Common families of human and animal non-enveloped viruses.
Chapter 1: "Permanent Maxillary and Mandibular Incisors"\n
Chapter 2: "The Permanent Maxillary and Mandibular Premolar Teeth"\n
Chapter 3: "Dental Anatomical Features and Caries: A Relationship to be Investigated"\n
Chapter 4: "Anatomy Applied to Block Anaesthesia"\n
Chapter 5: "Treatment Considerations for Missing Teeth"\n
Chapter 6: "Anatomical and Functional Restoration of the Compromised Occlusion: From Theory to Materials"\n
Chapter 7: "Evaluation of the Anatomy of the Lower First Premolar"\n
Chapter 8: "A Comparative Study of the Validity and Reproducibility of Mesiodistal Tooth Size and Dental Arch with the iTero Intraoral Scanner and the Traditional Method"\n
Chapter 9: "Identification of Lower Central Incisors"\n
The book is aimed toward dentists and can also be well used in education and research.',isbn:"978-1-78923-511-1",printIsbn:"978-1-78923-510-4",pdfIsbn:"978-1-83881-247-8",doi:"10.5772/65542",price:119,priceEur:129,priceUsd:155,slug:"dental-anatomy",numberOfPages:204,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"445cd419d97f339f2b6514c742e6b050",bookSignature:"Bağdagül Helvacioğlu Kivanç",publishedDate:"August 1st 2018",coverURL:"https://cdn.intechopen.com/books/images_new/5814.jpg",numberOfDownloads:13558,numberOfWosCitations:0,numberOfCrossrefCitations:5,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:9,numberOfDimensionsCitationsByBook:0,hasAltmetrics:0,numberOfTotalCitations:14,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"October 4th 2016",dateEndSecondStepPublish:"October 25th 2016",dateEndThirdStepPublish:"July 16th 2017",dateEndFourthStepPublish:"August 16th 2017",dateEndFifthStepPublish:"October 16th 2017",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"178570",title:"Dr.",name:"Bağdagül",middleName:null,surname:"Helvacıoğlu Kıvanç",slug:"bagdagul-helvacioglu-kivanc",fullName:"Bağdagül Helvacıoğlu Kıvanç",profilePictureURL:"https://mts.intechopen.com/storage/users/178570/images/7646_n.jpg",biography:"Bağdagül Helvacıoğlu Kıvanç is a dentist, a teacher, a researcher and a scientist in the field of Endodontics. She was born in Zonguldak, Turkey, on February 14, 1974; she is married and has two children. She graduated in 1997 from the Ankara University, Faculty of Dentistry, Ankara, Turkey. She aquired her PhD in 2004 from the Gazi University, Faculty of Dentistry, Department of Endodontics, Ankara, Turkey, and she is still an associate professor at the same department. She has published numerous articles and a book chapter in the areas of Operative Dentistry, Esthetic Dentistry and Endodontics. She is a member of Turkish Endodontic Society and European Endodontic Society.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Gazi University",institutionURL:null,country:{name:"Turkey"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"174",title:"Dentistry",slug:"dentistry"}],chapters:[{id:"56461",title:"Permanent Maxillary and Mandibular Incisors",doi:"10.5772/intechopen.69542",slug:"permanent-maxillary-and-mandibular-incisors",totalDownloads:2626,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"The permanent incisors are the front teeth that erupt between 6 and 8 years of age. They are eight in number, four upper and four lower, two centrals and two laterals. They have sharp biting surfaces designed for shearing and cutting of food materials into small chewable pieces. They are the teeth most visible to the others during eating, smiling and talking, and thus, they have high aesthetic value for the individuals. The unique characteristics, arch position, function, development and chronological age of each tooth will be highlighted. In addition, the different aspects with their geometric outlines, outlines and surface anatomy of these teeth will be described. A brief explanation about the pulp cavity, tooth socket and normal occlusion for each tooth will be included.",signatures:"Mohammed E. Grawish, Lamyaa M. Grawish and Hala M. Grawish",downloadPdfUrl:"/chapter/pdf-download/56461",previewPdfUrl:"/chapter/pdf-preview/56461",authors:[{id:"82989",title:"Prof.",name:"Mohammed",surname:"Grawish",slug:"mohammed-grawish",fullName:"Mohammed Grawish"}],corrections:null},{id:"62386",title:"The Permanent Maxillary and Mandibular Premolar Teeth",doi:"10.5772/intechopen.79464",slug:"the-permanent-maxillary-and-mandibular-premolar-teeth",totalDownloads:2759,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"The permanent premolar teeth are placed between the anterior teeth and molars. Eight premolars are found in the permanent dentition, four per arch and two in each quadrant. The main function of premolars is to assist the canines in regard to tear and pierce the food and supplement the grinding of the molars during mastication. The other functions are to support the corners of the mouth reinforce esthetics during smiling and maintain the vertical dimension. Detailed morphology of the permanent premolar teeth is narrated in a pointwise and systematic manner in this chapter.",signatures:"Işıl Çekiç Nagaş, Ferhan Eğilmez and Bağdagül Helvacioğlu Kivanç",downloadPdfUrl:"/chapter/pdf-download/62386",previewPdfUrl:"/chapter/pdf-preview/62386",authors:[{id:"178570",title:"Dr.",name:"Bağdagül",surname:"Helvacıoğlu Kıvanç",slug:"bagdagul-helvacioglu-kivanc",fullName:"Bağdagül Helvacıoğlu Kıvanç"}],corrections:null},{id:"57546",title:"Dental Anatomical Features and Caries: A Relationship to be Investigated",doi:"10.5772/intechopen.71337",slug:"dental-anatomical-features-and-caries-a-relationship-to-be-investigated",totalDownloads:1706,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Dental caries is a multifactor disease affecting a significant number of people throughout the world. However, in recent decades the widespread availability of fluoride and other preventive measures have resulted in a decline in the prevalence of caries among children and young adults. Currently, it is accepted that most carious dental lesions are restricted to specific anatomical sites. The aim of this chapter is to review the influence of dental anatomy on dental caries development while taking into account recent findings in cariology. Occlusal fissures in the first permanent molar are generally the first sites in the permanent dentition to develop caries. An increased risk of caries is also found in proximal contacting surfaces between two adjacent teeth. Moreover, a partially erupted tooth, which does not participate in mastication, is also at risk for caries since it may provide a more favorable environment for bacterial accumulation than a fully erupted tooth. Bacterial biofilm on the tooth is frequently a high risk caries environment. Understanding anatomical dental features is of great importance for guiding oral health hygiene and preventive measures. Finally, the development of dental disorders plays an important role in dental caries risk.",signatures:"Marcel Alves Avelino de Paiva, Dayane Franco Barros Mangueira\nLeite, Isabela Albuquerque Passos Farias, Antônio de Pádua\nCavalcante Costa and Fábio Correia Sampaio",downloadPdfUrl:"/chapter/pdf-download/57546",previewPdfUrl:"/chapter/pdf-preview/57546",authors:[{id:"138852",title:"Prof.",name:"Fabio",surname:"Sampaio",slug:"fabio-sampaio",fullName:"Fabio Sampaio"},{id:"213662",title:"Prof.",name:"Isabela Albuquerque",surname:"Passos Farias",slug:"isabela-albuquerque-passos-farias",fullName:"Isabela Albuquerque Passos Farias"},{id:"213663",title:"Prof.",name:"Dayane Franco",surname:"Barros Mangueira Leite",slug:"dayane-franco-barros-mangueira-leite",fullName:"Dayane Franco Barros Mangueira Leite"},{id:"213664",title:"BSc.",name:"Marcel Alves",surname:"Avelino De Paiva",slug:"marcel-alves-avelino-de-paiva",fullName:"Marcel Alves Avelino De Paiva"},{id:"213666",title:"Prof.",name:"Antonio De Pádua",surname:"Cavalcante Da Costa",slug:"antonio-de-padua-cavalcante-da-costa",fullName:"Antonio De Pádua Cavalcante Da Costa"}],corrections:null},{id:"56119",title:"Anatomy Applied to Block Anesthesia for Maxillofacial Surgery",doi:"10.5772/intechopen.69545",slug:"anatomy-applied-to-block-anesthesia-for-maxillofacial-surgery",totalDownloads:1529,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Anatomy is a basic knowledge that every clinician must have; however, its full management is not always achieved and gaps remain in daily practice. The aim of this chapter is to emphasize the most relevant aspects of head and neck anatomy, specifically related to osteology and neurology for the application of regional anesthesia techniques. This chapter presents a clear and concise text, useful for both undergraduate and graduate students and for the dentist and maxillofacial surgeon. The most relevant aspects of the bone and sensory anatomy relevant for the realization of regional anesthetic techniques in the oral and maxillofacial area are reviewed, including complementary figures and tables. The anatomy related to the techniques directed to the three major branches of the trigeminal nerve (ophthalmic nerve, maxillary nerve, and to the branches of the mandibular nerve) will be approached separately.",signatures:"Alex Vargas, Paula Astorga and Tomas Rioseco",downloadPdfUrl:"/chapter/pdf-download/56119",previewPdfUrl:"/chapter/pdf-preview/56119",authors:[{id:"199400",title:"Dr.",name:"Alex",surname:"Vargas",slug:"alex-vargas",fullName:"Alex Vargas"},{id:"202023",title:"Dr.",name:"Paula",surname:"Astorga",slug:"paula-astorga",fullName:"Paula Astorga"},{id:"205059",title:"Dr.",name:"Tomas",surname:"Rioseco",slug:"tomas-rioseco",fullName:"Tomas Rioseco"}],corrections:null},{id:"55902",title:"Treatment Considerations for Missing Teeth",doi:"10.5772/intechopen.69543",slug:"treatment-considerations-for-missing-teeth",totalDownloads:989,totalCrossrefCites:2,totalDimensionsCites:3,hasAltmetrics:0,abstract:"Specific terms are used to describe the nature of tooth agenesis. Hypodontia is most frequently used when describing the phenomenon of congenitally missing teeth. Many other terms to describe a reduction in the number of teeth appear in the literature: oligodontia, anodontia, aplasia of teeth, congenitally missing teeth, absence of teeth, agenesis of teeth and lack of teeth. The term hypodontia is used when one to six teeth, excluding third molars, are missing, and oligodontia when more than six teeth are absent (excluding the third molars). The long‐term management of hypodontia in the aesthetic zone is a particularly challenging situation. Although there are essentially two distinct approaches to manage this problem, that is space closure or opening for prosthetic replacements, implant or autotransplantation. These patients often manifest with many underlying skeletal and dental problems and a multidisciplinary approach for management of this condition is recommended. Two treatment approaches including space closure and space reopening are described in details in this chapter.",signatures:"Abdolreza Jamilian, Alireza Darnahal, Ludovica Nucci, Fabrizia\nD’Apuzzo and Letizia Perillo",downloadPdfUrl:"/chapter/pdf-download/55902",previewPdfUrl:"/chapter/pdf-preview/55902",authors:[{id:"171777",title:"Prof.",name:"Abdolreza",surname:"Jamilian",slug:"abdolreza-jamilian",fullName:"Abdolreza Jamilian"},{id:"171873",title:"Dr.",name:"Alireza",surname:"Darnahal",slug:"alireza-darnahal",fullName:"Alireza Darnahal"},{id:"173044",title:"Prof.",name:"Letizia",surname:"Perillo",slug:"letizia-perillo",fullName:"Letizia Perillo"},{id:"198961",title:"MSc.",name:"Fabrizia",surname:"D'Apuzzo",slug:"fabrizia-d'apuzzo",fullName:"Fabrizia D'Apuzzo"},{id:"206137",title:"Mrs.",name:"Ludovica",surname:"Nucci",slug:"ludovica-nucci",fullName:"Ludovica Nucci"}],corrections:null},{id:"55973",title:"Anatomical and Functional Restoration of the Compromised Occlusion: From Theory to Materials",doi:"10.5772/intechopen.69544",slug:"anatomical-and-functional-restoration-of-the-compromised-occlusion-from-theory-to-materials",totalDownloads:1288,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Many conditions can alter the occlusal interface, from tooth wear to tooth loss. The masticatory system is constituted by many components that can influence each other like muscles, joints, teeth and nervous system. This implies that (a) every change at occlusal level makes the other components to adapt and (b) an occlusal alteration may be the effect of an alteration occurred on muscles or joints. Keeping this in mind, traditional principles of occlusal rehabilitation are analysed, and the choice of the restorative materials is discussed.",signatures:"Nicola Mobilio and Santo Catapano",downloadPdfUrl:"/chapter/pdf-download/55973",previewPdfUrl:"/chapter/pdf-preview/55973",authors:[{id:"179565",title:"Dr.",name:"Nicola",surname:"Mobilio",slug:"nicola-mobilio",fullName:"Nicola Mobilio"},{id:"199397",title:"Prof.",name:"Santo",surname:"Catapano",slug:"santo-catapano",fullName:"Santo Catapano"}],corrections:null},{id:"57245",title:"Evaluation of the Anatomy of the Lower First Premolar",doi:"10.5772/intechopen.71038",slug:"evaluation-of-the-anatomy-of-the-lower-first-premolar",totalDownloads:889,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"This chapter provides information about the lower first premolars. This tooth is considered to be one of the most complex teeth and the dentistry graduation students usually have difficulties in identifying it. The aim of this chapter is to present a detailed morphological study of extracted lower first premolars. One hundred lower first premolars, belonging to the collection of the Laboratory of Anatomy of the Department of Morphology of the São Paulo State University (UNESP), School of Dentistry, Araraquara, SP, Brazil, were evaluated. Nine measurements were performed through direct observation without any instruments. Other 20 measurements were made by photographs and they were analyzed by the Image Tool 3.0 program. According to the results, it was concluded that most of the teeth presented the following features such as one lingual cusp; the distal occlusal pits were wider than the mesial occlusal pits; an enamel bridge linking the buccal and lingual cusps; the grooves in the lingual surface that emerged from the mesial and distal occlusal pits were absent, and where the grooves were present, they emerged from the mesial occlusal pit; one rectilinear root with no root grooves and where the root groove was present, it was observed in the mesial surface.",signatures:"Ticiana Sidorenko de Oliveira Capote, Suellen Tayenne Pedroso\nPinto, Marcelo Brito Conte, Juliana Álvares Duarte Bonini Campos\nand Marcela de Almeida Gonçalves",downloadPdfUrl:"/chapter/pdf-download/57245",previewPdfUrl:"/chapter/pdf-preview/57245",authors:[{id:"87871",title:"Prof.",name:"Ticiana",surname:"Capote",slug:"ticiana-capote",fullName:"Ticiana Capote"},{id:"199157",title:"Prof.",name:"Marcela",surname:"De Almeida Gonçalves",slug:"marcela-de-almeida-goncalves",fullName:"Marcela De Almeida Gonçalves"},{id:"199243",title:"BSc.",name:"Marcelo",surname:"Brito Conte",slug:"marcelo-brito-conte",fullName:"Marcelo Brito Conte"},{id:"199244",title:"Prof.",name:"Juliana",surname:"Álvares Duarte Bonini Campos",slug:"juliana-alvares-duarte-bonini-campos",fullName:"Juliana Álvares Duarte Bonini Campos"},{id:"217420",title:"Mrs.",name:"Suellen",surname:"Tayenne Pedroso Pinto",slug:"suellen-tayenne-pedroso-pinto",fullName:"Suellen Tayenne Pedroso Pinto"}],corrections:null},{id:"57752",title:"A Comparative Study of the Validity and Reproducibility of Mesiodistal Tooth Size and Dental Arch with iTeroTM Intraoral Scanner and the Traditional Method",doi:"10.5772/intechopen.70963",slug:"a-comparative-study-of-the-validity-and-reproducibility-of-mesiodistal-tooth-size-and-dental-arch-wi",totalDownloads:922,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Introduction: The introduction of intraoral scanning offers an alternative for measuring mesiodistal tooth sizes.",signatures:"Ignacio Faus-Matoses, Ana Mora, Carlos Bellot-Arcís, Jose Luis\nGandia-Franco and Vanessa Paredes-Gallardo",downloadPdfUrl:"/chapter/pdf-download/57752",previewPdfUrl:"/chapter/pdf-preview/57752",authors:[{id:"150456",title:"Prof.",name:"Vanessa",surname:"Paredes",slug:"vanessa-paredes",fullName:"Vanessa Paredes"},{id:"150458",title:"Prof.",name:"José-Luis",surname:"Gandia-Franco",slug:"jose-luis-gandia-franco",fullName:"José-Luis Gandia-Franco"},{id:"212242",title:"Prof.",name:"Ignacio",surname:"Faus",slug:"ignacio-faus",fullName:"Ignacio Faus"},{id:"212243",title:"Prof.",name:"Carlos",surname:"Bellot-Arcís",slug:"carlos-bellot-arcis",fullName:"Carlos Bellot-Arcís"},{id:"218390",title:"Prof.",name:"Ana",surname:"Mora",slug:"ana-mora",fullName:"Ana Mora"}],corrections:null},{id:"57378",title:"Identification of Lower Central Incisors",doi:"10.5772/intechopen.71341",slug:"identification-of-lower-central-incisors",totalDownloads:858,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Unlike the other teeth, the permanent lower central incisors have great symmetry between the proximal surfaces, being difficult to distinguish them. It was intended to facilitate the study of the anatomy of the lower central incisor for dentistry students, that this study searched for a better way to differentiate the third quadrant element (31) from the fourth quadrant element (41). The purpose of this chapter was to evaluate 100 permanent lower central incisors of the didactic collection of the Discipline of Anatomy of the Department of Morphology of the School of Dentistry of Araraquara - UNESP and to verify the presence of correlation between the some anatomical features. Besides, it was evaluated if there was difference between 31 and 41. It was verified that the systematic methodology used for the evaluation of the incisors in this study facilitated the identification of the teeth. There was no statistically significant difference between the measurements of 31 and 41. Distinguishing the right from the left central incisor is difficult, even for experienced practitioners. We could observe that the measurements do not facilitate the identification of teeth of different quadrants. Therefore, the anatomical features are relevant for the study of the dental anatomy in the identification of the lower central incisors.",signatures:"Marcela de Almeida Gonçalves, Bruno Luís Graciliano Silva, Marcelo\nBrito Conte, Juliana Álvares Duarte Bonini Campos and Ticiana\nSidorenko de Oliveira Capote",downloadPdfUrl:"/chapter/pdf-download/57378",previewPdfUrl:"/chapter/pdf-preview/57378",authors:[{id:"199157",title:"Prof.",name:"Marcela",surname:"De Almeida Gonçalves",slug:"marcela-de-almeida-goncalves",fullName:"Marcela De Almeida Gonçalves"},{id:"199243",title:"BSc.",name:"Marcelo",surname:"Brito Conte",slug:"marcelo-brito-conte",fullName:"Marcelo Brito Conte"},{id:"199244",title:"Prof.",name:"Juliana",surname:"Álvares Duarte Bonini Campos",slug:"juliana-alvares-duarte-bonini-campos",fullName:"Juliana Álvares Duarte Bonini Campos"},{id:"221435",title:"Mr.",name:"Bruno Luis Graciliano",surname:"Silva",slug:"bruno-luis-graciliano-silva",fullName:"Bruno Luis Graciliano Silva"},{id:"221438",title:"Prof.",name:"Ticiana Sidorenko De Oliveira",surname:"Capote",slug:"ticiana-sidorenko-de-oliveira-capote",fullName:"Ticiana Sidorenko De Oliveira Capote"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"7572",title:"Trauma in Dentistry",subtitle:null,isOpenForSubmission:!1,hash:"7cb94732cfb315f8d1e70ebf500eb8a9",slug:"trauma-in-dentistry",bookSignature:"Serdar Gözler",coverURL:"https://cdn.intechopen.com/books/images_new/7572.jpg",editedByType:"Edited by",editors:[{id:"204606",title:"Dr.",name:"Serdar",surname:"Gözler",slug:"serdar-gozler",fullName:"Serdar Gözler"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8837",title:"Human Teeth",subtitle:"Key Skills and Clinical Illustrations",isOpenForSubmission:!1,hash:"ac055c5801032970123e0a196c2e1d32",slug:"human-teeth-key-skills-and-clinical-illustrations",bookSignature:"Zühre Akarslan and Farid Bourzgui",coverURL:"https://cdn.intechopen.com/books/images_new/8837.jpg",editedByType:"Edited by",editors:[{id:"171887",title:"Prof.",name:"Zühre",surname:"Akarslan",slug:"zuhre-akarslan",fullName:"Zühre Akarslan"}],equalEditorOne:{id:"52177",title:"Prof.",name:"Farid",middleName:null,surname:"Bourzgui",slug:"farid-bourzgui",fullName:"Farid Bourzgui",profilePictureURL:"https://mts.intechopen.com/storage/users/52177/images/system/52177.png",biography:"Prof. Farid Bourzgui obtained his DMD and his DNSO option in Orthodontics at the School of Dental Medicine, Casablanca Hassan II University, Morocco, in 1995 and 2000, respectively. Currently, he is a professor of Orthodontics. He holds a Certificate of Advanced Study type A in Technology of Biomaterials used in Dentistry (1995); Certificate of Advanced Study type B in Dento-Facial Orthopaedics (1997) from the Faculty of Dental Surgery, University Denis Diderot-Paris VII, France; Diploma of Advanced Study (DESA) in Biocompatibility of Biomaterials from the Faculty of Medicine and Pharmacy of Casablanca (2002); Certificate of Clinical Occlusodontics from the Faculty of Dentistry of Casablanca (2004); University Diploma of Biostatistics and Perceptual Health Measurement from the Faculty of Medicine and Pharmacy of Casablanca (2011); and a University Diploma of Pedagogy of Odontological Sciences from the Faculty of Dentistry of Casablanca (2013). 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Park",coverURL:"https://cdn.intechopen.com/books/images_new/10437.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"96610",title:"Dr.",name:"Henry S.",middleName:null,surname:"Park",slug:"henry-s.-park",fullName:"Henry S. Park"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}}},ofsBook:{item:{type:"book",id:"11710",leadTitle:null,title:"Lifestyle-Related Diseases and Metabolic Syndrome",subtitle:null,reviewType:"peer-reviewed",abstract:"
\r\n\tObesity causes various lifestyle-related diseases such as heart disease, stroke, and type 2 diabetes, and the cluster of conditions that occur together is called “metabolic syndrome”. The risk of developing more than two lifestyle-related diseases in a person who develops metabolic syndrome is much higher than that in a normal person. Therefore, the prevention of lifestyle-related diseases and metabolic syndrome is one of the most discussed topics. This book aims to gather researchers who are active in lifestyle-related diseases and metabolic syndrome areas.
\r\n\tThe main goal of this book is (1) prevention and treatment of life-related diseases and metabolic syndrome, (2) mechanism of lifestyle-related diseases and metabolic syndrome, (3) effective functional compounds, foods, and diet to lifestyle-related diseases and metabolic syndrome, (4) relationship between metabolic syndrome and various diseases such as cancer, allergy, and aging. This book hopes to bring an overview of the recent advances of metabolic syndrome, and thus we welcome both review chapters and original chapters.
Complex systems are a large multidisciplinary research theme that has been studied using a combination of fundamental theory, derived especially from physics and computational modeling. This kind of systems is composed of a large number of elemental units that interact with each other, being called “agents” [1, 2, 62]. Examples of complex systems can be found in human societies, the brain, internet, ecosystems, biological evolution, stock markets, economies and many others.
The manner in which such a system manifests can\'t be predicted only by the behavior of individual elements or by adding their behavior, but is determined by the way the elements interact in order to influence global behavior. Very important properties of complex systems are those of emergence, self-organization, adaptability etc. [3, 4, 62].
An example of a complex system is represented by polymers. [Their structures present a multitude of organized networks starting from simple, linear chains of identical structural units to very complex sequences of amino acids that are chained together, thus forming the fundamental units of living fields. Probably one of the most interesting biological complex system is DNA that generates cells by employing a simple but very efficient code. It is the striking way in which individual cells organize into complex systems, such as organs and, subsequently, organisms. Research in the field of complex systems could provide new information on the realistic dynamics of polymers, solving troublesome problems such as protein folding. We note that the dynamics of such complex systems implies the quantum formalism] [1-4, 62].
Correspondingly, the theoretical models that describe the complex systems dynamics become more and more advanced [1-4]. For all that, this problem can be solved by taking into account that the complexity of the interaction process implies various temporal resolution scales, and the pattern evolution implies different degrees of freedom [5].
[In order to develop new theoretical models we must state the fact that the complex systems displaying chaotic behavior are recognized to acquire self-similarity (space-time structures can appear) in association with strong fluctuations at all possible space-time scales [1-4]. Afterwards, for temporal scales that are large with respect to the inverse of the highest Lyapunov exponent, the deterministic trajectories are replaced by a set of potential trajectories and the concept of definite positions by that of probability density] [62]. An interesting example is the collisions processes in complex systems, where the dynamics of the particles can be described by non-differentiable curves.
Since non-differentiability can be considered a universal property of complex systems, it is mandatory to develop a non-differentiable physics. In this way, by considering that the complexity of the interaction processes is replaced by non-differentiability, using the entire range of quantities from the standard physics (differentiable physics) is no longer required [19].
This topic was developed in the Scale Relativity Theory (SRT) [6, 7] and in the non-standard Scale Relativity Theory (NSSRT) [8-22]. [In the framework of SRT or NSSRT we assume that the movements of complex system entities take place on continuous but non-differentiable curves (fractal curves) so that all physical phenomena involved in the dynamics depend not only on the space-time coordinates but also on the space-time scales resolution. In this conjecture, the physical quantities that describe the dynamics of complex systems can be considered as fractal functions. In addition, the entities of the complex system may be reduced to and identified with their own trajectories. In this way, the complex system’s behavior will be identical to the one of a special interaction-less “fluid” by means of its geodesics in a non-differentiable (fractal) space] [6, 7, 62].
In such context notions as informational entropy, Onicescu informational energy etc become important in the Nature description. These notions will be correlated with the fractal part of the physical quantities that describe the dynamics of complex systems.
Independently of scale resolution, the motion, either on infragalactic scale (for instance, the planetary motion), or on atomic scale (for instance, the motion of the electron around its nucleus) takes place on conics (ellipses). Such motion in invariant with respect to the SL(2R) group. In what follows, we shall consider this invariance only with respect to the motion on atomic scale.
SL(2R) group is the group of transformations [23-26]
which makes invariant the areas in the phase space
Choosing
the infinitesimal transformations of the group have the expressions
Then the Lie algebra associated to the group becomes
where
are the vectors of the Lie base.
The general vector of the algebra (4) is given by the linear combination
The hamiltonian
According to (5), relation (7) becomes
whence the characteristic differential system
admits the integral
We notice that the differential system (9) is Hamilton\'s system of equations [25]
associated to the hamiltonian (1), where the symbol “
Among the solutions of the equation (1), we have also the Gaussian
In consequence, all invariant functions on the group (7) will be functions of the hamiltonian (10) and particularly, of the Gaussian (12).
If the quadratic form (10) is positive definite, that is, the condition
is fulfiled, then, by deriving the relations
with respect to the time and eliminating
These equations are formally equivalent to the equations of two linear oscillators of coordinates
Then the 2-form
has the meaning of the elementary surface in phase space
[In standard quantum mechanics, the impossibility of determining the variances of the position coordinate
Relating to this, it is unusual that the definitive nonzero variances
In such a conjecture the uncertainty relations result in a quite natural way from the momentum perturbations associated with the fractal potential, i.e. with the Shannon’s information.
Indeed, let be the probability density in the phase space,
where
Now, we introduce Shannon\'s informational entropy [27]:
Through Shannon\'s maximum informational entropy principle
with constraints (17), we get the normalized Gaussian distribution:
with
[We must note that the set of parameters
In such context, the statistical hypothesis are specified through a particular choice of the set of parameters
where
If
If for the group (24) we choose the same parameterization as the one given by relations (2), then the corresponding infinitesimal transformations
can be considered as an incompatible algebraic system in the unknowns
Thus, the action of the group (24) in the space of variables
The Lie algebra associated to the group (24) is
where
are the vectors of the base Lie. By the conditions
[where
If
Therefore, the “class” of statistical hypothesis associated to the Gaussians having the same mean, is given by the ergodic condition. This highlights the strong relationship existing among the energetic issues and the probabilistic ones] (see [71]).
For the informational energy we shall use Onicescu\'s relation [34, 62, 71]:
Thus, the informational energy corresponding to the normed Gaussians (20), which is subject to conditions (22), becomes
where
Thus we get
and therefore, if
The informational energy indicates the dispersion distribution (20) because the quantity
is a measure of the ellipses\' areas of equal probability
The class of statistical hypothesis which are specific to the Gaussians having the same mean is given by the constant value of the informational energy;
The constant informational energy is equivalent to the ergodic condition;
If the informational energy is constant, then the relations (21) and (34) give the egalitarian uncertainty relation
or the non-egalitarian one
In such context we can show that the constant value of the Onicescu informational energy implies, in the case of a linear oscillator, the Planck\'s quantification condition.
[The original theory of de Broglie on the wave-corpuscle duality was developed using a theorem found in Lorentz\'s transformation [35]. This theorem interlinks the local horologes cyclic frequency (in each point of a spatial domain) with a progressive wave frequency in phase with the horologes. This wave gives determines the distribution of the oscillators\' phases on the respective spatial domain. We desire to show that a distribution of this kind, in a true sense, can be determined without resorting to Lorentz\'s transformation [67].
The concept imagined by de Broglie, of equal pulsation horologes, can be evidenced by a periodic field, which is described by the local oscillators of equation
where
where
[This equation is invariant to the homographic transformation of
Any homographic function of this ratio will be again a projective parameter [67]. Among all other, the function
has primarily the advantage of being specific to each oscillator. But not only that: let be another function
which is specific to another oscillator. Since (42) and (43) are solutions of the equation (40), there exists a homographic relation between them:
which, made explicit, leads to the Barbilian group equations [37]:
[The group may be considered as a \'synchronization\' group among various oscillators, a process in which the values of each take part, meaning that not only their phases, but also their amplitudes are correlated. The usual synchronization, manifested through the difference among the oscillators\' phases as a whole, represents here just a particular case. Indeed, the group is involved for
When taking into consideration, for the group (45), the parameterization from [23], the following infinitesimal generators of the above-mentioned group will be obtained] [63]:
the following commutation relations
being involved. [Thus, a structure near-identical to group SL(2R)\'s Lie algebra is shown. In consequence, the Lie algebra of the group (45) is, again, a result of group SL(2R)\'s Lie algebra. Actually, as can be easily observed, the group (45) represents only another action of the group SL(2R), performed in variables
Once we fulfill the conditions of the theorem [38], the invariant functions can be found, simultaneously to the actions of the groups (5) and (46) as solutions of the equation
Explaining this equation by means of Equations (5) and (46) leads to their simple solution, by successive reduction, while simultaneously obtaining the invariant functions in the form
where
where
If considering Eq (50), then Eq (51) takes the form
where the following notation has been used:
We also noticed that
Eq (52) represents a family of conical shapes from the phase space
a condition also fulfilled if
where
Quite an interesting case appears when
where
The Gaussian distribution value obtained in such a manner represents only a particular case of the distribution that may occur, assuming in addition the obligation of satisfying the maximum principle of informational entropy under quadratic restrictions. The solutions of Eq (48) could be, however, much more general, being possibly selected from criteria involving group theory. In this context, the informational energy becomes
while the uncertainty relation (36) is
resulting that the concept of uncertainty is minimum only for
When the creation and annihilation operators refer to a harmonic oscillator, the uncertainty relations have the form from [33, 63] with
Onicescu informational energy can be correlated with the standard quantum mechanics and the second quantification (which indicates its utility, for instance in NDA-NRA dynamics) [39].
The structure of the group (45) is given by the equations (46) in the manner that the only non-zero structure constants are [26]:
Therefore, the invariant quadratic form is given by the “quadratic” tensor of the group,
or, more explicit, by (60),
This yields that the invariant metric of the group is given by the relation [50]
where
These 1-forms have the expressions:
in which case the metric (63) becomes
It should be mentioned here a property related to integral geometry: the group (45) is measurable. Indeed, it is simply transitive and, since his structure vector
that is, the inverse of the module of the linear system\'s determinant obtained through the infinitesimal transformations of the group (45). Therefore, in the field variables space
where
We now analyze the metric (65): it reduces to the metric of the Lobacevski\'s plan in Poincaré representation [26]:
for
it results
and so, the condition
Since by this restriction, the metric (68) in the variables (69) reduces to the Lobacevski\'s one in Beltrami\'s representation:
the condition (71) defines a parallel transport of vectors in a Levi-Civita meaning: the application point of the vector moves on the geodesic, the vector always making a constant angle with the tangent to the geodesic in the current point. Truly, using the fact that the plan\'s metric is conformal Euclidean, the angle between the initial vector and the vector transported through parallelism can be calculated as the integral of the equation (see [36, 68, 71] for details):
along the transport curve.
Now the variables
in an ambient space of the metric
Then the field equations derive from the variational principle [41]
relative to the Lagrange function
In such a context, Einstein\'s equations with
(
Thus, adopting as a starting point the variational principle (76), the essential goal of the analysis in the gravitational field domain is to produce metrics of Lobacevski\'s plan or metrics related to them. All these can be directly related to Einstein\'s equations (78). Moreover, by substituting the principle of independence of the simultaneous actions, in the form of linear composition in a point of various fields intensities (through the apriori invariance of fields\' action with respect to a certain group), we may conceive a gravity theory that has none of the contradictions inherently and commonly present in the current theory [44]. We observe that the SL(2R) group parameters can be interpreted as field amplitudes in a supergravitation model [23] (see also [71] for details).
In the field of cell\'s biology, we call vesicles those small bags wrapped in a membrane forming part of eukaryotic cell organelles. They are involved in proteins or enzymes transport and absorption, or meet other needs of the cell. Inside the membrane bag of a vesicle, there are macromolecules which require the ability to move outside the cell walls. The membrane encircling the bag merges with the outer wall of the cell to allow such macromolecules to penetrate the wall. The vesicles are important parts of the human cells, although they are also found in other multicellular organisms [66].
Cells found in humans, plants and animals use a variety of types of vesicles, depending on the type of cell and its specific intended function. For example, one type of vesicles, lysosomes, are necessary for the process of digestion. Lysosomes contain enzymes that breakdown food cells. With food absorption, a lysosome vesicle bonds to the food holding cell and releases enzymes by a process called phagocytosis. These enzymes break down food cells into smaller parts that can be better absorbed by other cells.
Secretory vesicles are frequently associated with nerve cells in humans or animals. Their membranes sacs contain neurotransmitters. Nervous system through hormonal signals activates these components. Through the process of exocytosis, the secretory vesicle\'s outer membrane adheres to the nerve terminal and releases neurotransmitters in the area of the nerve endings, named the synaptic cleft. Neurotransmitters transport information from one nerve terminal to the next, across the entire central nervous system, way up to the brain [66].
Vesicles, in their role as cellular mechanism are internally appointed for transport, uptake and storage of numerous imperative bodily functions. Without these tiny bags wrapped in membranes, cells could not make the exchange of materials necessary to maintain their healthy development and other crucial processes. As a conclusion, with no vesicles, humans and other pluricellular organisms could not have existed, because the essential cellular chemical processes would have no other method to pass onto another key materials [66].
Since there is increasing support that vesicle trafficking, including the release of EVs, is a highly important process in tumorigenesis, embryogenesis and tissue remodeling, in this paragraph we present an extensive discussion on the EVs convection in haptotaxis with hydrodynamical dissipation (i.e., a novel mechanism for vesicle migration).
Vesicles are closed membranes floating in an aqueous solution (see Fig. 1). These membranes act as a barrier that efficiently controls permeability. The vesicles mimic maybe the most primitive and mechanically flexible dividing interfaces between the inside and the outside of a cell. Generally, the fluid enclosed by the membrane is incompressible in order that the vesicle evolves at a constant volume. Moreover, the membrane exchanges no phospholipid molecules with the solution, its area remaining constant as time passes [64]. Helfrich [45] described very well the vesicle\'s bending energy in its equilibrium state, which is compatible with the constraints above, i.e. constant volume and area. Even if the model is relatively simple it generates various equilibrium profiles, such as, discocytes (resembling red blood cells), stomatocytes, as well as forms presenting higher topologies (such as n-genus torus) that have been also observed experimentally [46]. We identify works studying alignments of vesicle in shear flows [47], fluctuations out of equilibrium [48], lift forces [49, 50], migration of vesicle in the proximity of a substrate [51, 52] or in gravity fields [53] and also vesicle tumbling [54]. One may note several recent experiments dealing with vesicle migration [55-58].
Schematic view of a vesicle emphasizing its microscopic structure: a bilayer of phospholipidic molecules.
Considering the vesicle migration, we acknowledge that hydrodynamical dissipation in the neighboring fluid as well as inside the vesicle is present, and, in principle, between the two mono-layers which may glide with respect to each other. Furthermore, during motion on the substrate the dynamics of a vesicle may be restricted not only by the hydrodynamical flow but also by bonds breaking and restoring mechanisms that occur on the substrate (see [64]). It is obvious that the slowest mechanism limits the motion. Here we focus on a situation where hydrodynamics are the limiting factors and we give out dissipation associated with bonds on the substrate.
Let us imagine a vesicle that initially adheres on a flat surface. We then consider an adhesion gradient along the substrate. The vesicle then moves in the direction of increasing adhesion energy (see Fig. 2) - it is named haptotaxis (a motion induced by an adhesion gradient).
A highly permeable vesicle can be pulled into a fluid without opposing any resistance (and without modifying the inner area), whereas an impermeable one would be subjected to a drag force [64]. The assumption of local impermeability is legitimate. This entails that the fluid velocity at the membrane is equal that of the membrane itself [59].
Stationary vesicle profiles are depicted. The vesicle is moving from the left (smaller adhesion) to the right (stronger adhesion); a few discretization points are represented and the arrow allows following one of these at three successive times. One can observe here the rolling and sliding components of the vesicle’s motion.
On a vesicle\'s scale
If dissipation is dominated by bulk effects, as shown in [59], we are in the position to write down the basic governing equations for convective vesicles in a geometry depicted in Fig. 3, since we also know and it was proved the velocity field obeys Stokes equations [59].
Convective extracellular vesicles (EVs) geometry. A fluid layer of thickness
In an original atmospheric system, the non-even distribution of ascending water droplets is determined by the interplay between solar energy-induced thermal gradients, thermal diffusivity, friction, and gravity. Ultimately, the mathematics of this model shapes the umbrella-like or budding appearance of structures like cumulonimbus clouds. This model can better or uniquely describe those types of structural dynamics not explained under fractal, simple/linear and several other types of models.
Acknowledging that similar patterns occur in various biological spaces, we think that the same mathematical determinism can be ascribed. Thus, some histoarchitectural prototypic structures, like the capillary sprouting, embryologic organ, or even tumor buds of some types of cancer lesions might be in fact sculpted in that shape because gradients of molecular cues called morphogens can be deployed within the same manner water droplets can organize within nascent clouds.
Assuming that this organization also applies in biological systems, and that the EVs release can be considered among various processes organizing the budding tissue pattern, we think that the Lorenz model can govern their dynamics too. EVs would be particularly interesting as controllers of the tissue shape specification because they can include enzymatically active components (not found in conventional molecular morphogens), and thus might actively interact with the ECM fibers within their migration. Deployment of certain matrix degrading enzymes (MDEs) by EVs can modify this space while diffusing (event not produced by simple morphogens, attractive chemokines or repulsive semaphorins). This activity changes the topography of the ECM and creates spatial gradients directing the migration of subsequent EVs by haptotaxis - a mechanism better described for cell migration.
Let us consider the following thought biological experiment, equivalent to the B\\\'{enard experiment: a fluid layer of extracellular vesicles adherent on an ECM, in a haptotactic gradient. The fluid layer presents an unstable stratification of the potential density in a field of forces: the dense fluid is placed in front of the less dense one. We assume that in the basic state the layer of fluid of thickness d is subjected to a gradient of concentration
We examine the evolution of a concentration fluctuation
Two dissipative processes tend to maintain the fluid at rest:
friction (motion amortization through viscosity);
ECM degradation subsequent to MDE\'s activity allowing vesicle trespassing - which lowers the concentration of the ECM, thus diminishing the forward, or advancing force.
The instability cannot be developed unless the EV is accelerated enough to overcome the effect of these dissipative processes. The gradient of concentration
For a one component fluid, the mass, momentum and internal energy equations are the expressions (see the fractal - nonfractal transition method [8-22]):
where
and we use Einstein\'s summation convention (implicit sum over repeating indices). The stress tensor can be written
where
We start with the following assumptions:
the fluid is Newtonian; as a result the stress tensor is given by Eq. (83), where the viscous stress tensor is [8-22]
with coefficients
ECM degrading by MDEs from EVs is described by the Fourier equation
where
haptotactic energy expansion is linear
where we used the expression of the haptotactic energy
the fluid satisfies a state equation: consequently, its internal energy is (up to a constant factor)
where
in most liquids, thermal expansion is small. We choose everywhere a constant density, denoted by
With these approximations, the system of Eqs. (80) leads to the Boussinesq type system of equations
where
The first equation (87) represents the incompressibility condition for the fluid.
Convection occurs in the fluid layer when the forward, or advancing force, resulted from energy expansion, surpasses the viscous forces. We may define now a Rayleigh type number identical with the Eqs associated to fractal - nonfractal transition [61]
The density perturbation satisfies, according to Eq. (85)
On the other side, from the internal energy equation Eq. (79), it results
Replacing Eqs. (90) and (91) in Eq. (89), and taking into account Eq. (79), we get a biological Rayleigh number
where
Most of the time,
Within a biological context,
We choose as reference state the rest stationary state (
where
Integrating the second Eq. (93) with these boundary conditions, it results that, in the stationary reference state, the profile of the concentration in the vertical direction is linear
with
The characteristics of the system in this state are independent of the kinetic coefficients
As can be seen from Eqs. (96), the perturbations are functions of coordinate and time. Replacing Eqs. (96) in the evolution equations of the Boussinesq approximation Eqs. (87) and taking into account Eq. (94) and Eq. (95), we get, in the linear approximation, the following equations for the perturbations
where
Using the standard method from [8-22], it results the biological Lorentz system.
Some results are evident:
we build the first Lorenz model for extracellular vesicles migration;
in [50], and similar other references ([64] etc.), the EVs behavior, under shear flow close to a substrate, was proved to be quite similar to the one encountered in two dimensional simulations, so we are confident that the 2D assumptions captures the essential features of the 3D EVs;
different control parameter values for the Lorenz system can create shape distributions similar to the cordonal appearance of fingerprints (see Fig. 4, A), or complex skin tissue tiles like scale appendages in the amphibian covering (see Fig. 4, B);
the biological thought experiment equivalent to Bénard\'s experiment, involving a fluid layer of extracellular vesicles adherent to an extracellular matrix, in a haptotactic gradient can be
we analyze the problem of EVs migration in haptotaxis, though most of the reasoning applies to chemotaxis (migration of cells biased towards a gradient of diffusible MDEs) as well as to a variety of driving forces - all of which include the possibility to specify an active parameter value within the model;
the resulted system of equations exhibits complex behavior, hard to control, the two occurring convective rolls: either going in one direction, or in the opposite one - means patterning the EVs spreading.
Bénard-Rayleigh model patterns representative for biological instances: A) for fingerprint like distribution of skin cells, B) for fish or amphibian scales.
Considering the above, we can write the following conclusions :
We establish a relationship between the SL(2R) group and the canonic formalism. It particularly results that all invariant functions on the SL(2R) group will be functions on the hamiltonian and on the Gausssian;
We establish the statistical significations for coefficients of the hamiltonian by using Shannon\'s maximum informational entropy principle. Any statistical assumption is specified by particularly selecting the hamiltonian coefficients and the class of all these hypothesis by the transitivity manifolds of the group. In this manner, if the hamiltonian has energy significance, then through the transitivity manifolds, the motions of a representative point from the phase space on a surface of constant energy are in the same time on a surface of constant probability density (the ergodic hypothesis). Therefore, the class of the statistic hypothesis (which are characteristic to the Gaussians of the same average) is given by the ergodic hypothesis. In this way, we establish a fundamental relationship between energy and probability;
We prove that informational energy (in the sense of Onicescu) is a measure of the dispersion of a distribution. The class of the statistic hypothesis that are characteristic to the Gaussians of the same average is characterized by the constant value of the informational energy. In addition, it is equivalent to the ergodic hypothesis. For a constant value of the informational energy, we obtain uncertainty egalitarian relationships and, particularly, for the linear harmonic oscillator, we show that the informational energy is quantified;
Assuming that de Broglie\'s theory is materialized through a periodic field in a complex coordinate, we prove that it has a “hidden symmetry”, which is expressed by the homographical transformations group in three parameters. This group (also an achievement of SL(2R)) functions as a synchronization group both in phase and in amplitude, among the oscillators of the same ensemble. The simultaneous invariance related to two different achievements of SL(2R) implies (integrally through the invariant functions on the groups) an uncertainty relation in egalitarian form and the Stoler group of synchronization among oscillators from different ensembles (i.e., the second quantification when the creation and annihilation operators refer to a harmonic oscillator);
The synchronization group among the oscillators of the same ensemble admits three differentiable 1-forms and one differentiable 2-form which is absolutely invariant on the group. The existence of a parallel transport in Levi-Civita\'s sense, in which case the 2-form in Lobacevski\'s metric form in Poincare representation, implies through a variation principle, equations of Ernst type for the gravitational field of vacuum;
Complex measures in the study of certain physical systems dynamics need the use of a space-time endowed with a special topology, namely, the fractal space-time [6, 7] (see also [71] for details).
Bacteria, fungi (yeasts and molds), mycobacteria, prions, protozoa, and viruses are common pathogens infecting humans and animals. They typically exist within the host or in the environment. It has been observed that these microorganisms exhibit a notable difference in the natural survivability in the environment, as well as susceptibility to chemical and physical inactivation. For example, under ambient and dried conditions, human coronaviruses seem to lose their infectivity in a matter of several hours to several days [1], whereas endospores and prions may remain infectious for years to decades or even indefinitely [2, 3].
As more and more data have become available regarding the survivability and susceptibility of pathogens to microbicides, it has been observed that the pathogens seem to demonstrate an order of susceptibility to chemical and physical inactivation. E. H. Spaulding first proposed a classification system for the sterilization and disinfection of medical instruments based on the infection risk in 1939 [4]. On the basis of this classification, the concept of a hierarchy of pathogen susceptibility was proposed, in which microorganisms are placed into several groups and ranked from least susceptible to most susceptible. In this hierarchy concept, bacterial spores were ranked the least susceptible, followed by mycobacteria, non-enveloped viruses, fungi, vegetative bacteria, and enveloped viruses. The susceptibility hierarchy was also believed to be related to the biochemical and biophysical characteristics of a pathogen [5, 6].
This hierarchy concept has been slightly modified and expanded over the years. For example, prions were added and considered less susceptible to inactivation by microbicides than bacterial spores; small non-enveloped viruses were considered less susceptible than large non-enveloped viruses; and the order between mycobacteria and small non-enveloped viruses was sometimes reversed (Figure 1) [7, 8, 9, 10]. Additionally, it has been suggested that the hierarchy concept may be applied either “vertically” (i.e., ranking of susceptibility
Proposed hierarchy of susceptibility of pathogens to microbicides. Note: slightly different versions of the hierarchy concept have been proposed in the literature. Mycobacteria have been placed above small non-enveloped viruses, and molds have been placed above large non-enveloped viruses in certain versions. In some versions, the small and large non-enveloped viruses are combined; and yeasts and molds may be combined.
The hierarchy concept has been quite useful for enabling scientists to better understand the innate difference among various types of pathogens. In the case of newly emerged pathogens, especially, the hierarchy concept has helped stakeholders design and implement a disinfection strategy swiftly with a reasonable level of confidence. The concept also helps the contaminant control for food, pharmaceutical, and biopharmaceutical products, as it is impractical to test every possible contaminating pathogen, and a robust infectivity assay system may be lacking for certain pathogens (e.g., hepatitis E virus).
Despite its usefulness, the hierarchy concept should be interpreted with caution, as it may oversimply the differences and trending of pathogen susceptibilities. Further examination and refinement of the concept may be necessary; and several important questions should be answered. For example, how often do exceptions to the hierarchy occur and what are the underlying reasons? Could a trending be specific to a given type of chemistry? Is the hierarchy the same between susceptibility to both chemical and physical inactivation? Why do pathogens in the same group, or even the same family or genus, sometimes exhibit striking differences in susceptibility? Is there a way to identify and separate reliable/consistent trending versus blurred/variable trending? A deeper look at the efficacy data for various types of microbicidal actives, especially for non-enveloped viruses, may help stakeholders understand the scope, reliability, and limitation of the hierarchy concept so that it can be best utilized.
This chapter reviews the inactivation efficacy data from the literature against non-enveloped viruses for several commonly used types of chemistries, either in formulated or unformulated form, in an effort to generate a separate relative order of susceptibility among these non-enveloped viruses for each type of chemistry and to differentiate consistent versus variable trending. Physical inactivation approaches are not covered in this chapter, although a significant degree of variation also exists for physical treatments. It is not clear that the physical inactivation approaches, in general, are governed by the same hierarchy to susceptibility as is observed for chemical inactivation approaches [12].
Currently, there are a total of 21 families of viruses (including enveloped and non-enveloped) identified for humans [13], which represent only a small part of the entire paradigm of viruses in nature, whose host ranges extend from vertebrates to plants to bacteria. The most common families of non-enveloped viruses for humans and animals include
Family | Example virus | Abbreviation | Genus | Genome | Size (nm) |
---|---|---|---|---|---|
Adenovirus type 2 | AdV-2 | ds DNA | 70–90 | ||
Adenovirus type 5 | AdV-5 | ds DNA | 70–90 | ||
Adenovirus type 8 | AdV-8 | ds DNA | 70–90 | ||
Human astrovirus | HAstV | ss RNA | 28–35 | ||
Feline calicivirus | FCV | ss RNA | 28–40 | ||
Human norovirus | HuNoV | ss RNA | 28–40 | ||
Murine norovirus | MNV | ss RNA | 28–40 | ||
Tulane virus | TuV | ss RNA | 28–40 | ||
Porcine circovirus | PCV | ss DNA | ∼17 | ||
Hepatitis E virus | HEV | ss DNA | 32–34 | ||
Human papillomavirus | HPV | ds DNA | 50–60 | ||
Bovine parvovirus | BPV | ss DNA | 20–28 | ||
Canine parvovirus | CPV | ss DNA | 20–25 | ||
Human parvovirus B19 | B19V | ss DNA | 23–26 | ||
Minute virus of mice | MVM (MMV) | ss DNA | 20–25 | ||
Porcine parvovirus | PPV | ss DNA | 20–25 | ||
Bovine enterovirus | BEV | ss RNA | 30–32 | ||
Coxsackievirus | Cox | ss RNA | 30–32 | ||
Echovirus 11 | Echo11 | ss RNA | 30–32 | ||
Encephalomyocarditis virus | EMCV | ss RNA | 30–32 | ||
Enterovirus 71 | EV-71 | ss RNA | 30–32 | ||
Enterovirus D68 | EV-D68 | ss RNA | 30–32 | ||
Foot and mouth disease virus | FMDV | ss RNA | 30–32 | ||
Hepatitis A virus | HAV | ss RNA | 30–32 | ||
Poliovirus type 1 | PV1 | ss RNA | 30–32 | ||
Rhinovirus | RV | ss RNA | 30–32 | ||
Seneca Valley virus | SVV | ss RNA | 30–32 | ||
Bovine polyomavirus | BPyV | ds DNA | 40–50 | ||
Simian virus 40 | SV40 | ds DNA | 40–50 | ||
Bluetongue virus | BTV | ds RNA | 60–80 | ||
Reovirus type 3 | REO-3 | ds RNA | 60–80 | ||
Rotavirus | Rota | ds RNA | 60–80 |
Common families of human and animal non-enveloped viruses.
Among these, the
It is worth noting that viruses are typically classified taxonomically on the basis of virion properties (size, shape, envelope, physical, and chemical properties, etc.), genome organization, replication mechanism, antigenic properties, and biological properties [13, 14, 15]. The final classification is a combined consideration of these properties. However, the stability and susceptibility to inactivation of a virus may not relate to all of these properties and, as such, may not always align with the taxonomic classification system. For example, the susceptibility of a virus to surfactants may primarily be related to the envelope of the virion and not related to the genome structure or mode of replication.
The susceptibilities of non-enveloped viruses to chemicals have been found to be highly variable and somewhat hard to predict, since they do not always agree with the hierarchy concept. For example, according to the hierarchy concept as modified by Sattar [8], small non-enveloped viruses should be less susceptible than large non-enveloped viruses. Additionally, if there is a fixed hierarchy, all small non-enveloped viruses should either display similar levels of susceptibility or should demonstrate a definitive trend of relative susceptibility, regardless of the type of microbicide. Based on the literature, neither of these predictions appear to hold in every case. The relative order of susceptibility seems chemistry-dependent; and sometimes viruses within the same family or even genus have been found to exhibit unequivocal differences in their susceptibilities (reviewed in [16]). Any trending or hierarchy, therefore, must be reviewed in the context of the type of chemistry, and it should not be assumed that non-enveloped viruses within the same family or genus will always display similar susceptibilities to a given microbicide.
Viral inactivation may be achieved by chemical and/or physical methods. The subset of chemicals commonly used for inactivation of non-enveloped viruses includes alcohols, oxidizers, halogen compounds, quaternary ammonium compounds, phenolics, aldehydes, acids, and alkalines [17, 18, 19]. These differ with respect to efficacy, stability, toxicity, material or surface compatibility, cost, and sensitivity to organic soil load. Soil load is a term used to signify an organic matrix used to challenge the inactivating efficacy of a microbicide. It is intended to mimic secretions or excretions in which the virus would be released from an infected person or animal. Some chemistries (e.g., sodium hypochlorite, phenolics, and aldehydes) are mostly used for environmental or medical device disinfection. Other chemistries (e.g., ethanol) are more commonly used for hand hygiene, while some others (e.g., quaternary ammonium compounds) may be used for both environmental disinfection and skin antisepsis (Table 2).
Class | Chemical | Typical conc. | Usage | Mechanism of viral inactivation | Sensitivity to soil load |
---|---|---|---|---|---|
Alcohols | Ethanol | 50–95% | Disinfection; Antisepsis | Protein denaturation | + |
Isopropanol | 70–90% | Disinfection | Protein denaturation | + | |
Oxidizers | Sodium hypochlorite | 0.01–0.5% | Disinfection | Protein/genome damage | ++ |
Chlorine dioxide | 0.1–1 mg/L | Disinfection; Water treatment | Protein/genome damage | — | |
Hydrogen peroxide | 0.1–10% | Disinfection; Antisepsis | Lipid/protein/genome damage | + | |
Hypochlorous acid | 0.002–0.1% | Disinfection; Water treatment | Protein/genome damage | ++ | |
Peracetic acid | 0.01–1% | Disinfection; Sterilization | Protein denaturation | — | |
Povidone-iodine | 0.02–8% | Disinfection; Antisepsis | Protein/genome damage | ++ | |
Chlorohexidine | 0.02–0.2% | Antisepsis | Protein denaturation | + | |
QAC | BKC, DDAC, etc. | 0.01–0.2% | Disinfection | Lipid/protein damage | + |
Low pH | Acids | ≤ pH 4 | Sanitization; Biomanufacturing | Capsid/protein damage | — |
High pH | NaOH, etc. | ≥ pH 10 | Disinfection; Tissue processing | Capsid/genome damage | — |
Aldehydes | Glutaraldehyde | 0.02–2% | HLD; Sterilization | Crosslinking/protein & genome damage | — |
Formaldehyde | 0.1–5% | Disinfection/Preservation | Alkylating/protein & genome damage | — | |
OPA | 0.02–2% | HLD; Sterilization | Crosslinking/protein damage | — | |
Phenolics | Phenylphenol, etc. | 0.05–5% | Disinfection | Protein damage | — |
Common types of chemistries used for non-enveloped viral inactivation.
Abbreviations used: BKC, benzalkonium chloride; Conc, concentration; DDAC, didecyldimethylammonium chloride; HLD, high-level disinfection; NaOH, sodium hydroxide; OPA, ortho-phthaldehyde; QAC, quaternary ammonium compounds.
The virucidal efficacy of a product is not only determined by the type and concentration of the chemical, but is also heavily influenced by the formulation, pH, exposure (contact or dwell) time, organic soil load, temperature, and surface characteristics (as applicable), etc. [10, 20, 21, 22]. Given the differences between various testing methods, as well as the intrinsic variability of viral infectivity (titration) assays, a general conclusion on the efficacy of a particular type of active ingredient will be enhanced if the efficacy is derived from multiple sets of data and under various application conditions (such as the concentration of the microbicidal active(s), contact time, formulation matrix (as applicable), and organic soil load, etc.) Additionally, in order best to explore the relative ranking of susceptibility between viruses, or the lack thereof, efficacy data from side-by-side studies wherein the same test methodologies and conditions were used would be preferable. Care should be taken when comparing data from different studies, especially if the formulations, test methods, and test conditions were different.
Alcohols, primarily ethanol and isopropanol, are widely used for hand hygiene and environmental disinfection, and their efficacies against bacteria and viruses have been extensively studied [23, 24, 25]. Ethanol at a concentration of 70–90% and isopropanol at 70% have been broadly shown to be effective against enveloped viruses; however, their efficacies against non-enveloped viruses are much more variable.
The trending of the degree of susceptibility of non-enveloped viruses to ethanol and isopropanol is generally clearer and more consistent than it is for many other types of chemistries, thanks to the large amount of data in the literature. The relative ranking of susceptibility of non-enveloped viruses seems to differ between ethanol and isopropanol; and the ranking does not appear to align well with the classical virological taxonomy.
For ethanol, parvoviruses and the polyomavirus simian virus 40 have low susceptibility, while rotavirus (a reovirus) is susceptible (Table 3). Viruses in the
Virusa | Method | Soil/Matrixb | Log10 Reduction after | References | |||
---|---|---|---|---|---|---|---|
30 s | 1 min | 5 min | 10 min | ||||
PPV | Stainless steel | Erythrocytes + BSA | 0.3 | 0.6 | [26] | ||
MVM | Stainless steel | Erythrocytes + BSA | 0.3 | 0.7 | [26] | ||
HEV71 | Suspension test | Medium | < 1 | [27] | |||
HAV | Suspension test | Medium | 0.4 | [28] | |||
HAV | Suspension test | 20% fecal | 0.4 | [28] | |||
HuNoV | Suspension test | 20% stool | <0.5 | [29] | |||
TuV | Suspension test | Medium | <0.5 | [30] | |||
PV1 | Suspension test | 20% fecal | 0.3 | [28] | |||
PV1 | Suspension test | Medium | 0.4 | [31] | |||
PV1 | Glass | Medium | 2.3 | 1.0 | 5.0 | [31] | |
PV1 | Stainless steel | Erythrocytes + BSA | 2.1 | 1.8 | [26] | ||
PV1 | Suspension test | Medium | 4 | [28] | |||
FCV | Suspension test | Medium | 1.7 | 2.2 | [30] | ||
AdV-8 | Suspension test | Medium | 1.9 | [33] | |||
AdV-5 | Stainless steel | Erythrocytes + BSA | 2.4 | >4.1 | [26] | ||
AdV-5 | Stainless steel | Medium | ∼5 | [34] | |||
MNV | Suspension test | Medium | 5 | [30] | |||
Rotavirus | Suspension test | Medium | > 3.1 | [28] | |||
CPV | Stainless steel | Medium | 0.1 | [36] | |||
SV40 | Suspension test | Medium | <1 | [37] | |||
PV1 | Glass | Medium | 2.9 | 2.9 | 5.4 | [31] | |
TuV | Suspension test | Medium | <0.5 | [30] | |||
FCV | Suspension test | Medium | <0.5 | [30] | |||
HEV71 | Suspension test | Medium | <1 | [27] | |||
PV1 | Suspension test | medium | <1 | [37] | |||
PV1 | Glass | Medium | 1.2 | 1.3 | 1.0 | [31] | |
AdV-5 | Stainless steel | Medium | ∼1 | [34] | |||
AdV-8 | Suspension test | Medium | 2.0 | [33] | |||
MNV | Suspension test | Medium | 1.8 | 3.1 | [30] | ||
SV40 | Suspension test | Medium | >4 | [37] | |||
Rotavirus | Suspension test | Medium | > 4 | [42] |
Efficacy of alcohols against non-enveloped viruses.
See Table 1 for abbreviations used for viruses.
BSA, bovine serum albumin; medium, culture medium; RT, room temperature.
Entries in purple font indicate results from undiluted or diluted formulations with the indicated microbicidal active ingredients.
Interestingly, the above order of susceptibility does not appear to hold the same for isopropanol (Table 3). For example, the polyomavirus simian virus 40 is much more susceptible to isopropanol than many other non-enveloped viruses; and poliovirus appears to display a lower susceptibility, similar to that of hepatitis A virus and human enterovirus 71. Murine norovirus is still more susceptible than feline calicivirus to isopropanol, but not as susceptible as simian virus 40 or rotavirus. The apparent difference between adenovirus 5 and adenovirus 8 that has been observed for ethanol has not been observed for isopropanol.
An oxidizer or oxidizing agent is a chemical that has the ability to oxidize other molecules, i.e., to accept their electrons. Common oxidizing agents used for disinfection, sterilization, or antisepsis include hydrogen peroxide, peracetic acid, ozone, and halogen-containing compounds such as sodium hypochlorite (bleach), hypochlorous acid, povidone-iodine, chlorohexidine, and chlorine dioxide, etc. These compounds can react with and alter the proteins and nucleic acids of non-enveloped viruses and render them noninfectious. Oxidizers comprise a large group of chemicals, and the relative order of susceptibility of non-enveloped viruses to oxidizers seems to vary by specific type of active ingredient (Table 4).
Virusa | Method | Soil/Matrixb | Log10 Reduction after | References | |||
---|---|---|---|---|---|---|---|
≤ 1 min | 2 min | 5 min | 10 min | ||||
FCV | Suspension test | Medium | 3 | [29] | |||
FCV | Suspension test | 20% stool | 0.5 | [29] | |||
MNV | Suspension test | Medium | 3 | [29] | |||
MNV | Suspension test | 20% stool | 0.0 | [29] | |||
CPV | Stainless steel | 90% plasma | < 1 | [43] | |||
CPV | Stainless steel | 5% serum | 5 | [43] | |||
HAV | Stainless steel | 5% serum | 5 | [43] | |||
HAV | Stainless steel | 90% plasma | <1 | 5 | [43] | ||
HAV | Suspension test | PBS/20% fecal | 4 | [28] | |||
PV1 | Suspension test | PBS/20% fecal | 4 | [28] | |||
PPV | Stainless steel | Erythrocytes + BSA | 0.6 | 1.0 | [26] | ||
MVM | Stainless steel | Erythrocytes + BSA | 3.0 | 4.4 | [26] | ||
PV1 | Stainless steel | Erythrocytes + BSA | 2.8 | 4.5 | [26] | ||
AdV-5 | Stainless steel | Erythrocytes + BSA | 4 | [26] | |||
PV1 | Glass | Medium | 0.4 | 0.9 | [16] | ||
RV14 | Glass | Medium | >4.9 | [16] | |||
PPV | Stainless steel | Erythrocytes + BSA | 0.5 | [26] | |||
MVM | Stainless steel | Erythrocytes + BSA | 1.5 | [26] | |||
PV1 | Stainless steel | Erythrocytes + BSA | 3.9 | [26] | |||
AdV-5 | Stainless steel | Erythrocytes + BSA | 2.3 | [26] | |||
MNV | Suspension test | Medium | ∼3 | [52] | |||
HAV | Suspension test | Medium | ∼3 | [53] | |||
PV | Suspension test | Medium | >3 | [53] | |||
CPV | Stainless steel | BSA | 1.6 | [34] | |||
MVM | Stainless steel | BSA | 2.3-2.9 | [34] | |||
PPV | Stainless steel | BSA | 3.8-5.5 | [34] | |||
AdV-5 | Stainless steel | BSA | 4.9-5.8 | [34] |
Efficacy of oxidizers against non-enveloped viruses.
See Table 1 for abbreviations used for viruses.
BSA, bovine serum albumin; PBS, phosphate buffered saline; medium, culture medium; RT, room temperature.
Viral-inoculated lettuce was washed with PAA solution for a defined period of time.
Entries in purple font indicate results from undiluted original or diluted formulations with microbicidal active ingredients.
Parvoviruses are generally among the least susceptible viruses to various types of oxidizers, including sodium hypochlorite, hydrogen peroxide, and peracetic acid. However, for sodium hypochlorite, minute virus of mice appears to be more susceptible than porcine parvovirus and canine parvovirus. All picornaviruses appear to exhibit a similar degree of susceptibility to sodium hypochlorite; but within the family of
The trending for hydrogen peroxide seems more complex than that for sodium hypochlorite. For example, there seems a higher level of variability within the
For peracetic acid, hepatitis A virus also seems less susceptible than poliovirus. Both feline calicivirus and murine norovirus are susceptible to peracetic acid and so is adenovirus.
Quaternary ammonium compounds (QAC) are widely used as active ingredients for disinfectants. Among the advantages of QAC are good stability, dual function of disinfection and cleaning, surface activity, low toxicity, and lack of odor, etc. The potential limitation in the microbicidal efficacy and possible effect in promoting antimicrobial resistance of QAC have also been discussed in the literature [54, 55].
Quaternary ammonium compounds are generally efficacious on most vegetative bacteria and enveloped viruses. Their efficacies against non-enveloped viruses, however, are generally much weaker. Nevertheless, several non-enveloped viruses, such as rotavirus, rhinovirus, and coxsackievirus A11, have been shown to be susceptible to QAC. The susceptibility levels among the
Virusa | Method | Soil/matrixb | Log10 reduction after | References | |||
---|---|---|---|---|---|---|---|
30 s | 1 min | 10 min | 60 min | ||||
PPV | Stainless steel | Erythrocytes + BSA | 0.4 | [26] | |||
MVM | Stainless steel | Erythrocytes + BSA | 0.5 | [26] | |||
PV1 | Stainless steel | Erythrocytes + BSA | 0.5 | [26] | |||
AdV-5 | Stainless steel | Erythrocytes + BSA | 1.8 | [26] | |||
AdV-8 | Suspension test | Medium | 1.0-1.8 | [57] | |||
AdV-5 | Suspension test | Medium | 3.7-5.3 | [57] | |||
TuV | Suspension test | Medium | <0.5 | [30] | |||
PV1 | Suspension test | BSA/yeast extract | 0.0 | [58] | |||
AdV-25 | Suspension test | BSA/yeast extract | 0.3 | [58] | |||
Cox A11 | Suspension test | BSA/yeast extract | >5.1 | [58] | |||
FCV | Suspension test | Medium | <0.5 | [29] | |||
MNV | Suspension test | Medium | <0.5 | [29] | |||
Rhinovirus | Glass | Medium | >3.0 | >3.3 | [16] |
Efficacy of QAC against non-enveloped viruses.
See Table 1 for abbreviations used for viruses.
BSA, bovine serum albumin; medium, culture medium; QAC, quaternary ammonium compound.
Entries in purple font indicate results from original or diluted formulations with microbicidal active ingredients.
Acids and alkalines, either used alone or in combination with other active ingredients in formulated products, can be an effective means for viral inactivation. Acids may be used for disinfection, sanitization, textile or face mask pretreatment, or viral clearance during biopharmaceutical manufacturing. Alkalines may also be used for disinfection, sanitization, and viral clearance during biopharmaceutical manufacturing and can be effective against even the least susceptible of pathogens, the prions [58].
It has been widely reported that a low-pH treatment (typically at pH 4 and below) can effectively inactivate most enveloped viruses, although some enveloped viruses, such as bovine viral diarrhea virus, still exhibit a relatively low susceptibility to this treatment pH [22]. The range of susceptibilities of non-enveloped viruses to low pH seems quite scattered and often goes against the “conventional wisdom” that non-enveloped viruses are not susceptible to acidic pH (Table 6). For instance, in the family of
Virusa | Method | Soil/Matrixb | Log10 Reduction after | References | |||
---|---|---|---|---|---|---|---|
20 min | 30 min | 45 min | 1–2 hr | ||||
REO-3 | Suspension test | Medium | 1–3 | [59] | |||
PCV | Suspension test | Medium | >3 | [60] | |||
MVM | Suspension test | Medium | <1 | [61] | |||
MNV | Suspension test | Medium | <0.5 | [30] | |||
TuV | Suspension test | Medium | <0.5 | [30] | |||
PARV4 | Suspension test | Medium | 2–3 | [61] | |||
B19V | Suspension test | Medium | > 4 | [61] | |||
FCV | Suspension test | Medium | 6.3 | [30] | |||
FCV | Suspension test | Medium | >5 | [62] | |||
PV | Suspension test | Medium | <1 | [63] | |||
PV | Suspension test | Medium | <1 | [64] | |||
HAV | Suspension test | Medium | <1 | [64] | |||
MNV | Suspension test | Medium | <0.5 | [30] | |||
TuV | Suspension test | Medium | <0.5 | [30] | |||
Cox A9 | Suspension test | Medium | <1 | [65] | |||
FCV | Suspension test | Medium | ∼3 | [30] | |||
FCV | Suspension test | Medium | ∼4.7 | [62] | |||
RV | Suspension test | Medium | >3 | [65] | |||
FMDV | Suspension test | Medium | >3 | [65] | |||
MVM | Suspension test | Medium | <1 | [66] | |||
EV71 | Suspension test | Medium | <1 | [67] | |||
EV-D68 | Suspension test | Medium | ∼4–5 | <5 | [67] | ||
B19V | Suspension test | Medium | [66] |
Efficacy of low pH against non-enveloped viruses.
The
Feline calicivirus and murine norovirus in the family
Viruses, both enveloped and non-enveloped, are generally susceptible to high pH. At an environment of pH 12 or above, most if not all non-enveloped viruses would be inactivated, with extent depending both on temperature and contact time. Reovirus, simian virus 40, hepatitis A virus, canine parvovirus, poliovirus, murine norovirus, and Tulane virus seem to be less susceptible than minute virus of mice, feline calicivirus, adenovirus, rotavirus, and foot-and-mouth disease virus. It may be worth noting that the order of susceptibility to high pH seems to be in discord with the hierarchy concept by the greatest degree: in this case, an enveloped virus, bovine viral diarrhea virus, seems to be less susceptible than most, if not all, non-enveloped viruses [22]; parvoviruses are not necessarily less susceptible than many other non-enveloped viruses; and the size of the viral particle does not seem to matter much with regard to the degree of susceptibility (Table 7).
Virusa | Method | Soil/Matrixb | Log10 Reduction after | References | |||
---|---|---|---|---|---|---|---|
≤ 1 min | 10 min | 30 min | 1 hr | ||||
MNV | Suspension test | Medium | ∼2 | [30] | |||
TuV | Suspension test | Medium | ∼2.2 | [30] | |||
FCV | Suspension test | Medium | >5.5 | [30] | |||
REO-3 | Suspension test | Medium | 3 | [68] | |||
Cox B | Suspension test | Medium | 5 | [69] | |||
Echo 11 | Suspension test | Medium | 6 | [68] | |||
BVDV | Suspension test | Medium | 2.5 | [70] | |||
HAV | Suspension test | Medium | 2.7 | [59] | |||
SV40 | Suspension test | Medium | 3.9 | [70] | |||
HAV | Stainless steel | 5% serum | 3.0 | [43] | |||
HAV | Stainless steel | 90% plasma | 3.6 | [43] | |||
CPV | Stainless steel | 5% serum | 3.5 | [43] | |||
CPV | Stainless steel | 90% plasma | 5.2 | [43] | |||
MVM | Suspension test | Medium | >4.7 | [71] | |||
MVM | Suspension test | Medium | >4 | [66] | |||
CPV | Suspension test | Medium | 5.6 | [70] | |||
PV | Suspension test | Medium | 5.9 | [70] | |||
AdV-2 | Suspension test | Medium | >6.9 | [70] | |||
AdV-5 | Suspension test | Medium | >6 | [72] | |||
HAV | suspension test | Medium | 2.4 | [59] | |||
PV | suspension test | Medium | 4.1 | [63] | |||
Avian Reo | Suspension test | Medium | 4 | [73] | |||
PV | Suspension test | Medium | 5.1 | [73] | |||
Bovine Rota | Suspension test | Medium | >6 | [73] |
Efficacy of high pH against non-enveloped viruses.
Entries in purple font indicate results from undiluted or diluted formulations with microbicidal active ingredients.
Aldehydes, such as glutaraldehyde, formaldehyde, and
Virusa | Method | Soil/Matrixb | Log10 Reduction after | References | |||
---|---|---|---|---|---|---|---|
5 min | 10 min | 30 min | 60 min | ||||
HAV | Suspension test | Medium | 3.0 | [75] | |||
PPV | Stainless steel | BSA | 1.7–2.8 | [34] | |||
MVM | Stainless steel | BSA | 2.5–3.3 | [34] | |||
PV1 | Suspension test | Medium | >3 | [76] | |||
AdV-5 | Stainless steel | BSA | 4.9–6.3 | [34] | |||
PPV | Stainless steel | Erythrocytes + BSA | 3.6 | [26] | |||
MVM | Stainless steel | Erythrocytes + BSA | >4.4 | [26] | |||
AdV-5 | Suspension test | Medium | >5.0 | [77] | |||
Ortho-phthaldehyde, 0.55% | |||||||
PPV | Stainless steel | Erythrocytes + BSA | 3.6 | [26] | |||
MVM | Stainless steel | Erythrocytes + BSA | >4. | [26] |
Efficacy of aldehydes against non-enveloped viruses.
See Table 1 for abbreviations used for viruses.
BSA, bovine serum albumin; medium, culture medium; RT, room temperature.
Entries in purple font indicate results from original or diluted formulations with microbicidal active ingredients.
In the simplified hierarchy of susceptibility of pathogens to microbicides concept, small non-enveloped viruses are considered less susceptible than large non-enveloped viruses, and both groups of non-enveloped viruses are believed to be less susceptible than enveloped viruses. The hierarchy concept also assumes that the ranking applies to all types of microbicidal actives. Additionally, the hierarchy concept can generally lead to common notions that viruses that share similar virological properties (e.g., same family or genus of virus) may be expected to display similar degrees of susceptibility and that the smaller a virus is, the less susceptible it will be to microbicides in general.
These generalizations are correct, to a degree. For example, most enveloped viruses are indeed more susceptible than non-enveloped viruses to chemical inactivation. It should be noted though that exceptions to the hierarchy concept do exist, e.g., especially in the case of viral susceptibility to acids and alkalines [22], and exceptions are not uncommon for certain other chemistries. The hierarchy concept was never applied specifically to physical inactivation approaches, nor should it be. The evidence for heat inactivation, UV inactivation, and gamma irradiation indicates differing rankings of susceptibility to these modalities. Envelope status and particle size do not, in each case, relate to susceptibility for inactivation by these physical approaches [22, 78, 79, 80].
The validity of the hierarchy concept
The accuracy and usefulness of a hierarchy concept can be improved if the model is broken into separate chemistries for non-enveloped viruses, since many viruses do exhibit a reliable and consistent trend of susceptibility for a specific type of chemical. Table 9 and Figure 2 provide a summary of the relative order of susceptibility for selected non-enveloped viruses under specific types of chemistry.
Chemical | Lower susceptibility | Medium susceptibility | Higher susceptibility |
---|---|---|---|
Ethanol | Animal parvovirus | Poliovirus | Murine norovirus |
Simian virus 40 | Foot and mouth disease virus | Rhinovirus | |
Hepatitis A virus | Human norovirus | Adenovirus 5 | |
Enterovirus 71 | Feline calicivirus | Rotavirus | |
Adenovirus 2, 8 | |||
Isopropanol | Animal parvovirus | Adenovirus 5, 8 | Simian virus 40 |
Hepatitis A virus | Murine norovirus | Rotavirus | |
Enterovirus 71 | |||
Poliovirus | |||
Feline calicivirus | |||
NaOCl | Porcine parvovirus | Minute virus of mice | Feline calicivirus |
Hepatitis A virus | Hepatitis A virus | Adenovirus | |
Poliovirus | Rotavirus | ||
Enterovirus 71 | |||
Murine norovirus | |||
H2O2 | Animal parvovirus | Poliovirus | Rhinovirus |
Hepatitis A virus | Murine norovirus | Feline calicivirus | |
Adenovirus | Rotavirus | ||
PAA | Animal parvovirus | Poliovirus | Feline calicivirus |
Hepatitis A virus | Murine norovirus | ||
Adenovirus | |||
QAC | Animal parvovirus | Feline calicivirus | Rotavirus |
Poliovirus | Murine norovirus | Rhinovirus | |
Adenovirus 8, 25 | Adenovirus 5 | Coxsackievirus A11 | |
Low pH | Minute virus of mice | Human parvovirus 4 | Feline calicivirus |
Hepatitis A virus | Rhinovirus | ||
Poliovirus | Foot and mouth disease virus | ||
Enterovirus 71 | Enterovirus EV-D68 | ||
Coxsackievirus A9 | Human parvovirus B19 | ||
Murine norovirus | |||
Rotavirus | |||
Reovirus | |||
High pH | Bovine viral diarrhea virus | Reovirus | Murine minute virus |
Simian virus 40 | Feline calicivirus | ||
Hepatitis A virus | Adenovirus | ||
Canine parvovirus | Rotavirus | ||
Poliovirus | Foot and mouth disease virus | ||
Murine norovirus | |||
Tulane virus | |||
Aldehydes | Porcine parvovirus | Minute virus of mice | Poliovirus |
Hepatitis A virus | |||
Feline calicivirus | |||
Adenovirus | |||
Reovirus | |||
Rotavirus |
Relative order of susceptibility of non-enveloped viruses to chemical inactivation.
Abbreviations used: H2O2, hydrogen peroxide; NaOCl, sodium hypochlorite; PAA, peracetic acid; QAC, quaternary ammonium compound.
Relative order of susceptibility of non-enveloped viruses per microbicidal chemistry. Note: various types of adenoviruses exhibit different degrees of susceptibility to ethanol and quaternary ammonium compounds.
The Spaulding concept of the hierarchy of susceptibility of pathogens to microbicidal inactivation, along with its modifications, has been widely influential. Multiple industries as well as regulatory agencies have adopted or referenced this concept to various degrees [9, 10, 81, 82]. The concept does provide a good tool for understanding the innate differences and trending of susceptibility among various types of pathogens. For the most part, the hierarchy is insightful and valuable. It is particularly helpful when a pathogen is newly emerged, and limited or no knowledge is yet available regarding its level of susceptibility to microbicides [83, 84]. In fact, the United States Environmental Protection Agency (U.S. EPA) and Centers for Disease Control and Prevention (U.S. CDC) use the hierarchy concept as the basis of the Emerging Viral Pathogen Guidance for Antimicrobial Pesticides and public hygiene [10, 82, 85, 86] specifically to deal with just such a possibility.
It should be cautioned, however, that the hierarchy concept is largely oversimplified and by no means perfect [87]. For viruses, although enveloped viruses are usually more susceptible than non-enveloped viruses, certain enveloped viruses such as bovine viral diarrhea virus can be less susceptible than some non-enveloped viruses (e.g., feline calicivirus) under certain chemistries (e.g., low pH and high pH).
The accuracy and applicability of the hierarchy concept are more complex and limited among non-enveloped viruses. The trending is highly dependent on the type of chemistry; and the size of the virion is not always a primary determinant of viral susceptibility among non-enveloped viruses. If a clearer and more consistent trending can be identified among non-enveloped viruses, albeit only specific to a given type of chemistry, the knowledge should be useful.
To generalize an order of susceptibility, for a specific chemistry, data from side-by-side studies wherein viruses are evaluated concurrently by the same test method and under the same conditions should, ideally, be used. When results from different studies are used, caution should be taken to exclude conditional or case-specific differences that result from the test methodology and/or condition. For instance, a surface (carrier) test may give different log10 reduction results than a suspension test of the same microbicide or formulation under certain situations [88]. For example, the data of Kindermann et al. [47] and Tyler et al. [31] indicate that sodium hypochlorite causes a higher log10 reduction value (LRV) when tested in a suspension test than in a surface test. On the other hand, glutaraldehyde has been found to cause similar log reduction in either methodology, while hydrogen peroxide causes higher LRV in the surface test, which is thought to be likely related to the consumption of hydrogen peroxide by the protein in the virus-suspending solution [31].
The organic soil load in which the challenge virus is suspended prior to inoculation can also impact the viral inactivation outcome, especially for oxidizers, alcohols, and QAC. It would be inaccurate or even misleading if a result from a light organic load (e.g., 5% animal serum or phosphate-buffered saline) were to be directly compared with a test that used a heavier organic load (e.g., 90% blood or 20% fecal suspension). Tung
Other testing conditions may also affect the reduction results. For instance, a higher contact temperature may work in the favor of the virucide under investigation, which may result in a higher log reduction. Nemoto et al. [56] reported that a 0.125% glutaraldehyde solution completely inactivated rotavirus after 10 min under ambient temperature, but not when evaluated on ice. The pH and other components in the product formulation could also affect the viral reduction outcome, presumably by activating the chemical and/or by a synergistic or additive effect between the pH and the active chemical [22, 39, 89]. The efficacy of formulated versus non-formulated microbicides may differ even within the same type and concentration of active(s). For example, formulated QAC and ethanol products have been reported to exhibit strong activities against certain non-enveloped viruses albeit the efficacy may be weaker for non-formulated solutions [45, 54, 90, 91]. Therefore, the formulation of the microbicidal active must be considered. The viral stock (i.e., inoculum) preparation method and the challenge viral titer may also affect the reported viral reduction efficacy. For example, purified virus may be more susceptible than crude virus preparations [49]; viral clumps can make the virus less susceptible [92]; and a higher viral challenge titer could make the chemical harder to achieve an expected log10 reduction. Sometimes, viruses propagated in different host cell types may behave differently. It would therefore be ideal if all studies could use a standardized viral preparation and infectivity assay protocol. This is, of course, practically challenging. Last, but not least, the method for preparing the microbicide and the verification of the active concentration might also differ from lab to lab, thus potentially influencing the efficacy results obtained.
Despite these practically hard-to-avoid differences in test methodology and conditions, some generalizations on the pattern of susceptibility among non-enveloped viruses can still be made with confidence. For instance, it is quite apparent that the
The family
Different types of adenoviruses seem to exhibit varying degrees of susceptibility to ethanol and QAC. For example, adenovirus type 5 appears to be notably more susceptible to ethanol than are adenovirus types 2 and 8. In general, however, adenoviruses are more susceptible than many other non-enveloped viruses. Considering that adenovirus type 5 is listed as one of the allowable challenge viruses for a generic or “broad-spectrum” virucidal efficacy claim (i.e., a product that is effective for adenovirus type 5 may be considered effective against all viruses) [97, 98], this practice may not represent a challenge and lead to an insufficient safety margin, which is not supported by the published data.
Parvoviruses are among the smallest of non-enveloped viruses. The animal parvoviruses (e.g., minute virus of mice, porcine parvovirus, bovine parvovirus, canine parvovirus, etc.) are considered to exhibit very low susceptibility to chemical inactivation [99] and are commonly used as a worst-case model for viral inactivation studies. This literature review generally supports this notion, although it should be noted that the animal parvoviruses do not appear to represent a worst-case challenge for high-pH inactivation, and porcine parvovirus seems less susceptible than minute virus of mice at times. Additionally, human parvovirus B19 seems especially susceptible to acid treatment [100].
It has been observed that the particle size of a virus is not an exclusive or even a primary determinant of susceptibility to microbicides for non-enveloped viruses, albeit this characteristic may play a role. There are numerous reports demonstrating that larger non-enveloped viruses, such as adenoviruses and reoviruses, are less susceptible than some of the smaller non-enveloped viruses for certain chemistries. Interestingly though, rotavirus, a large non-enveloped virus, indeed seems to be the most susceptible among non-enveloped viruses, except to low pH.
The mechanisms underlying the large variation in susceptibility among non-enveloped viruses and the chemistry dependency are not always clear, but they could presumably be related to the physicochemical properties of the virus as well as the mechanisms of action of the chemical inactivants. For alcohols, for instance, it has been proposed that the hydrophobicity or hydrophilicity of the viral particles is an important determinant of susceptibility [101]. Poliovirus, which is hydrophilic, is more susceptible to ethanol than it is to isopropyl alcohol. This is attributed to the fact that ethanol is more hydrophilic than isopropanol. In comparison, the hydrophobic simian virus 40 is susceptible to isopropanol but not to ethanol [101]. Enterovirus 71 (EV71) and enterovirus EV-D68 (EV-D68) are both enteroviruses in the family
A review of the relative order of susceptibility for non-enveloped viruses under each chemistry reveals that the order for some chemicals (e.g. aldehydes) seems to fit the traditional hierarchy concept well (e.g., parvoviruses are less susceptible than larger viruses); but the order for some other chemistries (e.g., low pH) does not seem to agree with the concept as well.
The variability in viral susceptibility to physical treatments is not covered in this chapter; however, a marked degree of variation also exists for physical treatments, both within non-enveloped viruses and between enveloped and non-enveloped viruses [12, 16, 21, 49]. A comparison of the order of susceptibility of viruses to chemical versus physical treatments and an exploration of the underlying mechanisms would be interesting and revealing.
This chapter reviewed the literature on chemical inactivation of non-enveloped viruses, with an emphasis on the relative difference and trending of susceptibility among some relevant (from a public health perspective) non-enveloped viruses under each type of chemistry. The traditional concept of a hierarchy of susceptibility to microbicides provides a useful tool in understanding and predicting the susceptibility of a pathogen; however, the concept tends to be oversimplified. The order of susceptibility among non-enveloped viruses depends on the type of chemistry, and there is no universal order that holds true for all types of chemistries. Picornaviruses and caliciviruses exhibit a particularly high degree of intrafamily variation, and the order may even be reversed between viruses, depending on the chemistry. Additionally, larger non-enveloped viruses are not always more susceptible than some of the smaller non-enveloped viruses. It may be inappropriate to consider adenovirus type 5 as a worst-case non-enveloped virus; and even the animal parvoviruses, universally considered among the least susceptible to chemical inactivation, do not actually represent the least susceptible virus type for certain chemistries.
The author thanks Drs. Raymond Nims and M. Khalid Ijaz for the critical review of the manuscript and discussion.
The author declares no conflict of interest.
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',metaTitle:"Publication Agreement - Chapters",metaDescription:"IN TECH aims to guarantee that original material is published while at the same time giving significant freedom to our authors. For that matter, we uphold a flexible copyright policy meaning that there is no transfer of copyright to the publisher and authors retain exclusive copyright to their work.\n\nWhen submitting a manuscript the Corresponding Author is required to accept the terms and conditions set forth in our Publication Agreement as follows:",metaKeywords:null,canonicalURL:"/page/publication-agreement-chapters",contentRaw:'[{"type":"htmlEditorComponent","content":"The Corresponding Author (acting on behalf of all Authors) and INTECHOPEN LIMITED, incorporated and registered in England and Wales with company number 11086078 and a registered office at 5 Princes Gate Court, London, United Kingdom, SW7 2QJ conclude the following Agreement regarding the publication of a Book Chapter:
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The Corresponding Author (acting on behalf of all Authors) and INTECHOPEN LIMITED, incorporated and registered in England and Wales with company number 11086078 and a registered office at 5 Princes Gate Court, London, United Kingdom, SW7 2QJ conclude the following Agreement regarding the publication of a Book Chapter:
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\n\n7.3 Entire Agreement: This Publication Agreement constitutes the entire agreement between the parties in relation to its subject matter. It replaces and extinguishes all prior agreements, draft agreements, arrangements, collateral warranties, collateral contracts, statements, assurances, representations and undertakings of any nature made by or on behalf of the parties, whether oral or written, in relation to that subject matter. Each party acknowledges that in entering into this Publication Agreement it has not relied upon any oral or written statements, collateral or other warranties, assurances, representations or undertakings which were made by or on behalf of the other party in relation to the subject matter of this Publication Agreement at any time before its signature (together "Pre-Contractual Statements"), other than those which are set out in this Publication Agreement. Each party hereby waives all rights and remedies which might otherwise be available to it in relation to such Pre-Contractual Statements. Nothing in this clause shall exclude or restrict the liability of either party arising out of its pre-contract fraudulent misrepresentation or fraudulent concealment.
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\n\nLast updated: 2020-11-27
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It is an acute exaggerated clinical manifestation of thyrotoxic state. The exact incidence is unknown. It occurs in 1–2% of patients admitted for thyrotoxicosis. It has a mortality of 10–20%. This chapter would help us to understand its clinical manifestations, pathophysiology, and effective treatment. Terminal learning objective would be to diagnose impending storm early and start prompt treatment in day-to-day practice. The chapter would cover pathophysiology including triggers, clinical features including various diagnostic criteria, diagnosis, and treatment of thyroid storm. Indications of surgical treatment in storm will be discussed.",book:{id:"9077",slug:"goiter-causes-and-treatment",title:"Goiter",fullTitle:"Goiter - Causes and Treatment"},signatures:"Rahul Pandey, Sanjeev Kumar and Narendra Kotwal",authors:[{id:"309356",title:"Dr.",name:"Rahul",middleName:null,surname:"Pandey",slug:"rahul-pandey",fullName:"Rahul Pandey"},{id:"310903",title:"Dr.",name:"Sanjeev",middleName:null,surname:"Kumar",slug:"sanjeev-kumar",fullName:"Sanjeev Kumar"},{id:"310904",title:"Dr.",name:"Narendra",middleName:null,surname:"Kotwal",slug:"narendra-kotwal",fullName:"Narendra Kotwal"}]},{id:"70705",title:"Multinodular Goiter",slug:"multinodular-goiter",totalDownloads:963,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Multinodular goiter (MNG) is the most common disorder of the thyroid gland. It is highly endemic in iodine-deficient areas; MNG can be seen in almost all individuals with severe iodine-deficient areas. It starts as a diffuse enlargement of the thyroid gland and ends in a nodular enlarged thyroid. Though MNG can be sporadic, there is a strong correlation between occurrence of MNG and iodine deficiency. The characteristic feature of MNG is its functional and structural heterogeneity. The MNG usually presents as neck swelling; rarely it may produce pressure symptoms, i.e., dyspnea, hoarseness of voice, and dysphagia. It can also present with symptoms of hyperthyroidism particularly in long-standing goiter. Imaging particularly ultrasound is very useful to define characteristic of MNG and surrounding structure. The incidence of malignancy in MNG is 4–14%, and risk factors are family history of thyroid carcinoma, history of neck radiation, prior surgery, and presence of cervical lymphadenopathies. Management of MNG can be done by drugs, surgery, and radioiodine (I-131) depending on results of diagnostic evaluation and associated complications.",book:{id:"9077",slug:"goiter-causes-and-treatment",title:"Goiter",fullTitle:"Goiter - Causes and Treatment"},signatures:"Sanjay Saran",authors:[{id:"242737",title:"Dr.",name:"Sanjay",middleName:null,surname:"Saran",slug:"sanjay-saran",fullName:"Sanjay Saran"}]},{id:"61473",title:"Nuclear Medicine in the Assessment of Thyrotoxicosis Associated with Increased Thyroid Function and Radioiodine 131 Ablative Therapies",slug:"nuclear-medicine-in-the-assessment-of-thyrotoxicosis-associated-with-increased-thyroid-function-and-",totalDownloads:1463,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Nuclear medicine is directly involved in both the diagnosis and treatment of benign thyroid disease. Thyroid scintigraphy (most commonly with technetium-99 m pertechnetate) should be used as the imaging modality of choice for assessment of thyrotoxicosis, since it demonstrates the functional state of the thyroid gland. An adequate understanding of the pathophysiological mechanisms and characteristics of the patient is essential, as well as the different treatments of thyroid disorders that present with hyperthyroidism (Graves’ disease, toxic multinodular goiter, and toxic adenoma-Plummer’s disease). Therapeutic modalities include antithyroid drugs, radioiodine and surgery. Antithyroid drugs are the first line of therapy and regarding the use of radioiodine, current recommendations consider it a safe and effective therapeutic alternative in hyperthyroidism. Finally, we highlight the existence of some special situations (children, pregnancy, thyroid eye disease, chronic renal failure and dialysis patients) and the importance of radiation protection measures to the patient, the public and professionals.",book:{id:"6791",slug:"thyroid-disorders",title:"Thyroid Disorders",fullTitle:"Thyroid Disorders"},signatures:"Elena Espinosa Muñoz",authors:[{id:"241332",title:"M.Sc.",name:"Elena",middleName:null,surname:"Espinosa Muñoz",slug:"elena-espinosa-munoz",fullName:"Elena Espinosa Muñoz"}]},{id:"71040",title:"Hyperthyroidism",slug:"hyperthyroidism",totalDownloads:918,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Excess level of thyroid hormones in blood is thyrotoxicosis, which is responsible for clinical syndrome of hypermetabolism, sympathetic hyperactivity. Hyperthyroidism is the term used to denote the overproduction of thyroid hormones from the thyroid gland. Hyperthyroidism is possible with hyperactive thyroid gland due to multi/solitary nodular thyroid disease or Grave’s disease. Thyrotoxicosis associated with thyroiditis is not hyperthyroidism. Treatment of hyperthyroidism is with anti-thyroid drugs (ATT), radio-active iodine ablation (RAI), or thyroid surgery; whereas, treatment of thyroiditis is symptomatic.",book:{id:"9077",slug:"goiter-causes-and-treatment",title:"Goiter",fullTitle:"Goiter - Causes and Treatment"},signatures:"Rushikesh Maheshwari",authors:[{id:"300029",title:"Dr.",name:"Rushikesh",middleName:null,surname:"Maheshwari",slug:"rushikesh-maheshwari",fullName:"Rushikesh Maheshwari"}]},{id:"61460",title:"Thyroid Cancer: Diagnosis, Treatment and Follow-Up",slug:"thyroid-cancer-diagnosis-treatment-and-follow-up",totalDownloads:1552,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Thyroid cancer is the most common malignancy of the endocrine system and it is usually presented as nodular goiter, the last being extremely a common clinical and ultrasound finding. The widespread use of ultrasonography during the last decades has resulted in a dramatic increase in the prevalence of clinically inapparent thyroid nodules, which only in 5.0–10.0% harbor thyroid carcinoma. The goal of the initial sonographic assessment of thyroid nodules is to distinguish benign nodules that could be managed conservatively from those with suspicious or malignant features requiring further management, including fine needle aspiration biopsy (FNAB), some axillary molecular techniques and thyroid surgery. Since over 90% of malignant thyroid nodules are differentiated thyroid carcinomas (DTCs) with good prognosis, it is necessary to establish strict criteria for diagnosis, treatment and follow-up in order to minimize the potential harm of over-treatment of low-risk patients and to provide adequate therapy to patients at high risk. 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He has published seven patents in the Spanish Patent and Trademark Office. He has been a supervisor on 8 Ph.D. theses (11 more are under supervision), and 130 master theses. He is the founder of The IEEE IWOBI conference series and the president of its Steering Committee, as well as the founder of both the InnoEducaTIC and APPIS conference series. He is an evaluator of project proposals for the European Union (H2020), Medical Research Council (MRC, UK), Spanish Government (ANECA, Spain), Research National Agency (ANR, France), DAAD (Germany), Argentinian Government, and the Colombian Institutions. He has been a reviewer in different indexed international journals (<70) and conferences (<250) since 2001. He has been a member of the IASTED Technical Committee on Image Processing from 2007 and a member of the IASTED Technical Committee on Artificial Intelligence and Expert Systems from 2011. \n\nHe has held the general chair position for the following: ACM-APPIS (2020, 2021), IEEE-IWOBI (2019, 2020 and 2020), A PPIS (2018, 2019), IEEE-IWOBI (2014, 2015, 2017, 2018), InnoEducaTIC (2014, 2017), IEEE-INES (2013), NoLISP (2011), JRBP (2012), and IEEE-ICCST (2005)\n\nHe is an associate editor of the Computational Intelligence and Neuroscience Journal (Hindawi – Q2 JCR-ISI). He was vice dean from 2004 to 2010 in the Higher Technical School of Telecommunication Engineers at ULPGC and the vice dean of Graduate and Postgraduate Studies from March 2013 to November 2017. 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He has (co)authored more than 150 publications in indexed journals, international conferences and book chapters, 1 book (in Greek), 3 edited books, and 5 journal special issues. His publications have more than 2100 citations with h-index 27 (GoogleScholar). His research interests include computer/machine vision, machine learning, pattern recognition, computational intelligence. \nDr. Papakostas served as a reviewer in numerous journals, as a program\ncommittee member in international conferences and he is a member of the IAENG, MIR Labs, EUCogIII, INSTICC and the Technical Chamber of Greece (TEE).",institutionString:null,institution:{name:"International Hellenic University",institutionURL:null,country:{name:"Greece"}}},editorTwo:null,editorThree:null},{id:"25",title:"Evolutionary Computation",coverUrl:"https://cdn.intechopen.com/series_topics/covers/25.jpg",isOpenForSubmission:!0,annualVolume:11421,editor:{id:"136112",title:"Dr.",name:"Sebastian",middleName:null,surname:"Ventura Soto",slug:"sebastian-ventura-soto",fullName:"Sebastian Ventura Soto",profilePictureURL:"https://mts.intechopen.com/storage/users/136112/images/system/136112.png",biography:"Sebastian Ventura is a Spanish researcher, a full professor with the Department of Computer Science and Numerical Analysis, University of Córdoba. 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In the last five years, he has published more than 60 papers in international journals indexed in the JCR (around 70% of them belonging to first quartile journals) and he has edited some Springer books “Supervised Descriptive Pattern Mining” (2018), “Multiple Instance Learning - Foundations and Algorithms” (2016), and “Pattern Mining with Evolutionary Algorithms” (2016). He has also been involved in more than 20 research projects supported by the Spanish and Andalusian governments and the European Union. He currently belongs to the editorial board of PeerJ Computer Science, Information Fusion and Engineering Applications of Artificial Intelligence journals, being also associate editor of Applied Computational Intelligence and Soft Computing and IEEE Transactions on Cybernetics. Finally, he is editor-in-chief of Progress in Artificial Intelligence. 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(Eng.) in Telematics from the Universidad de Colima, Mexico. He obtained both his M.Sc. and Ph.D. from the University of Liverpool, England, in the field of Intelligent Systems. He is a full professor at the Universidad Autonoma de Queretaro, Mexico, and a member of the National System of Researchers (SNI) since 2009. Dr. Aceves Fernandez has published more than 80 research papers as well as a number of book chapters and congress papers. He has contributed in more than 20 funded research projects, both academic and industrial, in the area of artificial intelligence, ranging from environmental, biomedical, automotive, aviation, consumer, and robotics to other applications. He is also a honorary president at the National Association of Embedded Systems (AMESE), a senior member of the IEEE, and a board member of many institutions. 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He is currently a principal researcher in data analytics and optimisation at TECNALIA (Spain), a visiting fellow at the Basque Center for Applied Mathematics (BCAM) and a part-time lecturer at the University of the Basque Country (UPV/EHU). His research interests gravitate on the use of descriptive, prescriptive and predictive algorithms for data mining and optimization in a diverse range of application fields such as Energy, Transport, Telecommunications, Health and Industry, among others. In these fields he has published more than 240 articles, co-supervised 8 Ph.D. theses, edited 6 books, coauthored 7 patents and participated/led more than 40 research projects. 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He is currently a full professor in\nthe Department of Automation and Applied Informatics at the\nsame university. Dr. Voloşencu is the author of ten books, seven\nbook chapters, and more than 160 papers published in journals\nand conference proceedings. He has also edited twelve books and\nhas twenty-seven patents to his name. He is a manager of research grants, editor in\nchief and member of international journal editorial boards, a former plenary speaker, a member of scientific committees, and chair at international conferences. His\nresearch is in the fields of control systems, control of electric drives, fuzzy control\nsystems, neural network applications, fault detection and diagnosis, sensor network\napplications, monitoring of distributed parameter systems, and power ultrasound\napplications. 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