Representative non-syndromic and syndromic ichthyosis with causative genes. Modified citation from Ref. [3].
\\n\\n
IntechOpen was founded by scientists, for scientists, in order to make book publishing accessible around the globe. Over the last two decades, this has driven Open Access (OA) book publishing whilst levelling the playing field for global academics. Through our innovative publishing model and the support of the research community, we have now published over 5,700 Open Access books and are visited online by over three million academics every month. These researchers are increasingly working in broad technology-based subjects, driving multidisciplinary academic endeavours into human health, environment, and technology.
\\n\\nBy listening to our community, and in order to serve these rapidly growing areas which lie at the core of IntechOpen's expertise, we are launching a portfolio of Open Science journals:
\\n\\nAll three journals will publish under an Open Access model and embrace Open Science policies to help support the changing needs of academics in these fast-moving research areas. There will be direct links to preprint servers and data repositories, allowing full reproducibility and rapid dissemination of published papers to help accelerate the pace of research. Each journal has renowned Editors in Chief who will work alongside a global Editorial Board, delivering robust single-blind peer review. Supported by our internal editorial teams, this will ensure our authors will receive a quick, user-friendly, and personalised publishing experience.
\\n\\n"By launching our journals portfolio we are introducing new, dedicated homes for interdisciplinary technology-focused researchers to publish their work, whilst embracing Open Science and creating a unique global home for academics to disseminate their work. We are taking a leap toward Open Science continuing and expanding our fundamental commitment to openly sharing scientific research across the world, making it available for the benefit of all." Dr. Sara Uhac, IntechOpen CEO
\\n\\n"Our aim is to promote and create better science for a better world by increasing access to information and the latest scientific developments to all scientists, innovators, entrepreneurs and students and give them the opportunity to learn, observe and contribute to knowledge creation. Open Science promotes a swifter path from research to innovation to produce new products and services." Alex Lazinica, IntechOpen founder
\\n\\nIn conclusion, Natalia Reinic Babic, Head of Journal Publishing and Open Science at IntechOpen adds:
\\n\\n“On behalf of the journal team I’d like to thank all our Editors in Chief, Editorial Boards, internal supporting teams, and our scientific community for their continuous support in making this portfolio a reality - we couldn’t have done it without you! With your support in place, we are confident these journals will become as impactful and successful as our book publishing program and bring us closer to a more open (science) future.”
\\n\\nWe invite you to visit the journals homepage and learn more about the journal’s Editorial Boards, scope and vision as all three journals are now open for submissions.
\\n\\nFeel free to share this news on social media and help us mark this memorable moment!
\\n\\n\\n"}]',published:!0,mainMedia:{caption:"",originalUrl:"/media/original/237"}},components:[{type:"htmlEditorComponent",content:'
After years of being acknowledged as the world's leading publisher of Open Access books, today, we are proud to announce we’ve successfully launched a portfolio of Open Science journals covering rapidly expanding areas of interdisciplinary research.
\n\n\n\nIntechOpen was founded by scientists, for scientists, in order to make book publishing accessible around the globe. Over the last two decades, this has driven Open Access (OA) book publishing whilst levelling the playing field for global academics. Through our innovative publishing model and the support of the research community, we have now published over 5,700 Open Access books and are visited online by over three million academics every month. These researchers are increasingly working in broad technology-based subjects, driving multidisciplinary academic endeavours into human health, environment, and technology.
\n\nBy listening to our community, and in order to serve these rapidly growing areas which lie at the core of IntechOpen's expertise, we are launching a portfolio of Open Science journals:
\n\nAll three journals will publish under an Open Access model and embrace Open Science policies to help support the changing needs of academics in these fast-moving research areas. There will be direct links to preprint servers and data repositories, allowing full reproducibility and rapid dissemination of published papers to help accelerate the pace of research. Each journal has renowned Editors in Chief who will work alongside a global Editorial Board, delivering robust single-blind peer review. Supported by our internal editorial teams, this will ensure our authors will receive a quick, user-friendly, and personalised publishing experience.
\n\n"By launching our journals portfolio we are introducing new, dedicated homes for interdisciplinary technology-focused researchers to publish their work, whilst embracing Open Science and creating a unique global home for academics to disseminate their work. We are taking a leap toward Open Science continuing and expanding our fundamental commitment to openly sharing scientific research across the world, making it available for the benefit of all." Dr. Sara Uhac, IntechOpen CEO
\n\n"Our aim is to promote and create better science for a better world by increasing access to information and the latest scientific developments to all scientists, innovators, entrepreneurs and students and give them the opportunity to learn, observe and contribute to knowledge creation. Open Science promotes a swifter path from research to innovation to produce new products and services." Alex Lazinica, IntechOpen founder
\n\nIn conclusion, Natalia Reinic Babic, Head of Journal Publishing and Open Science at IntechOpen adds:
\n\n“On behalf of the journal team I’d like to thank all our Editors in Chief, Editorial Boards, internal supporting teams, and our scientific community for their continuous support in making this portfolio a reality - we couldn’t have done it without you! With your support in place, we are confident these journals will become as impactful and successful as our book publishing program and bring us closer to a more open (science) future.”
\n\nWe invite you to visit the journals homepage and learn more about the journal’s Editorial Boards, scope and vision as all three journals are now open for submissions.
\n\nFeel free to share this news on social media and help us mark this memorable moment!
\n\n\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"7549",leadTitle:null,fullTitle:"Basic Concepts Viewed from Frontier in Inorganic Coordination Chemistry",title:"Basic Concepts Viewed from Frontier in Inorganic Coordination Chemistry",subtitle:null,reviewType:"peer-reviewed",abstract:'This book is both a review of current research and an undergraduate textbook for inorganic chemistry at university level. In university undergraduate lectures, basic concepts are mainly explained and added examples of frontier research are optional. However, in many cases, frontier research is more interesting for students than basic studies. This book is aimed at undergraduates in inorganic chemistry. Each author introduces or reviews "frontier research topics" of inorganic coordination chemistry. Additionally, "basic concepts," as found in textbooks on this subject, indicate application examples of "frontier research topics."',isbn:"978-1-78984-865-6",printIsbn:"978-1-78984-864-9",pdfIsbn:"978-1-83881-835-7",doi:"10.5772/intechopen.76741",price:119,priceEur:129,priceUsd:155,slug:"basic-concepts-viewed-from-frontier-in-inorganic-coordination-chemistry",numberOfPages:152,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"7bbd9beaeefecb9ec112a0a09432d241",bookSignature:"Takashiro Akitsu",publishedDate:"December 19th 2018",coverURL:"https://cdn.intechopen.com/books/images_new/7549.jpg",numberOfDownloads:9038,numberOfWosCitations:20,numberOfCrossrefCitations:6,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:16,numberOfDimensionsCitationsByBook:0,hasAltmetrics:1,numberOfTotalCitations:42,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"April 9th 2018",dateEndSecondStepPublish:"May 15th 2018",dateEndThirdStepPublish:"July 14th 2018",dateEndFourthStepPublish:"October 2nd 2018",dateEndFifthStepPublish:"December 1st 2018",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"147861",title:"Dr.",name:"Takashiro",middleName:null,surname:"Akitsu",slug:"takashiro-akitsu",fullName:"Takashiro Akitsu",profilePictureURL:"https://mts.intechopen.com/storage/users/147861/images/system/147861.jpg",biography:"Takashiro Akitsu, Ph.D., is now a professor in the Department of Chemistry, Faculty of Science Division II, Tokyo University of Science, Japan. Studying crystal and electronic structures of chiral copper complexes, he graduated from Osaka University and obtained his Ph.D. in Physical and Inorganic Chemistry in 2000. Dr. Akitsu studied at the Institute for Protein Research (metalloproteins), Keio University (photo and magnetic functional organic/inorganic hybrid compounds), and Stanford University (physical and bioinorganic chemistry) before moving to Tokyo University of Science. He has published 220 articles and book chapters. He has also served as an editorial board member and peer reviewer for many journals and was involved in the organizing committees for several international conferences.",institutionString:"Tokyo University of Science",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"6",totalChapterViews:"0",totalEditedBooks:"6",institution:{name:"Tokyo University of Science",institutionURL:null,country:{name:"Japan"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"491",title:"Organometallic Chemistry",slug:"chemistry-inorganic-chemistry-organometallic-chemistry"}],chapters:[{id:"64111",title:"Introductory Chapter: Concepts in Textbook and a Study on Schiff Base Metal Complexes",doi:"10.5772/intechopen.81684",slug:"introductory-chapter-concepts-in-textbook-and-a-study-on-schiff-base-metal-complexes",totalDownloads:823,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:null,signatures:"Takashiro Akitsu",downloadPdfUrl:"/chapter/pdf-download/64111",previewPdfUrl:"/chapter/pdf-preview/64111",authors:[{id:"147861",title:"Dr.",name:"Takashiro",surname:"Akitsu",slug:"takashiro-akitsu",fullName:"Takashiro Akitsu"}],corrections:null},{id:"63759",title:"Modern Techniques in Synthesis of Organometallic Compounds of Germanium",doi:"10.5772/intechopen.79985",slug:"modern-techniques-in-synthesis-of-organometallic-compounds-of-germanium",totalDownloads:1230,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:1,abstract:"Germanium is one of the most significant semiconductors to be used for electronic devices due to small bandgap and high intrinsic mobility of holes and electrons. Germanium has received a large attention due to its extraordinary reactivity and properties. It is commonly used in fluorescent lamps and as catalyst as well to produce various types of plastic. Germanium nanomaterials have broad range of applications from photovoltaic devices to phase-change memory materials. Germanium forms complexes by reacting with numerous elements such as carbon, oxygen, nitrogen, hydrogen, and phosphorous as a part of several organic compounds. Germanium coordinates with these elements by single, double, and triple linkages. Interestingly, all such reactions occur at ambient temperature usually in tetrahydrofuran under vacuum. Germanium may also react directly with primary and secondary nitrogen in the presence of a suitable base, whereas with tertiary nitrogen, it may react directly even in the absence of a base. Nevertheless, this chapter describes the modern techniques in synthesis of organometallic compounds of germanium.",signatures:"Hina Hayat and Muhammad Adnan Iqbal",downloadPdfUrl:"/chapter/pdf-download/63759",previewPdfUrl:"/chapter/pdf-preview/63759",authors:[{id:"253633",title:"Dr.",name:"Muhammad Adnan",surname:"Iqbal",slug:"muhammad-adnan-iqbal",fullName:"Muhammad Adnan Iqbal"},{id:"253635",title:"Ms.",name:"Hina",surname:"Hayat",slug:"hina-hayat",fullName:"Hina Hayat"}],corrections:null},{id:"62941",title:"Inorganic Coordination Chemistry: Where We Stand in Cancer Treatment?",doi:"10.5772/intechopen.80233",slug:"inorganic-coordination-chemistry-where-we-stand-in-cancer-treatment-",totalDownloads:2114,totalCrossrefCites:5,totalDimensionsCites:10,hasAltmetrics:0,abstract:"Metals have unique characteristics such as variable coordination modes, redox activity, and reactivity being indispensable for several biochemical processes in cells. Due to their reactivity, their concentration is tightly regulated inside the cells, and abnormal concentrations are associated with many disorders, such as cancer. As such metal complexes turned out to be very attractive as potential anticancer agents. The discovery of cisplatin was a crucial moment, which prompted the interest in Pt(II) and other metal complexes as potential anticancer agents. This chapter highlights the state of the art on metal complexes in cancer therapy, highlighting their uptake mechanisms, biological targets, toxicity, and drug resistance. Finally, based on the importance of selective target of cancer cells, drug delivery systems will also be discussed.",signatures:"Pedro Pedrosa, Andreia Carvalho, Pedro V. Baptista and Alexandra R. Fernandes",downloadPdfUrl:"/chapter/pdf-download/62941",previewPdfUrl:"/chapter/pdf-preview/62941",authors:[{id:"253664",title:"Prof.",name:"Alexandra R",surname:"Fernandes",slug:"alexandra-r-fernandes",fullName:"Alexandra R Fernandes"}],corrections:null},{id:"63430",title:"Retracted: Coordination Chemistry of Networking Materials",doi:"10.5772/intechopen.80864",slug:"coordination-chemistry-of-networking-materials",totalDownloads:754,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The coordination chemistry explains the chemistry, physical properties, structure, bonding, and other properties of the compounds of d-block elements. In the current chapter, we have discussed the coordination chemistry of networking complexes of d-block elements. The networking complexes of d-block elements comprise of metal organic frameworks (MOF) also known as coordination polymers. In this context, the geometry around central metal atom of MOFs has been discussed to explain their different properties. Different theoretical approaches (like hybridization, valance bond theory, molecular orbital theory, and crystal field theory) have been utilized to explain the properties of some selected exemplary compounds, e.g., [Ag(1,4-pyrazine)1.5CF3SO3], [[Cu(3,4-Hpdc)2 (H2O)2]·2dmso]n, and [Zn(II)(SEPCPU)]n.",signatures:"Ataf Ali Altaf, Sumbal Naz and Amin Badshah",downloadPdfUrl:"/chapter/pdf-download/63430",previewPdfUrl:"/chapter/pdf-preview/63430",authors:[{id:"207725",title:"Dr.",name:"Ataf Ali",surname:"Altaf",slug:"ataf-ali-altaf",fullName:"Ataf Ali Altaf"},{id:"218332",title:"Prof.",name:"Amin",surname:"Badshah",slug:"amin-badshah",fullName:"Amin Badshah"},{id:"256040",title:"Ms.",name:"Sumbal",surname:"Naz",slug:"sumbal-naz",fullName:"Sumbal Naz"}],corrections:null},{id:"61968",title:"The Triply Bonded Al☰Sb Molecules: A Theoretical Prediction",doi:"10.5772/intechopen.78412",slug:"the-triply-bonded-al-sb-molecules-a-theoretical-prediction",totalDownloads:899,totalCrossrefCites:0,totalDimensionsCites:2,hasAltmetrics:0,abstract:"The effect of substitution on the potential energy surfaces of RAl☰SbR (R = F, OH, H, CH3, SiH3, SiMe(SitBu3)2, SiiPrDis2, Tbt, and Ar*) is investigated using density functional theories (M06-2X/Def2-TZVP, B3PW91/Def2-TZVP, and B3LYP/LANL2DZ + dp). The theoretical results demonstrated that all the triply bonded RAl☰SbR compounds with small substituents are unstable and can spontaneously rearrange to other doubly bonded isomers. That is, the smaller groups, such as R = F, OH, H, CH3 and SiH3, neither kinetically nor thermodynamically stabilize the triply bonded RAl☰SbR compounds. However, the triply bonded R’Al☰SbR´ molecules that feature bulkier substituents (R´ = SiMe(SitBu3)2, SiiPrDis2, Tbt, and Ar*) are found to possess the global minimum on the singlet potential energy surface and are both kinetically and thermodynamically stable. In particular, the bonding characters of the R’Al☰SbR´ species agree well with the valence-electron bonding model (model) as well as several theoretical analyses (the natural bond orbital, the natural resonance theory, and the charge decomposition analysis). That is to say, R’Al☰SbR´ molecules that feature groups are regarded as R′─Al\nSb─R′. Their theoretical evidence shows that both the electronic and the steric effects of bulkier substituent groups play a decisive role in making triply bonded R′Al☰SbR′ species synthetically accessible and isolable in a stable form.",signatures:"Jia-Syun Lu, Ming-Chung Yang and Ming-Der Su",downloadPdfUrl:"/chapter/pdf-download/61968",previewPdfUrl:"/chapter/pdf-preview/61968",authors:[{id:"199202",title:"Prof.",name:"Ming-Der",surname:"Su",slug:"ming-der-su",fullName:"Ming-Der Su"},{id:"199204",title:"Dr.",name:"Ming-Chung",surname:"Yang",slug:"ming-chung-yang",fullName:"Ming-Chung Yang"},{id:"245576",title:"Mr.",name:"Jia-Syun",surname:"Lu",slug:"jia-syun-lu",fullName:"Jia-Syun Lu"}],corrections:null},{id:"64241",title:"Periodic Trends among Interstellar Molecular Species: The Case of Oxygen- and Sulfur-Containing Species",doi:"10.5772/intechopen.80884",slug:"periodic-trends-among-interstellar-molecular-species-the-case-of-oxygen-and-sulfur-containing-specie",totalDownloads:1179,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Out of the 19 known S-containing interstellar molecules, 16 have the corresponding O-compound analogues marks out of the interstellar chemistry of sulfur and oxygen as a unique one among other observed interstellar periodic trends. However, the rule that the ratio of an interstellar sulfur molecule to its oxygen analogue is close to the cosmic S/O ratio is far from reality in many cases even when both species are observed from the same source. In this chapter, the effect of interstellar hydrogen bonding on the variation of the S/O abundance ratio with respect to the cosmic S/O ratio is investigated using high-level quantum chemical simulations. The detectability of the yet to be observed analogues of both S and O molecules is also examined. From the results, the deviation from the cosmic S/O ratio is largely due to hydrogen bonding on the surface of the dust grains. As the ratio of the binding energy of S- and O-species (binding energy of S/O) with water approaches unity, the S/O abundance ratio approaches cosmic S/O ratio. The more this ratio deviates from unity, the more the S/O abundance deviates from the cosmic S/O ratio. Regarding the detectability of the unknown analogues, it suffices to say that every known O-species is an indication of the presence and detectability of the S-analogue, while for every known S-species, the O-analogue is not only present in detectable abundance, it can be said to have even been overdue for astronomical detection.",signatures:"Etim Emmanuel, Lawal Usman, Khanal Govinda and Mbakara Idaresit",downloadPdfUrl:"/chapter/pdf-download/64241",previewPdfUrl:"/chapter/pdf-preview/64241",authors:[{id:"256167",title:"Dr.",name:"Emmanuel",surname:"Edet Etim",slug:"emmanuel-edet-etim",fullName:"Emmanuel Edet Etim"},{id:"256745",title:"Mr.",name:"Usman",surname:"Lawal",slug:"usman-lawal",fullName:"Usman Lawal"},{id:"257392",title:"Mr.",name:"Govinda",surname:"Khanal",slug:"govinda-khanal",fullName:"Govinda Khanal"},{id:"257393",title:"Ms.",name:"Idaresit",surname:"Mbakara",slug:"idaresit-mbakara",fullName:"Idaresit Mbakara"}],corrections:null},{id:"62661",title:"Mechanism of Interactions of Zinc(II) and Copper(II) Complexes with Small Biomolecules",doi:"10.5772/intechopen.79472",slug:"mechanism-of-interactions-of-zinc-ii-and-copper-ii-complexes-with-small-biomolecules",totalDownloads:2040,totalCrossrefCites:0,totalDimensionsCites:3,hasAltmetrics:0,abstract:"Over the past few decades, transition metal complexes have attracted considerable attention in medicinal inorganic chemistry, especially as synthetic metallonucleases and metal-based anticancer drugs that are able to bind to DNA under physiological conditions. The use of metal-based drugs presents the most important strategy in the development of new anticancer and antimicrobial agents. Negative side effects during treatment (such as vomiting, resistance, nephrotoxicity, ototoxicity, neurotoxicity and cardiotoxicity) prompted researchers to design new classes of DNA and protein targeting metal-based anticancer agents with potential in vitro selectivity and less toxicity. Knowledge of mechanism of the interaction zinc(II) and copper (II) ions with biomolecules and other relevant ligands is essential for understanding the cellular biology of delivery complexes to DNA and proteins. Results obtained from investigations provide useful information for the future design of potential zinc- and copper-based anticancer drugs. Different mechanism of interactions with selected biomolecules compared to platinum-based drugs has been observed.",signatures:"Tanja Soldatović",downloadPdfUrl:"/chapter/pdf-download/62661",previewPdfUrl:"/chapter/pdf-preview/62661",authors:[{id:"256260",title:"Dr.",name:"Tanja",surname:"Soldatovic",slug:"tanja-soldatovic",fullName:"Tanja Soldatovic"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"5891",title:"Descriptive Inorganic Chemistry Researches of Metal Compounds",subtitle:null,isOpenForSubmission:!1,hash:"7201c7d0481358aa6aabe036eb9ff095",slug:"descriptive-inorganic-chemistry-researches-of-metal-compounds",bookSignature:"Takashiro Akitsu",coverURL:"https://cdn.intechopen.com/books/images_new/5891.jpg",editedByType:"Edited by",editors:[{id:"147861",title:"Dr.",name:"Takashiro",surname:"Akitsu",slug:"takashiro-akitsu",fullName:"Takashiro 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Measles is a serious medical problem in Africa, Latin America, Europe, south-east Asia and eastern Mediterranean [1]. During the pre-vaccine era, 130 million measles cases occurred annually worldwide, and it was the leading cause of childhood deaths [2]. In Africa, about 13 million cases and 650,000 deaths occur annually, with sub-Saharan Africa having the highest morbidity and mortality [3]. In 2018, many developing countries reportedly confirmed measles through laboratory testing with high incidence rates. In AFRO region, Liberia confirmed 218 cases with 412.24% incidence rate. Similarly, Libya confirmed 286 cases with 98.84% incidence rate, Burkina Fasso confirmed 567 cases with 84.2% incidence rate and the southern part of the continent was not left out as Uganda confirmed 531 cases in the laboratory with incidence rate of 65.83%. In the Western Pacific region, Philippines confirmed 1677 cases with incidence rate of 118.5% while Malaysia confirmed 1374 cases with incidence rate of 80.35% [4]. In EURO region, Albania confirmed 1290 cases with incidence rate of 477.05%, Georgia reported 1091 laboratory confirmed cases with 374.74% incidence rate and Kyrgyzstan confirmed 376 cases in the laboratory with 75.22% incidence rate. In EMRO, Afghanistan reported 1846 laboratory confirmed cases with 62.64% incidence rate, Saudi Arabia reported 833 laboratory confirmed cases with 29.99% and 793 laboratory confirmed cases in Yemen with incidence rate of 344.36%. Venezuela in AMRO confirmed 5525 cases in the laboratory with an incidence rate of 23.03% [4].
\nDespite the comprehensive WHO and United Nations International Children Emergency Fund’s (UNICEF’s) measles-reduction strategy, and partnership of international organizations for measles mortality reduction, certain countries continue to face recurrent epidemics [5]. The optimal age for infantile measles vaccination is an important since maternal antibodies may neutralize the vaccine antigen before specific immune response develops. Delaying vaccination on the other hand may increase risk of complicated disease [6]. Measles vaccine effectiveness is 84% when administered at 9–11 months of age and 93% when given at ≥12 months of age [7]. First dose of measles-containing vaccine (MCV1) given at 9 months of age was introduced into the Expanded Programme on Immunization (EPI) in 1977 [8]. Since >93–95% population immunity is required to prevent measles epidemics, the WHO recommends all children receive two doses of measles vaccine [9]. In Nigeria just like in many developing countries, children are given monovalent measles vaccine at 9 months of age in the EPI [10]. In 2010 and continuing through 2014, DRC experienced the largest nationwide measles outbreak in Africa [11, 12, 13]. DRC is a key country for regional elimination efforts because of its large population, central location with nine international borders, and persistent reservoir of circulating measles viruses [14]. The Reaching Every District (RED) approach to strengthening immunization services has been implemented beginning in some developing countries like Democratic Republic of Congo (DRC). A second opportunity for measles vaccination, nationwide measles supplementary immunization activities (SIAs) using a phased approach intended to cover the country every 3 years [15].
\nFollowing a successful polio laboratory platform, The Global Measles and Rubella Laboratory Network (GMRLN) was developed. As at 2018, there are presently 723 laboratories established in 164 countries. It was proposed that in all districts in WHO AFRO surveillance performance should target ≥2 cases of non-measles febrile rash illness per 100,000 population and ≥1 suspected measles case investigated with blood specimens in ≥80% of districts [16]. Case-based surveillance with laboratory confirmation of suspected measles cases is in place in many developing countries. Integrated Disease Surveillance and Response (IDSR) was established for aggregate reporting of 18 infectious diseases, including measles. Through the IDSR, aggregate numbers of suspected measles cases and deaths are reported weekly from districts to national level. Through measles case-based surveillance, suspected measles cases were investigated using case investigation form and laboratory testing of blood specimen. Specimens are tested using standard enzyme-linked immunosorbent assays for measles-specific immunoglobulin M (IgM) antibodies. Suspected measles case was defined as an illness with maculopapular rash and fever and one or more symptoms of cough, coryza or conjunctivitis, or where clinician suspects measles. Laboratory-confirmed measles case on the other hand is defined as suspected measles case with positive laboratory test result for measles specific IgM in the absence of measles vaccination within 30 days of specimen collection. An epidemiologically-linked case is suspected measles case having contact (or living in same district) with laboratory-confirmed measles case whose rash onset was within preceding 30 days. Clinically-compatible case is suspected measles case without laboratory test result or established epidemiological link. PCR detection is carried out in specific laboratories with technology for confirm hemagglutinin (H) and nucleoprotein (NP) gene of measles virus.
\nMeasles virus is monotypic; however, genetic variations occur in the H and NP genes. Currently, the WHO recognizes 8 clades, A-H which consists of 24 genotypes and an additional provisional genotype, D11. Clades B, C, D, G and H each contain multiple genotypes (B1-3, C1-2, D1-10, G1-3 and H1-2) while clades A, E and F each contain single genotype (A, E and F) respectively [17, 18]. Epidemiological findings reveal circulation of several genotypes in Africa. Genotype A has been detected in South America, parts of China and South Africa over the last 40 years [19], and recently in a 3 year old child in Nigeria West Africa [20]. The most endemic genotype circulating in Africa is B3. Studies have shown clade B to be endemic in sub-Saharan Africa [21] with B3 genotype reported in Ghana, Gambia, Nigeria, Libya and Tunisia [20, 22, 23]. The measles viruses isolated in 1983 from Yaoundé, Cameroon, were designated as B1 genotype. However, in 2001 viruses belonging to B3 genotype were found in the country. B3 genotype has been reported in the Gambia. The B3 genotype (2001) in Cameroon were related to B3.1 subgroup, whereas the Gambian (1993) isolates corresponded to B3.2 subgroup. Geographical distribution for period 1993–2001 of these two viruses shows that B3.1 is found from Sudan to Nigeria and Ghana extending to Cameroon, whereas B3.2 genotype is found in West Africa. In Nigeria and Ghana, the viruses co-circulate [3, 14]. Nucleotide sequence analysis show strains from Senegal clustered in B3.1 and B3.3 sub-genotypes. Measles virus detected in Tunisia and Libya from 2002 to 2009 belonged to genotype B3. Viruses isolated from 2002 to 2007 and 2009 were subtype B3.1. Seven of isolates during 2008 and 2009 epidemic were divergent from the B3 isolates and can represent a new subtype of genotype B3 [21]. B3 strain circulates in Addis Ababa, Bahir Dar and possibly elsewhere in Ethiopia [24]. In a 2014 outbreak among refugees from Central African Republic in Cameroon, the genotype B3 found were similar to those circulating in Northern Cameroon in 2010–2011 [25]. Clade B viruses is reported to be endemic in central and western parts of sub-Saharan Africa while genotypes D2 and D4 has been continually detected in southern and eastern parts of Africa. D10 in Uganda is represented by Clade MVi/Kampala.UGA/51.00.1 with accession number AY923185.1. Genotype C2 is found to circulate widely in northern Africa [17, 26, 27, 28].
\nMeasles is characterized by fever of 38°C or more; maculopapular rash of 3 days or more; with one or combination of coryza, cough, conjunctivitis and Koplik spots in the oral mucosa of measles’ victims [29]. Mortality rates can exceed 10% in parts of the developing world. Sequela of measles includes giant cell pneumonia, inclusion body encephalitis and sub-acute sclerosing pan encephalitis [SSPE] [30]. A study carried out in the largest children’s hospital in Ibadan-Nigeria in West Africa observed several complications ranging from bronchopneumonia (60%), heart failure (12%), gastroenteritis (11%), protein losing malnutrition (8%), encephalitis (5%), croup (2%) and dehydration (2%) [10], whereas bacterial complication is the usual cause of death when measles kills malnourished children [31].
\nAfter routine and catch-up vaccinations in 2005 and 2006, as well as follow-up vaccination by 2008 in Nigeria, remarkable level of protection was observed in children. This is attributed to immunological dynamics which is an after-effect of these campaigns [32]. Herd immunity varies between heterogeneous populations in developing countries. Nigeria is the most populous country in Africa with a population of over 160million. In an assessment of immune status carried out in 2014, herd immunity against measles was 66.8% in Kano State and 73.0% in Ibadan, Oyo State. These are two largely different populations in the north and southern respectively [33]. When history of measles was compared with level of immunity, a significant association was observed between those who had measles and who had protective immunity. There was strong correlation between malnutrition and immune level, a lot of malnourished children who were vaccinated were not protected [33].
\nStrategies based on vaccination program have been implemented in order to reduce measles mortality. In 2008, countries in the WHO African Region adopted measles pre-elimination goal to be achieved by the end of 2012. Target was to achieve >98% reduction in estimated regional measles mortality. The goal was to have national measles incidence of <5 cases per 1,000,000 population per year, achieve >90% national coverage with MCV1 with >80% MCV1 coverage target. For SIAs, MCV coverage >95% was targeted in all districts [16]. In the WHO regions, highest percentage of reduction was in Eastern Mediterranean (90%) and African (89%) regions, accounting for 16 and 63% of global reduction [34, 35]. Relatively high measles vaccination in southern Nigeria in West Africa can be attributed to high level of literacy and awareness created by free use of mass media to disseminate information on vaccination activities, without fear of intimidation [33]. The Global Vaccine Action Plan (GVAP) set out a target of reaching 80% coverage with all vaccines including measles vaccine in all districts by 2020 [36]. Health policy decision-making based on spatially heterogeneous vaccination has resulted in shift from pursuing coverage targets at national-level to ensuring high coverage levels evenly distributed across provinces or districts [37]. While this likely represents a more effective strategy over targeting country-level goals, administrative area summaries may still mask important geographical inequities in coverage [38].
\nVaccination history of children is not documented in hospital’s records because many people do not properly keep children’s/wards’ vaccination records. This is coupled with high illiteracy level found in many developing countries [32]. Many people present as emergencies upon admission, at which point their parents cared less about vaccination status because they were overwhelmed by anxiety. There is need for enhanced comprehensive national vaccination campaigns with intense community engagement and diligent health workers including large number of ad-hoc staff. Weak government support across all levels is responsible for poor surveillance activities hence, their inability to detect new cases. Awareness creation should be intensified to inform concerned citizens about the essence and time of vaccination.
\nAbility to produce vaccines is a major setback for developing countries. Japan International Cooperation Agency (JICA) is currently supporting transfer of a Measles-Rubella vaccine manufacturing technology to Polyvac® in Vietnam, following the precedent set by multiple previous successful projects. Transfer of an oral polio vaccine (OPV) technology from Biken Co., Ltd. to Bio Farma in Indonesia was pivotal in the global polio eradication efforts. JICA supports UNICEF supply of vaccine cold chain equipment to India, Afghanistan, Angola, Liberia, Zambia and Zimbabwe which has significantly overcome the problem of vaccine failure resulting from inability of most immunization officers to maintain cold chain in remote areas.
\nGovernment bodies responsible for ensuring safety and effectiveness of vaccines face serious challenges when protecting the public from harm once the products are used in uncontrolled, real world context [39, 40, 41]. Regulations have been moving towards an approach that takes into account the full lifecycle of the vaccine. While this shift has been very slow in countries like Canada, there have been further calls for changes on how regulators safeguard public health and public healthcare resources [42]. This approaches are a far cry from the reality on ground in developing countries, because they utilize whatever vaccines are supplied by donor agencies or vendors who have passed through government’s registration processes.
\nMost countries grapple with unreliable immunization service funding. But in spite of active measles vaccination efforts in several developing countries, re-emergence of measles continues to occur [33]. An interplay of several factors affect immunization. These factors include break in cold-chain of measles vaccine due to long distance to vaccination centers, history of measles, intercurrent infections and malnutrition. In both developing and industrialized countries, loss of public confidence in vaccine due to real or spurious links to adverse events can curtail or even halt immunization activities. This is similar to reports about polio vaccine laced with sterilizing agents which led to decline in vaccination uptake in northern Nigeria. Despite the scientific evidence refuting links between the measles-mumps-rubella (MMR) vaccine and autism, there has been decline in coverage in some countries as a result of this. Measles is making a comeback in several industrialized countries, including Austria, Italy and the United Kingdom. This can be attributed to presence of migrants and refugees from developing countries especially those who are biased against vaccines in light spurious or religious sentiments.
\nMasking of geographical inequalities in vaccination because of poor administrative summaries is a big problem. Spatial clustering of unvaccinated children sustains disease transmission, even when high overall vaccination coverage is achieved. Continued measles virus circulation occurs as a result of missing age cohorts during routine vaccination. Access to high quality vaccines is important however, there is limited expertise to review technical product information in vaccine regulatory dossiers hence the inability to effectively register and supply vaccines in many developing countries. They lack appropriate expertise and certified personnel to perform good manufacturing practice (GMP) inspections leading to lengthy registration/review process and delays in vaccine registration even in emergency situations. Worrisome is the fact that there is limited compliance with good clinical practice standards for some clinical trials. Therefore, improving vaccine supply chain in developing countries is very important. A review of existing data shows freeze exposure occurred in 18–67% of vaccine shipments throughout various stages of storage. Also, heat denatures vaccines when cold chain is not maintained. Such may reduce vaccine potency, ultimately supplying potentially less-effective vaccines.
\nThe developing countries vaccine manufacturers’ network (DCVMN) is a public health driven, international alliance of manufacturers trying to strengthen vaccine supply through information and professional training programs, technology improvements, innovative vaccine research and development, encouraging transfer initiatives, to improve availability of safe, effective and affordable vaccines. Three goals were proposed for vaccines. First, to ensure uninterrupted supply of affordable and suitable vaccines for GAVI. Second, improve market dynamics information and expertise to solve vaccine access challenges. Third, strengthening global health and manufacturers’ partnerships to enable better alignment of goals, alignment with global strategy and coordination of internal investments [43].
\nCivil unrest is common in developing countries and this has led to migration of millions of people. There is increased movement by land, air and sea. In Northern Nigeria, activities of Boko Haram terrorist have caused several families to abandon their homelands and converge on Internally Displaced Peoples camps where health care services are poor and even non-existent in some cases. Many children are born in these camps, but vaccination activities may not be sustained at the desired national vaccination level. Wars and famines or other natural disasters increase mortality due to measles. In 2000, measles was responsible for 22% of deaths in children less than 5 years of age and 17% of deaths in children aged 5–14 years in Ethiopia [44]. Increased air travel by people within some regions in developing countries has been reported. For local flights, cabin air flow may not be as reliable a barrier to the spread of measles virus. Several measles reports, including index cases and apparent secondary cases on flights, have been reported in which transmission on board the aircraft appeared likely and which included seating information for both index (primary) and secondary case [45].
\nRegulations for safety and effectiveness of vaccines in the uncontrolled, real world context should be strengthened in developing countries. Perhaps the set of ethical considerations when fully operational in developed countries will be applied to them also. The World Health Assembly established 3 milestones towards eradication of measles. They intend to increase routine coverage with MCV1 by more than 90% nationally and more than 80% in every district; reduce and maintain annual measles incidence to less than 5 cases per million; and reduce estimated measles mortality by more than 95%. Based on current trends of measles vaccination coverage and incidence, and report of the strategic review, the WHO Strategic Advisory Group of Experts on Immunization (SAGE) concluded that the 2015 global milestones and measles elimination goals were not achieved because immunization coverage gaps exist. SAGE recommended focus on improving immunization and surveillance systems to ensure gains made thus far in measles control can be sustained. The situation in developing countries requires serious attention and strict compliance by stakeholders to ensure goals are met.
\nWe declare that there is no conflict of interest.
Keratinocytes are the principal epidermal cells constituting the outermost layer of the skin—the external and largest organ of the human body. They are immunologically active in that they produce various cytokines and chemokines, stimulating dendritic cells and lymphocytes to trigger inflammatory skin diseases, as well as they respond to cytokines produced from immune cells to establish skin lesions of inflammatory skin diseases, such as psoriasis and atopic dermatitis. They are also very efficient in avoiding harsh environmental assaults, such as chemical, mechanical, radiological, and microbial insults. The keratinocytes protect the dermal homeostasis by having a constant turnover whereby the basal (inner) layer differentiates into the cornified (outer) layer. Thus, they form a constant and perfect outer barrier to the inner dermal layers and the body. They also form a rigid mechanical barrier by cornification—constructing a brick-and-mortar type of structure with cornified cells and lipids, the defects in either of which cause hereditary skin disorders upon mutation. They also secrete various antimicrobial peptides, such as cathelicidin, psoriasin, defensin, and many S100 proteins, to protect the skin from infection. The nuclei of keratinocytes contain various alarmins, such as HMGB1, IL-33, and IL-1alpha, which can induce rapid and strong inflammation upon injury, but also can get promptly inactivated by the enzymes present in the inflammatory environment. However, malfunctioning of the keratinocytes at its immunological level or at a genetic/protein level can lead to pathological conditions such as psoriasis, atopic dermatitis, and hereditary skin disorders.
Keratinocytes, as the main component of outermost epidermal layer, should provoke and at the same time stop inflammation at appropriate time points to maintain a stable and healthy condition of not only the skin, but also the entire body. Keratinocytes harbor anti-inflammatory properties more than other types of cells do, such as lymphocytes, macrophages, and dendritic cells, as keratinocytes are always exposed to environmental insults. The mechanism of developing inflammatory conditions has been intensely investigated; however, the mechanism of ceasing inflammation has not been fully investigated. I speculate that a novel approach to maintaining healthy conditions would be unraveled when the mechanism of sequestrating inflammation is investigated and that epidermal keratinocytes are good candidates to investigate these mechanisms because they present pro- and anti-inflammatory properties in vivo and in vitro.
In this chapter, various cutaneous disorders have been discussed with emphasis on keratinocyte function and roles in pathogenesis. We have surveyed PubMed with each disease name, picked up the original literature with pivotal findings, reviewed articles covering the related area of interest, and wrote this chapter.
Epidermal keratinocytes form a stratified epithelium, consisting of basal, spinous, granular, and cornified layers starting from the dermal side. Epidermal keratinocytes exert their functions through structural components such as actin, microtubules, keratin filaments, desmosomes, hemidesmosomes, tight junctions, and adherence junctions; their motility, proliferation, and cytokine production being controlled by these structural proteins. Epidermal keratinocytes gradually differentiate through the layers—from the basal, spinous, and granular, ultimately to the cornified cell layer. They demonstrate various characteristic features owing to their differential function and according to their differentiation state, which are sometimes more complex than those of simple epithelial cells constituting the digestive tract and glands [1].
The primary and most important function of epidermal keratinocytes is their role as a physical barrier of the skin, in addition to their role as a responder to the external stimuli. The cornified cells, together with inter-cornified cell lipids, form cornified cell barriers to protect the inner body from harsh external environmental stimuli. The cornified cells, upon catalysis by transglutaminase 1, form a cornified cell envelope—a strong structure composed of filaggrin that aggregates keratin filaments, with various protein components such as involucrin, loricrin, SPR, and desmosomal proteins. Defects in the enzymes and protein components essential in forming cornified cell envelopes cause skin barrier dysfunction, resulting in skin disorders [2, 3].
Recent findings have revealed that some patients with atopic dermatitis (AD) harbor loss-of-function mutations in the filaggrin gene, resulting in severe skin barrier defects. Ichthyosis vulgaris (IV) is also caused by mutations in the filaggrin gene, but patients with this mutation develop either AD, IV, or both, indicating that mutations in the filaggrin gene alone are not enough to determine the phenotypes [4, 5, 6, 7]. Mutations in the transglutaminase 1 gene and other genes important in the cornification processes, such as ATP-binding cassette subfamily A member 12 (ABCA12), and arachidonate 12-lipoxygenase 12 s type (ALOX12), cause hereditary ichthyosis, also known as acquired recessive congenital ichthyosis [8]. Connexin is a component of the gap junction, and mutation in gap junction protein beta 3 (GJB3) gene, which encodes connexin (Cx31) causes erythrokeratodermia variabilis, in which inflammatory erythematous eruptions with hyperkeratinization gradually changes its form [9]. Mutations in the loricrin gene cause loricrin keratoderma, with characteristic finger constriction ring formation or congenital ichthyosiform erythroderma [10, 11].
Steroid sulfatase is an enzyme that catalyzes the degradation of cholesterol sulfate, a molecule that functions in the attachment of cornified cells. The mutation in its gene causes X-lined ichthyosis, with retarded detachment of cornified cells, termed as retention hyperkeratosis. Point mutations result in typical skin manifestations; whereas, mutations spanning bigger lengths of this gene involving the surrounding genomic region are accompanied by other syndromic symptoms, such as mental retardation, short stature, and epilepsy [12].
Some hereditary keratinizing disorders are accompanied by syndromic symptoms other than skin manifestations. Mutations in GJB2 gene, encoding Cx26, cause KID syndrome—with keratitis, ichthyosis, and deafness as triads, exhibiting papillomatous and spinous keratotic eruptions on the face and extremities, and with palmoplantar keratoderma and alopecia [13]. Mutation in the serine protease inhibitor SPINK5 causes Netherton syndrome, with atopic dermatitis-like skin eruptions, characteristic ichthyosis linearis circumflexa and bamboo hair [14]. Sjogren-Larsson syndrome is caused by a mutation in the fatty aldehyde dehydrogenase (ALDH3A2) gene, with clinical symptoms including ichthyosis, spastic limb paralysis, and mental retardation [15]. Figures 1 and 2 shows skin manifestations of several hereditary skin disorders. Table 1 shows a summary of the types of ichthyosis and their accompanying gene mutations.
Characteristic skin manifestation in hereditary skin disorders with mutation in genes expressed in keratinocytes. a) Bulla formation on the foot of a child having epidermolysis bullosa simplex (EBS) and with mutation in the
Ichthyosis vulgaris | AD | FLG | |
X-linked ichthyosis | XR | STS | |
Harlequin ichthyosis | AR | ABCA12 | |
Lamellar ichthyosis | AR | TGM1; NIPAL4; ALOX12B; ABCA12 | |
Congenital ichthyosiform erythroderma | AR | ALOXE3; ALOX12B; ABCA12; NIPAL4; TGM1 CYP4F22 | |
Epidermolytic ichthyosis | AD | KRT1; KRT10 | |
Superficial epidermolytic ichthyosis | AD | KRT2 | |
Loricrin keratoderma | AD | LOR | |
X-linked ichthyosis syndromic presentation | XR | STS and others | |
FPAP syndrome | XR | MBTPS2 | |
Netherton syndrome | AR | SPINK5 | |
Sjogren Larsson syndrome | AR | ALDH3A2 | |
Refsum syndrome | AR | PHYH; PEX7 | |
Gaucher syndrome II | AR | GBA | |
KID syndrome | AD | GJB2; GJB6 |
Representative non-syndromic and syndromic ichthyosis with causative genes. Modified citation from Ref. [3].
Keratins are the main intermediate filaments of epidermal keratinocytes. The keratin family consists of more than 50 members; acidic keratin and basic keratin monomers pair to form heterodimers, which are then organized into tetramers with an anti-parallel alignment. Tetramers of keratins are stored at the peripheral boundaries of cells for filament formation when needed. Lateral and longitudinal aggregations of these tetramers and octamers form keratin filaments. Local pH, osmotic conditions, and phosphorylation status are thought to be the driving forces of filament formation [16].
Simple epithelia consist of simple epithelial keratins, such as K8, K18, and K19. Basal cells of the simple and stratified epithelia express K5 and K14, while the suprabasal cells express K1 and K10 in the interfollicular epidermis, K3 and K12 in the corneal epithelium, K4 and K13 in the esophageal epithelium, and K6 and K16 in the oral epithelium. The follicular epidermis and palmoplantar epidermis express K6, K16, and K17. Their expression is tightly controlled by transcription factors in a differentiation- and localization-dependent manner.
Mutations in keratin genes cause various hereditary skin disorders [17]. Mutations either in
Characteristic skin manifestation and electron microscopic findings of genetic skin disorders. a) Clinical manifestation of X-liked ichthyosis (XI) patient, b) histopathology with hematoxylin and eosin staining, c) electron microscopic features in patients with XI and deletion in
Adherence machinery is indispensable for controlling keratinocyte cell motility, proliferation, and viability, as well as the epidermal barrier function by controlling cell attachment and cell tension. Keratinocytes have six major adherence mechanisms [23, 24]: 1) Hemidesmosomes, which connect basal keratinocytes to the dermal component, with cytoskeletal molecules such as keratins, 2) desmosomes, which connect neighboring keratinocytes, sustain the epidermal sheet structure and maintain tension by connecting to cytoskeletal molecules, such as keratins, 3) Adherence junctions, which control keratinocyte motility by connecting intracellular actin to E-cadherin in the adherence junctions to neighboring keratinocytes [25], 4) Gap junctions, which also have ion-transporter functions, indirectly control keratinocyte barrier function, 5) Tight junctions, which control the liquid interface in epithelia and consist of claudins and occludins [26], and 6) Focal adhesion—attachment of plaques connecting cells to the extracellular matrix, thereby, making connections to scaffolds to maintain the keratinocyte motility, proliferation, and viability.
Hemidesmosomal proteins are indispensable for maintaining normal dermal-epidermal structures (Figure 3) [27, 28]. Mutations in hemidesmosomal protein genes, such as integrin alpha 6 or beta 4, cause junctional epidermolysis bullosa [29]. Mutations in plectin, a constituent of desmosomes and hemidesmosomes, cause junctional type epidermolysis bullosa with pyloric atresia [30]. Collagen type VII localizes from just beneath lamina densa to support attachment of lamina densa to the dermal structure. Mutations in the collagen type VII gene cause dystrophic epidermolysis bullosa with prominent skin ulcer and scar formation [31, 32]. These severe EBs usually occur in patients with homozygous mutation or compound heterozygous mutations. A heterozygous mutation, the same mutation but which harbors on only one allele of the gene, causes a milder form of EB, leading to the development of nodular prurigo-like lesions or scar formations in autosomal dominant type dystrophic EB or development of palmoplantar keratoderma with alopecia and dental deformation in autosomal dominant type junctional EB. A recent study revealed that mutations in desmoplakin cause lethal acantholytic epidermolysis bullosa [33].
The structure of hemidesmosome. a) Electron microscopy of hemidesmosomes and basal lamina of a normal human subject. b) Schematic view of a hemidesmosome structure. Plectin forms a platform where keratin filaments and hemidesmosomal proteins bind, crosslinking keratin filaments with integrin beta4. Transmembrane protein bullous pemphigoid antigen 1 (BP180) connects hemidesmosomes to laminin 332, a component of the lamina densa. Bullous pemphigoid antigen 2 (BP230) is an intra-cytoplasmic protein that composes the hemidesmosome from inside the cells.
Atopic dermatitis patients present decreased filaggrin and ceramide contents in their cornified layers, along with decreased skin barrier function [34]. This dysfunctional barrier allows allergens to penetrate the skin, thus, resulting in sensitization to environmental allergens [35]. Peanut allergies are often observed in infants of families that consume large amounts of peanut and have detectable levels of peanut debris in the surrounding environment [36]. Exercise-induced food allergy also develops in relation to filaggrin mutation [37]. A previous study has shown that infants with frequent emollient hydration of skin showed a lower rate of bronchial asthma development compared to babies without emollient hydration of skin, indicating the importance of the skin barrier functioning in maintaining overall health and stable homeostasis [38]. Figure 4 illustrates the epidermal structure with barrier proteins.
Mutations in filaggrin and protease inhibitors can cause atopic dermatitis. Netherton syndrome is caused by a mutation in the serine protease inhibitor KAZAL type5 (
Lipid abnormalities could be another cause of atopic dermatitis, demonstrating the skin barrier dysfunction. A decrease in ceramide content of the cornified layer has been demonstrated in patients with atopic dermatitis, which is another cause of skin barrier dysfunction [42]. Ceramide constitutes almost 50% of the lipids in the corneal layer and is indispensable for skin barrier function. Mutations in genes involved in lipid metabolism are not known in atopic dermatitis, but gene metabolic diseases, such as Gauche disease and Nieman-Pick disease that are characterized by mutations in the glucocerebrosidase and sphingomyelin phosphodiesterase 1 gene, respectively, which are indispensable in ceramide synthesis, resulting in development of atopic dermatitis-like skin eruptions from early childhood. Abnormalities in lipid metabolism could be another cause of atopic dermatitis, which requires further investigation [43].
Skin barrier function is affected not only by genetic conditions but also by ordinary routines of daily life. People who often scrub too much during bathing, bathe for a long time period or very frequently, and especially those who scrub their skin with nylon towels or scrubbing brushes show very dry skin with small scales all over the body. These individuals often complain of severe itching, especially after bathing, often resulting in eczema development. Excessive use of detergent also causes barrier disruption by increasing the pH of the skin, resulting in enhanced enzymatic activity of proteinases in the cornified layers [44]. These lifestyle routines would exacerbate eczematous changes in individuals having a genetic predisposition that makes them more susceptible to barrier disruption.
Keratinocytes form not only mechanical barriers but also chemical or immunological barriers for humans. They express several antimicrobial peptides, such as cathelicidin, defensin, psoriasin, and various S100 proteins. These antimicrobial peptides prevent pathogenic microbes from colonizing the skin surface, thus conferring resistance to microbial infections [45]. Certain conditions such as atopic dermatitis have decreased production of antimicrobial peptides, leaving the individuals more susceptible to bacterial or viral infections through the skin [46, 47]. Filaggrin mutations are at times the direct cause of barrier disruption, but T helper (Th)2-skewed immune conditions can be another cause too, as Th2 type cytokines cause a less differentiated state of keratinocytes thus resulting in lower production of antimicrobial molecules and barrier proteins [48]. Mutations in filaggrin also cause ichthyosis vulgaris, which often co-exists in atopic dermatitis patients. However, not all patients with atopic dermatitis have ichthyosis vulgaris and vice versa, even in the presence of filaggrin gene mutations [7]. Thus, the filaggrin mutation alone cannot explain the pathogenesis of atopic dermatitis.
The structure of epidermis and its adhesion molecules. a) Schematic view of epidermis structure and its adhesion molecules. Basal keratinocytes attach to basement membrane through hemidesmosomes, having keratins such as
Psoriasis is another major inflammatory skin disorder that shows hyperproduction of antimicrobial peptides in the epidermis induced by skewed Th17 populations thus making patients resistant to skin infections [49, 50]. Cathelicidin—one of the antimicrobial peptides, complexes with self RNA or DNA to induce the activation of myeloid dendritic cells and plasmacytoid dendritic cells, respectively. This activation further triggers psoriatic inflammation, thus creating a positive feedback loop in pathogenesis of psoriasis [51, 52]. Recent advancements in translational research produced many “biologics”, which target inflammatory cytokines, such as IL-17, TNF, and IL-23, as a treatment option for psoriasis. These include anti-TNF antibodies (adalimumab [53], infliximab [54], certolizumab-pegol [55]), anti-IL-17 antibodies (secukinumab [56, 57], ixekizumab [58], brodalumab [59], bimekizumab [60]), anti-IL-12/23p40 antibody (ustekinumab [61, 62]), and anti-IL-23p19 antibodies (guselkumab [63], risankizumab [64, 65], thildrakizumab [66, 67, 68, 69]). Janus kinases (JAKs) are important intracellular signaling molecules downstream of cytokine receptors [70]. They are also deeply involved in inflammation in psoriasis, and JAK inhibitors have been developed as therapeutic options in psoriasis [71, 72, 73, 74, 75, 76].
Ichthyosis has also been shown to have a Th17-skewed immune balance [77], and Th17 is a potent inducer of antifungal immunity. However, ichthyosis patients often develop cutaneous superficial fungal infections [78, 79]. Taken together, this suggests that the immune imbalance by itself cannot explain the susceptibility to fungal infections, meanwhile also implicating the importance of proper functioning of the skin barrier to avoid superficial fungal infections.
As a barrier, keratinocytes respond to emergency conditions by releasing danger-associated molecular patterns (DAMPs) when acutely injured. IL-33 is one such emergency molecule, which resides in the nucleus in a steady-state, but is released when cells undergo necrosis to stimulate immune reactions [80]. IL-33 is a relatively recently identified member of the IL-1 family and functions mainly as a pro-inflammatory molecule, although under certain conditions, it can also work as an anti-inflammatory molecule. IL-1 alpha—the prototype of IL-1 family members, was identified as an alarmin several decades ago. The Koebner phenomenon in psoriasis is attributed to the release of IL-1 alpha from damaged keratinocytes, which induces psoriasis in regions after skin injury [81]. IL-1 alpha is an interesting cytokine that mainly functions as a soluble cytokine, but also shows a nuclear presence. It has been reported that IL-1 alpha repeatedly travels between the cytoplasm and nucleus, and is released into the extracellular space upon cell damage to provoke inflammation [82]. IL-33 has similar characteristics in that it resides in the nucleus too, is released during cell necrosis, and induces inflammation. IL-33, similar to IL-1 beta, is produced as a full-length pro-form. IL-33 pro-form is active, but even more, activated when digested by neutrophil elastases or cathepsin. It is, however, inactivated when digested by caspases, unlike IL-1 beta, which is activated by caspases during activation of NRLP3 inflammasomes. ST2L—a receptor of IL-33, is expressed on Th2 cells, group 2 innate lymphoid cells, and regulatory T cells, and its soluble form—sST2, blocks the interaction of IL-33 with ST2L [83].
IL-33 exhibits both pro-inflammatory and anti-inflammatory roles. As a Th2 cytokine, it stimulates ST2L-expressing cells, including mast cells, Th2, and ILC2 cells. This enhances Th2 type inflammation by inducing expression of Th2 type cytokines, such as IL-5 and IL-13. However, upon Th1 or Th17 activation, IL-33 may attenuate pathological conditions by skewing Th2 type inflammation. The graft versus host disease (GVHD) reaction [84] was reported to be attenuated by IL-33, and experimental autoimmune encephalomyelitis showed reduction in response to IL-33 action [85]. Graft rejection in heart transplantation was reported to be attenuated by treatment with IL-33 [86]. IL-33, by inducing regulatory T cell function, was shown to induce immunosuppression [87]. UVB-induced immunosuppression too has been shown to be attributed with IL-33 [87]. Immune dysregulation in coronavirus infection is hypothesized to be caused by the IL-1 family member of cytokines [88]. IL-33 has also been shown to induce neutrophilic infiltration in several animal models and disease conditions, which may be interpreted as a pro-inflammatory effect [89].
IL-33 has dual nuclear and soluble cytokine forms. Nuclear IL-33 functions as a transcriptional regulator. In acute wound healing processes, IL-33 functions by attenuating inflammation by affecting the NF kappa B activity and enhancing wound healing [90]. On the other hand, IL-33 as a cytokine enhances immune reactions in decubitus ulcer models (unpublished). Both IL-33 and IL-1 alpha, when in the nucleus, bind to chromatin and are not released easily, thus, forming a reservoir for inflammatory signals. The regulation of nuclear or cytoplasmic localization of IL-33 is not clear but maybe dependent on its nuclear localization signal. Tsuda et al. [91] revealed that there are several different forms of splice variants of naturally occurring IL-33, of which expression is regulated by distinct promoters [92]. These splice variants should have distinct roles, which could regulate the pro- or anti-inflammatory properties of IL-33.
In the steady-state, keratinocytes should remain silent as a constitutively active state could result in excessive inflammation, which in turn can harm the overall human health. Cultured keratinocytes usually require higher concentrations of cytokines to provoke inflammatory signals; for example, keratinocytes need TNF in the range of several ng/ml to produce inflammatory cytokines, while dendritic cells or lymphocytes require only several pg/ml of the same cytokine to produce an inflammatory effect to the same or even a greater extent [93, 94]. Keratinocytes by differentiating to cornified cells become resistant to environmental stimuli, such as UVB; i.e., they usually respond sensitively to UVB in monolayer culture, but they become resistant to UVB stimulation when they differentiate in 3D-culture [95]. Some chemokines, such as MIP3 alpha/CCL20 are produced more in suprabasal cells than from basal cells [96], but production of IL-1 receptor antagonist is enhanced when keratinocytes are differentiated [97], which may result in attenuation of inflammatory response in differentiated keratinocytes. IL-33 and IL-1 alpha, more clearly expressed in suprabasal cells [98], when in the nucleus bind to chromatin not to be released easily, thus forming the reservoir for inflammatory signals.
Epidermal keratinocytes protect humans from the outer environment by forming an efficient mechanical, chemical, and antimicrobial barrier. Mutations in various molecules present in the keratinocyte can cause hereditary disorders. The keratinocyte structure is maintained by many structural molecules, including keratins, actin, microtubules, and associated proteins and adhesion molecules. The barrier function depends on these structural molecules, as well as other antimicrobial and immunological components, such as infiltrating or resident immune cells, such as lymphocytes, dendritic cells, and macrophages. At the same time, keratinocytes are resistant to stimulation in comparison to other cell types, such as lymphocytes and dendritic cells, as shown in some pieces of literature that they respond to the same stimuli with much fewer attitudes compared to immune cells. IL-33, an alarmin released during insults into the skin, works as an alarmin to provoke inflammation, but at the same time often attenuates inflammation by activating regulatory T cells and skewing Th2 mediated inflammation. This relative unresponsiveness and dual-faced character with pro- and anti-inflammatory properties would be the characteristics of keratinocytes, which cover the entire body by facing environmental stimuli all the time. Thus, the differentiation and structural characteristics of epidermal keratinocytes prevent the skin from hypersensitivity to environmental stimuli.
The mechanism of developing inflammatory conditions has been intensively investigated, but the mechanism by which the inflammation status returns to the steady-state, or how inflammatory status remains under control to prevent excessive inflammation in healthy humans has not been fully investigated.
A novel approach to maintaining healthy conditions would be unraveled when the mechanism of sequestrating inflammation and returning to normal steady-state condition is investigated. Epidermal keratinocytes are good candidates to investigate these mechanisms because they present both pro- and anti-inflammatory properties in vivo and in vitro.
I thank all the members of our department for participating in clinical and basic research on patients.
The authors declare no conflict of interest.
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\\n\\nTERMINATION
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\\n\\nNo partnership: Nothing in this Publication Agreement is intended to, or shall be deemed to, establish or create any partnership or joint venture or the relationship of principal and agent or employer and employee between IntechOpen and the Author or any Co-Author, nor authorize any party to make or enter into any commitments for, or on behalf of, any other party.
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\n\nCORRESPONDING AUTHOR'S GRANT OF RIGHTS
\n\nSubject to the following Article, the Author grants to IntechOpen, during the full term of copyright, and any extensions or renewals of that term, the following:
\n\nThe foregoing licenses shall survive the expiry or termination of this Publication Agreement for any reason.
\n\nThe Author, on his or her own behalf and on behalf of any of the Co-Authors, reserves the following rights in the Work but agrees not to exercise them in such a way as to adversely affect IntechOpen's ability to utilize the full benefit of this Publication Agreement: (i) reprographic rights worldwide, other than those which subsist in the typographical arrangement of the Work as published by IntechOpen; and (ii) public lending rights arising under the Public Lending Right Act 1979, as amended from time to time, and any similar rights arising in any part of the world.
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\n\nSubject to the license granted above, the Author and Co-Authors retain patent, trademark and other intellectual property rights to the Work.
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\n\nThe Author shall respect confidentiality during and after the termination of this Agreement. The information contained in all correspondence and documents as part of the publishing activity between IntechOpen and the Author and Co-Authors are confidential and are intended only for the recipients. The contents of any communication may not be disclosed publicly and are not intended for unauthorized use or distribution. Any use, disclosure, copying, or distribution is prohibited and may be unlawful.
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\n\nThe Author and Co-Authors confirm that: (i) the Work is their original work and is not copied wholly or substantially from any other work or material or any other source; (ii) the Work has not been formally published in any other peer-reviewed journal or in a book or edited collection, and is not under consideration for any such publication; (iii) Authors and any applicable Co-Authors are qualifying persons under section 154 of the Copyright, Designs and Patents Act 1988; (iv) Authors and any applicable Co-Authors have not assigned, and will not during the term of this Publication Agreement purport to assign, any of the rights granted to IntechOpen under this Publication Agreement; and (v) the rights granted by this Publication Agreement are free from any security interest, option, mortgage, charge or lien.
\n\nThe Author and Co-Authors also confirm and warrant that: (i) he/she has the power to enter into this Publication Agreement on his or her own behalf and on behalf of each Co-Author; and (ii) has the necessary rights and/or title in and to the Work to grant IntechOpen, on behalf of themselves and any Co-Author, the rights and licences in this Publication Agreement. If the Work was prepared jointly by the Author and Co-Authors, the Author confirms that: (i) all Co-Authors agree to the submission, license and publication of the Work on the terms of this Publication Agreement; and (ii) the Author has the authority to enter into this biding Publication Agreement on behalf of each Co-Author. The Author shall: (i) ensure each Co-Author complies with all relevant provisions of this Publication Agreement, including those relating to confidentiality, performance and standards, as if a party to this Publication Agreement; and (ii) remain primarily liable for all acts and/or omissions of each Co-Author.
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\n\nTERMINATION
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They are considered as the biotechnologically valuable bacteria that are exploited for its secondary metabolite production. Approximately, 10,000 bioactive metabolites are produced by Actinobacteria, which is 45% of all bioactive microbial metabolites discovered. Especially Streptomyces species produce industrially important microorganisms as they are a rich source of several useful bioactive natural products with potential applications. Though it has various applications, some Actinobacteria have its own negative effect against plants, animals, and humans. On this context, this chapter summarizes the general characteristics of Actinobacteria, its habitat, systematic classification, various biotechnological applications, and negative impact on plants and animals.",book:{id:"5056",slug:"actinobacteria-basics-and-biotechnological-applications",title:"Actinobacteria",fullTitle:"Actinobacteria - Basics and Biotechnological Applications"},signatures:"Ranjani Anandan, Dhanasekaran Dharumadurai and Gopinath\nPonnusamy Manogaran",authors:[{id:"48914",title:"Dr.",name:"Dharumadurai",middleName:null,surname:"Dhanasekaran",slug:"dharumadurai-dhanasekaran",fullName:"Dharumadurai Dhanasekaran"}]},{id:"42319",doi:"10.5772/50364",title:"Lactic Acid Bacteria in Hydrogen-Producing Consortia: On Purpose or by Coincidence?",slug:"lactic-acid-bacteria-in-hydrogen-producing-consortia-on-purpose-or-by-coincidence-",totalDownloads:3792,totalCrossrefCites:31,totalDimensionsCites:89,abstract:null,book:{id:"2796",slug:"lactic-acid-bacteria-r-d-for-food-health-and-livestock-purposes",title:"Lactic Acid Bacteria",fullTitle:"Lactic Acid Bacteria - R & D for Food, Health and Livestock Purposes"},signatures:"Anna Sikora, Mieczysław Błaszczyk, Marcin Jurkowski and Urszula Zielenkiewicz",authors:[{id:"143688",title:"Dr.",name:"Urszula",middleName:null,surname:"Zielenkiewicz",slug:"urszula-zielenkiewicz",fullName:"Urszula Zielenkiewicz"},{id:"146985",title:"Dr.",name:"Anna",middleName:null,surname:"Sikora",slug:"anna-sikora",fullName:"Anna Sikora"},{id:"162424",title:"Prof.",name:"Mieczysław",middleName:null,surname:"Błaszczyk",slug:"mieczyslaw-blaszczyk",fullName:"Mieczysław Błaszczyk"},{id:"162425",title:"Mr.",name:"Marcin",middleName:null,surname:"Jurkowski",slug:"marcin-jurkowski",fullName:"Marcin Jurkowski"}]},{id:"42328",doi:"10.5772/47766",title:"Lactic Acid Bacteria as Source of Functional Ingredients",slug:"lactic-acid-bacteria-as-source-of-functional-ingredients",totalDownloads:7616,totalCrossrefCites:22,totalDimensionsCites:51,abstract:null,book:{id:"2796",slug:"lactic-acid-bacteria-r-d-for-food-health-and-livestock-purposes",title:"Lactic Acid Bacteria",fullTitle:"Lactic Acid Bacteria - R & D for Food, Health and Livestock Purposes"},signatures:"Panagiota Florou-Paneri, Efterpi Christaki and Eleftherios Bonos",authors:[{id:"140984",title:"Prof.",name:"Panagiota",middleName:null,surname:"Florou-Paneri",slug:"panagiota-florou-paneri",fullName:"Panagiota Florou-Paneri"},{id:"142773",title:"Dr.",name:"Efterpi",middleName:null,surname:"Christaki",slug:"efterpi-christaki",fullName:"Efterpi Christaki"},{id:"142774",title:"Dr.",name:"Eleftherios",middleName:null,surname:"Bonos",slug:"eleftherios-bonos",fullName:"Eleftherios Bonos"}]},{id:"42337",doi:"10.5772/50839",title:"Exopolysaccharides of Lactic Acid Bacteria for Food and Colon Health Applications",slug:"exopolysaccharides-of-lactic-acid-bacteria-for-food-and-colon-health-applications",totalDownloads:6379,totalCrossrefCites:18,totalDimensionsCites:46,abstract:null,book:{id:"2796",slug:"lactic-acid-bacteria-r-d-for-food-health-and-livestock-purposes",title:"Lactic Acid Bacteria",fullTitle:"Lactic Acid Bacteria - R & D for Food, Health and Livestock Purposes"},signatures:"Tsuda Harutoshi",authors:[{id:"141928",title:"Dr.",name:"Harutoshi",middleName:null,surname:"Tsuda",slug:"harutoshi-tsuda",fullName:"Harutoshi Tsuda"}]},{id:"42322",doi:"10.5772/51282",title:"The Current Status and Future Expectations in Industrial Production of Lactic Acid by Lactic Acid Bacteria",slug:"the-current-status-and-future-expectations-in-industrial-production-of-lactic-acid-by-lactic-acid-ba",totalDownloads:9095,totalCrossrefCites:18,totalDimensionsCites:46,abstract:null,book:{id:"2796",slug:"lactic-acid-bacteria-r-d-for-food-health-and-livestock-purposes",title:"Lactic Acid Bacteria",fullTitle:"Lactic Acid Bacteria - R & D for Food, Health and Livestock Purposes"},signatures:"Sanna Taskila and Heikki Ojamo",authors:[{id:"139705",title:"Dr.",name:null,middleName:null,surname:"Taskila",slug:"taskila",fullName:"Taskila"},{id:"142916",title:"Prof.",name:"Heikki",middleName:null,surname:"Ojamo",slug:"heikki-ojamo",fullName:"Heikki Ojamo"}]}],mostDownloadedChaptersLast30Days:[{id:"49873",title:"An Introduction to Actinobacteria",slug:"an-introduction-to-actinobacteria",totalDownloads:8089,totalCrossrefCites:29,totalDimensionsCites:101,abstract:"Actinobacteria, which share the characteristics of both bacteria and fungi, are widely distributed in both terrestrial and aquatic ecosystems, mainly in soil, where they play an essential role in recycling refractory biomaterials by decomposing complex mixtures of polymers in dead plants and animals and fungal materials. They are considered as the biotechnologically valuable bacteria that are exploited for its secondary metabolite production. Approximately, 10,000 bioactive metabolites are produced by Actinobacteria, which is 45% of all bioactive microbial metabolites discovered. Especially Streptomyces species produce industrially important microorganisms as they are a rich source of several useful bioactive natural products with potential applications. Though it has various applications, some Actinobacteria have its own negative effect against plants, animals, and humans. 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They cause diseases and infections when they get into the body and begin to reproduce and crowd out healthy bacteria or to grow into tissues that are normally sterile. To cure infectious diseases, researchers discovered antibacterial agents, which are considered to be the most promising chemotherapeutic agents. Keeping in mind the resistance phenomenon developing against antibacterial agents, new drugs are frequently entering into the market along with the existing drugs. In this chapter, we discussed a revised classification and function of the antibacterial agent based on a literature survey. The antibacterial agents can be classified into five major groups, i.e. type of action, source, spectrum of activity, chemical structure, and function.",book:{id:"5867",slug:"antibacterial-agents",title:"Antibacterial Agents",fullTitle:"Antibacterial Agents"},signatures:"Hamid Ullah and Saqib Ali",authors:[{id:"201024",title:"Dr.",name:"Hamid",middleName:null,surname:"Ullah",slug:"hamid-ullah",fullName:"Hamid Ullah"},{id:"202624",title:"Dr.",name:"Saqib",middleName:null,surname:"Ali",slug:"saqib-ali",fullName:"Saqib Ali"}]},{id:"58507",title:"Probiotics and Ruminant Health",slug:"probiotics-and-ruminant-health",totalDownloads:2820,totalCrossrefCites:5,totalDimensionsCites:9,abstract:"Probiotics are viable microorganisms with beneficial health effects for humans and animals. They are formulated into many functional foods and animal feed. There is a growing research interest in the application and benefits of probiotics in ruminant production. Several recent studies have evaluated the potential of probiotics in animal nutrition and health. In this chapter, we have reviewed current research on the benefits of probiotics on gut microbial communities in ruminants and their impact on ruminant production, health and overall wellbeing.",book:{id:"6425",slug:"probiotics-current-knowledge-and-future-prospects",title:"Probiotics",fullTitle:"Probiotics - Current Knowledge and Future Prospects"},signatures:"Sarah Adjei-Fremah, Kingsley Ekwemalor, Mulumebet Worku and\nSalam Ibrahim",authors:[{id:"107905",title:"Prof.",name:"Salam",middleName:null,surname:"Ibrahim",slug:"salam-ibrahim",fullName:"Salam Ibrahim"},{id:"218786",title:"Dr.",name:'Mulumebet "Millie"',middleName:null,surname:"Worku",slug:'mulumebet-"millie"-worku',fullName:'Mulumebet "Millie" Worku'},{id:"218789",title:"Dr.",name:"Kingsley",middleName:null,surname:"Ekwemalor",slug:"kingsley-ekwemalor",fullName:"Kingsley Ekwemalor"},{id:"223195",title:"Dr.",name:"Sarah",middleName:null,surname:"Adjei-Fremah",slug:"sarah-adjei-fremah",fullName:"Sarah Adjei-Fremah"}]},{id:"49285",title:"Morphological Identification of Actinobacteria",slug:"morphological-identification-of-actinobacteria",totalDownloads:8512,totalCrossrefCites:19,totalDimensionsCites:45,abstract:"Actinobacteria is a phylum of gram-positive bacteria with high G+C content. Among gram-positive bacteria, actinobacteria exhibit the richest morphological differentiation, which is based on a filamentous degree of organization like filamentous fungi. The actinobacteria morphological characteristics are basic foundation and information of phylogenetic systematics. Classic actinomycetes have well-developed radial mycelium, which can be divided into substrate mycelium and aerial mycelium according to morphology and function. Some actinobacteria can form complicated structures, such as spore, spore chain, sporangia, and sporangiospore. The structure of hyphae and ultrastructure of spore or sporangia can be observed with microscopy. Actinobacteria have different cultural characteristics in various kinds of culture media, which are important in the classification identification, general with spores, aerial hyphae, with or without color and the soluble pigment, different growth condition on various media as the main characteristics. The morphological differentiation of actinobacteria, especially streptomycetes, is controlled by relevant genes. Both morphogenesis and antibiotic production in the streptomycetes are initiated in response to starvation, and these events are coupled.",book:{id:"5056",slug:"actinobacteria-basics-and-biotechnological-applications",title:"Actinobacteria",fullTitle:"Actinobacteria - Basics and Biotechnological Applications"},signatures:"Qinyuan Li, Xiu Chen, Yi Jiang and Chenglin Jiang",authors:[{id:"175852",title:"Dr.",name:"Chen",middleName:null,surname:"Jiang",slug:"chen-jiang",fullName:"Chen Jiang"}]},{id:"68772",title:"Multidrug-Resistant Bacterial Foodborne Pathogens: Impact on Human Health and Economy",slug:"multidrug-resistant-bacterial-foodborne-pathogens-impact-on-human-health-and-economy",totalDownloads:1043,totalCrossrefCites:3,totalDimensionsCites:7,abstract:"The drug abuse known to occur during growth of animals intended for food production, because of their use as either a prophylactic or therapeutic treatment, promotes the emergence of bacterial drug resistance. It has been reported that at least 25% of the foodborne isolates show drug resistance to one or more classes of antimicrobials (FAO 2018). There are diverse mechanisms that promote drug resistance. It is known that the use of sub-therapeutic doses of antibiotics in animals intended for food production promotes mutations of some chromosomal genes such as gyrA-parC and mphA, which are responsible for quinolone and azithromycin resistance, respectively. Also, the horizontal transfer of resistance genes as groups (“cassettes”) or plasmids makes the spread of resistance to different bacterial genera possible, among which there could be pathogens. The World Health Organization considers the emergence of multidrug-resistant pathogenic bacteria as a health problem, since the illnesses caused by them complicate the treatment and increase the morbidity and mortality rates. 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She is now a lecturer at the University of Witwatersrand, South Africa, and a principal researcher at the Health Economics and Epidemiology Research Office (HE2RO), South Africa. Dr. Moolla holds a Ph.D. in Psychology with her research being focused on mental health and resilience. In her professional work capacity, her research has further expanded into the fields of early childhood development, mental health, the HIV and TB care cascades, as well as COVID. She is also a UNESCO-trained International Bioethics Facilitator.",institutionString:"University of the Witwatersrand",institution:{name:"University of the Witwatersrand",country:{name:"South Africa"}}},{id:"419588",title:"Ph.D.",name:"Sergio",middleName:"Alexandre",surname:"Gehrke",slug:"sergio-gehrke",fullName:"Sergio Gehrke",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000038WgMKQA0/Profile_Picture_2022-06-02T11:44:20.jpg",biography:"Dr. Sergio Alexandre Gehrke is a doctorate holder in two fields. The first is a Ph.D. in Cellular and Molecular Biology from the Pontificia Catholic University, Porto Alegre, Brazil, in 2010 and the other is an International Ph.D. in Bioengineering from the Universidad Miguel Hernandez, Elche/Alicante, Spain, obtained in 2020. In 2018, he completed a postdoctoral fellowship in Materials Engineering in the NUCLEMAT of the Pontificia Catholic University, Porto Alegre, Brazil. He is currently the Director of the Postgraduate Program in Implantology of the Bioface/UCAM/PgO (Montevideo, Uruguay), Director of the Cathedra of Biotechnology of the Catholic University of Murcia (Murcia, Spain), an Extraordinary Full Professor of the Catholic University of Murcia (Murcia, Spain) as well as the Director of the private center of research Biotecnos – Technology and Science (Montevideo, Uruguay). Applied biomaterials, cellular and molecular biology, and dental implants are among his research interests. He has published several original papers in renowned journals. In addition, he is also a Collaborating Professor in several Postgraduate programs at different universities all over the world.",institutionString:null,institution:{name:"Universidad Católica San Antonio de Murcia",country:{name:"Spain"}}},{id:"342152",title:"Dr.",name:"Santo",middleName:null,surname:"Grace Umesh",slug:"santo-grace-umesh",fullName:"Santo Grace Umesh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/342152/images/16311_n.jpg",biography:null,institutionString:null,institution:{name:"SRM Dental College",country:{name:"India"}}},{id:"333647",title:"Dr.",name:"Shreya",middleName:null,surname:"Kishore",slug:"shreya-kishore",fullName:"Shreya Kishore",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/333647/images/14701_n.jpg",biography:"Dr. Shreya Kishore completed her Bachelor in Dental Surgery in Chettinad Dental College and Research Institute, Chennai, and her Master of Dental Surgery (Orthodontics) in Saveetha Dental College, Chennai. She is also Invisalign certified. She’s working as a Senior Lecturer in the Department of Orthodontics, SRM Dental College since November 2019. She is actively involved in teaching orthodontics to the undergraduates and the postgraduates. Her clinical research topics include new orthodontic brackets, fixed appliances and TADs. She’s published 4 articles in well renowned indexed journals and has a published patency of her own. Her private practice is currently limited to orthodontics and works as a consultant in various clinics.",institutionString:null,institution:{name:"SRM Dental College",country:{name:"India"}}},{id:"323731",title:"Prof.",name:"Deepak M.",middleName:"Macchindra",surname:"Vikhe",slug:"deepak-m.-vikhe",fullName:"Deepak M. Vikhe",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/323731/images/13613_n.jpg",biography:"Dr Deepak M.Vikhe .\n\n\t\n\tDr Deepak M.Vikhe , completed his Masters & PhD in Prosthodontics from Rural Dental College, Loni securing third rank in the Pravara Institute of Medical Sciences Deemed University. He was awarded Dr.G.C.DAS Memorial Award for Research on Implants at 39th IPS conference Dubai (U A E).He has two patents under his name. He has received Dr.Saraswati medal award for best research for implant study in 2017.He has received Fully funded scholarship to Spain ,university of Santiago de Compostela. He has completed fellowship in Implantlogy from Noble Biocare. \nHe has attended various conferences and CDE programmes and has national publications to his credit. His field of interest is in Implant supported prosthesis. Presently he is working as a associate professor in the Dept of Prosthodontics, Rural Dental College, Loni and maintains a successful private practice specialising in Implantology at Rahata.\n\nEmail: drdeepak_mvikhe@yahoo.com..................",institutionString:null,institution:{name:"Pravara Institute of Medical Sciences",country:{name:"India"}}},{id:"204110",title:"Dr.",name:"Ahmed A.",middleName:null,surname:"Madfa",slug:"ahmed-a.-madfa",fullName:"Ahmed A. Madfa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204110/images/system/204110.jpg",biography:"Dr. Madfa is currently Associate Professor of Endodontics at Thamar University and a visiting lecturer at Sana'a University and University of Sciences and Technology. He has more than 6 years of experience in teaching. His research interests include root canal morphology, functionally graded concept, dental biomaterials, epidemiology and dental education, biomimetic restoration, finite element analysis and endodontic regeneration. Dr. Madfa has numerous international publications, full articles, two patents, a book and a book chapter. Furthermore, he won 14 international scientific awards. Furthermore, he is involved in many academic activities ranging from editorial board member, reviewer for many international journals and postgraduate students' supervisor. Besides, I deliver many courses and training workshops at various scientific events. Dr. Madfa also regularly attends international conferences and holds administrative positions (Deputy Dean of the Faculty for Students’ & Academic Affairs and Deputy Head of Research Unit).",institutionString:"Thamar University",institution:null},{id:"210472",title:"Dr.",name:"Nermin",middleName:"Mohammed Ahmed",surname:"Yussif",slug:"nermin-yussif",fullName:"Nermin Yussif",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/210472/images/system/210472.jpg",biography:"Dr. Nermin Mohammed Ahmed Yussif is working at the Faculty of dentistry, University for October university for modern sciences and arts (MSA). Her areas of expertise include: periodontology, dental laserology, oral implantology, periodontal plastic surgeries, oral mesotherapy, nutrition, dental pharmacology. She is an editor and reviewer in numerous international journals.",institutionString:"MSA University",institution:null},{id:"204606",title:"Dr.",name:"Serdar",middleName:null,surname:"Gözler",slug:"serdar-gozler",fullName:"Serdar Gözler",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204606/images/system/204606.jpeg",biography:"Dr. Serdar Gözler has completed his undergraduate studies at the Marmara University Faculty of Dentistry in 1978, followed by an assistantship in the Prosthesis Department of Dicle University Faculty of Dentistry. Starting his PhD work on non-resilient overdentures with Assoc. Prof. Hüsnü Yavuzyılmaz, he continued his studies with Prof. Dr. Gürbüz Öztürk of Istanbul University Faculty of Dentistry Department of Prosthodontics, this time on Gnatology. He attended training programs on occlusion, neurology, neurophysiology, EMG, radiology and biostatistics. In 1982, he presented his PhD thesis \\Gerber and Lauritzen Occlusion Analysis Techniques: Diagnosis Values,\\ at Istanbul University School of Dentistry, Department of Prosthodontics. As he was also working with Prof. Senih Çalıkkocaoğlu on The Physiology of Chewing at the same time, Gözler has written a chapter in Çalıkkocaoğlu\\'s book \\Complete Prostheses\\ entitled \\The Place of Neuromuscular Mechanism in Prosthetic Dentistry.\\ The book was published five times since by the Istanbul University Publications. Having presented in various conferences about occlusion analysis until 1998, Dr. Gözler has also decided to use the T-Scan II occlusion analysis method. Having been personally trained by Dr. Robert Kerstein on this method, Dr. Gözler has been lecturing on the T-Scan Occlusion Analysis Method in conferences both in Turkey and abroad. Dr. Gözler has various articles and presentations on Digital Occlusion Analysis methods. He is now Head of the TMD Clinic at Prosthodontic Department of Faculty of Dentistry , Istanbul Aydın University , Turkey.",institutionString:"Istanbul Aydin University",institution:{name:"Istanbul Aydın University",country:{name:"Turkey"}}},{id:"240870",title:"Ph.D.",name:"Alaa Eddin Omar",middleName:null,surname:"Al Ostwani",slug:"alaa-eddin-omar-al-ostwani",fullName:"Alaa Eddin Omar Al Ostwani",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/240870/images/system/240870.jpeg",biography:"Dr. Al Ostwani Alaa Eddin Omar received his Master in dentistry from Damascus University in 2010, and his Ph.D. in Pediatric Dentistry from Damascus University in 2014. Dr. Al Ostwani is an assistant professor and faculty member at IUST University since 2014. \nDuring his academic experience, he has received several awards including the scientific research award from the Union of Arab Universities, the Syrian gold medal and the international gold medal for invention and creativity. Dr. Al Ostwani is a Member of the International Association of Dental Traumatology and the Syrian Society for Research and Preventive Dentistry since 2017. He is also a Member of the Reviewer Board of International Journal of Dental Medicine (IJDM), and the Indian Journal of Conservative and Endodontics since 2016.",institutionString:"International University for Science and Technology.",institution:{name:"Islamic University of Science and Technology",country:{name:"India"}}},{id:"42847",title:"Dr.",name:"Belma",middleName:null,surname:"Işik Aslan",slug:"belma-isik-aslan",fullName:"Belma Işik Aslan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/42847/images/system/42847.jpg",biography:"Dr. Belma IşIk Aslan was born in 1976 in Ankara-TURKEY. After graduating from TED Ankara College in 1994, she attended to Gazi University, Faculty of Dentistry in Ankara. She completed her PhD in orthodontic education at Gazi University between 1999-2005. Dr. Işık Aslan stayed at the Providence Hospital Craniofacial Institude and Reconstructive Surgery in Michigan, USA for three months as an observer. She worked as a specialist doctor at Gazi University, Dentistry Faculty, Department of Orthodontics between 2005-2014. She was appointed as associate professor in January, 2014 and as professor in 2021. Dr. Işık Aslan still works as an instructor at the same faculty. She has published a total of 35 articles, 10 book chapters, 39 conference proceedings both internationally and nationally. Also she was the academic editor of the international book 'Current Advances in Orthodontics'. She is a member of the Turkish Orthodontic Society and Turkish Cleft Lip and Palate Society. She is married and has 2 children. Her knowledge of English is at an advanced level.",institutionString:"Gazi University Dentistry Faculty Department of Orthodontics",institution:null},{id:"178412",title:"Associate Prof.",name:"Guhan",middleName:null,surname:"Dergin",slug:"guhan-dergin",fullName:"Guhan Dergin",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178412/images/6954_n.jpg",biography:"Assoc. Prof. Dr. Gühan Dergin was born in 1973 in Izmit. He graduated from Marmara University Faculty of Dentistry in 1999. He completed his specialty of OMFS surgery in Marmara University Faculty of Dentistry and obtained his PhD degree in 2006. In 2005, he was invited as a visiting doctor in the Oral and Maxillofacial Surgery Department of the University of North Carolina, USA, where he went on a scholarship. Dr. Dergin still continues his academic career as an associate professor in Marmara University Faculty of Dentistry. He has many articles in international and national scientific journals and chapters in books.",institutionString:null,institution:{name:"Marmara University",country:{name:"Turkey"}}},{id:"178414",title:"Prof.",name:"Yusuf",middleName:null,surname:"Emes",slug:"yusuf-emes",fullName:"Yusuf Emes",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178414/images/6953_n.jpg",biography:"Born in Istanbul in 1974, Dr. Emes graduated from Istanbul University Faculty of Dentistry in 1997 and completed his PhD degree in Istanbul University faculty of Dentistry Department of Oral and Maxillofacial Surgery in 2005. He has papers published in international and national scientific journals, including research articles on implantology, oroantral fistulas, odontogenic cysts, and temporomandibular disorders. Dr. Emes is currently working as a full-time academic staff in Istanbul University faculty of Dentistry Department of Oral and Maxillofacial Surgery.",institutionString:null,institution:{name:"Istanbul University",country:{name:"Turkey"}}},{id:"192229",title:"Ph.D.",name:"Ana Luiza",middleName:null,surname:"De Carvalho Felippini",slug:"ana-luiza-de-carvalho-felippini",fullName:"Ana Luiza De Carvalho Felippini",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/192229/images/system/192229.jpg",biography:null,institutionString:"University of São Paulo",institution:{name:"University of Sao Paulo",country:{name:"Brazil"}}},{id:"256851",title:"Prof.",name:"Ayşe",middleName:null,surname:"Gülşen",slug:"ayse-gulsen",fullName:"Ayşe Gülşen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/256851/images/9696_n.jpg",biography:"Dr. Ayşe Gülşen graduated in 1990 from Faculty of Dentistry, University of Ankara and did a postgraduate program at University of Gazi. \nShe worked as an observer and research assistant in Craniofacial Surgery Departments in New York, Providence Hospital in Michigan and Chang Gung Memorial Hospital in Taiwan. \nShe works as Craniofacial Orthodontist in Department of Aesthetic, Plastic and Reconstructive Surgery, Faculty of Medicine, University of Gazi, Ankara Turkey since 2004.",institutionString:"Univeristy of Gazi",institution:null},{id:"255366",title:"Prof.",name:"Tosun",middleName:null,surname:"Tosun",slug:"tosun-tosun",fullName:"Tosun Tosun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255366/images/7347_n.jpg",biography:"Graduated at the Faculty of Dentistry, University of Istanbul, Turkey in 1989;\nVisitor Assistant at the University of Padua, Italy and Branemark Osseointegration Center of Treviso, Italy between 1993-94;\nPhD thesis on oral implantology in University of Istanbul and was awarded the academic title “Dr.med.dent.”, 1997;\nHe was awarded the academic title “Doç.Dr.” (Associated Professor) in 2003;\nProficiency in Botulinum Toxin Applications, Reading-UK in 2009;\nMastership, RWTH Certificate in Laser Therapy in Dentistry, AALZ-Aachen University, Germany 2009-11;\nMaster of Science (MSc) in Laser Dentistry, University of Genoa, Italy 2013-14.\n\nDr.Tosun worked as Research Assistant in the Department of Oral Implantology, Faculty of Dentistry, University of Istanbul between 1990-2002. \nHe worked part-time as Consultant surgeon in Harvard Medical International Hospitals and John Hopkins Medicine, Istanbul between years 2007-09.\u2028He was contract Professor in the Department of Surgical and Diagnostic Sciences (DI.S.C.), Medical School, University of Genova, Italy between years 2011-16. \nSince 2015 he is visiting Professor at Medical School, University of Plovdiv, Bulgaria. \nCurrently he is Associated Prof.Dr. at the Dental School, Oral Surgery Dept., Istanbul Aydin University and since 2003 he works in his own private clinic in Istanbul, Turkey.\u2028\nDr.Tosun is reviewer in journal ‘Laser in Medical Sciences’, reviewer in journal ‘Folia Medica\\', a Fellow of the International Team for Implantology, Clinical Lecturer of DGZI German Association of Oral Implantology, Expert Lecturer of Laser&Health Academy, Country Representative of World Federation for Laser Dentistry, member of European Federation of Periodontology, member of Academy of Laser Dentistry. Dr.Tosun presents papers in international and national congresses and has scientific publications in international and national journals. He speaks english, spanish, italian and french.",institutionString:null,institution:{name:"Istanbul Aydın University",country:{name:"Turkey"}}},{id:"171887",title:"Prof.",name:"Zühre",middleName:null,surname:"Akarslan",slug:"zuhre-akarslan",fullName:"Zühre Akarslan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/171887/images/system/171887.jpg",biography:"Zühre Akarslan was born in 1977 in Cyprus. She graduated from Gazi University Faculty of Dentistry, Ankara, Turkey in 2000. \r\nLater she received her Ph.D. degree from the Oral Diagnosis and Radiology Department; which was recently renamed as Oral and Dentomaxillofacial Radiology, from the same university. \r\nShe is working as a full-time Associate Professor and is a lecturer and an academic researcher. \r\nHer expertise areas are dental caries, cancer, dental fear and anxiety, gag reflex in dentistry, oral medicine, and dentomaxillofacial radiology.",institutionString:"Gazi University",institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"256417",title:"Associate Prof.",name:"Sanaz",middleName:null,surname:"Sadry",slug:"sanaz-sadry",fullName:"Sanaz Sadry",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/256417/images/8106_n.jpg",biography:null,institutionString:null,institution:null},{id:"272237",title:"Dr.",name:"Pinar",middleName:"Kiymet",surname:"Karataban",slug:"pinar-karataban",fullName:"Pinar Karataban",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/272237/images/8911_n.png",biography:"Assist.Prof.Dr.Pınar Kıymet Karataban, DDS PhD \n\nDr.Pınar Kıymet Karataban was born in Istanbul in 1975. After her graduation from Marmara University Faculty of Dentistry in 1998 she started her PhD in Paediatric Dentistry focused on children with special needs; mainly children with Cerebral Palsy. She finished her pHD thesis entitled \\'Investigation of occlusion via cast analysis and evaluation of dental caries prevalance, periodontal status and muscle dysfunctions in children with cerebral palsy” in 2008. She got her Assist. Proffessor degree in Istanbul Aydın University Paediatric Dentistry Department in 2015-2018. ın 2019 she started her new career in Bahcesehir University, Istanbul as Head of Department of Pediatric Dentistry. In 2020 she was accepted to BAU International University, Batumi as Professor of Pediatric Dentistry. She’s a lecturer in the same university meanwhile working part-time in private practice in Ege Dental Studio (https://www.egedisklinigi.com/) a multidisciplinary dental clinic in Istanbul. Her main interests are paleodontology, ancient and contemporary dentistry, oral microbiology, cerebral palsy and special care dentistry. She has national and international publications, scientific reports and is a member of IAPO (International Association for Paleodontology), IADH (International Association of Disability and Oral Health) and EAPD (European Association of Pediatric Dentistry).",institutionString:null,institution:null},{id:"202198",title:"Dr.",name:"Buket",middleName:null,surname:"Aybar",slug:"buket-aybar",fullName:"Buket Aybar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/202198/images/6955_n.jpg",biography:"Buket Aybar, DDS, PhD, was born in 1971. She graduated from Istanbul University, Faculty of Dentistry, in 1992 and completed her PhD degree on Oral and Maxillofacial Surgery in Istanbul University in 1997.\nDr. Aybar is currently a full-time professor in Istanbul University, Faculty of Dentistry Department of Oral and Maxillofacial Surgery. She has teaching responsibilities in graduate and postgraduate programs. Her clinical practice includes mainly dentoalveolar surgery.\nHer topics of interest are biomaterials science and cell culture studies. She has many articles in international and national scientific journals and chapters in books; she also has participated in several scientific projects supported by Istanbul University Research fund.",institutionString:null,institution:null},{id:"260116",title:"Dr.",name:"Mehmet",middleName:null,surname:"Yaltirik",slug:"mehmet-yaltirik",fullName:"Mehmet Yaltirik",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/260116/images/7413_n.jpg",biography:"Birth Date 25.09.1965\r\nBirth Place Adana- Turkey\r\nSex Male\r\nMarrial Status Bachelor\r\nDriving License Acquired\r\nMother Tongue Turkish\r\n\r\nAddress:\r\nWork:University of Istanbul,Faculty of Dentistry, Department of Oral Surgery and Oral Medicine 34093 Capa,Istanbul- TURKIYE",institutionString:null,institution:null},{id:"172009",title:"Dr.",name:"Fatma Deniz",middleName:null,surname:"Uzuner",slug:"fatma-deniz-uzuner",fullName:"Fatma Deniz Uzuner",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/172009/images/7122_n.jpg",biography:"Dr. Deniz Uzuner was born in 1969 in Kocaeli-TURKEY. After graduating from TED Ankara College in 1986, she attended the Hacettepe University, Faculty of Dentistry in Ankara. \nIn 1993 she attended the Gazi University, Faculty of Dentistry, Department of Orthodontics for her PhD education. After finishing the PhD education, she worked as orthodontist in Ankara Dental Hospital under the Turkish Government, Ministry of Health and in a special Orthodontic Clinic till 2011. Between 2011 and 2016, Dr. Deniz Uzuner worked as a specialist in the Department of Orthodontics, Faculty of Dentistry, Gazi University in Ankara/Turkey. In 2016, she was appointed associate professor. Dr. Deniz Uzuner has authored 23 Journal Papers, 3 Book Chapters and has had 39 oral/poster presentations. She is a member of the Turkish Orthodontic Society. Her knowledge of English is at an advanced level.",institutionString:null,institution:null},{id:"332914",title:"Dr.",name:"Muhammad Saad",middleName:null,surname:"Shaikh",slug:"muhammad-saad-shaikh",fullName:"Muhammad Saad Shaikh",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Jinnah Sindh Medical University",country:{name:"Pakistan"}}},{id:"315775",title:"Dr.",name:"Feng",middleName:null,surname:"Luo",slug:"feng-luo",fullName:"Feng Luo",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Sichuan University",country:{name:"China"}}},{id:"423519",title:"Dr.",name:"Sizakele",middleName:null,surname:"Ngwenya",slug:"sizakele-ngwenya",fullName:"Sizakele Ngwenya",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of the Witwatersrand",country:{name:"South Africa"}}},{id:"419270",title:"Dr.",name:"Ann",middleName:null,surname:"Chianchitlert",slug:"ann-chianchitlert",fullName:"Ann Chianchitlert",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Walailak University",country:{name:"Thailand"}}},{id:"419271",title:"Dr.",name:"Diane",middleName:null,surname:"Selvido",slug:"diane-selvido",fullName:"Diane Selvido",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Walailak University",country:{name:"Thailand"}}},{id:"419272",title:"Dr.",name:"Irin",middleName:null,surname:"Sirisoontorn",slug:"irin-sirisoontorn",fullName:"Irin Sirisoontorn",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Walailak University",country:{name:"Thailand"}}},{id:"355660",title:"Dr.",name:"Anitha",middleName:null,surname:"Mani",slug:"anitha-mani",fullName:"Anitha Mani",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"SRM Dental College",country:{name:"India"}}},{id:"355612",title:"Dr.",name:"Janani",middleName:null,surname:"Karthikeyan",slug:"janani-karthikeyan",fullName:"Janani Karthikeyan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"SRM Dental College",country:{name:"India"}}},{id:"334400",title:"Dr.",name:"Suvetha",middleName:null,surname:"Siva",slug:"suvetha-siva",fullName:"Suvetha Siva",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"SRM Dental College",country:{name:"India"}}}]}},subseries:{item:{id:"22",type:"subseries",title:"Applied Intelligence",keywords:"Machine Learning, Intelligence Algorithms, Data Science, Artificial Intelligence, Applications on Applied Intelligence",scope:"This field is the key in the current industrial revolution (Industry 4.0), where the new models and developments are based on the knowledge generation on applied intelligence. 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His research lines are biometrics, biomedical signals and images, data mining, classification system, signal and image processing, machine learning, and environmental intelligence. He has researched in 52 international and Spanish research projects, some of them as head researcher. He is co-author of 4 books, co-editor of 27 proceedings books, guest editor for 8 JCR-ISI international journals, and up to 24 book chapters. He has over 450 papers published in international journals and conferences (81 of them indexed on JCR – ISI - Web of Science). He has published seven patents in the Spanish Patent and Trademark Office. He has been a supervisor on 8 Ph.D. theses (11 more are under supervision), and 130 master theses. He is the founder of The IEEE IWOBI conference series and the president of its Steering Committee, as well as the founder of both the InnoEducaTIC and APPIS conference series. 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