Published rates of CP from population-based samples.
\\n\\n
IntechOpen Book Series will also publish a program of research-driven Thematic Edited Volumes that focus on specific areas and allow for a more in-depth overview of a particular subject.
\\n\\nIntechOpen Book Series will be launching regularly to offer our authors and editors exciting opportunities to publish their research Open Access. We will begin by relaunching some of our existing Book Series in this innovative book format, and will expand in 2022 into rapidly growing research fields that are driving and advancing society.
\\n\\nLaunching 2021
\\n\\nArtificial Intelligence, ISSN 2633-1403
\\n\\nVeterinary Medicine and Science, ISSN 2632-0517
\\n\\nBiochemistry, ISSN 2632-0983
\\n\\nBiomedical Engineering, ISSN 2631-5343
\\n\\nInfectious Diseases, ISSN 2631-6188
\\n\\nPhysiology (Coming Soon)
\\n\\nDentistry (Coming Soon)
\\n\\nWe invite you to explore our IntechOpen Book Series, find the right publishing program for you and reach your desired audience in record time.
\\n\\nNote: Edited in October 2021
\\n"}]',published:!0,mainMedia:{caption:"",originalUrl:"/media/original/132"}},components:[{type:"htmlEditorComponent",content:'With the desire to make book publishing more relevant for the digital age and offer innovative Open Access publishing options, we are thrilled to announce the launch of our new publishing format: IntechOpen Book Series.
\n\nDesigned to cover fast-moving research fields in rapidly expanding areas, our Book Series feature a Topic structure allowing us to present the most relevant sub-disciplines. Book Series are headed by Series Editors, and a team of Topic Editors supported by international Editorial Board members. Topics are always open for submissions, with an Annual Volume published each calendar year.
\n\nAfter a robust peer-review process, accepted works are published quickly, thanks to Online First, ensuring research is made available to the scientific community without delay.
\n\nOur innovative Book Series format brings you:
\n\nIntechOpen Book Series will also publish a program of research-driven Thematic Edited Volumes that focus on specific areas and allow for a more in-depth overview of a particular subject.
\n\nIntechOpen Book Series will be launching regularly to offer our authors and editors exciting opportunities to publish their research Open Access. We will begin by relaunching some of our existing Book Series in this innovative book format, and will expand in 2022 into rapidly growing research fields that are driving and advancing society.
\n\nLaunching 2021
\n\nArtificial Intelligence, ISSN 2633-1403
\n\nVeterinary Medicine and Science, ISSN 2632-0517
\n\nBiochemistry, ISSN 2632-0983
\n\nBiomedical Engineering, ISSN 2631-5343
\n\nInfectious Diseases, ISSN 2631-6188
\n\nPhysiology (Coming Soon)
\n\nDentistry (Coming Soon)
\n\nWe invite you to explore our IntechOpen Book Series, find the right publishing program for you and reach your desired audience in record time.
\n\nNote: Edited in October 2021
\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:"8798",leadTitle:null,fullTitle:"Cells of the Immune System",title:"Cells of the Immune System",subtitle:null,reviewType:"peer-reviewed",abstract:"The cells of the immune system are lymphocytes (T-cells, B-cells and NK (natural killer) cells), neutrophils, eosinophils, and monocytes/macrophages. This book is an overview of some types of these cells and their role in recognizing and/or reacting against foreign material. The immune system is characterized by collaboration between cells and proteins. The development of all cells of the immune system begins in the bone marrow with a hematopoietic stem cell. Two chapters deal with neutrophils, three chapters with T-cells, four chapters with eosinophils, and other chapters review the immunomodulation of macrophages, the role of transcription factor KLF4 in regulating plasticity of myeloid-derived suppressor cells, immune reconstitution after allogeneic hematopoietic stem cell transplantation, and role of sorption detoxification in the therapy of acute radiation sickness.",isbn:"978-1-78985-584-5",printIsbn:"978-1-78985-583-8",pdfIsbn:"978-1-83880-430-5",doi:"10.5772/intechopen.80249",price:119,priceEur:129,priceUsd:155,slug:"cells-of-the-immune-system",numberOfPages:246,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"4e8acf20a4e80bc7c97cb34d1672e53d",bookSignature:"Ota Fuchs and Seyyed Shamsadin Athari",publishedDate:"May 13th 2020",coverURL:"https://cdn.intechopen.com/books/images_new/8798.jpg",numberOfDownloads:10282,numberOfWosCitations:4,numberOfCrossrefCitations:7,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:17,numberOfDimensionsCitationsByBook:0,hasAltmetrics:1,numberOfTotalCitations:28,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"February 6th 2019",dateEndSecondStepPublish:"May 21st 2019",dateEndThirdStepPublish:"July 20th 2019",dateEndFourthStepPublish:"October 8th 2019",dateEndFifthStepPublish:"December 7th 2019",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"36468",title:"Dr.",name:"Ota",middleName:null,surname:"Fuchs",slug:"ota-fuchs",fullName:"Ota Fuchs",profilePictureURL:"https://mts.intechopen.com/storage/users/36468/images/system/36468.jpeg",biography:"Ota Fuchs graduated from the Chemical Technological University, Prague, Czech Republic, in 1971. He obtained his Ph.D. in Biochemistry from the Faculty of Natural Sciences, Charles University, Prague, in 1981. He is employed as a Senior Scientist at the Institute of Hematology and Blood Transfusion, Prague. He undertook as visiting scientist short-term affiliations at the Beatson Institute for Cancer Research, Glasgow, UK; Institute of Experimental Medicine of the Russian Academy of Medical Sciences in St Peterburg, Russia; and Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Canada. Dr. Fuchs was the principal investigator of five projects of the Internal Grant Agency of the Ministry of Health of the Czech Republic and one grant project of the Grant Agency of Czech Republic.",institutionString:"Institute of Hematology and Blood Transfusion",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"6",totalChapterViews:"0",totalEditedBooks:"4",institution:null}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:{id:"139889",title:"Dr.",name:"Seyyed Shamsadin",middleName:null,surname:"Athari",slug:"seyyed-shamsadin-athari",fullName:"Seyyed Shamsadin Athari",profilePictureURL:"https://mts.intechopen.com/storage/users/139889/images/system/139889.jpeg",biography:"Dr. Seyyed Shamsadin Athari is an assistant professor of immunology at the Department of Immunology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran. He has an allergy and asthma toxicology postdoctoral degree and asthma management and controlling network fellowship. He has published more than 90 manuscripts in international journals on immunology, allergy, and asthma and more than 28 books. He is also on the editorial board of more than 65 international journals in medical sciences and has more than 12 inventions in medical sciences and has recorded 12 gene sequences in the gene bank. Dr. Athari has been invited as a top speaker for more than 40 international congresses and symposiums and has received several scientific awards from different scientific societies as a young top researcher and young scientist.",institutionString:"Zanjan University of Medical Sciences",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"2",institution:{name:"Zanjan University of Medical Sciences",institutionURL:null,country:{name:"Iran"}}},coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1034",title:"Classical Immunology",slug:"classical-immunology"}],chapters:[{id:"71229",title:"Introductory Chapter: Development of Neutrophils and Their Role in Hematopoietic Microenvironment Regulation",doi:"10.5772/intechopen.91269",slug:"introductory-chapter-development-of-neutrophils-and-their-role-in-hematopoietic-microenvironment-reg",totalDownloads:788,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:null,signatures:"Ota Fuchs",downloadPdfUrl:"/chapter/pdf-download/71229",previewPdfUrl:"/chapter/pdf-preview/71229",authors:[{id:"36468",title:"Dr.",name:"Ota",surname:"Fuchs",slug:"ota-fuchs",fullName:"Ota Fuchs"}],corrections:null},{id:"67756",title:"Neutrophil Function Impairment Is a Host Susceptibility Factor to Bacterial Infection in Diabetes",doi:"10.5772/intechopen.86600",slug:"neutrophil-function-impairment-is-a-host-susceptibility-factor-to-bacterial-infection-in-diabetes",totalDownloads:1031,totalCrossrefCites:5,totalDimensionsCites:11,hasAltmetrics:0,abstract:"Diabetes mellitus is a highly prevalent noncommunicable disease globally. One of the main complications of diabetes is the increased susceptibility to bacterial infection. Neutrophils play a crucial role in inflammatory response against bacterial infections, once they are the first cells recruited to the sites of injury. In diabetes, there is a failure in the neutrophil functions, including migration, ROS production, phagocytosis, and bacterial killing, which are associated with the high incidence of bacterial infections. Herein, we point out pieces of evidence revealing the primary molecular mechanisms involved with impairment of neutrophil functions in diabetes, with relationship with high susceptibility to bacterial infections.",signatures:"Daniella Insuela, Diego Coutinho, Marco Martins, Maximiliano Ferrero and Vinicius Carvalho",downloadPdfUrl:"/chapter/pdf-download/67756",previewPdfUrl:"/chapter/pdf-preview/67756",authors:[{id:"296748",title:"Dr.",name:"Vinicius",surname:"Carvalho",slug:"vinicius-carvalho",fullName:"Vinicius Carvalho"},{id:"303254",title:"Dr.",name:"Daniella",surname:"Insuela",slug:"daniella-insuela",fullName:"Daniella Insuela"},{id:"303255",title:"Dr.",name:"Diego",surname:"Coutinho",slug:"diego-coutinho",fullName:"Diego Coutinho"},{id:"303256",title:"Dr.",name:"Maximiliano",surname:"Ferrero",slug:"maximiliano-ferrero",fullName:"Maximiliano Ferrero"},{id:"303257",title:"Dr.",name:"Marco Aurelio",surname:"Martins",slug:"marco-aurelio-martins",fullName:"Marco Aurelio Martins"}],corrections:null},{id:"69166",title:"Immune-Mediated Inflammation: Human T CD4 Helper Lymphocyte Diversity and Plasticity in Health and Disease",doi:"10.5772/intechopen.89230",slug:"immune-mediated-inflammation-human-t-cd4-helper-lymphocyte-diversity-and-plasticity-in-health-and-di",totalDownloads:767,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The CD4+ T helper (Th) cells have a critical role in organizing the adaptive immune response. The emerging cells of the differentiation after the immune synapse produce helper T cell subpopulations that activate, suppress, or regulate the immune response upon interaction with varying immune cells. There are two main Th cell functional categories: the “effector cells” and the “regulatory T cells.” Classic T helper lymphocytes can also be distinguished by their lineage according to the developmental microenvironment, the expression of cell adhesion-homing receptors, the profile of cytokines they are exposed to, and the involved transcription factors. Traditionally, the CD4+ and CD8+ phenotypes have been considered as helper and cytotoxic/suppressor T lymphocytes, respectively. Currently, the distinction is little rigorous. The immune response is exceedingly complex beyond the classic Th1 and Th2 effector cells’ involvement, and other populations of helper T lymphocytes like the Th17, Tfh, Th22, and Th9 lymphocytes have been phenotypically characterized. These lymphocytes also participate in the pathogenesis of several immune-mediated inflammatory disorders. Here, we revisit and discuss the essential aspects of the state of the art regarding phenotypic diversity and plasticity of TCD4 cells in the T lymphocyte repertoire frame and their potential implication in human inflammatory diseases.",signatures:"Rodolfo Alberto Kölliker Frers, Matilde Otero-Losada, María Inés Herrera, Sabrina Porta, Vanesa Cosentino, Eduardo Kerzberg, Lucas Udovin and Francisco Capani",downloadPdfUrl:"/chapter/pdf-download/69166",previewPdfUrl:"/chapter/pdf-preview/69166",authors:[{id:"120703",title:"Dr.",name:"Francisco",surname:"Capani",slug:"francisco-capani",fullName:"Francisco Capani"},{id:"193560",title:"Dr.",name:"Matilde",surname:"Otero-Losada",slug:"matilde-otero-losada",fullName:"Matilde Otero-Losada"},{id:"205589",title:"Dr.",name:"Rodolfo Alberto",surname:"Kölliker Frers",slug:"rodolfo-alberto-kolliker-frers",fullName:"Rodolfo Alberto Kölliker Frers"},{id:"306018",title:"BSc.",name:"Sabrina",surname:"Porta",slug:"sabrina-porta",fullName:"Sabrina Porta"},{id:"306019",title:"MSc.",name:"Vanesa",surname:"Cosentino",slug:"vanesa-cosentino",fullName:"Vanesa Cosentino"},{id:"306020",title:"Dr.",name:"Eduardo",surname:"Kersberg",slug:"eduardo-kersberg",fullName:"Eduardo Kersberg"},{id:"306021",title:"Dr.",name:"Lucas",surname:"Udovin",slug:"lucas-udovin",fullName:"Lucas Udovin"},{id:"306022",title:"Dr.",name:"María Inés",surname:"Herrera",slug:"maria-ines-herrera",fullName:"María Inés Herrera"}],corrections:null},{id:"70362",title:"Resident Memory T Cells",doi:"10.5772/intechopen.90334",slug:"resident-memory-t-cells",totalDownloads:947,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Until recently, T cells were thought to remain in circulation until recruitment of the inflammation and only a small number of T cells remained in the peripheral tissues without inflammation. However, studies have found that a group of T cells settled in the tissues and remained there for a long time. Those cells are named as tissue-resident memory T cells (TRM). TRM cells are transcriptionally, phenotypically, and functionally distinct from other T cells, which recirculate between blood, secondary lymphoid organs, and non-lymphoid tissues. They undergo a distinct proliferation that discriminates them from circulating T cells and their main cell surface markers are CD69, CD103, and CD49a. Upon exposure to the same or similar diseases, TRM cells provide a first line of adaptive cellular defense against infection in peripheral non-lymphoid tissues, such as skin, lungs, digestive, and urogenital tracts. This approach forms the basis of a novel vaccination strategy called “prime and pull”, which ensures long-term local immunity. On the other hand, abnormal activated and malignant TRM may contribute to numerous human inflammatory diseases such as psoriasis and vitiligo. Here in this chapter, we aimed to emphasize TRM cell location, migration, phenotypic structure, maintenance, and diseases associated with TRM cells.",signatures:"Hasan Akbaba",downloadPdfUrl:"/chapter/pdf-download/70362",previewPdfUrl:"/chapter/pdf-preview/70362",authors:[{id:"260489",title:"Dr.",name:"Hasan",surname:"Akbaba",slug:"hasan-akbaba",fullName:"Hasan Akbaba"}],corrections:null},{id:"67340",title:"Modulating the T Lymphocyte Immune Response via Secretome Produced miRNA: From Tolerance Induction to the Enhancement of the Anticancer Response",doi:"10.5772/intechopen.86598",slug:"modulating-the-t-lymphocyte-immune-response-via-secretome-produced-mirna-from-tolerance-induction-to",totalDownloads:848,totalCrossrefCites:0,totalDimensionsCites:3,hasAltmetrics:0,abstract:"T cells are key mediators of graft tolerance/rejection, development of autoimmunity, and the anticancer response. Consequently, differentially modifying the T cell response is a major therapeutic target. Most immunomodulatory approaches have focused on cytotoxic agents, cytokine modulation, monoclonal antibodies, mitogen activation, adoptive cell therapies (including CAR-T cells). However, these approaches do not persistently reorient the systemic immune response thus necessitating continual therapy. Previous murine studies from our laboratory demonstrated that the adoptive transfer of polymer-grafted (PEGylated) allogeneic leukocytes resulted in the induction of a persistent and systemic tolerogenic state. Further analyses demonstrated that miRNA isolated from the secretome of polymer-modified or control allogeneic responses effectively induced either a tolerogenic (TA1 miRNA) or proinflammatory (IA1 miRNA) response both in vitro and in vivo that was both systemic and persistent. In a murine Type 1 diabetes autoimmune model, the tolerogenic TA1 therapeutic effectively attenuated the disease process via the systemic upregulation of regulatory T cells while simultaneously downregulating T effector cells. In contrast, the proinflammatory IA1 therapeutic enhanced the anticancer efficacy of naïve PBMC by increasing inflammatory T cells and decreasing regulatory T cells. The successful development of this secretome miRNA approach may prove useful treating both autoimmune diseases and cancer.",signatures:"Mark D. Scott, Duncheng Wang, Wendy M. Toyofuku and Xining Yang",downloadPdfUrl:"/chapter/pdf-download/67340",previewPdfUrl:"/chapter/pdf-preview/67340",authors:[{id:"202243",title:"Dr.",name:"Mark",surname:"Scott",slug:"mark-scott",fullName:"Mark Scott"},{id:"205640",title:"BSc.",name:"Wendy",surname:"Toyofuku",slug:"wendy-toyofuku",fullName:"Wendy Toyofuku"},{id:"205641",title:"BSc.",name:"Xining",surname:"Yang",slug:"xining-yang",fullName:"Xining Yang"},{id:"296981",title:"Dr.",name:"Duncheng",surname:"Wang",slug:"duncheng-wang",fullName:"Duncheng Wang"}],corrections:null},{id:"67337",title:"Mucosal Macrophage Polarization Role in the Immune Modulation",doi:"10.5772/intechopen.86609",slug:"mucosal-macrophage-polarization-role-in-the-immune-modulation",totalDownloads:813,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Immunotherapy has advantages including few side effects and low probability of abuse by patients. Recently, functional materials with immunomodulatory functions, which act through reduction of free radicals, have been developed for cancer and anti-inflammatory therapy. However, the therapeutic application of natural functional materials involves a complex mechanism along with various organic factors. These substances, including polysaccharides and triterpenoids, have immunomodulatory effects. However, to our knowledge, the mechanism underlying the action of such substances in the physiological immunity of animals remains unclear. Immune cells, particularly macrophages, are crucial in the modulation of immune response. Macrophages polarise into two types, namely, M1 and M2, from the M0 form, based on the physiological microenvironment factors. M1 macrophages have functions in pathogen elimination through phagocytosis, oxidative damage, and complement system activation. M2 macrophages are involved in tissue recovery and tumour tissues containing ample M2 macrophages that release growth factors, which promote angiogenesis. In this study, we focus on the immunomodulation of the macrophage to further understand the effects of the physiological microenvironment factors on macrophage polarisation.",signatures:"Tsung-Meng Wu, Shiu-Nan Chen and Yu-Sheng Wu",downloadPdfUrl:"/chapter/pdf-download/67337",previewPdfUrl:"/chapter/pdf-preview/67337",authors:[{id:"116110",title:"Dr.",name:"Shiu-Nan",surname:"Chen",slug:"shiu-nan-chen",fullName:"Shiu-Nan Chen"},{id:"274564",title:"Prof.",name:"Yu-Sheng",surname:"Wu",slug:"yu-sheng-wu",fullName:"Yu-Sheng Wu"},{id:"276936",title:"Prof.",name:"Tsung-Meng",surname:"Wu",slug:"tsung-meng-wu",fullName:"Tsung-Meng Wu"}],corrections:null},{id:"69417",title:"KLF4-Mediated Plasticity of Myeloid-Derived Suppressor Cells (MDSCs)",doi:"10.5772/intechopen.89151",slug:"klf4-mediated-plasticity-of-myeloid-derived-suppressor-cells-mdscs-",totalDownloads:681,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:1,abstract:"Robustness of tissues refers to their capability to maintain normal functions despite perturbation such as injuries. Recent studies suggest a key role of the immune system in injury repair. In this process, several immune cell lineages exhibit considerable plasticity as they migrate toward the site of damage and contribute to repair. For example, myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of immature cells and possess phenotypic plasticity in cancer, a pathological status that is considered as “wounds that do not heal.” They are characterized by their potent ability to suppress immune responses. In cutaneous wound healing, MDSCs not only execute their immunosuppressive function to inhibit inflammation but also stimulate cell proliferation once they adopt a fate of a totally different cell type. At a molecular level, we found that Krüppel-like factor 4 (KLF4), a transcription factor with multiple roles in homeostasis and disease development plays a critical role in regulating MDSCs. In this review, KLF4-mediated plasticity of MDSCs and the underlying mechanisms are discussed.",signatures:"Daping Fan, Samir Raychoudhury and Walden Ai",downloadPdfUrl:"/chapter/pdf-download/69417",previewPdfUrl:"/chapter/pdf-preview/69417",authors:[{id:"306954",title:"Dr.",name:"Walden",surname:"Ai",slug:"walden-ai",fullName:"Walden Ai"},{id:"309713",title:"Dr.",name:"Daping",surname:"Fan",slug:"daping-fan",fullName:"Daping Fan"},{id:"312803",title:"Dr.",name:"Samir",surname:"Raychoudhury",slug:"samir-raychoudhury",fullName:"Samir Raychoudhury"}],corrections:null},{id:"71836",title:"Eosinophilic Phenotype: The Lesson from Research Models to Severe Asthma",doi:"10.5772/intechopen.92123",slug:"eosinophilic-phenotype-the-lesson-from-research-models-to-severe-asthma",totalDownloads:638,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Eosinophilic airway inflammation is a hallmark in the pathophysiological and clinical definition of asthma. In the last decades, asthma evolved in the recognition of different phenotypes identified by natural history, clinical and physiological characteristics, and the underlying immune mechanisms. Among these phenotypes, many have been associated with eosinophilic-driven inflammation. This is the case of either early-onset allergic Th2 asthma or late-onset persistent eosinophilic asthma. Both animal models and analysis from human samples have contributed to elucidate the role of eosinophils in the asthmatic inflammatory response and the synergic role of Th2 cytokines. In severe asthma, high numbers of eosinophils can persist despite treatment with inhaled and oral corticosteroids leading to the definition of severe refractory eosinophilic asthma. The combined role of IL-4-, IL-13- and IL-5-associated pathways has focused the view over the T2-type endotypes, wherein a specific biological pathway explains the observable properties of different phenotypes and the identifiable biomarkers can predict response to monoclonal antibodies directed against a selected immune target. In the era of precision medicine and personalized therapy, both the identification of Th2 molecules and eosinophils as targets and biomarkers have become the best clue for treating and monitoring severe asthma.",signatures:"Guida Giuseppe and Antonelli Andrea",downloadPdfUrl:"/chapter/pdf-download/71836",previewPdfUrl:"/chapter/pdf-preview/71836",authors:[{id:"50973",title:"Dr.",name:"Giuseppe",surname:"Guida",slug:"giuseppe-guida",fullName:"Giuseppe Guida"},{id:"319970",title:"Dr.",name:"Andrea",surname:"Antonelli",slug:"andrea-antonelli",fullName:"Andrea Antonelli"}],corrections:null},{id:"69136",title:"Eosinophilic Disorders: Extrinsic and Intrinsic Immune Response, New Diagnostic Perspectives, and Therapeutic Alternatives",doi:"10.5772/intechopen.89229",slug:"eosinophilic-disorders-extrinsic-and-intrinsic-immune-response-new-diagnostic-perspectives-and-thera",totalDownloads:871,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Eosinophils are immune response cells located in the peripheral blood, bone marrow, and lymph nodes, among others; an increase in the number of eosinophils in the peripheral blood above 5000/mm3 is associated with conditions ranging from infections (bacterial and parasitic) and allergy (asthma, rhinitis, or drugs), even neoplasms. Various study groups have classified them according to their etiology, thus facilitating their diagnosis and treatment. The WHO divides them as primary and secondary and also considers the number of eosinophils/mm3 and the involvement of white organs, while others have divided them into intrinsic and extrinsic. The former include mutations in the pluripotential hematopoietic cells, which lead to chronic myeloid leukemias with clonal expansion of eosinophils and extrinsic ones where the changes are related to a TH2 response activated by different cytosines such as IL-5. Current treatments are specifically aimed at modifying the clonal expansion of eosinophils with corticosteroids, hydroxyurea, interferon (peg) alpha, imatinib, among others, and bone marrow transplantation, while in extrinsic alterations corticosteroids and IL inhibitors are used −5 (mepolizumab).",signatures:"Maria-de-Lourdes Irigoyen-Coria, Vilma-Carolina Bekker-Mendez, Maria-Isabel Leyva-Carmona, Cecilia Rosel-Pech, Samuel Moreno-Olivares and David Solis-Hernandez",downloadPdfUrl:"/chapter/pdf-download/69136",previewPdfUrl:"/chapter/pdf-preview/69136",authors:[{id:"74720",title:"Dr.",name:"Vilma-Carolina",surname:"Bekker-Mendez",slug:"vilma-carolina-bekker-mendez",fullName:"Vilma-Carolina Bekker-Mendez"},{id:"306444",title:"B.Sc.",name:"Maria-de-Lourdes",surname:"Irigoyen-Coria",slug:"maria-de-lourdes-irigoyen-coria",fullName:"Maria-de-Lourdes Irigoyen-Coria"},{id:"306967",title:"Dr.",name:"Maria-Isabel",surname:"Leyva-Carmona",slug:"maria-isabel-leyva-carmona",fullName:"Maria-Isabel Leyva-Carmona"},{id:"306968",title:"B.Sc.",name:"David",surname:"Solís-Hernandez",slug:"david-solis-hernandez",fullName:"David Solís-Hernandez"},{id:"306977",title:"MSc.",name:"Cecilia",surname:"Rosel-Pech",slug:"cecilia-rosel-pech",fullName:"Cecilia Rosel-Pech"},{id:"309508",title:"Dr.",name:"Samuel",surname:"Moreno-Olivares",slug:"samuel-moreno-olivares",fullName:"Samuel Moreno-Olivares"}],corrections:null},{id:"68409",title:"Eosinophilic Cholangitis",doi:"10.5772/intechopen.86004",slug:"eosinophilic-cholangitis",totalDownloads:520,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"A variety of benign etiologies of biliary stricture may initially be mistaken for hilar cholangiocarcinoma. Consequently, many patients undergo surgery for a benign disease that could have been treated medically. Eosinophilic cholangitis (EC) is an uncommon, benign, self-limiting disease that should be considered when approaching a case of obstructive jaundice since it causes biliary stricture formation. Transmural eosinophilic infiltration of the biliary tree is characteristic of EC. It may initially be indistinguishable from hilar cholangiocarcinoma. We worked on a case of a patient who was referred to our hospital for jaundice and abdominal mass investigation with the provisional diagnosis of cholangiocarcinoma. During the workup, the index of suspicion for malignancy remained high as the typical laboratory and radiological findings for benign causes of biliary stricture were not present. Hence, the patient underwent left hepatectomy with caudate lobe resection and received a retrograde diagnosis of EC. The case demonstrates that EC could present in the elderly with cardinal signs of cancer and absence of the typical findings of EC which was not previously reported. Furthermore, this disorder has been reported to respond well to steroid therapy, hence, diagnostic criteria for EC would provide another treatment option for elderly and/or those who are not fit for surgery.",signatures:"Gilles Jadd Hoilat, Judie Noemie Hoilat, Mohamad Fekredeen Ayas, Sana Riaz and Divey Manocha",downloadPdfUrl:"/chapter/pdf-download/68409",previewPdfUrl:"/chapter/pdf-preview/68409",authors:[{id:"294042",title:"Dr.",name:"Gilles Jadd",surname:"Hoilat",slug:"gilles-jadd-hoilat",fullName:"Gilles Jadd Hoilat"},{id:"298929",title:"Dr.",name:"Judie Noemie",surname:"Hoilat",slug:"judie-noemie-hoilat",fullName:"Judie Noemie Hoilat"},{id:"298930",title:"Dr.",name:"Mohamad Fekredeen",surname:"Ayas",slug:"mohamad-fekredeen-ayas",fullName:"Mohamad Fekredeen Ayas"},{id:"310025",title:"Dr.",name:"Sana",surname:"Riaz",slug:"sana-riaz",fullName:"Sana Riaz"},{id:"312685",title:"Dr.",name:"Divey",surname:"Manocha",slug:"divey-manocha",fullName:"Divey Manocha"}],corrections:null},{id:"68968",title:"Eosinophilic Granulomatosis with Polyangiitis: The Beginning of a New Era",doi:"10.5772/intechopen.89054",slug:"eosinophilic-granulomatosis-with-polyangiitis-the-beginning-of-a-new-era",totalDownloads:541,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare type of anti-neutrophil cytoplasm antibody-associated vasculitis (AAV) with unique features, such as involvement of eosinophils in the pathogenesis, which requires different therapies from those used for other AAV. Conventional treatment includes glucocorticoids (GC) and immunosuppressants. GC are the cornerstone of the initial treatment of EGPA, but relapses are frequent. Cyclophosphamide is typically used in combination with GC for patients with life- and/or organ-threatening disease manifestations. Azathioprine and methotrexate are recommended to maintain remission after induction with cyclophosphamide or as a GC-sparing agent. Nowadays, a better comprehension of the physiopathology of EGPA has opened new therapeutic targets, such as interleukin-5, which has a key role in the refractory disease, relapses, and GC dependence, especially for asthma manifestations. Mepolizumab is the first anti-IL5 antibody approved to treat EGPA. Another anti-IL5 monoclonal antibody, reslizumab, and an anti-IL5 receptor monoclonal antibody, benralizumab, are now being investigated for EGPA.",signatures:"Carlos Melero Moreno, Marta Corral Blanco and Rocío Magdalena Díaz Campos",downloadPdfUrl:"/chapter/pdf-download/68968",previewPdfUrl:"/chapter/pdf-preview/68968",authors:[{id:"178740",title:"Dr.",name:"Carlos",surname:"Melero Moreno",slug:"carlos-melero-moreno",fullName:"Carlos Melero Moreno"},{id:"306316",title:"Dr.",name:"Rocío Magdalena",surname:"Díaz Campos",slug:"rocio-magdalena-diaz-campos",fullName:"Rocío Magdalena Díaz Campos"},{id:"306317",title:"Dr.",name:"Marta",surname:"Corral Blanco",slug:"marta-corral-blanco",fullName:"Marta Corral Blanco"}],corrections:null},{id:"69097",title:"Assessment of Immune Reconstitution Following Hematopoietic Stem Cell Transplantation",doi:"10.5772/intechopen.89198",slug:"assessment-of-immune-reconstitution-following-hematopoietic-stem-cell-transplantation",totalDownloads:998,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potential curative treatment for both congenital and hematological malignancies. Immune reconstitution after allogeneic hematopoietic stem cell transplantation is implicated in successful transplant outcomes such as overall survival and relapse-free survival. The reconstitution of immune cell subsets after HSCT occurs in different phases at different time points encompassing pre-engraftment, engraftment, and post-engraftment. The recovery of innate cellular immunity with the appearance of monocytes, dendritic cells, and natural killer cells in peripheral blood correlates with initiation of cellular engraftment. The cellular adaptive immunity is characterized by both thymic-independent expansion of T cells infused with graft and thymus-dependent expansion of naïve T cells derived from donor stem cells. The humoral immunity consists of B-cell reconstitution, which consists primarily of transitional and naïve subsets with the recovery of memory B cells that occur much later. In this review, we highlight the factors affecting immune reconstitution, the reconstitution of innate and adaptive immunity, techniques to assess immune reconstitution, and ways to enhance it.",signatures:"Meenakshi Singh, Selma Z. D’Silva and Abhishweta Saxena",downloadPdfUrl:"/chapter/pdf-download/69097",previewPdfUrl:"/chapter/pdf-preview/69097",authors:[{id:"217471",title:"Dr.",name:"Selma",surname:"D\\'Silva",slug:"selma-d'silva",fullName:"Selma D\\'Silva"},{id:"267032",title:"Dr.",name:"Meenakshi",surname:"Singh",slug:"meenakshi-singh",fullName:"Meenakshi Singh"},{id:"310438",title:"Dr.",name:"Abhishweta",surname:"Saxena",slug:"abhishweta-saxena",fullName:"Abhishweta Saxena"}],corrections:null},{id:"66927",title:"Sorption Detoxification as an Addition to Conventional Therapy of Acute Radiation Sickness and Iatrogenic Leukopenia",doi:"10.5772/intechopen.85690",slug:"sorption-detoxification-as-an-addition-to-conventional-therapy-of-acute-radiation-sickness-and-iatro",totalDownloads:839,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Leukopenia is an essential part of the clinical course of acute radiation sickness and is a side effect of anti-cancer treatment. In both situations, the main factors which determine the survival are the degree of bone marrow suppression and gastrointestinal tract damage due to the presence of a large pool of fast-dividing cells. Leuko- and neutropenia are main limiting factors which may contribute to chemotherapy failure. Hematopoietic cytokines the part of conventional therapy in this field, but their effects require boosting. That is why the use of means and methods of adsorption therapy is considered promising. Sorption therapy creates a basis for sorption detoxification, a doctrine of curative measures directed to the removal of toxic endogenous or exogenous compounds from body fluids. The most widely used types are the purification of blood or its components (hemosorption), oral administration of sorption materials (enterosorption) and application-sorption therapy of wounds and burns. In this chapter, the results of early and recent research and prospects for the use of carbon adsorption therapy for the treatment of acute radiation sickness and cytostatic myelosuppression are discussed.",signatures:"Oksana O. Shevchuk, Elisaveta A. Snezhkova, Anatoliy G. Bilous, Veronika V. Sarnatskaya, Kvitoslava I. Badakhivska, Larysa A. Sakhno, Vasyl F. Chekhun and Volodymyr G. Nikolaev",downloadPdfUrl:"/chapter/pdf-download/66927",previewPdfUrl:"/chapter/pdf-preview/66927",authors:[{id:"141767",title:"Prof.",name:"Anatolii",surname:"Belous",slug:"anatolii-belous",fullName:"Anatolii Belous"},{id:"296488",title:"Dr.",name:"Oksana",surname:"Shevchuk",slug:"oksana-shevchuk",fullName:"Oksana Shevchuk"},{id:"296490",title:"Dr.",name:"E.A.",surname:"Snezhkova",slug:"e.a.-snezhkova",fullName:"E.A. Snezhkova"},{id:"296491",title:"Dr.",name:"V.V.",surname:"Sarnatska",slug:"v.v.-sarnatska",fullName:"V.V. 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Saxena and Hridayesh Prakash",coverURL:"https://cdn.intechopen.com/books/images_new/8959.jpg",editedByType:"Edited by",editors:[{id:"158026",title:"Prof.",name:"Shailendra K.",surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena"}],equalEditorOne:{id:"287184",title:"Dr.",name:"Hridayesh",middleName:null,surname:"Prakash",slug:"hridayesh-prakash",fullName:"Hridayesh Prakash",profilePictureURL:"https://mts.intechopen.com/storage/users/287184/images/system/287184.jpg",biography:"Dr. Hridayesh Prakash is a fellow of the Royal Society of Biology, London. Currently, he is an associate professor at the Institute of Virology and Immunology, Amity University, NOIDA. He has expertise in innate immunity with a special interest in macrophage immunobiology, tumor immunology/immunotherapy, cell-based immunotherapies, pulmonary infection biology, and radiation biology. \n\nDr. Prakash conducts research to exploit various immunotherapeutics for managing persistent bacterial and viral Infections and gastric cancer. He is unraveling the therapeutic potential of M1 effector macrophages against solid tumors. He is also studying various mechanisms that certain pathogens like Helicobacter pylori, Chlamydia, and Mycobacteria are exploiting for polarizing M1 effector macrophages towards the M2 phenotype during chronic and persistent infections. 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Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],ofsBooks:[]},correction:{item:{id:"73312",slug:"corrigendum-to-the-generalized-weierstrass-system-in-three-dimensional-euclidean-space",title:"Corrigendum to: The Generalized Weierstrass System in Three-Dimensional Euclidean Space",doi:null,correctionPDFUrl:"https://cdn.intechopen.com/pdfs/73312.pdf",downloadPdfUrl:"/chapter/pdf-download/73312",previewPdfUrl:"/chapter/pdf-preview/73312",totalDownloads:null,totalCrossrefCites:null,bibtexUrl:"/chapter/bibtex/73312",risUrl:"/chapter/ris/73312",chapter:{id:"65349",slug:"the-generalized-weierstrass-system-in-three-dimensional-euclidean-space",signatures:"Paul Bracken",dateSubmitted:"July 13th 2018",dateReviewed:"November 21st 2018",datePrePublished:"January 25th 2019",datePublished:"May 22nd 2019",book:{id:"7342",title:"Manifolds II",subtitle:"Theory and Applications",fullTitle:"Manifolds II - Theory and Applications",slug:"manifolds-ii-theory-and-applications",publishedDate:"May 22nd 2019",bookSignature:"Paul Bracken",coverURL:"https://cdn.intechopen.com/books/images_new/7342.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"92883",title:"Prof.",name:"Paul",middleName:null,surname:"Bracken",slug:"paul-bracken",fullName:"Paul Bracken"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"92883",title:"Prof.",name:"Paul",middleName:null,surname:"Bracken",fullName:"Paul Bracken",slug:"paul-bracken",email:"paul.bracken@utrgv.edu",position:null,institution:{name:"The University of Texas Rio Grande Valley",institutionURL:null,country:{name:"United States of America"}}}]}},chapter:{id:"65349",slug:"the-generalized-weierstrass-system-in-three-dimensional-euclidean-space",signatures:"Paul Bracken",dateSubmitted:"July 13th 2018",dateReviewed:"November 21st 2018",datePrePublished:"January 25th 2019",datePublished:"May 22nd 2019",book:{id:"7342",title:"Manifolds II",subtitle:"Theory and Applications",fullTitle:"Manifolds II - Theory and Applications",slug:"manifolds-ii-theory-and-applications",publishedDate:"May 22nd 2019",bookSignature:"Paul Bracken",coverURL:"https://cdn.intechopen.com/books/images_new/7342.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"92883",title:"Prof.",name:"Paul",middleName:null,surname:"Bracken",slug:"paul-bracken",fullName:"Paul Bracken"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"92883",title:"Prof.",name:"Paul",middleName:null,surname:"Bracken",fullName:"Paul Bracken",slug:"paul-bracken",email:"paul.bracken@utrgv.edu",position:null,institution:{name:"The University of Texas Rio Grande Valley",institutionURL:null,country:{name:"United States of America"}}}]},book:{id:"7342",title:"Manifolds II",subtitle:"Theory and Applications",fullTitle:"Manifolds II - Theory and Applications",slug:"manifolds-ii-theory-and-applications",publishedDate:"May 22nd 2019",bookSignature:"Paul Bracken",coverURL:"https://cdn.intechopen.com/books/images_new/7342.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"92883",title:"Prof.",name:"Paul",middleName:null,surname:"Bracken",slug:"paul-bracken",fullName:"Paul Bracken"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}}},ofsBook:{item:{type:"book",id:"10775",leadTitle:null,title:"Hypersonic Vehicles",subtitle:"Applications, Recent Advances, and Perspectives",reviewType:"peer-reviewed",abstract:"Some sixty years after the experimental flights of the North American X-15 hypersonic rocket-powered aircraft, sustained hypervelocity travel is still the next frontier in high-speed transportation. Today, there is much excitement and interest regarding hypersonic vehicles. In fact, many aerospace agencies, large industries, and several start-ups are involved in design activities and experimental campaigns both in wind tunnels and in-flight with full-scale experimental flying test beds and prototypes to make hypersonic travel almost as easy and convenient as airliner travel. Achieving this goal will radically revolutionize the future of civil transportation. This book contains valuable contributions that focus on various design issues related to hypersonic aircraft.",isbn:"978-1-83969-933-7",printIsbn:"978-1-83969-932-0",pdfIsbn:"978-1-83969-934-4",doi:"10.5772/intechopen.94798",price:119,priceEur:129,priceUsd:155,slug:"hypersonic-vehicles-applications-recent-advances-and-perspectives",numberOfPages:130,isOpenForSubmission:!1,isSalesforceBook:!1,isNomenclature:!1,hash:"0eb40c595ae6a0a77f2bd4102c00a2e6",bookSignature:"Giuseppe Pezzella and Antonio Viviani",publishedDate:"May 4th 2022",coverURL:"https://cdn.intechopen.com/books/images_new/10775.jpg",keywords:null,numberOfDownloads:464,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfDimensionsCitations:0,numberOfTotalCitations:0,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"May 20th 2021",dateEndSecondStepPublish:"September 21st 2021",dateEndThirdStepPublish:"November 20th 2021",dateEndFourthStepPublish:"February 8th 2022",dateEndFifthStepPublish:"April 9th 2022",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"9 months",secondStepPassed:!0,areRegistrationsClosed:!0,currentStepOfPublishingProcess:5,editedByType:"Edited by",kuFlag:!1,biosketch:"Prof. Giuseppe Pezzella is a research engineer in the Physics of Fluids Department at CIRA since 2005. He is involved in national (e.g., PRORA) and international projects (e.g., EXPERT, HIGH-LIFT, FLPP-IXV, RASTAS-SPEAR, HEXAFLY, LAPCAT-II, SCRAMSPACE, HEXAFLY-INT).",coeditorOneBiosketch:"Dr. Antonio Viviani is a member of AIAA, AAAS-American Association for Advancement of Sciences, ELGRA-European Low Gravity Research Association, NYAS-New York Academy of Sciences, Physical Sciences Working Group of European Space Agency (1993-1999); Microgravity Sciences and Processes Committee of the IAF-International Astronautical Federation.",coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"14939",title:"Prof.",name:"Giuseppe",middleName:null,surname:"Pezzella",slug:"giuseppe-pezzella",fullName:"Giuseppe Pezzella",profilePictureURL:"https://mts.intechopen.com/storage/users/14939/images/system/14939.jpeg",biography:"Prof. Giuseppe Pezzella is a lecturer in aerodynamics and aerothermodynamics, Department of Engineering, University of Campania, Italy. He obtained an MSc in Aeronautical Engineering and a Ph.D. in Aerospace Engineering from the University of Naples “Federico II,” Italy, in 1999 and 2003, respectively. He has been a research engineer in the Physics of Fluids Department at the Italian Aerospace Research Centre (CIRA) since 2005, after a period spent at the University of Naples \\'Federico II” in the frame of post-doc activities. He is a specialized analyst in the fields of vehicles’ aerodynamics, aerothermodynamics, and aeroshape design. He was involved in national (e.g., PRORA) and international projects (e.g., EXPERT, HIGH-LIFT, FLPP-IXV, RASTAS-SPEAR, HEXAFLY, LAPCAT-II, SCRAMSPACE, HEXAFLY-INT). Prof. Pezzella is the author or co-author of about 100 publications including journal studies, conference papers, and edited books, and a reviewer of several international journals.",institutionString:'University of Campania "Luigi Vanvitelli"',position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"9",totalChapterViews:"0",totalEditedBooks:"3",institution:{name:'University of Campania "Luigi Vanvitelli"',institutionURL:null,country:{name:"Italy"}}}],coeditorOne:{id:"216136",title:"Prof.",name:"Antonio",middleName:null,surname:"Viviani",slug:"antonio-viviani",fullName:"Antonio Viviani",profilePictureURL:"https://mts.intechopen.com/storage/users/216136/images/system/216136.jpeg",biography:"Antonio Viviani has a graduate degree in Aeronautical Engineering and a Ph.D. in Aerospace Engineering from the University of Naples, Italy. He is a full professor in the Engineering Department, University of Campania, Italy. He is a member of several organizations including the American Institute of Aeronautics and Astronautics (AIAA), the American Association for Advancement of Sciences (AAAS), the European Low Gravity Research Association (ELGRA), and the International Academy of Astronautics (IAA). He also serves on many committees of the International Astronautical Federation (IAF), the International Academy of Astronautics (IAA), and the International Council of Aeronautical Sciences (ICAS).\n\nProf. Viviani has held several positions including vice president of ELGRA (1999–2003), vice chairman of the Committee of IAF Microgravity Sciences and Processes (2003–2006), and chairman of the Committee of IAF Microgravity Sciences and Processes (2006–2012). He is presently an IAA board of trustees member and IAA regional secretary for Italy; a representative for Italy in the ICAS member societies council; co-editor of Acta Astronautica; and on the editorial board of the International Journal of Aerospace Engineering. He was co-investigator of the experiment “Onset of Oscillatory Marangoni Flows,” Spacelab D2 - Space-Shuttle Columbia STS-55 (1993), and principal investigator of the experiments “Bubble Behavior under Low Gravity,” Mission Spacelab IML-2 - Space-Shuttle Columbia, STS-65 (1994); and “Non-linear Surface Tension Driven Bubble Migration,” Mission Spacelab LMS – Space Shuttle Columbia STS-78 (1996).",institutionString:'University of Campania "Luigi Vanvitelli"',position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"5",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:'University of Campania "Luigi Vanvitelli"',institutionURL:null,country:{name:"Italy"}}},coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"682",title:"Aerodynamics",slug:"aerospace-engineering-aerodynamics"}],chapters:[{id:"81064",title:"Introductory Chapter: The Challenge to Fly Faster and Higher",slug:"introductory-chapter-the-challenge-to-fly-faster-and-higher",totalDownloads:20,totalCrossrefCites:0,authors:[{id:"14939",title:"Prof.",name:"Giuseppe",surname:"Pezzella",slug:"giuseppe-pezzella",fullName:"Giuseppe Pezzella"},{id:"216136",title:"Prof.",name:"Antonio",surname:"Viviani",slug:"antonio-viviani",fullName:"Antonio Viviani"}]},{id:"79632",title:"Investigation of Hypersonic Conic Flows Generated by Magnetoplasma Light-Gas Gun Equipped with Laval Nozzle",slug:"investigation-of-hypersonic-conic-flows-generated-by-magnetoplasma-light-gas-gun-equipped-with-laval",totalDownloads:85,totalCrossrefCites:0,authors:[{id:"422154",title:"Dr.",name:"Pavel P.",surname:"Khramtsov",slug:"pavel-p.-khramtsov",fullName:"Pavel P. 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It was first reported by William little, who was an orthopedic surgeon, in 1843 as cerebral paresis [1, 2]. Little focused on joint contractures and deformities resulting from long-standing spasticity and paralysis. Additionally, he indicated that the cause of the spasticity and paralysis was often due to damage to the brain during infancy and, specifically, preterm birth and perinatal asphyxia [3].
\nThe most comprehensive study until then was published in 1862 by William Little. The association between a large number of patients’ clinical presentation and their birth history as recalled by the family was described in this study. Little differentiated between the congenital deformities observed at the time of birth, such as talipes equinovarus, and the limb deformities that developed subsequently to preterm, difficult, or traumatic births, which he termed as spastic rigidity. It was described as a disorder that appeared to strike children in the first year of life, affected developmental skill progression, and did not improve over time [4].
\nThen, Sarah McNutt described that it continued to raise the profile of the risks of long-term disability arising from birth trauma [5]. At the end of the nineteenth century, Sigmund Freud suggested that CP might be rooted in the brain’s development in the womb and related aberrant development to factors influencing the developing fetus [2, 6, 7]. In addition, in the early 1920s, some 30 years after Freud’s comments, an American orthopedic surgeon made the next major contribution for understanding of CP [8].
\nIn the twentieth century, newer documented concepts of cerebral palsy have been defined. Mac Keith and Polani [1, 8] described CP as “a persisting but not unchanging disorder of movement and posture, occurring in the early years of life due to a nonprogressive disorder of the brain, the result of interference during its development.” In 1964, Bax [9] reported a description of CP suggested by an international working group that has become a classic and is still used. It was expressed that CP is a disorder of movement and posture due to a defect or lesion of the immature brain. Although this definition is usually all that is cited by authors, some additional comments were added by Bax: “For practical purposes it is usual to exclude from cerebral palsy those disorders of posture and movement which are of short duration, due to progressive disease or due solely to mental deficiency.” Bax and his group felt that this simple sentence can be readily translated into other languages and hoped that it may be used universally. At that time, it was felt wiser not to define completely what they meant by immature brain, as any such description may be restricted services to those in need. Like its predecessors, this formulation of the CP concept placed an exclusive focus on motor aspects and also stressed the specific consequences of early as opposed to late-acquired brain damage. It was not formally included in the concept that cognitive, sensory, behavioral, and other associated impairments were very prevalent in people with disordered movement and posture due to a defect or lesion of the immature brain, a frequent significant disability. This definition continued to emphasize the motor impairment and acknowledged its variability, previously underscored in the MacKeith and Polani definition; it also excluded progressive disease, a point introduced in Bax’s annotation [8]. The heterogeneity of disorders covered by the term of CP, as well as advances in understanding of development in infants with early brain damage, led Mutch et al. [10] to modify the definition of CP in 1992 as follows: an umbrella term covering a group of nonprogressive, but often changing, motor impairment syndromes secondary to lesions or anomalies of the brain arising in the early stages of development.
\nTo underline the idea that a comprehensive approach to CP needs to be multidimensional and that management of patients with CP almost always requires a multidisciplinary setting, classes of disorders commonly accompanying CP have been identified and included in the revised definition [1]. And last definition of CP, which is comprised to prior assessments and identifications, was made in April 2006. CP describes a group of persistent disorders of the development of movement and posture causing activity limitations that are attributed to nonprogressive disturbances that occurred in the developing fetal or infant brain. The motor disorders of cerebral palsy are often accompanied by disturbances of sensation, perception, cognition, communication, and behavior by epilepsy and secondary musculoskeletal problems. This description was authored by the members of the executive committee functioning in panels enriched with expertise from consultants and by comments and suggestions from many reviewers responding to drafts provided to the international community. It is offered for international consensus and adoption, with the intent of providing a broad spectrum of audiences with a common conceptualization about cerebral palsy [1]. CP is defined as a group of nonprogressive, but often changing, motor impairment syndromes secondary to lesions or abnormalities of the brain and emerging in the early stages of development [10]. CP is a symptom complex rather than a disease. It is a concept derived from an insult to a growing, developing brain and therefore it is a dynamic changing clinical picture emanating from static pathology [11]. CP may be diagnosed during the first two years of life, especially when functional impairment is mild [12, 13].
\nThis specification contains the concept that CP is a group of neurodevelopmental disorders that involve numerous developing functions. As in other neurodevelopmental disorders, various manifestations of the disordered brain may appear more significantly in different persons or at different life periods, e.g., some aspects of the motor impairment, sensory loss, attentional difficulty, epilepsy, musculoskeletal dysfunction, intellectual disability, and many others maybe more prominent or more problematic at different periods of the life of a person with CP [1].
\nIn 2010, Blair again emphasized that CP is not a diagnosis but an “umbrella term for many clinical descriptions.” It has covered a wide variety of clinical conditions that meet the following four criteria:
\n- The presence of a disorder of movement or posture.
- Secondary to a cerebral abnormality.
- Arising early in development.
- By the time movement impairment exists, the cerebral abnormality is static.
There is no test, genetic, metabolic, immunologic, or otherwise, that demonstrates the existence or absence of CP because there is no specified cause, cerebral pathology, or even type of motor impairment resulting from nonprogressive cerebral pathology acquired early in life. Even as a clinical description, these criteria fail in several aspects to achieve the precision required of a definition [14, 15]. For example, specifying the age at which development is no longer considered “early.” There is no agreement on this age [16].
\nBecause it is difficult to definitively differentiate between pre- and neonatally acquired brain damage, all those not postneonatally acquired are usually considered together. The four criteria cannot be addressed until (a) motor development can be clearly recognized as being normal or disordered and (b) the possibility of progressive cerebral disease can be excluded. Signs suggesting disordered motor control may be recognized very early in life, but accurate prediction has only been confirmed by trained observers in the small proportion of persons with CP born very preterm [17]. Acquisition of the cerebral abnormality may precede recognition of the motor disorder by many months or even years. However, brain-impaired infants, particularly the most severely impaired, are at increased risk of dying before reaching an age at which the criteria for CP can be confirmed. Early death is a competing outcome. On the other hand, it is difficult to definitively exclude the possibility of progression or resolution at any age. Even if cerebral pathology is static, motor abilities change in all children over time, even if that development is grossly abnormal, making functional change an unreliable marker for progressive cerebral pathology. Conversely, a proportion of children described as CP at an early age catch up with their normally developing peers at a later age [18]. Therefore, the choice of an age that must be attained before being counted as CP, as well as the age beyond which development is no longer early, is arbitrary and depends on the interest in using the CP label. Treating clinicians are more flexible in applying the CP label because their primary concern is to balance the psychological effects of labeling a child having CP with the therapeutic opportunities that the label can afford. This balance can change with time. Registers with a long lifespan require primarily a constant definition over time, and this was the guiding principle of the recommendation by Badawi et al. [19] that conditions historically excluded from CP (not “diagnosed” as CP on account of having another diagnosis) continue to be excluded, even if meeting the criteria for CP. By contrast, reliability between current observers is the guiding principle of the more recent multicenter surveillance system in Europe, which adopted a flowchart to decision inclusion or exclusion of cases of cerebral palsy on registration [20]. However, the reality of barriers to achieving interobserver agreement of classification is demonstrated by the relatively poor agreement achieved with this flowchart [21]. Diagnosis of CP is not easy. It needs time to be confirmed. Premature diagnosis leading to over-ascertainment (because of transient anomalies in preterm babies) or under-ascertainment, as stated above, is not an unchanging condition with the clinical aspect in some cases altering as a child develops. There is consensus that 5 years of age was the optimal age for confirmation of diagnosis [22].
\nCP prevalence is usually reported around 2–3 per 1000 live births in both developed and developing countries for very different reasons [23, 24]. For term children, CP prevalence is 1 per 1000 live births. Additionally, for moderately preterm children (32–36 weeks’ gestation), forecasts are 6–10 times higher and for very preterm children (less than 32 weeks’ gestation), prevalence is 10 times higher than the moderately preterm children. CP rates for live births show a lower prevalence for babies of birthweight less than 1000 g than for those with a birthweight of 1000–1499 g. This paradoxical effect is caused from the high number of babies who do not live long enough to develop CP and it disappears when forecasting prevalence for neonatal survivors. Changes in perinatal and neonatal mortality accelerated in most countries from the 1960s, with a huge decrease up until the late 1980s, when there was an increase in the absolute number of children with CP. From 1990s, there has been a plateauing of mortality rates but a downward trend in CP rates, mainly in moderate and very low birthweight (VLBW) children. In most studies, the CP rates in children born at term or with normal birthweight seem rather stable over time. This finding is especially relevant since normal birthweight and term children represent at least one-half of children with CP and, thus, it may be connected to the persisting stagnation of CP prevalence, despite continuous improvement in perinatal care and in mortality rates [25–27].
\nThere were different rates of CP reported in recent five decades from different population. Published rates from geographically defined populations show significant differences, primarily due to variations in methods (Table 1). Variations within a reporting system over time tend to be smaller [28].
\nThe proportion of children described as CP increases with decreasing gestational age at birth. The advent of mechanical ventilation to neonatal intensive care has allowed survival of increasingly preterm births, creating a new source of high-risk neonates and perhaps a new cause of brain damage [27].
\nArea | \nYear range | \nNumber of cases | \nRate of per 1000 | \n
---|---|---|---|
Turkey [29–31] | \n1990–2006 1988–2003 1990–1995 | \n186 102 | \n4.4 1.1 5.5 | \n
Sweden [32] | \n1995–1998 | \n170 | \n1.9 | \n
Canada [33] | \n1991–1995 | \n\n | 2.7 | \n
U.S.A. [34] | \n2002 | \n416 | \n3.6 | \n
Australia [35] | \n1970–1998 1970–1972 1996–1998 | \n2950 | \n1.61 1.4 1.4 | \n
United Kingdom [36] | \n1984–2002 1984–1988 1999–2001 | \n1301 | \n2.0 2.5 1.2 | \n
Norway [37] | \n1996–1998 | \n374 | \n2.1 | \n
Danimark [38] | \n1971–1974 1975–1978 1979–1982 1983–1986 1987–1990 | \n\n | 1.7 1.6 2.6 3.0 2.4 | \n
France [39] | \n1980–1989 | \n261 | \n1.78 | \n
Published rates of CP from population-based samples.
The etiology of CP is very diverse and multifactorial. The causes are congenital, genetic, inflammatory, infectious, anoxic, traumatic, and metabolic. The injury to the developing brain may be prenatal, natal, or postnatal [40]. Due to the lack of a definitive test for CP, multiple and different possible causes also constitute a challenge in this context. For more than 30% of children, there are no risk factors or known etiology [41, 42] but some risk factors have repeatedly been observed to be related to CP [43]. CP may result from one or more etiologies and can occur at any stage from before conception to infancy, with the actual cause difficult to determine in all cases [41, 42, 44]. Known causes according to the timing of the brain insult can be classified, respectively, as prenatal, perinatal, and postnatal.
\nAmong the important known causes of cerebral palsy are congenital brain malformations including malformations of cortical development. Modern imaging techniques enable more children with these conditions to be identified [45, 46]. Currently, problems occurring during intrauterine development, congenital disorders, asphyxia occurring in any gestational age, and preterm birth are thought to account for the majority of cases [47]. Neuroimaging studies support the current thought that prenatal causes of CP, such as brain malformations, intrauterine vascular malformations, and infection, are more common than birth asphyxia [48]. Although intrapartum asphyxia was originally thought to be a major reason for CP, it accounts for only 10–20% of cases. The most frequent perinatal or neonatal etiologies in low birthweight infants are periventricular leukomalacia (PVL), periventricular hemorrhage, and cerebral infarction, but in infants of normal birthweight, the most common reason is hypoxicischemic encephalopathy. Knowledge about the cortical dysplasias, of which some have a genetic basis, is increasing rapidly [49]. Periventricular leukomalacia is a risk factor with 60–100% of patients with PVL developing CP. In general, congenital malformations are strongly associated with cerebral palsy [50–54]. Other known antenatal causes of cerebral palsy are vascular events demonstrated by brain imaging (for example, middle cerebral artery occlusion), and maternal TORCH (toxoplasmosis, rubella, cytomegalovirus, and herpes simplex) infections during the first and second trimesters of pregnancy are the known causes of long-term neurodevelopmental disabilities. In industrialized countries, the proportion of CP attributable to TORCH infections is estimated to be almost 5% [13]. The less common causes of cerebral palsy include metabolic disorders, maternal ingestion of toxins, and rare genetic syndromes [55].
\nAntepartum hemorrhage, obstructed labor, or cord prolapse can jeopardize the fetus causing hypoxia, but essential criteria must be fulfilled before cerebral palsy can be attributed to the acute intrapartum period [56, 57]. These criteria are metabolic acidosis in umbilical arterial cord, fetal scalp or very early neonatal blood samples, and early onset of severe or moderate neonatal encephalopathy in infants of >34 weeks gestation [57].
\nChildren with cerebral palsy, who have a history of neonatal encephalopathy, are more likely to have had signs of intrapartum hypoxia such as meconium staining of the amniotic fluid [58]. However, there may be no evidence of perinatal asphyxia in a significant percentage of children with neonatal encephalopathy [19]. In a systematic study, cerebral palsy was more strongly associated with encephalopathy [59]. Severe hypoglycaemia, untreated jaundice, and severe neonatal infection in neonatal period may be responsible for cerebral palsy [55].
\nInfection and injuries are responsible for most cases of postneonatally acquired cerebral palsy in developed countries. Thanks to introduction of new vaccines, meningitis and subsequent neurological sequelae were decreased in a large number of children. Accidental (motor vehicle accidents and near-drowning episodes) and nonaccidental injuries may responsible for cerebral palsy. Other reasons of postneonatally acquired cerebral palsy contain apparent life-threatening events, cerebrovascular accidents, and following surgery for congenital malformations. Meningitis, septicemia, malaria, and other conditions are the important causes of cerebral palsy in developing countries [55].
\nThe risk factors associated with CP may also be presented as maternal, paternal and sibling factors, prenatal factors, perinatal factors, and postnatal factors.
\nMaternal medical conditions are associated with cerebral palsy. These include intellectual disability, seizures [60], maternal thrombophilia [33], and thyroid disease [50, 60]; prior reproductive loss [61] and CP in a sibling have been reported as an association with CP in the Collaborative Perinatal Project of the National Institute of Neurological and Communicative Disorders and Stroke [60]. Adolescent pregnants are likely to have low gestational weeks, low birthweight, and birth traumas. Maternal age > 35 years was reported among risk factors of CP [13]. Öztürk et al. [30] also reported that mothers of children with CP were significantly younger, with an increase in adolescent pregnancies. Mothers of children with CP had low gestational weeks, low birthweight, and prolonged labor.
\nParental consanguinity [62, 63] and low economic status were found related to CP in two studies [64, 65].
\nPreeclampsia is associated with an increased risk of cerebral palsy in term infants [66] but this association does not seem to exist in preterm infants [67, 68]. It has been suggested that preeclampsia may lead to a release of catecholamines in preterm infants, which accelerates fetal maturation [69], but care is needed in comparing rates in infants of the same gestation, given that preeclampsia itself can be directly responsible for preterm births. Alternatively, the presence of preeclampsia may result in elective preterm delivery, avoiding the inflammatory responses of spontaneous preterm labors with all their associated problems.
\nChorioamnionitis and intrauterine infection and/or inflammation are well-known risk factors for CP. Prenatal maternal chorioamnionitis is accounting for as much as 12% of cerebral palsy in term infants and 28% in premature infants [13, 70, 71]. According to the inflammatory hypothesis, maternal infection can lead to elevated fetal blood and brain cytokine levels, which might result in central nervous damage and subsequent CP [13]. Nelson et al. reported that blood inflammatory cytokine levels in term infants that developed CP were significantly higher than control groups [72]. A number of studies have shown that even fever itself might be harmful. There may be toxic products of the infecting organisms or toxic effects of inflammatory mediators produced by the mother, infant, or placenta. It is tempting to consider that cytokines or other inflammatory mediators induced brain damage directly or indirectly [73, 74]. Gilles et al. [75] demonstrated that maternal trauma in pregnancy may be implicated as a possible cause of cerebral palsy. Antepartum hemorrhage is also associated with mortality, CP, and white matter damage in preterm infants [76].
\nMultiple pregnancies, also reported as a risk factor of CP, increase fourfold in twins and 18-fold in triplets [77]. These are associated with preterm delivery, poor intrauterine growth, birth defects, and intrapartum complications [78, 79].
\nIntrauterine growth restriction (IUGR) can be responsible to increase risk of neonatal morbidity and mortality, and also seems to affect brain development [80]. In some specific variance in the brain of IUGR infants, as restriction of the volume of gray matter, a reduced amount of the total DNA in glia cells and neurons, and changes in cerebral hemodynamic have been reported. This hypothesis supported by animal studies showed reduced oxygen delivery to the brain and retarded growth of the forebrain and cerebellum [81, 82]. Several mechanisms have been suggested for the relation between IUGR in term babies and CP. The abnormal growth may play a direct role in causing CP or utero brain injury. Alternatively, a separate process, such as placental insufficiency, could cause both the growth retardation and brain injury [83, 84].
\nTwo mutations have been detected, which predispose heterozygous carriers to venous thrombosis. One is a mutation localized to the factor V gene (factor V Leiden mutation, VL) and second is the gene for prothrombin [85, 86]. Nelson et al. reported that placental thrombosis, or neonatal stroke, may have occurred and resulted in CP [72].
\nMales are at higher risk of CP, perhaps because of the recently identified gender-specific neuronal vulnerabilities [15, 87]. In the fetus, CP has been associated with intrauterine growth restriction [88, 89] maternal factors [90, 91], other risk factors [92], and congenital anomalies not only of the brain, head, eyes, and face, but also with noncerebral anomalies (in the apparent absence of cerebral anomalies), particularly of the heart, limbs, and skeleton [93, 94]. The risk of CP also increases with the number of suboptimal factors affecting a pregnancy [50, 95].
\nAccording to the results of World Health Report, perinatal asphyxia and high-risk pregnancy were independent factors that correlated with CP in term and near-term newborns. In developing countries, 4–9 million infants experience birth asphyxia annually [96]. Major events likely to cause perinatal asphyxia include prolonged delivery, breech delivery, and emergency cesarean births [54, 97]. Though intrapartum factors producing asphyxia were traditionally accepted to be the principal cause of CP, this assumption was reconsidered during the 1980s and 1990s, and today it is suggested that 70–80% of cases of CP are due to prenatal factors and that birth asphyxia plays a relatively minor role. Although intrapartum asphyxia is believed to account for around 10% of CP in term and near-term infants, Swedish population-based CP report by the Hagberg group detected birth asphyxia to be the likely cause of CP in 28% of term children with CP [98]. However, “birth asphyxia” is a poorly defined term related to a sequence initiated by hypoxia and its clinical signs are nonspecific [43]. Using indirect signs of birth asphyxia, recent studies suggest that birth asphyxia might not be such an important cause of CP as was previously assumed, but that it might sometimes constitute one element of a multifactorial cause; neonatal signs associated with birth asphyxia might be early manifestations of CP from a variety of causes, of which birth asphyxia is only one; and the majority of pathways to CP commence antenatally [13, 43, 99]. Any factor causing a very preterm birth that lies on a potential causal path to CP must be remembered. Many etiologic studies control or stratify the risk of CP that also increases with the number of suboptimal factors affecting a pregnancy [100].
\nThe lower birthweights and shorter gestations associated with multiple birth contribute significantly to their higher risk of CP, but cannot be the only relevant factors because gestation-specific rates are higher for multiples than for singletons born at term or extremely preterm [101, 102]. The most important risk factor seems to be prematurity, and low birthweight with risk of CP increasing with decreasing gestational age and birthweight. About 28% of CP cases are born very preterm, compared to 1% of all births. As an effect of the success of neonatal intensive care during the last three decades, ensuring an increasing survival of children born extremely preterm, the prevalence of CP among preterm children has risen [103]. These groups of children may contribute significantly to the overall number of children with CP since they are at greater risk of developing CP. Although it can be expected that where mortality rates are high and CP rates are low, It may be that thanks to good clinical practice and developing technology mortality and CP prevalence rate will be reduced. Neonatal intensive care practices, including withdrawal of life support, may have an impact on local CP rates over time; this influence is difficult to assess [13, 104].
\nAbruptio placentae have also been suggested to be associated with a higher risk of CP, especially moderately preterm (32–36 weeks) groups [105]. Perinatal infections (bacterial, viral, and protozoal) may also cause the development of CP [106].
\nOther relations with cerebral palsy include prolonged rupture of the membranes in infants of all gestations [52] and in preterm babies [67]; the presence of meconium-stained fluid [107] and tight nuchal cord was also reported as associated with CP [108].
\nPostneonatally acquired CP is said to result from a recognized brain damaging event that is unrelated to factors in the antenatal or perinatal period, but there is a growing realization that the pathway to postneonatally acquired CP often begins before the postneonatal period [19]. The inclusion criteria for a postneonatal time range of the insult vary between reports. Some researchers have included cases acquired from neonatal causes that might have had their origin during pregnancy, labor, or delivery [109]. Although a strict definition of beyond 28 days is used by others [16], the upper age limit also varied from 2 to 10 years between researchers [110]. Population-based estimates of the frequency of postneonatally acquired CP, as a proportion of all CP, are reported in the literature to change between 1.4 and 24%, with higher rates in undeveloped and developing countries, and lower socio-economic groups [16]. The Surveillance of Cerebral Palsy in Europe, in a cohort of children from eight countries born between 1976 and 1990, reported that the rate of children whose CP was of postneonatal origin was 7.8% [39]. Pharoah et al. suggested that postnatal causes are generally resulted in spastic CP [111]. Most surveillance systems distinguish cases in which motor impairment is obviously acquired postneonatally, usually following cerebral infection or head trauma [16]. Other infection complications, cerebrovascular accidents, trauma, hypoxia, gastroenteritis, and other causes of acute encephalopathy, neoplasmas, and exposure toxins were other reasons that are reported [112]. Infection, however, remains an important cause of acquired CP despite a fall in the overall numbers more than 30 years of the study. With the introduction of new vaccines, the proportion of cases due to infection will be further decrease, providing there is adequate education and regular control [16].
\nCP is a nonprogressive but permanent disorder. The disease has been better understood by the researchers in due course of time, and then described as “CP is not a diagnosis but an umbrella term.” Though there are different rates according to the region, percentage of CP is not low in especially developing and undeveloped countries. Etiological factors of CP are very diverse and may be classified according to time period (prenatal, perinatal, postneonatal) and parenteral factors. It may be that, thanks to good clinical practice and developing technology, the prevalence of CP rate will be reduced and additionally most known risk factors will be avoided.
\nTeeth are a topic of interest to paleontologists because they are very well preserved. As a matter of fact, the dental remains have made it possible to study the evolution of mammals by analyzing their morphology. In developmental biology, the mouse model is an interesting model for studying dental development.
Humans have two dentitions (temporary and permanent) and different types of teeth, incisor, canine, premolar, and molar with different morphologies, whereas mice only have two types (incisor and molar) separated by a diastema from which the incisors have unlimited growth. Despite these differences, the dental development process is similar in humans and mice, and regulatory phenomena have been maintained over the evolution.
Teeth, such as mammary glands, hair, and feathers, develop from two adjacent tissues: the epithelium and the mesenchyme, although they all have different morphologies. Indeed, during development, the specific shape of each organ is defined in relation to epithelial-mesenchymal proliferation and to all the changes that the epithelium undergoes [1].
The embryological aspect of the molars was addressed in order to clarify the etiopathogenic aspect and to adapt therapeutic attitudes according to the diagnosis.
The objective of this chapter is to address the embryology of human molars by focusing on its molecular and morphological characteristics.
Teeth represent a new morphological feature of mammals [2, 3]. Molars are complex teeth able to become occluded. Interlocking intercuspation between upper and lower molars allows food to be crushed [4]. Evolutionary dietary radiations are related to the great diversity of the current mammalian molars. They are clarified in the fossil record, where new molar organizations are often related to significant line diversifications. Several theories have been advanced to explain the evolution of molars. Like all primates, Man is a placental mammal, and the ancestor of contemporary humans is
In 1965, the discovery of a fossil of a lower molar made it possible to show that on this Therian branch around 135 million years ago, these molars already existed. They were called tribosphenic by Simpson in 1936 [6]. These mandibular molars have six tubercles, three of which are pointed, high, sharp, and are arranged in a triangle and distal position. The three others tubercles are lower and are arranged in a central basin to receive the main palatal tubercle of the opposite teeth that have only three cusps. The fact of having six tubercles is of physiological interest when taking food.
Nearly 110 million years ago, the oldest placental mammals had a dental formula with 52 teeth, including 3 molars in a decreasing series, the first being the largest. This primitive disposition is found in modern man.
Around 75 million years ago, with the dinosaurs extinction, other species invaded space, and the dental formula was reduced to 44 teeth for all placental mammals including the man.
In the Catarrhini, the loss of one incisor and two premolars leads to a dental formula with 32 teeth found in monkeys of the ancient world (Afro-Eurasia), the Hominids, and the contemporary Men. It has been recognized for 45 million years [7].
In the genus Homo, the 32-teeth morphology does not differ much from the modern men, except for the great variability in size. Root morphology may vary from one group to another. The reduction in the number of cusps observed in humans can be considered as a specialization trait and not as a step backward. However, the reduction in the dental formula in the placentals and primates mainly affected the incisors, premolars, and even canines but not the molars.
Wisdom tooth agenesis, especially mandibular agenesis, is often considered as a sign of evolution. On the other hand, the presence of supernumerary teeth or hypergenesis is explained as a return to ancestral forms
The odontogenic epithelium is formed from the oral epithelium that lines the primary oral cavity called the “stomodeum.” It appears as a localized thickening of the oral epithelium, and it is formed by several cellular layers resulting from a series of localized mitoses affecting the oral epithelium. The mitotic spindle of dividing cells is oriented perpendicular to the basal membrane that separates the epithelium from the ectomesenchyma.
Epithelial thickening continues to proliferate and sinks into the underlying ectomesenchymal tissue forming a plunging wall (also called a primitive dental blade). This latter splits into two blades: vestibular and dental. The vestibular blade determines the formation of the buccal vestibule, which is the space between the cheek/lip and the dental arch.
In humans, as in rats and mice, the dental blade will give birth to the dental placodes that will be at the origin of the formation of future dental germs. Dental placodes are cellular clusters attached to the dental blade by a net of epithelial cells called the primary dental blade. Each dental arch initially contains 10 dental placodes. From the primary dental blade develops the secondary dental blade, which is at the origin of the 16 permanent teeth per arch.
Each placode will undergo morphological changes that are described as three successive stages: bud stage, cup stage, and bell stage [1].
Since the three molars are not preceded by temporary teeth, they evolve from the distal end of the initial dental blade, which proliferates in a posterior direction. The primary dental blade of the second temporary molar will cause the formation of four secondary dental blades. For each half of the arch, starting from the anterior area toward the posterior area, each of these four secondary dental blades will give the permanent germ of the following teeth: the first permanent molar, the second permanent molar, and the third permanent molar.
The secondary dental blades that are at the origin of the formation of the 1st and 2nd molar will orient themselves vertically as long as they have space that allows them to orient themselves in the mesenchyma. On the other hand, in most cases for the 3rd molar, orientation problems arise because there is not enough space for its secondary dental blade to be parallel to the other two blades [8].
All dental buds, with the exception of the second and third permanent molars, are present and begin to develop before birth [9]. The chronology of the appearance of molar germs remains variable according to the authors; however, it is often found that the germ of the first molar appears around the 4th or 5th month of intrauterine life. The one of the second molar appears around the 9th month or 1 year after birth.
The germ of the third molar does not appear until around 4 or 5 years of age. Mineralization begins between 7, 9, and 10 years, and the crown is completed between 12 and 16 years. The emergence in the oral cavity is between 17- and 21-year-olds; the tooth will then slide along the distal surface of the second molar to reach the occlusion level. Root building ends between the ages of 18 and 25 years. The place it has depends on the growth in the posterior region of the arch. The main activity of the dental blade is spread over a period of about 5 years. However, the dental blade near the third molar continues to be active until about 15 years of age [9].
A number of anomalies can occur during the development of the tooth. The development of excess dental blade can lead to an increase in the number of dental buds, resulting in too many teeth (supernumerary). A deficient dental blade can lead to a reduction in the number of teeth (hypodontia) [9].
Molars are multiradiculated teeth. Indeed, the vast majority of the first maxillary molars have three roots. The second maxillary molar has more frequent variations in the number of roots than the first maxillary molar, and the first mandibular molar and the second have two roots in the majority.
Root formation or radiculogenesis or rhizagenesis is the development of the root pulpo-dentinary organ in close relationship with cemenesis, the outline of the dentoalveolar ligament and the construction of the alveolar bone. It begins when the final dimensions are acquired. The Hertwig epithelial sheath is at the origin of root formation, depending on their number, shape, and size [10].
As for the crown, root development is governed by interactions involving the Hertwig epithelial sheath, basement membrane, mesenchymal papilla, and dental follicle.
The Hertwig epithelial sheath originates from the reflection zone or cervical loop which is the place where the external and internal adamantin epitheliums (EAE and EAI) meet to form a double epithelial layer. Hertwig epithelial sheath has an annular structure surrounded by a basal membrane that separates it from the pulpal and follicular mesenchyma. This basement membrane has anchoring fibrils on the pulp side. The internal epithelium faces the papilla and the external epithelium faces the dental follicle. The Hertwig epithelial sheath will emit tongues in the centripetal direction that will fuse in the central region of the papilla and form rings from which the roots can be identified. The number of strips emitted is proportional to the number of roots that each molar can have. For example, for the molar which will have two roots, two tongues are formed, and after fusion of two rings, each of the two will be at the origin of the formation of a root. These two leaves remain attached and progress in the underlying connective tissue in the apical direction defining the future shape of the dental root [11].
Root elongation and tissue formation are related to the coordinated proliferation of sheath epithelial cells and surrounding mesenchymal cells [12].
Root dentin forms in parallel with the proliferation in the apical direction of the Hertwig sheath. The latter gradually induces odontoblastic differentiation. The pulp parenchyma cells close to the anchor fibrils differentiate into odontoblasts. These odontoblasts produce preentine, which mineralizes to form dentin. The cells of the outer dental epithelium forming the outer layer of the sheath do not differentiate into ameloblasts as is the case for the crown. Then, the basement membrane degrades, and the epithelial blade involutes and gradually dissociates.
Developmental defects of the Hertwig sheath at the apical third of the root are at the origin of the formation of the lateral canals following a stop of dentinogenesis at this site due to the nondifferentiation of pulp fibroblasts into odontoblasts.
The cells of the sheath can undergo three spells: some can form the “Malassez epithelial debris,” others can die by apoptosis, while others can undergo epithelial-mesenchymal transformation.
As the sheath disintegrates, follicular cells near the surface of the root dentin differentiate into cementoblasts. These synthesize and deposit the cement matrix in contact with the dentin.
As the root development progresses, the epithelial ring forming the Hertwig epithelial sheath gradually shrinks as a result of a reduction in mitosis, thereby reducing the size of the root tube. This narrowing allows the development of one or more orifices (or foramina), which are the place where vascular and nervous elements intended for the pulp to pass through.
The development of the root ends with the construction of the apex, which is a slow process. In humans, for example, for the 1st permanent molar, this operation is performed until the age of 9–10 years. In the case of permanent teeth, this phenomenon lasts longer and requires more time than the development of the root itself.
In humans, dental development includes the morphogenesis of crowns and roots and results in the formation of the enamel organ, odontoblastic, ameloblastic, and cementoblastic differentiation. Huge advances in research have made it possible to understand the phenomena of molecular regulation of dental development.
Dental development follows a precisely controlled and regulated genetic program. The dental organ consists of an epithelial part that derives from the ectoderm and a mesenchymal part that derives from mesodermal cells on the one hand and cells from neural ridges on the other hand [13, 14, 15, 16].
The dental organ develops from a communication between the epithelium and the underlying mesenchyma. The communication language has been preserved throughout the evolution. This communication between the epithelium and the mesenchyma is done through signaling molecules and growth factors [17, 18, 19].
The studies carried out on the mouse molar have enabled us to gather a body of knowledge with many similarities to those of humans. However, the experimental data obtained in animals can be extrapolated relatively reliably to understand what is actually happening in humans.
Several families have been described, including:
TGF-beta (transforming growth factor beta) including BMP (bone morphogenetic proteins) activins and follistatin;
FGF (Fibroblast growth factors);
Hedgehog (only Sonic hedgehog (Shh) is known for its role in odontogenesis);
These molecules send their message to the nucleus through the signaling pathways and receptors on the cell membrane surface. Transcription factors will then modulate the expression of different target genes and induce changes in cell response and behavior (Figure 1) [25].
Signaling in tooth development [
Genes represented in “light blue” colored squares or rectangles are responsible, when inactivated, for stopping dental development.
It should be remembered that the odontogenic epithelium is formed at the first gill arch. The latter undergoes pharyngeal regionalization, resulting in the expression of Fgf8 and 9 (fibroblast growth factors 8 and 9) and Lhx-6 and -7 (LIM homeobox 6 and 7) in the oral part (rostral) and Gsc (goosecoid) in the aboral part (caudal). Indeed, the expression of Fgf8 in the odontogenic epithelium in the oral part of the first pharyngeal arch causes the expression of Lhx-7 in the underlying ectomesenchyma. In the aboral region, there is an important expression of Gsc in the ectomesenchyma. Gsc expression in the caudal region is not responsible for inhibiting Lhx-7 expression in this area; however, Lhx-7 expression in the rostral region will result in blocking Gsc gene expression in this.
In addition to Fgf8, a second BMP4 signaling molecule (bone morphogenetic protein 4) is expressed in the epithelium in the distal and therefore in the median region of the 1st arc.
The activation and inhibition of transcription factors allows the delimitation of the odontogenic territory by BMP4 and Fgf8a double signalling. (Figure 2) [19].
Pattern of gene expression in the developing tooth [
Mammalian teeth are meristic series. The determination of different morphology was explained by two theories:
The gradient theory proposed by Butler [26] which stipulates the presence of morphogenetic fields and that the determination of the shape of the tooth is a function of its position in the field independent of local factors.
The theory of clones proposed by Osborn [27] which stipulates that ectomesenchyma is already differentiated into three cellular clones, incisal, canine, and molar clones, before its migration. The proposal of this second concept suggested that the two theories are competing.
In 1995, the theory of odontogenic homeocode was developed by Sharpe [22], which represents a synthesis of the two theories: gradients and clones and shows that the latter two are complementary. These two concepts were explained in the light of the discovery of new genes and signaling molecules (Figure 3) [26, 27, 28].
(A) Regional field theory. (B) Clone theory. (C) Homeobox [
The identity of each tooth, including the molars, is characterized by its homeocode, which represents the combination of homeogens that defines the position and identity of the tooth. Indeed, different homeogens are expressed by the neural crest cells of the ectomesenchyma under the instructive induction of the oral epithelial cells. These homeogens are divergent and therefore of the nonhox type.
This odontogenic homeocode theory involves four homogenous genes: muscle segment homeodomain-homeobox 1 (Msx-1), muscle segment homeodomain-homeobox 2 (Msx-2), distal-less homeobox 1 (Dlx1), and goosecoide. In the molar sector, Msx-1 and Dlx-1 are expressed and Msx-2 and goosecoide are not expressed. In the canine sector, Msx-1, Msx-2, and goosecoide are expressed, and Dlx-1 is not expressed; in incisal sector, Msx-1 and goosecoide are expressed, Msx-2 and Dlx-1 are not expressed.
In the concept of morphogenetic fields, the consideration of various genetic factors and their epigenetic modulation influences dental development [29].
According to Mitsiadis’ work in 2006, the three models, gradients, clones, and homeocodes, could be grouped into a single model to explain dental identity. Indeed, dental identity, including molars, is given by the presence of morphogenetic fields defined by the diffusion of growth factors. The odontogenic epithelium expresses gradients of signaling molecules that are mainly Fgf, Bmp, Shh, and Wint that will diffuse to the underlying mesenchymal tissue containing neural peak cells. Depending on the location and instruction received by these cells, they will express a set of divergent genes in relation to concentrations of signaling molecules. The locally defined tooth type is related to the locally expressed divergent homeogen combinatorics of these ridge cells (Figure 4) [30].
Dental identity determination (adapted from Ref. [
The Mitsiadis model combines the three concepts: morphogenetic fields, clone, and odontogenic homeocode.
These three models should be viewed as complementary rather than contradictory and propose that this unifying view can be extended into the clinical setting using findings on dental patterning in individuals with missing teeth. The proposals are compatible with the unifying etiological model developed by Brook in 1984 based on human epidemiological and clinical findings. Indeed, this new synthesis can provide a sound foundation for clinical diagnosis, counseling, and management of patients with various anomalies of dental development, as well as suggesting hypotheses for future studies.
The root development process involves a set of signaling cascades. Various growth factors, including BMPs (bone morphogenetic proteins), EGF (epidermal growth factor), IGF (insulin-like growth factor), FGF (fibroblast growth factor), transcription factors Msx1, Msx2, Runx-2, Sonic Hedgehog (Shh), enamel proteins (secreted by HGH cells), and other proteins such as follistatin and activin A, are involved in the root development process. Indeed, they are involved in the growth and/or differentiation of odontoblasts and cementoblasts and/or in the mineralization of dentin and/or cementum [21, 31, 32, 33, 34, 35, 36].
Dental morphology is controlled by an epithelial signaling center called the enamel node. The node of the enamel is a particular and transient histological structure formed by a cellular cluster that appears at the basal part of the internal dental epithelium. The node of the primary enamel is present in the dental germs of all types of teeth including incisors.
Because the enamel nodes link cell differentiation to morphogenesis, Thesleff suggests that the latter can be considered as central regulators of dental development [37].
During molar development, the node of the secondary enamel is formed during the bell stage at the location of future cusp areas. At this point, the expression of signaling molecules precedes the folding and growth of the dental epithelium [38, 39].
The Slit1 gene is expressed in the nodes of the primary and secondary enamel during the formation of molar cusps [40].
The approaches provided by Line and Mitsiadis have advanced the clinic’s understanding of dental identity establishment based on gradient, clone, and homeocode theories [29, 30].
The multifactorial model involving genetic, epigenetic, and environmental determinants has provided better explanations and helped to understand missing and supernumerary teeth in monozygotic twins [41].
In humans, dental problems are observed during pathologies of dental development or syndromes.
Mutations in genes known as divergent homeobox genes encoding transcription factors such as MSX1 and PAX9 (paired domain box gene 9) are at the origin of oligodontia. Indeed, a mutation in the homeobox of the MSX1 gene (substitution of an arginine by a proline in the homeodomain region) is associated with the agenesis of third molars, indicating the involvement of MSX1 in the dentition pattern [42, 43, 44].
Also, mutations in the PAX9 gene cause oligodontia characteristic of molars [45, 46, 47, 48]. The severity of dental agenesis appears to be correlated with the ability of the mutated PAX9 protein to bind to DNA [49].
A misdirection mutation during the sequencing of the PAX9 gene may explain a different phenotype of hereditary oligodontia observed in humans, which affects not only molars but also other tooth lines; and is characterized by tooth small size in both types of dentition. This mutation is characterized by a replacement of the amino acid arginine by tryptophan in a region entirely preserved in all genes of the matched sequenced box [50].
In humans, Pitx2 expression deficiency associated with Rieger syndrome is characterized by oligodontia [51].
The biological process is the same for all teeth, including molars, regardless of their identity, but epithelial signaling and homeogenic combination differ from one tooth type to another.
The study of first molar of the mouse has allowed us to better understand and follow the stages of dental development in humans. The general pattern remains the same, unlike the training time, the complexity of the dental system, the presence of two types of teeth in humans, and unlimited incisors growth in mice.
The multidisciplinary approach between fundamental and clinical research is essential to clarify the relationship between molecular involvement and clinical manifestations.
Understanding the molecular mechanisms of dental anomalies, including those affecting human molars, helps to propose diagnostic hypotheses and thus to improve patient management.
Future research should focus on synergizing molecular and genetic approaches to further analyze the action mechanisms of key genes involved in the development of human molars.
The authors declare that they have no conflicts of interest with the contents of this article.
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He is the president of the Travel Medicine Committee of the Pan-American Infectious Diseases Association (API), as well as the president of the Colombian Association of Infectious Diseases (ACIN). He is a member of the Committee on Tropical Medicine, Zoonoses, and Travel Medicine of ACIN. He is a vice-president of the Latin American Society for Travel Medicine (SLAMVI) and a Member of the Council of the International Society for Infectious Diseases (ISID). Since 2014, he has been recognized as a Senior Researcher, at the Ministry of Science of Colombia. He is a professor at the Faculty of Medicine of the Fundacion Universitaria Autonoma de las Americas, in Pereira, Risaralda, Colombia. He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. He is currently the Editor in Chief of the journal Travel Medicine and Infectious Diseases. His Scopus H index is 47 (Google Scholar H index, 68).",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null},{id:"332819",title:"Dr.",name:"Chukwudi Michael",middleName:"Michael",surname:"Egbuche",slug:"chukwudi-michael-egbuche",fullName:"Chukwudi Michael Egbuche",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/332819/images/14624_n.jpg",biography:"I an Dr. Chukwudi Michael Egbuche. I am a Senior Lecturer in the Department of Parasitology and Entomology, Nnamdi Azikiwe University, Awka.",institutionString:null,institution:{name:"Nnamdi Azikiwe University",country:{name:"Nigeria"}}},{id:"284232",title:"Mr.",name:"Nikunj",middleName:"U",surname:"Tandel",slug:"nikunj-tandel",fullName:"Nikunj Tandel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/284232/images/8275_n.jpg",biography:'Mr. Nikunj Tandel has completed his Master\'s degree in Biotechnology from VIT University, India in the year of 2012. He is having 8 years of research experience especially in the field of malaria epidemiology, immunology, and nanoparticle-based drug delivery system against the infectious diseases, autoimmune disorders and cancer. He has worked for the NIH funded-International Center of Excellence in Malaria Research project "Center for the study of complex malaria in India (CSCMi)" in collaboration with New York University. The preliminary objectives of the study are to understand and develop the evidence-based tools and interventions for the control and prevention of malaria in different sites of the INDIA. Alongside, with the help of next-generation genomics study, the team has studied the antimalarial drug resistance in India. Further, he has extended his research in the development of Humanized mice for the study of liver-stage malaria and identification of molecular marker(s) for the Artemisinin resistance. At present, his research focuses on understanding the role of B cells in the activation of CD8+ T cells in malaria. Received the CSIR-SRF (Senior Research Fellow) award-2018, FIMSA (Federation of Immunological Societies of Asia-Oceania) Travel Bursary award to attend the IUIS-IIS-FIMSA Immunology course-2019',institutionString:"Nirma University",institution:{name:"Nirma University",country:{name:"India"}}},{id:"334383",title:"Ph.D.",name:"Simone",middleName:"Ulrich",surname:"Ulrich Picoli",slug:"simone-ulrich-picoli",fullName:"Simone Ulrich Picoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334383/images/15919_n.jpg",biography:"Graduated in Pharmacy from Universidade Luterana do Brasil (1999), Master in Agricultural and Environmental Microbiology from Federal University of Rio Grande do Sul (2002), Specialization in Clinical Microbiology from Universidade de São Paulo, USP (2007) and PhD in Sciences in Gastroenterology and Hepatology (2012). She is currently an Adjunct Professor at Feevale University in Medicine and Biomedicine courses and a permanent professor of the Academic Master\\'s Degree in Virology. She has experience in the field of Microbiology, with an emphasis on Bacteriology, working mainly on the following topics: bacteriophages, bacterial resistance, clinical microbiology and food microbiology.",institutionString:null,institution:{name:"Universidade Feevale",country:{name:"Brazil"}}},{id:"229220",title:"Dr.",name:"Amjad",middleName:"Islam",surname:"Aqib",slug:"amjad-aqib",fullName:"Amjad Aqib",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229220/images/system/229220.png",biography:"Dr. Amjad Islam Aqib obtained a DVM and MSc (Hons) from University of Agriculture Faisalabad (UAF), Pakistan, and a PhD from the University of Veterinary and Animal Sciences Lahore, Pakistan. Dr. Aqib joined the Department of Clinical Medicine and Surgery at UAF for one year as an assistant professor where he developed a research laboratory designated for pathogenic bacteria. Since 2018, he has been Assistant Professor/Officer in-charge, Department of Medicine, Manager Research Operations and Development-ORIC, and President One Health Club at Cholistan University of Veterinary and Animal Sciences, Bahawalpur, Pakistan. He has nearly 100 publications to his credit. His research interests include epidemiological patterns and molecular analysis of antimicrobial resistance and modulation and vaccine development against animal pathogens of public health concern.",institutionString:"Cholistan University of Veterinary and Animal Sciences",institution:null},{id:"62900",title:"Prof.",name:"Fethi",middleName:null,surname:"Derbel",slug:"fethi-derbel",fullName:"Fethi Derbel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62900/images/system/62900.jpeg",biography:"Professor Fethi Derbel was born in 1960 in Tunisia. He received his medical degree from the Sousse Faculty of Medicine at Sousse, University of Sousse, Tunisia. He completed his surgical residency in General Surgery at the University Hospital Farhat Hached of Sousse and was a member of the Unit of Liver Transplantation in the University of Rennes, France. He then worked in the Department of Surgery at the Sahloul University Hospital in Sousse. Professor Derbel is presently working at the Clinique les Oliviers, Sousse, Tunisia. His hospital activities are mostly concerned with laparoscopic, colorectal, pancreatic, hepatobiliary, and gastric surgery. He is also very interested in hernia surgery and performs ventral hernia repairs and inguinal hernia repairs. He has been a member of the GREPA and Tunisian Hernia Society (THS). During his residency, he managed patients suffering from diabetic foot, and he was very interested in this pathology. For this reason, he decided to coordinate a book project dealing with the diabetic foot. Professor Derbel has published many articles in journals and collaborates intensively with IntechOpen Access Publisher as an editor.",institutionString:"Clinique les Oliviers",institution:null},{id:"300144",title:"Dr.",name:"Meriem",middleName:null,surname:"Braiki",slug:"meriem-braiki",fullName:"Meriem Braiki",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/300144/images/system/300144.jpg",biography:"Dr. Meriem Braiki is a specialist in pediatric surgeon from Tunisia. She was born in 1985. She received her medical degree from the University of Medicine at Sousse, Tunisia. She achieved her surgical residency training periods in Pediatric Surgery departments at University Hospitals in Monastir, Tunis and France.\r\nShe is currently working at the Pediatric surgery department, Sidi Bouzid Hospital, Tunisia. Her hospital activities are mostly concerned with laparoscopic, parietal, urological and digestive surgery. She has published several articles in diffrent journals.",institutionString:"Sidi Bouzid Regional Hospital",institution:null},{id:"229481",title:"Dr.",name:"Erika M.",middleName:"Martins",surname:"de Carvalho",slug:"erika-m.-de-carvalho",fullName:"Erika M. de Carvalho",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229481/images/6397_n.jpg",biography:null,institutionString:null,institution:{name:"Oswaldo Cruz Foundation",country:{name:"Brazil"}}},{id:"186537",title:"Prof.",name:"Tonay",middleName:null,surname:"Inceboz",slug:"tonay-inceboz",fullName:"Tonay Inceboz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/186537/images/system/186537.jfif",biography:"I was graduated from Ege University of Medical Faculty (Turkey) in 1988 and completed his Med. PhD degree in Medical Parasitology at the same university. I became an Associate Professor in 2008 and Professor in 2014. I am currently working as a Professor at the Department of Medical Parasitology at Dokuz Eylul University, Izmir, Turkey.\n\nI have given many lectures, presentations in different academic meetings. I have more than 60 articles in peer-reviewed journals, 18 book chapters, 1 book editorship.\n\nMy research interests are Echinococcus granulosus, Echinococcus multilocularis (diagnosis, life cycle, in vitro and in vivo cultivation), and Trichomonas vaginalis (diagnosis, PCR, and in vitro cultivation).",institutionString:"Dokuz Eylül University",institution:{name:"Dokuz Eylül University",country:{name:"Turkey"}}},{id:"71812",title:"Prof.",name:"Hanem Fathy",middleName:"Fathy",surname:"Khater",slug:"hanem-fathy-khater",fullName:"Hanem Fathy Khater",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/71812/images/1167_n.jpg",biography:"Prof. Khater is a Professor of Parasitology at Benha University, Egypt. She studied for her doctoral degree, at the Department of Entomology, College of Agriculture, Food and Natural Resources, University of Missouri, Columbia, USA. She has completed her Ph.D. degrees in Parasitology in Egypt, from where she got the award for “the best scientific Ph.D. dissertation”. She worked at the School of Biological Sciences, Bristol, England, the UK in controlling insects of medical and veterinary importance as a grant from Newton Mosharafa, the British Council. Her research is focused on searching of pesticides against mosquitoes, house flies, lice, green bottle fly, camel nasal botfly, soft and hard ticks, mites, and the diamondback moth as well as control of several parasites using safe and natural materials to avoid drug resistances and environmental contamination.",institutionString:null,institution:{name:"Banha University",country:{name:"Egypt"}}},{id:"99780",title:"Prof.",name:"Omolade",middleName:"Olayinka",surname:"Okwa",slug:"omolade-okwa",fullName:"Omolade Okwa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/99780/images/system/99780.jpg",biography:"Omolade Olayinka Okwa is presently a Professor of Parasitology at Lagos State University, Nigeria. She has a PhD in Parasitology (1997), an MSc in Cellular Parasitology (1992), and a BSc (Hons) Zoology (1990) all from the University of Ibadan, Nigeria. She teaches parasitology at the undergraduate and postgraduate levels. She was a recipient of a Commonwealth fellowship supported by British Council tenable at the Centre for Entomology and Parasitology (CAEP), Keele University, United Kingdom between 2004 and 2005. She was awarded an Honorary Visiting Research Fellow at the same university from 2005 to 2007. \nShe has been an external examiner to the Department of Veterinary Microbiology and Parasitology, University of Ibadan, MSc programme between 2010 and 2012. She is a member of the Nigerian Society of Experimental Biology (NISEB), Parasitology and Public Health Society of Nigeria (PPSN), Science Association of Nigeria (SAN), Zoological Society of Nigeria (ZSN), and is Vice Chairperson of the Organisation of Women in Science (OWSG), LASU chapter. She served as Head of Department of Zoology and Environmental Biology, Lagos State University from 2007 to 2010 and 2014 to 2016. She is a reviewer for several local and international journals such as Unilag Journal of Science, Libyan Journal of Medicine, Journal of Medicine and Medical Sciences, and Annual Research and Review in Science. \nShe has authored 45 scientific research publications in local and international journals, 8 scientific reviews, 4 books, and 3 book chapters, which includes the books “Malaria Parasites” and “Malaria” which are IntechOpen access publications.",institutionString:"Lagos State University",institution:{name:"Lagos State University",country:{name:"Nigeria"}}},{id:"273100",title:"Dr.",name:"Vijay",middleName:null,surname:"Gayam",slug:"vijay-gayam",fullName:"Vijay Gayam",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/273100/images/system/273100.jpeg",biography:"Dr. Vijay Bhaskar Reddy Gayam is currently practicing as an internist at Interfaith Medical Center in Brooklyn, New York, USA. He is also a Clinical Assistant Professor at the SUNY Downstate University Hospital and Adjunct Professor of Medicine at the American University of Antigua. He is a holder of an M.B.B.S. degree bestowed to him by Osmania Medical College and received his M.D. at Interfaith Medical Center. His career goals thus far have heavily focused on direct patient care, medical education, and clinical research. He currently serves in two leadership capacities; Assistant Program Director of Medicine at Interfaith Medical Center and as a Councilor for the American\r\nFederation for Medical Research. As a true academician and researcher, he has more than 50 papers indexed in international peer-reviewed journals. He has also presented numerous papers in multiple national and international scientific conferences. His areas of research interest include general internal medicine, gastroenterology and hepatology. He serves as an editor, editorial board member and reviewer for multiple international journals. His research on Hepatitis C has been very successful and has led to multiple research awards, including the 'Equity in Prevention and Treatment Award” from the New York Department of Health Viral Hepatitis Symposium (2018) and the 'Presidential Poster Award” awarded to him by the American College of Gastroenterology (2018). He was also awarded 'Outstanding Clinician in General Medicine” by Venus International Foundation for his extensive research expertise and services, perform over and above the standard expected in the advancement of healthcare, patient safety and quality of care.",institutionString:"Interfaith Medical Center",institution:{name:"Interfaith Medical Center",country:{name:"United States of America"}}},{id:"93517",title:"Dr.",name:"Clement",middleName:"Adebajo",surname:"Meseko",slug:"clement-meseko",fullName:"Clement Meseko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/93517/images/system/93517.jpg",biography:"Dr. Clement Meseko obtained DVM and PhD degree in Veterinary Medicine and Virology respectively. He has worked for over 20 years in both private and public sectors including the academia, contributing to knowledge and control of infectious disease. Through the application of epidemiological skill, classical and molecular virological skills, he investigates viruses of economic and public health importance for the mitigation of the negative impact on people, animal and the environment in the context of Onehealth. \r\nDr. Meseko’s field experience on animal and zoonotic diseases and pathogen dynamics at the human-animal interface over the years shaped his carrier in research and scientific inquiries. He has been part of the investigation of Highly Pathogenic Avian Influenza incursions in sub Saharan Africa and monitors swine Influenza (Pandemic influenza Virus) agro-ecology and potential for interspecies transmission. He has authored and reviewed a number of journal articles and book chapters.",institutionString:"National Veterinary Research Institute",institution:{name:"National Veterinary Research Institute",country:{name:"Nigeria"}}},{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",biography:"Professor Dr. Shailendra K. Saxena is a vice dean and professor at King George's Medical University, Lucknow, India. His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. Dr. Saxena is a fellow of various international societies/academies including the Royal College of Pathologists, United Kingdom; Royal Society of Medicine, London; Royal Society of Biology, United Kingdom; Royal Society of Chemistry, London; and Academy of Translational Medicine Professionals, Austria. He was named a Global Leader in Science by The Scientist. He is also an international opinion leader/expert in vaccination for Japanese encephalitis by IPIC (UK).",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",country:{name:"India"}}},{id:"94928",title:"Dr.",name:"Takuo",middleName:null,surname:"Mizukami",slug:"takuo-mizukami",fullName:"Takuo Mizukami",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94928/images/6402_n.jpg",biography:null,institutionString:null,institution:{name:"National Institute of Infectious Diseases",country:{name:"Japan"}}},{id:"233433",title:"Dr.",name:"Yulia",middleName:null,surname:"Desheva",slug:"yulia-desheva",fullName:"Yulia Desheva",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/233433/images/system/233433.png",biography:"Dr. Yulia Desheva is a leading researcher at the Institute of Experimental Medicine, St. Petersburg, Russia. She is a professor in the Stomatology Faculty, St. Petersburg State University. She has expertise in the development and evaluation of a wide range of live mucosal vaccines against influenza and bacterial complications. Her research interests include immunity against influenza and COVID-19 and the development of immunization schemes for high-risk individuals.",institutionString:'Federal State Budgetary Scientific Institution "Institute of Experimental Medicine"',institution:null},{id:"238958",title:"Mr.",name:"Atamjit",middleName:null,surname:"Singh",slug:"atamjit-singh",fullName:"Atamjit Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/238958/images/6575_n.jpg",biography:null,institutionString:null,institution:null},{id:"333753",title:"Dr.",name:"Rais",middleName:null,surname:"Ahmed",slug:"rais-ahmed",fullName:"Rais Ahmed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/333753/images/20168_n.jpg",biography:null,institutionString:null,institution:null},{id:"252058",title:"M.Sc.",name:"Juan",middleName:null,surname:"Sulca",slug:"juan-sulca",fullName:"Juan Sulca",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252058/images/12834_n.jpg",biography:null,institutionString:null,institution:null},{id:"191392",title:"Dr.",name:"Marimuthu",middleName:null,surname:"Govindarajan",slug:"marimuthu-govindarajan",fullName:"Marimuthu Govindarajan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/191392/images/5828_n.jpg",biography:"Dr. M. Govindarajan completed his BSc degree in Zoology at Government Arts College (Autonomous), Kumbakonam, and MSc, MPhil, and PhD degrees at Annamalai University, Annamalai Nagar, Tamil Nadu, India. He is serving as an assistant professor at the Department of Zoology, Annamalai University. His research interests include isolation, identification, and characterization of biologically active molecules from plants and microbes. He has identified more than 20 pure compounds with high mosquitocidal activity and also conducted high-quality research on photochemistry and nanosynthesis. He has published more than 150 studies in journals with impact factor and 2 books in Lambert Academic Publishing, Germany. He serves as an editorial board member in various national and international scientific journals.",institutionString:null,institution:null},{id:"274660",title:"Dr.",name:"Damodar",middleName:null,surname:"Paudel",slug:"damodar-paudel",fullName:"Damodar Paudel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/274660/images/8176_n.jpg",biography:"I am DrDamodar Paudel,currently working as consultant Physician in Nepal police Hospital.",institutionString:null,institution:null},{id:"241562",title:"Dr.",name:"Melvin",middleName:null,surname:"Sanicas",slug:"melvin-sanicas",fullName:"Melvin Sanicas",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/241562/images/6699_n.jpg",biography:null,institutionString:null,institution:null},{id:"337446",title:"Dr.",name:"Maria",middleName:null,surname:"Zavala-Colon",slug:"maria-zavala-colon",fullName:"Maria Zavala-Colon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Puerto Rico, Medical Sciences Campus",country:{name:"United States of America"}}},{id:"338856",title:"Mrs.",name:"Nur Alvira",middleName:null,surname:"Pascawati",slug:"nur-alvira-pascawati",fullName:"Nur Alvira Pascawati",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Universitas Respati Yogyakarta",country:{name:"Indonesia"}}},{id:"441116",title:"Dr.",name:"Jovanka M.",middleName:null,surname:"Voyich",slug:"jovanka-m.-voyich",fullName:"Jovanka M. Voyich",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Montana State University",country:{name:"United States of America"}}},{id:"330412",title:"Dr.",name:"Muhammad",middleName:null,surname:"Farhab",slug:"muhammad-farhab",fullName:"Muhammad Farhab",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Agriculture Faisalabad",country:{name:"Pakistan"}}},{id:"349495",title:"Dr.",name:"Muhammad",middleName:null,surname:"Ijaz",slug:"muhammad-ijaz",fullName:"Muhammad Ijaz",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Veterinary and Animal Sciences",country:{name:"Pakistan"}}}]}},subseries:{item:{id:"9",type:"subseries",title:"Biotechnology - Biosensors, Biomaterials and Tissue Engineering",keywords:"Biotechnology, Biosensors, Biomaterials, Tissue Engineering",scope:"The Biotechnology - Biosensors, Biomaterials and Tissue Engineering topic within the Biomedical Engineering Series aims to rapidly publish contributions on all aspects of biotechnology, biosensors, biomaterial and tissue engineering. We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics can include but are not limited to: Biotechnology such as biotechnological products and process engineering; Biotechnologically relevant enzymes and proteins; Bioenergy and biofuels; Applied genetics and molecular biotechnology; Genomics, transcriptomics, proteomics; Applied microbial and cell physiology; Environmental biotechnology; Methods and protocols. Moreover, topics in biosensor technology, like sensors that incorporate enzymes, antibodies, nucleic acids, whole cells, tissues and organelles, and other biological or biologically inspired components will be considered, and topics exploring transducers, including those based on electrochemical and optical piezoelectric, thermal, magnetic, and micromechanical elements. Chapters exploring biomaterial approaches such as polymer synthesis and characterization, drug and gene vector design, biocompatibility, immunology and toxicology, and self-assembly at the nanoscale, are welcome. Finally, the tissue engineering subcategory will support topics such as the fundamentals of stem cells and progenitor cells and their proliferation, differentiation, bioreactors for three-dimensional culture and studies of phenotypic changes, stem and progenitor cells, both short and long term, ex vivo and in vivo implantation both in preclinical models and also in clinical trials.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/9.jpg",hasOnlineFirst:!0,hasPublishedBooks:!0,annualVolume:11405,editor:{id:"126286",title:"Dr.",name:"Luis",middleName:"Jesús",surname:"Villarreal-Gómez",slug:"luis-villarreal-gomez",fullName:"Luis Villarreal-Gómez",profilePictureURL:"https://mts.intechopen.com/storage/users/126286/images/system/126286.jpg",biography:"Dr. Luis Villarreal is a research professor from the Facultad de Ciencias de la Ingeniería y Tecnología, Universidad Autónoma de Baja California, Tijuana, Baja California, México. Dr. Villarreal is the editor in chief and founder of the Revista de Ciencias Tecnológicas (RECIT) (https://recit.uabc.mx/) and is a member of several editorial and reviewer boards for numerous international journals. He has published more than thirty international papers and reviewed more than ninety-two manuscripts. 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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:"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:"profile.detail",path:"/profiles/14787",hash:"",query:{},params:{id:"14787"},fullPath:"/profiles/14787",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)}()