Barely three months into the new year and we are happy to announce a monumental milestone reached - 150 million downloads.
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This achievement solidifies IntechOpen’s place as a pioneer in Open Access publishing and the home to some of the most relevant scientific research available through Open Access.
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We are so proud to have worked with so many bright minds throughout the years who have helped us spread knowledge through the power of Open Access and we look forward to continuing to support some of the greatest thinkers of our day.
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Thank you for making IntechOpen your place of learning, sharing, and discovery, and here’s to 150 million more!
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Among the clinical applications of Tissue Engineering are the production of artificial skin for burn patients, tissue engineered trachea, cartilage for knee-replacement procedures, urinary bladder replacement, urethra substitutes and cellular therapies for the treatment of urinary incontinence. The Tissue Engineering approach has major advantages over traditional organ transplantation and circumvents the problem of organ shortage. Tissues reconstructed from readily available biopsy material induce only minimal or no immunogenicity when reimplanted in the patient. This book is aimed at anyone interested in the application of Tissue Engineering in different organ systems. It offers insights into a wide variety of strategies applying the principles of Tissue Engineering to tissue and organ regeneration.",isbn:null,printIsbn:"978-953-307-688-1",pdfIsbn:"978-953-51-6449-4",doi:"10.5772/1146",price:139,priceEur:155,priceUsd:179,slug:"tissue-engineering-for-tissue-and-organ-regeneration",numberOfPages:468,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"5bef0b1c31f0555294c7d49580c8d241",bookSignature:"Daniel Eberli",publishedDate:"August 17th 2011",coverURL:"https://cdn.intechopen.com/books/images_new/637.jpg",numberOfDownloads:59175,numberOfWosCitations:62,numberOfCrossrefCitations:29,numberOfCrossrefCitationsByBook:2,numberOfDimensionsCitations:84,numberOfDimensionsCitationsByBook:3,hasAltmetrics:0,numberOfTotalCitations:175,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"November 4th 2010",dateEndSecondStepPublish:"December 2nd 2010",dateEndThirdStepPublish:"April 8th 2011",dateEndFourthStepPublish:"May 8th 2011",dateEndFifthStepPublish:"July 7th 2011",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"6495",title:"Dr.",name:"Daniel",middleName:null,surname:"Eberli",slug:"daniel-eberli",fullName:"Daniel Eberli",profilePictureURL:"https://mts.intechopen.com/storage/users/6495/images/1947_n.jpg",biography:"Daniel Eberli MD. Ph.D. is a scientific physician working in the translational field of urologic tissue engineering. He has a medical degree from the Medical School in Zurich, Switzerland, and a Ph.D. in Molecular Medicine from Wake Forest University, Winston Salem, NC. He currently has a faculty position at the Department of Urology at the University Hospital Zurich, where he devotes half of his time to patient care. He is a lecturer at the Medical School of Zurich and the Swiss Federal Institute of Technology. Together with his research team, he is working on novel biomaterials for bladder reconstruction, improving autonomic innervation, cellular treatment of incontinence and tracking of stem cells.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"4",institution:{name:"University Hospital of Zurich",institutionURL:null,country:{name:"Switzerland"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"980",title:"Tissue Engineering and Regenerative Medicine",slug:"tissue-engineering-and-regenerative-medicine"}],chapters:[{id:"18187",title:"Myocardial Tissue Engineering",doi:"10.5772/22870",slug:"myocardial-tissue-engineering",totalDownloads:2921,totalCrossrefCites:2,totalDimensionsCites:5,hasAltmetrics:0,abstract:null,signatures:"Tatsuya Shimizu",downloadPdfUrl:"/chapter/pdf-download/18187",previewPdfUrl:"/chapter/pdf-preview/18187",authors:[{id:"49606",title:"Prof.",name:"Tatsuya",surname:"Shimizu",slug:"tatsuya-shimizu",fullName:"Tatsuya Shimizu"}],corrections:null},{id:"18188",title:"Cardiac Muscle Engineering: Strategies to Deliver Stem Cells to the Damaged Site",doi:"10.5772/20178",slug:"cardiac-muscle-engineering-strategies-to-deliver-stem-cells-to-the-damaged-site",totalDownloads:2511,totalCrossrefCites:0,totalDimensionsCites:2,hasAltmetrics:0,abstract:null,signatures:"Giancarlo Forte, Stefania Pagliari, Francesca Pagliari, Paolo Di Nardo and Takao Aoyagi",downloadPdfUrl:"/chapter/pdf-download/18188",previewPdfUrl:"/chapter/pdf-preview/18188",authors:[{id:"37701",title:"Dr.",name:"Giancarlo",surname:"Forte",slug:"giancarlo-forte",fullName:"Giancarlo Forte"},{id:"62146",title:"Dr.",name:"Stefania",surname:"Pagliari",slug:"stefania-pagliari",fullName:"Stefania Pagliari"},{id:"62147",title:"Dr.",name:"Francesca",surname:"Pagliari",slug:"francesca-pagliari",fullName:"Francesca Pagliari"},{id:"62777",title:"Prof.",name:"Paolo",surname:"Di Nardo",slug:"paolo-di-nardo",fullName:"Paolo Di Nardo"},{id:"62778",title:"Prof.",name:"Takao",surname:"Aoyagi",slug:"takao-aoyagi",fullName:"Takao Aoyagi"}],corrections:null},{id:"18189",title:"Cardiovascular Tissue Engineering Based on Fibrin-Gel-Scaffolds",doi:"10.5772/19761",slug:"cardiovascular-tissue-engineering-based-on-fibrin-gel-scaffolds",totalDownloads:4630,totalCrossrefCites:10,totalDimensionsCites:21,hasAltmetrics:0,abstract:null,signatures:"Stefan Jockenhoevel and Thomas C. 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1. Introduction
This chapter provides a cursory description of a well-known phenomenon, namely that a significant percentage of people afflicted with certain prevalent disorders causing degenerative neuropathology, depressive and anxiety disorders, progressive loss of memory and communication function such as Autism Spectrum Disorder (ASD), intellectual challenges, as well as post-traumatic stress disorders present with a range of olfactory deficits. Here, we review our understanding of these deficits and their relation to various clinical manifestations such as neurological and neuropsychiatric diseases and disorders, disorders affecting mood, cognition, communication and memory and finally, olfactory deficits as secondary outcome of therapeutic drugs. At the outset, we will briefly describe the olfactory pathway from olfactory sensory neurons in the nasal epithelium to the olfactory bulb and on to olfactory cortical structures and subcortical structures involved in olfaction such as the amygdala. Then, we shall discuss olfaction in the context of normal age-based decline of physiological functions relating olfactory deficits to the onset of neurodegenerative pathology, decline in cognition, memory, ability to communicate as well as with episodes of depression and anxiety.
2. The olfactory system
The main role of the olfactory system is the detection of odors. This function is critical for food selection by detecting olfactory and gustatory signals. Moreover, our sense of smell plays a role in reproductive and neuroendocrine regulation and is relevant for memory, aggression, emotion, social organization, and recognition of prey and predators [1]. Social chemical stimuli or semiochemical signals are processed by the olfactory system in most mammals. These chemicals differ from general odorants and mediate physiological aspects of mating and aggression. These chemical signals are processed in the accessory olfactory bulb in the brain which is part of the vomeronasal system [1].
The olfactory pathway starts deep in the nasal cavity with an olfactory epithelium that sits on the superior conchae (Figure 1). This pseudostratified ciliated columnar epithelium houses olfactory sensory neurons, supporting cells (sustentacular cells), and basal stem cells. In addition, Bowman’s glands located in the connective tissue under the epithelium (lamina propria) send ducts to the surface of the epithelium and secrete a serous fluid that immerses the cilia of olfactory receptor neurons in a mucous layer to trap odorant molecules. Odorant molecules bind to olfactory receptor proteins in the cilia of olfactory sensory neuron dendrites. The number of cilia that emerges from the dendrite of an olfactory sensory neuron is relatively small, 20 to 30, compared to the ciliated cells that are found in the respiratory epithelium (~300 cilia). Air-borne odorant molecules in the air that we breathe in activate the olfactory receptor proteins in the olfactory cilia. Odorant molecules can find their way to the olfactory sensory neurons either through the nose (orthonasal stimulation) or from the mouth to the nose (retronasal stimulation) [2]. Often this retronasal olfactory stimulation is confused with taste, which takes place in taste buds in the tongue and soft palate of the oral cavity. However, food odors and the consistency of the food (‘crunchiness’) together with tastants contribute to the flavor or aroma of food. The membrane of olfactory sensory neuron cilia houses odorant receptor proteins and thereby activates these neurons in the nasal epithelium. The olfactory receptor proteins form a large gene family (1000 genes in rodents, 350 in humans, [3, 4]). Each olfactory sensory neuron sends an axon through the cribriform plate of the ethmoid bone to the ipsilateral main olfactory bulb in the brain (Figure 1). The axons of olfactory sensory neurons coalesce to form the olfactory nerve (cranial nerve I) and olfactory nerve layer of the main olfactory bulb.
Figure 1.
Schematic representation of olfactory pathways. Olfactory sensory neurons in the olfactory epithelium of the nasal cavity send their axons to form synapses with secondary sensory neurons in the olfactory bulb. A small number of neurons from the olfactory bulb participate in olfactory processing as they exchange information with both limbic system components and cortical structures.
The main olfactory bulb is a cortical structure of the cerebrum. However, the main olfactory bulb is not part of the neocortex but part of the allocortex as shown by its fetal development and cytoarchitecture. Neocortical structures undergo a prenatal phase that results in six layers, whereas allocortical structures have three or four layers in the mature brain [5]. While the main olfactory bulb presents itself as a small extension of the brain in humans, in rodents, the main olfactory bulb is a large structure that fills roughly a quarter of the length of the cranial cavity [6] and is dedicated to the processing of odorant information [1, 2, 7].
Several million sensory neurons are present in the olfactory epithelium. A given olfactory receptor protein is expressed by several thousand of them. The olfactory sensory neurons that express the same olfactory receptor protein send their axon to the same one or two glomeruli in the main olfactory bulb to form synaptic contacts (Figure 1). The dendrites of interneurons (juxtaglomerular cells) and output neurons (mitral and tufted neurons) in the olfactory bulb synapse with olfactory sensory neurons. Compared to the large number of olfactory sensory neurons, only relatively few output neurons innervate each glomerulus. These output neurons send their axons to higher order brain centers for brain processing of olfactory signals [8]. The precise sending of olfactory sensory neuron axons to specific glomeruli is critical for the discrimination of odorants [2]. The axons of output neurons leave the main olfactory bulb through the lateral olfactory tract and terminate in various higher order olfactory centers such as the anterior olfactory nucleus (AON), piriform cortex, the anterior parahippocampal cortex (entorhinal cortex), and the cortico-medial amygdala, all of which belong to limbic system (Figure 1) and are on the ipsilateral brain side. In contrast to other sensory modalities, the olfactory pathway routes sensory information directly from the olfactory bulb to cortical centers and bypasses the thalamus [1, 2].
The amygdala is a collection of nuclei in the limbic system [9]. The basolateral nucleus is the largest one and receives input from sensory cortices (vision, hearing) as well as direct auditory signals through a subcortical structure, the medial geniculate nucleus which is part of the thalamus. The olfactory bulb and piriform cortex send sensory information to the cortical and medial nuclei of the amygdala, the cortico-medial nucleus [10, 11]. In addition, the amygdala receives input from other cortical and subcortical brain systems, such as the prefrontal cortex with the anterior cingulate and orbitofrontal cortices. In turn, both piriform cortex and amygdala project to the orbitofrontal cortex to regulate emotion and associative learning. The amygdala is also connected with the entorhinal and hippocampal system for long-term memory [12]. Furthermore, the amygdala is a target for fibers from the hippocampus and rhinal (olfactory) cortices [10, 11]. Functionally, it has been established that odors have the ability to evoke strong emotions and trigger the recall of emotional memories and modulate cognition [11].
Not only does the olfactory bulb send axons to higher order olfactory centers (afferent fibers), an even larger number of centrifugal axons originating in higher olfactory centers innervate the olfactory bulb glomeruli (efferent fibers) [6, 13, 14]. These centrifugal neurons have been shown to provide modulatory feedback to neurons in the different layers of the main olfactory bulb which is important for experience-dependent modulation [13]. The origin of the centrifugal fibers is in the locus coeruleus (noradrenergic), the horizontal limb of the diagonal band of Broca (cholinergic), and the raphe nucleus (serotonergic) [15, 16, 17, 18]. The centrifugal fibers travel mainly through the anterior olfactory nucleus and the anterior commissure, and very little through the lateral olfactory tract [13].
3. Aging effects in the olfactory system
Age-associated impairment in the sense of olfaction has been well documented [19, 20, 21, 22, 23]. Akin to neurodegenerative pathology, a decline in olfactory acuity and olfactory dysfunction are common features of the normal aging process [24, 25, 26, 27] detectable in over 50% individuals ranging in age from 65 to 80 years and almost in 75% of those above 80 years [24, 28, 29, 30]. This decline in olfactory function is detected using different kinds of tests such as psychophysical, psychophysiological and electrophysiological tests that determine odor detection, identification and discrimination, odor related physiological changes in cardiac and respiratory system as well as odor-event related potentials [29]. However, studies analyzing the mechanism of non-pathological, normal chronological age-related decline of olfactory acuity and impaired olfactory function are limited, despite the fact that deficits in the olfactory sense are considered as important symptom for early and differential diagnosis of neurodegenerative disorders [28]. At the anatomical level, the sense of olfaction is affected by age-associated ossification and closure of foramina of the cribriform plate [29, 31]. There is evidence of a quantitative reduction in the olfactory epithelium and its replacement by respiratory epithelium in normal subjects of the aging population which is evident in biopsies of the upper nasal septum [32]. It is now clearly evident that in the course of normal aging, suboptimal olfaction and olfactory dysfunction are associated with a number of anatomical and physiological features such as age-associated thinning of the olfactory neuroepithelium, altered cellular patterns and regional distribution of nuclei of olfactory sensory and sustentacular cells [29], reduction of mucosal metabolizing enzymes and sensory loss of olfactory sensory cells to various odorants along with a cumulative effect of environmental exposure to the olfactory epithelium [30]. An additional causative factor is the parallel loss of olfactory function in direct correlation with a clear age-associated decline in the volume of the olfactory bulb in adults of both genders [33, 34, 35]. Other than the olfactory bulb, a reduction in volume of AON, amygdala, hippocampus and piriform cortex in the limbic system contribute to a loss of olfaction due to their pivotal role in olfactory processing [36]. Testing the sensitivity and response of isolated sensory neurons to odorant mixtures indicates a loss of olfactory sensitivity and specificity in neurons derived from older subjects [37]. In older individuals, there is evidence of decreased beta-event related synchronization in response to certain pleasant odorants and, therefore, these individuals rated such odorants as less pleasant, thereby, denoting a decline in olfactory processing [38]. A change in olfactory perception represents subtle olfactory dysfunction that appears to precede a number neurodegenerative disorders and is presumed due to loss of synaptic function [39, 40]. Subsequent studies have shown that loss in olfactory sensitivity and perception is heterogeneous and appears to be more specific to heavier molecules [41]. Inherent allelic variations of brain derived neurotrophic factor (BDNF) also affect and add to age-dependent olfactory decline [29, 42]. A comparative research study quantifying heritability of odor identification and cognition detected a role of common genes in both olfaction and cognition. However, heritability of odor identification was lower in contrast to that of cognition [43]. Quantitative analysis of olfaction using odor identification (OI) scale in community dwelling subjects of age group 70–79 years reveals association of higher risk of dementia with poor OI score [44] and reduction in OI has been linked to advanced physiological brain aging as well as with a number of neurodegenerative diseases [45]. An aging cortical synapse in limbic structures has been considered as a hallmark of age-associated decline in cognition [46]. However, such studies are still preliminary for the olfactory bulb, despite evidence of growth factor dependent induction of synaptic strength in olfactory bulb cell layers during odor-dependent social transmission of food preference [47]. Chronological age adds to the impact of environmental exposure through living and working conditions on all physiological systems and their functions [48]. Experimental analysis indicates age-dependent accumulation of somatic mutations using both proliferative and non-proliferative cell types from human brain tissue [49]. It further indicates the probability of mutation accumulation in neurons. Genome-wide single somatic nucleotide variant analysis on DNA of 159 single neurons of 15 normal individuals with a wide age range (4 months to 82 years) and 9 individuals diagnosed with early onset of neurodegeneration revealed linear increase in both sets, indicating age-dependent accumulation of somatic mutations as significant factor affecting neurodegeneration [50]. Research studies of classical neurodegenerative disorders have proposed that the observed variability of olfactory dysfunction in diverse neurological and neuropsychiatric diseases could aid in early differential diagnosis of Alzheimer’s disease (AD), Parkinson’s disease (PD), mild cognitive impairment (MCI), progressive supranuclear palsy (PSP) and frontotemporal lobar degeneration known as FTLD-TDP43 [51, 52, 53, 54]. A cell biology oriented experimental approach to detect the presence of neurodegeneration-associated proteins used nasal brushing to collect olfactory neurons from olfactory mucosa of normal subjects and detected four different characteristic proteins involved in neurodegenerative pathology: α-synuclein, transactive response DNA-binding protein 43 (TDP-43), hyperphosphorylated tau and β-amyloid proteins [55]. These findings have prompted an analysis of the parallel progression of loss of olfaction with onset of neurodegenerative pathology and/or decline in cognitive abilities as initial symptoms of neurological and neuropsychiatric disorders.
4. Alzheimer’s disease, dementia and olfactory deficits
Olfactory deficiencies are evident in a number of neurodegenerative disorders such as AD, dementia with Lewy bodies (DLB), frontotemporal dementia (FTD), MCI, PD and Huntington disease [40, 51, 56, 57, 58, 59]. In an extensive two year study with six-monthly follow up, all MCI patients with lower range of olfaction score but no subjective smelling loss detected by standard UPSIT (University of Pennsylvania Smell Identification Test) developed AD. In contrast, in a control group of higher olfaction score, AD occurrence was nil [60]. A similar association of lower olfaction score with development of AD pathology was evident in a multiethnic community cohort with UPSIT test [61]. In a comparative OI analysis of FTD and AD patients with normal age matched control individuals, OI score of FTD patients differed significantly with control group, however, there was a close resemblance in OI pattern of FTD patients with OI in AD patients [62]. An analysis using Pocket Small Test as indicator of OI performance in AD patients and healthy young and age matched control group of individuals detected reduced OI in an older control group than in a younger control group, and AD patients had even reduced OI compared to their age matched control group [27]. At the cellular level, a characteristic neuropathological feature of AD is the appearance of neurofibrillary tangles consisting of hyperphosphorylated tau protein [63]. In relation to olfactory dysfunction, the two key hallmarks of AD neuropathology are the detection of amyloid-beta (Aβ) and hyperphosphorylated tau protein in the olfactory system; both have been detected together with impaired olfaction much before a clinical presentation of the disease [57]. An analysis assessing OI as indicator of presymptomatic AD pathogenesis in cognitively normal aged individuals shows an association of reduced OI with lower cognitive score and older age as well as increased ratio of total tau protein to phosphorylated tau protein in cerebrospinal fluid [64]. Therefore, at the behavioral level, diminished OI has emerged as a practical and affordable biomarker of AD pathology [64] as well as prodromal symptom of AD [65].
5. Parkinson’s disease and olfactory impairment
A major factor leading to neurodegenerative PD pathology is the loss of dopaminergic neurons from the substantia nigra, resulting in slow but substantial loss of dopamine that eventually leads to many clinical motor symptoms such as bradykinesia, rigidity, tremor, instability of posture and decline of cognitive function [66]. The olfactory system is a severely affected non-motor system in PD patients with early appearance of olfactory dysfunction that remains independent of progressive PD symptoms, their duration and treatment [67]. Additional research studies have indicated association of olfactory dysfunction with PD for over three decades [25, 68]. Olfactory dysfunction, including hyposmia and decline in olfactory acuity, has been established as one of the earliest features of PD. These are detectable in approximately 90% of early stage PD patients, where they may precede the onset of the motor symptoms by a margin of years [69, 70, 71, 72, 73]. Hyposmia and progressive olfactory decline in PD patients have been attributed to central olfactory processing, since the olfactory epithelium biopsy samples of PD patients were normal [74]. Subsequent MRI studies indicate a varying degree of reduction in olfactory bulb volume and depth of olfactory sulcus in PD patients than in normal control individuals. These studies indicate an association of anatomical changes with altered olfaction in PD patients [75]. Lewy bodies and Lewy neurites comprised of α-synuclein are histological hallmarks of neurodegenerative pathology in PD [76]. The olfactory bulb and lower brainstem have been considered as the induction site for the onset of histopathological features comprising of both Lew bodies and Lewy neurites [73, 77]. Along with the peripheral nervous system, such histological aberrations also begin to appear in gut nerve plexa and the olfactory bulb, thereby indicating participation of olfactory bulb cell layers in the progression of neurodegenerative pathology of PD [78].
Dementia associated with PD, known as Parkinson’s disease dementia (PDD), is one of the most debilitating symptoms of PD and is difficult to predict during early stages of the disease. A research study using OSIT-J (odor stick identification test for Japanese) shows over 18 fold increase in risk of dementia for PD patients with severe hyposmia [79]. Indeed OI has emerged as a reliable tool for providing excellent diagnostic accuracy for PD distinguishing it from PD mimics [80].
6. Mood and communication disorders
In addition to aging, neurodegenerative and psychiatric conditions, olfactory deficits including low OI appear as characteristic feature of mild to severe major depressive disorders [81, 82]. As there is overlap in brain regions involved in AD, depression and olfactory processing, olfactory dysfunction could be the potential early biomarker of both AD and depressive disorders [83]. Similar to research studies using animal models that indicate a strong link between loss of olfaction and depressive behavior, a comparative analysis of age matched control individuals and patients diagnosed with depression showed loss of normal olfaction as marker of depression in humans [84]. Literature reviews of multiple research findings using specific parameters indicate a clear and consistent relation between depression and poor life quality in individuals from both clinical and community setting in age dependent manner [85]. Encoded olfactory stimuli activate emotional memory [86]; olfactory system and brain circuits participating in memory and cognition show a close anatomical link as well as frequent functional alteration in patients with depression [87, 88, 89]. Additional analysis clearly denotes a reciprocal relationship between olfaction and depression; patients with olfactory dysfunction show worsening depressive symptoms while olfactory performance is clearly reduced in depression patients in comparison to normal controls [90]. Moreover,
Declined olfactory acuity and olfactory dysfunction are also evident in individuals suffering with post-traumatic stress disorder (PTSD) and in patients diagnosed with major depressive disorder (MDD). PTSD leads to decreased olfactory bulb volume, thereby leading to decreased olfactory acuity, additional olfactory deficits and dysfunction [35]. MDD indicates decline in both primary and secondary olfactory processing [84, 91]. MDD patients denote lower score for olfactory threshold, odor discrimination in 40-point smell identification test in comparison to normal controls At the same time, patients with olfactory dysfunction show clear symptoms of depression that become acute in comparative analysis of hyposmic to anosmic subjects [90].
ASD adult patients show decline in odor identification ability [92]. Experimental evidence in two different mouse models of ASD indicates weaker and fewer synapses between olfactory sensory nerve terminals and olfactory bulb tufted cell layer; and weaker synapses between olfactory sensory nerve terminals and inhibitory periglomerular cells of the olfactory bulb [93]. Duplication of GABA receptor genes and deletion of TOP3B, topoisomerase involved in relaxation of supercoiled DNA contribute to autism susceptibility and have been assigned to gene families with specific contribution to neurodevelopmental disorders [94]. Out of 102 identified genes that contribute to ASD, most genes are expressed and enriched early in excitatory and inhibitory neuronal lineages and affect synapses [95].
7. Drugs
The regenerative ability of olfactory epithelium has made it an attractive target for exploring and evaluating therapeutic strategies to distinguish and treat drug induced olfactory disorders [96]. More than 86% of cancer patients of wide age range display smell and taste disorders that persist even after completion of chemotherapy for cancer [97]. However, not every therapeutic chemotherapy drugs has negative impact on olfactory acuity (personal communication). Bacopa monnieri extracts administration reverses bulbectomy induced neurochemical and histological alterations in mouse model of depression; cognition dysfunction is reversed through a mechanism that enhances synaptic plasticity related signaling, BDNF transcription and protection of cholinergic systems [98].
The flavonoid Naringenin functions as antidepressant by restoring serotonin and noradrenaline levels in brain tissue [99]. In bulbectomized mice, two weeks of Naringenin treatment ameliorated depression like behavioral alterations, decreased elevated pro-inflammatory cytokines and increased levels of BDNF and serotonin in hippocampus and cortex [100].
Depression with psychomotor agitation (PMA) is a putative psychiatric disorder associated with substance dependence, specifically, opioids. It remains unaffected by drug induced major depressive episodes indicating complex interplay of therapeutic drugs in treating depression [101].
The AON, a key area of the olfactory system, shows accumulation of characteristic neuropathological markers such as hyperphosphorylated tau, α-synuclein and β-amyloid proteins at the earliest stages of AD in a Somatostatin (SST) expressing subpopulation of interneurons. In the limbic system, the same accumulation is evident in same subpopulation of interneurons [102]. However, SST is unequally involved in two predominant neurodegenerative disorders with a very strong involvement in AD pathology but quite weaker participation in PD. In early stages of AD, SST is reduced in olfactory areas whereas it is preserved in non-demented PD cases [102]. Further analysis of SST related olfactory deficiencies will pave the way of SST based therapeutic approaches.
Olfactory dysfunctions unrelated to blocked nasal passages are present in a significant percentage of Covid-19 patients [103, 104, 105]. Altered expression of SARS-CoV-2 entry genes in supporting cells of the olfactory epithelium has been proposed as a mechanism underlying COVID-19-associated anosmia [106, 107].
8. Discussion and conclusions
The mammalian olfactory bulb has been termed the “brain inside the brain”, due to the presence of sensory inputs, neuronal lamination and contribution of new neural elements throughout the lifetime [108]. It plays a pivotal role in olfactory processing [8, 109]. In addition to AD, PD, MCI and depressive disorders, inadequate and/or improper olfactory function together with impaired olfactory processing exist in many other neurodegenerative and neuropsychiatric disorders. For instance, in the case of multiple sclerosis (MS), prevalence of olfactory dysfunction ranges from 20 to 45% of the MS population. However, the mechanism of loss of olfaction remains unknown, except for decreased olfactory bulb and brain volume [110, 111]. In patients with a diagnosis of a behavioral FTD variant, OI and odor discrimination did not show any difference from control cases, but there was a significant difference in the odor association test. It has been attributed to impaired olfactory processing [112]. Within the healthy population, impulsive tendencies exhibit some link to olfactory defects [113]. Narcolepsy is associated with hypocretin deficiency of the limbic system. Despite genetic predisposition, it has been postulated to increase by environmental substances that may access the olfactory bulb, triggering neuroinflammation and induce neurodegeneration [114].
Single cell transcriptome analysis during mouse olfactory neurogenesis in early development reveals that expression of olfactory receptor (OR) genes becomes progressively restricted to one gene per neuron in each mature neuron instead of several receptor genes that express in immature neurons [115, 116]. Expression of a single OR allele in olfactory sensory neurons is the outcome of coalescence of multiple intergenic enhancers to a multi-chromosomal hub that allows the expression of a single OR allele while the remaining OR genes converge into few heterochromatic compartments leading to effective transcriptional silencing [117]. Age associated chromosomal breakage and DNA damage lead to an increase in markers of genome instability [118] and requires many layers of regulatory functions such as inducing senescence [48], reducing accumulation of DNA damage and enhancing DNA repair pathways [119]. Genome protection from DNA damage to minimize aging effects is also an effective strategy to minimize risk factor for neurodegeneration [119]. This is likely to retain olfactory acuity and ability based on the model proposed by Bashkirova and Lomvardas [117].
Single cell RNA sequencing reveals differentially regulated and expressed genes as neuronal markers specific to adult born interneurons that may serve as molecular markers for synapse formation, synapse maintenance, and neural plasticity of adult brain circuits [120]. Research studies analyzing functional mechanisms of these markers and their regulation are likely to facilitate the understanding of decreased OI, olfactory dysfunction and onset of neurodegenerative pathology.
Olfactory ensheathing glial cells help olfactory bulb neurons to connect with both the peripheral and central nervous system, and, therefore, they have been widely used as therapeutic tools for neural repair and olfactory/neural regeneration for injuries and neurodegenerative pathological conditions [121]. Indeed, the olfactory bulb has emerged as an attractive target for many novel therapeutic approaches [122].
Another fast growing research topic addresses the role of microRNAs in regulating genes that participate in cognition and neurodegeneration [123, 124, 125] and olfactory acuity. Such findings would also add to a better understanding of the relationship between olfactory dysfunction and neurodegenerative pathologies.
Targeting synaptic deficits in AD patients and aging individuals by improving synaptic plasticity though alteration of structural deficits in dendritic spines through microRNA mediated regulatory pathways could be an effective and novel therapeutic strategy for AD as well as other neurodegenerative disorders [126].
Acknowledgments
This work was supported in part by grants from the National Science Foundation (NSF IOS-1355034) and the Charles and Mary Latham Trust Fund.
Conflict of interest
The authors declare that there is no conflict of interests regarding the publication of this chapter.
\n',keywords:"aging, Alzheimer’s disease, amygdala, dementia, hippocampus, limbic system, mood disorders, olfactory bulb, olfactory cortex, olfactory sensory neuron, Parkinson’s disease",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/73363.pdf",chapterXML:"https://mts.intechopen.com/source/xml/73363.xml",downloadPdfUrl:"/chapter/pdf-download/73363",previewPdfUrl:"/chapter/pdf-preview/73363",totalDownloads:504,totalViews:0,totalCrossrefCites:1,totalDimensionsCites:1,totalAltmetricsMentions:0,introChapter:null,impactScore:1,impactScorePercentile:68,impactScoreQuartile:3,hasAltmetrics:0,dateSubmitted:"November 28th 2019",dateReviewed:"September 4th 2020",datePrePublished:"September 28th 2020",datePublished:"October 21st 2020",dateFinished:"September 28th 2020",readingETA:"0",abstract:"Olfaction is an underestimated sensory modality in terms of its predictive value as an indicator of disorders. It is a well-known phenomenon that a significant percentage of people afflicted with certain prevalent disorders causing degenerative neuropathology, progressive loss of memory and communication function, normal age-based decline of physiological functions, intellectual challenges, depressive and anxiety disorders as well as post-traumatic stress disorders, present with a range of olfactory deficits. Here, we review our understanding of these deficits and their relation to various clinical manifestations such as neurological and neuropsychiatric diseases and disorders. At the outset, we will briefly describe the olfactory pathway from olfactory sensory neurons in the nasal epithelium to the olfactory bulb and on to olfactory cortical and subcortical structures involved in olfaction such as the amygdala.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/73363",risUrl:"/chapter/ris/73363",book:{id:"8732",slug:"sino-nasal-and-olfactory-system-disorders"},signatures:"Naina Bhatia-Dey and Thomas Heinbockel",authors:[{id:"70569",title:"Dr.",name:"Thomas",middleName:null,surname:"Heinbockel",fullName:"Thomas Heinbockel",slug:"thomas-heinbockel",email:"theinbockel@howard.edu",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRm0fQAC/Profile_Picture_2022-08-12T10:38:02.jpg",institution:{name:"Howard University",institutionURL:null,country:{name:"United States of America"}}},{id:"321965",title:"Dr.",name:"Naina",middleName:null,surname:"Naina Bhatia-Dey",fullName:"Naina Naina Bhatia-Dey",slug:"naina-naina-bhatia-dey",email:"naina.bhatiadey@Howard.edu",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Howard University",institutionURL:null,country:{name:"United States of America"}}}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. The olfactory system",level:"1"},{id:"sec_3",title:"3. Aging effects in the olfactory system",level:"1"},{id:"sec_4",title:"4. Alzheimer’s disease, dementia and olfactory deficits",level:"1"},{id:"sec_5",title:"5. Parkinson’s disease and olfactory impairment",level:"1"},{id:"sec_6",title:"6. Mood and communication disorders",level:"1"},{id:"sec_7",title:"7. Drugs",level:"1"},{id:"sec_8",title:"8. Discussion and conclusions",level:"1"},{id:"sec_9",title:"Acknowledgments",level:"1"},{id:"sec_12",title:"Conflict of interest",level:"1"}],chapterReferences:[{id:"B1",body:'Shipley, MT; Ennis, M. Functional organization of olfactory system. J. Neurobiol. 1996; 30: 123-176.'},{id:"B2",body:'Ennis M, Hamilton KA, Hayar A. Neurochemistry of the main olfactory system. In Handbook of Neurochemistry and Molecular Neurobiology: Sensory Neurochemistry; Springer: New York, NY, USA, 2007; 137-204.'},{id:"B3",body:'Buck L, Axel R. 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The potential therapeutic applications of olfactory ensheathing cells in regenerative medicine. Cell Transplant. 2014; 23:567-71. Doi.org/10.3727/096368914X678508'},{id:"B122",body:'Bhatia-Dey N and Heinbockel T. Endocannabinoid-Mediated Neuromodulation in the Olfactory Bulb: Functional and Therapeutic Significance. Int. J. Mol. Sci. 2020, 21: 2850. Doi:10.3390/ijms21082850'},{id:"B123",body:'Xu B, Karayiorgou M, Gogos JA. MicroRNAs in psychiatric and neurodevelopmental disorders. Brain Res. 2010; 1338:78-88. Doi.org/10.1016/j.brainres.2010.03.109'},{id:"B124",body:'Hernandez-Rapp J, Rainone S, Hébert SS. MicroRNAs underlying memory deficits in neurodegenerative disorders. Prog. Neuropsychopharmacol. Biol. Psychiatry 2017; 73:79-86. Doi.org/10.1016/j.pnpbp.2016.04.011'},{id:"B125",body:'Swarbrick S, Wragg, N, Ghosh S, and Stolzing A. Systematic review of miRNA as biomarkers in Alzheimer’s disease. Mol. Neurobiol. 2019; 56: 6156-6167. 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1. Introduction
Because of a global change in illness and death from infectious to noninfectious causes during the 20th century, life expectancy doubled and global population quadrupled [1]. Cardiovascular diseases (CVDs) have surpassed cancer as the main cause of mortality, with low- and middle-income countries bearing the brunt of the burden [2].
In 2015, the United States spent more than $200 billion on heart problems, including related medications and health-care services [3]. In 2017, the American Cardiology Association reported that more than 360,000 persons were diagnosed with coronary heart disease [4].
The principal therapy for preventing arterial thrombosis in CVD patients is platelet inhibitors [5, 6]. Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor is the standard medical treatment for patients with acute coronary syndrome (ACS) and those undergoing percutaneous coronary intervention (PCI) with an intracoronary stent [6].
Every year, about 1.2 million patients get DAPT after receiving a drug-eluting stent (DES). DAPT is used for a variety of cardiologic, neurologic, and surgical indications where the need to prevent thromboembolic events outweighs the risk of bleeding [7, 8]. DAPT is widely used to treat thrombotic stroke, coronary artery disease (CAD), peripheral vascular diseases, and transient ischemic attack (TIA). When compared to aspirin alone, DAPT with aspirin and clopidogrel has been shown to enhance clinical outcomes in patients with acute coronary syndrome or PCI [9, 10].
Despite the effectiveness of DAPT in preventing primary and subsequent myocardial infarction (MI) and stroke, there is an increased associated risk of spontaneous intracerebral hemorrhage (ICH) [11]. Interestingly, in-hospital mortality is greater in patients with ICH who are on DAPT compared to other antiplatelet agents [12, 13]. The goal of achieving efficient antiplatelet activity while avoiding gastrointestinal (GI) injury and bleeding has become a key focus in the management of thrombotic disease patients. This chapter is meant to explore on dual antiplatelet therapy highlighting the current guidelines and recent evidences on the indications, dosing, and duration of treatment using dual antiplatelet therapy.
2. Mechanisms of action of the components of DAPT
DAPT comprises of aspirin together with a P2Y12 inhibitor. These agents have different mechanisms of actions. This section will focus solely on the mechanism of action related to antithrombotic effects of dual antiplatelet therapy.
2.1 Mechanism of action of aspirin
Aspirin is an anti-inflammatory drug, which possesses both anti-inflammatory and antioxidant properties [14]. The primary mechanism of action of aspirin is centered on the irreversible inhibition of cyclooxygenase (COX 1) enzyme, thus preventing the conversion of arachidonic acid into prostaglandin G2 and prostaglandin H2, subsequently inhibiting thromboxane A2 synthesis. Aspirin acetylates and forms a covalent bond with serine residues in COX active site at position 529, thus inhibiting cox 1 enzyme [15, 16]. Other activities of aspirin include mitochondrial oxidative phosphorylation and modulation of NF-KB signals [14].
2.2 Mechanism of action of P2Y12 inhibitors
P2Y12 inhibitors, otherwise known as P2Y12 antagonists, act by blocking P2Y12 adenosine diphosphate (ADP) receptors on platelet surface membrane, subsequently inhibiting thrombocyte activation/aggregation [17]. P2Y12 inhibitors can be classified into two groups: thienopyridines and nucleoside/nucleotide derivatives [16].
Thienopyridines are competitive and irreversible P2Y12 inhibitors [16]. Drugs in this class can be further subdivided into three generations: first-, second-, and third-generation thienopyridines.
Ticlopidine is a first-generation thienopyridines that was withdrawn due to major side effects such as GI disorders, cytopenia, and allergies. Clopidogrel is a prodrug of second-generation thienopyridine derivatives, which is a drug of first choice in DAPT. Clopidogrel active metabolite binds to P2Y12 receptor to form an irreversible covalent bond, which inhibits ADP-dependent platelet activation and aggregation [18]. Dual antiplatelet therapy with aspirin and clopidogrel has been associated with more than 3% platelet reactivity [19] and 10% ischemic occurrences after 12 months of treatment.
Third-generation thienopyridine (prasugrel) was developed with rapid absorption and higher bioavailability than clopidogrel [16, 18].
Some drugs in this class are mainly reversible P2Y12 inhibitors such as ticagrelor and cangrelor. Ticagrelor is a more potent, efficacious, and fast acting P2Y12 inhibitor when compared with other P2Y12 inhibitors such as clopidogrel and prasugrel [20]. Ticagrelor acts by binding to P2Y12 receptor site other than the ADP binding site. In addition, ticagrelor binds to equilibrative nucleoside transporter 1 (ENT 1) in platelets and red blood cells to block the reuptake of adenosine [21].
The P2Y12 inhibitors have peculiar features, advantages and disadvantages, as well as adverse effects. These effects have been summarized in Table 1.
P2Y12 inhibitor
Advantages
Disadvantages
Adverse effects
Clopidogrel
First drug of choice among P2Y12 inhibitors
DAPT with clopidogrel is efficient in preventing MACE
Prevents the risk of thrombotic complications in patients with AF that are undergoing PCI
Highly effective in secondary prevention of cardiovascular and cerebrovascular events
Greatest efficacy in patients undergoing thrombolysis
Once-daily dosing
Quite affordable
Slow onset of antiplatelet effect.
High susceptibility to genetic variation and drug–drug interactions
Variability of response with a poor response associated with increased risk of thrombosis.
High platelet reactivity especially in diabetic patients subsequently leading to impaired antiplatelet response.
High risk of MACE in patients with vascular risk factors receiving clopidogrel therapy.
Jaundice
Seizures
Gastric ulceration
Bloody vomit
Haematuria
Slow or difficult speech
Muscle weakness
Dyspnea
Tachycardia
Pale skin
Ticagrelor
More potent, efficacious and fast acting P2Y12 inhibitor when compared with other P2Y12 inhibitors
Reduction in ischemic event rates unlike clopidogrel
Rapid and extensive platelet inhibition
Fast onset of effect and Reversible inhibition
Less susceptible to genetic variation and drug–drug interactions
Prevents non-fatal MI, ischaemic CVS events, stroke and other CVS related death
Low bioavailability.
Increased risk of non–CABG surgery bleeding when compared with clopidogrel
Twice-daily dosing
It is expensive
Dyspnea at rest, after exercise
Chest pain
Bleeding risk
Tachycardia, bradycardia or irregular heartbeat
Edema of the face, throat, tongue, lips, and eyes
Rashes
Prasugrel
Rapid absorption and higher bioavailability than clopidogrel
Lesser ischemic event rates following PCI unlike clopidogrel
Better efficacy in patients with diabetes and STEMI
Once-daily dosing
Fast and extensive platelet inhibition
High risk of major bleeding, especially in patients undergoing CABG surgery
It is expensive
Dyspnea
High bleeding risk
Purple patches on the skin
Muscle weakness
Cardiac arrhythmias
Headache
Jaundice
Confusion
Seizures
Stomach pain
Table 1.
Advantages, disadvantages, and side effects of P2Y12 inhibitors.
About 40% of patients with atrial fibrillation have a high risk of having CAD. DAPT prevents the risk of thrombotic complications in patients with atrial fibrillation that are undergoing percutaneous coronary intervention [24]. DAPT is preferable to triple therapy with an oral anticoagulant (OAC) due to low risk of bleeding and other thrombotic complications [24, 25, 26]. Clopidogrel is a drug of first choice; however, prasugrel and ticagrelor have been recently approved for treating patients with high ischemic risk and high risk of hemorrhage and stent thrombosis associated with clopidogrel [27].
However, prasugrel is contraindicated in patients undergoing treatment with aspirin and OAC due to the risk of hemorrhage [28].
3.2 Acute coronary syndrome
DAPT can be prescribed for prevention of ACS and other adverse cardiovascular (CVS) events. A combination of aspirin and ticagrelor or prasugrel is commonly recommended for treating patients with ACS within 6–12 months [29, 30]. DAPT is recommended for treating patients with ACS and atrial fibrillation who are at a risk of developing coronary artery disease, which may necessitate PCI with stents [31]. Clopidogrel can be replaced with ticagrelor in rare cases [32, 33]. Cangrelor, a potent intravenous P2Y12 inhibitor with fast onset of action, can be indicated for treating unconscious ACS patients on emergency who are unable to absorb an oral P2Y12 inhibitor [34].
3.3 Coronary artery disease
DAPT with aspirin and clopidogrel is recommended for patients with CAD in order to avert atherothrombotic events. In patients undergoing elective stent implantation, DAPT with aspirin and clopidogrel is usually recommended for 3–6 months [30, 35].
3.4 Myocardial infarction, ischemic events, and stroke
In previous years, DAPT with aspirin and clopidogrel or ticagrelor was formerly recommended for preventing recurrent stroke especially in patients with high risk of transient ischemic attack and noncardioembolic mild stroke [36]. However, DAPT has been found in previous studies to reduce the incidence of stroke and CVS-related death, thus making it effective for stroke prevention. Because DAPT reduces the risk of minor stroke and high transient ischemic attack in these patients, DAPT can be recommended in combination with aspirin and a P2Y12 inhibitor for acute treatment of patients with acute noncardioembolic minor ischemic stroke [37].
Novel and trending studies have compared the efficacy of other potent P2Y12 antagonist such as ticagrelor and prasugrel with clopidogrel especially in preventing nonfatal MI, ischemic CVS events, stroke, and other CVS-related death [38]. DAPT with aspirin and clopidogrel is also approved for treating patients with severe stenosis of the intracranial artery [39] and chronic symptomatic peripheral artery diseases (PADs) [40].
Dual antiplatelet therapy is indicated in patients on the line for transcatheter aortic valve implantation (TAVI) without high risk of hemorrhage for 3–6 months [17]. After revascularization, DAPT is usually indicated for 1–12 months in peripheral artery disease (PAD) patients [17]. It is worth to note that DAPT can be extended for more than 1 year in patients with atherosclerosis and mechanical prosthesis having high risk of coronary events [17].
3.6 Other indications of DAPT
DAPT can also be used in other nonconventional indications, which include diabetes, renal transplant, and carotid endarterectomy. In diabetes, DAPT consisting of aspirin and prasugrel or ticagrelor is indicated due to increased platelet reactivity [41]. DAPT administration reduces the risk of cardiovascular events in patients undergoing renal transplant. On the other hand, the risk of postoperative hemorrhage is increased with DAPT. Therefore, DAPT is strictly recommended for renal transplant patients with high risk of cardiovascular events [42]. DAPT can also be used for patients undergoing carotid endarterectomy [34].
4. Recent evidence and guidelines on DAPT use in patients
Antiplatelet therapy is an important pharmacological component in preventing atherothrombotic events. Aspirin, a widely used antiplatelet drug, has been found to reduce the risk of recurrent major adverse cardiovascular events (MACE) by around one-fifth [43]. However, the combination of antiplatelets has been reported to achieve better outcomes than the use of aspirin alone [10]. DAPT refers to a therapy that includes aspirin and a P2Y12 receptor inhibitor (clopidogrel, prasugrel, or ticagrelor). When compared to single antiplatelet medication, DAPT has been found to prevent recurrent major ischemic episodes in patients with ACS or undergoing PCI at the cost of an unavoidable increased risk of major bleeding [10]. Below are guidelines on the effective use of DAPT across various indications.
4.1 Use of DAPT after undergoing percutaneous coronary intervention
Clinical trials have shown that all the patients receiving PCI require DAPT as it reduces risk of short- and long-term thrombotic events when compared to aspirin. Current guidelines recommend a 6-month DAPT for patients with stable symptoms and a 12-month DAPT for those who have had an ACS [29].
Except for patients who have received a bioabsorbable drug-eluting stent, the clinical setting in which it occurs—stable or unstable—and the patient’s bleeding risk are the two most important factors to consider when determining the DAPT duration following PCI. When feasible, extended (at least 12 months) and potent DAPT should be used for these individuals.
4.2 DAPT in stable coronary artery disease
Platelet inhibition is critical for the treatment and prevention of short- and long-term thrombotic events. The cyclooxygenase-1 inhibitor aspirin and the platelet adenosine diphosphate P2Y12 receptor inhibitors clopidogrel, prasugrel, and ticagrelor are all available as oral antiplatelet medicines for secondary prevention in patients with CAD. The more recent powerful P2Y12 platelet receptor inhibitors prasugrel and ticagrelor have been tested in individuals with ACS, whereas aspirin and clopidogrel have been studied across the entire range of CAD [44].
A 6-month DAPT time is advised for individuals with stable illness following PCI; however, this might be decreased based on the patient’s bleeding risk or for safety considerations. The guidelines go beyond specifics and advocate for the use of metallic stents as a first-line therapy, even in patients who are only given a 1-month antiplatelet regimen for safety reasons [45, 46]. DAPT should be continued for 6 months in individuals who have had angioplasty with a drug-coated balloon. This guideline is based on the results of many clinical trials that employed empirical antiplatelet methods.
4.3 DAPT in acute coronary syndrome
The use of DAPT to inhibit platelet function after an acute coronary syndrome aims to reduce short- and long-term thrombotic consequences [47]. The stent protective effect of DAPT in the first weeks after percutaneous revascularization reduces the risk of stent thrombosis, a potentially fatal event caused by inflammation and endothelial damage associated with mechanical insult during PCI [48]. Long-term therapy has been demonstrated to reduce the risk of subsequent ischemia episodes caused not only by the culprit lesions/vessels, but also by the advancement of atherosclerosis, a phenomenon described as the “patient protective effect” [48].
Several antithrombotic medications have been proposed over time with the goal of offering the best thrombotic protection while minimizing hemorrhagic hazards. However, recent European guidelines advise the use of the two most modern and strong P2Y12 inhibitors (prasugrel and ticagrelor) in patients with or without PCI [49, 50]. The default DAPT length for patients with ACS treated with coronary stenting should be 12 months, while it may be fair to cut it to 6 months in patients with a high bleeding risk or to extend it to more than 12 months in certain cases. These choices should be made after a thorough assessment of the patients’ bleeding and ischemia risks. Although some criteria can aid in the identification of patients who will benefit the most, the requirement to validate surgical tools in clinical practice is well understood. This is especially essential if the DAPT is extended beyond 1 year. A longer dual antiplatelet duration may be considered for patients with this indication who have tolerated this length of DAPT without bleeding problems. In this sense, ticagrelor 60 mg twice daily is advised for patients with a history of myocardial infarction and a high ischemia risk.
4.4 DAPT immediately after transient ischemic attack (TIA) or minor stroke
According to recent BMJ Rapid Recommendations, patients with a mild ischemic stroke or a high-risk transient ischemic attack (TIA) should begin dual antiplatelet medication with aspirin and clopidogrel as soon as feasible after the incident, preferably within 24 hours [51]. Dual therapy is favored over aspirin alone, according to the guidelines, because there is a lower risk of recurrent stroke and functional disability with dual therapy. In addition, the guideline committee strongly recommends a shorter term of dual therapy (10–21 days, rather than 22–90 days). Most patients, however, should continue to take a single antiplatelet drug, such as aspirin, continuously. Patients with TIA or mild stroke may benefit from antiplatelet treatment with aspirin and clopidogrel. DAPT with clopidogrel and aspirin (acetylsalicylic acid) within the first 21 days after the index incident was observed to minimize the incidence of recurrent major ischemic events compared to aspirin alone [51]. The recommendations in this clinical practice guideline are based on a linked systematic review sparked by a randomized controlled trial published in August 2018 in the New England Journal of Medicine [52].
5. Management of bleeding associated with the use of DAPT
A higher reduction in thrombotic risk comes at the cost of an increase in significant bleedings, which occur in 1–8% of patients in the first year after starting DAPT [53, 54, 55]. Even less severe bleeding has been linked to an increased risk of death through indirect mechanisms such as unplanned hospitalization, the necessity for urgent operations, and the termination of DAPT [56]. Bleeding is reportedly linked to an increased risk of death and is also linked to the recurrence of ischemic events such myocardial infarction (MI) and stroke [57, 58].
5.1 Intracranial bleeding (ICB)
The most significant DAPT-related adverse event is intracranial bleeding (ICB). With recurrence rates of more than 15% and 3%, respectively, ICB is classed as lobar (affecting the cerebral cortex and underlying white matter) or deep (affecting the basal ganglia, thalamus, and brainstem). Antiplatelet therapy on admission was linked with a greater 24-hour in-hospital [59] and 3-month death rate compared to naive patients in a recent study on patients with ICB [60].
Patients with ICB should be observed and managed in an intensive care unit or a dedicated stroke unit with a high level of skill in the acute environment. All the anticoagulant and antiplatelet medications should be stopped immediately.
5.2 Gastrointestinal bleeding
GI hemorrhage is the most prevalent significant DAPT-related bleeding event following PCI [61, 62].
Owing to its direct suppression of cyclooxygenase-1, aspirin promotes GI bleeding by lowering the endothelium protective action of prostaglandins. P2Y12 inhibitors are thought to affect ulcer healing through limiting platelet aggregation, angiogenesis, and endothelial proliferation rather than being directly ulcerogenic. When compared to clopidogrel, ticagrelor and prasugrel have been linked to a greater incidence of GI bleeding [61].
Owing to its insidious nature, GI bleeding in patients with recent ACS and/or PCI poses a significant treatment challenge. The need to achieve hemostasis frequently necessitates the early termination of antithrombotic therapy. Furthermore, acute bleeding causes platelet activation, and the formation of a prothrombotic environment could explain why patients with GI bleeding who get DAPT after ACS have a higher risk of ischemic stroke [63].
Proton pump inhibitors (PPIs) should be prescribed alongside antiplatelet medication since gastrointestinal (GI) bleeding is the most prevalent major bleeding event [64]. PPIs are only recommended by the ACC/AHA for individuals who are at risk of bleeding (previous GI bleeding, advanced age, and concurrent use of warfarin, steroids, or nonsteroidal anti-inflammatory medicines); however, the ESC supports PPIs for all DAPT patients [7]. The disparity in recommendations stems from different interpretations of a big clinical research that found a pharmacokinetic interaction between clopidogrel and omeprazole, but no effect on cardiovascular events. Given the known cytochrome pharmacokinetic interaction, it is best to avoid co-prescribing clopidogrel with omeprazole/esomeprazole if at all possible [65]. However, there is no known interaction between PPIs and prasugrel.
5.3 Role of tranexamic acid (TXA) in management of DAPT induced bleeding
Antiplatelet drugs commonly block glycoprotein receptors in ACS because they are required for platelet aggregation. Tranexamic acid (TXA) has been demonstrated to be an effective drug for reduce antiplatelet-related bleeding in a number of clinical scenarios, including trauma, and has a good safety profile [66]. TXA has specifically been shown to increase in vitro platelet activity among coronary artery bypass graft (CABG) patients taking antiplatelet medication as well as demonstrating a reduction in operational blood loss [67]. By enhancing platelet function, TXA can be regarded a potential strategy for reducing bleeding problems associated with antiplatelet monotherapy or DAPT.
5.4 Role of platelet infusions in the management of DAPT-induced bleeding
Platelet concentrates (PCs) are sometimes infused to patients with ICH who are on antiplatelet medications to enhance primary hemostasis before neurosurgery. Platelet concentrates (PCs) are frequently given to patients on APT who develop ICH to overcome platelet inhibition induced by antiplatelet medications [68]. Preoperative transfusion of at least two PCs can enhance primary hemostasis in individuals who require decompression neurosurgery owing to ICH while on APT. Rebleeding could still be a concern especially in individuals with chronic ICH and those using P2Y12 inhibitors. Other options can be explored in the control of bleeding in patients on antiplatelet agents especially DAPT. The options include prothrombin complex concentrates [69] and fresh frozen plasma [70] although they are mostly used for bleeding associated with vitamin K antagonists and direct oral anticoagulants.
6. Conclusion
Antiplatelet agents have been widely utilized in patients with acute coronary syndrome for decades and are increasingly valued for their antithrombotic as well as anti-inflammatory characteristics. DAPT has been shown to be effective in improving the clinical outcomes of patients with ACS or PCI but is associated with high bleeding risk. Recent guidelines have been proposed not only to help reduce the tendency of bleeding in DAPT patients but also to ultimately improve patient overall quality of life.
Acknowledgments
The authors wish to thank the Provost, College of Pharmacy, Afe Babalola University, Professor Femi Oyewo and other lecturers for their support and outstanding encouragement during the course of writing this manuscript.
Conflict of interest
The authors declare no conflict of interest.
\n',keywords:"dual antiplatelet therapy, aspirin, P2Y12 inhibitors, acute coronary syndrome, coronary artery disease",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/81924.pdf",chapterXML:"https://mts.intechopen.com/source/xml/81924.xml",downloadPdfUrl:"/chapter/pdf-download/81924",previewPdfUrl:"/chapter/pdf-preview/81924",totalDownloads:15,totalViews:0,totalCrossrefCites:0,dateSubmitted:"April 24th 2022",dateReviewed:"May 3rd 2022",datePrePublished:"June 14th 2022",datePublished:null,dateFinished:"May 24th 2022",readingETA:"0",abstract:"Antiplatelet agents have been utilized to enhance outcomes in patients with acute coronary syndrome for decades and are increasingly valued for their antithrombotic as well as anti-inflammatory characteristics. Dual antiplatelet therapy (DAPT) is a combination of aspirin and a P2Y12 inhibitor. Different modes of action are employed by these drugs. Aspirin is an anti-inflammatory medication that also has antioxidant characteristics, while P2Y12 inhibitors act by inhibiting thrombocytes activation/aggregation. There are two types of P2Y12 inhibitors: thienopyridines and nucleoside/nucleotide compounds. Nucleoside/nucleotide derivatives are reversible direct-acting P2Y12 receptor antagonists that do not need hepatic metabolism, whereas thienopyridines are competitive and irreversible P2Y12 inhibitors. In patients with acute coronary syndrome or undergoing percutaneous coronary intervention for stable coronary artery disease, dual antiplatelet therapy, which contains aspirin and a P2Y12 receptor inhibitor, has consistently been shown to reduce recurrent major adverse cardiovascular events compared to aspirin monotherapy, but at the cost of an increased risk of major bleeding. This chapter is meant to elaborate on dual antiplatelet therapy highlighting the current guidelines and recent evidences on the indications, dosing, and duration of treatment using dual antiplatelet therapy.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/81924",risUrl:"/chapter/ris/81924",signatures:"Edidiong Orok, Funmilayo Adeniyi and Oluwole Akawa",book:{id:"11655",type:"book",title:"Atrial Fibrillation - Diagnosis and Management in the 21st Century",subtitle:null,fullTitle:"Atrial Fibrillation - Diagnosis and Management in the 21st Century",slug:null,publishedDate:null,bookSignature:"Prof. Ozgur Karcioglu and Associate Prof. Funda Karbek Akarca",coverURL:"https://cdn.intechopen.com/books/images_new/11655.jpg",licenceType:"CC BY 3.0",editedByType:null,isbn:"978-1-80356-123-3",printIsbn:"978-1-80356-122-6",pdfIsbn:"978-1-80356-124-0",isAvailableForWebshopOrdering:!0,editors:[{id:"221195",title:"Prof.",name:"Ozgur",middleName:null,surname:"Karcioglu",slug:"ozgur-karcioglu",fullName:"Ozgur Karcioglu"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:null,sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Mechanisms of action of the components of DAPT",level:"1"},{id:"sec_2_2",title:"2.1 Mechanism of action of aspirin",level:"2"},{id:"sec_3_2",title:"2.2 Mechanism of action of P2Y12 inhibitors",level:"2"},{id:"sec_5",title:"3. Indications for DAPT",level:"1"},{id:"sec_5_2",title:"3.1 Atrial fibrillation",level:"2"},{id:"sec_6_2",title:"3.2 Acute coronary syndrome",level:"2"},{id:"sec_7_2",title:"3.3 Coronary artery disease",level:"2"},{id:"sec_8_2",title:"3.4 Myocardial infarction, ischemic events, and stroke",level:"2"},{id:"sec_9_2",title:"3.5 Transcatheter aortic valve implantation (TAVI), peripheral artery disease, atherosclerosis, and mechanical prosthesis",level:"2"},{id:"sec_10_2",title:"3.6 Other indications of DAPT",level:"2"},{id:"sec_12",title:"4. Recent evidence and guidelines on DAPT use in patients",level:"1"},{id:"sec_12_2",title:"4.1 Use of DAPT after undergoing percutaneous coronary intervention",level:"2"},{id:"sec_13_2",title:"4.2 DAPT in stable coronary artery disease",level:"2"},{id:"sec_14_2",title:"4.3 DAPT in acute coronary syndrome",level:"2"},{id:"sec_15_2",title:"4.4 DAPT immediately after transient ischemic attack (TIA) or minor stroke",level:"2"},{id:"sec_17",title:"5. Management of bleeding associated with the use of DAPT",level:"1"},{id:"sec_17_2",title:"5.1 Intracranial bleeding (ICB)",level:"2"},{id:"sec_18_2",title:"5.2 Gastrointestinal bleeding",level:"2"},{id:"sec_19_2",title:"5.3 Role of tranexamic acid (TXA) in management of DAPT induced bleeding",level:"2"},{id:"sec_20_2",title:"5.4 Role of platelet infusions in the management of DAPT-induced bleeding",level:"2"},{id:"sec_22",title:"6. 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Clinically significant bleeding with Ticagrelor versus Clopidogrel in Korean patients with acute coronary syndromes intended for invasive management: A randomized clinical trial. Circulation. 2019;140(23):1865-1877. DOI: 10.1161/CIRCULATIONAHA.119.041766'},{id:"B56",body:'Halvorsen S, Storey RF, Rocca B, et al. Management of antithrombotic therapy after bleeding in patients with coronary artery disease and/or atrial fibrillation: Expert consensus paper of the European Society of Cardiology Working Group on thrombosis. Eur. 2017;38(19):1455-1462. DOI: 10.1093/eurheartj/ehw454'},{id:"B57",body:'Palmerini T, Bacchi Reggiani L, Della Riva D, Romanello M, Feres F, Abizaid A. Bleeding-related deaths in relation to the duration of dual-antiplatelet therapy after coronary stenting. Journal of the American College of Cardiology. 2017;69(16):2011-2022. DOI: 10.1016/j.jacc.2017.02.029'},{id:"B58",body:'Valgimigli M, Costa F, Lokhnygina Y, Clare R, Wallentin L, Moliterno D. Trade-off of myocardial infarction vs. bleeding types on mortality after acute coronary syndrome: Lessons from the thrombin receptor antagonist for clinical event reduction in acute coronary syndrome (TRACER) randomized trial. Eur. 2017;38(11):804-810. DOI: 10.1093/eurheartj/ehw525'},{id:"B59",body:'Franco L, Paciaroni M, Enrico M, Scoditti U, Guideri F, Chiti A. Mortality in patients with intracerebral hemorrhage associated with antiplatelet agents, oral anticoagulants or no antithrombotic therapy. European Journal of Internal Medicine. 2020;75:35-43. DOI: 10.1016/j.ejim.2019.12.016'},{id:"B60",body:'Roquer J, Vivanco Hidalgo R, Ois A, Rodríguez Campello A, Cuadrado GE. Antithrombotic pretreatment increases very-early mortality in primary intracerebral hemorrhage. Neurology. 2017;88(9):885-891. DOI: 10.1212/WNL.0000000000003659'},{id:"B61",body:'Becker R, Bassand J, Budaj A, et al. Bleeding complications with the P2Y12 receptor antagonists clopidogrel and ticagrelor in the PLATelet inhibition and patient outcomes (PLATO) trial. Eur. 2011;32:2933-2944'},{id:"B62",body:'Généreux P, Giustino G, Witzenbichler B, et al. Incidence, predictors, and impact of post-discharge bleeding after percutaneous coronary intervention. Journal of the American College of Cardiology. 2015;66:1036-1045'},{id:"B63",body:'Nikolsky E, Stone G, Kirtane A, et al. Gastrointestinal bleeding in patients with acute coronary syndromes: Incidence, predictors, and clinical implications: Analysis from the ACUITY (acute catheterization and urgent intervention triage strategy) trial. Journal of the American College of Cardiology. 2009;54(14):1293-1302. DOI: 10.1016/j.jacc.2009.07.019'},{id:"B64",body:'Agewall S, Cattaneo M, Collet J, et al. Expert position paper on the use of proton pump inhibitors in patients with cardiovascular disease and antithrombotic therapy. Eur. 2013;34(23):1708-713b. DOI: 10.1093/eurheartj/eht042'},{id:"B65",body:'Floyd C, Passacquale G, Ferro A. Comparative pharmacokinetics and pharmacodynamics of platelet adenosine diphosphate receptor antagonists and their clinical implications. Clinical Pharmacokinetics. 2012;51(7):429-442. DOI: 10.2165/11630740-000000000-00000'},{id:"B66",body:'Fischer K, Awudi E, Varon J, Surani S. Role of tranexamic acid in the clinical setting. Cureus. 2020;12:8221. DOI: 10.7759/cureus.8221\\'},{id:"B67",body:'Banihashem N, Khorasani M, Vaffai H, et al. The effect of low- dose tranexamic acid on postoperative blood loss in patients treated with clopidogrel and aspirin. Caspian Journal of Internal Medicine. 2019;10:156-161. DOI: 10.22088/cjim.10.2.156'},{id:"B68",body:'Fogarty P. Intracranial haemorrhage: Therapeutic interventions and anaesthetic management. British Journal of Anaesthesia. 2014;113(Suppl 2):17-25'},{id:"B69",body:'Johansen M, Wikkelsø A, Lunde J, Wetterslev J, Afshari A. Prothrombin complex concentrate for reversal of vitamin K antagonist treatment in bleeding and non-bleeding patients. Cochrane Database of Systematic Reviews. 2015;2015(7):CD010555. DOI: 10.1002/14651858.CD010555.pub2'},{id:"B70",body:'Straus S, Haxhibeqiri-Karabdic I, Grabovica SG, Granov N. A difference in bleeding and use of blood and blood products in patients who were preoperatively on aspirin or dual antiplatelet therapy before coronary artery bypass grafting. Med Arch. 2018;72(1):31-35. DOI: 10.5455/medarh.2018.72.31-35'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Edidiong Orok",address:"pharmorok@gmail.com",affiliation:'
Department of Clinical Pharmacy and Public Health, Afe Babalola University, Nigeria
Department of Pharmaceutical and Medicinal Chemistry, Afe Babalola University, Nigeria
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Dr. Wang is a member of the American Society of Mechanical Engineers (ASME), Institute of Electrical and Electronics Engineers (IEEE), American Association for the Advancement of Science (AAAS), Physiological Society of New Zealand (PSNZ), and Institution of Professional Engineers New Zealand (IPENZ). Her research interests include medical devices, electromagnetic sensing and imaging, and computational mechanics. Over the past five years, Dr. Wang has authored more than seventy peer-reviewed publications, two ASME books, seven book chapters, and ten issued patents. She is an active reviewer of numerous journals, books, and conferences. She has edited four books and three special issues of international journals. She has received multiple national and international awards from various professional societies and organizations. She is an active organizer of several international conferences, including the ASME International Mechanical Engineering Congress & Exposition and the International Conference on Computational & Experimental Engineering Sciences. She has been selected as the World’s Top 2% Scientists 2021 (by Stanford University).",institutionString:"Shenzhen Technology University",institution:{name:"Shenzhen Technology University",institutionURL:null,country:{name:"China"}}}]},generic:{page:{slug:"open-access-funding",title:"Open Access Funding",intro:"
IntechOpen’s Academic Editors and Authors have received funding for their work through many well-known funders, including: the European Commission, Bill and Melinda Gates Foundation, Wellcome Trust, Chinese Academy of Sciences, Natural Science Foundation of China (NSFC), CGIAR Consortium of International Agricultural Research Centers, National Institute of Health (NIH), National Science Foundation (NSF), National Aeronautics and Space Administration (NASA), National Institute of Standards and Technology (NIST), German Research Foundation (DFG), Research Councils United Kingdom (RCUK), Oswaldo Cruz Foundation, Austrian Science Fund (FWF), Foundation for Science and Technology (FCT), Australian Research Council (ARC).
Open Access publication costs can often be designated directly in the grants or in specific budgets allocated for that purpose. Many of the most important funding organisations encourage, and even request, that the projects they fund are made available at no cost to the wider public. IntechOpen strives to maintain excellent relationships with these funders and ensures compliance with mandates.
\\n\\n
In order to help Authors identify appropriate funding agencies and institutions, we have created a list, based on extensive research on various OA resources (including ROARMAP and SHERPA/JULIET) of organizations that have funds available. Before consulting our list we encourage you to petition your own institution or organization for Open Access funds or check the specifications of your grant with your funder to ascertain if publication costs are included. Where you are in receipt of a grant you should clarify:
\\n\\n
\\n\\t
Does your institution already have a budget for covering Open Access publication costs?
\\n\\t
Does your grant list Open Access publication fees as legitimate direct/indirect costs?
\\n
\\n\\n
If you are associated with any of the institutions in our list below, you can apply to receive OA publication funds by following the instructions provided in the links. Please consult the Open Access policies or grant Terms and Conditions of any institution with which you are linked to explore ways to cover your publication costs (also accessible by clicking on the link in their title).
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Please note that this list is not a definitive one and is updated regularly. To suggest possible modifications or the inclusion of your institution/funder, please contact us at funders@intechopen.com
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Please be aware that you must be a member, or grantee, of the institutions/funders listed in order to apply for their Open Access publication funds.
Open Access publication costs can often be designated directly in the grants or in specific budgets allocated for that purpose. Many of the most important funding organisations encourage, and even request, that the projects they fund are made available at no cost to the wider public. IntechOpen strives to maintain excellent relationships with these funders and ensures compliance with mandates.
\n\n
In order to help Authors identify appropriate funding agencies and institutions, we have created a list, based on extensive research on various OA resources (including ROARMAP and SHERPA/JULIET) of organizations that have funds available. Before consulting our list we encourage you to petition your own institution or organization for Open Access funds or check the specifications of your grant with your funder to ascertain if publication costs are included. Where you are in receipt of a grant you should clarify:
\n\n
\n\t
Does your institution already have a budget for covering Open Access publication costs?
\n\t
Does your grant list Open Access publication fees as legitimate direct/indirect costs?
\n
\n\n
If you are associated with any of the institutions in our list below, you can apply to receive OA publication funds by following the instructions provided in the links. Please consult the Open Access policies or grant Terms and Conditions of any institution with which you are linked to explore ways to cover your publication costs (also accessible by clicking on the link in their title).
\n\n
Please note that this list is not a definitive one and is updated regularly. To suggest possible modifications or the inclusion of your institution/funder, please contact us at funders@intechopen.com
\n\n
Please be aware that you must be a member, or grantee, of the institutions/funders listed in order to apply for their Open Access publication funds.
\n'}]},successStories:{items:[]},authorsAndEditors:{filterParams:{},profiles:[{id:"396",title:"Dr.",name:"Vedran",middleName:null,surname:"Kordic",slug:"vedran-kordic",fullName:"Vedran Kordic",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/396/images/7281_n.png",biography:"After obtaining his Master's degree in Mechanical Engineering he continued his education at the Vienna University of Technology where he obtained his PhD degree in 2004. He worked as a researcher at the Automation and Control Institute, Faculty of Electrical Engineering, Vienna University of Technology until 2008. 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On September, 29th 2006 he has won a post PhD fellowship from the university of Bologna (from October 2006 to October 2008), at the competitive examination he was ranked first in the industrial engineering area. He extensively served as referee for several international journals. He is author/coauthor of more than 100 research papers. He has been involved in some projects supported by MURST and European Community. His research interests include pattern recognition, bioinformatics, and biometric systems (fingerprint classification and recognition, signature verification, face recognition).",institutionString:null,institution:null},{id:"496",title:"Dr.",name:"Carlos",middleName:null,surname:"Leon",slug:"carlos-leon",fullName:"Carlos Leon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Seville",country:{name:"Spain"}}},{id:"512",title:"Dr.",name:"Dayang",middleName:null,surname:"Jawawi",slug:"dayang-jawawi",fullName:"Dayang Jawawi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Technology Malaysia",country:{name:"Malaysia"}}},{id:"528",title:"Dr.",name:"Kresimir",middleName:null,surname:"Delac",slug:"kresimir-delac",fullName:"Kresimir Delac",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/528/images/system/528.jpg",biography:"K. Delac received his B.Sc.E.E. degree in 2003 and is currentlypursuing a Ph.D. degree at the University of Zagreb, Faculty of Electrical Engineering andComputing. His current research interests are digital image analysis, pattern recognition andbiometrics.",institutionString:null,institution:{name:"University of Zagreb",country:{name:"Croatia"}}},{id:"557",title:"Dr.",name:"Andon",middleName:"Venelinov",surname:"Topalov",slug:"andon-topalov",fullName:"Andon Topalov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/557/images/1927_n.jpg",biography:"Dr. Andon V. Topalov received the MSc degree in Control Engineering from the Faculty of Information Systems, Technologies, and Automation at Moscow State University of Civil Engineering (MGGU) in 1979. He then received his PhD degree in Control Engineering from the Department of Automation and Remote Control at Moscow State Mining University (MGSU), Moscow, in 1984. From 1985 to 1986, he was a Research Fellow in the Research Institute for Electronic Equipment, ZZU AD, Plovdiv, Bulgaria. In 1986, he joined the Department of Control Systems, Technical University of Sofia at the Plovdiv campus, where he is presently a Full Professor. He has held long-term visiting Professor/Scholar positions at various institutions in South Korea, Turkey, Mexico, Greece, Belgium, UK, and Germany. And he has coauthored one book and authored or coauthored more than 80 research papers in conference proceedings and journals. His current research interests are in the fields of intelligent control and robotics.",institutionString:null,institution:{name:"Technical University of Sofia",country:{name:"Bulgaria"}}},{id:"585",title:"Prof.",name:"Munir",middleName:null,surname:"Merdan",slug:"munir-merdan",fullName:"Munir Merdan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/585/images/system/585.jpg",biography:"Munir Merdan received the M.Sc. degree in mechanical engineering from the Technical University of Sarajevo, Bosnia and Herzegovina, in 2001, and the Ph.D. degree in electrical engineering from the Vienna University of Technology, Vienna, Austria, in 2009.Since 2005, he has been at the Automation and Control Institute, Vienna University of Technology, where he is currently a Senior Researcher. His research interests include the application of agent technology for achieving agile control in the manufacturing environment.",institutionString:null,institution:null},{id:"605",title:"Prof",name:"Dil",middleName:null,surname:"Hussain",slug:"dil-hussain",fullName:"Dil Hussain",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/605/images/system/605.jpg",biography:"Dr. Dil Muhammad Akbar Hussain is a professor of Electronics Engineering & Computer Science at the Department of Energy Technology, Aalborg University Denmark. Professor Akbar has a Master degree in Digital Electronics from Govt. College University, Lahore Pakistan and a P-hD degree in Control Engineering from the School of Engineering and Applied Sciences, University of Sussex United Kingdom. Aalborg University has Two Satellite Campuses, one in Copenhagen (Aalborg University Copenhagen) and the other in Esbjerg (Aalborg University Esbjerg).\n· He is a member of prestigious IEEE (Institute of Electrical and Electronics Engineers), and IAENG (International Association of Engineers) organizations. \n· He is the chief Editor of the Journal of Software Engineering.\n· He is the member of the Editorial Board of International Journal of Computer Science and Software Technology (IJCSST) and International Journal of Computer Engineering and Information Technology. \n· He is also the Editor of Communication in Computer and Information Science CCIS-20 by Springer.\n· Reviewer For Many Conferences\nHe is the lead person in making collaboration agreements between Aalborg University and many universities of Pakistan, for which the MOU’s (Memorandum of Understanding) have been signed.\nProfessor Akbar is working in Academia since 1990, he started his career as a Lab demonstrator/TA at the University of Sussex. After finishing his P. hD degree in 1992, he served in the Industry as a Scientific Officer and continued his academic career as a visiting scholar for a number of educational institutions. In 1996 he joined National University of Science & Technology Pakistan (NUST) as an Associate Professor; NUST is one of the top few universities in Pakistan. In 1999 he joined an International Company Lineo Inc, Canada as Manager Compiler Group, where he headed the group for developing Compiler Tool Chain and Porting of Operating Systems for the BLACKfin processor. The processor development was a joint venture by Intel and Analog Devices. In 2002 Lineo Inc., was taken over by another company, so he joined Aalborg University Denmark as an Assistant Professor.\nProfessor Akbar has truly a multi-disciplined career and he continued his legacy and making progress in many areas of his interests both in teaching and research. 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Conventional methods for the removal of metal ions such as chemical precipitation and membrane filtration are extremely expensive when treating large amounts of water, inefficient at low concentrations of metal (incomplete metal removal) and generate large quantities of sludge and other toxic products that require careful disposal. Biosorption and bioaccumulation are ecofriendly alternatives. These alternative methods have advantages over conventional methods. Abundant natural materials like microbial biomass, agro-wastes, and industrial byproducts have been suggested as potential biosorbents for heavy metal removal due to the presence of metal-binding functional groups. Biosorption is influenced by various process parameters such as pH, temperature, initial concentration of the metal ions, biosorbent dose, and speed of agitation. Also, the biomass can be modified by physical and chemical treatment before use. The process can be made economical by regenerating and reusing the biosorbent after removing the heavy metals. Various bioreactors can be used in biosorption for the removal of metal ions from large volumes of water or effluents. The recent developments and the future scope for biosorption as a wastewater treatment option are discussed.",book:{id:"6137",slug:"biosorption",title:"Biosorption",fullTitle:"Biosorption"},signatures:"Sri Lakshmi Ramya Krishna Kanamarlapudi, Vinay Kumar\nChintalpudi and Sudhamani Muddada",authors:[{id:"238433",title:"Associate Prof.",name:"Sudhamani",middleName:null,surname:"Muddada",slug:"sudhamani-muddada",fullName:"Sudhamani Muddada"},{id:"244937",title:"Mrs.",name:"S L Ramyakrishna",middleName:null,surname:"Kanamarlapudi",slug:"s-l-ramyakrishna-kanamarlapudi",fullName:"S L Ramyakrishna Kanamarlapudi"},{id:"244938",title:"Mr.",name:"Vinay Kumar",middleName:null,surname:"Chintalpudi",slug:"vinay-kumar-chintalpudi",fullName:"Vinay Kumar Chintalpudi"}]},{id:"53211",doi:"10.5772/66416",title:"Biofloc Technology (BFT): A Tool for Water Quality Management in Aquaculture",slug:"biofloc-technology-bft-a-tool-for-water-quality-management-in-aquaculture",totalDownloads:16966,totalCrossrefCites:65,totalDimensionsCites:148,abstract:"Biofloc technology (BFT) is considered the new “blue revolution” in aquaculture. Such technique is based on in situ microorganism production which plays three major roles: (i) maintenance of water quality, by the uptake of nitrogen compounds generating in situ microbial protein; (ii) nutrition, increasing culture feasibility by reducing feed conversion ratio (FCR) and a decrease of feed costs; and (iii) competition with pathogens. The aggregates (bioflocs) are a rich protein-lipid natural source of food available in situ 24 hours per day due to a complex interaction between organic matter, physical substrate, and large range of microorganisms. This natural productivity plays an important role recycling nutrients and maintaining the water quality. 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So, air and water can potentially become polluted everywhere. Little is known about changes in pollution rates. The increase in water-related diseases provides a real assessment of the degree of pollution in the environment. This chapter summarizes water quality parameters from an ecological perspective not only for humans but also for other living things. According to its quality, water can be classified into four types. Those four water quality types are discussed through an extensive review of their important common attributes including physical, chemical, and biological parameters. These water quality parameters are reviewed in terms of definition, sources, impacts, effects, and measuring methods.",book:{id:"7718",slug:"water-quality-science-assessments-and-policy",title:"Water Quality",fullTitle:"Water Quality - Science, Assessments and Policy"},signatures:"Nayla Hassan Omer",authors:null},{id:"58138",title:"Water Pollution: Effects, Prevention, and Climatic Impact",slug:"water-pollution-effects-prevention-and-climatic-impact",totalDownloads:21554,totalCrossrefCites:18,totalDimensionsCites:38,abstract:"The stress on our water environment as a result of increased industrialization, which aids urbanization, is becoming very high thus reducing the availability of clean water. Polluted water is of great concern to the aquatic organism, plants, humans, and climate and indeed alters the ecosystem. The preservation of our water environment, which is embedded in sustainable development, must be well driven by all sectors. While effective wastewater treatment has the tendency of salvaging the water environment, integration of environmental policies into the actor firms core objectives coupled with continuous periodical enlightenment on the present and future consequences of environmental/water pollution will greatly assist in conserving the water environment.",book:{id:"6157",slug:"water-challenges-of-an-urbanizing-world",title:"Water Challenges of an Urbanizing World",fullTitle:"Water Challenges of an Urbanizing World"},signatures:"Inyinbor Adejumoke A., Adebesin Babatunde O., Oluyori Abimbola\nP., Adelani-Akande Tabitha A., Dada Adewumi O. and Oreofe Toyin\nA.",authors:[{id:"101570",title:"MSc.",name:"Babatunde Olufemi",middleName:null,surname:"Adebesin",slug:"babatunde-olufemi-adebesin",fullName:"Babatunde Olufemi Adebesin"},{id:"187738",title:"Dr.",name:"Adejumoke",middleName:"Abosede",surname:"Inyinbor",slug:"adejumoke-inyinbor",fullName:"Adejumoke Inyinbor"},{id:"188818",title:"Dr.",name:"Abimbola",middleName:null,surname:"Oluyori",slug:"abimbola-oluyori",fullName:"Abimbola Oluyori"},{id:"188819",title:"Mrs.",name:"Tabitha",middleName:null,surname:"Adelani-Akande",slug:"tabitha-adelani-akande",fullName:"Tabitha Adelani-Akande"},{id:"208501",title:"Dr.",name:"Adewumi",middleName:null,surname:"Dada",slug:"adewumi-dada",fullName:"Adewumi Dada"},{id:"208502",title:"Ms.",name:"Toyin",middleName:null,surname:"Oreofe",slug:"toyin-oreofe",fullName:"Toyin Oreofe"}]},{id:"45422",title:"Urban Waterfront Regenerations",slug:"urban-waterfront-regenerations",totalDownloads:14203,totalCrossrefCites:4,totalDimensionsCites:12,abstract:null,book:{id:"3560",slug:"advances-in-landscape-architecture",title:"Advances in Landscape Architecture",fullTitle:"Advances in Landscape Architecture"},signatures:"Umut Pekin Timur",authors:[{id:"165480",title:"Dr.",name:"Umut",middleName:null,surname:"Pekin Timur",slug:"umut-pekin-timur",fullName:"Umut Pekin Timur"}]},{id:"24941",title:"Tsunami in Makran Region and Its Effect on the Persian Gulf",slug:"tsunami-in-makran-region-and-its-effect-on-the-persian-gulf",totalDownloads:7575,totalCrossrefCites:4,totalDimensionsCites:7,abstract:null,book:{id:"406",slug:"tsunami-a-growing-disaster",title:"Tsunami",fullTitle:"Tsunami - A Growing Disaster"},signatures:"Mohammad Mokhtari",authors:[{id:"52451",title:"Dr.",name:"Mohammad",middleName:null,surname:"Mokhtari",slug:"mohammad-mokhtari",fullName:"Mohammad Mokhtari"}]},{id:"66307",title:"Bio-hydrogen and Methane Production from Lignocellulosic Materials",slug:"bio-hydrogen-and-methane-production-from-lignocellulosic-materials",totalDownloads:2953,totalCrossrefCites:6,totalDimensionsCites:8,abstract:"This chapter covers the information on bio-hydrogen and methane production from lignocellulosic materials. Pretreatment methods of lignocellulosic materials and the factors affecting bio-hydrogen production, both dark- and photo-fermentation, and methane production are addressed. Last but not least, the processes for bio-hydrogen and methane production from lignocellulosic materials are discussed.",book:{id:"7608",slug:"biomass-for-bioenergy-recent-trends-and-future-challenges",title:"Biomass for Bioenergy",fullTitle:"Biomass for Bioenergy - Recent Trends and Future Challenges"},signatures:"Apilak Salakkam, Pensri Plangklang, Sureewan Sittijunda, Mallika Boonmee Kongkeitkajorn, Siriporn Lunprom and Alissara Reungsang",authors:null}],onlineFirstChaptersFilter:{topicId:"12",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"82465",title:"Agroforestry: An Approach for Sustainability and Climate Mitigation",slug:"agroforestry-an-approach-for-sustainability-and-climate-mitigation",totalDownloads:6,totalDimensionsCites:0,doi:"10.5772/intechopen.105406",abstract:"Agroforestry Systems (AFS), or the association of trees with crops (or animals), is a strategy for land management and use that allows production within the sustainable development: (a) environmentally (production environmentally harmonic); (b) technically (integrating existing resources on the farm); (c) economically (increase in production), and (d) socially (equality of duties and opportunities, quality of life of the family group). As an intentional integration of trees or shrubs with crop and animal production, this practice makes environmental, economic, and social benefits to farmers. Given that there is a set of definitions, rather than a single definition of Agroforestry (AF) and AFS, it is justified to explore the historical evolution and the minimum coincidences of criteria to define them and apply them in the recovery of degraded areas. Knowing how to classify AFS allows us to indicate which type or group of AFS is suitable for a particular area with its characteristics. The greatest benefit that AFS can bring to degraded or sloping areas lies in their ability to combine soil conservation with productive functions. In other words, AF is arborizing agriculture and animal production to obtain more benefits including climate change adaptation and mitigation by ecosystem services.",book:{id:"11663",title:"Vegetation Dynamics, Changing Ecosystems and Human Responsibility",coverURL:"https://cdn.intechopen.com/books/images_new/11663.jpg"},signatures:"Ricardo O. Russo"},{id:"82754",title:"Impact of Revegetation on Ecological Restoration of a Constructed Soil in a Coal Mining in Southern Brazil",slug:"impact-of-revegetation-on-ecological-restoration-of-a-constructed-soil-in-a-coal-mining-in-southern-",totalDownloads:3,totalDimensionsCites:0,doi:"10.5772/intechopen.105895",abstract:"The main problems in the constructed soils are the generation of acid mine drainage promoted by the presence of coal debris in the overburden layer and the compaction of the topsoil promoted by the machine traffic when the material used in the overburden cover is more clayey. This book chapter aimed to show an overview of the impact of more than a decade of revegetation with different perennial grasses on the chemical, physical, and biological quality of constructed soil after coal mining. The study was carried out in a coal mining area, located in southern Brazil. The soil was constructed in early 2003 and the perennial grasses, Hemarthria altissima; Paspalum notatum cv. Pensacola; Cynodon dactylon cv Tifton; and Urochloa brizantha; were implanted in November/December 2003. In 11.5, 17.6 and 18 years of revegetation soil samples were collected and the chemical, physical, and biological attributes were determined. Our results show that liming is an important practice in the restoration of these strongly anthropized soils because this positively impacts the plants’ development, facilitating the roots system expansion. Biological attributes such as soil fauna and the microorganism’s population are the attributes that possibly takes longer to establish itself in these areas.",book:{id:"11663",title:"Vegetation Dynamics, Changing Ecosystems and Human Responsibility",coverURL:"https://cdn.intechopen.com/books/images_new/11663.jpg"},signatures:"Lizete Stumpf, Maria Bertaso De Garcia Fernandez, Pablo Miguel, Luiz Fernando Spinelli Pinto, Ryan Noremberg Schubert, Luís Carlos Iuñes de Oliveira Filho, Tania Hipolito Montiel, Lucas Da Silva Barbosa, Jeferson Diego Leidemer and Thábata Barbosa Duarte"},{id:"82936",title:"Soil Degradation Processes Linked to Long-Term Forest-Type Damage",slug:"soil-degradation-processes-linked-to-long-term-forest-type-damage",totalDownloads:2,totalDimensionsCites:0,doi:"10.5772/intechopen.106390",abstract:"Forest degradation impairs ability of the whole landscape adaptation to environmental change. The impacts of forest degradation on landscape are caused by a self-organization decline. At the present time, the self-organization decline was largely due to nitrogen deposition and deforestation which exacerbated impacts of climate change. Nevertheless, forest degradation processes are either reversible or irreversible. Irreversible forest degradation begins with soil damage. In this paper, we present processes of forest soil degradation in relation to vulnerability of regulation adaptability on global environmental change. The regulatory forest capabilities were indicated through soil organic matter sequestration dynamics. We devided the degradation processes into quantitative and qualitative damages of physical or chemical soil properties. Quantitative soil degradation includes irreversible loss of an earth’s body after claim, erosion or desertification, while qualitative degradation consists of predominantly reversible consequences after soil disintegration, leaching, acidification, salinization and intoxication. As a result of deforestation, the forest soil vulnerability is spreading through quantitative degradation replacing hitherto predominantly qualitative changes under continuous vegetation cover. Increasing needs to natural resources using and accompanying waste pollution destroy soil self-organization through biodiversity loss, simplification in functional links among living forms and substance losses from ecosystem. We concluded that subsequent irreversible changes in ecosystem self-organization cause a change of biome potential natural vegetation and the land usability decrease.",book:{id:"11457",title:"Forest Degradation Under Global Change",coverURL:"https://cdn.intechopen.com/books/images_new/11457.jpg"},signatures:"Pavel Samec, Aleš Kučera and Gabriela Tomášová"},{id:"82828",title:"Vegetation and Avifauna Distribution in the Serengeti National Park",slug:"vegetation-and-avifauna-distribution-in-the-serengeti-national-park",totalDownloads:6,totalDimensionsCites:0,doi:"10.5772/intechopen.106165",abstract:"In order to examine the bird species changes within different vegetation structures, the variations were compared between Commiphora-dominated vegetations with those of Vachellia tortilis and Vachellia robusta-dominated vegetations, and also compared the birds of grassland with those of Vachellia drepanolobium and Vachellia seyal-dominated vegetations. This study was conducted between February 2010 and April 2012. A total of 40 plots of 100 m × 100 m were established. Nonparametric Mann-Whitney U-test was used to examine differences in bird species between vegetations. Species richness estimates were obtained using the Species Diversity and Richness. A total of 171 bird species representing 103 genera, 12 orders, and 54 families were recorded. We found differences in bird species distribution whereby V. tortilis has higher bird species richness (102 species), abundance, and diversity when compared with Commiphora with 66 species and V. robusta with 59 species. These results suggest that variations in bird species abundance, diversity, and distribution could be attributed to differences in the structural diversity of vegetation. Therefore it is important to maintain different types of vegetation by keeping the frequency of fire to a minimum and prescribed fire should be employed and encouraged to control wildfire and so maintain a diversity of vegetation and birds community.",book:{id:"11663",title:"Vegetation Dynamics, Changing Ecosystems and Human Responsibility",coverURL:"https://cdn.intechopen.com/books/images_new/11663.jpg"},signatures:"Ally K. Nkwabi and Pius Y. Kavana"},{id:"82808",title:"Climate Change and Anthropogenic Impacts on the Ecosystem of the Transgressive Mud Coastal Region of Bight of Benin, Nigeria",slug:"climate-change-and-anthropogenic-impacts-on-the-ecosystem-of-the-transgressive-mud-coastal-region-of",totalDownloads:8,totalDimensionsCites:0,doi:"10.5772/intechopen.105760",abstract:"The transgressive mud coastal area of Bight of Benin is a muddy coastal complex that lies east of the Barrier/lagoon coast and stretches to the Benin River in the northwestern flank of the Niger Delta Nigeria. It constitutes a fragile buffer zone between the tranquil waters of the swamps and the menacing waves of the Atlantic Ocean. Extensive breaching of this narrow coastal plain results in massive incursion of the sea into the inland swamps with serious implications for national security and the economy. Climate change impacts from the results of meteorological information of the regions shows a gradual degradation in the past 30 years. Temperature, rainfall and humidity increase annually depict climate change, resulting from uncontrolled exploitation of natural resources is rapidly pushing the region towards ecological disasters. The ecosystem is very unique being the only transgressive mud coastal area of the Gulf of Guinea. The chapter describes the geomorphology, tidal hydrology, relief/drainage, topography, climate/meteorology, vegetation, economic characteristics, anthropogenic activities and their impacts on the ecosystem.",book:{id:"11663",title:"Vegetation Dynamics, Changing Ecosystems and Human Responsibility",coverURL:"https://cdn.intechopen.com/books/images_new/11663.jpg"},signatures:"Patrick O. Ayeku"},{id:"82697",title:"Analyzing the Evolution of Land-Use Changes Related to Vegetation, in the Galicia Region, Spain: From 1990 to 2018",slug:"analyzing-the-evolution-of-land-use-changes-related-to-vegetation-in-the-galicia-region-spain-from-1",totalDownloads:6,totalDimensionsCites:0,doi:"10.5772/intechopen.106015",abstract:"Considering the complex dynamics, patterns, and particularities that the Galicia region present—e.g., the fragility, shown to achieve sustainable development and growth—a study that analyzes the Land-Use related to the vegetation of this region is seen as pivotal to identifying barriers and opportunities for long-term sustainable development. Using GIS (Geographic Information Systems), the present chapter enables us to identify the dynamics and patterns of the evolution of the Land-Use Changes related to vegetation in the Galicia Region from 1990 to 2018 (years 1990, 2000, 2012, and 2018 using CORINE (Coordination of Information on the Environment) data). This study permits us to reinforce that the Land-Use Changes related to vegetation in the Galicia Region have undergone multiple changes—marked by increasing and decreasing periods. Also, can be considered a surveying baseline for the comparative analysis of similar works for different Land-Use Changes related to vegetation trends in Europe or worldwide. Land-Use Changes related to vegetation studies are reliable tools to evaluate the human activities and footprint of proposed strategies and policies in a territory. This chapter also enables us to understand that the main actors should design development policies to protect, preserve and conserve these incomparable landscapes, environments, ecosystems, and the region as a whole.",book:{id:"11663",title:"Vegetation Dynamics, Changing Ecosystems and Human Responsibility",coverURL:"https://cdn.intechopen.com/books/images_new/11663.jpg"},signatures:"Sérgio Lousada and José Manuel Naranjo Gómez"}],onlineFirstChaptersTotal:77},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:90,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:108,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:33,numberOfPublishedChapters:330,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:14,numberOfPublishedChapters:145,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:9,numberOfPublishedChapters:140,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:123,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:112,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:22,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:11,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:"2753-6580",doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. 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Much of biochemistry is devoted to enzymes, proteins that catalyze chemical reactions, enzyme structures, mechanisms of action and their roles within cells. Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. 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Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:2,paginationItems:[{id:"89",title:"Education",coverUrl:"https://cdn.intechopen.com/series_topics/covers/89.jpg",isOpenForSubmission:!1,annualVolume:null,editor:{id:"260066",title:"Associate Prof.",name:"Michail",middleName:null,surname:"Kalogiannakis",slug:"michail-kalogiannakis",fullName:"Michail Kalogiannakis",profilePictureURL:"https://mts.intechopen.com/storage/users/260066/images/system/260066.jpg",biography:"Michail Kalogiannakis is an Associate Professor of the Department of Preschool Education, University of Crete, and an Associate Tutor at School of Humanities at the Hellenic Open University. He graduated from the Physics Department of the University of Crete and continued his post-graduate studies at the University Paris 7-Denis Diderot (D.E.A. in Didactic of Physics), University Paris 5-René Descartes-Sorbonne (D.E.A. in Science Education) and received his Ph.D. degree at the University Paris 5-René Descartes-Sorbonne (PhD in Science Education). His research interests include science education in early childhood, science teaching and learning, e-learning, the use of ICT in science education, games simulations, and mobile learning. He has published over 120 articles in international conferences and journals and has served on the program committees of numerous international conferences.",institutionString:"University of Crete",institution:{name:"University of Crete",institutionURL:null,country:{name:"Greece"}}},editorTwo:{id:"422488",title:"Dr.",name:"Maria",middleName:null,surname:"Ampartzaki",slug:"maria-ampartzaki",fullName:"Maria Ampartzaki",profilePictureURL:"https://mts.intechopen.com/storage/users/422488/images/system/422488.jpg",biography:"Dr Maria Ampartzaki is an Assistant Professor in Early Childhood Education in the Department of Preschool Education at the University of Crete. Her research interests include ICT in education, science education in the early years, inquiry-based and art-based learning, teachers’ professional development, action research, and the Pedagogy of Multiliteracies, among others. She has run and participated in several funded and non-funded projects on the teaching of Science, Social Sciences, and ICT in education. She also has the experience of participating in five Erasmus+ projects.",institutionString:"University of Crete",institution:{name:"University of Crete",institutionURL:null,country:{name:"Greece"}}},editorThree:null},{id:"90",title:"Human Development",coverUrl:"https://cdn.intechopen.com/series_topics/covers/90.jpg",isOpenForSubmission:!0,annualVolume:11974,editor:{id:"191040",title:"Dr.",name:"Tal",middleName:null,surname:"Dotan Ben-Soussan",slug:"tal-dotan-ben-soussan",fullName:"Tal Dotan Ben-Soussan",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSBf1QAG/Profile_Picture_2022-03-18T07:56:11.jpg",biography:"Tal Dotan Ben-Soussan, Ph.D., is the director of the Research Institute for Neuroscience, Education and Didactics (RINED) – Paoletti Foundation. Ben-Soussan leads international studies on training and neuroplasticity from neurophysiological and psychobiological perspectives. As a neuroscientist and bio-psychologist, she has published numerous articles on neuroplasticity, movement and meditation. She acts as an editor and reviewer in several renowned journals and coordinates international conferences integrating theoretical, methodological and practical approaches on various topics, such as silence, logics and neuro-education. She lives in Assisi, Italy.",institutionString:"Research Institute for Neuroscience, Education and Didactics, Patrizio Paoletti Foundation",institution:null},editorTwo:null,editorThree:null}]},overviewPageOFChapters:{paginationCount:11,paginationItems:[{id:"83075",title:"Practices and Challenges of Community Services at Debre Markos University, Ethiopia: A Case Study",doi:"10.5772/intechopen.105896",signatures:"Adane Mengist",slug:"practices-and-challenges-of-community-services-at-debre-markos-university-ethiopia-a-case-study",totalDownloads:1,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Corporate Social Responsibility",coverURL:"https://cdn.intechopen.com/books/images_new/11602.jpg",subseries:{id:"86",title:"Business and Management"}}},{id:"82858",title:"Corporate Social Responsibility a Case of the Provision of Recreational Facilities",doi:"10.5772/intechopen.105608",signatures:"Peter Musa Wash, Shida Irwana Omar, Badaruddin Mohamed and Mohd Ismail Isa",slug:"corporate-social-responsibility-a-case-of-the-provision-of-recreational-facilities",totalDownloads:5,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Corporate Social Responsibility",coverURL:"https://cdn.intechopen.com/books/images_new/11602.jpg",subseries:{id:"86",title:"Business and Management"}}},{id:"82786",title:"Discussion of Purchasing Virtual Digital Nature and Tourism",doi:"10.5772/intechopen.105869",signatures:"Hiroko Oe and Yasuyuki Yamaoka",slug:"discussion-of-purchasing-virtual-digital-nature-and-tourism",totalDownloads:6,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"A New Era of Consumer Behavior - Beyond the Pandemic",coverURL:"https://cdn.intechopen.com/books/images_new/11581.jpg",subseries:{id:"88",title:"Marketing"}}},{id:"82289",title:"Consumer Culture and Abundance of Choices: Having More, Feeling Blue",doi:"10.5772/intechopen.105607",signatures:"Ondřej Roubal",slug:"consumer-culture-and-abundance-of-choices-having-more-feeling-blue",totalDownloads:7,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"A New Era of Consumer Behavior - Beyond the Pandemic",coverURL:"https://cdn.intechopen.com/books/images_new/11581.jpg",subseries:{id:"88",title:"Marketing"}}}]},overviewPagePublishedBooks:{paginationCount:1,paginationItems:[{type:"book",id:"11392",title:"Leadership in a Changing World",subtitle:"A Multidimensional Perspective",coverURL:"https://cdn.intechopen.com/books/images_new/11392.jpg",slug:"leadership-in-a-changing-world-a-multidimensional-perspective",publishedDate:"May 11th 2022",editedByType:"Edited by",bookSignature:"Muhammad Mohiuddin, Bilal Khalid, Md. 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That is exactly what he does, diving into Machine Learning algorithms and technologies to help TECNALIA to decide whether something is great in theory or will actually impact on the product or processes of its projects. So, he is expert at framing experiments, developing hypotheses, and proving whether they’re true or not, in order to investigate fundamental problems with a longer time horizon. He is also able to design and develop PoCs and system prototypes in simulation. He has participated in several national and internacional R&D projects.\n\nAs another relevant part of his everyday research work, he usually publishes his findings in reputed scientific refereed journals and international conferences, occasionally acting as reviewer and Programme Commitee member. Concretely, since 2018 he has published 9 JCR (8 Q1) journal papers, 9 conference papers (e.g. ECML PKDD 2021), and he has co-edited a book. He is also active in popular science writing data science stories for reputed blogs (KDNuggets, TowardsDataScience, Naukas). Besides, he has recently embarked on mentoring programmes as mentor, and has also worked as data science trainer.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"103779",title:"Prof.",name:"Yalcin",middleName:null,surname:"Isler",slug:"yalcin-isler",fullName:"Yalcin Isler",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRyQ8QAK/Profile_Picture_1628834958734",biography:"Yalcin Isler (1971 - Burdur / Turkey) received the B.Sc. degree in the Department of Electrical and Electronics Engineering from Anadolu University, Eskisehir, Turkey, in 1993, the M.Sc. degree from the Department of Electronics and Communication Engineering, Suleyman Demirel University, Isparta, Turkey, in 1996, the Ph.D. degree from the Department of Electrical and Electronics Engineering, Dokuz Eylul University, Izmir, Turkey, in 2009, and the Competence of Associate Professorship from the Turkish Interuniversity Council in 2019.\n\nHe was Lecturer at Burdur Vocational School in Suleyman Demirel University (1993-2000, Burdur / Turkey), Software Engineer (2000-2002, Izmir / Turkey), Research Assistant in Bulent Ecevit University (2002-2003, Zonguldak / Turkey), Research Assistant in Dokuz Eylul University (2003-2010, Izmir / Turkey), Assistant Professor at the Department of Electrical and Electronics Engineering in Bulent Ecevit University (2010-2012, Zonguldak / Turkey), Assistant Professor at the Department of Biomedical Engineering in Izmir Katip Celebi University (2012-2019, Izmir / Turkey). He is an Associate Professor at the Department of Biomedical Engineering at Izmir Katip Celebi University, Izmir / Turkey, since 2019. In addition to academics, he has also founded Islerya Medical and Information Technologies Company, Izmir / Turkey, since 2017.\n\nHis main research interests cover biomedical signal processing, pattern recognition, medical device design, programming, and embedded systems. He has many scientific papers and participated in several projects in these study fields. He was an IEEE Student Member (2009-2011) and IEEE Member (2011-2014) and has been IEEE Senior Member since 2014.",institutionString:null,institution:{name:"Izmir Kâtip Çelebi University",country:{name:"Turkey"}}},{id:"339677",title:"Dr.",name:"Mrinmoy",middleName:null,surname:"Roy",slug:"mrinmoy-roy",fullName:"Mrinmoy Roy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/339677/images/16768_n.jpg",biography:"An accomplished Sales & Marketing professional with 12 years of cross-functional experience in well-known organisations such as CIPLA, LUPIN, GLENMARK, ASTRAZENECA across different segment of Sales & Marketing, International Business, Institutional Business, Product Management, Strategic Marketing of HIV, Oncology, Derma, Respiratory, Anti-Diabetic, Nutraceutical & Stomatological Product Portfolio and Generic as well as Chronic Critical Care Portfolio. A First Class MBA in International Business & Strategic Marketing, B.Pharm, D.Pharm, Google Certified Digital Marketing Professional. Qualified PhD Candidate in Operations and Management with special focus on Artificial Intelligence and Machine Learning adoption, analysis and use in Healthcare, Hospital & Pharma Domain. Seasoned with diverse therapy area of Pharmaceutical Sales & Marketing ranging from generating revenue through generating prescriptions, launching new products, and making them big brands with continuous strategy execution at the Physician and Patients level. Moved from Sales to Marketing and Business Development for 3.5 years in South East Asian Market operating from Manila, Philippines. Came back to India and handled and developed Brands such as Gluconorm, Lupisulin, Supracal, Absolut Woman, Hemozink, Fabiflu (For COVID 19), and many more. In my previous assignment I used to develop and execute strategies on Sales & Marketing, Commercialization & Business Development for Institution and Corporate Hospital Business portfolio of Oncology Therapy Area for AstraZeneca Pharma India Ltd. Being a Research Scholar and Student of ‘Operations Research & Management: Artificial Intelligence’ I published several pioneer research papers and book chapters on the same in Internationally reputed journals and Books indexed in Scopus, Springer and Ei Compendex, Google Scholar etc. Currently, I am launching PGDM Pharmaceutical Management Program in IIHMR Bangalore and spearheading the course curriculum and structure of the same. I am interested in Collaboration for Healthcare Innovation, Pharma AI Innovation, Future trend in Marketing and Management with incubation on Healthcare, Healthcare IT startups, AI-ML Modelling and Healthcare Algorithm based training module development. I am also an affiliated member of the Institute of Management Consultant of India, looking forward to Healthcare, Healthcare IT and Innovation, Pharma and Hospital Management Consulting works.",institutionString:null,institution:{name:"Lovely Professional University",country:{name:"India"}}},{id:"310576",title:"Prof.",name:"Erick Giovani",middleName:null,surname:"Sperandio Nascimento",slug:"erick-giovani-sperandio-nascimento",fullName:"Erick Giovani Sperandio Nascimento",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y00002pDKxDQAW/ProfilePicture%202022-06-20%2019%3A57%3A24.788",biography:"Prof. Erick Sperandio is the Lead Researcher and professor of Artificial Intelligence (AI) at SENAI CIMATEC, Bahia, Brazil, also working with Computational Modeling (CM) and HPC. He holds a PhD in Environmental Engineering in the area of Atmospheric Computational Modeling, a Master in Informatics in the field of Computational Intelligence and Graduated in Computer Science from UFES. He currently coordinates, leads and participates in R&D projects in the areas of AI, computational modeling and supercomputing applied to different areas such as Oil and Gas, Health, Advanced Manufacturing, Renewable Energies and Atmospheric Sciences, advising undergraduate, master's and doctoral students. He is the Lead Researcher at SENAI CIMATEC's Reference Center on Artificial Intelligence. In addition, he is a Certified Instructor and University Ambassador of the NVIDIA Deep Learning Institute (DLI) in the areas of Deep Learning, Computer Vision, Natural Language Processing and Recommender Systems, and Principal Investigator of the NVIDIA/CIMATEC AI Joint Lab, the first in Latin America within the NVIDIA AI Technology Center (NVAITC) worldwide program. He also works as a researcher at the Supercomputing Center for Industrial Innovation (CS2i) and at the SENAI Institute of Innovation for Automation (ISI Automação), both from SENAI CIMATEC. He is a member and vice-coordinator of the Basic Board of Scientific-Technological Advice and Evaluation, in the area of Innovation, of the Foundation for Research Support of the State of Bahia (FAPESB). He serves as Technology Transfer Coordinator and one of the Principal Investigators at the National Applied Research Center in Artificial Intelligence (CPA-IA) of SENAI CIMATEC, focusing on Industry, being one of the six CPA-IA in Brazil approved by MCTI / FAPESP / CGI.br. He also participates as one of the representatives of Brazil in the BRICS Innovation Collaboration Working Group on HPC, ICT and AI. He is the coordinator of the Work Group of the Axis 5 - Workforce and Training - of the Brazilian Strategy for Artificial Intelligence (EBIA), and member of the MCTI/EMBRAPII AI Innovation Network Training Committee. He is the coordinator, by SENAI CIMATEC, of the Artificial Intelligence Reference Network of the State of Bahia (REDE BAH.IA). He leads the working group of experts representing Brazil in the Global Partnership on Artificial Intelligence (GPAI), on the theme \"AI and the Pandemic Response\".",institutionString:"Manufacturing and Technology Integrated Campus – SENAI CIMATEC",institution:null},{id:"1063",title:"Prof.",name:"Constantin",middleName:null,surname:"Volosencu",slug:"constantin-volosencu",fullName:"Constantin Volosencu",position:null,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. He has developed automation equipment for machine tools, spooling\nmachines, high-power ultrasound processes, and more.",institutionString:'"Politechnica" University Timişoara',institution:null},{id:"221364",title:"Dr.",name:"Eneko",middleName:null,surname:"Osaba",slug:"eneko-osaba",fullName:"Eneko Osaba",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/221364/images/system/221364.jpg",biography:"Dr. Eneko Osaba works at TECNALIA as a senior researcher. He obtained his Ph.D. in Artificial Intelligence in 2015. He has participated in more than twenty-five local and European research projects, and in the publication of more than 130 papers. He has performed several stays at universities in the United Kingdom, Italy, and Malta. Dr. Osaba has served as a program committee member in more than forty international conferences and participated in organizing activities in more than ten international conferences. He is a member of the editorial board of the International Journal of Artificial Intelligence, Data in Brief, and Journal of Advanced Transportation. He is also a guest editor for the Journal of Computational Science, Neurocomputing, Swarm, and Evolutionary Computation and IEEE ITS Magazine.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"275829",title:"Dr.",name:"Esther",middleName:null,surname:"Villar-Rodriguez",slug:"esther-villar-rodriguez",fullName:"Esther Villar-Rodriguez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/275829/images/system/275829.jpg",biography:"Dr. Esther Villar obtained a Ph.D. in Information and Communication Technologies from the University of Alcalá, Spain, in 2015. She obtained a degree in Computer Science from the University of Deusto, Spain, in 2010, and an MSc in Computer Languages and Systems from the National University of Distance Education, Spain, in 2012. Her areas of interest and knowledge include natural language processing (NLP), detection of impersonation in social networks, semantic web, and machine learning. Dr. Esther Villar made several contributions at conferences and publishing in various journals in those fields. Currently, she is working within the OPTIMA (Optimization Modeling & Analytics) business of TECNALIA’s ICT Division as a data scientist in projects related to the prediction and optimization of management and industrial processes (resource planning, energy efficiency, etc).",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"49813",title:"Dr.",name:"Javier",middleName:null,surname:"Del Ser",slug:"javier-del-ser",fullName:"Javier Del Ser",position:null,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:{name:"Tecnalia",country:{name:"Spain"}}},{id:"278948",title:"Dr.",name:"Carlos Pedro",middleName:null,surname:"Gonçalves",slug:"carlos-pedro-goncalves",fullName:"Carlos Pedro Gonçalves",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRcmyQAC/Profile_Picture_1564224512145",biography:'Carlos Pedro Gonçalves (PhD) is an Associate Professor at Lusophone University of Humanities and Technologies and a researcher on Complexity Sciences, Quantum Technologies, Artificial Intelligence, Strategic Studies, Studies in Intelligence and Security, FinTech and Financial Risk Modeling. He is also a progammer with programming experience in:\n\nA) Quantum Computing using Qiskit Python module and IBM Quantum Experience Platform, with software developed on the simulation of Quantum Artificial Neural Networks and Quantum Cybersecurity;\n\nB) Artificial Intelligence and Machine learning programming in Python;\n\nC) Artificial Intelligence, Multiagent Systems Modeling and System Dynamics Modeling in Netlogo, with models developed in the areas of Chaos Theory, Econophysics, Artificial Intelligence, Classical and Quantum Complex Systems Science, with the Econophysics models having been cited worldwide and incorporated in PhD programs by different Universities.\n\nReceived an Arctic Code Vault Contributor status by GitHub, due to having developed open source software preserved in the \\"Arctic Code Vault\\" for future generations (https://archiveprogram.github.com/arctic-vault/), with the Strategy Analyzer A.I. module for decision making support (based on his PhD thesis, used in his Classes on Decision Making and in Strategic Intelligence Consulting Activities) and QNeural Python Quantum Neural Network simulator also preserved in the \\"Arctic Code Vault\\", for access to these software modules see: https://github.com/cpgoncalves. He is also a peer reviewer with outsanding review status from Elsevier journals, including Physica A, Neurocomputing and Engineering Applications of Artificial Intelligence. Science CV available at: https://www.cienciavitae.pt//pt/8E1C-A8B3-78C5 and ORCID: https://orcid.org/0000-0002-0298-3974',institutionString:"University of Lisbon",institution:{name:"Universidade Lusófona",country:{name:"Portugal"}}},{id:"241400",title:"Prof.",name:"Mohammed",middleName:null,surname:"Bsiss",slug:"mohammed-bsiss",fullName:"Mohammed Bsiss",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/241400/images/8062_n.jpg",biography:null,institutionString:null,institution:null},{id:"276128",title:"Dr.",name:"Hira",middleName:null,surname:"Fatima",slug:"hira-fatima",fullName:"Hira Fatima",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/276128/images/14420_n.jpg",biography:"Dr. Hira Fatima\nAssistant Professor\nDepartment of Mathematics\nInstitute of Applied Science\nMangalayatan University, Aligarh\nMobile: no : 8532041179\nhirafatima2014@gmal.com\n\nDr. Hira Fatima has received his Ph.D. degree in pure Mathematics from Aligarh Muslim University, Aligarh India. Currently working as an Assistant Professor in the Department of Mathematics, Institute of Applied Science, Mangalayatan University, Aligarh. She taught so many courses of Mathematics of UG and PG level. Her research Area of Expertise is Functional Analysis & Sequence Spaces. She has been working on Ideal Convergence of double sequence. She has published 17 research papers in National and International Journals including Cogent Mathematics, Filomat, Journal of Intelligent and Fuzzy Systems, Advances in Difference Equations, Journal of Mathematical Analysis, Journal of Mathematical & Computer Science etc. She has also reviewed few research papers for the and international journals. She is a member of Indian Mathematical Society.",institutionString:null,institution:null},{id:"414880",title:"Dr.",name:"Maryam",middleName:null,surname:"Vatankhah",slug:"maryam-vatankhah",fullName:"Maryam Vatankhah",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Borough of Manhattan Community College",country:{name:"United States of America"}}},{id:"414879",title:"Prof.",name:"Mohammad-Reza",middleName:null,surname:"Akbarzadeh-Totonchi",slug:"mohammad-reza-akbarzadeh-totonchi",fullName:"Mohammad-Reza Akbarzadeh-Totonchi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Ferdowsi University of Mashhad",country:{name:"Iran"}}},{id:"414878",title:"Prof.",name:"Reza",middleName:null,surname:"Fazel-Rezai",slug:"reza-fazel-rezai",fullName:"Reza Fazel-Rezai",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"American Public University System",country:{name:"United States of America"}}},{id:"426586",title:"Dr.",name:"Oladunni A.",middleName:null,surname:"Daramola",slug:"oladunni-a.-daramola",fullName:"Oladunni A. Daramola",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Federal University of Technology",country:{name:"Nigeria"}}},{id:"357014",title:"Prof.",name:"Leon",middleName:null,surname:"Bobrowski",slug:"leon-bobrowski",fullName:"Leon Bobrowski",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Bialystok University of Technology",country:{name:"Poland"}}},{id:"302698",title:"Dr.",name:"Yao",middleName:null,surname:"Shan",slug:"yao-shan",fullName:"Yao Shan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Dalian University of Technology",country:{name:"China"}}},{id:"354126",title:"Dr.",name:"Setiawan",middleName:null,surname:"Hadi",slug:"setiawan-hadi",fullName:"Setiawan Hadi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Padjadjaran University",country:{name:"Indonesia"}}},{id:"125911",title:"Prof.",name:"Jia-Ching",middleName:null,surname:"Wang",slug:"jia-ching-wang",fullName:"Jia-Ching Wang",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"National Central University",country:{name:"Taiwan"}}},{id:"332603",title:"Prof.",name:"Kumar S.",middleName:null,surname:"Ray",slug:"kumar-s.-ray",fullName:"Kumar S. Ray",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Statistical Institute",country:{name:"India"}}},{id:"415409",title:"Prof.",name:"Maghsoud",middleName:null,surname:"Amiri",slug:"maghsoud-amiri",fullName:"Maghsoud Amiri",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Allameh Tabataba'i University",country:{name:"Iran"}}},{id:"357085",title:"Mr.",name:"P. Mohan",middleName:null,surname:"Anand",slug:"p.-mohan-anand",fullName:"P. Mohan Anand",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}},{id:"356696",title:"Ph.D. Student",name:"P.V.",middleName:null,surname:"Sai Charan",slug:"p.v.-sai-charan",fullName:"P.V. Sai Charan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}},{id:"357086",title:"Prof.",name:"Sandeep K.",middleName:null,surname:"Shukla",slug:"sandeep-k.-shukla",fullName:"Sandeep K. Shukla",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}}]}},subseries:{item:{id:"18",type:"subseries",title:"Proteomics",keywords:"Mono- and Two-Dimensional Gel Electrophoresis (1-and 2-DE), Liquid Chromatography (LC), Mass Spectrometry/Tandem Mass Spectrometry (MS; MS/MS), Proteins",scope:"With the recognition that the human genome cannot provide answers to the etiology of a disorder, changes in the proteins expressed by a genome became a focus in research. Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. The Proteomics topic aims to attract contributions on all aspects of MS-based proteomics that, by pushing the boundaries of MS capabilities, may address biological problems that have not been resolved yet.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/18.jpg",hasOnlineFirst:!0,hasPublishedBooks:!0,annualVolume:11414,editor:{id:"200689",title:"Prof.",name:"Paolo",middleName:null,surname:"Iadarola",slug:"paolo-iadarola",fullName:"Paolo Iadarola",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSCl8QAG/Profile_Picture_1623568118342",biography:"Paolo Iadarola graduated with a degree in Chemistry from the University of Pavia (Italy) in July 1972. He then worked as an Assistant Professor at the Faculty of Science of the same University until 1984. In 1985, Prof. Iadarola became Associate Professor at the Department of Biology and Biotechnologies of the University of Pavia and retired in October 2017. Since then, he has been working as an Adjunct Professor in the same Department at the University of Pavia. His research activity during the first years was primarily focused on the purification and structural characterization of enzymes from animal and plant sources. During this period, Prof. Iadarola familiarized himself with the conventional techniques used in column chromatography, spectrophotometry, manual Edman degradation, and electrophoresis). Since 1995, he has been working on: i) the determination in biological fluids (serum, urine, bronchoalveolar lavage, sputum) of proteolytic activities involved in the degradation processes of connective tissue matrix, and ii) on the identification of biological markers of lung diseases. In this context, he has developed and validated new methodologies (e.g., Capillary Electrophoresis coupled to Laser-Induced Fluorescence, CE-LIF) whose application enabled him to determine both the amounts of biochemical markers (Desmosines) in urine/serum of patients affected by Chronic Obstructive Pulmonary Disease (COPD) and the activity of proteolytic enzymes (Human Neutrophil Elastase, Cathepsin G, Pseudomonas aeruginosa elastase) in sputa of these patients. More recently, Prof. Iadarola was involved in developing techniques such as two-dimensional electrophoresis coupled to liquid chromatography/mass spectrometry (2DE-LC/MS) for the proteomic analysis of biological fluids aimed at the identification of potential biomarkers of different lung diseases. He is the author of about 150 publications (According to Scopus: H-Index: 23; Total citations: 1568- According to WOS: H-Index: 20; Total Citations: 1296) of peer-reviewed international journals. He is a Consultant Reviewer for several journals, including the Journal of Chromatography A, Journal of Chromatography B, Plos ONE, Proteomes, International Journal of Molecular Science, Biotech, Electrophoresis, and others. He is also Associate Editor of Biotech.",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorTwo:{id:"201414",title:"Dr.",name:"Simona",middleName:null,surname:"Viglio",slug:"simona-viglio",fullName:"Simona Viglio",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKDHQA4/Profile_Picture_1630402531487",biography:"Simona Viglio is an Associate Professor of Biochemistry at the Department of Molecular Medicine at the University of Pavia. She has been working since 1995 on the determination of proteolytic enzymes involved in the degradation process of connective tissue matrix and on the identification of biological markers of lung diseases. She gained considerable experience in developing and validating new methodologies whose applications allowed her to determine both the amount of biomarkers (Desmosine and Isodesmosine) in the urine of patients affected by COPD, and the activity of proteolytic enzymes (HNE, Cathepsin G, Pseudomonas aeruginosa elastase) in the sputa of these patients. Simona Viglio was also involved in research dealing with the supplementation of amino acids in patients with brain injury and chronic heart failure. She is presently engaged in the development of 2-DE and LC-MS techniques for the study of proteomics in biological fluids. The aim of this research is the identification of potential biomarkers of lung diseases. She is an author of about 90 publications (According to Scopus: H-Index: 23; According to WOS: H-Index: 20) on peer-reviewed journals, a member of the “Società Italiana di Biochimica e Biologia Molecolare,“ and a Consultant Reviewer for International Journal of Molecular Science, Journal of Chromatography A, COPD, Plos ONE and Nutritional Neuroscience.",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorThree:null,series:{id:"11",title:"Biochemistry",doi:"10.5772/intechopen.72877",issn:"2632-0983"},editorialBoard:[{id:"72288",title:"Dr.",name:"Arli Aditya",middleName:null,surname:"Parikesit",slug:"arli-aditya-parikesit",fullName:"Arli Aditya Parikesit",profilePictureURL:"https://mts.intechopen.com/storage/users/72288/images/system/72288.jpg",institutionString:null,institution:{name:"Indonesia International Institute for Life 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