Specific and blind docking studies with AutoDock were repeated three times.
\\n\\n
\\n"}]',published:!0,mainMedia:{caption:"Milestone",originalUrl:"/media/original/124"}},components:[{type:"htmlEditorComponent",content:'
Barely three months into the new year and we are happy to announce a monumental milestone reached - 150 million downloads.
\n\nThis achievement solidifies IntechOpen’s place as a pioneer in Open Access publishing and the home to some of the most relevant scientific research available through Open Access.
\n\nWe are so proud to have worked with so many bright minds throughout the years who have helped us spread knowledge through the power of Open Access and we look forward to continuing to support some of the greatest thinkers of our day.
\n\nThank you for making IntechOpen your place of learning, sharing, and discovery, and here’s to 150 million more!
\n\n\n\n\n'}],latestNews:[{slug:"intechopen-supports-asapbio-s-new-initiative-publish-your-reviews-20220729",title:"IntechOpen Supports ASAPbio’s New Initiative Publish Your Reviews"},{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"}]},book:{item:{type:"book",id:"5184",leadTitle:null,fullTitle:"Environmental Health Risk - Hazardous Factors to Living Species",title:"Environmental Health Risk",subtitle:"Hazardous Factors to Living Species",reviewType:"peer-reviewed",abstract:"This book, Environmental Health Risk - Hazardous Factors to Living Species, is intended to provide a set of practical discussions and relevant tools for making risky decisions that require actions to reduce environmental health risk against environmental factors that may adversely impact human health or ecological balances. We aimed to compile information from diverse sources into a single volume to give some real examples extending concepts of those hazardous factors to living species that may stimulate new research ideas and trends in the relevant fields.",isbn:"978-953-51-2402-3",printIsbn:"978-953-51-2401-6",pdfIsbn:"978-953-51-5435-8",doi:"10.5772/61472",price:119,priceEur:129,priceUsd:155,slug:"environmental-health-risk-hazardous-factors-to-living-species",numberOfPages:278,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"aa20266ad595ce73a9396f4ab0f8112e",bookSignature:"Marcelo L. Larramendy and Sonia Soloneski",publishedDate:"June 16th 2016",coverURL:"https://cdn.intechopen.com/books/images_new/5184.jpg",numberOfDownloads:26086,numberOfWosCitations:111,numberOfCrossrefCitations:89,numberOfCrossrefCitationsByBook:4,numberOfDimensionsCitations:207,numberOfDimensionsCitationsByBook:8,hasAltmetrics:1,numberOfTotalCitations:407,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"October 9th 2015",dateEndSecondStepPublish:"October 30th 2015",dateEndThirdStepPublish:"February 3rd 2016",dateEndFourthStepPublish:"May 3rd 2016",dateEndFifthStepPublish:"June 2nd 2016",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"14764",title:"Dr.",name:"Marcelo L.",middleName:null,surname:"Larramendy",slug:"marcelo-l.-larramendy",fullName:"Marcelo L. Larramendy",profilePictureURL:"https://mts.intechopen.com/storage/users/14764/images/system/14764.jpg",biography:"Marcelo L. Larramendy, Ph.D., serves as Professor of Molecular Cell Biology at the School of Natural Sciences and Museum (National University of La Plata, Argentina). Appointed Senior Researcher of the National Scientific and Technological Research Council of Argentina. Former Member of the Executive Committee of the Latin American Association of Environmental Mutagenesis, Teratogenesis and Carcinogenesis. Author of more than 450 contributions, including scientific publications, research communications and conferences worldwide. Recipient of several national and international awards. Prof. Larramendy is a regular Lecturer at the international A. Hollaender Courses organized by the IAEMS and former guest scientist at NIH (USA) and the University of Helsinki, (Finland). He is an expert in Genetic Toxicology and is, or has been, referee for more than 20 international scientific journals. Member of the International Panel of Experts at the International Agency for Research on Cancer (IARC, WHO, Lyon, France) in 2015 for the evaluation of DDT, 2,4-D and Lindane. Presently, Prof. Dr. Larramendy is Head of the Laboratory of Molecular Cytogenetics and Genotoxicology at the UNLP.",institutionString:"National University of La Plata",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"20",institution:{name:"National University of La Plata",institutionURL:null,country:{name:"Argentina"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:{id:"14863",title:"Dr.",name:"Sonia",middleName:null,surname:"Soloneski",slug:"sonia-soloneski",fullName:"Sonia Soloneski",profilePictureURL:"https://mts.intechopen.com/storage/users/14863/images/system/14863.jpg",biography:"Sonia Soloneski has a Ph.D. in Natural Sciences and is Assistant Professor of Molecular Cell Biology at the School of Natural Sciences and Museum of La Plata, National University of La Plata, Argentina. She is a member of the National Scientific and Technological Research Council (CONICET) of Argentina in the Genetic Toxicology field, the Latin American Association of Environmental Mutagenesis, Teratogenesis and Carcinogenesis (ALAMCTA), the Argentinean Society of Toxicology (ATA), the Argentinean Society of Biology (SAB) and the Society of Environmental Toxicology and Chemistry (SETAC). She has authored more than 380 contributions in the field, including scientific publications in peer-reviewed journals and research communications. She has served as a review member for more than 30 scientific international journals. She has been a plenary speaker in scientific conferences and a member of scientific committees. She is a specialist in issues related to Genetic Toxicology, Mutagenesis, and Ecotoxicology.",institutionString:"National University of La Plata",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"7",institution:{name:"National University of La Plata",institutionURL:null,country:{name:"Argentina"}}},coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"856",title:"Risk Management",slug:"environmental-sciences-environmental-health-risk-management"}],chapters:[{id:"50482",title:"Pesticides, Environmental Pollution, and Health",doi:"10.5772/63094",slug:"pesticides-environmental-pollution-and-health",totalDownloads:7018,totalCrossrefCites:55,totalDimensionsCites:129,hasAltmetrics:1,abstract:"In recent years, people have been exposed to several types of substances with broad spectrum due to the rapidly evolving technology. One of these chemical substance groups are pesticides. Pesticides have been an essential part of agriculture to protect crops and livestock from pest infestations and yield reduction for many decades. Despite their usefulness, pesticides could pose potential risks to food safety, the environment, and all living things. Concern about the environmental impact of repeated pesticide use has prompted research into the environmental fate of these agents, which can emigrate from treated fields to air, other land, and water bodies. The importance of agricultural pesticides for developing countries is undeniable. However, the issue of human health and environmental risks has emerged as a key problem for these countries in accordance to a number of studies. In the last five decades, pesticide usages increased the quantity and improved the quality of food. However, with the increasing amounts of their usage, concern about their adverse effects on nontarget organisms, including human beings, has also grown. The purpose of this publication is to explain the nature of pesticides and their history, classification, risks, and effects on health and the environment.",signatures:"Arzu Özkara, Dilek Akyıl and Muhsin Konuk",downloadPdfUrl:"/chapter/pdf-download/50482",previewPdfUrl:"/chapter/pdf-preview/50482",authors:[{id:"5974",title:"Prof.",name:"Muhsin",surname:"Konuk",slug:"muhsin-konuk",fullName:"Muhsin Konuk"},{id:"179732",title:"Dr.",name:"Dilek",surname:"Akyıl",slug:"dilek-akyil",fullName:"Dilek Akyıl"},{id:"179733",title:"Dr.",name:"Arzu",surname:"Özkara",slug:"arzu-ozkara",fullName:"Arzu Özkara"}],corrections:null},{id:"50454",title:"Modelling in Metal Risk Assessment",doi:"10.5772/62911",slug:"modelling-in-metal-risk-assessment",totalDownloads:2101,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Unique properties of metals that are largely different from the characteristics of organic substances should be considered in risk assessment. The bioavailability and toxicity of metals depend on their chemical speciation, that is, physical-chemical forms, in the environment, which is largely influenced by the environmental chemistry. Since metals in the environment are not always available while organisms have developed different processes to actively regulate the body burden, assessment of metal bioaccumulation might provide a better understanding of potential risks. Metal bioaccumulation is a prerequisite for metal toxicity, but is not the only determinant of metal toxicity. In addition to metal accumulation, metal toxicity is influenced by the subcellular partitioning of metals, which is controlled by the capacity of organisms to sequester and to detoxify metals. Different modelling approaches have been developed to address some of these factors. Both empirical and mechanistic equilibrium models have been developed and applied for characterising metal speciation in the environment. Metal bioaccumulation has been predicted by biodynamic models. The ability of organisms to detoxify metals has been taken into account in assessment based on the induction of metallothionein (MT) or subcellular partitioning. In addition, the interactions between organisms and metal ions have been taken into consideration in assessment of metal toxicity based on the accumulation of metal ions at biological surfaces.",signatures:"T.T. Yen Le",downloadPdfUrl:"/chapter/pdf-download/50454",previewPdfUrl:"/chapter/pdf-preview/50454",authors:[{id:"178989",title:"Dr.",name:"T.T. Yen",surname:"Le",slug:"t.t.-yen-le",fullName:"T.T. Yen Le"}],corrections:null},{id:"50341",title:"Soil Contamination Health Risks in Czech Proposal of Soil Protection Legislation",doi:"10.5772/62456",slug:"soil-contamination-health-risks-in-czech-proposal-of-soil-protection-legislation",totalDownloads:1546,totalCrossrefCites:6,totalDimensionsCites:9,hasAltmetrics:0,abstract:"A new system of soil contamination limit values proposed for Czech legislation is described. The system is based on the hierarchical limit values system with two levels. The first one—prevention limit—defined background values of risk elements (REs) and persistent organic pollutants (POPs) in Czech agricultural soils supported by the data from soil monitoring system. The second one—indication limit—is defined for human health protection by two principles, the protection of food chain and the protection of direct human health risks by inhalation, dermal and oral intake of RE and POPs in soil particles on the field. The practical application of limit values proposal was applied in the project focused on soil contamination influence on health and environmental risks in fluvial zones of Czech important river basins. The floodplain soils belong to the most contaminated soils in Europe generally and the project defined the potential fluvial areas with increased human health risks.",signatures:"Radim Vácha, Milan Sáňka, Jan Skála, Jarmila Čechmánková and\nViera Horváthová",downloadPdfUrl:"/chapter/pdf-download/50341",previewPdfUrl:"/chapter/pdf-preview/50341",authors:[{id:"85483",title:"Associate Prof.",name:"Radim",surname:"Vacha",slug:"radim-vacha",fullName:"Radim Vacha"}],corrections:null},{id:"50769",title:"Assessment of DNA Damage by Comet Assay in Buccal Epithelial Cells: Problems, Achievement, Perspectives",doi:"10.5772/62760",slug:"assessment-of-dna-damage-by-comet-assay-in-buccal-epithelial-cells-problems-achievement-perspectives",totalDownloads:1950,totalCrossrefCites:2,totalDimensionsCites:4,hasAltmetrics:0,abstract:"DNA damage risk assessment in comet assay by the use of buccal mucosa cells has great advantages in comparison with other cell type sample due to more safely, easier, cheaper, and non-invasive method for in vivo studies. According to the OECD Guidelines, the in vivo mammalian alkaline comet assay is well-established and validated method for measuring DNA strand breaks in single eukaryotic cells. Considering exposure to xenobiotics and endogenous damage inductors, buccal mucosa cells are the first to be in direct contact after exposure and this makes them an ideal biomatrices in evaluation of the level of individual genotoxicity to several compounds already mentioned. Their clinical diagnostic applicability confers a potential use in patients across time. However, the number of publications referring to the human buccal comet assay is low in the last two decades. This low growing interest may be explained by several factors, including its relative technical problems. Different procedures have been used in collecting and processing the samples. In order to have widespread acceptance and credibility in human population studies, the comet assay in buccal cells requires standardization of the protocol, of parameters analyzed, and a better knowledge of critical features affecting the assay outcomes, including the definition of the values of spontaneous DNA damage. There is a need for further collaborative work as in the HUMN (micronucleus assay on lymphocytes) and HUMNxL (micronucleus assay on buccal cells) collaborative projects. The creation of a network of laboratories will allow more focused validation studies, including the design of a classic, historic, prospective cohort study in order to explore the link between measures of genetic instability in the buccal mucosa and the risk of cancer and other chronic-degenerative diseases. One such network connection will start in 2016 as a COST project under the name “hCOMET—The comet assay as a human biomonitoring tool” launched by Prof. Andrew Collins.",signatures:"J. Sánchez-Alarcón, M. Milić, S. Gómez-Arroyo, J. M. R. Montiel-González and R. Valencia-Quintana",downloadPdfUrl:"/chapter/pdf-download/50769",previewPdfUrl:"/chapter/pdf-preview/50769",authors:[{id:"15052",title:"Dr.",name:"Sandra",surname:"Gomez-Arroyo",slug:"sandra-gomez-arroyo",fullName:"Sandra Gomez-Arroyo"},{id:"40591",title:"Dr.",name:"Mirta",surname:"Milić",slug:"mirta-milic",fullName:"Mirta Milić"},{id:"179537",title:"Dr.",name:"Rafael",surname:"Valencia-Quintana",slug:"rafael-valencia-quintana",fullName:"Rafael Valencia-Quintana"},{id:"180673",title:"MSc.",name:"Juana",surname:"Sánchez-Alarcón",slug:"juana-sanchez-alarcon",fullName:"Juana Sánchez-Alarcón"},{id:"185133",title:"MSc.",name:"J Mariano R",surname:"Montiel-González",slug:"j-mariano-r-montiel-gonzalez",fullName:"J Mariano R Montiel-González"}],corrections:null},{id:"50193",title:"Risks of Environmental Genotoxicants",doi:"10.5772/62454",slug:"risks-of-environmental-genotoxicants",totalDownloads:1715,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Humans have throughout their development been exposed to various environmental genotoxicants through food, air, water, and soil. Environmental exposure to genotoxic compounds may induce damage to human health and thereby increase risks of human cancers and other diseases. Environmental genotoxic chemicals have the ability to induce mutations. Such mutations can give rise to cancer in somatic cells. However, when germ cells are affected, the damage can also have an effect on the next and successive generations. Because of the potential health hazard represented by exposure to genotoxic chemicals, it is important that all chemicals for which there is possible human exposure be screened for genotoxic activity. If genotoxic hazard is detected, then the risks of exposure can be assessed and the use of the chemical controlled and when appropriate eliminated from the market and the environment. In this chapter, a general overview of the genotoxicity and the genotoxicity of some environmental genotoxicants are discussed. This is followed by a description of the genotoxic properties of some environmental genotoxicants such as bisphenols and mycotoxins, which are prominent environmental contaminates, and is believed to be genotoxic agents that contribute to the high incidence of carcinogenicity among populations.",signatures:"Sabry M. Attia and Gamaleldin I. Harisa",downloadPdfUrl:"/chapter/pdf-download/50193",previewPdfUrl:"/chapter/pdf-preview/50193",authors:[{id:"178995",title:"Prof.",name:"Sabry",surname:"Attia",slug:"sabry-attia",fullName:"Sabry Attia"},{id:"180300",title:"Prof.",name:"Gamaleldin",surname:"Harisa",slug:"gamaleldin-harisa",fullName:"Gamaleldin Harisa"},{id:"190926",title:"Prof.",name:"M. Abd Allah",surname:"Gamil",slug:"m.-abd-allah-gamil",fullName:"M. Abd Allah Gamil"}],corrections:null},{id:"50234",title:"Environmental Effects of Endocrine-Disrupting Chemicals: A Special Focus on Phthalates and Bisphenol A",doi:"10.5772/62455",slug:"environmental-effects-of-endocrine-disrupting-chemicals-a-special-focus-on-phthalates-and-bisphenol-",totalDownloads:2850,totalCrossrefCites:3,totalDimensionsCites:13,hasAltmetrics:0,abstract:"Several environmental chemicals are classified as endocrine-disrupting chemicals (EDCs). Many of them have an impact on reproductive functions and sex hormones because of their estrogenic and/or antiandrogenic properties. Phthalates and bisphenol A (BPA) are two well-known EDCs. They are abundant in the environment. Phthalates are usually classified as antiandrogens, whereas BPA is considered as estrogen-like EDC and xenoestrogen. Other than their endocrine-disrupting effects, these two chemicals are also known to have genotoxic and epigenetic effects. Besides, they are hepatotoxic and have substantial effects on other organs/systems (thyroid, kidney, neuroendocrine system, immune system, etc.). In this chapter, we will mainly focus on the toxic effects of different phthalate esters and BPA by discussing their availability in the environment, mechanism and mode of actions, their biotransformation and reproductive effects, and their effects on other systems (hepatic, renal, etc.). Besides, we discuss epidemiological studies that are conducted to reveal their effects on the reproductive and endocrine systems. This chapter provides the readers a compact piece of knowledge on these abundant substances and helps them to understand the action of these substances at the molecular and cellular levels.",signatures:"Pinar Erkekoglu and Belma Kocer-Gumusel",downloadPdfUrl:"/chapter/pdf-download/50234",previewPdfUrl:"/chapter/pdf-preview/50234",authors:[{id:"109978",title:"Prof.",name:"Pınar",surname:"Erkekoglu",slug:"pinar-erkekoglu",fullName:"Pınar Erkekoglu"},{id:"185037",title:"Dr.",name:"Belma",surname:"Kocer-Gumusel",slug:"belma-kocer-gumusel",fullName:"Belma Kocer-Gumusel"}],corrections:null},{id:"50264",title:"Occupational Exposure to Coal, Genotoxicity, and Cancer Risk",doi:"10.5772/62486",slug:"occupational-exposure-to-coal-genotoxicity-and-cancer-risk",totalDownloads:1966,totalCrossrefCites:4,totalDimensionsCites:7,hasAltmetrics:1,abstract:"Coal is a heterogeneous mixture containing large quantities of organic and inorganic matter, including carbon, hydrogen, oxygen, sulfur, nitrogen, and organometallic forms. The presence of mineral matter in coal may result in a number of environmental and human health problems related to its mining, preparation, and combustion. During coal mining activities, large quantities of coal dust, ashes, polycyclic aromatic hydrocarbons (PAHs), and heavy metals are released into the environment, forming a complex mixture. This mixture becomes one of the most important occupational risks for the health and safety of workers due to its synergistic, additive, and enhancing effects. Once inside the organism, this cocktail-like mixture can interact with cellular mechanisms related to the production of reactive oxygen species (ROS) and can cause damage in important macromolecules such as DNA, lipids, and proteins. In this review, human populations exposed to coal and coal burning were analyzed. Data from different studies were evaluated in relation to the effect of complex mixture exposure on DNA damage and mechanisms, and the background factors, such as gender, age, or smoking habit. The high temperatures that occur in combustion processes affect the characteristics of the resulting particles. The coal fly ash is released by combustion and its composition varies depending on the coal type and the method of collection used such as electrostatic precipitators. Compounds such as PAHs once activated by the organisms have been shown to have mutagenic and carcinogenic activity due to its ability to form adducts with purines. Moreover, metals that commonly are evaporated during the cooling process increase its toxicity. The particles when inhaled can pass from the alveoli into the bloodstream and affect extrapulmonary organs. Several studies have described the inflammatory cascade that triggers exposure to coal and coal fly ash particles; they have a complex composition capable of generating a persistent inflammatory process, resulting in diseases widely described as emphysema, bronchitis, pneumoconiosis, asthma, and cancer. Several human biomonitoring studies have been conducted evaluating the inflammatory process and the release of cytokines, polymorphisms involved in detoxification mechanisms, different biomarkers associated with occupational exposure, DNA damage, and the influence of oxidative stress in disease development. The relationship between chronic exposure to coal and coal ash particles and cancer is still widely debated. This review gave us a broad assessment about the associated mechanisms between cancer and exposure to coal and different findings around the world.",signatures:"Grethel León-Mejía , Milton Quintana Sosa , Paula Rohr , Katia\nKvitko, João Antonio Pêgas Henriques and Juliana da Silva",downloadPdfUrl:"/chapter/pdf-download/50264",previewPdfUrl:"/chapter/pdf-preview/50264",authors:[{id:"170192",title:"Dr.",name:"Katia",surname:"Kvitko",slug:"katia-kvitko",fullName:"Katia Kvitko"},{id:"170193",title:"Dr.",name:"Juliana",surname:"Da Silva",slug:"juliana-da-silva",fullName:"Juliana Da Silva"},{id:"180743",title:"MSc.",name:"Grethel",surname:"Leon-Mejia",slug:"grethel-leon-mejia",fullName:"Grethel Leon-Mejia"},{id:"180880",title:"Dr.",name:"Milton",surname:"Quintana",slug:"milton-quintana",fullName:"Milton Quintana"},{id:"181198",title:"Dr.",name:"Paula",surname:"Rohr",slug:"paula-rohr",fullName:"Paula Rohr"},{id:"181199",title:"Dr.",name:"Jose Antonio",surname:"Pegas Henriques",slug:"jose-antonio-pegas-henriques",fullName:"Jose Antonio Pegas Henriques"}],corrections:null},{id:"50003",title:"Immunological Risks Caused by Fibrous and Particulate Substances",doi:"10.5772/62749",slug:"immunological-risks-caused-by-fibrous-and-particulate-substances",totalDownloads:1301,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:1,abstract:"The immunological risks caused by fibrous and particulate substances, especially the effects caused by asbestos fibers and silica particles, are discussed in this chapter. Patients with silicosis often suffer from autoimmune diseases, such as rheumatoid arthritis, systemic sclerosis, and antineutrophil cytoplasmic antibody–related vasculitis. Silica particles, SiO2, may influence directly various immune cells resulting in the production of many autoantibodies and imbalance between responder and regulatory T cells. The core chemical content of asbestos fibers is Si and O, although the physical feature is different. Considering the complications in asbestos-exposed patients, malignant tumors, such as lung cancer and malignant mesothelioma, are the most important. To think about these situations, asbestos fibers may cause the reduction of antitumor immunity. The experimental findings and measurements of various immunological parameters in silicosis patients, as well as asbestos-exposed population, such as patients with pleural plaque and mesothelioma, are demonstrated and discussed in this chapter.",signatures:"Hidenori Matsuzaki, Suni Lee, Naoko Kumagai-Takei, Shoko\nYamamoto, Tamayo Hatayama, Kei Yoshitome, Hiroaki Hayashi,\nMegumi Maeda and Takemi Otsuki",downloadPdfUrl:"/chapter/pdf-download/50003",previewPdfUrl:"/chapter/pdf-preview/50003",authors:[{id:"34101",title:"Prof.",name:"Takemi",surname:"Otsuki",slug:"takemi-otsuki",fullName:"Takemi Otsuki"},{id:"48631",title:"Dr.",name:"Yasumitsu",surname:"Nishimura",slug:"yasumitsu-nishimura",fullName:"Yasumitsu Nishimura"}],corrections:null},{id:"50298",title:"Environmental Factors in Causation of Diabetes Mellitus",doi:"10.5772/62543",slug:"environmental-factors-in-causation-of-diabetes-mellitus",totalDownloads:2433,totalCrossrefCites:4,totalDimensionsCites:5,hasAltmetrics:1,abstract:"Environmental factors play a role in etiopathogenesis of diabetes. Environmental factors include polluted water, soil, unhealthy diet, stress, lack of physical activity, vitamin D deficiency, exposure to enteroviruses, and damage to immune cells.",signatures:"P.G. Raman",downloadPdfUrl:"/chapter/pdf-download/50298",previewPdfUrl:"/chapter/pdf-preview/50298",authors:[{id:"179146",title:"Dr.",name:"Poondy Gopalratnam",surname:"Raman",slug:"poondy-gopalratnam-raman",fullName:"Poondy Gopalratnam Raman"}],corrections:null},{id:"49818",title:"Amoxicillin in the Aquatic Environment, Its Fate and Environmental Risk",doi:"10.5772/62049",slug:"amoxicillin-in-the-aquatic-environment-its-fate-and-environmental-risk",totalDownloads:3208,totalCrossrefCites:14,totalDimensionsCites:37,hasAltmetrics:0,abstract:"Amoxicillin is a broad-spectrum antibiotic widely used for treating both human and animal diseases, and it belongs to a group that are excreted unchanged within urine and faeces; therefore, it is possible to find traces of this drug or its degradation products in environmental water bodies. In water, it is rapidly degraded by biotic and abiotic factors, yielding different intermediate products; these are suspected of being more resistant to degradation, and potentially more toxic, than the parent compound. In the water bodies, these compounds may produce toxic effects on the aquatic organisms from different trophic levels and produce an ecological imbalance. Amoxicillin may bioaccumulate in fish muscle tissues, with the possibility of the occurrence of these drugs in food, leading to a passive consumption of this antibiotic resulting in undesirable effects on consumer health such as immunoallergic responses. However, the main problem related with the presence of this antimicrobial compounds in fish tissues is the possibility of inducing bacterial resistance genes. At present, the available scientific knowledge is less than what is needed to fully assess the risks that amoxicillin pose to the environment, and it is still necessary to conduct large amount of research works before a thorough understanding of this severe environmental issue.",signatures:"Armando Elizalde-Velázquez, Leobardo Manuel Gómez-Oliván,\nMarcela Galar-Martínez, Hariz Islas-Flores, Octavio Dublán-García and Nely SanJuan-Reyes",downloadPdfUrl:"/chapter/pdf-download/49818",previewPdfUrl:"/chapter/pdf-preview/49818",authors:[{id:"179818",title:"Dr.",name:"Leobardo Manuel",surname:"Gómez-Oliván",slug:"leobardo-manuel-gomez-olivan",fullName:"Leobardo Manuel Gómez-Oliván"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"923",title:"Herbicides",subtitle:"Theory and Applications",isOpenForSubmission:!1,hash:"54a8eb808c05a5fe01c676e7047d4576",slug:"herbicides-theory-and-applications",bookSignature:"Sonia Soloneski and Marcelo L. 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\r\n\tHemophilia is an X-chromosome determined genetic abnormality leading to easy bleeding. The bleeding may be "spontaneous" due to light trauma or surgical intervention. Genetic counseling focuses on early diagnosis, prevention, and sociomedical consequences.
\r\n\tDiagnostic tools are advancing: micro-and nano-diagnostics, advanced molecular genetics, and diagnosis of the aberrant clotting factor synthesis development and the options for the staging of the genetic abnormality - severe, moderate, and mild expression.
\r\n\tTreatment developments and advances start with prevention, intra-uterine approaches, genetic manipulation, genetic engineering, the high specificity of replacement factors, and recombinant technology.
\r\n\tIn addition to the above, the book will provide an update on the prevention of transmission of pathogens and potentially toxic substances used to stabilize and preserve treatment commodities. The role of big data and artificial intelligence through both machine learning and the application of deep learning and digital footprinting will also be addressed.
\r\n\tIn the developing world, there is an urgent need to collect, preserve and process plasma for the manufacturing of high yield, safe, and stabilized cryoprecipitate, or pharmaceutical fractionation of purified and specific clotting factors, as well as improvement on diagnostic and sociomedical approaches with an emphasis on patient and family care, and management of bleeding episodes.
Burns are often called one of the most devastating types of trauma in medicine because their consequences have physical and mental dimensions.
\nSevere burns can cause death. Physical consequences of nonfatal burns include scars, contractures, and keloids. The victims suffer due to disfigurement and disability often leading to stigma and rejection by the society. Among mental consequences of burns are, for example, low self-esteem, depression, or anxiety.
\nBurns are type of trauma that can be caused by thermal energy, chemical agents, electricity, or radiation. According to the World Health Organization, burn is an injury to the skin or other organic tissues primarily caused by heat or due to radiation, radioactivity, electricity, friction, or contact with chemicals.
\nAccording to Juan P. Barret, trauma can be defined as bodily injury severe enough to pose a threat to life, limbs, tissues, and organs, but burn injury is different, because unlike other traumas, it can be quantified as to the exact percentage of body injured and can be viewed as a paradigm of injury from which many lessons can be learned about critical illness involving multiple organ systems [1].
\nAccording to the statistics of the World Health Organization, 180,000 deaths every year are caused by burns [2]. Majority of them occur in low- and middle-income countries. It is estimated that almost two thirds occur in the African and South-East Asia regions. The highest fire-related mortality rates are in Southeast Asia, 11.6 deaths per 100,000 population per year; in the Eastern Mediterranean, 6.4 deaths per 100,000 population per year; and in Africa, 6.1 deaths per 100,000 population per year [3].
\nAmong pediatric population the rate of deaths from burns is over seven times higher in low- and middle-income countries than in high-income countries. Lowest mortality rates due to burns in high-income countries are the successful result of preventive interventions of many kinds, such as promotion of the use of smoke detectors, the lowering of temperatures of hot water heaters, the installation of sprinkler systems, the promotion of flame-retardant children’s sleepwear, and the development of safer buildings and household fuels [3].
\nThe epidemiology of burns differs in different age groups and depends on sex [3]. For example, in low- and middle-income countries, fire-related burns are the sixth leading cause of death among 5–14-year-old victims and the eighth leading cause death among 15–29-year-old victims [3].
\nIn low- and middle-income countries, women (especially young) are at higher risk of burns [3]. However in high-income countries, men are at higher risk of burns.
\nIn pediatric population, it is estimated that worldwide approximately 1% of all children sustain a burn injury each year [4].
\nThe results of our studies conducted in Lower Silesia (the region of Poland) among children with burns indicate that boys are at higher risk of burn injury [5, 6].
\nThe analysis of mechanism of trauma revealed that the most common type of injury in children treated in ambulatory conditions by general practitioners (GP) and requiring hospitalization due to burns in Lower Silesia was thermal burns [5, 6]. The second reason for hospitalization and ambulatory treatment were chemical burns [5]. In the studied population, there were no cases of burns caused by radiation [5, 6].
\nAmong the pediatric patients hospitalized due to thermal injury in Lower Silesia, 2010–2012, burns were usually located in the upper limbs [5]. Trunk and lower limbs were also frequently affected [5].
\nThe detailed analysis of the thermal burns of upper limbs revealed that the hand and wrist were more often affected than forearm, arm, and shoulder. However, the detailed analysis of the thermal burns of lower limbs revealed that the injury affected more often the hip, tight, knee, and lower leg than ankle and feet [5].
\nMost of patients under 18 years old treated by GP due to burns in Lower Silesia of children were under 2 years old [6]. Moreover, in the studied population, the percentage of children hospitalized due to burns in Lower Silesia in 2010 according to individual age groups in age group under 2 years old was 0.5%, in children from 3 to 6 years old was 0.12%, in children from 7 to 12 years old was 0.06%, in children from 13 to 15 years old was 0.07%, and in children from 16 to 18 years old was 0.06% [5]. Similarly in the studied population, percentage of children hospitalized due to burns in Lower Silesia in 2011 according to individual age groups in age group under 2 years old was 0.54%, in children from 3 to 6 years old was 0.13%, in children from 7 to 12 years old was 0.06%, in children from 13 to 15 years old was 0.07%, and in children from 16 to 18 years old was 0.08% [5].
\nThe chemical injuries were less common in pediatric population of Lower Silesia in the analyzed period of time. However, it was noticed that this type of burns more frequently affects the upper gastrointestinal tract than thermal burns [5, 6].
\nThe obtained results are coherent with other studies realized in Polish pediatric population [7].
\nThere are many ways in which burn injury can be classified.
\nApart from the mechanism of injury, usually four criteria are taken into account: depth of injury, percent of body surface area involved, location of the burn, and association with other injuries [4].
\nAccording to the etiological factor (factor that caused the burn injury), we can distinguish thermal, electrical, and chemical injury and burns caused by radiation.
\nThe most common types of burns in children are thermal burns. Thermal injuries are caused by heat. They can be the result of hot liquids (scalds), hot solids (contact burns), and flames (flame burns). In pediatric population, especially in children under 2 years old, the most common type of burns is scalds.
\nAnatomic location is important in triage decision [4]. Burns can affect all parts of the body: head, neck, trunk, upper and lower extremities, perineum, and upper anterior abdominal wall (Figures 1–3).
\nThe child with the thermal burn of the knee (partial thickness burn).
The child with the thermal burn of the lower extremity (partial thickness burn).
The child with the thermal burn (superficial) of the trunk caused by hot water (scald).
International Classification of the Disease (ICD) is used by physicians, nurses, health-care providers, and researchers to classify the diseases and other health-care problems. It facilitated the comparison of date between different regions and is widely used for epidemiological purposes.
\nIn the ICD-11 burns are divided into burns of external body surface, specified by site; burns of the eye or internal organs; and burns of multiple or unspecified body regions. In the ICD-10 the group of burns of external surface included burns and corrosions of all depth divided into burns and corrosions of head and neck (T20); burns and corrosions of trunk (T21); burns and corrosions of shoulder and upper limb, except the wrist and hand (T22); burns and corrosions of the wrist and hand (T23); burns and corrosions of the hip and lower limb, except the ankle and foot (T24); and burns and corrosions of the ankle and foot (T25) [8].
\nBurns involve also inhalation injuries. Inhalation injuries should be suspected in patients with facial burns, singed nasal hairs, and carbonaceous sputum [4].
\nThe location is important in assessment of the risk of disability—the greatest is in the case of patients with affected face, eyes, feet, perineum, and hands [4].
\nThe skin is composed of two layers: epidermis and dermis. The epidermis is composed of stratified squamous epithelium, which acts as a barrier to infectious agents and also prevents fluid loss from the body [9].
\nAs children’s skin is thinner than adult’s skin, exposure to the same agent will cause deeper burns in an infant compared to adults. For example, water at 60°C will cause a full-thickness burn in less than 1 s in an infant and 20 s in an adult [10].
\nAt the emergency department, it is difficult to describe the thickness of burn injury because the appearance of burn wound evolves during first 24–48 h [9].
\nUsually in one pediatric patient, we observe burns of different depth.
\nAccording to depth of the skin affected, burns can be divided into superficial, partial-thickness, and full-thickness burns [9].
\nSuperficial burns involve only the epidermal layer; the skin is erythematosus.
\nIn partial-thickness burns, the whole epidermis and part of the dermis are affected. Most of authors distinguish superficial partial-thickness burns and deep partial-thickness burns. In the superficial partial-thickness burns, the papillary layer of the dermis is affected, and the erythema of the skin and blistering are observed. In the deep partial-thickness burns, the reticular layer of the dermis is affected, and the skin looks paler and has a speckled appearance due to thrombosis of superficial vessels. The deep partial-thickness burns are less painful than the superficial partial-thickness burns.
\nIn the full-thickness burns, the epidermis and dermis with epidermal appendages are affected [9]. This type of burns is usually the result of flame, prolonged contact with hot objects, and hot oil [9].
\nIn some old literatures, the classification involves first, second, third, and fourth degrees. The first degree corresponds with the superficial burns. The second degree A corresponds with the superficial partial-thickness burns; the second degree B corresponds with the deep partial-thickness burns. The third degree corresponds with the full-thickness burns. The fourth degree burns involve full depth of the skin and underlying fascia, muscles, or even bones [4].
\nThe extension of burn injury is expressed as percentage of total body surface area. There are several methods used to count the surface of burn.
\nIn the teenagers and adults, the extent of the skin involved is estimated on the basis of “rule of nines.” That means the surface of each upper extremity is 9% of total body surface area, each lower extremity is 18% of total body surface area, the anterior part of the trunk is 18% of the total body surface area, the posterior surface of the trunk is 18% of the total body surface area, the head is 9% of the total body surface area, and the perineum is 1% of the total body surface area [4]. There is a modified rule of nines for infants and children (Figure 4).
\nModified rule of nines in children in different age groups.
According to “rule of palm,” the inner surface of the patient’s palm is approximately 1% of total body surface area.
\nIn younger children the Lund and Bowder charts are used to estimate the extension of burn wound [4].
\nAccording to extent of body surface involved, ICD-10 classified burns into burns involving less than 10% of body surface (T31.0), burns involving 10–19% of body surface (T31.1), burns involving 20–29% of body surface (T31.2), burns involving 30–39% of body surface (T31.3), burns involving 40–49% of body surface (T31.4), burns involving 50–59% of body surface (T31.5), burns involving 60–69% of body surface (T31.6), burns involving 70–79% of body surface (T31.7), burns involving 80–89% of body surface (T31.8), and burns involving 90% or more of body surface (T31.9) [8].
\nThe extension of burn injury plays a crucial role in the process of decision-making about hospitalization of the patient. It is also important to count the amount of intravenous fluids that should be given to the patient.
\nAccording to Jackson it is possible to classify thermal burns into three zones of injury: the inner, the intermediate, and the outer zone. The inner zone is the zone of coagulative necrosis. The intermediate zone is the zone of stasis, while the outer zone is the zone of hyperemia [11].
\nPathophysiological effects of burn injury can be divided into local and systemic [11].
\nThe local effects include release of inflammatory mediators from the capillary walls, white blood cells, and platelets. These inflammatory mediators result in vasodilatation and increased vessel permeability that leads to fluid loss from the circulation into the interstitial space [11].
\nSystemic effects occur in extended burns (usually in those that burned surface area exceeds 20% of total body surface area) and include hypovolemia, immunosuppression, catabolism, loss of the protective function of the gut, and pulmonary edema [11].
\nA major burn injury leads to fluid and electrolyte imbalance with systemic intravascular losses of water, sodium, albumin, and red blood cells. If the intravascular volume is not rapidly restored, the shock develops [1]. Moreover, burns can lead to malnutrition and organ dysfunction due to metabolic disturbances (hypermetabolism and muscle catabolism) [1].
\nThe burns according to the cause of the injury can be divided into accidental and nonaccidental.
\nMost of burns in children are caused by the accident [12].
\nThere are several features that can make a health-care provider to suspect nonaccidental injury.
\nAmong them is delay in seeking medical help by parents. It is very important to write down all the details of mechanism of the injury provided by caregivers, because sometimes caregivers change the history of trauma with time. The non-accidental injury is suspected when the mechanism of injury given by parents is not coherent with the burn wound found in child and also when the history of trauma is not consistent with the developmental stage of the child. In older children the abnormal behavior, such as avoiding eye contact, can be observed.
\nCharacteristic for nonaccidental burns are burn wound caused by cigarettes. Also the so-called glove or sock burns are typical for nonaccidental injury. In many children with nonaccidental burns, additional sings of trauma can be found, for example, bruises, fractures, etc.
\nAccording to Adronicus et al., there were no differences between the groups in age or mortality between children with accidental and nonaccidental burn injuries. The authors found that in the group of children with nonaccidental injuries, burns involving both hands or both legs were more common; these patients were more likely to require skin grafting and treatment in the intensive care unit [12]. Moreover the abused/neglected children were more likely to come from single parent families [12].
\nThe appropriate first aid after burn injury is very important in reduction of burn depth, which means that it influences the requirement for surgical treatment, can shorten the hospitalization time, and results in better esthetic scar.
\nAccording to WHO, the person who gives the first aid to the burned child should stop the burning process by removing clothing and irrigating the burns; extinguishing flames by allowing the patient to roll on the ground, or by applying a blanket, or by using water or other fire-extinguishing liquids; use cool running water to reduce the temperature of the burn; in chemical burns, remove or dilute the chemical agent by irrigating with large volumes of water; and wrap the patient in a clean cloth or sheet and transport to the nearest appropriate facility for medical care [2].
\nWHO also pays attention on the actions that the person who gives the first aid to the burned child should not do; for example, do not start first aid before ensuring your own safety (switch off electrical current, wear gloves for chemicals, etc.); do not apply paste, oil, haldi (turmeric), or raw cotton to the burn; do not apply ice because it deepens the injury; avoid prolonged cooling with water because it will lead to hypothermia; do not open blisters until topical antimicrobials can be applied, such as by a health-care provider; do not apply any material directly to the wound as it might become infected; and avoid application of topical medication until the patient has been placed under appropriate medical care [2].
\nThe person who gives first aid to the child after the burn injury is usually the person that was present during the accident—in most of cases—the parent. Unfortunately, the own results indicate that parents do not provide first aid to burned children correctly. The most common mistakes were no cooling the burn wound and no analgesics used [13].
\nThe aim of prehospital care is stabilizing ABCDEs (airway, breathing, circulation, disabilities, and environment control), preventing ongoing burn injury and provision of analgesia, covering area involved, and rapid transfer to emergency department [9].
\nIt is worth to underline that also first aid provided by medical stuff in the place of the injury is not correct. The situation seems surprising, because in Poland young doctors are trained in first aid (including first aid in burns) during studies.
\nNessler et al. conducted the pilot study (the anonymous questionnaire) among young doctors in Malopolska region (Poland) to evaluate the knowledge of burn first aid, because many patients admitted to burn centers in Poland receive inadequate treatment just after burn injury. The questionnaire verified the respondents’ knowledge about appropriate first aid provided several minutes after burn trauma and included questions about possibilities of actions after burn trauma in cases of burned patients. The obtained results were alarming, which revealed that the knowledge of burn first aid among young doctors is not satisfactory—none of the respondents answered correctly to all the questions. Only in 75% respondents knew that burn wound require cooling with running water, whereas only 25% respondents knew how to react after chemical injury [14].
\nIt seems that more attention should be paid on education of caregivers of small children and medical stuff about first aid in burns.
\nCare for burned pediatric patient is a challenge for medical and paramedical staff. Treatment of burns is multidisciplinary. According to Juan P. Barret and David N. Herndon, in the burn team, apart from surgeons who specialize in the treatment of burns (general, pediatric, and plastic surgeons), should work also nurses (experienced with care for burned patients), intensive care professionals, scrub and anesthesia nurses, case managers (acute and reconstructive), anesthesiologists, respiratory therapists, rehabilitation therapists, dietitians, psychosocial experts, social workers, volunteers, microbiologists, research personnel, quality control personnel, and workers of support services [1].
\nThe triage decision is based on the extent of burn, body surface area involved, type of burn, associated injuries, any complicating medical or social problems, and availability of ambulatory management [4].
\nIn addition to what has been mentioned above, the criteria that are taken into account to decide if the patient requires hospitalization or referral to the center of burns are anatomic location of the injury and age of the patient.
\nThe most important aspect in pediatric population is age—all the children younger than 1 year old should be hospitalized. Moreover all patients with third-degree burns should be treated in the hospital. Apart from depth of the injury, also extension of burn is taken into account. Hospitalization should be considered in children from families with lower socioeconomic status. Pediatric patients with burns on the face, hands, feet, genitalia, perineum, and joints; all patients with inhalation injuries and electrical or chemical burns; and also patients with associated injury should be hospitalized. Moreover, each patient with suspected nonaccidental injury should be admitted to the hospital. In Poland children with burns are hospitalized in departments of pediatric surgery (with personnel educated about care of burnt patients) or burn centers (children with major burns).
\nIt is possible to classify burn injury according to the severity into minor, moderate, and major [1]. Patients with moderate and major burns require hospital treatment. Minor burns are burns covering less than 15% total body surface area in adults and less than 10% total body surface area in children; less than 3% total body surface area is full-thickness burn; they do not involve the head, feet, hands, or perineum [1]. Moderate burns are burns covering 15–25% total body surface area in adults and 10–15% total body surface area in children, full-thickness burns 3–10% total body surface area, and superficial partial-thickness burns of the head, hands, feet, or perineum [1]. Each case of suspected child abuse is classified as moderate burn [1]. Moreover, in this group, all patients have burn injury and concomitant trauma, significant preexisting disease, and extreme age (neonate and infants). Major burns cover more than 25% total body surface area in adults and more than 15% total body surface area in children [1]. In this group are full-thickness burns of more than 10% total body surface area, deep burns of the head, hands, feet, and perineum, inhalation injuries, chemical burns, and electrical burns [1].
\nInitial treatment follows the ABCDEs of resuscitation. The aim is to stabilize the airway, breathing, and circulation [9].
\nAirway management should also include assessment for the presence of airway or inhalation injury [4]. In the cases of suspected airway burns, early intubation can be considered [9]. Children with stridor due to upper airway compromise also require urgent intubation [9]. Potential indications for ventilation are excessive burns that cover over 60–70% of total body surface area, full-thickness circumferential chest burns, and severe inhalation lung injury causing pulmonary edema and hypoxemia [9].
\nAll children with burns over 20% of total body surface area should have intravenous access (peripheral access through non-burnt skin is preferred) [9]. Fluid resuscitation rates should be calculated using the time of burn, patient’s body mass, and the surface of burn with the use, for example, of Parkland formula [9]. To determine the adequacy of fluid replacement, monitoring of urinary output is useful [9]. Some patients require nasogastric tube. Important issue in care of burned patient is analgesia.
\nThe treatment of burns can be conservative and operative. Fortunately, most of children do not require surgical treatment, which is reserved for patients with deep (third degree) burns. Conservative treatment is indicated in children with superficial, partial-thickness burns.
\nAmong the most often realized surgical procedures are escharotomy (rare), excision of the dead tissue, and skin grafting [1]. Escharotomy is indicated in patients with circumferential burns on the chest or limbs. The aim of escharotomy is to release the constrictive eschar. The burned skin should be released by incisions with electrocautery within the lines of escharotomy. Early excision of necrotic tissues and grafting is indicated in patients with full-thickness burns. In Poland burn wounds are covered with autografts (donor site is usually tight, less often scalp or back). Skin grafts can be split-skin grafts and full-thickness skin grafts. Most pediatric patients require split-skin grafts. Full-thickness skin grafts can be necessary in specific areas, such as the face (lips, eyelids, nose), hand/fingers, toes, and genitalia. In cases of extensive burns, it is possible to use meshed skin grafts.
\nBurn wound dressings play crucial role in the care for patient with burns. Burn dressing should protect the burn wound from further harm, such as desiccation, mechanical trauma, and infection. Moreover, they can facilitate the process of healing and relief pain [10]. The current literature is still inconclusive with regard to the gold standard burn dressing for the pediatric population [15]. In Poland burn wound is usually treated with silver sulfadiazine. However, it is commonly known that the ideal dressing for children should alleviate pain, decrease length of hospital stay, and minimize the risk of complications [15].
\nThe consequences of burns are mostly related with the loss of skin functions. The skin is the largest organ in the body and plays a crucial role in regulating body’s temperature by preventing heat loss to the environment. It also prevents water loss from the body and acts as a barrier to infective organisms [9].
\nIt is important to underline the fact that children have a greater ratio of surface area to volume of the body, increased metabolic rate, increased heat loss (less fat and shivering), and increased evaporative water loss [10].
\nPossible complications of burns include variety of problems, for example, sepsis, hypovolemia, hypothermia, carbon monoxide poisoning, cyanide poisoning, gastric ulcers, cardiac dysfunction, hypermetabolic state, renal failure, transient antidiuresis, and anemia [4]. Another possible complication is laryngeal edema that can be treated with endotracheal intubation and tracheostomy [4]. Moreover, due to edema, compartment syndrome can develop, which means that the patient requires escharotomy [4]. Escharotomy technique involves making longitudinal incisions in segments with inelastic circumferential burns, usually of full thickness [1]. Possible contractures should be treated with physical therapy. Due to the risk of psychological trauma, it is important to provide to burn patients psychological rehabilitation [4]. The possible complications from respiratory system include pulmonary infiltrates, pulmonary edema, pneumonia, and bronchospasm [4]. Inhalation injuries may result in bronchospasm, airway inflammation, and impaired pulmonary function [4]. Moreover, they can result in difficulties in eating and drinking [4].
\nAmong long-term consequences of burns in children are physical scarring and emotional impact of disfiguring burns [4].
\nThe risk of burn is the highest in children under 2 years old and in boys [5, 6]. Most of burns occur at home, when the child is under the supervision of parent. Appropriate supervision seems even more important than safe environment in prevention of burns in children [16].
\nMost of burns in children less than 2 years old occur when their mother or father is in the same room. The researchers found that family characteristics play a crucial role in increasing the likelihood of the injury. Lower maternal education, young age of mother and unemployment, and lone parenthood are identified risk factors of burns in children [17].
\nIt is worth to underline that economic situation of the family is also important, because differences in the income result in differences in living conditions. The home environment plays an important role in the risk of burn injury among children.
\nAmong effective strategies that reduce number of flame burns in pediatric population are installation of smoke alarms and smoke detectors [16].
\nAccording to the WHO, the possible modifications of the environment that can reduce the number of thermal injuries among children are improved heating and lighting equipment at homes [16].
\nThe own review of the studies about environmental risk factors of burns in children indicates that effective strategy in prevention of scalds in pediatric population is lowering the temperature in the water heaters [17]. Moreover, several studies identified the lack of hot water supply in the household as a risk factor of scalds in children [17].
\nThe arrangement of the apartment that decreases the likelihood of childhood injury includes limited access to the cooking area (and hot fluids). The own review of the studies about environmental risk factors of burns in children indicates that most burn accidents occur in the kitchen [17]. Kitchen without door was found to increase risk of burn injury [17]. The WHO also pays attention to the arrangement of the apartment and separation of cooking area from living area [16].
\nBurns are preventable, so prevention strategies should address the hazards for specific burn injuries, education for vulnerable populations and training of communities in first aid. According to the European Report on Child Injury Prevention, there are many cost-effective strategies to prevent burns in children, for example, combination of approaches—involving legislation, engineering, environmental modification, and education [16].
\nSimple changes in the children’s environment and increasing awareness of caregivers can lead to decrease in the number of this type of injuries.
\nTo sum up, burns are injuries that affect approximately 1% of all children per year. Their consequences can have physical and mental dimension. Serious burns can lead to death.
\nMost of these injuries are preventable. Simple changes in the children’s environment and increasing awareness of caregivers can lead to decrease in the number of burns in children. Moreover, the first aid given to burn children soon after the injury usually is not adequate (no cooling thermal burns and no analgesia). It is important to underline that also medical staff is not always well educated in providing first aid to burned patients.
\nThus, education (medical stuff, paramedical stuff, and caregivers) about first aid in burns and increasing awareness of caregivers about the unsafe behaviors (such as leaving the mug with hot tea at the edge of the table, where the child can easily reach), avoiding the situations that puts child at risk of burn, seems to be one of the most important parts of prevention.
\nMoreover, legislation interventions such as laws to enforce smoke detectors, smoke alarms installation, or regulation of hot water at homes are promising strategies to reduce the number of burned children.
\nHealth improvement can be also obtained by reducing number of pediatric patients with burns, correct first aid given after the injury, and organization of specialized health-care centers and rehabilitation services for victims of burns.
\nI confirm there are no conflicts of interest.
The molecular machines of the cell, i.e., proteins, are essential to many cellular processes such as signal transduction and cell regulation. Proteins seldom act alone in the cell, but they function through interacting with other small or macromolecules. Therefore, understanding protein interactions at the atomic level is critical to understanding biological processes [1]. Primary structure, i.e., amino acid sequence, of the interacting proteins is a necessary but insufficient source of information at the atomic level. After being synthesized, proteins fold and acquire a stable native structure, i.e., tertiary structure that can be defined in a three-dimensional (3D) plane in order to be functional. It is known that proteins with different sequence information can have similar functional structures, that is, different amino acid sequences can show similar folding trends in 3D space and structure is more conserved than sequence [2]. Therefore, it is crucial to understand the interaction details at the structural level. Proteins physically interact with their partners via non-covalent associations, namely H-bond, hydrophobic, and electrostatic interactions, with the exception of covalent disulfide bridges. These intermolecular physical forces also dominate the protein folding process.
The 3D structure of the macromolecules can be determined using the experimental methods such as X-ray crystallography, nuclear magnetic resonance (NMR), and cryo-EM and then deposited in the Protein Data Bank (PDB) (https://www.rcsb.org). However, there is a huge gap between the number of known protein sequences and structures [3, 4]. Computational modeling approaches that can predict 3D structures of macromolecules can help to bridge this gap. A recent machine learning algorithm developed by DeepMind, called AlphaFold [5], can predict 3D structures of proteins using the sequence information with high accuracy and has been accepted as a breakthrough in the structural biology field. In 1 year, approximately 1 million new structures have been predicted and deposited at AlphaFold Protein Structure Database (https://alphafold.ebi.ac.uk/). In order to have a complete understanding of the proteome, computational techniques are not only needed for modeling single protein structures, but also the interactions between them.
Molecular docking is a method used to predict the structures of proteins in complex with other proteins, nucleic acids, or small molecules. It can be defined as predicting the appropriate low-energy binding pose of the ligand in complex with the target structure, by randomly colliding proteins and their potential partners in space, first creating a rigid complex structure model, and then focusing on the binding sites of that model with flexible interface refinement [6]. Energy minimization of randomly docked conformations in space requires a multidimensional calculation. Initially developed molecular docking method was treating ligands and receptors as rigid bodies without considering any conformational changes [7]. However, interactions between proteins can become quite complex even with small changes in the conformation of the structures [7], and docking algorithms may not physically solve this complex problem correctly [8]. The main factor that creates computational difficulties in docking algorithms is when the protein backbone changes its conformation significantly upon binding [9, 10]. To address this problem, different techniques that consider backbone flexibility have been successfully implemented in docking algorithms [10].
Many diseases today, such as cancer, are likely to be linked to problems in protein-protein interactions and targeting them can therefore enable the development of next-generation therapeutic methods [11]. Modeling the complex structures formed by proteins with other proteins or small molecules holds the key to understand many biological processes such that modeling enzyme-substrate or protein-drug interactions can reveal insights into binding sites/interface regions, function, and mechanism of action. The main protein–small-molecule docking applications in drug discovery include drug repositioning, structure- and ligand-based (pharmacophore−/shape-based) drug design approaches using virtual and reverse screening [11, 12, 13, 14]. Today, with the continuously developing technology; targeted drug design, drug target search, evaluation of the side effects of existing drugs, or finding new targets for these drugs can be achieved with the help of molecular modeling and machine learning methods [12]. Deep learning neural network models have strong computational ability on big data and attract attention in structural biology field [15]. There are antibiotic discovery studies using deep neural networks [16] and deep learning studies adapted to drug design [17].
In this chapter, we focus on the protein–small-molecule docking fundamentals and the steps of the docking algorithm and procedure in detail. We then give recent successful applications in drug design and discovery that use different docking approaches, namely virtual screening, reverse screening, and machine learning. Lastly, we comparatively analyze some of the available protein–small-molecule docking tools using the structure of SARS-CoV-2 main protease in complex with a non-covalent inhibitor Jun8-76-3A as a case study.
Protein–small-molecule interactions are essential for the sustainability of biological processes such as enzymatic catalysis and overall homeostasis in the body [18]. The engineering of protein–small-molecule interactions is one of the computational approaches used to solve critical problems in biology [18]. protein–small-molecule docking, i.e., modeling the interaction between chemical compounds and their target protein receptors at the atomic level, is an effective tool in drug design. In the structure-based design of small-molecule drugs, a good estimation of the binding pose is required to clearly demonstrate important interactions and design drugs with increased selectivity and efficacy [19]. The procedures that can be followed and the tools that can be used before, during, and after molecular docking are explained in the following subsections and summarized in Figure 1.
The procedures that can be followed and the tools that can be used before, during, and after protein-ligand molecular docking in drug design.
Before starting the docking studies, first of all, the most suitable protein and ligand structures should be selected [20]. There are databases to access the experimentally determined structures of target proteins such as PDB, Uniprot, and Therapeutic Target Database (TTD). If the experimental structure is not available, modeled structures can be obtained from AlphaFold Database or can be modeled using relevant structure modeling software. The most frequently used databases for getting the small-molecule ligand/chemical structures are: DrugBank [21], PubChem [22], ZINC [23], ChEMBL [24], and Chemspider [25] (Figure 1). DrugBank, Chemspider, and ZINC databases include more than 500,000, 100 million, and 230 million compounds/drug molecules, respectively.
The molecular docking algorithms may require preliminary preparation of the structures that are obtained in PDB format (lacking H atoms). There are tools available for such preliminary preparations such as Open Babel [26] and AutoDockTools (Figure 1) [27].
It is also of crucial importance to guide docking with preliminary information on the binding site. Otherwise, there are no binding site constraints, blind docking takes place, and it is more difficult to detect the correct binding poses when the ligand search space is large. There are various guiding algorithms for active site prediction that can be used when binding sites are not known. Some of them can be listed as: GRID [28], SurfNet [29], COACH [30], SCFbio [31], CASTp [32], DeepSite [33], and PUResNet (Figure 1) [34].
The capabilities of docking algorithms can differ from each other, and in this respect, it is important to carefully choose the algorithm to use in accordance with the purpose of the study before starting the docking.
There are many approaches and algorithms for molecular docking, based on different parameters, and they aim to perform the protein-ligand docking with the best performance [12]. The steps of molecular docking algorithms can be summarized as follows: molecule flexibility, conformational search algorithms (ligand sampling), and scoring functions (Figure 2) [12, 35].
Methods for protein-ligand molecular docking.
During molecular docking, structures can be considered rigid or flexible. Rigid docking takes into account only the translation and rotation degrees of freedom. Providing flexibility means also considering the rotation about single bonds so that they have the same bond lengths and angles but different torsion angles. Although flexible docking approach is more realistic than rigid docking, when there are many rotatable bonds, the ligand conformational search space becomes so large that it is difficult to find the correct binding pose with the lowest binding free energy (global minimum solution). Some algorithms, such as HADDOCK [36], first treat the structures as rigid to increase time efficiency and then perform flexibility improvements on the poses of molecules with the best energy scores. Molecular docking software can be grouped according to the flexibility treatments of molecules such as Rigid Docking, Semi-Flexible Docking, and Soft Docking [35, 37].
In rigid docking, protein and ligand molecules are treated as rigid entities [37, 38]. During docking, the positions of the molecules change without losing their shape [37], i.e., only translation and rotation but no conformational degrees of freedom are considered.
Semi-flexible docking is based on the principle of keeping the protein structure rigid and letting the ligand structure be flexible by allowing rotatable bonds. Thus, various conformational poses of the ligand on the protein are sampled [35, 37, 38]. It gives more accurate results than rigid docking [37].
In soft docking, van der Waals interactions between atoms are softened, making the structures of both receptor and ligand molecules implicitly flexible as overlap is allowed to a small extent [39, 40]. Soft docking process is carried out realistically by ensuring that both the protein and the ligand are rotatable as in their natural states [37, 38]. It is an advantageous method due to its computational efficiency and ease of application [35, 37].
Conformational search algorithms can identify different conformational orientations (poses) of the ligand sampled around the experimentally determined active site or other binding sites on the protein [35, 41, 42]. These algorithms are generally classified as: shape matching, systematic, stochastic, and simulation methods [35, 38, 43].
Shape matching algorithms have the advantage of speed over other algorithms [35, 44] and adopt a sampling principle in which the conformation of the ligand should be structurally complementary to the protein binding site [38]. It ensures that the ligand is positioned in such a way that best complements the molecular surface of the binding site on the protein [35]. Some example software using shape matching are: DOCK [45], FLOG [46], EUDOC [47], Surflex [48], LibDOCK [49], SANDOCK [50], and MDock [51].
Using systematic search algorithms, a large number of possible binding poses can be obtained by gradually changing the degrees of freedom of the ligands [35, 52] toward the direction of minimum energy. Systematic search algorithms can be divided into two as exhaustive search and fragmentation (incremental structure) [35, 41, 53]. Exhaustive search algorithm is based on systematically generating flexible ligand conformations by rotating the rotatable bonds in the ligand [35]. If the number of rotatable bonds is large, there is a combinatorial explosion in the number of poses, i.e., the search space, so that some filtering and optimization procedures are applied for practical purposes [35]. Glide [54] and FRED [55] are example docking software using exhaustive conformational search algorithms. In the fragmentation method, the ligand is divided into smaller fragments, each fragment is placed and augmented at the binding site gradually through covalent bonding to the previous one [35]. DOCK [56], LUDI [57], FlexX [58], and eHiTs [59] are example software using fragmentation.
The algorithms used in stochastic search methods are more efficient but do not guarantee an accurate result as they are based on generating random ligand conformations, and therefore, the docking process is iterative in these algorithms [41, 44]. Monte Carlo, swarm optimization, evolutionary algorithms, and Tabu search methods are among the most used stochastic algorithms [35, 38, 52]. Example software using stochastic conformational search method include AutoDock [60], GOLD [61], DockThor [62], and MolDock [63].
Simulations of the obtained ligand poses (simulation methods) represent protein and ligand flexibility better than the other algorithms but have a slow flow and can make insufficient sampling [38, 44]. For this reason, they are used as a complement to other conformational search methods [38].
In the previously described conformational search step, many structures are created and most of them should be eliminated by selecting the biologically appropriate structures. Therefore, the possible poses created by conformational search algorithms are evaluated and ranked by using a scoring function [35]. The scoring function is a measure to evaluate the docking poses obtained [35, 38, 52] in terms of their binding free energies [11, 44, 64].
With the scoring functions that estimate the binding energies of the created complex structures, various physicochemical properties should be evaluated in order to distinguish good results from the bad ones. These physicochemical properties can be intermolecular interactions, desolvation from solvent, electrostatic and entropic effects, etc. [65]. As the number of evaluated parameters increases, the accuracy of the scoring function will increase; but the computational load will also increase. Therefore, scoring functions with ideal efficiency, especially when working with large ligand sets, are those that are balanced in terms of accuracy and speed [11]. The scoring functions can be classified as: force-field-based, empirical, knowledge-based, and consensus scoring.
The Force Field Scoring Function (FFSF) is designed to work with multiple force fields such as AMBER [66], CHARMM [67], GROMOS [68], and OPLS [69] individually or in combination. The designed FFSFs estimate the free energy of ligand binding by considering van der Waals energy terms such as electrostatic interactions and hydrogen bonds [35, 38].
Empirical scoring functions use simpler energy terms to estimate the free energy of ligand binding such as hydrogen bonds and ionic interaction, and they can be calculated more easily and faster than FFSFs [35, 38, 52]. Some examples of empirical scoring functions are GlideScore [54], PLP [70], LigScore [71], LUDI [72], SCORE [73], and X-Score [74].
Knowledge-based scoring functions use statistical analysis of protein-ligand complex structures to derive protein-ligand distance [44]. These functions can show high performance in a short time [52]. They can also model some uncommon interactions, such as sulfur-aromatic, that other functions do not address [44].
Consensus scoring function, not a specific scoring system, aims at an effective scoring with a combination of multiple scoring functions with the idea of minimizing the possible error margins of existing scoring systems [35, 38, 44].
After performing protein-ligand docking studies, the accuracy of pose estimations needs to be evaluated [41, 52]. The best way to evaluate the docking algorithm is to compare the predicted binding pose of the ligand with position of the reference ligand in the experimentally determined structure, if possible. The structural comparison is quantified by using root mean squared deviation (RMSD) (Eq. 1), with the unit of Å [41, 75]. It is preferred that this value is between 2 and 4 Å or less for a good docking. RMSD calculations are simple, but this metric is not normalized to number of atoms and therefore should not be considered as an absolute measure [76]. As a more systematic approach, in order to ensure the consistency of the docking algorithm used, it should be checked whether the same poses are obtained by repeating the docking process [52] at least 50 times and clustering the poses of the side chains and references according to a certain threshold value [77]. With this method, whether the docking algorithm correctly and consistently creates a pose in the right position can be determined [41, 44, 78].
Eq. (1) Root mean squared deviation for the coordinates of two molecules, a and b, with N atoms.
Modeling successes and capabilities of docking algorithms are being evaluated in a competition called CAPRI (Critical Assessment of Protein Interactions) (https://www.capri-docking.org/) since 2001 [79, 80]. Experimentally determined complex structures that have not yet been published in PDB are submitted to CAPRI and without knowing the experimental structure of the complex, the participants try to predict the most similar structure to the experimentally determined complex structure through docking algorithms [79]. A solution set of 10 models is presented to the CAPRI committee for evaluation based on the geometry similarity and biological relevance of the predicted complex structures. The results of CAPRI show very good predictions for easy targets with simple conformational changes, but rather worse ones for difficult targets with conformational changes upon binding [9].
Computational methods have become an important part of the drug discovery process with increasing accuracy of algorithms. Various docking methods based on different algorithms are constantly being developed to determine the structural relationships of potential drug molecules and their targets [44]. In addition, studies in this area shed light on the candidate drugs in terms of the pharmacodynamic properties, affinity, and selectivity [11]. The main molecular docking applications in drug discovery include drug repositioning (repurposing), structure- and ligand-based drug design approaches using virtual and reverse screening [11, 12, 13, 14].
Drug repositioning seeks out new targets for natural compounds, drugs currently in use, or candidate ligands to reveal their unknown therapeutic potentials [81]. Many successful repositioning studies are available in the literature [81, 82, 83]. Virtual screening (VS) and reverse screening (RS) techniques are frequently used in drug discovery and repositioning. VS offers a more effective and rational approach compared with traditional methods [36]. The atomic-level analyzable results presented to us by virtual screening studies guide us in understanding the function of the target and in new drug discoveries [5, 36, 55]. In the RS approach, interest is on a single ligand molecule, and there is a search for a biological target for this molecule [12]. Unlike virtual screening (VS), the search library consists of potential target receptors. RS approach has the potential to lead studies such as testing toxicity or side effects of the existing drugs [38]. The potential side effects of a drug need to be evaluated in the drug discovery process. Molecular docking studies can offer an important perspective in this regard, and there are inverse (reverse) docking studies that provide bioactivity data by detecting off-target bindings [25]. Lastly, the subclasses of Artificial Intelligence (AI): Machine Learning (ML) and Deep Learning (DL) methods have significant contributions in pharmaceutical industry [84]. AI can be applied to different steps such as drug design with VS,
Virtual screening (VS) approach uses a target receptor and a library of small molecules. Libraries can be created manually, or already existing libraries can be used. The library consists of a large number of chemically diverse bioactive small molecules with a high probability of binding to the receptor. This virtual computing technique is considered as the
Ligand-based VS methods conduct research by identifying common properties of compound sequences, such as molecular volume and protonation state [11]. In addition to chemical similarity [88] and rule-based [89] software included in filtration strategies, there are also various software such as freely add-on pharmacophore and quantitative structure-activity relationship (QSAR) models [87, 90]. The most commonly used ligand-based virtual screening method is the QSAR method. Ligand-based VS does not contain structural information about the receptor, it only scans using receptor sites known to be active and tries to detect active ligand molecules [85].
Structure-based VS methods are often used when the receptor has different conformations. The aim is to predict receptor binding affinity by processing structural information using a variety of techniques, such as binding site similarity and pharmacophore mapping. By estimating the different binding modes, the molecules are sorted for evaluation [11]. Analysis of the predicted poses can be done manually using visualization programs. It has been reported that nAPOLI, a web server developed in recent years, analyzes results automatically [91].
Structure-based pharmacophore generation is one of the most frequently used methods for small molecules in the virtual screening method. Here, 3D pharmacophore model interfaces of the scaffolds of the ligands are created, and ligands that will adapt to the binding site and provide the desired bioactivity are selected. Some of the programs that use pharmacophore modeling are HipHop [92], PHASE [93], MOE, which are commercial, SCAMPI [94], PharmaGist [95], ALADDIN [96], which are suitable for academic use.
A recent example of VS application on the non-structural protein of SARS-CoV-2, nsp1, one of the virulence factors causing viral infection, is by G. O. Timo
Reverse screening (RS) is also called inverse docking, reverse docking, inverse virtual screening, or target screening. Libraries are more limited for target hunting and profiling [12] and can be created manually using the most common accessible databases such as PDB [98] and TTD [12, 99]. But this process requires a long preparation time and effort. There are various algorithms used to detect interactions by reverse screening. Some web platforms (INVDOCK [100], idTarget [101], ACTP [102], etc.) have been developed for reverse docking, which use libraries prepared for specific diseases and docked using programs such as standard AutoDock and AutoDock Vina [12].
A recently developed Consensus Reverse Docking System (CRDS) detects potential binding sites by screening approximately 5200 candidate proteins for the ligand molecule using three different scoring methods [103]. In another example, Stepanova
Machine learning techniques take information from biological data and make predictions about them, thus contributing to building a structural model [9]. Once a model is built, it must be improved so that the state with the lowest potential energy (global minimum) can be reached. Global minimum means a stable and sterically acceptable structure, and reaching it without being stuck at the local minima is very important in the field of bioinformatics and computational structural biology. A recent machine learning algorithm developed by DeepMind, called AlphaFold [5], implements deep learning and can predict 3D structures of proteins using the sequence information with high accuracy and has been accepted as a breakthrough in the structural biology field.
Machine learning makes classifications by learning on datasets and needs human intervention to evaluate possible outcomes. Deep learning is a more advanced model having the neural network with ability to decide the right result without human intervention (Figure 3). Machine learning can use supervised or unsupervised learning. Supervised learning performs machine learning on datasets that we know about, whereas unsupervised learning detects and labels similarities and orientations in a created cluster [38, 90].
Schematic illustration of artificial intelligence subfields: Machine learning and deep learning.
The training set used in machine learning constitutes the performance of the algorithm. Machine learning studies in the field of virtual screening are generally focused on improving the performance of the scoring function [85]. Studies have shown that working with small subsets of the same family, which consists of similar structures, gives better scoring results rather than working with large data from different complexes [105]. Working with subsets of interest is also a better approach in terms of computational requirements [38].
Machine learning and deep learning can describe more diverse data than other computational systems and can be representative of structural biology. Nonparametric machine learning has great potential to be the next step in computer-based programming to improve the accuracy of molecular docking studies [41]. Machine learning can be used to refine predetermined function data as well as provide high-quality data to complement pharmaceutical discovery research and development.
As a case study for comparing different protein-ligand docking tools, the crystal structure of the SARS-CoV-2 (COVID-19) main protease in complex with its non-covalent inhibitor Jun8-76-3A (PDB ID: 7KX5) is used as the experimental reference structure to evaluate the accuracies of the complex structures predicted using AutoDock Vina, HADDOCK, and SwissDock programs and changing some of the parameters to test their effects on prediction capabilities. The inhibitor in the experimental protein structure is removed and then molecular docking is performed using the initial coordinates of the main protease structure of SARS-CoV-2 and its inhibitor Jun8-76-3A, separately.
AutoDock is a free software that predicts the binding compatibility of small ligands to macromolecule targets with a flexible-rigid (semi-flexible) docking approach [27]. It uses a grid-based method to place the ligand in the active region determined on the macromolecule [106]. AutoDockTools (http://mgltools.scripps.edu/downloads) is the user interface to produce and examine grid information required for the preparation of the protein and ligand structures in the relevant format and the configuration file [27].
As a docking input in AutoDock Vina, a configuration file, which contains the coordinate information of the protein and ligand structures and the ligand-binding region on the receptor, is required. For docking the case study ligand to the receptor using AutoDock Vina, the structure file was downloaded from RCSB PDB database (https://www.rcsb.org) in .pdb format (PDB ID:7KX5). AutoDockTools (v1.5.6) interface was used to prepare input files, such that, water molecules in the relevant protein structure were deleted, polar H bonds were added to the structure and both the receptor and ligand structures were saved in .pdbqt file format. After preparing the ligand and protein structures, the most important input information for AutoDock is the docking parameter. The docking parameter involves determining the coordinates of the ligand-binding region on the target protein. While determining the docking parameter, if the binding region on the protein is not known, blind docking can be performed by putting the whole protein in the grid box (Figure 4A), or a small grid box can be placed in the specific known/predicted ligand-binding region on the protein (Figure 4B). Lastly, after determining the region on the protein where the ligand is to be bound by using the “grid box” in AutoDockTools, the protein coordinates were specified in the input configuration file. Preparing all the required inputs, docking was performed using AutoDock Vina by repeating each docking process three times in order to observe the consistency of the algorithm (Table 1).
Grid box usage in docking: (A) blind docking with a grid box of size:
Mode | Specific docking | Blind docking | ||||||
---|---|---|---|---|---|---|---|---|
Affinity (kcal/mol) | Affinity (kcal/mol) | |||||||
Rep1 | Rep 2 | Rep 3 | AVG | Rep1 | Rep2 | Rep3 | AVG | |
1 | −8.9 | −8.8 | −8.9 | −8.9 | −8.9 | −8.9 | −9.0 | −8.9 |
2 | −7.3 | −8.7 | −7.3 | −7.8 | −8.2 | −8.2 | −8.3 | −8.2 |
3 | −7.2 | −7.2 | −7.3 | −7.2 | −8.1 | −8.0 | −8.1 | −8.1 |
4 | −6.8 | −7.0 | −7.0 | −6.9 | −7.9 | −7.8 | −8.0 | −7.9 |
5 | −6.8 | −6.9 | −7.0 | −6.9 | −7.9 | −7.5 | −8.0 | −7.8 |
6 | −6.8 | −6.8 | −6.9 | −6.8 | −7.7 | −7.4 | −7.8 | −7.6 |
7 | −6.7 | −6.5 | −6.8 | −6.7 | −7.7 | −7.4 | −7.8 | −7.6 |
8 | −6.4 | −6.4 | −6.8 | −6.5 | −7.6 | −7.2 | −7.6 | −7.5 |
9 | −6.3 | −6.4 | −6.7 | −6.4 | −7.5 | −6.9 | −7.4 | −7.3 |
Specific and blind docking studies with AutoDock were repeated three times.
In order to examine the accuracy of the docking results, the poses obtained from AutoDock Vina were aligned with the original PDB structure by using the PyMol program [107]. When the energies of the poses predicted with specific docking (i.e., using specific grid on the binding site) and blind docking are compared, although the energy scores of the blind docking results are better, the comparison of the poses with the reference ligand shows that the most accurate binding is achieved with specific docking (Figure 5). Alignment of the first poses (with the lowest energy score) predicted with specific docking (green) and blind docking studies (blue) with the reference ligand (red) shows that the specific docking pose was in a more similar position with the reference ligand (green vs. red), than the blind docking pose (blue vs. red).
Crystal SARS-CoV-2 main protease structure (white, PDB ID: 7KX5_chain (A) in complex with the blind docking (blue), specific docking (green) poses predicted with AutoDock Vina and the reference ligand Jun8-76-3A inhibitor (red, PDB ID: 7KX5_chain B). This figure was drawn with PyMol 2.5.2.
An integrative platform called High Ambiguity-Driven biomolecular DOCKing (HADDOCK) is used for molecular docking of two or more molecules [108] and is a popular algorithm [36]. Although it is mainly suitable for protein-protein interactions, it can also be applied to model the protein–small-molecule complexes [109]. HADDOCK automatically decides the most suitable configuration of the ligand according to the given restrictions [108]. Protein-protein docking is more complex than protein–small-molecule docking, as the proteins are flexible and the conformational space is larger [110].
HADDOCK does not require CPU and allows the user to see all the docking steps from start to finish. It should be noted that the success of HADDOCK studies is directly related with the amount of data entered into the system [36]. HADDOCK allows processing different types of molecules with the help of different platforms such as WHATIF, ProDRG, PDB. There is no need to create different conformer sequences as the system selects the most compatible conformers based on the shape constraints. With restriction files, we can set clear target sites, binding distances, or select active or passive residues (areas that are likely to interact). Defining semi-flexible regions is also allowed.
HADDOCK algorithm consists of three stages: rigid-body minimization and randomization of orientations (it0), semi-flexible simulated annealing in torsion angle space (it1), and refinement in 3D space with explicit solvent (water) (https://www.bonvinlab.org/education/HADDOCK-protein-protein-basic/). it0 stage treats structures as rigid solids and 1000 poses with the best score are selected. it1 optimizes orientations by allowing different docking poses from it0 to have different flexible regions defined. Two-hundred models with the best energy pass to the final stage. In the final step, a complex solvent medium (DMSO or water) is considered to improve the interaction energy and the final models are automatically aggregated.
To dock the case study inhibitor-protein complex (PDB ID:7XK5), the guideline tutorial (HADDOCK small-molecule binding site screening protocol) [111] was followed and two different approaches were tested: (i) using an unambiguous (distance) restraint file, indicating the target that should bind the ligand, (ii) by defining the active and passive residues. This case study consists of a pre-docking for the detection of the binding region and a second docking for the detection of binding pose.
First, we tested HADDOCK’s accuracy of binding site detection. Two different binding sites were detected in the top 10 clusters with the best energy scores and 70% (7 out of 10) of the clusters were in the correct binding site (Figure 6A). Secondly, an ambiguous and unambiguous restraint file was created by identifying the region with the highest number of interactions between the ligand and the receptor. The restraint files can be created manually or using the link in the protocol. However, it may be necessary to make corrections in the distance restraints. The structure with the best energy is visualized in Figure 6B. Secondly, active and passive residues were defined on the system, and the pose with the best energy result is visualized in Figure 6C. HADDOCK results are summarized in Table 2.
Crystal SARS-CoV-2 main protease structure (gray, PDB ID: 7KX5_chain (A) in complex with the docking poses (blue) predicted with HADDOCK and reference ligand Jun8-76-3A inhibitor (red, PDB ID: 7KX5_chain B). A. Top 10 clusters for binding site determination. B. Pose with the best energy using ambiguous/unambiguous restraints.
Binding site detection | Ambiguous/Unambiguous restraints | Active/passive restraints | |
---|---|---|---|
HADDOCK score | −53.4 ± 1.5 | −52.1 ± 0.5 | −21.9 ± 2.7 |
Cluster size | 69 | 5 | 13 |
RMSD from the overall lowest-energy structure | 0.3 ± 0.2 | 0.1 ± 0.1 | 0.2 ± 0.0 |
Van der Waals energy | −40.3 ± 1.2 | −41.6 ± 0.2 | −32.4 ± 4.5 |
Electrostatic energy | −22.1 ± 1.9 | −15.2 ± 6.0 | −25.8 ± 7.3 |
Desolvation energy | −10.9 ± 2.5 | −9.0 ± 0.2 | −6.7 ± 0.3 |
Restraints violation energy | 0.0 ± 0.00 | 0.7 ± 0.2 | 198.5 ± 78.0 |
Buried Surface Area | 795.4 ± 21.9 | 781.6 ± 5.2 | 783.0 ± 9.4 |
Z-Score | −1.7 | −2.4 | −1.3 |
HADDOCK results.
Comparison of the results shows that HADDOCK is successful in detecting the binding site. However, according to the results obtained in the second stage, the algorithm was not successful enough to find the correct conformation of the ligand in binding site. Defining ambiguous/unambiguous restraint files or selecting active and passive residues did not make a significant contribution in detecting the correct binding pose (Figure 6B and C). Docking with both approaches was repeated several times and no significant similarity was detected.
SwissDock is a database to improve protein–small-molecule docking using amino acid sequence information from genome projects. Moreover, it is a web browser and programmatic interface that enables creating three-dimensional protein models from protein amino acid sequences [112]. It also has user interfaces such as Swiss-Pdb Viewer (DeepView) to simultaneously analyze several proteins [113]. Using the SwissDock web server, the starting crystal structures of the target proteins can be searched and fetched from protein and ligand structure databases. If there is no crystal structure available to compare, it provides homology modeling of the studied protein. During the docking process, the user does not have to do any calculations because all calculations are handled by the server side [112]. As a docking constraint, the ligand binding region can be defined or blind docking can be applied with no information.
Using the case study, both specific and blind dockings were performed on the SwissDock server, and the results were compared. The server presented 256 poses. The best scores obtained by specific docking (green) blind docking (blue) were −9.88 and −9.35 kcal/mol, respectively (Figure 7). Although both of the predicted poses did not show the same conformation with the reference ligand, it was observed that the pose obtained from the specific docking (green) was more similar to the reference ligand (red) (Figure 7).
Crystal SARS-CoV-2 main protease structure (white, PDB ID: 7KX5_chain (A) in complex with the blind docking (blue), specific docking (green) poses predicted by SwissDock and the reference ligand Jun8-76-3A inhibitor (red, PDB ID: 7KX5_chain B). This figure was drawn with PyMol 2.5.2.
Molecular docking is a computational method that predicts the 3D structures of receptor-ligand complexes. Modeling the atomic details of the ligand pose with the receptor protein by molecular docking can assist in understanding protein structure-function relationship and in drug design studies in several ways. Computational modeling approaches complement and/or lead experiments by eliminating irrelevant drug candidates and selecting the ones with the best binding properties. With the continuously developing technology, there are many different approaches and algorithms for molecular docking studies, and they are successfully used in therapeutic applications such as targeted drug design, drug target search, evaluation of the side effects of existing drugs, or finding new targets for these drugs.
The crystal structure of the SARS-CoV-2 (COVID-19) main protease in complex with its non-covalent inhibitor Jun8-76-3A (PDB ID: 7KX5) was used as an experimental reference case study to compare and evaluate the prediction accuracies of AutoDock Vina, HADDOCK, and SwissDock programs as well as to test the effects of some parameters on their prediction capabilities. One of the main observations is that the ligand poses with the lowest binding energy scores are not necessarily the best solution. Therefore, docking results should always be evaluated in terms of biological relevance. Moreover, when
In summary, before starting the molecular docking, it is of crucial importance to obtain detailed information on the target protein and ligand from various sources and servers and to decide which docking algorithm to use. Moreover, the top predicted poses with the best scores should not be unquestioningly accepted as the best solutions but further structural analyses and evaluations should be incorporated in the decision process.
We would like to thank dear Merve DEMİR AKYÜZ and Merve YÜCETÜRK (a.k.a Merves), who are fourth-year undergraduate students at Molecular Biology and Genetics Department of Istanbul Medeniyet University, for their contribution to the writing of the introduction section.
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Reynolds and Steven M. Day",coverURL:"https://cdn.intechopen.com/books/images_new/7904.jpg",editedByType:"Edited by",editors:[{id:"220737",title:"Dr.",name:"Robert",middleName:null,surname:"J. Reynolds",slug:"robert-j.-reynolds",fullName:"Robert J. 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Everyone must undergo this phase of life at his or her own time and pace. In the broader sense, ageing reflects all the changes taking place over the course of life. These changes start from birth—one grows, develops and attains maturity. To the young, ageing is exciting. Middle age is the time when people notice the age-related changes like greying of hair, wrinkled skin and a fair amount of physical decline. Even the healthiest, aesthetically fit cannot escape these changes. Slow and steady physical impairment and functional disability are noticed resulting in increased dependency in the period of old age. According to World Health Organization, ageing is a course of biological reality which starts at conception and ends with death. It has its own dynamics, much beyond human control. However, this process of ageing is also subject to the constructions by which each society makes sense of old age. In most of the developed countries, the age of 60 is considered equivalent to retirement age and it is said to be the beginning of old age. In this chapter, you understand the details of ageing processes and associated physiological changes.",book:{id:"6381",slug:"gerontology",title:"Gerontology",fullTitle:"Gerontology"},signatures:"Shilpa Amarya, Kalyani Singh and Manisha Sabharwal",authors:[{id:"226573",title:"Ph.D.",name:"Shilpa",middleName:null,surname:"Amarya",slug:"shilpa-amarya",fullName:"Shilpa Amarya"},{id:"226593",title:"Dr.",name:"Kalyani",middleName:null,surname:"Singh",slug:"kalyani-singh",fullName:"Kalyani Singh"},{id:"243264",title:"Dr.",name:"Manisha",middleName:null,surname:"Sabharwal",slug:"manisha-sabharwal",fullName:"Manisha Sabharwal"}]},{id:"55388",doi:"10.5772/intechopen.68944",title:"Beauty, Body Image, and the Media",slug:"beauty-body-image-and-the-media",totalDownloads:7768,totalCrossrefCites:5,totalDimensionsCites:12,abstract:"This chapter analyses the role of the mass media in people’s perceptions of beauty. We summarize the research literature on the mass media, both traditional media and online social media, and how they appear to interact with psychological factors to impact appearance concerns and body image disturbances. There is a strong support for the idea that traditional forms of media (e.g. magazines and music videos) affect perceptions of beauty and appearance concerns by leading women to internalize a very slender body type as ideal or beautiful. Rather than simply being passive recipients of unrealistic beauty ideals communicated to them via the media, a great number of individuals actually seek out idealized images in the media. Finally, we review what is known about the role of social media in impacting society’s perception of beauty and notions of idealized physical forms. Social media are more interactive than traditional media and the effects of self‐presentation strategies on perceptions of beauty have just begun to be studied. This is an emerging area of research that is of high relevance to researchers and clinicians interested in body image and appearance concerns.",book:{id:"5925",slug:"perception-of-beauty",title:"Perception of Beauty",fullTitle:"Perception of Beauty"},signatures:"Jennifer S. Mills, Amy Shannon and Jacqueline Hogue",authors:[{id:"202110",title:"Dr.",name:"Jennifer S.",middleName:null,surname:"Mills",slug:"jennifer-s.-mills",fullName:"Jennifer S. Mills"}]},{id:"59227",doi:"10.5772/intechopen.73385",title:"Differentiating Normal Cognitive Aging from Cognitive Impairment No Dementia: A Focus on Constructive and Visuospatial Abilities",slug:"differentiating-normal-cognitive-aging-from-cognitive-impairment-no-dementia-a-focus-on-constructive",totalDownloads:1353,totalCrossrefCites:3,totalDimensionsCites:6,abstract:"Constructive and visuospatial abilities in normal and in pathological aging (cognitive impairment, no dementia, CIND) are investigated. The sample includes 188 participants over 60 years of age, divided in 2 groups: healthy subjects (MMSE ≥28), without cognitive complaints, and individuals with CIND (MMSE between 24 and 27 and subjective cognitive complains). Drawing of cube and drawing of house, Benton Visual Retention Test (BVRT), and Block design are used to test the hypothesis that short visuoconstructive and visuospatial tests can distinguish normal from pathological cognitive aging in its very early stages. Results proved the discriminative sensitivity of BVRT general assessment criteria and of omissions and distortions in CIND. The diagnostic sensitivity of a modification of Moore and Wike [1984] scoring system for house and cube drawing tasks was confirmed as well. Drawing of cube and house could be used for quick screening of CIND in subjects over 60. Principal component analysis with oblimin rotation was performed to explore the different dimensions in the visuospatial and visuoconstructive abilities in old age. A four-factor structure was established, all four factors explaining 71% of the variance.",book:{id:"6381",slug:"gerontology",title:"Gerontology",fullTitle:"Gerontology"},signatures:"Radka Ivanova Massaldjieva",authors:[{id:"75907",title:"Associate Prof.",name:"Radka Ivanova",middleName:null,surname:"Massaldjieva",slug:"radka-ivanova-massaldjieva",fullName:"Radka Ivanova Massaldjieva"}]},{id:"59658",doi:"10.5772/intechopen.74748",title:"Ageing Better in the Netherlands",slug:"ageing-better-in-the-netherlands",totalDownloads:1193,totalCrossrefCites:1,totalDimensionsCites:4,abstract:"The Dutch National Care for the Elderly Programme was an initiative organized by the Netherlands Organisation for Health Research and Development (ZonMw) between 2008 and 2016. The aim of the programme was to collect knowledge about frail elderly, to assess their needs and to provide person-centred and integrated care better suited to their needs. The budget of EUR 88 million was provided by the Dutch Ministry of Health, Welfare and Sports. Putting the needs of elderly people at the heart of the programme and ensuring their active participation were key to the programme’s success. The programme outcomes included the establishment of eight geriatric networks around the medical universities with 650 organisations and the completion of 218 projects. These projects, involving 43,000 elderly people and 8500 central caregivers, resulted in the completion of 45 PhD theses and the publication of more than 400 articles and the development of 300 practice toolkits, one database and a website, www.beteroud.nl. The Dutch National Care for the Elderly Programme has since developed into a movement and continues under the consortium Ageing Better, made up of eight organisations. Through the use of ambassadors, Ageing Better promotes the message that ageing is not a disease but a new phase of life.",book:{id:"6381",slug:"gerontology",title:"Gerontology",fullTitle:"Gerontology"},signatures:"Betty Meyboom-de Jong, Klaske Wynia and Anjo Geluk-Bleumink",authors:[{id:"224997",title:"Emeritus Prof.",name:"Betty",middleName:null,surname:"Meyboom-De Jong",slug:"betty-meyboom-de-jong",fullName:"Betty Meyboom-De Jong"},{id:"232900",title:"Dr.",name:"Klaske",middleName:null,surname:"Wynia",slug:"klaske-wynia",fullName:"Klaske Wynia"},{id:"232901",title:"Mrs.",name:"Anjo",middleName:null,surname:"Geluk-Bleumink",slug:"anjo-geluk-bleumink",fullName:"Anjo Geluk-Bleumink"}]},{id:"55890",doi:"10.5772/intechopen.69529",title:"Mindfulness Meditation and the Perception of Beauty: Implications for an Ecological Well-Being",slug:"mindfulness-meditation-and-the-perception-of-beauty-implications-for-an-ecological-well-being",totalDownloads:1428,totalCrossrefCites:2,totalDimensionsCites:3,abstract:"Meditation is a first-person method for contemplating ourselves and the world, with more than 2500 years of history, rooted in the philosophical and contemplative traditions of the east. The present chapter aims to explore this worldview in order to demonstrate its relevance to our capacity for the appreciation of beauty. To this end, the aesthetic experience, the contemplative experience and their relationship with the practice of mindfulness are analysed. We suggest that the contemplative meditative experience bestows a state of consciousness and acceptance of life which places the practitioner in a progressive encounter with a self-concept that begins to detach from a static sense of the self and from the categories that define it, so that it may be experienced as an ongoing mental event, removed from cultural ideals of beauty or positivity. The result of this de-identification from the static self is a greater degree of psychological flexibility and a more genuine way of seeing the world, leading to a new perception of the self that is connected to an experience of freedom, and contributes to one’s own well-being, as well as to that of others and of the environment.",book:{id:"5925",slug:"perception-of-beauty",title:"Perception of Beauty",fullTitle:"Perception of Beauty"},signatures:"Álvaro I. Langer, Carlos Schmidt and Edwin Krogh",authors:[{id:"199843",title:"Dr.",name:"Álvaro",middleName:null,surname:"Langer",slug:"alvaro-langer",fullName:"Álvaro Langer"},{id:"201865",title:"MSc.",name:"Carlos",middleName:null,surname:"Schmidt",slug:"carlos-schmidt",fullName:"Carlos Schmidt"},{id:"201866",title:"Dr.",name:"Edwin",middleName:null,surname:"Krogh",slug:"edwin-krogh",fullName:"Edwin Krogh"}]}],mostDownloadedChaptersLast30Days:[{id:"60564",title:"Ageing Process and Physiological Changes",slug:"ageing-process-and-physiological-changes",totalDownloads:6996,totalCrossrefCites:19,totalDimensionsCites:34,abstract:"Ageing is a natural process. Everyone must undergo this phase of life at his or her own time and pace. In the broader sense, ageing reflects all the changes taking place over the course of life. These changes start from birth—one grows, develops and attains maturity. To the young, ageing is exciting. Middle age is the time when people notice the age-related changes like greying of hair, wrinkled skin and a fair amount of physical decline. Even the healthiest, aesthetically fit cannot escape these changes. Slow and steady physical impairment and functional disability are noticed resulting in increased dependency in the period of old age. According to World Health Organization, ageing is a course of biological reality which starts at conception and ends with death. It has its own dynamics, much beyond human control. However, this process of ageing is also subject to the constructions by which each society makes sense of old age. In most of the developed countries, the age of 60 is considered equivalent to retirement age and it is said to be the beginning of old age. In this chapter, you understand the details of ageing processes and associated physiological changes.",book:{id:"6381",slug:"gerontology",title:"Gerontology",fullTitle:"Gerontology"},signatures:"Shilpa Amarya, Kalyani Singh and Manisha Sabharwal",authors:[{id:"226573",title:"Ph.D.",name:"Shilpa",middleName:null,surname:"Amarya",slug:"shilpa-amarya",fullName:"Shilpa Amarya"},{id:"226593",title:"Dr.",name:"Kalyani",middleName:null,surname:"Singh",slug:"kalyani-singh",fullName:"Kalyani Singh"},{id:"243264",title:"Dr.",name:"Manisha",middleName:null,surname:"Sabharwal",slug:"manisha-sabharwal",fullName:"Manisha Sabharwal"}]},{id:"55388",title:"Beauty, Body Image, and the Media",slug:"beauty-body-image-and-the-media",totalDownloads:7764,totalCrossrefCites:5,totalDimensionsCites:12,abstract:"This chapter analyses the role of the mass media in people’s perceptions of beauty. We summarize the research literature on the mass media, both traditional media and online social media, and how they appear to interact with psychological factors to impact appearance concerns and body image disturbances. There is a strong support for the idea that traditional forms of media (e.g. magazines and music videos) affect perceptions of beauty and appearance concerns by leading women to internalize a very slender body type as ideal or beautiful. Rather than simply being passive recipients of unrealistic beauty ideals communicated to them via the media, a great number of individuals actually seek out idealized images in the media. Finally, we review what is known about the role of social media in impacting society’s perception of beauty and notions of idealized physical forms. Social media are more interactive than traditional media and the effects of self‐presentation strategies on perceptions of beauty have just begun to be studied. This is an emerging area of research that is of high relevance to researchers and clinicians interested in body image and appearance concerns.",book:{id:"5925",slug:"perception-of-beauty",title:"Perception of Beauty",fullTitle:"Perception of Beauty"},signatures:"Jennifer S. Mills, Amy Shannon and Jacqueline Hogue",authors:[{id:"202110",title:"Dr.",name:"Jennifer S.",middleName:null,surname:"Mills",slug:"jennifer-s.-mills",fullName:"Jennifer S. Mills"}]},{id:"56505",title:"Aesthetics of the Naked Human Body: From Pornography (Sexualised Lust Object) to Iconography (Aesthetics of Human Nobility and Wisdom) in an Anthropology of Physical Beauty",slug:"aesthetics-of-the-naked-human-body-from-pornography-sexualised-lust-object-to-iconography-aesthetics",totalDownloads:2100,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"In many religious circles and philosophies of life, the human body is excluded from the realm of spirituality and meaning. Due to a dualistic approach, nudity is viewed as merely a physical and corporeal category. In social media, there is the real danger that the naked human body is exploited for commercial gain. Advertisements often leave the impression that the body, very specifically the genitals, is designed merely for physical desire and corporeal chemistry. They become easily objects for lust, excluded from the beauty of graceful existence and noble courage. It is argued that the naked human body is not designed for pornographic exploitation and promiscuous sensuality but for compassionate intimacy and nurturing care in order to instil a humane dimension in human and sexual encounters. In this regard, antiquity and the Michelangelesque perspective can contribute to a paradigm shift from abusive exploitation to the beauty of vulnerable sensitivity. In order to foster an integrative approach to theory formation in anthropology, the methodology of stereometric thinking is proposed.",book:{id:"5925",slug:"perception-of-beauty",title:"Perception of Beauty",fullTitle:"Perception of Beauty"},signatures:"Daniel J Louw",authors:[{id:"200645",title:"Prof.",name:"Daniel",middleName:"Johannes",surname:"Louw",slug:"daniel-louw",fullName:"Daniel Louw"}]},{id:"56059",title:"A Plastic Surgeon’s Perspective on Stereotyping and the Perception of Beauty",slug:"a-plastic-surgeon-s-perspective-on-stereotyping-and-the-perception-of-beauty",totalDownloads:1918,totalCrossrefCites:0,totalDimensionsCites:1,abstract:"In the world of plastic surgery, misconceptions may lead to irrational requests or outcomes not appreciated by patients. Those who manage aesthetics should always listen and recognize the variability of cultural identities, desires, attitudes, anxieties and uncertainties of the patient. Emerging from a diversity of cultures and its transforming trends, the scope of cosmetic surgery and its practice reflect not only the individual’s personality, but also the culture as a whole. When counseling an individual, one has to recognize that even in groups of seemingly identical social or cultural standards; there are subtle differences in expectations. To illustrate the potential for inaccuracy of ethnic profiling in the field of plastic surgery authors quote their own work on Asian subjects and facial beauty and resort to experience of others. To reaffirm their opinion and to exemplify how sometimes “fine” differences in the perception of beauty exist, an original study that evaluates the preferences among selected groups of Latina women in respect to buttock aesthetics has been included. This dissertation will focus on how cultural factors influence beauty perception; strengthen the fact that beauty is in the eye of the beholder and how variable differences exist even between small subgroups.",book:{id:"5925",slug:"perception-of-beauty",title:"Perception of Beauty",fullTitle:"Perception of Beauty"},signatures:"Johanna D’Agostino and Marek Dobke",authors:[{id:"17590",title:"Dr.",name:"Marek K.",middleName:null,surname:"Dobke",slug:"marek-k.-dobke",fullName:"Marek K. Dobke"},{id:"201244",title:"Dr.",name:"Johanna",middleName:null,surname:"D'Agostino",slug:"johanna-d'agostino",fullName:"Johanna D'Agostino"}]},{id:"80326",title:"Anti-Senescence Therapy",slug:"anti-senescence-therapy",totalDownloads:110,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"The development of therapeutic strategies aimed at the aging process of cells has attracted increasing attention in recent decades due to the involvement of this process in the development of many chronic and age-related diseases. Interestingly, preclinical studies have shown the success of a number of anti-aging approaches in the treatment of a range of chronic diseases. These approaches are directed against aging processes such as oxidative stress, telomerase shortening, inflammation, and deficient autophagy. Many strategies has been shown to be effective in delaying aging, including antiaging strategies based on establishing healthy lifestyle habits and pharmacological interventions aimed at disrupting senescent cells and senescent-associated secretory phenotype. Caloric restriction and intermittent fasting were reported to activate autophagy and reduce inflammation. In turn, immune-based strategies, senolytic agents, and senomorphics mediate their effects either by eliminating senescent cells through inducing apoptosis or by disrupting pathways by which senescent cells mediate their detrimental effects. In addition, given the association of the decline in the regenerative potential of stem cells with aging, many experimental and clinical studies indicate the effectiveness of stem cell transplantation in preventing or slowing the progress of age-related diseases by enhancing the repairing mechanisms and the secretion of many growth factors and cytokines.",book:{id:"10935",slug:null,title:"Mechanisms and Management of Senescence",fullTitle:"Mechanisms and Management of Senescence"},signatures:"Raghad Alshadidi",authors:null}],onlineFirstChaptersFilter:{topicId:"235",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"82112",title:"Comparative Senescence and Lifespan",slug:"comparative-senescence-and-lifespan",totalDownloads:17,totalDimensionsCites:0,doi:"10.5772/intechopen.105137",abstract:"The word senescence is derived from the Latin word “senex” (meaning old). In biology, senescence is a process by which a cell ages and permanently stops dividing. Senescence is a natural universal phenomenon affecting all living organisms (e.g., humans, animals, and plants). It is the process of growing old (aging). The underlying mechanisms of senescence and aging at the cellular level are not fully understood. Senescence is a multifactorial process that can be induced by several stimuli including cellular stress, DNA damage, telomere shortening, and oncogene activation. The most popular theory to explain aging is the free radical theory. Senescence plays a role in the development of several age-related chronic diseases in humans (e.g., ischemic heart disease, osteoporosis, and cancer). Lifespan is a biological characteristic of every species. The lifespan of living organisms ranges from few hours (with mayfly) to potential eternity (with jellyfish and hydra). The maximum theoretical lifespan in humans is around 120 years. The lifespan in humans is influenced by multiple factors including genetic, epigenetic, lifestyle, environmental, metabolic, and endocrine factors. There are several ways to potentially extend the lifespan of humans and eventually surpass the maximum theoretical lifespan of 120 years. The tools that can be proposed include lifestyle, reduction of several life-threatening diseases and disabilities, hormonal replacement, antioxidants, autophagy inducers, senolytic drugs, stem cell therapy, and gene therapy.",book:{id:"10935",title:"Mechanisms and Management of Senescence",coverURL:"https://cdn.intechopen.com/books/images_new/10935.jpg"},signatures:"Hassan M. Heshmati"},{id:"81638",title:"Aging and Neuropsychiatric Disease: A General Overview of Prevalence and Trends",slug:"aging-and-neuropsychiatric-disease-a-general-overview-of-prevalence-and-trends",totalDownloads:30,totalDimensionsCites:0,doi:"10.5772/intechopen.103102",abstract:"The increasing trend of life-expectancy is becoming a significant demographic, societal and economic challenge. Currently, global number of people above sixty years of age is 900 million, while United Nations expect this number to rise to over 1.4 billion in 2030 and over 2.5 billion by 2050. Concordant to this trend, numerous physiological changes are associated with aging and brain-related ones are associated with neuropsychiatric diseases. The main goal of this chapter is to identify the most important neuropsychiatric diseases to assess in older patients to help to promote health and prevent diseases and complications associated with chronic illness, as these changes are progressive and require important psychological and setting-related social adjustments. Findings identify several health-aspects highly present in elderly: stroke, white matter lesions, dementia rise with age, changes in levels of neurotransmitters and hormones, depression as well as the bereavement following loss of the loved one, and the most common neurodegenerative disease—Alzheimer’s disease and Parkinson’s. In conclusion, studying the aging process should include all developmental, circumstantial, and individual aspects of aging. This offers opportunities to improve the health of elderly by using a wide range of skills and knowledge. Thus, further studies are necessary to elucidate what can be done do to improve the aging process and health of elderly in the future.",book:{id:"10935",title:"Mechanisms and Management of Senescence",coverURL:"https://cdn.intechopen.com/books/images_new/10935.jpg"},signatures:"Jelena Milić"},{id:"80326",title:"Anti-Senescence Therapy",slug:"anti-senescence-therapy",totalDownloads:110,totalDimensionsCites:0,doi:"10.5772/intechopen.101585",abstract:"The development of therapeutic strategies aimed at the aging process of cells has attracted increasing attention in recent decades due to the involvement of this process in the development of many chronic and age-related diseases. Interestingly, preclinical studies have shown the success of a number of anti-aging approaches in the treatment of a range of chronic diseases. These approaches are directed against aging processes such as oxidative stress, telomerase shortening, inflammation, and deficient autophagy. Many strategies has been shown to be effective in delaying aging, including antiaging strategies based on establishing healthy lifestyle habits and pharmacological interventions aimed at disrupting senescent cells and senescent-associated secretory phenotype. Caloric restriction and intermittent fasting were reported to activate autophagy and reduce inflammation. In turn, immune-based strategies, senolytic agents, and senomorphics mediate their effects either by eliminating senescent cells through inducing apoptosis or by disrupting pathways by which senescent cells mediate their detrimental effects. In addition, given the association of the decline in the regenerative potential of stem cells with aging, many experimental and clinical studies indicate the effectiveness of stem cell transplantation in preventing or slowing the progress of age-related diseases by enhancing the repairing mechanisms and the secretion of many growth factors and cytokines.",book:{id:"10935",title:"Mechanisms and Management of Senescence",coverURL:"https://cdn.intechopen.com/books/images_new/10935.jpg"},signatures:"Raghad Alshadidi"},{id:"79828",title:"Cellular Senescence in Bone",slug:"cellular-senescence-in-bone",totalDownloads:119,totalDimensionsCites:0,doi:"10.5772/intechopen.101803",abstract:"Senescence is an irreversible cell-cycle arrest process induced by environmental, genetic, and epigenetic factors. An accumulation of senescent cells in bone results in age-related disorders, and one of the common problems is osteoporosis. Deciphering the basic mechanisms contributing to the chronic ailments of aging may uncover new avenues for targeted treatment. This review focuses on the mechanisms and the most relevant research advancements in skeletal cellular senescence. To identify new options for the treatment or prevention of age-related chronic diseases, researchers have targeted hallmarks of aging, including telomere attrition, genomic instability, cellular senescence, and epigenetic alterations. First, this chapter provides an overview of the fundamentals of bone tissue, the causes of skeletal involution, and the role of cellular senescence in bone and bone diseases such as osteoporosis. Next, this review will discuss the utilization of pharmacological interventions in aging tissues and, more specifically, highlight the role of senescent cells to identify the most effective and safe strategies.",book:{id:"10935",title:"Mechanisms and Management of Senescence",coverURL:"https://cdn.intechopen.com/books/images_new/10935.jpg"},signatures:"Danielle Wang and Haitao Wang"},{id:"79668",title:"Identification of RNA Species That Bind to the hnRNP A1 in Normal and Senescent Human Fibroblasts",slug:"identification-of-rna-species-that-bind-to-the-hnrnp-a1-in-normal-and-senescent-human-fibroblasts",totalDownloads:81,totalDimensionsCites:0,doi:"10.5772/intechopen.101525",abstract:"hnRNP A1 is a member of the hnRNPs (heterogeneous nuclear ribonucleoproteins) family of proteins that play a central role in regulating genes responsible for cell proliferation, DNA repair, apoptosis, and telomere biogenesis. Previous studies have shown that hnRNPA1 had reduced protein levels and increased cytoplasmic accumulation in senescent human diploid fibroblasts. The consequence of reduced protein expression and altered cellular localization may account for the alterations in gene expression observed during senescence. There is limited information for gene targets of hnRNP A1 as well as its in vivo function. In these studies, we performed RNA co-immunoprecipitation experiments using hnRNP A1 as the target protein to identify potential mRNA species in ribonucleoprotein (RNP) complexes. Using this approach, we identified the human double minute 2 (HDM2) mRNA as a binding target for hnRNP A1 in young and senescent human diploid fibroblasts cells. It was also observed that alterations of hnRNP A1 expression modulate HDM2 mRNA levels in young IMR-90 cells. We also demonstrated that the levels of HDM2 mRNA increased with the downregulation of hnRNP A1 and decrease with the overexpression of hnRNP A1. Although we did not observe a significant decrease in HDM2 protein level, a concomitant increase in p53 protein level was detected with the overexpression of hnRNP A1. Our studies also show that hnRNP A1 directly interacts with HDM2 mRNA at a region corresponding to its 3′ UTR (untranslated region of a gene). The results from this study demonstrate that hnRNP A1 has a novel role in participating in the regulation of HDM2 gene expression.",book:{id:"10935",title:"Mechanisms and Management of Senescence",coverURL:"https://cdn.intechopen.com/books/images_new/10935.jpg"},signatures:"Heriberto Moran, Shanaz A. Ghandhi, Naoko Shimada and Karen Hubbard"},{id:"79295",title:"Genetic and Epigenetic Influences on Cutaneous Cellular Senescence",slug:"genetic-and-epigenetic-influences-on-cutaneous-cellular-senescence",totalDownloads:135,totalDimensionsCites:0,doi:"10.5772/intechopen.101152",abstract:"Skin is the largest human organ system, and its protective function is critical to survival. The epithelial, dermal, and subcutaneous compartments are heterogeneous mixtures of cell types, yet they all display age-related skin dysfunction through the accumulation of an altered phenotypic cellular state called senescence. Cellular senescence is triggered by complex and dynamic genetic and epigenetic processes. A senescence steady state is achieved in different cell types under various and overlapping conditions of chronological age, toxic injury, oxidative stress, replicative exhaustion, DNA damage, metabolic dysfunction, and chromosomal structural changes. These inputs lead to outputs of cell-cycle withdrawal and the appearance of a senescence-associated secretory phenotype, both of which accumulate as tissue pathology observed clinically in aged skin. This review details the influence of genetic and epigenetic factors that converge on normal cutaneous cellular processes to create the senescent state, thereby dictating the response of the skin to the forces of both intrinsic and extrinsic aging. From this work, it is clear that no single biomarker or process leads to senescence, but that it is a convergence of factors resulting in an overt aging phenotype.",book:{id:"10935",title:"Mechanisms and Management of Senescence",coverURL:"https://cdn.intechopen.com/books/images_new/10935.jpg"},signatures:"Tapash Jay Sarkar, Maiko Hermsmeier, Jessica L. Ross and G. 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The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}},{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}}]},series:{item:{id:"6",title:"Infectious Diseases",doi:"10.5772/intechopen.71852",issn:"2631-6188",scope:"This series will provide a comprehensive overview of recent research trends in various Infectious Diseases (as per the most recent Baltimore classification). Topics will include general overviews of infections, immunopathology, diagnosis, treatment, epidemiology, etiology, and current clinical recommendations for managing infectious diseases. Ongoing issues, recent advances, and future diagnostic approaches and therapeutic strategies will also be discussed. This book series will focus on various aspects and properties of infectious diseases whose deep understanding is essential for safeguarding the human race from losing resources and economies due to pathogens.",coverUrl:"https://cdn.intechopen.com/series/covers/6.jpg",latestPublicationDate:"August 2nd, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:13,editor:{id:"131400",title:"Prof.",name:"Alfonso J.",middleName:null,surname:"Rodriguez-Morales",slug:"alfonso-j.-rodriguez-morales",fullName:"Alfonso J. Rodriguez-Morales",profilePictureURL:"https://mts.intechopen.com/storage/users/131400/images/system/131400.png",biography:"Dr. Rodriguez-Morales is an expert in tropical and emerging diseases, particularly zoonotic and vector-borne diseases (especially arboviral diseases). He is the president of the Travel Medicine Committee of the Pan-American Infectious Diseases Association (API), as well as the president of the Colombian Association of Infectious Diseases (ACIN). He is a member of the Committee on Tropical Medicine, Zoonoses, and Travel Medicine of ACIN. He is a vice-president of the Latin American Society for Travel Medicine (SLAMVI) and a Member of the Council of the International Society for Infectious Diseases (ISID). Since 2014, he has been recognized as a Senior Researcher, at the Ministry of Science of Colombia. He is a professor at the Faculty of Medicine of the Fundacion Universitaria Autonoma de las Americas, in Pereira, Risaralda, Colombia. He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. He is currently the Editor in Chief of the journal Travel Medicine and Infectious Diseases. His Scopus H index is 47 (Google Scholar H index, 68).",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null},editorTwo:null,editorThree:null},subseries:{paginationCount:5,paginationItems:[{id:"3",title:"Bacterial Infectious Diseases",coverUrl:"https://cdn.intechopen.com/series_topics/covers/3.jpg",editor:{id:"205604",title:"Dr.",name:"Tomas",middleName:null,surname:"Jarzembowski",slug:"tomas-jarzembowski",fullName:"Tomas Jarzembowski",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKriQAG/Profile_Picture_2022-06-16T11:01:31.jpg",biography:"Tomasz Jarzembowski was born in 1968 in Gdansk, Poland. He obtained his Ph.D. degree in 2000 from the Medical University of Gdańsk (UG). After specialization in clinical microbiology in 2003, he started studying biofilm formation and antibiotic resistance at the single-cell level. In 2015, he obtained his D.Sc. degree. His later study in cooperation with experts in nephrology and immunology resulted in the designation of the new diagnostic method of UTI, patented in 2017. He is currently working at the Department of Microbiology, Medical University of Gdańsk (GUMed), Poland. Since many years, he is a member of steering committee of Gdańsk branch of Polish Society of Microbiologists, a member of ESCMID. He is also a reviewer and a member of editorial boards of a number of international journals.",institutionString:"Medical University of Gdańsk, Poland",institution:null},editorTwo:{id:"484980",title:"Dr.",name:"Katarzyna",middleName:null,surname:"Garbacz",slug:"katarzyna-garbacz",fullName:"Katarzyna Garbacz",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003St8TAQAZ/Profile_Picture_2022-07-07T09:45:16.jpg",biography:"Katarzyna Maria Garbacz, MD, is an Associate Professor at the Medical University of Gdańsk, Poland and she is head of the Department of Oral Microbiology of the Medical University of Gdańsk. She has published more than 50 scientific publications in peer-reviewed journals. She has been a project leader funded by the National Science Centre of Poland. Prof. Garbacz is a microbiologist working on applied and fundamental questions in microbial epidemiology and pathogenesis. Her research interest is in antibiotic resistance, host-pathogen interaction, and therapeutics development for staphylococcal pathogens, mainly Staphylococcus aureus, which causes hospital-acquired infections. Currently, her research is mostly focused on the study of oral pathogens, particularly Staphylococcus spp.",institutionString:"Medical University of Gdańsk, Poland",institution:null},editorThree:null,editorialBoard:[{id:"190041",title:"Dr.",name:"Jose",middleName:null,surname:"Gutierrez Fernandez",slug:"jose-gutierrez-fernandez",fullName:"Jose Gutierrez Fernandez",profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institutionString:null,institution:{name:"University of Granada",institutionURL:null,country:{name:"Spain"}}},{id:"156556",title:"Prof.",name:"Maria Teresa",middleName:null,surname:"Mascellino",slug:"maria-teresa-mascellino",fullName:"Maria Teresa Mascellino",profilePictureURL:"https://mts.intechopen.com/storage/users/156556/images/system/156556.jpg",institutionString:"Sapienza University",institution:{name:"Sapienza University of Rome",institutionURL:null,country:{name:"Italy"}}},{id:"164933",title:"Prof.",name:"Mónica Alexandra",middleName:null,surname:"Sousa Oleastro",slug:"monica-alexandra-sousa-oleastro",fullName:"Mónica Alexandra Sousa Oleastro",profilePictureURL:"https://mts.intechopen.com/storage/users/164933/images/system/164933.jpeg",institutionString:"National Institute of Health Dr Ricardo Jorge",institution:{name:"National Institute of Health Dr. Ricardo Jorge",institutionURL:null,country:{name:"Portugal"}}}]},{id:"4",title:"Fungal Infectious Diseases",coverUrl:"https://cdn.intechopen.com/series_topics/covers/4.jpg",editor:{id:"174134",title:"Dr.",name:"Yuping",middleName:null,surname:"Ran",slug:"yuping-ran",fullName:"Yuping Ran",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bS9d6QAC/Profile_Picture_1630330675373",biography:"Dr. Yuping Ran, Professor, Department of Dermatology, West China Hospital, Sichuan University, Chengdu, China. Completed the Course Medical Mycology, the Centraalbureau voor Schimmelcultures (CBS), Fungal Biodiversity Centre, Netherlands (2006). International Union of Microbiological Societies (IUMS) Fellow, and International Emerging Infectious Diseases (IEID) Fellow, Centers for Diseases Control and Prevention (CDC), Atlanta, USA. Diploma of Dermatological Scientist, Japanese Society for Investigative Dermatology. Ph.D. of Juntendo University, Japan. Bachelor’s and Master’s degree, Medicine, West China University of Medical Sciences. Chair of Sichuan Medical Association Dermatology Committee. General Secretary of The 19th Annual Meeting of Chinese Society of Dermatology and the Asia Pacific Society for Medical Mycology (2013). In charge of the Annual Medical Mycology Course over 20-years authorized by National Continue Medical Education Committee of China. Member of the board of directors of the Asia-Pacific Society for Medical Mycology (APSMM). Associate editor of Mycopathologia. Vice-chief of the editorial board of Chinses Journal of Mycology, China. Board Member and Chair of Mycology Group of Chinese Society of Dermatology.",institutionString:null,institution:{name:"Sichuan University",institutionURL:null,country:{name:"China"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"302145",title:"Dr.",name:"Felix",middleName:null,surname:"Bongomin",slug:"felix-bongomin",fullName:"Felix Bongomin",profilePictureURL:"https://mts.intechopen.com/storage/users/302145/images/system/302145.jpg",institutionString:null,institution:{name:"Gulu University",institutionURL:null,country:{name:"Uganda"}}},{id:"45803",title:"Ph.D.",name:"Payam",middleName:null,surname:"Behzadi",slug:"payam-behzadi",fullName:"Payam Behzadi",profilePictureURL:"https://mts.intechopen.com/storage/users/45803/images/system/45803.jpg",institutionString:"Islamic Azad University, Tehran",institution:{name:"Islamic Azad University, Tehran",institutionURL:null,country:{name:"Iran"}}}]},{id:"5",title:"Parasitic Infectious Diseases",coverUrl:"https://cdn.intechopen.com/series_topics/covers/5.jpg",editor:{id:"67907",title:"Dr.",name:"Amidou",middleName:null,surname:"Samie",slug:"amidou-samie",fullName:"Amidou Samie",profilePictureURL:"https://mts.intechopen.com/storage/users/67907/images/system/67907.jpg",biography:"Dr. Amidou Samie is an Associate Professor of Microbiology at the University of Venda, in South Africa, where he graduated for his PhD in May 2008. He joined the Department of Microbiology the same year and has been giving lectures on topics covering parasitology, immunology, molecular biology and industrial microbiology. He is currently a rated researcher by the National Research Foundation of South Africa at category C2. He has published widely in the field of infectious diseases and has overseen several MSc’s and PhDs. His research activities mostly cover topics on infectious diseases from epidemiology to control. His particular interest lies in the study of intestinal protozoan parasites and opportunistic infections among HIV patients as well as the potential impact of childhood diarrhoea on growth and child development. He also conducts research on water-borne diseases and water quality and is involved in the evaluation of point-of-use water treatment technologies using silver and copper nanoparticles in collaboration with the University of Virginia, USA. He also studies the use of medicinal plants for the control of infectious diseases as well as antimicrobial drug resistance.",institutionString:null,institution:{name:"University of Venda",institutionURL:null,country:{name:"South Africa"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"188881",title:"Dr.",name:"Fernando José",middleName:null,surname:"Andrade-Narváez",slug:"fernando-jose-andrade-narvaez",fullName:"Fernando José Andrade-Narváez",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRIV7QAO/Profile_Picture_1628834308121",institutionString:null,institution:{name:"Autonomous University of Yucatán",institutionURL:null,country:{name:"Mexico"}}},{id:"269120",title:"Dr.",name:"Rajeev",middleName:"K.",surname:"Tyagi",slug:"rajeev-tyagi",fullName:"Rajeev Tyagi",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRaBqQAK/Profile_Picture_1644331884726",institutionString:"CSIR - Institute of Microbial Technology, India",institution:null},{id:"336849",title:"Prof.",name:"Ricardo",middleName:null,surname:"Izurieta",slug:"ricardo-izurieta",fullName:"Ricardo Izurieta",profilePictureURL:"https://mts.intechopen.com/storage/users/293169/images/system/293169.png",institutionString:null,institution:{name:"University of South Florida",institutionURL:null,country:{name:"United States of America"}}}]},{id:"6",title:"Viral Infectious Diseases",coverUrl:"https://cdn.intechopen.com/series_topics/covers/6.jpg",editor:{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",biography:"Professor Dr. Shailendra K. Saxena is a vice dean and professor at King George's Medical University, Lucknow, India. His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. 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Rodriguez-Morales",hash:"61c627da05b2ace83056d11357bdf361",volumeInSeries:3,fullTitle:"Current Topics in Neglected Tropical Diseases",editors:[{id:"131400",title:"Prof.",name:"Alfonso J.",middleName:null,surname:"Rodriguez-Morales",slug:"alfonso-j.-rodriguez-morales",fullName:"Alfonso J. Rodriguez-Morales",profilePictureURL:"https://mts.intechopen.com/storage/users/131400/images/system/131400.png",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"7064",title:"Current Perspectives in Human Papillomavirus",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7064.jpg",slug:"current-perspectives-in-human-papillomavirus",publishedDate:"May 2nd 2019",editedByType:"Edited by",bookSignature:"Shailendra K. 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Saxena",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",institutionURL:null,country:{name:"India"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null}]},subseriesFiltersForPublishedBooks:[{group:"subseries",caption:"Bacterial Infectious Diseases",value:3,count:2},{group:"subseries",caption:"Parasitic Infectious Diseases",value:5,count:4},{group:"subseries",caption:"Viral Infectious Diseases",value:6,count:7}],publicationYearFilters:[{group:"publicationYear",caption:"2022",value:2022,count:2},{group:"publicationYear",caption:"2021",value:2021,count:4},{group:"publicationYear",caption:"2020",value:2020,count:3},{group:"publicationYear",caption:"2019",value:2019,count:3},{group:"publicationYear",caption:"2018",value:2018,count:1}],authors:{paginationCount:302,paginationItems:[{id:"280338",title:"Dr.",name:"Yutaka",middleName:null,surname:"Tsutsumi",slug:"yutaka-tsutsumi",fullName:"Yutaka Tsutsumi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/280338/images/7961_n.jpg",biography:null,institutionString:null,institution:{name:"Fujita Health University",country:{name:"Japan"}}},{id:"116250",title:"Dr.",name:"Nima",middleName:null,surname:"Rezaei",slug:"nima-rezaei",fullName:"Nima Rezaei",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/116250/images/system/116250.jpg",biography:"Professor Nima Rezaei obtained an MD from Tehran University of Medical Sciences, Iran. He also obtained an MSc in Molecular and Genetic Medicine, and a Ph.D. in Clinical Immunology and Human Genetics from the University of Sheffield, UK. He also completed a short-term fellowship in Pediatric Clinical Immunology and Bone Marrow Transplantation at Newcastle General Hospital, England. Dr. Rezaei is a Full Professor of Immunology and Vice Dean of International Affairs and Research, at the School of Medicine, Tehran University of Medical Sciences, and the co-founder and head of the Research Center for Immunodeficiencies. He is also the founding president of the Universal Scientific Education and Research Network (USERN). Dr. Rezaei has directed more than 100 research projects and has designed and participated in several international collaborative projects. He is an editor, editorial assistant, or editorial board member of more than forty international journals. He has edited more than 50 international books, presented more than 500 lectures/posters in congresses/meetings, and published more than 1,100 scientific papers in international journals.",institutionString:"Tehran University of Medical Sciences",institution:{name:"Tehran University of Medical Sciences",country:{name:"Iran"}}},{id:"180733",title:"Dr.",name:"Jean",middleName:null,surname:"Engohang-Ndong",slug:"jean-engohang-ndong",fullName:"Jean Engohang-Ndong",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180733/images/system/180733.png",biography:"Dr. Jean Engohang-Ndong was born and raised in Gabon. After obtaining his Associate Degree of Science at the University of Science and Technology of Masuku, Gabon, he continued his education in France where he obtained his BS, MS, and Ph.D. in Medical Microbiology. He worked as a post-doctoral fellow at the Public Health Research Institute (PHRI), Newark, NJ for four years before accepting a three-year faculty position at Brigham Young University-Hawaii. Dr. Engohang-Ndong is a tenured faculty member with the academic rank of Full Professor at Kent State University, Ohio, where he teaches a wide range of biological science courses and pursues his research in medical and environmental microbiology. Recently, he expanded his research interest to epidemiology and biostatistics of chronic diseases in Gabon.",institutionString:"Kent State University",institution:{name:"Kent State University",country:{name:"United States of America"}}},{id:"188773",title:"Prof.",name:"Emmanuel",middleName:null,surname:"Drouet",slug:"emmanuel-drouet",fullName:"Emmanuel Drouet",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/188773/images/system/188773.png",biography:"Emmanuel Drouet, PharmD, is a Professor of Virology at the Faculty of Pharmacy, the University Grenoble-Alpes, France. As a head scientist at the Institute of Structural Biology in Grenoble, Dr. Drouet’s research investigates persisting viruses in humans (RNA and DNA viruses) and the balance with our host immune system. He focuses on these viruses’ effects on humans (both their impact on pathology and their symbiotic relationships in humans). He has an excellent track record in the herpesvirus field, and his group is engaged in clinical research in the field of Epstein-Barr virus diseases. He is the editor of the online Encyclopedia of Environment and he coordinates the Universal Health Coverage education program for the BioHealth Computing Schools of the European Institute of Science.",institutionString:null,institution:{name:"Grenoble Alpes University",country:{name:"France"}}},{id:"131400",title:"Prof.",name:"Alfonso J.",middleName:null,surname:"Rodriguez-Morales",slug:"alfonso-j.-rodriguez-morales",fullName:"Alfonso J. Rodriguez-Morales",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/131400/images/system/131400.png",biography:"Dr. Rodriguez-Morales is an expert in tropical and emerging diseases, particularly zoonotic and vector-borne diseases (especially arboviral diseases). He is the president of the Travel Medicine Committee of the Pan-American Infectious Diseases Association (API), as well as the president of the Colombian Association of Infectious Diseases (ACIN). He is a member of the Committee on Tropical Medicine, Zoonoses, and Travel Medicine of ACIN. He is a vice-president of the Latin American Society for Travel Medicine (SLAMVI) and a Member of the Council of the International Society for Infectious Diseases (ISID). Since 2014, he has been recognized as a Senior Researcher, at the Ministry of Science of Colombia. He is a professor at the Faculty of Medicine of the Fundacion Universitaria Autonoma de las Americas, in Pereira, Risaralda, Colombia. He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. He is currently the Editor in Chief of the journal Travel Medicine and Infectious Diseases. His Scopus H index is 47 (Google Scholar H index, 68).",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null},{id:"332819",title:"Dr.",name:"Chukwudi Michael",middleName:"Michael",surname:"Egbuche",slug:"chukwudi-michael-egbuche",fullName:"Chukwudi Michael Egbuche",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/332819/images/14624_n.jpg",biography:"I an Dr. Chukwudi Michael Egbuche. I am a Senior Lecturer in the Department of Parasitology and Entomology, Nnamdi Azikiwe University, Awka.",institutionString:null,institution:{name:"Nnamdi Azikiwe University",country:{name:"Nigeria"}}},{id:"284232",title:"Mr.",name:"Nikunj",middleName:"U",surname:"Tandel",slug:"nikunj-tandel",fullName:"Nikunj Tandel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/284232/images/8275_n.jpg",biography:'Mr. Nikunj Tandel has completed his Master\'s degree in Biotechnology from VIT University, India in the year of 2012. He is having 8 years of research experience especially in the field of malaria epidemiology, immunology, and nanoparticle-based drug delivery system against the infectious diseases, autoimmune disorders and cancer. He has worked for the NIH funded-International Center of Excellence in Malaria Research project "Center for the study of complex malaria in India (CSCMi)" in collaboration with New York University. The preliminary objectives of the study are to understand and develop the evidence-based tools and interventions for the control and prevention of malaria in different sites of the INDIA. Alongside, with the help of next-generation genomics study, the team has studied the antimalarial drug resistance in India. Further, he has extended his research in the development of Humanized mice for the study of liver-stage malaria and identification of molecular marker(s) for the Artemisinin resistance. At present, his research focuses on understanding the role of B cells in the activation of CD8+ T cells in malaria. Received the CSIR-SRF (Senior Research Fellow) award-2018, FIMSA (Federation of Immunological Societies of Asia-Oceania) Travel Bursary award to attend the IUIS-IIS-FIMSA Immunology course-2019',institutionString:"Nirma University",institution:{name:"Nirma University",country:{name:"India"}}},{id:"334383",title:"Ph.D.",name:"Simone",middleName:"Ulrich",surname:"Ulrich Picoli",slug:"simone-ulrich-picoli",fullName:"Simone Ulrich Picoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334383/images/15919_n.jpg",biography:"Graduated in Pharmacy from Universidade Luterana do Brasil (1999), Master in Agricultural and Environmental Microbiology from Federal University of Rio Grande do Sul (2002), Specialization in Clinical Microbiology from Universidade de São Paulo, USP (2007) and PhD in Sciences in Gastroenterology and Hepatology (2012). She is currently an Adjunct Professor at Feevale University in Medicine and Biomedicine courses and a permanent professor of the Academic Master\\'s Degree in Virology. She has experience in the field of Microbiology, with an emphasis on Bacteriology, working mainly on the following topics: bacteriophages, bacterial resistance, clinical microbiology and food microbiology.",institutionString:null,institution:{name:"Universidade Feevale",country:{name:"Brazil"}}},{id:"229220",title:"Dr.",name:"Amjad",middleName:"Islam",surname:"Aqib",slug:"amjad-aqib",fullName:"Amjad Aqib",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229220/images/system/229220.png",biography:"Dr. Amjad Islam Aqib obtained a DVM and MSc (Hons) from University of Agriculture Faisalabad (UAF), Pakistan, and a PhD from the University of Veterinary and Animal Sciences Lahore, Pakistan. Dr. Aqib joined the Department of Clinical Medicine and Surgery at UAF for one year as an assistant professor where he developed a research laboratory designated for pathogenic bacteria. Since 2018, he has been Assistant Professor/Officer in-charge, Department of Medicine, Manager Research Operations and Development-ORIC, and President One Health Club at Cholistan University of Veterinary and Animal Sciences, Bahawalpur, Pakistan. He has nearly 100 publications to his credit. His research interests include epidemiological patterns and molecular analysis of antimicrobial resistance and modulation and vaccine development against animal pathogens of public health concern.",institutionString:"Cholistan University of Veterinary and Animal Sciences",institution:{name:"University of Agriculture Faisalabad",country:{name:"Pakistan"}}},{id:"333753",title:"Dr.",name:"Rais",middleName:null,surname:"Ahmed",slug:"rais-ahmed",fullName:"Rais Ahmed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/333753/images/20168_n.jpg",biography:null,institutionString:null,institution:{name:"University of Agriculture Faisalabad",country:{name:"Pakistan"}}},{id:"62900",title:"Prof.",name:"Fethi",middleName:null,surname:"Derbel",slug:"fethi-derbel",fullName:"Fethi Derbel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62900/images/system/62900.jpeg",biography:"Professor Fethi Derbel was born in 1960 in Tunisia. He received his medical degree from the Sousse Faculty of Medicine at Sousse, University of Sousse, Tunisia. He completed his surgical residency in General Surgery at the University Hospital Farhat Hached of Sousse and was a member of the Unit of Liver Transplantation in the University of Rennes, France. He then worked in the Department of Surgery at the Sahloul University Hospital in Sousse. Professor Derbel is presently working at the Clinique les Oliviers, Sousse, Tunisia. His hospital activities are mostly concerned with laparoscopic, colorectal, pancreatic, hepatobiliary, and gastric surgery. He is also very interested in hernia surgery and performs ventral hernia repairs and inguinal hernia repairs. He has been a member of the GREPA and Tunisian Hernia Society (THS). During his residency, he managed patients suffering from diabetic foot, and he was very interested in this pathology. For this reason, he decided to coordinate a book project dealing with the diabetic foot. Professor Derbel has published many articles in journals and collaborates intensively with IntechOpen Access Publisher as an editor.",institutionString:"Clinique les Oliviers",institution:null},{id:"300144",title:"Dr.",name:"Meriem",middleName:null,surname:"Braiki",slug:"meriem-braiki",fullName:"Meriem Braiki",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/300144/images/system/300144.jpg",biography:"Dr. Meriem Braiki is a specialist in pediatric surgeon from Tunisia. She was born in 1985. She received her medical degree from the University of Medicine at Sousse, Tunisia. She achieved her surgical residency training periods in Pediatric Surgery departments at University Hospitals in Monastir, Tunis and France.\r\nShe is currently working at the Pediatric surgery department, Sidi Bouzid Hospital, Tunisia. Her hospital activities are mostly concerned with laparoscopic, parietal, urological and digestive surgery. She has published several articles in diffrent journals.",institutionString:"Sidi Bouzid Regional Hospital",institution:null},{id:"229481",title:"Dr.",name:"Erika M.",middleName:"Martins",surname:"de Carvalho",slug:"erika-m.-de-carvalho",fullName:"Erika M. de Carvalho",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229481/images/6397_n.jpg",biography:null,institutionString:null,institution:{name:"Oswaldo Cruz Foundation",country:{name:"Brazil"}}},{id:"186537",title:"Prof.",name:"Tonay",middleName:null,surname:"Inceboz",slug:"tonay-inceboz",fullName:"Tonay Inceboz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/186537/images/system/186537.jfif",biography:"I was graduated from Ege University of Medical Faculty (Turkey) in 1988 and completed his Med. PhD degree in Medical Parasitology at the same university. I became an Associate Professor in 2008 and Professor in 2014. I am currently working as a Professor at the Department of Medical Parasitology at Dokuz Eylul University, Izmir, Turkey.\n\nI have given many lectures, presentations in different academic meetings. I have more than 60 articles in peer-reviewed journals, 18 book chapters, 1 book editorship.\n\nMy research interests are Echinococcus granulosus, Echinococcus multilocularis (diagnosis, life cycle, in vitro and in vivo cultivation), and Trichomonas vaginalis (diagnosis, PCR, and in vitro cultivation).",institutionString:"Dokuz Eylül University",institution:{name:"Dokuz Eylül University",country:{name:"Turkey"}}},{id:"71812",title:"Prof.",name:"Hanem Fathy",middleName:"Fathy",surname:"Khater",slug:"hanem-fathy-khater",fullName:"Hanem Fathy Khater",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/71812/images/1167_n.jpg",biography:"Prof. Khater is a Professor of Parasitology at Benha University, Egypt. She studied for her doctoral degree, at the Department of Entomology, College of Agriculture, Food and Natural Resources, University of Missouri, Columbia, USA. She has completed her Ph.D. degrees in Parasitology in Egypt, from where she got the award for “the best scientific Ph.D. dissertation”. She worked at the School of Biological Sciences, Bristol, England, the UK in controlling insects of medical and veterinary importance as a grant from Newton Mosharafa, the British Council. Her research is focused on searching of pesticides against mosquitoes, house flies, lice, green bottle fly, camel nasal botfly, soft and hard ticks, mites, and the diamondback moth as well as control of several parasites using safe and natural materials to avoid drug resistances and environmental contamination.",institutionString:null,institution:{name:"Banha University",country:{name:"Egypt"}}},{id:"99780",title:"Prof.",name:"Omolade",middleName:"Olayinka",surname:"Okwa",slug:"omolade-okwa",fullName:"Omolade Okwa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/99780/images/system/99780.jpg",biography:"Omolade Olayinka Okwa is presently a Professor of Parasitology at Lagos State University, Nigeria. She has a PhD in Parasitology (1997), an MSc in Cellular Parasitology (1992), and a BSc (Hons) Zoology (1990) all from the University of Ibadan, Nigeria. She teaches parasitology at the undergraduate and postgraduate levels. She was a recipient of a Commonwealth fellowship supported by British Council tenable at the Centre for Entomology and Parasitology (CAEP), Keele University, United Kingdom between 2004 and 2005. She was awarded an Honorary Visiting Research Fellow at the same university from 2005 to 2007. \nShe has been an external examiner to the Department of Veterinary Microbiology and Parasitology, University of Ibadan, MSc programme between 2010 and 2012. She is a member of the Nigerian Society of Experimental Biology (NISEB), Parasitology and Public Health Society of Nigeria (PPSN), Science Association of Nigeria (SAN), Zoological Society of Nigeria (ZSN), and is Vice Chairperson of the Organisation of Women in Science (OWSG), LASU chapter. She served as Head of Department of Zoology and Environmental Biology, Lagos State University from 2007 to 2010 and 2014 to 2016. She is a reviewer for several local and international journals such as Unilag Journal of Science, Libyan Journal of Medicine, Journal of Medicine and Medical Sciences, and Annual Research and Review in Science. \nShe has authored 45 scientific research publications in local and international journals, 8 scientific reviews, 4 books, and 3 book chapters, which includes the books “Malaria Parasites” and “Malaria” which are IntechOpen access publications.",institutionString:"Lagos State University",institution:{name:"Lagos State University",country:{name:"Nigeria"}}},{id:"273100",title:"Dr.",name:"Vijay",middleName:null,surname:"Gayam",slug:"vijay-gayam",fullName:"Vijay Gayam",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/273100/images/system/273100.jpeg",biography:"Dr. Vijay Bhaskar Reddy Gayam is currently practicing as an internist at Interfaith Medical Center in Brooklyn, New York, USA. He is also a Clinical Assistant Professor at the SUNY Downstate University Hospital and Adjunct Professor of Medicine at the American University of Antigua. He is a holder of an M.B.B.S. degree bestowed to him by Osmania Medical College and received his M.D. at Interfaith Medical Center. His career goals thus far have heavily focused on direct patient care, medical education, and clinical research. He currently serves in two leadership capacities; Assistant Program Director of Medicine at Interfaith Medical Center and as a Councilor for the American\r\nFederation for Medical Research. As a true academician and researcher, he has more than 50 papers indexed in international peer-reviewed journals. He has also presented numerous papers in multiple national and international scientific conferences. His areas of research interest include general internal medicine, gastroenterology and hepatology. He serves as an editor, editorial board member and reviewer for multiple international journals. His research on Hepatitis C has been very successful and has led to multiple research awards, including the 'Equity in Prevention and Treatment Award” from the New York Department of Health Viral Hepatitis Symposium (2018) and the 'Presidential Poster Award” awarded to him by the American College of Gastroenterology (2018). He was also awarded 'Outstanding Clinician in General Medicine” by Venus International Foundation for his extensive research expertise and services, perform over and above the standard expected in the advancement of healthcare, patient safety and quality of care.",institutionString:"Interfaith Medical Center",institution:{name:"Interfaith Medical Center",country:{name:"United States of America"}}},{id:"93517",title:"Dr.",name:"Clement",middleName:"Adebajo",surname:"Meseko",slug:"clement-meseko",fullName:"Clement Meseko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/93517/images/system/93517.jpg",biography:"Dr. Clement Meseko obtained DVM and PhD degree in Veterinary Medicine and Virology respectively. He has worked for over 20 years in both private and public sectors including the academia, contributing to knowledge and control of infectious disease. Through the application of epidemiological skill, classical and molecular virological skills, he investigates viruses of economic and public health importance for the mitigation of the negative impact on people, animal and the environment in the context of Onehealth. \r\nDr. Meseko’s field experience on animal and zoonotic diseases and pathogen dynamics at the human-animal interface over the years shaped his carrier in research and scientific inquiries. He has been part of the investigation of Highly Pathogenic Avian Influenza incursions in sub Saharan Africa and monitors swine Influenza (Pandemic influenza Virus) agro-ecology and potential for interspecies transmission. He has authored and reviewed a number of journal articles and book chapters.",institutionString:"National Veterinary Research Institute",institution:{name:"National Veterinary Research Institute",country:{name:"Nigeria"}}},{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",biography:"Professor Dr. Shailendra K. Saxena is a vice dean and professor at King George's Medical University, Lucknow, India. His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. Dr. Saxena is a fellow of various international societies/academies including the Royal College of Pathologists, United Kingdom; Royal Society of Medicine, London; Royal Society of Biology, United Kingdom; Royal Society of Chemistry, London; and Academy of Translational Medicine Professionals, Austria. He was named a Global Leader in Science by The Scientist. 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