\\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:"6520",leadTitle:null,fullTitle:"Leishmaniases as Re-emerging Diseases",title:"Leishmaniases as Re-emerging Diseases",subtitle:null,reviewType:"peer-reviewed",abstract:"Leishmania parasites plague the mammalian host causing high morbidity and mortality. The parasites persist in the hostile milieu, crippling its defensive arsenal. In the face of mounting resistance to an antiquated drug arsenal, new approaches are urgently desired to keep the infection at bay. Furthermore, to strengthen the leishmaniasis elimination drive, particular emphasis has to be laid on identification of new targets and vaccination strategies. This book gives a brief glimpse of the epidemiology of leishmaniasis, immune evasion, vaccination, and therapeutic modalities that may work by untangling the immunological cross-wires of pathogenic cross-talk. The Conventional treatment and its drawbacks, the prospects of phytotherapy and nanomedicines, are also discussed. The identification of drug targets with the aim of designing inhibitors is also exemplified.",isbn:"978-1-78984-102-2",printIsbn:"978-1-78984-101-5",pdfIsbn:"978-1-83881-521-9",doi:"10.5772/intechopen.71150",price:119,priceEur:129,priceUsd:155,slug:"leishmaniases-as-re-emerging-diseases",numberOfPages:232,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"031e09b818ab5c32386616f72b05ee73",bookSignature:"Farhat Afrin and Hassan Hemeg",publishedDate:"October 10th 2018",coverURL:"https://cdn.intechopen.com/books/images_new/6520.jpg",numberOfDownloads:12440,numberOfWosCitations:15,numberOfCrossrefCitations:22,numberOfCrossrefCitationsByBook:1,numberOfDimensionsCitations:41,numberOfDimensionsCitationsByBook:1,hasAltmetrics:1,numberOfTotalCitations:78,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"September 26th 2017",dateEndSecondStepPublish:"October 17th 2017",dateEndThirdStepPublish:"December 16th 2017",dateEndFourthStepPublish:"March 6th 2018",dateEndFifthStepPublish:"May 5th 2018",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"186948",title:"Dr.",name:"Farhat",middleName:null,surname:"Afrin",slug:"farhat-afrin",fullName:"Farhat Afrin",profilePictureURL:"https://mts.intechopen.com/storage/users/186948/images/5872_n.jpg",biography:"Dr. Farhat Afrin, an Assistant Professor in Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Taibah University, Madina, Saudi Arabia, received Ph.D. from Indian Institute of Chemical Biology, Kolkata, India. Earlier, she served at the Department of Biotechnology, Hamdard University, New Delhi, India for 16 years. She also worked at the National Institutes of Health, Bethesda, MD, USA and Centre for Immunology and Infection, University of York, UK. She is a recipient of several honors including American Association of Immunologists Young Faculty Travel Grant, Commonwealth Academic Staff fellowship, Department of Biotechnology Overseas Associateship. Her research interest is parasite immunology with emphasis on Leishmania immunotherapeutics. She has published over 55 papers in Journals of International repute and is an Academic Editor, Editorial Board member and reviewer of several Journals and Editor of few books.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"2",institution:{name:"Taibah University",institutionURL:null,country:{name:"Saudi Arabia"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:{id:"187330",title:"Dr.",name:"Hassan",middleName:null,surname:"Hemeg",slug:"hassan-hemeg",fullName:"Hassan Hemeg",profilePictureURL:"https://mts.intechopen.com/storage/users/187330/images/system/187330.jpg",biography:"Dr. Hassan A. Hemeg completed his Masters in Pathological Science at the Sheffield University, UK, and Ph.D. from King Abdulaziz University, Jeddah, Saudi Arabia. He has earned several honors such as a Fellow of the Institute of Biomedical Science, UK, and Certified Canadian Accreditation Specialist for Health Care Facilities. He acquired training in Microbiology from Sheffield and Bristol Universities, the U.K. and U.S. Department of Labor, Occupational Safety and Health Administration. He is a member, Secretary, and Chairman of several Committees. His research interest is in the field of antimicrobial resistance. He has published several papers in Journals of International repute and is co-editor of few books. Presently, he is an Associate Professor and consultant of medical microbiology in the Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Taibah University, Madina, Saudi Arabia where he also served as Vice Dean.",institutionString:"Taibah University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Taibah University",institutionURL:null,country:{name:"Saudi Arabia"}}},coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1046",title:"Infectious Diseases",slug:"infectious-diseases"}],chapters:[{id:"63033",title:"Introductory Chapter: Leishmaniasis: An Emerging Clinical Syndrome",doi:"10.5772/intechopen.79662",slug:"introductory-chapter-leishmaniasis-an-emerging-clinical-syndrome",totalDownloads:1021,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:null,signatures:"Farhat Afrin and Hassan A. Hemeg",downloadPdfUrl:"/chapter/pdf-download/63033",previewPdfUrl:"/chapter/pdf-preview/63033",authors:[{id:"186948",title:"Dr.",name:"Farhat",surname:"Afrin",slug:"farhat-afrin",fullName:"Farhat Afrin"},{id:"187330",title:"Dr.",name:"Hassan",surname:"Hemeg",slug:"hassan-hemeg",fullName:"Hassan Hemeg"}],corrections:null},{id:"60273",title:"Visceral Leishmaniasis",doi:"10.5772/intechopen.75907",slug:"visceral-leishmaniasis",totalDownloads:781,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Clinically, leishmaniasis is of three types—visceral leishmaniasis (VL) or kala-azar, cutaneous leishmaniasis (CL) and mucocutaneous leishmaniasis (MCL). Post-kala-azar dermal leishmaniasis (PKDL) is considered as a complication of VL. VL is characterized by fever, anemia and splenomegaly in a VL-endemic area (malaria excluded). A subject with such symptoms should be subjected to an rK39 strip test. Confirmation of diagnosis is made by demonstration of the parasite (Leishmania donovani) from samples obtained by aspiration of bone marrow or iliac crest puncture. Miltefosine, stibogluconate, amphotericin B, liposomal amphotericin B and paromomycin are effective available anti-leishmaniasis drugs. Vector (Phleblotomus argentipes) control for reduction of transmission and early diagnosis and complete treatment are essential elements of case management. There is no effective vaccine against VL. This review on VL aims at providing state-art knowledge on epidemiology, diagnosis and case-management and vaccine development.",signatures:"Sujit K. Bhattacharya, Ajanta Ghosal, Sudeshna Ganguly, Sandipan\nGanguly, Sabahat Azim and Shanta Dutta",downloadPdfUrl:"/chapter/pdf-download/60273",previewPdfUrl:"/chapter/pdf-preview/60273",authors:[{id:"85327",title:"Dr.",name:"Shanta",surname:"Dutta",slug:"shanta-dutta",fullName:"Shanta Dutta"},{id:"225207",title:"Dr.",name:"Sujit",surname:"Bhattacharya",slug:"sujit-bhattacharya",fullName:"Sujit Bhattacharya"},{id:"240594",title:"Ms.",name:"Ajanta",surname:"Ghosal",slug:"ajanta-ghosal",fullName:"Ajanta Ghosal"},{id:"240595",title:"Dr.",name:"Sudeshna",surname:"Ganguly",slug:"sudeshna-ganguly",fullName:"Sudeshna Ganguly"},{id:"240596",title:"Dr.",name:"Sandipan",surname:"Ganguly",slug:"sandipan-ganguly",fullName:"Sandipan Ganguly"},{id:"240597",title:"Dr.",name:"Sabahat",surname:"Azim",slug:"sabahat-azim",fullName:"Sabahat Azim"}],corrections:null},{id:"62412",title:"Leishmaniases in West Africa: Past and Current",doi:"10.5772/intechopen.77009",slug:"leishmaniases-in-west-africa-past-and-current",totalDownloads:888,totalCrossrefCites:0,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Leishmaniases are vector-borne diseases. Cutaneous leishmaniasis (CL) is endemic in West Africa. Sporadic and anecdotal cases of visceral leishmaniasis (VL) have been reported in the past. Recent data showed the changing of epidemiology of leishmaniases in West Africa, with the occurrence of outbreak of CL due to Leishmania major in urban and rural areas. CL is transmitted by Phlebotomus duboscqi. The role of Sergentomyia (Spelaeomyia) darlingi as vector in rural areas has been evoked but not confirmed. Cases of VL due to Leishmania spp. have been described in West Africa; however, parasites species were not identified and dogs were suspected to be the reservoir. No humans’ case of symptomatic VL due to L. infantum has been described in West Africa. Recent data in rural areas of Senegal confirmed dog as reservoir of L. infantum. In the same study in Senegal, Sergentomyia sandflies were found infected with L. infantum, indicating a possible role in leishmaniasis transmission. Coinfection leishmaniases-HIV is reported but rare. In this chapter, we included most recent publications and propose an updated landscape of CL and VL epidemiology in West Africa.",signatures:"Abdoulaye Kassoum Kone, Mahamadou A. Thera, Babacar Faye and\nOgobara K. Doumbo†",downloadPdfUrl:"/chapter/pdf-download/62412",previewPdfUrl:"/chapter/pdf-preview/62412",authors:[{id:"141449",title:"Dr.",name:"Abdoulaye Kassoum",surname:"Kone",slug:"abdoulaye-kassoum-kone",fullName:"Abdoulaye Kassoum Kone"},{id:"220804",title:"Prof.",name:"Ogobara",surname:"Doumbo",slug:"ogobara-doumbo",fullName:"Ogobara Doumbo"},{id:"249084",title:"Prof.",name:"Mahamadou Ali",surname:"Thera",slug:"mahamadou-ali-thera",fullName:"Mahamadou Ali Thera"},{id:"253775",title:"Dr.",name:"Babacar",surname:"Faye",slug:"babacar-faye",fullName:"Babacar Faye"}],corrections:null},{id:"59910",title:"Immune Evasion Strategies",doi:"10.5772/intechopen.75169",slug:"immune-evasion-strategies",totalDownloads:1210,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Leishmania is the causative protozoan parasite of leishmaniasis. Distinct species provoke localized/diffuse cutaneous leishmaniasis or visceral leishmaniasis. Leishmania parasites have developed diverse strategies to evade the host immune response expressed through various cells, especially macrophages, NK cells, and dendritic cells. Participating in some of these strategies are Leishmania surface molecules, such as lipophosphoglycan (LPG) and protease gp63, which are thus considered virulence factors. LPG has been shown to modulate proinflammatory responses. For example, L. major LPG activates NK cells through toll-like receptor-2 (TLR2), while L. mexicana LPG elicits a differential production of cytokines in human dendritic cells and monocytes. Moreover, L. mexicana LPG activates MAP kinases in macrophages, which in turn enhance proinflammatory cytokine production through TLRs. Additionally, Leishmania exosomes have been found to strongly affect macrophage signaling and functions. Furthermore, proteins secreted by Leishmania promastigotes and amastigotes modulate the production of proinflammatory cytokines in human macrophages. Since Leishmania is an obligate intracellular parasite, its promastigotes utilize several mechanisms to survive and duplicate inside host cells, including the inhibition of apoptosis. It is now clear that MAPK p38, JNK, ERK 1/2, and PI3K/Akt participate in the inhibition of both natural and induced apoptosis of macrophages, neutrophils, and dendritic cells.",signatures:"M. Magdalena Aguirre-Garcia, Alma R. Escalona-Montaño, Arturo\nA. Wilkins-Rodríguez and Laila Gutiérrez-Kobeh",downloadPdfUrl:"/chapter/pdf-download/59910",previewPdfUrl:"/chapter/pdf-preview/59910",authors:[{id:"227636",title:"Dr.",name:"M. Magdalena",surname:"Aguirre-García",slug:"m.-magdalena-aguirre-garcia",fullName:"M. Magdalena Aguirre-García"},{id:"233494",title:"Dr.",name:"Laila",surname:"Gutiérrez-Kobeh",slug:"laila-gutierrez-kobeh",fullName:"Laila Gutiérrez-Kobeh"},{id:"239828",title:"MSc.",name:"Alma R.",surname:"Escalona-Montaño",slug:"alma-r.-escalona-montano",fullName:"Alma R. Escalona-Montaño"},{id:"239829",title:"BSc.",name:"Arturo Alfredo",surname:"Wilkins-Rodriguez",slug:"arturo-alfredo-wilkins-rodriguez",fullName:"Arturo Alfredo Wilkins-Rodriguez"}],corrections:null},{id:"60934",title:"Vaccines for Human Leishmaniasis: Where Do We Stand and What Is Still Missing?",doi:"10.5772/intechopen.75000",slug:"vaccines-for-human-leishmaniasis-where-do-we-stand-and-what-is-still-missing-",totalDownloads:1527,totalCrossrefCites:9,totalDimensionsCites:19,hasAltmetrics:0,abstract:"Responsible for up to 30,000 deaths annually, leishmaniasis is a complex spectrum of diseases endemic in 97 countries around the globe. Disease control relies heavily on the early diagnosis and treatment of the active cases (relevant for anthroponotic disease), although it is widely accepted that a prophylactic vaccine for human leishmaniasis is the way to achieve the successful elimination of human disease (taking in consideration the vast list of non-human reservoirs that enable the perpetuation of parasites all around the globe). The notion that infection leads to strong and long-lasting immunity against leishmaniasis supports vaccination as an achievable goal. However, and in spite of the different candidates tested along the years, till date, we still do not have an approved vaccine for humans. In this chapter, we will explore the last advances made in the field of vaccines against Leishmania without forgetting the historical perspective, essential to the understanding of the road already undergone. We will then discuss the correlates of disease and protection, still neither consensual nor definitive, as well as the issue of pre-clinical to clinical translation. The complete understanding of these issues will be essential for the approval of a successful vaccine for human leishmaniasis.",signatures:"Pedro Cecílio, Fabiano Oliveira and Anabela Cordeiro da Silva",downloadPdfUrl:"/chapter/pdf-download/60934",previewPdfUrl:"/chapter/pdf-preview/60934",authors:[{id:"169577",title:"Dr.",name:"Anabela",surname:"Cordeiro-Da-Silva",slug:"anabela-cordeiro-da-silva",fullName:"Anabela Cordeiro-Da-Silva"},{id:"228166",title:"MSc.",name:"Pedro",surname:"Cecilio",slug:"pedro-cecilio",fullName:"Pedro Cecilio"},{id:"240391",title:"Dr.",name:"Luiz",surname:"Oliveira",slug:"luiz-oliveira",fullName:"Luiz Oliveira"}],corrections:null},{id:"60110",title:"Vaccines for Visceral Leishmaniasis: Hopes and Hurdles",doi:"10.5772/intechopen.75184",slug:"vaccines-for-visceral-leishmaniasis-hopes-and-hurdles",totalDownloads:1024,totalCrossrefCites:1,totalDimensionsCites:3,hasAltmetrics:0,abstract:"The leishmaniases are vector-borne parasitic diseases with multiple disease phenotypes that range from self-healing cutaneous ulcers to disfiguring post-kala-azar dermal leishmaniasis and fatal visceral leishmaniasis (VL). Infected individuals can develop subclinical infections or overt disease. Current treatments are toxic and expensive. The only successful control measure is case detection and drug treatment. Resistance to anti-leishmanial drugs are increasing with few drugs in the pipeline. The Leishmania parasites are good candidates for vaccine development, with no change in its antigenic coat and extensive cross-reactivity between species. First-generation vaccines are safe, immunogenic with inconclusive efficiency. These vaccines presented the leishmanin skin test (LST) as a potentially good surrogate marker of immunogenicity/protection that can help in future vaccine studies. First-generation vaccines are the only leishmaniasis vaccines that progressed to phase III. Second-generation vaccines are safe and immunogenic, but none progressed to phase III. Third-generation vaccines recently entered human testing. Alternative approaches include in silico prediction of immunogenic Leishmania epitopes with in vitro immunogenicity testing. New adjuvants can help in the quest to develop efficacious leishmaniasis vaccines. Failure of second- and third-generation vaccines to reach phase III, rising drug resistance and continued VL pandemics make it a necessity to revisit first-generation vaccines.",signatures:"Eltahir Awad Gasim Khalil",downloadPdfUrl:"/chapter/pdf-download/60110",previewPdfUrl:"/chapter/pdf-preview/60110",authors:[{id:"75587",title:"Prof.",name:"Eltahir Awad",surname:"Khalil",slug:"eltahir-awad-khalil",fullName:"Eltahir Awad Khalil"}],corrections:null},{id:"60766",title:"The Polyamine Pathway as a Potential Target for Leishmaniases Chemotherapy",doi:"10.5772/intechopen.75867",slug:"the-polyamine-pathway-as-a-potential-target-for-leishmaniases-chemotherapy",totalDownloads:1050,totalCrossrefCites:0,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Considering the limitations of the current leishmaniases chemotherapy and the lack of effective vaccines, the identification of novel drugs and/or vaccine approaches for the leishmaniases treatment and control is urgently required. In fact, a rational strategy for the parasite control can be based on the identification of essential metabolic pathways of the parasite. One of the most important pathways is the polyamine biosynthesis. Leishmania is auxotrophic for many amino acids, such as l-arginine, a precursor of ornithine, putrescine, and spermidine. These metabolites are essential for parasite replication and establishment of infection in the mammalian host. In addition, Leishmania has a specific and complex machinery to uptake and metabolize exogenous sources of those molecules. In this chapter, we will focus on the main aspects of the polyamine pathway as a potential target for infection control aiming for new targets for Leishmania chemotherapy.",signatures:"Juliana Ide Aoki, Sandra Marcia Muxel, Juliane Cristina Ribeiro\nFernandes and Lucile Maria Floeter-Winter",downloadPdfUrl:"/chapter/pdf-download/60766",previewPdfUrl:"/chapter/pdf-preview/60766",authors:[{id:"224583",title:"Dr.",name:"Juliana",surname:"Ide Aoki",slug:"juliana-ide-aoki",fullName:"Juliana Ide Aoki"},{id:"225123",title:"Ph.D.",name:"Sandra Marcia",surname:"Muxel",slug:"sandra-marcia-muxel",fullName:"Sandra Marcia Muxel"},{id:"225124",title:"Prof.",name:"Lucile Maria",surname:"Floeter-Winter",slug:"lucile-maria-floeter-winter",fullName:"Lucile Maria Floeter-Winter"},{id:"239452",title:"B.Sc.",name:"Juliane Cristina",surname:"Ribeiro Fernandes",slug:"juliane-cristina-ribeiro-fernandes",fullName:"Juliane Cristina Ribeiro Fernandes"}],corrections:null},{id:"60199",title:"3-Hydroxy-3-Methylglutaryl-CoA Reductase (HMGR) Enzyme of the Sterol Biosynthetic Pathway: A Potential Target against Visceral Leishmaniasis",doi:"10.5772/intechopen.75480",slug:"3-hydroxy-3-methylglutaryl-coa-reductase-hmgr-enzyme-of-the-sterol-biosynthetic-pathway-a-potential-",totalDownloads:823,totalCrossrefCites:2,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Sterol biosynthetic pathway is explored for its therapeutic potential for Visceral Leishmaniasis. In Leishmania, this pathway produces ergosterol which is absent in host and therefore is a promising strategy to combat proliferation of both extracellular and intracellular forms of the parasite with minimal host toxicity. The present chapter focuses on 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) enzyme which is the rate-limiting enzyme of the ergosterol biosynthesis. HMGR gene of L. donovani was biochemically and biophysically characterized for the first time. HMGR over expressing transgenic parasites were generated to evaluate its role in parasite growth and infection ability. A series of statins like atorvastatin, simvastatin and mevastatin were evaluated for its therapeutic efficacy and mode of action elucidated. Atorvastatin and mevastatin were found to be killing both the promastigote and amastigote forms of the parasite without exhibiting host cytotoxicity. Besides, non-statin class of molecules like resveratrol and glycyrrhizic acid were also analyzed for antileishmanial potential. Two antidepressants, ketanserin and mianserin were found to kill both L. donovani promastigotes and intracellular amastigotes with no apparent toxicity to the host cells. Since targeting of the sterol biosynthetic pathway enzymes may be useful therapeutically, the present work may have implications in treatment of Leishmaniasis.",signatures:"Sushma Singh and N. Kishore Babu",downloadPdfUrl:"/chapter/pdf-download/60199",previewPdfUrl:"/chapter/pdf-preview/60199",authors:[{id:"226109",title:"Dr.",name:"Sushma",surname:"Singh",slug:"sushma-singh",fullName:"Sushma Singh"}],corrections:null},{id:"60506",title:"Alternative Treatment for Leishmaniasis",doi:"10.5772/intechopen.75895",slug:"alternative-treatment-for-leishmaniasis",totalDownloads:1209,totalCrossrefCites:5,totalDimensionsCites:6,hasAltmetrics:0,abstract:"Leishmaniasis remains as one of the most important neglected diseases in the world and, after all these years, its treatment is still a problem, mainly because of the side effects caused by the first- and second-line drugs and the indiscriminate treatment, which leads to increasing cases of parasite resistance. The search for alternative therapies for the treatment of leishmaniasis is extremely important. In this context, the use of natural products arises as a promising alternative, combining the empirical knowledge disseminated in the population with researches that aim to scientifically prove the therapeutic effects of plants. Based on this, the use of medicinal plants is considered a desirable and accessible tool in the treatment of these diseases and considered by pharmacognosy as a valuable source for the development of new drugs and as adjuvant for conventional therapies.",signatures:"Renata Mondêgo de Oliveira, Solange de Araújo Melo, Tatiane\nAranha da Penha-Silva, Fernando Almeida-Souza and Ana Lucia\nAbreu-Silva",downloadPdfUrl:"/chapter/pdf-download/60506",previewPdfUrl:"/chapter/pdf-preview/60506",authors:[{id:"223173",title:"Dr.",name:"Ana Lucia",surname:"Abreu-Silva",slug:"ana-lucia-abreu-silva",fullName:"Ana Lucia Abreu-Silva"},{id:"233682",title:"Dr.",name:"Solange",surname:"Araújo Melo",slug:"solange-araujo-melo",fullName:"Solange Araújo Melo"},{id:"233684",title:"Dr.",name:"Tatiane",surname:"Aranha da Penha-Silva",slug:"tatiane-aranha-da-penha-silva",fullName:"Tatiane Aranha da Penha-Silva"},{id:"233685",title:"MSc.",name:"Renata",surname:"Mondego De Oliveira",slug:"renata-mondego-de-oliveira",fullName:"Renata Mondego De Oliveira"}],corrections:null},{id:"62245",title:"Natural Compounds and Extracts from Mexican Medicinal Plants with Anti-Leishmanial Activity: An Update",doi:"10.5772/intechopen.77247",slug:"natural-compounds-and-extracts-from-mexican-medicinal-plants-with-anti-leishmanial-activity-an-updat",totalDownloads:883,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Leishmaniasis is considered an emerging, uncontrolled disease, and is endemic in 98 countries. Annually, about 2 million cases of cutaneous and 500,000 cases of visceral type leishmaniasis are recorded, and 60,000 persons die from the disease. In Mexico, cutaneous leishmaniasis is known as chiclero’s ulcer and is reported in 22 states; it is considered a health problem. For its treatment, pentavalent antimonial drugs are administered; these drugs cause severe side effects, are costly, and drug-resistant cases have been reported and have been developing for >70 years. One alternative to the drugs that are currently available is to find active molecules in medicinal plants; dihydrocorynantheine, corynantheine, and corynantheidine are active against Leishmania major, while harmane, pleiocarpin, buchtienin, luteolin, and quercetin are active against L. donovani. In Mexico, about 20 medicinal plants have been evaluated against L. mexicana, among which the most active are Tridax procumbens, Tridax procumbens, Pentalinon andrieuxii, Lantana camara, Schinus molle, and Prosopis laevigata. From some of these plants, active compounds with IC50 ≤ 30 μg/mL or μM have been isolated, such as 3(S)-16,17-didehydrofalcarinol or Oxylipin, cholestra-4,20,24-trien-3-one or pentalinosterol, 24-methylcholest-4-24(28)-dien-3-one, cholest-4-en-3-one, 6,7-dihy-droneridie-none, neridienone, cholest-5,20,24-trien-3β-ol, and isocordoin. Today, the only pentalinonsterol has been synthesized and assayed in the visceral leishmaniasis experimental model using BALB/c mice infected with L. donovani. Liposome formulation of this compound administered by intravenous route at 2.5 mg/kg showed a significant reduction of parasite load in mouse liver and spleen.",signatures:"María Adelina Jiménez-Arellanes and Rosalba León-Díaz",downloadPdfUrl:"/chapter/pdf-download/62245",previewPdfUrl:"/chapter/pdf-preview/62245",authors:[{id:"172408",title:"Ph.D.",name:"Maria Adelina",surname:"Jiménez-Arellanes",slug:"maria-adelina-jimenez-arellanes",fullName:"Maria Adelina Jiménez-Arellanes"},{id:"228234",title:"Dr.",name:"Gabriel",surname:"Gutiérrez Rebolledo",slug:"gabriel-gutierrez-rebolledo",fullName:"Gabriel Gutiérrez Rebolledo"},{id:"238807",title:"Dr.",name:"Rosalba",surname:"León-Díaz",slug:"rosalba-leon-diaz",fullName:"Rosalba León-Díaz"}],corrections:null},{id:"60372",title:"Nanomedicines for Cutaneous Leishmaniasis",doi:"10.5772/intechopen.75750",slug:"nanomedicines-for-cutaneous-leishmaniasis",totalDownloads:1049,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:1,abstract:"Leishmaniasis is a vector-borne disease caused by Leishmania parasites, which cause a range of clinical manifestations in man. These are didactically classified into cutaneous leishmaniasis (CL), the most common form of the disease, and visceral leishmaniasis (VL), the life-threatening form. There are so far no vaccines approved for humans. Conventional drugs pose limitations ranging from low efficacy and high cost to systemic toxicity. Low efficacy derives in part from difficult drug access to the parasites, which rides themselves inside macrophage phagosomes. This prompts to high dosage, with consequent increased toxicity. Difficult intracellular drug access can be overcome with nanomedicines such as biocompatible lipid and polymeric nanoparticles that can be phagocytosed by the infected macrophages. Besides cell membranes, appropriate drug nanostructuring may allow tissue barrier penetration and drug administration through higher compliance routes such as skin and intestine, in contrast to the usual intravenous and intramuscular routes. In general, CL and VL are both treated with toxic systemic injections, disregard of disease severity. This chapter will review and discuss studies with nanomedicines that have reached the market such as liposomal amphotericin B for intravenous administration, and innovative preclinical studies aiming at developing effective cutaneous and oral drugs with focus on CL.",signatures:"Ariane Sousa-Batista and Bartira Rossi-Bergmann",downloadPdfUrl:"/chapter/pdf-download/60372",previewPdfUrl:"/chapter/pdf-preview/60372",authors:[{id:"64710",title:"Prof.",name:"Bartira",surname:"Rossi-Bergmann",slug:"bartira-rossi-bergmann",fullName:"Bartira Rossi-Bergmann"},{id:"226010",title:"Dr.",name:"Ariane",surname:"Sousa-Batista",slug:"ariane-sousa-batista",fullName:"Ariane Sousa-Batista"}],corrections:null},{id:"61799",title:"Crossing Biological Barriers for Leishmaniasis Therapy: From Nanomedicinal Targeting Perspective",doi:"10.5772/intechopen.75911",slug:"crossing-biological-barriers-for-leishmaniasis-therapy-from-nanomedicinal-targeting-perspective",totalDownloads:976,totalCrossrefCites:3,totalDimensionsCites:4,hasAltmetrics:0,abstract:"Despite past 60 years of extensive research in antileishmanial drug development, the successful therapy of this disease cannot be achieved at full potential. The biological barriers encountered by the therapeutic modalities favor the disseminations of the disease like intramacrophage location of parasite, lack of oral bioavailability, permeability across the cutaneous tissue, and active efflux of the drug. Nanomedicines are specifically engineered nano-sized delivery systems. The goal of designing a nanomedicine is to achieve the specific therapeutic objective via targeting the specific cells and intracellular locations, pharmacological receptors, enzymes and proteins, crossing biological barriers, and navigation through endocytic pathways. This chapter will cover various nanomedicinal approaches like targeting the macrophages, pathological organs, efflux pumps, metabolic enzymes, redox biology of Leishmania by using polymeric and metal nanocarriers to overcome all the biological barriers thus providing a successful alternative over the conventional therapies.",signatures:"Gul Shahnaz, Hafiz Shoaib Sarwar and Masoom Yasinzai",downloadPdfUrl:"/chapter/pdf-download/61799",previewPdfUrl:"/chapter/pdf-preview/61799",authors:[{id:"223107",title:"Dr.",name:"Gul",surname:"Shahnaz",slug:"gul-shahnaz",fullName:"Gul Shahnaz"},{id:"223834",title:"Mr.",name:"Hafiz Shoaib",surname:"Sarwar",slug:"hafiz-shoaib-sarwar",fullName:"Hafiz Shoaib Sarwar"},{id:"233850",title:"Dr.",name:"Masoom",surname:"Yasinzai",slug:"masoom-yasinzai",fullName:"Masoom Yasinzai"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"5892",title:"Vaccines",subtitle:null,isOpenForSubmission:!1,hash:"7e74624c8b1de1d2014376e45df2c8dc",slug:"vaccines",bookSignature:"Farhat Afrin, Hassan Hemeg and Hani Ozbak",coverURL:"https://cdn.intechopen.com/books/images_new/5892.jpg",editedByType:"Edited by",editors:[{id:"186948",title:"Dr.",name:"Farhat",surname:"Afrin",slug:"farhat-afrin",fullName:"Farhat Afrin"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3092",title:"Anopheles mosquitoes",subtitle:"New insights into malaria vectors",isOpenForSubmission:!1,hash:"c9e622485316d5e296288bf24d2b0d64",slug:"anopheles-mosquitoes-new-insights-into-malaria-vectors",bookSignature:"Sylvie Manguin",coverURL:"https://cdn.intechopen.com/books/images_new/3092.jpg",editedByType:"Edited by",editors:[{id:"50017",title:"Prof.",name:"Sylvie",surname:"Manguin",slug:"sylvie-manguin",fullName:"Sylvie Manguin"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"825",title:"Current Topics in Tropical Medicine",subtitle:null,isOpenForSubmission:!1,hash:"ef65e8eb7a2ada65f2bc939aa73009e3",slug:"current-topics-in-tropical-medicine",bookSignature:"Alfonso J. 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Several scoring systems have been developed to help clinicians in the diagnosis of acute appendicitis. The best-known scores are the Alvarado score, the modified Alvarado score, the Pediatric Appendicitis Score, the Appendicitis Inflammatory Response score, and the RIPASA score. These tools not only can be used for diagnostic purposes but also for stratification, separating those patients who require observation and workup from those who can be assigned for certain specific treatment. The aim of these scores is to reduce the number of negative appendectomies without increasing the number of perforations.
\nThe Alvarado score was described in 1986 [1] and since then has been evaluated and validated in many studies. It consists of three symptoms, three clinical signs, and two laboratory tests. This system uses a simple mnemonics (
The basic laboratory tests are a complete blood count (CBC) to look for leukocytosis (>10,000 cells/mm3) and a differential white blood count (WBC) looking for left
Direct tenderness on the right lower quadrant can be replaced by direct percussion with the fist, as a mallet, on the right lumbar area in cases of retrocecal appendicitis which occurs in 75–85% of cases.
\nRebound pain can be replaced by other indirect signs such as the Rovsing sign, Dunphy sign (cough test) or the Markle’s test (heel-drop jarring test), pain on walking, pain with jolts or bumps in the road, and the inspiration test. Uncommon tests of peritoneal irritation such as the psoas and the obturator tests can replace the rebound pain test also. In children who are unable to communicate well, cutaneous hyperesthesia can be added to replace the migration symptom.
\nIn order of decreasing importance, the best predictive factors proved to be localized tenderness on the right lower quadrant, leukocytosis, migration of pain, shift to the left, temperature elevation, nausea or vomiting, anorexia or acetone in the urine, and direct rebound pain. Two points are assigned to the more important factors (tenderness and leukocytosis) and a value of 1 for each one of the others, for a possible total score of 10. A score of 4–5 is compatible with the diagnosis of acute appendicitis, a score of 7 or 8 indicates a probable appendicitis, and a score of 9 or 10 indicates a very probable appendicitis. To this score the clinician could subtract two points if the patient complains of headache because this symptom is very rare in cases of acute appendicitis. In this particular situation, the patient may need further investigation to rule out a different disorder.
\nScores of 5 or 6 are in a gray area, and in this case, the clinician may want to observe the patient for a short time (reevaluate every 4–6 hours) for 12–24 hours, and if the score remains, the same consider other tests such as ultrasound or diagnostic laparoscopy. When the score is 3 or 4, the clinician has two options: the patient could be kept under observation and repeat the tests or, even more, order additional tests such as an US or a CT scan if they are available in that particular setting. Another option is to rely on the clinical impression of the examiner because, as I already mentioned in my original article, “there is always an intangible ingredient in the diagnosis of acute appendicitis.”
\nThe modified Alvarado score (MAS) [2] is a simplification of the Alvarado score by eliminating the neutrophil count because a differential WBC count is not available in certain facilities. The results are similar to the original score but with less capacity to detect the early stages of acute appendicitis.
\nThe Pediatric Appendicitis Score (PAS), developed by Samuel in 2002 [3], is a modification of the Alvarado score in which the rebound sign has been replaced by cough/percussion/hopping tenderness in the right lower quadrant, and the elevation of temperature has been increased to 38°C. In this score the sign of tenderness in the right lower quadrant, the most relevant feature of the score, was given one point only.
\nThe Appendicitis Inflammatory Response (AIR) score [4] is based along the same principles of the Alvarado score assigning patients to low, medium, or high probability of acute appendicitis. It was developed by Andersson and Andersson in 2008 and was constructed from eight independent variables (right lower quadrant pain, rebound tenderness, muscular defense, WBC count, proportion of neutrophils, CRP, body temperature, and vomiting). The AIR score contains rebound tenderness or muscular defense that is divided in three groups—light, medium, and strong—which makes these signs subjective and very difficult to evaluate, and this may deviate the final score one way or another. Besides this, the AIR score omits the symptom of migration of pain which is a very important and specific symptom in the diagnosis of acute appendicitis.
\nThe Raja Isteri Pengiran Anak Saleha Appendicitis (RIPASA) score [5] was developed for the diagnosis of acute appendicitis in Brunei, Darussalam, in 2008. It contains 14 patient characteristics: gender, age, and symptoms, right iliac fossa (RIF) pain, migration to the RIF, anorexia, nausea and vomiting, duration of symptoms, and clinical signs RIF tenderness, guarding, rebound tenderness, Rovsing sign, and fever. It also contains two laboratory tests (WBC and urinalysis) and an additional parameter related to a foreign national card record. Some authors found that the Alvarado score was disappointing in the diagnosis of acute appendicitis in Asian and Mid-Eastern populations, so they decided to have a different score more suitable to them. Chong [6] found that the RIPASA score of >7.5 correctly classified 98% patients confirmed with histological findings of acute appendicitis in comparison with 68.3% patients with an Alvarado score of >7. However, RIPASA and Alvarado scores correctly classified 81.3% and 87.9% patients without acute appendicitis into the true negative groups with scores of >7.5 and <7, respectively. The negative appendectomy rate was 14.66% for the RIPASA score and 13.75% for the Alvarado score.
\nKhadda et al. [7] found that the RIPASA score has a sensitivity of 97.7% and a specificity of 77.4% and a negative appendectomy rate of 13.7% which is higher than many reports that had used the Alvarado score such as Menon et al. [8], in Pakistan, who reported a negative appendectomy rate of 1.9%. In other study, Pouget-Baudry et al. [9], in France, reported 3 out of 174 patients with a normal appendix on histological examination which equals to 1.72%. The good thing is that Khadda recognized that the Alvarado score is the simplest of all the scores used in current practice. Furthermore, Gaikwad et al. [10], in India, found that the false-positive rate is reduced to zero when ultrasonography is added to the Alvarado score.
\nGoel et al. [11], in India, evaluated the efficacy of the Alvarado score and the RIPASA score finding that the Alvarado score has a better specificity than the RIPASA score (100 vs. 50%) and also a better negative appendectomy rate (0 vs. 5%). Similar results were reported by Karami et al. [12], in Iran, who found that the Alvarado score was 100% specific as compared with the RIPASA and the AIR scores (91.6% for both).
\nMalik et al. [13], in Ireland, found that the RIPASA score has a PPV of 84.06% and a NPV of 72.86% with a negative appendectomy rate of 15.94% and an accuracy of 80%. This is the first study evaluating the utility of the RIPASA score predicting acute appendicitis in a Western population. However, Rodrigues and Sindhu [14], in India, found that the Alvarado score had a greater specificity, PPV, and positive likelihood than the RIPASA score. The negative appendectomy in this study was quite high (18.09%) as compared to different negative appendectomy rates reported with the Alvarado score that range between 0 and 10%. Similar results were reported by Rathod et al. [15] with a negative appendectomy rate of 20.69% and a perforated appendicitis of 8.05%. This indicates that the RIPASA score can reduce the number of complicated appendectomies at the expense of a high negative appendectomy rate.
\nIn a recent study in India, Regar et al. [16] found that the Alvarado score is more specific (80%) than the RIPASA score (60%). The PPV of the Alvarado score was 98.46% as compared to 97.83% of the RIPASA score. The negative appendectomy rate for the Alvarado score was lower that the RIPASA score (1.54 vs. 2.17%).
\nIn another recent study, Sinnet et al. [17], in India, found that the RIPASA score has more sensitivity than the Alvarado score (95.5 vs. 65%) but has less specificity (65 vs. 90%). The PPV was 92.89% for the RIPASA score and 96.6% for the Alvarado score which indicates that the negative appendectomy rate is higher for the RIPASA score than the Alvarado score (7.61 vs. 3.33%).
\nIn a study to assess the reliability and practical application of the Alvarado, Eskelinen, Ohmann, and RIPASA scoring systems, Erdem et al. [18], in Turkey, found that the Alvarado score had the best negative appendectomy rate (12%) than the RIPASA score (25%). The negative appendectomy rate for the Ohmann and the Eskelinen scores was 22 and 21%, respectively.
\nDiaz-Barrientos et al. [19], in Mexico, found that the RIPASA score showed no advantage over the Modified Alvarado score taking into consideration that the ROC curve area was 0.59 for the RIPASA score vs. 0.71 for the modified Alvarado score.
\nIn another study, in Mexico, Reyes-Garcia et al. [20] found 15.7% cases of necrotic appendicitis and 14.3% cases of perforated appendix when using the RIPASA score. The negative appendectomy rate was also high (18.6%).
\nGolden et al. [21] compared the physician-determined decision with the RIPASA, the Alvarado, and the modified Alvarado score systems in order to measure the physician gestalt in the diagnosis of acute appendicitis. They found that at the higher “rule-in” cutoff threshold, the RIPASA score had a high sensitivity (78%) but a low specificity (36%). Conversely, the modified Alvarado score had a low sensitivity (47%) and a high specificity (81%). The original Alvarado score had test characteristics between these two values. They also calculated the test characteristics for the clinical scoring systems at lower “rule-out” threshold. The NPV for each score varied from 75% for the modified Alvarado score to 89% for the RIPASA score. The NPV for the physician-determined decision was 83%. The area under the curve (AUC) was greatest for the Alvarado score and the physician-determined decision (72% for both), 70% for the MAS score, and 67% for the RIPASA score. These authors concluded that the physician-determined probability estimates were accurate as these scoring systems, which proves that the physician gestalt works well in the diagnosis of acute appendicitis.
\nAll of these findings on the RIPASA score indicate that we need more studies to find out why the differences among the Western and South Asian and Middle Eastern populations. It is possible that these differences have to do with the anatomical position of the appendix and not precisely with the physiopathological process of acute appendicitis or the cultural differences of these populations.
\nThere are other less-known scores similar to the Alvarado score such as the Adult Appendicitis score of Sammalkorpi et al. [22] that was constructed by logistic regression analysis using multiple imputations for missing values. This score contains four symptoms and clinical signs including the sign of guarding divided into three graduations (mild, moderate, and severe) which is in reality a very subjective sign. It also contains two laboratory tests (WBC and CRP) divided at different levels that are very difficult to memorize. They reported sensitivities and specificities similar to the Alvarado score and areas under the ROC curve of 0.882 for the new score and 0.790 for the Alvarado score. The negative appendectomy rate for this new score is 18.2% which is much higher than the usual reported rates with the Alvarado score.
\nThe Tzanakis scoring system [23] is a very simplified score that contains two clinical signs only: right abdominal tenderness (four points) and rebound tenderness (three points). The only laboratory test is a white blood cell count (WBC) greater than 12.000 cells/mm^3 (two points). The score relies on positive ultrasound scan findings (six points).
\nSigdel et al. [24] carried out a prospective study of the Tzanakis score to compare this score with the Alvarado score and reported a sensitivity of 91.4% for the Tzanakis score and 81% for the Alvarado score. The specificity for both scores was the same (66.6%). The ROC curve gave an AUC of 0.867 for the Tzanakis score and 0.81 for the Alvarado score. The negative appendectomy rate was reported as 6% which is certainly low and is due to the addition of the ultrasound studies that are not available in many health facilities. The overall diagnostic accuracy for the Tzanakis score was 91.48% vs. 81.91% for the Alvarado score.
\nIn a study to compare the sensitivity, specificity, and diagnostic accuracy of the Tzanakis score (TS) and the modified Alvarado score (MAS), Sharma et al. [25], in India, found that the sensitivity for the MAS was higher than the TS score (97.7 vs. 82.0%), but the specificity for the TS was higher (36.38 vs. 18%). The PPV for both scores was the same (19%), and the accuracy for the MAS was better than the TS (89 vs. 79%). They concluded that the MAS was better than the TS since in the TS there are chances of observer bias. Besides this, they could not wait till a leukocyte count goes up to 12,000 cells/cm3 if clinical suspicion is present.
\nKumar et al. [26], in India, found that the Tzanakis score is an effective modality in the establishment of accuracy in the diagnosis of acute appendicitis, but the limitation is observer bias which may vary the scoring results.
\nThe Lintula score [27] was developed from 35 symptoms and clinical signs recorded for 131 Finnish children with abdominal pain and was modeled using logistic regression. This complicated score uses gender, intensity of pain, relocation of pain, vomiting, pain in the right lower quadrant, fever, guarding, bowel sounds, and rebound tenderness with different grades. Some of these signs are very difficult to evaluate which may alter the final scoring.
\nKonan et al. [28], in a study to compare the Alvarado and the Lintula scores in patients older than 65 years of age, found that the Alvarado score was better predictor than the Lintula score. Both scores have a high sensitivity and specificity in the diagnosis of acute appendicitis.
\nOjuka and Sangoro [29], in a prospective study, carried out at Kenyatta National Hospital, found that the ROC curves for Lintula and Alvarado scores are almost identical (0.6824 and 0.6966), respectively. However, the sensitivity for the Lintula score is lower than the Alvarado score (60.8 vs. 83.3%), and the overall accuracy for the Lintula score was also lower (69.6 vs. 70.4%).
\nThe Ohmann score [30] was developed in Germany using a computer-aided diagnosis. The variables of the score are tenderness, no micturition difficulties, steady pain, leukocytosis count >10,000 cells/mm3, age >50 years, relocation of pain to the right lower quadrant, and rigidity. In spite of this computerized system, there was no improvement in the number of perforations or complications.
\nIn an analysis of scores in the diagnosis of acute appendicitis in women, Horzic et al. [31] compared the modified Alvarado score, Ohmann score, and Eskelinen score finding that all patients with the modified Alvarado score of 7 or more had acute appendicitis (100% specificity) which can be used to determine the need for immediate appendectomy.
\nRecently, Wilasrusmee et al. [32] developed a new appendicitis score for patients with suspected appendicitis and compared it with the Alvarado score. This score, also known as RAMA-AS, includes seven variables (migration of pain, progression of pain, pain aggravation by cough or movement, temperature of 37.8°C or more, and rebound tenderness). Also, it includes two laboratory tests (WBC >10,000 cells/mm3 and neutrophils <75%). In the evaluation of the variables of the score, there are serious questions. For example, they gave great importance to rebound tenderness (the only sign of the score) which contradicts the literature that always mentions direct tenderness in the right lower quadrant as the main variable. Besides this, their own statistic shows that rebound tenderness is present in 23.9%, whereas tenderness in the right lower quadrant is present in 88.4% of their cases. Another significant discrepancy is that they gave more importance to pain aggravation than anorexia (56.3 vs. 76.1%). Another objectionable symptom is progression of pain since this is a very subjective symptom that is difficult to evaluate. The C-statistics reported by Wilasrusmee et al. are better than the Alvarado score, but the RAMA-AS score did not perform well in the external data when compared to the derived data. Using the score in practice is not as easy as claimed by this group since it requires the use of the Fagan nomogram. In addition, the calculation of the score is difficult to obtain because the evaluation of the parameters is given in fractional numbers. For all of these reasons, the new score will need external evaluations to establish its usefulness in the real practice.
\nKhanafer et al. [33] made some modifications to the Alvarado score (AS) and the Pediatric Appendicitis score (PAS) to screen children at low risk for appendicitis who could be carefully observed at home without the need for laboratory investigation. In this study, a total of 180 children were enrolled with an average age of 11.2 years of which 56.7% were female. According to their findings, children with a score of >7 for the modified PAS and AS may be safely sent home with close follow-up, while those above this cut-off would benefit from a referral for further evaluation in the ED. They found similar sensitivities for all the scores but reduced specificities and predictive values for the modified PAS and AS scores. As expected, the ROC curves showed a reduced AUC using the modified scores. The negative appendectomy rate was 5.2% only.
\nA good diagnostic score for acute appendicitis should be simple, easy to memorize, repeatable, economical, and easy to apply in an emergency setting. It should contain elements with a good statistical significance. Also, a good diagnostic score for acute appendicitis could be useful for statistical purposes by providing a more precise indexing of the disease. For example, it could be used, as a clinical indicator, in the International Classification of Diseases at a fifth digit level.
\nObesity and chronic noncommunicable diseases, such as diabetes and cardiovascular disease, lead to the main causes of disability and premature mortality worldwide. In recent decades, the prevalence of obesity in the world has increased exponentially in children and adolescents, going from 0.7% to 5.6% in boys and from 0.9% to 7.8% in girls, between 1975 and 2016 [1]. Simultaneously, the incidence of type 2 diabetes (T2D) in the youth increased from 9 to 12.5 cases per 100,000 between 2003 and 2012 [2]. Additionally to the increase in obesity and diabetes, the development of unhealthy habits, such as inadequate diet and sedentary lifestyle in young people, have contributed to the development of cardiovascular diseases (CVD) at an early age [3]. Data from the National Health and Nutrition Examination Survey (NHANES) estimated a prevalence of ischemic heart disease of 0.5–0.6% in the United States for the period 2011–2014 in young adults between 20 and 39 years old. This trend is increasing, and it is expected that by 2030, 43.9% of the US adult population will have some type of cardiovascular disease [4].
The attempts to prevent or palliate the current wave of obesity and the following noncommunicable diseases should be funded at the beginning of human life. An interesting hypothesis is proposed: The Developmental Origins of Health and Disease (DOHaD) that is derived from the Barker hypothesis, which proposed that nutrition during the intrauterine period and exposure to infections after birth determine susceptibility to disease and death from coronary artery disease. This hypothesis has evolved, and currently, critical periods have been identified in fetal life and early childhood, which will determine growth, metabolism, neurogenesis, and future disease risk, expanding the hypothesis to other disorders, such as obesity, diabetes, cardiovascular disease, allergies, and neurological alterations, throughout the life. The DOHaD concept is based on epigenetics and explains the possibility of variations in the programming of the fetus and the infant through the modification of environmental factors, such as diet and infections, in these window periods [5].
Another main component involved in the early life stages is the gut microbiota, defined as the microbial ecosystem that colonizes the gastrointestinal tract, depending on perinatal and environmental factors, such as diet. Its balance is associated with health and its imbalance with the presence of various diseases, although the mechanisms involved have not been fully elucidated; and as with the DOHaD theory, window periods have been identified where its modulation is possible, especially in the perinatal period and up to preschool age [5, 6]. Thus, the aim of this chapter is to discuss the role of the perinatal maternal and infant diet and the gut microbiota to explain the development of chronic noncommunicable diseases from the DOHaD perspective, as key factors in the modulation of epigenetic programming mechanisms, to identify the areas of opportunity for preventive purposes in early childhood.
Gut microbiota establishment is determined by several perinatal factors, including gestational pathologies, type of birth, type of feeding, prenatal and perinatal use of antibiotics, complementary feeding, and environmental pollutants [7]. From gestation to the first 2 years of life, these events influence the establishment of the microbiota. Hence, it affects the metabolic and immune response and has a subsequent impact on human health [8].
In the last century, the paradigm dictated that the womb was a sterile environment and that the first microbiota colonized the newborn at the birth time [9]. Even though this is yet a discussion topic, there is evidence pointing toward prenatal exposure to microbes [10]. Despite these, reports of low bacterial abundance and diversity and, in most cases, the lack of culturable bacteria leads to a reasonable doubt about whether it is an established microbiota or only transient exposure to DNA or microbial products that is occurring in the womb [11].
The first major event in microbial colonization for the newborn occurs at birth. Type of birth determines the first gut microbiota composition. Vaginally delivered infant’s fecal microbiota is enriched with
First microbiota evolves to adapt to the biochemical environment and in a dependent way on the nutrient availability in the gut [14]. In this sense, whether the infant is breastfed or not, impacts the gut microbiota composition. Ho
Breastfeeding meets all the infant macro and micronutrient requirements during the first 6 months, besides human milk oligosaccharides have a probiotic effect promoting a healthy gut microbiota. Also, human milk provides bioactive compounds that favor immune development, such as immunoglobulins, leukocytes, and antimicrobial peptides. Moreover, human milk harbors its own microbiota, the genera with potential probiotic use as
Before 6 months of age, microbial metabolic pathways related to carbohydrate metabolism are higher in non-exclusively breastfed infants [15]. Once other foods aside from breast milk are introduced into the infant diet, functional shifts toward polysaccharides and protein metabolism occur in gut microbiota. However, these changes are not noticeable until breastfeeding cessation. Microbiota composition turns to an adult-like profile with a high abundance of
The evidence on prenatal and perinatal factors influencing the composition of the gut microbiota highlights the importance of microbial colonization as a critical process in early human life. Healthy microbiota is indispensable for immune system shaping and development, and its metabolites promote the integrity of the intestinal mucosa.
Maternal diet is key for offspring development and future disease risk, and this is mediated by epigenetic modifications. In the gestational stage, maternal diet influences offspring epigenetics directly, after birth this influence continues through breastfeeding. Breast milk composition contributes to epigenetics directly as well as through the gut microbiota, which also modulates infant health and development.
During pregnancy, maternal nutrition is a determinant for in utero development, birth weight, and future disease risk. This has been confirmed in studies on the Dutch famine (1944–1945), a period of severe shortage of food in the Netherlands, which have shown that maternal undernutrition during gestation had lasting consequences on the offspring’s health. Also, prenatal exposure to the Dutch famine had transgenerational effects highlighting the influence of maternal nutrition over offspring epigenetics [17].
Epigenetic modifications are heritable biochemical markers in the genome that will not change its sequence but will determine gene expression, adapting to diverse environmental factors [18]. There are several epigenetic mechanisms, including DNA methylation, histone modification, and miRNA. DNA methylation is the most studied mechanism, and it relies on one-carbon metabolism. This pathway consists of two cycles, one dependent and one independent of folate. In the first cycle, folate acts as a methyl donor where homocysteine is re-methylated to form methionine. In the second cycle, betaine, and its precursor choline, act as methyl donors. Through this pathway, methionine is turned into S-Adenosylmethionine, the universal methyl donor, which will contribute to DNA methylation [19]. Therefore, DNA methylation depends on methyl donor supply, such as folate, choline, and betaine.
Dietary sources of methyl donors vary according to culture and geographic region. The best sources in Western diets are meat, dairy, and grains; while, in Mediterranean diets, fish, legumes, whole grains, and vegetables are the main sources [20]. According to Taylor
In the gestational stage, offspring’s DNA methylation patterns are formed, and maternal intake of methyl donors contributes to proper development and growth. Pauwels
There are strong interactions between maternal dietary intake and offspring DNA methylation and health. A high maternal betaine status during pregnancy is associated with lower offspring adiposity; in contrast, a low maternal folate status is associated with a future risk of childhood overweight and obesity [25, 26]. These findings highlight the impact of maternal nutrition during gestation on the offspring’s metabolic health.
After birth, the maternal diet continues, influencing DNA methylation through breastfeeding. Therefore, breastfed infants have higher DNA methylation in childhood, compared with formula-fed children [18]. In addition, Briollais
Compounds such as lipids, oligosaccharides, B vitamins, and betaine, are influenced by dietary intake [28]. Changes in breast milk content will have an impact on infant health, growth, and the development of gut microbiota. Fat and energy content in breast milk is associated with adipose tissue gain in breastfed infants [29]. Additionally, the intake of methyl donors through breast milk could have a direct effect on DNA methylation or could modulate epigenetic modifications via the infant gut microbiota. In two different populations, it was found that betaine concentration in breast milk was associated with infant growth in the first years of life, and betaine concentration was related with the abundance of
The development of the gut microbiota occurs in early life, and breast milk has the optimal composition for promoting its proper establishment. For instance, a study that evaluated the fecal microbiota of exclusive breastfed and formula-fed infants found that formula-fed children had a rapid maturation of the gut microbiota, which is associated with future obesity risk [32]. In addition, different types of breastfeeding have an impact on the gut microbiota, breastfed infants with skin-to-skin contact have a healthier microbiota than those fed from a bottle [33].
Many aspects of health are determined by the early gut microbiota, including infant growth. Children with a rapid maturation of the gut microbiota and a high abundance of
The gut microbiota produces a great number of metabolites that participate in epigenetic regulations. Butyrate and propionate produced by
Epigenetics play a big role in determining infant development and health, and from conception to the postnatal stage, the maternal diet is key for supplying nutrients and components that are necessary for epigenetic regulation. During lactation, breast milk influences epigenetics directly or through the gut microbiota. There is a need for more evidence to elucidate the interactions between breast milk composition, infant gut microbiota, and epigenetic modifications; and to emphasize the importance of maternal diet to ensure proper offspring development, health, and minimize future disease risk.
The main physiological effects observed in the host by gut microbiota could be explained by their metabolite production. There are different products identified and the most studied are short-chain fatty acids (SCFA), where acetate, butyrate, and propionate are the most common and with the most known effects [36]. Other metabolites include trimethylamine-N-oxide (TMAO), obtained from compounds containing choline [37, 38]; secondary bile acids [39]; free anthocyanidins and protocatechuic acid, derived from flavonoid anthocyanins [38], and indolepropionic acid, produced from tryptophan [40]. The ones with beneficial effects on host health are SCFA, anthocyanidins, and indole compounds, and we are going to focus on the first ones.
SCFAs are produced in the bowel lumen by fermentation of dietary fiber [41] by anaerobic bacteria such as
These molecules exercise their effects by direct or indirect pathways [37]. Direct mechanisms include local or systemic effects, where the microbiota-gut-brain axis is the most studied systemic example [42]; and indirect ways include the effects of these metabolites in other microbes that could modify their function [37].
SCFAs are associated with the maintenance of gut epithelium integrity and protection of the intestinal barrier [36, 37]. Their principal mechanism is as an energy source for enterocytes, but also butyrate and indole derivatives have been associated with aryl hydrocarbon receptor (AhR) ligands, a nuclear receptor whose activation is reported to modulate cell proliferation, immune response, gene expression, and epithelial barrier function [43]. This association with a healthy intestinal epithelium had been explained by the “Warburg effect” or “butyrate paradox.” Briefly, fiber-rich diets, associated with an increase in SCFA-producing bacteria, induce normal colonocyte proliferation and apoptosis in neoplastic cells, when metabolism is promoted by glucose [37, 38].
Furthermore, butyrate is important for the maintenance of intestinal barrier integrity because increases the expression of tight junction proteins, such as claudin-1, claudin-7, zonula occludens-1 (ZO-1), and ZO-2 [36, 38, 44]. Also, SCFAs can modulate mucin glycoprotein in the mucus layer [45], induce epithelial cell production of RegIIIγ and β-defensins, antimicrobial peptides [46], and reduce luminal pH [36]. All these functions help to avoid the proliferation of pathogenic bacteria and reduce the translocation of molecules to the systemic circulation.
Besides local effects, microbiota metabolites can travel across the intestinal epithelium to systemic circulation or the central nervous system. This can impact different cells via extracellular receptors previously known as G protein-coupled receptors (GPRs) 43, 41, 81, 109A, and 91 [37]. For instance, propionate has a high affinity to GPR41, now called free fatty acid receptor 3 (Ffar3), which modulates cyclic adenosine monophosphate (cAMP); and to GPR43, now Ffar2, which increases the activity of calcium/protein kinase C (PKC) [36]. Butyrate also has activity on GPR 41 and is the only ligand of GPR109A, now hydrocarboxylic acid receptor 2 (HCA2), which also increases cAMP. Depending on the stimulated cells, effects can be seen in the endocrine, immune, and neurologic systems. For example, activation of the HCA2 receptor in dendritic cells and macrophages is associated with stimulation of T cells into the Treg phenotype [47, 48].
SCFAs also act as inhibitors of histone deacetylases (HDACs). When N-acetyl lysine on DNA histones loses its acetyl group, a more tightly wrapped double chain is formed. HDACs are enzymes that remove this acetyl group, altering DNA transcription by limiting access to transcriptional factors [37]. SCFAs can modify the transcription of a broad range of genes by inhibiting HDACs. Besides, butyrate can act as a ligand of nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ) to modulate the transcription of genes associated with lipolysis and adipogenesis [38, 49]. These different pathways help understand the systemic effects that SCFA can have in several organs, depending on which receptor is activated and the dominant SCFA.
The most beneficial effects of SCFAs are associated with an anti-inflammatory profile. They help to regulate cytokine expression, promoting the production of IL-10, and subsequently, differentiation of Treg cells by the Ffar2 mechanism [36, 37]. Besides, due to their capacity for inhibiting HDACs, SCFAs can impede the activation of nuclear factor-kappa β (NF-κB) [38], a protein complex mainly associated with inflammation. When its RelA/p65 subunit is acetylated, NF-κB can increase gene expression of pro-inflammatory cytokines, such as IL17, IL-1b, IL-6, and IL-12 [50], and enhance transcription of growth factors, adhesion molecules, and immune receptors [36]. Altogether, when the production of pro-inflammatory cytokines is reduced and Treg cells are predominant, the immune response is more regulated, and the risk of inflammatory pathologies is decreased.
SCFAs can suppress the NLRP3 inflammasome and promote an adequate immunologic response by directing T cell differentiation in appropriate phenotypes [36]. For example, reducing systemic inflammation in allergic reactions by modification of T helper type 2 cell numbers [37]. Besides, SCFAs are associated with decreased IL-8 in macrophages and neutrophils, TNF-α in mononuclear cells, and nitric oxide synthase in monocytes [51]. Similarly, butyrate can reduce prostaglandin synthesis by inhibiting COX-2 transcription [50]. All these effects help support the anti-inflammatory profile associated with a fiber-rich diet.
Moreover, SCFAs can influence humoral response. In plasmatic cells, acetate can increase retinoic acid conversion from vitamin A, facilitating response to CD4+ T cell and IgA production [47, 52]. Besides, butyrate and propionate favor antigen affinity inhibiting somatic hypermutation and enhancing class-switch DNA recombination in B cells [53]. SCFAs also influence the proliferation and migration of immune cells, not only as energy sources but through MPAK signal transduction and cascades associated with Ffar2 and Ffar3 receptors [51]. HDACs inhibition activity modulates lymphocyte function, increasing Th1, Th17, and innate lymphoid cells2 (ILC2) and ILC3 [47]. In summary, SCFAs not only allow a more balanced immune response but a more efficient and effective one.
SCFAs have proved to impact immune system development in early life. Exposure to SCFAs during the weaning period is associated with a tolerogenic phenotype and lower risk of inflammatory pathologies later in life, improving CD25+ Treg cells, humoral response, and gut epithelium integrity; confirming microbiota’s role in immune system development [54].
Microbiota and their metabolites participate in the bidirectional communication between gut and brain, called the microbiota-gut-brain axis [42]. When SCFAs translocate from intestinal epithelium, they can travel by system circulation, immune system, or enteric-cerebral nervous pathway to provoke changes in distal organs [37, 49].
In the nervous system, butyrate is associated with an increase in cholinergic neurons in the gastrointestinal tract to facilitate motility, propionate with sympathetic activation to greater energy expenditure, and acetate with satiety by hypothalamic stimulation [55]. Similarly, along the gastrointestinal tract, there are enteroendocrine cells (EECs) that sense luminal content and release hormones in the systemic circulation. SCFAs can increase the release of glucagon-like peptide 1 (GLP-1) and peptide YY (PYY), affecting appetite signals and influencing weight control [49]. Therefore, SCFAs can modify autonomic functions and behavior, separately from CNS influence [56].
Another mechanism by which SCFAs alter neurological functions is by direct communication through the vagus nerve and enteric nervous system. SCFAs can alter the expression of GABA receptors [49], production of endothelial nitric oxide, anti-inflammatory and pro-inflammatory components in cerebral microcirculation [55], and increase neurogenesis [56]. Likewise, microbiota’s metabolites are associated especially with microglia maturation and function, involving Toll-like receptors (TLRs) [49] and blood–brain barrier integrity [55]. These effects on CNS immune cells explain why SCFAs are associated with less risk of neuroinflammatory disorders.
There are still many mechanisms to be elucidated that could explain all the beneficial effects that microbiota’s metabolites in eubiosis could have on host health. However, so far, our diet and early life events are one of the most important interventions to secure a healthy immune and neurologic system, through microbiota modulation.
Throughout life, the structure of the intestinal microbiota can be affected by different factors, such as diet, drugs, the host’s immune system, and even the intestinal mucosa itself. Changes in the microbiota can be transient or long-lasting. However, most of the time, alterations in multiple factors are required to generate changes in the microbiota that become harmful to health. This is because the microbiota has resilience, also known as the ability to adapt, to some extent, to changes in the availability of nutrients or environmental conditions [57]. However, when negative conditions are maintained over time, for example, when breastfeeding is not provided or when there is an inadequate dietary pattern or lifestyle in the early years of life, a persistent imbalance of bacterial communities is generated, known as dysbiosis [58].
In addition, some elements have been identified that can amplify or drive changes in the microbiota, making the imbalance more evident and leading directly to dysbiosis. Among them are an increase in the richness of bacteriophages with lytic action in the intestinal environment [59] and the secretion of bacteriocins as a bacterial competition strategy in the intestinal ecosystem. Both situations are enhanced when there is some type of stress [60]. For example, oxidative stress also leads to dysbiosis by promoting the increase of specific bacterial communities and causing the activation of the immune system, as well as the development of subclinical inflammation [57]. This, together with the local and systemic effects of imbalanced SCFAs, described in Section 4 of this chapter, links dysbiosis with the pathophysiological processes of some noncommunicable metabolic diseases, such as obesity, T2D, and CVD [58], as is shown in Figure 1.
Perinatal determinants of the first microbiota and effects of protective or harmful interventions for child health through life. BMI: Body mass index, SCFA: Short-chain fatty acids, TMAO: Trimethylamine-n-oxide, T2D: Type 2 diabetes, ACVD: Atheroesclerotic cardiovascular disease.
Different studies have confirmed that there is an imbalance in the intestinal microbiota of obese children when compared to healthy children with normal weight. In general, an increase in the Firmicutes/Bacteroidetes (F/B) ratio has been described in some populations [61]; while in others, no differences have been found at the phylum level [62]. In the systematic review by Indiani
The specific mechanisms by which these associations could explain the early development of obesity from the DOHaD perspective are diverse. In the Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort [67], 935 mother-infant dyads were followed from pregnancy through the first 3 years. Their results explain the intergenerational transmission of overweight and obesity, where having an obese mother and being born by cesarean section increases the risk 5 times for obesity at 1 and 3 years. In this model, the abundance of some specific families of Firmicutes, such as Lachnospiraceae, were sequentially associated with the development of obesity. This association increased in children with obese mothers and was even higher in those born by cesarean section.
Bacteria belonging to the phylum Firmicutes are mostly SCFA producers, such as butyrate and acetate. This supports the findings of Riva
In obese Canadian children [70], prebiotic supplementation for 16 weeks was associated with a normalized rate of weight gain, decreased percent body fat, and changes in gut microbiota structure, characterized by the increase of
There is increasing evidence of the role of the microbiota in the development of type 2 diabetes (T2D) in youth. In a murine study [71], it was found that during pregnancy, maternal gut microbiota provides protection against obesity and diabetes, through mechanisms related to the SCFA receptors GRP41 and GRP43, which are part of the FFAR family of receptors. This axis participates in the prenatal development of the metabolic and neural systems, driving the development of enteroendocrine cells and pancreatic beta cells. In this way, the deficiency in the signaling of this pathway caused sympathetic dysfunction, compromising energy metabolism, and inducing hyperglycemia.
As in children with obesity, adult patients with T2D have heterogeneous results regarding the F/B ratio [72, 73]. In a study conducted in China [74], it was found that when separating patients with T2D according to the presence or absence of chronic complications, the group without chronic complications presented a higher F/B ratio than those with complications, at the expense of increased Proteobacteria in the latter. Furthermore, some opportunistic pathogens have been identified as part of the microbiota of T2D patients, such as
Seeking to integrate the previous observations, different mechanisms have been proposed that link the microbiota with the regulation of glycemia. Among them is the production of SCFA due to its effects already described and the increase in the secretion of incretins such as GLP-1 and its role in the differentiation of enteroendocrine cells. In addition, there is evidence regarding their participation in the metabolism of bile acids (BA) and the consequent induction of local and peripheral signals, and the regulation of adipose tissue by promoting white adipose tissue browning and by acting as a trigger for metabolic inflammation [76].
The microbiota and its metabolites also modulate the risk and progression of atherosclerosis. Changes in the microbiota diversity and structure have been described in people with atherosclerotic cardiovascular disease (ACVD). As cardiovascular disease is a complication of obesity as well as diabetes, the identified mechanisms coincide with those we have described for these diseases. For example, in a study with 218 patients with ACVD [77], an increased abundance of Enterobacteriaceae and
Given that both cardiovascular disease and T2D have a pre-pathogenic period that can last for decades, and because overweight development usually begins in childhood, the perinatal period and early childhood represent a window of opportunity for their prevention and risk modulation.
There are different ways to gauge the window of opportunity during pregnancy and lactation periods. Firstly, the mother’s diet and physical activity during the preconceptional and pregnancy periods can induce favorable epigenetic modifications in early life. Second, the delivery way influences the intestinal microbiota composition of the newborn, where the advantage is vaginal delivery, followed by breastfeeding. At this point is quite important the physical contact between mother and child. Exclusive breastfeeding in the first 6 months, depending on the mother’s diet, can stimulate the best epigenetic activity to keep a normal growth rate, avoiding a rapid development by direct action or through the intestinal microbiota functionality. After 6 months, a proper food introduction is essential for promoting present and future child’s health, and for inducing a favorable intestinal microbiota balance.
As previously described, DNA methylation is crucial for processes epigenetically regulated. In the early embryogenic stage, most parental gametic methylation signs are erased before the acquisition of marks at implantation and beyond. Just after conception, the external environment influences early embryonic events, which are crucial for the DOHaD concept [79]. Therefore, the mother’s diet, energy balance, composition as well as her nutritional status, and physical condition are determinant during the periconceptional period [80]. Depending on the nutrient balance and richness of the women’s diet in methyl donor compounds, epigenetics modulation will promote normal growth to prevent accelerated fetal growth.
Dietary recommendations during pregnancy are related to amounts of energy, macro-, and micronutrients, such as vitamins and minerals. Dietary reference intake is 340 extra calories during the 2nd pregnancy trimester and 452 for the third one [81]. Pregnant women require a diverse diet, including fruits, vegetables, legumes, nuts, seeds, grains, and tubers, as well as animal-origin products such as dairy, meat, poultry, fish, and eggs. In contrast, pregnant women should avoid some raw seafood, alcohol, and caffeine.
Often health-related practices of a particular cultural group, based on its beliefs, negatively or positively affect the science-based dietary recommendations. For instance, Western diet patterns can fulfill the extra calories for pregnancy, mainly with animal-based products and supplements of vitamins and minerals. Although animal-origin foods contain enough choline, during pregnancy the folate requirement is 600 ug/d and the fiber recommendation is high (28–30 g/d), so supplements are needed [81]. Plant origin fiber is the best recommendation because fruits and vegetables contain in addition to fiber, some very important compounds with antioxidant activity, as well the methyl donor compounds such as betaine and folates, present in leafy green vegetables, broccoli, beans, and peas.
In addition to a diverse and balanced diet, during pregnancy physical activity is necessary for improving glucose tolerance and insulin activity, preventing excessive weight gain. The mother’s emotional well-being is important for the fetus, and fitness promotes an easier delivery.
The delivery mode defines the structure of the neonatal microbiota with an advantage of vaginal delivery over C-section delivery, and it is a key factor for the right development of the immune system [82]. The vaginal microbiota is the source of bacterial colonization for the neonate, with implications for the neonate and the mother’s health. Before delivery, the vaginal microbiota is mainly dominated by Lactobacillus, and just after delivery, it becomes diverse and similar to the neonatal oral microbiota [83].
In some cases, vaginal delivery is not possible, and C-section is done; additionally, because of strong causes, such as illness and drug treatments, feeding is through milk formulas. Apparently, the window of opportunity is lost, but there are other techniques to ensure healthy microbiota, for example, the use of probiotics, prebiotics, synbiotics, and postbiotics (PPSP) either by the mother or by the newborn. Prebiotics are nondigestible components of food that selectively promote the growth of beneficial bacteria in the intestine; while probiotics are live microorganisms that, administered in adequate amounts, confer a health benefit. On the other hand, synbiotics are a combination of prebiotics and probiotics, while postbiotics are an emerging option, which are soluble products or metabolites (such as SCFA) of commensal bacteria or bacterial components that provide benefits to the host [84]. The use of a combination of strains principally
There are still hospitals that pull apart the newborn from the mother if there was a C-section delivery, premature birth, or another reason associated with the mother or newborn’s health. Independently of the delivery mode, skin-to-skin contact between mother and child just after the first hour of life improves the possibility of exclusive breastfeeding in the lactation period. This technique helps to reduce neonatal morbidity due to multiple benefits; for instance, stabilizes cardiopulmonary function, and reduces the risk of hypoglycemia, hypothermia, and infections. After delivery, the effect on the mother is a reduction in anxiety and postpartum bleeding [85]. Everywhere, the neonatal intensive care units should promote family participative care, assisting skin-to-skin contact between the mother and newborn as soon as possible, for the establishment of breastfeeding [86].
Regarding general dietary recommendations during breastfeeding, there are higher requirements for carbohydrates and energy intake of up to 500 extra calories, from the beginning to 6 months of lactation. In addition, choline, dietary fiber, and water intake should be higher during the breastfeeding period than during pregnancy [81]. Besides a balanced diet with animal and vegetable sources, mothers should avoid some raw seafood, alcohol, smoking, and caffeine. It is very important to have the best diet for the mother and child’s well-being. Installation of breastfeeding is mandatory to induce a good balance of the child’s intestinal microbiota, for appropriate immune system development and general child health.
Once and again, microbiota appears in this chapter. It is because the community of different microorganisms in the intestinal tract produces metabolites and cell detritus involved in human metabolic functions. Furthermore, the microbiota influences the immune and central nervous systems; as such, the inhibition of the feeding activity promotes neurons, which ultimately decreases appetite [87]. Therefore, microbiota in dysbiosis could be implicated in metabolic disorders, such as obesity.
A strategy to help the infant to maintain the balance and achieve the stability of its microbiota is to make a correct introduction of solid foods in its diet or complementary feeding. It starts when breast milk or formula composition is not sufficient to accomplish the nutritional requirements of infants, usually from six to 23 months. Breastfeeding can continue at the same time as complementary feeding; the focus is to provide nutrients enough to meet the nutritional requirements of infants. A complementary feeding that is carried out in a staggered manner allows the microbiota to adapt and enrich itself in diversity; thus, it becomes more stable. The problem is that if neglected, complementary feeding has the potential to contribute to childhood overweight and obesity [88].
PPSPs have shown beneficial potential for treating overweight and obesity in children. The proposed mechanism is the modulation of the structure of the microbiota, the profile of microbial metabolites, and the improvement of the intestinal barrier mechanism [84, 89]. In patients with T2D, the use of PPSP decreases fasting blood glucose, total cholesterol, triglycerides, and insulinemia, as demonstrated in the meta-analysis by Bock et al. [90]. However, more studies are still needed to define its role in the prevention and/or treatment of chronic noncommunicable diseases, especially during pregnancy and early childhood.
The task to accomplish a good approach to raising a healthy child across the life course looks so difficult, but any effort pays off with profit. A well-planned pregnancy followed by a balanced and diverse diet, a vaginal delivery with immediate breastfeeding, skin-to-skin contact between mother and newborn, and basic care for the first months is crucial for the metabolic programming of the baby. However, also a carefully complementary feeding from 6 to 24 months, as well as an adequate lifestyle, will help maintain eubiosis, the proper maturation, and functioning of the immune system, and reduce the risk of developing early chronic diseases.
There is evidence that demonstrates the relationship between alterations in the intestinal microbiota and the risk of developing chronic noncommunicable diseases throughout life, such as obesity, T2D, and stroke. The involved mechanisms derive from the local and systemic effect of microbiota products, such as SCFAs, indoles, anthocyanins, TMAOs, and BA, as modulators of the inflammatory response and lipid metabolism, among others. Perinatal and early childhood factors modulate the first microbiota and early metabolic programming by epigenetic mechanisms. Thus, the intestinal microbiota is an additional component to the epigenetic mechanisms that strengthen the DOHaD theory and that should be considered in the establishment of preventive measures in the first 1000 days of life.
The authors declare no conflict of interest.
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Zawada Jr."}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7978",title:"Vitamin A",subtitle:null,isOpenForSubmission:!1,hash:"dad04a658ab9e3d851d23705980a688b",slug:"vitamin-a",bookSignature:"Leila Queiroz Zepka, Veridiana Vera de Rosso and Eduardo Jacob-Lopes",coverURL:"https://cdn.intechopen.com/books/images_new/7978.jpg",editedByType:"Edited by",editors:[{id:"261969",title:"Dr.",name:"Leila",middleName:null,surname:"Queiroz Zepka",slug:"leila-queiroz-zepka",fullName:"Leila Queiroz Zepka"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7033",title:"Vitamin C",subtitle:"an Update on Current Uses and Functions",isOpenForSubmission:!1,hash:"719a5742e3271393fe43864e13e996cd",slug:"vitamin-c-an-update-on-current-uses-and-functions",bookSignature:"Jean Guy LeBlanc",coverURL:"https://cdn.intechopen.com/books/images_new/7033.jpg",editedByType:"Edited by",editors:[{id:"67023",title:"Dr.",name:"Jean Guy",middleName:null,surname:"LeBlanc",slug:"jean-guy-leblanc",fullName:"Jean Guy LeBlanc"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7263",title:"Vitamin E in Health and Disease",subtitle:null,isOpenForSubmission:!1,hash:"6bd8e547b4f3ad7f1675a36b8dbde8f2",slug:"vitamin-e-in-health-and-disease",bookSignature:"Jose Antonio Morales-Gonzalez",coverURL:"https://cdn.intechopen.com/books/images_new/7263.jpg",editedByType:"Edited by",editors:[{id:"109774",title:"Dr.",name:"Jose Antonio",middleName:null,surname:"Morales-Gonzalez",slug:"jose-antonio-morales-gonzalez",fullName:"Jose Antonio Morales-Gonzalez"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6709",title:"B Group Vitamins",subtitle:"Current Uses and Perspectives",isOpenForSubmission:!1,hash:"f34959a0fcc33a2c6fb3d03e9ec544bf",slug:"b-group-vitamins-current-uses-and-perspectives",bookSignature:"Jean Guy LeBlanc and Graciela Savoy de Giori",coverURL:"https://cdn.intechopen.com/books/images_new/6709.jpg",editedByType:"Edited by",editors:[{id:"67023",title:"Dr.",name:"Jean Guy",middleName:null,surname:"LeBlanc",slug:"jean-guy-leblanc",fullName:"Jean Guy LeBlanc"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6549",title:"Genotyping",subtitle:null,isOpenForSubmission:!1,hash:"6eb6c927e6cba4965ea3bbf741f82911",slug:"genotyping",bookSignature:"Ibrokhim Abdurakhmonov",coverURL:"https://cdn.intechopen.com/books/images_new/6549.jpg",editedByType:"Edited by",editors:[{id:"213344",title:"Prof.",name:"Ibrokhim Y.",middleName:null,surname:"Abdurakhmonov",slug:"ibrokhim-y.-abdurakhmonov",fullName:"Ibrokhim Y. Abdurakhmonov"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5940",title:"Vitamin C",subtitle:null,isOpenForSubmission:!1,hash:"e23e79359167bb9d4a53edd78c7b5038",slug:"vitamin-c",bookSignature:"Amal H. Hamza",coverURL:"https://cdn.intechopen.com/books/images_new/5940.jpg",editedByType:"Edited by",editors:[{id:"188326",title:"Associate Prof.",name:"Amal",middleName:null,surname:"Hamza",slug:"amal-hamza",fullName:"Amal Hamza"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],booksByTopicTotal:13,seriesByTopicCollection:[],seriesByTopicTotal:0,mostCitedChapters:[{id:"56013",doi:"10.5772/intechopen.69660",title:"Vitamin C: An Antioxidant Agent",slug:"vitamin-c-an-antioxidant-agent",totalDownloads:7779,totalCrossrefCites:26,totalDimensionsCites:55,abstract:"Vitamin C or ascorbic acid (AsA) is a naturally occurring organic compound with antioxidant properties, found in both animals and plants. It functions as a redox buffer which can reduce, and thereby neutralize, reactive oxygen species. It is a cofactor for enzymes involved in regulating photosynthesis, hormone biosynthesis, and regenerating other antioxidants; which also regulates cell division and growth, is involved in signal transduction, and has roles in several physiological processes, such as immune stimulation, synthesis of collagen, hormones, neurotransmitters, and iron absorption, has also roles in detoxifying the body of heavy metals. Severe deficiency of vitamin C causes scurvy, whereas limited vitamin C intake causes symptoms, such as increased susceptibility to infections, loosening of teeth, dryness of the mouth and eyes, loss of hair, dry itchy skin, fatigue, and insomnia. In contrast, vitamin C can also act as a prooxidant, especially in the presence of transition metals, such as iron and copper, starting different hazardous radical reactions. Vitamin C can both act as a strong, efficient, and cheap antioxidant agent and, at the same time, behave as a radical promoter. Further investigations are needed to illuminate the dual roles of vitamin C",book:{id:"5940",slug:"vitamin-c",title:"Vitamin C",fullTitle:"Vitamin C"},signatures:"Fadime Eryılmaz Pehlivan",authors:[{id:"200567",title:"Dr.",name:"Fadime",middleName:null,surname:"Eryılmaz Pehlivan",slug:"fadime-eryilmaz-pehlivan",fullName:"Fadime Eryılmaz Pehlivan"}]},{id:"56440",doi:"10.5772/intechopen.70162",title:"Vitamin C: Sources, Functions, Sensing and Analysis",slug:"vitamin-c-sources-functions-sensing-and-analysis",totalDownloads:6391,totalCrossrefCites:14,totalDimensionsCites:25,abstract:"Vitamin C is a water-soluble compound found in living organisms. It is an essential nutrient for various metabolism in our body and also serves as a reagent for the preparation of many materials in the pharmaceutical and food industry. In this perspective, this chapter can develop interest and curiosity among all practicing scientists and technologists by expounding the details of its sources, chemistry, multifunctional properties and applications.",book:{id:"5940",slug:"vitamin-c",title:"Vitamin C",fullTitle:"Vitamin C"},signatures:"Sudha J. Devaki and Reshma Lali Raveendran",authors:[{id:"187911",title:"Associate Prof.",name:"Sudha",middleName:null,surname:"J Devaki",slug:"sudha-j-devaki",fullName:"Sudha J Devaki"},{id:"204937",title:"Mrs.",name:"Reshma",middleName:null,surname:"Laly Ravindran",slug:"reshma-laly-ravindran",fullName:"Reshma Laly Ravindran"}]},{id:"50921",doi:"10.5772/63712",title:"Menaquinones, Bacteria, and Foods: Vitamin K2 in the Diet",slug:"menaquinones-bacteria-and-foods-vitamin-k2-in-the-diet",totalDownloads:3301,totalCrossrefCites:10,totalDimensionsCites:21,abstract:"Vitamin K2 is a collection of isoprenologues that mostly originate from bacterial synthesis, also called menaquinones (MKs). Multiple bacterial species used as starter cultures for food fermentation are known to synthesize MK. Therefore, fermented food is the best source of vitamin K2. In the Western diet, dairy products are one of the best known and most commonly consumed group of fermented products.",book:{id:"5169",slug:"vitamin-k2-vital-for-health-and-wellbeing",title:"Vitamin K2",fullTitle:"Vitamin K2 - Vital for Health and Wellbeing"},signatures:"Barbara Walther and Magali Chollet",authors:[{id:"184784",title:"Dr.",name:"Barbara",middleName:null,surname:"Walther",slug:"barbara-walther",fullName:"Barbara Walther"},{id:"188194",title:"Mrs.",name:"Magali",middleName:null,surname:"Chollet",slug:"magali-chollet",fullName:"Magali Chollet"}]},{id:"66098",doi:"10.5772/intechopen.84445",title:"Golden Rice: To Combat Vitamin A Deficiency for Public Health",slug:"golden-rice-to-combat-vitamin-a-deficiency-for-public-health",totalDownloads:3336,totalCrossrefCites:12,totalDimensionsCites:17,abstract:"Vitamin A deficiency (VAD) has been recognised as a significant public health problem continuously for more than 30 years, despite current interventions. The problem is particularly severe in populations where rice is the staple food and diversity of diet is limited, as white rice contains no micronutrients. Golden Rice is a public-sector product designed as an additional intervention for VAD. There will be no charge for the nutritional trait, which has been donated by its inventors for use in public-sector rice varieties to assist the resource poor, and no limitations on what small farmers can do with the crop—saving and replanting seed, selling seed and selling grain are all possible. Because Golden Rice had to be created by introducing two new genes—one from maize and the other from a very commonly ingested soil bacterium—it has taken a long time to get from the laboratory to the field. Now it has been formally registered as safe as food, feed, or in processed form by four industrialised counties, and applications are pending in developing countries. The data are summarised here, and criticisms addressed, for a public health professional audience: is it needed, will it work, is it safe and is it economic? Adoption of Golden Rice, the next step after in-country registration, requires strategic and tactical cooperation across professions, non-governmental organisations (NGOs) and government departments often not used to working together. Public health professionals need to play a prominent role.",book:{id:"7978",slug:"vitamin-a",title:"Vitamin A",fullTitle:"Vitamin A"},signatures:"Adrian Dubock",authors:[{id:"273220",title:"Ph.D.",name:"Adrian",middleName:null,surname:"Dubock",slug:"adrian-dubock",fullName:"Adrian Dubock"}]},{id:"62836",doi:"10.5772/intechopen.79350",title:"The Role of Thiamine in Plants and Current Perspectives in Crop Improvement",slug:"the-role-of-thiamine-in-plants-and-current-perspectives-in-crop-improvement",totalDownloads:1554,totalCrossrefCites:7,totalDimensionsCites:11,abstract:"Current research is focusing on selecting potential genes that can alleviate stress and produce disease-tolerant crop variety. The novel paradigm is to investigate the potential of thiamine as a crop protection molecule in plants. Thiamine or vitamin B1 is important for primary metabolism for all living organisms. The active form, thiamine pyrophosphate (TPP), is a cofactor for the enzymes involved in the synthesis of amino acids, tricarboxylic acid cycle and pentose phosphate pathway. Recently, thiamine is shown to have a role in the processes underlying protection of plants against biotic and abiotic stresses. The aim of this chapter is to review the role of thiamine in plant growth and disease protection and also to highlight that TPP and its intermediates are involved in management of stress. The perspectives on its potential for manipulating the biosynthesis pathway in crop improvement will also be discussed.",book:{id:"6709",slug:"b-group-vitamins-current-uses-and-perspectives",title:"B Group Vitamins",fullTitle:"B Group Vitamins - Current Uses and Perspectives"},signatures:"Atiqah Subki, Aisamuddin Ardi Zainal Abidin and Zetty Norhana\nBalia Yusof",authors:[{id:"240031",title:"Dr.",name:"Zetty-Norhana Balia",middleName:null,surname:"Yusof",slug:"zetty-norhana-balia-yusof",fullName:"Zetty-Norhana Balia Yusof"},{id:"261167",title:"Mr.",name:"Aisamuddin Ardi",middleName:null,surname:"Zainal Abidin",slug:"aisamuddin-ardi-zainal-abidin",fullName:"Aisamuddin Ardi Zainal Abidin"},{id:"261169",title:"Ms.",name:"Atiqah",middleName:null,surname:"Subki",slug:"atiqah-subki",fullName:"Atiqah Subki"}]}],mostDownloadedChaptersLast30Days:[{id:"56440",title:"Vitamin C: Sources, Functions, Sensing and Analysis",slug:"vitamin-c-sources-functions-sensing-and-analysis",totalDownloads:6391,totalCrossrefCites:14,totalDimensionsCites:25,abstract:"Vitamin C is a water-soluble compound found in living organisms. It is an essential nutrient for various metabolism in our body and also serves as a reagent for the preparation of many materials in the pharmaceutical and food industry. In this perspective, this chapter can develop interest and curiosity among all practicing scientists and technologists by expounding the details of its sources, chemistry, multifunctional properties and applications.",book:{id:"5940",slug:"vitamin-c",title:"Vitamin C",fullTitle:"Vitamin C"},signatures:"Sudha J. Devaki and Reshma Lali Raveendran",authors:[{id:"187911",title:"Associate Prof.",name:"Sudha",middleName:null,surname:"J Devaki",slug:"sudha-j-devaki",fullName:"Sudha J Devaki"},{id:"204937",title:"Mrs.",name:"Reshma",middleName:null,surname:"Laly Ravindran",slug:"reshma-laly-ravindran",fullName:"Reshma Laly Ravindran"}]},{id:"56013",title:"Vitamin C: An Antioxidant Agent",slug:"vitamin-c-an-antioxidant-agent",totalDownloads:7779,totalCrossrefCites:26,totalDimensionsCites:55,abstract:"Vitamin C or ascorbic acid (AsA) is a naturally occurring organic compound with antioxidant properties, found in both animals and plants. It functions as a redox buffer which can reduce, and thereby neutralize, reactive oxygen species. It is a cofactor for enzymes involved in regulating photosynthesis, hormone biosynthesis, and regenerating other antioxidants; which also regulates cell division and growth, is involved in signal transduction, and has roles in several physiological processes, such as immune stimulation, synthesis of collagen, hormones, neurotransmitters, and iron absorption, has also roles in detoxifying the body of heavy metals. Severe deficiency of vitamin C causes scurvy, whereas limited vitamin C intake causes symptoms, such as increased susceptibility to infections, loosening of teeth, dryness of the mouth and eyes, loss of hair, dry itchy skin, fatigue, and insomnia. In contrast, vitamin C can also act as a prooxidant, especially in the presence of transition metals, such as iron and copper, starting different hazardous radical reactions. Vitamin C can both act as a strong, efficient, and cheap antioxidant agent and, at the same time, behave as a radical promoter. Further investigations are needed to illuminate the dual roles of vitamin C",book:{id:"5940",slug:"vitamin-c",title:"Vitamin C",fullTitle:"Vitamin C"},signatures:"Fadime Eryılmaz Pehlivan",authors:[{id:"200567",title:"Dr.",name:"Fadime",middleName:null,surname:"Eryılmaz Pehlivan",slug:"fadime-eryilmaz-pehlivan",fullName:"Fadime Eryılmaz Pehlivan"}]},{id:"69402",title:"Vitamin D Deficiency and Diabetes Mellitus",slug:"vitamin-d-deficiency-and-diabetes-mellitus",totalDownloads:1578,totalCrossrefCites:1,totalDimensionsCites:2,abstract:"Vitamin D (VD) is a molecule that can be synthesized directly in the humans’ body or enter the organism with food in the form of inactive precursors. To exert its biological action, VD undergoes two-stage hydroxylation (at the 25th and 1st position) catalyzed by cytochromes P450, the presence of which has already been shown in almost all tissues of the human body. The product of hydroxylation is hormone-active form of vitamin D–1,25(OH)2D. 1,25(OH)2D binds to specific vitamin D receptor (VDR) and regulates the expression of genes involved in bone remodeling (classical function) and genes that control immune response, hormone secretion, cell proliferation, and differentiation (nonclassical functions). VD deficiency is prevalent around the globe and may be one of the key factors for diabetes development. The direct association between vitamin D deficiency and type 1 (T1D) and type 2 (T2D) diabetes has been proven. Detection of VDR in pancreas and adipose tissue, skeletal muscles, and immune cells allowed implying the antidiabetic role of vitamin D by enhancing insulin synthesis and exocytosis, increasing the expression of the insulin receptor, and modulating immune cells’ functions. This chapter summarizes data about relationship between VD insufficiency/deficiency and development of T1D and T2D, and their complications.",book:{id:"7038",slug:"vitamin-d-deficiency",title:"Vitamin D Deficiency",fullTitle:"Vitamin D Deficiency"},signatures:"Ihor Shymanskyi, Olha Lisakovska, Anna Mazanova and Mykola Veliky",authors:null},{id:"76108",title:"Vitamin D Metabolism",slug:"vitamin-d-metabolism",totalDownloads:460,totalCrossrefCites:0,totalDimensionsCites:1,abstract:"Vitamin D plays an important role in bone metabolism. Vitamin D is a group of biologically inactive, fat-soluble prohormones that exist in two major forms: ergocalciferol (vitamin D2) produced by plants in response to ultraviolet irradiation and cholecalciferol (vitamin D3) derived from animal tissues or 7-dehydrocholesterol in human skin by the action of ultraviolet rays present in sunlight. Vitamin D, which is biologically inactive, needs two-step hydroxylation for activation. All of these steps are of crucial for Vitamin D to show its effect properly. In this section, we will present vitamin D synthesis and its action steps in detail.",book:{id:"10631",slug:"vitamin-d",title:"Vitamin D",fullTitle:"Vitamin D"},signatures:"Sezer Acar and Behzat Özkan",authors:[{id:"29878",title:"Dr.",name:"Behzat",middleName:null,surname:"Özkan",slug:"behzat-ozkan",fullName:"Behzat Özkan"},{id:"348287",title:"Dr.",name:"Sezer",middleName:null,surname:"Acar",slug:"sezer-acar",fullName:"Sezer Acar"}]},{id:"50754",title:"Medicinal Chemistry of Vitamin K Derivatives and Metabolites",slug:"medicinal-chemistry-of-vitamin-k-derivatives-and-metabolites",totalDownloads:1904,totalCrossrefCites:2,totalDimensionsCites:2,abstract:"Vitamin K acts as a cofactor for γ‐glutamyl carboxylase. Recently, various biological activities of vitamin K have been reported. Anti‐proliferative activities of vitamin K, especially in vitamin K3, are well known. In addition, various physiological and pharmacological functions of vitamin K2, such as transcription modulators as nuclear steroid and xenobiotic receptor (SXR) ligands and anti‐inflammatory effects, have been revealed in the past decade. Characterization of vitamin K metabolites is also important for clinical application of vitamin K and its derivatives. In this chapter, recent progress on the medicinal chemistry of vitamin K derivatives and metabolites is discussed.",book:{id:"5169",slug:"vitamin-k2-vital-for-health-and-wellbeing",title:"Vitamin K2",fullTitle:"Vitamin K2 - Vital for Health and Wellbeing"},signatures:"Shinya Fujii and Hiroyuki Kagechika",authors:[{id:"180528",title:"Dr.",name:"Hiroyuki",middleName:null,surname:"Kagechika",slug:"hiroyuki-kagechika",fullName:"Hiroyuki Kagechika"},{id:"180529",title:"Dr.",name:"Shinya",middleName:null,surname:"Fujii",slug:"shinya-fujii",fullName:"Shinya Fujii"}]}],onlineFirstChaptersFilter:{topicId:"42",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"81286",title:"Potassium Derangements: A Pathophysiological Review, Diagnostic Approach, and Clinical Management",slug:"potassium-derangements-a-pathophysiological-review-diagnostic-approach-and-clinical-management",totalDownloads:40,totalDimensionsCites:0,doi:"10.5772/intechopen.103016",abstract:"Potassium is an essential cation critical in fluid and electrolyte balance, acid–base regulation, and neuromuscular functions. The normal serum potassium is kept within a narrow range of 3.5–5.2 meq/L while the intracellular concentration is approximately 140–150 meq/L. The total body potassium is about 45–55 mmol/kg; thus, a 70 kg male has an estimated ~136 g and 60 kg female has ~117 g of potassium. In total, 98% of the total body potassium is intracellular. Skeletal muscle contains ~80% of body potassium stores. The ratio of intracellular to extracellular potassium concentration (Ki/Ke) maintained by Na+/K+ ATPase determines the resting membrane potential. Disturbances of potassium homeostasis lead to hypo- and hyperkalemia, which if severe, can be life-threatening. Prompt diagnosis and management of these problems are important.",book:{id:"10794",title:"Potassium in Human Health",coverURL:"https://cdn.intechopen.com/books/images_new/10794.jpg"},signatures:"Sairah Sharif and Jie Tang"},{id:"79194",title:"Potassium in Solid Cancers",slug:"potassium-in-solid-cancers",totalDownloads:148,totalDimensionsCites:0,doi:"10.5772/intechopen.101108",abstract:"Electrolyte disorders are a frequent finding in cancer patients. In the majority of cases the etiologies of such disorders are common to all cancer types (i.e. diuretic-induced hyponatremia or hypokalemia). Sometimes, electrolyte disorders are caused by paraneoplastic syndromes or are due to cancer therapy. Potassium is one of the most important electrolytes of the human body since it is involved in the regulation of muscle contraction, maintenance of the integrity of the skeleton, blood pressure and nerve transmission as well as in the normal function of cells. Potassium homeostasis is strictly regulated since the gap between the recommended daily dietary intake (120 mEq/day) and the levels stored in the extracellular fluid (around 70 mEq) is huge. Alterations of potassium homeostasis are frequent in cancer patients as well alterations in potassium channels, the transmembrane proteins that mediate potassium fluxes within the cells. The present chapter is focused on the clinical significance of potassium homeostasis and potassium channels in patients with solid tumors.",book:{id:"10794",title:"Potassium in Human Health",coverURL:"https://cdn.intechopen.com/books/images_new/10794.jpg"},signatures:"Jessica Iorio, Lisa Lastraioli and Elena Lastraioli"},{id:"78820",title:"Potassium Homeostasis",slug:"potassium-homeostasis",totalDownloads:119,totalDimensionsCites:0,doi:"10.5772/intechopen.100368",abstract:"The average potassium intake in the United States population ranges from 90 to 120 mEq/day. About 98% of the total body’s potassium is intracellular, and only 2% is present in the extracellular compartment. This distributional proportion is essential for cellular metabolic reactions and maintaining a gradient for resting membrane potential. A loss of this gradient results in hyper- or hypopolarization of the cell membrane, especially in cardiac muscles leading to life-threatening arrhythmias. Multiple mechanisms in human maintain homeostasis. Transient initial changes are due to transcellular shifts activating sodium-potassium ATPase pumps on the cell membrane. The kidneys essentially take part in excess potassium excretion, maintaining total body stores constant within normal range. Gastrointestinal secretion of potassium is insignificant in individuals with normal renal function, however plays an essential role in individuals with compromised renal function. So far, a classic feedback mechanism was thought to maintain potassium homeostasis; however, a recently recognized feedforward mechanism acting independently also helps preserve potassium homeostasis. Hence, potassium homeostasis is vital for humans to function at a normal level.",book:{id:"10794",title:"Potassium in Human Health",coverURL:"https://cdn.intechopen.com/books/images_new/10794.jpg"},signatures:"Shakuntala S. Patil and Sachin M. Patil"},{id:"78193",title:"Potassium and Cardiac Surgery",slug:"potassium-and-cardiac-surgery",totalDownloads:198,totalDimensionsCites:1,doi:"10.5772/intechopen.99735",abstract:"Potassium homeostasis affects cardiac rhythm and contractility, along with vascular reactivity and vascular smooth muscle proliferation. This chapter will focus on potassium dynamics during and after cardiac surgery involving cardioplegic arrest and cardiopulmonary bypass (CPB). Hyperkalemic, hypothermic solutions are frequently used to induce cardioplegic arrest and protect the heart during cardiac surgery involving CPB. Common consequences of hyperkalemic cardioplegic arrest and reperfusion include microvascular dysfunction involving several organ systems and myocardial dysfunction. Immediately after CPB, blood potassium levels often drop precipitously due to a variety of factors, including CPB -induced electrolyte depletion and frequent, long-term administration of insulin during and after surgery. Meanwhile, some patients with pre-existing kidney dysfunction may experience postoperative hyperkalemia following cardioplegia. Any degree of postoperative hyper/hypokalemia significantly elevates the risk of cardiac arrythmias and subsequent myocardial failure. Therefore, proper management of blood potassium levels during and after cardioplegia/CPB is crucial for optimizing patient outcomes following cardiac surgery.",book:{id:"10794",title:"Potassium in Human Health",coverURL:"https://cdn.intechopen.com/books/images_new/10794.jpg"},signatures:"Shawn Kant, Frank W. 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The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}},{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}}]},series:{item:{id:"14",title:"Artificial Intelligence",doi:"10.5772/intechopen.79920",issn:"2633-1403",scope:"Artificial Intelligence (AI) is a rapidly developing multidisciplinary research area that aims to solve increasingly complex problems. In today's highly integrated world, AI promises to become a robust and powerful means for obtaining solutions to previously unsolvable problems. This Series is intended for researchers and students alike interested in this fascinating field and its many applications.",coverUrl:"https://cdn.intechopen.com/series/covers/14.jpg",latestPublicationDate:"June 11th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:9,editor:{id:"218714",title:"Prof.",name:"Andries",middleName:null,surname:"Engelbrecht",slug:"andries-engelbrecht",fullName:"Andries Engelbrecht",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRNR8QAO/Profile_Picture_1622640468300",biography:"Andries Engelbrecht received the Masters and PhD degrees in Computer Science from the University of Stellenbosch, South Africa, in 1994 and 1999 respectively. He is currently appointed as the Voigt Chair in Data Science in the Department of Industrial Engineering, with a joint appointment as Professor in the Computer Science Division, Stellenbosch University. Prior to his appointment at Stellenbosch University, he has been at the University of Pretoria, Department of Computer Science (1998-2018), where he was appointed as South Africa Research Chair in Artifical Intelligence (2007-2018), the head of the Department of Computer Science (2008-2017), and Director of the Institute for Big Data and Data Science (2017-2018). 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He is a full professor of signal processing and pattern recognition and is head of the Signals and Communications Department at ULPGC, teaching from 2001 on subjects on signal processing and learning theory. 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. He is an evaluator of project proposals for the European Union (H2020), Medical Research Council (MRC, UK), Spanish Government (ANECA, Spain), Research National Agency (ANR, France), DAAD (Germany), Argentinian Government, and the Colombian Institutions. He has been a reviewer in different indexed international journals (<70) and conferences (<250) since 2001. He has been a member of the IASTED Technical Committee on Image Processing from 2007 and a member of the IASTED Technical Committee on Artificial Intelligence and Expert Systems from 2011. \n\nHe has held the general chair position for the following: ACM-APPIS (2020, 2021), IEEE-IWOBI (2019, 2020 and 2020), A PPIS (2018, 2019), IEEE-IWOBI (2014, 2015, 2017, 2018), InnoEducaTIC (2014, 2017), IEEE-INES (2013), NoLISP (2011), JRBP (2012), and IEEE-ICCST (2005)\n\nHe is an associate editor of the Computational Intelligence and Neuroscience Journal (Hindawi – Q2 JCR-ISI). He was vice dean from 2004 to 2010 in the Higher Technical School of Telecommunication Engineers at ULPGC and the vice dean of Graduate and Postgraduate Studies from March 2013 to November 2017. He won the “Catedra Telefonica” Awards in Modality of Knowledge Transfer, 2017, 2018, and 2019 editions, and awards in Modality of COVID Research in 2020.\n\nPublic References:\nResearcher ID http://www.researcherid.com/rid/N-5967-2014\nORCID https://orcid.org/0000-0002-4621-2768 \nScopus Author ID https://www.scopus.com/authid/detail.uri?authorId=6602376272\nScholar Google https://scholar.google.es/citations?user=G1ks9nIAAAAJ&hl=en \nResearchGate https://www.researchgate.net/profile/Carlos_Travieso",institutionString:null,institution:{name:"University of Las Palmas de Gran Canaria",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"23",title:"Computational Neuroscience",coverUrl:"https://cdn.intechopen.com/series_topics/covers/23.jpg",isOpenForSubmission:!0,editor:{id:"14004",title:"Dr.",name:"Magnus",middleName:null,surname:"Johnsson",slug:"magnus-johnsson",fullName:"Magnus Johnsson",profilePictureURL:"https://mts.intechopen.com/storage/users/14004/images/system/14004.png",biography:"Dr Magnus Johnsson is a cross-disciplinary scientist, lecturer, scientific editor and AI/machine learning consultant from Sweden. \n\nHe is currently at Malmö University in Sweden, but also held positions at Lund University in Sweden and at Moscow Engineering Physics Institute. \nHe holds editorial positions at several international scientific journals and has served as a scientific editor for books and special journal issues. \nHis research interests are wide and include, but are not limited to, autonomous systems, computer modeling, artificial neural networks, artificial intelligence, cognitive neuroscience, cognitive robotics, cognitive architectures, cognitive aids and the philosophy of mind. \n\nDr. Johnsson has experience from working in the industry and he has a keen interest in the application of neural networks and artificial intelligence to fields like industry, finance, and medicine. \n\nWeb page: www.magnusjohnsson.se",institutionString:null,institution:{name:"Malmö University",institutionURL:null,country:{name:"Sweden"}}},editorTwo:null,editorThree:null},{id:"24",title:"Computer Vision",coverUrl:"https://cdn.intechopen.com/series_topics/covers/24.jpg",isOpenForSubmission:!0,editor:{id:"294154",title:"Prof.",name:"George",middleName:null,surname:"Papakostas",slug:"george-papakostas",fullName:"George Papakostas",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002hYaGbQAK/Profile_Picture_1624519712088",biography:"George A. Papakostas has received a diploma in Electrical and Computer Engineering in 1999 and the M.Sc. and Ph.D. degrees in Electrical and Computer Engineering in 2002 and 2007, respectively, from the Democritus University of Thrace (DUTH), Greece. Dr. Papakostas serves as a Tenured Full Professor at the Department of Computer Science, International Hellenic University, Greece. Dr. Papakostas has 10 years of experience in large-scale systems design as a senior software engineer and technical manager, and 20 years of research experience in the field of Artificial Intelligence. Currently, he is the Head of the “Visual Computing” division of HUman-MAchines INteraction Laboratory (HUMAIN-Lab) and the Director of the MPhil program “Advanced Technologies in Informatics and Computers” hosted by the Department of Computer Science, International Hellenic University. He has (co)authored more than 150 publications in indexed journals, international conferences and book chapters, 1 book (in Greek), 3 edited books, and 5 journal special issues. His publications have more than 2100 citations with h-index 27 (GoogleScholar). His research interests include computer/machine vision, machine learning, pattern recognition, computational intelligence. \nDr. Papakostas served as a reviewer in numerous journals, as a program\ncommittee member in international conferences and he is a member of the IAENG, MIR Labs, EUCogIII, INSTICC and the Technical Chamber of Greece (TEE).",institutionString:null,institution:{name:"International Hellenic University",institutionURL:null,country:{name:"Greece"}}},editorTwo:null,editorThree:null},{id:"25",title:"Evolutionary Computation",coverUrl:"https://cdn.intechopen.com/series_topics/covers/25.jpg",isOpenForSubmission:!0,editor:{id:"136112",title:"Dr.",name:"Sebastian",middleName:null,surname:"Ventura Soto",slug:"sebastian-ventura-soto",fullName:"Sebastian Ventura Soto",profilePictureURL:"https://mts.intechopen.com/storage/users/136112/images/system/136112.png",biography:"Sebastian Ventura is a Spanish researcher, a full professor with the Department of Computer Science and Numerical Analysis, University of Córdoba. Dr Ventura also holds the positions of Affiliated Professor at Virginia Commonwealth University (Richmond, USA) and Distinguished Adjunct Professor at King Abdulaziz University (Jeddah, Saudi Arabia). Additionally, he is deputy director of the Andalusian Research Institute in Data Science and Computational Intelligence (DaSCI) and heads the Knowledge Discovery and Intelligent Systems Research Laboratory. He has published more than ten books and over 300 articles in journals and scientific conferences. Currently, his work has received over 18,000 citations according to Google Scholar, including more than 2200 citations in 2020. In the last five years, he has published more than 60 papers in international journals indexed in the JCR (around 70% of them belonging to first quartile journals) and he has edited some Springer books “Supervised Descriptive Pattern Mining” (2018), “Multiple Instance Learning - Foundations and Algorithms” (2016), and “Pattern Mining with Evolutionary Algorithms” (2016). He has also been involved in more than 20 research projects supported by the Spanish and Andalusian governments and the European Union. He currently belongs to the editorial board of PeerJ Computer Science, Information Fusion and Engineering Applications of Artificial Intelligence journals, being also associate editor of Applied Computational Intelligence and Soft Computing and IEEE Transactions on Cybernetics. Finally, he is editor-in-chief of Progress in Artificial Intelligence. He is a Senior Member of the IEEE Computer, the IEEE Computational Intelligence, and the IEEE Systems, Man, and Cybernetics Societies, and the Association of Computing Machinery (ACM). Finally, his main research interests include data science, computational intelligence, and their applications.",institutionString:null,institution:{name:"University of Córdoba",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"26",title:"Machine Learning and Data Mining",coverUrl:"https://cdn.intechopen.com/series_topics/covers/26.jpg",isOpenForSubmission:!0,editor:{id:"24555",title:"Dr.",name:"Marco Antonio",middleName:null,surname:"Aceves Fernandez",slug:"marco-antonio-aceves-fernandez",fullName:"Marco Antonio Aceves Fernandez",profilePictureURL:"https://mts.intechopen.com/storage/users/24555/images/system/24555.jpg",biography:"Dr. Marco Antonio Aceves Fernandez obtained his B.Sc. (Eng.) in Telematics from the Universidad de Colima, Mexico. He obtained both his M.Sc. and Ph.D. from the University of Liverpool, England, in the field of Intelligent Systems. He is a full professor at the Universidad Autonoma de Queretaro, Mexico, and a member of the National System of Researchers (SNI) since 2009. Dr. Aceves Fernandez has published more than 80 research papers as well as a number of book chapters and congress papers. He has contributed in more than 20 funded research projects, both academic and industrial, in the area of artificial intelligence, ranging from environmental, biomedical, automotive, aviation, consumer, and robotics to other applications. He is also a honorary president at the National Association of Embedded Systems (AMESE), a senior member of the IEEE, and a board member of many institutions. 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Dr. Aydin is currently a Fellow of Higher Education Academy, UK, a member of EPSRC College, a senior member of IEEE and a senior member of ACM. In addition to being a member of advisory committees of many international conferences, he is an Editorial Board Member of various peer-reviewed international journals. He has served as guest editor for a number of special issues of peer-reviewed international journals.",institutionString:null,institution:{name:"University of the West of England",institutionURL:null,country:{name:"United Kingdom"}}},editorTwo:null,editorThree:null}]},overviewPageOFChapters:{paginationCount:19,paginationItems:[{id:"82196",title:"Multi-Features Assisted Age Invariant Face Recognition and Retrieval Using CNN with Scale Invariant Heat Kernel Signature",doi:"10.5772/intechopen.104944",signatures:"Kamarajugadda Kishore Kumar and Movva Pavani",slug:"multi-features-assisted-age-invariant-face-recognition-and-retrieval-using-cnn-with-scale-invariant-",totalDownloads:6,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Pattern Recognition - New Insights",coverURL:"https://cdn.intechopen.com/books/images_new/11442.jpg",subseries:{id:"26",title:"Machine Learning and Data Mining"}}},{id:"82063",title:"Evaluating Similarities and Differences between Machine Learning and Traditional Statistical Modeling in Healthcare Analytics",doi:"10.5772/intechopen.105116",signatures:"Michele Bennett, Ewa J. 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(Eng.) in Telematics from the Universidad de Colima, Mexico. He obtained both his M.Sc. and Ph.D. from the University of Liverpool, England, in the field of Intelligent Systems. He is a full professor at the Universidad Autonoma de Queretaro, Mexico, and a member of the National System of Researchers (SNI) since 2009. Dr. Aceves Fernandez has published more than 80 research papers as well as a number of book chapters and congress papers. He has contributed in more than 20 funded research projects, both academic and industrial, in the area of artificial intelligence, ranging from environmental, biomedical, automotive, aviation, consumer, and robotics to other applications. He is also a honorary president at the National Association of Embedded Systems (AMESE), a senior member of the IEEE, and a board member of many institutions. His research interests include intelligent and embedded systems.",institutionString:"Universidad Autonoma de Queretaro",institution:{name:"Autonomous University of Queretaro",institutionURL:null,country:{name:"Mexico"}}}]},{type:"book",id:"7726",title:"Swarm Intelligence",subtitle:"Recent Advances, New Perspectives and Applications",coverURL:"https://cdn.intechopen.com/books/images_new/7726.jpg",slug:"swarm-intelligence-recent-advances-new-perspectives-and-applications",publishedDate:"December 4th 2019",editedByType:"Edited by",bookSignature:"Javier Del Ser, Esther Villar and Eneko Osaba",hash:"e7ea7e74ce7a7a8e5359629e07c68d31",volumeInSeries:2,fullTitle:"Swarm Intelligence - Recent Advances, New Perspectives and Applications",editors:[{id:"49813",title:"Dr.",name:"Javier",middleName:null,surname:"Del Ser",slug:"javier-del-ser",fullName:"Javier Del Ser",profilePictureURL:"https://mts.intechopen.com/storage/users/49813/images/system/49813.png",biography:"Prof. Dr. Javier Del Ser received his first PhD in Telecommunication Engineering (Cum Laude) from the University of Navarra, Spain, in 2006, and a second PhD in Computational Intelligence (Summa Cum Laude) from the University of Alcala, Spain, in 2013. He is currently a principal researcher in data analytics and optimisation at TECNALIA (Spain), a visiting fellow at the Basque Center for Applied Mathematics (BCAM) and a part-time lecturer at the University of the Basque Country (UPV/EHU). His research interests gravitate on the use of descriptive, prescriptive and predictive algorithms for data mining and optimization in a diverse range of application fields such as Energy, Transport, Telecommunications, Health and Industry, among others. In these fields he has published more than 240 articles, co-supervised 8 Ph.D. theses, edited 6 books, coauthored 7 patents and participated/led more than 40 research projects. He is a Senior Member of the IEEE, and a recipient of the Biscay Talent prize for his academic career.",institutionString:"Tecnalia Research & Innovation",institution:null}]},{type:"book",id:"7656",title:"Fuzzy Logic",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7656.jpg",slug:"fuzzy-logic",publishedDate:"February 5th 2020",editedByType:"Edited by",bookSignature:"Constantin Volosencu",hash:"54f092d4ffe0abf5e4172a80025019bc",volumeInSeries:3,fullTitle:"Fuzzy Logic",editors:[{id:"1063",title:"Prof.",name:"Constantin",middleName:null,surname:"Volosencu",slug:"constantin-volosencu",fullName:"Constantin Volosencu",profilePictureURL:"https://mts.intechopen.com/storage/users/1063/images/system/1063.png",biography:"Prof. Dr. Constantin Voloşencu graduated as an engineer from\nPolitehnica University of Timișoara, Romania, where he also\nobtained a doctorate degree. He is currently a full professor in\nthe Department of Automation and Applied Informatics at the\nsame university. Dr. Voloşencu is the author of ten books, seven\nbook chapters, and more than 160 papers published in journals\nand conference proceedings. He has also edited twelve books and\nhas twenty-seven patents to his name. He is a manager of research grants, editor in\nchief and member of international journal editorial boards, a former plenary speaker, a member of scientific committees, and chair at international conferences. His\nresearch is in the fields of control systems, control of electric drives, fuzzy control\nsystems, neural network applications, fault detection and diagnosis, sensor network\napplications, monitoring of distributed parameter systems, and power ultrasound\napplications. 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