Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
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We wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
IntechOpen is proud to announce that 191 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
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Throughout the years, the list has named a total of 261 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\n
We wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
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The scope was to present reviews of established methods and new approaches in construction practice and in digital technology tools like building information modeling. The book is divided in four sections dealing with geological aspects of tunneling, analysis and design, new challenges in tunnel construction, and tunneling in the digital era. Topics from site investigation and rock mass failure mechanisms, analysis and design approaches, and innovations in tunnel construction through digital tools are covered in 10 chapters. The references provided will be useful for further reading.",isbn:"978-1-78985-466-4",printIsbn:"978-1-78985-465-7",pdfIsbn:"978-1-78985-914-0",doi:"10.5772/intechopen.77496",price:119,priceEur:129,priceUsd:155,slug:"tunnel-engineering-selected-topics",numberOfPages:294,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"c0c03565105a25fb6cfe85f83885afe3",bookSignature:"Michael Sakellariou",publishedDate:"March 18th 2020",coverURL:"https://cdn.intechopen.com/books/images_new/7690.jpg",numberOfDownloads:15115,numberOfWosCitations:1,numberOfCrossrefCitations:13,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:16,numberOfDimensionsCitationsByBook:1,hasAltmetrics:1,numberOfTotalCitations:30,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"January 29th 2019",dateEndSecondStepPublish:"March 14th 2019",dateEndThirdStepPublish:"May 13th 2019",dateEndFourthStepPublish:"August 1st 2019",dateEndFifthStepPublish:"September 30th 2019",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"16550",title:"Dr.",name:"Michael",middleName:null,surname:"Sakellariou",slug:"michael-sakellariou",fullName:"Michael Sakellariou",profilePictureURL:"https://mts.intechopen.com/storage/users/16550/images/system/16550.jpg",biography:"Michael Sakellariou is a professor emeritus of Geomechanics and Engineering Structures at the National Technical University of Athens (NTUA). He studied Civil Engineering and Rural and Surveying Engineering at NTUA. He holds an MSc in Engineering Rock Mechanics from Imperial College London, and he obtained his PhD in Applied Mechanics from NTUA (1989). In his professional career, he was collaborator of engineering companies in major infrastructure projects. His teaching experience covers engineering mechanics, continuum mechanics, geotechnical engineering, soil mechanics and foundations, and engineering materials at undergraduate and postgraduate levels. His interests cover experimental mechanics, analytical and computational methods in geotechnical engineering, application of artificial intelligent and GIS in geotechnical engineering, structures monitoring using optical fiber sensors, and tectonic fault stress analysis.",institutionString:"National Technical University of Athens",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"2",institution:{name:"National Technical University of Athens",institutionURL:null,country:{name:"Greece"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"284",title:"Civil Engineering",slug:"technology-civil-engineering"}],chapters:[{id:"70990",title:"Engineering Geology and Tunnels",doi:"10.5772/intechopen.90462",slug:"engineering-geology-and-tunnels",totalDownloads:1997,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Currently, knowledge and understanding of the role of geological material and its implication in tunnel design is reinforced with advances in site investigation methods, the development of geotechnical classification systems and the consequent quantification of rock masses. However, the contribution of engineering geological information in tunnelling cannot be simply presented solely by a rock mass classification value. What is presented in this chapter is that the first step is not to start performing numerous calculations but to define the potential failure mechanisms. After defining the failure mechanism that is most critical, selection of the suitable design parameters is undertaken. This is then followed by the analysis and performance of the temporary support system based on a more realistic model. The specific failure mechanism is controlled and contained by the support system. A tunnel engineer must early assess all the critical engineering geological characteristics of the rock mass and the relevant mode of failure, for the specific factors of influence, and then decide either he or she will rely on a rock mass classification value to characterise all the site-specific conditions. Experiences from the tunnel behaviour of rock masses in different geological environments in Alpine mountain ridges are presented in this chapter.",signatures:"Vassilis Marinos",downloadPdfUrl:"/chapter/pdf-download/70990",previewPdfUrl:"/chapter/pdf-preview/70990",authors:[{id:"298713",title:"Associate Prof.",name:"Vassilis",surname:"Marinos",slug:"vassilis-marinos",fullName:"Vassilis Marinos"}],corrections:null},{id:"68534",title:"Advanced Geological Prediction",doi:"10.5772/intechopen.88406",slug:"advanced-geological-prediction",totalDownloads:1115,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Due to the particularity of the tunnel project, it is difficult to find out the exact geological conditions of the tunnel body during the survey stage. Once it encounters unfavorable geological bodies such as faults, fracture zones, and karst, it will bring great challenges to the construction and will easily cause major problems, economic losses, and casualties. Therefore, it is necessary to carry out geological forecast work in the tunnel construction process, which is of great significance for tunnel safety construction and avoiding major disaster accident losses. This lecture mainly introduces the commonly used methods of geological forecast in tunnel construction, the design principles, and contents of geological forecast and combines typical cases to show the implementation process of comprehensive geological forecast. Finally, the development direction of geological forecast theory, method, and technology is carried out. Prospects provide a useful reference for promoting the development of geological forecast of tunnels.",signatures:"Shaoshuai Shi, Xiaokun Xie, Siming Tian, Zhijie Wen, Lin Bu, Zongqing Zhou, Shuguang Song and Ruijie Zhao",downloadPdfUrl:"/chapter/pdf-download/68534",previewPdfUrl:"/chapter/pdf-preview/68534",authors:[{id:"249088",title:"Dr.",name:"Shaoshuai",surname:"Shi",slug:"shaoshuai-shi",fullName:"Shaoshuai Shi"},{id:"296501",title:"Dr.",name:"Xie",surname:"Xiaokun",slug:"xie-xiaokun",fullName:"Xie Xiaokun"},{id:"302553",title:"Prof.",name:"Zhijie",surname:"Wen",slug:"zhijie-wen",fullName:"Zhijie Wen"},{id:"302554",title:"Prof.",name:"Siming",surname:"Tian",slug:"siming-tian",fullName:"Siming Tian"},{id:"302555",title:"Prof.",name:"Zongqing",surname:"Zhou",slug:"zongqing-zhou",fullName:"Zongqing Zhou"},{id:"302556",title:"Dr.",name:"Shuguang",surname:"Song",slug:"shuguang-song",fullName:"Shuguang Song"}],corrections:null},{id:"70869",title:"Topics of Analytical and Computational Methods in Tunnel Engineering",doi:"10.5772/intechopen.90849",slug:"topics-of-analytical-and-computational-methods-in-tunnel-engineering",totalDownloads:998,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"In this chapter, a selection of tunneling topics is presented, following the evolution of methods and tools from analytical to computational era. After an introductory discussion of the importance of elasticity and plasticity in tunneling, some practical topics are presented as paradigms to show the successful application of them in achieving a solution. The circular and horseshoe tunnel sections served as the basis of the elastic analysis of deep tunnels. Practical aspects such as influence zone and elastic convergences in both cases are examined. In the case of circular tunnels, the estimation of plastic zone formation is discussed for a selection of strength criteria. After a detailed discussion of the influence of surface proximity, the elastic and plastic analysis of shallow tunnels is examined in some detail. The presentation is completed by a short presentation of computational methods. An overview of recent developments and a classification of the methods are presented, and then some problems for the case of anisotropic rocks have been presented using finite element method (FEM). The last topic is the application of artificial intelligence (AI) tools in interpreting data and in estimating the relative importance of parameters involved in the problem of tunneling-induced surface settlements. In the conclusions a short discussion of the main topics presented follows.",signatures:"Michael G. Sakellariou",downloadPdfUrl:"/chapter/pdf-download/70869",previewPdfUrl:"/chapter/pdf-preview/70869",authors:[{id:"16550",title:"Dr.",name:"Michael",surname:"Sakellariou",slug:"michael-sakellariou",fullName:"Michael Sakellariou"}],corrections:null},{id:"69298",title:"Impact of Tunnels and Underground Spaces on the Seismic Response of Overlying Structures",doi:"10.5772/intechopen.89338",slug:"impact-of-tunnels-and-underground-spaces-on-the-seismic-response-of-overlying-structures",totalDownloads:849,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Depending on the circumstances, the design and construction of tunnels and underground spaces may be very challenging. In the case of an underground project located at a relatively shallow depth in an urban area, the design and construction will probably be more demanding since there is a potential interaction between the underground project and the overlying pre-existing structure(s) that are founded at the ground surface, such as buildings, bridges, etc. This interaction is generally related to the (usually differential) settlements at the ground surface due to the excavation and the consequent distress of the overlying structures. Nevertheless, in areas that are characterized by seismicity, this interaction may be more complicated, since, apart from the aforementioned static interaction, various phenomena of soil dynamics and dynamic interaction may take place, dominating thus the seismic excitation, response, and distress of the overlying structure(s). The current chapter deals with this interesting topic of geotechnical earthquake engineering. After a literature review, some indicative numerical analyses have been performed in order to determine the impact of the main parameters involved. Although the problem is generally complex and multi-parametrical, the numerical results are indicative of the dynamic interaction between the underground project, the ground, and the overlying structure(s).",signatures:"Prodromos Psarropoulos",downloadPdfUrl:"/chapter/pdf-download/69298",previewPdfUrl:"/chapter/pdf-preview/69298",authors:[{id:"298007",title:"Dr.",name:"Prodromos",surname:"Psarropoulos",slug:"prodromos-psarropoulos",fullName:"Prodromos Psarropoulos"}],corrections:null},{id:"70605",title:"Designing a Tunnel",doi:"10.5772/intechopen.90182",slug:"designing-a-tunnel",totalDownloads:2798,totalCrossrefCites:3,totalDimensionsCites:4,hasAltmetrics:0,abstract:"Designing a tunnel is always a challenge. For shallow tunnels under cities due to the presence of buildings, bridges, important avenues, antiquities, etc. at the surface and other infrastructures in the vicinity of underground tunnels, parameters like vibrations and ground settlements must be tightly controlled. Urban tunnels are often made in soils with very low values of overburden. Risks of collapse and large deformations at the surface are high; thus negative impact on old buildings are likely to occur if appropriate measures are not taken in advance, when designing and constructing the tunnel. For deep tunnels with high overburden and low rock mass properties, squeezing conditions and excessive loads around the excavation can jeopardize the stability of the tunnel, leading to extensive collapse. The aim of the chapter is to give details on advance computational modelling and analytical methodologies, which can be used in order to design shallow and deep tunnels and to present real case studies from around the world, from very shallow tunnels in India with only 4.5 m overburden to a deep tunnel in Venezuela with extreme squeezing conditions under 1300 m overburden.",signatures:"Spiros Massinas",downloadPdfUrl:"/chapter/pdf-download/70605",previewPdfUrl:"/chapter/pdf-preview/70605",authors:[{id:"295762",title:"Dr.",name:"Spiros",surname:"Massinas",slug:"spiros-massinas",fullName:"Spiros Massinas"}],corrections:null},{id:"67810",title:"Transit-Oriented Development Interactions on Existing Metro Systems: The Need for the Design of Adequate Structural Monitoring System and the Experience from International Projects",doi:"10.5772/intechopen.86923",slug:"transit-oriented-development-interactions-on-existing-metro-systems-the-need-for-the-design-of-adequ",totalDownloads:1050,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Contemporary metro transport systems present unrivaled efficiency for the commuting population. The development of the urban environment is interwoven with the metro transit systems. The transit-oriented development (TOD) is an upcoming topic in the design of the contemporary and of the future city and metro system alike. It entails the development of a microcell of the city centered around the metro station. Typically, bulky TOD buildings rise over and around the station and tunnel. The structural engineering aspect of these mega projects is highly complex. Major part of the complexity is due to complicated interactions between the oversite building and the underlying tunnel or station with its track-rail system. A significant number of issues arise, like methods to bridge over the tunnel or station, structural isolation, induced displacements to the track-rail system, tunnel movements and impact to tracks, vibration induction to the TOD building, and a plenitude of similar problems. It is highly important to design a structural monitoring system that will provide a validation tool of the structural-dynamic performance of the closed system TOD-tunnel/station. The distilled experience from international projects is presented.",signatures:"Evangelos Astreinidis",downloadPdfUrl:"/chapter/pdf-download/67810",previewPdfUrl:"/chapter/pdf-preview/67810",authors:[{id:"295208",title:"Dr.",name:"Evangelos",surname:"Astreinidis",slug:"evangelos-astreinidis",fullName:"Evangelos Astreinidis"}],corrections:null},{id:"67958",title:"Innovative Concepts in TBM Tunnels",doi:"10.5772/intechopen.87965",slug:"innovative-concepts-in-tbm-tunnels",totalDownloads:1324,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Tunnel boring machine (TBM) tunnels are increasingly used in the construction of transport infrastructure, allowing for reduction of the environmental impact and cost and time of construction. Despite these advantages, TBM tunnels still face major challenges such as further cost reduction, the structural safety under earthquakes, and the improvement of safety during operation in the case of traffic tunnels (rail and road tunnels). To overcome these challenges, three innovative and very cost-effective concepts for the construction of TBM tunnels were recently developed by the author: the tunnel of improved seismic behavior (TISB) concept for improving structural safety of tunnels on soft ground in seismic areas and the tunnel multi-floor (TMF) and tunnel multi-gallery (TMG) concepts for road and rail tunnels, respectively, which allow an even greater cost reduction and improvement of safety in operation. In this paper these concepts are presented as well as their application in some specific cases, emphasizing the obtained added value.",signatures:"Silvino Pompeu-Santos",downloadPdfUrl:"/chapter/pdf-download/67958",previewPdfUrl:"/chapter/pdf-preview/67958",authors:[{id:"294864",title:"Dr.",name:"Silvino",surname:"Pompeu-Santos",slug:"silvino-pompeu-santos",fullName:"Silvino Pompeu-Santos"}],corrections:null},{id:"68148",title:"Design of Immersed Tunnel and How We Research Submerged Floating Tunnel",doi:"10.5772/intechopen.88169",slug:"design-of-immersed-tunnel-and-how-we-research-submerged-floating-tunnel",totalDownloads:1234,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"This chapter begins with the discussion of the immersed tunnel design, concerning its reason of existence, historical review, general design, transverse and longitudinal design, the interaction, and the critical issues. The discussion is founded on the author’s 10 year experience in building the Hong Kong-Zhuhai-Macao Bridge (HZMB) immersed tunnel as a site design engineer. The experience of building immersed tunnel is transferable to build the submerged floating tunnel, which has never been built. In author’s opinion, the submerged floating tunnel (SFT) technique will be the next generation of IMT technique. In the second part of this chapter, the author proceeds to discuss the strategy of SFT research and the latest development in CCCC SFT Technical Joint Research Team.",signatures:"Wei Lin, Ming Lin, Haiqing Yin and Xiaodong Liu",downloadPdfUrl:"/chapter/pdf-download/68148",previewPdfUrl:"/chapter/pdf-preview/68148",authors:[{id:"294918",title:"Mr.",name:"Wei",surname:"Lin",slug:"wei-lin",fullName:"Wei Lin"},{id:"308878",title:"Dr.",name:"Haiqing",surname:"Yin",slug:"haiqing-yin",fullName:"Haiqing Yin"},{id:"308879",title:"Dr.",name:"Xiaodong",surname:"Liu",slug:"xiaodong-liu",fullName:"Xiaodong Liu"},{id:"308937",title:"Mr.",name:"Ming",surname:"Lin",slug:"ming-lin",fullName:"Ming Lin"}],corrections:null},{id:"68102",title:"Digital Construction Strategies and BIM in Railway Tunnelling Engineering",doi:"10.5772/intechopen.87942",slug:"digital-construction-strategies-and-bim-in-railway-tunnelling-engineering",totalDownloads:2544,totalCrossrefCites:4,totalDimensionsCites:4,hasAltmetrics:1,abstract:"Technology has been a strong driver for industrial efficiency in the twenty-first century. Rapid growth in infrastructure projects such as tunnels is synonymous with both disruptive and supportive technologies that automate operations. The sector has rapidly risen to the challenge from buyers demanding a more digitalised experience when looking to (re)design new tunnels. Currently there are projects in the United Kingdom, Greece and Italy investing in tunnels for their transport networks to help commuters to travel quicker. We could argue that construction has evolved because the tunnels developed nowadays are expected to last for several generations but such an argument is count intuitive. Think of having to spend billions of pounds for a tunnel that does not provide an enhanced travel experience and in a few years’ time requiring a major investment to remodel in order to operate it. This chapter discusses what, why and how digital construction can add value during the lifecycle of a tunnel.",signatures:"Georgios Kapogiannis and Attwell Mlilo",downloadPdfUrl:"/chapter/pdf-download/68102",previewPdfUrl:"/chapter/pdf-preview/68102",authors:[{id:"296272",title:"Dr.",name:"Georgios",surname:"Kapogiannis",slug:"georgios-kapogiannis",fullName:"Georgios Kapogiannis"},{id:"302733",title:"Mr.",name:"Attwell",surname:"Mlilo",slug:"attwell-mlilo",fullName:"Attwell Mlilo"}],corrections:null},{id:"68331",title:"BIM and Advanced Computer-Based Tools for the Design and Construction of Underground Structures and Tunnels",doi:"10.5772/intechopen.88315",slug:"bim-and-advanced-computer-based-tools-for-the-design-and-construction-of-underground-structures-and-",totalDownloads:1211,totalCrossrefCites:2,totalDimensionsCites:2,hasAltmetrics:1,abstract:"Technology and digitalization are continuously producing changes in sectors and fields of human activities. Infrastructure industry needs this support in various and extensive ways, since it affects involved parties and society overall. Even though many individual branches have been transformed, design and construction show some kind of reluctance on encouraging and implementing comprehensive digitalization. A major reason is the significantly high complexity of infrastructure projects and the extended chains of work procedures and activities that are produced. All those are applying through the whole time scale of buildings’ existence. Considering that safety and durability remain always the ultimate goal, every new method and concept shall be exhaustively tested, in order to prove its value and efficiency. The current chapter aims to define and prove technology contribution all along the infrastructure sector, concentrating in tunnels and underground structures. Since evolution is proceeding in accelerated rates, future perspectives are also analyzed to provide broader visions and set indicative standpoints for potential and incentives.",signatures:"Panayotis Kontothanasis, Vicky Krommyda and Nikolaos Roussos",downloadPdfUrl:"/chapter/pdf-download/68331",previewPdfUrl:"/chapter/pdf-preview/68331",authors:[{id:"296644",title:"Dr.",name:"Panagiotis",surname:"Kontothanasis",slug:"panagiotis-kontothanasis",fullName:"Panagiotis Kontothanasis"},{id:"305011",title:"MSc.",name:"Vicky",surname:"Krommyda",slug:"vicky-krommyda",fullName:"Vicky Krommyda"},{id:"305130",title:"MSc.",name:"Nikolaos",surname:"Roussos",slug:"nikolaos-roussos",fullName:"Nikolaos Roussos"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"5915",title:"Granular 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\r\n\tAn inverse problem, which starts with the causes and then calculates the effects, covers many fields of science. In many cases, models of given inverse problems can be linearized which allows the use of methods of linear algebra for their solutions. Effective tools of linear algebra in linear inverse problems are, in particular, generalized inverse matrices as one of the ways to represent (pseudo)solutions to singular (differential) matrix equations. Nowadays, the theory of generalized inverses is one of the hot topics of linear algebra in various aspects, such as elements of the ring, operators of Hilbert space, or matrices with real, complex, and quaternion entries. Matrices over quaternion algebra are also useful tools in a lot of applied inverse problems, among them in signal and color image processing, quantum physics, etc. In recent years, methods of simultaneous decompositions for tensors have been actively used in different inverse problems. In particular, a product singular value decomposition of a quaternion tensor triplet (higher-order PSVD) has various applications in digital watermarking technology. The main goals of this book are both to give the last achievements in various areas of linear algebra, such as generalized inverses and their applications in solving matrix equations and matrix minimization problems, decompositions of matrices and tensors, new developments in theories of quaternion matrices, and operators of Hilbert space, etc. It is also important to consider new applying models of inverse problems that can be linearized.
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\n
1. Introduction
\n
\n
1.1. Background
\n
To date, purulent bacterial meningitis (PBM) remains a global health challenge. Meningococcal meningitis occurs in small clusters throughout the World with seasonal variation, accounts for a variable proportion of epidemic bacterial meningitis, and is one of the leading causes of such meningitis globally with a burden that, in 2012 encompassed 395,230 deaths, or 0.7% of global mortality [1, 2].
\n
Meningococcal disease or meningococcal meningitis is caused by bacterium Neisseria meningitidis, also called meningococcus. Meningococcal bacteria may cause infection, which occurs in different compartment of the body, called invasive meningococcal disease (IMD), including skin, gastrointestinal tract, or respiratory tract, among others. Ultimately, the bacteria may pass through the bloodstream and reach the nervous system causing meningococcal meningitis. After an incubation period of 2–10 days, clinical presentation starts with symptoms similar to influenza (flu-like), which cause nausea, vomiting, rash, increased sensitivity to light, and confusion. Symptoms of meningococcal disease appear usually as a sudden onset of fever, headache, and stiff neck. When treated, most patients with meningococcal meningitis recover completely with appropriate antibiotic therapy and rapid medical attention. Also, meningitis can cause severe brain damage and be fatal for 50% of untreated cases.
\n
There is no animal reservoir, and N. meningitidis is obligate commensals of human and can colonize the nasopharyngeal mucosa without affecting the host, a phenomenon known as carriage. Such asymptomatic carriage of meningococcus is the most prevalent form of meningococcal infection. In none-epidemic settings, approximately 10–35% of healthy individuals carry N. meningitidis in the upper airway [3, 4]. Thus, only in very rare cases, N. meningitidis is the cause of invasive meningococcal disease. N. meningitidis is transmitted from person-to-person through respiratory droplets or throat secretions from carriers or eventually patients. The risk of transmission and spread increases in particular by close and prolonged contact (e.g., kissing, sneezing, coughing, promiscuity, and sharing food or drinking utensils) with an infected person (symptomatic or asymptomatic (i.e., carrier). Moreover, such risk increases with recent upper respiratory infection, while young children and teen-agers are at greatest risk of infection.
\n
Several types of meningococcal vaccines are available including Meningococcal Polysaccharide vaccines as bivalent (groups A and C), trivalent (groups A, C and W), or tetravalent (groups A, C, Y and W). Tetravalent A, C, Y, and W conjugate vaccines have been licensed since 2005 for use in children and adults in Canada, the United States of America, and Europe. Since 1999, meningococcal conjugate vaccines against group C have been available and widely used. (e.g., Meningococcal conjugate vaccine; Meningococcal polysaccharide vaccine; Serogroup B Meningococcal B) and are recommended vaccines as the best that can prevent meningitis infection. As of June 2015, over 220 million persons aged 1–29-year old received meningococcal A conjugate vaccine against the most meningitis type prevalent among 15 countries of the African belt [2].
\n
\n
\n
1.2. Epidemic pattern of Meningococcal meningitis in Europe
\n
There is a reported reduction of morbidity of Invasive Meningococcal Disease (IMD) in the European countries (i.e., EU/EEA): The total number of confirmed cases of the IMD fell from 7995 to 3463 for the period from 1999 to 2012. In countries with a meningococcal serogroup C vaccination program, the number of cases fell from 4840 to 2380, in countries where systematic immunization campaigns are not applied incidence decreased from 3155 cases to 1083 cases [5, 6]. Therefore, a reduction of IMD mortality in EU/EEA countries was reported that diminished from 0.163 to 0.055 per 100,000 people from 1992 to 2012 [7]. Although, IMD is relatively rare in Europe (0.68 cases/100,000 people in 2012), country-specific rates of confirmed IMD range from 0.11 to 1.77 cases per 100,000 people [8].
\n
Worldwide, most IMD cases are caused by serogroups B and C. Serogroup Y prevalence has been increasing but remains less frequent than B and C. An overall decreasing trend has been observed over the last 10 years, partly attributable to the introduction of serogroup C conjugate vaccine to national immunization schedules in several European countries.
\n
Finally, it is of importance to strengthen surveillance of meningococcal disease in order to reduce burden of the disease (including patient and carrier) and to evaluate the impact of the ongoing vaccination programs, and support decision-makers with respect to the availability of new vaccines [6].
\n
\n
\n
\n
2. Meningococcal infection biosurveillance and Public Health response and control in Ukraine
\n
The purpose of epidemiological surveillance of meningococcal infection (MI) is to prevent deaths and reduce disease morbidity risk groups. A retrospective epidemiological analysis of MI must include data monitoring morbidity risk groups (e.g., children aged of 0–1 and 1–4 years old), and other young people as which came as socio-organized as group indicators (i.e., including school, kindergartens, orphanages, vocational colleges, university, among others). Equally important is the analysis of total mortality and mortality by risk groups and their dynamics. In addition, data are analyzed from microbiological monitoring of “indicator groups.” Moreover, there is a national serological monitoring of MI pathogens.
\n
In epidemic foci of MI, patients with IMD are hospitalized and isolated while and a 10 days’ medical observation of contact-persons is conducted (thermometry and examination of the skin and mucous membranes of the nasopharynx). Bacteriological tests are done twice among organized groups and once at home (i.e., family contact) within epidemic foci. Surveillance of other purulent meningitis is carried out as for meningococcal infection.
\n
In Ukraine, since the 1920s, MI cases introduced are registered as well as Haemophilus influenzae type B Hib-meningitis cases are registered since 2010. From 2012, pneumococcal meningitis (PM) and all other bacterial meningitis are also registered. Vaccination against Hib-infection was included in the routine immunization program in 2006 by the Ministry of Health, while it is considering now to introduce a national vaccination campaigns against meningococcal and pneumococcal disease. As of 2013, an estimated of 68.9% of Ukrainians lives in urban areas including the 68.2% of the population over 45 years old [8].
\n
Since 2007, there is a Central Reference Laboratory for invasive bacterial diseases (IBD) characterizing and supervising the dynamic of IBD pathogens in order to forecast and reduce (preventive measures) the incidence of IBD. The State institution “Ukrainian Centre for Disease Control and monitoring of the Ministry of Health of Ukraine” is a reference as part of the IBD-laboratory WHO and UNICEF networks. A sentinel surveillance system included all patients younger than 5 years clinically suspected of meningitis and hospitalized as hospital in-patient of either the department of infectious disease or intensive care unit.
\n
\n
\n
3. Temporal and spatialdynamics of meningococcal infection in Ukraine
\n
\n
3.1. Place and time of meningococcal infection and other purulent meningitis
\n
Purulent bacterial meningitis (PBM) is a group of diseases of multi-bacterial etiology that determines the nature of the treatment, laboratory diagnostic approach and epidemiological characteristics for control and prevention. Indeed, PBM transmission and clinical presentation are fully dependent on the etiologic agent and concurrent risk factor. PBM etiology will ensure a successful causal treatment and important information regarding the whole nosology of the meningitis and epidemiology pattern. Bacteriological etiological diagnosis of PBM has been carried out for 24 years (1992–2015) in Ukraine (Ukrainian Centre for Disease Control and monitoring of the Ministry of Health): 37,843 cases were registered as PBM, among them, 18,878 were of purulent meningitis of meningococcal origin and other IMD. The ratio of meningococcal meningitis to non-meningococcal meningitis was about more or less of 1:1 (i.e., 49.89 to 50.11%) (\nFigure 1\n).
\n
Figure 1.
Incidence dynamics of different etiological forms of bacterial meningitis (Ukraine, 1992–2015). Legend: Abscissa = time (year); Ordinate = case of bacterial meningitis per 100,000 people; Empty diamond = Meningococcal Disease (MD); Empty square = Other Meningitis (caused by Staphylococcus aureus, Streptococcus groups A and B, Klebsiella pneumoniae, Escherichia coli, Listeria monocytogenes and PBM of unknown etiology); Empty circle = PBM pneumococcus (Purulent Bacterial Meningitis caused by Streptococcus pneumonia); Cross = Haemophilus influenzae type b (Hib).
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The use of microbiological monitoring of PBM in Ukraine allowed to determine the etiological origin of 37,843 cases from 1992 to 2012. The basic etiological agents PBM included: Meningococci (49.89%); Pneumococci (6.34%); Staphylococci, Streptococci and others (Escherichia spp., Listeria spp., etc.) (17.30%); Hib-infection (0.71%), and pathogens of unknown etiology (25.77%). Among the 21,359 registered cases of MI, 9986 cases (46.75%) were confirmed to be of bacteriological origin. Bacteriological confirmation of MI ranges from 33.71% in 1993 to 55.95% 9 years after (2002) (\nFigure 2\n).
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Figure 2.
Etiological structure of purulent meningitis cases in Ukraine (1992–2012). Legend: Abscissa = Time (year); Ordinate = relative percentage of the bacterial meningitis etiology; oblique lines = Meningococcal Infection (MI); vertical lines = Staphylococcal and Other PBM (caused by Staphylococcus aureus, Streptococcus groups A and B, Klebsiella pneumoniae, Escherichia coli, Listeria monocytogenes and other PBM); horizontal lines = PBM of unknown etiology); points = PBM pneumococcus (Purulent Bacterial Meningitis caused by Streptococcus pneumoniae); black = Haemophilus influenzae type b (Hib-PBM).
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Meningococcal infection predominated among all bacterial meningitis during the whole period of observation. However, half of all non-meningococcal meningitis as well as IMD did not have bacteriological confirmation the bacteriological tests were done almost in all patients but were not positive for half of all meningococcal meningitis. Thus, the total sensitivity of bacteriological tests was inadequate (nearly 50%).
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3.2. Time series of morbidity and mortality of meningococcal infection in Ukraine
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In 1969, an incidence of less than 0.9 per 100,000 people of MI was recorded. Since then, the incidence began to rise and lasted until 1985. For decade (1973–2012), MI incidence (including all clinical forms) ranged from 6.7 (1985) to 0.83 (2012) per 100,000 people. Instead, in the long term, of IMD and mortality appear be very specific and different dynamics, while IMD incidence is much lower and ranges from 2.22 (1974) to 0.75 (2012) per 100,000 people with a mortality from 0.84 (1983) to 0.09 (\nFigure 3\n).
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Figure 3.
Morbidity and mortality dynamics of meningococcal infection in Ukraine of a decade of observation (1973–2015). Legend: Abscissa = time (year); Ordinate = patient meningococcal infection per 100,000 people; line with empty square = Meningococcal Infection (total MI, all clinic forms); line with empty diamond = Invasive Meningococcal Disease (IMD); line with empty triangle = total Mortality of Meningococcal Infection.
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There is a significant decrease morbidity and mortality of MI for the last 33 years in Ukraine. Between 1983 and 2015 the incidence of MI decreased by 7.2 times. Between 1973 and 2015 the incidence of MI decreased by 5.4 times. In 2012 in Ukraine, IMD incidence (0.75 per 100,000) was comparable to the one of EU (0.7 per 100,000). However, death rate in Ukraine (0.09 per 100,000) was higher than in the EU (0.06 per 100,000). Also, this has to take into account that half of the cases of MI in Ukraine are not bacteriologically confirmed.
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3.3. Seasonality of meningococcal infection in Ukraine
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From 1992 to 2015, most IMD cases occurred in winter and spring, as for other respiratory diseases in Ukraine. IMD incidence peaked up in March, while the lowest number of cases was reported in August (\nFigure 4\n). During that same period of time, 938 cases of IMD were regularly reported on the monthly base, and seasonal increase was registered when the number of monthly cases exceeded 78 (938 cases / 12 month = 78.2 ≈ 78). Seasonal incidence rise was lasted for 6 months (from December to June) with a cumulative total number of 554 cases corresponding 59.06% annual incidence (i.e., seasonal coefficient with regard to the 9.84% average for each of these months. A 334 (40.94%) as of MI cases occurred during the seasonal rise with a monthly increase of 6.82%. One can ultimately evaluate the cases associated with seasonal risk factors that were in 18.66%, i.e. (9.84% – 6.82%) × 6 months = 18.66%.
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Figure 4.
Seasonal distribution of meningococcal infection in Ukraine (1992–2015). Legend: Abscissa = time (months); Ordinate = absolute number of cases of meningococcal infection; Gray line = the average monthly number of Meningococcal Infection (MI) cases of long-term; Empty diamond = number of Meningococcal Infection (MI) cases by month.
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Thus, the impact of seasonal factors on the annual incidence is very moderate, that is, annual incidence of MI is due to the seasonality of not more than one-fifth of part. Over 80% of incidence of MI depends on the action of permanent factors. Our hypothesis is that the proportion of susceptible population and the frequency of contacts between people (at risk of infection) are the basic are a permanent risk of MI transmission. We also assume that its values are slightly slowly changing throughout the year. Such seasonal rise was observed in Europe from December to June is also characterized by a seasonality pattern as it is in Ukraine, with the highest rate reporting during winter [8].
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3.4. Geographical distribution
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The incidence of MI is unevenly distributed on a geographical ground and expressed by ANOVA MI incidence for the 1992–2013 period of times among administrative units of Ukraine. Estimated value (Fisher’s test = 8.52, > critical value of 1.52) rejects the null hypothesis of no effect of geographical factors on the incidence of MI. Indeed, \nFigure 5\n shows the uneven geographical distribution of the disease by administrative units with low, medium, and high levels of incidence.
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Figure 5.
Incidence of meningococcal disease in Ukraine by oblast (1992–2013). Legend: light-gray = Low incidence of Meningococcal Disease (less than 25 percentiles, IR<1.69); moderately gray = Middle incidence of Meningococcal Disease (between 25 and 75 percentile, IR = 1.69 ÷ 2.18); gray = High incidence of Meningococcal Disease (higher 75 percentile, IR > 2.18).
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At first, the geographical distribution of MI incidence depends on population age pyramid including, the total population of the study area, the urban population and the child population of 0–14 or 0–4-year old. We therefore calculated the corresponding correlation coefficients, but ultimately lacked of statistical significance between prevalence and administrative units. MI incidence correlation coefficients, when compared to different group, were equal to: 0.3260 versus population density; 0.036 versus total population; 0.1711 versus urban population percentage; 0.1370 versus children aged 0–14; and 0.1968 versus the children aged 0–4 years. We believe that the lack of statistical significance between these indicators suggest sporadic (or random) spatial nature distribution of the disease. Also, ANOVA analysis shows significant differences in the incidence among oblasts, but the correlation analysis of individual factors (population density, age structure, etc.) by oblasts did not show any incidence because the population density and age structure are indirect factors. Thus, we can assume that geographical factors of each individual territory are quite stable, while geography has a limited effect on changes in incidence of MI in Ukraine. Geographical distribution of MI incidence is useful for comparing performance in different areas, but it cannot account for observed differences more likely linked to the multicomponent result with other causal factors. Also, the variable power of causal factors in any oblast could explain the differences in the incidence oblasts. In our case, the geographical distribution of the incidence of MI is a little informative because do not allowed to identify direct factors (i.e., risk of infection and/or risk of susceptibility).
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3.5. Age distribution
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The total incidence of MI decreased over the study period in Ukraine among all age groups, while it remains the highest among young children (\nFigure 6\n).
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Figure 6.
Dynamics of the incidence of meningococcal infection in Ukraine by age group (1990–2014). Legend: Abscissa = time (year); Ordinate = person with meningococcal infection per 100,000 people by age group; Triangle = Incidence of Meningococcal Disease among the population aged over 15 years; Square = Incidence of Meningococcal Disease among children aged 0-14 years; Diamond = Incidence of Meningococcal Disease among the total population.
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In Ukraine, the proportion of MI infected children under 14 years represented 77.17% of all cases as compared to 49.81% among the same xc of age of other European countries at large [8]. Thus, children under 14 years in Ukraine are at a major risk for MI infection, and mortality rates account for 78.35% (\nFigure 7\n). Altogether, there is a strong direct relationship of MI incidence among age groups that exactly fit the local pyramid of age.
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Figure 7.
Mortality of meningococcal infectious disease among you children by class of age (Ukraine, 1965–2012). Legend: Legend: Abscissa = time (year); Ordinate = person with meningococcal infection per 100,000 people by age class; Empty circle = Incidence of Meningococcal Disease among children aged 0-14 years; Square = Incidence of Meningococcal Disease among children aged 0-1 years; Diamond = Incidence of Meningococcal Disease among the total population; Triangle = Incidence of Meningococcal Disease among children aged 0-4 years.
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The correlation coefficient between the total number of cases of MI and the number of population for the years was r = 0.9676 (1990–2014). The correlation coefficient between the overall incidence and the total population was r = 0.9556 (\nFigure 8\n).
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Figure 8.
The dynamics of relationship between the overall incidence of meningococcal infection and the general population (Ukraine, 1990–2014). Legend: Abscissa = time (year); Ordinate = case of meningococcal infection per 100,000 people; Diamond = number of the total population; Triangle = Incidence of Meningococcal Disease among the total population.
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The correlation coefficient between number of the MI cases among children 0–14 years of age and number of children was of 0.9531. The correlation coefficient between the MI incidence among children 0–14 years of age and number of children was of 0.8163. The correlation coefficient between the total incidence of MI and the number of children was 0.9239. The correlation coefficient between the total number of cases of MI and the number of children was 0.9420.
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All of the above present a direct and strong statistical correlation between the dynamics of age structure, the population and the incidence of MI. Peak incidence and mortality of meningococcal disease occurred in Ukraine in the mid-80s, also corresponding to this time of national birth rates or a “baby boom.”
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Children\'s age is an indirect risk factor for invasive meningococci disease (IMD), while youngest children are more susceptibility to the pathogen, including predisposing factor of IMD and high transmission risk among over-crowded communities (i.e., school, recreation area, etc.). Incidence may also be reduced when the relative number of children decreases, and the whole population is aging (as it is in Ukraine and Europe). Indeed, during the study period, the number of children relatively decreased by twofold among general population, while the total number of population also decreased in Ukraine. Thus, we believe that the incidence of IMD in different age groups defined different levels of susceptibility of the pathogen for these groups.
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3.6. Spatial rural as compared to urban distribution of meningococcal infection
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In \nFigure 9\n, we see that the frequency of MI between cities and villages differ slightly. In cities, the total number and density of the population is greater than in the villages. This is evidenced by the result of ANOVA analysis of MI incidence for the period of 1990–2014 years for the urban and rural population of Ukraine. Estimated value of Fisher criterion (1.2) is less than the critical value (4.04). Thus, we have confirmed the statistical null hypothesis of no effect of residence on the incidence of MI.
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Figure 9.
Dynamics of meningococcal infection in Ukraine in rural and urban areas (1990–2014). Legend: Abscissa = time (year); Ordinate = case of meningococcal infection per 100,000 people; Circle = Incidence of Meningococcal Disease in urban settings; Square = Incidence of Meningococcal Disease in rural; Triangle = Incidence of Meningococcal Disease among total population.
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These data may indicate that the percentage of the susceptible population in cities and towns are approximately equal. He also points to the sporadic incidence of MI in Ukraine.
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3.7. Meningococcal carriage
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Indeed, as a first factor in favor of such observations, one has to consider that meningococcus carriage is the most widespread form of meningococcal infection, that is, for one patient with IMD there is an estimate of more than thousands asymptomatic carriers of the pathogen. Carriage rates can range between 1 and 50% while varies with age, socioeconomic status, and connected with the predominant strain circulating in the area, and a number that appears not to vary with season or herd immunity. However, nasopharyngeal carriage surveillance is not recommended neither reported as a practical useful public health tool [9]. Also, data on nasopharyngeal carriage are available from state bacteriological laboratory in Ukraine (Ukrainian Centre for Disease Control and monitoring of the Ministry of Health of Ukraine) (\nFigure 10\n). Indeed, diagnostic tests are run annually by the Sanitary-epidemiological service of Ukraine using nasopharyngeal swab. This approach was conducted in order to identify the level of circulating N. meningitidis in Ukraine among the healthy children and adolescents and also among all persons who had contact with MI patients, while contact persons represent all age groups or the general population. Such study was carried out in all 26 regions (oblasts) of Ukraine.
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Figure 10.
Meningococcal carriage dynamics among different population group survey in Ukraine (1992–2012). Legend: Abscissa = time (year); Ordinate = absolute number of carriers of meningococci; Circle = Prevalence (%) of meningococcal carriage among the healthy children and adolescents; Diamond = Prevalence (%) of meningococcal carriage among persons who had contact with MI patients (all age groups or the general population).
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From 1992 to 2012, 890,061 people (average of 42,384/year) were investigated, moreover, 482,435 healthy people (average of 23,973/year) of all ages who have had contact with confirmed patients with MI, were also tested for meningococcal carriage in Ukraine. The results of these time series of MI carriers are shown in \nFigure 9\n and show the risk among healthy children and adolescents as an average of 0.99% as compared to 1.97% of the general population. Ultimately, such risk of infection is a factor of emergence of IMD and determines the level of prevalence of a small percentage of carriers is due to the large stratum of old adults and the low sensitivity of bacterial tests in Ukraine. The risk of infection is a necessary susceptibility factor for the emergence of IMI and therefore constantly determines the level of prevalence of meningococcal carriage.
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3.8. Meningococcus serogroup distribution
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In 1992–2012, information on the meningococcus serogroups was reported for 9484 IMD cases in Ukraine. The meningococcus B serogroup was responsible for 48.9% of IMD, followed by the meningococcus A serogroup (15.78%) and the meningococcus C serogroup (13.21%). The meningococcus D, X, Y, Z, 29E and W135 made up to 3.19% of IMD cases. Non-capsular strains represented 18.91%. During that same period, total information on serogroup was reported for 15,868 carriers. The meningococcus serogroup B was responsible for 36.15% of carriers of meningococcal infections, followed by serogroup C (7.74%) and serogroup A (7.17%). The meningococcus serogroups D, X, Y, Z, 29E and W135 represented 6.75% of carriers’ meningococcal infections the known serogroup. Not typed strain represented 42.19% of carriers of meningococcal infections (\nFigure 11\n).
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Figure 11.
Distribution of meningococcus serogroups among patients with meningococcal disease (n = 9484) and healthy carriers of (n = 15,868), Ukraine, 1992–2012. Legend: Abscissa = Meningococcus serogroups; Ordinate = cases of meningococcal disease (%); red bar = healthy carriers of MI-pathogen (%); blue bar = patients with meningococcal disease (%).
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In 2012, information on serogroup was reported for 3234 of confirmed IMD cases in EU countries including 68% of serogroup B, 17% of serogroup C (17%), and a total of 93% included B and C, Y [8]. It is clearly seen that in the EU and also in Ukraine IM case are due mostly to serogroup B, while serogroups B and C are less represented in Ukraine than in EU.
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In 2008, serogroup C incidence of was 0.21 per 100,000 in Ukraine. In 2012, it dropped to 0.08 per 100,000. From 2008 to 2012, this index was slightly higher than the 0.1 per 100,000 in EU/EEA countries [9]. Thus, in the Ukraine, currently, the incidence of serogroup C is not different for EU/EEA but in Ukraine not carried out vaccination against Men C. This fact does not negate the benefits of vaccination but requires further detailed study. When one compares the incidence Men type C in EU with routine vaccination and Ukraine, where routine vaccination against MI has never been carried out, the effectiveness of Men C vaccination appears negligible because the incidence Men type C in EU and Ukraine is not different.
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In Europe and Ukraine, decline in the incidence of other serogroups (A and B) was not the result of specific interventions. We believe that demographic situation in Ukraine population has decreased from 52 to 45 million over the past 25 years. Birth rate decreases, and therefore, child population falls, altogether this will certainly not contribute to an increase incidence of IMD in Ukraine for the coming decade. The introduction of routine vaccination of IMD in Ukraine requires careful study because there is limited funding for public health.
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4. Clinics
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Among the 18,914 cases of IMD reported in Ukraine, 38.4% were meningococcemia, 29.9% were meningococcemia with meningitis, 27.9% meningitis and others 2.8% were of different minor etiologies. Other clinical forms have not been also clearly recognized and characterized as pneumonia or mixed clinical forms.
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Also, the distribution of clinical forms of IMD in Ukraine is very different from the one observed in the EU countries in which meningitis prevails for 43.0%. Meningococcemia and meningococcemia with meningitis represent, respectively, 21.0 and 29.0% of total IMD in the EU [10].
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Case fatality rate (CFR) of Meningococcal disease in Ukraine for the period considered (1992–2012) was of: 12.1% for IMD (n = 18,914); 18.9% for Meningococcemia (n = 7448); 10.1% for Meningococcemia (n = 5660); 5.94% of Meningitis (n = 5273); and 5.6% for others undefined clinical forms (n = 538).
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In 2012, overall CFR in EU/EEA countries was 7.9%, (3185 confirmed IMD cases). The highest CFR reported (n = 1563) among cases presenting septicemia was 18.8%, followed by cases meningitis with septicemia of 11.1%, and then by cases with meningitis (3.7%) [11]. In Ukraine, the higher observed overall CFR of IMD greater than in the EU can be attributed to the frequency of septicemia.
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Meningococcal disease CFR among children in Ukraine during the period of 2010–2015 ranged from 14.7 to 19.1% occurring as follows with respect to the age class: first year of life, 66%; 1–3-year old, 30%; over three-year old, 4%. Among 77% of patient death occurred during the first 24 h after onset.
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According to the children’s infectious hospital of Kiev, for the past 15 years, serotypes prevail as follows: meningococcal serogroup B, 57%; serogroup A, 19%; serogroup C, 20%; and other serogroup, 4%. Meningococcemia was diagnosed in 47% of patient with meningococcemia, 41% meningitis, while 12–76% of children with meningococcal disease had a complicated course of the disease, including septic shock, brain edema, multiple organ failure, disseminated intravascular coagulation syndrome, among others.
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5. Multiple linear regression model
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From this data set and temporal series, some tentative models were developed for a better understanding to the disease dynamics. Assuming that the proportion of susceptible individuals is a constant value a reported to a large population (eventually of genetic origin), this could explain the main feature of the epidemic process of meningococcal disease and ecological characteristics of meningococcus commensality.
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Also, meningococcus as a species may exist as a non-pathogenic microorganism. IMD will then arise only among susceptible people who have a genetic predisposition while in any large population, such a percentage is very small (<1%).
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In order to calculate the percentage of susceptible population to IMD, it is possible to calculate it as a risk of susceptibility (RS), the percentage of susceptible, i.e. approximate proportion of the population susceptible” (APPS) to IMD. In order to calculate APPS, we first calculate the annual estimated number of carriers, AAQC (infected people without clinical manifestations):
where AAQC = annual approximate quantity of carriers (infected people without clinical manifestations); CPR = carrier prevalence rate (from the ratio of the carriers detected among people examinees); N = the census of the population of the studied territory; 365 = days (i.e., a year); D = average duration of carriage status (not detected after 14 days).
where PR = prevalence rate; IR = incidence rate; D = average day duration for one case of carriage [12].
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Ultimately, AAQC formula allows to convert the data of sample surveys (i.e., prevalence of meningococcal carriage showed (\nFigure 9\n) to indicators of incidence (or the annual approximate number of carriers). Thus, we calculated the AAQC among healthy children for the period 1992–2012 years. The AAQC of children was calculated from 2,206,475 persons. The proportion of IMD cases (i.e., % susceptible) presented an average of 0.0360% ± 0.0189, that is: in overall, one IMD patient associated with 5271 carriers in during 1990–2012.
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Moreover, this way we calculated indicators for period of time from 1992 to 2012 for the general population. The annual average number of carriers in the general healthy population was 24,990,502 persons (variation of 15,480,263–34,746,741 per year). The proportion of IMD cases (i.e., % susceptible) had an average of 0.0036% (0.0022–0.0058% per year), that is: one IMB patient associated an average of 29,729 carriers.
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In overall, this is consistent with the fact that the IMD incidence among children exceeds IMD incidence in the general population (or adult) by 10-fold or more.
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The total risk of disease (RD) is expressed as a product of risk of infection (RI) to risk of susceptibility (RS) where RD = RI × RS. Thus, in our paradigm, RS and RI are the final and necessary causes of IMD emergence and spread to human population. All other causes that may affect IMD incidence will act indirectly through RI and RS.
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Therefore, we built multiple regression models of the epidemic process of MI, where the incidence of IMD is the dependent variable, while independent variables are the level of meningococcal carriage (RI) and the proportion of the susceptible population (RS). The construct of the regression model was by deriving multiple regression method [12]. Multiple linear regression models of IMD in Ukraine were therefore developed [13]. We used for the model the data presented in the figures 6 and 10.
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Our first model takes the following form of the regression equation:
where Y1 = IMD incidence per 100,000 children 0–14 years; −7.43 (or “a”) = constant, which corresponds to the mathematical expectation Х1 and Х2 if Y = 0; Х1 = prevalence of carriage among healthy children aged 0–14 (%); Х2 = approximate proportion of the population susceptible to the IMD among children aged 0–14, or APPS (%); 8.26 (or “b1”) = regression coefficient showing the change of level Y, if Х1 is changed to 1%; 227.63 (or “b2”) = regression coefficient showing the change of level Y, if Х2 is changed to 1%.
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Note that the influence of the regression coefficients (b1 and b2) and constant “a” at incidence Y is statistically significant (Student exact test: b1 = 14.56 with p = 2.13 × 10−11; b2 = 15.39 with p = 8.38 × 10−12; a = 7.54 with p = 5.59 × 10−7).
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In the model, the coefficient of multiple correlation R = 0.9697 and its standard error is equal to 0.5069 (R2 = 0.9404, i.e. 94.04%) that statistically significance explains IMD incidence and shows the high descriptive properties of the model. Ultimately, this model appears highly significant (Fisher’s exact test = 142.04 p < 0.05 at 95% confidence) describing the totality of the properties of the epidemic process of MD among children aged 0–14. Analysis of the residuals values of the model did not find any autocorrelation. Overall, the model encompasses all properties and is statistically significant.
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Our second model takes the following form of the regression equation:
where Y2 = IMD incidence per 100,000 population; Х1 = prevalence of carriage among persons who had contact with IMD patients (or among total population), %; Х2 = approximate proportion of the population susceptible to the IMD among total population, APPSIMD, %. The model has excellent descriptive properties and statistically significant. The coefficient of multiple correlation r = 0.9937 and its standard error is equal to 0.0645, accordingly with r2 = 0.9875. Residuals analysis of the model did not find any autocorrelation (i.e., almost normal distribution.)
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Model limitation: Our models use aggregated data form a survey, and therefore, our model does not allow for an adequate formal residual analysis. In order to perform such type of analysis, it requires to build at least 50 times of such models from necessary data sets. Also, our models do not take into account the potential heterogeneity of the pathogen.
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6. Conclusion
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Altogether the present and past surveillance of bacterial meningitis in Ukraine provide a unique source for a comprehensive understanding of the disease dynamics and, most importantly, allow to develop tools and strategies for control and prevention.
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Thus, the results of mathematical modeling of IMD using the available time series of data suggest that the nature of the main manifestations of the epidemic caused by the MI process demonstrates the prevalence of meningococcal carriage and provides a measure of the of susceptible populations, which are both factors strongly associated and allow the assessment of immediate risk of IMD in country. The proposed multiple linear regression model of epidemic process of meningococcal disease will improve epidemiological surveillance of the disease. Moreover, such models will provide a strong mean for assessing the quality of vaccination against invasive bacterial infections as well as diphtheria.
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Acknowledgments
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The authors would like to acknowledge the United States Department of Defense, Defense, Threat Reduction Agency (DTRA), Cooperative Biological Engagement Program (CBEP) for their support to develop this manuscript. While DTRA/CBEP did not support the research described in this publication, the Program supported the presentation of this research in an international forum and supported grantsmanship training related to the development of this manuscript. The contents of this publication are the responsibility of the authors and do not necessarily reflect the views of DTRA or the United States Government.
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\n',keywords:"meningitis, meningococcemia, time series, modeling, Ukraine",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/54925.pdf",chapterXML:"https://mts.intechopen.com/source/xml/54925.xml",downloadPdfUrl:"/chapter/pdf-download/54925",previewPdfUrl:"/chapter/pdf-preview/54925",totalDownloads:1076,totalViews:206,totalCrossrefCites:0,totalDimensionsCites:0,totalAltmetricsMentions:0,introChapter:null,impactScore:0,impactScorePercentile:10,impactScoreQuartile:1,hasAltmetrics:0,dateSubmitted:"May 5th 2016",dateReviewed:"March 7th 2017",datePrePublished:null,datePublished:"August 30th 2017",dateFinished:"April 21st 2017",readingETA:"0",abstract:"Meningococcal disease in Ukraine represents an important cause of mortality mostly among the child population of less than five-year old. The present study illustrates the advancement on understanding of Meningococcal epidemiology across the national level by using20 years of data provided by the Ministry of Health of Ukraine on a constant survey of the disease. This unique set of data includes: demography (census); disease incidence from 1973 to 2015 (i.e., purulent meningitis etiologic diagnostic); Meningococcal disease mortality; anonymized demographic data (sex, age, leaving area/city/village); Comparative etiology of purulent meningitis; serogroups of invasive meningococcal disease; carriers prevalence; a set of clinical data (meningitis, meningococcemia, nasopharyngitis, etc.); and a set of environmental data (season, etc.). The dynamic of the disease is described for over the past 20-year period of time including incidence, prevalence, spatial distribution, seasonality, and risk factors. Existing state of the art of meningococcal infection epidemiology is presented for the all country. Ultimately, time series analysis of record and spatial distribution over such a long period of time supported the development of original construct of various models encompassing risk and vulnerability, and ways to improve epidemiological surveillance, and develop vaccination strategies in country.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/54925",risUrl:"/chapter/ris/54925",book:{id:"5487",slug:"meningoencephalitis-disease-which-requires-optimal-approach-in-emergency-manner"},signatures:"Hennadii Mokhort, Sergey Kramarev and Jean-Paul J. Gonzalez",authors:[{id:"190955",title:"Dr.",name:"Jean-Paul",middleName:null,surname:"Gonzalez",fullName:"Jean-Paul Gonzalez",slug:"jean-paul-gonzalez",email:"jean.paul.gonzalez@georgetown.edu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/190955/images/5304_n.jpg",institution:{name:"Georgetown University",institutionURL:null,country:{name:"United States of America"}}},{id:"191092",title:"Prof.",name:"Sergey",middleName:null,surname:"Kramarev",fullName:"Sergey Kramarev",slug:"sergey-kramarev",email:"kamaev@yandex.ru",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Ministry of Health",institutionURL:null,country:{name:"Brazil"}}},{id:"191093",title:"Associate Prof.",name:"Hennadii",middleName:"A.",surname:"Mokhort",fullName:"Hennadii Mokhort",slug:"hennadii-mokhort",email:"hennadii.mokhort@nmu.ua",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Bogomolets National Medical University",institutionURL:null,country:{name:"Ukraine"}}}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_1_2",title:"1.1. Background",level:"2"},{id:"sec_2_2",title:"1.2. Epidemic pattern of Meningococcal meningitis in Europe",level:"2"},{id:"sec_4",title:"2. Meningococcal infection biosurveillance and Public Health response and control in Ukraine",level:"1"},{id:"sec_5",title:"3. Temporal and spatialdynamics of meningococcal infection in Ukraine",level:"1"},{id:"sec_5_2",title:"3.1. Place and time of meningococcal infection and other purulent meningitis",level:"2"},{id:"sec_6_2",title:"3.2. Time series of morbidity and mortality of meningococcal infection in Ukraine",level:"2"},{id:"sec_7_2",title:"3.3. Seasonality of meningococcal infection in Ukraine",level:"2"},{id:"sec_8_2",title:"3.4. Geographical distribution",level:"2"},{id:"sec_9_2",title:"3.5. Age distribution",level:"2"},{id:"sec_10_2",title:"3.6. Spatial rural as compared to urban distribution of meningococcal infection",level:"2"},{id:"sec_11_2",title:"3.7. Meningococcal carriage",level:"2"},{id:"sec_12_2",title:"3.8. Meningococcus serogroup distribution",level:"2"},{id:"sec_14",title:"4. Clinics",level:"1"},{id:"sec_15",title:"5. Multiple linear regression model",level:"1"},{id:"sec_16",title:"6. Conclusion",level:"1"},{id:"sec_17",title:"Acknowledgments",level:"1"}],chapterReferences:[{id:"B1",body:'\nJafri RZ, Ali A, Messonnier NE, et al. Global epidemiology of invasive meningococcal disease. Population Health Metrics. 2013;11:17. DOI: 10.1186/1478-7954-11-17\n'},{id:"B2",body:'\nWHO. Meningococcal Meningitis Fact Sheet N°141. Updated November, 2015\n'},{id:"B3",body:'\nOrr HJ, Gray SJ, Macdonald M, Stuart JM. Saliva and meningococcal transmission. Emerging Infectious Diseases. 2003;9:1314-1315\n'},{id:"B4",body:'\nChristensen H, May M, Bowen L, Hickman M, Trotter CL. Meningococcal carriage by age: A systematic review and meta-analysis. The Lancet Infectious Diseases. 2010;10(12):853-861\n'},{id:"B5",body:'\nThe European Union Invasive Bacterial Infections Surveillance Network (EU-IBIS), 2006\n'},{id:"B6",body:'\nECDC. European Centre for Disease Prevention and Control (ECDC). Annual Epidemiological Report Vaccine-preventable Diseases –Invasive Bacterial Diseases 2014. Stockholm: European Centre for Disease Prevention and Control (ECDC); 2014\n'},{id:"B7",body:'\nMortality indicator database: Mortality indicators by 67 causes of death, age and sex (HFA-MDB), 2015. Available from: http://data.euro.who.int/hfamdb/tables/tableA.php?w=1024&h=768\n\n'},{id:"B8",body:'\nEuropean Centre for Disease Prevention and Control (ECDC), 2015\n'},{id:"B9",body:'\nECDC, 2015. Available from: http://ecdc.europa.eu/en/publications/Publications/Meningococcal-disease-scouts-EU-August-2015.pdf\n\n'},{id:"B10",body:'\nUNICEF, 2015. Available from: http://www.unicef.org/ukraine/about.html#Basic\n'},{id:"B11",body:'\nWHO, Control of epidemic meningococcal disease. WHO Practical Guidelines. 2nd ed. 1998\n'},{id:"B12",body:'\nAhlbom A, Norell S. Introduction to Modern Epidemiology. Newton Lower Falls: Epidemiology Resources Inc. and New England Epidemiology Institute; 1990\n'},{id:"B13",body:'\nGlantz SA, Slinker BK. Primer of Applied Regression and Analysis of Variance. New York: McGraw–Hill; 1990\n'}],footnotes:[],contributors:[{corresp:null,contributorFullName:"Hennadii Mokhort",address:null,affiliation:'
Bogomolets National Medical University, Kyiv, Ukraine
Bogomolets National Medical University, Kyiv, Ukraine
Ministry of Health of Ukraine, Kyiv, Ukraine
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Kansas State University, Center of Excellence for Emerging Zoonosis and Animal Diseases CEEZAD, Manhattan KS, USA
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\n
1. Introduction
\n
Paraneoplastic pemphigus (PNP) was first described in 1990 by Anhalt et al. as a rare autoimmune disease that causes ulcerated lesions and vesicular eruptions in the mucocutaneous regions [1]. In 2001, the researcher Nguyen et al. introduced the term multiorganic autoimmune paraneoplastic syndrome, since it is a systemic disease that can affect the kidneys, bladder, and smooth and striated muscles [2]. PNP is a disease triggered mainly by B-cell lymphomas and malignant hematological diseases [3]. Other neoplasms also demonstrate the onset of this disease, as well as carcinoma of the stomach, lung, and colon [3]. The patients with PNP present high mortality rates, being around 90% of the cases, besides presenting an extremely complex and difficult diagnosis, since it resembles several other diseases [4, 5]. The treatment and management of this disease are often ineffective, as it is an extremely aggressive and lethal disease.
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In this chapter, we will address the epidemiological aspects, the main triggers, pathophysiology, main manifestations, diagnosis, differential diagnoses, treatments used, prognosis, and the quality of life of patients affected by PNP.
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\n
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2. Epidemiology
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Because PNP is an extremely rare disease, there is still no data on the incidence of this disease in the world population [3]. To date, about 500 cases have been reported in the literature, with PNP representing 3–5% of all cases of pemphigus in the population [6, 7, 8]. The vast majority of affected patients demonstrate lymphoproliferative disorders (LPD) [9]. Although this disease can affect children and adolescents, the most common age group is between 45 and 70 years of age and is not correlated with place of origin, race, and sex [7, 10, 11, 12, 13, 14].
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3. Association with malignancy and genetic background
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PNP can be triggered by several types of neoplasias; however, about 84% of all patients present neoplasias or hematological disorders [3, 7, 15]. Non-Hodgkin’s lymphoma is the most common disorder with 38.6% of cases, followed by chronic lymphocytic leukemia and Castleman disease with 18.4% each (Table 1). Among the non-hematological neoplasms, sarcomas present approximately 8.6% of the cases, such as leiomyosarcoma, malignant nerve sheath tumor, poorly differentiated sarcoma, reticular cell sarcoma, dendritic cell sarcoma, liposarcoma, and inflammatory myofibroblastoma [15, 16, 17]. Other less common diseases described in the literature that provide PNP are malignant thymoma, squamous cell carcinoma of the esophagus, colon carcinoma, CD8+ T-cell lymphoma, retroperitoneal Kaposi’s sarcoma, and lymphoepithelioma-like carcinoma [18, 19, 20, 21, 22, 23]. Although the PNP is triggered by several neoplasias, the manifestations of this disease may precede the hematological disorders and other malignancies, thus requiring the frequent and continuous follow-up of these patients [15]. In addition, there are reports of the occurrence of PNP without a detecting the cause [24, 25].
\n
\n
\n
\n\n
\n
Neoplasms
\n
Frequencies (%)
\n
\n\n\n
\n
Non-Hodgkin’s lymphoma
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38.6
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\n
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Chronic lymphocytic leukemia
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18.4
\n
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Castleman disease
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18.4
\n
\n
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Sarcoma
\n
8.6
\n
\n
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Others
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16
\n
\n\n
Table 1.
Paraneoplastic pemphigus associated with neoplasms.
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It is known that the major histocompatibility complex (MHC) has important relationships in increasing the susceptibility of autoimmune diseases. Although there are few papers that analyze the relationship between PNP and genetics, some studies in the Caucasian and Chinese population showed the relationships of the HLA class II alleles DRB1*03 and HLA-Cw*14 in the PNP’s trigger [26, 27]. HLA-Cw* 14 proved to be a more specific allele type of PNP. Its importance has been associated with PNP, regardless of whether it is a Castleman disease or other tumors, in addition to Castleman disease. [26]. However, to date, these studies are preliminary studies that suggest the association between genetic factors and PNP. To better understand this relationship, it is important to conduct studies with larger numbers of patients and that are affected by different tumors, as well as the realization of this association in different populations.
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4. Pathogenesis
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PNP even being a disease not yet known at the present time, it is known that both autoantibodies, as cell-mediated immunity, are involved [28]. Certainly, it deduces that the immune system is paramount in the pathophysiology of this disease.
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4.1 Autoantibodies
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PNP triggers immune changes with the production of autoantibodies capable of acting on various proteins in the body. The major target proteins of the autoantibodies are desmoglein 1 (DSG-1) and desmoglein 3 (DSG-3); desmocollins 1, 2, and 3; desmoplakins 1 and 2; BP230; BP130; and envoplakin, in addition to several other epitopes affected by autoantigens found in the individual [29]. These characteristics demonstrate the immunological complexity of the disease.
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Proteins of the plakin family, such as desmoplakins 1 and 2, envoplakin, periplakin, plectin and BP230, demonstrate the major targets of autoantibodies [30]. In contrast, the proteins of the cadherin family are the second most affected, with proteins such as DSG-1 and DSG-3 and desmocollin [31]. It is known that the presence of autoantibodies to some proteins are not related to the clinical practice of the patients, although there is a study that has mentioned DSG-3 relation with genital involvement [32].
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Other autoantibodies such as alpha-2 macroglobulin-like 1 (A2ML1), a broad-range protease inhibitor, have been shown to be important in some patients. This protein has been shown to increase in the oral mucosa, intestine, esophagus, and muscles. However, its true function in the epithelium is unknown [33, 34].
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PNP studies with tumor resection demonstrate that tumors have the capacity to secrete autoantibodies capable of affecting the proteins of the epidermal region [35]. While knowing that most PNPs are involved in neoplastic and LPD diseases, triggering by solid tumors is still poorly understood and demonstrates other mechanisms involved in the production of autoantibodies to plakin proteins.
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The involvement of the humoral immunity of PNP presents the desmoplakins 1 and 2, envoplakin, periplakin, BP230, A2ML1, and DSG-1 and DSG-3 as the main proteins of concern [1]. However, 16% of all affected do not demonstrate the presence of these autoantibodies, and this makes, in some cases, the accomplishment of the early diagnosis difficult. A study conducted in patients with PNP and who developed muscle weakness demonstrated autoantibodies against neuromuscular junction proteins and muscle tissue. These muscle-associated proteins were autoantibodies to anti-acetylcholinesterase receptors and anti-titin and anti-ryanodine receptor [36].
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4.2 Cellular immunity
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Cellular immunity has evidenced important roles in the immunophenotyping of PNP. Pathological analyses have demonstrated inflammatory infiltrates with the presence of CD8+ T cells, CD68+ monocytes, and non-major histocompatibility complex-restricted CD56+ in the subepidermal region [2, 37]. Besides that, in the places of affection, the increase in tumor necrosis factor, as well as interferon gamma, was evidenced [38]. These findings show the importance of cellular immunity in the pathogenesis of the disease, since they present abundantly in the sites of PNP involvement.
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5. Clinical features
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PNP presents several symptoms and clinical evolutions. The first symptoms as well as the progression of the disease are very varied from one patient to another. However, there are more frequent clinical features of these individuals.
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\n
5.1 Oral lesions
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The oral mucosa is often affected in patients with PNP [3, 39, 40]. Oral symptoms may be the first symptoms in these patients, even before skin lesions [41]. The most common symptoms are oral and labial erosions with bleeding that may be associated with blisters, macules, papules, vesicles, and erythema (Figure 1). In addition, these patients may present a positive Nikolsky sign [41].
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Figure 1.
Severe erosive mucositis with hematic crusting on the lips and oral mucosa.
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PNP lesions may be similar to oral manifestations of other diseases. Pemphigus vulgaris is a disease that initially triggers blisters and ulcers in the oral mucosa (especially on the cheeks) and may even reach the body. Erythema multiforme also affects the region of the oral mucosa with the appearance of erythema, edema, and some superficial erosions with formation of pseudomembrane. Lichen planus causes erythematous lesions where Wickham striae are present and may in rare cases develop erosions. In most cases of oral lichen planus, these are asymptomatic manifestations with few complications. Even though these diseases show some similarity to PNP, they are less aggressive, lethal, painful, and incapacitating, with less ability to spread to all mucosal and other body sites when compared to PNP [28, 42, 43].
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5.2 Secondary mucosal lesions
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Lesions can also affect regions such as the oropharynx, esophagus, stomach, duodenum, large intestine, conjunctiva, and anogenital region [2, 3, 7, 39, 41, 44, 45]. The involvement of the oropharynx and esophagus commonly triggers painful sensations and dysphagia [4]. The anogenital lesions demonstrate red-violet erythema in the glans or its surroundings (Figure 2). In some cases, lichen planus presents a possible differential diagnosis. However, unlike red-violet lesions, lichen planus forms linear white streaks that may arise in the glans, scrotum, and vulva, in addition to the presence of dyspareunia and pruritus [43]. In these patients, both necrosis and loss of epidermis are absent, unlike patients with PNP who present this clinical [43].
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Figure 2.
Red-violet lesion in the genital organ.
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About 70% of the patients present conjunctival lesions such as bilateral bulbar conjunctival hyperemia, diffuse papillary tarsal conjunctival reactions, conjunctival epithelium desquamation, forniceal shortening, painful ocular irritation, poor vision, conjunctival and corneal erosions, and pseudomembranous conjunctivitis [2, 46, 47].
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\n
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5.3 Skin lesions
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Skin lesions usually appear soon after the onset of mucosal involvement [48]. The most affected sites are the dorsal region (Figure 3), head, and neck (Figure 4), in addition to the nearby extremities [4, 39, 49]. Patients with PNP started the study in very different ways, with the first signs being erythema, bullous and vesicular lesions, papules, skin scaling with Nikolsky sign, exfoliative erythema, and ulcers with hematic crust. Often, the first clinical sign on the skin is erythema that may progress with bullous and ulcerated lesions [24, 50]. Unlike adults, PNP in the skin of children appears in the form of lichenoid lesions, rather than bullous lesions.
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Figure 3.
Extensive erosions and blisters in the dorsal region.
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Figure 4.
Confluent erosions with hematic crusts in the head and neck region.
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Similar to PNP, bullous pemphigoid (BP) provides blistering with erythematous base or normal skin. However, BP lesions occur more frequently in the lower abdomen and lower limbs, and in most individuals, mucosal lesions are not affected [51]. In addition, pruritus is present in the vast majority of these patients, unlike PNP, which show painful and disseminated lesions mainly in the upper body and mucosal regions [28, 51].
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Already erythema multiforme shows prodromal symptoms such as fever and myalgia before the appearance of lesions on the mucosal and skin. Their skin lesions change in feature according to the course of the disease and resemble insect bites or hives that result in the well-known targetoid lesions that are common in this disease. Although cases of necrosis and blisters occur in the center of the lesions, this disease shows less aggression and fewer blisters and ulcers with hematic crusts than the patients affected by PNP [42].
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Lichen planus affects flexor surfaces of the wrists, forearm, and legs. These lesions have round reticular white lines such as Wickham striae. They may arise in places that suffer trauma (Koebner’s phenomenon), in addition to making the site pigmented after inflation, thus demonstrating clinical differences in cutaneous erosions seen in the course of PNP progression [43].
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The graft versus host disease causes rash and maculopapular rash that present itching and can spread to the entire body, less in the scalp. In very severe cases, there may be some sites with necrosis at the base of epidermal rete pegs [52]. Generally, these severe cases are differentiated from the PNP both by the patient’s clinical history and by skin biopsy that demonstrate distinct histopathological characteristics.
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5.4 Pulmonary manifestations
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Approximately 92.8% of the cases described in the literature show pulmonary involvement [3]. The pulmonary clinical signs of PNP are dyspnea, obstructive pulmonary disease, and bronchiolitis obliterans. The resolution of pulmonary problems is of extreme importance, since it is the main cause of death in individuals with PNP [53]. The patients with the greatest pulmonary involvement are Chinese children and patients with Castleman disease [53]. Studies show that 71% of the patients had bronchiolitis obliterans organizing pneumonia, and they give worse prognosis even if treatment of the neoplasia occurs [12, 54].
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6. Histopathological examination
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The pathological analyses demonstrate many varied aspects, since they show them peculiar characteristics according to the evaluated lesions [55]. When analyzing the biopsy of blisters, we found acantholysis with inflammatory infiltrates (Figure 5) [55]. However, when it presents inflammatory maculopapular lesions, the most common findings are lichenoid interface dermatitis [55]. In the presence of lesions with the presence of blisters and maculopapular lesions, mixed characteristics of each type of lesion may occur in the pathology. The findings with dyskeratosis and suprabasal acantholysis are one of the most important characteristics that lead to the definitive diagnosis of PNP [6]. Dyskeratosis is an abnormal formation of epidermal keratinization, whereas acantholysis is the loss of adhesion between skin cells [28]. These findings may help in the diagnosis even when there is no possibility of performing direct immunofluorescence (DIF) or when they are negative [39, 55]. DIF is a laboratory technique capable of detecting the deposition of autoantibodies and immune cells in the sites affected by the disease. The use of DIF demonstrates an extremely important technique for the diagnosis of PNP, since it can analyze both specific autoantibodies and cytotoxic cells of the human immune system, such as CD8+ T cells that act by attacking several layers with keratin and demonstrating intracellular staining of cementum and/or marking of epidermal dermal junctions in band [28, 55].
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Figure 5.
Histopathological examination of the biopsy specimen showing keratinocyte apoptosis and acantholysis (hematoxylin and eosin, original magnification × 100).
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\n
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7. Immunological studies
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The use of DIF demonstrates great importance in the diagnosis of PNP even though approximately 50% of the cases show negative [3]. This technique shows a staining in IgG deposition intracellular chicken wire pattern (linear formation of autoantibodies deposition) along the dermoepidermal junction in both the linear form, as granulate [15]. The presence of IgG deposition in the dermoepidermal region is very characteristic of the PNP; however, only 25% presents this pattern [56].
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The use of indirect immunofluorescence (IIF) shows involvement of the epidermis by the deposition of IgG in the intercellular regions. Other techniques used as cytoplasmic fluorescence (intracellular staining) demonstrate a prominent basal staining. IIF marking is extremely strong in the layers of the epithelium, and this, alerting to PNP investigation, since it shows high specificity [56].
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Other serological methods may also be used, such as immunoprecipitation, immunoblot and anti-EP enzyme-linked immunosorbent assay (ELISA) [57, 58, 59]. Studies evidenced 95 and 100% sensitivity in radioactive and nonradioactive immunoprecipitation techniques, respectively, and this demonstrates that immunoprecipitation is the most serologically sensitive test for PNP diagnosis [57, 60, 61]. Currently the immunoprecipitation is considered gold standard in the diagnosis of PNP, that is, the main criterion to diagnose [62, 63].
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8. Diagnosis
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The criteria for diagnosis according to Anhalt et al. in 1990 are based on five criteria, such as clinical characteristics, histopathological analysis, direct and indirect immunofluorescence, and immunoprecipitation [1]. These criteria have been modified and adapted. In 1993, researchers included to perform the diagnosis the presence of three main criteria or two major and two minor [63]. Already in 2002, Mimouni et al. reviewed the Anhalt criteria and considered four minimum criteria of high confidence in diagnosis (Table 2) [12]. DIF is a nonessential criterion because of its low sensitivity. As for IIF on rat bladder epithelia and monkey esophagus, they were considered useful for tracking and detecting PNP [57, 64]. Negative IIF cannot exclude PNP, and other techniques such as immunoblotting and immunoprecipitation should be used to confirm or rule out a diagnosis.
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\n
\n\n
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1. Clinical features of severe and protracted mucosal involvement and polymorphic cutaneous eruptions
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\n
\n
2. Histologic features of acantholysis or lichenoid or interface dermatitis
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\n
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3. Demonstration of antiplakin autoantibodies
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\n
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4. The presence of an underlying neoplasm, especially lymphoproliferative tumors
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\n\n
Table 2.
Minimum criteria for diagnosis.
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9. Differential diagnosis
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The diagnosis of PNP can be complex and difficult to perform because there are several similar diseases (Table 3). PNP and pemphigus vulgaris (PV) are very similar clinically, but some details differentiate them. PNP develops with inflammatory papules or macules that progress to blisters, while PV presents bullous lesions with a reddish background. Molecularly, the PNP presents some antibodies specific for this disease, such as the presence of anti-A2ML1, anti-envoplakin, and anti-periplakin, and demonstrates patterns of IgG deposition on cell surfaces with accumulation in the basement membrane zone [57, 64, 65, 66]. Even though bullous autoimmune diseases resemble each other, PNP differentiates it by the presence of antibody that stains the mouse bladder. In bullous pemphigoid (PB), BP230 and BP180 can be found, as well as in PNP. However, the use of DIF differentiates them by the IgG deposition patterns found in the PNP. The involvement by morbilliform-like erythema, toxic epidermal necrolysis, and Stevens-Johnson syndrome can also be confused with PNP. However, the detection of antibodies, pathological analysis of the lesions, and the patient’s clinic can differentiate these diseases [1, 10, 39, 57, 64, 65, 66].
\n
\n
\n
\n
\n\n
\n
Disease
\n
Causers
\n
Pathophysiology
\n
\n\n\n
\n
Pemphigus vulgaris
\n
Autoimmune reaction
\n
Autoantigens anti-desmoglein 1,3
\n
\n
\n
Bullous pemphigoid
\n
Autoimmune reaction
\n
Autoantigens anti-BP180 and anti-BP230
\n
\n
\n
Lichen planus
\n
Autoimmune reaction
\n
Autoantigens anti-keratinocyte and antinuclear
\n
\n
\n
Erythema multiforme
\n
hypersensitivity by infection, viruses and drugs
\n
Infiltration of cytotoxic T cell and increased tumor necrosis factor-α
\n
\n
\n
Toxic epidermal necrolysis
\n
Drug reaction that affects more than 30% of the body
\n
Infiltration of cytotoxic T cell, natural killer, and increased granulysin
\n
\n
\n
Stevens-Johnson syndrome
\n
Drug reaction that affects less than 10% of the body
\n
Infiltration of cytotoxic T cell, natural killer, and increased granulysin
\n
\n
\n
Drug eruption
\n
Drug reaction
\n
Perivascular infiltration by lymphocytes, eosinophils, and increased histamine and leukotrienes
\n
\n\n
Table 3.
Differential diagnosis.
\n
Despite some cases that both clinically and histologically resemble each other, it is important to perform other techniques to rule out differential diagnoses. The use of otorhinolaryngological examination is very important to differentiate the diseases that affect the mucous membranes. Well-done physical examination of the oral cavity, histopathological analysis characteristics, cutaneous involvement, and the presence of IIF strongly suggest for the diagnosis of PNP [40, 44, 67].
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\n
\n
10. Treatment
\n
Effective treatment for PNP is still a major puzzle because of its rarity. Although several drugs are used in the literature, PNP has shown great resistance when compared to other forms of pemphigus [50, 68]. When there is suspicion or evidence of PNP, the performance of the six steps described on 2011 by Frew et al. may provide better management of individuals (Table 4) [69]. Stabilization of patients, according to the first step, is the most important step, since it is the major cause of death in patients [69].
\n
\n
\n\n
\n
1. Stabilization of vital parameters
\n
\n
\n
2. Assessment of any underlying malignancy
\n
\n
\n
3. Diagnosis of PNP
\n
\n
\n
4. Removal and therapy for the triggering tumor
\n
\n
\n
5. Treatment of PNP
\n
\n\n
Table 4.
Management of the patient with suspected PNP.
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Currently, the first-line treatment for PNP is still high doses of corticosteroids [70]. This treatment improves the cutaneous lesions, but the mucosal involvement is little altered. The use of other drugs also shows little efficacy in the lesions of the mucosa, this resistance being the characteristic of the disease [69, 71].
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Several studies have shown that the combination of drugs has been effective and safe. These associations were prednisolone used with other therapies, such as mycophenolate mofetil, cyclosporine A, azathioprine, plasmapheresis, and intravenous immunoglobulin [72, 73, 74, 75, 76, 77]. Even though treatment is more effective, mucosal involvement is still resistant to such combined therapies [71].
\n
The use of monoclonal antibody has been effective in the treatment of PNP in some case reports described in the literature. Administration of rituximab, an anti-CD20, has shown good PNP therapy due to B-cell lymphoma [78, 79]. This therapy is based on an infusion of 375 mg/m2 weekly for 4 weeks followed by eight weekly infusions for 4 weeks of corticosteroid and administration of other immunosuppressive drugs such as cyclosporine A [69].
\n
The use of alemtuzumab, a humanized monoclonal antibody that binds to CD52, has been reported. Reported in the treatment of PNP remission in patients whose presence of chronic lymphoid leukemia [80]. Alemtuzumab has been used in a patient with resistance to other drugs such as corticosteroids, intravenous immunoglobulin, and cyclosporine A. In this patient, intravenous 30 mg was infused three times a week for 3 months. Even though there was improvement in both skin and mucosal lesions, the patient continued maintenance treatment with 500 mg of mycophenolate mofetil and 5 mg of prednisone [80]. Although there are several treatment alternatives, new therapies that reduce the resistance of PNP to drugs are still fundamental. Daclizumab, a monoclonal antibody against T-cell interleukin-2, has been shown to be a promising therapy [81].
\n
It is known that in order to avoid large amounts of autoantibodies released into the bloodstream during tumor excision surgery, it is necessary to block blood flow and prevent compression of neoplastic tissue. In addition, the use of intravenous immunoglobulin before and during operations has demonstrated a significant reduction in mortality caused by bronchiolitis obliterans. Even after complete tumor resolution, immunoglobulin administration is required until 2 years to provide remission of autoimmunity triggered by PNP [82, 83].
\n
In addition to the treatment of neoplasia and PNP, other ducts must be performed. When there is loss of skin integrity or immunosuppression, antimicrobial therapy is recommended early to prevent sepsis. Medications for pain control are also useful, since patients have pain in regions with ulceration and erosions [50].
\n
Although there are several treatments stipulated in the literature, there are still no known drugs that reduce the mortality of patients, since the PNP proves highly resistant to more aggressive therapies. However, it is known that management, diagnosis, and early treatment are indispensable methods for a better response of the patients in the prescribed procedures.
\n
\n
\n
11. Prognosis
\n
The prognosis of PNP is extremely poor. Mortality can reach 90% of the cases in the first year, 41% of mortality in the second year, and 38% of death in the third year with the disease [84]. Commonly, death is triggered by systemic complications such as bronchiolitis obliterans, sepsis, and bleeding in the gastrointestinal tract [6, 50]. It is known that regardless of the cure or control of the neoplasia, the PNP progresses, demonstrating itself autonomous to the triggering factor [6, 10, 11, 13, 50]. Patients who exhibit morbilliform erythema and necrosis of skin biopsy keratinocytes demonstrate a worse overall survival [84]. In some cases, the removal of Castleman disease and benign thymoma has shown better results than other underlying diseases [84, 85].
\n
Even with a high mortality rate, the prognosis depends very much on the proper management of the patient, such as monitoring of vital signs, control of oral and skin lesions, treatment of the triggering disease, and prevention of sepsis and bronchitis obliterans. For this, it is essential to follow the patient closely and treat the disease aggressively [50].
\n
\n
\n
12. Quality of life
\n
Studies have mentioned severe losses in the quality of life of patients with pemphigus. The main criteria that impair the quality of life were the greater severity of the disease, anxiety, and depression. However, there was no clear measurement of gender, age, type of pemphigus, duration of disease, skin involvement, disease activity, itching, burning sensation in the skin, or treatment in use [86]. There is still a great need in the standardization and validation of PNP-specific questionnaires, as this proves to be extremely important in order to know and enable actions at key points by multidisciplinary teams.
\n
\n
\n
13. Conclusions
\n
PNP demonstrates a great challenge for physicians, since it presents several clinical aspects and varied degrees of bodily involvement. Early diagnosis, management of the patient, treatment of the underlying neoplasia, and aggressive treatment for PNP are of paramount importance for the best prognosis of the patient, since it is an extremely lethal disease. For this, more studies are needed to better understand the disease and cooperation between multidisciplinary teams involving dermatologists, oncologists, hematologists, otorhinolaryngologists, surgeons, ophthalmologists, immunologists, psychologists, nurses, and social workers.
\n
\n
Acknowledgments
\n
The author would like to acknowledge the help of Dr. Paulo Prata and the School of Health Sciences Barretos, São Paulo, Brazil.
\n
\n
Conflict of interest
\n
The author has declared no conflicts of interest.
\n
\n
Appendices and nomenclature
\n
\n\n\nA2ML1\n\n
alpha-2 macroglobulin-like 1
\n\n\n\nBP\n\n
bullous pemphigoid
\n\n\n\nDIF\n\n
direct immunofluorescence
\n\n\n\nDSG\n\n
desmoglein
\n\n\n\nIIF\n\n
indirect immunofluorescence
\n\n\n\nLPD\n\n
lymphoproliferative disorders
\n\n\n\nPNP\n\n
paraneoplastic pemphigus
\n\n\n
\n
\n',keywords:"paraneoplastic pemphigus, neoplasms disease, autoimmune disease",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/67359.pdf",chapterXML:"https://mts.intechopen.com/source/xml/67359.xml",downloadPdfUrl:"/chapter/pdf-download/67359",previewPdfUrl:"/chapter/pdf-preview/67359",totalDownloads:710,totalViews:0,totalCrossrefCites:0,dateSubmitted:"October 29th 2018",dateReviewed:"February 5th 2019",datePrePublished:"May 26th 2019",datePublished:"September 25th 2019",dateFinished:"May 26th 2019",readingETA:"0",abstract:"Paraneoplastic pemphigus is a multiorganic autoimmune disease, usually triggered by neoplasias, mainly of lymphoproliferative origin such as chronic lymphocytic leukemia, multiple myeloma, non-Hodgkin’s lymphoma, Castleman disease, and thymoma. This disorder is characterized by the presence of autoantibodies that react against proteins, such as desmoplakins, desmocollins, and others existing in cell junctions. The prognosis is reserved, and the mortality rate of the disease is very high, thus proving to be an additional challenge in the therapeutic management of onco-hematological diseases. The objective of this chapter is to solve the main clinical aspects of paraneoplastic pemphigus in lymphoproliferative hematological diseases, anatomopathological and immunofluorescence characteristics, as well as associations with the main differential diagnoses and therapeutic management. We will also describe the main differential diagnoses of paraneoplastic pemphigus, such as various types of pemphigus including induced drug, bullous pemphigoid, drug eruption, lichen planus, graft versus host disease, erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis. In addition, the prognosis and quality of life will be mentioned.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/67359",risUrl:"/chapter/ris/67359",signatures:"Richard Lucas Konichi-Dias",book:{id:"7054",type:"book",title:"Current Trends in Cancer Management",subtitle:null,fullTitle:"Current Trends in Cancer Management",slug:"current-trends-in-cancer-management",publishedDate:"September 25th 2019",bookSignature:"Liliana Streba, Dan Ionut Gheonea and Michael Schenker",coverURL:"https://cdn.intechopen.com/books/images_new/7054.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",isbn:"978-1-83880-006-2",printIsbn:"978-1-83880-005-5",pdfIsbn:"978-1-83962-207-6",isAvailableForWebshopOrdering:!0,editors:[{id:"92199",title:"Dr.",name:"Liliana",middleName:null,surname:"Streba",slug:"liliana-streba",fullName:"Liliana Streba"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"278101",title:"Dr.",name:"Richard",middleName:null,surname:"Konichi-Dias",fullName:"Richard Konichi-Dias",slug:"richard-konichi-dias",email:"richardkonichi95@gmail.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. Epidemiology",level:"1"},{id:"sec_3",title:"3. Association with malignancy and genetic background",level:"1"},{id:"sec_4",title:"4. Pathogenesis",level:"1"},{id:"sec_4_2",title:"4.1 Autoantibodies",level:"2"},{id:"sec_5_2",title:"4.2 Cellular immunity",level:"2"},{id:"sec_7",title:"5. Clinical features",level:"1"},{id:"sec_7_2",title:"5.1 Oral lesions",level:"2"},{id:"sec_8_2",title:"5.2 Secondary mucosal lesions",level:"2"},{id:"sec_9_2",title:"5.3 Skin lesions",level:"2"},{id:"sec_10_2",title:"5.4 Pulmonary manifestations",level:"2"},{id:"sec_12",title:"6. Histopathological examination",level:"1"},{id:"sec_13",title:"7. Immunological studies",level:"1"},{id:"sec_14",title:"8. Diagnosis",level:"1"},{id:"sec_15",title:"9. Differential diagnosis",level:"1"},{id:"sec_16",title:"10. Treatment",level:"1"},{id:"sec_17",title:"11. Prognosis",level:"1"},{id:"sec_18",title:"12. Quality of life",level:"1"},{id:"sec_19",title:"13. Conclusions",level:"1"},{id:"sec_20",title:"Acknowledgments",level:"1"},{id:"sec_20",title:"Conflict of interest",level:"1"},{id:"sec_21",title:"Appendices and nomenclature",level:"1"}],chapterReferences:[{id:"B1",body:'Anhalt GJ, Kim SC, Stanley JR, et al. Paraneoplastic pemphigus. An autoimmune mucocutaneous disease associated with neoplasia. The New England Journal of Medicine. 1990;323:1729-1735'},{id:"B2",body:'Nguyen VT, Ndoye A, Bassler KD, et al. Classification, clinical manifestations, and immunopathological mechanisms of the epithelial variant of paraneoplastic autoimmune multiorgan syndrome: A reappraisal of paraneoplastic pemphigus. Archives of Dermatology. 2001;137:193-206'},{id:"B3",body:'Paolino G, Didona D, Magliulo G, et al. Paraneoplastic pemphigus: Insight into the autoimmune pathogenesis, clinical features and therapy. International Journal of Molecular Sciences. 2017;18:2532. DOI: 10.3390/ijms18122532'},{id:"B4",body:'Anhalt GJ. Paraneoplastic pemphigus. 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Recommendations for the use of rituximab (anti-CD20 antibody) in the treatment of autoimmune bullous skin diseases. Journal der Deutschen Dermatologischen Gesellschaft. 2008;6:366-373'},{id:"B79",body:'Hainsworth JD, Burris HA, Morrissey LH, et al. Rituximab monoclonal antibody as initial systemic therapy for patients with low-grade non-Hodgkin lymphoma. Blood. 2000;95:3052-3056'},{id:"B80",body:'Hohwy T, Bang K, Steiniche T, et al. Alemtuzumab-induced remission of both severe paraneoplastic pemphigus and leukaemic bone marrow infiltration in a case of treatment-resistant B-cell chronic lymphocytic leukaemia. European Journal of Haematology. 2004;73:206-209'},{id:"B81",body:'Lee SE, Kim S-C. Paraneoplastic pemphigus. Dermatologica Sinica. 2010;28:1-14'},{id:"B82",body:'Zhu X, Zhang B. Paraneoplastic pemphigus. The Journal of Dermatology. 2007;34:503-511'},{id:"B83",body:'Anhalt GJ. Paraneoplastic pemphigus. Advances in Dermatology. 1997;12:77-96. Discussion 97'},{id:"B84",body:'Leger S, Picard D, Ingen-Housz-Oro S, et al. Prognostic factors of paraneoplastic pemphigus. Archives of Dermatology. 2012;148:1165-1172'},{id:"B85",body:'Wang J, Zhu X, Li R, et al. Paraneoplastic pemphigus associated with castleman tumor: A commonly reported subtype of paraneoplastic pemphigus in China. Archives of Dermatology. 2005;141:1285-1293'},{id:"B86",body:'Rencz F, Gulácsi L, Tamási B, et al. Health-related quality of life and its determinants in pemphigus: A systematic review and meta-analysis. The British Journal of Dermatology. 2015;173:1076-1080'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Richard Lucas Konichi-Dias",address:"richardkonichi95@gmail.com",affiliation:'
School of Health Sciences, Dr. Paulo Prata-FACISB, Barretos, Sao Paulo, Brazil
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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.
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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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secondary metabolites are having the great application in human health and nutritional aspect. Plant cell and organ culture systems are feasible option for the production of secondary metabolites that are of commercial importance in pharmaceuticals, food additives, flavors, and other industrial materials. The stress, including various elicitors or signal molecules, often induces the secondary metabolite production in the plant tissue culture system. The recent developments in elicitation of plant tissue culture have opened a new avenue for the production of secondary metabolite compounds. Secondary metabolite synthesis and accumulation in cell and organ cultures can be triggered by the application of elicitors to the culture medium. Elicitors are the chemical compounds from abiotic and biotic sources that can stimulate stress responses in plants, leading to the enhanced synthesis and accumulation of secondary metabolites or the induction of novel secondary metabolites. Elicitor type, dose, and treatment schedule are major factors determining the effects on the secondary metabolite production. The number of parameters, such as elicitor concentrations, duration of exposure, cell line, nutrient composition, and age or stage of the culture, is also important factors influencing the successful production of biomass and secondary metabolite accumulation. This chapter reviews the various abiotic and biotic elicitors applied to cultural system and their stimulating effects on the accumulation of secondary metabolites.",book:{id:"5066",slug:"abiotic-and-biotic-stress-in-plants-recent-advances-and-future-perspectives",title:"Abiotic and Biotic Stress in Plants",fullTitle:"Abiotic and Biotic Stress in Plants - Recent Advances and Future Perspectives"},signatures:"Poornananda M. Naik and Jameel M. Al–Khayri",authors:[{id:"176282",title:"Prof.",name:"Jameel M.",middleName:null,surname:"Al-Khayri",slug:"jameel-m.-al-khayri",fullName:"Jameel M. Al-Khayri"},{id:"176284",title:"Dr.",name:"Poornananda M.",middleName:null,surname:"Naik",slug:"poornananda-m.-naik",fullName:"Poornananda M. Naik"}]},{id:"49274",doi:"10.5772/61368",title:"Reactive Oxygen Species and Antioxidant Enzymes Involved in Plant Tolerance to Stress",slug:"reactive-oxygen-species-and-antioxidant-enzymes-involved-in-plant-tolerance-to-stress",totalDownloads:4956,totalCrossrefCites:50,totalDimensionsCites:110,abstract:"Plants are continuously exposed to several stress factors in field, which affect their production. These environmental adversities generally induce the accumulation of reactive oxygen species (ROS), which can cause severe oxidative damage to plants. ROS are toxic molecules found in various subcellular compartments. The equilibrium between the production and detoxification of ROS is sustained by enzymatic and nonenzymatic antioxidants. Due to advances in molecular approaches during the last decades, nowadays it is possible to develop economically important transgenic crops that have increased tolerance to stresses. This chapter discusses the oxidative stress and damage to plants. In addition, it reports the involvement of antioxidant enzymes in the tolerance of plants to various stresses.",book:{id:"5066",slug:"abiotic-and-biotic-stress-in-plants-recent-advances-and-future-perspectives",title:"Abiotic and Biotic Stress in Plants",fullTitle:"Abiotic and Biotic Stress in Plants - Recent Advances and Future Perspectives"},signatures:"Andréia Caverzan, Alice Casassola and Sandra Patussi Brammer",authors:[{id:"176303",title:"Dr.",name:"Alice",middleName:null,surname:"Casassola",slug:"alice-casassola",fullName:"Alice Casassola"},{id:"176409",title:"Dr.",name:"Andréia",middleName:null,surname:"Caverzan",slug:"andreia-caverzan",fullName:"Andréia Caverzan"},{id:"176410",title:"Dr.",name:"Sandra",middleName:null,surname:"Patussi Brammer",slug:"sandra-patussi-brammer",fullName:"Sandra Patussi Brammer"}]}],mostDownloadedChaptersLast30Days:[{id:"66996",title:"Ethiopian Common Medicinal Plants: Their Parts and Uses in Traditional Medicine - Ecology and Quality Control",slug:"ethiopian-common-medicinal-plants-their-parts-and-uses-in-traditional-medicine-ecology-and-quality-c",totalDownloads:4174,totalCrossrefCites:6,totalDimensionsCites:11,abstract:"The main purpose of this review is to document medicinal plants used for traditional treatments with their parts, use, ecology, and quality control. Accordingly, 80 medicinal plant species were reviewed; leaves and roots are the main parts of the plants used for preparation of traditional medicines. The local practitioners provided various traditional medications to their patients’ diseases such as stomachaches, asthma, dysentery, malaria, evil eyes, cancer, skin diseases, and headaches. The uses of medicinal plants for human and animal treatments are practiced from time immemorial. Stream/riverbanks, cultivated lands, disturbed sites, bushlands, forested areas and their margins, woodlands, grasslands, and home gardens are major habitats of medicinal plants. Generally, medicinal plants used for traditional medicine play a significant role in the healthcare of the majority of the people in Ethiopia. The major threats to medicinal plants are habitat destruction, urbanization, agricultural expansion, investment, road construction, and deforestation. Because of these, medicinal plants are being declined and lost with their habitats. Community- and research-based conservation mechanisms could be an appropriate approach for mitigating the problems pertinent to the loss of medicinal plants and their habitats and for documenting medicinal plants. Chromatography; electrophoretic, macroscopic, and microscopic techniques; and pharmaceutical practice are mainly used for quality control of herbal medicines.",book:{id:"8502",slug:"plant-science-structure-anatomy-and-physiology-in-plants-cultured-in-vivo-and-in-vitro",title:"Plant Science",fullTitle:"Plant Science - Structure, Anatomy and Physiology in Plants Cultured in Vivo and in Vitro"},signatures:"Admasu Moges and Yohannes Moges",authors:[{id:"249746",title:"Ph.D.",name:"Admasu",middleName:null,surname:"Moges",slug:"admasu-moges",fullName:"Admasu Moges"},{id:"297761",title:"MSc.",name:"Yohannes",middleName:null,surname:"Moges",slug:"yohannes-moges",fullName:"Yohannes Moges"}]},{id:"63148",title:"Domestic Livestock and Its Alleged Role in Climate Change",slug:"domestic-livestock-and-its-alleged-role-in-climate-change",totalDownloads:15946,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"It is very old wisdom that climate dictates farm management strategies. In recent years, however, we are increasingly confronted with claims that agriculture, livestock husbandry, and even food consumption habits are forcing the climate to change. We subjected this worrisome concern expressed by public institutions, the media, policy makers, and even scientists to a rigorous review, cross-checking critical coherence and (in)compatibilities within and between published scientific papers. Our key conclusion is there is no need for anthropogenic emissions of greenhouse gases (GHGs), and even less so for livestock-born emissions, to explain climate change. Climate has always been changing, and even the present warming is most likely driven by natural factors. The warming potential of anthropogenic GHG emissions has been exaggerated, and the beneficial impacts of manmade CO2 emissions for nature, agriculture, and global food security have been systematically suppressed, ignored, or at least downplayed by the IPCC (Intergovernmental Panel on Climate Change) and other UN (United Nations) agencies. Furthermore, we expose important methodological deficiencies in IPCC and FAO (Food Agriculture Organization) instructions and applications for the quantification of the manmade part of non-CO2-GHG emissions from agro-ecosystems. However, so far, these fatal errors inexorably propagated through scientific literature. Finally, we could not find a clear domestic livestock fingerprint, neither in the geographical methane distribution nor in the historical evolution of mean atmospheric methane concentration. In conclusion, everybody is free to choose a vegetarian or vegan lifestyle, but there is no scientific basis, whatsoever, for claiming this decision could contribute to save the planet’s climate.",book:{id:"7491",slug:"forage-groups",title:"Forage Groups",fullTitle:"Forage Groups"},signatures:"Albrecht Glatzle",authors:[{id:"252990",title:"Dr.",name:"Albrecht",middleName:null,surname:"Glatzle",slug:"albrecht-glatzle",fullName:"Albrecht Glatzle"}]},{id:"66714",title:"Biotic and Abiotic Stresses in Plants",slug:"biotic-and-abiotic-stresses-in-plants",totalDownloads:5911,totalCrossrefCites:60,totalDimensionsCites:106,abstract:"Plants are subjected to a wide range of environmental stresses which reduces and limits the productivity of agricultural crops. Two types of environmental stresses are encountered to plants which can be categorized as (1) Abiotic stress and (2) Biotic stress. The abiotic stress causes the loss of major crop plants worldwide and includes radiation, salinity, floods, drought, extremes in temperature, heavy metals, etc. On the other hand, attacks by various pathogens such as fungi, bacteria, oomycetes, nematodes and herbivores are included in biotic stresses. As plants are sessile in nature, they have no choice to escape from these environmental cues. Plants have developed various mechanisms in order to overcome these threats of biotic and abiotic stresses. They sense the external stress environment, get stimulated and then generate appropriate cellular responses. They do this by stimuli received from the sensors located on the cell surface or cytoplasm and transferred to the transcriptional machinery situated in the nucleus, with the help of various signal transduction pathways. This leads to differential transcriptional changes making the plant tolerant against the stress. The signaling pathways act as a connecting link and play an important role between sensing the stress environment and generating an appropriate biochemical and physiological response.",book:{id:"8015",slug:"abiotic-and-biotic-stress-in-plants",title:"Abiotic and Biotic Stress in Plants",fullTitle:"Abiotic and Biotic Stress in Plants"},signatures:"Audil Gull, Ajaz Ahmad Lone and Noor Ul Islam Wani",authors:null},{id:"62573",title:"Introductory Chapter: Terpenes and Terpenoids",slug:"introductory-chapter-terpenes-and-terpenoids",totalDownloads:7635,totalCrossrefCites:29,totalDimensionsCites:56,abstract:null,book:{id:"6530",slug:"terpenes-and-terpenoids",title:"Terpenes and Terpenoids",fullTitle:"Terpenes and Terpenoids"},signatures:"Shagufta Perveen",authors:[{id:"192992",title:"Prof.",name:"Shagufta",middleName:null,surname:"Perveen",slug:"shagufta-perveen",fullName:"Shagufta Perveen"},{id:"192994",title:"Dr.",name:"Areej",middleName:null,surname:"Al-Taweel",slug:"areej-al-taweel",fullName:"Areej Al-Taweel"}]},{id:"62876",title:"Introduction to Phytochemicals: Secondary Metabolites from Plants with Active Principles for Pharmacological Importance",slug:"introduction-to-phytochemicals-secondary-metabolites-from-plants-with-active-principles-for-pharmaco",totalDownloads:5894,totalCrossrefCites:11,totalDimensionsCites:30,abstract:"Phytochemicals are substances produced mainly by plants, and these substances have biological activity. In the pharmaceutical industry, plants represent the main source to obtain various active ingredients. They exhibit pharmacological effects applicable to the treatment of bacterial and fungal infections and also chronic-degenerative diseases such as diabetes and cancer. However, the next step in science is to find new ways to obtain it. In this chapter, we discuss about the main groups of phytochemicals, in addition to presenting two case studies. One of the most important secondary metabolites is currently Taxol, which is a natural compound of the taxoid family and is also known for its antitumor activity against cancer located in breasts, lungs, and prostate and is also effective with Kaposi’s sarcoma. Our case studies will be about Taxol, extracted from an unexplored plant species, and the production of Taxol by its endophytic fungi.",book:{id:"6794",slug:"phytochemicals-source-of-antioxidants-and-role-in-disease-prevention",title:"Phytochemicals",fullTitle:"Phytochemicals - Source of Antioxidants and Role in Disease Prevention"},signatures:"Nadia Mendoza and Eleazar M. Escamilla Silva",authors:[{id:"51406",title:"Dr.",name:"Eleazar",middleName:"Máximo",surname:"Escamilla Silva",slug:"eleazar-escamilla-silva",fullName:"Eleazar Escamilla Silva"},{id:"243304",title:"Ph.D. Student",name:"Nadia",middleName:null,surname:"Mendoza",slug:"nadia-mendoza",fullName:"Nadia Mendoza"}]}],onlineFirstChaptersFilter:{topicId:"41",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"82159",title:"Chlorophyll and Its Role in Freshwater Ecosystem on the Example of the Volga River Reservoirs",slug:"chlorophyll-and-its-role-in-freshwater-ecosystem-on-the-example-of-the-volga-river-reservoirs",totalDownloads:15,totalDimensionsCites:0,doi:"10.5772/intechopen.105424",abstract:"The present chapter has the aim to considerate the most significant aspects of chlorophyll (Chl) applications in the ecological study of fresh waters on the example of the Volga River reservoirs. Throughout the cascade of seven large reservoirs, Chl varied in wide range from 2.5–9 to over 100 μg/L with mean values of 16.5–41.2, 6.7–44.0, and 3.6–10.6 μg/L in the Upper, Middle, and Lower Volga, respectively. Mean Chl values that constantly decrease from the Upper Volga to Lower Volga, characterize Ivankovo, Uglich, and Cheboksary reservoirs as eutrophic, Saratov and Volgograd reservoirs as mesotrophic, while Gorky and Kuibyshev reservoirs in some years are mesotrophic or eutrophic. Chl seasonal dynamics in the Rybinsk reservoir that is dynamics of phytoplankton biomass, is characterized by spring, summer, and, in some years, autumn maxima. Water temperature and water regime of the reservoir are the main factors in Chl dynamics. Years with low-water conditions are favorable for the high Chl concentrations and intensive development of algae. Seasonally average Chl that make from 5 to 22 μg/L during 1969–2019, show variations in trophic state of reservoir from mesotrophic (Chl < 10 μg/L), to moderately eutrophic (10–15 μg/L), and eutrophic (15–22 μg/L).",book:{id:"11324",title:"Chlorophylls",coverURL:"https://cdn.intechopen.com/books/images_new/11324.jpg"},signatures:"Natalya Mineeva"},{id:"82027",title:"Underutilized Grasses Production: New Evolving Perspectives",slug:"underutilized-grasses-production-new-evolving-perspectives",totalDownloads:21,totalDimensionsCites:0,doi:"10.5772/intechopen.105375",abstract:"Globally, over-reliance on major food crops (wheat, rice and maize) has led to food basket’s shrinking, while climate change, environmental pollution and deteriorating soil fertility demand the cultivation of less exhaustive but nutritious grasses. Unlike neglected grasses (grass species restricted to their centres of origin and only grown at the subsistence level), many underutilized grasses (grass species whose yield or usability potential remains unrealized) are resistant and resilient to abiotic stresses and have multiple uses including food (Coix lacryma-jobi), feed (Eragrostis amabilis and Cynodon dactylon), esthetic value (Miscanthus sinensis and Imperata cylindrica), renewable energy production (Spartina pectinata and Andropogon gerardii Vitman) and contribution to ecosystem services (Saccharum spontaneum). Lack of agricultural market globalization, urbanization and prevalence of large commercial enterprises that favor major grasses trade, improved communication means that promoted specialization in favor of established crops, scant planting material of underutilized grasses and fewer research on their production technology and products development are the prime challenges posed to underutilized grasses promotion. Integration of agronomic research with novel plant protection measures and plant breeding and molecular genetics approaches for developing biotic and abiotic stresses tolerant cultivars along with the development of commercially attractive food products hold the future key for promoting underutilized grasses for supplanting food security and sustainably multiplying economic outcomes.",book:{id:"10895",title:"Grasses and Grassland - New Perspectives",coverURL:"https://cdn.intechopen.com/books/images_new/10895.jpg"},signatures:"Muhammad Aamir Iqbal, Sadaf Khalid, Raees Ahmed, Muhammad Zubair Khan, Nagina Rafique, Raina Ijaz, Saira Ishaq, Muhammad Jamil, Aqeel Ahmad, Amjad Shahzad Gondal, Muhammad Imran, Junaid Rahim and Umar Ayaz Aslam Sheikh"},{id:"81218",title:"Murburn Model of Photosynthesis: Effect of Additives like Chloride and Bicarbonate",slug:"murburn-model-of-photosynthesis-effect-of-additives-like-chloride-and-bicarbonate",totalDownloads:30,totalDimensionsCites:2,doi:"10.5772/intechopen.103132",abstract:"Oxygenic photosynthesis essentially involves photo-lysis (splitting of water to release oxygen), photo-reduction (formation of NADPH), and photo-phosphorylation (synthesis of ATP) reactions. These reactions use photoactive pigments such as chlorophylls and carotenoids. Z-scheme and Kok-Joliot cycle, the acclaimed and deterministic model of photosynthesis, are founded on the classical enzyme reaction mechanisms that depend solely on affinity-based interactions of enzymes with the substrates at defined active sites, for explaining electron/moiety transfers. In contrast, the new murburn model is built on stochastic collisions between diffusible reactive species (DRS) and other milieu components (including enzymes, substrates and ions). This novel perspective explains fast kinetics and action spectrum, and affords a spontaneously probable/evolvable biochemical system. The murburn perspective proposes that the photo-excitation of pigments in the chloroplast leads to effective charge separation and DRS-formation. DRS are stabilized/utilized by a pool of redox-active components via disordered/parallel bimolecular interactions at the thylakoid membrane interface. Herein, we provide details of how murburn model is a thermodynamically, kinetically, and mechanistically viable mechanism for the formation of ATP, NADPH and oxygen. The murburn model also provides more viable explanations for several classical experimental observations in photosynthesis (Emerson enhancement effect, Jagendorf/Racker experiments, etc.) and the non-specific effects of diverse additives (such as chloride and bicarbonate).",book:{id:"11324",title:"Chlorophylls",coverURL:"https://cdn.intechopen.com/books/images_new/11324.jpg"},signatures:"Kelath Murali Manoj, Nikolai Bazhin, Yanyou Wu and Afsal Manekkathodi"},{id:"81388",title:"Electronic Structure of Chlorophyll Monomers and Oligomers",slug:"electronic-structure-of-chlorophyll-monomers-and-oligomers",totalDownloads:40,totalDimensionsCites:0,doi:"10.5772/intechopen.104089",abstract:"This chapter deals with the electronic structure of chlorophyll molecules and their complexes. Different theoretical and quantum chemical calculation methods are used to study the molecular and electronic structure of chlorophylls. Studied spectral region covers ultraviolet and infrared spectral regions, containing blue side of the Soret band, as also traditional Qy band region. Thus, there are not only focusing on the traditional Qy, Qx, and Soret transitions of chlorophylls but also high-energy transitions (in this region also proteins and nuclei acids absorb light). The aim is to show the effect of molecular conformation on the electronic states and thus on the absorption and emission spectra of monomers and oligomers. In chlorophyll-protein complexes, such conformation effect finetuning the spectral transitions and increases overlap between donor and acceptor states of energy transfer processes. Also, the role of vibronic transition in the shape of absorption and emission spectra of the studied systems will be considered.",book:{id:"11324",title:"Chlorophylls",coverURL:"https://cdn.intechopen.com/books/images_new/11324.jpg"},signatures:"Juha Matti Linnanto"},{id:"81038",title:"Earth’s Energy Budget Impact on Grassland Diseases",slug:"earth-s-energy-budget-impact-on-grassland-diseases",totalDownloads:18,totalDimensionsCites:0,doi:"10.5772/intechopen.99971",abstract:"The change in climate have caused different biotic and abiotic factors to be more prominent when management plan is executed. The increase in temperature have then cause frequent drought that may attract alien species of vectors to spread novel diseases among the native plants. However, the change in climate varies in different countries. Thus, common diseases that threatens food security such as Xanthomonas spp., Pseudomonas spp are in limelight of research. Vectors lifecycle may cause plant diseases to by cyclative. Therefore, to find the break in the vector’s lifecycle will be a method to eradicate harmful population in grassland. Modern days will then call for innovative method and limitations should be considered. Climate change have also impacted pathogens migration and mating pattern. The need for innovative management is constantly on the rise.",book:{id:"10895",title:"Grasses and Grassland - New Perspectives",coverURL:"https://cdn.intechopen.com/books/images_new/10895.jpg"},signatures:"Ang Jia Wei Germaine"},{id:"81107",title:"Can Genus Trichoderma Manage Plant Diseases under Organic Agriculture?",slug:"can-genus-trichoderma-manage-plant-diseases-under-organic-agriculture",totalDownloads:95,totalDimensionsCites:0,doi:"10.5772/intechopen.103762",abstract:"Organic agriculture has been coming up as one of the promising segments of crop production systems in India. There are numerous reasons for it, however; human health, sustainable environment, soil health, etc. are the important ones. As per the latest information, India has about 1.5% of total cultivable land under organic agriculture. The occurrence of plant diseases in this crop production system is one of the limiting factors. For the management of plant diseases in organically grown crops, there are limited resources since there is a restriction on the use of synthetic fungicides. Under such a situation, bio-pesticides have the potency to take care of plant diseases. Although there are certain fungal and bacterial candidates well efficient in controlling diseases, genus Trichoderma has occupied a prestigious position among them. It is capable of managing seed and soil-borne plant diseases. Presently it is available in wettable powder (WP) and liquid formulations in variable concentrations for the application.",book:{id:"11317",title:"Trichoderma - Technology and Uses",coverURL:"https://cdn.intechopen.com/books/images_new/11317.jpg"},signatures:"Kishor Chand Kumhar, Dalvinder Pal Singh and Anil Kumar"}],onlineFirstChaptersTotal:15},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:108,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:141,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:123,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:22,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:11,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:"14",title:"Artificial Intelligence",doi:"10.5772/intechopen.79920",issn:"2633-1403",scope:"Artificial Intelligence (AI) is a rapidly developing multidisciplinary research area that aims to solve increasingly complex problems. In today's highly integrated world, AI promises to become a robust and powerful means for obtaining solutions to previously unsolvable problems. This Series is intended for researchers and students alike interested in this fascinating field and its many applications.",coverUrl:"https://cdn.intechopen.com/series/covers/14.jpg",latestPublicationDate:"July 5th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:9,editor:{id:"218714",title:"Prof.",name:"Andries",middleName:null,surname:"Engelbrecht",slug:"andries-engelbrecht",fullName:"Andries Engelbrecht",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRNR8QAO/Profile_Picture_1622640468300",biography:"Andries Engelbrecht received the Masters and PhD degrees in Computer Science from the University of Stellenbosch, South Africa, in 1994 and 1999 respectively. He is currently appointed as the Voigt Chair in Data Science in the Department of Industrial Engineering, with a joint appointment as Professor in the Computer Science Division, Stellenbosch University. Prior to his appointment at Stellenbosch University, he has been at the University of Pretoria, Department of Computer Science (1998-2018), where he was appointed as South Africa Research Chair in Artifical Intelligence (2007-2018), the head of the Department of Computer Science (2008-2017), and Director of the Institute for Big Data and Data Science (2017-2018). In addition to a number of research articles, he has written two books, Computational Intelligence: An Introduction and Fundamentals of Computational Swarm Intelligence.",institutionString:null,institution:{name:"Stellenbosch University",institutionURL:null,country:{name:"South Africa"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:4,paginationItems:[{id:"14",title:"Cell and Molecular Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/14.jpg",isOpenForSubmission:!0,editor:{id:"165627",title:"Dr.",name:"Rosa María",middleName:null,surname:"Martínez-Espinosa",slug:"rosa-maria-martinez-espinosa",fullName:"Rosa María Martínez-Espinosa",profilePictureURL:"https://mts.intechopen.com/storage/users/165627/images/system/165627.jpeg",biography:"Dr. Rosa María Martínez-Espinosa has been a Spanish Full Professor since 2020 (Biochemistry and Molecular Biology) and is currently Vice-President of International Relations and Cooperation development and leader of the research group 'Applied Biochemistry” (University of Alicante, Spain). Other positions she has held at the university include Vice-Dean of Master Programs, Vice-Dean of the Degree in Biology and Vice-Dean for Mobility and Enterprise and Engagement at the Faculty of Science (University of Alicante). She received her Bachelor in Biology in 1998 (University of Alicante) and her PhD in 2003 (Biochemistry, University of Alicante). She undertook post-doctoral research at the University of East Anglia (Norwich, U.K. 2004-2005; 2007-2008).\nHer multidisciplinary research focuses on investigating archaea and their potential applications in biotechnology. She has an H-index of 21. She has authored one patent and has published more than 70 indexed papers and around 60 book chapters.\nShe has contributed to more than 150 national and international meetings during the last 15 years. Her research interests include archaea metabolism, enzymes purification and characterization, gene regulation, carotenoids and bioplastics production, antioxidant\ncompounds, waste water treatments, and brines bioremediation.\nRosa María’s other roles include editorial board member for several journals related\nto biochemistry, reviewer for more than 60 journals (biochemistry, molecular biology, biotechnology, chemistry and microbiology) and president of several organizing committees in international meetings related to the N-cycle or respiratory processes.",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"15",title:"Chemical Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",isOpenForSubmission:!0,editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",slug:"sukru-beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",biography:"Dr. Şükrü Beydemir obtained a BSc in Chemistry in 1995 from Yüzüncü Yıl University, MSc in Biochemistry in 1998, and PhD in Biochemistry in 2002 from Atatürk University, Turkey. He performed post-doctoral studies at Max-Planck Institute, Germany, and University of Florence, Italy in addition to making several scientific visits abroad. He currently works as a Full Professor of Biochemistry in the Faculty of Pharmacy, Anadolu University, Turkey. Dr. Beydemir has published over a hundred scientific papers spanning protein biochemistry, enzymology and medicinal chemistry, reviews, book chapters and presented several conferences to scientists worldwide. He has received numerous publication awards from various international scientific councils. He serves in the Editorial Board of several international journals. Dr. Beydemir is also Rector of Bilecik Şeyh Edebali University, Turkey.",institutionString:null,institution:{name:"Anadolu University",institutionURL:null,country:{name:"Turkey"}}},editorTwo:{id:"13652",title:"Prof.",name:"Deniz",middleName:null,surname:"Ekinci",slug:"deniz-ekinci",fullName:"Deniz Ekinci",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYLT1QAO/Profile_Picture_1634557223079",biography:"Dr. Deniz Ekinci obtained a BSc in Chemistry in 2004, MSc in Biochemistry in 2006, and PhD in Biochemistry in 2009 from Atatürk University, Turkey. He studied at Stetson University, USA, in 2007-2008 and at the Max Planck Institute of Molecular Cell Biology and Genetics, Germany, in 2009-2010. Dr. Ekinci currently works as a Full Professor of Biochemistry in the Faculty of Agriculture and is the Head of the Enzyme and Microbial Biotechnology Division, Ondokuz Mayıs University, Turkey. He is a member of the Turkish Biochemical Society, American Chemical Society, and German Genetics society. Dr. Ekinci published around ninety scientific papers, reviews and book chapters, and presented several conferences to scientists. He has received numerous publication awards from several scientific councils. Dr. Ekinci serves as the Editor in Chief of four international books and is involved in the Editorial Board of several international journals.",institutionString:null,institution:{name:"Ondokuz Mayıs University",institutionURL:null,country:{name:"Turkey"}}},editorThree:null},{id:"17",title:"Metabolism",coverUrl:"https://cdn.intechopen.com/series_topics/covers/17.jpg",isOpenForSubmission:!0,editor:{id:"138626",title:"Dr.",name:"Yannis",middleName:null,surname:"Karamanos",slug:"yannis-karamanos",fullName:"Yannis Karamanos",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002g6Jv2QAE/Profile_Picture_1629356660984",biography:"Yannis Karamanos, born in Greece in 1953, completed his pre-graduate studies at the Université Pierre et Marie Curie, Paris, then his Masters and Doctoral degree at the Université de Lille (1983). He was associate professor at the University of Limoges (1987) before becoming full professor of biochemistry at the Université d’Artois (1996). He worked on the structure-function relationships of glycoconjugates and his main project was the investigations on the biological roles of the de-N-glycosylation enzymes (Endo-N-acetyl-β-D-glucosaminidase and peptide-N4-(N-acetyl-β-glucosaminyl) asparagine amidase). From 2002 he contributes to the understanding of the Blood-brain barrier functioning using proteomics approaches. He has published more than 70 papers. His teaching areas are energy metabolism and regulation, integration and organ specialization and metabolic adaptation.",institutionString:null,institution:{name:"Artois University",institutionURL:null,country:{name:"France"}}},editorTwo:null,editorThree:null},{id:"18",title:"Proteomics",coverUrl:"https://cdn.intechopen.com/series_topics/covers/18.jpg",isOpenForSubmission:!0,editor:{id:"200689",title:"Prof.",name:"Paolo",middleName:null,surname:"Iadarola",slug:"paolo-iadarola",fullName:"Paolo Iadarola",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSCl8QAG/Profile_Picture_1623568118342",biography:"Paolo Iadarola graduated with a degree in Chemistry from the University of Pavia (Italy) in July 1972. He then worked as an Assistant Professor at the Faculty of Science of the same University until 1984. In 1985, Prof. Iadarola became Associate Professor at the Department of Biology and Biotechnologies of the University of Pavia and retired in October 2017. Since then, he has been working as an Adjunct Professor in the same Department at the University of Pavia. His research activity during the first years was primarily focused on the purification and structural characterization of enzymes from animal and plant sources. During this period, Prof. Iadarola familiarized himself with the conventional techniques used in column chromatography, spectrophotometry, manual Edman degradation, and electrophoresis). Since 1995, he has been working on: i) the determination in biological fluids (serum, urine, bronchoalveolar lavage, sputum) of proteolytic activities involved in the degradation processes of connective tissue matrix, and ii) on the identification of biological markers of lung diseases. In this context, he has developed and validated new methodologies (e.g., Capillary Electrophoresis coupled to Laser-Induced Fluorescence, CE-LIF) whose application enabled him to determine both the amounts of biochemical markers (Desmosines) in urine/serum of patients affected by Chronic Obstructive Pulmonary Disease (COPD) and the activity of proteolytic enzymes (Human Neutrophil Elastase, Cathepsin G, Pseudomonas aeruginosa elastase) in sputa of these patients. More recently, Prof. Iadarola was involved in developing techniques such as two-dimensional electrophoresis coupled to liquid chromatography/mass spectrometry (2DE-LC/MS) for the proteomic analysis of biological fluids aimed at the identification of potential biomarkers of different lung diseases. He is the author of about 150 publications (According to Scopus: H-Index: 23; Total citations: 1568- According to WOS: H-Index: 20; Total Citations: 1296) of peer-reviewed international journals. He is a Consultant Reviewer for several journals, including the Journal of Chromatography A, Journal of Chromatography B, Plos ONE, Proteomes, International Journal of Molecular Science, Biotech, Electrophoresis, and others. He is also Associate Editor of Biotech.",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorTwo:{id:"201414",title:"Dr.",name:"Simona",middleName:null,surname:"Viglio",slug:"simona-viglio",fullName:"Simona Viglio",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKDHQA4/Profile_Picture_1630402531487",biography:"Simona Viglio is an Associate Professor of Biochemistry at the Department of Molecular Medicine at the University of Pavia. She has been working since 1995 on the determination of proteolytic enzymes involved in the degradation process of connective tissue matrix and on the identification of biological markers of lung diseases. She gained considerable experience in developing and validating new methodologies whose applications allowed her to determine both the amount of biomarkers (Desmosine and Isodesmosine) in the urine of patients affected by COPD, and the activity of proteolytic enzymes (HNE, Cathepsin G, Pseudomonas aeruginosa elastase) in the sputa of these patients. Simona Viglio was also involved in research dealing with the supplementation of amino acids in patients with brain injury and chronic heart failure. She is presently engaged in the development of 2-DE and LC-MS techniques for the study of proteomics in biological fluids. The aim of this research is the identification of potential biomarkers of lung diseases. 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He also obtained an MSc in Molecular and Genetic Medicine, and a Ph.D. in Clinical Immunology and Human Genetics from the University of Sheffield, UK. He also completed a short-term fellowship in Pediatric Clinical Immunology and Bone Marrow Transplantation at Newcastle General Hospital, England. Dr. Rezaei is a Full Professor of Immunology and Vice Dean of International Affairs and Research, at the School of Medicine, Tehran University of Medical Sciences, and the co-founder and head of the Research Center for Immunodeficiencies. He is also the founding president of the Universal Scientific Education and Research Network (USERN). Dr. Rezaei has directed more than 100 research projects and has designed and participated in several international collaborative projects. He is an editor, editorial assistant, or editorial board member of more than forty international journals. He has edited more than 50 international books, presented more than 500 lectures/posters in congresses/meetings, and published more than 1,100 scientific papers in international journals.",institutionString:"Tehran University of Medical Sciences",institution:{name:"Tehran University of Medical Sciences",country:{name:"Iran"}}},{id:"180733",title:"Dr.",name:"Jean",middleName:null,surname:"Engohang-Ndong",slug:"jean-engohang-ndong",fullName:"Jean Engohang-Ndong",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180733/images/system/180733.png",biography:"Dr. Jean Engohang-Ndong was born and raised in Gabon. After obtaining his Associate Degree of Science at the University of Science and Technology of Masuku, Gabon, he continued his education in France where he obtained his BS, MS, and Ph.D. in Medical Microbiology. He worked as a post-doctoral fellow at the Public Health Research Institute (PHRI), Newark, NJ for four years before accepting a three-year faculty position at Brigham Young University-Hawaii. Dr. Engohang-Ndong is a tenured faculty member with the academic rank of Full Professor at Kent State University, Ohio, where he teaches a wide range of biological science courses and pursues his research in medical and environmental microbiology. Recently, he expanded his research interest to epidemiology and biostatistics of chronic diseases in Gabon.",institutionString:"Kent State University",institution:{name:"Kent State University",country:{name:"United States of America"}}},{id:"188773",title:"Prof.",name:"Emmanuel",middleName:null,surname:"Drouet",slug:"emmanuel-drouet",fullName:"Emmanuel Drouet",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/188773/images/system/188773.png",biography:"Emmanuel Drouet, PharmD, is a Professor of Virology at the Faculty of Pharmacy, the University Grenoble-Alpes, France. As a head scientist at the Institute of Structural Biology in Grenoble, Dr. Drouet’s research investigates persisting viruses in humans (RNA and DNA viruses) and the balance with our host immune system. He focuses on these viruses’ effects on humans (both their impact on pathology and their symbiotic relationships in humans). He has an excellent track record in the herpesvirus field, and his group is engaged in clinical research in the field of Epstein-Barr virus diseases. He is the editor of the online Encyclopedia of Environment and he coordinates the Universal Health Coverage education program for the BioHealth Computing Schools of the European Institute of Science.",institutionString:null,institution:{name:"Grenoble Alpes University",country:{name:"France"}}},{id:"131400",title:"Prof.",name:"Alfonso J.",middleName:null,surname:"Rodriguez-Morales",slug:"alfonso-j.-rodriguez-morales",fullName:"Alfonso J. Rodriguez-Morales",position:null,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},{id:"332819",title:"Dr.",name:"Chukwudi Michael",middleName:"Michael",surname:"Egbuche",slug:"chukwudi-michael-egbuche",fullName:"Chukwudi Michael Egbuche",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/332819/images/14624_n.jpg",biography:"I an Dr. Chukwudi Michael Egbuche. I am a Senior Lecturer in the Department of Parasitology and Entomology, Nnamdi Azikiwe University, Awka.",institutionString:null,institution:{name:"Nnamdi Azikiwe University",country:{name:"Nigeria"}}},{id:"284232",title:"Mr.",name:"Nikunj",middleName:"U",surname:"Tandel",slug:"nikunj-tandel",fullName:"Nikunj Tandel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/284232/images/8275_n.jpg",biography:'Mr. Nikunj Tandel has completed his Master\'s degree in Biotechnology from VIT University, India in the year of 2012. He is having 8 years of research experience especially in the field of malaria epidemiology, immunology, and nanoparticle-based drug delivery system against the infectious diseases, autoimmune disorders and cancer. He has worked for the NIH funded-International Center of Excellence in Malaria Research project "Center for the study of complex malaria in India (CSCMi)" in collaboration with New York University. The preliminary objectives of the study are to understand and develop the evidence-based tools and interventions for the control and prevention of malaria in different sites of the INDIA. Alongside, with the help of next-generation genomics study, the team has studied the antimalarial drug resistance in India. Further, he has extended his research in the development of Humanized mice for the study of liver-stage malaria and identification of molecular marker(s) for the Artemisinin resistance. At present, his research focuses on understanding the role of B cells in the activation of CD8+ T cells in malaria. Received the CSIR-SRF (Senior Research Fellow) award-2018, FIMSA (Federation of Immunological Societies of Asia-Oceania) Travel Bursary award to attend the IUIS-IIS-FIMSA Immunology course-2019',institutionString:"Nirma University",institution:{name:"Nirma University",country:{name:"India"}}},{id:"334383",title:"Ph.D.",name:"Simone",middleName:"Ulrich",surname:"Ulrich Picoli",slug:"simone-ulrich-picoli",fullName:"Simone Ulrich Picoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334383/images/15919_n.jpg",biography:"Graduated in Pharmacy from Universidade Luterana do Brasil (1999), Master in Agricultural and Environmental Microbiology from Federal University of Rio Grande do Sul (2002), Specialization in Clinical Microbiology from Universidade de São Paulo, USP (2007) and PhD in Sciences in Gastroenterology and Hepatology (2012). She is currently an Adjunct Professor at Feevale University in Medicine and Biomedicine courses and a permanent professor of the Academic Master\\'s Degree in Virology. She has experience in the field of Microbiology, with an emphasis on Bacteriology, working mainly on the following topics: bacteriophages, bacterial resistance, clinical microbiology and food microbiology.",institutionString:null,institution:{name:"Universidade Feevale",country:{name:"Brazil"}}},{id:"229220",title:"Dr.",name:"Amjad",middleName:"Islam",surname:"Aqib",slug:"amjad-aqib",fullName:"Amjad Aqib",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229220/images/system/229220.png",biography:"Dr. Amjad Islam Aqib obtained a DVM and MSc (Hons) from University of Agriculture Faisalabad (UAF), Pakistan, and a PhD from the University of Veterinary and Animal Sciences Lahore, Pakistan. Dr. Aqib joined the Department of Clinical Medicine and Surgery at UAF for one year as an assistant professor where he developed a research laboratory designated for pathogenic bacteria. Since 2018, he has been Assistant Professor/Officer in-charge, Department of Medicine, Manager Research Operations and Development-ORIC, and President One Health Club at Cholistan University of Veterinary and Animal Sciences, Bahawalpur, Pakistan. He has nearly 100 publications to his credit. His research interests include epidemiological patterns and molecular analysis of antimicrobial resistance and modulation and vaccine development against animal pathogens of public health concern.",institutionString:"Cholistan University of Veterinary and Animal Sciences",institution:{name:"University of Agriculture Faisalabad",country:{name:"Pakistan"}}},{id:"333753",title:"Dr.",name:"Rais",middleName:null,surname:"Ahmed",slug:"rais-ahmed",fullName:"Rais Ahmed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/333753/images/20168_n.jpg",biography:null,institutionString:null,institution:{name:"University of Agriculture Faisalabad",country:{name:"Pakistan"}}},{id:"62900",title:"Prof.",name:"Fethi",middleName:null,surname:"Derbel",slug:"fethi-derbel",fullName:"Fethi Derbel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62900/images/system/62900.jpeg",biography:"Professor Fethi Derbel was born in 1960 in Tunisia. He received his medical degree from the Sousse Faculty of Medicine at Sousse, University of Sousse, Tunisia. He completed his surgical residency in General Surgery at the University Hospital Farhat Hached of Sousse and was a member of the Unit of Liver Transplantation in the University of Rennes, France. He then worked in the Department of Surgery at the Sahloul University Hospital in Sousse. Professor Derbel is presently working at the Clinique les Oliviers, Sousse, Tunisia. His hospital activities are mostly concerned with laparoscopic, colorectal, pancreatic, hepatobiliary, and gastric surgery. He is also very interested in hernia surgery and performs ventral hernia repairs and inguinal hernia repairs. He has been a member of the GREPA and Tunisian Hernia Society (THS). During his residency, he managed patients suffering from diabetic foot, and he was very interested in this pathology. For this reason, he decided to coordinate a book project dealing with the diabetic foot. Professor Derbel has published many articles in journals and collaborates intensively with IntechOpen Access Publisher as an editor.",institutionString:"Clinique les Oliviers",institution:null},{id:"300144",title:"Dr.",name:"Meriem",middleName:null,surname:"Braiki",slug:"meriem-braiki",fullName:"Meriem Braiki",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/300144/images/system/300144.jpg",biography:"Dr. Meriem Braiki is a specialist in pediatric surgeon from Tunisia. She was born in 1985. She received her medical degree from the University of Medicine at Sousse, Tunisia. She achieved her surgical residency training periods in Pediatric Surgery departments at University Hospitals in Monastir, Tunis and France.\r\nShe is currently working at the Pediatric surgery department, Sidi Bouzid Hospital, Tunisia. Her hospital activities are mostly concerned with laparoscopic, parietal, urological and digestive surgery. She has published several articles in diffrent journals.",institutionString:"Sidi Bouzid Regional Hospital",institution:null},{id:"229481",title:"Dr.",name:"Erika M.",middleName:"Martins",surname:"de Carvalho",slug:"erika-m.-de-carvalho",fullName:"Erika M. de Carvalho",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229481/images/6397_n.jpg",biography:null,institutionString:null,institution:{name:"Oswaldo Cruz Foundation",country:{name:"Brazil"}}},{id:"186537",title:"Prof.",name:"Tonay",middleName:null,surname:"Inceboz",slug:"tonay-inceboz",fullName:"Tonay Inceboz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/186537/images/system/186537.jfif",biography:"I was graduated from Ege University of Medical Faculty (Turkey) in 1988 and completed his Med. PhD degree in Medical Parasitology at the same university. I became an Associate Professor in 2008 and Professor in 2014. I am currently working as a Professor at the Department of Medical Parasitology at Dokuz Eylul University, Izmir, Turkey.\n\nI have given many lectures, presentations in different academic meetings. I have more than 60 articles in peer-reviewed journals, 18 book chapters, 1 book editorship.\n\nMy research interests are Echinococcus granulosus, Echinococcus multilocularis (diagnosis, life cycle, in vitro and in vivo cultivation), and Trichomonas vaginalis (diagnosis, PCR, and in vitro cultivation).",institutionString:"Dokuz Eylül University",institution:{name:"Dokuz Eylül University",country:{name:"Turkey"}}},{id:"71812",title:"Prof.",name:"Hanem Fathy",middleName:"Fathy",surname:"Khater",slug:"hanem-fathy-khater",fullName:"Hanem Fathy Khater",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/71812/images/1167_n.jpg",biography:"Prof. Khater is a Professor of Parasitology at Benha University, Egypt. She studied for her doctoral degree, at the Department of Entomology, College of Agriculture, Food and Natural Resources, University of Missouri, Columbia, USA. She has completed her Ph.D. degrees in Parasitology in Egypt, from where she got the award for “the best scientific Ph.D. dissertation”. She worked at the School of Biological Sciences, Bristol, England, the UK in controlling insects of medical and veterinary importance as a grant from Newton Mosharafa, the British Council. Her research is focused on searching of pesticides against mosquitoes, house flies, lice, green bottle fly, camel nasal botfly, soft and hard ticks, mites, and the diamondback moth as well as control of several parasites using safe and natural materials to avoid drug resistances and environmental contamination.",institutionString:null,institution:{name:"Banha University",country:{name:"Egypt"}}},{id:"99780",title:"Prof.",name:"Omolade",middleName:"Olayinka",surname:"Okwa",slug:"omolade-okwa",fullName:"Omolade Okwa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/99780/images/system/99780.jpg",biography:"Omolade Olayinka Okwa is presently a Professor of Parasitology at Lagos State University, Nigeria. She has a PhD in Parasitology (1997), an MSc in Cellular Parasitology (1992), and a BSc (Hons) Zoology (1990) all from the University of Ibadan, Nigeria. She teaches parasitology at the undergraduate and postgraduate levels. She was a recipient of a Commonwealth fellowship supported by British Council tenable at the Centre for Entomology and Parasitology (CAEP), Keele University, United Kingdom between 2004 and 2005. She was awarded an Honorary Visiting Research Fellow at the same university from 2005 to 2007. \nShe has been an external examiner to the Department of Veterinary Microbiology and Parasitology, University of Ibadan, MSc programme between 2010 and 2012. She is a member of the Nigerian Society of Experimental Biology (NISEB), Parasitology and Public Health Society of Nigeria (PPSN), Science Association of Nigeria (SAN), Zoological Society of Nigeria (ZSN), and is Vice Chairperson of the Organisation of Women in Science (OWSG), LASU chapter. She served as Head of Department of Zoology and Environmental Biology, Lagos State University from 2007 to 2010 and 2014 to 2016. She is a reviewer for several local and international journals such as Unilag Journal of Science, Libyan Journal of Medicine, Journal of Medicine and Medical Sciences, and Annual Research and Review in Science. \nShe has authored 45 scientific research publications in local and international journals, 8 scientific reviews, 4 books, and 3 book chapters, which includes the books “Malaria Parasites” and “Malaria” which are IntechOpen access publications.",institutionString:"Lagos State University",institution:{name:"Lagos State University",country:{name:"Nigeria"}}},{id:"273100",title:"Dr.",name:"Vijay",middleName:null,surname:"Gayam",slug:"vijay-gayam",fullName:"Vijay Gayam",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/273100/images/system/273100.jpeg",biography:"Dr. Vijay Bhaskar Reddy Gayam is currently practicing as an internist at Interfaith Medical Center in Brooklyn, New York, USA. He is also a Clinical Assistant Professor at the SUNY Downstate University Hospital and Adjunct Professor of Medicine at the American University of Antigua. He is a holder of an M.B.B.S. degree bestowed to him by Osmania Medical College and received his M.D. at Interfaith Medical Center. His career goals thus far have heavily focused on direct patient care, medical education, and clinical research. He currently serves in two leadership capacities; Assistant Program Director of Medicine at Interfaith Medical Center and as a Councilor for the American\r\nFederation for Medical Research. As a true academician and researcher, he has more than 50 papers indexed in international peer-reviewed journals. He has also presented numerous papers in multiple national and international scientific conferences. His areas of research interest include general internal medicine, gastroenterology and hepatology. He serves as an editor, editorial board member and reviewer for multiple international journals. His research on Hepatitis C has been very successful and has led to multiple research awards, including the 'Equity in Prevention and Treatment Award” from the New York Department of Health Viral Hepatitis Symposium (2018) and the 'Presidential Poster Award” awarded to him by the American College of Gastroenterology (2018). He was also awarded 'Outstanding Clinician in General Medicine” by Venus International Foundation for his extensive research expertise and services, perform over and above the standard expected in the advancement of healthcare, patient safety and quality of care.",institutionString:"Interfaith Medical Center",institution:{name:"Interfaith Medical Center",country:{name:"United States of America"}}},{id:"93517",title:"Dr.",name:"Clement",middleName:"Adebajo",surname:"Meseko",slug:"clement-meseko",fullName:"Clement Meseko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/93517/images/system/93517.jpg",biography:"Dr. Clement Meseko obtained DVM and PhD degree in Veterinary Medicine and Virology respectively. He has worked for over 20 years in both private and public sectors including the academia, contributing to knowledge and control of infectious disease. Through the application of epidemiological skill, classical and molecular virological skills, he investigates viruses of economic and public health importance for the mitigation of the negative impact on people, animal and the environment in the context of Onehealth. \r\nDr. Meseko’s field experience on animal and zoonotic diseases and pathogen dynamics at the human-animal interface over the years shaped his carrier in research and scientific inquiries. He has been part of the investigation of Highly Pathogenic Avian Influenza incursions in sub Saharan Africa and monitors swine Influenza (Pandemic influenza Virus) agro-ecology and potential for interspecies transmission. He has authored and reviewed a number of journal articles and book chapters.",institutionString:"National Veterinary Research Institute",institution:{name:"National Veterinary Research Institute",country:{name:"Nigeria"}}},{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",biography:"Professor Dr. Shailendra K. Saxena is a vice dean and professor at King George's Medical University, Lucknow, India. His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. Dr. Saxena is a fellow of various international societies/academies including the Royal College of Pathologists, United Kingdom; Royal Society of Medicine, London; Royal Society of Biology, United Kingdom; Royal Society of Chemistry, London; and Academy of Translational Medicine Professionals, Austria. He was named a Global Leader in Science by The Scientist. He is also an international opinion leader/expert in vaccination for Japanese encephalitis by IPIC (UK).",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",country:{name:"India"}}},{id:"94928",title:"Dr.",name:"Takuo",middleName:null,surname:"Mizukami",slug:"takuo-mizukami",fullName:"Takuo Mizukami",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94928/images/6402_n.jpg",biography:null,institutionString:null,institution:{name:"National Institute of Infectious Diseases",country:{name:"Japan"}}},{id:"233433",title:"Dr.",name:"Yulia",middleName:null,surname:"Desheva",slug:"yulia-desheva",fullName:"Yulia Desheva",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/233433/images/system/233433.png",biography:"Dr. Yulia Desheva is a leading researcher at the Institute of Experimental Medicine, St. Petersburg, Russia. She is a professor in the Stomatology Faculty, St. Petersburg State University. She has expertise in the development and evaluation of a wide range of live mucosal vaccines against influenza and bacterial complications. 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\r\n\tBiodiversity provides food security and constitutes a gene pool for biotechnology, especially in the field of agriculture and medicine, and promotes the development of ecotourism.
\r\n
\r\n\tCurrently, biologists admit that we are witnessing the first phases of the seventh mass extinction caused by human intervention. It is estimated that the current rate of extinction is between a hundred and a thousand times faster than it was when man first appeared. The disappearance of species is caused not only by an accelerated rate of extinction, but also by a decrease in the rate of emergence of new species as human activities degrade the natural environment. The conservation of biological diversity is "a common concern of humanity" and an integral part of the development process. Its objectives are “the conservation of biological diversity, the sustainable use of its components, and the fair and equitable sharing of the benefits resulting from the use of genetic resources”.
\r\n
\r\n\tThe following are the main causes of biodiversity loss:
\r\n
\r\n\t• The destruction of natural habitats to expand urban and agricultural areas and to obtain timber, minerals and other natural resources.
\r\n
\r\n\t• The introduction of alien species into a habitat, whether intentionally or unintentionally which has an impact on the fauna and flora of the area, and as a result, they are reduced or become extinct.
\r\n
\r\n\t• Pollution from industrial and agricultural products, which devastate the fauna and flora, especially those in fresh water.
\r\n
\r\n\t• Global warming, which is seen as a threat to biological diversity, and will become increasingly important in the future.
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\r\n\tThe environment is subject to severe anthropic effects. Among them are those associated with pollution, resource extraction and overexploitation, loss of biodiversity, soil degradation, disorderly land occupation and planning, and many others. These anthropic effects could potentially be caused by any inadequate management of the environment. However, ecosystems have a resilience that makes them react to disturbances which mitigate the negative effects. It is critical to understand how ecosystems, natural and anthropized, including urban environments, respond to actions that have a negative influence and how they are managed. It is also important to establish when the limits marked by the resilience and the breaking point are achieved and when no return is possible. The main focus for the chapters is to cover the subjects such as understanding how the environment resilience works, the mechanisms involved, and how to manage them in order to improve our interactions with the environment and promote the use of adequate management practices such as those outlined in the United Nations’ Sustainable Development Goals.
\r\n\tPollution is caused by a wide variety of human activities and occurs in diverse forms, for example biological, chemical, et cetera. In recent years, significant efforts have been made to ensure that the environment is clean, that rigorous rules are implemented, and old laws are updated to reduce the risks towards humans and ecosystems. However, rapid industrialization and the need for more cultivable sources or habitable lands, for an increasing population, as well as fewer alternatives for waste disposal, make the pollution control tasks more challenging. Therefore, this topic will focus on assessing and managing environmental pollution. It will cover various subjects, including risk assessment due to the pollution of ecosystems, transport and fate of pollutants, restoration or remediation of polluted matrices, and efforts towards sustainable solutions to minimize environmental pollution.
\r\n\tWater is not only a crucial substance needed for biological life on Earth, but it is also a basic requirement for the existence and development of the human society. Owing to the importance of water to life on Earth, early researchers conducted numerous studies and analyses on the liquid form of water from the perspectives of chemistry, physics, earth science, and biology, and concluded that Earth is a "water polo". Water covers approximately 71% of Earth's surface. However, 97.2% of this water is seawater, 21.5% is icebergs and glaciers, and only 0.65% is freshwater that can be used directly by humans. As a result, the amount of water reserves available for human consumption is limited. The development, utilization, and protection of freshwater resources has become the focus of water science research for the continued improvement of human livelihoods and society.
\r\n
\r\n\tWater exists as solid, liquid, and gas within Earth’s atmosphere, lithosphere, and biosphere. Liquid water is used for a variety of purposes besides drinking, including power generation, ecology, landscaping, and shipping. Because water is involved in various environmental hydrological processes as well as numerous aspects of the economy and human society, the study of various phenomena in the hydrosphere, the laws governing their occurrence and development, the relationship between the hydrosphere and other spheres of Earth, and the relationship between water and social development, are all part of water science. Knowledge systems for water science are improving continuously. Water science has become a specialized field concerned with the identification of its physical, chemical, and biological properties. In addition, it reveals the laws of water distribution, movement, and circulation, and proposes methods and tools for water development, utilization, planning, management, and protection. Currently, the field of water science covers research related to topics such as hydrology, water resources and water environment. It also includes research on water related issues such as safety, engineering, economy, law, culture, information, and education.
",coverUrl:"https://cdn.intechopen.com/series_topics/covers/41.jpg",keywords:"Water, Water Resources, Freshwater, Hydrological Processes, Utilization, Protection"}],annualVolumeBook:{},thematicCollection:[],selectedSeries:null,selectedSubseries:null},seriesLanding:{item:{id:"7",title:"Biomedical Engineering",doi:"10.5772/intechopen.71985",issn:"2631-5343",scope:"Biomedical Engineering is one of the fastest-growing interdisciplinary branches of science and industry. The combination of electronics and computer science with biology and medicine has improved patient diagnosis, reduced rehabilitation time, and helped to facilitate a better quality of life. Nowadays, all medical imaging devices, medical instruments, or new laboratory techniques result from the cooperation of specialists in various fields. The series of Biomedical Engineering books covers such areas of knowledge as chemistry, physics, electronics, medicine, and biology. 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Dr. Koprowski has authored more than a hundred research papers with dozens in impact factor (IF) journals and has authored or co-authored six books. Additionally, he is the author of several national and international patents in the field of biomedical devices and imaging. Since 2011, he has been a reviewer of grants and projects (including EU projects) in biomedical engineering.",institutionString:null,institution:{name:"University of Silesia",institutionURL:null,country:{name:"Poland"}}},subseries:[{id:"7",title:"Bioinformatics and Medical Informatics",keywords:"Biomedical Data, Drug Discovery, Clinical Diagnostics, Decoding Human Genome, AI in Personalized Medicine, Disease-prevention Strategies, Big Data Analysis in Medicine",scope:"Bioinformatics aims to help understand the functioning of the mechanisms of living organisms through the construction and use of quantitative tools. The applications of this research cover many related fields, such as biotechnology and medicine, where, for example, Bioinformatics contributes to faster drug design, DNA analysis in forensics, and DNA sequence analysis in the field of personalized medicine. Personalized medicine is a type of medical care in which treatment is customized individually for each patient. Personalized medicine enables more effective therapy, reduces the costs of therapy and clinical trials, and also minimizes the risk of side effects. Nevertheless, advances in personalized medicine would not have been possible without bioinformatics, which can analyze the human genome and other vast amounts of biomedical data, especially in genetics. The rapid growth of information technology enabled the development of new tools to decode human genomes, large-scale studies of genetic variations and medical informatics. The considerable development of technology, including the computing power of computers, is also conducive to the development of bioinformatics, including personalized medicine. In an era of rapidly growing data volumes and ever lower costs of generating, storing and computing data, personalized medicine holds great promises. Modern computational methods used as bioinformatics tools can integrate multi-scale, multi-modal and longitudinal patient data to create even more effective and safer therapy and disease prevention methods. Main aspects of the topic are: Applying bioinformatics in drug discovery and development; Bioinformatics in clinical diagnostics (genetic variants that act as markers for a condition or a disease); Blockchain and Artificial Intelligence/Machine Learning in personalized medicine; Customize disease-prevention strategies in personalized medicine; Big data analysis in personalized medicine; Translating stratification algorithms into clinical practice of personalized medicine.",annualVolume:11403,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/7.jpg",editor:{id:"351533",title:"Dr.",name:"Slawomir",middleName:null,surname:"Wilczynski",fullName:"Slawomir Wilczynski",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035U1loQAC/Profile_Picture_1630074514792",institutionString:null,institution:{name:"Medical University of Silesia",institutionURL:null,country:{name:"Poland"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"5886",title:"Dr.",name:"Alexandros",middleName:"T.",surname:"Tzallas",fullName:"Alexandros Tzallas",profilePictureURL:"https://mts.intechopen.com/storage/users/5886/images/system/5886.png",institutionString:"University of Ioannina, Greece & Imperial College London",institution:{name:"University of Ioannina",institutionURL:null,country:{name:"Greece"}}},{id:"257388",title:"Distinguished Prof.",name:"Lulu",middleName:null,surname:"Wang",fullName:"Lulu Wang",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRX6kQAG/Profile_Picture_1630329584194",institutionString:"Shenzhen Technology University",institution:{name:"Shenzhen Technology University",institutionURL:null,country:{name:"China"}}},{id:"225387",title:"Prof.",name:"Reda R.",middleName:"R.",surname:"Gharieb",fullName:"Reda R. Gharieb",profilePictureURL:"https://mts.intechopen.com/storage/users/225387/images/system/225387.jpg",institutionString:"Assiut University",institution:{name:"Assiut University",institutionURL:null,country:{name:"Egypt"}}}]},{id:"8",title:"Bioinspired Technology and Biomechanics",keywords:"Bioinspired Systems, Biomechanics, Assistive Technology, Rehabilitation",scope:'Bioinspired technologies take advantage of understanding the actual biological system to provide solutions to problems in several areas. Recently, bioinspired systems have been successfully employing biomechanics to develop and improve assistive technology and rehabilitation devices. The research topic "Bioinspired Technology and Biomechanics" welcomes studies reporting recent advances in bioinspired technologies that contribute to individuals\' health, inclusion, and rehabilitation. 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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. 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