Comparison of fundamentals.
\r\n\tThe book will be useful to students, postdocs and researchers interested in dealing with several interesting aspects of discrete behaviours in geometry and dynamics.
",isbn:null,printIsbn:"979-953-307-X-X",pdfIsbn:null,doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,isSalesforceBook:!1,isNomenclature:!1,hash:"d776a31d1f62e07a4c3600ab1ad6e374",bookSignature:"Dr. Dumitru Baleanu",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/9327.jpg",keywords:"Discrete, Lagrangian, Hamiltonian, Dynamics, Fractional calculus, Euler-Lagrange equations, Computer graphics, Computational, Mechanics, Smooth, Curvatures, Numerical methods",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"September 11th 2019",dateEndSecondStepPublish:"October 2nd 2019",dateEndThirdStepPublish:"December 1st 2019",dateEndFourthStepPublish:"February 19th 2020",dateEndFifthStepPublish:"April 19th 2020",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"3 years",secondStepPassed:!0,areRegistrationsClosed:!0,currentStepOfPublishingProcess:5,editedByType:null,kuFlag:!1,biosketch:null,coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"105623",title:"Dr.",name:"Dumitru",middleName:null,surname:"Baleanu",slug:"dumitru-baleanu",fullName:"Dumitru Baleanu",profilePictureURL:"https://mts.intechopen.com/storage/users/105623/images/system/105623.jpg",biography:"Dumitru Baleanu received a B.Sc. degree in Physics from the University of Craiova, Romania, in 1988, an M.Sc. degree from the University of Bucharest, Romania, in 1989, and a Ph.D. degree from the Institute of Atomic Physics, Romania, in 1996. He is Professor at the Institute of Space Sciences, Romania, and since 2000 he is visiting staff member at Cankaya University, Turkey. He published 500 papers in journals indexed in SCI. He is a co-editor of five books published by Springer. He is coauthor of three books published by Elsevier and World Scientific. He is an editorial board member of six ISI journals and is on the 2015 Highly Cited Researcher list in mathematics. His Hirsch index is 33.",institutionString:"Cankaya University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"4",institution:{name:"Çankaya University",institutionURL:null,country:{name:"Turkey"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"15",title:"Mathematics",slug:"mathematics"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"304289",firstName:"Rebekah",lastName:"Pribetic",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/304289/images/13255_n.png",email:"rebekah@intechopen.com",biography:null}},relatedBooks:[{type:"book",id:"2278",title:"Advances in Wavelet Theory and Their Applications in Engineering, Physics and Technology",subtitle:null,isOpenForSubmission:!1,hash:"43f8c4f3571860f51c18deef213fa8cb",slug:"advances-in-wavelet-theory-and-their-applications-in-engineering-physics-and-technology",bookSignature:"Dumitru Baleanu",coverURL:"https://cdn.intechopen.com/books/images_new/2278.jpg",editedByType:"Edited by",editors:[{id:"105623",title:"Dr.",name:"Dumitru",surname:"Baleanu",slug:"dumitru-baleanu",fullName:"Dumitru Baleanu"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1861",title:"Wavelet Transforms and Their Recent Applications in Biology and Geoscience",subtitle:null,isOpenForSubmission:!1,hash:"17f3d0e20293bdad1d8f4c760e6826b3",slug:"wavelet-transforms-and-their-recent-applications-in-biology-and-geoscience",bookSignature:"Dumitru Baleanu",coverURL:"https://cdn.intechopen.com/books/images_new/1861.jpg",editedByType:"Edited by",editors:[{id:"105623",title:"Dr.",name:"Dumitru",surname:"Baleanu",slug:"dumitru-baleanu",fullName:"Dumitru Baleanu"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"4730",title:"Wavelet Transform and Some of Its Real-World Applications",subtitle:null,isOpenForSubmission:!1,hash:"4adb45be00eb4a384e30c1e3b4d944e3",slug:"wavelet-transform-and-some-of-its-real-world-applications",bookSignature:"Dumitru Baleanu",coverURL:"https://cdn.intechopen.com/books/images_new/4730.jpg",editedByType:"Edited by",editors:[{id:"105623",title:"Dr.",name:"Dumitru",surname:"Baleanu",slug:"dumitru-baleanu",fullName:"Dumitru Baleanu"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7653",title:"Wavelet Transform and Complexity",subtitle:null,isOpenForSubmission:!1,hash:"74bd7559ad44e50940d35974905e98ee",slug:"wavelet-transform-and-complexity",bookSignature:"Dumitru Baleanu",coverURL:"https://cdn.intechopen.com/books/images_new/7653.jpg",editedByType:"Edited by",editors:[{id:"105623",title:"Dr.",name:"Dumitru",surname:"Baleanu",slug:"dumitru-baleanu",fullName:"Dumitru Baleanu"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1591",title:"Infrared Spectroscopy",subtitle:"Materials Science, Engineering and Technology",isOpenForSubmission:!1,hash:"99b4b7b71a8caeb693ed762b40b017f4",slug:"infrared-spectroscopy-materials-science-engineering-and-technology",bookSignature:"Theophile Theophanides",coverURL:"https://cdn.intechopen.com/books/images_new/1591.jpg",editedByType:"Edited by",editors:[{id:"37194",title:"Dr.",name:"Theophile",surname:"Theophanides",slug:"theophile-theophanides",fullName:"Theophile Theophanides"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3161",title:"Frontiers in Guided Wave Optics and Optoelectronics",subtitle:null,isOpenForSubmission:!1,hash:"deb44e9c99f82bbce1083abea743146c",slug:"frontiers-in-guided-wave-optics-and-optoelectronics",bookSignature:"Bishnu Pal",coverURL:"https://cdn.intechopen.com/books/images_new/3161.jpg",editedByType:"Edited by",editors:[{id:"4782",title:"Prof.",name:"Bishnu",surname:"Pal",slug:"bishnu-pal",fullName:"Bishnu Pal"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"371",title:"Abiotic Stress in Plants",subtitle:"Mechanisms and Adaptations",isOpenForSubmission:!1,hash:"588466f487e307619849d72389178a74",slug:"abiotic-stress-in-plants-mechanisms-and-adaptations",bookSignature:"Arun Shanker and B. Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3092",title:"Anopheles mosquitoes",subtitle:"New insights into malaria vectors",isOpenForSubmission:!1,hash:"c9e622485316d5e296288bf24d2b0d64",slug:"anopheles-mosquitoes-new-insights-into-malaria-vectors",bookSignature:"Sylvie Manguin",coverURL:"https://cdn.intechopen.com/books/images_new/3092.jpg",editedByType:"Edited by",editors:[{id:"50017",title:"Prof.",name:"Sylvie",surname:"Manguin",slug:"sylvie-manguin",fullName:"Sylvie Manguin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"72",title:"Ionic Liquids",subtitle:"Theory, Properties, New Approaches",isOpenForSubmission:!1,hash:"d94ffa3cfa10505e3b1d676d46fcd3f5",slug:"ionic-liquids-theory-properties-new-approaches",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/72.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"2270",title:"Fourier Transform",subtitle:"Materials Analysis",isOpenForSubmission:!1,hash:"5e094b066da527193e878e160b4772af",slug:"fourier-transform-materials-analysis",bookSignature:"Salih Mohammed Salih",coverURL:"https://cdn.intechopen.com/books/images_new/2270.jpg",editedByType:"Edited by",editors:[{id:"111691",title:"Dr.Ing.",name:"Salih",surname:"Salih",slug:"salih-salih",fullName:"Salih Salih"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"55725",title:"Comprehensive Overview of Alzheimer’s Disease Neurodegeneration, from Amyloid-β to Neuroinflammatory Modulation",doi:"10.5772/intechopen.69463",slug:"comprehensive-overview-of-alzheimer-s-disease-neurodegeneration-from-amyloid-to-neuroinflammatory-mo",body:'Scientific progress has given enormous benefits to human population. In this regard, the continuous advances in biomedicine have constituted one of the more relevant achievements of the last centuries. Increased rate of newborn survival, control of devastating infectious pathologies, chirurgical management of systemic pathologies, and increased life expectancy of the world population are some of the milestones reached because of science development.
Although positive, the increased longevity of world population has led to two critical events, which have huge implications in human health. On one side, our biological system must work for a longer period of time. Considering that no machine can work indefinitely without failure, the alteration/impairment of our cellular and molecular mechanisms should be considered as part of the price to live longer and as an open door for the development of several diseases. On the other side, we must consider that a longer life span also implies an increased exposition time to different kinds of xenobiotics. Environmental pollutant levels have increased along with the population growth, and although huge efforts have been committed to reduce the usage of the more toxic chemicals worldwide, just a rapid revision of the lists published by the International Agency for Research on Cancer (http://www.iarc.fr) allows us to understand and to dimension the threats usually faced during our life span. Accordingly, the increased incidence and prevalence of several chronic-degenerative pathologies, including cancer and neurodegenerative disorders, should not be a surprise. Indeed, age and the exposition to environmental pollutants are considered as the main risk factors for the establishment and progression of these pathologies. Thus, to properly face this specific type of alterations, a complex equation should be solved, including deep knowledge of the cellular and molecular mechanisms behind each disorder and the environmental elements able to induce, perpetuate, and/or accelerate the pathophysiological processes.
In the present chapter, we will focus our efforts to summarize the most relevant aspects regarding Alzheimer’s disease (AD) and the key elements of its pathophysiological process. Moreover, we will include relevant information and discussion about some aspects of neuroinflammatory modulation.
Described more than a century ago, Alzheimer’s disease (AD) constitutes nowadays an extremely complex public health threat. With up to 10% of people over 65 years old affected by this pathology and up to 50% of people over 85, AD is the most common form of dementia worldwide. Moreover, the cost associated to AD has been estimated in USD 818 billion. Additionally, the social implications should be considered when the total impact of the disease is addressed. Indeed, according to Alzheimer’s Research International, in most cases, the relatives of an AD patient are those who take care of the patient health, causing a huge impact in the familial economy as well as social stress [1].
To date, two presentation forms have been reported for AD: the familial or early-onset AD (EOAD) and the late-onset AD (LOAD). As suggested by its name, the main characteristic of EOAD is its presentation before the 65 years old, with cases reported from the 30s to 60s and with a high genetic background at least in three genes (amyloid precursor protein,
Etiological factors of AD. A simplified view. Alzheimer’s disease is a highly complex disease. Although several risk factors have been identified, the etiology of this disorder remains elusive. Environmental factors, such as exposure to common pollutants; aging, which not only accounts for a decrease in the natural defenses of the organism but also increases the exposure time to the environmental contaminants; and the genetic susceptibility, such as the ApoE ε4 allele or presenilin mutations, create the perfect conditions to facilitate the establishment and progression of AD.
Clinically, AD progresses from the compromise of the short-term memory to long-term memory loss and cognitive impairment. The selective neuronal death within memory and learning brain areas is at the basis of these clinical alterations. Indeed, frontal cortex, limbic area, and hippocampus atrophies along with extracellular accumulation of amyloid-β (Aβ) plaques and intra-neuronal neurofibrillary tangles (NFTs), constituted by hyperphosphorylated
On the other hand, it is important to realize that AD affects the whole brain. In this regard, we must consider the health status of neurons, of course, but also pay attention to the status of the glial cells and additional surrounding structures, such as the blood-brain barrier (BBB) [5]. Several research groups have demonstrated that the molecular alterations occurring during AD not only alter neurons but also microglia, astrocytes, pericytes, and endothelial cells, as well; and more importantly, each of these cells will respond to the molecular insults triggering a subsequent series of molecular events able to affect itself as well as the neighboring cells and tissues [5–7]. Whether these subsequent events are just the consequence or part of the cause/progression of AD is still matter of research.
Since its description in 1906 by Dr. Alois Alzheimer, several hypotheses have been proposed to explain the pathobiology of the disease. Based on initial neurochemical studies of AD brains, an altered metabolism of acetylcholine (ACh) in the basal forebrain of AD patients was reported. This finding leads to the formulation of the “cholinergic hypothesis” of AD in which the ACh deficiency at the cortical level is considered responsible, at least in part, of the cognitive and behavioral impairment observed during disease progression. Moreover, ACh deficiency has been linked to NFT formation, and an increased activity of the ACh-esterase (AChE) has been found surrounding the Aβ plaques [8]. On the other hand, “
As mentioned previously, the amyloid hypothesis states that AD will result from the increased accumulation of Aβ within the brain. Accordingly, several authors have suggested that the accumulation will result from an altered equilibrium between the production and elimination rate of Aβ from the brain [10–12]. Aβ constitutes a small posttranscriptional processing product of the ubiquitous amyloid precursor protein (APP), a transmembrane protein, coded in chromosome 21, which has been linked to nerve differentiation and cell adhesion and signaling. Physiologically, APP can undergo two clearly defined processing pathways. The non-amyloidogenic processing is carried out by the alpha (α) and gamma (γ) secretases, which lead to the release of the soluble APPα (sAPPα) and the p3 fragment. On the other hand, when this process is carried out by the beta (β) and γ secretases, the amyloidogenic pathway is established and leads to the release of the sAPPβ and the neurotoxic Aβ peptide (Figure 2) [9, 12].
Apolipoprotein processing pathways. APP can be processed according two known paths. The non-amyloidogenic pathway will require α- and γ-secretase activity and will lead to the release of the sAPPα and the p3 peptide, both small peptides with a poorly understood function. On the other hand, when β- and γ-secretases work sequentially, the formation of the sAPPβ and the Aβ peptide, the main neurotoxic agent described in AD, will be favored. Importantly, external factors can increase the expression levels/activity of β-secretase, suggesting the potential upregulation of the amyloidogenic processing of the APP. sAPPα/β, soluble APP fragment α/β; p3, 3-KDa peptide; BACE, β-site APP cleaving enzyme.
Ranging from 37 to 49 amino acids, Aβ constitutes the critical molecular event at the basis of the AD establishment and progression [9]. Although Aβ can interact with other molecular elements and organelles, a relevant feature of this peptide is its ability to self-aggregate, being able to constitute monomers, oligomers, fibrils, or bigger aggregates, such as plaques [3, 8]. Importantly, each of these forms has its own implications in terms of reactivity and toxicity. During several years, the plaques were considered the most harmful element of the AD pathophysiology. Indeed, the dystrophic neurites, reactive astrocytes and microglia, and increased activity of AChE commonly found around the plaques were considered as clear indicators that these formations were responsible for the progression of the pathology [8]. However, currently, it has been accepted that the oligomeric Aβ is the most neurotoxic form, which needs to be controlled to avoid AD progression. Evidently, any circumstance able to favors the amyloidogenic processing of the APP, would increase the risk of developing AD due to increased levels of Aβ [9, 11]. Down syndrome (chromosome 21 trisomy leads to an additional copy of the APP gene), upregulation of γ-secretase activity (presenilins 1 and 2), upregulation of the β-site APP cleaving enzyme (BACE, β-secretase) activity, downregulation of non-amyloidogenic APP processing enzyme (A disintegrin and metalloprotease, ADAM, 9–10 and 17) activity, and increased APP enzymatic processing hotspots within the plasma membrane (lipid raft) are some of the conditions able to increase the Aβ production rate within the brain, causing its subsequent accumulation [11–16].
On the other hand, the Aβ removal occurs mainly through the blood stream and, in a lesser extent, through the cerebrospinal fluid (CSF). Apolipoprotein E (ApoE) constitutes the Aβ chaperone, necessary to mobilize the peptide from the interstitial fluid (ISF) to the blood-brain barrier (BBB) transport system and/or to the choroid plexus to its final elimination from the brain [9, 10]. Although several members of the ATP-binding cassette family of transporters, such as ABCB1, ABCC2, and ABCG4, can be linked to the Aβ removal, the low-density lipoprotein receptor-related protein/ApoE receptor (LRP/APOER) is the main responsible of the Aβ clearance through the BBB. Contrarily, the receptor for advanced glycation end products (RAGE), a transmembrane receptor of the immunoglobulin superfamily located at the luminal side of the cerebral microvasculature, allows the influx of Aβ from the blood stream to the brain parenchyma [5, 6, 9, 17].
When the balance between production and clearance is altered, the Aβ levels start to increase within the brain interstitial fluid (ISF) where finally it will start to aggregate and exert its neurotoxic effects in the surrounding cells. Although Aβ-derived damage is considered as an extracellular process, it has been also suggested that the intracellular accumulation of Aβ might play a relevant role at the early stages of the disease. In this regard, APP has been found in different cell compartments including the Golgi apparatus, endoplasmic reticulum, endosomes, lysosomes, and mitochondria. Moreover, cell uptake has been also evidenced through the α7 nicotinic acetylcholine receptor, suggesting that in the presence of increased extracellular levels of Aβ, the peptide can enter the cell and starts to accumulate within the intracellular space, probably causing the first cellular alterations, including
Although no hypothesis can be discarded, amyloid hypothesis is considered as the most relevant one because the molecular cascade and cellular effects observed during AD can be tracked backward to the Aβ peptide. Moreover, in vitro, in vivo, and human studies have evidenced that Aβ-directed interventions can prevent or slow the progression of the disease. In the same way, more recently, studies focused to improve the clearance of Aβ from the brain have shown promising results as potential AD drugs [4, 10, 18].
As pointed previously, AD pathophysiology is a very complex disease, with a multifactorial etiology which, to date, is still matter of intense research. Moreover, even when we have been able to establish that the clinical signs correlate with the impairment of the neuronal network and neuronal loss, the broad range of molecular alterations still seem like little islands in the sea. In this regard, Aβ has been proposed as a central element in the pathology and as the starting point for all the molecular and cellular alterations found at the different stages of the disease. However, several questions, like how disease spreads across the brain, are still open. During the recent years, the neuroinflammatory response has been identified as a relevant feature of the AD brain, and it has been suggested that disease progression might be due, at least in part, to a chronic neuroinflammatory state of the brain [19–21]. Again, Aβ can be located at the center of this process leading to additional alterations which can further promote an exacerbated inflammatory response within the brain.
Inflammation is a fundamental physiological process to solve tissue damage. In general, pathogens and/or toxic elements disturb the cellular environment, triggering a whole range of responses including complement cascade activation and cytokine release from the injured cell and from the immune cells located at the site of the insult. The final goal of such response is to eliminate the initial cause of distress and cell debris and to repair of the damaged tissue. In this regard, pro-inflammatory and anti-inflammatory cytokines, such as tumor necrosis factor 1 (TNF-1α), interleukins (IL-1, IL-8, IL-10), interferon (INF-γ), and transforming growth factor 1 (TGF-1), along with complement proteins, develop a coordinated response to constitute a solid first line of defense against many unspecific damaging agents [19, 21]. Although this mechanism is common to the whole organism, the central nervous system (CNS) and the brain possess some particularities, which need to be addressed.
The CNS is a highly specialized structure, and neurons are recognized to require specific microenvironmental conditions to carry out its functions and to ensure that neuronal network is properly functioning. Although the CNS is partially isolated, preventing both external and internal elements to alter the brain homeostasis, eventually, some external insults, such as pathogens or environmental pollutants, and/or endogenous conditions, such as autoimmune diseases, sterile pathological processes, and aging, among others, will reach the brain parenchyma and induce neuronal damage that will require an efficient immune response to control and to prevent the spreading of the damage. It is important to consider that the brain parenchyma constitutes an anti-inflammatory environment with high expression of relevant anti-inflammatory mediators, such as transforming growth factor b (TGFb) and interleukin (IL)-10 [22, 23]. Although common systemic immune cells and molecules, such as cluster of differentiation 11b- and 11c (CD11b, CD11c)-positive cells, can be found in the CNS during the immune/inflammatory response, these factors mainly localize close to BBB-damaged areas, suggesting that its migration might be due to an increased BBB permeability [24]. Interestingly, an important feature of the anti-inflammatory molecules localized in the brain is to prevent peripheral immune cell proliferation. This condition establishes microglia and astrocytes as the specialized cells responsible to carry out the immune surveillance and to act as the first line of response against harmful events within the brain. Even when these characteristics might prompt us to consider the brain, and the CNS, as an immune-incompetent organ, it has been proposed that the mentioned conditions are necessary to prevent strong and uncontrolled immune/inflammatory responses, which can cause further neuronal damage [24]. However, under pathologic conditions, such as AD, in which a harmful molecule, such as Aβ, accumulates and aggregates within the neurons and ISF, a chronic inflammatory condition can still be triggered leading to the involvement of the different cells and structures within the brain, including neurons and brain microvasculature, among others (Figure 3). Interestingly, during recent years, the Aβ-driven neuroinflammation has become significantly relevant and currently is considered as a critical target to control AD [5, 25]. Moreover, it has been demonstrated that permanent exposure to Aβ due to an increased production or deficient clearance from the brain will lead to a chronic inflammatory state, which results in a harmful environment for the neurons, causing additional damage and ultimately further neuronal death. Importantly, the inflammatory mechanisms triggered by Aβ are driven mostly through the Toll-like receptor (TLR) family [20].
Amyloid-β-mediated effects on cells and organelles. Whether as oligomers or fibrils, Aβ is able to induce several effects on cells and on subcellular compartments. Aβ-derived damage and/or response will trigger a cascade of events, which ultimately will affect a wide range of CNS elements. Neuroinflammation is a common outcome of Aβ exposure. Upon Aβ challenge, neurons will release pro-inflammatory mediators. Moreover, neurons can internalize the Aβ affecting the neuronal trafficking and leading to cytoskeleton alterations, such as NFT formation. On the other hand, astrocytes and microglia will be activated inducing the production and release of pro-inflammatory mediators, which in turn can further activate surrounding glial cells and neurons. In the same way, Aβ will also deposit around cerebral microvasculature, leading not only to the release of additional inflammatory molecules but also to the disruption of the BBB sealing, allowing the extravasation of blood components to the brain parenchyma, altering the CNS microenvironment. Similarly, it has been demonstrated that Aβ can enter the mitochondria where it will cause mitochondrial dysfunction with an increased production of ROS, which will increase the oxidative stress within the surrounding cells, further inducing an inflammatory response. These events will occur simultaneously and together will sustain a persistent inflammatory response which will perpetuate and enhance the initial Aβ damage.
The TLR family constitutes a relevant group of the pattern recognition receptors (PRRs), a subtype of the damage-associated molecular patterns (DAMPs), which are endogenous indicatives of cell damage. As PRRs, TLRs are necessary not only to unleash the initial immune response but also to connect this first unspecific defense with the secondary adaptive immunity [20]. In this regard, TLRs have been demonstrated to be present in several cell components and in immunocompetent cells of the brain, including astrocytes, microglia, neurons, and oligodendrocytes, suggesting that each of these cells can sense and react to harmful molecular patterns [26, 27]. Moreover, it has been demonstrated that microglia and neurons express all TLR subtypes, whereas astrocytes express a more limited repertoire, including TLR2, TLR3, TLR4, TLR9, and TLR11 [28, 29]. Several members of the TLR family have been described, depending on the species, and these can be divided into two main groups: those expressed on the plasma membrane, such as TLRs 1, 2, 4, 5, and 6, and those expressed on endosomes, such as TLR 3, 7, 8, and 9. In general terms, TLRs signal through the myeloid differentiation factor 88 (MyD88) pathway. Accordingly, MyD88 recruitment leads to the activation of interleukin 1 receptor-associated kinase (IRAK) family of proteins, which in turn results in the activation of tumor necrosis factor receptor-associated factor 6 (TRAF6), causing the recruitment of transforming growth factor-b-activated kinase-1 (TAK1). TAK1 along with TAK1-binding proteins (TABs) activates the IKK complex, resulting in the phosphorylation of IkB factor, which induces the release of nuclear factor-kB (NF-kB) and enables its translocation to the nucleus and subsequent expression of inflammatory-related genes. However, some TLRs, such as TLRs 3 and 4, can signal via an additional pathway mediated by TIR-containing adaptor inducing interferon-β (IFN-β) (TRIF). Although this pathway results in the release of NF-kB, it also causes, via the IKKe/TANK-binding kinase 1 (TBK1), the phosphorylation of interferon regulatory factors 3 and 7 (IRF3–IRF7), inducing IFN-β expression. At the end of these TLR-related molecular cascades, we observe the production and release of several molecular mediators, such as cytokines, chemokines, complement proteins, and enzymes, including IL-1, IL-6, IL-10, IL-11, IL-12, tumor necrosis factor (TNF), TGF, IFN, CCL2, CCL5, CXCL8, and CXCL10, among others [26–29]. Among the several effects exerted by these molecules, these can further activate the TLRs, reactivating the inflammatory cascade.
Relevantly, Aβ has been demonstrated to interact with several members of the TLR subfamily of receptors, including TLR2 and TLR4, inducing an immune response with the subsequent release of pro-inflammatory molecules, including several members of the interleukin family, such as IL-1β, IL-6, IL-12, TNFα, cyclooxygenase 2 (COX2), and inducible nitric oxide synthase (iNOS) [30]. As previously mentioned, microglia, astrocytes, neurons, and oligodendrocytes express several members of TLRs, making them able to respond both to the Aβ insult and to the inflammatory mediators released in response to Aβ [20]. In this regard, it has been demonstrated that IL-6 levels are significantly elevated in AD and that its increased expression can be achieved by both direct production after primary Aβ exposure of the microglia, astrocytes, and/or neurons and as a secondary response to pro-inflammatory mediators such as IL-1β [31].
As mentioned, Aβ induces the secretion of pro-inflammatory molecules and/or exerts mechanical damage to the neurons, altering its delicate metabolism and leading to neuronal dead. Moreover, it will induce the release of additional inflammatory mediators, such as reactive oxygen and nitrogen species (ROS and RNS), which are able to interact with several biomolecules, including membrane lipids, nucleic acids, and proteins. As a result, synapses, dendritic projections, myelin sheath, and cell structure will be altered, compromising neuronal functionality [32–34]. Additionally, it is well known that increased BBB permeability is one of the primary alterations in AD, leading to the loss of brain isolation allowing systemic components to enter the brain parenchyma, altering the neuronal microenvironment [5]. As this condition is sustained in time, such variation will further damage neurons triggering and spreading the inflammatory response [9].
On the other hand, several authors have proposed that Aβ can also drive the hyperphosphorylation of
Astrocytes are fundamental to sustain brain homeostasis. These cells carry out several critical functions for neuronal function including, but not limited to, offering metabolic support to neurons and synapses and regulation of the neurotransmitter concentration. Astrocytes also play a relevant role in the inflammatory response [35]. Indeed, reactive astrocytes are a common feature of neuroinflammation and are usually considered as an indicator of the inflammatory state of the brain. In this regard, it has been demonstrated that the activation of TLR and NF-κB within astrocytes induces the production of pro-inflammatory molecules including IL-1; IL-6; TNF; chemokines, such as CCL2 and CC3CL1; and proteins of the major histocompatibility complex (MHC). Additionally, astrocytes have been syndicated as the responsible for the excitotoxicity damage because of glutamate release during harmful stimuli [21, 36]. Importantly, in response to the inflammatory signals, astrocytes can proliferate, migrate, and produce further inflammatory mediators, some of which are able to act in a paracrine manner activating the surrounding cells, including microglia, neurons, resting astrocytes, and endothelial cells [37].
On the other hand, a particularity of astrocytes is that these cells produce the ApoE, the main Aβ chaperone which allows the removal of the peptide from the brain. Altered astrocytes or genetic conditions, such as ApoE ε4 allele expression, will cause an impaired ApoE activity leading to a reduced rate of Aβ clearance, facilitating its accumulation and triggering the inflammatory response observed upon Aβ exposure [10]. In the same way, it must be noticed that astrocytes are in close contact with the BBB through the astrocytic end-feet, being able to sense the intracerebral microenvironment but also to be the first to response to increased BBB permeability [5–7].
Microglia reach the brain before the BBB closure and are defined as the main effectors of the immune response acting as the macrophages of the brain. Microglia remain in a “resting” state until diverse stimuli trigger the activation of these cells inducing the inflammatory response. It has been demonstrated that the resting state is maintained because of the interaction between the microglial chemokine (C-X-C motif) receptor 1 (CXCR1) and CD200L, with the neuronal CX3CL1 and CD200, respectively [38, 39]. As expected, activation of the microglia will be induced when these inhibitory interactions are loss or inflammatory signals are sensed by the resting microglia. In this regard, activated microglia is being able to phagocyte the surrounding tissue, proliferate, and migrate where needed. Moreover, activated microglia will release additional pro-inflammatory molecules, such as TNF-α or IL-1β, as well as ROS and RNS [37].
Among the several receptors that allow the microglia to sense the surrounding environment, the Toll-like receptors (TLR 1-9) and its co-receptor CD14 are the most important for microglial activation. Regarding Aβ, certainly, TLR2 and TLR4 are fundamental and drive main of the microglial reactions to Aβ, including phagocytosis [20]. Relevantly, during the last few years, an important genetic component has emerged regarding microglial response. Complement receptor 1 (CR1), cluster of differentiation 33 (CD33), and triggering receptor expressed on myeloid cells 2 (TREM2) have been related to microglial-mediated Aβ phagocytosis. Although it has been evidenced that these three genes help to sustain the phagocytic phenotype of the microglial cells, TREM2 has emerged as a potential biomarker due to its increased levels found in the CSF in AD [40–42]. Moreover, it has been reported that TREM2 mutations, such as arginine 47 to histidine (R47H), are critical for Aβ plaque formation because of an impaired function and expression of the receptor within the microglia. Indeed, such mutations seem to facilitate TREM2 ADAM/γ-secretase processing, as evidenced by the increased levels of the soluble TREM2 fragment within the plasma and CSF in AD [43]. The significance of such findings is just emerging, and intense research are focused to elucidate the roles of TREM2 and its soluble fragment in the pathophysiology of neurodegenerative disorders.
Although the concept of the BBB was proposed in the 1900s, only recently it has attracted high attention due to its relevance in the neurodegenerative disorders. Importantly, along with the blood-CSF barrier and the arachnoid epithelium, the BBB is a fundamental part of the brain isolation system. Indeed, several researchers have demonstrated, using hydrophilic compounds, that polar solutes were unable to cross the BBB because of occluding tight junctions (TJ) established between adjacent endothelial brain cells [5]. Moreover, brain endothelial cells evidenced the expression of a highly complex proteome, necessary to efficiently conduct the traffic of different molecules form the brain to the blood stream and vice versa. These characteristics clearly demonstrate that the BBB is an active player in maintaining the cerebral microenvironment. Furthermore, it is widely known that Aβ transport across the BBB is the main way to remove the Aβ from the brain. Due to its electrochemical characteristics, Aβ requires specialized transport to cross the BBB [6, 7]. The LRP1 and LRP2 and some members of the ABC family of transporters are related to brain Aβ clearance. Evidently, any pathological condition able to alter the brain microvasculature and, particularly, the endothelial cells will have a tremendous impact in the brain homeostasis and can affect the Aβ levels within the brain. In this regard, it has been demonstrated that Aβ accumulates around the blood vessels, leading to neurovascular dysfunction and cerebral amyloid angiopathy. Indeed, several changes take place in the cerebral blood vessels of AD patients, including loss of vascular density, decreased luminal diameter of vessels and capillaries, and thickness of vessel walls. More importantly, several of these alterations occur at the early stages of the disease. In attention to this observation, several authors have suggested that the BBB alteration might not be only a consequence of the neurodegenerative process but could be the basis of the pathological changes observed during the course of the disease [5–7, 9].
Although an organelle, mitochondria should be addressed because one of the critical features of the Aβ-mediated damage precisely relates with mitochondrial dysfunction [3, 5]. Moreover, mitochondria constitute the power supply within cells, and each of the functions that have been reported in this section requires important amounts of energy to be carried out. In this regard, mitochondrial activity will depend on cellular status, and pathological conditions able to modify internal cell environment will absolutely have an impact on mitochondrial fate. Increased oxidative status or proapoptotic stimuli will trigger different cellular mechanisms conducted to control cell death and the destruction of cell organelles, such as the mitochondria. In this regard, it has been demonstrated that beyond inflammatory cascade, Aβ is able to induce several proapoptotic signaling including endoplasmic reticulum stress, with the intracellular release of Ca2+ which will overload the mitochondria, and ROS-mediated apoptosis through the apoptosis signal-regulated kinase (ASK1) and favors the apoptosis through the B-cell lymphoma 2 (BCL2)-beclin1 (BECN1) complex, among others [44, 45]. Moreover, it has been found that Aβ can also enter the mitochondria, leading directly to mitochondrial dysfunction and to altered energy metabolism within cells. Along with the reduction of available ATP, altered mitochondria will also increase the production of ROS contributing to increase the brain oxidative status and resulting in the production of additional pro-inflammatory mediators, such as IL-6 [44–47]. In this regard, once released to the extracellular compartment, ROS can further trigger the inflammatory pathways in the neighboring cells inducing the activation of the NF-kB-dependent pro-inflammatory cascade [20].
As evidenced previously, the inflammatory response has demonstrated to be highly relevant in several neurodegenerative disorders, including AD, Parkinson’s disease, Huntington’s disease, multiple sclerosis, and amyotrophic lateral sclerosis. In these disorders, inflammation verifies since the early stages of the neurodegenerative process, and it is believed that it can also accelerate the spread of the disease across different brain areas. Moreover, several experimental therapeutic approaches have evidenced that controlling neuroinflammation might improve the disease outcome. Accordingly, during the last decades, huge efforts have been committed to understand neuroinflammation and how to control such process. Although several molecular pathways can be tracked down to explain the neuroinflammatory cascade, some of these pathways, such as nuclear receptors (NR) and the Wnt signaling, seem to develop a critical role in this kind of processes because it usually plays a pivotal role in the cellular physiology.
Nuclear receptors (NR) constitute a highly conserved superfamily of proteins [48]. These receptors act sensing the intra- and extracellular microenvironments and exert several functions including embryogenesis, reproduction, metabolism, inflammation, immunity, and lipid signaling. An important feature of its structure is that several domains can be recognized which upon activation, mainly through ligand binding, will induce conformational changes allowing the exposure of functional domains to the consensus nucleotide sequence present in the target genes, inducing their expression [49].
Peroxisome proliferator-activated receptors (PPARs) are classified as type II NR, which are characterized by the formation of heterodimers with the retinoid X receptor (RXR). PPARs possess a four-region structure including an amino terminal region, AF-1, which functions as a constitutive ligand-independent transactivation domain: the DNA-binding domain (DBD), constituted by two zinc fingers which recognize and bind the specific DNA nucleotide sequences termed peroxisome proliferator response element (PPRE), which consists of two AGGTCA sequences separated by a single nucleotide. Importantly, this domain contains the necessary elements to allow dimerization with the RXR. Next, the Hinge region is found and is believed to allow to connect the DBD to the ligand-binding domain (LBD). The LBD is a well-conserved domain among species, which is characterized by the presence of the ligand-binding pocket, a 12–13 anti-parallel α-helix structure. Within this region, there is also a ligand-dependent transactivation (AF-2) domain, which is intimately involved with both the generation of the ligand-binding pocket and interaction with transcription coactivators. Three PPAR isoforms have been described. Generally, PPARα is expressed in the liver, kidney, and skeletal muscle; PPARβ/δ is widely expressed, including the CNS; and PPARγ is highly expressed in fat tissue [49]. Importantly, several researchers have demonstrated the expression of the three PPAR isoforms within the brain, including the hippocampus, the critical brain area related to memory (Figure 4) [50].
PPARs and Wnt pathways. The figure represents the common molecular cascades associated to PPARs and Wnt signaling. Type II nuclear receptors, such as PPARs, form heterodimers with the RXR. The PPAR/RXR dimer binds to the DNA through the consensus sequence (PPRE), inducing the expression of target genes. PPAR, peroxisome proliferator-activated receptor; PPRE, peroxisome proliferator response element. On the other hand, the Wnt signaling pathway can be divided into canonical Wnt signaling and noncanonical Wnt pathways. During activation, canonical Wnt ligands interact with the Fz-LRP5/Fz-LRP6 complex receptor, this situation leads to the disassembly of the β-catenin destruction complex, which prevents GSK3β-mediated β-catenin phosphorylation. Thus, β-catenin can translocate to the nucleus where it binds to the TCF/Lef, initiating the transcription of Wnt-related genes. The noncanonical Wnt pathway, known as Wnt/Ca2+, can be triggered by noncanonical Wnt ligands. In this case, Fz will induce the release of calcium from intracellular stores, leading to the activation of calcineurin, CamKII, and PKC. In the same way, the noncanonical Wnt/PCP pathway also requires noncanonical Wnt ligands, which will interact with the Fz receptor and will activate Dvl. However, at this point, Dvl induces the activation of RhoA and Rac, which ultimately will lead to cytoskeletal rearrangement. Fz, Frizzled receptor; LRP, low-density lipoprotein receptor-related protein; GSK3β, glycogen synthase kinase 3β; TCF/Lef, T-cell factor/lymphoid enhancer factor; PCP, planar cell polarity; RhoA, Ras homolog gene family member A; ROCK, rho-associated protein kinase; Rac1, Ras-related C3 botulinum toxin substrate 1; JNK, c-Jun N-terminal kinase; PKC, protein kinase C; and CamKII, calcium/calmodulin kinase II.
Activation of the PPAR/RXR heterodimer will lead not only to the DNA binding but also to the exposure of the AF-2 domain, which will interact with the LXXLL motifs present in several PPAR coactivators, including the receptor family p160/steroid coactivator (SRC), p300/CREB-binding protein (CBP) complex, the switching/sucrose non-fermenting (SWI/SNF) chromatin remodeling complex, the PPAR interacting complex (PRIC) 285, and PRIC320/chromodomain helicase DNA-binding protein 9 (CHD9) [51]. Each of these coactivators, which have enzymatic activity, increases the transcriptional activity of the PPARs mainly through the chromatin remodeling and/or stabilization of the PPAR-DNA binding. Additionally, PPARγ-coactivator 1(PGC-1α), a nonenzymatic PPAR coactivator, needs to be mentioned because it has demonstrated to be critically involved in the mitochondrial function, thermogenesis, andenergy homeostasis. PGC-1α also requires the AF-2/LXXLL association to increase PPAR transcription. Moreover, PGC-1α-PPAR binding induces a conformational change in PGC-1α that promotes its binding to SRC-1 and CBP/p300, further enhancing the transcriptional activity. It has been proposed that in the brain, PGC-1α plays an important role in mitochondrial oxidative metabolism and in the maintenance of intracellular calcium levels [52, 53].
As pointed in previous sections, increased levels of Aβ will induce microglial and astrocyte activation and neuronal alterations and can compromise additional cells and structures, such as the BBB. As the result of such increased levels of Aβ, production of several cytokines (TNF-α, IL-1β, S100β) and chemokines (MIP-1α, MIP-1β) as well as oxidative stress-associated molecules will be enhanced. Relevantly, PPARs have demonstrated very interesting properties regarding the modulation of the inflammatory response. In this regard, the most studied isoforms are the PPARα and γ. Inhibition of activator protein 1 (AP-1) and NF-κB signaling is one of the well-known effects of PPARα and γ activation [54]. However, signal transducer and activator of transcription (STAT-1), nuclear factor of activated T cells (NFAT), early growth response protein 1 (Egr-1), and Jun and GATA-3 expression are also inhibited by PPARγ [54]. Moreover, PPARα activation also leads to reduced expression of T-box transcription factor (T-bet) and to the impairment of its binding to the DNA, limiting the expression of the pro-inflammatory cytokine IFN-γ. On the other hand, PPARα induces the expression of GATA-binding protein 3 (GATA3), a master regulator of the anti-inflammatory molecule IL-4 [55]. Because of the PPARα and γ activation, the expression of several pro-inflammatory cytokines, including IL-1, IL-4, IL-6, IL-8, IL-12, and TNF-α; vasoactive mediators, including cyclooxygenase 2 (COX-2), iNOS, and endothelin-1; expression of adhesion molecules, such as ICAM-1; chemokines, such as MCP-1, MCP-3, and INF-γ-inducible protein 10 (IP-10); and metalloproteases, such as MMP-9, are often reduced [17, 38, 55, 56]. Regarding the PPARβ/PPARδ, it is also believed that NF-κB blockade might be part of its mechanism of action, but its role against neuroinflammation is known to be related to the regulation of pro-inflammatory molecules, including C-C motif chemokine ligand 2 (CCL2), IL-6, and IL-1β [57].
An additional relevant feature of the PPARs is its ability to eventually induce an improvement in the Aβ clearance ratio from the brain ISF. It has been evidenced that increased levels of ApoE, the Aβ chaperone, can improve Aβ removal rate lowering its levels and preventing its aggregation [10]. Interestingly, ApoE is a target gene of the liver X receptor (LXR), another type II NR, which in turn is a target gene of the PPARs. Although indirectly, this genetic cross relation can explain the beneficial effects observed after PPAR agonist administration in in vivo models of AD [5, 9].
The Wnt signaling constitutes a relevant molecular system related to several physiological processes, including cell proliferation and differentiation. Wnt proteins are highly conserved among different species, and beyond its physiological roles, several studies have demonstrated the involvement of this family of proteins in pathological processes of the CNS, including neurodegenerative disorders, such as AD [58].
Classically, Wnt signaling can be divided in the canonical and noncanonical Wnt pathways. In the first one, also known as the β-catenin-dependent pathway, Wnt proteins bind to the Frizzled receptor/low-density lipoprotein receptor-related protein 5/Frizzled receptor/low-density lipoprotein receptor-related protein 6 (Fz-LRP5/Fz-LRP6), inducing the activation of the disheveled protein and the interaction between LRP5 and LRP6 with Axin. This interaction causes the disassembly of the β-catenin destruction complex constituted by the adenoma polyposis coli (APC), Axin, GSK3b, and casein kinase 1 (CK1), preventing the β-catenin phosphorylation and allowing its translocation to the cell nucleus where it will bind to the T-cell factor/lymphoid enhancer factor (TCF/Lef) transcription factor to induce the expression of Wnt target genes. Without the positive input of the Wnt ligands, the destruction complex remains active inducing the β-catenin phosphorylation and the subsequent proteasomal degradation. On the other hand, the noncanonical Wnt pathway can also be divided into two additional cascades: the Wnt/planar cell polarity (Wnt/PCP) pathway, which requires the binding of Wnt ligands and signals through disheveled-Rho and Rac GTPases, inducing c-Jun N-terminal kinase (JNK) activity and leading to actin cytoskeleton modeling, and the Wnt/Ca2+ pathway in which the binding of Wnt ligands to the Fz receptor induces the release of Ca2+ from intracellular compartments, including the ER, causing the activation of several calcium-related proteins, such as protein kinase C (PKC) and calcium-/calmodulin-dependent protein kinase (Ca2+/CamKII) (Figure 4) [20, 58].
The Wnt signaling has emerged as a very promiscuous pathway. It has been possible to identify the crosstalk between both canonical and noncanonical signals which exert a modulatory effect over its counterpart. Moreover, Wnt pathways can also interact with additional molecular pathways, including the NF-kB, fork head box O (FOXO), Notch, hypoxia-inducible factor 1a (HIF1a), and JNK [52]. Indeed, several elements of the Wnt cascade seem to constitute molecular master switches that can be accessed through diverse mechanisms. This condition is of most relevance regarding the inflammatory response. Indeed, Wnt signaling has been directly associated with the control of the inflammatory process, mainly because of its ability to modulate the NF-kB pathway. However, the complex interaction established between this pathway and the master coordinators of the inflammatory response within cells has been constantly obviated. Moreover, it is well noticed that the canonical and noncanonical pathways exert, usually, opposed actions [20, 59]. While the canonical Wnt prevents the inflammatory cascade by blocking the NF-kB pathway, interacting with RelA, the noncanonical pathway has been reported to promote the inflammatory response, actin, through the PI3K, Rac1, and MAPK, and to the subsequent release of pro-inflammatory molecules. However, it must be considered that some noncanonical Wnt ligands, such as the Wnt5a, can exert an anti-inflammatory effect and vice versa [20].
We have recently suggested that in attention to the Wnt pathway-mediated NF-kB modulation, a crosstalk between the Wnt and TLR pathways seems to be evident [20]. Moreover, different authors have demonstrated that TLR activation downregulates the canonical Wnt signaling pathway. Indeed, TLR4 activation can block the Fz-LRP5/Fz-LRP6 complex inhibiting the canonical Wnt signaling [60]. Contrarily, the activation of the Wnt/Ca2+ induces the expression of the suppressor of cytokine signaling 1 (SOCS-1) and of protein inhibitors of activated STAT 1 (PIAS-1), causing a reduced expression of some signal transducers of the TLR cascade, such as IRAK members and MyD88. In the same way, the MyD88-mediated TLR activity results in the activation of the nemo-like kinase (NLK), which directly interacts with the nuclear β-catenin-TCF/Lef complex. On the other hand, it has recently been demonstrated that MyD88-independent TLR signaling activates the IKKe/TBK1, which can directly phosphorylate Akt, leading to GSK3β inhibition, the key β-catenin degradation-driven protein. Moreover, the blockade of the GSK3β activity prevents the binding of NF-kB with the cAMP response element-binding protein (CREB)-binding protein (CBP), suggesting that GSK3β activity modulates the TLR-dependent cytokine production [61–64].
Interestingly, lithium, a well-known canonical Wnt signaling agonist because of GSK3β inhibition, allows to further address the role of Wnt signaling in neuroinflammation. In this regard, it has been demonstrated that lithium not only reduces the expression of pro-inflammatory mediators, such as IL-6, but it also reduces TLR4 expression in astrocytes [65]. Whether these effects are mediated directly by Wnt signaling or as a part of a secondary mechanism, GSK3β seems to play a pivotal role not only in the Wnt singling itself but also as the master switch in the context of the inflammatory response.
During the recent years, the relevance of the inflammatory process in the neurodegenerative disorders, such as AD, has evolved from a consequence of such pathological events to an early sign of brain distress. Moreover, the severity and chronicity of the inflammatory response within the brain parenchyma are believed to favor the progression and spreading of these diseases across the brain.
Understanding the inflammatory cascade, triggered after Aβ exposure, and the critical nodes which allow control the process is a fundamental goal to develop new and efficient therapeutical alternatives to fight AD. In this regard, our knowledge regarding Aβ-related inflammation has increased dramatically in the last years; however, relevant questions about the molecular mechanisms involved in such response are still open, with new players appearing each day. Nuclear receptors and Wnt signaling are two of the main cellular pathways able to modulate several cellular processes. Moreover, independently each of them has proven to be involved in the Aβ-induced inflammatory response; however, little is known about its interactions as part of the inflammatory molecular network. On the other hand, one of the more recent cases of new players identified to be relevant in neuroinflammation is constituted by the TREM2 protein, which favors Aβ microglial phagocytosis. Already known, this protein and its processing have recently emerged as novel and interesting biomarker and as a target to unveil some of the questions about the neuroinflammatory process observed during AD.
Nowadays, the quality of products, including services, appears the mandatory criterion that must be taken into account by companies all over the world. In order to better organize their activities, the companies design, implement, and then review business management systems.
ISO standards offer a framework that covers different areas and give companies support regarding the design and implementation of the management systems.
To ensure a certain degree of quality in all the levels and areas, the company designs and sets in place the quality management system (QMS), in accordance with the fundamentals presented in ISO 9000 [1] and the requirements given by ISO 9001 [2].
In the last decade, to have a quality system implemented in the company appears not enough to identify all the problems and solve them or to face in a reliable way the changing environment. After some time, the systems need to be evaluated in order to identify their performance. For realizing the self-assessment of the QMS, the standard ISO 9004 [3] comes in handy.
To offer a broader alternative to ISO 9004, the excellence models have been developed and reviewed to facilitate benchmarking and maturity level assessment in terms of performance [4, 5, 6, 7, 8]. One of the most developed and used Excellence Model is the European Foundation for Quality Management (EFQM) Excellence Model [4, 5, 6].
As the industry evolved taking into account the quality of products, processes, machines, and systems, another problem appeared that it is not covered in total by the tools used in order to analyze the performance (ISO 9004 [3] and Excellence Models [4, 5, 6]). The excellence models were the starting point of finding solutions for a sustainable development of companies.
In order to achieve sustainable development for a company, the three pillars, namely society (social responsibility), economic growth, and the environment protection, must be taken into account [9].
In 2010, ISO drafted and published the standard ISO 26000 [10] that offer companies’ guidelines considering two of the three pillars (society and environment). Its purpose is to harmonize the social behavior of enterprises worldwide [10, 11, 12].
An important item in sustainability is the establishing of key performance indicators and the manner in which they have to report them. To have guidelines for reporting, the Stitching Global Reporting Initiative (GRI) and ISO have developed a framework for companies presented in GRI1 Foundation [13]. The next three standards cover the part of general disclosures [14], materials [15], and economic performances [16]. The first four GRI standards are applied in all fields.
Nowadays, searching companies’ websites, more and more companies exhibit their strategy in terms of customer focus and sustainability. Moreover, sustainability strategies are promoted to increase customer loyalty showing the approaches for sustainable development so as to harmonize stakeholders into more sensitive balance between environment – human – development – policies.
One may analyze the structure of ISO standards concerning quality management, i.e., the fundamentals (ISO 9000 [1]), the requirements (ISO 9001 [2]), and the guidance for sustained success that may be considered an assessment framework and tool for the QMS maturity (ISO 9004 [3]). The QMS principles are accompanied by possible actions, these actions being translated into requirements in ISO 9001 [2]. This means that one may not focus unbalanced on one or another component of the system, the whole, as a system, appears relevant, and all aspects should be considered irrespective of the priority order selected by the organization to address the fundamental through approaches.
Once implemented, the organization may step into the next level of performance, applying the self-assessment regularly in order to define improvement plans and act accordingly. In this context, ISO 9004 offers a maturity assessment tool [3] finalized with a radar diagram for better evidence of the areas with more potential or emergency need for improvement. Such a radar, together with the detailed maturity assessment, may be used by the management team (top and middle) as a prioritizing tool for the decision-making process.
If organizations maintain into the improvement cycle according to ISO 9001 requirements, certainly certain benefits may be reported on long term, but, in order to proactive reply to the global changes, ISO standards appear too basic to release organizational adaptability and people real engagement. The management team has the option to support improvement projects, even beyond the ISO requirements, such as motivating people through different mechanisms to balance professional to private life or involvement in community responsibility projects. On short term, the tangible effect may be more satisfaction and engagement of people.
Based on the experience of different contexts, in function of the organizational capability, a significant step ahead may be embracing extended fundamentals of an excellence model, such as EFQM [3, 4] or other similar business models. Table 1 presents in comparison the fundamentals showing the consistency in progression of these principles.
Quality management principles [2] | Fundamental concepts EFQM model [4] | Fundamental concepts updated EFQM model [5] |
---|---|---|
Achieving Balanced Results | Sustaining Outstanding Results | |
Customer focus | Adding Value for Customers | Adding Value for Customers |
Leadership | Leading with Vision, Inspiration & Integrity | Leading with Vision, Inspiration & Integrity |
Engagement of people | Succeeding through People | Succeeding through the Talent of People |
Process approach | Managing by Processes | Managing with Agility |
Improvement | Nurturing Creativity & Innovation | Harnessing Creativity & Innovation |
Evidence-based decision making | ||
Relationship management | Building Partnerships | Developing Organizational Capability |
Taking Responsibility for a Sustainable Future | Creating a Sustainable Future |
Comparison of fundamentals.
Once a sound management system set in place and a deep commitment of the management team for these fundamentals, the use of the excellence model framework is naturally adopted. Even more complex, more evidence-based, more refined, and in-depth interconnected, the excellence model offers to the management team the framework for assessment on a broader and more discrete perspective in order to define action plans for improvement. Similarly, but more complex, all fundamentals should be considered, each of them having corresponding criteria and subcriteria, and the same maturing assessment is proceeded, revealing finally the areas for improvement.
The difference, but the added value of the excellence model, lies into the more refined evidence research for more organizational cells and layers, seen in the progression of PDCA (Approach – Deployment – Assessment & Refinement) of the assessment so as to identify, prioritize, and implement sustainable approaches.
Even if the model changed the role from an assessment tool [4, 5] to a framework for defining the direction so as to cocreate together with others a sustainable ecosystem [6], in order to understand the capabilities and to address the necessary changes, the assessment grid (Table 2) is given for connecting to evidences while analyzing the reality, in order to define priorities for present and future.
Type of evidences | Attributes | Rating % |
---|---|---|
Lack of indicators Lack of procedures Interfaces undefined | No evidence or anecdotal/Unable to demonstrate | 0% |
Indicators set in place, but no monitoring and connection with the approaches Improvement plan drafted Procedures for critical issues Interfaces coordination in an unformal way | Partial Conformity/Some evidence/Limited ability to demonstrate | 25% |
Improvement plan documented and monitored Procedures/processes set in place, documented and functional Functional interfaces Rare or minor disruptive processes/few or minor non-conformities Monitored indicators as decision-making process threshold/framework | Effective/Evidence/Able to demonstrate | 50% |
Regular improvement of the documented processes Regular update of procedures for better and more fluent functioning Interfaces regular monitoring together with process stakeholders | Efficient/Clear evidence/Fully able to demonstrate | 75% |
Innovative approaches set in place Practices reference for benchmarking at global level Anticipation of needs and their evolution Committed and motivated actors Continuous learning from the implemented approaches to explore perceived opportunities | Excellent/Comprehensive evidence/Recognized as global role model | 100% |
Assessment grid for enablers.
Disruptive processes appear nevertheless in any environments and nowadays change, balance, technology, transformation may not be avoided; moreover, after a long period of stop-and-start, with direction research in the pandemic time, which revealed clearly that previous solutions should be reviewed and soundly transformed, a diagnostic of the entity’s reality is needed.
The RADAR tool has been developed on the basis of the Deming cycle (Plan-Do-Check-Act) but adding the organization’s reason of existence in the ecosystem, measured through the results composed by perceptions and outcomes/outputs/indicators, all of these benchmarked versus targets.
The assessment/diagnostic tool allows the management team to analyze in depth the working style in order to manage more effective and efficient, but to enable the strategy and plans definition in clear priority and consistent follow-up. The starting point is the results aimed to achieve, once determined, approaches are set in place to deliver these results, approaches become operational through deployments, and their effectiveness, efficiency, and sustainability are assessed and refined. The assessment framework is detailed in Table 3 for enablers and Table 4 for results.
Element | Detail | Rating % | Organization reality | |
---|---|---|---|---|
What are the results aimed to achieve as follows the Strategy | Search evidence and assess | Strengths and Areas for improvement | ||
Plan and develop sound and integrated | Sound—considering relevant stakeholders needs build Approaches with real rationale and define processes to support them | Search evidence and assess | Strengths and Areas for improvement | |
Integrated—considering the Strategy to achieve the Results, build and connect the Approaches in a sustainable and synergetic structure | ||||
Implemented—approaches are implemented in relevant areas with time refinement based on the stakeholders present and future needs | Search evidence and assess | Strengths and Areas for improvement | ||
Systematic—approaches are operational and enable resilience and agility; Approaches are planned and executed soundly | ||||
Measurement—regular measurements of approaches effectiveness & efficiency, regular measurements of effectiveness & efficiency of carried out deployments, appropriate measurements selected and regularly monitored | Search evidence and assess | Strengths and Areas for improvement | ||
Learning and creativity—internal and external good practices/practices to avoid and improvement opportunities are internalized and valorized, approaches and deployments are updated with creativity | ||||
Improvement and innovation—outputs from measurements and learning and creativity are feeding evaluation, prioritization, planning and implementation of improvements and innovations | ||||
Summary per Enabler subcriterion | Consolidated rating | Strengths and Areas for improvement |
Radar assessment framework for enablers.
Element | Detail | Rating % | Organization reality |
---|---|---|---|
Results should be comprehensive, reliable, accurate and consistent with the strategy | Scope and relevance—performance seen as strategy to fulfill relevant stakeholders needs and expectations is demonstrated by coherent and sustained key results (KPI) | Search evidence in relevant areas and assess | Strengths and Areas for improvement |
Integrity—results are accurate and reliable and ensure confidence | |||
Segmentation—to reveal meaningful insights | |||
Trends—sustained positive performance at least 3 years | Search evidence in relevant areas and assess | Strengths and Areas for improvement | |
Targets—are set and are consistently achieved, in line with the strategic objectives | |||
Comparisons—external comparisons are made and these are favorable, in line with the strategic objectives | |||
Confidence—the performance level will be sustained as enablers—results relationship is conditioned | |||
Summary per Result subcriterion | Consolidated rating | Strengths and Areas for improvement |
Assessment framework for results.
For a better understanding of how the day-to-day activity of the organization should be framed into the excellence assessment, some guidance is presented in Table 5. Current tools, developments, and ways of working may be associated to enablers, but the management thinking design should always be mirrored by the results (perceptions and outcomes) assessment and their evolution understanding, compared with targets and adequately/dynamically benchmarked. The cause-effect relation helps in understanding the “why” behind the organization’s approach, the “how” to deploy the approaches, and the achievements as a result, in practice the consequence of all these actions.
Enabler | Subcriterion | Possible approach | Possible deployment |
---|---|---|---|
Leadership | Leaders develop the Mission, Vision, Values, Ethics and act as models | Define the core business purpose for a sustainable future and consequently the Values and Ethics | Vision, Mission, Values are developed and integrated into the Strategy and communicated regularly to all stakeholders |
Define and review leaders code of conduct/agreed behaviors to explicit the leaders role model | Enable assessment, review, improvement of individual performance, mainly those of leaders | ||
360° Appraisal - evaluate leaders performance based on feedback from all levels of interaction top, down and lateral | Deploy a sound process of assessment of the individual performance so as to build a culture of trust and ethics | ||
Leaders define, monitor, review and improve the management system and the performance | Set strategic measures to monitor performance in line with the stakeholders needs and expectations, such as Balanced Scorecard | Management team assess progression against targets set so as to achieve the strategic goals; composite indicators are regularly analyzed as part of the decision process | |
Management board meetings for regular review and refinement in line with the business | Strategic objectives are cascaded into the reporting processes (financial, operational a.s.o) | ||
Leaders engage with external stakeholders | Regular contact of senior management with key customers, partners and community representatives | Define business to business strategic level and review it regularly in line with the strategic goals | |
Reporting and public communication, such as Sustainability report (UN Global Compact) | The reports content, format and circulation concern business key financial, environmental and societal progression, in line with international initiatives committed for, if the case | ||
Leaders reinforce the culture of excellence with organization’s people | Define the culture of excellence by adopting a business model in line with an excellence model, such as EFQM | Consider excellence as a reference in the planning processes; leaders actively involve people in improvements | |
Leaders ensure that the organization is flexible and manage changes effectively | Annual Board Meeting—the Board communicate the plans and gain support/commitment for their implementation | The management team agrees the strategic plans and gain support, if the case, from shareholders | |
Annual kick-off event—leaders communicate the overall strategy and the annual objectives | Leaders adopt organization’s objectives and cascade them to individual ones in their teams | ||
Strategy | Strategy is based on understanding both stakeholders’ needs and expectations and external environment | Understanding developments, opportunities, threats on the desired and current market | Relate market analysis with strategic partners, knowledge management and research and development, connect with academics a.s.o. |
Understand any updates concerning legal and regulatory compliance | Legal and operational teams should cooperate to identify and implement the regulatory and compliance framework and correspondent actions to set in place | ||
Strategy is based on deeply understanding internal performance and capabilities | Perform an in-depth self-assessment conducted internally or externally; Cross check with control systems results | Perform an in-depth self-assessment to identify priorities for the action plans; Consider objectively the organization’s capabilities | |
Strategy and policies are developed and updated to ensure sustainability | SWOT analysis may reveal internal and external perspectives (Strengths, Weaknesses, Opportunities and Threats) | Balance internal and external perspectives in strategy, policies and strategic plans | |
Strategy and policies are communicated and deployed/documented | Strategy mapping—strategy is geographically segmented and aligned with stakeholders’ expectations | Strategy maps may be communication tools and review tools for the management team to check performance and update the objectives, plans, processes | |
Cascade objectives—align personal and teams’ objectives although the organization with the strategic ones | Start from top level and progressively break down through functional streamlines and individuals; Connect individual objectives with internal communication and the appraisal process | ||
People | People plans are aligned with the organization strategy | People engagement rather than people satisfaction | Enable people’s contribution to their full capacity to the organization goals; Link people engagement to customer loyalty and key results |
Recruiting process—attract, evaluate and select new and potential talented people | Promote mobility, link to remuneration and benefits policies, adapt to the level of people to be recruited, third part/external service may be used | ||
Succession planning—identify potential successors for the key roles and prepare them adequately | Prepare business continuity planning on immediate and long-term perspective and review regularly the planning | ||
People’s knowledge and skills are developed | Appraisal process—assess individual performance and behaviors against a set of agreed objectives, competences, attitudes | Align organization’s overall objectives to people individual performance and objectives; Link to people survey and to performance related incentives (salary, bonus, promotion…penalty) | |
Personal development and training—align individual needs to competences needed for the role as derived by the strategic objectives | HR strategy is aligned to people capabilities, organizational needs to fulfill the strategic goals and the appraisal process; Training plans are drafted and implemented, results of training are assessed and valorized | ||
Management development programs and/or people certification | Talent management plans set in place; Staff certification for roles needing it or for professionals in industry/sector setting the requirement, eventually on regular basis | ||
People are aligned, engaged and empowered | Process improvement teams—improvement as culture in a structural process | Privilege cross-functional teams; Involve (experts) facilitators or include training to guide the process | |
5S—workplace and flows organization methodology | Empowering people to improve the workplace and the processes they are involved in; Facilitate processes’ standardization | ||
Objectives’ cascade—align individuals to strategic objectives | Connect to strategic planning process (ex-ante) and the appraisal process and people motivation policies objectively supported by people performance (ex-post) | ||
People communicate effectively throughout the organization | Internal communication—clear communication channels top, down, horizontal, inter-departments/units | Ensure a bilateral way of communication to support dialog and information transfer, based on needs of people and teams; Use surveys to assess the effectiveness | |
Electronic communication media | Encourage communication and networking through e-means (intranet, blogs, social networking a.s.o.), but maintain and valorize physical interaction, too | ||
Workers council | Develop a sustainable partnership with the workers’ structures, if any | ||
People are recognized, rewarded and cared for | Rewards and benefits | Develop a flexible benefit package aligned to overall HR strategy | |
Salary benchmarking | Screen the connection between people’s motivation incentives and benefit package in the region, industry, sector etc. (external service may be used) | ||
Health and safety | Implement legal and regulatory compliance in term of occupational safety and health; Bonus as medical insurance, welfare, facilities for family | ||
Partnership and resources | Partners and suppliers are managed for sustainable benefit | Suppliers’ selection criteria | Suppliers’ audits, assessment |
Establish, develop and manage relationship with partners | Partnership-related processes clearly defined, monitored and assessed; Partners’ performance reported (impact on KPI) and related to Strategy | ||
Finances are managed to secure sustained success | Budgeting process, with data in compliance to legal regulation, stock exchange a.s.o. | Ensure budget are aligned to strategic objectives; Budget allocations are cascaded and aligned with processes and reviewed, correlated with the Results | |
Procurement processes, lengths of supply chains | Responsible purchasing is a key for CSR strategy | ||
Buildings, equipment, materials and natural resources are managed in a sustainable way | Buildings’ policy and facilities management to ensure a safe working environment with all necessary facilities for achieving the Strategy | Effective management of sites, locations, outsourced facilities Assess people satisfaction Report sustainability Review the policies | |
Environmental management system Information security management system | Consider ISO certifications (ISO 14001, 27001 a.o.) | ||
Technology is managed to support strategy | Possible IT outsourcing Internal digital transformation processes | IT maintenance, support, other services IT policies aligned to strategic goal People training and support | |
Information and knowledge are managed to build operational capability | Knowledge management system Ensure data security, availability, integrity | Build a knowledge management system Capitalize the organizations’ knowledge | |
Processes, Products and Services | Processes are designed and managed to optimize the value for stakeholders | Process approach and risk-based thinking | ISO 9001 implementation/certification |
Lean Six Sigma | DMAIC to understand performance dynamics and identify improvement options Monitor customer experience | ||
Products and services are developed to create value for customers | Research and development | Sustainability issues, production techniques, end life cycle monitored, recycling, buy-back, research on as-used components | |
Focus groups to collect and generate new ideas, direct feedback | Involve customer in testing new products Collect regularly the Voice of Customer (VOC) | ||
Products and services are effectively promoted and marketed | Strategy of marketing / product launching, including target audience, value proposition, pricing, promotion | Clear definition of target audience; Use effective channels for reaching audience Assess the marketing campaign through the effective results | |
Products and services are produced, delivered and managed | Supply chain management to ensure effective delivery of products and services to customer | Connect CSR into the supply chain management | |
Customer relationships are managed and enhanced | Customer relationship management—a system set in place tracking contacts, accompanied details of expectations | Connect to product development, marketing-sales and performance indicators | |
Customer centers | Sometimes outsourced Dependent on customer strategy adopted | ||
Customer surveys, the most common tool to collect customer experience | Frequency, segmentation, use of results to drive improvements and review of strategy |
Guidance for enablers.
Considering the evolution of the industrial fields nowadays and the requirements stated by the standards and laws, companies have adopted more often the concept of sustainability. The sustainability development of a company is given by the three pillars of sustainability (see Figure 1): society (social responsibility), economic growth, and the environment protection. The three pillars are embedded within the company’s management systems.
Sustainability pillars.
Since the first pillar of sustainability—economic growth—has been defined, this has appeared important for companies to remain in competition in their field of activity. In order to maintain a constant economic growth, companies define strategic objectives and continuously implement these objectives in all areas of improvement identified using several types of performance models. This pillar may relate to the first two enablers presented in Table 5: Leadership and Strategy.
Second and third pillars of sustainability development cover the other three enablers presented in Table 5: people, partnership and resources, and some parts of processes, products, and services.
The three pillars are, also, reflected in the Business Continuity Plan of companies, plan required by the legal norms in each country. Every company must consider and establish possible actions to keep under control the impact on the society and environment in any given situation.
In order to support companies and harmonize their social behavior, the International Organization for Standardization (ISO) has created the standard “
The standard contains voluntary guidance, but it does not need a certification. Table 6 presents an example of steps that can be followed in order to implement the standard. Before implementing the ISO 26000, the most important step is to identify the stakeholders of the company and the impact they have on the social responsibility decisions that will be taken and implemented (see Figure 2).
Steps | Possible actions | |
---|---|---|
Plan | Identify the need benefits of implementing SR standard in the company | Establish the SR characteristics |
Identify the relationship between SR and sustainability | ||
Define the policy and the strategy | Identify stakeholders | |
Identify and create a common ground between the values of the company and the SR values | ||
Analyze the SR principles | ||
Analyze and identify the needed areas for the company considering the seven core subjects of SR | ||
DO | Integrate in the existing management system the SR requirements | Adopt the SR principles |
Establish the SR objectives | ||
Establish the KPI (key performance indicators) for SR | ||
State the action plan | ||
Implement the possible actions | Establish the way of reporting the KPI | |
Raise awareness in the company | ||
Integrate the action plan in the company systems | ||
Communicate and set the reporting means for all the stakeholders | Identify the most effective way of communication | |
Engage the stakeholders taking into account their impact on the company decisions regarding SR | ||
Analyze the SR influence | ||
Report the KPI established | ||
Check | Evaluate | Monitor the SR performance |
Analyze the data obtained | ||
Act | Improve | Identify possible action in order to improve the SR performance Track the improvements impact |
Implementation of the ISO 26000 standard.
Stakeholders.
The NEN Handbook “The implementation of SR – Best practices and tools for ISO 26000” offers a set of detailed free tools that can be used to implement the Social Responsibility (SR) in companies (see Table 6).
In order to implement the SR principles and objectives in the organization management, first of all, the relevant areas of interest correlated with the core subjects of ISO 26000 should be identified. In Table 7 are presented some relevant areas that can be important for different companies.
Core subject | Relevant areas of interest | Stakeholders |
---|---|---|
Organizational Governance | The application of the SR principles ensures an elevated level of organizational governance | The organization leaders Employers |
A joint effort is needed, considering the size of the Organization, to achieve the desired results associated with SR. | ||
The most effective mechanism to implement is to maintain the motivation of the stakeholders and to proper develop of the principles of Social Responsibility | ||
Human Rights | Establish transparent and effective complaint and redress mechanisms | The organization leaders Employers Customers Suppliers Society Local government |
“Equal rights for all employees and workers (such as gender equality) Strive for diversity in the employee group” | ||
Freedom of opinion and expression | ||
Contribution to economic, social and cultural rights | ||
“No child labor and no forced labor Freedom of association or collective bargaining “ | ||
Labor Practices | Contracts for employees with clear and correct mentions | The organization leaders Employers |
Equal and equitable opportunities for all employees | ||
Contracts with clear and fair mentions to subcontractors, suppliers and partners | ||
Protection of personal and private data of employees | ||
Social protection for employees | ||
Collaboration and openness to dialog with independent representatives representing the interests of employees | ||
Continuous communication with local communities or other local stakeholders | ||
Implementation of occupational medicine systems | ||
Emergency assistance | ||
Handling/Handling of Dangerous Equipment | ||
Preventive Medical Investigations | ||
Staff development and training plan | ||
Training program for new employees | ||
Environment | Respecting and promoting the following principles:
| The organization leaders Employers Customers Suppliers Society Local government |
Pollution prevention through management:
| ||
Sustainable use of resources through the effective use of the following:
| The organization leaders Employers Society | |
Climate change mitigation through effective management of greenhouse gas emissions, Reducing vulnerability to floods | The organization leaders Society | |
Valorization and protection of biodiversity | ||
Valorization and Sustainable use of land and natural resources Restoration of ecosystems | ||
Progress on ecological urban and rural development | ||
Fair Operating Practices | Clear rules regarding the accepted level of giving and receiving business gifts Respecting the local culture | The organization leaders Employers Costumers Suppliers |
Verification of certificates and declarations of origin | ||
Establishing rules and boundaries regarding political lobbying | ||
Similar level of information available to all providers and contractors | ||
Contracts including clear terms and fair prices in relation to suppliers and | ||
Honest pricing policy with suppliers | ||
Implement appropriate vigilance mechanisms | ||
Payment of fair compensation for intellectual and physical property rights | ||
Consumer Issues | Clear, honest and complete information about the products or services delivered and their impact. | The organization leaders Customers Employers |
Mechanisms for returning and withdrawing the product from the market. | ||
Reliable, accurate, and verifiable information about the impact of products/services on the environment, society or economy | ||
Adequate and relevant information on: product health and safety, possible negative impacts, maintenance, assembly or recycling. | ||
Products that can be recycled or repaired and reused | ||
Accessible and efficient customer complaint mechanism | ||
Mechanisms for proper installation, use, repair, maintenance, return and recycling | ||
Clear and fair guarantee and implementation mechanism | ||
Mechanism for resolving disputes, resolving disputes, and mediating at a minimum cost to consumers | ||
Transparent mechanism for obtaining, using, securing, and deleting personal data | ||
The right of the customer/consumer to verify personal data | ||
Protection policy for the provision of essential services to all consumers | ||
Education and awareness program for customers/consumers regarding the purchase conditions, comparison of key functions, impact of use, etc. | ||
Community involvement and development | Analysis of communities affected by core activities | The organization leaders Society |
Review of supporting the Millennium Development Goals or local development goals | ||
Education and learning program for communities | ||
Plan for respecting cultural traditions and protecting cultural heritage | ||
Participation in local and national skills development programs, including apprenticeships | ||
Plan for the direct creation of local jobs | ||
Collaboration with universities or institutions in stimulating and providing technology at accessible local conditions | ||
Providing fair opportunities for local suppliers and SMEs | ||
Fair fiscal policy | ||
Program to support communities with essential health care services, access to clean water, good sanitation | ||
Activities to stimulate the improvement of the infrastructure for transport, water, electricity, communications, etc. |
The core subjects from ISO 26000 [10].
Companies that have implemented ISO 26000 and monitor sustainability should annually report the key performance indicators they set. In order to do that, they can use the reporting framework given by the GRI.
Analyzing the common ground of the excellence models (EFQM) or sustainability, one may notice that for both approaches the companies must:
Set objectives considering the fundamental concepts that the company has adopted and internalized in the company’s culture
Identify KPI for both and then ways and tools to monitor them
Evaluate the performance on a regular basis
Report the results
Relaunch the cycle considering the performance and results versus the targets and comparing to the competitors when resetting the objectives.
Considering a company that adopted both excellence and sustainability concepts and codefined the company’s values starting from these fundamentals, one may propose the structure of the company’s management system looking similar to the Greek temple, as presented in Figure 3.
Company structure.
The foundation to build a surviving business may embed the fundamental concepts of excellence and sustainability, the pillars for maintaining the business in the global competition should arise from the two models, merging the enablers and the results of excellence with the criteria to assess sustainability, and finally, the company assesses and reports regularly the KPI and the other metrics in order to better comply with the values, to differentiate among competitors, and to better serve the stakeholders.
This work has been funded from the Erasmus + project “Boosting Sustainable Digital Education for European Universities (BoostEdU),” no. 2020-1-CZ01-KA226-HE-094408. The European Commission has no responsibility concerning the content of this deliverable.
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His studies in robotics lead him not only to a PhD degree but also inspired him to co-found and build the International Journal of Advanced Robotic Systems - world's first Open Access journal in the field of robotics.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"441",title:"Ph.D.",name:"Jaekyu",middleName:null,surname:"Park",slug:"jaekyu-park",fullName:"Jaekyu Park",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/441/images/1881_n.jpg",biography:null,institutionString:null,institution:{name:"LG Corporation (South Korea)",country:{name:"Korea, South"}}},{id:"465",title:"Dr.",name:"Christian",middleName:null,surname:"Martens",slug:"christian-martens",fullName:"Christian Martens",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Rheinmetall (Germany)",country:{name:"Germany"}}},{id:"479",title:"Dr.",name:"Valentina",middleName:null,surname:"Colla",slug:"valentina-colla",fullName:"Valentina Colla",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/479/images/358_n.jpg",biography:null,institutionString:null,institution:{name:"Sant'Anna School of Advanced Studies",country:{name:"Italy"}}},{id:"494",title:"PhD",name:"Loris",middleName:null,surname:"Nanni",slug:"loris-nanni",fullName:"Loris Nanni",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/494/images/system/494.jpg",biography:"Loris Nanni received his Master Degree cum laude on June-2002 from the University of Bologna, and the April 26th 2006 he received his Ph.D. in Computer Engineering at DEIS, University of Bologna. 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. He has contributed in stochastic estimation of control area especially, in the Multiple Target Tracking and Interactive Multiple Model (IMM) research, Ball & Beam Control Problem, Robotics, Levitation Control. He has contributed in developing Algorithms for Fingerprint Matching, Computer Vision and Face Recognition. He has been supervising Pattern Recognition, Formal Languages and Distributed Processing projects for several years. He has reviewed many books on Management, Computer Science. Currently, he is an active and permanent reviewer for many international conferences and symposia and the program committee member for many international conferences.\nIn teaching he has taught the core computer science subjects like, Digital Design, Real Time Embedded System Programming, Operating Systems, Software Engineering, Data Structures, Databases, Compiler Construction. In the Engineering side, Digital Signal Processing, Computer Architecture, Electronics Devices, Digital Filtering and Engineering Management.\nApart from his Academic Interest and activities he loves sport especially, Cricket, Football, Snooker and Squash. He plays cricket for Esbjerg city in the second division team as an opener wicket keeper batsman. 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In this chapter, you understand the details of ageing processes and associated physiological changes.",book:{id:"6381",slug:"gerontology",title:"Gerontology",fullTitle:"Gerontology"},signatures:"Shilpa Amarya, Kalyani Singh and Manisha Sabharwal",authors:[{id:"226573",title:"Ph.D.",name:"Shilpa",middleName:null,surname:"Amarya",slug:"shilpa-amarya",fullName:"Shilpa Amarya"},{id:"226593",title:"Dr.",name:"Kalyani",middleName:null,surname:"Singh",slug:"kalyani-singh",fullName:"Kalyani Singh"},{id:"243264",title:"Dr.",name:"Manisha",middleName:null,surname:"Sabharwal",slug:"manisha-sabharwal",fullName:"Manisha Sabharwal"}]},{id:"56330",doi:"10.5772/intechopen.69932",title:"Russian Scientific Trends on Specific Language Impairment in Childhood",slug:"russian-scientific-trends-on-specific-language-impairment-in-childhood",totalDownloads:1955,totalCrossrefCites:0,totalDimensionsCites:23,abstract:"In Russia, there are many decades of experience in the scientific study of the problem of impaired language development in children. Today, the term “Systemic speech-and-language underdevelopment (SLU)” has firmly established in Russian science and practice, implying a complex developmental disorder of speech and language in children with a primary normal hearing and a conserved intellect, in which the main components of the language system are violated: vocabulary, grammar, phonetics, and, as a consequence, dialogic and monologic speech. Traditionally, a differentiated level-by-level analysis of the speech and language abilities of children is used. The variability of the manifestations and severity of speech-and-language disorders were initially systematized and characterized in four levels of underdevelopment: from the complete absence of phrase speech to the availability of simple and complex sentences with lexico-grammatical errors. Effective algorithms of speech therapist work with SLU are introduced. The effectiveness of the application of these models and algorithms on the material of various language groups is proved.",book:{id:"5957",slug:"advances-in-speech-language-pathology",title:"Advances in Speech-language Pathology",fullTitle:"Advances in Speech-language Pathology"},signatures:"Tatiana Tumanova and Tatiana Filicheva",authors:[{id:"204529",title:"Dr.",name:"Tatiana Volodarovna",middleName:null,surname:"Tumanova",slug:"tatiana-volodarovna-tumanova",fullName:"Tatiana Volodarovna Tumanova"},{id:"208704",title:"Dr.",name:"Tatiana Borisovna",middleName:null,surname:"Filicheva",slug:"tatiana-borisovna-filicheva",fullName:"Tatiana Borisovna Filicheva"}]},{id:"36452",doi:"10.5772/38931",title:"Qualitative Research Methods in Psychology",slug:"qualitative-research-methods-in-psychology",totalDownloads:35899,totalCrossrefCites:13,totalDimensionsCites:17,abstract:null,book:{id:"1997",slug:"psychology-selected-papers",title:"Psychology",fullTitle:"Psychology - Selected Papers"},signatures:"Deborah Biggerstaff",authors:[{id:"123274",title:"Dr.",name:"Deborah",middleName:null,surname:"Biggerstaff",slug:"deborah-biggerstaff",fullName:"Deborah Biggerstaff"}]},{id:"56560",doi:"10.5772/intechopen.70235",title:"The Role of Speech and Language Therapist in Autism Spectrum Disorders Intervention – An Inclusive Approach",slug:"the-role-of-speech-and-language-therapist-in-autism-spectrum-disorders-intervention-an-inclusive-app",totalDownloads:2373,totalCrossrefCites:2,totalDimensionsCites:16,abstract:"The chapter describes the possibilities of involving a speech-language therapist in the assessment of the pragmatic level of communication in autism spectrum disorders (ASD), where one of the most frequently impaired areas is communication pragmatics. These difficulties lead to a disruption of social interaction, which might be one of the obstacles to speech-language intervention in these children. The text is based on an originally developed testing material aimed at selected pragmatic-oriented communication situations relating to everyday activities and real life. Based on a comparison of domestic and international resources in this area, as well as mediated and own empirical experience, our assessment approach is based on the conclusion that pragmatics can be understood in different contexts and perspectives. The text presents the results of a partial survey comparing the performance of children with ASD and children with typical development. The assessment focused on the children’s election of the correct picture of a pair of pictures that represent usual communication and social situations. The results of the research suggest fewer incorrect responses in children with ASD and in different areas compared with children with typical development. However, the results of a qualitative analysis indicate a necessity to expand the assessment of communication pragmatics by adding an individually specific qualitative analysis of children’s performance.",book:{id:"5957",slug:"advances-in-speech-language-pathology",title:"Advances in Speech-language Pathology",fullTitle:"Advances in Speech-language Pathology"},signatures:"Kateřina Vitásková and Lucie Kytnarová",authors:[{id:"203061",title:"Associate Prof.",name:"Kateřina",middleName:null,surname:"Vitásková",slug:"katerina-vitaskova",fullName:"Kateřina Vitásková"},{id:"212035",title:"MSc.",name:"Lucie",middleName:null,surname:"Kytnarová",slug:"lucie-kytnarova",fullName:"Lucie Kytnarová"}]}],mostDownloadedChaptersLast30Days:[{id:"73271",title:"Social Media and Its Effects on Beauty",slug:"social-media-and-its-effects-on-beauty",totalDownloads:3088,totalCrossrefCites:0,totalDimensionsCites:1,abstract:"Beauty is concerned with physical and mental health as both are intimately related. Short-term decisions to alter one’s body structure irrespective of genetic, environmental, occupational and nutritional needs can leave medium- and long-term effects. This chapter analyzes the role of social media and its effects on the standards of beauty. The researchers have summarized the literature on how social media plays a role in affecting beauty trends, body image and self-esteem concerns. There is support that social media affects individuals negatively, in pushing them to engage in life threatening beauty trends due to social compliance and acceptance in society. The aim was to review social networking sites’ impact on perception of standards of beauty and newer unrealistic trends gaining popularity that could alter opinions and also cause harm to individuals in the long run. This is an emerging area of research that is of high importance to the physical and mental health in the beauty, health and hospitality industry with the latter being manifested in depression, anxiety and fear of non-acceptability and being seen as a social gauche.",book:{id:"7811",slug:"beauty-cosmetic-science-cultural-issues-and-creative-developments",title:"Beauty",fullTitle:"Beauty - Cosmetic Science, Cultural Issues and Creative Developments"},signatures:"Mavis Henriques and Debasis Patnaik",authors:[{id:"320016",title:"Ph.D. Student",name:"Mavis",middleName:"Lilian",surname:"Henriques",slug:"mavis-henriques",fullName:"Mavis Henriques"},{id:"320978",title:"Dr.",name:"Debasis",middleName:null,surname:"Patnaik",slug:"debasis-patnaik",fullName:"Debasis Patnaik"}]},{id:"60564",title:"Ageing Process and Physiological Changes",slug:"ageing-process-and-physiological-changes",totalDownloads:7024,totalCrossrefCites:19,totalDimensionsCites:34,abstract:"Ageing is a natural process. Everyone must undergo this phase of life at his or her own time and pace. In the broader sense, ageing reflects all the changes taking place over the course of life. These changes start from birth—one grows, develops and attains maturity. To the young, ageing is exciting. Middle age is the time when people notice the age-related changes like greying of hair, wrinkled skin and a fair amount of physical decline. Even the healthiest, aesthetically fit cannot escape these changes. Slow and steady physical impairment and functional disability are noticed resulting in increased dependency in the period of old age. According to World Health Organization, ageing is a course of biological reality which starts at conception and ends with death. It has its own dynamics, much beyond human control. However, this process of ageing is also subject to the constructions by which each society makes sense of old age. In most of the developed countries, the age of 60 is considered equivalent to retirement age and it is said to be the beginning of old age. In this chapter, you understand the details of ageing processes and associated physiological changes.",book:{id:"6381",slug:"gerontology",title:"Gerontology",fullTitle:"Gerontology"},signatures:"Shilpa Amarya, Kalyani Singh and Manisha Sabharwal",authors:[{id:"226573",title:"Ph.D.",name:"Shilpa",middleName:null,surname:"Amarya",slug:"shilpa-amarya",fullName:"Shilpa Amarya"},{id:"226593",title:"Dr.",name:"Kalyani",middleName:null,surname:"Singh",slug:"kalyani-singh",fullName:"Kalyani Singh"},{id:"243264",title:"Dr.",name:"Manisha",middleName:null,surname:"Sabharwal",slug:"manisha-sabharwal",fullName:"Manisha Sabharwal"}]},{id:"27237",title:"Emotional Intelligence",slug:"emotional-intelligence",totalDownloads:5779,totalCrossrefCites:6,totalDimensionsCites:9,abstract:null,book:{id:"679",slug:"emotional-intelligence-new-perspectives-and-applications",title:"Emotional Intelligence",fullTitle:"Emotional Intelligence - New Perspectives and Applications"},signatures:"Adrian Furnham",authors:[{id:"85492",title:"Prof.",name:"Adrian",middleName:null,surname:"Furnham",slug:"adrian-furnham",fullName:"Adrian Furnham"}]},{id:"70731",title:"Theoretical Perspective of Traditional Counseling",slug:"theoretical-perspective-of-traditional-counseling",totalDownloads:1610,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"This chapter discusses the theoretical perspective of traditional counseling from an African context. Traditional counseling involves a broad perspective that enhances learning for transformation and integration of sociocultural values that are peculiar to each human society. A cursory review of the literature suggests that the concept of traditional counseling is rooted in traditional systems of knowledge and sociocultural customs and practices, and it promotes a collective approach to problem identification, resolution, and management. The traditional counseling process centers on four aspects: traditional counselor, client, family, and community. The key elements that inform the theoretical framework of traditional counseling from an African perspective are: cultural context, collective belief system, and initiation rituals Traditional systems of knowledge deemed essential for each generation are passed on successively to the next generation by elderly people who do not only have the necessary wisdom and experience, but are also adorned with social competences and skills.",book:{id:"9136",slug:"counseling-and-therapy",title:"Counseling and Therapy",fullTitle:"Counseling and Therapy"},signatures:"Hector Chiboola",authors:[{id:"314172",title:"Prof.",name:"Hector",middleName:null,surname:"Chiboola",slug:"hector-chiboola",fullName:"Hector Chiboola"}]},{id:"55388",title:"Beauty, Body Image, and the Media",slug:"beauty-body-image-and-the-media",totalDownloads:7775,totalCrossrefCites:5,totalDimensionsCites:12,abstract:"This chapter analyses the role of the mass media in people’s perceptions of beauty. We summarize the research literature on the mass media, both traditional media and online social media, and how they appear to interact with psychological factors to impact appearance concerns and body image disturbances. There is a strong support for the idea that traditional forms of media (e.g. magazines and music videos) affect perceptions of beauty and appearance concerns by leading women to internalize a very slender body type as ideal or beautiful. Rather than simply being passive recipients of unrealistic beauty ideals communicated to them via the media, a great number of individuals actually seek out idealized images in the media. Finally, we review what is known about the role of social media in impacting society’s perception of beauty and notions of idealized physical forms. Social media are more interactive than traditional media and the effects of self‐presentation strategies on perceptions of beauty have just begun to be studied. This is an emerging area of research that is of high relevance to researchers and clinicians interested in body image and appearance concerns.",book:{id:"5925",slug:"perception-of-beauty",title:"Perception of Beauty",fullTitle:"Perception of Beauty"},signatures:"Jennifer S. Mills, Amy Shannon and Jacqueline Hogue",authors:[{id:"202110",title:"Dr.",name:"Jennifer S.",middleName:null,surname:"Mills",slug:"jennifer-s.-mills",fullName:"Jennifer S. 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In the current study, we describe an example in which the teacher plays an important role in creating the Computer-Supported Collaborative Learning (CSCL) in this environment to encourage peer learning while coping with complicated material. We believe that one of the important components in guiding such peer work is the teacher’s ability to sense each group’s progress and to employ empathy in the classroom as a tool for coping with the difficulty and challenge of acquiring new knowledge and for creating a productive dialog between groups that disagree. In this example, the process of Information Communication Technology (ICT) implementation encouraged the preservice teachers (PSTs) to create an alternative set of symbols, which eventually served as a “language” and help them understand the biochemical processes.",book:{id:"11443",title:"Empathy - Advanced Research and Applications",coverURL:"https://cdn.intechopen.com/books/images_new/11443.jpg"},signatures:"Dana Sachyani and Ilana Ronen"},{id:"83099",title:"Values-Flow in Contextual Psychotherapy: The ‘What’, ‘Why’, and ‘How’ of Sustainable Values-Based Behaviour",slug:"values-flow-in-contextual-psychotherapy-the-what-why-and-how-of-sustainable-values-based-behaviour",totalDownloads:6,totalDimensionsCites:0,doi:"10.5772/intechopen.106594",abstract:"Flow - enjoyed and fully absorbed engagement in meaningful and contextually bounded activities - is widely underutilised in psychotherapy and mental health settings. Two gold standard therapies, Acceptance and Commitment Therapy (ACT) and Dialectical Behaviour Therapy (DBT), while powerful and effective in many ways, would benefit from systematic models that move from initiating positive change to sustaining meaningful change. This chapter introduces ‘Values-Flow’ – an approach aimed at building commitment and sustainable engagement in psychotherapy and values-based behaviour in working adults struggling with sub-optimal functioning. We first introduce Values-Flow and describe how it may benefit psychotherapy skills practice in everyday life. Next, we discuss why Values-Flow is relevant and enhances the practice of ACT and DBT strategies, helping to sustain engagement and creative practice of values-based actions outside of sessions. We then describe the ‘Values-Flow’ framework, which incorporates VIVA (Virtue, Involve, Vital, Accepting) and ARIA (Attend, Reflect, Inform, Act) tools that develop commitment for values-based practice in daily life. We conclude with a case-example of how Values-Flow can build commitment and sustainable engagement in homework completion in psychotherapy.",book:{id:"11444",title:"Happiness - Biopsychosocial and Anthropological Perspectives",coverURL:"https://cdn.intechopen.com/books/images_new/11444.jpg"},signatures:"Cedomir Ignjatovic, Margaret L. Kern and Lindsay G. Oades"},{id:"83100",title:"Factors Affecting the Happiness of Korean University Students",slug:"factors-affecting-the-happiness-of-korean-university-students",totalDownloads:6,totalDimensionsCites:0,doi:"10.5772/intechopen.106296",abstract:"As of 2020, in Korea, as 72.5% of high-school graduates go on to college and college period has an impact on the social development of Korean youth, it is very important to increase the sense of happiness of college students. However, there are new terminologies to express the situation in which how young people in Korea feel the difficulties in their lives, such as “Hell Chosun, 88-Dollar-Generation, N-Give-up-Generation, and Spoon-Social-Rank.” This chapter summarizes the factors related to the happiness of college students in South Korea, such as depression, interpersonal relationships, and self-efficacy, to suggest educational programs to promote the happiness of young people in Korea.",book:{id:"11444",title:"Happiness - Biopsychosocial and Anthropological Perspectives",coverURL:"https://cdn.intechopen.com/books/images_new/11444.jpg"},signatures:"Soo-Koung Jun"},{id:"83107",title:"Helping BIPOC LGBTQIA+ Families Through Inclusive Therapy and Advocacy",slug:"helping-bipoc-lgbtqia-families-through-inclusive-therapy-and-advocacy",totalDownloads:3,totalDimensionsCites:0,doi:"10.5772/intechopen.106695",abstract:"Families are phenomenological and unique. All families are valuable, but historically, many family types have been underrepresented. Families with members who identify in the BIPOC LGBTQIA+ communities have historically been underrepresented and marginalized. Helping BIPOC LGBTQIA+ families involves both clinical work and advocacy. Advocacy for the professional identity of counseling, marriage and family therapy, and related helpers involves various aspects. These aspects include leadership theory and integration, importance of professional identity, the need to continue to infuse multiculturalism within the counseling and family therapy identities, and continued skills for counselors to learn inclusive advocacy. Skills and implications for advocacy as they relate to clients who intersect among the LGBTQAI+ and BIPOC communities, will be described.",book:{id:"11781",title:"Family Therapy - Recent Advances in Clinical and Crisis Settings",coverURL:"https://cdn.intechopen.com/books/images_new/11781.jpg"},signatures:"Lucy Parker-Barnes, Noel McKillip and Carolyn Powell"},{id:"83027",title:"Coping Strategies and Meta-Worry in Adolescents’ Adjustment during COVID-19 Pandemic",slug:"coping-strategies-and-meta-worry-in-adolescents-adjustment-during-covid-19-pandemic",totalDownloads:4,totalDimensionsCites:0,doi:"10.5772/intechopen.106258",abstract:"With the beginning of the COVID-19 pandemic, several limitations and stressful changes have been introduced in adolescent’s daily life. Particularly, Italian teenagers were the first among western populations to experience fears of infection, home confinement, and social restrictions due to a long lockdown period (10 weeks). This study explores the role of coping strategies (task-oriented, emotion-oriented, and avoidance coping) and meta-beliefs about worry as vulnerability factors associated with adolescents’ anxiety. A community sample of adolescents (N = 284, aged 16–18 y.o.) answered questionnaires assessing anxiety symptoms (RCMAS-2), meta-cognitive beliefs and processes about worry (MCQ-C), and coping strategies (CISS). Results show that 37% of participants report clinically elevated anxiety. Emotion-centered coping predicted higher anxiety, whereas task-centered coping resulted associated with decreased anxiety. Cognitive monitoring about their own worry contributes, but to a lesser extent, to higher levels of anxiety. The implications for the intervention are discussed, especially the need to enhance the coping skills of adolescents and mitigate the stress of the COVID-19 pandemic, which could last for a long time.",book:{id:"10671",title:"Adolescences",coverURL:"https://cdn.intechopen.com/books/images_new/10671.jpg"},signatures:"Loredana Benedetto, Ilenia Schipilliti and Massimo Ingrassia"},{id:"83023",title:"Gestational Tryptophan Fluctuation Underlying Ontogenetic Origin of Neuropsychiatric Disorders",slug:"gestational-tryptophan-fluctuation-underlying-ontogenetic-origin-of-neuropsychiatric-disorders",totalDownloads:5,totalDimensionsCites:0,doi:"10.5772/intechopen.106421",abstract:"Neuropsychiatry underlies personality development and social functioning. Borderline personality disorder exhibits high trait aggression and is associated with tryptophan hydroxylase polymorphisms. The acute tryptophan depletion reduces plasma and cerebrospinal fluid tryptophan availability and brain serotonin concentrations, leading to alterations in personality and trait-related behaviors. Tryptophan is essential for fatal neurodevelopment and immunomodulation in pregnancy. Gestational tryptophan fluctuation induced by maternal metabolic disorders or drug administrations may account for the maternal-fetal transmission determining neurogenesis and microbial development, consequentially shaping the long-standing patterns of thinking and behavior. However, it is not possible to assess the gestational tryptophan exposure effects on fetal brain and gastrointestinal system in humans for ethical reasons. The maternal–fetal microbe transmission in rodents during gestation, vaginal delivery, and breastfeeding is inevitable. Chicken embryo may be an alternative and evidence from the chicken embryo model reveals that gestational tryptophan fluctuation, i.e., exposed to excessive tryptophan or its metabolite, serotonin, attenuates aggressiveness and affects peer sociometric status. This chapter discusses the gestational tryptophan fluctuation as a risk factor of personality disorders in offspring and the prevention of personality disorders by dietary tryptophan control and medication therapy management during pregnancy.",book:{id:"11782",title:"Personality Traits - The Role in Psychopathology",coverURL:"https://cdn.intechopen.com/books/images_new/11782.jpg"},signatures:"Xiaohong Huang, Xiaohua Li and Heng-Wei Cheng"}],onlineFirstChaptersTotal:68},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:11,numberOfPublishedChapters:91,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:333,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:11,numberOfPublishedChapters:144,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:126,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:113,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:23,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:13,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:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}},{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}}]},series:{item:{id:"11",title:"Biochemistry",doi:"10.5772/intechopen.72877",issn:"2632-0983",scope:"Biochemistry, the study of chemical transformations occurring within living organisms, impacts all areas of life sciences, from molecular crystallography and genetics to ecology, medicine, and population biology. Biochemistry examines macromolecules - proteins, nucleic acids, carbohydrates, and lipids – and their building blocks, structures, functions, and interactions. 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. This Biochemistry Series will address the current research on biomolecules and the emerging trends with great promise.",coverUrl:"https://cdn.intechopen.com/series/covers/11.jpg",latestPublicationDate:"August 17th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:33,editor:{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"Blumenberg",slug:"miroslav-blumenberg",fullName:"Miroslav Blumenberg",profilePictureURL:"https://mts.intechopen.com/storage/users/31610/images/system/31610.jpg",biography:"Miroslav Blumenberg, Ph.D., was born in Subotica and received his BSc in Belgrade, Yugoslavia. He completed his Ph.D. at MIT in Organic Chemistry; he followed up his Ph.D. with two postdoctoral study periods at Stanford University. Since 1983, he has been a faculty member of the RO Perelman Department of Dermatology, NYU School of Medicine, where he is codirector of a training grant in cutaneous biology. 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:3,paginationItems:[{id:"7",title:"Bioinformatics and Medical Informatics",coverUrl:"https://cdn.intechopen.com/series_topics/covers/7.jpg",isOpenForSubmission:!0,editor:{id:"351533",title:"Dr.",name:"Slawomir",middleName:null,surname:"Wilczynski",slug:"slawomir-wilczynski",fullName:"Slawomir Wilczynski",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035U1loQAC/Profile_Picture_1630074514792",biography:"Professor Sławomir Wilczyński, Head of the Chair of Department of Basic Biomedical Sciences, Faculty of Pharmaceutical Sciences, Medical University of Silesia in Katowice, Poland. His research interests are focused on modern imaging methods used in medicine and pharmacy, including in particular hyperspectral imaging, dynamic thermovision analysis, high-resolution ultrasound, as well as other techniques such as EPR, NMR and hemispheric directional reflectance. Author of over 100 scientific works, patents and industrial designs. Expert of the Polish National Center for Research and Development, Member of the Investment Committee in the Bridge Alfa NCBiR program, expert of the Polish Ministry of Funds and Regional Policy, Polish Medical Research Agency. Editor-in-chief of the journal in the field of aesthetic medicine and dermatology - Aesthetica.",institutionString:null,institution:{name:"Medical University of Silesia",institutionURL:null,country:{name:"Poland"}}},editorTwo:null,editorThree:null},{id:"8",title:"Bioinspired Technology and Biomechanics",coverUrl:"https://cdn.intechopen.com/series_topics/covers/8.jpg",isOpenForSubmission:!0,editor:{id:"144937",title:"Prof.",name:"Adriano",middleName:"De Oliveira",surname:"Andrade",slug:"adriano-andrade",fullName:"Adriano Andrade",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRC8QQAW/Profile_Picture_1625219101815",biography:"Dr. Adriano de Oliveira Andrade graduated in Electrical Engineering at the Federal University of Goiás (Brazil) in 1997. He received his MSc and PhD in Biomedical Engineering respectively from the Federal University of Uberlândia (UFU, Brazil) in 2000 and from the University of Reading (UK) in 2005. He completed a one-year Post-Doctoral Fellowship awarded by the DFAIT (Foreign Affairs and International Trade Canada) at the Institute of Biomedical Engineering of the University of New Brunswick (Canada) in 2010. Currently, he is Professor in the Faculty of Electrical Engineering (UFU). He has authored and co-authored more than 200 peer-reviewed publications in Biomedical Engineering. He has been a researcher of The National Council for Scientific and Technological Development (CNPq-Brazil) since 2009. He has served as an ad-hoc consultant for CNPq, CAPES (Coordination for the Improvement of Higher Education Personnel), FINEP (Brazilian Innovation Agency), and other funding bodies on several occasions. He was the Secretary of the Brazilian Society of Biomedical Engineering (SBEB) from 2015 to 2016, President of SBEB (2017-2018) and Vice-President of SBEB (2019-2020). He was the head of the undergraduate program in Biomedical Engineering of the Federal University of Uberlândia (2015 - June/2019) and the head of the Centre for Innovation and Technology Assessment in Health (NIATS/UFU) since 2010. He is the head of the Postgraduate Program in Biomedical Engineering (UFU, July/2019 - to date). He was the secretary of the Parkinson's Disease Association of Uberlândia (2018-2019). Dr. Andrade's primary area of research is focused towards getting information from the neuromuscular system to understand its strategies of organization, adaptation and controlling in the context of motor neuron diseases. His research interests include Biomedical Signal Processing and Modelling, Assistive Technology, Rehabilitation Engineering, Neuroengineering and Parkinson's Disease.",institutionString:null,institution:{name:"Federal University of Uberlândia",institutionURL:null,country:{name:"Brazil"}}},editorTwo:null,editorThree:null},{id:"9",title:"Biotechnology - Biosensors, Biomaterials and Tissue Engineering",coverUrl:"https://cdn.intechopen.com/series_topics/covers/9.jpg",isOpenForSubmission:!0,editor:{id:"126286",title:"Dr.",name:"Luis",middleName:"Jesús",surname:"Villarreal-Gómez",slug:"luis-villarreal-gomez",fullName:"Luis Villarreal-Gómez",profilePictureURL:"https://mts.intechopen.com/storage/users/126286/images/system/126286.jpg",biography:"Dr. Luis Villarreal is a research professor from the Facultad de Ciencias de la Ingeniería y Tecnología, Universidad Autónoma de Baja California, Tijuana, Baja California, México. Dr. Villarreal is the editor in chief and founder of the Revista de Ciencias Tecnológicas (RECIT) (https://recit.uabc.mx/) and is a member of several editorial and reviewer boards for numerous international journals. He has published more than thirty international papers and reviewed more than ninety-two manuscripts. His research interests include biomaterials, nanomaterials, bioengineering, biosensors, drug delivery systems, and tissue engineering.",institutionString:null,institution:{name:"Autonomous University of Baja California",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null}]},overviewPageOFChapters:{paginationCount:27,paginationItems:[{id:"83092",title:"Novel Composites for Bone Tissue Engineering",doi:"10.5772/intechopen.106255",signatures:"Pugalanthipandian Sankaralingam, Poornimadevi Sakthivel and Vijayakumar Chinnaswamy Thangavel",slug:"novel-composites-for-bone-tissue-engineering",totalDownloads:7,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Biomimetics - Bridging the Gap",coverURL:"https://cdn.intechopen.com/books/images_new/11453.jpg",subseries:{id:"8",title:"Bioinspired Technology and Biomechanics"}}},{id:"82800",title:"Repurposing Drugs as Potential Therapeutics for the SARS-Cov-2 Viral Infection: Automatizing a Blind Molecular Docking High-throughput Pipeline",doi:"10.5772/intechopen.105792",signatures:"Aldo Herrera-Rodulfo, Mariana Andrade-Medina and Mauricio Carrillo-Tripp",slug:"repurposing-drugs-as-potential-therapeutics-for-the-sars-cov-2-viral-infection-automatizing-a-blind-",totalDownloads:10,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Molecular Docking - Recent Advances",coverURL:"https://cdn.intechopen.com/books/images_new/11451.jpg",subseries:{id:"7",title:"Bioinformatics and Medical Informatics"}}},{id:"82582",title:"Protecting Bioelectric Signals from Electromagnetic Interference in a Wireless World",doi:"10.5772/intechopen.105951",signatures:"David Marcarian",slug:"protecting-bioelectric-signals-from-electromagnetic-interference-in-a-wireless-world",totalDownloads:4,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Biosignal Processing",coverURL:"https://cdn.intechopen.com/books/images_new/11153.jpg",subseries:{id:"7",title:"Bioinformatics and Medical Informatics"}}},{id:"82586",title:"Fundamentals of Molecular Docking and Comparative Analysis of Protein–Small-Molecule Docking Approaches",doi:"10.5772/intechopen.105815",signatures:"Maden Sefika Feyza, Sezer Selin and Acuner Saliha Ece",slug:"fundamentals-of-molecular-docking-and-comparative-analysis-of-protein-small-molecule-docking-approac",totalDownloads:29,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Molecular Docking - Recent Advances",coverURL:"https://cdn.intechopen.com/books/images_new/11451.jpg",subseries:{id:"7",title:"Bioinformatics and Medical Informatics"}}}]},overviewPagePublishedBooks:{paginationCount:12,paginationItems:[{type:"book",id:"6692",title:"Medical and Biological Image Analysis",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/6692.jpg",slug:"medical-and-biological-image-analysis",publishedDate:"July 4th 2018",editedByType:"Edited by",bookSignature:"Robert Koprowski",hash:"e75f234a0fc1988d9816a94e4c724deb",volumeInSeries:1,fullTitle:"Medical and Biological Image Analysis",editors:[{id:"50150",title:"Prof.",name:"Robert",middleName:null,surname:"Koprowski",slug:"robert-koprowski",fullName:"Robert Koprowski",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYTYNQA4/Profile_Picture_1630478535317",biography:"Robert Koprowski, MD (1997), PhD (2003), Habilitation (2015), is an employee of the University of Silesia, Poland, Institute of Computer Science, Department of Biomedical Computer Systems. For 20 years, he has studied the analysis and processing of biomedical images, emphasizing the full automation of measurement for a large inter-individual variability of patients. Dr. Koprowski has authored more than a hundred research papers with dozens in impact factor (IF) journals and has authored or co-authored six books. Additionally, he is the author of several national and international patents in the field of biomedical devices and imaging. Since 2011, he has been a reviewer of grants and projects (including EU projects) in biomedical engineering.",institutionString:null,institution:{name:"University of Silesia",institutionURL:null,country:{name:"Poland"}}}]},{type:"book",id:"7218",title:"OCT",subtitle:"Applications in Ophthalmology",coverURL:"https://cdn.intechopen.com/books/images_new/7218.jpg",slug:"oct-applications-in-ophthalmology",publishedDate:"September 19th 2018",editedByType:"Edited by",bookSignature:"Michele Lanza",hash:"e3a3430cdfd6999caccac933e4613885",volumeInSeries:2,fullTitle:"OCT - Applications in Ophthalmology",editors:[{id:"240088",title:"Prof.",name:"Michele",middleName:null,surname:"Lanza",slug:"michele-lanza",fullName:"Michele Lanza",profilePictureURL:"https://mts.intechopen.com/storage/users/240088/images/system/240088.png",biography:"Michele Lanza is Associate Professor of Ophthalmology at Università della Campania, Luigi Vanvitelli, Napoli, Italy. His fields of interest are anterior segment disease, keratoconus, glaucoma, corneal dystrophies, and cataracts. His research topics include\nintraocular lens power calculation, eye modification induced by refractive surgery, glaucoma progression, and validation of new diagnostic devices in ophthalmology. \nHe has published more than 100 papers in international and Italian scientific journals, more than 60 in journals with impact factors, and chapters in international and Italian books. He has also edited two international books and authored more than 150 communications or posters for the most important international and Italian ophthalmology conferences.",institutionString:'University of Campania "Luigi Vanvitelli"',institution:{name:'University of Campania "Luigi Vanvitelli"',institutionURL:null,country:{name:"Italy"}}}]},{type:"book",id:"7560",title:"Non-Invasive Diagnostic Methods",subtitle:"Image Processing",coverURL:"https://cdn.intechopen.com/books/images_new/7560.jpg",slug:"non-invasive-diagnostic-methods-image-processing",publishedDate:"December 19th 2018",editedByType:"Edited by",bookSignature:"Mariusz Marzec and Robert Koprowski",hash:"d92fd8cf5a90a47f2b8a310837a5600e",volumeInSeries:3,fullTitle:"Non-Invasive Diagnostic Methods - Image Processing",editors:[{id:"253468",title:"Dr.",name:"Mariusz",middleName:null,surname:"Marzec",slug:"mariusz-marzec",fullName:"Mariusz Marzec",profilePictureURL:"https://mts.intechopen.com/storage/users/253468/images/system/253468.png",biography:"An assistant professor at Department of Biomedical Computer Systems, at Institute of Computer Science, Silesian University in Katowice. Scientific interests: computer analysis and processing of images, biomedical images, databases and programming languages. 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He received his post-doctoral training in oncology and cancer proteomics for two years at the Cancer Research Institute of Human Medical University in China. In 2001, he went to the University of Tennessee Health Science Center (UTHSC) in USA, where he was a post-doctoral researcher and focused on mass spectrometry and cancer proteomics. Then, he was appointed as an Assistant Professor of Neurology, UTHSC in 2005. He moved to the Cleveland Clinic in USA as a Project Scientist/Staff in 2006 where he focused on the studies of eye disease proteomics and biomarkers. He returned to UTHSC as an Assistant Professor of Neurology in the end of 2007, engaging in proteomics and biomarker studies of lung diseases and brain tumors, and initiating the studies of predictive, preventive, and personalized medicine (PPPM) in cancer. In 2010, he was promoted to Associate Professor of Neurology, UTHSC. Currently, he is a Professor at Xiangya Hospital of Central South University in China, Fellow of Royal Society of Medicine (FRSM), the European EPMA National Representative in China, Regular Member of American Association for the Advancement of Science (AAAS), European Cooperation of Science and Technology (e-COST) grant evaluator, Associate Editors of BMC Genomics, BMC Medical Genomics, EPMA Journal, and Frontiers in Endocrinology, Executive Editor-in-Chief of Med One. He has\npublished 116 peer-reviewed research articles, 16 book chapters, 2 books, and 2 US patents. His current main research interest focuses on the studies of cancer proteomics and biomarkers, and the use of modern omics techniques and systems biology for PPPM in cancer, and on the development and use of 2DE-LC/MS for the large-scale study of human proteoforms.",institutionString:null,institution:{name:"Xiangya Hospital Central South University",country:{name:"China"}}},{id:"40482",title:null,name:"Rizwan",middleName:null,surname:"Ahmad",slug:"rizwan-ahmad",fullName:"Rizwan Ahmad",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/40482/images/system/40482.jpeg",biography:"Dr. Rizwan Ahmad is a University Professor and Coordinator, Quality and Development, College of Medicine, Imam Abdulrahman bin Faisal University, Saudi Arabia. Previously, he was Associate Professor of Human Function, Oman Medical College, Oman, and SBS University, Dehradun. Dr. Ahmad completed his education at Aligarh Muslim University, Aligarh. He has published several articles in peer-reviewed journals, chapters, and edited books. His area of specialization is free radical biochemistry and autoimmune diseases.",institutionString:"Imam Abdulrahman Bin Faisal University",institution:{name:"Imam Abdulrahman Bin Faisal University",country:{name:"Saudi Arabia"}}},{id:"41865",title:"Prof.",name:"Farid A.",middleName:null,surname:"Badria",slug:"farid-a.-badria",fullName:"Farid A. Badria",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/41865/images/system/41865.jpg",biography:"Farid A. Badria, Ph.D., is the recipient of several awards, including The World Academy of Sciences (TWAS) Prize for Public Understanding of Science; the World Intellectual Property Organization (WIPO) Gold Medal for best invention; Outstanding Arab Scholar, Kuwait; and the Khwarizmi International Award, Iran. He has 250 publications, 12 books, 20 patents, and several marketed pharmaceutical products to his credit. He continues to lead research projects on developing new therapies for liver, skin disorders, and cancer. Dr. Badria was listed among the world’s top 2% of scientists in medicinal and biomolecular chemistry in 2019 and 2020. He is a member of the Arab Development Fund, Kuwait; International Cell Research Organization–United Nations Educational, Scientific and Cultural Organization (ICRO–UNESCO), Chile; and UNESCO Biotechnology France",institutionString:"Mansoura University",institution:{name:"Mansoura University",country:{name:"Egypt"}}},{id:"329385",title:"Dr.",name:"Rajesh K.",middleName:"Kumar",surname:"Singh",slug:"rajesh-k.-singh",fullName:"Rajesh K. Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329385/images/system/329385.png",biography:"Dr. Singh received a BPharm (2003) and MPharm (2005) from Panjab University, Chandigarh, India, and a Ph.D. (2013) from Punjab Technical University (PTU), Jalandhar, India. He has more than sixteen years of teaching experience and has supervised numerous postgraduate and Ph.D. students. He has to his credit more than seventy papers in SCI- and SCOPUS-indexed journals, fifty-five conference proceedings, four books, six Best Paper Awards, and five projects from different government agencies. He is currently an editorial board member of eight international journals and a reviewer for more than fifty scientific journals. He received Top Reviewer and Excellent Peer Reviewer Awards from Publons in 2016 and 2017, respectively. He is also on the panel of The International Reviewer for reviewing research proposals for grants from the Royal Society. He also serves as a Publons Academy mentor and Bentham brand ambassador.",institutionString:"Punjab Technical University",institution:{name:"Punjab Technical University",country:{name:"India"}}},{id:"142388",title:"Dr.",name:"Thiago",middleName:"Gomes",surname:"Gomes Heck",slug:"thiago-gomes-heck",fullName:"Thiago Gomes Heck",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/142388/images/7259_n.jpg",biography:null,institutionString:null,institution:{name:"Universidade Regional do Noroeste do Estado do Rio Grande do Sul",country:{name:"Brazil"}}},{id:"336273",title:"Assistant Prof.",name:"Janja",middleName:null,surname:"Zupan",slug:"janja-zupan",fullName:"Janja Zupan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/336273/images/14853_n.jpeg",biography:"Janja Zupan graduated in 2005 at the Department of Clinical Biochemistry (superviser prof. dr. Janja Marc) in the field of genetics of osteoporosis. Since November 2009 she is working as a Teaching Assistant at the Faculty of Pharmacy, Department of Clinical Biochemistry. In 2011 she completed part of her research and PhD work at Institute of Genetics and Molecular Medicine, University of Edinburgh. She finished her PhD entitled The influence of the proinflammatory cytokines on the RANK/RANKL/OPG in bone tissue of osteoporotic and osteoarthritic patients in 2012. From 2014-2016 she worked at the Institute of Biomedical Sciences, University of Aberdeen as a postdoctoral research fellow on UK Arthritis research project where she gained knowledge in mesenchymal stem cells and regenerative medicine. She returned back to University of Ljubljana, Faculty of Pharmacy in 2016. She is currently leading project entitled Mesenchymal stem cells-the keepers of tissue endogenous regenerative capacity facing up to aging of the musculoskeletal system funded by Slovenian Research Agency.",institutionString:null,institution:{name:"University of Ljubljana",country:{name:"Slovenia"}}},{id:"357453",title:"Dr.",name:"Radheshyam",middleName:null,surname:"Maurya",slug:"radheshyam-maurya",fullName:"Radheshyam Maurya",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/357453/images/16535_n.jpg",biography:null,institutionString:null,institution:{name:"University of Hyderabad",country:{name:"India"}}},{id:"418340",title:"Dr.",name:"Jyotirmoi",middleName:null,surname:"Aich",slug:"jyotirmoi-aich",fullName:"Jyotirmoi Aich",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000038Ugi5QAC/Profile_Picture_2022-04-15T07:48:28.png",biography:"Biotechnologist with 15 years of research including 6 years of teaching experience. Demonstrated record of scientific achievements through consistent publication record (H index = 13, with 874 citations) in high impact journals such as Nature Communications, Oncotarget, Annals of Oncology, PNAS, and AJRCCM, etc. Strong research professional with a post-doctorate from ACTREC where I gained experimental oncology experience in clinical settings and a doctorate from IGIB where I gained expertise in asthma pathophysiology. A well-trained biotechnologist with diverse experience on the bench across different research themes ranging from asthma to cancer and other infectious diseases. An individual with a strong commitment and innovative mindset. Have the ability to work on diverse projects such as regenerative and molecular medicine with an overall mindset of improving healthcare.",institutionString:"DY Patil Deemed to Be University",institution:null},{id:"349288",title:"Prof.",name:"Soumya",middleName:null,surname:"Basu",slug:"soumya-basu",fullName:"Soumya Basu",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035QxIDQA0/Profile_Picture_2022-04-15T07:47:01.jpg",biography:"Soumya Basu, Ph.D., is currently working as an Associate Professor at Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune, Maharashtra, India. With 16+ years of trans-disciplinary research experience in Drug Design, development, and pre-clinical validation; 20+ research article publications in journals of repute, 9+ years of teaching experience, trained with cross-disciplinary education, Dr. Basu is a life-long learner and always thrives for new challenges.\r\nHer research area is the design and synthesis of small molecule partial agonists of PPAR-γ in lung cancer. She is also using artificial intelligence and deep learning methods to understand the exosomal miRNA’s role in cancer metastasis. Dr. Basu is the recipient of many awards including the Early Career Research Award from the Department of Science and Technology, Govt. of India. She is a reviewer of many journals like Molecular Biology Reports, Frontiers in Oncology, RSC Advances, PLOS ONE, Journal of Biomolecular Structure & Dynamics, Journal of Molecular Graphics and Modelling, etc. She has edited and authored/co-authored 21 journal papers, 3 book chapters, and 15 abstracts. She is a Board of Studies member at her university. She is a life member of 'The Cytometry Society”-in India and 'All India Cell Biology Society”- in India.",institutionString:"Dr. D.Y. Patil Vidyapeeth, Pune",institution:{name:"Dr. D.Y. Patil Vidyapeeth, Pune",country:{name:"India"}}},{id:"354817",title:"Dr.",name:"Anubhab",middleName:null,surname:"Mukherjee",slug:"anubhab-mukherjee",fullName:"Anubhab Mukherjee",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y0000365PbRQAU/ProfilePicture%202022-04-15%2005%3A11%3A18.480",biography:"A former member of Laboratory of Nanomedicine, Brigham and Women’s Hospital, Harvard University, Boston, USA, Dr. Anubhab Mukherjee is an ardent votary of science who strives to make an impact in the lives of those afflicted with cancer and other chronic/acute ailments. He completed his Ph.D. from CSIR-Indian Institute of Chemical Technology, Hyderabad, India, having been skilled with RNAi, liposomal drug delivery, preclinical cell and animal studies. He pursued post-doctoral research at College of Pharmacy, Health Science Center, Texas A & M University and was involved in another postdoctoral research at Department of Translational Neurosciences and Neurotherapeutics, John Wayne Cancer Institute, Santa Monica, California. In 2015, he worked in Harvard-MIT Health Sciences & Technology as a visiting scientist. He has substantial experience in nanotechnology-based formulation development and successfully served various Indian organizations to develop pharmaceuticals and nutraceutical products. He is an inventor in many US patents and an author in many peer-reviewed articles, book chapters and books published in various media of international repute. Dr. Mukherjee is currently serving as Principal Scientist, R&D at Esperer Onco Nutrition (EON) Pvt. Ltd. and heads the Hyderabad R&D center of the organization.",institutionString:"Esperer Onco Nutrition Pvt Ltd.",institution:null},{id:"319365",title:"Assistant Prof.",name:"Manash K.",middleName:null,surname:"Paul",slug:"manash-k.-paul",fullName:"Manash K. Paul",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/319365/images/system/319365.png",biography:"Manash K. Paul is a scientist and Principal Investigator at the University of California Los Angeles. He has contributed significantly to the fields of stem cell biology, regenerative medicine, and lung cancer. His research focuses on various signaling processes involved in maintaining stem cell homeostasis during the injury-repair process, deciphering the lung stem cell niche, pulmonary disease modeling, immuno-oncology, and drug discovery. He is currently investigating the role of extracellular vesicles in premalignant lung cell migration and detecting the metastatic phenotype of lung cancer via artificial intelligence-based analyses of exosomal Raman signatures. Dr. Paul also works on spatial multiplex immunofluorescence-based tissue mapping to understand the immune repertoire in lung cancer. Dr. Paul has published in more than sixty-five peer-reviewed international journals and is highly cited. He is the recipient of many awards, including the UCLA Vice Chancellor’s award and the 2022 AAISCR-R Vijayalaxmi Award for Innovative Cancer Research. He is a senior member of the Institute of Electrical and Electronics Engineers (IEEE) and an editorial board member for several international journals.",institutionString:"University of California Los Angeles",institution:{name:"University of California Los Angeles",country:{name:"United States of America"}}},{id:"311457",title:"Dr.",name:"Júlia",middleName:null,surname:"Scherer Santos",slug:"julia-scherer-santos",fullName:"Júlia Scherer Santos",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/311457/images/system/311457.jpg",biography:"Dr. Júlia Scherer Santos works in the areas of cosmetology, nanotechnology, pharmaceutical technology, beauty, and aesthetics. Dr. Santos also has experience as a professor of graduate courses. Graduated in Pharmacy, specialization in Cosmetology and Cosmeceuticals applied to aesthetics, specialization in Aesthetic and Cosmetic Health, and a doctorate in Pharmaceutical Nanotechnology. Teaching experience in Pharmacy and Aesthetics and Cosmetics courses. She works mainly on the following subjects: nanotechnology, cosmetology, pharmaceutical technology, aesthetics.",institutionString:"Universidade Federal de Juiz de Fora",institution:{name:"Universidade Federal de Juiz de Fora",country:{name:"Brazil"}}},{id:"219081",title:"Dr.",name:"Abdulsamed",middleName:null,surname:"Kükürt",slug:"abdulsamed-kukurt",fullName:"Abdulsamed Kükürt",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/219081/images/system/219081.png",biography:"Dr. Kükürt graduated from Uludağ University in Turkey. He started his academic career as a Research Assistant in the Department of Biochemistry at Kafkas University. In 2019, he completed his Ph.D. program in the Department of Biochemistry at the Institute of Health Sciences. He is currently working at the Department of Biochemistry, Kafkas University. He has 27 published research articles in academic journals, 11 book chapters, and 37 papers. He took part in 10 academic projects. He served as a reviewer for many articles. He still serves as a member of the review board in many academic journals. He is currently working on the protective activity of phenolic compounds in disorders associated with oxidative stress and inflammation.",institutionString:null,institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"178366",title:"Dr.",name:"Volkan",middleName:null,surname:"Gelen",slug:"volkan-gelen",fullName:"Volkan Gelen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178366/images/system/178366.jpg",biography:"Volkan Gelen is a Physiology specialist who received his veterinary degree from Kafkas University in 2011. Between 2011-2015, he worked as an assistant at Atatürk University, Faculty of Veterinary Medicine, Department of Physiology. In 2016, he joined Kafkas University, Faculty of Veterinary Medicine, Department of Physiology as an assistant professor. Dr. Gelen has been engaged in various academic activities at Kafkas University since 2016. There he completed 5 projects and has 3 ongoing projects. He has 60 articles published in scientific journals and 20 poster presentations in scientific congresses. His research interests include physiology, endocrine system, cancer, diabetes, cardiovascular system diseases, and isolated organ bath system studies.",institutionString:"Kafkas University",institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"418963",title:"Dr.",name:"Augustine Ododo",middleName:"Augustine",surname:"Osagie",slug:"augustine-ododo-osagie",fullName:"Augustine Ododo Osagie",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/418963/images/16900_n.jpg",biography:"Born into the family of Osagie, a prince of the Benin Kingdom. I am currently an academic in the Department of Medical Biochemistry, University of Benin. Part of the duties are to teach undergraduate students and conduct academic research.",institutionString:null,institution:{name:"University of Benin",country:{name:"Nigeria"}}},{id:"192992",title:"Prof.",name:"Shagufta",middleName:null,surname:"Perveen",slug:"shagufta-perveen",fullName:"Shagufta Perveen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/192992/images/system/192992.png",biography:"Prof. Shagufta Perveen is a Distinguish Professor in the Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. Dr. Perveen has acted as the principal investigator of major research projects funded by the research unit of King Saud University. She has more than ninety original research papers in peer-reviewed journals of international repute to her credit. She is a fellow member of the Royal Society of Chemistry UK and the American Chemical Society of the United States.",institutionString:"King Saud University",institution:{name:"King Saud University",country:{name:"Saudi Arabia"}}},{id:"49848",title:"Dr.",name:"Wen-Long",middleName:null,surname:"Hu",slug:"wen-long-hu",fullName:"Wen-Long Hu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49848/images/system/49848.jpg",biography:"Wen-Long Hu is Chief of the Division of Acupuncture, Department of Chinese Medicine at Kaohsiung Chang Gung Memorial Hospital, as well as an adjunct associate professor at Fooyin University and Kaohsiung Medical University. Wen-Long is President of Taiwan Traditional Chinese Medicine Medical Association. He has 28 years of experience in clinical practice in laser acupuncture therapy and 34 years in acupuncture. He is an invited speaker for lectures and workshops in laser acupuncture at many symposiums held by medical associations. He owns the patent for herbal preparation and producing, and for the supercritical fluid-treated needle. Dr. Hu has published three books, 12 book chapters, and more than 30 papers in reputed journals, besides serving as an editorial board member of repute.",institutionString:"Kaohsiung Chang Gung Memorial Hospital",institution:{name:"Kaohsiung Chang Gung Memorial Hospital",country:{name:"Taiwan"}}},{id:"298472",title:"Prof.",name:"Andrey V.",middleName:null,surname:"Grechko",slug:"andrey-v.-grechko",fullName:"Andrey V. Grechko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/298472/images/system/298472.png",biography:"Andrey Vyacheslavovich Grechko, Ph.D., Professor, is a Corresponding Member of the Russian Academy of Sciences. He graduated from the Semashko Moscow Medical Institute (Semashko National Research Institute of Public Health) with a degree in Medicine (1998), the Clinical Department of Dermatovenerology (2000), and received a second higher education in Psychology (2009). Professor A.V. Grechko held the position of Сhief Physician of the Central Clinical Hospital in Moscow. He worked as a professor at the faculty and was engaged in scientific research at the Medical University. Starting in 2013, he has been the initiator of the creation of the Federal Scientific and Clinical Center for Intensive Care and Rehabilitology, Moscow, Russian Federation, where he also serves as Director since 2015. He has many years of experience in research and teaching in various fields of medicine, is an author/co-author of more than 200 scientific publications, 13 patents, 15 medical books/chapters, including Chapter in Book «Metabolomics», IntechOpen, 2020 «Metabolomic Discovery of Microbiota Dysfunction as the Cause of Pathology».",institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"199461",title:"Prof.",name:"Natalia V.",middleName:null,surname:"Beloborodova",slug:"natalia-v.-beloborodova",fullName:"Natalia V. Beloborodova",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/199461/images/system/199461.jpg",biography:'Natalia Vladimirovna Beloborodova was educated at the Pirogov Russian National Research Medical University, with a degree in pediatrics in 1980, a Ph.D. in 1987, and a specialization in Clinical Microbiology from First Moscow State Medical University in 2004. She has been a Professor since 1996. Currently, she is the Head of the Laboratory of Metabolism, a division of the Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Moscow, Russian Federation. N.V. Beloborodova has many years of clinical experience in the field of intensive care and surgery. She studies infectious complications and sepsis. She initiated a series of interdisciplinary clinical and experimental studies based on the concept of integrating human metabolism and its microbiota. Her scientific achievements are widely known: she is the recipient of the Marie E. Coates Award \\"Best lecturer-scientist\\" Gustafsson Fund, Karolinska Institutes, Stockholm, Sweden, and the International Sepsis Forum Award, Pasteur Institute, Paris, France (2014), etc. Professor N.V. Beloborodova wrote 210 papers, five books, 10 chapters and has edited four books.',institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"354260",title:"Ph.D.",name:"Tércio Elyan",middleName:"Azevedo",surname:"Azevedo Martins",slug:"tercio-elyan-azevedo-martins",fullName:"Tércio Elyan Azevedo Martins",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/354260/images/16241_n.jpg",biography:"Graduated in Pharmacy from the Federal University of Ceará with the modality in Industrial Pharmacy, Specialist in Production and Control of Medicines from the University of São Paulo (USP), Master in Pharmaceuticals and Medicines from the University of São Paulo (USP) and Doctor of Science in the program of Pharmaceuticals and Medicines by the University of São Paulo. Professor at Universidade Paulista (UNIP) in the areas of chemistry, cosmetology and trichology. Assistant Coordinator of the Higher Course in Aesthetic and Cosmetic Technology at Universidade Paulista Campus Chácara Santo Antônio. Experience in the Pharmacy area, with emphasis on Pharmacotechnics, Pharmaceutical Technology, Research and Development of Cosmetics, acting mainly on topics such as cosmetology, antioxidant activity, aesthetics, photoprotection, cyclodextrin and thermal analysis.",institutionString:null,institution:{name:"University of Sao Paulo",country:{name:"Brazil"}}},{id:"334285",title:"Ph.D. Student",name:"Sameer",middleName:"Kumar",surname:"Jagirdar",slug:"sameer-jagirdar",fullName:"Sameer Jagirdar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334285/images/14691_n.jpg",biography:"I\\'m a graduate student at the center for biosystems science and engineering at the Indian Institute of Science, Bangalore, India. I am interested in studying host-pathogen interactions at the biomaterial interface.",institutionString:null,institution:{name:"Indian Institute of Science Bangalore",country:{name:"India"}}},{id:"329248",title:"Dr.",name:"Md. Faheem",middleName:null,surname:"Haider",slug:"md.-faheem-haider",fullName:"Md. Faheem Haider",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329248/images/system/329248.jpg",biography:"Dr. Md. Faheem Haider completed his BPharm in 2012 at Integral University, Lucknow, India. In 2014, he completed his MPharm with specialization in Pharmaceutics at Babasaheb Bhimrao Ambedkar University, Lucknow, India. He received his Ph.D. degree from Jamia Hamdard University, New Delhi, India, in 2018. He was selected for the GPAT six times and his best All India Rank was 34. Currently, he is an assistant professor at Integral University. Previously he was an assistant professor at IIMT University, Meerut, India. He has experience teaching DPharm, Pharm.D, BPharm, and MPharm students. He has more than five publications in reputed journals to his credit. Dr. Faheem’s research area is the development and characterization of nanoformulation for the delivery of drugs to various organs.",institutionString:"Integral University",institution:{name:"Integral University",country:{name:"India"}}},{id:"329795",title:"Dr.",name:"Mohd Aftab",middleName:"Aftab",surname:"Siddiqui",slug:"mohd-aftab-siddiqui",fullName:"Mohd Aftab Siddiqui",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329795/images/system/329795.png",biography:"Dr. Mohd Aftab Siddiqui is an assistant professor in the Faculty of Pharmacy, Integral University, Lucknow, India, where he obtained a Ph.D. in Pharmacology in 2020. He also obtained a BPharm and MPharm from the same university in 2013 and 2015, respectively. His area of research is the pharmacological screening of herbal drugs/natural products in liver cancer and cardiac diseases. He is a member of many professional bodies and has guided many MPharm and PharmD research projects. Dr. Siddiqui has many national and international publications and one German patent to his credit.",institutionString:"Integral University",institution:null}]}},subseries:{item:{id:"5",type:"subseries",title:"Parasitic Infectious Diseases",keywords:"Blood Borne Parasites, Intestinal Parasites, Protozoa, Helminths, Arthropods, Water Born Parasites, Epidemiology, Molecular Biology, Systematics, Genomics, Proteomics, Ecology",scope:"Parasitic diseases have evolved alongside their human hosts. In many cases, these diseases have adapted so well that they have developed efficient resilience methods in the human host and can live in the host for years. Others, particularly some blood parasites, can cause very acute diseases and are responsible for millions of deaths yearly. Many parasitic diseases are classified as neglected tropical diseases because they have received minimal funding over recent years and, in many cases, are under-reported despite the critical role they play in morbidity and mortality among human and animal hosts. The current topic, Parasitic Infectious Diseases, in the Infectious Diseases Series aims to publish studies on the systematics, epidemiology, molecular biology, genomics, pathogenesis, genetics, and clinical significance of parasitic diseases from blood borne to intestinal parasites as well as zoonotic parasites. We hope to cover all aspects of parasitic diseases to provide current and relevant research data on these very important diseases. In the current atmosphere of the Coronavirus pandemic, communities around the world, particularly those in different underdeveloped areas, are faced with the growing challenges of the high burden of parasitic diseases. At the same time, they are faced with the Covid-19 pandemic leading to what some authors have called potential syndemics that might worsen the outcome of such infections. 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