Rare tumors: Pearls and pitfalls in diagnosis, surgical management, and prognosis.
\\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\\nWe 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
\\n"}]',published:!0,mainMedia:{caption:"Highly Cited",originalUrl:"/media/original/117"}},components:[{type:"htmlEditorComponent",content:'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.
\n\nThroughout 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\nReleased 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\nWe 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
\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"8899",leadTitle:null,fullTitle:"Modelling and Control of Switched Reluctance Machines",title:"Modelling and Control of Switched Reluctance Machines",subtitle:null,reviewType:"peer-reviewed",abstract:"Today, switched reluctance machines (SRMs) play an increasingly important role in various sectors due to advantages such as robustness, simplicity of construction, low cost, insensitivity to high temperatures, and high fault tolerance. They are frequently used in fields such as aeronautics, electric and hybrid vehicles, and wind power generation. This book is a comprehensive resource on the design, modeling, and control of SRMs with methods that demonstrate their good performance as motors and generators.",isbn:"978-1-78984-455-9",printIsbn:"978-1-78984-454-2",pdfIsbn:"978-1-83968-160-8",doi:"10.5772/intechopen.82219",price:139,priceEur:155,priceUsd:179,slug:"modelling-and-control-of-switched-reluctance-machines",numberOfPages:372,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"e19068f7f6c92b5643a3f8fbf2f895e0",bookSignature:"Rui Esteves Araújo and José Roberto Camacho",publishedDate:"September 9th 2020",coverURL:"https://cdn.intechopen.com/books/images_new/8899.jpg",numberOfDownloads:9091,numberOfWosCitations:4,numberOfCrossrefCitations:7,numberOfCrossrefCitationsByBook:1,numberOfDimensionsCitations:13,numberOfDimensionsCitationsByBook:0,hasAltmetrics:1,numberOfTotalCitations:24,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"October 29th 2018",dateEndSecondStepPublish:"March 1st 2019",dateEndThirdStepPublish:"May 29th 2019",dateEndFourthStepPublish:"June 3rd 2019",dateEndFifthStepPublish:"August 15th 2019",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!0,featuredMarkup:null,editors:[{id:"31663",title:"Prof.",name:"Rui",middleName:"Esteves",surname:"Araújo",slug:"rui-araujo",fullName:"Rui Araújo",profilePictureURL:"https://mts.intechopen.com/storage/users/31663/images/system/31663.jpeg",biography:"Rui Esteves Araújo received the Electrical Engineering diploma, the M.Sc. and Ph.D. degrees from the University of Porto, Porto, Portugal, in 1987, 1992, and 2001, respectively. From 1987 to 1988, he was an Electrotechnical Engineer in Project Department, Adira Company, Porto, Portugal, and from 1988 to 1989, he was researcher with INESC, Porto, Portugal. Since 1989, he has been with the University of Porto, where he is currently an Assistant Professor with the Department of Electrical and Computer Engineering, Faculty of Engineering, University of Porto. He is senior researcher in the INESC TEC, focusing on control of power converters and drives, and its industrial applications to motion control, electric vehicles and renewable energies",institutionString:"University of Porto",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"5",totalChapterViews:"0",totalEditedBooks:"2",institution:{name:"University of Porto",institutionURL:null,country:{name:"Portugal"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:{id:"111173",title:"Dr.",name:"José",middleName:"Roberto",surname:"Camacho",slug:"jose-camacho",fullName:"José Camacho",profilePictureURL:"https://mts.intechopen.com/storage/users/111173/images/system/111173.jpeg",biography:"José Roberto Camacho was born in Taquaritinga, SP, Brazil,\nin 1954. He received a BSc and MSc in Electrical Engineering\nfrom Universidade Federal de Uberlândia, MG, Brazil in 1978\nand Universidade Federal de Santa Catarina, Florianópolis, SC,\nBrazil in 1987, respectively. He also received a PhD in Electrical\nEngineering from Canterbury University, New Zealand, in 1993.\nFrom 1979 to 1994, he was a lecturer at the School of Electrical\nEngineering, Universidade Federal de Uberlândia, MG, Brasil. Since 1994, he has\nbeen a professor at the same school and university. His research interests include\nalternative energy and electricity for rural areas, electromagnetism and electromagnetic devices, engineering mathematics, small hydroelectric plants, and new\ndevices and techniques for energy production.",institutionString:"Federal University of Uberlandia",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Federal University of Uberlândia",institutionURL:null,country:{name:"Brazil"}}},coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"738",title:"Electromechanics",slug:"electromechanics"}],chapters:[{id:"69801",title:"Modeling and Simulation of Switched Reluctance Machines",doi:"10.5772/intechopen.89851",slug:"modeling-and-simulation-of-switched-reluctance-machines",totalDownloads:1014,totalCrossrefCites:1,totalDimensionsCites:3,hasAltmetrics:0,abstract:"This chapter discusses the modeling and simulation approaches for switched reluctance machines (SRMs). First, it presents the modeling methods for SRMs including analytical models, Artificial intelligence based models, and lookup tables based models. Furthermore, it introduces the finite element method (FEM) and experimental measurement methods to obtain high fidelity magnetic characteristics for SRMs. Step-by-step procedure is explained for SRM modeling and analysis using FEM. The direct and indirect measurement methods of SRM magnetic characteristics are included, comparison between the measured and FEM-calculated characteristics is achieved, and good agreement is seen. In addition, this chapter gives the mathematical modeling of SRM, and explains its model development using MATLAB/Simulink environment. Simulation and experimental results are obtained, a very good agreement is observed.",signatures:"Mahmoud Hamouda and László Számel",downloadPdfUrl:"/chapter/pdf-download/69801",previewPdfUrl:"/chapter/pdf-preview/69801",authors:[{id:"293824",title:"Dr.",name:"Mahmoud",surname:"Hamouda",slug:"mahmoud-hamouda",fullName:"Mahmoud Hamouda"}],corrections:null},{id:"72132",title:"Switched Reluctance Motor Modeling and Loss Estimation Review",doi:"10.5772/intechopen.92228",slug:"switched-reluctance-motor-modeling-and-loss-estimation-review",totalDownloads:506,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Switched reluctance machines (SRM) are an alternative to conventional and permanent magnet (PM)-based machines. They are simple, robust and fault tolerant, and able to reach very high speeds with high efficiency. However, they operate with high torque pulsation and are noisy. Also, a nonconventional power converter type and specific control schemes must be included. Furthermore, SRM operation is characterized by high nonlinear features, which makes it difficult to be modeled and controlled. SRM energy conversion principles are a keystone to understand its operation. SRM efficiency increases with speed, where core and mechanical losses are more significant. For this machine, core loss estimation is a complex task, due to the nonlinear behavior of the magnetic materials. In addition, flux waveforms are not sinusoidal and particular waveforms appear in different core sections. Empirical formulas are usually considered in core loss estimation, but this is insufficient for SRM.",signatures:"Pedro Sousa Melo and Rui E. Araújo",downloadPdfUrl:"/chapter/pdf-download/72132",previewPdfUrl:"/chapter/pdf-preview/72132",authors:[{id:"31663",title:"Prof.",name:"Rui",surname:"Araújo",slug:"rui-araujo",fullName:"Rui Araújo"},{id:"156160",title:"Mr.",name:"Pedro",surname:"Melo",slug:"pedro-melo",fullName:"Pedro Melo"}],corrections:null},{id:"72137",title:"Review of Rotary Switched Reluctance Machine Design and Parameters Effect Analysis",doi:"10.5772/intechopen.92409",slug:"review-of-rotary-switched-reluctance-machine-design-and-parameters-effect-analysis",totalDownloads:469,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The switched reluctance machine (SRM) has gained much interest in industrial applications, wind power systems, and electric vehicles. This happened because its main disadvantages, such as the ripple in the torque, were overcome due to continuous research and its advantages, such as simple and robust construction, ability to operate at high speeds and variable speeds, insensitivity to high temperatures, and fault tolerance, have made the SRM the right machine for many applications. The SRM project is apparently similar to the traditional machine design, but diverges on several points due to the unique features of the SRM. Over the years, several authors have proposed different project methodologies for SRM, each with its own particularities and often contradicting each other. Thus, for a beginner designer, the SRM project is a challenge from choosing the right design methodology to choosing the values of some dimensions, which are often empirical. This chapter aims to offer the beginner designer a detailed review of the main SRM design methodologies. In addition, an effect analysis will provide useful insights on how each design variable affects machine performance. The designer will thus have important data on which to base his choices during the SRM design.",signatures:"Ana Camila Ferreira Mamede, José Roberto Camacho and Rui Esteves Araújo",downloadPdfUrl:"/chapter/pdf-download/72137",previewPdfUrl:"/chapter/pdf-preview/72137",authors:[{id:"31663",title:"Prof.",name:"Rui",surname:"Araújo",slug:"rui-araujo",fullName:"Rui Araújo"},{id:"111173",title:"Dr.",name:"José",surname:"Camacho",slug:"jose-camacho",fullName:"José Camacho"},{id:"272832",title:"MSc.",name:"Ana Camila",surname:"F. Mamede",slug:"ana-camila-f.-mamede",fullName:"Ana Camila F. Mamede"}],corrections:null},{id:"69088",title:"Using Optimization Algorithms in the Design of SRM",doi:"10.5772/intechopen.89123",slug:"using-optimization-algorithms-in-the-design-of-srm",totalDownloads:424,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Switched reluctance motors (SRM) are increasingly used in various industries and vehicles, in addition, in household appliances and in medical equipment. This chapter presents the results of research on the geometric optimization of the magnetic circuit of the switched reluctance motor (SRM) and optimization of the control algorithm. The developed optimization method of magnetic circuit geometry is based on the existing Monte Carlo method. It also allows finding global maxima and minima of an objective function. The main differences of the developed method are as follows: it includes the normal distribution and searches for the geometric shape of the rotor pole as smooth curves (the air gap is not necessarily constant). The problem of optimal control was solved using the Pontryagin’s maximum principle. The initial conditions for the auxiliary functions were determined using the Newton-Raphson method. The recommendations on the practical implementation of the optimal control algorithm are given.",signatures:"Petrushin Alexandr Dmitrievich, Kashuba Alexandr Viktorovich and Petrushin Dmitry Alexandrovich",downloadPdfUrl:"/chapter/pdf-download/69088",previewPdfUrl:"/chapter/pdf-preview/69088",authors:[{id:"296922",title:"Ph.D. Student",name:"Alexander",surname:"Kashuba",slug:"alexander-kashuba",fullName:"Alexander Kashuba"},{id:"297040",title:"Dr.",name:"Alexander",surname:"Petrushin",slug:"alexander-petrushin",fullName:"Alexander Petrushin"},{id:"297382",title:"Prof.",name:"Dmitry",surname:"Petrushin",slug:"dmitry-petrushin",fullName:"Dmitry Petrushin"}],corrections:null},{id:"71433",title:"Scaling Laws in Low-Speed Switched Reluctance Machines",doi:"10.5772/intechopen.91436",slug:"scaling-laws-in-low-speed-switched-reluctance-machines",totalDownloads:421,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"In low-speed applications, switched reluctance machine (SRM) design methodologies are generally driven by criteria related to the number of pole pair combinations in the stator and rotor of regular machines. In this chapter, a set of scaling laws are developed in order to compare magnetic topologies of regular and non-regular machines. Through the introduction of constraints, the proposed methodology integrates thermal and magnetic saturation phenomena. Within a selected set of short flux-path topologies and using finite element analysis, it is possible to verify which topology is the most appropriate. As an illustrative application, the chosen topology—a modular one—is compared with a regular prototype of a switched reluctance generator designed for a wind energy turbine by using a linear model in conjunction with the scaling laws. The evaluation of the two topologies shows the significant increase of power per unit of mass and lower losses of the modular topology than the regular one. The application of scale model methodology is extensive to the design of higher-speed machines. Valuing the dimensional and similarity arguments, certain assumptions of the machine design gain a special emphasis in this work, bringing the discussion of these machines to another paradigm.",signatures:"Pedro Lobato, Joaquim A. Dente and Armando J. Pires",downloadPdfUrl:"/chapter/pdf-download/71433",previewPdfUrl:"/chapter/pdf-preview/71433",authors:[{id:"291017",title:"Prof.",name:"Pedro",surname:"Lobato",slug:"pedro-lobato",fullName:"Pedro Lobato"}],corrections:null},{id:"69070",title:"Linear Switched Reluctance Motors",doi:"10.5772/intechopen.89166",slug:"linear-switched-reluctance-motors",totalDownloads:820,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:1,abstract:"This chapter deals with linear switched reluctance machines (LSRMs). Linear switched reluctance machines are the counterpart of the rotary switched reluctance machine (SRM), and now they have aroused great interest in the field of electrical machines and drives. In this chapter, first, a mathematical model is presented, and then a procedure for the design of this kind of machines is proposed. Next, a linear switched reluctance force actuator, based on the before designed procedure, is simulated. In addition, experimental proofs of the goodness of the design process and of the accuracy of the simulation of the linear switched reluctance force actuator are given.",signatures:"Jordi Garcia-Amoros, Pere Andrada and Baldui Blanque",downloadPdfUrl:"/chapter/pdf-download/69070",previewPdfUrl:"/chapter/pdf-preview/69070",authors:[{id:"293465",title:"Dr.",name:"Jordi",surname:"Garcia-Amoros",slug:"jordi-garcia-amoros",fullName:"Jordi Garcia-Amoros"},{id:"306523",title:"Dr.",name:"Pere",surname:"Andrada",slug:"pere-andrada",fullName:"Pere Andrada"},{id:"306524",title:"Dr.",name:"Baldui",surname:"Blanque",slug:"baldui-blanque",fullName:"Baldui Blanque"}],corrections:null},{id:"70401",title:"Design of Ultrahigh-Speed Switched Reluctance Machines",doi:"10.5772/intechopen.90485",slug:"design-of-ultrahigh-speed-switched-reluctance-machines",totalDownloads:472,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"High-speed electric machines have been a timely topic in recent years. Switched reluctance machines (SRMs) are very competitive candidates for high-speed applications in high-temperature environments, due to the single material rotor without permanent magnets (PM). In this chapter, recent research on ultrahigh-speed SRMs (UHSSRMs) for applications from 100,000 rpm to 1,000,000 rpm is reviewed regarding the design and control. First, the proposed control methods in the literature for ultrahigh speeds over 100,000 rpms are introduced. A direct position control using low-cost nonintrusive reflective sensors is described in detail. Experiments are conducted to validate the method on a 4/2 SRM at 100,000 rpm. Next, for even higher speeds up to 1,000,000 rpm, a high-strength, high-torque-density, and high-efficiency rotor structure is introduced. Finally, the complete design of a 1,000,000 rpm SRM is proposed and prototyped using aerostatic air bearings with the help of electromagnetic finite element analysis (FEA) tools.",signatures:"Cheng Gong and Thomas Habetler",downloadPdfUrl:"/chapter/pdf-download/70401",previewPdfUrl:"/chapter/pdf-preview/70401",authors:[{id:"124164",title:"Dr.",name:"Thomas",surname:"Habetler",slug:"thomas-habetler",fullName:"Thomas Habetler"},{id:"293491",title:"Dr.",name:"Cheng",surname:"Gong",slug:"cheng-gong",fullName:"Cheng Gong"}],corrections:null},{id:"70448",title:"Switched Reluctance Motor Drives: Fundamental Control Methods",doi:"10.5772/intechopen.90476",slug:"switched-reluctance-motor-drives-fundamental-control-methods",totalDownloads:1073,totalCrossrefCites:1,totalDimensionsCites:3,hasAltmetrics:0,abstract:"The switched reluctance motor has been gaining interest both at the academic and industrial levels. Its most appreciated characteristics are the nonuse of rare elements and the low construction price. The control of the switched reluctance motor is not as easy as other traditional machines. In the control, it is necessary to reduce the torque ripple as much as possible, which has been the most studied problem in the field. This chapter aims to give the reader a concise but focused knowledge on how the switched reluctance motor can be controlled. Fundamental control methods and their impact in the motor performance are described. A simulation section is presented, where the simulation files are provided for the reader. The simulations are based on the theory described and have the advantage of using a non-linear switched reluctance motor model from a real motor.",signatures:"Manuel Fernando Sequeira Pereira, Ana Mamede and Rui Esteves Araújo",downloadPdfUrl:"/chapter/pdf-download/70448",previewPdfUrl:"/chapter/pdf-preview/70448",authors:[{id:"31663",title:"Prof.",name:"Rui",surname:"Araújo",slug:"rui-araujo",fullName:"Rui Araújo"},{id:"272832",title:"MSc.",name:"Ana Camila",surname:"F. Mamede",slug:"ana-camila-f.-mamede",fullName:"Ana Camila F. Mamede"},{id:"289589",title:"Ph.D. Student",name:"Manuel",surname:"Pereira",slug:"manuel-pereira",fullName:"Manuel Pereira"}],corrections:null},{id:"68973",title:"Mathematical Modeling of Switched Reluctance Machines: Development and Application",doi:"10.5772/intechopen.89061",slug:"mathematical-modeling-of-switched-reluctance-machines-development-and-application",totalDownloads:677,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The usage of switched reluctance machines (SRMs) grows following the power electronics development. For this reason, a precise mathematical model is crucial for the development of SRM automatic control projects due to the nonlinearities caused by the machine topology and working principle. This chapter focuses on SRM characterization procedure, enlightening the nonlinear characteristics and the importance of the magnetization curves to accomplish precise automatic control of SRM. Different methods found in the literature are commented. The blocked rotor test is detailed, and an automatic acquirement system to obtain the SRM magnetization curves is reasoned. Magnetization curves are processed to create the mathematical model of the SRM. The computational algorithm used to process the acquired data is presented with the purpose of clarifying the production of the lookup tables used in the mathematical model. The developed mathematical model is implemented in Matlab/Simulink® environment. The system simulates the SRM operating both in motoring and generating mode. The mathematical simulation results are compared to experimental results. The developed model is accurate and may be used to study SRM behavior and control systems for SRM applications.",signatures:"Marcelo Vinícius de Paula, Thiago de Almada Lopes, Tárcio André dos Santos Barros, Paulo Sergio Nascimento Filho and Ernesto Ruppert Filho",downloadPdfUrl:"/chapter/pdf-download/68973",previewPdfUrl:"/chapter/pdf-preview/68973",authors:[{id:"151910",title:"MSc.",name:"Tárcio",surname:"Barros",slug:"tarcio-barros",fullName:"Tárcio Barros"}],corrections:null},{id:"70315",title:"Some Basic and Key Issues of Switched-Reluctance Machine Systems",doi:"10.5772/intechopen.89169",slug:"some-basic-and-key-issues-of-switched-reluctance-machine-systems",totalDownloads:1244,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Although switched-reluctance machine (SRM) possesses many structural advantages and application potential, it is rather difficult to successfully control with high performance being comparable to other machines. Many critical affairs must be properly treated to obtain the improved operating characteristics. This chapter presents the basic and key technologies of switched-reluctance machine in motor and generator operations. The contents in this chapter include: (1) structures and governing equations of SRM; (2) some commonly used SRM converters; (3) estimation of key parameters and performance evaluation of SRM drive; (4) commutation scheme, current control scheme, and speed control scheme of SRM drive; (5) some commonly used front-end converters and their operation controls for SRM drive; (6) reversible and regenerative braking operation controls for SRM drive; (7) some tuning issues for SRM drive; (8) operation control and some tuning issues of switched-reluctance generators; and (9) experimental application exploration for SRM systems—(a) wind generator and microgrid and (b) EV SRM drive.",signatures:"Chang-Ming Liaw, Min-Ze Lu, Ping-Hong Jhou and Kuan-Yu Chou",downloadPdfUrl:"/chapter/pdf-download/70315",previewPdfUrl:"/chapter/pdf-preview/70315",authors:[{id:"37616",title:"Prof.",name:"Chang-Ming",surname:"Liaw",slug:"chang-ming-liaw",fullName:"Chang-Ming Liaw"},{id:"306461",title:"Mr.",name:"Min-Ze",surname:"Lu",slug:"min-ze-lu",fullName:"Min-Ze Lu"},{id:"306463",title:"Mr.",name:"Ping-Hong",surname:"Jhou",slug:"ping-hong-jhou",fullName:"Ping-Hong Jhou"},{id:"306464",title:"Mr.",name:"Kuan-Yu",surname:"Chou",slug:"kuan-yu-chou",fullName:"Kuan-Yu Chou"}],corrections:null},{id:"69319",title:"A Review of Classic Torque Control Techniques for Switched Reluctance Motors",doi:"10.5772/intechopen.89450",slug:"a-review-of-classic-torque-control-techniques-for-switched-reluctance-motors",totalDownloads:511,totalCrossrefCites:3,totalDimensionsCites:3,hasAltmetrics:0,abstract:"In this chapter, the most relevant electronic torque control methods established in the current literature are addressed. The electronic torque control methods are divided into two technical topologies. The first one aims to control the average torque produced by the switched reluctance machine and is ideal for applications that require wide speed range of operation. The second topology enrolls the instantaneous torque production and is required in low torque ripple applications. Different torque control methods are addressed, for instance, direct average torque control, current profiling through torque sharing functions, direct torque control, and direct instantaneous torque control. Detailed information regarding the working principle and implementation of the methods is presented. Mathematical simulations are conducted in Matlab/Simulink® environment to elucidate the methods. Finally, a comparison of all addressed methods regarding the torque ripple minimization capabilities is presented.",signatures:"Marcelo Vinícius de Paula, Tárcio André dos Santos Barros and Pedro José Dos Santos Neto",downloadPdfUrl:"/chapter/pdf-download/69319",previewPdfUrl:"/chapter/pdf-preview/69319",authors:[{id:"151910",title:"MSc.",name:"Tárcio",surname:"Barros",slug:"tarcio-barros",fullName:"Tárcio Barros"},{id:"298462",title:"M.Sc.",name:"Marcelo Vinicius",surname:"De Paula",slug:"marcelo-vinicius-de-paula",fullName:"Marcelo Vinicius De Paula"}],corrections:null},{id:"69105",title:"Average Rated Torque Calculations for Switched Reluctance Machines Based on Vector Analysis",doi:"10.5772/intechopen.89097",slug:"average-rated-torque-calculations-for-switched-reluctance-machines-based-on-vector-analysis",totalDownloads:645,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"An average rated torque estimation for generally saturable switched reluctance (SR) machines based on vector analysis is described. The proposed analytical method enables the switched reluctance machine designers to compute quickly and relatively accurately the rated torque of the machine. This approach offers simplicity, accuracy, and intuitive insight characteristic to analytical solutions of magnetically nonlinear problems otherwise achievable only with time-consuming computer-based numerical simulation tools. The suggested analytical methodology, therefore, offers immediate answers regarding the rated torque performance at the early stages of the machine sizing and design process. In this chapter, the switched reluctance machine rated torque calculation is derived based on the analytically estimated flux-linkage characteristic map and the knowledge of the DC bus voltage of the machine. It is further demonstrated that the proposed analytical rated torque calculations, based on vector analysis, enable construction of highly accurate instantaneous phase current profiles using a graphical method and thus aiding intuition and providing valuable insight into the nonlinear switched reluctance machine operation and control requirements. The proposed method will be found particularly suitable for those studying the nonlinear design and control of switched reluctance machine technologies for electric vehicle traction and industrial applications.",signatures:"Aleksas Stuikys and Jan Sykulski",downloadPdfUrl:"/chapter/pdf-download/69105",previewPdfUrl:"/chapter/pdf-preview/69105",authors:[{id:"294111",title:"Dr.",name:"Aleksas",surname:"Stuikys",slug:"aleksas-stuikys",fullName:"Aleksas Stuikys"},{id:"296987",title:"Prof.",name:"Jan",surname:"Sykulski",slug:"jan-sykulski",fullName:"Jan Sykulski"}],corrections:null},{id:"69115",title:"Numerical and Experimental Analysis of Vibrations in a Three-Phase Linear Switched Reluctance Actuator",doi:"10.5772/intechopen.89214",slug:"numerical-and-experimental-analysis-of-vibrations-in-a-three-phase-linear-switched-reluctance-actuat",totalDownloads:430,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"This chapter focuses on the analysis and characterization of the vibrations produced by switched reluctance actuators. The emphasis stands on the linear configuration of this type of machine. The complexity of the mechanical system and the materials is used to define the modal frequencies. Moreover, the power controller topology, the excitation regimes, and the switching frequency used for the actuator operation can excite the natural modes and put restrictions on its usage. The analysis considers both numerical and experimental methodologies. The numerical technique relies on the finite element method (FEM) using the 3D model of the actuator to find its natural frequencies up to ∼1.3 kHz. The experimental characterization counts on the operational modal responses and the acoustic noise emitted. We identify the regions of interest to measure the local accelerations and collect data for post-processing and record the audible noise emitted for signal analysis. The popular discrete Fourier transform and the joint wavelet-Fourier analysis are used for signal analysis. The reliability and the suitability of this approach are verified comparing both the numerical and the experimental outcomes and support the identification of the switching frequencies with high potential to excite the natural modes under the regular operation of the machine and to choose the proper control strategy.",signatures:"José António da Costa Salvado, Maria do Rosário Alves Calado and António Eduardo Vitória do Espírito-Santo",downloadPdfUrl:"/chapter/pdf-download/69115",previewPdfUrl:"/chapter/pdf-preview/69115",authors:[{id:"12810",title:"Prof.",name:"Maria Do Rosário",surname:"Calado",slug:"maria-do-rosario-calado",fullName:"Maria Do Rosário Calado"},{id:"20427",title:"Prof.",name:"António",surname:"Espírito Santo",slug:"antonio-espirito-santo",fullName:"António Espírito Santo"},{id:"143602",title:"Ph.D.",name:"José",surname:"Salvado",slug:"jose-salvado",fullName:"José Salvado"}],corrections:null},{id:"69173",title:"Control and Dynamic Simulation of Linear Switched Reluctance Generators for Direct Drive Conversion Systems",doi:"10.5772/intechopen.89291",slug:"control-and-dynamic-simulation-of-linear-switched-reluctance-generators-for-direct-drive-conversion-",totalDownloads:385,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"This chapter addresses the dynamic simulation and control of linear switched reluctance generators for direct drive conversion systems. The electromechanical energy conversion principles of linear switched reluctance machines are briefly explained. A detailed mathematical model is developed for linear switched reluctance generators. The different types of control strategies adopted for switched reluctance generators are referred. The hysteresis controller is applied to control the conversion system with constant damping load. The proposed control strategy also includes a DC/DC isolated converter to control the system DC bus voltage by adjusting the energy flow between the conversion system and the resistive load. The mathematical model is applied to simulate the behavior of a tubular linear switched reluctance generator as power take-off system in an ocean wave point absorber device. To accomplish this task, the dynamic equations of the point absorber are presented and integrated with the linear switched reluctance generator dynamic model. In the simulation process, the system is driven by a regular ocean wave and operates with constant damping load. 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The integration of experimental methods with computational methods is invaluable both in the development of promising new bioactive compounds and in the molecular characterization of protein-ligand or protein-protein interactions. Molecular docking, in one of these molecular modeling methods, is a unique approach to revealing key interactions in important molecular recognition processes and to accurately predict receptor-ligand binding free energies. Today, the molecular docking method has not only enabled the discovery of new drugs and therapeutic agents but also opened different windows to the submicroscopic world of interacting partner molecules by providing a unique atomistic perspective in the explanation of important intermolecular phenomena.
\r\n\r\n\tThe topics covered in this book are mainly:
\r\n\t1. Emphasizing the unique power of the molecular docking method in new drug discovery;
\r\n\t2. Demonstration of how the molecular docking technique has led to the discovery of new molecules in cancer therapy, proteasome, and STAT3 inhibition, and the treatment of Alzheimer's disease;
\r\n\t3. Underlining the importance of molecular docking-based modeling methods in the various branches of biotechnology
\r\n\tWe hope that this book will be a common point where researchers working in the fields of life sciences and drug development will eventually meet.
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From chapter submission and review, to approval and revision, copy-editing and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. Whether that be identifying an exceptional author and proposing an editorship collaboration, or contacting researchers who would like the opportunity to work with IntechOpen, I establish and help manage author and editor acquisition and contact."}},relatedBooks:[{type:"book",id:"8068",title:"Cytotoxicity",subtitle:"Definition, Identification, and Cytotoxic Compounds",isOpenForSubmission:!1,hash:"20a09223d92829b5478b5f241f6a03ce",slug:"cytotoxicity-definition-identification-and-cytotoxic-compounds",bookSignature:"Erman Salih Istifli and Hasan Basri Ila",coverURL:"https://cdn.intechopen.com/books/images_new/8068.jpg",editedByType:"Edited by",editors:[{id:"179007",title:"Dr.",name:"Erman Salih",surname:"Istifli",slug:"erman-salih-istifli",fullName:"Erman Salih Istifli"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6969",title:"Lymphocytes",subtitle:null,isOpenForSubmission:!1,hash:"1aa8ac01c934ebdeedd5d7813036beef",slug:"lymphocytes",bookSignature:"Erman Salih Istifli and Hasan Basri İla",coverURL:"https://cdn.intechopen.com/books/images_new/6969.jpg",editedByType:"Edited by",editors:[{id:"179007",title:"Dr.",name:"Erman Salih",surname:"Istifli",slug:"erman-salih-istifli",fullName:"Erman Salih Istifli"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10198",title:"Response Surface Methodology in Engineering Science",subtitle:null,isOpenForSubmission:!1,hash:"1942bec30d40572f519327ca7a6d7aae",slug:"response-surface-methodology-in-engineering-science",bookSignature:"Palanikumar Kayaroganam",coverURL:"https://cdn.intechopen.com/books/images_new/10198.jpg",editedByType:"Edited by",editors:[{id:"321730",title:"Prof.",name:"Palanikumar",surname:"Kayaroganam",slug:"palanikumar-kayaroganam",fullName:"Palanikumar Kayaroganam"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1591",title:"Infrared Spectroscopy",subtitle:"Materials Science, Engineering and Technology",isOpenForSubmission:!1,hash:"99b4b7b71a8caeb693ed762b40b017f4",slug:"infrared-spectroscopy-materials-science-engineering-and-technology",bookSignature:"Theophile Theophanides",coverURL:"https://cdn.intechopen.com/books/images_new/1591.jpg",editedByType:"Edited by",editors:[{id:"37194",title:"Dr.",name:"Theophile",surname:"Theophanides",slug:"theophile-theophanides",fullName:"Theophile Theophanides"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3161",title:"Frontiers in Guided Wave Optics and Optoelectronics",subtitle:null,isOpenForSubmission:!1,hash:"deb44e9c99f82bbce1083abea743146c",slug:"frontiers-in-guided-wave-optics-and-optoelectronics",bookSignature:"Bishnu Pal",coverURL:"https://cdn.intechopen.com/books/images_new/3161.jpg",editedByType:"Edited by",editors:[{id:"4782",title:"Prof.",name:"Bishnu",surname:"Pal",slug:"bishnu-pal",fullName:"Bishnu Pal"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3092",title:"Anopheles mosquitoes",subtitle:"New insights into malaria vectors",isOpenForSubmission:!1,hash:"c9e622485316d5e296288bf24d2b0d64",slug:"anopheles-mosquitoes-new-insights-into-malaria-vectors",bookSignature:"Sylvie Manguin",coverURL:"https://cdn.intechopen.com/books/images_new/3092.jpg",editedByType:"Edited by",editors:[{id:"50017",title:"Prof.",name:"Sylvie",surname:"Manguin",slug:"sylvie-manguin",fullName:"Sylvie Manguin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"371",title:"Abiotic Stress in Plants",subtitle:"Mechanisms and Adaptations",isOpenForSubmission:!1,hash:"588466f487e307619849d72389178a74",slug:"abiotic-stress-in-plants-mechanisms-and-adaptations",bookSignature:"Arun Shanker and B. 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The mechanisms of generation of free radicals occur mostly in the mitochondria, cell membranes and cytoplasm. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are formed as unavoidable by-products of metabolism. During the metabolic processes, these radicals act as mediators for the transfer of electrons in various biochemical reactions. Its production, in appropriate proportions, is possible to generate adenosine triphosphate (ATP) through the electron transport chain; fertilization of the ovum; activation of genes and participation of defense mechanisms during the infection process [1]. The continuous production of free radicals during the metabolic processes culminated in the development of antioxidant defense mechanisms (enzymes and substances such as glutathione, metallothionein, vitamin A, vitamin C and vitamin E). These are intended to limit the intracellular levels of these reactive species and control the occurrence of damage caused by them. However, excessive production can lead to oxidative damage. The structural modifications in the molecules of nucleic acids, proteins and lipids caused by increased concentration of reactive oxygen species (ROS) and/or reactive nitrogen species (RNS) lead to various metabolic changes that may contribute to the development of neurological diseases, cardiovascular diseases, cancer, among others [2].
\nThe installation process of oxidative stress arises from an imbalance between oxidants and antioxidants in favor of excessive generation of free radicals or removal speed thereof. This process leads to the oxidation of biomolecules with consequent loss of its biological functions and/or homeostatic imbalances, whose manifestation is the potential oxidative damage to cells and tissues. Accumulation of ROS/RNS can result in a number of deleterious effects such as lipid peroxidation, protein oxidation and DNA damage [3].
\nDNA and RNA are chemically unstable and vulnerable to hydrolysis, nonenzymatic methylation and oxidation, due to its susceptibility to endogenous and exogenous damage. The endogenous genotoxic agents are mainly produced by cellular metabolism and composed of ROS and RNS, estrogen metabolites and aldehydes produced by lipid peroxidation [4, 5].
\nThere are two major endogenous oxidants causing nucleic acids damage: hydroxyl radicals (HO•) and peroxynitrite (ONO2−). One major source of ROS is the mitochondrial respiration because up to 5% of oxygen undergoes single electron transfer and generates superoxide anion radical (O2−). The superoxide dismutase (SOD) converts O2− to hydrogen peroxide that should be reduced by catalase (CAT) or glutathione peroxidase (GPx), however when transition metals are present, it is reduced to hydroxyl radicals (HO•). These radicals have a high reactivity, so it must be generated close to DNA or RNA in order to oxidize them. The generation of peroxynitrite (ONO2−) occurs by the reaction of nitric oxide (NO) and superoxide, both produced simultaneously in macrophages. Although these specimens can directly oxidize the nucleic acids, there is a secondary synergic mechanism of RNS to break the oxidative balance: the RNS are able to inhibit the enzyme FAPY glycosylase, a DNA repair mechanism to oxidation [6].
\nOxidative stress can lead to different lesions in DNA, including direct modification of nucleotide bases, training sites apurinic/apyrimidinic, single strand break and much less frequently, breaking double strands. Considering all the bases of the nucleotides, guanine is most susceptible to oxidative changes because it has lower reduction potential and hydroxyl radicals interact with the imidazole ring of this nitrogenous base at positions C4, C5 and C8 [7].
\nThe most studied marker for DNA oxidation is 8-hydroxydeoxyguanosine, a product of guanosine oxidation by HO• [6, 8]. This product is able to pair with adenine, generating a GC/TA mutation upon replication [6]. It is also known that oxidative stress regulates DNA methylation, playing a role in epigenetics regulation. Epigenetics constitutes several mechanisms of controlling gene expression without changing DNA sequence, but responding fast and precisely to environmental changes. One of the most characterized methods of epigenetic regulation is DNA methylation. The methylation of DNA CpG islands is mediated by DNA methyltransferases (DNMTs), but when the ROS or RNS interacts with cytosine, it is chemically modified from 5-methylcytosine to 5-hydroxymethylcytosine, which prevents DNMT binding and alters methylation patterns [9].
\nFor RNA oxidation, the most relevant marker is the homologue 8-hydroxyguanosine. It has been made clear that RNA is more often oxidized than DNA, due to its cellular location closer to ROS and RNS occurrence. The major consequences of RNA oxidization are the breakage of the strand and ribosomal dysfunction, preventing correct protein production [8].
\nThe effects of oxidation in proteins can be observed in impaired protein folding, side-chain oxidation and backbone fragmentation, resulting in loss of function and stop a variety of biochemical processes. Among the amino acids, the cysteines and methionines are more easily oxidizable, but this reaction is reversible through disulfite reductases activity. However, the cysteine can also suffer irreversible oxidation reactions leading to the formation of S-carboxymethylcysteine and S-(2-Succinyl)cysteine, which implies the formation of fumarate and dicarbonyl groups covalently bound to cysteine residues. When the amino acids lysine, proline, arginine and threonine are oxidized, occurs the production of carbonyl derivatives, which are used as markers for oxidative stress. In the oxidation of aromatic amino acids, such as tyrosine, different products are formed due to interaction with ROS – dityrosine or RNS – 3-nitrotyrosine [8].
\nThese oxidized-modified proteins are usually recognized and degraded in the cells, but some of them can accumulate over time and lead to cellular dysfunction. A physiological example is the lipofuscin, a brown-yellow pigment that is a product of iron-catalyzed oxidation (polymerization) of proteins and lipids, as it is extremely resistant to proteolysis, it accumulates and it is used as an aging marker [10].
\nIn biological systems, lipid peroxidation occurs in two forms, one enzymatically, involving the participation of cyclooxygenase and lipoxygenase in the oxidation of fatty acids and other nonenzyme medium, involving transition metal, the reactive species oxygen, nitrogen and others [11]. Excess peroxidation results are very damaging to the cell, despite contribute to the inflammatory response, due to its importance in the cascade reaction from arachidonic acid to prostaglandin formation. The action of free radicals on lipids leads to the formation of lipid hydroperoxides and aldehydes, such as malondialdehyde, 4-hydroxynonenal and isoprostanes that contribute further to increased cellular toxicity and can be detected in biological samples to measure oxidative stress. Lipid peroxidation disrupts the normal structure and function of lipid bilayers surrounding both the cell itself and in the membranes of organelles. In particular, the lipid peroxidation can alter membrane permeability, transportation and fluidity [12]. The chronicity of the process in question has important implications for the etiologic process of many chronic diseases, including atherosclerosis, diabetes, obesity, neurodegenerative disorders and cancer [1].
\nThe antioxidant defense system has the primary objective to maintain the oxidative process within physiological limits and subject to regulation by preventing oxidative damage from spreading, culminating in systemic irreparable damage. The enzymatic defense system includes enzymes such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). These enzymes act through mechanisms of preventing and/or controlling the formation of free radicals and species nonradical, involved with the initiation of chain reactions that culminate in propagation and process amplification and, consequently, the occurrence of oxidative damage. CAT and GPx enzymes act with the same purpose, to prevent the hydrogen peroxide accumulation. Such integrated action is of great importance, since this reactive species through the reactions of Fenton and Haber-Weiss, with the participation of iron and copper metals, culminates in the generation of OH• radical against which there is no enzyme system defense [13, 14].
\nThe human organism is constantly exposed to a vast number of molecules that can lead to oxidative stress, such as drugs and alcohol. However, there is a conserved cellular component to oxidative stress response, which is constituted by over 100 genes responsible for detoxification and antioxidant protein production. The first line of the antioxidant defense to exogenous toxins includes the enzymes involved in phase I and II metabolism. The phase I metabolism is responsible for increased compound polarity through oxidation, reduction or hydrolysis reactions. The phase II metabolism, in the other hand, is responsible for facilitating the cellular export of those compounds; its reactions are mainly glucuronidation, acetylation and sulfation [15].
\nThe enzymes that compose the cytochrome P450 are the most responsible for oxidation of drugs, chemicals and various endogenous substrates, such as eicosanoids, cholesterol, vitamin D3 and arachidonic acid [16]. The P450 is a superfamily of heme-thiolated enzymes with over 2000 members [17]. In humans, 57 functional genes and 58 pseudogenes are grouped according to the sequence similarity in 18 families and 44 subfamilies. The CYP-enzymes that belong to the families 1, 2 and 3 are responsible for metabolizing up to 90% of the drugs, this phase I drug oxidation system is frequently redundant, but many drugs are metabolized to a clinical concentration by one or few CYPs only [18].
\nIn steroidogenic tissues (converts cholesterol into pregnenolone via the P450 side chain cleavage enzyme) there is a prevalence of CYP450 enzymes located in mitochondria and the electron transport system is very susceptible to oxidative stress. During the electron transport, a leakage of electron to the ultimate acceptor leads to their binding to oxygen, being considered a primary source of ROS, this may result in acceleration of ROS production in mitochondria. In this context, it is considered the effectiveness of electron transfer from NADPH to CYP enzymes for monooxygenation of substrates as a source of ROS because during the uncoupling reaction, without the presence of any substrates, the electron-transfer chain oxidizes NADPH and yields ROS. During CYP2E1 metabolism is frequently observed this kind of uncoupling reactions, thus this enzyme is strongly associated to ROS production and oxidative stress [16]. The enzyme CYP2E1 is associated with the metabolism of small molecules, and can be induced by ethanol, obesity, diabetes and polyunsaturated fatty acids; this induction is related to toxicity and oxidative stress. Another mechanism of CYP2E1 activation is the reduction of glutathione levels, upon acetaminophen administration, for example. Besides, this drug increases lipid peroxidation and protein carbonylation, enhancing the ROS production due to higher activity of CYP2E1 and being associated to hepatotoxicity mediated by MAP-kinase pathway [16, 19].
\nGlutathione S-transferase (GST) is a family of intracellular enzymes that prevent the action of endogenous and exogenous toxins on the cells. GSTs are multifunctional enzymes that participate in the phase II of the xenobiotic metabolism and catalyze the nucleophilic attack of the reduced form of glutathione (GSH) to potentially hazardous compounds. How are involved in the metabolism of many carcinogens, environmental pollutants and cancer-fighting drugs, it is therefore reasonable to assume that the lack of specific isoenzymes has a significant effect on the tolerance of an organism to carcinogens [20]. Human GSTs are categorized into cytosolic/nuclear, mitochondrial and microsomal. Based on their amino acid sequences and/or nucleotide substrate specificity and immunological properties, seven classes of cytosolic GSTs are described: Alpha, Mu, Pi, Sigma, Theta, Omega and Zeta. Microsomal GSTs are designated MAPEG (membrane-associated proteins in eicosanoid and glutathione metabolism) and the only mitochondrial GST confirmed in humans is GST-kappa, which is also present in peroxisomes. GSTs are normally found in biological medium as homo or heterodimers and these dimers have two active sites whose activities are independent. After combining with reduced glutathione (GSH), these enzymes have higher specificity for a second substrate (the electrophilic). GST enzymes participate in the metabolism of endogenous and exogenous compounds, for example, polycyclic aromatic hydrocarbons, phenylalanine and tyrosine amino acids, testosterone and progesterone. These enzymes target endogenous compounds, maybe derived from peroxidation of polyunsaturated fatty acids present in cell membranes and the activity of reactive oxygen species [21–23].
\nConclusive evidence suggests that oxidative stress is a major contributor to the pathophysiology of a variety of neurodegenerative diseases, including Alzheimer\'s, Parkinson\'s, Huntington’s, tardive dyskinesia (TD), epilepsy and acute diseases of the central nervous system, such as spinal cord injuries and/or brain traumatic. The human brain is vulnerable to oxidative stress due to many facts such as (i) metabolism of catecholamines; (ii) decrease in antioxidants; (iii) presence of transition metals; (iv) occurrence of brain trauma/injury; and also (v) the brain is a organ that proportionally requires more oxygen and (vi) expresses low levels of antioxidant enzymes, which contribute to formation of ROS. As a consequence of redox unbalance in brain, one of the most affected structures is the lipid membrane [24].
\nParkinson’s disease (PD) is characterized by loss of dopaminergic neurons in the substantia nigra pars compacta of the brain, leading to rigidity or slowing movements and postural instability. Most of the cases of PD are idiopathic and some cases are genetic-related, but in general context, aging is a determinant factor. In both idiopathic and genetic cases of PD, the oxidative stress plays a critical role in pathogenesis, being a common underlying mechanism. There is an elevated level of oxidized lipids, proteins and DNA associated with decreased glutathione level in the brain of PD patients. This increased susceptibility to oxidative damage in the dopaminergic neurons is due to (i) the presence of ROS generating enzymes, such as tyrosine hydroxylase and monoamine oxidase and (ii) these neurons contain iron, a catalyser of Fenton reaction (Fe(II) + H2O2-> Fe(III) + OH• + OH−) that leads to superoxide radicals and hydrogen peroxide production [25].
\nA fact of Alzheimer’s disease is the dysregulation of iron and copper homeostasis and various evidence of oxidative stress, mainly RNA oxidation. Neurons usually do not store big amounts of iron, but with aging there is an accumulation of iron in the brain, especially in microglia, astrocytes and neurons from cortex and hippocampus. If iron levels increase much more than ferritin, an iron-storage protein, it becomes free to catalyze Fenton’s reaction [26].
\nThe tardive dyskinesia (TD) is an adverse effect of antipsychotic use, it affects up to 25% of schizophrenic patients. However, as the majority of patients do not develop TD, it is considered that genetics factors may define its occurrence but TD pathophysiology remains unclear. One of the strongest hypotheses suggests that it is caused by oxidative stress originated from neurotoxic free-radical production upon antipsychotic medication. This affirmation is supported by genetic polymorphisms evaluated in genes that encode a mitochondrial enzyme that prevents oxidative damage due to energetic metabolism (manganese superoxide dismutase) and a cytosolic flavoenzyme that prevents quinone reduction (NADPH quinone oxidoreductase), playing a role in antioxidant defense [27].
\nMetabolic syndrome is a term that designates a cluster of health problems often associated to modern life style, including obesity, insulin resistance, dyslipidemia, impaired glucose tolerance and high blood pressure. The metabolic syndrome is diagnosed when at least three of the following alterations are present: visceral obesity (waist circumference >102 cm in men or >88 cm in women); raised arterial blood pressure (>130/85 mm Hg); dysglycemia (fasting plasma glucose >100 mg dL); raised triglyceride concentrations (>150 mg dL) and low high-density lipoprotein (HDL) cholesterol (<40 mg dL in men or < 50 mg dL in women) [28].
\nThe oxidative stress is related to metabolic syndrome in several ways: (i) H2O2 promotes insulin signaling, being associated with increased insulin resistance; (ii) superoxide anion is generated by angiotensin stimulation of NADPH and angiotensin II/angiotensin II type I receptor (AT1R), which plays a critical role in blood pressure control; (iii) hyperglycaemia leads to overproduction of superoxide by mitochondrial electron transfer chain, activating oxidative stress; (iv) elevated low-density lipoprotein (LDL) and low high-density lipoprotein (HDL) are correlated with oxidative stress and the dyslipidemia treatment with rosuvastatin is known to reduce oxidative stress through raise of antioxidant enzymes [28].
\nDue to oxidative DNA damage there is a direct correlation between diabetes and cancer. Diabetic patients present high levels of ROS because of elevated glucose, fatty acids and insulin blood levels; combined to lower antioxidative capacity derived from reduced glutathione synthesis. To support those findings, it has been proved that polymorphisms in peroxisome proliferator-activated receptor-γ coactivator-1α (PPARGC1A) – a protein that regulates mitochondrial electron transport, leads to decontrolled redox activity [29].
\nAtherosclerosis is defined as an arterial disease characterized by fibrous and cholesterol rich plaques. Atherosclerosis progression causes blood flow obstruction, hemorrhage due to rupture and thrombosis leading to strokes or myocardial infarctions. Many risk factors are associated with atherosclerosis development, the most widely known are serum low-density lipoprotein (LDL) cholesterol, low serum high-density lipoprotein (HDL) cholesterol, diabetes, hypertension, smoking, aging and oxidative stress [30].
\nDuring LDL oxidation, a progressive process and very important for the beginning of the formation of atheromatous plaque, the cholesterol is target of oxidants, which generate a variety of oxysterols. On the other hand, lipid peroxidation products (MDA and 4-HNE) can react with histidine, cysteine or lysine residues of proteins, leading to formation of stable Michael adducts with a hemiacetal structure or to Schiff bases that undergo a rearrangement generating the Amadori products. These aldehydes can derivatize Lys residues of apoB, which decreases the number of positive charges and interferes on LDL binding to LDLR and scavenger receptors [31].
\nIn endothelial cells, besides stimulating the antioxidant defense (mainly by glutathione), Nrf2 (nuclear factor (erythroid-derived 2)-like 2) suppresses inflammation-associated expression of adhesion molecules and cytokines, which are associated with the early stage of atherogenesis [29]. NAD(P)H oxidases (NOXs) are major sources of ROS in the vasculature, producing superoxide from molecular oxygen using NAD(P)H as the electron donor and endothelial NO synthase (eNOS) produce NO which represents a key element in the vasoprotective function of the endothelium. However, pathological conditions associated with oxidative stress may become eNOS inefficient and promote the rapid inactivation of NO by excess superoxide [32].
\nThere is growing evidence that reversal of oxidative stress with antioxidants can reduce the degree of myocardial ischemic injury and heart dysfunction [33].
\nThe pathological effects of NO and O2− in virus infection are in clear contrast to their beneficial antimicrobial effects in bacterial and fungal infections. In virus infections, NO and ONOO−, which are primitive host-defense molecules, cause nonspecific oxidative damage in virus-infected tissue, leading to various pathological events. Virus-induced oxidative stress has been reported during HIV, influenza virus, HBV, hepatitis C virus, encephalomyocarditis virus (EMCV), respiratory syncytial virus (RSV), dengue virus (DENV) and others [34].
\nStudies including rotavirus-infected patients showed that viral infection stimulates NO production, decreases superoxide dismutase and glutathione peroxidase activities and increases inducible nitric oxide synthase (iNOS) mRNA and iNOS expression in murine ileum [35].
\nInfluenza virus is probably the best characterized pathogen modulating redox homeostasis. Influenza-induced ROS production has been associated with host immune and inflammatory responses, as well as modulation of viral replication. Oxygen radicals and their derivatives are recognized as principal mediators of influenza virus-induced lung injury [36].
\nWithin the Flaviviridae family, hepatitis C virus infection promotes oxidative stress and manipulates antioxidant systems, leading to liver damage and chronic disease. Elevated levels of reactive oxygen species (ROS) are considered as a major factor contributing to HCV-associated pathogenesis. HCV core protein is considered as a major regulator affecting the release of ROS from mitochondria. In this context, mitochondria play a crucial role for the production of ROS in HCV-infected cells. Several pathways are affected upon HCV infection to result in an induction of autophagy that interferes with various steps of the viral life cycle to promote a permanent viral infection. The assembly and release of viral particles are closely linked to the VLDL synthesis and occur via the secretory pathway. Elevated glucose production, enhanced fatty acid uptake or upregulation of genes involved in lipid and cholesterol synthesis may contribute to oxidative stress-induced insulin resistance linked to HCV infection [36].
\nInduction of iNOS and production of NO, accumulation of ROS and RNS, as well as perturbation of the reduced glutathione (GSH) content are all signatures of Dengue virus (DENV) infection in different human cells and animal models. DENV infection resulted in an intracellular accumulation of NAD(P)H oxidase (NOX2)-derived ROS in monocyte-derived dendritic cells (Mo-DCs). Alteration in the redox status of DENV-infected patients has been associated with increased inflammatory responses, cell death and correlated with different parameters associated with dengue disease [37].
\nThe HPV infection, although necessary, is not sufficient to cause cancer and several studies have been devoted to the search for concurrent carcinogenic factors. Among these cofactors, many evidence support the role of ROS. It is clear that viral infection induces ROS that in turn causes damage to all types of biological macromolecules. Two different types of cooperative mechanisms are presumed to occur between ROS and HPV: (i) the ROS genotoxic activity and the HPV-induced genomic instability concur independently to the generation of the molecular damage necessary for the emergence of neoplastic clones. This first mode is merely a particular form of cocarcinogenesis and (ii) ROS specifically interacts with one or more molecular stages of neoplastic initiation and/or progression induced by the HPV infection [38, 39].
\nTherefore, it seems reasonable to hypothesize that, while in most cases the cells react to HPV infection and can overcome the virus-induced ROS by activating apoptosis leading to termination of viral replication and lesion regression, in some of the infected cells a steady state balance between ROS generation and detoxification is established, partly due to viral-induced antioxidant response. Thus, infected cells can aberrantly proliferate, paving the way to neoplastic progression HPV, exploit host cell survival mechanisms, through modulation of redox homeostasis, increasing the activity of catalase, SOD among other, as an adaptive response to the high ROS conditions of preneoplastic lesions. Elevated GST and GSH provide the HPV hosting cell with improved oxidative damage detoxifying systems, but suppression of p53 and iNOS together with induction of vascular endothelial growth factor (VEGF) and resistance to ROS leads to the suppression of apoptosis and generates an oxidant fitting cell phenotype. Therefore, the tumor cell adapts their metabolism in order to support their growth and survival, creating a paradox of high ROS production in the presence of high antioxidant levels [38, 39].
\nMany signaling pathways that regulate the metabolism of ROS are also linked to tumorigenesis [40, 41]. However, ROS can also promote tumor formation by inducing DNA mutations and pro-oncogenic signaling pathways. The production of low level of ROS is required for homeostatic signaling events. It can be driven by NAD(P)H and NAD(P)H oxidase (NOX), leading to the increase of cell proliferation and survival through the posttranslational modification of kinases and phosphatases. At moderate levels, ROS induce the expression of stress-responsive genes such as
The regulation of oxidative stress is an important factor not only for tumor development but also for the responses to anticancer therapies. As high ROS levels are harmful to cells, oxidative stress can have a tumor-suppressive effect. This imparts pressure on cancer cells to adapt by developing strong antioxidant mechanisms. But despite having an enhanced antioxidant system, cancer cells maintain higher ROS levels than normal cells. At high levels, ROS can cause damage to macromolecules, including DNA; induce the activation of protein kinase Cδ (PKCδ), triggering senescence; and/or cause permeabilization of the mitochondria, leading to the release of cytochrome
The role of ROS in carcinogenic process can be either pro or anti oncogenic, and it can be summarized as follows: (i) regulating tumor development and signaling pathways for cell progression through ERK1/2 activation and ligand-independent RTK activation; (ii) regulating chronic inflammation for example through NF-kB activation; (iii) controlling tumor suppressor expression and cell cycle inhibitors; (iv) mediating angiogenesis by the release of vascular endothelial growth factor (VEGF) and angiopoietin; (v) favoring metastasis and tissue invasion due to metalloproteinase secretion; (vi) avoiding cellular death by activating SRC and PI3K/AKT pathway. Additionally, generating ROS is the mechanism of attack used by most of chemotherapies and radiotherapy [43, 44].
\nKeap1 (Kelch-like ECH-associated protein 1) sequesters Nrf2 (nuclear factor erythroid-derived 2) in the cytoplasm by binding to its aminoterminal regulatory domain. Keap1 is a sulfhydryl (S)-rich protein, and several cysteine residues mediate the Keap1–inducer interaction. When the interaction between Keap1 and Nrf2 disrupts, it allows Nrf2 to translocate to the nucleus. In the nucleus, Nrf2 controls several different antioxidant pathways by activating the expression of GSTs and other genes. This control is important to avoid cellular wear caused by oxidative stress, thus hindering the onset of various diseases.
The interindividual variation of the activity of antioxidant enzymes, for example, GST, considered by both environmental factors (e.g., diet and exposure to toxins such as cigarette) and genetic, is directly related to the etiology of cancer. Cytosolic GST present polymorphisms in humans and, this is probably the cause for differences in interindividual response to xenobiotics. The first studies in this area have addressed the correlation between GSTM1 null and/or GSTT1 null genotypes and a higher incidence of lung cancer, bladder, breast, colorectal head/neck. The discovery of allelic variants of GSTP1, encoding enzymes with reduced catalytic activity, led many researchers to examine the hypothesis that the combinations of polymorphisms of the Mu class, Pi and Theta of GST contribute to disorders with environmental factors [45, 46]. Studies with mice that exhibited a homozygous deletion of Nrf2 showed that Nrf2 is critical for inducing hepatic glutathione S-transferase (GST), NAD(P)H: quinone oxidoreductase (NQO1) and regulating levels of glutathione (Figure 1) [47].
\n\nBesides genetic variants of GST, changes in phase I enzyme activity as encoded by the cytochrome P450 family can also have implications for the metabolism of specific nitrosamines from the tobacco, alcohol and other carcinogenic substances [48].
\nThe GST enzymes are part of an integrated protection system, so it is important to note that the efficiency of this system depends on the combined action of other enzymes, such as γ-glutamylcysteine synthase γGluCysS) and glutathione synthase, in order to provide glutathione as well as carriers to facilitate the elimination of glutathione conjugates [21].
\n\nThe modulation of intracellular ROS levels is crucial for cellular homeostasis, and different ROS levels can induce different biological responses. It can occur due to the accumulation of intrinsic and/or environmental factors, such as hypoxia, enhanced cellular metabolic activity, mitochondrial dysfunction, increased activity of oxidases, lipoxygenases and cyclooxygenases. The accumulation of free radicals can lead to important changes in the structure of nucleic acids, proteins and lipids, altering their functions with consequent impact on cellular metabolism. These changes create conditions favorable to the onset of different diseases. The determination of oxidative stress markers and plasma antioxidants can suggest a targeted therapy against deficiencies in cell protection systems and it could be useful in an attempt to minimize complications caused by increased oxidative stress, leading to a better prognosis of various diseases.
\nBrain tumors according to their location and growth rate can produce very typical clinical manifestations [1], in addition to the classic characteristics of imaging studies that provide the possibility of approaching the diagnosis of the specific type of tumor and guide to establish the treatment modality [2]. However, when the incidence of some of these tumors is very low and they present with very varied clinical manifestations, added to the radiological findings that do not provide too much information to approximate the diagnosis, these cases condition stricter study protocols where the undoubtedly diagnoses alters the treatment modality for each particular case [3]. For this reason, knowledge of the existence of some of these tumors should be the subject of study, to understand the difficulty in diagnosis and treatment, seeking to reduce errors in addressing these cases and improve the result.
The first case presented in this chapter corresponds to an intracranial Rosai-Dorfman disease (RDD), which was manifested as an apparent multiple meningiomatosis that affected the anterior fossa, the sphenoidal plane, and the clivus. RDD is a non-Langerhans histiocytosis described in 1965 by Pierre P. Destombes and then characterized by J. Rosai and R. Dorfman [4, 5]. RDD has a prevalence of 1 in 200,000 and an incidence of 100 cases per year. It can occur at any age but is usually more common in adolescents [6]. The typical clinical manifestations of this disease are the presence of painless bilateral cervical lymphadenopathy added to the presence of fatigue, fever, and weight loss, associated with elevated erythrocyte sedimentation rate, anemia, fever, and hypergammaglobulinemia. Extranodal involvement occurs in less than 43% of cases, mostly in the skin, nasal cavity, and bone [7]. The central nervous system (CNS) is affected in less than 5% of cases, the isolated affection is possible, without systemic manifestations. There are approximately 200 reported cases of intracranial RDD [8, 9]. This case illustrates a patient with multiple intracranial lesions, where the symptoms and characteristics per image simulated the presence of multiple meningiomas, where the RDD finding was made until the moment of the histopathological study.
A 59-year-old male patient with a history of gradual right hearing loss that later presents the same symptoms in the contralateral ear. His current condition began 8 months ago with a high-intensity holo-cranial headache that predominated in the mornings accompanied by occasional dizziness. Three months before his hospital admission, he reported non-quantified weight loss, asthenia, and adynamia.
Two months before hospital admission, the patient reported decreased visual acuity and compromise of the temporal hemifields added to hyposmia. The reason for hospital admission in our institution was the presence of two generalized tonic–clonic seizures lasting more than one minute (less than five minutes), these seizures were characterized by the absence of aura, with a postictal period of 20 minutes. The second seizure required hospital admission for control. On physical examination, the cognitive functions were preserved, evaluation of the cranial nerves demonstrate hyposmia and bitemporal hemianopia. Fundoscopy showed edema of the papilla in the left eye and an atrophic papilla of the right eye. Regarding the complementary studies, the electroencephalogram showed abnormal bifrontal activity. Computed campimetry confirmed the bitemporal hemianopia, and regarding the neuroimaging studies, the computed tomography (CT)-scan showed three isodense with homogeneous enhancement lesions located in the midline in the floor of the anterior fossa in the cribriform plate, the sphenoidal plane with extension to the tuberculum sellae, and the middle and lower portion of clivus. The magnetic resonance imaging (MRI) revealed isointense lesions with peritumoral edema, with intense and homogeneous gadolinium-enhancement demonstrating a dural attachment (Figure 1A–F).
Pre-operative brain magnetic resonance imaging (MRI) studies. Non-contrasted brain MRI shows an isointense olfactory groove lesion with perilesional edema in the T1-weighted (A), T2-weighted (B), and FLAIR (C). Contrasted brain MRI reveals three homogeneous enhancement lesions with dural attachment (yellow arrows in the sagittal section) in the floor of the anterior fossa in the crista Galli and cribriform plate, the sphenoidal plane with extension to the tuberculum sellae, and the middle and lower portion of clivus, observed in the coronal (D), sagittal (E), and axial sections (F). Histopathological analysis. G. Positive immunohistochemical profile for S100 protein. Furthermore, other immunochemical profiles show positive expression of CD68 (macrophages), CD20 (B lymphocytes), and CD2 (T lymphocytes), in which lymphagocytosis was observed. IgG and IgG4 positivity were also identified. A negative expression for CD30 and CD15 (reed Stenberg cells), and CD1A (Langerhans cells) was observed. H. H&E Stain: Mixed inflammatory infiltrate with plasma cells, lymphocytes, and macrophages, no evidence of meningothelial cells, emperipolesis was observed (black arrow).
The diagnosis of multiple meningiomas was established, supported by the neuroimaging features and previous experience. The surgical plan was to resect the two main symptomatic lesions (olfactory groove and tuberculum sellae). The surgical approach was made through a bicoronal incision to perform a bifrontal craniotomy and a sub-frontal approach. The surgical approach allowed a complete resection of the lesions, after the olfactory groove lesion resection was possible to access the lesion of the tuberculum sellae. Debulking of the lesions was made with an ultrasonic aspirator, and according to meningioma surgery principles, it was decided to perform anterior fossa drilling to reduce the recurrence probability. The tumor lesions showed low vascularity and close contact with the optic chiasm (Figure 2). Immediately post-operative the patient remained without complications and was discharged five days after surgery, the CT scan performed 5 days after surgery showed complete resection of the lesions (olfactory groove and tuberculum sellae), with residual lesion of the middle and lower portion of clivus (Figure 2F). Due to the residual lesion, the patient was observed for the clinical oncology service to decide adjuvant management.
(A) Preoperative enhanced coronal head CT-scan with an olfactory groove lesion (square). Surgical procedure: Approach to the anterior fossa lesion. Perimeter dissection of the anterior cranial fossa lesion (asterisk) is shown (B-C). Debulking with ultrasonic aspiration (D) and complete resection of olfactory groove (E) is demonstrated. (F) Sagittal section of postoperative CT with complete resection (arrow).
Histopathological findings established the diagnosis of RDD (Figure 1G and H). In the subsequent follow-up, extension studies were carried out, which were ruled out other infiltrates with a thoracic and abdomen-pelvic CT. The patient received treatment with prednisone and remain asymptomatic without clivus lesion growth at 8 months follow-up.
For the diagnostic process of RDD, it is important to consider the observations by imaging studies that usually mimic the characteristics of a meningioma, either as one or multiple extra-axial lesions with homogeneous contrast enhancement surrounded by vasogenic perilesional edema, they can arrive to present a dural tail and its location is very diverse [1]. Proton MRI spectroscopy improves the specificity of preoperative diagnoses in some patients; for example, in meningiomas, alanine is usually elevated in spectroscopy, with a peak at 1.48 ppm, in a patient with RDD disease, spectroscopy revealed an increased choline level [10]. In a review of 10 cases, a dural tail was found in all cases. Therefore, in data suggestive of meningioma obtained by neuroimaging studies, RDD is a differential diagnosis [11]. Zhu et al. [11] concluded that, unlike meningiomas, a typical hypointensity non-related to calcification on T2-weighted or fluid attenuation inversion recovery (FLAIR) images could suggest the RDD diagnosis.
Histopathological characteristics correspond to a large lymphohistiocytic infiltrate, with a large or vesicular nucleus, well-defined nuclear membranes and a single and prominent nucleolus. The main characteristic is the intracytoplasmic presence of lymphocytes and, to a lesser extent, intact erythrocytes, plasma cells, and neutrophils (“emperipolesis”), however, it may be absent in 30% of leptomeningeal lesions [7, 9]. Associated with histiocyte proliferation, a perivascular plasmacytic infiltrate can be observed. From the immunohistochemical point of view, they are characterized by presenting protein S100 +, CD68 +, CD11c +, MAC387 +, lysozyme +/−, being negative for CD1a, a positive marker in Langerhans cell histiocytosis [10, 12].
Related to the management of this disease is primarily with surgery, seeking to eliminate the mass effect and the associated neurological sequelae. Total resection is the main objective, although a partial resection is allowed in case the lesions are in complex regions. The optimal management of residual disease remains unclear due to the rarity of the disease [13]. The use of radiotherapy has shown some efficacy of residual or recurrent disease, postoperative doses of 20 Gy in 10 fractions in 2 weeks after subtotal resection has shown a good effect in reducing symptoms and reducing the size of the lesions [14]. The use of chemotherapeutic agents such as alkaloids and anthracyclines, alkylating agents, and methotrexate have shown variable efficacy [15]. Rivera et al. [16] reported the use of the modified CHOP regimen in two cases of intracranial RDD observing a long-term remission [16].
Adeleye et al. [17] reported a series of 111 cases of RDD involving the CNS [17]. Of the population studied, 77% presented intracranial disease, which received various treatments with surgery, radiotherapy and chemotherapy. 37% of the study population had a long-term follow-up beyond one year (41% of these patients had no recurrence of the disease), where a relapse or growth of the most residual tumor was determined in 12%. Therefore, active monitoring after the surgery is prudent; however, it is not well established how often to follow up with imaging studies and when it would be prudent to classify the disease as remitted. Rivera et al. [18] reported the longest reported follow-up time (7 years) [18], of two patients with intracranial RDD with surgical resection and chemotherapeutic management with the modified CHOP scheme consisting of 8 cycles of cyclophosphamide (1 g), Vincristine (2 mg), doxorubicin (50 mg), and prednisone (50 mg) for 5 days every 3 weeks. Where it was observed that during follow-up there were no recurrences. Due to the low incidence of the disease, it is difficult to standardize diagnostic, therapeutic and prognosis. For this reason, we propose a simple algorithm for the diagnosis and management of intracranial RDD (Figure 3). Table 1 describes the fundamental aspects in the management of this pathology.
Algorithm for management and diagnosis (clinical suspect) for intracranial Rosai-Dorfman disease. Clinical suspicion is obtained by clinical evaluation and imaging studies. The differential diagnosis is made with meningioma, corroborating it by the histopathological and immunohistochemical study. Relative to management, the presence of residual tumor after surgery suggests performing radiotherapy with or without chemotherapy. Strict monitoring after surgery is recommended due to the risk of recurrence.
Illustrative case | Pearls and pitfalls |
---|---|
Intracranial Rosai-Dorfman Disease (RDD) |
|
Choroid plexus papilloma (Tumoral compression of the facial colliculus) |
|
Neuroenteric cyst (NEC) on posterior fossa |
|
Rare tumors: Pearls and pitfalls in diagnosis, surgical management, and prognosis.
RDD, Rosai-Dorfman disease; MRI, Magnetic resonance imaging; FLAIR, Fluid attenuation inversion recovery; HFS, Hemifacial spasm; EMG, Electromyography; NEC, Neuroenteric cyst; DWI, Diffusion-weighted imaging; CA 19-9, carbohydrate antigen 19-9; CSF, Cerebrospinal fluid.
As a second case, we have an extremely rare cause of hemifacial spasm (HFS). HFS is an involuntary neuromuscular disorder in which it affects the facial musculature, which usually has as its primary cause a mechanical compression over the cisternal portion of the facial nerve in the root entry zone by an aberrant or ecstatic vessel in the 60–70% of the cases [19]. Etiology’s different than vascular compression are called secondary causes, which correspond commonly to those pathologies that occupy the space in the cerebellopontine angle such as: aneurysms, arteriovenous malformations or tumor growths. Compression of the facial colliculus due to the presence of a tumor is an extremely rare cause, representing less than 0.6% of HFS cases [20]. What makes this case even more exceptional is that the tumor that was conditioning the compression of the facial colliculus was a choroid plexus papilloma (CPP), an uncommon benign intraventricular neuroepithelial tumor [21, 22].
A 43-year-old female who presents left severe HFS, associated with headaches, symptoms started 6 months before presentation at our service, characterized by the onset of periocular and expression muscles, increasing in intensity and frequency. The patient had the antecedent of one episode of left facial palsy 6 years ago with full recuperation 2 months later. The first management was with botulin toxin, showing a low response to initial treatment. Clinical examination at our functional neurosurgery service, found left HFS with labial commissure deviation, palpebral occlusion, and extension of the spasm to the neck. The patient did not refer pain and has no evidence of facial palsy. HSF presented every 2 min with a 15 seconds duration. Other cranial nerves did not show any alterations, and hearing was not affected. Clinical assessment was complemented with Brain MRI with gadolinium, showing a tumoral growth in the floor of the fourth ventricle that homogeneously captured gadolinium without infiltrating the floor of the fourth ventricle (Figure 4A and B). Preoperative and intraoperative electromyography (EMG) recordings were considered for the management. The preoperative register showed normal auditory and motor-evoked potentials. EMG was free from synchronic neuromyotonic discharges in muscles innervated by the left facial nerve, corresponding to the HFS clinically founded.
Neuroimaging: Preoperative gadolinium-enhanced T1-weighted MRI showed that the right side of the fourth ventricle was occupied by a hyperintense tumor (arrows). (A) Axial view. (B) Sagittal view. T1-weighted sequences with gadolinium showing complete resection of the tumor. (C) Axial view. (D) Sagittal view. Histopathology: Choroid plexus papilloma. (E) HE x40: Cylindrical coating epithelium with flat apical domain and multiple microvilli (arrow). Cells have round-to-oval nuclei, moderate amount of acidophilous cytoplasm, and some focally pseudostratified (arrowhead) and oriented to the basal domain. (F) HE ×10: Lesion mimics the papillary architecture of a normal choroid plexus with thin fibrovascular stems and coated by a simple cylindrical epithelium. (G) HE ×4: Epithelial neoplasia. (H) Intraoperative neuromonitoring: Electromyographic activity shows synchronic neuromyotonic discharges in muscles innervated by the left facial nerve (blue arrow). Cessation of irritative activity over the left orbicularis oculi and orbicularis oris after en-bloc removal of the tumor (green arrow).
It was decided to perform surgery to remove the tumor growth of the superior colliculus to improve the clinical status of the HFS. A telovelar approach with intraoperative neurophysiology recordings of the facial nerve was performed. The surgical procedure was performed with the patient in the prone position and head fixation. An incision of 1 cm was made above the inion up to the C2 spinous process, the C1 posterior arch was recognized, and the tectorial membrane was dissected. Conventional suboccipital craniectomy was conducted. Dural opening in Y was realized before transverse sinus identification. Under the microscopic vision, the tela choridea was opened, and the tumor was identified. The tumor had a pearly appearance. After dissection complete resection was made. At the extraction of the tumor, there was a nervous hyperexcitability correction in intraoperative EMG recording of the facial musculature (Figure 4). Motor-evoked potentials did not show alterations during the surgical intervention. Postoperative histopathology examination demonstrates CPP in the fourth ventricle (Figure 4E–G). The clinical outcome of the patient in the immediate postoperative period was a diminution in the intensity and frequency of spasms. At 12 months of follow-up, complete symptom resolution was observed without associated neurological deficits. Postoperative MRI at 1 year of follow-up showed complete resection of the tumor (Figure 4C and D).
HFS’s most common pathophysiological mechanism corresponds in 60–70% of the cases to mechanical compression over the cisternal portion of the facial nerve in the root entry zone by an aberrant or ecstatic vessel in the 60–70% of the cases. Conversely, secondary common etiologies are pontocerebellar angle tumors, traumas, demyelination conditions, and infections. Therefore, the tumors in adults related to HFS are rare (0.3–2.5%), and the tumoral compression at the facial colliculus level, at the floor of the fourth ventricle is considered an exceptional etiology, being gliomas, subependymomas, ependymomas the neoplasia’s reported [19]. The pathological mechanism of HFS is unclear. However, different theories suggest that the direct compression of the facial nerve in its cisternal portion by a vascular structure is the most related mechanism of injury, which leads to local demyelination. On the other hand, another hypothesis suggests a central/nuclear origin, that states change in the reorganization of functional connections within the facial nerve nucleus, generating irritative activity that produces abnormal discharges, precipitating HFS. A hypothesis that would be more related to the mechanism of HFS production in the presence of a tumor mass growing in the superior colliculus. This case supports the central theory of direct facial nucleus irritability, generating a hyperexcitability state that precipitates the discharges [23]. Microvascular decompression is the most frequent surgical treatment used for HFS. It is usually indicated when a vascular contact is found by MRI, which is usually effective management in more than 80% of cases [24]. However, because in this case a vascular contact was not found, the surgical management is different, focused on the complete resection of the tumor. Therefore, due to the uncertainty that may exist in the clinical outcome as it is an infrequent presentation, intraoperative monitoring is a very useful tool that helps to define the effectiveness that surgical intervention could have in symptomatic improvement, observing changes in symptoms, and synchronic neuromyotonic discharges during resection [25].
In conclusion, secondary HFS are infrequent conditions. Direct compression by tumors at the facial colliculus level associated with HFS is an exceptional case. Clinical findings do not allow differentiation between primary and secondary HFS, for this reason we recommend an adequate evaluation of the brain MRI, supported by electrodiagnostic studies. Tumoral compression at the facial colliculus level at the floor of the fourth ventricle is an exceptional etiology, and there is very few information in the medical literature about management and diagnosis. Therefore, about our experience, in Table 1 we describe the fundamental aspects in the management of this pathology.
Neuroenteric cysts (NEC) are rare benign (the malignant transformation is extremely rare) lesions of the spinal axis composed of heterotopic endodermal tissue generally located in the intradural extramedullary space in the lower cervical and upper thoracic spine, comprising 0.03% of intracranial lesions and 16% of cystic lesions of the CNS, they can found rarely intracranially, examples in the posterior fossa are ventral to the brainstem or in the cerebellopontine angle, and they present with hydrocephalus, headache, and cranial nerve deficits [26, 27]. The origin of these lesions is not completely understood, histologically are composed of cuboidal epithelium that resembles the gastrointestinal or respiratory tract. Therefore, are thought to arise from rostrally located vestigial remnants of the neuroenteric canal [28]. The consensus for treatment is complete surgical resection, when possible, partial resection should be avoided because of the high risk of recurrence. However, due to their rarity, there is a lack of information about management [29]. On the other hand, Klippel-Feil syndrome (KFS) is defined as the fusion of two or more cervical vertebrae, with a classic triad of limitation of cervical movements, short neck (brevicollis), and low hair implantation in 52% of patients [30]. Association between NEC and KFS has not been described.
A 21-year-old male patient began his current disease with a severe occipital headache of one month of evolution, the headache was aggravated by Valsalva maneuvers, occasionally associated with nausea and emesis. Physical examination showed brevicollis with restricted range of motion, low hair implantation (KFS). Moreover, examination shows papilledema, dysdiadochokinesia, and right dysmetria. Head CT exhibited a heterogeneous cystic lesion located on the posterior fossa, conditioning an obstructive hydrocephalus, for which an urgent ventriculoperitoneal shunt was placed (demonstrating clear cerebrospinal fluid). Sagittal section of a spine CT (Figure 5A) that demonstrates C1-C2 and C3-C4 anterior and posterior elements fusion, without thoracic, lumbar, or sacral alterations. Anteroposterior and lateral static and dynamic cervical spine radiographs and spine CT exposed lordosis rectification, flexion, and extension limitation. Brain MRI showed (Figure 5B and C) an infratentorial lesion, dorsal to the right cerebellar hemisphere, ovoid shape, with regular and defined borders, composed of a nodular portion in contact with pia mater, and multiple punctate flow absences, isointense on T1, heterogeneously hyperintense on T2 and FLAIR sequences, with diffusion restriction on its central portion and contrast enhancement, whose measurements were 17 × 14 × 15 mm in major axes, and spectroscopy displayed increased N-Acetyl-Aspartate and choline peaks (Figure 5D); another remaining cystic portion was hyperintense on T1, hypointense on T2, FLAIR, and apparent diffusion coefficient, without diffusion restriction or contrast enhancement, whose measurements were 46 × 49 × 46 mm. Due to data compatible with KFS, simple contrasted thoracoabdominal CT, echocardiography, and renal function tests were obtained; otorhinolaryngology assessment cursed without hearing alterations, and medical genetics confirmed the syndromic diagnosis.
(A) Cervical spine computed tomography (CT) with evidence of C1-C2 and C3-C4 anterior elements fusion (white arrow). Presurgical brain contrast-enhanced T1-weighted magnetic resonance imaging (MRI). (B) Axial section, there is evidence of an extra-axial lesion in the posterior fossa, which is contrast enhanced and displaces the cerebellum and brainstem ventrally, collapsing the fourth ventricle (white arrow). (C) MRI sagittal section. (D) Spectroscopy without choline (Cho) elevation according to the indicated voxel on T2-sequence hypointense lesion. Intraoperative images: (E) The tumor capsule with a good cleavage plane presents liquid content of oily material inside the capsule. (F) Histopathology image: HE (400X), demonstrate a cyst wall and proteinaceous content with some spaces for cholesterol crystals.
A total complete surgical resection was decided. Subsequently, a midline suboccipital craniectomy was performed. The surgical procedure involves resection of the C1 posterior arch and tumor excision, obtaining a cystic lesion with a mural nodule at the inferolateral right torcular level, with leakage of greenish fluid (Figure 5E). Complete resection of the capsule was achieved, with a histopathological study that reported smooth, opaque, light gray color walls, with tortuous vessels, and peripheral solid, anfractuous, gray-green areas of firm consistency, clear brown content, and soft consistency compatible with NEC, positive to alcian blue and negative to periodic acid-Schiff stains (Figure 5F). The patient had a favorable clinical evolution, receiving medical discharge to home after 3 weeks, with adequate follow-up 9 months after surgery, identifying by MRI a residual nodular image adhered to the straight sinus.
NEC was described for the first time in 1928 and the first intracranial NEC was reported in 1962 [26], with more than one hundred cases reported since then [31]. Relative to the epidemiological characteristics of the patients, frequency is higher in men, and the age of presentation ranges from the neonatal period to 70 years. Regarding intracranial location, the initial findings are at the second or third decades of life. The predominant localization is on the posterior fossa (90%), specifically at prepontine and prebulbar cisterns, cisterna magna, cerebellopontine angle, fourth ventricle, and dorsal to the cerebellum. The etiopathogenesis is due to abnormal endodermal-ectodermal adhesion during gastrulation at embryological development, with the persistence of endodermal elements near the notochord in the neuroaxis, which would explain the association with spinal disorders (spina bifida, diastematomyelia, and vertebral body alterations). Supratentorial localizations are exceptional. Infratentorial lesions usually present headache, nausea, and cranial nerve alterations such as vertigo, hearing loss, tinnitus, hypoesthesia, or trigeminal neuralgia. Diagnosis can be suspected in recurrent meningitis due to a fistula to the aerodigestive tract that causes slow growth because of active secretion from epithelial cells. Accompanying disorders are intestinal malformations and cutaneous abnormalities. Clinical manifestations can be acute or insidious, with a course ranging from 4 months to 40 years [30, 32].
Regarding the characteristics observable by neuroimaging studies in the diagnosis of NEC, in head CT is hypodense lesions without contrast enhancement. However, density depends on protein concentration. MRI shows heterogeneous lesions (well-defined, extra-axial, rounded or lobulated cysts), hyperintense on T1, T2 and FLAIR, without contrast enhancement, with slight diffusion restriction in Diffusion-weighted imaging due to xanthogranulomatous changes or presence of melanin, hemosiderin, proteins, mucopolysaccharides and cholesterol. Differential diagnoses on the posterior fossa are mainly cystic lesions; arachnoid cysts, epidermoid cyst, dermoid cyst, neurocysticercosis, or metastases, cholesteatoma, ependymoma, schwannoma, hemangioblastoma, and pilocytic astrocytoma [33, 34]. During surgery macroscopically visualization corresponds to yellow, milky white, gray, or red cysts, with thin walls similar to arachnoid, and transparent, mucoid or xanthochromic liquid content, unusually blood, pus, calcifications, or keratinized debris adhering to the adjacent pia mater. Histopathological studies reveal benign lesions with simple, pseudostratified, columnar epithelium and collagenous fibrous connective tissue lined with gastrointestinal epithelium, with the presence of goblet cells [26]. In immunohistochemistry, they are positive for cytokeratin, epithelial membrane antigen, and carcinoembryonic antigen. Degeneration to adenocarcinoma is extremely unusual and only occurs in intracranial locations (9 patients reported) [27]. In these cases, carbohydrate antigen 19–9 (CA 19–9) is positive [26], elevated MIB-1 labeling index suggests malignancy [27]. No correlation between imaging findings and pathology has been found [35].
The surgical treatment recommended for NEC is complete resection. Wang et al. [35] described a technique that shows an improvement in prognosis and limits recurrence [35]. If resection is partial, remnants adhered to neurovascular structures should be electro-coagulated to avoid reaccumulation. Surgical approaches depend on the location and the optimal visualization of the lesion and adjacent structures to minimize the risk of neurological deficits [36]. Cystoperitoneal and ventriculoperitoneal shunts are second-line procedures recommended in recurrence with high difficulty for a new excision [28]. Postoperative complications are aseptic meningitis, abducens nerve palsy, pseudomeningocele, and cerebrospinal fluid fistula [36]. Although the prognosis is mostly favorable, one-third of patients experience a symptomatic recurrence in a period of 2 months to 32 years [36]. Minimum follow-up is recommended for 10 years, every 6 months at the first 2 years [35] and can be complemented with CA 19–9 measurement on cerebrospinal fluid to determine recurrence [37].
In this case report, we did not find a specific genetic alteration that explains the relationship between KFS and NEC. The commonly associated disorders in KFS are mostly spinal disorders how congenital scoliosis and spina bifida occulta, in some cases this disease is related to hearing alterations, genitourinary defects, cardiovascular anomalies, and other skeletal abnormalities [38]. The association between KFS and intracranial tumors is mainly related to teratomas, and dermoid cysts [39]. The diagnosis of KFS is usually incidental, the cervical spine X-rays show scoliosis, vertebral fusion, and instability, spinal CT with three-dimensional reconstruction is useful in surgical planning, and the spinal MRI is useful to detect neurologically (spinal compression, stenosis, and syringomyelia). Surgical treatment is based on the detection and management of associated systemic alterations, only 43% of patients will require decompression and spinal stabilization depending on risk patterns determined by Samartzis classification. Our patient did not require surgical management of this malformation due to the lack of clinical repercussion [40].
In conclusion, NEC prognosis is generally favorable, but a significant proportion of individuals undergoing partial resection experience recurrence. The association between KFS and NEC can be related to the persistence of embryological structures. The correct diagnostic approach must be carried out to choose the optimal surgical approach. Therefore, about our experience, in the points of Table 1, we describe the fundamental aspects in the management of this pathology.
Because these intracranial tumors are uncommon, studies that compare the benefits of various management strategies about outcomes and prognosis factors are lacking. Therefore, the level of evidence of management recommendations is low. However, we consider the knowledge of these entities important, so we determine the important characteristics in the diagnosis, management, and prognosis to establish a comprehensive review of these neoplasms. Carbohydrate antigen 19-9 Central nervous system Choroid plexus papilloma Computed tomography Electromyography Fluid attenuation inversion recovery Hemifacial spasm Klippel-Feil syndrome Magnetic resonance imaging Neuroenteric cysts Rosai-Dorfman diseaseAcronyms and abbreviations
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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. 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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. 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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. 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His research interests include epidemiological patterns and molecular analysis of antimicrobial resistance and modulation and vaccine development against animal pathogens of public health concern.",institutionString:"Cholistan University of Veterinary and Animal Sciences",institution:null},{id:"62900",title:"Prof.",name:"Fethi",middleName:null,surname:"Derbel",slug:"fethi-derbel",fullName:"Fethi Derbel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62900/images/system/62900.jpeg",biography:"Professor Fethi Derbel was born in 1960 in Tunisia. He received his medical degree from the Sousse Faculty of Medicine at Sousse, University of Sousse, Tunisia. He completed his surgical residency in General Surgery at the University Hospital Farhat Hached of Sousse and was a member of the Unit of Liver Transplantation in the University of Rennes, France. He then worked in the Department of Surgery at the Sahloul University Hospital in Sousse. Professor Derbel is presently working at the Clinique les Oliviers, Sousse, Tunisia. His hospital activities are mostly concerned with laparoscopic, colorectal, pancreatic, hepatobiliary, and gastric surgery. He is also very interested in hernia surgery and performs ventral hernia repairs and inguinal hernia repairs. He has been a member of the GREPA and Tunisian Hernia Society (THS). During his residency, he managed patients suffering from diabetic foot, and he was very interested in this pathology. For this reason, he decided to coordinate a book project dealing with the diabetic foot. Professor Derbel has published many articles in journals and collaborates intensively with IntechOpen Access Publisher as an editor.",institutionString:"Clinique les Oliviers",institution:null},{id:"300144",title:"Dr.",name:"Meriem",middleName:null,surname:"Braiki",slug:"meriem-braiki",fullName:"Meriem Braiki",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/300144/images/system/300144.jpg",biography:"Dr. Meriem Braiki is a specialist in pediatric surgeon from Tunisia. She was born in 1985. She received her medical degree from the University of Medicine at Sousse, Tunisia. She achieved her surgical residency training periods in Pediatric Surgery departments at University Hospitals in Monastir, Tunis and France.\r\nShe is currently working at the Pediatric surgery department, Sidi Bouzid Hospital, Tunisia. Her hospital activities are mostly concerned with laparoscopic, parietal, urological and digestive surgery. She has published several articles in diffrent journals.",institutionString:"Sidi Bouzid Regional Hospital",institution:null},{id:"229481",title:"Dr.",name:"Erika M.",middleName:"Martins",surname:"de Carvalho",slug:"erika-m.-de-carvalho",fullName:"Erika M. de Carvalho",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229481/images/6397_n.jpg",biography:null,institutionString:null,institution:{name:"Oswaldo Cruz Foundation",country:{name:"Brazil"}}},{id:"186537",title:"Prof.",name:"Tonay",middleName:null,surname:"Inceboz",slug:"tonay-inceboz",fullName:"Tonay Inceboz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/186537/images/system/186537.jfif",biography:"I was graduated from Ege University of Medical Faculty (Turkey) in 1988 and completed his Med. PhD degree in Medical Parasitology at the same university. I became an Associate Professor in 2008 and Professor in 2014. I am currently working as a Professor at the Department of Medical Parasitology at Dokuz Eylul University, Izmir, Turkey.\n\nI have given many lectures, presentations in different academic meetings. I have more than 60 articles in peer-reviewed journals, 18 book chapters, 1 book editorship.\n\nMy research interests are Echinococcus granulosus, Echinococcus multilocularis (diagnosis, life cycle, in vitro and in vivo cultivation), and Trichomonas vaginalis (diagnosis, PCR, and in vitro cultivation).",institutionString:"Dokuz Eylül University",institution:{name:"Dokuz Eylül University",country:{name:"Turkey"}}},{id:"71812",title:"Prof.",name:"Hanem Fathy",middleName:"Fathy",surname:"Khater",slug:"hanem-fathy-khater",fullName:"Hanem Fathy Khater",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/71812/images/1167_n.jpg",biography:"Prof. Khater is a Professor of Parasitology at Benha University, Egypt. She studied for her doctoral degree, at the Department of Entomology, College of Agriculture, Food and Natural Resources, University of Missouri, Columbia, USA. She has completed her Ph.D. degrees in Parasitology in Egypt, from where she got the award for “the best scientific Ph.D. dissertation”. She worked at the School of Biological Sciences, Bristol, England, the UK in controlling insects of medical and veterinary importance as a grant from Newton Mosharafa, the British Council. Her research is focused on searching of pesticides against mosquitoes, house flies, lice, green bottle fly, camel nasal botfly, soft and hard ticks, mites, and the diamondback moth as well as control of several parasites using safe and natural materials to avoid drug resistances and environmental contamination.",institutionString:null,institution:{name:"Banha University",country:{name:"Egypt"}}},{id:"99780",title:"Prof.",name:"Omolade",middleName:"Olayinka",surname:"Okwa",slug:"omolade-okwa",fullName:"Omolade Okwa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/99780/images/system/99780.jpg",biography:"Omolade Olayinka Okwa is presently a Professor of Parasitology at Lagos State University, Nigeria. She has a PhD in Parasitology (1997), an MSc in Cellular Parasitology (1992), and a BSc (Hons) Zoology (1990) all from the University of Ibadan, Nigeria. She teaches parasitology at the undergraduate and postgraduate levels. She was a recipient of a Commonwealth fellowship supported by British Council tenable at the Centre for Entomology and Parasitology (CAEP), Keele University, United Kingdom between 2004 and 2005. She was awarded an Honorary Visiting Research Fellow at the same university from 2005 to 2007. \nShe has been an external examiner to the Department of Veterinary Microbiology and Parasitology, University of Ibadan, MSc programme between 2010 and 2012. She is a member of the Nigerian Society of Experimental Biology (NISEB), Parasitology and Public Health Society of Nigeria (PPSN), Science Association of Nigeria (SAN), Zoological Society of Nigeria (ZSN), and is Vice Chairperson of the Organisation of Women in Science (OWSG), LASU chapter. She served as Head of Department of Zoology and Environmental Biology, Lagos State University from 2007 to 2010 and 2014 to 2016. She is a reviewer for several local and international journals such as Unilag Journal of Science, Libyan Journal of Medicine, Journal of Medicine and Medical Sciences, and Annual Research and Review in Science. \nShe has authored 45 scientific research publications in local and international journals, 8 scientific reviews, 4 books, and 3 book chapters, which includes the books “Malaria Parasites” and “Malaria” which are IntechOpen access publications.",institutionString:"Lagos State University",institution:{name:"Lagos State University",country:{name:"Nigeria"}}},{id:"273100",title:"Dr.",name:"Vijay",middleName:null,surname:"Gayam",slug:"vijay-gayam",fullName:"Vijay Gayam",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/273100/images/system/273100.jpeg",biography:"Dr. Vijay Bhaskar Reddy Gayam is currently practicing as an internist at Interfaith Medical Center in Brooklyn, New York, USA. He is also a Clinical Assistant Professor at the SUNY Downstate University Hospital and Adjunct Professor of Medicine at the American University of Antigua. He is a holder of an M.B.B.S. degree bestowed to him by Osmania Medical College and received his M.D. at Interfaith Medical Center. His career goals thus far have heavily focused on direct patient care, medical education, and clinical research. He currently serves in two leadership capacities; Assistant Program Director of Medicine at Interfaith Medical Center and as a Councilor for the American\r\nFederation for Medical Research. As a true academician and researcher, he has more than 50 papers indexed in international peer-reviewed journals. He has also presented numerous papers in multiple national and international scientific conferences. His areas of research interest include general internal medicine, gastroenterology and hepatology. He serves as an editor, editorial board member and reviewer for multiple international journals. His research on Hepatitis C has been very successful and has led to multiple research awards, including the 'Equity in Prevention and Treatment Award” from the New York Department of Health Viral Hepatitis Symposium (2018) and the 'Presidential Poster Award” awarded to him by the American College of Gastroenterology (2018). He was also awarded 'Outstanding Clinician in General Medicine” by Venus International Foundation for his extensive research expertise and services, perform over and above the standard expected in the advancement of healthcare, patient safety and quality of care.",institutionString:"Interfaith Medical Center",institution:{name:"Interfaith Medical Center",country:{name:"United States of America"}}},{id:"93517",title:"Dr.",name:"Clement",middleName:"Adebajo",surname:"Meseko",slug:"clement-meseko",fullName:"Clement Meseko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/93517/images/system/93517.jpg",biography:"Dr. Clement Meseko obtained DVM and PhD degree in Veterinary Medicine and Virology respectively. He has worked for over 20 years in both private and public sectors including the academia, contributing to knowledge and control of infectious disease. Through the application of epidemiological skill, classical and molecular virological skills, he investigates viruses of economic and public health importance for the mitigation of the negative impact on people, animal and the environment in the context of Onehealth. \r\nDr. Meseko’s field experience on animal and zoonotic diseases and pathogen dynamics at the human-animal interface over the years shaped his carrier in research and scientific inquiries. He has been part of the investigation of Highly Pathogenic Avian Influenza incursions in sub Saharan Africa and monitors swine Influenza (Pandemic influenza Virus) agro-ecology and potential for interspecies transmission. He has authored and reviewed a number of journal articles and book chapters.",institutionString:"National Veterinary Research Institute",institution:{name:"National Veterinary Research Institute",country:{name:"Nigeria"}}},{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",biography:"Professor Dr. Shailendra K. Saxena is a vice dean and professor at King George's Medical University, Lucknow, India. His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. Dr. Saxena is a fellow of various international societies/academies including the Royal College of Pathologists, United Kingdom; Royal Society of Medicine, London; Royal Society of Biology, United Kingdom; Royal Society of Chemistry, London; and Academy of Translational Medicine Professionals, Austria. He was named a Global Leader in Science by The Scientist. He is also an international opinion leader/expert in vaccination for Japanese encephalitis by IPIC (UK).",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",country:{name:"India"}}},{id:"94928",title:"Dr.",name:"Takuo",middleName:null,surname:"Mizukami",slug:"takuo-mizukami",fullName:"Takuo Mizukami",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94928/images/6402_n.jpg",biography:null,institutionString:null,institution:{name:"National Institute of Infectious Diseases",country:{name:"Japan"}}},{id:"233433",title:"Dr.",name:"Yulia",middleName:null,surname:"Desheva",slug:"yulia-desheva",fullName:"Yulia Desheva",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/233433/images/system/233433.png",biography:"Dr. Yulia Desheva is a leading researcher at the Institute of Experimental Medicine, St. Petersburg, Russia. She is a professor in the Stomatology Faculty, St. Petersburg State University. She has expertise in the development and evaluation of a wide range of live mucosal vaccines against influenza and bacterial complications. Her research interests include immunity against influenza and COVID-19 and the development of immunization schemes for high-risk individuals.",institutionString:'Federal State Budgetary Scientific Institution "Institute of Experimental Medicine"',institution:null},{id:"238958",title:"Mr.",name:"Atamjit",middleName:null,surname:"Singh",slug:"atamjit-singh",fullName:"Atamjit Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/238958/images/6575_n.jpg",biography:null,institutionString:null,institution:null},{id:"333753",title:"Dr.",name:"Rais",middleName:null,surname:"Ahmed",slug:"rais-ahmed",fullName:"Rais Ahmed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/333753/images/20168_n.jpg",biography:null,institutionString:null,institution:null},{id:"252058",title:"M.Sc.",name:"Juan",middleName:null,surname:"Sulca",slug:"juan-sulca",fullName:"Juan Sulca",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252058/images/12834_n.jpg",biography:null,institutionString:null,institution:null},{id:"191392",title:"Dr.",name:"Marimuthu",middleName:null,surname:"Govindarajan",slug:"marimuthu-govindarajan",fullName:"Marimuthu Govindarajan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/191392/images/5828_n.jpg",biography:"Dr. M. Govindarajan completed his BSc degree in Zoology at Government Arts College (Autonomous), Kumbakonam, and MSc, MPhil, and PhD degrees at Annamalai University, Annamalai Nagar, Tamil Nadu, India. He is serving as an assistant professor at the Department of Zoology, Annamalai University. His research interests include isolation, identification, and characterization of biologically active molecules from plants and microbes. He has identified more than 20 pure compounds with high mosquitocidal activity and also conducted high-quality research on photochemistry and nanosynthesis. He has published more than 150 studies in journals with impact factor and 2 books in Lambert Academic Publishing, Germany. He serves as an editorial board member in various national and international scientific journals.",institutionString:null,institution:null},{id:"274660",title:"Dr.",name:"Damodar",middleName:null,surname:"Paudel",slug:"damodar-paudel",fullName:"Damodar Paudel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/274660/images/8176_n.jpg",biography:"I am DrDamodar Paudel,currently working as consultant Physician in Nepal police Hospital.",institutionString:null,institution:null},{id:"241562",title:"Dr.",name:"Melvin",middleName:null,surname:"Sanicas",slug:"melvin-sanicas",fullName:"Melvin Sanicas",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/241562/images/6699_n.jpg",biography:null,institutionString:null,institution:null},{id:"337446",title:"Dr.",name:"Maria",middleName:null,surname:"Zavala-Colon",slug:"maria-zavala-colon",fullName:"Maria Zavala-Colon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Puerto Rico, Medical Sciences Campus",country:{name:"United States of America"}}},{id:"338856",title:"Mrs.",name:"Nur Alvira",middleName:null,surname:"Pascawati",slug:"nur-alvira-pascawati",fullName:"Nur Alvira Pascawati",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Universitas Respati Yogyakarta",country:{name:"Indonesia"}}},{id:"441116",title:"Dr.",name:"Jovanka M.",middleName:null,surname:"Voyich",slug:"jovanka-m.-voyich",fullName:"Jovanka M. Voyich",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Montana State University",country:{name:"United States of America"}}},{id:"330412",title:"Dr.",name:"Muhammad",middleName:null,surname:"Farhab",slug:"muhammad-farhab",fullName:"Muhammad Farhab",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Agriculture Faisalabad",country:{name:"Pakistan"}}},{id:"349495",title:"Dr.",name:"Muhammad",middleName:null,surname:"Ijaz",slug:"muhammad-ijaz",fullName:"Muhammad Ijaz",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Veterinary and Animal Sciences",country:{name:"Pakistan"}}}]}},subseries:{item:{id:"20",type:"subseries",title:"Animal Nutrition",keywords:"Sustainable Animal Diets, Carbon Footprint, Meta Analyses",scope:"An essential part of animal production is nutrition. Animals need to receive a properly balanced diet. One of the new challenges we are now faced with is sustainable animal diets (STAND) that involve the 3 P’s (People, Planet, and Profitability). We must develop animal feed that does not compete with human food, use antibiotics, and explore new growth promoters options, such as plant extracts or compounds that promote feed efficiency (e.g., monensin, oils, enzymes, probiotics). These new feed options must also be environmentally friendly, reducing the Carbon footprint, CH4, N, and P emissions to the environment, with an adequate formulation of nutrients.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/20.jpg",hasOnlineFirst:!0,hasPublishedBooks:!0,annualVolume:11416,editor:{id:"175967",title:"Dr.",name:"Manuel",middleName:null,surname:"Gonzalez Ronquillo",slug:"manuel-gonzalez-ronquillo",fullName:"Manuel Gonzalez Ronquillo",profilePictureURL:"https://mts.intechopen.com/storage/users/175967/images/system/175967.png",biography:"Dr. Manuel González Ronquillo obtained his doctorate degree from the University of Zaragoza, Spain, in 2001. He is a research professor at the Faculty of Veterinary Medicine and Animal Husbandry, Autonomous University of the State of Mexico. He is also a level-2 researcher. He received a Fulbright-Garcia Robles fellowship for a postdoctoral stay at the US Dairy Forage Research Center, Madison, Wisconsin, USA in 2008–2009. He received grants from Alianza del Pacifico for a stay at the University of Magallanes, Chile, in 2014, and from Consejo Nacional de Ciencia y Tecnología (CONACyT) to work in the Food and Agriculture Organization’s Animal Production and Health Division (AGA), Rome, Italy, in 2014–2015. He has collaborated with researchers from different countries and published ninety-eight journal articles. He teaches various degree courses in zootechnics, sheep production, and agricultural sciences and natural resources.\n\nDr. Ronquillo’s research focuses on the evaluation of sustainable animal diets (StAnD), using native resources of the region, decreasing carbon footprint, and applying meta-analysis and mathematical models for a better understanding of animal production.",institutionString:null,institution:{name:"Universidad Autónoma del Estado de México",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null,series:{id:"13",title:"Veterinary Medicine and Science",doi:"10.5772/intechopen.73681",issn:"2632-0517"},editorialBoard:[{id:"175762",title:"Dr.",name:"Alfredo J.",middleName:null,surname:"Escribano",slug:"alfredo-j.-escribano",fullName:"Alfredo J. 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