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\\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:"intechopen-supports-asapbio-s-new-initiative-publish-your-reviews-20220729",title:"IntechOpen Supports ASAPbio’s New Initiative Publish Your Reviews"},{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"}]},book:{item:{type:"book",id:"9894",leadTitle:null,fullTitle:"Advanced Ceramic Materials",title:"Advanced Ceramic Materials",subtitle:null,reviewType:"peer-reviewed",abstract:"This book examines exciting advancements in the field of ceramics, including nanotechnology, clean energy, and tribology as well as fundamental concepts like defects and structure. It is a comprehensive discussion on how today’s ceramics are processed and used in many of today’s critical technologies. It discusses current techniques for synthesizing durable and cost-effective ceramic components with biocompatibility, complexity, and high precision. This book is a comprehensive reference for researchers, engineers, dental clinicians, biologists, academics, and students interested in ceramics.",isbn:"978-1-83881-212-6",printIsbn:"978-1-83881-204-1",pdfIsbn:"978-1-83881-213-3",doi:"10.5772/intechopen.87703",price:119,priceEur:129,priceUsd:155,slug:"advanced-ceramic-materials",numberOfPages:296,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"9adbe58d10d5ca2b61e9ff2b6b138f40",bookSignature:"Mohsen Mhadhbi",publishedDate:"May 5th 2021",coverURL:"https://cdn.intechopen.com/books/images_new/9894.jpg",numberOfDownloads:6465,numberOfWosCitations:0,numberOfCrossrefCitations:11,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:15,numberOfDimensionsCitationsByBook:0,hasAltmetrics:0,numberOfTotalCitations:26,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"May 29th 2020",dateEndSecondStepPublish:"August 5th 2020",dateEndThirdStepPublish:"October 4th 2020",dateEndFourthStepPublish:"December 23rd 2020",dateEndFifthStepPublish:"February 21st 2021",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"228366",title:"Dr.",name:"Mohsen",middleName:null,surname:"Mhadhbi",slug:"mohsen-mhadhbi",fullName:"Mohsen Mhadhbi",profilePictureURL:"https://mts.intechopen.com/storage/users/228366/images/system/228366.png",biography:"Dr. Mohsen Mhadhbi obtained his Ph.D. from the University of Sfax, Tunisia. He is currently an Assistant Professor of Chemistry at the National Institute of Research and Physicochemical Analysis, Tunisia. His research interests include nanomaterials, energy, powder technology, ceramics, composites, modeling, and simulations. Dr. Mhadhbi has published works in national and international journals and books. He is a teacher in Materials Science and has supervised several researchers in this field. He is also a member of various scientific associations and an editorial board member and reviewer of many reputable scientific journals.",institutionString:"National Institute of Research and Physicochemical Analysis",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"2",institution:{name:"Tunis El Manar University",institutionURL:null,country:{name:"Tunisia"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"155",title:"Ceramics",slug:"ceramics"}],chapters:[{id:"75967",title:"Recent Advances in Ceramic Materials for Dentistry",doi:"10.5772/intechopen.96890",slug:"recent-advances-in-ceramic-materials-for-dentistry",totalDownloads:813,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Dental ceramics constitute a heterogeneous group of materials with desirable optical and mechanical proprieties combined with chemical stability. They are inorganic non-metallic materials used in several applications. These materials are biocompatible to tissue, highly esthetic, with satisfying resistance to tensile and shear stress. Over the past years, several developments in new ceramic materials in dental restoration were achieved, including processing techniques and high mechanical properties. Thus, concepts on the structure and strengthening mechanisms of dental ceramic materials are also discussed. The dental practitioner requires best knowledge concerning indications, limitations, and correct use of started materials. The purpose of this book chapter is to overview advances in new ceramic materials and processes, which are used in dentistry. The properties of these materials are also discussed.",signatures:"Mohsen Mhadhbi, Faïçal Khlissa and Chaker Bouzidi",downloadPdfUrl:"/chapter/pdf-download/75967",previewPdfUrl:"/chapter/pdf-preview/75967",authors:[{id:"228366",title:"Dr.",name:"Mohsen",surname:"Mhadhbi",slug:"mohsen-mhadhbi",fullName:"Mohsen Mhadhbi"},{id:"324375",title:"Dr.",name:"Faïçal",surname:"Khlissa",slug:"faical-khlissa",fullName:"Faïçal Khlissa"},{id:"324535",title:"Dr.",name:"Chaker",surname:"Bouzidi",slug:"chaker-bouzidi",fullName:"Chaker Bouzidi"}],corrections:null},{id:"74215",title:"Ferroelectric Glass-Ceramic Systems for Energy Storage Applications",doi:"10.5772/intechopen.93855",slug:"ferroelectric-glass-ceramic-systems-for-energy-storage-applications",totalDownloads:537,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"An overview of ferroelectric glass ceramics, some literature review and some of the important previous studies were focused in this chapter. Nanocrystalline glass–ceramics containing ferroelectric perovskite-structured phases have been included. All modified glasses having ferroelectric ceramics which prepared by different methods are discussed, that producing nanocrystalline glass–ceramics. Then particular tested to their use as dielectric energy storage materials. These materials exhibit promising dielectric properties, indicating good potential for high energy density capacitors as a result of their nanocrystalline microstructures. The results of the analysis are summarised in this chapter to provide an overview of the energy storage characteristics of the different materials produced during the study.",signatures:"Abdulkarim Ziedan Khalf",downloadPdfUrl:"/chapter/pdf-download/74215",previewPdfUrl:"/chapter/pdf-preview/74215",authors:[{id:"323331",title:"Dr.",name:"Abdulkarim",surname:"Khalf",slug:"abdulkarim-khalf",fullName:"Abdulkarim Khalf"}],corrections:null},{id:"74064",title:"From the Laser Plume to the Laser Ceramics",doi:"10.5772/intechopen.94464",slug:"from-the-laser-plume-to-the-laser-ceramics",totalDownloads:613,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The main stages of preparation of ceramic active elements of solid-state lasers are considered. The physical principles of laser synthesis of nanopowders are described. The features and processes taking place during compaction and compacts sintering are specified. Also we report on the investigation of characteristics of highly transparent ceramics on the basis of nanopowders synthesized in laser plume. It is shown that this approach enables to increase the “orange peel” formation threshold in the ceramics with strongly disordered crystalline structure. It opens the road to relatively simple synthesis technology from oxide materials and application of this ceramics as the gain media with oscillation efficiency higher than 50% and also leads to simplification of the synthesis technology of magnetoactive ceramics and to production of highly transparent YAG samples without the use of sintering heterovalent additives.",signatures:"Vladimir Osipov, Vyacheslav Platonov, Vladislav Shitov and Vladimir Solomonov",downloadPdfUrl:"/chapter/pdf-download/74064",previewPdfUrl:"/chapter/pdf-preview/74064",authors:[{id:"97328",title:"Prof.",name:"Vladimir",surname:"Solomonov",slug:"vladimir-solomonov",fullName:"Vladimir Solomonov"},{id:"328400",title:"Prof.",name:"Vladimir",surname:"Osipov",slug:"vladimir-osipov",fullName:"Vladimir Osipov"},{id:"329374",title:"Dr.",name:"Vecheslav",surname:"Platonov",slug:"vecheslav-platonov",fullName:"Vecheslav Platonov"},{id:"329375",title:"MSc.",name:"Vladislav",surname:"Shitov",slug:"vladislav-shitov",fullName:"Vladislav Shitov"}],corrections:null},{id:"73127",title:"The Investigation on the Fabrication and Characterization of the Multicomponent Ceramics Based on PZT and the Relaxor PZN-PMnN Ferroelectric Materials",doi:"10.5772/intechopen.93534",slug:"the-investigation-on-the-fabrication-and-characterization-of-the-multicomponent-ceramics-based-on-pz",totalDownloads:502,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:"This chapter presents the investigation of fabrication and the physical properties of the Pb(Zr1−xTix)O3-Pb(Zn1/3Nb2/3)O3-Pb(Mn1/3Nb2/3)O3 multicomponent ceramics. The multicomponent yPb(Zr1−xTix)O3-(0.925 − y)Pb(Zn1/3Nb2/3)O3-0.075Pb(Mn1/3Nb2/3)O3 (PZT-PZN-PMnN) ceramics were synthesized by conventional solid-state reaction method (MO) combined with the B-site oxide mixing technique (BO). Research results show that the electrical properties of PZT-PZN-PMnN ceramics are optimal at a PZT content of 0.8 mol and Zr/Ti ratio of 48/52. At these contents, the ceramics have the following optimal properties: electromechanical coupling factor, kp = 0.62 and kt = 0.51; piezoelectric constant (d31) of 130 pC/N; mechanical quality factor (Qm) of 1112; dielectric loss (tan δ) of 0.005; high remanent polarization (Pr) of 30.4 μC.cm−2; and low coercive field (EC) of 6.2 kV.cm−1. Investigation of the domain structure of the two ferroelectric phases (tetragonal and rhombohedral) in the ZnO-doped PZT-PZN-PMnN with compositions at near the morphotropic phase boundary is described as follows: the 90 and 180° domains exist in the tetragonal phase, while the 71, 109, and 90° domains are located in the rhombohedral phase, and the widths of these domains were about 100 nm. Besides, the ceramics exhibited excellent temperature stability, which makes them a promising material for high-intensity ultrasound applications.",signatures:"Le Dai Vuong, Vo Thanh Tung and Phan Dinh Gio",downloadPdfUrl:"/chapter/pdf-download/73127",previewPdfUrl:"/chapter/pdf-preview/73127",authors:[{id:"241214",title:"Dr.",name:"Le",surname:"Dai Vuong",slug:"le-dai-vuong",fullName:"Le Dai Vuong"},{id:"326085",title:"Prof.",name:"Vo",surname:"Thanh Tung",slug:"vo-thanh-tung",fullName:"Vo Thanh Tung"}],corrections:null},{id:"73186",title:"Self-Healing of Concrete through Ceramic Nanocontainers Loaded with Corrosion Inhibitors and Microorganisms",doi:"10.5772/intechopen.93514",slug:"self-healing-of-concrete-through-ceramic-nanocontainers-loaded-with-corrosion-inhibitors-and-microor",totalDownloads:412,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Self-healing was considered for repairing of destruction of reinforced concrete on bridges, houses, etc., that comes from corrosion of reinforcement metals as well as cracking in cement. The work was accomplished at producing and assessing through incorporate ceramic nanocontainers loaded with microorganisms. We produced various types of organic and inorganic nanocontainers that were incorporated into the cement that can act as carriers for the transport of bacteria. The microorganisms used in the work are Escherichia coli and Staphylococcus aureus. Precipitation of CaCO3 was observed by both bacteria. As microspheres do not affect the submersion of the mineral by the microorganism, additional studies were carried out to assess the interaction between transmission microsystems and bacterium. The mechanism of self-healing of building materials in this work was based on CaCO3 precipitation, through the ureolytic action of bacteria. When a crack appears in the cement, then the bacterium trapped in a nanocontainers is released and comes into contact with the water. In this way, the microorganism begins to metabolize and precipitate the mineral, in a way that eventually observes healing of the crack. CaCO3 microbial precipitation was based on the breakdown of urea (CO (NH2)2) into CO32− and NH3. Due to the high pK value of the NH3/NH4+ system (pKa = 9.2), the breakdown reaction led to an increase in pH, favoring the release of carbonated ions (CO32−), and in an environment rich in calcium ions (Ca2+), CaCO3 precipitation took place.",signatures:"George Kordas",downloadPdfUrl:"/chapter/pdf-download/73186",previewPdfUrl:"/chapter/pdf-preview/73186",authors:[{id:"306484",title:"Emeritus Prof.",name:"George",surname:"Kordas",slug:"george-kordas",fullName:"George Kordas"}],corrections:null},{id:"73538",title:"New Bismuth Sodium Titanate Based Ceramics and Their Applications",doi:"10.5772/intechopen.93921",slug:"new-bismuth-sodium-titanate-based-ceramics-and-their-applications",totalDownloads:555,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Ferroelectric materials are widely investigated due to their excellent properties and versatile applications. At present, the dominant materials are lead-containing materials, such as Pb (Zr,Ti)O3 solid solutions. However, the use of lead gives rise to environmental concerns, which is the driving force for the development of alternative lead-free ferroelectric materials. (Bi0.5Na0.5)TiO3-based ceramics are considered to be one of the most promising lead-free materials to replace lead-containing ferroelectric ceramics due to their excellent ferroelectric properties, relaxation characteristics, and high Curie point. After decades of efforts, great progress has been made in the phase structure characterization and properties improvement of BNT based ceramics. However, most of the studies on BNT system mainly focuses on its piezoelectric properties and application of piezoelectric sensors and strain actuators, little attention is paid to its ferroelectric properties and related applications. In this chapter, new BNT-based ceramics via composition modification and special focuses on the ferroelectric properties, phase transition behaviors under external fields and related applications, such as application in energy storage, pulsed power supply and pyroelectric detection were proposed.",signatures:"Hengchang Nie, Genshui Wang and Xianlin Dong",downloadPdfUrl:"/chapter/pdf-download/73538",previewPdfUrl:"/chapter/pdf-preview/73538",authors:[{id:"324929",title:"Dr.",name:"Hengchang",surname:"Nie",slug:"hengchang-nie",fullName:"Hengchang Nie"},{id:"332042",title:"Dr.",name:"Genshui",surname:"Wang",slug:"genshui-wang",fullName:"Genshui Wang"},{id:"332043",title:"Dr.",name:"Xianlin",surname:"Dong",slug:"xianlin-dong",fullName:"Xianlin Dong"}],corrections:null},{id:"74295",title:"Investigation of Structural, Magnetic and Electrical Properties of Chromium Substituted Nickel Ceramic Nanopowders",doi:"10.5772/intechopen.94941",slug:"investigation-of-structural-magnetic-and-electrical-properties-of-chromium-substituted-nickel-cerami",totalDownloads:322,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Nano-ceramic of NiCrxFe2-xO4 (0.1 ≤ x ≤ 1.0) ferrites were synthesized by citrate-gel auto combustion method. The structural parameter such as lattice parameter, X-ray density, bulk density and porosity variations with Cr doping were studied. The average crystallite size is in the range 8.5–10.5 nm. The surface morphology and elemental analysis was studied with SEM (EDAX) spectrum and the structural information analyzed with FTIR spectra. Magnetic properties were discussed with Cr3+ion concentration. Electrical parameters like dc resistivity and drift mobility were reported with function of temperature and dopent concentration from room temperature to well beyond Curie temperature and explained with hopping mechanism between Fe2+↔Fe3+ ions. The activation energies in ferri and para magnetic regions were investigated. Dielectric parameters like dielectric constant, dielectric loss and ac conductivity were investigated variation with frequency and composition.",signatures:"Rapolu Sridhar, D. Ravinder, J. Laxman Naik, K. Vijaya Kumar, N. Maramu and S. Katlakunta",downloadPdfUrl:"/chapter/pdf-download/74295",previewPdfUrl:"/chapter/pdf-preview/74295",authors:[{id:"289636",title:"Prof.",name:"Ravinder",surname:"Dachepalli",slug:"ravinder-dachepalli",fullName:"Ravinder Dachepalli"},{id:"346605",title:"Dr.",name:"Nyathani",surname:"Maramu",slug:"nyathani-maramu",fullName:"Nyathani Maramu"},{id:"346606",title:"Dr.",name:"Sadhana",surname:"Katlakunta",slug:"sadhana-katlakunta",fullName:"Sadhana Katlakunta"}],corrections:null},{id:"74406",title:"The Effect of Ceramic Wastes on Physical and Mechanical Properties of Eco-Friendly Flowable Sand Concrete",doi:"10.5772/intechopen.95041",slug:"the-effect-of-ceramic-wastes-on-physical-and-mechanical-properties-of-eco-friendly-flowable-sand-con",totalDownloads:377,totalCrossrefCites:4,totalDimensionsCites:5,hasAltmetrics:0,abstract:"This work aims to study the valorization and recycling of ceramic wastes (wall tiles) as a fine aggregate instead of sand in the manufacturing of flowable sand concrete (FSC). For this, the sand is substituted with the ceramic wastes at different dosages (0, 5, 10, 15, 20, and 25% by volume of the sand). The influence of the ceramic wastes addition on the physical (workability, density) and mechanical (compressive, flexural and elastic modulus) properties of FSC was studied. The results show that the use of ceramic waste as partial replacement of sand contributes to reduce the workability, bulk density and improves the mechanical strengths of FSC according to the use of 25% of wall tiles waste.",signatures:"Mohamed Guendouz, Djamila Boukhelkhal, Alexandra Bourdot, Oussama Babachikh and Amine Hamadouche",downloadPdfUrl:"/chapter/pdf-download/74406",previewPdfUrl:"/chapter/pdf-preview/74406",authors:[{id:"323550",title:"Dr.",name:"Mohamed",surname:"Guendouz",slug:"mohamed-guendouz",fullName:"Mohamed Guendouz"},{id:"326866",title:"Dr.",name:"Alexandra",surname:"Bourdot",slug:"alexandra-bourdot",fullName:"Alexandra Bourdot"},{id:"326867",title:"Dr.",name:"Djamila",surname:"Boukhelkhal",slug:"djamila-boukhelkhal",fullName:"Djamila Boukhelkhal"},{id:"338169",title:"Mr.",name:"Oussama",surname:"Babachikh",slug:"oussama-babachikh",fullName:"Oussama Babachikh"},{id:"338170",title:"Mr.",name:"Amine",surname:"Hamadouche",slug:"amine-hamadouche",fullName:"Amine Hamadouche"}],corrections:null},{id:"73232",title:"Ceramics Coated Metallic Materials: Methods, Properties and Applications",doi:"10.5772/intechopen.93814",slug:"ceramics-coated-metallic-materials-methods-properties-and-applications",totalDownloads:718,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Surface coating can allow the bulk materials to remain unchanged, while the surface functionality is engineered to afford a more wanted characteristic. Ceramic coatings are considered as ideal coatings on metal which can significantly improve the surface properties of metal materials including anti-fouling, self-cleaning, corrosion resistance, wear resistance, oil/water separation and biocompatibility. Furthermore, various techniques have been utilized to fabricate a range of different ceramic coatings with more desirable properties on metal materials, which make the materials widely used in service environment. This chapter focus will be on the types, fabrication methods, surface properties and applications of ceramics coated metal materials.",signatures:"Dongmian Zang and Xiaowei Xun",downloadPdfUrl:"/chapter/pdf-download/73232",previewPdfUrl:"/chapter/pdf-preview/73232",authors:[{id:"324466",title:"M.D.",name:"Xiaowei",surname:"Xun",slug:"xiaowei-xun",fullName:"Xiaowei Xun"},{id:"325574",title:"Dr.",name:"Dongmian",surname:"Zang",slug:"dongmian-zang",fullName:"Dongmian Zang"}],corrections:null},{id:"73977",title:"Nanostructured Multilayer Composite Coatings for Cutting Tools",doi:"10.5772/intechopen.94363",slug:"nanostructured-multilayer-composite-coatings-for-cutting-tools",totalDownloads:435,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The chapter deals with the specific features concerning the application of wear-resistant coatings to improve the performance properties of ceramic cutting tools. The paper discusses the theoretical background associated with the specific operation conditions and wear of ceramic cutting tools and influencing the choice of the compositions and structures of wear-resistant coatings. The studies were focused on the application of the Ti-(Ti,Al)N-(Zr,Nb,Ti,Al)N multilayer composite coating with a nanostructured wear-resistant layer, as well as the (Cr,Al,Si)N–(DLC–Si)–DLC–(DLC–Si) and (Cr,Al,Si)N–DLC composite coatings in order to improve the cutting properties of ceramic tools. The chapter presents the results of the comparative cutting tests for the tools with the coatings under study, uncoated tools, and tools with the Ti-(Ti,Al)N commercial coating. The wear mechanisms typical for ceramic cutting tools with coatings of various compositions have been investigated.",signatures:"Sergey Grigoriev, Alexey Vereschaka, Marina Volosova, Caterina Sotova, Nikolay Sitnikov, Filipp Milovich and Nikolay Andreev",downloadPdfUrl:"/chapter/pdf-download/73977",previewPdfUrl:"/chapter/pdf-preview/73977",authors:[{id:"196459",title:"Dr.",name:"Alexey",surname:"Vereschaka",slug:"alexey-vereschaka",fullName:"Alexey Vereschaka"},{id:"207607",title:"Dr.",name:"Nikolay",surname:"Sitnikov",slug:"nikolay-sitnikov",fullName:"Nikolay Sitnikov"},{id:"264336",title:"Dr.",name:"Catherine",surname:"Sotova",slug:"catherine-sotova",fullName:"Catherine Sotova"},{id:"329434",title:"Prof.",name:"Sergey",surname:"Grigoriev",slug:"sergey-grigoriev",fullName:"Sergey Grigoriev"},{id:"329437",title:"Dr.",name:"Filipp",surname:"Milovich",slug:"filipp-milovich",fullName:"Filipp Milovich"},{id:"329438",title:"Dr.",name:"Nikolay",surname:"Andreev",slug:"nikolay-andreev",fullName:"Nikolay Andreev"},{id:"330235",title:"Dr.",name:"Marina",surname:"Volosova",slug:"marina-volosova",fullName:"Marina Volosova"}],corrections:null},{id:"74485",title:"Three-Dimensionally Ordered Macroporous-Mesoporous Bioactive Glass Ceramics for Drug Delivery Capacity and Evaluation of Drug Release",doi:"10.5772/intechopen.95290",slug:"three-dimensionally-ordered-macroporous-mesoporous-bioactive-glass-ceramics-for-drug-delivery-capaci",totalDownloads:447,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Bioactive glass ceramics (BGCs) have been used in orthopedic and dentistry due to having better osteoconductive and osteostimulative properties. This study aimed to evaluate and compare the drug release properties of two different BGCs; 45S5 and S53P4. The BGCs were composed with four phases of SiO2 – CaO – Na2O – P2O5 system, synthesized by sol–gel method using dual templates; a block-copolymer as mesoporous templates and polymer colloidal crystals as macroporous templates, called three-dimensionally ordered macroporous-mesoporous bioactive glass ceramics (3DOM-MBGCs). In vitro bioactivity test performed by soaking the 3DOM-MBGCs in simulated body fluid (SBF) at 37°C. The results indicated that, the 45S5 have the ability to grow hydroxyapatite-like layer on the surfaces faster than S53P4. Gentamicin drug was used to examine in vitro drug release properties in phosphate buffer solution (PBS). The amount of drug release was quantified through UV/Vis spectroscopy by using o-phthaldialdehyde reagent. S53P4 showed high drug loading content. The outcome of drug release in PBS showed that both S53P4 and 45S5 exhibited a slowly continuous gentamicin release. The resultant drug release profiles were fitted to the Peppas-Korsmeyer model to establish the predominant drug release mechanisms, which revealed that the kinetics of drug release from the glasses mostly dominated by Fickian diffusion mechanism.",signatures:"Reedwan Bin Zafar Auniq, Namon Hirun and Upsorn Boonyang",downloadPdfUrl:"/chapter/pdf-download/74485",previewPdfUrl:"/chapter/pdf-preview/74485",authors:[{id:"328197",title:"Assistant Prof.",name:"Upsorn",surname:"Boonyang",slug:"upsorn-boonyang",fullName:"Upsorn Boonyang"},{id:"338371",title:"Dr.",name:"Namon",surname:"Hirun",slug:"namon-hirun",fullName:"Namon Hirun"},{id:"338373",title:"Mrs.",name:"Reedwan",surname:"Bin-Zafar Auniq",slug:"reedwan-bin-zafar-auniq",fullName:"Reedwan Bin-Zafar Auniq"}],corrections:null},{id:"75213",title:"Challenges in Rietveld Refinement and Structure Visualization in Ceramics",doi:"10.5772/intechopen.96065",slug:"challenges-in-rietveld-refinement-and-structure-visualization-in-ceramics",totalDownloads:744,totalCrossrefCites:3,totalDimensionsCites:4,hasAltmetrics:0,abstract:"The most common and basic characterization in the field of material science is the almighty X-ray diffraction (XRD). In every institute, every research report and every manuscript, concerning material properties, the X-ray diffraction pattern is essentially found. Although the basis of these works relies on the fact that X-ray diffraction pattern was found to be matching with some structure in a database, the in depth significance of the various characteristic diffraction manifestations of various physical characters are rarely discussed. Most of the researchers (especially beginners) are either not aware of the prowess of X-ray based characterizations, or have not been introduced to it properly or may be sometimes they are not interested in its results at all. The decreased interest (later) in the results from such studies might be for not being productive enough for time spending or non-effectiveness in justifying the motivation of the work. The former two are more related to the availability and accessibility of study material for the development of core concepts. Most of the institutes always do not have access to the span-wide scientific literature and the researchers joining these institutions are partly affected. In this context the effective open-access and free availability of intech-open, it is prudent to at least attempt to accumulate, assimilated and aggregate the concepts related to X-ray diffraction in a single package. 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Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"43439",title:"Genetic and Environmental Factors in Autism",doi:"10.5772/53295",slug:"genetic-and-environmental-factors-in-autism",body:'Autism is a neurodevelopmental disorder characterized by impaired social interaction, and verbal and nonverbal communication as well as limited and repetitive behaviours. Although symptomatology of autism may be noticed around early months, diagnosis generally occurs around 24-36 months, however in some cases diagnosis may be delayed to adulthood [1]. Since behavioural symptoms and the degree of functional impairment are variable, the autistic disorder is described as a heterogenous symptom cluster of varying etiological and pathological basis [2]. Described as a multifactorial disorder created by interaction of neurologic, immunologic, environmental, and genetic factors, autistic disorder has no definite cause [3, 4]. In many cases in whom the etiology remains unclear are diagnosed as idiopathic autism or non-syndromic autism [5, 6]. Seventy percent of cases with idiopathic autism have basic symptoms without physical abnormalities whereas 30% have complex autism in which dysmorphic features are detected such as microcephaly and/or structural brain malformations [7]. Autism is associated with other syndromes such as Fragile X syndrome, Down Syndrome, and tuberosclerosis in 5-25% of the cases ([8, 9]. Although phenotypic heterogeneity is the biggest challenge for research efforts directed to identify autism etiology [10], currently it is widely accepted that environmental and genetic factors play essential role in genesis of autistic disorder thanks to a recent advance in research techniques related to biological factors and widespread studies in this field [11, 12].
Autistic disorder is a multifactorial genetic disorder not following classical Mendelian inheritance. Impairment in social interaction and verbal communication as well as genetic differentiation in rigid-repetitive behaviours indicates that different features in autistic disorder may be caused by different genes associated with distinct brain regions and be related to cognitive impairment and functional abnormalities [13].
Genetic studies in the field of autistic disorder have mainly focused on molecular genetic studies, assessment of chromosomal abnormalities, twin studies and family studies. In families having an autistic child the recurrence rate has been reported as 3-8% [14, 15, 16]. The studies on twins and adopted children are important in identifying the actual importance of genetic factors. Concordance among twins enables to measure heritability, and thus to assess what percentage of the phenotype is affected by genetic factors. Monozygotic (identical) twins share 100% of the genetic material whereas dizygotic (fraternal) twins share 50% of the genetic material. Monozygotic twins’ higher rate of concordance compared to dizygotic twins may be used for calculation of heritability. Twin studies generally showed a higher concordance rate for monozygotic twins compared to dizygotic twins. The concordance rate of monozygotic twins is at least 60% when diagnostic criteria for autism (DSM-IV) are used whereas the number is as high as 71% for autism spectrum and 92% for a broader spectrum of verbal/social interaction disorders [11, 12, 16, 17]. On the other hand, the concordance rate of dizygotic twins has been reported as 1-30% [9, 17-20]. Twin studies demonstrated an average autism inheritance of 90% [21]. On the basis of these studies autism is considered to be among the most inherited psychiatric diseases [22, 23].
Although autism has a high inheritance rate, its mode of inheritance remains unclear. Multi-gene interactions and multiple loci are believed to play role in genetic susceptibility to the disease [24]. There are 3 basic approaches in this area: 1) in whole genome scanning method, it is aimed to predict the localization of a disease, about chromosomal localization of which we have no preliminary information, by starting from common genetic determinants in a community composed of multiplex families (families with more than one involved member). 2) cytogenetic studies guide molecular studies by showing inherited or de novo chromosomal anomalies in involved persons or families. 3) candidate gene studies examine the relationship of genes known to affect brain development in associated regions or alternatively, a selected precursor gene considered to hypothetically contribute to autism pathogenesis.
It has been demonstrated that structural chromosomal variations comprising also copy number variations play an important role in etiology of autism. De novo copy number variations have been identified in 7-10% of sporadic autism cases [25, 26].
In studies employing genome scanning method to reveal genetic etiology of autism, cogent evidence for an association with chromosomes 2, 7, 1, and 17, especially long arm of chromosomes 2 (2q) and 7 (7q) has been obtained. Other chromosomes less associated with autism are chromosomes 1, 9, 13, 15, 19, 22, and X chromosome [14, 16, 27]. Although a lot of genomic regions have been explored for etiology, consistent results for a limited number of regions such as 7q11, 7q31, 22q11 have been obtained [16, 28, 29]. Particularly 15q11-q13 region on chromosome 15 has been widely related to autism. It has been suggested that duplications in this region of chromosome 15 may contribute to autism development. There exist in this area a series of potential candidate genes containing gamma aminobutyric acid A (GABAA) receptor gene complex [30]. These duplications inherited maternally have been reported to be present in 1-3% of individuals with idiopathic autism [31, 32].
Another region related to autism is a deletion region located on chromosome 16p11. This region has also been demonstrated to be in relationship with Asperger Syndrome, mental retardation, and developmental abnormalities [33, 34].
It has been showed that, in individuals with autism, there is a significant increase in the frequency of allelic variations of HOXA1 gene (7p15). HOXA1 and HOXB1, which have a critical role for development of fetal caudal medullary structures, are only expressed at the third week following fertilization, a period when neural tube is formed, and they appear to be partly associated with development of superior olivary, facial and abducens nuclei. It has been suggested that HOXA1 has a role in autism tendency and is associated with early phase of brain stem development in autism etiology [16, 35]. On the other hand, there are studies where no significant association with HOXA1 gene variants and autism could be demonstrated [36, 37].
Engrailed-2 (EN-2) which is the human homologue of drosophila engrailed gene and located on the long arm of Chromosome 7 (7q36) is a homeobox gene having a critical role in midbrain and cerebellar development. Temporal and spatial pattern of engrailed gene expression occurs simultaneously with the development of cerebellar precursor cells. Thus, it has been suggested to be important to determine correct cell number in cerebellum [38]. Petit and his colleagues (1995) reported a significant association between
MET oncogene coding pleiotropic MET receptor thyrosine kinase is located on the long arm of Chromosome 7. MET signalization has a role in neocortex and cerebellar growth and maturation, and immune functions. MET gene and its ligand, hepatocyte growth factor (HGF), have been related to autism. Studies conducted by Campbell and his colleagues ([41,42] showed that C allele in the promoter region of MET gene decreases MET promoter activity by two fold and decreased MET gene expression is associated with autism tendency.
Another gene on Chromosome 7 is CNTNAP2 (contactin-associated-protein-like 2) gene. CNTNAP2 gene has been associated in various studies with autism, language delay, and epilepsy [43-45].
FOXP2 (forkhead box P2), a forkhead transcription factor gene, is a member of family forkhead known as the key regulators of embryogenesis; it encodes a transcription factor containing polyglutamine and is associated with development of lingual functions. In a study in Chinese society, FOXP2 gene located in the 7q31 region was linked with autism pathogenesis [46]. However, other studies did not replicate these findings [47, 48].
Another gene investigated for autism relationship is Wingless-Int (Wnt2) gene located on the long arm of Chromosome 7 (7q31-33). Wnt genes encode glycoproteins rich in cysteine, which regulate various cellular movements during the embryonic development [49]. It has been shown that Wnt has a role in regulation of activity-dependent dendritic branching in hippocampal pyramidal neurons [50]. Wnt2 gene was linked with autism in a study by Wassink and his colleagues [51].
Reelin is an important extracellular matrix glycoprotein that has an important role in development of neuronal migration, lamination, and connection during embryonic brain development and is associated with a signal pathway forming the basis of neuro-conduction, memory formation, and synaptic plasticity [52]. It is responsible for lamination in embryonic period whereas it has a role in cell signalization and synaptic plasticity in adulthood period [53]. Decrease in reelin expression has been associated with autism. RELN gene, which is located in 7q22 region and encodes reelin protein which is important in neurodevelopment, involves a polymorphic GGC repeat in 5’ region. Long GGC alleles of RELN gene cause blunt gene expression; therefore, they are considered to be linked with autism [52]. There are studies reporting a significant relationship between RELN alleles with larger numbers of CGG repeats and autism [52, 54] while there are also negative studies in terms of such a relationship [55]. Besides the genetic complexity in the etiopathogenesis of this disorder, non-replication of the results of different studies should also be taken into consideration.
Neuroligins are cellular adhesion molecules located at the postsynaptic side of the synapse. Neuroligins and neuroxins, neuronal cell surface proteins, form an asymmetrical intercellular connection by adhering to each other. Interaction of neuroligins with beta neuroxins forms functional synapses [56]. Neuroligin family is composed of 5 members, i.e. NLGN1, NLGN2, NLGN3, NLGN4, and NLGN4Y. Although all of the neuroligin family is linked with autism spectrum disorder [57], the most robust evidence comes from NLGN3 (Xq13) and NLGN4 (Xp22.3) genes. Jamain and colleagues [58] found that mutations in NLGN3 and NLGN4, two X-linked neuroligin genes, are associated with autism spectrum disorders [58]. Following this, it has been demonstrated that a 2-base-pair deletion in NLGN4 gene causes premature stop codon in mental-retarded men with or without autism. This finding indicates that NLGN4 gene is not only associated with autism, but also with mental retardation [59]. Since mutations in neuroligin genes impair the functions of synaptic cell adhesion molecules, they are considered to be related with autism and neurodevelopmental defects in mental retardation [60]. Since neuroligins are abundant particularly in excitatory synapses, a defect in synaptogenesis has been suggested to result in derangement in cognitive development and communication [59]. Nonetheless, some other studies revealed negative results [61].
Genetic studies examining the relationship of neuroxins, the connection partners of neuroligins, with autism revealed that a mutation in neuroxin 1beta gene results in autism susceptibility [62]. Structural variants of neuroxin 1alpha gene have also been linked with autism [63].
Another protein adhering to neuroligins is SHANK3. Some forms of autism are considered to stem from a single gene, and particularly from a rare allele having a major effect. Doctor Joseph Buxbaum has reported that one of these genes is SHANK3 gene located on Chromosome 22 (22q13) which is responsible for 1% of autism and some forms of mental retardation, microcephaly, and delay in expressive language [34]. SHANK proteins are believed to be the primary regulator of postsynaptic density thanks to their ability to form multimeric complexes with postsynaptic receptors, signal molecules, and cellular skeleton proteins found in dendritic spikes. Postsynaptic density is the measurement of how synapses are linked to each other. A mutation in SHANK3 gene has been reported to be related with autism spectrum disorders [64]. Role of various mutations in Neuroligin/neuroxin/SHANK3 complex in development of autism spectrum disorders provide potential evidence for synaptic alterations in etiology of the disorder.
A large-scale study by Wang and his colleagues [65] revealed a significant relationship between a single nucleotide polymorphism located in the 5p14.1 region and autism spectrum disorders. The associated single nucleotide polymorphism is located in a region placed between cadherin 10 (CDH 10) and cadherin 9 (CDH 9) genes. CDH 9 and CDH 10 encode type II classic cadherins of the cadherin family, which are transmembraneous glycoprotiens responsible for calcium-dependent cell-cell adhesion. This finding shows the role of neuronal cellular adhesion molecules in autism pathogenesis [65].
Neurotrophins have many functions such as neuronal survival, target innervation, and synaptogenesis in development of peripheral and central nervous system. Neurotrophins exert their biologic functions by binding to a Trk tyrosine kinase receptor which is a high-affinity receptor. Neurotrophin family has 4 members. These are nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 and neurotrophin-4. BDNF is the most important member of neurotrophin family. BDNF has many roles in neuronal differentiation such as neuronal survival, dendritic and axonal growth/branching, synapse formation, and neuronal plasticity [66, 67]. Various studies have investigated the relationship between BDNF gene and autism. Nishimura and colleagues [68] detected an increase in BDNF expression in autistic individuals. Subsequent studies confirmed the potential role of BDNF gene mutations in autism pathogenesis [69]. A recent study in which serum BDNF levels significantly increased in autistic children found no significant impact of genetic variations of BDNF gene on autism risk; however, a significant relationship between neurotrophic tyrosine kinase receptor type 2 (NTRK2) and autism was reported [70]. A large-scale study on patients diagnosed with autism spectrum disorder and mental retardation without autism diagnoses showed that, when compared to control group, autism spectrum disorders and mental retardation had a significant increase in serum neurotrophin 4 and BDNF (both are Trk B ligands) [71, 72]. On the other hand, no changes were observed in NGF (trk A ligand) and neurotrophin 3 (Trk C ligand) levels. In light of these findings, it has been suggested that trkB ligands may be overexpressed or secreted in central nervous system of autistic or mental retarded children during infantile period. It has also been suggested that the effect of BDNF and neurotrophin- 4 on activity-dependent dendritic growth and branching [66] may be related to early and transient brain development seen in autistic infants [67, 73]. This increase in BDNF expression and/or secretion was suggested to be linked with the role of Metil-CpG-binding protein 2 (MeCP2) gene in BDNF transcription [74]. A mutation in MeCP2 gene encoding a protein functioning as a general transcriptional receptor is responsible for Rett Syndrome. It has been shown that MeCP2 selectively bind to BDNF promoter III and suppresses BDNF gene expression. MeCP2 has an important role in regulation of neuronal activity [75]. It has been suggested that MeCP2 mutations located on Xq28 locus may be a risk factor for autism by affecting BDNF expression and dendritic differentiation in cortex. In a study investigating MeCP2 gene mutation in autistic individuals for that purpose, 2 girls exhibited de novo mutations [67, 76].
Another gene linked with autism is the Fragile X mental retardation 1 (FMR1) gene encoding Fragile X mental retardation protein (FMRP). FMR1 is associated with autism secondary to Fragile X syndrome [28]. However, fragile X mutations may be found in 7-8% idiopathic autism patients [77]. FMRP is a selective RNA-binding protein; it transports RNAs to dendrites and regulates local translation of synaptic mRNAs as a response to activation of metabotropic glutamate receptors. This protein is considered to have a role in synaptic plasticity and development of synaptic connections between neural cells. Impaired mRNA translation in the absence of FMRP leads to an alteration in protein-synthesis-dependent plasticity [28, 78].
Autism risk is higher than general population in neurofibromatosis, tuberosclerosis, or Cowden Syndrome, a rare syndrome which is characterized by multiple tumor-like growths called hamartomas and affects the intellectual abilities. These diseases develop due to dominant mutations in tumor suppressor genes NF1, TSC1/TSC2, and PTEN. Mutations in these autism-associated genes affect synaptic protein level by impairing cellular translation. Alterations in protein level results in abnormal synaptic functions [28].
Angelman syndrome and Prader-Willi syndrome mainly develop due to genetic deletions in 15q11-q13 locus or disomy (condition where two copies of a chromosome comes from a single parent) belonging to a single parent [79]. Deficiencies in paternal genes cause Prader-Willi syndrome; Angelman Syndrome which is more commonly associated with autism may be caused by deletion or mutation in maternal ubiquitin protein ligase gene UBE3A or ATP10C [80, 81]. Other rare single gene defects associated with autism are found in Williams Syndrome, Sotos Syndrome, hipomelanozis Ito, and Moebius Syndrome [82-85].
Since serotonin reuptake inhibitors have favourable effects on rituals and routines in autistic individuals and serotonin transporter gene has important role in serotonergic neurotransmission, serotonin transport gene has been investigated as candidate gene in autism. One of the polymorphisms examined in this gene is the one that is formed by long (L) and short (S) alleles owing to different number of insertion/deletion repeats of a 44-base-pair sequence in the transcriptional control region. Cook and his colleagues [86] reported a significant relationship between autism and short allele while Klauck and his colleagues [87] revealed a significant relationship between autism and long allele. A subsequent study did not duplicate these findings [88]. A different polymorphism investigated at the serotonin transport gene is the variable number of tandem repeats (VNTR) polymorphism due to repeat of a 17-base-pair region at 2nd intron of the gene 9,10, and 12 times. This polymorphism could not be related to autism [89]. Evidence has been accumulated on the relationship of many serotonin genes, notably serotonin receptor (HTR) 1B, HTR2A, HTR3A, and HTR5A, with autism [90-93].
Glutamate is the main excitatory neurotransmitter associated with cognitive functions such as memory and learning. Autism has been hypothesized as a hypoglutamatergic disorder by virtue of neuroanatomic studies and the similarities glutamate antagonists generate in healthy persons [94]. It has been demonstrated in genome scanning studies that one of the candidate regions for autism is 6q21 region [95]. This region contains glutamate receptor 6 (GluR6) gene. A study by Jamain and his colleagues [96] found a significant relationship between GluR6 gene and autism. It has been thought that GluR6 dysfunction may contribute the deterioration of communication and learning process in autism and any dysregulation of GluR expression may be related to an increase in the rate of epileptic disorder in autistic children [96]. Other glutamatergic receptor genes associated with autism are metabotropic GluR8 and GRIN2A (glutamate receptor, ionotropic, N-methyl-D-aspartate 2A) [97, 98].
Gama aminobutyric acid (GABA) is the major inhibitor neurotransmitter in the brain. GABAA receptors are formed by different homologous subunits. Among GABA receptor subunit genes, GABRA4 with 4p12 location has been shown to play a role in etiology of autism and increases autism risk by interaction with GABRB1 [99]. Other genes associated with autism in some other studies are GABRG3, GABRA5, GABRB3 located on 15q11-q13, and GABRA2 located on 4p [100-102]. Contrary to these findings, there are other studies with negative results in terms of the relationship between GABA receptor genes and autism in various ethnic groups [103].
Proenkephalin, prodinorphine of opioid metabolism; tyrosine hydroxylase, dopamin beta hydroxylase (DBH), D2, D3, and D5 dopamin receptors, monoaminooxidase A (MAOA) and B genes of monoaminergic system have no major role in etiology of autism shown in studies [104, 105]. However, a recent study revealed a significant relationship between MAOA gene and autism [106].
Mutations detected in autism in conjunction with all other genetic factors explored so far have been reported to explain no more than 20% of cases with autism spectrum disorder. Thus, a gene-dosage model has been proposed according to which the susceptibility for autism is determined by the sum of effects of threshold genetic and non-genetic factors [107, 108]. For autism etiology, it has been suggested that the detected chromosomal abnormalities in combination with other undetected loci cause autism. It has been considered that the inconsistencies between the results of the studies aimed to determine the role of genetic factors may be the product of genetic heterogeneity, clinical heterogeneity, and sample size and ethnic differences among different studies [109].
In addition to effects of a number of genes of small effect, various environmental factors are believed to be responsible for susceptibility to autism. Development of autism seems to be dependent on interaction of susceptibility genes with each other and with the environment [110]. It has been claimed that among environmental factors related to autism are toxins (environment-polluting matters, insecticides, thimerosal in vaccines, lead), viruses (prenatal exposure to influenza, rubella, and cytomegalovirus infections), and premature birth with premature retinopathy [111-115]. Although there has been a debate regarding the relationship of autism with thimerosal in measles, rubella, and mumps vaccines; further careful evaluation of data could not support the relationship between autism and vaccines [116, 117]. The relationship between exposure to Rh immune globulin, which contained the preservative thimerosal until 2001 in the United States, and autism has also been investigated; however, no significant association has been revealed between exposure of antepartum RhIg preserved with thimerosal and an increase in risk of autistic disorder. The latter findings are in accordance with the consensus that exposure to ethymercury in thimerosal is not the cause of increased prevalence of autism [118].
Other factors related to intrauterine environment are maternal hypothyroxinemia [119], maternal influenza [120], and high levels of sex hormone exposure related to infertility treatment [121].Thalidomide and anticonvulsant exposure in pregnancy is correlated to an increase in autism risk [122, 123]. Rasalam and his colleagues [124] showed that 8.9% of children exposed to sodium valproate in intrauterine life later develop autistic spectrum disorders such as autism or Asperger syndrome. Recently, Hadjikhani [125] have suggested that serotonin reuptake inhibitor use in pregnancy increases autism risk by causing hyperserotoninemia and indirectly affecting amygdala and oxytocin levels.
In many studies, the pre-perinatal complication rates in autistic disorder have been studied and a higher pregnancy-related complication rate has been demonstrated in autistic children [126, 127]. In a recent meta-analysis [128], the most strong risk factors for autism were advanced maternal and paternal age, maternal gestational hemorrhage, gestational diabetes, maternal prenatal drug use (particularly psychoactive drugs), and birth in a foreign country following immigration of mother. Both advanced maternal and paternal age are associated with autism. The underlying mechanism is unclear. Maternal age may be related to autism due to increased risk of chromosomal abnormalities in ova of increased age or because of unstable trinucleotide repeats [128]. The relationship between paternal age and autism is considered to result from imprinted genes (genes showing different expression patterns depending on the parent it originates), de novo spontaneous mutations that accumulate with advancing age in spermatagonia, or confounder effects of sociocultural environmental factors [129]. Another potential risk factor for autism is maternal birth abroad [130]. It has been suggested that this factor may result from absence of immunization that mother would develop against widespread infectious agents of the country in which she gives birth. Another possible explanation is about the potential role of maternal stress because of immigration [131]. A more detailed investigation on the relationship between mother immigration and autism is needed. It has been demonstrated in some studies that gestational hemorrhage increases autism risk by causing fetal hypoxia [130]. Among other factors considered to cause hypoxia and associated with increased autism risk in some studies are fetal distress, maternal hypertension, prolonged labor, cord complications, low Apgar score, and cesarean section [132]. Gestational diabetes is another risk factor, with unknown biologic mechanism [128].
Some studies demonstrated that prenatal stress increases autism risk [133, 134]. However, due to limitations that these studies are based on retrospective expressions of mothers and these mothers are generally susceptible for experiencing stressful life events outside pregnancy period, these studies need to be supported by further studies. Spontaneous abortions, pre-perinatal complications, congenital anomalies, and neurologic/immunologic abnormalities are among the negative impacts of prenatal stress. Prenatal stress also has various negative effects on brain development such as a delay in myelinization, an increase in sensitivity of amygdala to glucocorticoids, and abnormal development in dopaminergic system [135-137]. Autistic disorder is associated with a functional derangement in brain areas related to social cognitive functions in which amygdala and orbitofrontal cortex plays an important role. Orbitofrontal cortex is susceptible to effects of prenatal stress especially in the middle of gestation. Normal functioning of orbitofrontal cortex - amygdala axis is very important for social cognitive function. Therefore, it has been suggested that damage in orbitofrontal region may cause main deficits in autism that underlies inadequate responses to other people’s mental status and that impairs self-organization of social-emotional behaviours [137, 138]. Prenatal stress may impair brain development by many mechanisms including: a) fetal hypoxia due to reducing of uterine and placental circulation, b) impairment of hypothalamus-hypophysis-adrenal axis by stimulation of secretion of maternal stress hormones that can cross placenta, c) generation of pregnancy and birth complications, d) epigenetic effects on expression of stress response-related genes [137].
It has been reported that exposure of environmental stress factors at 21-32nd weeks with a prominent peak at 25-28th weeks is associated with an increase in possibility of development of autism [134]. When data regarding progressively worsening developmental process are considered [139], it has been argued that postnatal environmental exposures in genetically susceptible children may be etiologically important [140]. Expression and the impact of many genes is influenced by environmental factors. Thus, the effect of environmental factors in etiology of autism is believed to be indirect by influencing genetic functions [140, 141].
In line with studies aimed to understand the neurobiology of autism, the presence of alterations in regional brain anatomy and functional neuronal communicative network has been currently proved. The main role among factors underlying abnormal brain development belongs to genetic factors. Evidence regarding that autism is a primarily genetic disorder is progressively increasing. Although environmental factors alone can explain a few cases, they are believed to increase autism risk by interacting with genetic susceptibility. Although data collected so far contribute to the ever-increasing body of knowledge about neurobiology of autism, they do not influence diagnosis and treatment of autism. Use of these data is aimed in future in differentiation of autism from other neurodevelopmental disorders and in diagnostic and therapeutic processes.
Acute pancreatitis (AP) is an acute inflammatory disorder of the pancreas with a complex and variable course. Most patients develop only mild to moderate disease meaning no or just transient organ failure during the first 48 hours after the onset, but about 20–30% develops a severe form with local complications such as necrosis and often associated with single or multiple organs dysfunction and necessity of intensive care unit (ICU) admission. Severe AP is associated with persistent hemodynamic instability, respiratory distress with mechanical ventilation requirement, kidney failure, and is burdened by high mortality. ICU patients are often sedated and receive careful pain management, as well as careful hydration control [1, 2].
Patients with AP typically present with acute abdominal pain and significant depletion of intravascular volume. The main goal of initial treatment is to alleviate symptoms and prevent complications [3]. Fluid management and pain control are two central aspects of multidisciplinary care of AP, seem to impact on evolution, and influence the outcome. Management in the early hours gives the impression to be very important, when patients are usually assessed and assisted in the emergency department or general surgical ward.
Most patients have a self-limiting disease that resolves with supportive measures, and clinical choices can adjust the course of disease, reduce the hospitalization and health costs [4, 5].
Early intravenous volume resuscitation reduces pancreatic hypoperfusion and multiorgan failure, but fluid overload has been associated with worse outcome, and maintaining proper hydration could be challenging.
Pain relief has a positive impact because of reduced stress response, sympathetic-induced vasoconstriction, and pulmonary complications. A modern and effective multimodal analgesic approach aims to achieve patient’s satisfaction and minimize side effects.
AP can evolve and worsen so it is required to routinely reassess the clinical parameters and personalize the fluidic and analgesic therapy [6].
There is evidence that the incidence of AP has been rising in recent years, probably due to the increase in the average age, obesity, and some drug therapy for chronic disease treatment too. As a result, they are patients with significant comorbidities that require a considerable health effort, which may involve several healthcare professionals.
This is why multidisciplinary management could be helpful, with the purpose of improving patient’s outcome and hospital stay.
The AP treatment is currently symptomatic, and fluid management is a cornerstone of its therapy as well as being the intervention most likely to improve clinical outcomes. Patients are frequently hypovolemic due to decrease oral intake, vomiting, fever, tachypnea, and fluid sequestration associated with pancreatic and systemic inflammation. Pancreatic hypoperfusion may be attenuated by fluid resuscitation, therefore preventing pancreatic necrosis and lowering mortality [4, 7, 8].
Using experimental animal studies, it has been estimated that approximately two liters of fluid diffuse from the intravascular space to the interstitium, during the first 6 hours [7].
Fluid therapy to prevent hypovolemia and organ hypoperfusion comes from sepsis care, which has some pathophysiological similarities with AP.
After initial pancreatic acinar injury, the high amount of proteolytic enzymes produces local inflammation, proinflammatory cytokine, and vasoactive mediators release, with an increase in vascular permeability. Locally it results in interstitial fluid extravasation with edema of the gland, capillary vasoconstriction, and the production of microthrombi, which further worsen pancreatic perfusion. Cytokines such as interleukin (IL)-1, IL-6, IL-8 and systemic mediators such as tumor necrosis factor alpha (TNF-α) usually amplify this vicious circle and induce systemic inflammation, which can lead to systemic inflammatory response syndrome (SIRS).
SIRS is an exaggerated defense response of the body to a noxious stressor, which can be represented by infection, trauma, surgery, acute inflammation, ischemia, or reperfusion. Even though the purpose is defensive, the dysregulated cytokine storm can cause a massive inflammatory cascade leading to reversible or irreversible end-organ dysfunction and even death [9]. This storm represents the link between sepsis and AP, which is initially an aseptic inflammatory disease.
Likewise, as in septic patients, a low intravascular volume results in a decreased tissue perfusion, which can cause multiorgan failure, which increases complications and mortality rate. At the same time, overly aggressive hydration, especially in patients with preexisting kidney disease or hearth failure, increases the need for mechanical ventilation, the rates of infections, and thus mortality [1, 3].
Fluid dynamics are fundamentally different in mild and severe pancreatitis. The first one is easier to manage, because it is enough to restore the fluid deficit owing to vomiting, lower intake, and insensible losses. But the second one is characterized by vascular leakage with extravasation of protein-rich fluid, liquid sequestration, and hypoperfusion [10].
At the same time, we know that a mild form can evolve into a severe one, because in a sense they represent a pathophysiological continuum. Therefore, the revaluation is crucial to direct the right hydration and the evolution of the disease itself.
Unfortunately, there is still some degree of uncertainty about total amount of fluid, optimal infusion rate, and the type of solution.
Clinical data on the amount of fluid needed to prevent necrosis or to improve outcome are contradictory. In the past, an aggressive fluidic resuscitation meant a considerable and very rapid volume load, which could correspond of 2 liters bolus in the first hour and a subsequent maintenance of 20 ml/kg/h.
Even in some recent reviews, the initial volume of fluid administered varied substantially and also the strategy of maintenance—with or without initial bolus—was not uniform, with infusion’s rates that vary from 1 to 15 ml/kg/h. Currently, however, it has emerged that a very early volume load in the course of AP may be beneficial, while rapid volume loads in advanced stages are harmful [7]. Hence, after fluid resuscitation in the first 12–24 hours, infusion should generally be curtailed, to avoid respiratory complications or abdominal compartment syndrome.
In fact, after 20–40 minutes of infusion, only 20% of crystalloid remains in the intravascular space because most inevitably migrates to the interstitium, further worsening the oxygen diffusion. This is why too much fluid is as harmful as too little.
The value of early goal-directed therapy in these patients remains unknown. It is evident that an excessively rigid protocol of fluid management is illogical because “one size doesn’t fit all,” while it may be more beneficial to identify some personalized therapeutic end points [4].
Intravascular volume and an adequate perfusing pressure need to be restored, but infusion rate should be carefully tailored to individual patients, considering factors such as age and comorbidities. Fluid resuscitation should focus on improving heart rate, mean arterial pressure, central venous pressure, urine output, blood urea nitrogen concentration, and serum lactate.
It appeared that colloid administration could improve the outcome. But actually hydroxyethyl starch (HES) fluids are not recommended in AP because subsequent studies failed to demonstrate improved mortality and instead found increasing rate of kidney injury or need for renal replacement therapy [11]. In fact, the American Gastroenterological Association (AGA) suggests against the use of HES fluids, however, with very low quality of evidence.
The use of high volumes of normal saline—0.9% sodium chloride—has also been shown to have harmful effects on plasma electrolyte balance, leading to hyperchloremic acidosis. The large chloride load results in acidosis that could promote or exacerbate inflammation and renal injury.
Now isotonic balanced crystalloids are the preferred fluid. Particularly strong evidences came from the SMART trial of 2018, which found a reduction rate of the composite outcome of death from any cause, new renal-replacement therapy, or persistent renal dysfunction in patients given balanced crystalloid than saline [6, 12].
A recent study indeed reports a shorter hospital stay and fewer ICU admissions in the group of patients randomized to receive Ringer’s lactate, which is a balanced crystalloid isotonic versus plasma and seems to have an anti-inflammatory effect.
It is worth remembering that all these fluids are artificial solutions, which differ from human plasma composition. This is true also for balanced crystalloid, which varies in its electrolyte concentration, osmolality, and pH. Clinicians must then choose the better fluid to prescribe and its adequate amount, depending on the specific patient [13].
Based on multiple studies, a continuous infusion of 3 ml/kg/h would constitute aggressive and 1.5 ml/kg/h nonaggressive fluid therapy. As a general guidance, the choice of fluid should be a balanced crystalloid and the volume infused around 3–4 liters in the first 24 hours. There also should be predefined checkpoint at 6 or 8 hours to assess volemia and the other perfusion parameters [10, 14].
As outlined before, initial management of AP within the first 48–72 hours of admission can modify the course of disease and length of hospital stay [5].
In the early phase, the goal is to restore circulating blood volume and improve peripheral tissue oxygenation. Easy clinical markers of adequate hemodynamic function are heart rate, blood pressure, respiratory rate, O2 saturation, and urine output [8].
Fluid resuscitation is indicated to rapidly optimize tissue perfusion targets. In Figure 1, a practical approach is schematized, starting from resuscitation with 500–1000 ml of balanced crystalloid that is meant to normalize macrocirculation parameters such as blood pressure and heart rate and also microcirculation features such as refill time and skin color.
Early fluid resuscitation strategy.
Obviously, this fluidic load is commensurate to the magnitude of hypotension and volume must be adjusted to the patient’s age, weight, and preexisting renal injury or heart disease.
Subsequently, it is suggested to replace the ongoing losses with a continuous infusion of about 3 ml/kg/h during the first 12 hours and can be reduced to 1.5 ml/kg/h if physiological parameters improve or when patients resume hydration by mouth.
Caution is recommended to avoid fluid overload, and fluid administration should be guided by frequent reassessment of the hemodynamic status. However, it is particularly important to check blood pressure, heart rate, and pulse saturation every 6 or 8 hours, according to the severity of patient’s disease, with the purpose of knowing if intravascular volume is adequate to ensure a good organ perfusion and oxygenation.
Most authorities recommend titrating intravenous fluids administration to specific measurable targets of perfusion, which in a nonintensive environment, may be well represented by effective diuresis and lactate reduction. These are two indicators of adequate organ perfusion and indirectly suggest that the availability of oxygen is appropriate [6].
It is extremely important to follow the evolution of the patient’s clinical conditions to tailor our therapies. If there is no parameter improvement but rather diuresis contracts, lactates increase, respiratory insufficiency arises, or patient becomes hemodynamically unstable despite ongoing hydration, ICU transfer is indicated.
Acute abdominal pain is the commonest presenting symptom of AP and the leading reason for hospital admission. It was already identified as the most popular finding by the board of International Symposium on Acute Pancreatitis of 1992 and still represents one of the three diagnostic criteria of the revised Atlanta Classification [15].
Pain consistent with AP is localized in the epigastric region and radiates like a belt around the trunk into the back. It is usually constant and described as deep and penetrating, due probably to retroperitoneal localization of pancreas. Pain may be exacerbated by eating, drinking, or lying supine and is often associated with nausea and vomiting [16, 17].
Its pathogenesis is complex and multifactorial: pancreatic acinar cell injury triggers the synthesis and release of pro-inflammatory cytokines and chemokines such as leukotrienes, bradykinin and arachidonic acid metabolites, and pancreatic proteases such as trypsin stimulate sensory neurons, which release substance P and calcitonin-gene-related peptide. This sophisticated signal net tends to self-amplify and involve the immune system with leukocytes activation too [18].
Whereas for almost all patients with AP experience pain, its relief is a clinical priority. Patients must receive satisfactory analgesia after hospital admission and until they need, tailored on subjective perception and modulated according with day-by-day pain variation, in order not to compromise their quality of life. Providing good analgesia is associated with enhanced lung function and reduced deep vein thrombosis: if pain is well controlled, patients can breathe deeply, sitting on chair and walking around. All these activities reduce length of stay and improve outcome.
Unfortunately, no guidelines provide sufficient details regarding analgesia administration in AP, and best current recommendation is to adhere to the acute pain management in the perioperative setting.
Several randomized controlled trials (RCTs) analyze the feasibility of a specific strategy or compare safety and efficacy of different analgesics, but clinicians who daily work in surgery or emergency wards probably do not find it very useful [19].
This is the reason why we revise the most recent literature and provide some simple indications about type, dose, route, and frequency of analgesia administration, in accordance with the current evidence.
Numerous studies have focused on comparing the efficacy of different classes of intravenous analgesic, in order to choose only one of these to manage AP pain, but a more modern approach is growing.
There is consistent evidence that multimodal analgesic approach should be used when treating postoperative pain, and it is possible to extend this concept to the management of acute pain in general, because it means achieve better pain control minimizing side effects. Combined different classes of analgesics such as nonsteroidal anti-inflammatory drugs (NSAIDs), paracetamol, and opioids, which act through several mechanisms and bind different receptors, enable to reach a satisfying analgesic plain, using a lower dose of each one [20].
NSAIDs inhibit prostaglandins production acting on phospholipase A2 and cyclooxygenases (COXs) and thus relieve pain by reduction of pro-inflammatory cytokines cascade. NSAIDs have been shown a protective effect against AP in elective contest such as endoscopic retrograde cholangiopancreatography (ERCP), probably because COX-1 and COX-2 inhibition downregulates local inflammation and mediators spread [21, 22].
Paracetamol is the most popular analgesic and antipyretic drug in the world and has the well-known advantage of being used even in patients at increased risk of bleeding, but its mechanism of action is still unclear. It has a central effect, when given as a rapid intravenous bolus over 15 minutes, which is mediated by serotoninergic descending pathway, inhibits cyclooxygenases (especially COX-3 isoenzyme), and acts via the endocannabinoid system. Therefore, its analgesic effect comes from a quite different process respect of NSAIDs and justifies their association [23].
Opioids are the most frequently prescribed analgesics for pain relief of patients with AP. All opioids used in clinical practice today exert their action on μ receptors, with some having additional activity on κ and δ. Opioid receptors are distributed throughout the central nervous system (CNS) and in the dorsal horn. They have two main effects: block incoming nociceptive afferents (medulla and brainstem) and increase the inhibitory activity of the descending pathways (periaqueductal gray). They act on multiple sites of the CNS, also lowering negative affective connotation of pain [24].
They are the most powerful analgesics available and beyond relieving pain they have the advantageous property of making patients feel relaxed and promote sleep. People who are sick in fact are often distressed, anxious, insomnious because of discomfort, and sometimes oppositive to treatment.
Despite old beliefs about the risk of the Oddi’s sphincter spasms after systemic administration, several studies have clarified that opioids do not negatively impact on the course of AP and could be safely administered, and their use may decrease the need for supplementary analgesia [25, 26].
It is known that opioids expose to a greater risk of nausea, vomiting, and stypsis and that is why the association with non-opioids helps to reduce the total amount of their administration but allowing to obtain an analgesia level that would be unthinkable with paracetamol alone.
No evidence or recommendation about any restriction in pain medication is available. Of course, NSAIDs should be avoided in patients with acute or chronic kidney injury.
Ensuring proper analgesia avoids the chronicization of pain and therefore the long-lasting intake of anti-inflammatory drugs or even worse opioids addiction.
Furthermore, pain is a potentially treatable cause of delirium, a condition that frequently affects elderly or multipathological patients admitted to hospital especially in the case of prolonged hospitalizations, as the case for AP in general. Delirium is an acute and fluctuating disturbance of consciousness with reduced ability to focus, maintain, or shift attention, accompanied by change in cognition. It includes psychomotor disturbances, disorder of the sleep–wake cycle, and emotional instability. It also causes poor patient cooperation, complicating medical and nursing care.
It is of clinical interest because it correlates with length of hospitalization, long-term cognitive dysfunction, and mortality; therefore, it is a costly health condition and significantly impacts on outcome and patient performance.
Delirium has multifactorial causes, but there is convincing evidence that sleep deprivation is a risk factor for the development and in our patients, insomnia is frequently pain-related [27].
Good pain management is providing timely coverage during all day. Both surgical and oncologic pain are controlled by prescription of one medication, or a combination of medications, that is given at regularly intervals through the day, for maximum control of baseline pain. This is the around-the-clock medication (ATC), and we could agree that a patient with AP deserve to receive at least paracetamol 1 g every 6 hours and one NSAIDs, for example, ketorolac 30 mg or ketoprofen 100 mg, every 8 hours (Figure 2) [28, 29].
An example of multimodal analgesia schematic approach.
In addition, we should also include a rescue therapy, to cover breakthrough pain that is not adequately covered by ATC and morphine 3 mg could be a good option because it’s easily managed in the surgery ward and nursing staff are confident with. It is possible to administer again the same dosage after 30 minutes, which is the time for morphine to achieve maximum effect and the recommended dose is 10–15 mg within 24 hours, depending on the patient’s age and kidney function. In fact, morphine has a long half-life and produces some active metabolites, and its elimination is dependent on kidney excretion, so it can easily accumulate in subjects with impaired renal function and cause undesirable effects such as respiratory depression. Old people are more sensitive to pharmacodynamic effect of opioids, and clinicians must be aware of this and pay more attention with their prescription [30].
Knowing that AP is an overly complex pathology and associated pain can range from mild to severe, it would be advisable to contact the anesthesiologist if the administered morphine exceeds 10 mg, because it might be reasonable to upgrade the analgesia strategy. A multidisciplinary approach to patient care is the key for a more comprehensive assessment and his greater satisfaction.
A patient-controlled analgesia (PCA) pump is a computerized machine that gives a programmed amount of analgesic, usually an opioid, when the patient presses a button (bolus or demand dose). The drug might be delivered only as a bolus, or also with a continuous background infusion (basal rate) depending on the pharmacokinetic and dynamic of the drug itself, the entity of pain, and the patient performance.
Anesthesiologist presets the dosage in order to make the infusion absolutely safe [31].
PCA is a widespread technique already used to treat acute and chronic pain, in postoperative setting and emergency department. It has proven to be more effective than non-patient opioid injections because patients can self-administer small dose of analgesic, this results in better pain control and higher satisfaction, moreover with a net reduction in opioid consumption [32].
It is universally recognized that undertreatment of pain has important impact, including hemodynamic fluctuation with tachycardia and hypertension, peripheral vasoconstriction, which can cause poor peripheral perfusion, activation of the stress response with increased cortisol production and hyperglycemia, and not least patient discomfort.
One of the problems with pain management is time from patient complain and drug administration. Unfortunately, sometimes it takes a lot because of department organization, and there is strong evidence that poorly controlled pain is much harder to relieve than and indeed increases the incidence of chronic pain.
PCA therapy increases patient satisfaction, decreases pain scores, and reduces opioid consumption [33, 34].
Morphine is used for the management of moderate to severe pain. It is metabolized in the liver with formation of several metabolites, among which morphine-6-glucuronide is actually responsible for the observed response. It is predominantly excreted in the urine, and its half-life elimination is about 2–4 hours, partly still under active metabolites. It is a drug with a high interindividual variability both as regards the pain reduction and side effects such as respiratory depression, constipation, nausea, and itching. Also for this it is important to choose an adequate administration protocol (Table 1) [35].
MORPHINE PCA | ||||
---|---|---|---|---|
Loading dose | Bolus | Lockout | Continuous infusion | 4-hour limit |
3–5 mg | 1–3 mg | 20 min | 0.2– 0.5 mg/h | 10–15 mg |
Schematic morphine PCA administration.
The bolus is the dose of morphine delivered each time the patient presses the button, and it might range from 1 to 3 mg depending on patient’s physical characteristics: we will prefer lower dosages in elderly and frailty subjects. Morphine has an onset time of 15 minutes, but a slower peak effect, and it needs at least 30 minutes to exert its action. This is why the lockout interval, or time after a bolus in which another one is not allowed even if patient presses the button, is 20 minutes to permit the analgesic effect and prevent overdosing. Because of its long context-sensitive half time, after an adequate loading dose, the demand dose alone might be enough without background infusion, to reach satisfactory analgesia.
The 4-hour limit defines the maximum allowed amount of medication to be administered within that period, is usually less than the dose given if the patient presses the button every time, and acts as a safety mechanism.
The loading dose is a starting bolus that you can administer with the pump or manually with the aim to achieve more rapidly the patient well-being and having adequate stable concentration.
Among opioids, sufentanil has the highest therapeutic index, hence the safest to use. It is enormously powerful; therefore, it ensures excellent analgesia, but at the same time, it benefits from a much lower incidence of respiratory depression.
Is a highly lipophilic opioid and has a small volume of distribution. It has a time to peak effect after bolus of approximately 6–8 minutes, thus the patient will be able to manage in a satisfactory and punctual way his own analgesia, profiting from a rapid achievement of the effect.
It does not produce active metabolites and its excretion is not conditioned by renal function, as is the case for morphine, so it has a higher safety profile in elderly or patients with renal failure.
Its high therapeutic index and predictable pharmacokinetics make it the ideal candidate for administration via PCA pump as schematized in Table 2 [36].
SUFENTANIL PCA | ||||
---|---|---|---|---|
Loading dose | Bolus | Lockout | Continuous infusion | 4 hours limit |
5–10 μg | 2–5 μg | 15 min | 2–5 μg/h | 40 μg |
Schematic of sufentanil PCA administration.
Sufentanil has a faster half-life of elimination than morphine and a sensitive context half-life that is too short, this is the reason why it is advisable to couple with a background infusion of about 2–5 μg/h to reach a stable concentration and maintain the analgesic effect between boluses. The continuous infusion will administer 72–120 μg in 24 hours, which represents a reasonable and harmless amount.
In most cases it may be enough to set a low infusion (2 μg/hour) and instead prefer a more consistent bolus (5 μg).
The lockout may be shorter than what we usually set for morphine, because the sufentanil reaches peak effect more quickly, therefore 10–15 minutes are enough to ensure the effect perception, avoiding excessive self-administering.
It is preferable to give a loading dose before starting PCA infusion to immediately relieve patient’s condition and maybe observe the effectiveness of it [37].
Ketamine is an old hypnotic that is back in vogue because at low concentration acts as a fantastically painkiller and has safe profile because it does not impact on respiratory drive.
It inhibits N-methyl-D-aspartate receptor (NMDA-R) of glutamate, which is the main excitatory neurotransmitter: blocks nociceptive peripheral afferents into posterior dorsal horn, propagation through spinal cord, brainstem. and then higher centers projections.
Ketamina acts synergistically with opioids and hence has an opioid-sparing effect. Blocking the NMDA receptor prevents the calcium channel opening and its entry into the cell, which would lead to a lowering of the pain threshold and a lack of pain control with opioids.
Adding a little amount of ketamine, for example, 40–50 mg, to the PCA pump could be an excellent way to improve the patient’s analgesic management, reducing side effects and above all avoiding the need to increase morphine or sufentanil dosages. It also appears that this drug has the pleasant effect of mood improving, which can represent an added value to our therapy.
This approach significantly enhances activity of both morphine and sufentanil, improves their efficacy, and reduces tolerance to opioids [38, 39, 40].
AP causes severe pain, which sometimes is difficult to adequately control with intravenous analgesics, therefore epidural analgesia becomes a good treatment option. Epidural analgesia is an essential component of perioperative medicine because it guarantees an excellent pain control, reduces opioid consumption, and improves recovery especially after major surgery. It is currently used for labor pain management in the delivery room because it allows to modulate analgesia according to the various stages of labor, with great mothers’ satisfaction. It is also employed in ICU after severe chest trauma.
There is recent evidence from both preclinical and clinical trials supporting beneficial effects of epidural analgesia in AP. These studies suggest that epidural analgesia increases arterial perfusion of pancreas and redistribution of blood flow to nonperfused pancreatic regions [41, 42].
AP resulting from an inappropriate activation of trypsinogen leads to local injury and inflammation with increased capillary permeability, edema, augmented leukocyte adhesion, free radical production, and enhanced coagulation activity. This inflammatory vicious circle releases proinflammatory cytokines (IL-1, IL-6, IL-8) and systemic mediators (TNF-α) that discharge into the circulatory stream triggering a systemic inflammatory state.
Pancreatic tissue has been shown to be extremely sensitive to hypoxemia and ischemia, conditions that can lead to tissue necrosis and which strictly depend on microcirculation. Inadequate microvascular perfusion and hypoxia may play a significant role in early disease progression.
Thoracic epidural analgesia (TEA) induces a selective segmental sympathetic block, which, in addition of pain removal, increases splanchnic perfusion and reduces ischemic damage. TEA was found to improve gut mucosal perfusion and liver injury in sepsis too. It reduces pro-inflammatory state and improve outcome [43, 44, 45].
Significant complications related to the use of TEA are epidural hematoma, infection, and nerve damage. In spite of most of the research being done on patients admitted to ICU and thus with critical conditions, epidural has proved to be a safe technique [46]. This suggests that it can be used safely even in subjects with mild to moderate AP who are admitted to emergency or surgical department, if needed, for example, in obese or pneumopatic patients for whom we prefer to avoid opioids.
One of the reasons that creates reticence in the use of TEA is the fear of its hypotensive effect but, as for obstetrical analgesia, is possible to use low local anesthetics’ concentrations with none or minimal hemodynamic impact.
Pancreas sympathetic afferent innervations originate from both thoracic and lumbar spinal cord (T6–L2 metamers). The epidural catheter might be placed at the thoracic level (indicatively between T8 and T10) and analgesia can be driven with an elastomeric continuous infusion or with a patient-controlled epidural analgesia (PCEA) with only mandatory bolus or demand dose.
In any case, the use of low anesthetic concentrations is recommended, for example, ropivacaine 0.05%–0.075% administered with bolus of 5–7 ml, to minimize the block extension regarding the risk of hypotension. If it is not enough to meet patient satisfaction, is possible to increase this concentration to 0.1%–0.125%. The association of an opioid is always indicated, and sufentanil 0.2–0.5 μg/ml may be a desirable choice because of is lipophilicity.
Combination with an opioid results in better analgesia with smaller dose of anesthestic [43].
A successful strategy of pain management starts with measuring the patient’s pain.
The numeric rating scale (NRS) consists of a numeric version of the visual analog scale and is one of the most commonly used to assess pain severity (Figure 3). It helps healthcare professionals in quantifying a very subjective condition such as pain, in order to modulate analgesic administration and understand if current therapy works. On the other hand, it encourages patients to become active participants in pain assessment and management, and this is reflected on a well perception of care during hospital staying [47].
Numeric rating scale.
Scores also help in sharing information between different health professionals, speak the same language, and easily reassess patient’s response.
NRS starts with zero that means no pain and well-being, numbers from 1 to 3 correspond to mild pain, from 4 to 6 moderate pain and above severe pain. Number 10 identifies worst possible pain.
As mentioned above, not only is it important to ensure adequate analgesia during all phases of hospitalization, but also to choose the most appropriate strategy for the single patient.
The schematic approach in Figure 4 suggests assessing NRS score of the patient and if it is inferior to 5, is possible to start with a simple intravenous analgesia round the clock at fixed hours. Instead, if NRS is more than 5, is better to choose a stronger approach like a pump or the epidural. So, it would be advisable to involve the anesthesiologist and planning the better strategy for the patient.
Step up pain control.
AP is a complex disease, and a growing understanding of its pathophysiology has proven that pancreatic microcirculation is crucial in the development of necrosis. Current evidence supports the benefit of a proper fluid administration and pain relief in optimizing tissue perfusion and reducing AP worsening.
Early fluid resuscitation is the key to optimize pancreatic perfusion, reduce local necrosis, prevent hemodynamic deterioration and the systemic impact of disease. At the same time, it is important not to overload the patient, because a fluid excess worsens the outcome.
Working as a multidisciplinary team allows to optimize patient management based on individual skill. With this in mind, anesthesiologists propose a more precise and modern approach to pain control with multimodal analgesia and step-up management with PCA and TEA.
A particularly important aspect of care is frequent reassessment of the patient’s clinical conditions, physiological and humoral parameters, and even more considering their evolution trend, to tailoring fluid administration and analgesia.
Personalization of care not only improves outcome of patients, but also reduces their hospital stays.
None declared.
Thanks to Dr. Antonio Farnia, for all his useful suggestions.
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Radiotherapy and Nuclear Medicine Technology has always been my aspiration and my life. As years passed I accumulated a tremendous amount of skills and knowledge in Radiotherapy and Nuclear Medicine, Conventional Radiology, Radiation Protection, Bioinformatics Technology, PACS, Image processing, clinically and lecturing that will enable me to provide a valuable service to the community as a Researcher and Consultant in this field. My method of translating this into day to day in clinical practice is non-exhaustible and my habit of exchanging knowledge and expertise with others in those fields is the code and secret of success.",institutionString:null,institution:{name:"Majmaah University",country:{name:"Saudi Arabia"}}},{id:"313277",title:"Dr.",name:"Bartłomiej",middleName:null,surname:"Płaczek",slug:"bartlomiej-placzek",fullName:"Bartłomiej Płaczek",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/313277/images/system/313277.jpg",biography:"Bartłomiej Płaczek, MSc (2002), Ph.D. (2005), Habilitation (2016), is a professor at the University of Silesia, Institute of Computer Science, Poland, and an expert from the National Centre for Research and Development. His research interests include sensor networks, smart sensors, intelligent systems, and image processing with applications in healthcare and medicine. He is the author or co-author of more than seventy papers in peer-reviewed journals and conferences as well as the co-author of several books. He serves as a reviewer for many scientific journals, international conferences, and research foundations. Since 2010, Dr. Placzek has been a reviewer of grants and projects (including EU projects) in the field of information technologies.",institutionString:"University of Silesia",institution:{name:"University of Silesia",country:{name:"Poland"}}},{id:"35000",title:"Prof.",name:"Ulrich H.P",middleName:"H.P.",surname:"Fischer",slug:"ulrich-h.p-fischer",fullName:"Ulrich H.P Fischer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/35000/images/3052_n.jpg",biography:"Academic and Professional Background\nUlrich H. P. has Diploma and PhD degrees in Physics from the Free University Berlin, Germany. He has been working on research positions in the Heinrich-Hertz-Institute in Germany. Several international research projects has been performed with European partners from France, Netherlands, Norway and the UK. He is currently Professor of Communications Systems at the Harz University of Applied Sciences, Germany.\n\nPublications and Publishing\nHe has edited one book, a special interest book about ‘Optoelectronic Packaging’ (VDE, Berlin, Germany), and has published over 100 papers and is owner of several international patents for WDM over POF key elements.\n\nKey Research and Consulting Interests\nUlrich’s research activity has always been related to Spectroscopy and Optical Communications Technology. Specific current interests include the validation of complex instruments, and the application of VR technology to the development and testing of measurement systems. He has been reviewer for several publications of the Optical Society of America\\'s including Photonics Technology Letters and Applied Optics.\n\nPersonal Interests\nThese include motor cycling in a very relaxed manner and performing martial arts.",institutionString:null,institution:{name:"Charité",country:{name:"Germany"}}},{id:"341622",title:"Ph.D.",name:"Eduardo",middleName:null,surname:"Rojas Alvarez",slug:"eduardo-rojas-alvarez",fullName:"Eduardo Rojas Alvarez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/341622/images/15892_n.jpg",biography:null,institutionString:null,institution:{name:"University of Cuenca",country:{name:"Ecuador"}}},{id:"215610",title:"Prof.",name:"Muhammad",middleName:null,surname:"Sarfraz",slug:"muhammad-sarfraz",fullName:"Muhammad Sarfraz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/215610/images/system/215610.jpeg",biography:"Muhammad Sarfraz is a professor in the Department of Information Science, Kuwait University. His research interests include computer graphics, computer vision, image processing, machine learning, pattern recognition, soft computing, data science, intelligent systems, information technology, and information systems. Prof. Sarfraz has been a keynote/invited speaker on various platforms around the globe. He has advised various students for their MSc and Ph.D. theses. He has published more than 400 publications as books, journal articles, and conference papers. He is a member of various professional societies and a chair and member of the International Advisory Committees and Organizing Committees of various international conferences. Prof. Sarfraz is also an editor-in-chief and editor of various international journals.",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"32650",title:"Prof.",name:"Lukas",middleName:"Willem",surname:"Snyman",slug:"lukas-snyman",fullName:"Lukas Snyman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/32650/images/4136_n.jpg",biography:"Lukas Willem Snyman received his basic education at primary and high schools in South Africa, Eastern Cape. He enrolled at today's Nelson Metropolitan University and graduated from this university with a BSc in Physics and Mathematics, B.Sc Honors in Physics, MSc in Semiconductor Physics, and a Ph.D. in Semiconductor Physics in 1987. After his studies, he chose an academic career and devoted his energy to the teaching of physics to first, second, and third-year students. After positions as a lecturer at the University of Port Elizabeth, he accepted a position as Associate Professor at the University of Pretoria, South Africa.\r\n\r\nIn 1992, he motivates the concept of 'television and computer-based education” as means to reach large student numbers with only the best of teaching expertise and publishes an article on the concept in the SA Journal of Higher Education of 1993 (and later in 2003). The University of Pretoria subsequently approved a series of test projects on the concept with outreach to Mamelodi and Eerste Rust in 1993. In 1994, the University established a 'Unit for Telematic Education ' as a support section for multiple faculties at the University of Pretoria. In subsequent years, the concept of 'telematic education” subsequently becomes well established in academic circles in South Africa, grew in popularity, and is adopted by many universities and colleges throughout South Africa as a medium of enhancing education and training, as a method to reaching out to far out communities, and as a means to enhance study from the home environment.\r\n\r\nProfessor Snyman in subsequent years pursued research in semiconductor physics, semiconductor devices, microelectronics, and optoelectronics.\r\n\r\nIn 2000 he joined the TUT as a full professor. Here served for a period as head of the Department of Electronic Engineering. Here he makes contributions to solar energy development, microwave and optoelectronic device development, silicon photonics, as well as contributions to new mobile telecommunication systems and network planning in SA.\r\n\r\nCurrently, he teaches electronics and telecommunications at the TUT to audiences ranging from first-year students to Ph.D. level.\r\n\r\nFor his research in the field of 'Silicon Photonics” since 1990, he has published (as author and co-author) about thirty internationally reviewed articles in scientific journals, contributed to more than forty international conferences, about 25 South African provisional patents (as inventor and co-inventor), 8 PCT international patent applications until now. Of these, two USA patents applications, two European Patents, two Korean patents, and ten SA patents have been granted. A further 4 USA patents, 5 European patents, 3 Korean patents, 3 Chinese patents, and 3 Japanese patents are currently under consideration.\r\n\r\nRecently he has also published an extensive scholarly chapter in an internet open access book on 'Integrating Microphotonic Systems and MOEMS into standard Silicon CMOS Integrated circuitry”.\r\n\r\nFurthermore, Professor Snyman recently steered a new initiative at the TUT by introducing a 'Laboratory for Innovative Electronic Systems ' at the Department of Electrical Engineering. The model of this laboratory or center is to primarily combine outputs as achieved by high-level research with lower-level system development and entrepreneurship in a technical university environment. Students are allocated to projects at different levels with PhDs and Master students allocated to the generation of new knowledge and new technologies, while students at the diploma and Baccalaureus level are allocated to electronic systems development with a direct and a near application for application in industry or the commercial and public sectors in South Africa.\r\n\r\nProfessor Snyman received the WIRSAM Award of 1983 and the WIRSAM Award in 1985 in South Africa for best research papers by a young scientist at two international conferences on electron microscopy in South Africa. He subsequently received the SA Microelectronics Award for the best dissertation emanating from studies executed at a South African university in the field of Physics and Microelectronics in South Africa in 1987. In October of 2011, Professor Snyman received the prestigious Institutional Award for 'Innovator of the Year” for 2010 at the Tshwane University of Technology, South Africa. This award was based on the number of patents recognized and granted by local and international institutions as well as for his contributions concerning innovation at the TUT.",institutionString:null,institution:{name:"University of South Africa",country:{name:"South Africa"}}},{id:"317279",title:"Mr.",name:"Ali",middleName:"Usama",surname:"Syed",slug:"ali-syed",fullName:"Ali Syed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/317279/images/16024_n.png",biography:"A creative, talented, and innovative young professional who is dedicated, well organized, and capable research fellow with two years of experience in graduate-level research, published in engineering journals and book, with related expertise in Bio-robotics, equally passionate about the aesthetics of the mechanical and electronic system, obtained expertise in the use of MS Office, MATLAB, SolidWorks, LabVIEW, Proteus, Fusion 360, having a grasp on python, C++ and assembly language, possess proven ability in acquiring research grants, previous appointments with social and educational societies with experience in administration, current affiliations with IEEE and Web of Science, a confident presenter at conferences and teacher in classrooms, able to explain complex information to audiences of all levels.",institutionString:null,institution:{name:"Air University",country:{name:"Pakistan"}}},{id:"75526",title:"Ph.D.",name:"Zihni Onur",middleName:null,surname:"Uygun",slug:"zihni-onur-uygun",fullName:"Zihni Onur Uygun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/75526/images/12_n.jpg",biography:"My undergraduate education and my Master of Science educations at Ege University and at Çanakkale Onsekiz Mart University have given me a firm foundation in Biochemistry, Analytical Chemistry, Biosensors, Bioelectronics, Physical Chemistry and Medicine. After obtaining my degree as a MSc in analytical chemistry, I started working as a research assistant in Ege University Medical Faculty in 2014. In parallel, I enrolled to the MSc program at the Department of Medical Biochemistry at Ege University to gain deeper knowledge on medical and biochemical sciences as well as clinical chemistry in 2014. In my PhD I deeply researched on biosensors and bioelectronics and finished in 2020. Now I have eleven SCI-Expanded Index published papers, 6 international book chapters, referee assignments for different SCIE journals, one international patent pending, several international awards, projects and bursaries. In parallel to my research assistant position at Ege University Medical Faculty, Department of Medical Biochemistry, in April 2016, I also founded a Start-Up Company (Denosens Biotechnology LTD) by the support of The Scientific and Technological Research Council of Turkey. Currently, I am also working as a CEO in Denosens Biotechnology. The main purposes of the company, which carries out R&D as a research center, are to develop new generation biosensors and sensors for both point-of-care diagnostics; such as glucose, lactate, cholesterol and cancer biomarker detections. My specific experimental and instrumental skills are Biochemistry, Biosensor, Analytical Chemistry, Electrochemistry, Mobile phone based point-of-care diagnostic device, POCTs and Patient interface designs, HPLC, Tandem Mass Spectrometry, Spectrophotometry, ELISA.",institutionString:null,institution:{name:"Ege University",country:{name:"Turkey"}}},{id:"267434",title:"Dr.",name:"Rohit",middleName:null,surname:"Raja",slug:"rohit-raja",fullName:"Rohit Raja",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/267434/images/system/267434.jpg",biography:"Dr. Rohit Raja received Ph.D. in Computer Science and Engineering from Dr. CVRAMAN University in 2016. His main research interest includes Face recognition and Identification, Digital Image Processing, Signal Processing, and Networking. Presently he is working as Associate Professor in IT Department, Guru Ghasidas Vishwavidyalaya (A Central University), Bilaspur (CG), India. He has authored several Journal and Conference Papers. He has good Academics & Research experience in various areas of CSE and IT. He has filed and successfully published 27 Patents. He has received many time invitations to be a Guest at IEEE Conferences. He has published 100 research papers in various International/National Journals (including IEEE, Springer, etc.) and Proceedings of the reputed International/ National Conferences (including Springer and IEEE). He has been nominated to the board of editors/reviewers of many peer-reviewed and refereed Journals (including IEEE, Springer).",institutionString:"Guru Ghasidas Vishwavidyalaya",institution:{name:"Guru Ghasidas Vishwavidyalaya",country:{name:"India"}}},{id:"246502",title:"Dr.",name:"Jaya T.",middleName:"T",surname:"Varkey",slug:"jaya-t.-varkey",fullName:"Jaya T. Varkey",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/246502/images/11160_n.jpg",biography:"Jaya T. Varkey, PhD, graduated with a degree in Chemistry from Cochin University of Science and Technology, Kerala, India. She obtained a PhD in Chemistry from the School of Chemical Sciences, Mahatma Gandhi University, Kerala, India, and completed a post-doctoral fellowship at the University of Minnesota, USA. She is a research guide at Mahatma Gandhi University and Associate Professor in Chemistry, St. Teresa’s College, Kochi, Kerala, India.\nDr. Varkey received a National Young Scientist award from the Indian Science Congress (1995), a UGC Research award (2016–2018), an Indian National Science Academy (INSA) Visiting Scientist award (2018–2019), and a Best Innovative Faculty award from the All India Association for Christian Higher Education (AIACHE) (2019). She Hashas received the Sr. Mary Cecil prize for best research paper three times. She was also awarded a start-up to develop a tea bag water filter. \nDr. Varkey has published two international books and twenty-seven international journal publications. She is an editorial board member for five international journals.",institutionString:"St. Teresa’s College",institution:null},{id:"250668",title:"Dr.",name:"Ali",middleName:null,surname:"Nabipour Chakoli",slug:"ali-nabipour-chakoli",fullName:"Ali Nabipour Chakoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/250668/images/system/250668.jpg",biography:"Academic Qualification:\r\n•\tPhD in Materials Physics and Chemistry, From: Sep. 2006, to: Sep. 2010, School of Materials Science and Engineering, Harbin Institute of Technology, Thesis: Structure and Shape Memory Effect of Functionalized MWCNTs/poly (L-lactide-co-ε-caprolactone) Nanocomposites. Supervisor: Prof. Wei Cai,\r\n•\tM.Sc in Applied Physics, From: 1996, to: 1998, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Determination of Boron in Micro alloy Steels with solid state nuclear track detectors by neutron induced auto radiography, Supervisors: Dr. M. Hosseini Ashrafi and Dr. A. Hosseini.\r\n•\tB.Sc. in Applied Physics, From: 1991, to: 1996, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Design of shielding for Am-Be neutron sources for In Vivo neutron activation analysis, Supervisor: Dr. M. Hosseini Ashrafi.\r\n\r\nResearch Experiences:\r\n1.\tNanomaterials, Carbon Nanotubes, Graphene: Synthesis, Functionalization and Characterization,\r\n2.\tMWCNTs/Polymer Composites: Fabrication and Characterization, \r\n3.\tShape Memory Polymers, Biodegradable Polymers, ORC, Collagen,\r\n4.\tMaterials Analysis and Characterizations: TEM, SEM, XPS, FT-IR, Raman, DSC, DMA, TGA, XRD, GPC, Fluoroscopy, \r\n5.\tInteraction of Radiation with Mater, Nuclear Safety and Security, NDT(RT),\r\n6.\tRadiation Detectors, Calibration (SSDL),\r\n7.\tCompleted IAEA e-learning Courses:\r\nNuclear Security (15 Modules),\r\nNuclear Safety:\r\nTSA 2: Regulatory Protection in Occupational Exposure,\r\nTips & Tricks: Radiation Protection in Radiography,\r\nSafety and Quality in Radiotherapy,\r\nCourse on Sealed Radioactive Sources,\r\nCourse on Fundamentals of Environmental Remediation,\r\nCourse on Planning for Environmental Remediation,\r\nKnowledge Management Orientation Course,\r\nFood Irradiation - Technology, Applications and Good Practices,\r\nEmployment:\r\nFrom 2010 to now: Academic staff, Nuclear Science and Technology Research Institute, Kargar Shomali, Tehran, Iran, P.O. Box: 14395-836.\r\nFrom 1997 to 2006: Expert of Materials Analysis and Characterization. Research Center of Agriculture and Medicine. Rajaeeshahr, Karaj, Iran, P. O. Box: 31585-498.",institutionString:"Atomic Energy Organization of Iran",institution:{name:"Atomic Energy Organization of Iran",country:{name:"Iran"}}},{id:"248279",title:"Dr.",name:"Monika",middleName:"Elzbieta",surname:"Machoy",slug:"monika-machoy",fullName:"Monika Machoy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248279/images/system/248279.jpeg",biography:"Monika Elżbieta Machoy, MD, graduated with distinction from the Faculty of Medicine and Dentistry at the Pomeranian Medical University in 2009, defended her PhD thesis with summa cum laude in 2016 and is currently employed as a researcher at the Department of Orthodontics of the Pomeranian Medical University. She expanded her professional knowledge during a one-year scholarship program at the Ernst Moritz Arndt University in Greifswald, Germany and during a three-year internship at the Technical University in Dresden, Germany. She has been a speaker at numerous orthodontic conferences, among others, American Association of Orthodontics, European Orthodontic Symposium and numerous conferences of the Polish Orthodontic Society. She conducts research focusing on the effect of orthodontic treatment on dental and periodontal tissues and the causes of pain in orthodontic patients.",institutionString:"Pomeranian Medical University",institution:{name:"Pomeranian Medical University",country:{name:"Poland"}}},{id:"252743",title:"Prof.",name:"Aswini",middleName:"Kumar",surname:"Kar",slug:"aswini-kar",fullName:"Aswini Kar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252743/images/10381_n.jpg",biography:"uploaded in cv",institutionString:null,institution:{name:"KIIT University",country:{name:"India"}}},{id:"204256",title:"Dr.",name:"Anil",middleName:"Kumar",surname:"Kumar Sahu",slug:"anil-kumar-sahu",fullName:"Anil Kumar Sahu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204256/images/14201_n.jpg",biography:"I have nearly 11 years of research and teaching experience. I have done my master degree from University Institute of Pharmacy, Pt. Ravi Shankar Shukla University, Raipur, Chhattisgarh India. I have published 16 review and research articles in international and national journals and published 4 chapters in IntechOpen, the world’s leading publisher of Open access books. I have presented many papers at national and international conferences. I have received research award from Indian Drug Manufacturers Association in year 2015. My research interest extends from novel lymphatic drug delivery systems, oral delivery system for herbal bioactive to formulation optimization.",institutionString:null,institution:{name:"Chhattisgarh Swami Vivekanand Technical University",country:{name:"India"}}},{id:"253468",title:"Dr.",name:"Mariusz",middleName:null,surname:"Marzec",slug:"mariusz-marzec",fullName:"Mariusz Marzec",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/253468/images/system/253468.png",biography:"An assistant professor at Department of Biomedical Computer Systems, at Institute of Computer Science, Silesian University in Katowice. Scientific interests: computer analysis and processing of images, biomedical images, databases and programming languages. He is an author and co-author of scientific publications covering analysis and processing of biomedical images and development of database systems.",institutionString:"University of Silesia",institution:{name:"University of Silesia",country:{name:"Poland"}}},{id:"212432",title:"Prof.",name:"Hadi",middleName:null,surname:"Mohammadi",slug:"hadi-mohammadi",fullName:"Hadi Mohammadi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/212432/images/system/212432.jpeg",biography:"Dr. Hadi Mohammadi is a biomedical engineer with hands-on experience in the design and development of many engineering structures and medical devices through various projects that he has been involved in over the past twenty years. Dr. Mohammadi received his BSc. and MSc. degrees in Mechanical Engineering from Sharif University of Technology, Tehran, Iran, and his PhD. degree in Biomedical Engineering (biomaterials) from the University of Western Ontario. He was a postdoctoral trainee for almost four years at University of Calgary and Harvard Medical School. He is an industry innovator having created the technology to produce lifelike synthetic platforms that can be used for the simulation of almost all cardiovascular reconstructive surgeries. He’s been heavily involved in the design and development of cardiovascular devices and technology for the past 10 years. He is currently an Assistant Professor with the University of British Colombia, Canada.",institutionString:"University of British Columbia",institution:{name:"University of British Columbia",country:{name:"Canada"}}},{id:"254463",title:"Prof.",name:"Haisheng",middleName:null,surname:"Yang",slug:"haisheng-yang",fullName:"Haisheng Yang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/254463/images/system/254463.jpeg",biography:"Haisheng Yang, Ph.D., Professor and Director of the Department of Biomedical Engineering, College of Life Science and Bioengineering, Beijing University of Technology. He received his Ph.D. degree in Mechanics/Biomechanics from Harbin Institute of Technology (jointly with University of California, Berkeley). Afterwards, he worked as a Postdoctoral Research Associate in the Purdue Musculoskeletal Biology and Mechanics Lab at the Department of Basic Medical Sciences, Purdue University, USA. He also conducted research in the Research Centre of Shriners Hospitals for Children-Canada at McGill University, Canada. Dr. Yang has over 10 years research experience in orthopaedic biomechanics and mechanobiology of bone adaptation and regeneration. He earned an award from Beijing Overseas Talents Aggregation program in 2017 and serves as Beijing Distinguished Professor.",institutionString:null,institution:{name:"Beijing University of Technology",country:{name:"China"}}},{id:"89721",title:"Dr.",name:"Mehmet",middleName:"Cuneyt",surname:"Ozmen",slug:"mehmet-ozmen",fullName:"Mehmet Ozmen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/89721/images/7289_n.jpg",biography:null,institutionString:null,institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"265335",title:"Mr.",name:"Stefan",middleName:"Radnev",surname:"Stefanov",slug:"stefan-stefanov",fullName:"Stefan Stefanov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/265335/images/7562_n.jpg",biography:null,institutionString:null,institution:{name:"Medical University Plovdiv",country:{name:"Bulgaria"}}},{id:"242893",title:"Ph.D. Student",name:"Joaquim",middleName:null,surname:"De Moura",slug:"joaquim-de-moura",fullName:"Joaquim De Moura",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/242893/images/7133_n.jpg",biography:"Joaquim de Moura received his degree in Computer Engineering in 2014 from the University of A Coruña (Spain). In 2016, he received his M.Sc degree in Computer Engineering from the same university. He is currently pursuing his Ph.D degree in Computer Science in a collaborative project between ophthalmology centers in Galicia and the University of A Coruña. His research interests include computer vision, machine learning algorithms and analysis and medical imaging processing of various kinds.",institutionString:null,institution:{name:"University of A Coruña",country:{name:"Spain"}}},{id:"294334",title:"B.Sc.",name:"Marc",middleName:null,surname:"Bruggeman",slug:"marc-bruggeman",fullName:"Marc Bruggeman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/294334/images/8242_n.jpg",biography:"Chemical engineer graduate, with a passion for material science and specific interest in polymers - their near infinite applications intrigue me. \n\nI plan to continue my scientific career in the field of polymeric biomaterials as I am fascinated by intelligent, bioactive and biomimetic materials for use in both consumer and medical applications.",institutionString:null,institution:null},{id:"255757",title:"Dr.",name:"Igor",middleName:"Victorovich",surname:"Lakhno",slug:"igor-lakhno",fullName:"Igor Lakhno",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255757/images/system/255757.jpg",biography:"Igor Victorovich Lakhno was born in 1971 in Kharkiv (Ukraine). \nMD – 1994, Kharkiv National Medical Univesity.\nOb&Gyn; – 1997, master courses in Kharkiv Medical Academy of Postgraduate Education.\nPh.D. – 1999, Kharkiv National Medical Univesity.\nDSC – 2019, PL Shupik National Academy of Postgraduate Education \nProfessor – 2021, Department of Obstetrics and Gynecology of VN Karazin Kharkiv National University\nHead of Department – 2021, Department of Perinatology, Obstetrics and gynecology of Kharkiv Medical Academy of Postgraduate Education\nIgor Lakhno has been graduated from international training courses on reproductive medicine and family planning held at Debrecen University (Hungary) in 1997. Since 1998 Lakhno Igor has worked as an associate professor in the department of obstetrics and gynecology of VN Karazin National University and an associate professor of the perinatology, obstetrics, and gynecology department of Kharkiv Medical Academy of Postgraduate Education. Since June 2019 he’s been a professor in the department of obstetrics and gynecology of VN Karazin National University and a professor of the perinatology, obstetrics, and gynecology department. He’s affiliated with Kharkiv Medical Academy of Postgraduate Education as a Head of Department from November 2021. Igor Lakhno has participated in several international projects on fetal non-invasive electrocardiography (with Dr. J. A. Behar (Technion), Prof. D. Hoyer (Jena University), and José Alejandro Díaz Méndez (National Institute of Astrophysics, Optics, and Electronics, Mexico). He’s an author of about 200 printed works and there are 31 of them in Scopus or Web of Science databases. Igor Lakhno is a member of the Editorial Board of Reproductive Health of Woman, Emergency Medicine, and Technology Transfer Innovative Solutions in Medicine (Estonia). He is a medical Editor of “Z turbotoyu pro zhinku”. Igor Lakhno is a reviewer of the Journal of Obstetrics and Gynaecology (Taylor and Francis), British Journal of Obstetrics and Gynecology (Wiley), Informatics in Medicine Unlocked (Elsevier), The Journal of Obstetrics and Gynecology Research (Wiley), Endocrine, Metabolic & Immune Disorders-Drug Targets (Bentham Open), The Open Biomedical Engineering Journal (Bentham Open), etc. He’s defended a dissertation for a DSc degree “Pre-eclampsia: prediction, prevention, and treatment”. Three years ago Igor Lakhno has participated in a training course on innovative technologies in medical education at Lublin Medical University (Poland). Lakhno Igor has participated as a speaker in several international conferences and congresses (International Conference on Biological Oscillations April 10th-14th 2016, Lancaster, UK, The 9th conference of the European Study Group on Cardiovascular Oscillations). His main scientific interests: are obstetrics, women’s health, fetal medicine, and cardiovascular medicine. \nIgor Lakhno is a consultant at Kharkiv municipal perinatal center. He’s graduated from training courses on endoscopy in gynecology. He has 28 years of practical experience in the field.",institutionString:null,institution:null},{id:"244950",title:"Dr.",name:"Salvatore",middleName:null,surname:"Di Lauro",slug:"salvatore-di-lauro",fullName:"Salvatore Di Lauro",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0030O00002bSF1HQAW/ProfilePicture%202021-12-20%2014%3A54%3A14.482",biography:"Name:\n\tSALVATORE DI LAURO\nAddress:\n\tHospital Clínico Universitario Valladolid\nAvda Ramón y Cajal 3\n47005, Valladolid\nSpain\nPhone number: \nFax\nE-mail:\n\t+34 983420000 ext 292\n+34 983420084\nsadilauro@live.it\nDate and place of Birth:\nID Number\nMedical Licence \nLanguages\t09-05-1985. Villaricca (Italy)\n\nY1281863H\n474707061\nItalian (native language)\nSpanish (read, written, spoken)\nEnglish (read, written, spoken)\nPortuguese (read, spoken)\nFrench (read)\n\t\t\nCurrent position (title and company)\tDate (Year)\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. Private practise.\t2017-today\n\n2019-today\n\t\n\t\nEducation (High school, university and postgraduate training > 3 months)\tDate (Year)\nDegree in Medicine and Surgery. University of Neaples 'Federico II”\nResident in Opthalmology. Hospital Clinico Universitario Valladolid\nMaster in Vitreo-Retina. IOBA. University of Valladolid\nFellow of the European Board of Ophthalmology. Paris\nMaster in Research in Ophthalmology. University of Valladolid\t2003-2009\n2012-2016\n2016-2017\n2016\n2012-2013\n\t\nEmployments (company and positions)\tDate (Year)\nResident in Ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl.\nFellow in Vitreo-Retina. IOBA. University of Valladolid\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. \n\t2012-2016\n2016-2017\n2017-today\n\n2019-Today\n\n\n\t\nClinical Research Experience (tasks and role)\tDate (Year)\nAssociated investigator\n\n' FIS PI20/00740: DESARROLLO DE UNA CALCULADORA DE RIESGO DE\nAPARICION DE RETINOPATIA DIABETICA BASADA EN TECNICAS DE IMAGEN MULTIMODAL EN PACIENTES DIABETICOS TIPO 1. Grant by: Ministerio de Ciencia e Innovacion \n\n' (BIO/VA23/14) Estudio clínico multicéntrico y prospectivo para validar dos\nbiomarcadores ubicados en los genes p53 y MDM2 en la predicción de los resultados funcionales de la cirugía del desprendimiento de retina regmatógeno. Grant by: Gerencia Regional de Salud de la Junta de Castilla y León.\n' Estudio multicéntrico, aleatorizado, con enmascaramiento doble, en 2 grupos\nparalelos y de 52 semanas de duración para comparar la eficacia, seguridad e inmunogenicidad de SOK583A1 respecto a Eylea® en pacientes con degeneración macular neovascular asociada a la edad' (CSOK583A12301; N.EUDRA: 2019-004838-41; FASE III). Grant by Hexal AG\n\n' Estudio de fase III, aleatorizado, doble ciego, con grupos paralelos, multicéntrico para comparar la eficacia y la seguridad de QL1205 frente a Lucentis® en pacientes con degeneración macular neovascular asociada a la edad. (EUDRACT: 2018-004486-13). Grant by Qilu Pharmaceutical Co\n\n' Estudio NEUTON: Ensayo clinico en fase IV para evaluar la eficacia de aflibercept en pacientes Naive con Edema MacUlar secundario a Oclusion de Vena CenTral de la Retina (OVCR) en regimen de tratamientO iNdividualizado Treat and Extend (TAE)”, (2014-000975-21). Grant by Fundacion Retinaplus\n\n' Evaluación de la seguridad y bioactividad de anillos de tensión capsular en conejo. Proyecto Procusens. Grant by AJL, S.A.\n\n'Estudio epidemiológico, prospectivo, multicéntrico y abierto\\npara valorar la frecuencia de la conjuntivitis adenovírica diagnosticada mediante el test AdenoPlus®\\nTest en pacientes enfermos de conjuntivitis aguda”\\n. National, multicenter study. Grant by: NICOX.\n\nEuropean multicentric trial: 'Evaluation of clinical outcomes following the use of Systane Hydration in patients with dry eye”. Study Phase 4. Grant by: Alcon Labs'\n\nVLPs Injection and Activation in a Rabbit Model of Uveal Melanoma. Grant by Aura Bioscience\n\nUpdating and characterization of a rabbit model of uveal melanoma. Grant by Aura Bioscience\n\nEnsayo clínico en fase IV para evaluar las variantes genéticas de la vía del VEGF como biomarcadores de eficacia del tratamiento con aflibercept en pacientes con degeneración macular asociada a la edad (DMAE) neovascular. Estudio BIOIMAGE. IMO-AFLI-2013-01\n\nEstudio In-Eye:Ensayo clínico en fase IV, abierto, aleatorizado, de 2 brazos,\nmulticçentrico y de 12 meses de duración, para evaluar la eficacia y seguridad de un régimen de PRN flexible individualizado de 'esperar y extender' versus un régimen PRN según criterios de estabilización mediante evaluaciones mensuales de inyecciones intravítreas de ranibizumab 0,5 mg en pacientes naive con neovascularización coriodea secunaria a la degeneración macular relacionada con la edad. CP: CRFB002AES03T\n\nTREND: Estudio Fase IIIb multicéntrico, randomizado, de 12 meses de\nseguimiento con evaluador de la agudeza visual enmascarado, para evaluar la eficacia y la seguridad de ranibizumab 0.5mg en un régimen de tratar y extender comparado con un régimen mensual, en pacientes con degeneración macular neovascular asociada a la edad. CP: CRFB002A2411 Código Eudra CT:\n2013-002626-23\n\n\n\nPublications\t\n\n2021\n\n\n\n\n2015\n\n\n\n\n2021\n\n\n\n\n\n2021\n\n\n\n\n2015\n\n\n\n\n2015\n\n\n2014\n\n\n\n\n2015-16\n\n\n\n2015\n\n\n2014\n\n\n2014\n\n\n\n\n2014\n\n\n\n\n\n\n\n2014\n\nJose Carlos Pastor; Jimena Rojas; Salvador Pastor-Idoate; Salvatore Di Lauro; Lucia Gonzalez-Buendia; Santiago Delgado-Tirado. Proliferative vitreoretinopathy: A new concept of disease pathogenesis and practical\nconsequences. Progress in Retinal and Eye Research. 51, pp. 125 - 155. 03/2016. DOI: 10.1016/j.preteyeres.2015.07.005\n\n\nLabrador-Velandia S; Alonso-Alonso ML; Di Lauro S; García-Gutierrez MT; Srivastava GK; Pastor JC; Fernandez-Bueno I. Mesenchymal stem cells provide paracrine neuroprotective resources that delay degeneration of co-cultured organotypic neuroretinal cultures.Experimental Eye Research. 185, 17/05/2019. DOI: 10.1016/j.exer.2019.05.011\n\nSalvatore Di Lauro; Maria Teresa Garcia Gutierrez; Ivan Fernandez Bueno. Quantification of pigment epithelium-derived factor (PEDF) in an ex vivo coculture of retinal pigment epithelium cells and neuroretina.\nJournal of Allbiosolution. 2019. ISSN 2605-3535\n\nSonia Labrador Velandia; Salvatore Di Lauro; Alonso-Alonso ML; Tabera Bartolomé S; Srivastava GK; Pastor JC; Fernandez-Bueno I. Biocompatibility of intravitreal injection of human mesenchymal stem cells in immunocompetent rabbits. Graefe's archive for clinical and experimental ophthalmology. 256 - 1, pp. 125 - 134. 01/2018. DOI: 10.1007/s00417-017-3842-3\n\n\nSalvatore Di Lauro, David Rodriguez-Crespo, Manuel J Gayoso, Maria T Garcia-Gutierrez, J Carlos Pastor, Girish K Srivastava, Ivan Fernandez-Bueno. A novel coculture model of porcine central neuroretina explants and retinal pigment epithelium cells. Molecular Vision. 2016 - 22, pp. 243 - 253. 01/2016.\n\nSalvatore Di Lauro. Classifications for Proliferative Vitreoretinopathy ({PVR}): An Analysis of Their Use in Publications over the Last 15 Years. Journal of Ophthalmology. 2016, pp. 1 - 6. 01/2016. DOI: 10.1155/2016/7807596\n\nSalvatore Di Lauro; Rosa Maria Coco; Rosa Maria Sanabria; Enrique Rodriguez de la Rua; Jose Carlos Pastor. Loss of Visual Acuity after Successful Surgery for Macula-On Rhegmatogenous Retinal Detachment in a Prospective Multicentre Study. Journal of Ophthalmology. 2015:821864, 2015. DOI: 10.1155/2015/821864\n\nIvan Fernandez-Bueno; Salvatore Di Lauro; Ivan Alvarez; Jose Carlos Lopez; Maria Teresa Garcia-Gutierrez; Itziar Fernandez; Eva Larra; Jose Carlos Pastor. Safety and Biocompatibility of a New High-Density Polyethylene-Based\nSpherical Integrated Porous Orbital Implant: An Experimental Study in Rabbits. Journal of Ophthalmology. 2015:904096, 2015. DOI: 10.1155/2015/904096\n\nPastor JC; Pastor-Idoate S; Rodríguez-Hernandez I; Rojas J; Fernandez I; Gonzalez-Buendia L; Di Lauro S; Gonzalez-Sarmiento R. Genetics of PVR and RD. Ophthalmologica. 232 - Suppl 1, pp. 28 - 29. 2014\n\nRodriguez-Crespo D; Di Lauro S; Singh AK; Garcia-Gutierrez MT; Garrosa M; Pastor JC; Fernandez-Bueno I; Srivastava GK. Triple-layered mixed co-culture model of RPE cells with neuroretina for evaluating the neuroprotective effects of adipose-MSCs. Cell Tissue Res. 358 - 3, pp. 705 - 716. 2014.\nDOI: 10.1007/s00441-014-1987-5\n\nCarlo De Werra; Salvatore Condurro; Salvatore Tramontano; Mario Perone; Ivana Donzelli; Salvatore Di Lauro; Massimo Di Giuseppe; Rosa Di Micco; Annalisa Pascariello; Antonio Pastore; Giorgio Diamantis; Giuseppe Galloro. Hydatid disease of the liver: thirty years of surgical experience.Chirurgia italiana. 59 - 5, pp. 611 - 636.\n(Italia): 2007. ISSN 0009-4773\n\nChapters in books\n\t\n' Salvador Pastor Idoate; Salvatore Di Lauro; Jose Carlos Pastor Jimeno. PVR: Pathogenesis, Histopathology and Classification. Proliferative Vitreoretinopathy with Small Gauge Vitrectomy. Springer, 2018. ISBN 978-3-319-78445-8\nDOI: 10.1007/978-3-319-78446-5_2. \n\n' Salvatore Di Lauro; Maria Isabel Lopez Galvez. Quistes vítreos en una mujer joven. Problemas diagnósticos en patología retinocoroidea. Sociedad Española de Retina-Vitreo. 2018.\n\n' Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor Jimeno. iOCT in PVR management. OCT Applications in Opthalmology. pp. 1 - 8. INTECH, 2018. DOI: 10.5772/intechopen.78774.\n\n' Rosa Coco Martin; Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor. amponadores, manipuladores y tinciones en la cirugía del traumatismo ocular.Trauma Ocular. Ponencia de la SEO 2018..\n\n' LOPEZ GALVEZ; DI LAURO; CRESPO. OCT angiografia y complicaciones retinianas de la diabetes. PONENCIA SEO 2021, CAPITULO 20. (España): 2021.\n\n' Múltiples desprendimientos neurosensoriales bilaterales en paciente joven. Enfermedades Degenerativas De Retina Y Coroides. SERV 04/2016. \n' González-Buendía L; Di Lauro S; Pastor-Idoate S; Pastor Jimeno JC. Vitreorretinopatía proliferante (VRP) e inflamación: LA INFLAMACIÓN in «INMUNOMODULADORES Y ANTIINFLAMATORIOS: MÁS ALLÁ DE LOS CORTICOIDES. 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Possible contributions can address (but are not limited to) the following research topics: Bioinspired design and control of exoskeletons, orthoses, and prostheses; Experimental evaluation of the effect of assistive devices (e.g., influence on gait, balance, and neuromuscular system); Bioinspired technologies for rehabilitation, including clinical studies reporting evaluations; Application of neuromuscular and biomechanical models to the development of bioinspired technology.',annualVolume:11404,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/8.jpg",editor:{id:"144937",title:"Prof.",name:"Adriano",middleName:"De Oliveira",surname:"Andrade",fullName:"Adriano Andrade",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRC8QQAW/Profile_Picture_1625219101815",institutionString:null,institution:{name:"Federal University of Uberlândia",institutionURL:null,country:{name:"Brazil"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"49517",title:"Prof.",name:"Hitoshi",middleName:null,surname:"Tsunashima",fullName:"Hitoshi Tsunashima",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYTP4QAO/Profile_Picture_1625819726528",institutionString:null,institution:{name:"Nihon University",institutionURL:null,country:{name:"Japan"}}},{id:"425354",title:"Dr.",name:"Marcus",middleName:"Fraga",surname:"Vieira",fullName:"Marcus Vieira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003BJSgIQAX/Profile_Picture_1627904687309",institutionString:null,institution:{name:"Universidade Federal de Goiás",institutionURL:null,country:{name:"Brazil"}}},{id:"196746",title:"Dr.",name:"Ramana",middleName:null,surname:"Vinjamuri",fullName:"Ramana Vinjamuri",profilePictureURL:"https://mts.intechopen.com/storage/users/196746/images/system/196746.jpeg",institutionString:"University of Maryland, Baltimore County",institution:{name:"University of Maryland, Baltimore County",institutionURL:null,country:{name:"United States of America"}}}]},{id:"9",title:"Biotechnology - Biosensors, Biomaterials and Tissue Engineering",keywords:"Biotechnology, Biosensors, Biomaterials, Tissue Engineering",scope:"The Biotechnology - Biosensors, Biomaterials and Tissue Engineering topic within the Biomedical Engineering Series aims to rapidly publish contributions on all aspects of biotechnology, biosensors, biomaterial and tissue engineering. We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics can include but are not limited to: Biotechnology such as biotechnological products and process engineering; Biotechnologically relevant enzymes and proteins; Bioenergy and biofuels; Applied genetics and molecular biotechnology; Genomics, transcriptomics, proteomics; Applied microbial and cell physiology; Environmental biotechnology; Methods and protocols. Moreover, topics in biosensor technology, like sensors that incorporate enzymes, antibodies, nucleic acids, whole cells, tissues and organelles, and other biological or biologically inspired components will be considered, and topics exploring transducers, including those based on electrochemical and optical piezoelectric, thermal, magnetic, and micromechanical elements. Chapters exploring biomaterial approaches such as polymer synthesis and characterization, drug and gene vector design, biocompatibility, immunology and toxicology, and self-assembly at the nanoscale, are welcome. Finally, the tissue engineering subcategory will support topics such as the fundamentals of stem cells and progenitor cells and their proliferation, differentiation, bioreactors for three-dimensional culture and studies of phenotypic changes, stem and progenitor cells, both short and long term, ex vivo and in vivo implantation both in preclinical models and also in clinical trials.",annualVolume:11405,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/9.jpg",editor:{id:"126286",title:"Dr.",name:"Luis",middleName:"Jesús",surname:"Villarreal-Gómez",fullName:"Luis Villarreal-Gómez",profilePictureURL:"https://mts.intechopen.com/storage/users/126286/images/system/126286.jpg",institutionString:null,institution:{name:"Autonomous University of Baja California",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"35539",title:"Dr.",name:"Cecilia",middleName:null,surname:"Cristea",fullName:"Cecilia Cristea",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYQ65QAG/Profile_Picture_1621007741527",institutionString:null,institution:{name:"Iuliu Hațieganu University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"40735",title:"Dr.",name:"Gil",middleName:"Alberto Batista",surname:"Gonçalves",fullName:"Gil Gonçalves",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYRLGQA4/Profile_Picture_1628492612759",institutionString:null,institution:{name:"University of Aveiro",institutionURL:null,country:{name:"Portugal"}}},{id:"211725",title:"Associate Prof.",name:"Johann F.",middleName:null,surname:"Osma",fullName:"Johann F. 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