Charateristics of common childhood cancers in India.
\\n\\n
Dr. Pletser’s experience includes 30 years of working with the European Space Agency as a Senior Physicist/Engineer and coordinating their parabolic flight campaigns, and he is the Guinness World Record holder for the most number of aircraft flown (12) in parabolas, personally logging more than 7,300 parabolas.
\\n\\nSeeing the 5,000th book published makes us at the same time proud, happy, humble, and grateful. This is a great opportunity to stop and celebrate what we have done so far, but is also an opportunity to engage even more, grow, and succeed. It wouldn't be possible to get here without the synergy of team members’ hard work and authors and editors who devote time and their expertise into Open Access book publishing with us.
\\n\\nOver these years, we have gone from pioneering the scientific Open Access book publishing field to being the world’s largest Open Access book publisher. Nonetheless, our vision has remained the same: to meet the challenges of making relevant knowledge available to the worldwide community under the Open Access model.
\\n\\nWe are excited about the present, and we look forward to sharing many more successes in the future.
\\n\\nThank you all for being part of the journey. 5,000 times thank you!
\\n\\nNow with 5,000 titles available Open Access, which one will you read next?
\\n\\nRead, share and download for free: https://www.intechopen.com/books
\\n\\n\\n\\n
\\n"}]',published:!0,mainMedia:null},components:[{type:"htmlEditorComponent",content:'
Preparation of Space Experiments edited by international leading expert Dr. Vladimir Pletser, Director of Space Training Operations at Blue Abyss is the 5,000th Open Access book published by IntechOpen and our milestone publication!
\n\n"This book presents some of the current trends in space microgravity research. The eleven chapters introduce various facets of space research in physical sciences, human physiology and technology developed using the microgravity environment not only to improve our fundamental understanding in these domains but also to adapt this new knowledge for application on earth." says the editor. Listen what else Dr. Pletser has to say...
\n\n\n\nDr. Pletser’s experience includes 30 years of working with the European Space Agency as a Senior Physicist/Engineer and coordinating their parabolic flight campaigns, and he is the Guinness World Record holder for the most number of aircraft flown (12) in parabolas, personally logging more than 7,300 parabolas.
\n\nSeeing the 5,000th book published makes us at the same time proud, happy, humble, and grateful. This is a great opportunity to stop and celebrate what we have done so far, but is also an opportunity to engage even more, grow, and succeed. It wouldn't be possible to get here without the synergy of team members’ hard work and authors and editors who devote time and their expertise into Open Access book publishing with us.
\n\nOver these years, we have gone from pioneering the scientific Open Access book publishing field to being the world’s largest Open Access book publisher. Nonetheless, our vision has remained the same: to meet the challenges of making relevant knowledge available to the worldwide community under the Open Access model.
\n\nWe are excited about the present, and we look forward to sharing many more successes in the future.
\n\nThank you all for being part of the journey. 5,000 times thank you!
\n\nNow with 5,000 titles available Open Access, which one will you read next?
\n\nRead, share and download for free: https://www.intechopen.com/books
\n\n\n\n
\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"5350",leadTitle:null,fullTitle:"ICT - Energy Concepts for Energy Efficiency and Sustainability",title:"ICT - Energy Concepts for Energy Efficiency and Sustainability",subtitle:null,reviewType:"peer-reviewed",abstract:"In a previous volume (ICT-Energy-Concepts Towards Zero-Power ICT; referenced below as Vol. 1), we addressed some of the fundamentals related to bridging the gap between the amount of energy required to operate portable/mobile ICT systems and the amount of energy available from ambient sources. The only viable solution appears to be to attack the gap from both sides, i.e. to reduce the amount of energy dissipated during computation and to improve the efficiency in energy-harvesting technologies. In this book, we build on those concepts and continue the discussion on energy efficiency and sustainability by addressing the minimisation of energy consumption at different levels across the ICT system stack, from hardware to software, as well as discussing energy consumption issues in high-performance computing (HPC), data centres and communication in sensor networks.\n
\r\n\tAcademicians and policy-makers are always searching for new econometric methods to answer specific policy questions. More importantly, the advent in the advances of computing power has enabled more advanced econometric techniques to be computed with ease. Econometrics uses statistical methods and real-world data to predict and establish specific trends within economics and other social sciences.
\r\n\r\n\tThis volume attempts to explore the practical aspects of econometrics to economics, and other social sciences that use econometric methods. This volume is expected to cover a broad range of topics that include but are not limited to spatial econometrics, time series, forecasting, and machine learning, This volume hopes to attract dynamic stochastic general equilibrium (DSGE) models which are gaining prominence in applied macroeconomics. This proposed volume could serve as a reference for academicians, researchers, policy-makers, graduate students, and very abled undergraduate students who are seeking current research on the various applications of econometrics as used in research and to answer specific policy questions.
",isbn:"978-1-80356-525-5",printIsbn:"978-1-80356-524-8",pdfIsbn:"978-1-80356-526-2",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,isNomenclature:!1,hash:"bc8ab49e2cf436c217a49ca8c12a22eb",bookSignature:"Dr. Brian Sloboda",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11601.jpg",keywords:"Bayesian, Spatial Durbin Models, Spatial Autocorrelation, Spatial Panel Regression, Forecasting Models, Cointegration, Dynamic Factor Modes, State-Space Models, Causality, Clustering, Dynamic Stochastic General Equilibrium (DSGE), Loss Curves",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"March 9th 2022",dateEndSecondStepPublish:"May 13th 2022",dateEndThirdStepPublish:"July 12th 2022",dateEndFourthStepPublish:"September 30th 2022",dateEndFifthStepPublish:"November 29th 2022",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"15 days",secondStepPassed:!0,areRegistrationsClosed:!1,currentStepOfPublishingProcess:3,editedByType:null,kuFlag:!1,biosketch:"A mission-driven educator with expertise in Applied Econometrics, Regional Economics, and Labor Economics. Also, a skilled communicator who excels at interacting with students and motivating them to achieve their educational and career goals.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"452331",title:"Dr.",name:"Brian",middleName:null,surname:"Sloboda",slug:"brian-sloboda",fullName:"Brian Sloboda",profilePictureURL:"https://mts.intechopen.com/storage/users/452331/images/system/452331.jpg",biography:"Professional Profile Accredited as an Accredited Professional Statistician™ (PSTAT) by the American Statistical Association (ASA). Reaccredited through Aug.2022.\n\nComputer-proficient researcher skilled in statistical and econometric software, including E-Views, STATA, SPSS, and SAS Studio®. Working knowledge of MATHLAB and Dynare.\n\nResearch Fellow, Global Labor Organization (GLO), Oct.2017 to present\nAcademic and Professional Profiles \nResearch gate Profile:https: // www. researchgate. net/ profile/ Brian_ Sloboda\nORCID:https: // orcid. org/ 0000-0003-0007-1725\nGoogle Scholar Profile https: // scholar. google. com/ citations? user= RSLTrCsAAAAJ&hl= en\nEducation: Ph.D. Economics, Southern Illinois University at Carbondale,1997.\nThesis: The Economic Impact of Southern Illinois University on the State of Illinois: The Human Capital Approach\nM.S. Economics, Southern Illinois University at Carbondale,1992.\nB.A. Economics, Rowan University,1990.Minor: Mathematics.\nFields of Interest: Regional Economics, Economic Growth, Labor Economics, Economic and Statistical Education",institutionString:"University of Maryland, Global Campus",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:null}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"7",title:"Business, Management and Economics",slug:"business-management-and-economics"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"429339",firstName:"Jelena",lastName:"Vrdoljak",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/429339/images/20012_n.jpg",email:"jelena.v@intechopen.com",biography:"As an Author Service Manager, my responsibilities include monitoring and facilitating all publishing activities for authors and editors. From chapter submission and review to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. 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Mycotoxins may be generated in foodstuffs at different stages from production to transfer and preservation processes. Chemical stability and persistence of mycotoxins make them long-lasting, and even after elimination of fungi, mycotoxins may exist in foodstuffs [1].
Aflatoxin (AF) is the most abundant type of mycotoxins found in foodstuffs. Chemists isolated AF from
Chemical structure of AFs (Adapted from Marin and Taranu [
AFs commonly contaminate cereals and cereal-based foods such as rice, maize, sorghum, millet, groundnuts, dried cassava, and many others during the storage and poor processing conditions. AFs not only contaminate foodstuff but are also found in edible tissues, milk, and eggs after consumption of contaminated feed by farm animals [1, 6]. Trout, rats, ducklings, cattle, poultry, and swine are some of the many animals that have been shown to be sensitive to AF [6]. According to AFB1 concentration, the organs may be classed as follows: gonads, liver, kidney, spleen, bursa cloacalis, thymus, endocrine glands, muscles, lungs, and brain [7]. Petr et al. [8] revealed that AFB1 was determined in the blood, kidney, liver, and testis to maximum 8–10 h after a single intraperitoneal (i.p.) injection at 0.1 mg/kg AFB1.
AFs are a group of naturally occurring food-borne poisons that have been associated with death and disease in humans and animals. They are of great worldwide concern due to their toxic effects on human and animal health [9]. Among all AFs, AFB1 is the most toxic, mutagenic, and carcinogenic to both humans and livestock and is classified into group I as human carcinogen by the International Agency for Research on Cancer [10]. The extent of the carcinogenicity of AF depends on the presence of human health factors including hepatitis B virus infection, nutritional status, sex, and age as well as the amount of AF exposure [11, 12]. In transgenic mice, it was shown that overexpression of the hepatitis B virus large peptide envelope acted synergistically with AFB1 to have an effect on neoplastic development and other forms of chronic liver damage [13].
The immunotoxic potential of AF is known in many species, including laboratory and domestic animals [14]. In pigs, AF causes the decreases in blastogenic responses to mitogen, the reductions in complement titers, the decreases in macrophage activation, and the depression of delayed hypersensitivity responses [15]. Poultry is known to be extremely sensitive to the toxic effects of AFB1. Consumption of AFB1-contaminated feed causes a myriad of other effects either directly or indirectly associated with this toxicity: reduced feed utilization and efficiency, reduced growth rate, decreased body and organ weights [16], lowered egg production and reproductivity [17], immunosuppression [18], and increased susceptibility to disease [19].
AFs undergo biotransformation mainly in the liver. There are two types of biotransformations: Phase 1 and Phase 2. Phase 1 reactions are generally oxidative, reductive, or hydrolytic processes and provide a necessary chemical structure for Phase 2 reactions, which are generally conjugation reactions. Phase 1 reactions may result in activation as well as detoxification of a compound, whereas Phase 2 reactions, depending on conjugated cellular constituents, may lead either to detoxification or formation of biochemical lesions. Phase 1 is mostly mediated by the cytochrome P450 (CYP450) enzyme systems. Phase 2 metabolism involves sulfate, glucuronide, glutathione (GSH), and amino acid conjugation reactions (Figure 2) [20].
Metabolism of AF in the liver. 1A2, CYP1A2; 3A4, CYP3A4; 3A5, CYP3A5; GST, glutathione-
AB1 is oxidized by CYP450 subfamilies and specific isoforms of enzymes to several products. Only one of these, AFB1 epoxide, appears to be mutagenic, and others are detoxification products. The putative AFB1 epoxide is generally accepted as the active electrophilic form of AFB1, which may attack nucleophilic nitrogen, oxygen, and sulfur heteroatoms in cellular constituents [22]. The CYP450-mediated oxidation to the extremely reactive AFB1-8,9-epoxide is considered the primary (Phase 1) bioactivation pathway for AFB1 [23]. This conversion of AFB1, to the epoxide, is the phase of reaction that enables covalent binding to cellular macromolecules (e.g., DNA and/or protein) to occur. This reaction can involve a number of isozymes of CYP450 including 1A2 and 3A4 [24]. The AFB1-8,9-epoxide reacts with the N7 atom of guanine to form a pro-mutagenic DNA adduct (AF-N7-guanine). The DNA adducts are fairly resistant to DNA repair processes, and this causes gene mutation and thus the development of cancers especially the hepatocellular carcinomas (Figure 2) [21, 25].
CYP450 3A4, which can both activate and detoxicate AFB1, is found in the liver and small intestine. In the small intestine, the first contact after oral exposure, epoxidation, would not lead to liver cancer. CYP450 3A4 has been shown to play a major role in the activation of AFB1 due to its intrinsic activity toward this substrate, and the high level of this enzyme is present in human liver. CYP450 1A2 and some other human CYP450s also contribute, but they play a lesser role, even at relatively low AFB1 concentration [26, 27]. CYP450 3A4 forms mostly the genotoxic AFB-2,3-epoxide, whereas CYP450 1A2 forms both the exo- and nongenotoxic endoisomers [26]. CYP450 1A2 has high affinity for the bioactivation of AFB1 at low substrate concentrations following dietary exposure [21]. Some of the AFB1 intermediates go through far more metabolism in Phase 2 by binding with GSH in order to create the polar and less toxic compound that are simply excreted in urine and bile. However, AFBO and AFB1-dihydroxide intermediates led to carcinogenicity, while AFB2 causes acute toxicity, liver necrosis, and cellular metabolizing enzyme inhibition (Figure 2) [28].
Phase 2 reactions that lead to the detoxification involve conjugation to glucuronic acid, sulfate, and GSH. The AFB metabolites of Phase 1 metabolism undergo Phase 2 enzymatic metabolism by glutathione-S-transferases (GSTs) that primarily catalyze conjugation reactions. After Phase 1 oxidation, AF can be readily conjugated with SH groups (in Phase 2 reactions) allowing for further detoxification and elimination of the toxin. In a number of mammalian species, the AFB1-8,9-epoxide is efficiently conjugated with reduced GSH in a reaction catalyzed by GST (Figure 3) [29, 30].
Metabolism of AFB1. Glutathione and glutathione-S-transferase involved in detoxification of activated AFB1.
Free radicals are highly reactive species that have an unpaired electron, e.g., hydroxyl (·OH) and superoxide radicals (O ̄2) which have potential to cause tissue damage (Figure 4). Although free radicals are highly reactive and potentially damaging, they are also an integral part of some cellular processes. Extracellular secretion of free radicals by leucocytes and microphages evokes immune response against bacteria, viruses, degenerated cells, and other foreign substances. Intracellular secretion of free radicals stimulates different cell signaling pathways and triggers oxidative stress defense response as well as apoptosis [31]. Due to perilous nature of free radicals, cells have a counter mechanism known as antioxidant defense to keep the free radical levels under check. Unfortunately, when certain conditions promote the excess production of free radicals or deplete the antioxidant defense that leads the cell to oxidative damage, oxidative stress is said to exist. Oxygen-derived free radicals are referred as reactive oxygen species (ROS). Oxygen radicals are produced as a consequence of the normal process of reduction of oxygen to water and represent by products of oxidative cellular metabolism. The main sites of ROS produced in living organisms are mitochondrial electron transport system, peroxisomal fatty acid, CYP450, and phagocytic cells [32]. ROS can react with DNA to cause breaks in the DNA chain and mutation, which could initiate carcinogenesis. Free radicals can react with membrane lipids leading to peroxidation of polyunsaturated fatty acid (PUFA) residues (Figure 4) [33, 34].
Different endogenous sources for ROS/reactive nitrogen species (RNS), antioxidant defense. Hydroxynonenal (HNE) is one of the end products of lipid peroxidation (adapted from Hardas [
The majority of lipid peroxidation events that occur within the cell are result of free radical chain reaction. Oxidative damage to lipids generally results in formation of cytotoxic aldehyde and ketone derivatives. Typically free radicals have a very short half-life; therefore, the damage caused by them is localized. Unlike free radicals, lipid peroxidation products have a longer half-life, and so they can diffuse into bilayer and can cause oxidative damage away from their site of production. For a given fatty acid, multiple aldehydic or ketonic products can arise as a result of lipid peroxidation, depending upon which allylic carbon gets attacked to initiate the chain reaction [36, 37]. Malondialdehyde (MDA) is a significant final product, which composes via the degeneration of certain primary and secondary lipid peroxidation products [38]. The MDA formation promotes the alteration of membrane fluidity and enhances of membrane fragility. Furthermore, MDA blocks particular enzyme reactions and causes mutagenicity and carcinogenicity by creating DNA adducts [39, 40].
Although ROS and reactive nitrogen species (RNS) are generated under normal physiological conditions, their levels are efficiently regulated by antioxidant enzymes and molecules to maintain the cellular redox balance. Oxidative stress is defined as a disturbance in the balance between antioxidants and prooxidants, with increased levels of prooxidants leading to potential damage. This imbalance can be due to the decrease of endogenous antioxidants, low intake of dietary antioxidants, and/or increased formation of free radicals and other reactive species. In any case, either of both circumstances occurring together or separately eventually will lead to deleterious modifications of biomolecules and multitude of downstream consequences. Oxidative stress has been implicated in vast array of conditions including cancer, arthritis, cardiovascular diseases, diabetes, aging, and neurodegenerative disorders [33, 41, 42].
Oxidative stress plays a major role in aflatoxicosis. Oxidative stress may be due to direct effect of AFs themselves or by their metabolites. AFB1, a mutagenic food contaminant, is widely recognized as one of the most potent hepatocarcinogens in humans and experimental animals. Metabolizing AFB1 increases the production of free radicals and lipid peroxides, resulting in cell damage [43, 44]. AFB1 is activated in the liver by CYP450 to AFB1-8,9-epoxide, which forms adducts with both DNA and protein. The toxic effects of AFs mostly arise from the binding of this particular epoxide derivative to DNA. AFs form after a series of highly organized oxidation-reduction reactions. Several studies provided evidences indicating that CYP450 enzymes generate superoxide hydrogen peroxide (H2O2) as intermediate compounds, and these ROS can cause apoptosis and other cell pathologies [45–47]. AFB1 is able to induce ROS generation, which causes oxidative stress. The genetic toxicity of AFB1 is partly due to the accumulation of ROS such as O2−, ·OH, and H2O2 radical during the metabolic processing of AFB1 by CYP450 in the liver (Figure 5). These species may attack soluble cell compounds as well as membranes, eventually leading to the impairment of cell functioning and cytolysis [48].
Effect of AFs on the oxidative stress, the alleviating role of antioxidants (adapted from Marin and Taranu [
It has been reported that there is free radical generation during AFB1 metabolism, and oxidative damage is one type of damage caused by AFB1 [49, 50]. Oxidative damage induced by these ROS can, in turn, cause tissue damage by a variety of mechanisms including DNA damage, lipid peroxidation, protein oxidation, and depletion of thiols. The oxidative stress caused by AFB1 may be one of the underlining mechanisms for AFB1-induced cell injury and DNA damage, which eventually lead to tumorigenesis [37]. Studies have revealed that AFB1 alters cell cycle and apoptosis-signaling pathways in liver cell models [43, 47, 51, 52]. AFB1 can cause an increase in ROS formation in animals’ target organs including rat liver, duck liver, and mouse lung [37, 44, 53]. It is indicated that AFB1 induced an important liver cell injury, as shown by the significant increase in nitric oxide, but also a strong lipid peroxidation in the liver and kidney, accompanied with a significant decrease in total antioxidant capacity in rats [53], mice [54], and chicken [55]. Also, it was shown that a strong inducible nitric oxide synthase (iNOS) and nitrotyrosine immunoreactivity were observed in the livers of chicks administered with 300 ppb of AF. Moreover, AFB1 carcinogenicity is associated with altered expression of many p53-target genes and induction of mutations, principally the p53 codon 249 hotspot mutation [13, 48].
AFs are claimed as potential risk factor of hepatocarcinoma, and the oxidative stress is considered to be a main factor in the initiation and the progression of liver cirrhosis, which is known to be a pioneer of human hepatocellular carcinoma [11]. The oxidative damage caused by AF is considered to be the main mechanism leading to the subsequent hepatotoxicity [56]. AFB1 may disturb the integrity of cell membranes by stimulating phospholipid A2 to initiate lipid peroxidation in cells [57]. Animals fed with AF-contaminated diet suffer from oxidative stress as indicated by the significant increment of lipid peroxidation and the significant reduction of enzymatic antioxidant such as SOD and GSH-Px [54, 58, 59]. According to the pioneering work of Shen et al. [60], AFB1 promotes lipid peroxidation in rat liver, and lipid peroxidation is intimately linked with liver cell injury. A time- and dose-dependent increase in 8-hydroxy-2′-deoxyguanosine (8-OHdG) was observed in DNA after a single intraperitoneal injection of AFB1. It reveals that AFB1 leads to oxidative DNA damage in rat liver, which may participate in ·OH as the initiating species. Therefore, factors having an effect on formation or action of .OH would affect the generation of 8-OHdG.
It is well known that a possible mechanism of AF cytotoxicity is the induction of oxidative stress. The induction of oxidative stress is commonly related to an imbalance between the oxidants and the antioxidant systems [49]. It is explained by its effect on mitochondria; increased lipid peroxidation; increased adduct formation with DNA, RNA, and protein; or all the three. Damage to mitochondria can lead to mitochondrial diseases and may be responsible for aging mechanisms. The damage can cause mitochondrial DNA (adducts and mutation), mitochondrial membranes, as well as disruption of energy production (production of adenosine triphosphate) [61]. The mycotoxin alters energy-linked functions of adenosine diphosphate (ADP) phosphorylation and flavin adenine dinucleotide (FAD) and nicotinamide adenine dinucleotide (NAD)-linked oxidizing substrates and α-ketoglutarate-succinate cytochrome reductases [62, 63]. It causes ultrastructural changes in mitochondria and also induces mitochondria-directed apoptosis [51]. AFB1 induced the production of free radicals and the reduction of antioxidant defenses in livers of murine, human lymphocytes, and bovine peripheral blood mononuclear cells [51, 64, 65].
AFB1 primarily causes hepatocellular carcinoma and cholangiocarcinoma in the liver [11]. Among various types of known AFs, AFB1 is the most potent hepatocarcinogen; however, G1 and B2 also cause cancers but with reduced potency. It causes liver tumors in mice, rats, fish, marmosets, tree shrews, and monkeys following the administration by various routes. The types of cancers described in research animals include hepatocellular carcinoma, cholangiocellular cancer, and adenocarcinoma of the gallbladder [66].
Besides, the liver tumors have also been reported to develop AF feeding in lacrimal glands, squamous cells of the tongue, esophagus, trachea, lung adenomas, osteogenic sarcoma, and carcinoma of the pancreas [66–68]. Carcinoma of the colon has been reported by many researchers [67, 69]. AF exposure contributes to the risk for development of hepatocellular carcinoma in ducklings [70]. AFB1 can cause hepatocarcinogenesis and mutation in rat liver (Figure 6) [71]. Ghebranious and Sell [13] proposed that some mutant proteins may act as a promoting agent for AFB1 hepatocarcinogenesis. AF and p53 expressions interact to produce malignant liver tumors transgenic in mice.
Overview of metabolic pathways leading to toxicity and carcinoma of AFB1 [
Polyunsaturated lipids are essential for cells, being important constituents of cell membranes, endoplasmic reticulum, and mitochondria. Thus, the disruption of their structural properties could have consequences for cellular function. Lipid peroxidation is one of the main factors responsible for structural and functional alterations of the cell membrane following oxidative stress [39] and initiation of carcinogenesis [37, 54].
It remains unknown if the mycotoxins promote the lipid peroxidation directly through the enhancement of the ROS formation or the enhancement of the tissue sensitivity to the peroxidation is the result of the compromised antioxidant defense, but it appears that both processes are taken part. AFB1-mediated cell injury may be due to the release of free radicals that initiate lipid peroxidation. The initiation of lipid peroxidation is caused by the attack of any species that has sufficient reactivity to remove a hydrogen atom from a methylene group upon a PUFA [37, 54]. The peroxidation of PUFAs can be realized not only through nonenzymatic free radical-induced pathways but also through processes that are catalyzed by enzymes as cyclooxygenase and lipoxygenase [39]. It is shown that also 8,9-epoxide increases lipid peroxidation, followed by loss of membrane stability and the blockage of the membrane-bound enzyme activity [73]. Evaluation of the lipid damage is based on measurement of Thiobarbituric acid reactive substances (TBARS) or MDA by the TBA test and conjugated dienes. AFB1 induced an increase in the TBARS concentration in the liver [74] or in human hepatoma cells [75]. The increase of the lipid peroxide synthesis is observed not only in the liver but also in the kidney and brain [7, 35, 41]. This alteration was associated with a significant increase in conjugated diene formation. Concentrations of MDA+ 4-hydroxyalkenals as an index of lipid peroxidation are increased by AFB1 in the liver, lung, brain, and testis, but not the kidney of male Wistar rats [76]. 4-Hydroxynonenal (4-HNE), a major electrophilic by-product of lipid peroxidation caused by oxidative stress, interacts with DNA to form exocyclic guanine products, which have been shown to increase in a rat model of hepatocarcinogenesis. AFB1 induces lipid peroxidation in rat liver, which may be an underlying mechanism of carcinogenesis [44, 77].
ROS can also lead to oxidation of amino acid residue side chains, formation of protein-protein cross-linkages, and oxidation of the protein backbone resulting in protein fragmentation, and the modified forms of proteins will accumulate in organism [78]. By its capacity to generate ROS, AFB1 can promote the ROS-mediated oxidative damages in proteins (Figure 6) [79].
AFB1 could inhibit some (serine) proteolytic enzymes responsible for the degradation of damaged proteins, with consequent relevant implications in hepatocarcinogenesis [79, 80]. It has been suggested that numerous action of AFs may be brought about their interactions with the proteasome, the main enzyme family account for the decomposition of most of cytosolic and nuclear proteins in eukaryotic cells. In fact, AFB1 brings about an inhibition of cellular 20S proteasomes, affecting the cellular defense against oxidative stress. Because 20S proteasome is the proteolytic machinery responsible for removing oxidized proteins, its inhibition could contribute to a higher protein carbonyl content observed in cultured hepatoma cell lysates [81].
The reduction of protein synthesis in animals treated with AFs may affect certain metal ions, which play an important role in free radical production and liberation. Inhibition of protein synthesis caused by AFs alters serum protein composition, resulting in suppression of the production of nonspecific humoral substances important to native defense [82]. At higher doses, AFB1 lowers the level of IgG and IgA in chick resulting in decreased acquired immunity. Antibodies to AFB1 have been reported in humans [83, 84].
Oxidative DNA damage is a general definition for all types of changes (structural or functional) of DNA, due to the interaction of ROS with DNA. The connection of ·OH to the C8 position of DNA guanine forms C8-OH-adduct radical [85], which is eventually altered to 8-OH-guanine (8-OH-Gua) by one-electron oxidation [86]. While impaired lipids and proteins can be removed by metabolic cycle of these compounds, damaged DNA has to be fixed in situ or destroyed by apoptotic processes; conversely, mutations result in the absence of these [87]. In humans, 8-OH-Gua glycosylase is the primary enzyme for the repair of 8-OH-Gua in short-patch base excision repair. The excised form of 8-OH-Gua is a pro-mutagenic adduct, 8-OHdG, which is excreted into urine without further metabolism and is stable for a significant time. 8-OHdG is widely considered as a key biomarker of oxidative DNA damage [60, 88].
The toxic and carcinogenic effects of AFB1 are intimately linked with its biotransformation [12]. There is a tendency for AFs especially AFB1 to convert into the epoxide and produce DNA adducts resulting in the formation of DNA strand breaks and mutations [88, 89]. It is well known that AFB1 is activated by the hepatic CYP450 enzyme system to form a highly reactive product, AFB1-8,9-epoxide, which subsequently connects to nucleophilic sites in DNA and the major adduct 8,9-dihydro-8-(N7-guanyl)-9-hydroxy-AFB1 (AFB1-N7-Gua) is formed. The formation of AFB1-DNA adducts is regarded as a critical step in the initiation of AFB1-induced hepatocarcinogenesis (Figure 7).
Metabolic activation of AFB1 (adapted from Kobertz et al. [
The activity of antioxidant enzymes could induce as a result to the oxidative stress or could diminish through direct or indirect action of the mycotoxins. A part of the oxidative metabolism intermediates of AFB1 composes a substrate for the Phase 2 detoxification enzymes. In a vast range of animal species, the fundamental way to detoxify the AFB1 is through the conjugation of AFBO with GSH. This way of detoxification is the principal way of AFB1 excretion in many animal species. The reaction is catalyzed by GST [89]. It is observed that in mice, the reduced sensibility to AFs is correlated with the constitutive increase of GST isoenzyme [29]. GSH and GST are effective antioxidant enzymes that take part in the protection of tissues from harmful effects of AFB1 (Figure 3) [90, 91]. GSH is used as a cofactor by GST that conjugates GSH with endogenous substances like estrogens, exogenous electrophiles like AFs and its metabolites, and other various xenobiotics. The increased depletion of GSH leads to abnormally high levels of ROS in cells. AF is one of the main actors in depletion of GSH. The depletion of GSH affects metabolic processes such as catalysis of molecular oxygen (O2) to H2O2 by GSH-Px, and thus the integrity of the cell membranes disrupts. Its reduction further enhances the damage to critical cellular components (DNA, lipids, proteins) by the AFB1-8,9-epoxides that form adducts. GST catalyzes the conjugation of AFB1-8,9-epoxide with GSH to form AFB1-GSH conjugate, thereby decreasing the intracellular GSH content [37]. The AF-GSH product undergoes the sequential metabolism in the liver and kidneys in which it is excreted as a mercapturic acid (AF-N-acetylcysteine) in urine [91, 92]. It has been reported that AF administration results in excessive lipid peroxidation [53] with concomitant decrease in GSH [58], increased protein oxidation, and DNA damage in rat liver. The activity of GSH-Px, which is a constituent of GSH redox cycle, decreases during AFB1 administration. The reduction in GSH-Px activity by AFB1 may be due to a decrease in the availability of GSH and also alterations in their protein structure by ROS. The studies revealed that there were obvious increases in MDA and/or nitric oxide (NO) levels and decreases in both nonenzymatic antioxidant GSH level and enzymatic antioxidant GSH-Px, catalase (CAT), glutathione reductase (GR), and GST activities after administration with AFB1 in vivo or in vitro [41, 51, 64, 65].
The study showed that administration of AFB1 produced a marked oxidative impact as evidenced by a significant increase in MDA in the liver, kidneys, and heart of AF-treated rats. These alterations might have been triggered either by the direct effects of AFB1 or by the metabolites formed by AF and the free radicals, which were generated during the formation of these metabolites. Initiation of LPO by AFB1 is noted as one of the principal appearances of ROS-induced oxidative damage. The mechanism of free radical damage also includes ROS-induced peroxidation of polyunsaturated fatty acids in the cell membrane lipid bilayer which causes a chain reaction of LPO, thus damaging the cellular membrane, causing further oxidation of membrane lipids and proteins, and leading to DNA damage. The study also showed that a significant increase in the oxidative stress was accompanied by a concomitant decrease in the enzyme activities involved in the disposal of O2− and peroxides, namely, CAT and SOD, as well as GSH levels and its related enzymes (GST, GSH-Px). A significant increase observed in tissue MDA levels in AFB1-treated animals indicated that AF led to the generation of the high level of free radicals, which could not be tolerated by the cellular antioxidant defense system. A significant decrease in these enzyme activities could be explained by their consumption during the conversion of free radicals into less harmful or harmless metabolites [49].
Lycopene is an acyclic hydrocarbon carotenoid responsible for the intense red color of tomatoes (Figure 8). Lycopene does not exhibit provitamin A activity since it lacks the β-ionone ring structure which is characteristic in carotenoids that are precursors for vitamin A [93, 94]. Lycopene is a natural pigment and imparts a red color in the foods containing it. In foods, lycopene is found predominantly in its trans-form (approximately 95.4% of total lycopene content), whereas serum and tissues contain more cis-isomers of lycopene [95–97]. Lycopene is nontoxic and Generally Recognized as Safe by the US FDA (21 CFR 73.585) and the European Union (Directive 94/36/EC) for the use as a food additive and colorant [98].
Structure of all-trans lycopene (C40H56).
Lycopene acts as an antioxidant by virtue of its conjugated p-electron system, which can react with oxygen radical species such as peroxy and hydroxy radicals as well as non-radical species such as ozone and H2O2 [99].
Lycopene has a robust antioxidant defense system, attributed to its acyclic structure, numerous conjugated double bonds, and high hydrophobicity, and thus prevents the onset of carcinogenesis and atherogenesis processes by protecting/stabilizing biomolecules such as DNA, proteins, lipids, and lipoproteins. Lycopene, as the main carotenoid in tomato products, possesses the greatest ability to quench singlet oxygen compared to the other carotenoids. It also scavenges the free radicals
Lycopene is capable of acting as an antioxidant by virtue of its many conjugated double bonds. It is the most efficient neutralizer of singlet oxygen among all carotenoids and has also been found to be a potent scavenger of free radicals [94, 95]. The lycopene molecule reacts with free radicals to form a short-lived intermediate species, which later end up as lycopene decomposition products including apocarotenals, apocarotenones, and epoxides. Being a highly hydrophobic molecule, the greatest scavenging ability of lycopene is seen in lipophilic environments [94, 103]. After supplementing subjects with lycopene from different dietary sources, serum TBARS (a biomarker for lipid peroxidation) is significantly reduced, whereas nonsignificant reductions are observed in biomarkers for protein and DNA oxidation. Hence, lycopene may be a biologically important antioxidant by protecting membrane lipids from being oxidized which in turn preserves the integrity of cellular membranes [104].
Much of the evidence for the antioxidant function of lycopene comes from studies conducted with in vitro systems, and virtually all of them indicate lycopene to function as a superior dietary antioxidant. Being is a strong antioxidant, lycopene has been shown to reduce the amount of oxidative DNA damage and also decrease lipid peroxidation in cell culture and in rats in vivo [105–107]. Di Mascio et al. [108] compared the singlet oxygen quenching ability of various carotenoids, α-tocopherol, bile acids, and retinoic acid. They found lycopene to be the most efficient quencher among all, with a greater than twofold quenching potency. Lycopene is the most efficient carotenoid in reducing TBARS formation by 75% compared to control in multilamellar liposomes. In a study examining the relative ability of several antioxidants in reducing carotenoid cations, it was found that lycopene was the most superior carotenoid antioxidant and the lycopene cation radical was the most stable carotenoid cation radical [109].
There are many reports indicating that lycopene is effective on inhibition of tumor formation and growth induced by chemical carcinogens in animals [107]. To sum up, in Figure 9, AFB1 has two important metabolic pathways: Phase 1 includes metabolism and metabolic activation, and Phase 2 is detoxification [30]. AFM1, AFQ1, AFP1, and AFB1-8,9-epoxide are important Phase 1 metabolites, and also AFB-N7-Gua and AFB-albumin complexes are specific markers formed, respectively, in the tissues and “serum or urine” during the AFB1 metabolic activation. The main Phase 2 detoxification outcome of AFB1-8,9-epoxide is AFB-N-acetyl cysteine (AFB-NAC) complex. AFB1 Phase 1 metabolism and the metabolic activation of AFB1 are inhibited by lycopene. Moreover, lycopene highly activates the enzymes responsible for Phase 2 detoxification and causes to enhance production of AFB-NAC excreted in urine. As shown in decreased urinary levels of AFP1, AFQ1, and AFM1 in lycopene-pretreated or lycopene-intervened animals, lycopene pretreatment or intervention significantly blocks Phase 1 metabolism of AFB1. This indicates that lycopene may selectively inhibit Phase 1 metabolic enzymes such as 3A4, 2A6, and 1A2. Depending on the relative potency in decreasing levels of these specific AFB1 metabolites in urine, lycopene appears to be a moderate competitive inhibitor of 3A4 and 2A6 enzymes and a weak or reversible inhibitor of 1A2 enzyme (more potent inhibition of AFP1 and AFQ1 than AFM1). Reducing levels of AFB-albumin adducts in serum, reducing levels of AFB-N7-Gua excreted in urine, and reducing levels of AFB-N7-Gua adduct in the liver, DNA confirmed the inhibitory effect of lycopene on Phase 1 metabolism. These data clearly demonstrate that lycopene pretreatment or intervention effectively blocks AFB1 metabolism and also metabolic activation. AFB-NAC is the major detoxifying metabolic product of AFB1-8,9-epoxide. Lycopene pretreatment and intervention elevated significantly AFB-NAC levels in urine excretion, which suggests that activity of GSTs was greatly induced [30].
AFB1 metabolic activation, biomarkers, and possible mechanisms of lycopene modulation [
AFB1 also induces formation of ROS [44], lipid peroxidation, and formation of 8-OHdG in vivo and in vitro [60]. Lycopene could increase the activity of GSH-Px, GST, and GR in several animal models including rats [111]. The antioxidant capacity of lycopene is at extremely high levels and lessens not only the oxidative damage of DNA in particular rates but also lessens lipid peroxidation both in vitro and in vivo [105–107]. It has also been documented that lycopene intervention reduces the 8-OHdG levels of urine even in recurring exposures to AFB1 (Figure 10).
Inhibition of toxicity and cancer by lycopene in AFB1-exposed cells. Chemoprotective effects of lycopene effects are shown by arrows: ↑, increase; ↓, decrease (adapted from Reddy et al. [
Administration of lycopene alleviates the negative effects of AF. Lycopene removes free radicals produced by AF while improving the body’s antioxidant enzymes such as GSH, GSH-Px, and CAT to prevent the oxidative damage caused by AF, enhancing the body antioxidant capacity, reducing the levels of lipid peroxidation, and maintaining cell membrane permeability. For this reason, natural antioxidant lycopene can be regarded as a good therapeutic agent against aflatoxicosis [112].
Current concepts derived from intensive research on biotransformation, mechanisms of toxicity, the effect on oxidative stress of AF, and protective effect of lycopene on AF damage were summarily presented in this chapter. AFB1 exerts its effects after conversion to the reactive compound AFB1 epoxide by means of CYP450-dependent enzymes. This epoxide can form derivatives with cellular macromolecules, including proteins, RNA and DNA. Biomonitoring of AFB1 metabolites such as AFB1-N7-guanine has demonstrated that AFs constitute an important risk factor for hepatocellular carcinoma in highly exposed populations. Oxidative stress formed due to AF is associated with biochemical disturbances in oxidant/antioxidant balance system, which may cause AF toxicity. When administered together with AF, lycopene was determined that it exhibited strong positive effect on AF-induced oxidative stress parameters. It could be concluded that the lycopene being a nontoxic, highly promising natural “eco-friendly” antioxidant compound has a protective effect against AF toxicity. When administered together with AF, lycopene was determined that it exhibited a strong positive effect on AF-induced oxidative stress parameters.
Pediatric cancers have never been an area of attention of cancer control in India, as majority of cancers occur in adults. Globally, it is reported that up to 85% of pediatric cancers occur in the developing world with a 5-year survival rate of less than 10%. On an average, in India, pediatric cancers account for less than 5% of all cancer cases. Nearly 45,000 new cancer cases are diagnosed in children every year in India. The main focus in pediatric care has been on control and reduction of infectious disease related mortality, which is in striking contrast with the developed world [1].
More than 0.2 million cases of childhood cancers are diagnosed across the globe every year. In the developed world, majority of these are cured, with a 5- year survival rate of 95%. However, the first step towards the control of childhood cancers in developing countries like India is to find out the incidence of cancers, to take directed measures in terms of control and treatment facilities. The main sources of such data are cancer registries [2].
Compared to the West, with average incidence of 75 to 150 childhood cancers per million children, the average incidence of childhood cancers in India is high. The age standardized incidence of cancers in India in the age group 0–14 years is highest in the Chennai Urban registry (124/million children) and lowest in the Ahmedabad rural registry (38/million children). The reasons for higher incidence in urban areas as compared to rural areas are not clear. However, cancer contributes to only 2% of cancer related deaths in childhood as per available data. It was never a priority, in comparison to infectious diseases control, the main cause of mortality among children in India. Another contrast with developed world is the preponderance of cancers in boys, except in North-East India. The main reason is probably gender bias in seeking healthcare. However, the reasons for disproportionately higher rate of Hodgkin’s disease in male children, up to 20 times more incidence than in females, are not known [3, 4].
One decade ago, the estimated gap between the developed and developing world in the survival rates in pediatric cancers was about 60–70% - a great divide. The reasons are many.
Because of high prevalence and mortality due to infectious diseases in children in India than cancer mortality - 58% of all deaths in the age group of 5–14 years, and half of these are due to diarrhea and pneumonia - and improved outcomes of infectious diseases by simple medication that can be delivered at peripheral centers, the emphasis has been high in this domain.
The Pediatric Hematology and Oncology (PHO) chapter of Indian Academy of Pediatrics (IAP) was established in 1987, with a focus on capacity building through training initiatives across all aspects of childhood cancers. Its flagship program was the
In order to foster collaborative efforts in childhood cancers, both in terms of uniformity of care as well as shared databases, Dr Bharat Agarwal, Dr Purna Kurkure and Dr Anupam Sachdeva formed
The Indian Pediatric Hematology Oncology Group (IPHOG) was formed in 1987 at the 24th Annual Conference of the
Some of the identified barriers were: delayed diagnosis, nihilism about childhood cancers, abandonment of treatment, lack of experience, inadequate infrastructure to treat emergent toxicities, expectation of cure, and, unwillingness to opt for retreatment at relapse [5].
Practical solutions that are already being followed by some institutions in India are as follows:
Educating primary care providers, especially pediatricians, about the diagnosis of childhood cancers and early referral to specialized centers
Twinning, a process of collaboration between a hospital in a developing country with another in the developed world
Establishing a reliable blood component support system
Training nursing staff and other valuable trained human resources like social workers
Measures to prevent abandonment after diagnosis of cancer in a child by providing logistic support in the form of transportation and free shelter to the family as well as employment with modest wages to parents
A systems for reminding and follow up with the parents of a child shortly after missing the scheduled visit
Fellowship and other training programs in medical colleges with well-established pediatrics departments
Countering nihilism and misinformation by untrained or improperly trained health care workers, emphasizing curability in the majority
Cancer registration, an essential part to decipher patterns presentation, care and outcomes research, was started in India only in 1960s, in a small way. Until 1964, data was gathered through cancer surveys to estimate the incidence and trends. This was grossly inadequate for any conclusions and meaningful planning of need based services.
The first registry in India was started in Bombay (current Mumbai) in 1964 followed by Pune in 1973 and then in Aurangabad in late seventies [6]. However, cancer registration as a complete coordinated program was started only in 1982, with the Indian Council for Medical Research (ICMR) taking steps towards establishing the National Cancer Registry Program (NCRP).
The beginning was humble with three population based and three hospital-based registries, which is now expanded to 36 population based and over a hundred hospital-based cancer registries.
We have come a long way in these 6 decades. The existing registries cover about only 15% of the country’s population [7]. We still lack population-based registries in some of the bigger states like Andhra Pradesh, Uttar Pradesh, Odisha and Rajasthan, where we depend on hospital-based registries. Cancer registration is not mandatory in our country. Collection in population-based registries is also through active methods, involving lot of time and manpower.
To overcome these hurdles, ICMR, through the establishment of National Centre for Disease Informatics and Research (NCDIR), initiated a program called, Cancer Atlas, to fill in these gaps, by abstracting information directly from pathology labs in Hospitals and Medical colleges, where, up to 85% of the cancer cases are confirmed microscopically. Another welcome step is that cancer case reporting is now mandatory in the states like Kerala, Karnataka, Gujarat and Manipur.
Relying on Population Based Cancer registries may be grossly insufficient to estimate the burden of cancer in children. Lack of awareness among public, particularly parents, to recognize and report symptoms likely to be from cancer in children, lack of accessible pediatric cancer services in many parts of the country, financial constraints of the family, resulting in dropout from treatments or even death before being seen at a specialized facility for treatment, are some glaring lacunae. As such, the burden estimated may not reflect the actual scenario in Indian society. India shares this common problem with other countries. The same is detailed in UICC’s outreach program for childhood cancers called “My Child Matters”™.
To help in this aspect, a few Voluntary and non-governmental organizations (NGO) are reaching out to maintain databases of pediatric cancers in India, such as the Jiv Daya Foundation from Dallas, USA, that funds a cloud based program called “Indian Pediatric Oncology Database” [8].
Although India is making rapid strides in the development in several areas like agriculture and space technology, there is glaring deficiency and disparity in delivering much needed primary medical care. While this is in part due to the difficult to reach terrain of this vast sub-continent, the main reasons appear to be a reluctance of the well trained doctor to serve remote areas due lack of basic civic amenities. Lack of political will, compounded by lack of awareness of the curability and pessimism about cancer in both law makers themselves, as well the medical fraternity further worsen the problem (Table 1).
Type of cancer | Most common presentation Symptoms and Features of disease | Reason for late diagnosis and Barriers in completion of treatment | Estimated 5-year Survival in India from available data |
---|---|---|---|
Acute Lymphocytic Leukemia and Acute Myeloid Leukemia [9, 10, 11] |
|
| ALL: 45–81% AML: 35.5% (North India) Induction Mortality: 18% |
Lymphoma |
|
| Hodgkin’s Lymphoma:90% NHL: Early stage: 91% Advanced stage 61% |
Central Nervous system tumors [15] |
|
| Data Not available |
Retinoblastoma [16] |
|
| 5 years OS: South India: 92% North India: 63% |
Neuroblastoma [17] |
|
| 3 year OS: Early stage:60.7% Advanced stage: 35.7% |
Wilms Tumor [18] |
|
| 5 year OS: 70–85% |
Charateristics of common childhood cancers in India.
This pessimism is predominant in pediatric cancers as there are insufficient points of care. Most cancers are under diagnosed due to lack of adequate diagnostic facilities, and, when diagnosed, are treated by pediatricians with limited knowledge about oncology, or adult oncologists with limited knowledge about pediatric cancers.
The first pediatric oncology center was established in 1970, at the Cancer Institute, Chennai, by Professor V Shanta, a great visionary in the field of cancer education and training. Another landmark is the establishment of first dedicated Pediatric Oncology Unit in Mumbai at the Tata Memorial Hospital, in the 1990s, by Prof. Shripad Banavali. This center also pioneered the training program and award of a sub-specialty doctoral degree pediatric oncology. The main advantage of such dedicated centers is access to advanced diagnostic services like Immunophenotyping, PET CT, cytogenetics, blood component therapy and trained nurses manning clinics catering to venous access devices [19].
In early 2000, pediatric oncology developed as a specialized branch in India. It is the combined responsibility of academicians in various pediatric departments to build and develop a sustainable pediatric oncology program. The reasons are obvious: it is still not sustainable for a pediatric oncologist to restrict practice to just pediatric oncology, in the community. The earnings from care of only childhood cancer patients being meager, most practice non-malignant hematology as well as general pediatrics. Medical Oncologists with a training in pediatric oncology happily practice both adult and pediatric oncology.
The Indian Association of Cancer Chemotherapists was founded in the early 60s by surgeons who practiced adjuvant chemotherapy for their operated patients. Most of its members were eminent cancer surgeons like Dr. Roy Choudhury of Kolkata and Dr. N C Mishra of Lucknow. It was renamed as the Indian Society for Medical and Pediatric Oncology at an annual conference of the Society in Ahmedabad, Gujarat, in late 80s (personal communication, Professor Pankaj M Shah – Former Director, Gujarat Cancer and Research Institute). Cancer oriented pediatricians still band together as the pediatric oncology sub chapter of the Indian Academy of Pediatrics.
Along with ISMPO, several other Oncology Networks like ICON (Indian Cooperative Oncology Network), and INPOG (Indian National Pediatric Oncology Group) help of pediatric oncologists in collaborating across the nation and with experts abroad to share ideas, knowledge, and expertise.
There is a drastic improvement in the outcomes of childhood cancers over the past two decades ago. The reasons are many, including dedicated training programs, establishment of pediatric cancer centers, and, most importantly adoption and collaboration of treatment protocols from the developed world.
One such example of collaboration is adoption of the acute lymphoblastic leukemia and lymphoma protocols developed by Prof Ian Magrath of the National Cancer Institute, USA, specifically for the developing world [MCP 841 & MCP 842 protocols]. With the guidance from Prof. Magrath’s International Network for Cancer Treatment and Research (INCTR), the outcomes of the patients on this protocol improved by three times from 20 to 60%. The protocol also paved the way for adequate platelet transfusion protocols mandating intramuscular l-asparaginase as well as immunophenotyping of acute lymphoblastic leukemia and lymphoma into cALLa positive and T cell leukemias [20, 21].
There are several volunteer groups and non-governmental organizations (NGOs) that provide much needed help to the patient and family who travel to a city from the moffusil. The St. Jude’s Children Homes specialize in establishing homes in or near the premises of major childhood cancer treatment centers, in cities, for housing the child with family as a unit, throughout the course of its treatment. Several organizations also provide technical, logistic and financial assistance with travel, food, shelter, paperwork as well as drugs.
The Pediatric Oncology sub-chapter of the Indian Academy of Pediatrics created a training program for pediatricians, called NTP-PPO (National Training Program – Practical Pediatric Oncology). Over the years, through this program, nearly 50 workshops have been conducted and about 2000 pediatricians have been trained to identify, diagnose, and refer children with cancers to appropriate centers. Pediatricians are also trained in management of febrile neutropenia, venous access and maintenance chemotherapy. Since most of them practice in the community, their services are often of paramount importance in ensuring continuity of care.
There are other programs for intensive pediatric oncology training, such as a one-year program by IAP and 2-year Fellowship by the National Board of Examinations, which works under the aegis of Ministry of Health and Family Welfare, Government of India [22].
Delay in referral is a big hindrance for timely management of pediatric cancers. Some delay is due to logistics: not so easy to negotiate monsoon inundated roads in remote rural areas. A sheer lack of awareness even among radiologists and orthopedic specialists is one reason for delay in diagnosis of Ewing’s Sarcoma and Osteosarcoma, which are often treated as tubercular osteomyelitis [22].
There are several early obstacles in access to essential medications for cancer patients in India. Several attempts were made by the government to bridge this gap. One such successful attempt was providing access to generics. The other big step is inclusion of some of antineoplastic drugs like imatinib in the Essential Medicines List (EML). In many states, such as Andhra Pradesh, Tamil Nadu, Rajasthan and Kerala, the government has evolved schemes like the
Pediatric palliative care is in a naïve state in most parts of the world, and so is in India. With very few dedicated pediatric palliative care centers and many cultural barriers, provision of palliative care is still mostly rudimentary [24].
A bright example for such development in India is collaboration between Nawaj Mehdi Jung (MNJ) Hospital in Telangana State with the Canadian branch of International Network for Cancer Treatment and Research in 2007 [25]. Such an exercise to prevent and treat pain in the children diagnosed with cancer irrespective of the end point resulted in enrolment of more pediatric patients, reduction in dropouts from treatment and those lost to follow up, with an increase in survival. In India, it is estimated that 1.6 million pediatric patients with various ailments are in need of pediatric palliative care. However, it will be a difficult task to train enough personnel to be able to serve this population. A first step towards such goal is the initiation of training program in MNJ hospital. In 2010, the Indian Association of Palliative Care (IAPC) established a separate pediatric palliative care unit in the state of Maharashtra, in collaboration with the International Children Palliative Care Cetwork (ICPCN) [26].
India, along with other low and middle income countries, has been the hub spot for leading the developments in management of pediatric cancers. Together, these countries account for nearly 90% of all diagnosed childhood cancers across the globe. In India, majority of population is from rural areas, where, awareness about symptoms of childhood cancer symptoms, the knowledge of diagnosis and even referral among physicians is low, contributing to avoidable delays in instituting treatment, with resultant inferior cure rates. Prohibitive costs in private sector coupled with unavailability of facilities in public sector, render outcomes to be very poor even in cancers like Hodgkin’s lymphoma that are otherwise curable by simple protocols. Although there are policies at national level addressing the prevention and control of cancers as a whole, there is no special emphasis on pediatric cancers. However, there is light at the end of tunnel in the form of several schemes, like coverage of pediatric cancers under the newly -launched
India, which is the fastest growing nation among developing countries in terms of human resources, development and cancer incidence in children should lead by example by improving quality of care and accessibility to Cancer care to children, in particular. Finally, it is especially important to remember that pediatric oncology departments as standalone units cannot serve and deliver comprehensive care required by a child. Collaboration between pediatricians, radiologists, surgeons, anesthetists, neurosurgeons, urologists, psychiatrists and other subspecialties would help in achieving the quality of care.
There is severe paucity in the data of exact incidence, prevalence, morbidity, mortality, and survivorship data of pediatric cancers in India. However, based on the available registry data, both population based and hospital based, the most common malignancies diagnosed in India in children are Leukemias, Lymphomas, CNS tumors, Retinoblastoma and Malignant Bone Tumors (Figure 1).
Pediatric oncology centers in India in various decades.
The authors declare no conflict of interest.
IntechOpen implements a robust policy to minimize and deal with instances of fraud or misconduct. As part of our general commitment to transparency and openness, and in order to maintain high scientific standards, we have a well-defined editorial policy regarding Retractions and Corrections.
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\\n\\nIntechOpen wishes to emphasize that the final decision on whether a Retraction, Statement of Concern, or a Correction will be issued rests with the Academic Editor. The publisher is obliged to act upon any reports of scientific misconduct in its publications and to make a reasonable effort to facilitate any subsequent investigation of such claims.
\\n\\nIn the case of Retraction or removal of the Work, the publisher will be under no obligation to refund the APC.
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\n\nA formal Retraction will be issued when there is clear and conclusive evidence of any of the following:
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\n\n2. STATEMENTS OF CONCERN
\n\nA Statement of Concern detailing alleged misconduct will be issued by the Academic Editor or publisher following a 3rd party report of scientific misconduct when:
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\n\n3. CORRECTIONS
\n\nA Correction will be issued by the Academic Editor when:
\n\n3.1. ERRATUM
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\n\n3.2. CORRIGENDUM
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\n\n4. FINAL REMARKS
\n\nIntechOpen wishes to emphasize that the final decision on whether a Retraction, Statement of Concern, or a Correction will be issued rests with the Academic Editor. The publisher is obliged to act upon any reports of scientific misconduct in its publications and to make a reasonable effort to facilitate any subsequent investigation of such claims.
\n\nIn the case of Retraction or removal of the Work, the publisher will be under no obligation to refund the APC.
\n\nThe general principles set out above apply to Retractions and Corrections issued in all IntechOpen publications.
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\n\nPolicy last updated: 2017-09-11
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which depolymerizes the cellulose into glucose. Cellulases are produced by a diverse array of microbes including fungi, bacteria, yeast and actinomycetes. Considerable research for understanding the mechanism of cellulases began in early 1950s because of the significant use of these enzymes in various industries. This review provides a general account structure and availability of lignocellulosic biomass, pretreatment strategies for effective digestion, cellulase producing organisms, cellulase activity assay, and enzymology of cellulose degradation. Cellulase production, optimization, purification and characterization studies in addition to the industrial application of cellulase have also been discussed. At last a brief account of present market scenario of cellulases and future prospects of the study are also taken into account.",book:{id:"8150",slug:"elements-of-bioeconomy",title:"Elements of Bioeconomy",fullTitle:"Elements of Bioeconomy"},signatures:"Namita Singh, Anita Devi, Manju Bala Bishnoi, Rajneesh Jaryal, Avni Dahiya, Oleksandr Tashyrev and Vira Hovorukha",authors:[{id:"278205",title:"Prof.",name:"Namita",middleName:null,surname:"Singh",slug:"namita-singh",fullName:"Namita Singh"},{id:"282352",title:"Dr.",name:"Anita",middleName:null,surname:"Devi",slug:"anita-devi",fullName:"Anita Devi"},{id:"282353",title:"MSc.",name:"Avni",middleName:null,surname:"Dahiya",slug:"avni-dahiya",fullName:"Avni Dahiya"},{id:"282354",title:"MSc.",name:"Manju Bala",middleName:null,surname:"Bishnoi",slug:"manju-bala-bishnoi",fullName:"Manju Bala Bishnoi"},{id:"282355",title:"Dr.",name:"Oleksandr",middleName:null,surname:"Tashyrev",slug:"oleksandr-tashyrev",fullName:"Oleksandr Tashyrev"},{id:"282356",title:"Dr.",name:"Rajneesh",middleName:null,surname:"Jaryal",slug:"rajneesh-jaryal",fullName:"Rajneesh Jaryal"},{id:"282939",title:"Dr.",name:"Vira",middleName:null,surname:"Hovorukha",slug:"vira-hovorukha",fullName:"Vira Hovorukha"}]},{id:"56708",doi:"10.5772/intechopen.69096",title:"Human Development and Research-Development-Extension Relationships",slug:"human-development-and-research-development-extension-relationships",totalDownloads:1733,totalCrossrefCites:1,totalDimensionsCites:5,abstract:"Human capital is the most important strategic factor for development; as new technologies emerge, the market demand for better and healthier products and consumer demand in terms of quality and delivery time are changing. In today’s world, it becomes increasingly important to know how information can be accessed, how it is adopted, and how it can be assimilated. In this respect, each country allocates budget for training, education, and extension according to its own conditions. This budget may be intended for rural community-based social assistance, but the economic and welfare effect is essential. In this way, it is aimed to increase the living standards of the families living in the rural areas. This will naturally contribute to national income and to the prosperity of society. The subject has been discussed generally in the world, especially in the case of Turkey. According to this, all over the world, particularly in developing countries, research and extension (R&E) is very important and should be considered at least as much as research and development (R&D). However, it will be ensured that societies meet with the technology produced. For this, the development of human resources should be emphasized and a suitable atmosphere should be prepared for this widespread prosperity.",book:{id:"5819",slug:"research-and-development-evolving-trends-and-practices-towards-human-institutional-and-economic-sectors-growth",title:"Research and Development Evolving Trends and Practices",fullTitle:"Research and Development Evolving Trends and Practices - Towards Human, Institutional and Economic Sectors Growth"},signatures:"Orhan Özçatalbaş",authors:[{id:"170206",title:"Prof.",name:"Dr. Orhan",middleName:null,surname:"Özçatalbaş",slug:"dr.-orhan-ozcatalbas",fullName:"Dr. Orhan Özçatalbaş"}]},{id:"66110",doi:"10.5772/intechopen.84770",title:"Gold Recovery Process from Primary and Secondary Resources Using Bioadsorbents",slug:"gold-recovery-process-from-primary-and-secondary-resources-using-bioadsorbents",totalDownloads:1996,totalCrossrefCites:2,totalDimensionsCites:3,abstract:"Bioadsorbents were prepared in a simple manner only by treating in boiling concentrated sulfuric acid from various biomass materials such as various polysaccharides, persimmon tannin, cotton, paper and biomass wastes such as orange juice residue and microalgae residue after extracting biofuel. These bioadsorbents exhibited high selectivity only to gold over other metals and extraordinary high loading capacity for gold(III), which were elucidated to be attributable to the selective reduction of gold(III) ion to elemental gold due to its highest oxidation-reduction potential of gold(III) of metal ions, catalyzed by the surface of bioadsorbents prepared in boiling sulfuric acid. By using these biosorbents, recovery of gold from actual samples of printed circuit boards of spent mobile phones and Mongolian gold ore was investigated. Recovery of trace concentration of gold(I) from simulated spent alkaline cyanide solution was also investigated using the bioadsorbent. Application of bioadsorbents to some recovery processes of gold from cyanide solutions was proposed.",book:{id:"8150",slug:"elements-of-bioeconomy",title:"Elements of Bioeconomy",fullTitle:"Elements of Bioeconomy"},signatures:"Katsutoshi Inoue, Durga Parajuli, Manju Gurung, Bimala Pangeni, Kanjana Khunathai, Keisuke Ohto and Hidetaka Kawakita",authors:[{id:"198951",title:"Prof.",name:"Keisuke",middleName:null,surname:"Ohto",slug:"keisuke-ohto",fullName:"Keisuke Ohto"},{id:"259238",title:"Dr.",name:"Hidetaka",middleName:null,surname:"Kawakita",slug:"hidetaka-kawakita",fullName:"Hidetaka Kawakita"},{id:"289372",title:"Dr.",name:"Katsutoshi",middleName:null,surname:"Inoue",slug:"katsutoshi-inoue",fullName:"Katsutoshi Inoue"},{id:"298633",title:"Dr.",name:"Bimala",middleName:null,surname:"Pangeni",slug:"bimala-pangeni",fullName:"Bimala Pangeni"},{id:"298634",title:"Dr.",name:"Manju",middleName:null,surname:"Gurung",slug:"manju-gurung",fullName:"Manju Gurung"},{id:"298635",title:"Dr.",name:"Kanjana",middleName:null,surname:"Khunathai",slug:"kanjana-khunathai",fullName:"Kanjana Khunathai"},{id:"298636",title:"Dr.",name:"Durga",middleName:null,surname:"Parajuli",slug:"durga-parajuli",fullName:"Durga Parajuli"}]},{id:"66428",doi:"10.5772/intechopen.84833",title:"Review of Biofuel Technologies in WtL and WtE",slug:"review-of-biofuel-technologies-in-wtl-and-wte",totalDownloads:1177,totalCrossrefCites:1,totalDimensionsCites:2,abstract:"Processing of biomass feedstocks to produce energy, fuels, and chemicals via a combination of different applied technologies is considered a promising pathway to achieve sustainable waste management, with many environmental and economic benefits. In this chapter, we review the current state of the main processes associated with energy recovery and biofuel production under the concept of waste biorefineries. The reviewed technologies are classified into thermochemical, biological, and chemical, including combustion, gasification, steam explosion, pyrolysis, hydrothermal liquefaction, and torrefaction; anaerobic digestion, fermentation, enzymatic treatment, and microbial electrolysis; and hydrolysis, solvent extraction, transesterification, and supercritical conversion. Their brief history, current status, and future developments are discussed within a perspective of valorization and managing of current waste streams with no solution.",book:{id:"8150",slug:"elements-of-bioeconomy",title:"Elements of Bioeconomy",fullTitle:"Elements of Bioeconomy"},signatures:"Bruno B. Garcia, Gonçalo Lourinho, Paulo Brito and Pedro Romano",authors:[{id:"261653",title:"Prof.",name:"Paulo",middleName:null,surname:"Brito",slug:"paulo-brito",fullName:"Paulo Brito"},{id:"261654",title:"Prof.",name:"Pedro",middleName:null,surname:"Romano",slug:"pedro-romano",fullName:"Pedro Romano"},{id:"291751",title:"B.Sc.",name:"Bruno B.",middleName:"B",surname:"Garcia",slug:"bruno-b.-garcia",fullName:"Bruno B. 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This chapter shows how these issues can be addressed starting with measuring and modeling energy consumption patterns by collecting an energy consumption dataset at device level. The open dataset allows to extract typical usage patterns and subsequently to model test scenarios for energy management algorithms. Section 3 discusses means for analyzing measured data and for providing detailed feedback about energy consumption to increase customers’ energy awareness. Section 4 shows how renewable energy sources can be integrated in a smart microgrid and how energy production can be accurately predicted. Section 5 introduces a self-organizing local energy system that autonomously coordinates production and consumption via an agent-based energy auction system. The final section discusses how the proposed methods contribute to sustainable growth and gives an outlook to future research.",book:{id:"5819",slug:"research-and-development-evolving-trends-and-practices-towards-human-institutional-and-economic-sectors-growth",title:"Research and Development Evolving Trends and Practices",fullTitle:"Research and Development Evolving Trends and Practices - Towards Human, Institutional and Economic Sectors Growth"},signatures:"Wilfried Elmenreich, Tamer Khatib and Andrea Monacchi",authors:[{id:"163771",title:"Dr.",name:"Wilfried",middleName:null,surname:"Elmenreich",slug:"wilfried-elmenreich",fullName:"Wilfried Elmenreich"},{id:"197214",title:"Dr.",name:"Andrea",middleName:null,surname:"Monacchi",slug:"andrea-monacchi",fullName:"Andrea Monacchi"}]}],mostDownloadedChaptersLast30Days:[{id:"66110",title:"Gold Recovery Process from Primary and Secondary Resources Using Bioadsorbents",slug:"gold-recovery-process-from-primary-and-secondary-resources-using-bioadsorbents",totalDownloads:1996,totalCrossrefCites:2,totalDimensionsCites:3,abstract:"Bioadsorbents were prepared in a simple manner only by treating in boiling concentrated sulfuric acid from various biomass materials such as various polysaccharides, persimmon tannin, cotton, paper and biomass wastes such as orange juice residue and microalgae residue after extracting biofuel. These bioadsorbents exhibited high selectivity only to gold over other metals and extraordinary high loading capacity for gold(III), which were elucidated to be attributable to the selective reduction of gold(III) ion to elemental gold due to its highest oxidation-reduction potential of gold(III) of metal ions, catalyzed by the surface of bioadsorbents prepared in boiling sulfuric acid. By using these biosorbents, recovery of gold from actual samples of printed circuit boards of spent mobile phones and Mongolian gold ore was investigated. Recovery of trace concentration of gold(I) from simulated spent alkaline cyanide solution was also investigated using the bioadsorbent. Application of bioadsorbents to some recovery processes of gold from cyanide solutions was proposed.",book:{id:"8150",slug:"elements-of-bioeconomy",title:"Elements of Bioeconomy",fullTitle:"Elements of Bioeconomy"},signatures:"Katsutoshi Inoue, Durga Parajuli, Manju Gurung, Bimala Pangeni, Kanjana Khunathai, Keisuke Ohto and Hidetaka Kawakita",authors:[{id:"198951",title:"Prof.",name:"Keisuke",middleName:null,surname:"Ohto",slug:"keisuke-ohto",fullName:"Keisuke Ohto"},{id:"259238",title:"Dr.",name:"Hidetaka",middleName:null,surname:"Kawakita",slug:"hidetaka-kawakita",fullName:"Hidetaka Kawakita"},{id:"289372",title:"Dr.",name:"Katsutoshi",middleName:null,surname:"Inoue",slug:"katsutoshi-inoue",fullName:"Katsutoshi Inoue"},{id:"298633",title:"Dr.",name:"Bimala",middleName:null,surname:"Pangeni",slug:"bimala-pangeni",fullName:"Bimala Pangeni"},{id:"298634",title:"Dr.",name:"Manju",middleName:null,surname:"Gurung",slug:"manju-gurung",fullName:"Manju Gurung"},{id:"298635",title:"Dr.",name:"Kanjana",middleName:null,surname:"Khunathai",slug:"kanjana-khunathai",fullName:"Kanjana Khunathai"},{id:"298636",title:"Dr.",name:"Durga",middleName:null,surname:"Parajuli",slug:"durga-parajuli",fullName:"Durga Parajuli"}]},{id:"56708",title:"Human Development and Research-Development-Extension Relationships",slug:"human-development-and-research-development-extension-relationships",totalDownloads:1733,totalCrossrefCites:1,totalDimensionsCites:5,abstract:"Human capital is the most important strategic factor for development; as new technologies emerge, the market demand for better and healthier products and consumer demand in terms of quality and delivery time are changing. In today’s world, it becomes increasingly important to know how information can be accessed, how it is adopted, and how it can be assimilated. In this respect, each country allocates budget for training, education, and extension according to its own conditions. This budget may be intended for rural community-based social assistance, but the economic and welfare effect is essential. In this way, it is aimed to increase the living standards of the families living in the rural areas. This will naturally contribute to national income and to the prosperity of society. The subject has been discussed generally in the world, especially in the case of Turkey. According to this, all over the world, particularly in developing countries, research and extension (R&E) is very important and should be considered at least as much as research and development (R&D). However, it will be ensured that societies meet with the technology produced. For this, the development of human resources should be emphasized and a suitable atmosphere should be prepared for this widespread prosperity.",book:{id:"5819",slug:"research-and-development-evolving-trends-and-practices-towards-human-institutional-and-economic-sectors-growth",title:"Research and Development Evolving Trends and Practices",fullTitle:"Research and Development Evolving Trends and Practices - Towards Human, Institutional and Economic Sectors Growth"},signatures:"Orhan Özçatalbaş",authors:[{id:"170206",title:"Prof.",name:"Dr. Orhan",middleName:null,surname:"Özçatalbaş",slug:"dr.-orhan-ozcatalbas",fullName:"Dr. Orhan Özçatalbaş"}]},{id:"68851",title:"Introductory Chapter: Objectives and Scope of Bioeconomy",slug:"introductory-chapter-objectives-and-scope-of-bioeconomy",totalDownloads:970,totalCrossrefCites:0,totalDimensionsCites:0,abstract:null,book:{id:"8150",slug:"elements-of-bioeconomy",title:"Elements of Bioeconomy",fullTitle:"Elements of Bioeconomy"},signatures:"Krzysztof Biernat",authors:[{id:"155009",title:"Prof.",name:"Krzysztof",middleName:null,surname:"Biernat",slug:"krzysztof-biernat",fullName:"Krzysztof Biernat"}]},{id:"68007",title:"Overview of the Process of Enzymatic Transformation of Biomass",slug:"overview-of-the-process-of-enzymatic-transformation-of-biomass",totalDownloads:1378,totalCrossrefCites:4,totalDimensionsCites:5,abstract:"Cellulase is an enzyme which depolymerizes the cellulose into glucose. Cellulases are produced by a diverse array of microbes including fungi, bacteria, yeast and actinomycetes. Considerable research for understanding the mechanism of cellulases began in early 1950s because of the significant use of these enzymes in various industries. This review provides a general account structure and availability of lignocellulosic biomass, pretreatment strategies for effective digestion, cellulase producing organisms, cellulase activity assay, and enzymology of cellulose degradation. Cellulase production, optimization, purification and characterization studies in addition to the industrial application of cellulase have also been discussed. At last a brief account of present market scenario of cellulases and future prospects of the study are also taken into account.",book:{id:"8150",slug:"elements-of-bioeconomy",title:"Elements of Bioeconomy",fullTitle:"Elements of Bioeconomy"},signatures:"Namita Singh, Anita Devi, Manju Bala Bishnoi, Rajneesh Jaryal, Avni Dahiya, Oleksandr Tashyrev and Vira Hovorukha",authors:[{id:"278205",title:"Prof.",name:"Namita",middleName:null,surname:"Singh",slug:"namita-singh",fullName:"Namita Singh"},{id:"282352",title:"Dr.",name:"Anita",middleName:null,surname:"Devi",slug:"anita-devi",fullName:"Anita Devi"},{id:"282353",title:"MSc.",name:"Avni",middleName:null,surname:"Dahiya",slug:"avni-dahiya",fullName:"Avni Dahiya"},{id:"282354",title:"MSc.",name:"Manju Bala",middleName:null,surname:"Bishnoi",slug:"manju-bala-bishnoi",fullName:"Manju Bala Bishnoi"},{id:"282355",title:"Dr.",name:"Oleksandr",middleName:null,surname:"Tashyrev",slug:"oleksandr-tashyrev",fullName:"Oleksandr Tashyrev"},{id:"282356",title:"Dr.",name:"Rajneesh",middleName:null,surname:"Jaryal",slug:"rajneesh-jaryal",fullName:"Rajneesh Jaryal"},{id:"282939",title:"Dr.",name:"Vira",middleName:null,surname:"Hovorukha",slug:"vira-hovorukha",fullName:"Vira Hovorukha"}]},{id:"67691",title:"The Use of Waste Management Techniques to Enhance Household Income and Reduce Urban Water Pollution",slug:"the-use-of-waste-management-techniques-to-enhance-household-income-and-reduce-urban-water-pollution",totalDownloads:1013,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"Appropriate waste management options are major concerns in the developing world. Current methods include incineration in the open and accumulation of wastes in designated places where they constitute nuisance to the environment. Apart from air pollution from the incinerators, leachates from decomposed wastes are either washed off where they serve as source of pollutants to the adjourning streams and rivers or contaminate groundwater through deep percolation. We present viable options for managing agricultural wastes in this chapter. The options presented are so simple and sustainable such that it can be managed by individuals. Hence, they are independent of the government bureaucratic bottlenecks that have been the bane of the previous government interventions. If embraced, it will also serve as sources of income for the concerned household, hence enhance their livelihood.",book:{id:"8150",slug:"elements-of-bioeconomy",title:"Elements of Bioeconomy",fullTitle:"Elements of Bioeconomy"},signatures:"Olayiwola A. Akintola, Olufunmilayo O. Idowu, Suraju A. 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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"}}}}]},series:{item:{id:"10",title:"Physiology",doi:"10.5772/intechopen.72796",issn:"2631-8261",scope:"Modern physiology requires a comprehensive understanding of the integration of tissues and organs throughout the mammalian body, including the cooperation between structure and function at the cellular and molecular levels governed by gene and protein expression. While a daunting task, learning is facilitated by identifying common and effective signaling pathways mediated by a variety of factors employed by nature to preserve and sustain homeostatic life. \r\nAs a leading example, the cellular interaction between intracellular concentration of Ca+2 increases, and changes in plasma membrane potential is integral for coordinating blood flow, governing the exocytosis of neurotransmitters, and modulating gene expression and cell effector secretory functions. Furthermore, in this manner, understanding the systemic interaction between the cardiovascular and nervous systems has become more important than ever as human populations' life prolongation, aging and mechanisms of cellular oxidative signaling are utilised for sustaining life. \r\nAltogether, physiological research enables our identification of distinct and precise points of transition from health to the development of multimorbidity throughout the inevitable aging disorders (e.g., diabetes, hypertension, chronic kidney disease, heart failure, peptic ulcer, inflammatory bowel disease, age-related macular degeneration, cancer). With consideration of all organ systems (e.g., brain, heart, lung, gut, skeletal and smooth muscle, liver, pancreas, kidney, eye) and the interactions thereof, this Physiology Series will address the goals of resolving (1) Aging physiology and chronic disease progression (2) Examination of key cellular pathways as they relate to calcium, oxidative stress, and electrical signaling, and (3) how changes in plasma membrane produced by lipid peroxidation products can affect aging physiology, covering new research in the area of cell, human, plant and animal physiology.",coverUrl:"https://cdn.intechopen.com/series/covers/10.jpg",latestPublicationDate:"May 14th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:11,editor:{id:"35854",title:"Prof.",name:"Tomasz",middleName:null,surname:"Brzozowski",slug:"tomasz-brzozowski",fullName:"Tomasz Brzozowski",profilePictureURL:"https://mts.intechopen.com/storage/users/35854/images/system/35854.jpg",biography:"Prof. Dr. Thomas Brzozowski works as a professor of Human Physiology and is currently Chairman at the Department of Physiology and is V-Dean of the Medical Faculty at Jagiellonian University Medical College, Cracow, Poland. His primary area of interest is physiology and pathophysiology of the gastrointestinal (GI) tract, with the major focus on the mechanism of GI mucosal defense, protection, and ulcer healing. He was a postdoctoral NIH fellow at the University of California and the Gastroenterology VA Medical Center, Irvine, Long Beach, CA, USA, and at the Gastroenterology Clinics Erlangen-Nuremberg and Munster in Germany. He has published 290 original articles in some of the most prestigious scientific journals and seven book chapters on the pathophysiology of the GI tract, gastroprotection, ulcer healing, drug therapy of peptic ulcers, hormonal regulation of the gut, and inflammatory bowel disease.",institutionString:null,institution:{name:"Jagiellonian University",institutionURL:null,country:{name:"Poland"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:4,paginationItems:[{id:"10",title:"Animal Physiology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/10.jpg",isOpenForSubmission:!0,annualVolume:11406,editor:{id:"202192",title:"Dr.",name:"Catrin",middleName:null,surname:"Rutland",slug:"catrin-rutland",fullName:"Catrin Rutland",profilePictureURL:"https://mts.intechopen.com/storage/users/202192/images/system/202192.png",biography:"Catrin Rutland is an Associate Professor of Anatomy and Developmental Genetics at the University of Nottingham, UK. She obtained a BSc from the University of Derby, England, a master’s degree from Technische Universität München, Germany, and a Ph.D. from the University of Nottingham. She undertook a post-doctoral research fellowship in the School of Medicine before accepting tenure in Veterinary Medicine and Science. Dr. Rutland also obtained an MMedSci (Medical Education) and a Postgraduate Certificate in Higher Education (PGCHE). She is the author of more than sixty peer-reviewed journal articles, twelve books/book chapters, and more than 100 research abstracts in cardiovascular biology and oncology. She is a board member of the European Association of Veterinary Anatomists, Fellow of the Anatomical Society, and Senior Fellow of the Higher Education Academy. 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From\r\n1964 to 1974, he worked as Assistant in Biochemistry at the School of MedicineUniversidad Nacional de La Plata, Argentina. From 1974 to 1976, he was a Fellowof the National Institutes of Health (NIH) at the University of Connecticut, Health Center, USA. From 1985 to 2004, he served as a Full Professor oBiochemistry at the Universidad Nacional de La Plata, Argentina. He is Member ofthe National Research Council (CONICET), Argentina, and Argentine Society foBiochemistry and Molecular Biology (SAIB). His laboratory has been interested for manyears in the lipid peroxidation of biological membranes from various tissues and different species. Professor Catalá has directed twelve doctoral theses, publishedover 100 papers in peer reviewed journals, several chapters in books andtwelve edited books. Angel Catalá received awards at the 40th InternationaConference Biochemistry of Lipids 1999: Dijon (France). W inner of the Bimbo PanAmerican Nutrition, Food Science and Technology Award 2006 and 2012, South AmericaHuman Nutrition, Professional Category. 2006 award in pharmacology, Bernardo\r\nHoussay, in recognition of his meritorious works of research. Angel Catalá belongto the Editorial Board of Journal of lipids, International Review of Biophysical ChemistryFrontiers in Membrane Physiology and Biophysics, World Journal oExperimental Medicine and Biochemistry Research International, W orld Journal oBiological Chemistry, Oxidative Medicine and Cellular Longevity, Diabetes and thePancreas, International Journal of Chronic Diseases & Therapy, International Journal oNutrition, Co-Editor of The Open Biology Journal.",institutionString:null,institution:{name:"National University of La Plata",institutionURL:null,country:{name:"Argentina"}}},editorTwo:null,editorThree:null},{id:"12",title:"Human Physiology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/12.jpg",isOpenForSubmission:!0,annualVolume:11408,editor:{id:"195829",title:"Prof.",name:"Kunihiro",middleName:null,surname:"Sakuma",slug:"kunihiro-sakuma",fullName:"Kunihiro Sakuma",profilePictureURL:"https://mts.intechopen.com/storage/users/195829/images/system/195829.jpg",biography:"Professor Kunihiro Sakuma, Ph.D., currently works in the Institute for Liberal Arts at the Tokyo Institute of Technology. He is a physiologist working in the field of skeletal muscle. He was awarded his sports science diploma in 1995 by the University of Tsukuba and began his scientific work at the Department of Physiology, Aichi Human Service Center, focusing on the molecular mechanism of congenital muscular dystrophy and normal muscle regeneration. His interest later turned to the molecular mechanism and attenuating strategy of sarcopenia (age-related muscle atrophy). His opinion is to attenuate sarcopenia by improving autophagic defects using nutrient- and pharmaceutical-based treatments.",institutionString:null,institution:{name:"Tokyo Institute of Technology",institutionURL:null,country:{name:"Japan"}}},editorTwo:null,editorThree:{id:"331519",title:"Dr.",name:"Kotomi",middleName:null,surname:"Sakai",slug:"kotomi-sakai",fullName:"Kotomi Sakai",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000031QtFXQA0/Profile_Picture_1637053227318",biography:"Senior researcher Kotomi Sakai, Ph.D., MPH, works at the Research Organization of Science and Technology in Ritsumeikan University. She is a researcher in the geriatric rehabilitation and public health field. She received Ph.D. from Nihon University and MPH from St.Luke’s International University. Her main research interest is sarcopenia in older adults, especially its association with nutritional status. Additionally, to understand how to maintain and improve physical function in older adults, to conduct studies about the mechanism of sarcopenia and determine when possible interventions are needed.",institutionString:null,institution:{name:"Ritsumeikan University",institutionURL:null,country:{name:"Japan"}}}},{id:"13",title:"Plant Physiology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/13.jpg",isOpenForSubmission:!0,annualVolume:11409,editor:{id:"332229",title:"Prof.",name:"Jen-Tsung",middleName:null,surname:"Chen",slug:"jen-tsung-chen",fullName:"Jen-Tsung Chen",profilePictureURL:"https://mts.intechopen.com/storage/users/332229/images/system/332229.png",biography:"Dr. Jen-Tsung Chen is currently a professor at the National University of Kaohsiung, Taiwan. He teaches cell biology, genomics, proteomics, medicinal plant biotechnology, and plant tissue culture. Dr. Chen\\'s research interests include bioactive compounds, chromatography techniques, in vitro culture, medicinal plants, phytochemicals, and plant biotechnology. He has published more than ninety scientific papers and serves as an editorial board member for Plant Methods, Biomolecules, and International Journal of Molecular Sciences.",institutionString:"National University of Kaohsiung",institution:{name:"National University of Kaohsiung",institutionURL:null,country:{name:"Taiwan"}}},editorTwo:null,editorThree:null}]},overviewPageOFChapters:{paginationCount:17,paginationItems:[{id:"81791",title:"Self-Supervised Contrastive Representation Learning in Computer Vision",doi:"10.5772/intechopen.104785",signatures:"Yalin Bastanlar and Semih Orhan",slug:"self-supervised-contrastive-representation-learning-in-computer-vision",totalDownloads:12,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Pattern Recognition - New Insights",coverURL:"https://cdn.intechopen.com/books/images_new/11442.jpg",subseries:{id:"26",title:"Machine Learning and Data Mining"}}},{id:"79345",title:"Application of Jump Diffusion Models in Insurance Claim Estimation",doi:"10.5772/intechopen.99853",signatures:"Leonard Mushunje, Chiedza Elvina Mashiri, Edina Chandiwana and Maxwell Mashasha",slug:"application-of-jump-diffusion-models-in-insurance-claim-estimation-1",totalDownloads:2,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Data Clustering",coverURL:"https://cdn.intechopen.com/books/images_new/10820.jpg",subseries:{id:"26",title:"Machine Learning and Data Mining"}}},{id:"81557",title:"Object Tracking Using Adapted Optical Flow",doi:"10.5772/intechopen.102863",signatures:"Ronaldo Ferreira, Joaquim José de Castro Ferreira and António José Ribeiro Neves",slug:"object-tracking-using-adapted-optical-flow",totalDownloads:10,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Information Extraction and Object Tracking in Digital Video",coverURL:"https://cdn.intechopen.com/books/images_new/10652.jpg",subseries:{id:"24",title:"Computer Vision"}}},{id:"81558",title:"Thresholding Image Techniques for Plant Segmentation",doi:"10.5772/intechopen.104587",signatures:"Miguel Ángel Castillo-Martínez, Francisco Javier Gallegos-Funes, Blanca E. Carvajal-Gámez, Guillermo Urriolagoitia-Sosa and Alberto J. 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(Eng.) in Telematics from the Universidad de Colima, Mexico. He obtained both his M.Sc. and Ph.D. from the University of Liverpool, England, in the field of Intelligent Systems. He is a full professor at the Universidad Autonoma de Queretaro, Mexico, and a member of the National System of Researchers (SNI) since 2009. Dr. Aceves Fernandez has published more than 80 research papers as well as a number of book chapters and congress papers. He has contributed in more than 20 funded research projects, both academic and industrial, in the area of artificial intelligence, ranging from environmental, biomedical, automotive, aviation, consumer, and robotics to other applications. He is also a honorary president at the National Association of Embedded Systems (AMESE), a senior member of the IEEE, and a board member of many institutions. His research interests include intelligent and embedded systems.",institutionString:"Universidad Autonoma de Queretaro",institution:{name:"Autonomous University of Queretaro",institutionURL:null,country:{name:"Mexico"}}}]},{type:"book",id:"7726",title:"Swarm Intelligence",subtitle:"Recent Advances, New Perspectives and Applications",coverURL:"https://cdn.intechopen.com/books/images_new/7726.jpg",slug:"swarm-intelligence-recent-advances-new-perspectives-and-applications",publishedDate:"December 4th 2019",editedByType:"Edited by",bookSignature:"Javier Del Ser, Esther Villar and Eneko Osaba",hash:"e7ea7e74ce7a7a8e5359629e07c68d31",volumeInSeries:2,fullTitle:"Swarm Intelligence - Recent Advances, New Perspectives and Applications",editors:[{id:"49813",title:"Dr.",name:"Javier",middleName:null,surname:"Del Ser",slug:"javier-del-ser",fullName:"Javier Del Ser",profilePictureURL:"https://mts.intechopen.com/storage/users/49813/images/system/49813.png",biography:"Prof. Dr. Javier Del Ser received his first PhD in Telecommunication Engineering (Cum Laude) from the University of Navarra, Spain, in 2006, and a second PhD in Computational Intelligence (Summa Cum Laude) from the University of Alcala, Spain, in 2013. He is currently a principal researcher in data analytics and optimisation at TECNALIA (Spain), a visiting fellow at the Basque Center for Applied Mathematics (BCAM) and a part-time lecturer at the University of the Basque Country (UPV/EHU). His research interests gravitate on the use of descriptive, prescriptive and predictive algorithms for data mining and optimization in a diverse range of application fields such as Energy, Transport, Telecommunications, Health and Industry, among others. In these fields he has published more than 240 articles, co-supervised 8 Ph.D. theses, edited 6 books, coauthored 7 patents and participated/led more than 40 research projects. He is a Senior Member of the IEEE, and a recipient of the Biscay Talent prize for his academic career.",institutionString:"Tecnalia Research & Innovation",institution:null}]},{type:"book",id:"7656",title:"Fuzzy Logic",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7656.jpg",slug:"fuzzy-logic",publishedDate:"February 5th 2020",editedByType:"Edited by",bookSignature:"Constantin Volosencu",hash:"54f092d4ffe0abf5e4172a80025019bc",volumeInSeries:3,fullTitle:"Fuzzy Logic",editors:[{id:"1063",title:"Prof.",name:"Constantin",middleName:null,surname:"Volosencu",slug:"constantin-volosencu",fullName:"Constantin Volosencu",profilePictureURL:"https://mts.intechopen.com/storage/users/1063/images/system/1063.png",biography:"Prof. Dr. Constantin Voloşencu graduated as an engineer from\nPolitehnica University of Timișoara, Romania, where he also\nobtained a doctorate degree. He is currently a full professor in\nthe Department of Automation and Applied Informatics at the\nsame university. Dr. Voloşencu is the author of ten books, seven\nbook chapters, and more than 160 papers published in journals\nand conference proceedings. He has also edited twelve books and\nhas twenty-seven patents to his name. He is a manager of research grants, editor in\nchief and member of international journal editorial boards, a former plenary speaker, a member of scientific committees, and chair at international conferences. His\nresearch is in the fields of control systems, control of electric drives, fuzzy control\nsystems, neural network applications, fault detection and diagnosis, sensor network\napplications, monitoring of distributed parameter systems, and power ultrasound\napplications. 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