Barely three months into the new year and we are happy to announce a monumental milestone reached - 150 million downloads.
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This achievement solidifies IntechOpen’s place as a pioneer in Open Access publishing and the home to some of the most relevant scientific research available through Open Access.
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We are so proud to have worked with so many bright minds throughout the years who have helped us spread knowledge through the power of Open Access and we look forward to continuing to support some of the greatest thinkers of our day.
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Thank you for making IntechOpen your place of learning, sharing, and discovery, and here’s to 150 million more!
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\n'}],latestNews:[{slug:"intechopen-supports-asapbio-s-new-initiative-publish-your-reviews-20220729",title:"IntechOpen Supports ASAPbio’s New Initiative Publish Your Reviews"},{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"}]},book:{item:{type:"book",id:"7446",leadTitle:null,fullTitle:"Frontiers in Ophthalmology and Ocular Imaging",title:"Frontiers in Ophthalmology and Ocular Imaging",subtitle:null,reviewType:"peer-reviewed",abstract:'Imagination is the key to any discovery, and its presence in the science to improve vision is no exception. Vision science is racing forward, spurred on by a host of exciting novel research discoveries and the efforts of scientists. This book, a collection of reviewed and relevant research chapters, intends to provide readers with a comprehensive overview of the latest and most advanced findings in several aspects of ophthalmology, ophthalmic pathology, ocular imaging, and certain treatments and surgical strategies. It is an excellent, well-integrated review of treatment options in eye disease that aims to provide a thorough overview of the recent developments written by international authors. "Frontiers in Ophthalmology and Ocular Imaging" can be used as an important reference for clinically oriented ophthalmologists and scientists.',isbn:"978-1-83880-807-5",printIsbn:"978-1-83880-806-8",pdfIsbn:"978-1-83880-808-2",doi:"10.5772/intechopen.75372",price:119,priceEur:129,priceUsd:155,slug:"frontiers-in-ophthalmology-and-ocular-imaging",numberOfPages:134,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"d4df56dcf926403ffd771798a94289ea",bookSignature:"Alireza Ziaei",publishedDate:"June 12th 2019",coverURL:"https://cdn.intechopen.com/books/images_new/7446.jpg",numberOfDownloads:6589,numberOfWosCitations:1,numberOfCrossrefCitations:2,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:3,numberOfDimensionsCitationsByBook:0,hasAltmetrics:1,numberOfTotalCitations:6,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"June 28th 2018",dateEndSecondStepPublish:"July 19th 2018",dateEndThirdStepPublish:"September 17th 2018",dateEndFourthStepPublish:"December 6th 2018",dateEndFifthStepPublish:"February 4th 2019",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"271630",title:"Dr.",name:"Alireza",middleName:null,surname:"Ziaei",slug:"alireza-ziaei",fullName:"Alireza Ziaei",profilePictureURL:"https://mts.intechopen.com/storage/users/271630/images/system/271630.jpg",biography:"Dr. Alireza Ziaei, MD, is a physician-scientist at Harvard Medical School, Boston, USA. He is a recipient of numerous awards, including the National Excellent Researcher Award, National Young Investigator Award, and Science Excellence Prize. His main areas of interest are medical image processing and analysis, molecular basis and pathology pathways of ophthalmic disease, radiological detection, and image-guided therapy. He has considerable experience in biomedical research at Schepens Eye Research Institute, Massachusetts Eye and Ear, with a focus on corneal and ocular surface diseases, and at National Center for Image-Guided Therapy, Brain Tumor Consortium, and BCH Neuroimaging Center on radiological cancer detection at Harvard BWH/BCH hospitals. Dr. Ziaei’s seminal work has been recognized several times. He has published and presented numerous articles in highly ranked peer-reviewed journals and conferences worldwide. Dr. Ziaei has been a scientific member of the Association for Research in Vision and Ophthalmology (ARV), American Academy of Ophthalmology (AAO), International Society for Magnetic Resonance in Medicine (ISMRM), Radiological Society of North America (RSNA), International Society for Brain Mapping and Therapeutics (ISBMT), Tear Film and Ocular Surface Society (TFOS), and Massachusetts Medical Society (MMS). He serves as an executive editor, editorial board member, and scientific reviewer of reputed journals and scientific societies, including Nature International Journal of Science, Journal of Magnetic Resonance Imaging, Abdominal Radiology, Investigative Ophthalmology & Visual Science (IOVS), American Journal of Ophthalmology (AJO), Journal of Clinical & Experimental Ophthalmology, and Journal of Cell Biology.",institutionString:"Harvard Medical School",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"2",institution:{name:"Harvard University",institutionURL:null,country:{name:"United States of America"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1094",title:"Ophthalmic Pathology",slug:"ophthalmic-pathology"}],chapters:[{id:"66746",title:"Corneal Dystrophies and Degenerations",doi:"10.5772/intechopen.84426",slug:"corneal-dystrophies-and-degenerations",totalDownloads:1286,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The cornea is a complex structure with complex functions aiming to protect the internal ocular tissues and transmit and refract the coming light rays. Corneal dystrophies are a group of relatively infrequent genetic corneal disorders in which an abnormal material accumulates in the cornea causing variable loss of its clarity. On the other hand, corneal degenerations are more common and usually result from physiologic changes related to aging, particular disease, or long-standing environmental insults to the cornea. Ectatic corneal disorders are usually characterized by bilateral loss of corneal biomechanical strength leading to progressive thinning and bulging of the cornea with resultant astigmatism and decreased visual acuity. In this chapter, we will describe the basic embryological, anatomical, histologic, and physiological features of the cornea. Then, we will go over the clinical, histopathologic, medical, and surgical aspects of dystrophic, degenerative, and ectatic corneal disorders.",signatures:"Hind Alkatan, Norah Alkheraiji and Tariq Alzahem",downloadPdfUrl:"/chapter/pdf-download/66746",previewPdfUrl:"/chapter/pdf-preview/66746",authors:[{id:"223782",title:"Dr.",name:"Hind",surname:"Alkatan",slug:"hind-alkatan",fullName:"Hind Alkatan"},{id:"262049",title:"Dr.",name:"Tariq",surname:"Al-Zahem",slug:"tariq-al-zahem",fullName:"Tariq Al-Zahem"},{id:"284385",title:"Dr.",name:"Norah",surname:"Alkheraiji",slug:"norah-alkheraiji",fullName:"Norah Alkheraiji"}],corrections:null},{id:"65573",title:"Optical Coherence Tomography in the Management of Glaucoma and Macular Diseases",doi:"10.5772/intechopen.82657",slug:"optical-coherence-tomography-in-the-management-of-glaucoma-and-macular-diseases",totalDownloads:757,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Optical coherence tomography (OCT) is a non contact, non invasive and reproducible imaging technique that produces thin slices of tissue section images. OCT identifies retinal nerve fiber damage before detection of visual field changes making it a handy and effective tool in early detection and monitoring in glaucoma. Retinal fiber layer thickness measurements provide vital knowledge of extent of neural damage. This enables the clinician to counsel the patient and take the best decision towards achieving glaucoma control. Early and quantifiable macular thickness measurements are obtained, allowing for detection of clinically significant diabetic macular edema. OCT allows monitoring of the impact of laser or other interventions. Changes in age-related macular degeneration are relatively easily determined and impact of treatment interventions monitored. In conclusion, OCT is a vital emerging tool in the evaluation and management glaucoma and macular diseases in all parts of the World, including low income countries of sub-Saharan Africa.",signatures:"Lawan Abdu",downloadPdfUrl:"/chapter/pdf-download/65573",previewPdfUrl:"/chapter/pdf-preview/65573",authors:[{id:"30695",title:"Prof.",name:"Lawan",surname:"Abdu",slug:"lawan-abdu",fullName:"Lawan Abdu"}],corrections:null},{id:"64846",title:"Topical NSAIDs in Prevention of Postcataract Macular Edema",doi:"10.5772/intechopen.82321",slug:"topical-nsaids-in-prevention-of-postcataract-macular-edema",totalDownloads:940,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Postoperative macular edema is considered one cause of diminished vision after cataract surgery. It was approved that inflammatory mediators especially prostaglandins play a key role in macular edema formation especially in the presence of risk factors that affect blood-retinal barrier such as diabetes, uveitis, tear of posterior capsule, and vitreous loss. So, anti-inflammatory medications like corticosteroids and NSAIDs are the cornerstone of macular edema managements. In spite of using corticosteroids as gold standard for treatment of ocular inflammation, they cannot be used for prolonged period due to associated adverse effects. Lastly, there were many studies about benefits of NSAIDs in management and prevention of macular edema to avoid the side effects of corticosteroids.",signatures:"Ahmed Alnagdy, Ahmed M. Eissa and Amr El-Kannishy",downloadPdfUrl:"/chapter/pdf-download/64846",previewPdfUrl:"/chapter/pdf-preview/64846",authors:[{id:"259323",title:"Dr.",name:"Ahmed",surname:"Alnagdy",slug:"ahmed-alnagdy",fullName:"Ahmed Alnagdy"}],corrections:null},{id:"65026",title:"Prevalence and Association of Diabetic Retinopathy with Diabetic Foot Ulcer: A Cross-Sectional Observational Study",doi:"10.5772/intechopen.82667",slug:"prevalence-and-association-of-diabetic-retinopathy-with-diabetic-foot-ulcer-a-cross-sectional-observ",totalDownloads:788,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:1,abstract:"We aimed to elucidate prevalence and association of diabetic retinopathy (DR) in patients with diabetic foot ulcer (DFU) from Pakistan. In this cross-sectional study, about 225 DFU patients who underwent ophthalmic examinations within 6 months of diagnosis of foot ulceration were included. The medical records of 305 diabetic patients without DFU were included as controls. The association of DR with DFU was assessed by comparing DFU patients with proliferative DR (PDR) and DFU patients without PDR. Out of 225 DFU patients, 215 patients (95.6%) had DR and 169 patients (75.1%) had PDR. The prevalence of DFU was significantly greater (P = 0.0527) among the male diabetic patients, whereas advanced age of these patients (≥41 years) had a significant effect (P = 0.0286) on development and progression of PDR. A longer duration of diabetes (≥10 years) was identified as a significant contributing factor for the development of both DFU (P = 0.0029) and PDR (P = 0.0299). Moreover, the risk of PDR increased in diabetic patients with higher DFU grades (grade 3 and grade 4). In conclusion, retinopathy was prevalent in DFU patients. Therefore, DFU patients with advancing age and longer duration of diabetes should undergo retinal examinations for timely diagnosis and management of DR.",signatures:"Shaista Zafar, Kashif Rahim, Inayat Ullah Khan, Muhammad Yasin, Muhammad Dawood and Shamim Saleha",downloadPdfUrl:"/chapter/pdf-download/65026",previewPdfUrl:"/chapter/pdf-preview/65026",authors:[{id:"209678",title:"Dr.",name:"Shamim",surname:"Saleha",slug:"shamim-saleha",fullName:"Shamim Saleha"},{id:"279284",title:"Dr.",name:"Shaista",surname:"Zafar",slug:"shaista-zafar",fullName:"Shaista Zafar"},{id:"279285",title:"Dr.",name:"Kashif",surname:"Rahim",slug:"kashif-rahim",fullName:"Kashif Rahim"},{id:"279287",title:"Dr.",name:"Inayat Ullah",surname:"Khan",slug:"inayat-ullah-khan",fullName:"Inayat Ullah Khan"},{id:"279288",title:"MSc.",name:"Muhammad",surname:"Yasin",slug:"muhammad-yasin",fullName:"Muhammad Yasin"},{id:"279290",title:"MSc.",name:"Muhammad",surname:"Dawood",slug:"muhammad-dawood",fullName:"Muhammad Dawood"}],corrections:null},{id:"65782",title:"Clinical Evaluation of Horizontal Pediatric Strabismus and the Management Challenges",doi:"10.5772/intechopen.82547",slug:"clinical-evaluation-of-horizontal-pediatric-strabismus-and-the-management-challenges",totalDownloads:856,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Pediatric strabismus is not uncommon. Poor knowledge and religious and cultural practices result in inattention to the child’s need and stigmatization. Horizontal strabismus consisting of esotropia and exotropia constitutes the common types presenting. Childhood ocular deviations are associated with uncorrected refractive errors, diseases causing obstruction of the visual axis such as cataract, and intra ocular tumors commonly retinoblastoma. In parts of the developing world, there is poor documentation and recollection of medical events at family and community levels. Squint in a child is not a painful dramatic condition that can prompt quick action from the parents or caregiver. There is generalized inequity in access to health care. Pediatric ophthalmic services are at best in developmental stage, and purpose design service centers are quite few. Neglect of the causes and timely treatment of amblyopia can retard child’s development resulting in dependency and aggravation of poverty circle. A comprehensive approach to management of childhood eye diseases including strabismus is desirable in the low income developing countries. Provision of health insurance as a citizen’s right will reduce most of the health challenges.",signatures:"Lawan Abdu",downloadPdfUrl:"/chapter/pdf-download/65782",previewPdfUrl:"/chapter/pdf-preview/65782",authors:[{id:"30695",title:"Prof.",name:"Lawan",surname:"Abdu",slug:"lawan-abdu",fullName:"Lawan Abdu"}],corrections:null},{id:"64797",title:"Congenital Nasolacrimal Duct Obstruction and the Visual System",doi:"10.5772/intechopen.82546",slug:"congenital-nasolacrimal-duct-obstruction-and-the-visual-system",totalDownloads:894,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Congenital nasolacrimal duct obstruction (CNLDO), previously considered a benign disease, affects 20% of the children globally. It is described by a collection of symptoms in which continuous epiphora and intermittent discharge are present in either one or both the eyes. CNLDO usually resolves in most healthy infants in the first few couple of months; however, it may persist for a number of years in some children. There has been a lot of recent deliberation on how a constant watery eye affects the visual development during the phase of emmetropization in children. A connection between CNLDO and anisometropia has been hypothesized. Multiple factors which include developmental and environmental aspects are thought to play a contributory role in the development of anisometropia by and large; particularly hypermetropic anisometropia, raising the chances of developing amblyopia in children with CNLDO. Published literature on CNLDO had shown inconclusive evidence on this anecdotal propinquity. This chapter discusses CNLDO; etiology, pathogenesis, treatment modalities, surgical intervention, and its role in inducing refractive errors; and its propensity to cause amblyopia.",signatures:"Adnan Aslam Saleem",downloadPdfUrl:"/chapter/pdf-download/64797",previewPdfUrl:"/chapter/pdf-preview/64797",authors:[{id:"266795",title:"Dr.",name:"Adnan",surname:"Saleem",slug:"adnan-saleem",fullName:"Adnan Saleem"}],corrections:null},{id:"65546",title:"Advances in Vitreoretinal Surgery",doi:"10.5772/intechopen.83019",slug:"advances-in-vitreoretinal-surgery",totalDownloads:1069,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:1,abstract:"Vitreoretinal surgery has been radically changed over the past 10 years by the development of new techniques, smaller gauge instrumentation, and improvements in vitrectomy machines. The indications for vitrectomy have expanded dramatically, and inoperable conditions have become amenable to surgical treatment. In addition to improvements in intraocular instruments, various dyes become available and enable better visualization and a more complete removal of vitreous and membranes. In this chapter, we issued latest developments in the surgical field of retina that enable improved surgical outcomes and less complications.",signatures:"Baris Komur",downloadPdfUrl:"/chapter/pdf-download/65546",previewPdfUrl:"/chapter/pdf-preview/65546",authors:[{id:"209512",title:"Dr.",name:"Baris",surname:"Komur",slug:"baris-komur",fullName:"Baris Komur"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"10293",title:"Eyesight and Imaging",subtitle:"Advances and New Perspectives",isOpenForSubmission:!1,hash:"2c4e3e515bebe6053f3f1f57e4854462",slug:"eyesight-and-imaging-advances-and-new-perspectives",bookSignature:"Alireza Ziaei and Michele Lanza",coverURL:"https://cdn.intechopen.com/books/images_new/10293.jpg",editedByType:"Edited by",editors:[{id:"271630",title:"Dr.",name:"Alireza",surname:"Ziaei",slug:"alireza-ziaei",fullName:"Alireza 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Cement",doi:null,correctionPDFUrl:"https://cdn.intechopen.com/pdfs/81454.pdf\r\n",downloadPdfUrl:"/chapter/pdf-download/81454",previewPdfUrl:"/chapter/pdf-preview/81454",totalDownloads:null,totalCrossrefCites:null,bibtexUrl:"/chapter/bibtex/81454",risUrl:"/chapter/ris/81454",chapter:{id:"77888",slug:"production-of-sustainable-concrete-by-using-challenging-environmentally-friendly-materials-instead-o",signatures:"Abebe Demissew Gashahun",dateSubmitted:"April 13th 2021",dateReviewed:"July 5th 2021",datePrePublished:"September 23rd 2021",datePublished:"May 4th 2022",book:{id:"10668",title:"Sustainability of Concrete With Synthetic and Recycled Aggregates",subtitle:null,fullTitle:"Sustainability of Concrete With Synthetic and Recycled Aggregates",slug:"sustainability-of-concrete-with-synthetic-and-recycled-aggregates",publishedDate:"May 4th 2022",bookSignature:"Hosam M. 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\r\n\tWhen the scientific literature is examined, it is seen that microeconomic fundamentals are increasingly used in explaining macroeconomic dynamics in the last two decades. It has been acknowledged that the effects of microeconomic factors on macroeconomic variables operate through different channels, while the production function is at the center of this relationship. Accordingly, it has become important to explain the changes in total factor productivity and this has led to the investigation of the results of technology shocks. Herein, it should be noted that technology shocks are not only valid for macroeconomic variables, they can also be determinative on financial variables and especially on the financial performance of enterprises. Within this context, the adaptation of quantitative techniques can be crucial for the investigation of the effects of technology shocks in future periods. The adaptation of quantitative models to explain the relationships between micro and macro dynamics also allows consideration of key issues such as the oil market, housing market, tourism sector, environmental economics and entrepreneurship. Therefore, this book intends to provide the reader with a comprehensive overview of the interactions between microeconomic and macroeconomic dynamics in terms of selected topics.
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1. Introduction
\n
Both ulcerative colitis (UC) and Crohn’s disease (CD), usually referred to as inflammatory bowel disease (IBD), are examples of complex disorders, which include inflammatory and autoimmune features with prominent intestinal immune dysregulation. Cells of the innate and the adaptive immune system have been identified as the key players of IBD. Cytokines are central components of the inflammatory pathways that take place during the active and chronic phases of IBD. However, a clear picture of these processes is still missing. Since the inflammation is located in the intestinal mucosa, the latter is the main source of biomarkers in IBD allowing various immunological pathways to be explored in the gut. Thus, the determination of cytokine expression profile could help to elucidate the local immune responses during intestinal inflammation. Expression of IBD-related proteins such as cytokines, chemokines, adhesion molecules, and their corresponding cellular and soluble receptors has revealed their significant role in the pro- and anti-inflammatory processes in the inflamed gut mucosa. Indeed, the implication of some cytokines in the immunopathogenesis of IBD is investigated intensively and proved in experimental models of intestinal inflammation. Lack of enough investigation in humans, however, predetermines the need for further studies since it is proved that the common clinical phenotype of colitis may result from largely diverse genetic or immunological backgrounds.
\n
\n
2. Intestinal inflammation and cytokines
\n
Since the pathogenesis of IBD is related to both dysregulated innate and adaptive immune pathways, which contribute to the aberrant intestinal inflammatory response in genetically susceptible individuals, the main focus of research attempts is directed to the initiation, perpetuation, and cessation of gut inflammation associated with IBD [1].
\n
Cytokines are abundantly produced by the cells of the gut-associated immune system maintaining lymphocyte homeostasis under both steady-state and inflammatory conditions. These small, cell-signaling protein molecules act in a paracrine, autocrine, or endocrine manner, coordinate the communication between immune and non-immune cells of the intestinal compartment, and modify acute and chronic inflammatory responses at both local and systemic levels [2]. Moreover, elevation of pro-inflammatory cytokines is considered to be associated with the severity of gut inflammation [3]. Therefore, it is no surprise that cytokines have been a major therapeutic management of IBD [4].
\n
It is believed that dysregulated immune mechanisms are related to T cells in the gut in IBD pathogenesis. Unregulated T lymphocytes activities can lead to autoimmunity, especially during inflammation when they can cause excessive tissue damage [5]. The ability of CD4+ T helper (Th) cells to alter the magnitude and outcome of the intestinal tissue-damaging inflammatory responses is mostly dependent on the production of distinct profiles of cytokines. Traditionally, the lesions in CD patients have been associated with a predominant activation of Th1 cells and production of large quantities of IFNγ under the stimulus of IL-12 through STAT4 signaling. By contrast, the lesions in UC patients were believed to be driven by Th2 cytokines, such as IL-4 and IL-13, through STAT6 activation. In the mouse model of IBD, CD3+ (T cell) depletion results in dramatic reduction of the gross pathology, neutrophil influx, and expression of pro-inflammatory cytokines and chemokines [6]. The cytokine expression pattern that strictly follows the polarization model of Th1 versus Th2, however, does not appear to be fully applicable in IBD. Nearly 20 years ago, Mosmann and Coffman concluded their paradigm with the prediction: “… further divisions of helper T cells may have to be recognized before a complete picture of helper T cell function can be obtained” [7, 8]. Indeed, several recent studies had led to the identification of more complex networks of cytokine interaction in IBD tissue, thus shedding light on the role of a distinct subset of T cells in the pathogenesis of IBD—Th17 cells. On the other hand, another T cell subpopulation, namely T regulatory cells (Tregs), is implicated in gut homeostasis and tolerance induction, and it is believed that Th17 and Tregs are in a mutually polarizing relationship [9]. An overview of the main cells and cytokines involved in intestinal inflammation is presented in Figure 1.
\n
Figure 1.
T-helper cells and cytokines interactions in normal and inflamed mucosa of IBD patients. The fate of naïve T cell depends on the interactions with the antigen-presenting cells (i.e. dendritic cells, macrophages) and the secreted cytokines. In normal mucosa, the abundant TGFβ1 directs naïve Th0 cells to Treg differentiation which secrete IL-10 and TGFβ1. “Danger” signals through TLR activation (on antigen-presenting cells), followed by secretion of IL-6, IL-23, IL-1, etc., with the simultaneous presence of TGFβ1, all favor the development of Th17 cells. The latter secrete many cytokines, for example, IL-21 acts as an autocrine positive regulator but IL-25 and IL-27 inhibit Th17 cells in autocrine manner. Th17 cells could also secrete IL-17 cytokines, TNFα, and in special circumstances—IFNγ; thus, Th17 cells play an intermediate role between innate and adaptive immune response, especially during inflammation in the intestinal mucosa. The balance between Th17 cells and Tregs is desired to maintain the immune homeostasis in the gut. However, Tregs and Th17 cells can convert into each other demonstrating same plasticity, depending on the cytokine milieu. Nevertheless, there are other players in the inflamed mucosa such as Th1, Th2, and Th22 cells. Legend: black arrow—cell differentiation; green arrow—secretion; pink arrow—possible secretion; red arrow—inhibition; TCR—T cell receptor; TLR—Toll-like receptor; MHCII—major histocompatibility complex—Class II; TL1A—TNFα-like 1 A.
\n
Thus, the effector response is largely determined by the combination of cytokines that predominate in the intestinal mucosa, and it defines the mucosal T cell immunophenotype in each case [2].
\n
2.1. Innate immune response and related cytokines
\n
Dendritic cells (DCs), macrophages, epithelial cells, and myofibroblasts are able to recognize pathogen-associated molecular patterns (PAMPs) through their pattern-recognition receptors including Toll-like and NOD-like receptors. This recognition results in nuclear factor (NF)-kB activation with gene transcription and production of pro-inflammatory cytokines, such as IL-1 and TNFα, ensuring an effective innate response against microbial antigens. That also triggers antigen presentation, maturation, and up-regulation of co-stimulatory molecules which lead to efficient adaptive immunity involving T cell activation [10]. There is evidence for down-regulated protein level of TLR-3 in IBD, whereas TLR-2 and TLR-4 are up-regulated in intestinal mucosa of active IBD [11]. A specific mutation in NOD2 gene induces loss of NF-kB function during TLR-2 activation with a subsequent increased risk of infection with commensal bacteria and increased susceptibility to the ileal form of CD [12]. Recent studies suggest that increased mucosal permeability in the intestinal mucosa during IBD flare allows infiltration of a large number of granulocytes into the colonic mucosa. These leukocytes are activated, have a prolonged survival time, and release various pro-inflammatory cytokines (e.g. IL-1β, IL-6, TNFα, IL-18), which exacerbate and maintain the inflammation in the gut [13].
\n
2.1.1. TNFα
\n
TNFα links the innate and the adaptive immune responses and has crucial importance in the pathogenesis of IBD by inducing the differentiation of stromal cells into myofibroblasts and promoting their production of matrix metalloproteinases. The latter induce enterocyte apoptosis and digestion of gut basement membrane [10]. TNFα also exerts its pro-inflammatory effect through cytokines such as INFγ, IL-1β, and IL-6 [12].
\n
TNFα is a well-established inflammatory mediator in CD whereas contradictory reports exist in UC [12]. There is a lack of studies on the mucosal expression of TNFα and the prediction of the clinical course, and only a few reports announced the predictive value of mucosal TNFα concentrations and the response to therapy in IBD patients. In fact, increased levels of TNFα and IL-15 have been previously reported in intestinal biopsies from IBD patients in remission without biopsy alterations [14]. Interestingly, the presence of TNFα in non-affected areas of IBD mucosa may not be sufficient to trigger mechanisms of mucosal damage. In preliminary reports, normalizing of mucosal TNFα seemed to predict a longstanding remission after stopping of anti-TNFα therapy in UC [12].
\n
Certain TNFα polymorphisms (i.e. TNFα-308 A allele) are associated with increased serum levels of TNFα and therefore with higher susceptibility of IBD [15].
\n
\n
2.1.2. TNF-like cytokine 1A
\n
TNF-like cytokine 1A (TL1A) is a novel member of TNF superfamily of proteins, produced by endothelial cells, macrophages, lamina propria T cells and plasma cells, monocytes, and monocyte-derived DCs [16]. Association with its functional receptor provides co-stimulatory signals for activation of T lymphocytes, leading to cell proliferation, cytokine secretion, and amplification of pro-inflammatory pathways, as well as induction of apoptosis in target cells [2]. Several studies have clearly demonstrated that TL1A and its receptor are up-regulated at mucosal protein and mRNA levels in IBD patients. TL1A is localized in the lamina propria and shows preferential expression on plasma cells and mucosal DCs. Of great importance is the fact that TL1A was shown to increase IL-13 secretion by natural killer T (NKT) cells, which are considered to be central to the mucosal injury that takes place in UC pathogenesis. Furthermore, TL1A induces IFNγ secretion in synergy with stimulation via TCR or IL-12/IL-18 [2]. TL1A expression is induced by TNFα and IL-1α as well and since the latter are abundantly expressed in the inflamed mucosa of UC patients, they may provide a strong stimulus for enhanced TL1A expression. On the other hand, several microorganisms were shown directly to stimulate TL1A secretion by DCs via TLR-signaling (TLR-4), LPS-induced and NFkB-dependent pathway [16]. Moreover, there is an inhibitory component of the TL1A receptor which could augment pro-inflammatory pathways at the intestinal mucosa by rendering activated lymphocytes resistant to apoptosis. Thus, increased expression of this inhibitory TL1A receptor may offer a survival advantage to effector lymphocytes, preventing their elimination and perpetuating tissue injury [2].
\n
\n
2.1.3. IL-8
\n
IL-8, as a member of the CXC chemokines family, is not only a strong chemoattractant for neutrophils, monocytes, etc. but also triggers the secretion of superoxide anions and lysosomal enzymes in neutrophils, thus contributing to the tissue damage during inflammation. IL-8 mRNA expression in the inflamed mucosa is shown to be significantly higher than the level in non-inflamed mucosa of IBD patients or in the normal mucosa of non-IBD patients [13].
\n
\n
\n
2.2. Th1 profile-related cytokines
\n
Th1 cells are an essential part of the adaptive immune response, mainly against intracellular microorganisms and protozoa. The master transcription factors for Th1 definition are STAT4 and T-bet. Th1 cells in gut mucosa which are induced by increased levels of IL-12 and IL-18 are thought to cause intestinal inflammation in CD patients via production of high amounts of IFNγ. The latter induces enterocyte apoptosis and triggers the release of TNFα by activated mucosal macrophages. Th1 cells by themselves appear as an important source of TNFα [10].
\n
2.2.1. IFNγ
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IFNγ is a mediator of intestinal inflammation in CD, but contradictory reports exist for UC. However, increased levels of IFNγ have been observed in the inflamed mucosa from UC patients too. IFNγ levels also correlated with the clinical activity but not with the endoscopic score in UC, whereas no correlation to the clinical activity was observed in CD patients [12].
\n
\n
2.2.2. IL-12
\n
The role of IL-12 in intestinal inflammation will be discussed later along with IL-23.
\n
\n
2.2.3. IL-1
\n
IL-1 exists in two forms, IL-1α and IL-1β, encoded by different genes but exhibit almost identical functions [16]. The major sources of IL-1 are activated myeloid cells and its production can be induced by bacterial lipopolysaccharide, TNFα, IFNα, IFN-β, IFN-γ, as well as IL-1. IL-1 was found to promote Th17 development in the presence of IL-6 and TGFβ, and also to potentiate their actions in humans but not in mice. Moreover, it has been reported that IL-1 can increase their effect on Th17 definition. However, the mechanism through which IL-1 influences Th17 differentiation is not fully determined yet [17]. Some suggestions include that IL-1β or IL-1α cooperates with IL-23 to enhance IL-17 production independent of TCR stimulation. Additionally, IL-1 may suppress the inhibitory effect which IL-2 exerts on Th17 cell production through induction of IL-1R, IL-23R, and transcription factor RORγt [16].
\n
IL-1β was shown to be increased in CD and UC patients, whereas the IL-1-receptor/IL-1β ratio was negatively associated with the IBD activity. When comparing the IBD patients with controls, a significant variation in genotype frequency of the IL-1β promoter polymorphism was found. Higher levels of the pro-inflammatory cytokine IL-1β would be expected to increase the likelihood of developing IBD since higher levels of such cytokines occur in this disease [15].
\n
\n
2.2.4. IL-18
\n
IL-18 is another member of the IL-1 pro-inflammatory cytokine family. IL-18 is an epithelial-derived cytokine that has been proposed to promote barrier function in the intestine, but its effects on intestinal T cells are poorly understood. Although IL-18 is mainly responsible for inducing IFNγ production and Th1 differentiation, this cytokine might be involved in Th17 cell definition as well. Antigen-presenting cells express IL-18R on their surface and its binding with the cytokine is required for generation of Th17 cells through an IL-23-dependent mechanism. Moreover, IL-18 synergizes with IL-23 in the induction of Th17 cell [16] However, there are more reliable proofs about the involvement of IL-18R in Th17 cell definition, but not for IL-18 itself. Probably this action might be fulfilled through binding of an unknown alternative ligand, distinct from IL-18, to the receptor [17]. In contrast, Maloy et al. [18] demonstrated that during steady state, intestinal epithelial cells constitutively secrete IL-18, which acts directly on IL-18R1-expressing CD4+ T cells to limit colonic Th17 cell differentiation. In addition, they found that IL-18R1 signaling was critical for Tregs-mediated control of intestinal inflammation, though IL-18R1 is not required for Tregs development [18]. Thus, since IL-18 may regulate differentially homeostatic and inflammatory subsets of T cells, this finding has potential for treatment of IBD and other chronic inflammatory disorders.
\n
IL-18 was found elevated in the inflamed colonic mucosa of UC and CD patients and polymorphisms in the IL-18R1-IL-18RAP locus are associated with IBD susceptibility [18]. Moreover, the local expression of IL-18 has been shown to be associated with the grade of inflammation [19].
\n
\n
\n
2.3. Th2 profile-related cytokines
\n
Th2 cells, another important part of the adaptive immune system, are mainly involved in the effector responses against extracellular parasites, including helminths, as well as in allergy pathogenesis. They are defined by the transcription factors STAT6 and GATA3 [7]. The importance of Th2 response in IBD is still under debate. In UC, the inflammatory response is less skewed along specific pathways, even though there is enhanced production of IL-4, IL-5, and IL-13, cytokines made by Th2 cells, unlike CD where Th1 activation has been mainly employed in pathogenesis [20].
\n
2.3.1. IL-13
\n
IL-13 exerts the potential to increase intestinal permeability and induce both enterocyte differentiation and apoptosis. IL-13 is released mainly by Th2 cells but another source of that cytokine is NKT cells. NKT cells express surface CD161 but not invariant T cell receptor, which is a well-established characteristic of this population. They produce IL-13 in response to stimulation of antigen-presenting cells expressing surface CD1d. Most probably, these atypical NKT cells are stimulated to produce IL-13 in the colonic mucosa by flora-derived microbial products [2]. This was observed in patients with UC, but not in CD patients. Further studies revealed that CD161-expressing NKT cells showed IL-13-dependent cytotoxic activity against colon epithelial cells [2]. Moreover, IL-13 independently exerts harmful effects on epithelial barrier function, such as derangement of tight junction integrity, decreased restitution velocity, etc. [2]. Therefore, blockade of IL-13 downstream signaling may be an effective anti-inflammatory approach in UC which requires further investigations.
\n
\n
2.3.2. IL-11
\n
IL-11 is a member of the IL-6 cytokine family and exerts pleiotropic effects on various cell types as it acts synergistically with other cytokines such as IL-3 and IL-4, thus it has been implicated in Th2-mediated sensitization and inflammation. IL-11 also prevents cell death and inhibits inflammation at sites of tissue injury. IL-11 mediates anti-inflammatory effects by down-regulation of LPS-induced NFkB activation, thus preventing transcription of inflammatory genes [12]. This may be implemented in IBD therapy, but still needs additional verification.
\n
\n
2.3.3. IL-33
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IL-33 is the latest identified member of the IL-1 family of cytokines. mRNA and protein expression of IL-33 was detected in normal colonic cells both at the surface epithelium and in crypts, as well as in inflamed bowel onto lamina propria mononuclear cells (CD11b+ monocytes/macrophages and CD19+ B cells), endothelial cells, and subepithelial myofibroblasts. During active intestinal inflammation, IL-33 actively participates in the epithelial-immune cell crosstalk that takes place in IBD mucosa. IL-33 expression is augmented under stimulation with IL-1β and TNFα, two cytokines that are enriched at the inflamed mucosa and are of pathogenic relevance in UC, as well as after TLR-3 and TGFβ signals [2].
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Regarding mucosal expression, up-regulation of IL-33 appears to be specific for UC, as it was not observed in CD colonic inflammation [2]. Moreover, IL-33-expressing myofibroblasts were absent in fissuring areas in patients with colonic CD. Therefore, these observations may provide information of distinctive pathway between the two forms of IBD [2].
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IL-33 was shown also to induce particularly the expression of Th2 effector molecules IL-5 and IL-13. Given the central role of IL-13 in UC, IL-33 may be involved in UC pathogenesis through the induction of IL-13 secretion. It has been proposed that IL-33 may function as “alarmin” for the gut-associated immune system activating toward intestinal inflammation or perpetuating the ongoing one [2].
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2.4. Prerequisite cytokines for Th17 development
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To emphasize the importance of Th17 in intestinal inflammation, here we start with the description of the prerequisite cytokines for the development of Th17 cells from naïve T cells.
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2.4.1. TGFβ1
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Transforming growth factor β (TGFβ) is a potent cytokine with multi-faceted regulatory and inhibitory activities and has two forms—TGFβ1 and TGFβ2. TGFβ1 is a pleiotropic cytokine best known for its potential to induce peripheral tolerance in the absence of IL-6 [12]. One of the mechanisms by which TGFβ1 is able to maintain tolerance is to support the survival of naturally occurring FoxP3+ Tregs (nTregs) in thymus. In addition, along with IL-2 and retinoic acid, TGFβ1 promotes the differentiation of induced Tregs (iTregs). Another mechanism of TGFβ-induced tolerance is to suppress the innate immune cells such as DCs and NK cells [5].
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TGFβ1 also regulates the development of resident macrophages in the normal intestine, which possess some unusual features such as constitutive production of IL-10 and TNFα, refractory to TLR stimulation, high expression of MHCII and CXCR1, and avid phagocytic activity. Thus, this is another mechanism through which TGFβ1 favours local homeostasis [21].
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TGFβ1 plays an important role under inflammatory conditions. In the presence of IL-6, TGFβ1 drives the differentiation of Th17 cells which promotes further inflammation and augmentation of ongoing autoimmune conditions. In addition, TGFβ1 in combination with IL-4 promotes the differentiation of IL-9-producing and IL-10-producing T cells, which surprisingly lack suppressive function and also promote tissue inflammation [12]. Increased protein levels of TGFβ1 are found in the mucosa of both CD and UC patients, whose levels correlated with the severity of disease in CD but not in UC patients [5, 12]. We also found significantly higher gene and protein levels of TGFß1 in the inflamed mucosa of CD patients alone [22]. This is not surprising since the tissue remodeling properties of TGFβ1 are well-established. Interestingly, TGFβ1 orchestrates the differentiation of both Tregs and Th17 cells in a concentration-dependent manner—low doses induce Th17 cell differentiation while higher doses inhibit Th17 cell development and promote Tregs [5, 11].
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2.4.2. IL-6
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IL-6 is a pleiotropic cytokine with regulatory effects on inflammation development. In addition to its stimulatory effects (i.e. induction of acute phase proteins), IL-6 also has inhibitory functions (i.e. cessation of the antiviral antibody response after certain immunizations). Recent studies have demonstrated that IL-6 has a crucial role in the regulation of the balance between Th17 cells and Tregs [23]. IL-6 activates a receptor complex consisting of IL-6R and the signal transducing subunit gp130 which activates downstream STAT1 and STAT3. STAT3 regulates IL-6-induced expression of RORγt and RORα, the crucial transcription factors for Th17 cells. In contrast to STAT3 activation, STAT1 inhibits the development of Th17 cells. Although IL-6 activates both STAT1 and STAT3, it has been demonstrated that in Th17 cell activation, they play two different roles—STAT3 maintains while STAT1 suppresses it [23]. Furthermore, STAT family members activated by various cytokines provide both positive and negative regulation for Th17 development (i.e. IL-27 inhibits Th17 differentiation through STAT1) [23]. TGFβ1 can induce gene activation of both FoxP3 and RORγt, but FoxP3 is able to associate with RORγt, thus inhibiting its transcriptional activation. Nevertheless, in the presence of IL-6 this inhibition is abrogated, so IL-6 could act as a potent promoter of Th17 instead of Tregs differentiation. All facts taken together, IL-6 appears as the main partner of TGFβ in priming naïve T cells to IL-17 production, playing a pivotal role in Th17 polarization and initiation of inflammatory immune response. Currently, it is also accepted that IL-6 is able to induce expression of IL-23R in T cells, making them responsive to IL-23 which sustains the Th17 phenotype [17].
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Increased levels of IL-6 and its soluble receptor are up-regulated in active CD patients, and mucosal IL-6 levels were correlated with the degree of clinical activity in CD and UC [12]. In consent with these findings, in a group of 37 IBD patients, we also found both mRNA transcripts of TGFβ1 and IL-6 up-regulated in patients’ mucosa compared to the mucosa of non-IBD persons, along with increased IL-17 mRNA in inflamed tissue [22, 24].
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Several polymorphisms regarding the IL-6 gene are described to be also associated with susceptibility to IBD development, such as IL-6 174 [15].
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Although anti-IL-6 antibodies therapy has become a novel therapeutic strategy for some inflammatory and autoimmune disease, including CD, IL-6 inhibitory treatment acts primarily on initial CD4+ T cells response including Th17 differentiation, rather than on the effector phase [23]. However, it still remains controversial whether this antibody can inhibit Th17 differentiation in a manner that is clinically meaningful.
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2.4.3. IL-23
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IL-12 and IL-23 share the common p40 subunit, but whereas IL-12 drives the classical Th1 response characterized by IFNγ production, IL-23 maintains an IL-17-secreting T cell population. Th1 responses may develop normally in the absence of IL-23, but in IBD patients, their manifestations require the presence of IL-23. The systemic inflammatory response and the elevated concentrations of pro-inflammatory cytokines in the serum are driven by IL-12 while the local intestinal inflammation and production of IL-17 in the intestinal mucosa are controlled by IL-23 [11, 12, 25].
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IL-23 is crucial in orchestrating the crosstalk between innate and adaptive immunity with a key role in driving early responses to microbes. In a recent study, Kamada et al. showed that IL-23 is secreted preferentially by a subset of sentinel mucosal cells expressing both macrophage (i.e. CD14, CD33, CD68) and DC markers (i.e. CD205, CD209) [26]. These cells are present in a large number in CD-involved tissue and produce IL-12 and IL-23 in response to environmental danger signals [8, 26]. The presence of pathogens or pathogen-related products (such as lipopolysaccharide) can strongly influence the production of IL-12 and/or IL-23 depending on the microbial agent. This happens within a few hours after exposure and these early events in pathogen encounter are likely to shape subsequent responses toward IL-12 or IL-23 expression [8]. It was shown that some of the pathogenic functions of IL-23 in the gut are mediated by atypical T cell populations, such as γδT cells, invariant NK cells, and innate lymphoid cells, inducing them to secrete Th17-related cytokines and contributing to intestinal inflammation [10]. IL-23 might be also closely associated with the neutrophil influx [12].
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The precise function of IL-23 in Th17 regulation is still not entirely clear, although there are a lot of speculations. IL-23 failed to induce the differentiation of naïve T cells into Th17 cells due to lack of IL-23R on naïve T cells [16]. It was subsequently demonstrated that IL-23R is not expressed on naïve T cells. Instead, IL-23 acts as a survival signal for Th17 cells by the mechanism probably similar to TNFα [23, 27].
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The synthesis of the common p40 subunit for both IL-12 and IL-23, and the functional heterodimeric IL-23 is enhanced in the gut of CD patients [11]. Along with other authors’ findings, we detected up-regulated mRNA levels of IL-23 in inflamed mucosa, as well as significantly increased serum level of IL-23 among IBD patients in comparison with non-IBD persons [24], and we suggest that anti-IL-23 therapy could be beneficial for IBD patients.
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Identification of multiple single nucleotide polymorphisms (SNPs) in the IL-23 receptor gene that has been associated with both UC and CD suggested that the IL-23 axis might play a central role in chronic inflammation. IL-23R SNPs that influence IBD susceptibility have provided a new picture of the way the local immune response can promote intestinal tissue damage [11]. Small differences in cytokine levels as a result of gene polymorphisms may have an important effect on the inflammatory response and thus, influence the pathophysiology of IBD [15]. Interestingly, one of these polymorphisms, Arg381Gln, confers protection against developing CD [20]. Nonetheless, the mechanism through which these SNPs confer either risk or protection from IBD remains unknown [15].
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2.5. Th17 cells and produced cytokines
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The discovery of an IL-23-dependent T cell population that produces IL-17 but not IFNγ or IL-4 suggested there is an additional Th cell subset. Th17 cells have derived their name from their ability to produce IL-17, also termed IL-17A. Th17 cells also produce other cytokines including IL-17F, IL-21, IL-22, TNFα, and IL-6 [17, 23]. However, analysis at the single cell level has revealed that not all Th17 cells secrete the whole spectrum of cytokines, probably reflecting the heterogeneity of this cell’s subset [25]. The IL-17 cytokine family also includes IL-17B, IL-17C, IL-17D (IL-27), IL-17E (IL-25), and IL-17A/F (Figure 1). The cytokines IL-27 and IL-25 have lowest protein homology to IL-17A. They are not produced by Th17 cells but act as negative regulators on the Th17 subset development. IL-27 is structurally related to IL-6 and is able to attenuate chronic inflammation by promoting IL-10 production [17]. In line with this, IL-27 and IFNγ are responsible for the inhibition of Th17 development in a STAT1-dependent manner [23], as described above. Another negative regulator of Th17 cells is IL-25, identified as a genetic homologue of IL-17, produced by Th2 and mast cells. IL-25 is involved in the expression of the Th2 cytokines IL-5 and IL-13, thus, favors Th2 responses. IL-25 deficiency is involved in pathologic inflammation, associated with increased expression of IL-17 and IL-23 [17].
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CCR6, presented not only on Th17 cells, but also on Tregs, B cells, neutrophils and immature DC, plays a critical role in the migration of these cells to the sites of inflammation. TGFβ1 was shown to be the main factor for induction of CCR6 mRNA expression in Th17 cells and DCs [19]. IL-17-producing Th memory cells selectively express both CCR6 and CCR4, unlike Th cells producing IFNγ or both IFNγ and IL-17 which express CCR6 and CXCR3 [16]. Indeed, CCR4 is important for homing to the gut, where most RORγt+IL-17+ T cells are found [16].
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The relationship among Th1, Th2, and Th17 cells is complex and still not clear. Th1- and Th2-related cytokines inhibit Th17 cell differentiation while IL-17 is not able to suppress Th1 or Th2 cells, or does it weakly. The suppression of IFNγ and IL-4 or their absence represents a way by which TGFβ1 could promote Th17 cell development. TGFβ1-driven Th17 cell differentiation can also occur in the absence of IFNγ and IL-4 [11]. In parallel with these findings, it was reported that IL-17-producing cells could be generated independent of the specific cytokines and transcription factors required for Th1 and Th2 differentiation [17]. Moreover, Th17 cells could develop from naïve T cells only in the combined presence of IL-6 and TGFβ1 [12, 20]. Thus, TGFβ induction of Th17 cells and also of Tregs, which are usually contradictory acting, is dependent on the presence of IL-6. This explains the apparent discrepancy of TGFβ1 involvement in both anti- and pro-inflammatory events in the intestine mucosa [17].
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2.5.1. IL-17
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IL-17 is an effector cytokine in gut immunity, which may have either pro-inflammatory or tissue-protective effects in the mucosa depending on the experimental or clinical model used. On one hand, IL-17 contributes to the mucosal barrier function by several mechanisms which, upon activation, result in a mucosal immune response toward pathogens [6]. IL-17 also promotes tight junction formation and increases trans-epithelial resistance in polarized intestinal epithelial cells by stimulating the production of antimicrobial peptides such as lipocalin-2, β-defensins, and calprotectin. This suggests that the latter are involved in the maintenance of immunological homeostasis and/or in the control of specific inflammatory pathways [19]. Thus, the Th-17-related cytokines mediate protective effects in host gut against various bacteria and fungi, particularly at mucosal surfaces [10, 11]. Interestingly, pathogens that have evolved to take advantage of various aspects of the mucosal response gain an edge over the resident commensal bacteria and colonize the gut with priority. Despite that Th17 responses appear to be detrimental by promoting pathogen colonization of the mucosa, in the end, they result in decrease in bacterial dissemination from the mucosa that protects the host by inducing slight inflammation [6]. In line with this, it was shown that Th17 cells are constitutively present in the human and mouse intestinal mucosa and that Th phenotype is driven by the commensal bacteria in the gut. Additionally, stimulation of DCs with TLR ligands (e.g. fungal Dectin-1) induces synthesis of IL-6, TNFα, and IL-23 that promotes the differentiation of Th17 cells [11]. From this point of view, blocking Th-17 cytokines could have more deleterious than beneficial effects for the host [25].
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On the other hand, IL-17 might mediate tissue inflammation by triggering several inflammatory pathways and by inducing various pro-inflammatory cytokines (e.g. IL-1, IL-6, TNFα, G-CSF, GM-CSF), chemokines (e.g. IL-18, CXCL-1, CXCL8, MIP-1), and enzymes (COX-2, matrix metalloproteinases). Both IL-17 and IL-22 stimulate granulopoiesis by inducing expression of the granulocyte colony stimulating factor (G-CSF) and IL-17A which rapidly recruits neutrophils to the inflammatory site. This mechanism has important evolutionary significance [25]. The neutrophil response gains time for the induction of the following antimicrobial Th1- IFNγ response which takes several days to develop. Once the appropriate immune effector functions occur, the IL-12/IFNγ axis becomes the dominant pathway in host defence. This is important for initial control of the infection, but if the IL-23/IL-17 immune pathway becomes dysregulated, there is a danger of autoimmune pathology development, such as IBD. These observations, including the fact that T-bet is expressed at lower level in Th17 cells, led McKenzie et al. to favour the hypothesis of a common lineage precursor of Th1 and Th17 cells [8]. Furthermore, the tissue localization and timing of IL-12 versus IL-23 responses explain the idea that IL-12/IFNγ axis is involved in systemic inflammatory conditions (such as lupus), whereas the IL-23/IL-17 axis appears to regulate tissue-specific disorders (such as IBD) [8].
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Another layer of complexity to the mucosal existence of Th17 cells is other cell types, which can secrete IL-17-related cytokines: γδT cells (secreting IL-17 in response to IL-23), NK, NKT cells (able to produce IL-17 and IL-22), and DCs (can secrete IL-22 in response to bacterial infection). Paneth cells, which are common in the ileum, also secrete IL-17A [6, 19]. As all these cells express the IL-23 receptor, the secretion of IL-23 by DCs comprises a trigger which potentiates early T cell activation and adaptive immunity development [6]. Thus, it appears that early activation of both adaptive and atypical innate-like T cells can lead to the expression of IL-17 and IL-22. However, dysregulated production of IL-17, IL-22, and TNFα in local tissue can result in chronic immune-mediated tissue destruction [8].
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Studies in murine models of IBD strongly suggest that Th17 cells and their related cytokines contribute to tissue-damaging immune responses in the gut [25]. Up-regulation of Th17-related cytokines, however, does not represent a specific hallmark of IBD in humans, as increased levels of IL-17A and other Th17-related-markers have been seen in patients with rheumatoid arthritis, multiple sclerosis, psoriasis, etc. [11]. Immunohistochemistry studies have shown that in active UC, the IL-17-expressing cells were located mainly within the lamina propria, while in active CD, these cells were scattered throughout the submucosa and muscularis propria of the gut. Corresponding with this, it was shown that RNA transcripts for IL-17A and IL-17F were up-regulated in the inflamed mucosa of UC and CD patients [3, 11, 22, 28]. Both IL-17 and IL-23 are correlated to the severity of UC [12]. More recently, Annunziato et al. demonstrated that the number of IL-17-producing T cells is higher in CD than in normal gut mucosa, and some of these cells also produce IFNγ [29].
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Th17 cells have shown possession of functional plasticity. Some of the IL-17A-producing cells simultaneously express IFNγ (Figure 1). Majority of IL-17/ IFNγ-producing cells express CD161, a well-known marker of NKT cells, also identified recently on IL-17-producing memory T cells [11]. Th17 cells can be converted into Th1 cells if they receive appropriate stimuli, such as IL-12 which enhances the expression of Th1-related markers (i.e. T-bet and IFNγ) and down-regulates RORγt and IL-17. Additionally, recent studies have shown that treatment of intestinal lymphocytes with IL-23 can facilitate the production of either IL-17A or IFNγ in UC or CD, respectively [11].
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This is in consent with the demonstration that some of the pathogenic effects of IL-23 in the gut are linked to the ability of this cytokine to turn on IFNγ production. Switching from IL-17A to IFNγ production occurs if Th17 cells are activated by a lack of TGFβ1 [25]. Th17 cells and their possible conversion to Treg direction is going to be described later.
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This very complex and non-equivocal relationship of both pro-inflammatory and tissue-protective effects of IL-17 in the gut may explain the unsuccessful anti-IL-17 therapy in CD patients [10].
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2.5.2. IL-21
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IL-21, an IL-2-related cytokine produced by Th17 cells in response to IL-6, increases the expansion of this cell subtype by a positive autoregulatory feedback loop. IL-21, which is up-regulated in inflamed IBD mucosa, induces Th1 and Th17 immune responses in the mucosa [10], but a mixture of both Th1 and Th17 cytokines is needed to promote full pathology in the gut. In this context, a promising inducer could be IL-21, whose activity seems to be necessary for expanding both Th1 and Th17 cell responses in the intestine. [25]. As we have already noticed, IL-21 is overproduced in the gut mucosa of IBD patients, but the vast majority of IL-21-producing CD4+ T cells co-express IFNγ but not IL-17A. This fact suggests that Th1 but not Th17 cells are the major sources of IL-21 in the human gut [11]. There is evidence that IL-21 also enhances the expression of Th1-related transcriptional factors and IFNγ production in NK cells [11].
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IL-21, like IL-17, stimulates gut fibroblasts to produce tissue-degrading matrix-metalloproteinases and enhances the secretion of chemoattractants (i.e. MIP-3α) by epithelial cells [10, 11]. IL-21, like IL-6, could also initiate Th17 differentiation together with TGFβ1 [23], even in the absence of IL-6 [16, 17]. IL-21 enhances the expression of IL-23R in Th17 cells, through a process that is dependent on STAT3 and RORγt, making these cells responsive to IL-23. IL-21 as well exerts additional biological functions that could contribute to its pro-inflammatory effect in the gut like inhibition of the peripheral differentiation of Tregs and making CD4+ T cells resistant to Treg-mediated immune suppression [11].
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2.5.3. IL-22
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IL-22 is a member of the IL-10 cytokine family and a Th17-related cytokine but it appears to be differentially regulated. IL-22 provides signals through a heterodimer comprising IL-22R and IL-10Rβ. The IL-22 receptor is highly expressed in tissues such as epithelial cells of the gastrointestinal tract. Via STAT3 signaling pathway, the activation of proliferative and/or anti-apoptotic programs starts, and this allows maintenance of epithelial barriers of the gut [5]. Most of the Th17 cytokines are highly dependent on the transcription factor RORγt for their expression, unlike IL-22 whose expression is dependent on the transcription factor aryl hydrocarbon receptor [5]. Th22 cells are another Th subpopulation characterized by the expression of this transcription factor and secretion of mainly IL-22 [5].
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IL-22 has a dual functional nature in modulating the responses during tissue remodeling. IL-22 promotes induction of acute inflammatory proteins, mucins, and antimicrobial peptides (i.e. β-defensins), which are important for tissue integrity during inflammation. This mechanism ensures proper organ function and escape of potentially harmful effects by restricting the passage of luminal commensal flora and food antigens to the lamina propria [5, 25, 30]. It is important to point out that this process depends on the inflammatory context (the overall cytokine milieu and the tissues involved). Thus, IL-22 is important for control of pathogenic bacteria that need to translocate through host epithelial barriers to disseminate, especially in the gastrointestinal tract [5]. IL-22 also enhances intestinal barrier integrity by stimulating epithelial cell growth, goblet cell restitution, and mucus production, thus contributing to the healing of damaged tissue.
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On the other hand, IL-22 can cause further inflammation by stimulating colonic fibroblasts to secrete inflammatory cytokines (e.g. TNFα, IL-8, IL-11, and leukaemia inhibitory factor), IL-6, chemokines, and matrix metalloproteinases [11]. It is not surprising that IL-22 is highly expressed during chronic inflammation [5] in mucosal samples of patients with active CD, because of the known dysbacteriosis and expected pathological microbial agents, and to a lesser degree in patients with UC, where autoimmune phenomena are more common.
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IL-22 is also expressed by innate immune cells such as CD11c+ and NK cells located in the colon. The latter cells do not secrete IFNγ and are not highly cytotoxic [30]. IL-23, a traditional activator of NK cells, induces IL-22 expression in NK cells. Unlike TGFβ and IL-10 that directly modulate the immune response, IL-22 does not have direct effects on immune cells since these cells lack the expression of IL-22R [30]. This way, TGFβ1 and IL-10 are involved in maintaining immune homeostasis under steady-state conditions instead.
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IL-22 is an ideal therapeutic candidate since it specifically modulates tissue remodeling and does not have direct effects on the immune response. Treatment with recombinant cytokine or gene therapy delivery of IL-22 may alleviate tissue destruction during inflammation owing to its selective modulation of tissue responses [5].
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2.6. Role of FoxP3+ Tregs and related cytokines in gut inflammation
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The main function of Tregs is to modulate the adaptive immune responses, and forkhead/winged helix transcription factor forkhead box P3 (FoxP3) is the master transcription factor for Tregs [23]. Two main subpopulations of Tregs have been best described: naïve (nTregs) and inducible Tregs (iTregs). The latter is believed to be derived by peripheral transformation of naïve T cells stimulated by IL-19, vitamin D3, antigens, and TGFβ1. So far, Treg function in IBD is not completely characterized [12].
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Tregs are crucially involved in the maintenance of gut mucosal homeostasis by suppressing abnormal immune responses against the commensal flora or dietary antigens. They exert their function by producing the anti-inflammatory cytokines IL-10 and TGFβ, thus preventing both the activation and the effector function of T cells. Additionally, the regulatory activities of the immune response through mediators such as IL-10 and TGFβ still need to be profiled, especially those that might take place in the unaffected areas of IBD patients [14]. A certain number of Th17 and CD4+CD25+FoxP3+ Tregs cell is presented in the intestine even in the healthy state, partly due to the presence of enteric bacteria which favor the production of both Th17 and Tregs. DCs in the intestine or mesenteric lymph nodes also actively promote the production of both cell types. However, there are points of divergence, for example, the retinoic acid produced by DCs in the intestine induces only Tregs. In spite of the essential function of IL-2 as a growth factor of effector T cells, including Tregs, IL-2 has an inhibitory effect on Th17 cell production. Furthermore, IL-2 deficiency leads to systemic autoimmune disease, partly because of its involvement in the differentiation and survival of Tregs [16]. Recent studies have revealed that IL-2 deficiency promotes differentiation of Th17 cell subset in a STAT5-dependent mechanism. At present, the recognized precise mechanism is exerted by suppression of IL-17 expression by directly binding to the IL-17 gene promoter of STAT5 [16].
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The importance of Tregs in maintaining immune homeostasis was once again emphasized with the X-linked IPEX syndrome (immune dysregulation, polyendocrinopathy, enteropathy), caused by mutation of FoxP3. IPEX patients quite often complain of gastrointestinal symptoms, suggesting that Tregs dysfunction may be involved in human IBD too [31].
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A significant increase in production of Tregs in active-phase IBD mucosal lesions, as well as decreased numbers of Tregs in peripheral blood of IBD patients was described [9]. However, in active IBD a reduced number of peripheral Tregs have been reported to be reverted by anti-TNF treatment [12]. Indeed, Tregs are increased in the intestinal mucosa of IBD patients in comparison with the mucosa of healthy volunteers [22, 24, 27, 32]. Tregs isolated from inflamed tissue display no obvious defect in their suppressive function, at least in vitro [9]. However, Monteleone et al. found that Tregs obtained from the active-phase IBD mucosal lesions possess an ability to suppress T cell activation [11, 25]. Since Th17 cells appear to be resistant to the Tregs-mediated immunosuppression, it is likely that during chronic inflammatory process, such as in IBD, Tregs may be dysfunctional and might augment rather than suppress Th17-mediated immune responses [11]. At first, this phenomenon was explained as a feedback loop associated with an increase in the Treg cell attracted by IL-2 which is produced locally at sites of inflammation. On the other hand, however, up-regulated Th17 cells in response to increased production of pro-inflammatory cytokines were postulated [27]. Th17 cells, but not Tregs, are induced in the presence of pro-inflammatory cytokines, in addition to TGFβ1. Thus, Treg dysfunction may not be intrinsic but rather due to extrinsic milieu of activated cells that are resistant to suppression, and pro-inflammatory settings in the affected IBD mucosa [9, 33].
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Plasticity of Tregs and Th17 is further demonstrated by the possibility of conversion between both subsets [27, 33]. Hu et al. have reported that Tregs express membrane-bound TGFβ and in the presence of IL-6, they convert to Th17 cells [34]. This could be an important warning regarding cell therapy with Tregs to treat chronic immune disease, including IBD, because the “homeostatic” Tregs may convert to pathogenic Th17 cells during inflammation where IL-6 is abundant [27]. Numerous studies have shown that in inflammatory cytokine environment, Tregs can lose FoxP3 expression and acquire expression of other transcription factors that define another lineage of CD4+ T cells as well as effector function. As we have already mentioned, exposure of Tregs to IL-6 results in a partial conversion to Th17 cells. Interestingly, although most IL-17-producing cells lost FoxP3 expression, some cells express both FoxP3 and IL-17. It is unclear, however, whether the resultant cells are suppressive [9]. So, once again it must be mentioned that the Th17/Tregs balance appears to play a very crucial role in IBD development [27].
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2.6.1. IL-10
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IL-10 is secreted by many types of immune cells including Th2, Tregs, Tr1 (IL-10-producing FoxP3-CD4+ T cells), Th3 (TGFβ and IL-10-producing CD4+ T cells induced in oral tolerance), NKT cells, B cells, macrophages, and DCs [5]. IL-10 binds to its heterodimeric receptor, composed of unique for IL-10 subunit (IL-10Rα) and shared with IL-22 subunit (IL-10Rβ). Although not completely sufficient, STAT3 is required for the inhibitory functions of IL-10. Importantly, STAT3 induces the expression of transcription factors that regulate various cytokine signaling pathways including IL-6. IL-10 down-regulates IL-12 production and expression of co-stimulatory molecules in macrophages and DCs, thereby reducing the Th1 response generation [5].
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IL-10 is a key regulator of the immune system by limiting the inflammatory responses that could otherwise cause tissue damage. IL-10 is essential for homeostasis of the immune system, especially in the gastrointestinal tract where the tolerance is most needed. Evidence for that is the highly-susceptible-to-colitis IL-10-deficient mice which develop aberrant immune responses to commensal bacteria. This colitis is more severe when combined with a deficiency in TGFβ signaling [5].
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Small intestine and colonic lamina propria showed the highest frequency of IL-10-expressing cells. Recent findings show that macrophages in the lamina propria preferentially induce IL-10-producing cells while DCs promote the generation of Th17 cells. On one hand, blocking IL-10 during infection can result in more severe pathology or even fatality of the host, but on the other hand, high production of IL-10 is associated with sustained chronic infections and its blockade promotes pathogen clearance. Thus, once again, the milieu of the intestines favors the generation of IL-10-producing T cells leading to tolerance against commensal bacteria, whereas the expression of IL-10 in peripheral tissues under infectious conditions leads to suppression of the immune response [5]. In line with this, when IL-10 was previously found to be abundantly expressed by macrophages in areas of dense inflammatory infiltrate, it had been directly related to the attenuation of the mucosal inflammation [14]. Knowing nowadays about the dual role of IL-10, it is not unexpected that IL-10 is presented at a higher level in the inflamed mucosa of IBD patients [13]. These findings were confirmed by us as well [24].
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Some IL-10 gene polymorphisms have been associated with susceptibility to IBD (i.e. IL-10—1082) and more significantly with UC alone. Whether the polymorphisms are directly involved in regulating cytokine production, and consequently disease pathophysiology of IBD, or serve merely as markers that are in linkage disequilibrium with susceptibility genes, is still unclear [15].
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The involvement of IL-10 in the regulation of the pathogenic function of Th17 cells has been definitively demonstrated in experiments where non-pathogenic Th17 subtype expressing IL-10 is generated by IL-6 and TGFβ1, even though in the absence of IL-23. These cells also prevent the induction of the disease in an IL-10-dependent manner [35]. Even though IL-10 effectively treats colitis in mouse models and suppresses inflammatory cytokine production in vitro in intestinal cells of patients with IBD, clinical trials using recombinant IL-10 to treat IBD in humans have been largely disappointing, irrespective of the acceptable side-effect profile of the therapy [36].
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2.7. Role of innate lymphoid cells in gut inflammation
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Innate lymphoid cells (ILCs) are recently described cells that have been involved in both maintenance and loss of gut homeostasis. ILCs are phenotypically and functionally distinct subsets of cells that inhabit the intestinal mucosa. However, they produce cytokines associated with effector T-cell responses early in inflammatory lesions of patients with IBD [37]. The novel family of cells comprises three subsets: ILC1, ILC2, and ILC3 [38]. ILC1 express the transcription factor T-bet resembling Th1 cells with production of IFN-γ and TNF; thus, they contribute to host resistance to intestinal pathogens. ILC2 produce Th2 cytokines, such as IL-5 and IL-13, and they are dependent on the transcription factor GATA-3. ILC3 which express the transcription factor RORγt produce IL-17A and IL-22 mirroring Th17 cells [37]. ILC3 is involved in gut homeostasis by secreting IL-22 and promoting IL-10 and antimicrobial peptide production. Epithelial stress-induced ligands and inflammatory conditions may switch ILC3 to ILC1 secreting TNF and IFN-γ under the influence of IL-12. The pro-inflammatory cytokines of ILC1 and ILC3 lead mainly to epithelial apoptosis and neutrophil recruitment. ILC2 are able to contribute to IBD complications by producing the fibrogenic cytokine IL-13 [37].
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Since ILCs might be substantial drivers of mucosal inflammation, targeting ILC subsets may be a new exciting treatment option for IBD patients.
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3. Conclusion
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From a clinical perspective, IBD is a chronic persistent disease characterized by repeated relapses and remissions. One explanation could be that memory Th cells created during the disease development persist in the body, including during remission, in a manner that is dependent on the various cytokine presentations. Effector cytokines in the mucosa may induce inflammation at the time of the initial episode and during relapses. However, the ambiguity and contradictory actions of given cytokines confound the understanding of their interactions in dynamics of the immune response, and that leads to lack of synonymous conclusions about them. There is still strong need for further investigation, particularly in the gut mucosa, to fully comprehend their roles in the complex dynamic network of the immune mediators.
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Th17 cells have been shown to play a central role in murine and human IBD. Inhibition of the Th17 pathway may be a promising treatment for IBD, with respect to the role of other subsets of Th1 and Th2 cells. The data in the literature and our own experience make us believe that in order to achieve immune homeostasis in the gut, pro-inflammatory and anti-inflammatory responses that define the mucosal cell immunophenotype, should achieve balance. Thus, following the clinical periods of remissions and relapses, it is important to observe their immunological equivalents in the gut and possibly in whole blood, namely regulatory and pro-inflammatory cytokines secreted by different types of immunocompetent cells.
\n
\n
Acknowledgments
\n
We would like to thank the Medical University of Sofia, Bulgaria [Grant No.22/2012] and the Medical Faculty of Trakia University, Stara Zagora, Bulgaria [Grant No.4/2012] for the financial support of our studies regarding cytokines expression in inflamed mucosa. We are also immensely grateful to Stoyanka Petrova and Radislav Nakov for coordination of the financial support for this publication. We would also like to show our gratitude to Iliya Karakolev and Kalina Toumangelova-Yuzeir for assistance with some aspects of the methodology.
\n
\n',keywords:"IBD, cytokines, mucosal inflammation, Th17, Tregs",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/51376.pdf",chapterXML:"https://mts.intechopen.com/source/xml/51376.xml",downloadPdfUrl:"/chapter/pdf-download/51376",previewPdfUrl:"/chapter/pdf-preview/51376",totalDownloads:2476,totalViews:471,totalCrossrefCites:2,totalDimensionsCites:5,totalAltmetricsMentions:0,introChapter:null,impactScore:3,impactScorePercentile:87,impactScoreQuartile:4,hasAltmetrics:0,dateSubmitted:"November 2nd 2015",dateReviewed:"May 18th 2016",datePrePublished:null,datePublished:"October 26th 2016",dateFinished:"June 27th 2016",readingETA:"0",abstract:"Cells of the innate and the adaptive immune system have been identified as the key players in inflammatory bowel disease (IBD) pathogenesis, and the cytokines are central components of the inflammatory pathways that take place in the gut mucosa during the active and chronic phases of IBD. The effector cell response is largely determined by the type of cytokines that predominate in the intestinal mucosa. Here we describe the main cytokine players in intestinal inflammation during IBD—related to innate immune responses (tumor necrosis factor α—TNFα), TNF-like cytokine 1A, IL-8), and related to adaptive immune responses—Th1 (IL-1β, IL-18, IFNγ, IL-12), Th2 (IL-4, IL-5, IL-13, IL-11, IL-33), Th17 (IL-17A, IL-17F, IL-21, IL-22, IL-25, IL-27), cytokines required for Th17 development (IL-6, TGFβ, IL-23), anti-inflammatory cytokine IL-10 and Tregs along with IL-2. Recently described innate lymphoid cells (ILCs) could also be potential sources of IFN-γ, TNF, IL-5, IL-13, IL-17, and IL-22. The effects of cytokines in the gut are described in conjunction with the clinical implication and available biologic therapy. The data in the literature and our own results make us believe that in order to achieve immune homeostasis in the gut, pro-inflammatory and anti-inflammatory responses that define the mucosal cell immunophenotype should achieve balance.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/51376",risUrl:"/chapter/ris/51376",book:{id:"5204",slug:"new-insights-into-inflammatory-bowel-disease"},signatures:"Tsvetelina Velikova, Dobroslav Kyurkchiev, Ekaterina Ivanova-\nTodorova, Zoya Spassova, Spaska Stanilova and Iskra Altankova",authors:[{id:"69749",title:"Prof.",name:"Spaska",middleName:null,surname:"Stanilova",fullName:"Spaska Stanilova",slug:"spaska-stanilova",email:"stanilova@mf.uni-sz.bg",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/69749/images/system/69749.jpg",institution:{name:"Trakia University",institutionURL:null,country:{name:"Bulgaria"}}},{id:"180979",title:"Dr.",name:"Tsvetelina",middleName:null,surname:"Velikova",fullName:"Tsvetelina Velikova",slug:"tsvetelina-velikova",email:"ts_velikova@abv.bg",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180979/images/system/180979.jpg",institution:{name:"Lozenetz Hospital",institutionURL:null,country:{name:"Bulgaria"}}},{id:"184270",title:"Prof.",name:"Zoya",middleName:null,surname:"Spasova",fullName:"Zoya Spasova",slug:"zoya-spasova",email:"zoya.spassova@hotmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"184271",title:"Dr.",name:"Ekaterina",middleName:null,surname:"Ivanova-Todorova",fullName:"Ekaterina Ivanova-Todorova",slug:"ekaterina-ivanova-todorova",email:"katty_iv@yahoo.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"184272",title:"Prof.",name:"Dobroslav",middleName:null,surname:"Kyurkchiev",fullName:"Dobroslav Kyurkchiev",slug:"dobroslav-kyurkchiev",email:"dsk666@gmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"184273",title:"Prof.",name:"Iskra",middleName:null,surname:"Altankova",fullName:"Iskra Altankova",slug:"iskra-altankova",email:"altankova@yahoo.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Intestinal inflammation and cytokines",level:"1"},{id:"sec_2_2",title:"2.1. Innate immune response and related cytokines",level:"2"},{id:"sec_2_3",title:"2.1.1. TNFα",level:"3"},{id:"sec_3_3",title:"2.1.2. TNF-like cytokine 1A",level:"3"},{id:"sec_4_3",title:"2.1.3. IL-8",level:"3"},{id:"sec_6_2",title:"2.2. Th1 profile-related cytokines",level:"2"},{id:"sec_6_3",title:"2.2.1. IFNγ",level:"3"},{id:"sec_7_3",title:"2.2.2. IL-12",level:"3"},{id:"sec_8_3",title:"2.2.3. IL-1",level:"3"},{id:"sec_9_3",title:"2.2.4. IL-18",level:"3"},{id:"sec_11_2",title:"2.3. Th2 profile-related cytokines",level:"2"},{id:"sec_11_3",title:"2.3.1. IL-13",level:"3"},{id:"sec_12_3",title:"2.3.2. IL-11",level:"3"},{id:"sec_13_3",title:"2.3.3. IL-33",level:"3"},{id:"sec_15_2",title:"2.4. Prerequisite cytokines for Th17 development",level:"2"},{id:"sec_15_3",title:"2.4.1. TGFβ1",level:"3"},{id:"sec_16_3",title:"2.4.2. IL-6",level:"3"},{id:"sec_17_3",title:"2.4.3. IL-23",level:"3"},{id:"sec_19_2",title:"2.5. Th17 cells and produced cytokines",level:"2"},{id:"sec_19_3",title:"2.5.1. IL-17",level:"3"},{id:"sec_20_3",title:"2.5.2. IL-21",level:"3"},{id:"sec_21_3",title:"2.5.3. IL-22",level:"3"},{id:"sec_23_2",title:"2.6. Role of FoxP3+ Tregs and related cytokines in gut inflammation",level:"2"},{id:"sec_23_3",title:"2.6.1. IL-10",level:"3"},{id:"sec_25_2",title:"2.7. Role of innate lymphoid cells in gut inflammation",level:"2"},{id:"sec_27",title:"3. Conclusion",level:"1"},{id:"sec_28",title:"Acknowledgments",level:"1"}],chapterReferences:[{id:"B1",body:'Blumberg R. Inflammation in the intestinal tract: pathogenesis and treatment. Dig Dis. 2009;27(4):455–64. DOI: 10.1159/000235851'},{id:"B2",body:'Bamias G, Kaltsa G, Ladas SD. Cytokines in the pathogenesis of ulcerative colitis. Discov Med. 2011;11(60):459–67.'},{id:"B3",body:'Fujino S, Andoh A, Bamba S, Ogawa A, Hata K, Araki Y, Bamba T, Fujiyama Y. 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Department of Clinical Laboratory and Clinical Immunology, Medical University of Sofia, University Hospital St. Ivan Rilski, Sofia, Bulgaria
Clinical Immunology, University Hospital Lozenets, Sofia University, Sofia, Bulgaria
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1. Introduction
Maternal health, which is a core part of women’s health during pregnancy, childbirth and the postpartum period, contributes massively to attaining an optimal public health state, as women make up half of the world’s population and economies for development [1].
Pregnancy and childbirth should be joyous experiences for every woman and her household. However, this is not the case for some families as the joy is cut short at delivery, and a joyous occasion becomes a tragedy. Beyond the family, these deaths have detrimental effects on the socio-economic aspects of a country and the world at large [2].
Several factors contribute to these deaths, which are caused chiefly by the lack of appropriate care during pregnancy, childbirth, and post-delivery periods, with the bedrock of these care ingrained in the community. Community-based Birth Attendants (healthcare providers) provide this care for approximately 7 out of 10 women of reproductive age [3, 4].
2. Maternal and child mortality: incidence, causes and implications
Maternal mortality is defined as the loss of a woman’s life resulting from pregnancy complication or death with 42 days after childbirth, notwithstanding the period or site of the pregnancy, emanating from issues that are linked or escalated by the management of the pregnancy but from accidental or incidental causes. Whereas, Early childhood mortality include Neonatal mortality (the probability of a child dying within the first month), Infant mortality (the probability of dying before the first birthday), Post-neonatal mortality (the difference between infant and neonatal mortality), Child mortality (the probability of dying between the first and the fifth birthday) and Under-5 mortality (the probability of dying between birth and the fifth birthday) [5].
Every year, women’s lives are lost to complications of childbirth and pregnancy. According to the World Health Organisation, in 2017, 810 women died every day from preventable causes related to pregnancy and childbirth, with 94% of these deaths occurring in low and lower middle-income countries. In Nigeria, maternal mortality is reported to be 545 deaths per 100,000 live births and is currently known to have the second-highest number of maternal mortality (making up approximately 20% of all global maternal mortality) and perinatal mortality in the world, with unskilled TBAs assisting up to 90% of the deliveries that lead to these high statistics [4, 5].
Maternal deaths are due to complications that arise either during pregnancy or as a result of childbirth. While some conditions may exist before the pregnancy, the state of pregnancy can potentially worsen them. According to the WHO’s International Classification of Diseases-Maternal Mortality (WHO ICD-MM), maternal deaths can be direct, indirect or unspecified [4, 5].
The direct causes are those resulting from obstetric complications of the pregnancy state, be it pregnancy, labour, or puerperium), including those related to interventions, omissions of treatment, or a combination of all. These include unsafe abortions, obstructed labour, excessive blood loss, infections. On the other hand, indirect deaths result from previously existing diseases or diseases developed in the pregnancy state that was aggravated by the physiologic effects of pregnancy. These include anaemia, high blood pressure and sugar, malaria, heart disease [4, 5].
However, according to Odeyemi et al. [6] also Maduka and Ogu [7], the common most reported causes of maternal deaths in Nigeria, direct and indirect, are obstetric haemorrhage leading to anaemia, pregnancy-induced hypertension, obstructed labour, unsafe abortion, ectopic pregnancy, placenta abruptio, ruptured uterus and puerperal sepsis.
Other unspecified maternal deaths are those during pregnancy, childbirth or puerperium for which the underlying cause cannot be determined. These are further divided into nine groups, which are; Pregnancies with abortive outcomes; Hypertensive disorders in pregnancy, childbirth and the puerperium; Obstetric haemorrhage; Pregnancy-related infection such as Human immunodeficiency virus/acquired immunodeficiency syndrome, and malaria; Other obstetric Complications; Unanticipated complications of management; Non-obstetric complications; Unknown/undetermined and finally, Coincidental causes [6, 7].
When women die, there are social and economic consequences that extend beyond her family. For the children left behind, evidence shows increased mortality risk, decreased nutrition and higher chances of not going to school. There is also the consequence of a reduced labour force for the community, which results in reduced productivity. There is evidence to show that maternal mortality has a statistically significant negative effect on GDP in the WHO African region [1, 2, 8].
In most instances, maternal deaths are preventable. This is possible through timely management of mothers by skilled professionals in an environment that is supportive and adequately equipped. Skilled professionals in this context are not limited to doctors, nurses or midwives. They include those health workers who live within the community, such as the Community-based Birth Attendants (CBAs) and other healthcare providers [9, 10].
3. CBAs as a strategy to reduce maternal and child mortality
Traditional birth attendant (TBA), which makes up the large part of CBAs, according to the World Health Organisation, is a person (usually a woman) who assists a pregnant woman at childbirth; she may have acquired her skills by delivering her babies alone or by working with other TBAs. Other groups also classified and acting as CBAs are CHOs, CHEWs, JCHEWs, auxiliary nurses, including faith-based birth attendants and even some trained midwives and nursing officers who offer service at homes and in the communities away from health facilities. In contrast, a trained or skilled TBA “is an individual who has received a form of short course training to enhance his/her knowledge and skills through the modern health care sector [11].
Over 50% of the 130 million deliveries globally are attended to by Community-based and Traditional birth attendants. These Community-based healthcare providers are largely unskilled (i.e. TBAs) and have no formal education or knowledge on the management of childbirth-related complications, while some are semiskilled or with outdated skills (i.e. auxiliary nurses) and, therefore, are unable to prevent or treat these complications during pregnancy or childbirth that leads to maternal and/or perinatal morbidities and mortalities [7, 12].
Significantly, Women of reproductive age living in developing and underdeveloped areas with weak health systems and suboptimal healthcare delivery – accounting for 94% of all maternal mortality globally where an estimate of about 45% of the death occurred during pregnancy; 35% during childbirth, and 20% during the postpartum period – continue to make use of TBAs during childbirth. This causes a negative ripple effect, with the unideal, inappropriate and unethical practice steadily increasing [6, 7].
Even though reports have shown a reduction in the maternal mortality rate over the years, this reduction rate has been very slow. The 2018 National Demographic Health Survey from Nigeria showed that skilled providers assisted 68% of births in urban areas compared with only 28% in rural areas, leaving the remaining 72% to the help of other unskilled Community-based Birth Attendants (CBAs) and other healthcare providers. Also, the study reflected that about 60% of the women in rural areas had a problem with accessing healthcare. These gaps highlight the importance of the availability of skilled community to women needing their services the most for necessary care [5].
A study done by Fagbamigbe et al. in 2017, to identify the cause of the marginal decline in maternal mortality rate in Nigeria identified an increased use in skilled birth attendants during delivery. The study showed a 6% increment in the use of skilled birth attendants between 1990 and 2013. The World Health Organisation also recorded a drop in maternal mortality rate by 53% during that period. Some of the factors responsible for the increased rate of skilled birth attendants use include creating the national midwives’ service scheme, equipping primary health care centres, providing empowerment programs, and so on. Other determinants affecting women’s usage of skilled birth attendants include proximity to the health facility, socio-economic status, and previous positive experience [4, 9].
Regarding health equity, the role of community birth attendants also comes to mind as they help ensure that women in rural communities are not left behind in terms of their maternal health care. Aside from being instrumental and playing a massive role in reducing maternal mortality, they also provide certain personalised care for their patients such as; counselling, home visitations, support during labor, charging cheaper rates, and allowing for payment of services by barter or in instalments. This is quite important for most women as a report has shown that the perception of skilled birth attendants as being hostile and disclosing confidential information are some of the hindering factors to receiving care from skilled birth attendants. Therefore, to significantly reduce the burden of maternal mortality in Nigeria, the role of the CBAs is of crucial importance and cannot be undermined [9, 11, 12].
4. Integration of CBAs in health service provision
The UN sustainable development goal to reduce the global maternal mortality ratio to <70 per 100,000 live births by 2030 seems impossible due to the prevalence of high maternal mortality rate globally (211 deaths per 100,000 live births in 2017) and in developing countries, especially Nigeria where there were about 917 deaths per 100,000 births in 2017. This is a product of these places’ weak operational health systems – lacking well-trained, adequately informed, technology and quality inclined healthcare providers, well-maintained and equipped facilities, logistics and functional policies. Likewise, studies have shown that the risk of maternal and perinatal death is increased dramatically when there is unskilled birth assistance (done mainly by TBAs and other CBAs) [7].
The health workforce is the bedrock to achieving a good health system and its outcome. Hence, every healthcare provider, including the CBAs – who are a link between the community and health service providers especially, skilled birth attendants, and are always available, accessible, affordable and socioculturally acceptable in communities (especially the low socio-economic, rural, underserved, hard-to-reach and grassroots) – cannot be ruled out of the optimal healthcare provision and human resources allocation [9, 11, 12, 13, 14, 15].
Due to this, including the slow uptake and shortage of SBAs, several countries have opened up the proposal to officially adopt CBAs as part of the flowchart for maternity care and attempted to integrate CBAs into their health system – following the failure to suppress them. However, the results and techniques have differed from LMIC like Bangladesh and Kenya to HIC like China. Nevertheless, studies have shown that health education and training programs for TBAs are instrumental in upskilling them to promptly recognise warning signs of emergencies and know when to transfer the woman to the hospital [7, 9, 11, 12, 16].
Integrating them into the health system in Nigeria is challenging because, despite the widespread acceptance and use of these service providers, they are illegal. This is one of the major bottlenecks in integrating them into health services. Due to this problem, they can only function within the limits of the law as referral points, points of community entry, and they can help prevent harm to the mother and child. However, there is not enough SBA in the country, and as a result, policies such as task shifting and sharing will need to be adjusted to reflect and accommodate the current circumstance [7, 12, 15, 16].
The first step has to eliminate this problem and recognise them legally with well-defined roles and limits to serve their communities. They can regularly report to the local government medical officers, primary health centres, or the public health board with frequent assessments and updated recertification training. Some of the Knowledge and skills for procedures needed to ensure safe delivery and maternal and perinatal survival are the proper use, and implementation of aseptic techniques, uterotonics, anticonvulsants, antibiotics, blood transfusion, and more is lacking among them. Therefore, they should be trained to prevent and recognise complications by teaching them significant aspects of maternal care, including Family planning (FP), Misoprostol Use, Measurement of blood loss, Antepartum care, normal labour, Postpartum care for mothers, Postnatal care for neonates and so on. However, very importantly, these knowledge and skills should be fashioned and effectively implemented to fit their cadre, strict community level duties, in line with the task shifting and sharing policy in Nigeria [6, 7, 10, 12, 15].
5. Presumptive actions of CBAs in maternal healthcare service delivery
In the majority of the countries most affected by maternal mortality, uptake of family planning is low. Given that the CBAs are usually respected voices or authorities in their community, training them on family planning counselling and making them advocates will make it more appealing to the women. There is also a personal relationship and closeness between CBAs and their patrons still largely absent in the typical hospital or clinic dynamic. A reduction in the number of birthing events correlated strongly with a decrease in maternal deaths [15, 17].
Years ago, the prevention or treatment of postpartum haemorrhage in small villages or towns without electricity or the need for injections was near impossible. For example, in LMICs like Tanzania, they estimate blood loss using the quantity of soaked clothes fabrics and can be taught other standardised methods that are excellent steps at spotting postpartum haemorrhage. They can learn the local equivalence of 500mls of blood to know when to refer the women for advanced and emergency care in health facilities. Also, with the advent of misoprostol, it is possible to train these CBAs to administer it safely in their centres. This will reduce the risk of death due to postpartum haemorrhage, reducing one of the most emergent causes of maternal mortality [15, 18, 19].
CBAs can also encourage their patrons to get advanced care after birth and take vaccines in health centres. These are aspects of care that the majority of the CBAs generally do not offer in their regular plans, especially postpartum care. Notably, attempts to use “promise of financial compensation” to encourage the CBAs to refer their clients to the hospital for postpartum care have shown varying results. Teaching CBAs to clean women and care for them and their babies after delivery can save many lives lost to maternal and child mortality [14, 19].
Likewise, CBAs having good knowledge and counselling skills on HIV/AIDS and Prevention of Mother-To-Child Transmission of HIV (PMTCT) with good knowledge on specific measures of infection prevention and control can help them to protect themselves, their patients and the entire community while opting for orthodox medicine as the management of the various viral infection (COVID-19 inclusive), rather than the use of native or herbal remedies to cure them [18, 20].
All of these and more trainings, regular feedback, and a proper referral system will help create a genuinely integrated health service that has the interests of the healthcare consumers at the fore of its priorities. Hence, this is not the time to “gatekeep” but to be proactive by integrating CBAs via a full-on multifaceted project because human resources for health, including SBAs, are not growing fast enough to meet the community’s needs. Therefore, all the stakeholders should be given a seat at the table to deliberate the methods, limits, appropriate policies and legislation [7, 13, 21].
6. Challenges and progress so far: discussion of field reports
Various challenges exist that hinder the maximisation of CBA roles to reduce maternal and child mortality and the general healthcare provision system as a whole. These challenges have been identified through an extensive review of literature and fieldwork.
Through our field works of Training-The-T/CBAs (Project TTT) at SHI, 162 CBAs has been reached since 2018, and some of the issues common to them all irrespective of location are palpable ignorance and reluctance to learn or adopt new methods. This reluctance is influenced by their confidence in their old traditional ways and how long they have been using them and getting away with the outcomes. For example, during the FGD on family planning before TTT at Orile-Iganmu (a Semi-Urban community in Lagos state, the megacity of Nigeria), the head of the TBAs (a herbalist) that has practised for over 30 years and trained countless other TBAs stated confidently in his native language and translated that “BTL is tying of the cervix and meant for people that have done abortions in the past because their cervix and vagina have become wide and the “spring“ there does not close. Therefore, the other forms of contraceptives like OCPs and condoms do not work for them…”; whilst only 2 of the 162 CBAs reported that FP prevents (unsafe) abortion and none of them reported that FP prevents STIs in their pre-assessment questionnaires [22, 23, 24].
Also, other aspects found to be erroneously managed and discussed among them during an FGD among the same cohort and another recruited into the TTT Project in Ilo-Ajegunle (another semi-urban community in Lagos) were postpartum psychosis during and after labour, partners’ inclusion in family planning, postdated pregnancy lasting up to one and half years, exclusive breastfeeding and other breastfeeding issues. Likewise, immunisation of mother and child and efficient data collection of their activities with the client were also lacking among the majority (Tables 1–3) [22, 23, 24].
TTT project location
Community type
State
C/TBAs recruited by
Osogbo
Semiurban
Osun
Traditional and TBAs leader
Orile-Iganmu
Semiurban
Lagos
Traditional and TBAs leader
Ilo-Ajegunle
Semiurban
Lagos
OIC and CHO in the community PHC
Ifako-Ijaiye
Semiurban
Lagos
CHO in the community PHC
Ojokoro
Semiurban
Lagos
CHO in the community PHC
Onipanu-Ota
Rural
Ogun
TBAs representative
Baale-Ajuwon
Rural
Ogun
Faith-based/Religious birthing attendants head
Table 1.
Details of field work (project locations) and methods through which C/TBAs trained were mobilised and recruited.
Age group
% (n = 162)
18–35 years
11.2
36–45 years
33.6
46–65 years
51.5
Above 65 years
3.7
Gender
% (n = 162)
Male
21.50
Female
78.50
Highest educational level
% (n = 162)
Primary education
21.4
Secondary education
46.8
Postsecondary education/Tertiary/Colleges
14.7
Informal or no education
17.1
Type of initial training had to become a TBA
% (n = 162)
Formally trained
52
Informally trained
48
Table 2.
Sociodemographic data of birthing attendants (community-based/traditional) reached.
NB: n is total number of Birthing Attendants reached by the TTT Project.
Data collection was by self-administered semi structured questionnaire, interview based and Focused Group Discussions. Data collation was between January 2018 till March 2021.
Cadre of birthing attendants reached (n = 162)
%
TBAs
38.00
CBAs
11.70
Faith Based
33.10
Nursing Officers
1.30
Auxiliary Nurses
12.70
JCHEWs
1.30
CHOs
1.30
CHEWs
0.60
Table 3.
Cadre of the birthing attendants reached via the TTT.
NB: n is total number of Birthing Attendants reached by the TTT Project.
Another occurrence was during the FGM session at the same training in Osogbo (the capital of the traditional and religious state), where more than 80% of the participant CBAs vehemently supported that FGM was a compulsory family tradition and right to protect the female. Also that they relied on their “Opele” – divining oracle – and herbs for complex and prolonged/obstructed deliveries rather than refer to a health facility, which has been working for them. However, the untold consequences of these actions and strong beliefs are the morbidity and mortality cases recorded among the mothers and babies that patronise them when they return home to commence their everyday lives. Some of the highlighted morbidity outcomes in the babies leading to permanent damages are neonatal jaundice, mismanagement of the first golden minute of life. While in the mothers are puerperal sepsis, postpartum haemorrhage, to mention a few [22, 23, 24, 25].
Furthermore, another challenge was the lack of a comprehensive and all-inclusive database of every functioning CBAs in communities despite having a regulating body or a converging association or point of meeting with their assigned CHOs in their resident community PHCs. Hence, they cannot all be tracked, trained, or their activities monitored, with some even hiding under the guise of running a “private hospital” instead of the actual traditional homes or centres they run. These can be due to age, level of exposure, type and level of education/training, the difference in religion, location/locality, beliefs and practices [24, 25, 26].
Some evidence supporting this from data collated through our TTT project showed that of the 162 reached and trained; 51.5% were between the ages of 46–65, 33.6% between 36 and 45 years, rarely the elderly who trained them showed (they made up only 3.7%) and the young one who are currently receiving the informal training (18–35 years’ participant made up just 11.2%). Keep in mind that age should not be a limitation to acquiring knowledge. Likewise, primarily those who had some form of formal training wanted more, as 52.0% of participants had some formal training to become birth attendants or community healthcare providers versus 48.0% who were informally trained. While 21.4% had primary education, 46.8% had secondary education, 14.7% had postsecondary education (including college of health technology), and 17.1% had informal or no education [24].
Furthermore, the percentage of all participants attending the training by qualification and initial training recorded; 38.0% were TBAs, 33.1% faith-based birth attendants, 12.7% Auxiliary nurses, 11.7% CBAs, 1.3% Nursing Officers, 1.3% CHOs, 1.3% JCHEWs and 0.6% CHEW (SHI 2020 Annual report) [24]. This lower attendance of CBAs with higher qualifications might be attributed to the perceived need or aim of more training, mode of community entry, reachable circle and target of CBAs mobiliser [23, 24].
At a community entry meeting with one of the CBAs by the SHI strategy team (i.e. the contact person we were able to reach) in Baale-Ajuwon (a rural community in Ogun state), she emphasised in her native language that “as a faith-based CBA, I try not to mingle with the TBAs because of their diabolic ways…”, hence for the training would only reach out to the faith-based CBA like herself. This also shows the disharmony between the cadres of CBAs hindering them from learning and benefiting from each other to progress and be able to offer the best to their clients. Also participant sex percentage was 21.5% male to 78.5% female. It was found that where women were the CBA leaders, mostly women only tend to come for the trainings and be more expressive, as opposed to where men were the leaders - the meetings were more dominated by men with women less expressive and taking permission from the men to air their opinions [22, 23, 24]. This shows the gender disparity and inequality even at the level of community health care.
However, despite these challenges hindering their roles, some progress has been made such as the increase in the knowledge and attitude towards FP, Safe delivery, hygiene practices in the workspace, immunisation, exclusive breastfeeding and empowerment with IEC and educative materials for themselves and their clients; all of which play a huge role in reducing maternal and child morbidity and mortality in their communities and the world at large. As during follow-up visits to the CBAs in FDG, they report more patronage on account of the free birthing kits and FP counselling services they offer – courtesy of the Safer Hands Health Initiative [22, 23, 24, 25, 26].
7. The future and CBAS: recommendations
Currently and in the nearest future, the “irreplaceable” roles of CBAs in healthcare delivery services cannot be dismissed or disregarded. Hence, prompt actions must be taken to reduce the maternal, perinatal and child morbidity and mortality in Nigeria and globally associated with them. Some of which include;
Legalising the roles of CBAs and building a controlled framework to integrate them into the formal healthcare system. Also, incorporating community stakeholders input and participation can help improve healthcare service delivery and programs [7, 12, 13].
Strengthening effective communication between CBAs and skilled health workers to avoid disharmony and counter-productivity in the grassroots healthcare system. This can be achieved by creating a conducive and functional referral system and emergency line for CBAs to their community healthcare centres or medical practitioners in charge. This would also increase their access to healthcare facilities.
Trainings, educational conferences and empowerment at all levels (local, national and international) should be periodically and continuously done to cross-learn from what is obtainable and yield positive outcomes in other developed places. Also, with a day dedicated to them (i.e. International day of CBAs) to recognise their ethical works, referrals and reported/documented activities [16, 19, 24]. This would inform their activities, exposure and incline them towards quality care delivery.
Likewise, incentivising their efforts to recruit a robust database of every CBAs in their communities – as they know themselves – and enrol their trainees for proper/formal healthcare training in schools. Incentives could be per referral/enrollment or after a target number set is met, and it could be in the form of money, materials, or more opportunities like scholarships for formal enrollment, training, and attachment in recognised institutions [16, 19, 24]. This would encourage them to come out, be trained and get acquainted with policies, protocols, infrastructural and healthcare advancements. Owing to that fact that over 50% of the TTT participants reported that government policies had no impact on their activities and approximately 40% had no idea of any government policies affecting their work, while only about 9% reported that the government was putting in some efforts to make their works good but can still do better [22, 23, 24].
Finally, increasing quality community health education for women, men and their families – which are socioculturally appropriate and sensitive – is essential. As this would inform their healthcare decisions, improve their health-seeking behaviours, and positively influence paternal attitudes towards healthcare which is also an important factor for the overall well-being and economic status of women and their families [14, 17, 18, 26].
8. Conclusion
Birth attended by CBAs, especially TBAs, is associated more with maternal and child morbidity and mortality in Nigeria and globally, as most TBAs are unskilled. Currently, Nigeria is leading in maternal and child morbidity and mortality with the high patronage of TBAs as opposed to a skilled birth attendant or going to health facilities. Therefore, to reduce these maternal and perinatal deaths and, in turn, achieve the global Sustainable Development Goals (SDGs), it is pertinent to upscale the role of these CBAs for more skilled birth attendance and other delivery services by training them and possibly integrating them into the formal health system.
Acknowledgments
The author(s) would like to acknowledge the entire members of the CBA groups reached out to across various communities for making this possible, the CHOs and IOC who served as mobilizers, Prof. Kofo Odeyemi for her continuous supervision of the project, Dr. Doyin Ogunyemi for her contributions and Birthing Kit Foundation Australia (BFKA) for their continuous provision of birthing kits used as incentives for the CBAs.
Conflict of interest
The authors declare no conflict of interest.
Thanks
Thanks to every partner, strategy team members and volunteers of Safer Hands Health Initiative, for the collation of data and being an integral part of this project.
Appendices and Nomenclature
CBAs
Community-based birth attendants
TBAs
Traditional birth attendants
SBAs
Skilled birth attendants
OIC
Officer in charge
CHOs
Community health officers
PHCs
Primary healthcare centres
CHEWs
Community health extension workers
JCHEWs
Junior Community health extension workers
TTT
Training the traditional/community-based birth attendants
SDGs
Sustainable development goals
FP
Family planning
BTL
Bilateral tubal ligation
FGM
Female genital mutilation
GDP
Gross domestic profit
STIs
Sexually transmitted infections
WHO
World health organisation
SHI
Safer hands health initiative
LMICs
Low middle income countries
HICs
High-income countries
FGD
Focused group discussion
\n',keywords:"maternal & child mortality, perinatal care, access to health, public health, community-based birth attendants, traditional birth attendants, community health, socioeconomic condition",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/80204.pdf",chapterXML:"https://mts.intechopen.com/source/xml/80204.xml",downloadPdfUrl:"/chapter/pdf-download/80204",previewPdfUrl:"/chapter/pdf-preview/80204",totalDownloads:85,totalViews:0,totalCrossrefCites:0,dateSubmitted:"October 11th 2021",dateReviewed:"November 26th 2021",datePrePublished:"January 24th 2022",datePublished:null,dateFinished:"January 24th 2022",readingETA:"0",abstract:"Community-based Birth Attendants (CBAs) provide maternal, child, sexual and reproductive information and services to a large part of the population in rural, marginalised and hard-to-reach communities (especially in underdeveloped and developing regions). In Nigeria, they cater for ~70% of the reproductive population who patronise them in their various communities due to accessibility, affordability and social acceptance for pregnancy-related care, delivery, other sexual and reproductive healthcare concerns. CBAs could be skilled, semiskilled but are largely unskilled. Their level of skill, knowledge, attitude, and practice in their community concerning different health issues is a huge determinant of their clients’ health outcomes, which has also been skewed over time. Studies have shown that the knowledge of these CBAs continues to be impeded despite attempts at training them and unifying their practices, due to the deep-seated disunity that affects their uptake of thought interventions. These divisions are drawn along the lines of religion, initial training/education and gender differences. Therefore, continuous education on safe and current hygienic practices; increases their capacity, knowledge and skills for correct information dissemination and service delivery. Likewise, future assimilation into the formal health system with legal framework will help regulate their practices, thereby reducing maternal and child morbidity and mortality.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/80204",risUrl:"/chapter/ris/80204",signatures:"Mary Agoyi, Roland Ojo, Toyosi Afolabi, Olakunmi Ogunyemi, Sekinat Adejumobi and Adeyemi Awoniyi",book:{id:"11005",type:"book",title:"Mortality Rates in Middle and Low-Income Countries",subtitle:null,fullTitle:"Mortality Rates in Middle and Low-Income Countries",slug:null,publishedDate:null,bookSignature:"Dr. Umar Bacha",coverURL:"https://cdn.intechopen.com/books/images_new/11005.jpg",licenceType:"CC BY 3.0",editedByType:null,isbn:"978-1-83969-970-2",printIsbn:"978-1-83969-969-6",pdfIsbn:"978-1-83969-971-9",isAvailableForWebshopOrdering:!0,editors:[{id:"244265",title:"Dr.",name:"Umar",middleName:null,surname:"Bacha",slug:"umar-bacha",fullName:"Umar Bacha"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:null,sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Maternal and child mortality: incidence, causes and implications",level:"1"},{id:"sec_3",title:"3. CBAs as a strategy to reduce maternal and child mortality",level:"1"},{id:"sec_4",title:"4. Integration of CBAs in health service provision",level:"1"},{id:"sec_5",title:"5. Presumptive actions of CBAs in maternal healthcare service delivery",level:"1"},{id:"sec_6",title:"6. Challenges and progress so far: discussion of field reports",level:"1"},{id:"sec_7",title:"7. The future and CBAS: recommendations",level:"1"},{id:"sec_8",title:"8. Conclusion",level:"1"},{id:"sec_9",title:"Acknowledgments",level:"1"},{id:"sec_12",title:"Conflict of interest",level:"1"},{id:"sec_9",title:"Thanks",level:"1"},{id:"sec_10",title:"Appendices and Nomenclature",level:"1"}],chapterReferences:[{id:"B1",body:'Olonade O, Olawande TI, Alabi OJ, Imhonopi D. Maternal mortality and maternal health care in Nigeria: Implications for socio-economic development. Open Access Maced J Med Sci. 2019;7(5):849-855'},{id:"B2",body:'Molla M, Mitiku I, Worku A, Yamin AE. Impacts of maternal mortality on living children and families: A qualitative study from Butajira Ethiopia. Reproductive Health. 2015;12(1):S6'},{id:"B3",body:'Ebuehi OM, Akintujoye I. Perception and utilization of traditional birth attendants by pregnant women attending primary health care clinics in a rural Local Government Area in Ogun State Nigeria. International Journal of Women\'s Health. 2012;4:25-34'},{id:"B4",body:'World Health Organization. Maternal Mortality [Internet] . [cited 2021 Nov 13]. Available from: https://www.who.int/news-room/fact-sheets/detail/maternal-mortality'},{id:"B5",body:'Nigeria National Population Commission (NPC) and International Coaching Federation (ICF) ‘Nigeria Demographic and Health Survey (NDHS) 2018 Key Indicators Report’, Abuja, Nigeria, and Rockville, Maryland, USA. [Internet]. 2019 . [cited 2021 May 13]. Available from: http://cs-sunn.org/wp-content/uploads/2018/10/NDHS-2018.pdf'},{id:"B6",body:'Odeyemi K, Abidoye G, Akin-Adenekan O, Akinsola O, Ekanem E, Osilaja O, et al. Causes of maternal mortality in Lagos State. Nigeria. Annals of Tropical Medicine and Public Health. 2014;7:177'},{id:"B7",body:'Maduka O, Ogu R. Preventing Maternal Mortality During Childbirth: The Scourge of Delivery with Unskilled Birth Attendants [Internet]. Childbirth. IntechOpen; 2020. [cited 2021 Nov 13]. Available from: https://www.intechopen.com/chapters/70849'},{id:"B8",body:'Kirigia JM, Oluwole D, Mwabu GM, Gatwin D, Kainyu LH. Effects of maternal mortality on gross domestic product (GDP) in the WHO African region. Afri J Health Sci. 2006;13:86-95'},{id:"B9",body:'Fagbamigbe AF, Hurricane-Ike EO, Yusuf OB, Idemudia ES. Trends and drivers of skilled birth attendant use in Nigeria (1990-2013): Policy implications for child and maternal health. International Journal of Women\'s Health. 2017;9:843-853'},{id:"B10",body:'Okereke E, Ishaku SM, Unumeri G, Mohammed B, Ahonsi B. Reducing maternal and newborn mortality in Nigeria—a qualitative study of stakeholders’ perceptions about the performance of community health workers and the introduction of community midwifery at primary healthcare level. Human Resources for Health. 2019;17(1):102'},{id:"B11",body:'Ogbo FA, Trinh FF, Ahmed KY, Senanayake P, Rwabilimbo AG, Uwaibi NE, et al. Prevalence, trends, and drivers of the utilization of unskilled birth attendants during democratic governance in Nigeria from 1999 to 2018. International Journal of Environmental Research and Public Health. 2020;17(1):372'},{id:"B12",body:'Sulayman H, Adaji S. Integration of traditional birth attendants (TBAs) into the health sector for improving maternal health in Nigeria: A systematic review. Sub-Saharan African Journal of Medicine. 2019;6(2):55-62'},{id:"B13",body:'Wilunda C, Dall’Oglio G, Scanagatta C, Segafredo G, Lukhele BW, Takahashi R, et al. Changing the role of traditional birth attendants in Yirol West County South Sudan. PLoS One. 2017;12(11):e0185726. DOI: 10.1371/journal.pone.0185726'},{id:"B14",body:'Envuladu EE, Agbo HA, Lassa S, Kigbi JH, Zoakah AI. Factors determining the choice of a place of delivery among pregnant women in Russa village of Jos North, Nigeria; achieving the MDGs 4 and 5. Int J Med Biomed Res. 2013;2:23-29'},{id:"B15",body:'Prata N, Passano P, Rowen T, Bell S, Walsh J, Potts M. Where there are (few) skilled birth attendants. Journal of Health, Population, and Nutrition. 2011;29(2):81-91. DOI: 10.3329/jhpn.v29i2.7812'},{id:"B16",body:'Kitui JE, Dutton V, Bester D, et al. Traditional Birth Attendant reorientation and Motherpacks incentive’s effect on health facility delivery uptake in Narok County, Kenya: An impact analysis. BMC Pregnancy and Childbirth. 2017;17(125). DOI: 10.1186/s12884-017-1307-7'},{id:"B17",body:'Olakunde BO, Adeyinka DA, Mavegam BO, Olakunde OA, Yahaya HB, Ajiboye OA, et al. Factors associated with skilled attendants at birth among married adolescent girls in Nigeria: Evidence from the Multiple Indicator Cluster Survey, 2016/2017. International Health. 2019;11(6):545-550'},{id:"B18",body:'Olufunke F, Olajumoke A, Andy EC, Omolara D, Katherine K, Andrew S, et al. Applying a Client-centered approach to maternal and neonatal networks of care: Case studies from urban and rural Nigeria. Health Systems & Reform. 2020;6:2. DOI: 10.1080/23288604.2020.1841450'},{id:"B19",body:'Chukwuma A, Mbachu C, McConnell M, et al. The impact of monetary incentives on referrals by traditional birth attendants for postnatal care in Nigeria. BMC Pregnancy and Childbirth. 2019;19(150):150. DOI: 10.1186/s12884-019-2313-8'},{id:"B20",body:'Balogun M, Odeyemi K. Knowledge and practice of prevention of mother-to-child transmission of HIV among traditional birth attendants in Lagos State, Nigeria. The Pan African Medical Journal. 2010;5:7'},{id:"B21",body:'WHO. WHO Integrating health services WHO/HIS/SDS/2018.50 [Internet]. 2018 . Available from: https://www.who.int/docs/default-source/primary-health-care-conference/linkages.pdf [Accessed: 13 Oct 2021]'},{id:"B22",body:'Agoyi MO. Training The Traditional Birth Attendants (TTT) Project [Internet]. 2020 . Available from: https://saferhandsinitiative.org/training-the-traditional-birth-attendants-ttt-project [Accessed: 13 Oct 2021]'},{id:"B23",body:'Agoyi MO. Hygienic Practices and Service Delivery of CBAs During The COVID-19 Pandemic Project [Internet]. 2020 . Available from: https://saferhandsinitiative.org/hygienic-practices-and-service-delivery-of-cbas-during-the-covid-19-pandemic-2 [Accessed: 13 Oct 2021]'},{id:"B24",body:'Safer Hands Health Initiative Annual Report 2020 [Internet]. 2021 . Available from: https://saferhandsinitiative.org/reports [Accessed: 13 Oct 2021]'},{id:"B25",body:'Safer Hands Health Initiative. TBAs: The ones there, when we are not [Internet]. 2021 . Available from: https://saferhandsinitiative.org/tbas-the-ones-there-when-we-are-not [Accessed: 13 Oct 2021]'},{id:"B26",body:'Amutah-Onukagha N, Rodriguez M, Opara I, Gardner M, Assan MA, Hammond R, et al. Progresses and challenges of utilizing traditional birth attendants in maternal and child health in Nigeria. International Journal of MCH and AIDS. 2017;6(2):130-138. DOI: 10.21106/ijma.204'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Mary Agoyi",address:"kemisolaagoyi@gmail.com",affiliation:'
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Turner",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Calgary",institutionURL:null,country:{name:"Canada"}}},{id:"216996",title:"Ph.D.",name:"Filomena",surname:"Costa",slug:"filomena-costa",fullName:"Filomena Costa",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Minho",institutionURL:null,country:{name:"Portugal"}}},{id:"220680",title:"Prof.",name:"Teresa",surname:"Tavares",slug:"teresa-tavares",fullName:"Teresa Tavares",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Minho",institutionURL:null,country:{name:"Portugal"}}}]},generic:{page:{slug:"open-access-funding",title:"Open Access Funding",intro:"
IntechOpen’s Academic Editors and Authors have received funding for their work through many well-known funders, including: the European Commission, Bill and Melinda Gates Foundation, Wellcome Trust, Chinese Academy of Sciences, Natural Science Foundation of China (NSFC), CGIAR Consortium of International Agricultural Research Centers, National Institute of Health (NIH), National Science Foundation (NSF), National Aeronautics and Space Administration (NASA), National Institute of Standards and Technology (NIST), German Research Foundation (DFG), Research Councils United Kingdom (RCUK), Oswaldo Cruz Foundation, Austrian Science Fund (FWF), Foundation for Science and Technology (FCT), Australian Research Council (ARC).
Open Access publication costs can often be designated directly in the grants or in specific budgets allocated for that purpose. Many of the most important funding organisations encourage, and even request, that the projects they fund are made available at no cost to the wider public. IntechOpen strives to maintain excellent relationships with these funders and ensures compliance with mandates.
\\n\\n
In order to help Authors identify appropriate funding agencies and institutions, we have created a list, based on extensive research on various OA resources (including ROARMAP and SHERPA/JULIET) of organizations that have funds available. Before consulting our list we encourage you to petition your own institution or organization for Open Access funds or check the specifications of your grant with your funder to ascertain if publication costs are included. Where you are in receipt of a grant you should clarify:
\\n\\n
\\n\\t
Does your institution already have a budget for covering Open Access publication costs?
\\n\\t
Does your grant list Open Access publication fees as legitimate direct/indirect costs?
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If you are associated with any of the institutions in our list below, you can apply to receive OA publication funds by following the instructions provided in the links. Please consult the Open Access policies or grant Terms and Conditions of any institution with which you are linked to explore ways to cover your publication costs (also accessible by clicking on the link in their title).
\\n\\n
Please note that this list is not a definitive one and is updated regularly. To suggest possible modifications or the inclusion of your institution/funder, please contact us at funders@intechopen.com
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Please be aware that you must be a member, or grantee, of the institutions/funders listed in order to apply for their Open Access publication funds.
Open Access publication costs can often be designated directly in the grants or in specific budgets allocated for that purpose. Many of the most important funding organisations encourage, and even request, that the projects they fund are made available at no cost to the wider public. IntechOpen strives to maintain excellent relationships with these funders and ensures compliance with mandates.
\n\n
In order to help Authors identify appropriate funding agencies and institutions, we have created a list, based on extensive research on various OA resources (including ROARMAP and SHERPA/JULIET) of organizations that have funds available. Before consulting our list we encourage you to petition your own institution or organization for Open Access funds or check the specifications of your grant with your funder to ascertain if publication costs are included. Where you are in receipt of a grant you should clarify:
\n\n
\n\t
Does your institution already have a budget for covering Open Access publication costs?
\n\t
Does your grant list Open Access publication fees as legitimate direct/indirect costs?
\n
\n\n
If you are associated with any of the institutions in our list below, you can apply to receive OA publication funds by following the instructions provided in the links. Please consult the Open Access policies or grant Terms and Conditions of any institution with which you are linked to explore ways to cover your publication costs (also accessible by clicking on the link in their title).
\n\n
Please note that this list is not a definitive one and is updated regularly. To suggest possible modifications or the inclusion of your institution/funder, please contact us at funders@intechopen.com
\n\n
Please be aware that you must be a member, or grantee, of the institutions/funders listed in order to apply for their Open Access publication funds.
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On September, 29th 2006 he has won a post PhD fellowship from the university of Bologna (from October 2006 to October 2008), at the competitive examination he was ranked first in the industrial engineering area. He extensively served as referee for several international journals. He is author/coauthor of more than 100 research papers. He has been involved in some projects supported by MURST and European Community. 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Delac received his B.Sc.E.E. degree in 2003 and is currentlypursuing a Ph.D. degree at the University of Zagreb, Faculty of Electrical Engineering andComputing. His current research interests are digital image analysis, pattern recognition andbiometrics.",institutionString:null,institution:{name:"University of Zagreb",country:{name:"Croatia"}}},{id:"557",title:"Dr.",name:"Andon",middleName:"Venelinov",surname:"Topalov",slug:"andon-topalov",fullName:"Andon Topalov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/557/images/1927_n.jpg",biography:"Dr. Andon V. Topalov received the MSc degree in Control Engineering from the Faculty of Information Systems, Technologies, and Automation at Moscow State University of Civil Engineering (MGGU) in 1979. He then received his PhD degree in Control Engineering from the Department of Automation and Remote Control at Moscow State Mining University (MGSU), Moscow, in 1984. From 1985 to 1986, he was a Research Fellow in the Research Institute for Electronic Equipment, ZZU AD, Plovdiv, Bulgaria. In 1986, he joined the Department of Control Systems, Technical University of Sofia at the Plovdiv campus, where he is presently a Full Professor. He has held long-term visiting Professor/Scholar positions at various institutions in South Korea, Turkey, Mexico, Greece, Belgium, UK, and Germany. And he has coauthored one book and authored or coauthored more than 80 research papers in conference proceedings and journals. His current research interests are in the fields of intelligent control and robotics.",institutionString:null,institution:{name:"Technical University of Sofia",country:{name:"Bulgaria"}}},{id:"585",title:"Prof.",name:"Munir",middleName:null,surname:"Merdan",slug:"munir-merdan",fullName:"Munir Merdan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/585/images/system/585.jpg",biography:"Munir Merdan received the M.Sc. degree in mechanical engineering from the Technical University of Sarajevo, Bosnia and Herzegovina, in 2001, and the Ph.D. degree in electrical engineering from the Vienna University of Technology, Vienna, Austria, in 2009.Since 2005, he has been at the Automation and Control Institute, Vienna University of Technology, where he is currently a Senior Researcher. His research interests include the application of agent technology for achieving agile control in the manufacturing environment.",institutionString:null,institution:null},{id:"605",title:"Prof",name:"Dil",middleName:null,surname:"Hussain",slug:"dil-hussain",fullName:"Dil Hussain",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/605/images/system/605.jpg",biography:"Dr. Dil Muhammad Akbar Hussain is a professor of Electronics Engineering & Computer Science at the Department of Energy Technology, Aalborg University Denmark. Professor Akbar has a Master degree in Digital Electronics from Govt. College University, Lahore Pakistan and a P-hD degree in Control Engineering from the School of Engineering and Applied Sciences, University of Sussex United Kingdom. Aalborg University has Two Satellite Campuses, one in Copenhagen (Aalborg University Copenhagen) and the other in Esbjerg (Aalborg University Esbjerg).\n· He is a member of prestigious IEEE (Institute of Electrical and Electronics Engineers), and IAENG (International Association of Engineers) organizations. \n· He is the chief Editor of the Journal of Software Engineering.\n· He is the member of the Editorial Board of International Journal of Computer Science and Software Technology (IJCSST) and International Journal of Computer Engineering and Information Technology. \n· He is also the Editor of Communication in Computer and Information Science CCIS-20 by Springer.\n· Reviewer For Many Conferences\nHe is the lead person in making collaboration agreements between Aalborg University and many universities of Pakistan, for which the MOU’s (Memorandum of Understanding) have been signed.\nProfessor Akbar is working in Academia since 1990, he started his career as a Lab demonstrator/TA at the University of Sussex. After finishing his P. hD degree in 1992, he served in the Industry as a Scientific Officer and continued his academic career as a visiting scholar for a number of educational institutions. In 1996 he joined National University of Science & Technology Pakistan (NUST) as an Associate Professor; NUST is one of the top few universities in Pakistan. In 1999 he joined an International Company Lineo Inc, Canada as Manager Compiler Group, where he headed the group for developing Compiler Tool Chain and Porting of Operating Systems for the BLACKfin processor. The processor development was a joint venture by Intel and Analog Devices. In 2002 Lineo Inc., was taken over by another company, so he joined Aalborg University Denmark as an Assistant Professor.\nProfessor Akbar has truly a multi-disciplined career and he continued his legacy and making progress in many areas of his interests both in teaching and research. 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De Oliveira, D.A.C. Albuquerque, T.G.S. Cruz, F.M. Yamaji and F.L. Leite",authors:[{id:"1164",title:"Dr.",name:"Fabio",middleName:"Lima",surname:"Leite",slug:"fabio-leite",fullName:"Fabio Leite"},{id:"136651",title:"MSc.",name:"Ricardo",middleName:null,surname:"De Oliveira",slug:"ricardo-de-oliveira",fullName:"Ricardo De Oliveira"},{id:"136652",title:"M.Sc.",name:"Diego",middleName:"Aparecido Carvalho",surname:"Albuquerque",slug:"diego-albuquerque",fullName:"Diego Albuquerque"},{id:"136653",title:"Prof.",name:"Tersio",middleName:null,surname:"Cruz",slug:"tersio-cruz",fullName:"Tersio Cruz"},{id:"136657",title:"Prof.",name:"Fabio",middleName:null,surname:"Yamaji",slug:"fabio-yamaji",fullName:"Fabio Yamaji"}]},{id:"49054",doi:"10.5772/60952",title:"Anion Exchange Resins as Effective Sorbents for Removal of Acid, Reactive, and Direct Dyes from Textile Wastewaters",slug:"anion-exchange-resins-as-effective-sorbents-for-removal-of-acid-reactive-and-direct-dyes-from-textil",totalDownloads:3184,totalCrossrefCites:24,totalDimensionsCites:47,abstract:"Coloured wastewaters are a consequence of batch processes in both dye-manufacturing and dye-consuming industries. Dyes are widely used in a number of industries, such as textile and leather dyeing, food, cosmetics, paper printing, gasoline, with the textile industry as the largest consumer. Dyeing as a fundamental operation during textile fibre processing causes the production of more or less coloured wastewaters, depending on the degree of fixation of dyes on substrates, which varies with the nature of substances, desired intensity of coloration, and application method. Dye bearing effluents are considered to be a very complex and inconsistent mixture of many pollutants ranging from dyes, dressing substances, alkalis, oils, detergents, salts of organic and inorganic acids to heavy metals.Thus after dyeing wastewaters are characterized not only by intensive and difficult for removal colour but also by high pH, suspended and dissolved solids, chemical and biochemical oxygen demands. Ion exchange is a very versatile and effective tool for treatment of aqueous hazardous wastes including dyes. The role of ion exchange in dye effluents treatment is to reduce the magnitude of hazardous load by converting them into a form in which they can be reused, leaving behind less toxic substances in their places or to facilitate ultimate disposal by reducing the hydraulic flow of the stream bearing toxic substances. Another significant feature of the ion exchange process is that it has the ability to separate as well as to concentrate pollutants. Taking into account high capacity and selectivity of ion exchange resins for different dyes, they seem to be proper materials for dyes sorption from textile effluents. The aim of the paper is to study the removal of the acid, reactive and direct textile dyes such as C.I. Acid Orange 7, C.I. Reactive Black 5 and C.I. Direct Blue 71 on the commercially available anion exchangers (Lewatit MonoPlus MP 62, Lewatit MonoPlus MP 64, Lewatit MonoPlus MP 500, Lewatit MonoPlus M 500, Amberlite IRA 67, Amberlite IRA 478RF, Amberlite IRA 458 and Amberlite IRA 958) differing not only in basicity of the functional groups but also in composition and structure of the matrix. Comparison of the sorption parameters obtained by the batch method taking into account influence of phase contact time, dyes initial concentration and solution pH were discussed in detail. Desorption conditions depending on the dyes sorption mechanism were also presented. Influence of the auxiliaries typically present in textile effluents such as inorganic electrolytes and different surfactants on the amounts of dyes retained by the anion exchangers was presented. The adsorption behaviour of the polyacrylic Amberlite IRA 958 demonstrates that it can be a promising adsorbent for the textile wastewater treatment. The results obtained with raw textile wastewaters purification confirmed this statement.",book:{id:"4599",slug:"ion-exchange-studies-and-applications",title:"Ion Exchange",fullTitle:"Ion Exchange - Studies and Applications"},signatures:"Monika Wawrzkiewicz and Zbigniew Hubicki",authors:[{id:"141883",title:"Prof.",name:"Zbigniew",middleName:null,surname:"Hubicki",slug:"zbigniew-hubicki",fullName:"Zbigniew Hubicki"},{id:"173310",title:"Dr.",name:"Monika",middleName:null,surname:"Wawrzkiewicz",slug:"monika-wawrzkiewicz",fullName:"Monika Wawrzkiewicz"}]},{id:"52110",doi:"10.5772/64935",title:"Electrodeposition from Deep Eutectic Solvents",slug:"electrodeposition-from-deep-eutectic-solvents",totalDownloads:3485,totalCrossrefCites:7,totalDimensionsCites:29,abstract:"Deep eutectic solvents constitute a class of compounds sharing many similarities with properly named ionic liquids. The accepted definition of ionic liquid is a fluid (liquid for T<100 °C) consisting of ions, while DES are eutectic mixtures of Lewis or Brønsted acids and bases. Their most attractive properties are the wide potential windows and the chemical properties largely different from aqueous solutions. In the last few decades, the possibility to electrodeposit decorative and functional coatings employing deep eutectic solvents as electrolytes has been widely investigated. A large number of the deposition procedures described in literature, however, cannot find application in the industrial practice due to competition with existing processes, cost or difficult scalability. From one side, there is the real potential to replace existing plating protocols and to find niche applications for high added-value productions; to the other one, this paves the path towards the electrodeposition of metals and alloys thermodynamically impossible to be obtained via usual aqueous solution processes. The main aim of this chapter is therefore the critical discussion of the applicability of deep eutectic solvents to the electrodeposition of metals and alloys, with a particular attention to the industrial and applicative point of view.",book:{id:"5381",slug:"progress-and-developments-in-ionic-liquids",title:"Ionic Liquids",fullTitle:"Progress and Developments in Ionic Liquids"},signatures:"R. Bernasconi, G. Panzeri, A. Accogli, F. Liberale, L. Nobili and L.\nMagagnin",authors:[{id:"188210",title:"Associate Prof.",name:"Luca",middleName:null,surname:"Magagnin",slug:"luca-magagnin",fullName:"Luca Magagnin"},{id:"194387",title:"MSc.",name:"Roberto",middleName:null,surname:"Bernasconi",slug:"roberto-bernasconi",fullName:"Roberto Bernasconi"},{id:"194388",title:"MSc.",name:"Gabriele",middleName:null,surname:"Panzeri",slug:"gabriele-panzeri",fullName:"Gabriele Panzeri"},{id:"194389",title:"MSc.",name:"Alessandra",middleName:null,surname:"Accogli",slug:"alessandra-accogli",fullName:"Alessandra Accogli"},{id:"194390",title:"MSc.",name:"Francesco",middleName:null,surname:"Liberale",slug:"francesco-liberale",fullName:"Francesco Liberale"},{id:"194391",title:"Prof.",name:"Luca",middleName:null,surname:"Nobili",slug:"luca-nobili",fullName:"Luca Nobili"}]},{id:"25422",doi:"10.5772/28293",title:"Electrochemical Polymerization of Aniline",slug:"electrochemical-polymerization-of-aniline",totalDownloads:11460,totalCrossrefCites:3,totalDimensionsCites:29,abstract:null,book:{id:"607",slug:"electropolymerization",title:"Electropolymerization",fullTitle:"Electropolymerization"},signatures:"Milica M. Gvozdenović, Branimir Z. Jugović, Jasmina S. Stevanović, Tomislav Lj. Trišović and Branimir N. Grgur",authors:[{id:"73400",title:"Dr.",name:"Milica",middleName:null,surname:"Gvozdenović",slug:"milica-gvozdenovic",fullName:"Milica Gvozdenović"},{id:"78801",title:"Dr.",name:"Branimir",middleName:null,surname:"Jugović",slug:"branimir-jugovic",fullName:"Branimir Jugović"},{id:"78807",title:"Dr.",name:"Jasmina",middleName:null,surname:"Stevanović",slug:"jasmina-stevanovic",fullName:"Jasmina Stevanović"},{id:"120374",title:"Dr.",name:"Tomislav",middleName:null,surname:"Trišović",slug:"tomislav-trisovic",fullName:"Tomislav Trišović"},{id:"120376",title:"Prof.",name:"Branimir",middleName:null,surname:"Grgur",slug:"branimir-grgur",fullName:"Branimir Grgur"}]}],mostDownloadedChaptersLast30Days:[{id:"52110",title:"Electrodeposition from Deep Eutectic Solvents",slug:"electrodeposition-from-deep-eutectic-solvents",totalDownloads:3484,totalCrossrefCites:7,totalDimensionsCites:29,abstract:"Deep eutectic solvents constitute a class of compounds sharing many similarities with properly named ionic liquids. The accepted definition of ionic liquid is a fluid (liquid for T<100 °C) consisting of ions, while DES are eutectic mixtures of Lewis or Brønsted acids and bases. Their most attractive properties are the wide potential windows and the chemical properties largely different from aqueous solutions. In the last few decades, the possibility to electrodeposit decorative and functional coatings employing deep eutectic solvents as electrolytes has been widely investigated. A large number of the deposition procedures described in literature, however, cannot find application in the industrial practice due to competition with existing processes, cost or difficult scalability. From one side, there is the real potential to replace existing plating protocols and to find niche applications for high added-value productions; to the other one, this paves the path towards the electrodeposition of metals and alloys thermodynamically impossible to be obtained via usual aqueous solution processes. The main aim of this chapter is therefore the critical discussion of the applicability of deep eutectic solvents to the electrodeposition of metals and alloys, with a particular attention to the industrial and applicative point of view.",book:{id:"5381",slug:"progress-and-developments-in-ionic-liquids",title:"Ionic Liquids",fullTitle:"Progress and Developments in Ionic Liquids"},signatures:"R. Bernasconi, G. Panzeri, A. Accogli, F. Liberale, L. Nobili and L.\nMagagnin",authors:[{id:"188210",title:"Associate Prof.",name:"Luca",middleName:null,surname:"Magagnin",slug:"luca-magagnin",fullName:"Luca Magagnin"},{id:"194387",title:"MSc.",name:"Roberto",middleName:null,surname:"Bernasconi",slug:"roberto-bernasconi",fullName:"Roberto Bernasconi"},{id:"194388",title:"MSc.",name:"Gabriele",middleName:null,surname:"Panzeri",slug:"gabriele-panzeri",fullName:"Gabriele Panzeri"},{id:"194389",title:"MSc.",name:"Alessandra",middleName:null,surname:"Accogli",slug:"alessandra-accogli",fullName:"Alessandra Accogli"},{id:"194390",title:"MSc.",name:"Francesco",middleName:null,surname:"Liberale",slug:"francesco-liberale",fullName:"Francesco Liberale"},{id:"194391",title:"Prof.",name:"Luca",middleName:null,surname:"Nobili",slug:"luca-nobili",fullName:"Luca Nobili"}]},{id:"74147",title:"Electrochemical Impedance Spectroscopy (EIS): A Review Study of Basic Aspects of the Corrosion Mechanism Applied to Steels",slug:"electrochemical-impedance-spectroscopy-eis-a-review-study-of-basic-aspects-of-the-corrosion-mechanis",totalDownloads:2640,totalCrossrefCites:9,totalDimensionsCites:20,abstract:"AC impedance measurements have been applied for over twenty years in electrochemistry and physics to investigate the electrical properties of conductive materials and their interfaces using an external electrical impulse (VOLTAGE, V or CURRENT, I) as driving force. Furthermore, its application has recently appeared to be destined in the Biotechnology field as an effective tool for rapid microbiologic diagnosis of living organism in situ. However, there is no doubt that the electrochemical impedance spectroscopy (EIS) is still one of the most useful techniques around the world for metal corrosion control and its monitoring. Corrosion has long been recognized as one of the most expensive stumbling blocks that concern many industries and government agencies, because it is a steel destructive phenomenon that occurs due to the chemical interaction with aqueous environments and takes place at the interface between metal and electrolyte producing an electrical charge transfer or ion diffusion process. Consequently, it is experimentally possible to determine through the EIS technique the mechanism and control that kinectics of corrosion reactions encounter. First, EIS data is collected through a potentiostat/galvanostat apparatus. After, it is fitted to a mathematical model (i.e. an equivalent electrical circuit, EEC) for its interpretation and analysis, fundamentally seeking a meaningful physical interpretation. Finally, this review reports some basic aspects of the corrosion mechanism applied to steels through the experimental EIS response using Nyquist or Bode plots. Examples are given for different applied electrochemical impedance cases in which steel is under study intentionally exposed to a corrosive aqueous solution by applying a sinusoidal potential at various test conditions.",book:{id:"10054",slug:"electrochemical-impedance-spectroscopy",title:"Electrochemical Impedance Spectroscopy",fullTitle:"Electrochemical Impedance Spectroscopy"},signatures:"Héctor Herrera Hernández, Adriana M. Ruiz Reynoso, Juan C. Trinidad González, Carlos O. González Morán, José G. Miranda Hernández, Araceli Mandujano Ruiz, Jorge Morales Hernández and Ricardo Orozco Cruz",authors:[{id:"114381",title:"Dr.",name:"Jorge",middleName:null,surname:"Morales-Hernandez",slug:"jorge-morales-hernandez",fullName:"Jorge Morales-Hernandez"},{id:"215540",title:"Dr.",name:"Araceli",middleName:null,surname:"Mandujano Ruiz",slug:"araceli-mandujano-ruiz",fullName:"Araceli Mandujano Ruiz"},{id:"268773",title:"Dr.",name:"Hector",middleName:null,surname:"Herrera Hernandez",slug:"hector-herrera-hernandez",fullName:"Hector Herrera Hernandez"},{id:"268774",title:"Dr.",name:"Carlos O.",middleName:null,surname:"Gonzalez Moran",slug:"carlos-o.-gonzalez-moran",fullName:"Carlos O. Gonzalez Moran"},{id:"314695",title:"Dr.",name:"Adriana Mercedes",middleName:null,surname:"Ruiz Reynoso",slug:"adriana-mercedes-ruiz-reynoso",fullName:"Adriana Mercedes Ruiz Reynoso"}]},{id:"62242",title:"Oxygen Reduction Reaction",slug:"oxygen-reduction-reaction",totalDownloads:4020,totalCrossrefCites:8,totalDimensionsCites:18,abstract:"In this chapter, the oxygen reduction reaction (ORR), which is one of the most important reactions in energy conversion systems such as fuel cells, including its reaction kinetics, is presented. Recent developments in electrocatalysts for ORR in fuel cells, including low and non-Pt electrocatalysts, metal oxides, transition metal macrocycles and chalgogenides, are discussed. Understanding of the interdependence of size, shape and activity of the electrocatalysts is evaluated. The recent development of ORR electrocatalysts with novel nanostructures is also reported. The mechanism catalysed by these electrocatalysts is presented. Finally, the perspectives of future trends for ORR are discussed.",book:{id:"6778",slug:"electrocatalysts-for-fuel-cells-and-hydrogen-evolution-theory-to-design",title:"Electrocatalysts for Fuel Cells and Hydrogen Evolution",fullTitle:"Electrocatalysts for Fuel Cells and Hydrogen Evolution - Theory to Design"},signatures:"Lindiwe Khotseng",authors:[{id:"236596",title:"Dr.",name:"Lindiwe Eudora",middleName:null,surname:"Khotseng",slug:"lindiwe-eudora-khotseng",fullName:"Lindiwe Eudora Khotseng"}]},{id:"40709",title:"The Role of Ion Exchange Chromatography in Purification and Characterization of Molecules",slug:"the-role-of-ion-exchange-chromatography-in-purification-and-characterization-of-molecules",totalDownloads:12949,totalCrossrefCites:2,totalDimensionsCites:9,abstract:null,book:{id:"2549",slug:"ion-exchange-technologies",title:"Ion Exchange Technologies",fullTitle:"Ion Exchange Technologies"},signatures:"Hidayat Ullah Khan",authors:[{id:"140538",title:"Dr.",name:"Hidayat",middleName:null,surname:"Khan",slug:"hidayat-khan",fullName:"Hidayat Khan"}]},{id:"49055",title:"Ion Exchange Method for Removal and Separation of Noble Metal Ions",slug:"ion-exchange-method-for-removal-and-separation-of-noble-metal-ions",totalDownloads:3025,totalCrossrefCites:6,totalDimensionsCites:12,abstract:"Ion exchange has been widely applied in technology of chemical separation of noble metal ions. This is associated with dissemination of methods using various ion exchange resins which are indispensable in many fields of chemical industry. Due to small amounts of noble elements in nature and constant impoverishment of their natural raw materials, of particular importance are physicochemical methods of their recovery from the second sources e.g. worn out converters of exhausted gases, chemical catalysts, dental alloys, anodic sludges from cooper and nickiel electrorefining as well as waste waters and running off waters from refineries containing trace amount of noble metals. It should be stated that these waste materials are usually pyro- and hydrometallurgically processed. Recovery of noble metals, from such raw materials requires individual approach to each material and application of selective methods for their removal. Moreover, separation of noble metals, particularly platinum metals and gold from geological samples, industrial products, synthetic mixtures along with other elements is a problem of significant importance nowadays. In the paper the research on the applicability of different types of ion exchangers for the separation of noble metals will be presented. The effect of the different parameters on their separation will be also discussed. The examples of the removal of noble metals chlorocomplexes will also be presented in detail.",book:{id:"4599",slug:"ion-exchange-studies-and-applications",title:"Ion Exchange",fullTitle:"Ion Exchange - Studies and Applications"},signatures:"Zbigniew Hubicki, Monika Wawrzkiewicz, Grzegorz Wójcik, Dorota\nKołodyńska and Anna Wołowicz",authors:[{id:"141883",title:"Prof.",name:"Zbigniew",middleName:null,surname:"Hubicki",slug:"zbigniew-hubicki",fullName:"Zbigniew Hubicki"},{id:"173610",title:"Dr.",name:"Dorota",middleName:null,surname:"Kołodyńska",slug:"dorota-kolodynska",fullName:"Dorota Kołodyńska"}]}],onlineFirstChaptersFilter:{topicId:"505",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:90,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:33,numberOfPublishedChapters:330,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:14,numberOfPublishedChapters:145,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:9,numberOfPublishedChapters:139,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:122,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:112,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:21,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:10,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:"2753-6580",doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. 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:"6",title:"Infectious Diseases",doi:"10.5772/intechopen.71852",issn:"2631-6188",scope:"This series will provide a comprehensive overview of recent research trends in various Infectious Diseases (as per the most recent Baltimore classification). Topics will include general overviews of infections, immunopathology, diagnosis, treatment, epidemiology, etiology, and current clinical recommendations for managing infectious diseases. Ongoing issues, recent advances, and future diagnostic approaches and therapeutic strategies will also be discussed. This book series will focus on various aspects and properties of infectious diseases whose deep understanding is essential for safeguarding the human race from losing resources and economies due to pathogens.",coverUrl:"https://cdn.intechopen.com/series/covers/6.jpg",latestPublicationDate:"August 2nd, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:13,editor:{id:"131400",title:"Prof.",name:"Alfonso J.",middleName:null,surname:"Rodriguez-Morales",slug:"alfonso-j.-rodriguez-morales",fullName:"Alfonso J. Rodriguez-Morales",profilePictureURL:"https://mts.intechopen.com/storage/users/131400/images/system/131400.png",biography:"Dr. Rodriguez-Morales is an expert in tropical and emerging diseases, particularly zoonotic and vector-borne diseases (especially arboviral diseases). He is the president of the Travel Medicine Committee of the Pan-American Infectious Diseases Association (API), as well as the president of the Colombian Association of Infectious Diseases (ACIN). He is a member of the Committee on Tropical Medicine, Zoonoses, and Travel Medicine of ACIN. He is a vice-president of the Latin American Society for Travel Medicine (SLAMVI) and a Member of the Council of the International Society for Infectious Diseases (ISID). Since 2014, he has been recognized as a Senior Researcher, at the Ministry of Science of Colombia. He is a professor at the Faculty of Medicine of the Fundacion Universitaria Autonoma de las Americas, in Pereira, Risaralda, Colombia. He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. He is currently the Editor in Chief of the journal Travel Medicine and Infectious Diseases. His Scopus H index is 47 (Google Scholar H index, 68).",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null},editorTwo:null,editorThree:null},subseries:{paginationCount:4,paginationItems:[{id:"3",title:"Bacterial Infectious Diseases",coverUrl:"https://cdn.intechopen.com/series_topics/covers/3.jpg",isOpenForSubmission:!0,editor:{id:"205604",title:"Dr.",name:"Tomas",middleName:null,surname:"Jarzembowski",slug:"tomas-jarzembowski",fullName:"Tomas Jarzembowski",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKriQAG/Profile_Picture_2022-06-16T11:01:31.jpg",biography:"Tomasz Jarzembowski was born in 1968 in Gdansk, Poland. He obtained his Ph.D. degree in 2000 from the Medical University of Gdańsk (UG). After specialization in clinical microbiology in 2003, he started studying biofilm formation and antibiotic resistance at the single-cell level. In 2015, he obtained his D.Sc. degree. His later study in cooperation with experts in nephrology and immunology resulted in the designation of the new diagnostic method of UTI, patented in 2017. He is currently working at the Department of Microbiology, Medical University of Gdańsk (GUMed), Poland. Since many years, he is a member of steering committee of Gdańsk branch of Polish Society of Microbiologists, a member of ESCMID. He is also a reviewer and a member of editorial boards of a number of international journals.",institutionString:"Medical University of Gdańsk, Poland",institution:null},editorTwo:{id:"484980",title:"Dr.",name:"Katarzyna",middleName:null,surname:"Garbacz",slug:"katarzyna-garbacz",fullName:"Katarzyna Garbacz",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003St8TAQAZ/Profile_Picture_2022-07-07T09:45:16.jpg",biography:"Katarzyna Maria Garbacz, MD, is an Associate Professor at the Medical University of Gdańsk, Poland and she is head of the Department of Oral Microbiology of the Medical University of Gdańsk. She has published more than 50 scientific publications in peer-reviewed journals. She has been a project leader funded by the National Science Centre of Poland. Prof. Garbacz is a microbiologist working on applied and fundamental questions in microbial epidemiology and pathogenesis. Her research interest is in antibiotic resistance, host-pathogen interaction, and therapeutics development for staphylococcal pathogens, mainly Staphylococcus aureus, which causes hospital-acquired infections. Currently, her research is mostly focused on the study of oral pathogens, particularly Staphylococcus spp.",institutionString:"Medical University of Gdańsk, Poland",institution:null},editorThree:null},{id:"4",title:"Fungal Infectious Diseases",coverUrl:"https://cdn.intechopen.com/series_topics/covers/4.jpg",isOpenForSubmission:!0,editor:{id:"174134",title:"Dr.",name:"Yuping",middleName:null,surname:"Ran",slug:"yuping-ran",fullName:"Yuping Ran",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bS9d6QAC/Profile_Picture_1630330675373",biography:"Dr. Yuping Ran, Professor, Department of Dermatology, West China Hospital, Sichuan University, Chengdu, China. Completed the Course Medical Mycology, the Centraalbureau voor Schimmelcultures (CBS), Fungal Biodiversity Centre, Netherlands (2006). International Union of Microbiological Societies (IUMS) Fellow, and International Emerging Infectious Diseases (IEID) Fellow, Centers for Diseases Control and Prevention (CDC), Atlanta, USA. Diploma of Dermatological Scientist, Japanese Society for Investigative Dermatology. Ph.D. of Juntendo University, Japan. Bachelor’s and Master’s degree, Medicine, West China University of Medical Sciences. Chair of Sichuan Medical Association Dermatology Committee. General Secretary of The 19th Annual Meeting of Chinese Society of Dermatology and the Asia Pacific Society for Medical Mycology (2013). In charge of the Annual Medical Mycology Course over 20-years authorized by National Continue Medical Education Committee of China. Member of the board of directors of the Asia-Pacific Society for Medical Mycology (APSMM). Associate editor of Mycopathologia. Vice-chief of the editorial board of Chinses Journal of Mycology, China. Board Member and Chair of Mycology Group of Chinese Society of Dermatology.",institutionString:null,institution:{name:"Sichuan University",institutionURL:null,country:{name:"China"}}},editorTwo:null,editorThree:null},{id:"5",title:"Parasitic Infectious Diseases",coverUrl:"https://cdn.intechopen.com/series_topics/covers/5.jpg",isOpenForSubmission:!0,editor:{id:"67907",title:"Dr.",name:"Amidou",middleName:null,surname:"Samie",slug:"amidou-samie",fullName:"Amidou Samie",profilePictureURL:"https://mts.intechopen.com/storage/users/67907/images/system/67907.jpg",biography:"Dr. Amidou Samie is an Associate Professor of Microbiology at the University of Venda, in South Africa, where he graduated for his PhD in May 2008. He joined the Department of Microbiology the same year and has been giving lectures on topics covering parasitology, immunology, molecular biology and industrial microbiology. He is currently a rated researcher by the National Research Foundation of South Africa at category C2. He has published widely in the field of infectious diseases and has overseen several MSc’s and PhDs. His research activities mostly cover topics on infectious diseases from epidemiology to control. His particular interest lies in the study of intestinal protozoan parasites and opportunistic infections among HIV patients as well as the potential impact of childhood diarrhoea on growth and child development. He also conducts research on water-borne diseases and water quality and is involved in the evaluation of point-of-use water treatment technologies using silver and copper nanoparticles in collaboration with the University of Virginia, USA. He also studies the use of medicinal plants for the control of infectious diseases as well as antimicrobial drug resistance.",institutionString:null,institution:{name:"University of Venda",institutionURL:null,country:{name:"South Africa"}}},editorTwo:null,editorThree:null},{id:"6",title:"Viral Infectious Diseases",coverUrl:"https://cdn.intechopen.com/series_topics/covers/6.jpg",isOpenForSubmission:!0,editor:{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",biography:"Professor Dr. Shailendra K. Saxena is a vice dean and professor at King George's Medical University, Lucknow, India. His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. Dr. Saxena is a fellow of various international societies/academies including the Royal College of Pathologists, United Kingdom; Royal Society of Medicine, London; Royal Society of Biology, United Kingdom; Royal Society of Chemistry, London; and Academy of Translational Medicine Professionals, Austria. He was named a Global Leader in Science by The Scientist. 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Saxena",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",institutionURL:null,country:{name:"India"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null}]},subseriesFiltersForPublishedBooks:[{group:"subseries",caption:"Bacterial Infectious Diseases",value:3,count:2},{group:"subseries",caption:"Parasitic Infectious Diseases",value:5,count:4},{group:"subseries",caption:"Viral Infectious Diseases",value:6,count:7}],publicationYearFilters:[{group:"publicationYear",caption:"2022",value:2022,count:2},{group:"publicationYear",caption:"2021",value:2021,count:4},{group:"publicationYear",caption:"2020",value:2020,count:3},{group:"publicationYear",caption:"2019",value:2019,count:3},{group:"publicationYear",caption:"2018",value:2018,count:1}],authors:{paginationCount:250,paginationItems:[{id:"274452",title:"Dr.",name:"Yousif",middleName:"Mohamed",surname:"Abdallah",slug:"yousif-abdallah",fullName:"Yousif Abdallah",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/274452/images/8324_n.jpg",biography:"I certainly enjoyed my experience in Radiotherapy and Nuclear Medicine, particularly it has been in different institutions and hospitals with different Medical Cultures and allocated resources. Radiotherapy and Nuclear Medicine Technology has always been my aspiration and my life. As years passed I accumulated a tremendous amount of skills and knowledge in Radiotherapy and Nuclear Medicine, Conventional Radiology, Radiation Protection, Bioinformatics Technology, PACS, Image processing, clinically and lecturing that will enable me to provide a valuable service to the community as a Researcher and Consultant in this field. My method of translating this into day to day in clinical practice is non-exhaustible and my habit of exchanging knowledge and expertise with others in those fields is the code and secret of success.",institutionString:null,institution:{name:"Majmaah University",country:{name:"Saudi Arabia"}}},{id:"313277",title:"Dr.",name:"Bartłomiej",middleName:null,surname:"Płaczek",slug:"bartlomiej-placzek",fullName:"Bartłomiej Płaczek",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/313277/images/system/313277.jpg",biography:"Bartłomiej Płaczek, MSc (2002), Ph.D. (2005), Habilitation (2016), is a professor at the University of Silesia, Institute of Computer Science, Poland, and an expert from the National Centre for Research and Development. His research interests include sensor networks, smart sensors, intelligent systems, and image processing with applications in healthcare and medicine. He is the author or co-author of more than seventy papers in peer-reviewed journals and conferences as well as the co-author of several books. He serves as a reviewer for many scientific journals, international conferences, and research foundations. Since 2010, Dr. Placzek has been a reviewer of grants and projects (including EU projects) in the field of information technologies.",institutionString:"University of Silesia",institution:{name:"University of Silesia",country:{name:"Poland"}}},{id:"35000",title:"Prof.",name:"Ulrich H.P",middleName:"H.P.",surname:"Fischer",slug:"ulrich-h.p-fischer",fullName:"Ulrich H.P Fischer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/35000/images/3052_n.jpg",biography:"Academic and Professional Background\nUlrich H. P. has Diploma and PhD degrees in Physics from the Free University Berlin, Germany. He has been working on research positions in the Heinrich-Hertz-Institute in Germany. Several international research projects has been performed with European partners from France, Netherlands, Norway and the UK. He is currently Professor of Communications Systems at the Harz University of Applied Sciences, Germany.\n\nPublications and Publishing\nHe has edited one book, a special interest book about ‘Optoelectronic Packaging’ (VDE, Berlin, Germany), and has published over 100 papers and is owner of several international patents for WDM over POF key elements.\n\nKey Research and Consulting Interests\nUlrich’s research activity has always been related to Spectroscopy and Optical Communications Technology. Specific current interests include the validation of complex instruments, and the application of VR technology to the development and testing of measurement systems. He has been reviewer for several publications of the Optical Society of America\\'s including Photonics Technology Letters and Applied Optics.\n\nPersonal Interests\nThese include motor cycling in a very relaxed manner and performing martial arts.",institutionString:null,institution:{name:"Charité",country:{name:"Germany"}}},{id:"341622",title:"Ph.D.",name:"Eduardo",middleName:null,surname:"Rojas Alvarez",slug:"eduardo-rojas-alvarez",fullName:"Eduardo Rojas Alvarez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/341622/images/15892_n.jpg",biography:null,institutionString:null,institution:{name:"University of Cuenca",country:{name:"Ecuador"}}},{id:"215610",title:"Prof.",name:"Muhammad",middleName:null,surname:"Sarfraz",slug:"muhammad-sarfraz",fullName:"Muhammad Sarfraz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/215610/images/system/215610.jpeg",biography:"Muhammad Sarfraz is a professor in the Department of Information Science, Kuwait University. His research interests include computer graphics, computer vision, image processing, machine learning, pattern recognition, soft computing, data science, intelligent systems, information technology, and information systems. Prof. Sarfraz has been a keynote/invited speaker on various platforms around the globe. He has advised various students for their MSc and Ph.D. theses. He has published more than 400 publications as books, journal articles, and conference papers. He is a member of various professional societies and a chair and member of the International Advisory Committees and Organizing Committees of various international conferences. Prof. Sarfraz is also an editor-in-chief and editor of various international journals.",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"32650",title:"Prof.",name:"Lukas",middleName:"Willem",surname:"Snyman",slug:"lukas-snyman",fullName:"Lukas Snyman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/32650/images/4136_n.jpg",biography:"Lukas Willem Snyman received his basic education at primary and high schools in South Africa, Eastern Cape. He enrolled at today's Nelson Metropolitan University and graduated from this university with a BSc in Physics and Mathematics, B.Sc Honors in Physics, MSc in Semiconductor Physics, and a Ph.D. in Semiconductor Physics in 1987. After his studies, he chose an academic career and devoted his energy to the teaching of physics to first, second, and third-year students. After positions as a lecturer at the University of Port Elizabeth, he accepted a position as Associate Professor at the University of Pretoria, South Africa.\r\n\r\nIn 1992, he motivates the concept of 'television and computer-based education” as means to reach large student numbers with only the best of teaching expertise and publishes an article on the concept in the SA Journal of Higher Education of 1993 (and later in 2003). The University of Pretoria subsequently approved a series of test projects on the concept with outreach to Mamelodi and Eerste Rust in 1993. In 1994, the University established a 'Unit for Telematic Education ' as a support section for multiple faculties at the University of Pretoria. In subsequent years, the concept of 'telematic education” subsequently becomes well established in academic circles in South Africa, grew in popularity, and is adopted by many universities and colleges throughout South Africa as a medium of enhancing education and training, as a method to reaching out to far out communities, and as a means to enhance study from the home environment.\r\n\r\nProfessor Snyman in subsequent years pursued research in semiconductor physics, semiconductor devices, microelectronics, and optoelectronics.\r\n\r\nIn 2000 he joined the TUT as a full professor. Here served for a period as head of the Department of Electronic Engineering. Here he makes contributions to solar energy development, microwave and optoelectronic device development, silicon photonics, as well as contributions to new mobile telecommunication systems and network planning in SA.\r\n\r\nCurrently, he teaches electronics and telecommunications at the TUT to audiences ranging from first-year students to Ph.D. level.\r\n\r\nFor his research in the field of 'Silicon Photonics” since 1990, he has published (as author and co-author) about thirty internationally reviewed articles in scientific journals, contributed to more than forty international conferences, about 25 South African provisional patents (as inventor and co-inventor), 8 PCT international patent applications until now. Of these, two USA patents applications, two European Patents, two Korean patents, and ten SA patents have been granted. A further 4 USA patents, 5 European patents, 3 Korean patents, 3 Chinese patents, and 3 Japanese patents are currently under consideration.\r\n\r\nRecently he has also published an extensive scholarly chapter in an internet open access book on 'Integrating Microphotonic Systems and MOEMS into standard Silicon CMOS Integrated circuitry”.\r\n\r\nFurthermore, Professor Snyman recently steered a new initiative at the TUT by introducing a 'Laboratory for Innovative Electronic Systems ' at the Department of Electrical Engineering. The model of this laboratory or center is to primarily combine outputs as achieved by high-level research with lower-level system development and entrepreneurship in a technical university environment. Students are allocated to projects at different levels with PhDs and Master students allocated to the generation of new knowledge and new technologies, while students at the diploma and Baccalaureus level are allocated to electronic systems development with a direct and a near application for application in industry or the commercial and public sectors in South Africa.\r\n\r\nProfessor Snyman received the WIRSAM Award of 1983 and the WIRSAM Award in 1985 in South Africa for best research papers by a young scientist at two international conferences on electron microscopy in South Africa. He subsequently received the SA Microelectronics Award for the best dissertation emanating from studies executed at a South African university in the field of Physics and Microelectronics in South Africa in 1987. In October of 2011, Professor Snyman received the prestigious Institutional Award for 'Innovator of the Year” for 2010 at the Tshwane University of Technology, South Africa. This award was based on the number of patents recognized and granted by local and international institutions as well as for his contributions concerning innovation at the TUT.",institutionString:null,institution:{name:"University of South Africa",country:{name:"South Africa"}}},{id:"317279",title:"Mr.",name:"Ali",middleName:"Usama",surname:"Syed",slug:"ali-syed",fullName:"Ali Syed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/317279/images/16024_n.png",biography:"A creative, talented, and innovative young professional who is dedicated, well organized, and capable research fellow with two years of experience in graduate-level research, published in engineering journals and book, with related expertise in Bio-robotics, equally passionate about the aesthetics of the mechanical and electronic system, obtained expertise in the use of MS Office, MATLAB, SolidWorks, LabVIEW, Proteus, Fusion 360, having a grasp on python, C++ and assembly language, possess proven ability in acquiring research grants, previous appointments with social and educational societies with experience in administration, current affiliations with IEEE and Web of Science, a confident presenter at conferences and teacher in classrooms, able to explain complex information to audiences of all levels.",institutionString:null,institution:{name:"Air University",country:{name:"Pakistan"}}},{id:"75526",title:"Ph.D.",name:"Zihni Onur",middleName:null,surname:"Uygun",slug:"zihni-onur-uygun",fullName:"Zihni Onur Uygun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/75526/images/12_n.jpg",biography:"My undergraduate education and my Master of Science educations at Ege University and at Çanakkale Onsekiz Mart University have given me a firm foundation in Biochemistry, Analytical Chemistry, Biosensors, Bioelectronics, Physical Chemistry and Medicine. After obtaining my degree as a MSc in analytical chemistry, I started working as a research assistant in Ege University Medical Faculty in 2014. In parallel, I enrolled to the MSc program at the Department of Medical Biochemistry at Ege University to gain deeper knowledge on medical and biochemical sciences as well as clinical chemistry in 2014. In my PhD I deeply researched on biosensors and bioelectronics and finished in 2020. Now I have eleven SCI-Expanded Index published papers, 6 international book chapters, referee assignments for different SCIE journals, one international patent pending, several international awards, projects and bursaries. In parallel to my research assistant position at Ege University Medical Faculty, Department of Medical Biochemistry, in April 2016, I also founded a Start-Up Company (Denosens Biotechnology LTD) by the support of The Scientific and Technological Research Council of Turkey. Currently, I am also working as a CEO in Denosens Biotechnology. The main purposes of the company, which carries out R&D as a research center, are to develop new generation biosensors and sensors for both point-of-care diagnostics; such as glucose, lactate, cholesterol and cancer biomarker detections. My specific experimental and instrumental skills are Biochemistry, Biosensor, Analytical Chemistry, Electrochemistry, Mobile phone based point-of-care diagnostic device, POCTs and Patient interface designs, HPLC, Tandem Mass Spectrometry, Spectrophotometry, ELISA.",institutionString:null,institution:{name:"Ege University",country:{name:"Turkey"}}},{id:"267434",title:"Dr.",name:"Rohit",middleName:null,surname:"Raja",slug:"rohit-raja",fullName:"Rohit Raja",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/267434/images/system/267434.jpg",biography:"Dr. Rohit Raja received Ph.D. in Computer Science and Engineering from Dr. CVRAMAN University in 2016. His main research interest includes Face recognition and Identification, Digital Image Processing, Signal Processing, and Networking. Presently he is working as Associate Professor in IT Department, Guru Ghasidas Vishwavidyalaya (A Central University), Bilaspur (CG), India. He has authored several Journal and Conference Papers. He has good Academics & Research experience in various areas of CSE and IT. He has filed and successfully published 27 Patents. He has received many time invitations to be a Guest at IEEE Conferences. He has published 100 research papers in various International/National Journals (including IEEE, Springer, etc.) and Proceedings of the reputed International/ National Conferences (including Springer and IEEE). He has been nominated to the board of editors/reviewers of many peer-reviewed and refereed Journals (including IEEE, Springer).",institutionString:"Guru Ghasidas Vishwavidyalaya",institution:{name:"Guru Ghasidas Vishwavidyalaya",country:{name:"India"}}},{id:"246502",title:"Dr.",name:"Jaya T.",middleName:"T",surname:"Varkey",slug:"jaya-t.-varkey",fullName:"Jaya T. Varkey",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/246502/images/11160_n.jpg",biography:"Jaya T. Varkey, PhD, graduated with a degree in Chemistry from Cochin University of Science and Technology, Kerala, India. She obtained a PhD in Chemistry from the School of Chemical Sciences, Mahatma Gandhi University, Kerala, India, and completed a post-doctoral fellowship at the University of Minnesota, USA. She is a research guide at Mahatma Gandhi University and Associate Professor in Chemistry, St. Teresa’s College, Kochi, Kerala, India.\nDr. Varkey received a National Young Scientist award from the Indian Science Congress (1995), a UGC Research award (2016–2018), an Indian National Science Academy (INSA) Visiting Scientist award (2018–2019), and a Best Innovative Faculty award from the All India Association for Christian Higher Education (AIACHE) (2019). She Hashas received the Sr. Mary Cecil prize for best research paper three times. She was also awarded a start-up to develop a tea bag water filter. \nDr. Varkey has published two international books and twenty-seven international journal publications. She is an editorial board member for five international journals.",institutionString:"St. Teresa’s College",institution:null},{id:"250668",title:"Dr.",name:"Ali",middleName:null,surname:"Nabipour Chakoli",slug:"ali-nabipour-chakoli",fullName:"Ali Nabipour Chakoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/250668/images/system/250668.jpg",biography:"Academic Qualification:\r\n•\tPhD in Materials Physics and Chemistry, From: Sep. 2006, to: Sep. 2010, School of Materials Science and Engineering, Harbin Institute of Technology, Thesis: Structure and Shape Memory Effect of Functionalized MWCNTs/poly (L-lactide-co-ε-caprolactone) Nanocomposites. Supervisor: Prof. Wei Cai,\r\n•\tM.Sc in Applied Physics, From: 1996, to: 1998, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Determination of Boron in Micro alloy Steels with solid state nuclear track detectors by neutron induced auto radiography, Supervisors: Dr. M. Hosseini Ashrafi and Dr. A. Hosseini.\r\n•\tB.Sc. in Applied Physics, From: 1991, to: 1996, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Design of shielding for Am-Be neutron sources for In Vivo neutron activation analysis, Supervisor: Dr. M. Hosseini Ashrafi.\r\n\r\nResearch Experiences:\r\n1.\tNanomaterials, Carbon Nanotubes, Graphene: Synthesis, Functionalization and Characterization,\r\n2.\tMWCNTs/Polymer Composites: Fabrication and Characterization, \r\n3.\tShape Memory Polymers, Biodegradable Polymers, ORC, Collagen,\r\n4.\tMaterials Analysis and Characterizations: TEM, SEM, XPS, FT-IR, Raman, DSC, DMA, TGA, XRD, GPC, Fluoroscopy, \r\n5.\tInteraction of Radiation with Mater, Nuclear Safety and Security, NDT(RT),\r\n6.\tRadiation Detectors, Calibration (SSDL),\r\n7.\tCompleted IAEA e-learning Courses:\r\nNuclear Security (15 Modules),\r\nNuclear Safety:\r\nTSA 2: Regulatory Protection in Occupational Exposure,\r\nTips & Tricks: Radiation Protection in Radiography,\r\nSafety and Quality in Radiotherapy,\r\nCourse on Sealed Radioactive Sources,\r\nCourse on Fundamentals of Environmental Remediation,\r\nCourse on Planning for Environmental Remediation,\r\nKnowledge Management Orientation Course,\r\nFood Irradiation - Technology, Applications and Good Practices,\r\nEmployment:\r\nFrom 2010 to now: Academic staff, Nuclear Science and Technology Research Institute, Kargar Shomali, Tehran, Iran, P.O. Box: 14395-836.\r\nFrom 1997 to 2006: Expert of Materials Analysis and Characterization. Research Center of Agriculture and Medicine. Rajaeeshahr, Karaj, Iran, P. O. Box: 31585-498.",institutionString:"Atomic Energy Organization of Iran",institution:{name:"Atomic Energy Organization of Iran",country:{name:"Iran"}}},{id:"248279",title:"Dr.",name:"Monika",middleName:"Elzbieta",surname:"Machoy",slug:"monika-machoy",fullName:"Monika Machoy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248279/images/system/248279.jpeg",biography:"Monika Elżbieta Machoy, MD, graduated with distinction from the Faculty of Medicine and Dentistry at the Pomeranian Medical University in 2009, defended her PhD thesis with summa cum laude in 2016 and is currently employed as a researcher at the Department of Orthodontics of the Pomeranian Medical University. She expanded her professional knowledge during a one-year scholarship program at the Ernst Moritz Arndt University in Greifswald, Germany and during a three-year internship at the Technical University in Dresden, Germany. She has been a speaker at numerous orthodontic conferences, among others, American Association of Orthodontics, European Orthodontic Symposium and numerous conferences of the Polish Orthodontic Society. She conducts research focusing on the effect of orthodontic treatment on dental and periodontal tissues and the causes of pain in orthodontic patients.",institutionString:"Pomeranian Medical University",institution:{name:"Pomeranian Medical University",country:{name:"Poland"}}},{id:"252743",title:"Prof.",name:"Aswini",middleName:"Kumar",surname:"Kar",slug:"aswini-kar",fullName:"Aswini Kar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252743/images/10381_n.jpg",biography:"uploaded in cv",institutionString:null,institution:{name:"KIIT University",country:{name:"India"}}},{id:"204256",title:"Dr.",name:"Anil",middleName:"Kumar",surname:"Kumar Sahu",slug:"anil-kumar-sahu",fullName:"Anil Kumar Sahu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204256/images/14201_n.jpg",biography:"I have nearly 11 years of research and teaching experience. I have done my master degree from University Institute of Pharmacy, Pt. Ravi Shankar Shukla University, Raipur, Chhattisgarh India. I have published 16 review and research articles in international and national journals and published 4 chapters in IntechOpen, the world’s leading publisher of Open access books. I have presented many papers at national and international conferences. I have received research award from Indian Drug Manufacturers Association in year 2015. My research interest extends from novel lymphatic drug delivery systems, oral delivery system for herbal bioactive to formulation optimization.",institutionString:null,institution:{name:"Chhattisgarh Swami Vivekanand Technical University",country:{name:"India"}}},{id:"253468",title:"Dr.",name:"Mariusz",middleName:null,surname:"Marzec",slug:"mariusz-marzec",fullName:"Mariusz Marzec",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/253468/images/system/253468.png",biography:"An assistant professor at Department of Biomedical Computer Systems, at Institute of Computer Science, Silesian University in Katowice. Scientific interests: computer analysis and processing of images, biomedical images, databases and programming languages. He is an author and co-author of scientific publications covering analysis and processing of biomedical images and development of database systems.",institutionString:"University of Silesia",institution:{name:"University of Silesia",country:{name:"Poland"}}},{id:"212432",title:"Prof.",name:"Hadi",middleName:null,surname:"Mohammadi",slug:"hadi-mohammadi",fullName:"Hadi Mohammadi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/212432/images/system/212432.jpeg",biography:"Dr. Hadi Mohammadi is a biomedical engineer with hands-on experience in the design and development of many engineering structures and medical devices through various projects that he has been involved in over the past twenty years. Dr. Mohammadi received his BSc. and MSc. degrees in Mechanical Engineering from Sharif University of Technology, Tehran, Iran, and his PhD. degree in Biomedical Engineering (biomaterials) from the University of Western Ontario. He was a postdoctoral trainee for almost four years at University of Calgary and Harvard Medical School. He is an industry innovator having created the technology to produce lifelike synthetic platforms that can be used for the simulation of almost all cardiovascular reconstructive surgeries. He’s been heavily involved in the design and development of cardiovascular devices and technology for the past 10 years. He is currently an Assistant Professor with the University of British Colombia, Canada.",institutionString:"University of British Columbia",institution:{name:"University of British Columbia",country:{name:"Canada"}}},{id:"254463",title:"Prof.",name:"Haisheng",middleName:null,surname:"Yang",slug:"haisheng-yang",fullName:"Haisheng Yang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/254463/images/system/254463.jpeg",biography:"Haisheng Yang, Ph.D., Professor and Director of the Department of Biomedical Engineering, College of Life Science and Bioengineering, Beijing University of Technology. He received his Ph.D. degree in Mechanics/Biomechanics from Harbin Institute of Technology (jointly with University of California, Berkeley). Afterwards, he worked as a Postdoctoral Research Associate in the Purdue Musculoskeletal Biology and Mechanics Lab at the Department of Basic Medical Sciences, Purdue University, USA. He also conducted research in the Research Centre of Shriners Hospitals for Children-Canada at McGill University, Canada. Dr. Yang has over 10 years research experience in orthopaedic biomechanics and mechanobiology of bone adaptation and regeneration. He earned an award from Beijing Overseas Talents Aggregation program in 2017 and serves as Beijing Distinguished Professor.",institutionString:null,institution:{name:"Beijing University of Technology",country:{name:"China"}}},{id:"89721",title:"Dr.",name:"Mehmet",middleName:"Cuneyt",surname:"Ozmen",slug:"mehmet-ozmen",fullName:"Mehmet Ozmen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/89721/images/7289_n.jpg",biography:null,institutionString:null,institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"265335",title:"Mr.",name:"Stefan",middleName:"Radnev",surname:"Stefanov",slug:"stefan-stefanov",fullName:"Stefan Stefanov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/265335/images/7562_n.jpg",biography:null,institutionString:null,institution:{name:"Medical University Plovdiv",country:{name:"Bulgaria"}}},{id:"242893",title:"Ph.D. Student",name:"Joaquim",middleName:null,surname:"De Moura",slug:"joaquim-de-moura",fullName:"Joaquim De Moura",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/242893/images/7133_n.jpg",biography:"Joaquim de Moura received his degree in Computer Engineering in 2014 from the University of A Coruña (Spain). In 2016, he received his M.Sc degree in Computer Engineering from the same university. He is currently pursuing his Ph.D degree in Computer Science in a collaborative project between ophthalmology centers in Galicia and the University of A Coruña. His research interests include computer vision, machine learning algorithms and analysis and medical imaging processing of various kinds.",institutionString:null,institution:{name:"University of A Coruña",country:{name:"Spain"}}},{id:"294334",title:"B.Sc.",name:"Marc",middleName:null,surname:"Bruggeman",slug:"marc-bruggeman",fullName:"Marc Bruggeman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/294334/images/8242_n.jpg",biography:"Chemical engineer graduate, with a passion for material science and specific interest in polymers - their near infinite applications intrigue me. \n\nI plan to continue my scientific career in the field of polymeric biomaterials as I am fascinated by intelligent, bioactive and biomimetic materials for use in both consumer and medical applications.",institutionString:null,institution:null},{id:"255757",title:"Dr.",name:"Igor",middleName:"Victorovich",surname:"Lakhno",slug:"igor-lakhno",fullName:"Igor Lakhno",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255757/images/system/255757.jpg",biography:"Igor Victorovich Lakhno was born in 1971 in Kharkiv (Ukraine). \nMD – 1994, Kharkiv National Medical Univesity.\nOb&Gyn; – 1997, master courses in Kharkiv Medical Academy of Postgraduate Education.\nPh.D. – 1999, Kharkiv National Medical Univesity.\nDSC – 2019, PL Shupik National Academy of Postgraduate Education \nProfessor – 2021, Department of Obstetrics and Gynecology of VN Karazin Kharkiv National University\nHead of Department – 2021, Department of Perinatology, Obstetrics and gynecology of Kharkiv Medical Academy of Postgraduate Education\nIgor Lakhno has been graduated from international training courses on reproductive medicine and family planning held at Debrecen University (Hungary) in 1997. Since 1998 Lakhno Igor has worked as an associate professor in the department of obstetrics and gynecology of VN Karazin National University and an associate professor of the perinatology, obstetrics, and gynecology department of Kharkiv Medical Academy of Postgraduate Education. Since June 2019 he’s been a professor in the department of obstetrics and gynecology of VN Karazin National University and a professor of the perinatology, obstetrics, and gynecology department. He’s affiliated with Kharkiv Medical Academy of Postgraduate Education as a Head of Department from November 2021. Igor Lakhno has participated in several international projects on fetal non-invasive electrocardiography (with Dr. J. A. Behar (Technion), Prof. D. Hoyer (Jena University), and José Alejandro Díaz Méndez (National Institute of Astrophysics, Optics, and Electronics, Mexico). He’s an author of about 200 printed works and there are 31 of them in Scopus or Web of Science databases. Igor Lakhno is a member of the Editorial Board of Reproductive Health of Woman, Emergency Medicine, and Technology Transfer Innovative Solutions in Medicine (Estonia). He is a medical Editor of “Z turbotoyu pro zhinku”. Igor Lakhno is a reviewer of the Journal of Obstetrics and Gynaecology (Taylor and Francis), British Journal of Obstetrics and Gynecology (Wiley), Informatics in Medicine Unlocked (Elsevier), The Journal of Obstetrics and Gynecology Research (Wiley), Endocrine, Metabolic & Immune Disorders-Drug Targets (Bentham Open), The Open Biomedical Engineering Journal (Bentham Open), etc. He’s defended a dissertation for a DSc degree “Pre-eclampsia: prediction, prevention, and treatment”. Three years ago Igor Lakhno has participated in a training course on innovative technologies in medical education at Lublin Medical University (Poland). Lakhno Igor has participated as a speaker in several international conferences and congresses (International Conference on Biological Oscillations April 10th-14th 2016, Lancaster, UK, The 9th conference of the European Study Group on Cardiovascular Oscillations). His main scientific interests: are obstetrics, women’s health, fetal medicine, and cardiovascular medicine. \nIgor Lakhno is a consultant at Kharkiv municipal perinatal center. He’s graduated from training courses on endoscopy in gynecology. He has 28 years of practical experience in the field.",institutionString:null,institution:null},{id:"244950",title:"Dr.",name:"Salvatore",middleName:null,surname:"Di Lauro",slug:"salvatore-di-lauro",fullName:"Salvatore Di Lauro",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0030O00002bSF1HQAW/ProfilePicture%202021-12-20%2014%3A54%3A14.482",biography:"Name:\n\tSALVATORE DI LAURO\nAddress:\n\tHospital Clínico Universitario Valladolid\nAvda Ramón y Cajal 3\n47005, Valladolid\nSpain\nPhone number: \nFax\nE-mail:\n\t+34 983420000 ext 292\n+34 983420084\nsadilauro@live.it\nDate and place of Birth:\nID Number\nMedical Licence \nLanguages\t09-05-1985. Villaricca (Italy)\n\nY1281863H\n474707061\nItalian (native language)\nSpanish (read, written, spoken)\nEnglish (read, written, spoken)\nPortuguese (read, spoken)\nFrench (read)\n\t\t\nCurrent position (title and company)\tDate (Year)\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. Private practise.\t2017-today\n\n2019-today\n\t\n\t\nEducation (High school, university and postgraduate training > 3 months)\tDate (Year)\nDegree in Medicine and Surgery. University of Neaples 'Federico II”\nResident in Opthalmology. Hospital Clinico Universitario Valladolid\nMaster in Vitreo-Retina. IOBA. University of Valladolid\nFellow of the European Board of Ophthalmology. Paris\nMaster in Research in Ophthalmology. University of Valladolid\t2003-2009\n2012-2016\n2016-2017\n2016\n2012-2013\n\t\nEmployments (company and positions)\tDate (Year)\nResident in Ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl.\nFellow in Vitreo-Retina. IOBA. University of Valladolid\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. \n\t2012-2016\n2016-2017\n2017-today\n\n2019-Today\n\n\n\t\nClinical Research Experience (tasks and role)\tDate (Year)\nAssociated investigator\n\n' FIS PI20/00740: DESARROLLO DE UNA CALCULADORA DE RIESGO DE\nAPARICION DE RETINOPATIA DIABETICA BASADA EN TECNICAS DE IMAGEN MULTIMODAL EN PACIENTES DIABETICOS TIPO 1. Grant by: Ministerio de Ciencia e Innovacion \n\n' (BIO/VA23/14) Estudio clínico multicéntrico y prospectivo para validar dos\nbiomarcadores ubicados en los genes p53 y MDM2 en la predicción de los resultados funcionales de la cirugía del desprendimiento de retina regmatógeno. Grant by: Gerencia Regional de Salud de la Junta de Castilla y León.\n' Estudio multicéntrico, aleatorizado, con enmascaramiento doble, en 2 grupos\nparalelos y de 52 semanas de duración para comparar la eficacia, seguridad e inmunogenicidad de SOK583A1 respecto a Eylea® en pacientes con degeneración macular neovascular asociada a la edad' (CSOK583A12301; N.EUDRA: 2019-004838-41; FASE III). Grant by Hexal AG\n\n' Estudio de fase III, aleatorizado, doble ciego, con grupos paralelos, multicéntrico para comparar la eficacia y la seguridad de QL1205 frente a Lucentis® en pacientes con degeneración macular neovascular asociada a la edad. (EUDRACT: 2018-004486-13). Grant by Qilu Pharmaceutical Co\n\n' Estudio NEUTON: Ensayo clinico en fase IV para evaluar la eficacia de aflibercept en pacientes Naive con Edema MacUlar secundario a Oclusion de Vena CenTral de la Retina (OVCR) en regimen de tratamientO iNdividualizado Treat and Extend (TAE)”, (2014-000975-21). Grant by Fundacion Retinaplus\n\n' Evaluación de la seguridad y bioactividad de anillos de tensión capsular en conejo. Proyecto Procusens. Grant by AJL, S.A.\n\n'Estudio epidemiológico, prospectivo, multicéntrico y abierto\\npara valorar la frecuencia de la conjuntivitis adenovírica diagnosticada mediante el test AdenoPlus®\\nTest en pacientes enfermos de conjuntivitis aguda”\\n. National, multicenter study. Grant by: NICOX.\n\nEuropean multicentric trial: 'Evaluation of clinical outcomes following the use of Systane Hydration in patients with dry eye”. Study Phase 4. Grant by: Alcon Labs'\n\nVLPs Injection and Activation in a Rabbit Model of Uveal Melanoma. Grant by Aura Bioscience\n\nUpdating and characterization of a rabbit model of uveal melanoma. Grant by Aura Bioscience\n\nEnsayo clínico en fase IV para evaluar las variantes genéticas de la vía del VEGF como biomarcadores de eficacia del tratamiento con aflibercept en pacientes con degeneración macular asociada a la edad (DMAE) neovascular. Estudio BIOIMAGE. IMO-AFLI-2013-01\n\nEstudio In-Eye:Ensayo clínico en fase IV, abierto, aleatorizado, de 2 brazos,\nmulticçentrico y de 12 meses de duración, para evaluar la eficacia y seguridad de un régimen de PRN flexible individualizado de 'esperar y extender' versus un régimen PRN según criterios de estabilización mediante evaluaciones mensuales de inyecciones intravítreas de ranibizumab 0,5 mg en pacientes naive con neovascularización coriodea secunaria a la degeneración macular relacionada con la edad. CP: CRFB002AES03T\n\nTREND: Estudio Fase IIIb multicéntrico, randomizado, de 12 meses de\nseguimiento con evaluador de la agudeza visual enmascarado, para evaluar la eficacia y la seguridad de ranibizumab 0.5mg en un régimen de tratar y extender comparado con un régimen mensual, en pacientes con degeneración macular neovascular asociada a la edad. CP: CRFB002A2411 Código Eudra CT:\n2013-002626-23\n\n\n\nPublications\t\n\n2021\n\n\n\n\n2015\n\n\n\n\n2021\n\n\n\n\n\n2021\n\n\n\n\n2015\n\n\n\n\n2015\n\n\n2014\n\n\n\n\n2015-16\n\n\n\n2015\n\n\n2014\n\n\n2014\n\n\n\n\n2014\n\n\n\n\n\n\n\n2014\n\nJose Carlos Pastor; Jimena Rojas; Salvador Pastor-Idoate; Salvatore Di Lauro; Lucia Gonzalez-Buendia; Santiago Delgado-Tirado. Proliferative vitreoretinopathy: A new concept of disease pathogenesis and practical\nconsequences. Progress in Retinal and Eye Research. 51, pp. 125 - 155. 03/2016. DOI: 10.1016/j.preteyeres.2015.07.005\n\n\nLabrador-Velandia S; Alonso-Alonso ML; Di Lauro S; García-Gutierrez MT; Srivastava GK; Pastor JC; Fernandez-Bueno I. Mesenchymal stem cells provide paracrine neuroprotective resources that delay degeneration of co-cultured organotypic neuroretinal cultures.Experimental Eye Research. 185, 17/05/2019. DOI: 10.1016/j.exer.2019.05.011\n\nSalvatore Di Lauro; Maria Teresa Garcia Gutierrez; Ivan Fernandez Bueno. Quantification of pigment epithelium-derived factor (PEDF) in an ex vivo coculture of retinal pigment epithelium cells and neuroretina.\nJournal of Allbiosolution. 2019. ISSN 2605-3535\n\nSonia Labrador Velandia; Salvatore Di Lauro; Alonso-Alonso ML; Tabera Bartolomé S; Srivastava GK; Pastor JC; Fernandez-Bueno I. Biocompatibility of intravitreal injection of human mesenchymal stem cells in immunocompetent rabbits. Graefe's archive for clinical and experimental ophthalmology. 256 - 1, pp. 125 - 134. 01/2018. DOI: 10.1007/s00417-017-3842-3\n\n\nSalvatore Di Lauro, David Rodriguez-Crespo, Manuel J Gayoso, Maria T Garcia-Gutierrez, J Carlos Pastor, Girish K Srivastava, Ivan Fernandez-Bueno. A novel coculture model of porcine central neuroretina explants and retinal pigment epithelium cells. Molecular Vision. 2016 - 22, pp. 243 - 253. 01/2016.\n\nSalvatore Di Lauro. Classifications for Proliferative Vitreoretinopathy ({PVR}): An Analysis of Their Use in Publications over the Last 15 Years. Journal of Ophthalmology. 2016, pp. 1 - 6. 01/2016. DOI: 10.1155/2016/7807596\n\nSalvatore Di Lauro; Rosa Maria Coco; Rosa Maria Sanabria; Enrique Rodriguez de la Rua; Jose Carlos Pastor. Loss of Visual Acuity after Successful Surgery for Macula-On Rhegmatogenous Retinal Detachment in a Prospective Multicentre Study. Journal of Ophthalmology. 2015:821864, 2015. DOI: 10.1155/2015/821864\n\nIvan Fernandez-Bueno; Salvatore Di Lauro; Ivan Alvarez; Jose Carlos Lopez; Maria Teresa Garcia-Gutierrez; Itziar Fernandez; Eva Larra; Jose Carlos Pastor. Safety and Biocompatibility of a New High-Density Polyethylene-Based\nSpherical Integrated Porous Orbital Implant: An Experimental Study in Rabbits. Journal of Ophthalmology. 2015:904096, 2015. DOI: 10.1155/2015/904096\n\nPastor JC; Pastor-Idoate S; Rodríguez-Hernandez I; Rojas J; Fernandez I; Gonzalez-Buendia L; Di Lauro S; Gonzalez-Sarmiento R. Genetics of PVR and RD. Ophthalmologica. 232 - Suppl 1, pp. 28 - 29. 2014\n\nRodriguez-Crespo D; Di Lauro S; Singh AK; Garcia-Gutierrez MT; Garrosa M; Pastor JC; Fernandez-Bueno I; Srivastava GK. Triple-layered mixed co-culture model of RPE cells with neuroretina for evaluating the neuroprotective effects of adipose-MSCs. Cell Tissue Res. 358 - 3, pp. 705 - 716. 2014.\nDOI: 10.1007/s00441-014-1987-5\n\nCarlo De Werra; Salvatore Condurro; Salvatore Tramontano; Mario Perone; Ivana Donzelli; Salvatore Di Lauro; Massimo Di Giuseppe; Rosa Di Micco; Annalisa Pascariello; Antonio Pastore; Giorgio Diamantis; Giuseppe Galloro. Hydatid disease of the liver: thirty years of surgical experience.Chirurgia italiana. 59 - 5, pp. 611 - 636.\n(Italia): 2007. ISSN 0009-4773\n\nChapters in books\n\t\n' Salvador Pastor Idoate; Salvatore Di Lauro; Jose Carlos Pastor Jimeno. PVR: Pathogenesis, Histopathology and Classification. Proliferative Vitreoretinopathy with Small Gauge Vitrectomy. Springer, 2018. ISBN 978-3-319-78445-8\nDOI: 10.1007/978-3-319-78446-5_2. \n\n' Salvatore Di Lauro; Maria Isabel Lopez Galvez. Quistes vítreos en una mujer joven. Problemas diagnósticos en patología retinocoroidea. Sociedad Española de Retina-Vitreo. 2018.\n\n' Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor Jimeno. iOCT in PVR management. OCT Applications in Opthalmology. pp. 1 - 8. INTECH, 2018. DOI: 10.5772/intechopen.78774.\n\n' Rosa Coco Martin; Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor. amponadores, manipuladores y tinciones en la cirugía del traumatismo ocular.Trauma Ocular. Ponencia de la SEO 2018..\n\n' LOPEZ GALVEZ; DI LAURO; CRESPO. OCT angiografia y complicaciones retinianas de la diabetes. PONENCIA SEO 2021, CAPITULO 20. (España): 2021.\n\n' Múltiples desprendimientos neurosensoriales bilaterales en paciente joven. Enfermedades Degenerativas De Retina Y Coroides. SERV 04/2016. \n' González-Buendía L; Di Lauro S; Pastor-Idoate S; Pastor Jimeno JC. Vitreorretinopatía proliferante (VRP) e inflamación: LA INFLAMACIÓN in «INMUNOMODULADORES Y ANTIINFLAMATORIOS: MÁS ALLÁ DE LOS CORTICOIDES. RELACION DE PONENCIAS DE LA SOCIEDAD ESPAÑOLA DE OFTALMOLOGIA. 10/2014.",institutionString:null,institution:null},{id:"243698",title:"Dr.",name:"Xiaogang",middleName:null,surname:"Wang",slug:"xiaogang-wang",fullName:"Xiaogang Wang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243698/images/system/243698.png",biography:"Dr. Xiaogang Wang, a faculty member of Shanxi Eye Hospital specializing in the treatment of cataract and retinal disease and a tutor for postgraduate students of Shanxi Medical University, worked in the COOL Lab as an international visiting scholar under the supervision of Dr. David Huang and Yali Jia from October 2012 through November 2013. Dr. Wang earned an MD from Shanxi Medical University and a Ph.D. from Shanghai Jiao Tong University. Dr. Wang was awarded two research project grants focused on multimodal optical coherence tomography imaging and deep learning in cataract and retinal disease, from the National Natural Science Foundation of China. He has published around 30 peer-reviewed journal papers and four book chapters and co-edited one book.",institutionString:null,institution:null},{id:"7227",title:"Dr.",name:"Hiroaki",middleName:null,surname:"Matsui",slug:"hiroaki-matsui",fullName:"Hiroaki Matsui",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Tokyo",country:{name:"Japan"}}},{id:"312999",title:"Dr.",name:"Bernard O.",middleName:null,surname:"Asimeng",slug:"bernard-o.-asimeng",fullName:"Bernard O. Asimeng",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Ghana",country:{name:"Ghana"}}},{id:"318905",title:"Prof.",name:"Elvis",middleName:"Kwason",surname:"Tiburu",slug:"elvis-tiburu",fullName:"Elvis Tiburu",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Ghana",country:{name:"Ghana"}}},{id:"336193",title:"Dr.",name:"Abdullah",middleName:null,surname:"Alamoudi",slug:"abdullah-alamoudi",fullName:"Abdullah Alamoudi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Majmaah University",country:{name:"Saudi Arabia"}}},{id:"318657",title:"MSc.",name:"Isabell",middleName:null,surname:"Steuding",slug:"isabell-steuding",fullName:"Isabell Steuding",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Harz University of Applied Sciences",country:{name:"Germany"}}},{id:"318656",title:"BSc.",name:"Peter",middleName:null,surname:"Kußmann",slug:"peter-kussmann",fullName:"Peter Kußmann",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Harz University of Applied Sciences",country:{name:"Germany"}}}]}},subseries:{item:{id:"9",type:"subseries",title:"Biotechnology - Biosensors, Biomaterials and Tissue Engineering",keywords:"Biotechnology, Biosensors, Biomaterials, Tissue Engineering",scope:"The Biotechnology - Biosensors, Biomaterials and Tissue Engineering topic within the Biomedical Engineering Series aims to rapidly publish contributions on all aspects of biotechnology, biosensors, biomaterial and tissue engineering. We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics can include but are not limited to: Biotechnology such as biotechnological products and process engineering; Biotechnologically relevant enzymes and proteins; Bioenergy and biofuels; Applied genetics and molecular biotechnology; Genomics, transcriptomics, proteomics; Applied microbial and cell physiology; Environmental biotechnology; Methods and protocols. Moreover, topics in biosensor technology, like sensors that incorporate enzymes, antibodies, nucleic acids, whole cells, tissues and organelles, and other biological or biologically inspired components will be considered, and topics exploring transducers, including those based on electrochemical and optical piezoelectric, thermal, magnetic, and micromechanical elements. Chapters exploring biomaterial approaches such as polymer synthesis and characterization, drug and gene vector design, biocompatibility, immunology and toxicology, and self-assembly at the nanoscale, are welcome. Finally, the tissue engineering subcategory will support topics such as the fundamentals of stem cells and progenitor cells and their proliferation, differentiation, bioreactors for three-dimensional culture and studies of phenotypic changes, stem and progenitor cells, both short and long term, ex vivo and in vivo implantation both in preclinical models and also in clinical trials.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/9.jpg",hasOnlineFirst:!0,hasPublishedBooks:!0,annualVolume:11405,editor:{id:"126286",title:"Dr.",name:"Luis",middleName:"Jesús",surname:"Villarreal-Gómez",slug:"luis-villarreal-gomez",fullName:"Luis Villarreal-Gómez",profilePictureURL:"https://mts.intechopen.com/storage/users/126286/images/system/126286.jpg",biography:"Dr. Luis Villarreal is a research professor from the Facultad de Ciencias de la Ingeniería y Tecnología, Universidad Autónoma de Baja California, Tijuana, Baja California, México. Dr. Villarreal is the editor in chief and founder of the Revista de Ciencias Tecnológicas (RECIT) (https://recit.uabc.mx/) and is a member of several editorial and reviewer boards for numerous international journals. He has published more than thirty international papers and reviewed more than ninety-two manuscripts. His research interests include biomaterials, nanomaterials, bioengineering, biosensors, drug delivery systems, and tissue engineering.",institutionString:null,institution:{name:"Autonomous University of Baja California",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null,series:{id:"7",title:"Biomedical Engineering",doi:"10.5772/intechopen.71985",issn:"2631-5343"},editorialBoard:[{id:"35539",title:"Dr.",name:"Cecilia",middleName:null,surname:"Cristea",slug:"cecilia-cristea",fullName:"Cecilia Cristea",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYQ65QAG/Profile_Picture_1621007741527",institutionString:null,institution:{name:"Iuliu Hațieganu University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"40735",title:"Dr.",name:"Gil",middleName:"Alberto Batista",surname:"Gonçalves",slug:"gil-goncalves",fullName:"Gil Gonçalves",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYRLGQA4/Profile_Picture_1628492612759",institutionString:null,institution:{name:"University of Aveiro",institutionURL:null,country:{name:"Portugal"}}},{id:"211725",title:"Associate Prof.",name:"Johann F.",middleName:null,surname:"Osma",slug:"johann-f.-osma",fullName:"Johann F. 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Chapters exploring biomaterial approaches such as polymer synthesis and characterization, drug and gene vector design, biocompatibility, immunology and toxicology, and self-assembly at the nanoscale, are welcome. Finally, the tissue engineering subcategory will support topics such as the fundamentals of stem cells and progenitor cells and their proliferation, differentiation, bioreactors for three-dimensional culture and studies of phenotypic changes, stem and progenitor cells, both short and long term, ex vivo and in vivo implantation both in preclinical models and also in clinical trials.",annualVolume:11405,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/9.jpg",editor:{id:"126286",title:"Dr.",name:"Luis",middleName:"Jesús",surname:"Villarreal-Gómez",fullName:"Luis Villarreal-Gómez",profilePictureURL:"https://mts.intechopen.com/storage/users/126286/images/system/126286.jpg",institutionString:null,institution:{name:"Autonomous University of Baja California",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"35539",title:"Dr.",name:"Cecilia",middleName:null,surname:"Cristea",fullName:"Cecilia Cristea",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYQ65QAG/Profile_Picture_1621007741527",institutionString:null,institution:{name:"Iuliu Hațieganu University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"40735",title:"Dr.",name:"Gil",middleName:"Alberto Batista",surname:"Gonçalves",fullName:"Gil Gonçalves",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYRLGQA4/Profile_Picture_1628492612759",institutionString:null,institution:{name:"University of Aveiro",institutionURL:null,country:{name:"Portugal"}}},{id:"211725",title:"Associate Prof.",name:"Johann F.",middleName:null,surname:"Osma",fullName:"Johann F. 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