/6.jpg",keywords:"Novel Viruses, Virus Transmission, Virus Evolution, Molecular Virology, Control and Prevention, Virus-host Interaction"}],annualVolumeBook:{},thematicCollection:[{type:"book",id:"11672",title:"Chemokines Updates",subtitle:null,isOpenForSubmission:!0,hash:"c00855833476a514d37abf7c846e16e9",slug:null,bookSignature:"Prof. Murat Şentürk",coverURL:"https://cdn.intechopen.com/books/images_new/11672.jpg",editedByType:null,submissionDeadline:"May 6th 2022",editors:[{id:"14794",title:"Prof.",name:"Murat",middleName:null,surname:"Şentürk",slug:"murat-senturk",fullName:"Murat Şentürk",profilePictureURL:"https://mts.intechopen.com/storage/users/14794/images/system/14794.jpeg",biography:"Dr. Murat Şentürk obtained a baccalaureate degree in Chemistry in 2002, a master’s degree in Biochemistry in 2006, and a doctorate degree in Biochemistry in 2009 from Atatürk University, Turkey. Dr. Şentürk currently works as an professor of Biochemistry in the Department of Basic Pharmacy Sciences, Faculty of Pharmacy, Ağri Ibrahim Cecen University, Turkey. \nDr. Şentürk published over 120 scientific papers, reviews, and book chapters and presented several conferences to scientists. \nHis research interests span enzyme inhibitor or activator, protein expression, purification and characterization, drug design and synthesis, toxicology, and pharmacology. \nHis research work has focused on neurodegenerative diseases and cancer treatment. Dr. Şentürk serves as the editorial board member of several international journals.",institutionString:"Ağrı İbrahim Çeçen University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Ağrı İbrahim Çeçen University",institutionURL:null,country:{name:"Turkey"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null}],selectedSeries:null,selectedSubseries:null},seriesLanding:{item:{id:"11",title:"Biochemistry",doi:"10.5772/intechopen.72877",issn:"2632-0983",scope:"Biochemistry, the study of chemical transformations occurring within living organisms, impacts all areas of life sciences, from molecular crystallography and genetics to ecology, medicine, and population biology. Biochemistry examines macromolecules - proteins, nucleic acids, carbohydrates, and lipids – and their building blocks, structures, functions, and interactions. Much of biochemistry is devoted to enzymes, proteins that catalyze chemical reactions, enzyme structures, mechanisms of action and their roles within cells. Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. This Biochemistry Series will address the current research on biomolecules and the emerging trends with great promise.",coverUrl:"https://cdn.intechopen.com/series/covers/11.jpg",latestPublicationDate:"July 5th, 2022",hasOnlineFirst:!0,numberOfOpenTopics:4,numberOfPublishedChapters:320,numberOfPublishedBooks:32,editor:{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"Blumenberg",fullName:"Miroslav Blumenberg",profilePictureURL:"https://mts.intechopen.com/storage/users/31610/images/system/31610.jpg",biography:"Miroslav Blumenberg, Ph.D., was born in Subotica and received his BSc in Belgrade, Yugoslavia. He completed his Ph.D. at MIT in Organic Chemistry; he followed up his Ph.D. with two postdoctoral study periods at Stanford University. Since 1983, he has been a faculty member of the RO Perelman Department of Dermatology, NYU School of Medicine, where he is codirector of a training grant in cutaneous biology. Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}},subseries:[{id:"14",title:"Cell and Molecular Biology",keywords:"Omics (Transcriptomics; Proteomics; Metabolomics), Molecular Biology, Cell Biology, Signal Transduction and Regulation, Cell Growth and Differentiation, Apoptosis, Necroptosis, Ferroptosis, Autophagy, Cell Cycle, Macromolecules and Complexes, Gene Expression",scope:"The Cell and Molecular Biology topic within the IntechOpen Biochemistry Series aims to rapidly publish contributions on all aspects of cell and molecular biology, including aspects related to biochemical and genetic research (not only in humans but all living beings). We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics include, but are not limited to: Advanced techniques of cellular and molecular biology (Molecular methodologies, imaging techniques, and bioinformatics); Biological activities at the molecular level; Biological processes of cell functions, cell division, senescence, maintenance, and cell death; Biomolecules interactions; Cancer; Cell biology; Chemical biology; Computational biology; Cytochemistry; Developmental biology; Disease mechanisms and therapeutics; DNA, and RNA metabolism; Gene functions, genetics, and genomics; Genetics; Immunology; Medical microbiology; Molecular biology; Molecular genetics; Molecular processes of cell and organelle dynamics; Neuroscience; Protein biosynthesis, degradation, and functions; Regulation of molecular interactions in a cell; Signalling networks and system biology; Structural biology; Virology and microbiology.",annualVolume:11410,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/14.jpg",editor:{id:"165627",title:"Dr.",name:"Rosa María",middleName:null,surname:"Martínez-Espinosa",fullName:"Rosa María Martínez-Espinosa",profilePictureURL:"https://mts.intechopen.com/storage/users/165627/images/system/165627.jpeg",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"79367",title:"Dr.",name:"Ana Isabel",middleName:null,surname:"Flores",fullName:"Ana Isabel Flores",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRpIOQA0/Profile_Picture_1632418099564",institutionString:null,institution:{name:"Hospital Universitario 12 De Octubre",institutionURL:null,country:{name:"Spain"}}},{id:"328234",title:"Ph.D.",name:"Christian",middleName:null,surname:"Palavecino",fullName:"Christian Palavecino",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000030DhEhQAK/Profile_Picture_1628835318625",institutionString:null,institution:{name:"Central University of Chile",institutionURL:null,country:{name:"Chile"}}},{id:"186585",title:"Dr.",name:"Francisco Javier",middleName:null,surname:"Martin-Romero",fullName:"Francisco Javier Martin-Romero",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSB3HQAW/Profile_Picture_1631258137641",institutionString:null,institution:{name:"University of Extremadura",institutionURL:null,country:{name:"Spain"}}}]},{id:"15",title:"Chemical Biology",keywords:"Phenolic Compounds, Essential Oils, Modification of Biomolecules, Glycobiology, Combinatorial Chemistry, Therapeutic peptides, Enzyme Inhibitors",scope:"Chemical biology spans the fields of chemistry and biology involving the application of biological and chemical molecules and techniques. In recent years, the application of chemistry to biological molecules has gained significant interest in medicinal and pharmacological studies. This topic will be devoted to understanding the interplay between biomolecules and chemical compounds, their structure and function, and their potential applications in related fields. Being a part of the biochemistry discipline, the ideas and concepts that have emerged from Chemical Biology have affected other related areas. This topic will closely deal with all emerging trends in this discipline.",annualVolume:11411,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",institutionString:null,institution:{name:"Anadolu University",institutionURL:null,country:{name:"Turkey"}}},editorTwo:{id:"13652",title:"Prof.",name:"Deniz",middleName:null,surname:"Ekinci",fullName:"Deniz Ekinci",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYLT1QAO/Profile_Picture_1634557223079",institutionString:null,institution:{name:"Ondokuz Mayıs University",institutionURL:null,country:{name:"Turkey"}}},editorThree:null,editorialBoard:[{id:"219081",title:"Dr.",name:"Abdulsamed",middleName:null,surname:"Kükürt",fullName:"Abdulsamed Kükürt",profilePictureURL:"https://mts.intechopen.com/storage/users/219081/images/system/219081.png",institutionString:null,institution:{name:"Kafkas University",institutionURL:null,country:{name:"Turkey"}}},{id:"241413",title:"Dr.",name:"Azhar",middleName:null,surname:"Rasul",fullName:"Azhar Rasul",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRT1oQAG/Profile_Picture_1635251978933",institutionString:null,institution:{name:"Government College University, Faisalabad",institutionURL:null,country:{name:"Pakistan"}}},{id:"178316",title:"Ph.D.",name:"Sergey",middleName:null,surname:"Sedykh",fullName:"Sergey Sedykh",profilePictureURL:"https://mts.intechopen.com/storage/users/178316/images/system/178316.jfif",institutionString:null,institution:{name:"Novosibirsk State University",institutionURL:null,country:{name:"Russia"}}}]},{id:"17",title:"Metabolism",keywords:"Biomolecules Metabolism, Energy Metabolism, Metabolic Pathways, Key Metabolic Enzymes, Metabolic Adaptation",scope:"Metabolism is frequently defined in biochemistry textbooks as the overall process that allows living systems to acquire and use the free energy they need for their vital functions or the chemical processes that occur within a living organism to maintain life. Behind these definitions are hidden all the aspects of normal and pathological functioning of all processes that the topic ‘Metabolism’ will cover within the Biochemistry Series. Thus all studies on metabolism will be considered for publication.",annualVolume:11413,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/17.jpg",editor:{id:"138626",title:"Dr.",name:"Yannis",middleName:null,surname:"Karamanos",fullName:"Yannis Karamanos",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002g6Jv2QAE/Profile_Picture_1629356660984",institutionString:null,institution:{name:"Artois University",institutionURL:null,country:{name:"France"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"243049",title:"Dr.",name:"Anca",middleName:null,surname:"Pantea Stoian",fullName:"Anca Pantea Stoian",profilePictureURL:"https://mts.intechopen.com/storage/users/243049/images/system/243049.jpg",institutionString:null,institution:{name:"Carol Davila University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"203824",title:"Dr.",name:"Attilio",middleName:null,surname:"Rigotti",fullName:"Attilio Rigotti",profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institutionString:null,institution:{name:"Pontifical Catholic University of Chile",institutionURL:null,country:{name:"Chile"}}},{id:"300470",title:"Dr.",name:"Yanfei (Jacob)",middleName:null,surname:"Qi",fullName:"Yanfei (Jacob) Qi",profilePictureURL:"https://mts.intechopen.com/storage/users/300470/images/system/300470.jpg",institutionString:null,institution:{name:"Centenary Institute of Cancer Medicine and Cell Biology",institutionURL:null,country:{name:"Australia"}}}]},{id:"18",title:"Proteomics",keywords:"Mono- and Two-Dimensional Gel Electrophoresis (1-and 2-DE), Liquid Chromatography (LC), Mass Spectrometry/Tandem Mass Spectrometry (MS; MS/MS), Proteins",scope:"With the recognition that the human genome cannot provide answers to the etiology of a disorder, changes in the proteins expressed by a genome became a focus in research. Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. The Proteomics topic aims to attract contributions on all aspects of MS-based proteomics that, by pushing the boundaries of MS capabilities, may address biological problems that have not been resolved yet.",annualVolume:11414,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/18.jpg",editor:{id:"200689",title:"Prof.",name:"Paolo",middleName:null,surname:"Iadarola",fullName:"Paolo Iadarola",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSCl8QAG/Profile_Picture_1623568118342",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorTwo:{id:"201414",title:"Dr.",name:"Simona",middleName:null,surname:"Viglio",fullName:"Simona Viglio",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKDHQA4/Profile_Picture_1630402531487",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorThree:null,editorialBoard:[{id:"72288",title:"Dr.",name:"Arli Aditya",middleName:null,surname:"Parikesit",fullName:"Arli Aditya Parikesit",profilePictureURL:"https://mts.intechopen.com/storage/users/72288/images/system/72288.jpg",institutionString:null,institution:{name:"Indonesia International Institute for Life Sciences",institutionURL:null,country:{name:"Indonesia"}}},{id:"40928",title:"Dr.",name:"Cesar",middleName:null,surname:"Lopez-Camarillo",fullName:"Cesar Lopez-Camarillo",profilePictureURL:"https://mts.intechopen.com/storage/users/40928/images/3884_n.png",institutionString:null,institution:{name:"Universidad Autónoma de la Ciudad de México",institutionURL:null,country:{name:"Mexico"}}},{id:"81926",title:"Dr.",name:"Shymaa",middleName:null,surname:"Enany",fullName:"Shymaa Enany",profilePictureURL:"https://mts.intechopen.com/storage/users/81926/images/system/81926.png",institutionString:"Suez Canal University",institution:{name:"Suez Canal University",institutionURL:null,country:{name:"Egypt"}}}]}]}},libraryRecommendation:{success:null,errors:{},institutions:[]},route:{name:"chapter.detail",path:"/chapters/51365",hash:"",query:{},params:{id:"51365"},fullPath:"/chapters/51365",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)}()