Summary of creative engineering design methods.
\\n\\n
IntechOpen Book Series will also publish a program of research-driven Thematic Edited Volumes that focus on specific areas and allow for a more in-depth overview of a particular subject.
\\n\\nIntechOpen Book Series will be launching regularly to offer our authors and editors exciting opportunities to publish their research Open Access. We will begin by relaunching some of our existing Book Series in this innovative book format, and will expand in 2022 into rapidly growing research fields that are driving and advancing society.
\\n\\nLaunching 2021
\\n\\nArtificial Intelligence, ISSN 2633-1403
\\n\\nVeterinary Medicine and Science, ISSN 2632-0517
\\n\\nBiochemistry, ISSN 2632-0983
\\n\\nBiomedical Engineering, ISSN 2631-5343
\\n\\nInfectious Diseases, ISSN 2631-6188
\\n\\nPhysiology (Coming Soon)
\\n\\nDentistry (Coming Soon)
\\n\\nWe invite you to explore our IntechOpen Book Series, find the right publishing program for you and reach your desired audience in record time.
\\n\\nNote: Edited in October 2021
\\n"}]',published:!0,mainMedia:{caption:"",originalUrl:"/media/original/132"}},components:[{type:"htmlEditorComponent",content:'With the desire to make book publishing more relevant for the digital age and offer innovative Open Access publishing options, we are thrilled to announce the launch of our new publishing format: IntechOpen Book Series.
\n\nDesigned to cover fast-moving research fields in rapidly expanding areas, our Book Series feature a Topic structure allowing us to present the most relevant sub-disciplines. Book Series are headed by Series Editors, and a team of Topic Editors supported by international Editorial Board members. Topics are always open for submissions, with an Annual Volume published each calendar year.
\n\nAfter a robust peer-review process, accepted works are published quickly, thanks to Online First, ensuring research is made available to the scientific community without delay.
\n\nOur innovative Book Series format brings you:
\n\nIntechOpen Book Series will also publish a program of research-driven Thematic Edited Volumes that focus on specific areas and allow for a more in-depth overview of a particular subject.
\n\nIntechOpen Book Series will be launching regularly to offer our authors and editors exciting opportunities to publish their research Open Access. We will begin by relaunching some of our existing Book Series in this innovative book format, and will expand in 2022 into rapidly growing research fields that are driving and advancing society.
\n\nLaunching 2021
\n\nArtificial Intelligence, ISSN 2633-1403
\n\nVeterinary Medicine and Science, ISSN 2632-0517
\n\nBiochemistry, ISSN 2632-0983
\n\nBiomedical Engineering, ISSN 2631-5343
\n\nInfectious Diseases, ISSN 2631-6188
\n\nPhysiology (Coming Soon)
\n\nDentistry (Coming Soon)
\n\nWe invite you to explore our IntechOpen Book Series, find the right publishing program for you and reach your desired audience in record time.
\n\nNote: Edited in October 2021
\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"5313",leadTitle:null,fullTitle:"Update on Dementia",title:"Update on Dementia",subtitle:null,reviewType:"peer-reviewed",abstract:"The dementia challenge is the largest health effort of the times we live in. The whole society has to move to a realization of the significance of prioritization to make an attempt in the direction of mental health promotion and dementia risk reduction. New priorities for research are needed to go far beyond the usual goal of constructing a disease course-modifying medication. Moreover, a full empowerment and engagement of men and women living with dementia and their caregivers, overcoming stigma and discrimination should be promoted. The common efforts and the final aim will have to be the progress of a ''dementia-constructive'' world, where people with dementia can take advantage of equal opportunities.",isbn:"978-953-51-2655-3",printIsbn:"978-953-51-2654-6",pdfIsbn:"978-953-51-4178-5",doi:"10.5772/61983",price:159,priceEur:175,priceUsd:205,slug:"update-on-dementia",numberOfPages:558,isOpenForSubmission:!1,isInWos:1,isInBkci:!0,hash:"6b264ef130a59fe71274c3811750e6c3",bookSignature:"Davide Vito Moretti",publishedDate:"September 28th 2016",coverURL:"https://cdn.intechopen.com/books/images_new/5313.jpg",numberOfDownloads:46639,numberOfWosCitations:63,numberOfCrossrefCitations:45,numberOfCrossrefCitationsByBook:2,numberOfDimensionsCitations:93,numberOfDimensionsCitationsByBook:3,hasAltmetrics:1,numberOfTotalCitations:201,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"November 19th 2015",dateEndSecondStepPublish:"December 10th 2015",dateEndThirdStepPublish:"March 29th 2016",dateEndFourthStepPublish:"June 27th 2016",dateEndFifthStepPublish:"July 27th 2016",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,8,9",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"147154",title:"Dr.",name:"Davide",middleName:"Vito",surname:"Moretti",slug:"davide-moretti",fullName:"Davide Moretti",profilePictureURL:"https://mts.intechopen.com/storage/users/147154/images/4806_n.jpg",biography:"Dr. Davide Vito Moretti is a consultant neurologist and senior researcher at the National Institute of Research and Cure for Mental Disorders and Dementia, St. John of God Institute, Brescia, Italy. Since 2014, he is a professor of Neurophysiology at the UniLudes University in Lugano. He received his medical degree from the Catholic University in Rome and completed his residency in neurology and fellowship in movement disorders at the State University in Trieste. Moreover, he received his PhD in Neurophysiology at the Sapienza University of Rome.\nDr. Moretti is currently involved in research and care of subjects with Alzheimer’s disease and dementia in the Memory Clinic/Alzheimer Operative Unit of the St. John of God Institute. Moreover, he is the chief of the clinical neurophysiology unit and of the Alzheimer’s disease rehabilitation operative unit. Since March 2015, he is also the head of the whole rehabilitation in dementia line research in the St. John of God Institute.\nHis research is primarily concerned about Alzheimer’s disease both in prodromic and in clinically evident phase of the disease, Parkinson’s disease, movement disorders, and clinical neurophysiology.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Centro San Giovanni di Dio Fatebenefratelli",institutionURL:null,country:{name:"Italy"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1171",title:"Developmental Cognitive Neuroscience",slug:"developmental-cognitive-neuroscience"}],chapters:[{id:"52167",title:"Alternative Splicing and Alzheimer’s Disease",doi:"10.5772/64513",slug:"alternative-splicing-and-alzheimer-s-disease",totalDownloads:1876,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Alzheimer’s disease is a neurodegenerative process whose origin is unknown. It has been associated with this process at least two important proteins: the first is the β-amyloid forming amyloid plaques and the second protein is Tau, which has been determined to precipitates inside the neuron because hyperphosphorylation, causing instability in the axon. Tau microtubule-associated protein (MAP) is essential for the development of neuronal cell polarity. Tau protein is preferentially localized in the axons, whereas MAP2, another neuronal specific microtubule-associated protein, is localized in the somatodendritic domain. Previous studies have demonstrated that the localization of these proteins depends, at least in part, on messenger RNA (mRNA) subcellular localization, that is, Tau mRNA into the axon and MAP2 mRNA into the dendrite. Tau protein has an essential role in the pathology of Alzheimer’s disease, and hyperphosphorylated Tau promotes destabilization of microtubules. Tau alternative splicing generates six isoforms in the adult human brain due to the inclusion or exclusion of exons 2, 3, and 10. The failure in the splicing process of exon 10 generates a tauopathy, which can be carried out by the amyloid peptide; however, the splicing of other exons is less studied. The impact of amyloid peptide on the alternative splicing of exons 2, 3, and 6 caused formed cell processes to retract in differentiated cells and altered the expression of exons 2/3 in cell culture. Expression of exon 6 was repressed under β-amyloid treatment. The molecular mechanism for this amyloid-Tau interaction remains to be determined, but may have potential implications for the understanding of the underlying neuropathological processes in Alzheimer’s disease.",signatures:"Gonzalo Emiliano Aranda Abreu, Sonia Lilia Mestizo Gutiérrez,\nMaría Elena Hernández Aguilar and Fausto Rojas Durán",downloadPdfUrl:"/chapter/pdf-download/52167",previewPdfUrl:"/chapter/pdf-preview/52167",authors:[{id:"72314",title:"Dr.",name:"Gonzalo Emiliano",surname:"Aranda Abreu",slug:"gonzalo-emiliano-aranda-abreu",fullName:"Gonzalo Emiliano Aranda Abreu"},{id:"186065",title:"Dr.",name:"Sonia Lilia",surname:"Mestizo Gutiérrez",slug:"sonia-lilia-mestizo-gutierrez",fullName:"Sonia Lilia Mestizo Gutiérrez"},{id:"186066",title:"Dr.",name:"María Elena",surname:"Hernández Aguilar",slug:"maria-elena-hernandez-aguilar",fullName:"María Elena Hernández Aguilar"},{id:"186067",title:"Dr.",name:"Fausto",surname:"Rojas Durán",slug:"fausto-rojas-duran",fullName:"Fausto Rojas Durán"}],corrections:null},{id:"51676",title:"Neuroinflammation and Neurodegeneration",doi:"10.5772/64545",slug:"neuroinflammation-and-neurodegeneration",totalDownloads:3466,totalCrossrefCites:6,totalDimensionsCites:11,hasAltmetrics:0,abstract:"Pathophysiological processes of neurodegenerative diseases are not clearly defined. However, an important body of evidence points toward the role of various inflammatory processes. The microglial cell is the main representative of the immune system in the central nervous system (CNS). This cell type can sense foreign or harmful pathogens and trigger its own activation and the generation of neuroinflammatory processes through phagocytosis and the release of cytokines, in order to maintain the cellular microenvironment. However, after maintaining a permanent state of activation due to sustained stimulation over time, microglial cells may generate a focus of persistent inflammation that in some cases precedes or enhances the neurodegenerative process. Thus, neuroinflammatory microenvironment becomes toxic and harmful for the neuronal cell, which degenerates and releases various factors that in turn activate the inflammatory response of microglia, potentiating the neurodegenerative cycle. In this chapter, we discuss the evidence on the role of microglial cell activation in neurodegenerative conditions and the association between neuroinflammatory processes and age-related neurological diseases. Finally, we outline how this new approach can help us to find new ways to understand neurodegenerative processes and to orientate the search for new therapies.",signatures:"Inelia Morales, Gonzalo A. Farías, Nicole Cortes and Ricardo B.\nMaccioni",downloadPdfUrl:"/chapter/pdf-download/51676",previewPdfUrl:"/chapter/pdf-preview/51676",authors:[{id:"137002",title:"Dr.",name:"Gonzalo",surname:"Farias",slug:"gonzalo-farias",fullName:"Gonzalo Farias"},{id:"183194",title:"Dr.",name:"Ricardo",surname:"Maccioni",slug:"ricardo-maccioni",fullName:"Ricardo Maccioni"},{id:"183196",title:"MSc.",name:"Inelia",surname:"Morales",slug:"inelia-morales",fullName:"Inelia Morales"},{id:"183197",title:"MSc.",name:"Nicole",surname:"Cortes",slug:"nicole-cortes",fullName:"Nicole Cortes"}],corrections:null},{id:"51651",title:"High-Fat and Cholesterol Intake Affects Brain Homeostasis and Could Accelerate the Development of Dementia: A Systemic View",doi:"10.5772/64357",slug:"high-fat-and-cholesterol-intake-affects-brain-homeostasis-and-could-accelerate-the-development-of-de",totalDownloads:1886,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:'Alzheimer’s disease is the most common type of dementia in occidental countries. The majority of the cases develop the disease for no genetic reasons; therefore, it is crucial to establish which environmental factors trigger the development of the disease. It has been proposed that nutritional habits, especially main components of Western countries’ diet such as saturated fat or cholesterol, increase the risk for development of Alzheimer’s disease (AD) and/or accelerate the onset of the disease, which is a big concern in countries where obesity is a public health problem. It is crucial to understand the links between alimentary habits and the development of AD and other types of dementia. A possible mechanism is the disruption of blood–brain barrier (BBB), which is the protection of the brain from circulating blood. Such disruptions can result from consuming high-fat diet (HFD) or high-cholesterol diet (HCD) and inflammation produced by alteration in brain vasculature resulted for chronic consumption of such type of diets. What has named a "Systemic view" comprises the idea that; what happens outside of the brain environment does affect brain functioning and the modifications experienced in the brain environment resulted from the influence of external factors will affect the entire body. In the current chapter, we will review the state of the art in the studies of the impact of a diet rich in fat or cholesterol on the brain and how the alterations induced in other organs can impact brain functioning increasing the susceptibility of development of dementia.',signatures:"Marco Antonio Meraz-Ríos and Perla Leal-Galicia",downloadPdfUrl:"/chapter/pdf-download/51651",previewPdfUrl:"/chapter/pdf-preview/51651",authors:[{id:"114746",title:"Dr.",name:"Marco",surname:"Meraz-Ríos",slug:"marco-meraz-rios",fullName:"Marco Meraz-Ríos"},{id:"187600",title:"Dr.",name:"Perla",surname:"Leal-Galicia",slug:"perla-leal-galicia",fullName:"Perla Leal-Galicia"}],corrections:null},{id:"51637",title:"Plasma Biomarkers in Alzheimer’s Disease",doi:"10.5772/64512",slug:"plasma-biomarkers-in-alzheimer-s-disease",totalDownloads:1902,totalCrossrefCites:2,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Biomarker study on dementia has developed widely. In applying biomarkers, there seems to be several utilizations such as presymptomatic- and early-stage detection, differential diagnosis, and evaluation of treatment effect. Currently, most reliable fluid markers are amyloid peptide (Aβ) with microtubule-associated protein tau (TAU) and phosphorylated TAU (P-TAU) detected in cerebrospinal fluid (CSF). Aβ42 correlates with plaque pathology, TAU reflects the intensity of neuroaxonal degeneration, and P-TAU may correlate with neurofibrillary tangle (NFT) pathology. An attenuation of the level of Aβ42 and elevation in the ratio of Aβ42 relative to the shorter major species of Aβ42 peptide with 40 amino acid residues (Aβ40) has been identified as significant events in the early stage of Alzheimer’s disease (AD) pathology. In addition, there is great interest in blood-based markers of AD since blood extraction is much less invasive. Moreover, plasma biomarkers can be measured at relatively low expense once a standard system of measurement is established. Although there is not yet an established or validated diagnostic test for plasma biomarkers, there is great interest in blood-based markers. We will summarize reported biomarkers, describe our novel potential plasma biomarker for AD (annexin A5), offering a strategy for selecting candidates, and show our results and evaluation.",signatures:"Hitoshi Sohma and Yasuo Kokai",downloadPdfUrl:"/chapter/pdf-download/51637",previewPdfUrl:"/chapter/pdf-preview/51637",authors:[{id:"179340",title:"Prof.",name:"Hitoshi",surname:"Sohma",slug:"hitoshi-sohma",fullName:"Hitoshi Sohma"},{id:"180263",title:"Prof.",name:"Yasuo",surname:"Kokai",slug:"yasuo-kokai",fullName:"Yasuo Kokai"}],corrections:null},{id:"51964",title:"Alzheimer’s-Related Amyloid Beta Peptide Aggregates in the Ageing Retina: Implications for Sight Loss and Dementia",doi:"10.5772/64790",slug:"alzheimer-s-related-amyloid-beta-peptide-aggregates-in-the-ageing-retina-implications-for-sight-loss",totalDownloads:1896,totalCrossrefCites:2,totalDimensionsCites:4,hasAltmetrics:0,abstract:"Although visual problems are reported by patients with Alzheimer’s disease and dementia, studies into this particular aspect of neuropathology are scarce. The growing awareness of complex pathological processes in the ageing retina and brain, however, enables us to consider this from a new perspective. Here we discuss the latest findings on the wide-ranging visual defects experienced by those suffering from Alzheimer’s disease and dementia. We propose that events leading to chronic degeneration of the retina and the brain in fact share many striking similarities. In particular, we discuss the role of the Alzheimer’s-related amyloid beta (Aβ) group of peptides that has been shown to accumulate in senescent retinas, correlated with increased risk of retinal degeneration. The high photo-oxidative retinal environment creates ideal conditions for Aβ aggregation, evidenced by high Aβ loads reported in aged and donor eyes from patients with age-related macular degeneration. Consequently, longitudinal and non-invasive retinal assessments may provide invaluable information on incipient pathology and disease progression in the retina as well as the senescent brain. Such insights may not only lead to identifying new pathogenic mechanisms in the retina with implications for understanding Alzheimer’s disease but reveal the underlying causes of visual abnormalities reported in patients with dementia.",signatures:"J. Arjuna Ratnayaka and Savannah Lynn",downloadPdfUrl:"/chapter/pdf-download/51964",previewPdfUrl:"/chapter/pdf-preview/51964",authors:[{id:"183572",title:"Dr.",name:"J Arjuna",surname:"Ratnayaka",slug:"j-arjuna-ratnayaka",fullName:"J Arjuna Ratnayaka"},{id:"183847",title:"Ms.",name:"Savannah A.",surname:"Lynn",slug:"savannah-a.-lynn",fullName:"Savannah A. Lynn"}],corrections:null},{id:"51804",title:"Proteomic Study of Degenerative Protein Modifications in the Molecular Pathology of Neurodegeneration and Dementia",doi:"10.5772/64693",slug:"proteomic-study-of-degenerative-protein-modifications-in-the-molecular-pathology-of-neurodegeneratio",totalDownloads:1643,totalCrossrefCites:2,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Dementia is a major public health burden, and the World Health Organization has identified this disorder as a major public health priority. There are limited treatment options due to poor understanding of key mechanism of dementia pathogenesis. Dementia has been regarded as a proteinopathy in which alterations of brain protein structure and function are the key features of the disorder. Proteinopathy can be triggered by degenerative protein modifications (DPMs), misfolding, aggregation, and deposition of the malformed proteins. Despite the clinical significance of alteration in protein abundances, DPMs, protein misfolding, and aggregation, the molecular mechanism that promotes these changes remains inadequately understood, mostly due to technical challenges. Proteomic is a powerful, sensitive, and advanced tool to study the progressive brain tissue damage that critically dysregulates key enzymes, accumulates modified proteins, and causes protein misfolding and aggregation, resulting in cognitive decline and dementia. The proteomic profiling of protein abundances and correlating DPMs with protein misfolding and aggregation have potential to elucidate underlying molecular mechanism of the disease. This chapter summarizes the recent proteomic developments for studying brain proteome, DPMs, and protein aggregation mechanism that may lead to dementia. We attempted to correlate DPMs and its impact on protein aggregation and deposition in brain tissues.",signatures:"Sunil S. Adav and Siu Kwan Sze",downloadPdfUrl:"/chapter/pdf-download/51804",previewPdfUrl:"/chapter/pdf-preview/51804",authors:[{id:"184065",title:"Dr.",name:"Siu Kwan",surname:"Sze",slug:"siu-kwan-sze",fullName:"Siu Kwan Sze"},{id:"187076",title:"Dr.",name:"Sunil S",surname:"Adav",slug:"sunil-s-adav",fullName:"Sunil S Adav"}],corrections:null},{id:"52003",title:"Brain Lipids in the Pathophysiology and Treatment of Alzheimer’s Disease",doi:"10.5772/64757",slug:"brain-lipids-in-the-pathophysiology-and-treatment-of-alzheimer-s-disease",totalDownloads:2132,totalCrossrefCites:2,totalDimensionsCites:13,hasAltmetrics:1,abstract:"Alzheimer’s disease (AD) is a neurodegenerative disorder that causes severe and progressive cognitive impairment. The discovery of specific mutations related to AD supported the amyloid cascade hypothesis, which postulates that the accumulation of the amyloid-β (Aβ) peptide triggers neuronal death and dementia. However, most drugs that aim to prevent Aβ accumulation or tau phosphorylation have consistently failed in clinical trials. This would suggest that the amyloid pathology lies downstream of (an)other cellular event(s) that is/are responsible for AD pathogenesis. In this context, several lipid alterations have been described in the brain and in peripheral fluids of patients with AD, suggesting the involvement of lipids in the etiology of this condition. Indeed, the central nervous system (CNS) has the highest lipid content in the body, next to adipose tissue, and it is thought that normalization of brain membrane lipid levels would revert AD-related pathogenic events. In this sense, novel hydroxylated derivatives of docosahexaenoic acid (DHA) such as natural resolvins or synthetic hydroxy-DHA (HDHA, DHALifort) can modulate membrane lipid composition and show remarkable beneficial effects on AD hallmarks, such as prevention of amyloid production and tau phosphorylation, and cognitive restoration in animal models. Therefore, normalization of the neuronal lipid environment by hydroxyl-DHA and/or other lipids may constitute a promising therapy for AD treatment, memory loss and, possibly, other types of dementia.",signatures:"Manuel Torres, Xavier Busquets and Pablo V. Escribá",downloadPdfUrl:"/chapter/pdf-download/52003",previewPdfUrl:"/chapter/pdf-preview/52003",authors:[{id:"184164",title:"Prof.",name:"Pablo",surname:"Escribá",slug:"pablo-escriba",fullName:"Pablo Escribá"},{id:"191108",title:"Prof.",name:"Xavier",surname:"Busquets",slug:"xavier-busquets",fullName:"Xavier Busquets"},{id:"191260",title:"Dr.",name:"Manuel",surname:"Torres",slug:"manuel-torres",fullName:"Manuel Torres"}],corrections:null},{id:"52048",title:"Beta Amyloid Peptides: Extracellular and Intracellular Mechanisms of Clearance in Alzheimer’s Disease",doi:"10.5772/64744",slug:"beta-amyloid-peptides-extracellular-and-intracellular-mechanisms-of-clearance-in-alzheimer-s-disease",totalDownloads:2234,totalCrossrefCites:4,totalDimensionsCites:8,hasAltmetrics:0,abstract:"Alzheimer’s disease (AD) is a neurodegenerative disease and the most common form of dementia, characterized by the overproduction and accumulation of different amyloid-β peptide peptides (Aβ) within different areas in the brain conducting to memory loss and dementia. The Aβ cascade hypothesis of AD was originally proposed by Selkoe in 1991 by the theory that accumulation of Aβ42 is the initial trigger for neurodegeneration. The Aβ cascade hypothesis assumes that changes in the production or accumulation of Aβ are responsible for AD pathology. Different Aβ clearance mechanisms are also affected by AD pathology. Studies from the past years have revealed that the blocking of Aβ production is not effective for reducing the brain Aβ levels. However, the relevance of Aβ clearance in AD, especially in late-onset sporadic AD (LOAD), has been heightened, and the study of the Aβ clearance mechanisms has elucidated new possible therapeutic targets. This chapter summarizes recent data underlying the idea of the reduced Aβ clearance and subsequent Aβ spread in AD. We discuss the Aβ clearance mechanisms altered in AD, and the Aβ clearance through autophagy in more detail, a more recent mechanism proposed, and the new strategies to eliminate Aβ42 inducing autophagy.",signatures:"Luis F. Hernández-Zimbrón, Elisa Gorostieta-Salas, Mei-Li Díaz-\nHung, Roxanna Pérez-Garmendia, Gohar Gevorkian and Hugo\nQuiroz-Mercado",downloadPdfUrl:"/chapter/pdf-download/52048",previewPdfUrl:"/chapter/pdf-preview/52048",authors:[{id:"75951",title:"BSc.",name:"Hugo",surname:"Quiroz-Mercado",slug:"hugo-quiroz-mercado",fullName:"Hugo Quiroz-Mercado"},{id:"181180",title:"Dr.",name:"Luis Fernando",surname:"Hernandez-Zimbron",slug:"luis-fernando-hernandez-zimbron",fullName:"Luis Fernando Hernandez-Zimbron"},{id:"181277",title:"Dr.",name:"Roxanna",surname:"Pérez-Garmendia",slug:"roxanna-perez-garmendia",fullName:"Roxanna Pérez-Garmendia"},{id:"181278",title:"BSc.",name:"Elisa",surname:"Gorostieta-Salas",slug:"elisa-gorostieta-salas",fullName:"Elisa Gorostieta-Salas"},{id:"181279",title:"MSc.",name:"Mei-Li",surname:"Díaz-Hung",slug:"mei-li-diaz-hung",fullName:"Mei-Li Díaz-Hung"},{id:"190226",title:"Dr.",name:"Gohar",surname:"Gevorkian-Markosian",slug:"gohar-gevorkian-markosian",fullName:"Gohar Gevorkian-Markosian"}],corrections:null},{id:"52062",title:"Alzheimer's Disease: From Animal Models to the Human Syndrome",doi:"10.5772/64619",slug:"alzheimer-s-disease-from-animal-models-to-the-human-syndrome",totalDownloads:2295,totalCrossrefCites:0,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Some animal models, genetically modified (such as murine) and sporadic (as others species), enable the study of the origin of specific lesions observed in human neurodegenerative diseases. In particular, Alzheimer's disease (AD) models have been designed to test the hypothesis that certain lesions are associated with functional and morphological changes beginning with memory loss and impairment in activities of daily life. This review compares and evaluates the phenotypes of different AD animal models, on the basis of the specific objectives of each study, with the purpose of encompassing their contributions to the comprehension of the AD signs and symptoms in humans. All these models contribute to the comprehension of the human AD mechanisms regarding the heterogeneity of AD phenotypes: the overlap between AD and age‐related changes, the variability of AD onset (early or late), the probable reactiveness of amyloid‐β and tau proteins, the scarcity of senile plaques and/or neurofibrillary tangles in some AD cases, the spatial correlation of the pathology and cerebral blood vessels, and the immunological responses (microglial aging) and synaptopathy. Altogether, these considerations may contribute to find therapies to treat and prevent this disease.",signatures:"Erika Orta‐Salazar, Isaac Vargas‐Rodríguez, Susana A Castro‐\nChavira, Alfredo I. Feria‐Velasco and Sofía Díaz‐Cintra",downloadPdfUrl:"/chapter/pdf-download/52062",previewPdfUrl:"/chapter/pdf-preview/52062",authors:[{id:"184728",title:"Dr.",name:"Erika Maria",surname:"Orta Salazar",slug:"erika-maria-orta-salazar",fullName:"Erika Maria Orta Salazar"},{id:"185118",title:"Ph.D. Student",name:"Isaac",surname:"Vargas-Rodríguez",slug:"isaac-vargas-rodriguez",fullName:"Isaac Vargas-Rodríguez"},{id:"185119",title:"Ph.D. Student",name:"Susana Angelica",surname:"Castro-Chavira",slug:"susana-angelica-castro-chavira",fullName:"Susana Angelica Castro-Chavira"},{id:"185120",title:"Ph.D.",name:"Alfredo I",surname:"Feria-Velasco",slug:"alfredo-i-feria-velasco",fullName:"Alfredo I Feria-Velasco"},{id:"185121",title:"Ph.D.",name:"Sofia",surname:"Diaz-Cintra",slug:"sofia-diaz-cintra",fullName:"Sofia Diaz-Cintra"}],corrections:null},{id:"51441",title:"Risk Factors for Alzheimer’s Disease",doi:"10.5772/64270",slug:"risk-factors-for-alzheimer-s-disease",totalDownloads:1760,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Alzheimer’s disease (AD) is the most common form of dementia in the elderly. Currently there is no effective treatment available. Senile plaques and neurofibrillary tangles are hallmarks of AD pathology, and patients demonstrate cognitive complaints with deficits in various neuropsychological domains. Familial AD (FAD) accounts for 0.5% of all AD cases and usually presents before the age of 65 years. Approximately 50% of the FAD patients carry mutations in one of the following genes: APP, PSEN1, and PSEN2. Inheriting any of these genetic mutations increases Aβ42 production, which has been linked to AD pathogenesis. Late-onset AD represents the majority of AD cases, with evidence suggesting impaired Aβ clearance. However, the etiology of late-onset AD is more complex. Several findings suggest that multiple risk genes and factors may contribute to the pathogenesis of LOAD. In this chapter, we elaborate some of these factors and their involvements in the development of AD.",signatures:"Dongming Cai and Farida El Gaamouch",downloadPdfUrl:"/chapter/pdf-download/51441",previewPdfUrl:"/chapter/pdf-preview/51441",authors:[{id:"183531",title:"Prof.",name:"Dongming",surname:"Cai",slug:"dongming-cai",fullName:"Dongming Cai"},{id:"183867",title:"Dr.",name:"Farida",surname:"El Gaamouch",slug:"farida-el-gaamouch",fullName:"Farida El Gaamouch"}],corrections:null},{id:"51355",title:"Normal Aging and Dementia",doi:"10.5772/64203",slug:"normal-aging-and-dementia",totalDownloads:1871,totalCrossrefCites:6,totalDimensionsCites:8,hasAltmetrics:0,abstract:"Normal aging begins after 60 years of age. According to Harman, the accumulation of free radicals, which results from weakening of repair and protective mechanisms, takes place in the aging brain. It is believed that especially in the population of the most elderly there is increased incidence of both dementia and depression. The causes of these central nervous system disorders in the aging human body are changes at the molecular level, such as changes in the biochemical parameters, the accumulation of mutations in nuclear and mitochondrial DNA, and epigenetic changes. Biomarkers associated with aging of the brain include accumulated deposits of β-amyloid (Aβ), disturbed cholesterol homeostasis, altered neuroimaging parameters, and impaired glucose metabolism. Genetic factors are also responsible for normal aging, for example, SIRT1, AKT1, and CDKN1A, and among them the longevity genes, such as FOXO3A and CETP. Dementia as well as cognitive decline may be modified by poly-T variants of TOMM40 and APOE alleles via influencing the level of apolipoprotein E (apoE) in the brain and in the plasma as well as by its ability of Aβ clearance.",signatures:"Michał Prendecki, Jolanta Florczak-Wyspianska, Marta Kowalska,\nMargarita Lianeri, Wojciech Kozubski and Jolanta Dorszewska",downloadPdfUrl:"/chapter/pdf-download/51355",previewPdfUrl:"/chapter/pdf-preview/51355",authors:[{id:"31962",title:"Dr.",name:"Jolanta",surname:"Dorszewska",slug:"jolanta-dorszewska",fullName:"Jolanta Dorszewska"},{id:"83372",title:"Prof.",name:"Wojciech",surname:"Kozubski",slug:"wojciech-kozubski",fullName:"Wojciech Kozubski"},{id:"183236",title:"Dr.",name:"Jolanta",surname:"Florczak-Wyspianska",slug:"jolanta-florczak-wyspianska",fullName:"Jolanta Florczak-Wyspianska"},{id:"186409",title:"MSc.",name:"Michal",surname:"Prendecki",slug:"michal-prendecki",fullName:"Michal Prendecki"},{id:"186528",title:"MSc.",name:"Marta",surname:"Kowalska",slug:"marta-kowalska",fullName:"Marta Kowalska"},{id:"186529",title:"Dr.",name:"Margarita",surname:"Lianeri",slug:"margarita-lianeri",fullName:"Margarita Lianeri"}],corrections:null},{id:"52137",title:"Changes in Visual Cortex in Healthy Aging and Dementia",doi:"10.5772/64562",slug:"changes-in-visual-cortex-in-healthy-aging-and-dementia",totalDownloads:1704,totalCrossrefCites:2,totalDimensionsCites:4,hasAltmetrics:0,abstract:"This chapter reviews the differences in specific structural and functional characteristics of human visual cortex among young adults, healthy aging adults, and patients with dementia, with a primary focus on those with Alzheimer’s disease (AD). Such visual cortex changes have been shown to underlie many of the behavioral deficits that develop in healthy aging and AD. Measurements of disordered visual cortex in dementia patients may be possible early in the course of neurodegeneration and thus may be useful for improving early diagnosis of these devastating diseases.",signatures:"Alyssa A. Brewer and Brian Barton",downloadPdfUrl:"/chapter/pdf-download/52137",previewPdfUrl:"/chapter/pdf-preview/52137",authors:[{id:"115304",title:"Dr.",name:"Alyssa",surname:"Brewer",slug:"alyssa-brewer",fullName:"Alyssa Brewer"},{id:"149246",title:"Dr.",name:"Brian",surname:"Barton",slug:"brian-barton",fullName:"Brian Barton"}],corrections:null},{id:"52368",title:"Clusterin (APOJ) in Alzheimer’s Disease: An Old Molecule with a New Role",doi:"10.5772/64233",slug:"clusterin-apoj-in-alzheimer-s-disease-an-old-molecule-with-a-new-role",totalDownloads:2229,totalCrossrefCites:5,totalDimensionsCites:7,hasAltmetrics:0,abstract:"Clusterin (CLU), initially identified in 1983 as a “clustering factor” in ram rete testis fluid, is a multifaceted protein that was re-discovered and subsequently renamed eight times from 1983 to 1992. CLU exists as multiple protein isoforms including the 80 kDa glycosylated mature/secreted form of CLU (mCLU) and the smaller non-modified nuclear and intracellular forms of CLU (nCLU and icCLU, respectively). These isoforms, which are expressed at the highest levels in the brain, are suggested to play distinct roles in various disease processes such as those involving inflammation and apoptosis. Currently, CLU, also known as apolipoprotein J (APOJ) which belongs to the same protein family as apolipoprotein E (APOE), is the third most significant genetic risk factor for the development of late-onset Alzheimer’s disease (LOAD); however, an extensive gap exists in the literature in understanding the physiological roles of CLU in normal brain and the pathogenic mechanisms conferred by CLU polymorphisms in the onset of LOAD. In this chapter, we discuss the status of the current knowledge regarding the generation and regulation of CLU protein isoforms, the clinical evidence and possible mechanisms involved in LOAD, and provide our perspectives for future studies.",signatures:"Sarah K. Woody and Liqin Zhao",downloadPdfUrl:"/chapter/pdf-download/52368",previewPdfUrl:"/chapter/pdf-preview/52368",authors:[{id:"182716",title:"Prof.",name:"Liqin",surname:"Zhao",slug:"liqin-zhao",fullName:"Liqin Zhao"},{id:"187597",title:"Ms.",name:"Sarah",surname:"Woody",slug:"sarah-woody",fullName:"Sarah Woody"}],corrections:null},{id:"51440",title:"New Targets for Diagnosis and Treatment Against Alzheimer’s Disease: The Mitochondrial Approach",doi:"10.5772/64327",slug:"new-targets-for-diagnosis-and-treatment-against-alzheimer-s-disease-the-mitochondrial-approach",totalDownloads:2105,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Alzheimer’s disease (AD) is a neurodegenerative disorder and the most common form of dementia. AD is characterized by brain presence of senile plaques, which are formed by aggregates of Aβ peptide and neurofibrillary tangles (NFTs), formed by pathological forms of tau protein. Evidence suggests that these elements affect neurons compromising energy supply, antioxidant response and synaptic activity. AD principally affects the memory and cognitive functions of the patients, and currently, successful strategies for diagnosis and early treatment are lacking. In this scenario, accumulative evidence suggests that mitochondrial dysfunction precedes the establishment of tau and Aβ pathology and contributes to synaptic degeneration observed in AD. Therefore, reducing mitochondrial injury may have beneficial effects for neuronal dysfunction and cognitive decline observed in AD patients. Interestingly, the examination of peripheral cells from AD patients also presents mitochondrial dysfunction, suggesting that tracking these mitochondrial defects in peripheral cells could be a potential mechanism of early diagnosis of AD. In this chapter, we analyse current evidence that suggests that mitochondrial injury is an important factor in the pathogenesis of AD and how studying this process could reveal new strategies to mitigate neurodegeneration and to develop new diagnostic methods for an early detection of AD.",signatures:"María José Pérez, Claudia Jara, Ernesto Muñoz‐Urrutia and Rodrigo\nA. Quintanilla",downloadPdfUrl:"/chapter/pdf-download/51440",previewPdfUrl:"/chapter/pdf-preview/51440",authors:[{id:"182849",title:"Dr.",name:"Rodrigo",surname:"Quintanilla",slug:"rodrigo-quintanilla",fullName:"Rodrigo Quintanilla"},{id:"183872",title:"MSc.",name:"María José",surname:"Pérez",slug:"maria-jose-perez",fullName:"María José Pérez"},{id:"183873",title:"Dr.",name:"Claudia",surname:"Jara",slug:"claudia-jara",fullName:"Claudia Jara"},{id:"183874",title:"MSc.",name:"Ernesto",surname:"Muñoz",slug:"ernesto-munoz",fullName:"Ernesto Muñoz"}],corrections:null},{id:"51819",title:"The Impact of the Eye in Dementia: The Eye and its Role in Diagnosis and Follow‐up",doi:"10.5772/64490",slug:"the-impact-of-the-eye-in-dementia-the-eye-and-its-role-in-diagnosis-and-follow-up",totalDownloads:2951,totalCrossrefCites:4,totalDimensionsCites:6,hasAltmetrics:0,abstract:"Over the last few decades, the importance of ophthalmic examination in neurodegenerative diseases of the CNS has reportedly increased. The retina is an extension of the CNS and thus should not be surprising to find abnormal results in both the test exploring visual processing and those examining the retina of patients with CNS degeneration. Current in vivo imaging techniques are allowing ophthalmologists to detect and quantify data consistent with the histopathological findings described in the retinas of Alzheimer’s disease (AD) patients and may help to reveal unsuspected retinal and optic‐nerve repercussions of other CNS diseases. In this chapter, we perform an analysis of the physiological changes in ocular and cerebral ageing. We analyse the ocular manifestations in CNS disorders such as stroke, AD and Parkinson’s disease. In addition, the pathophysiology of both the eye and the visual pathway in AD are described. The value of the visual psychophysical tests in AD diagnosis is reviewed as well as the main findings of the optical coherence tomography as a contribution to the diagnosis and monitoring of the disease. Finally, we examine the association of two neurodegenerative diseases, AD and glaucoma, as mere coincidence or possible role in the progression of the neurodegeneration.",signatures:"Elena Salobrar‐García, Ana I. Ramírez, Rosa de Hoz, Pilar Rojas, Juan\nJ. Salazar, Blanca Rojas, Raquel Yubero, Pedro Gil, Alberto Triviño\nand José M. Ramírez",downloadPdfUrl:"/chapter/pdf-download/51819",previewPdfUrl:"/chapter/pdf-preview/51819",authors:[{id:"142707",title:"Prof.",name:"José M.",surname:"Ramírez",slug:"jose-m.-ramirez",fullName:"José M. Ramírez"},{id:"142864",title:"Prof.",name:"Alberto",surname:"Triviño",slug:"alberto-trivino",fullName:"Alberto Triviño"},{id:"145761",title:"Prof.",name:"Juan J",surname:"Salazar",slug:"juan-j-salazar",fullName:"Juan J Salazar"},{id:"145765",title:"Prof.",name:"Rosa",surname:"De Hoz",slug:"rosa-de-hoz",fullName:"Rosa De Hoz"},{id:"145766",title:"Prof.",name:"Blanca",surname:"Rojas",slug:"blanca-rojas",fullName:"Blanca Rojas"},{id:"145767",title:"Prof.",name:"Ana I.",surname:"Ramírez",slug:"ana-i.-ramirez",fullName:"Ana I. Ramírez"},{id:"183853",title:"MSc.",name:"Elena",surname:"Salobrar-García",slug:"elena-salobrar-garcia",fullName:"Elena Salobrar-García"},{id:"183854",title:"MSc.",name:"Pilar",surname:"Rojas",slug:"pilar-rojas",fullName:"Pilar Rojas"},{id:"183858",title:"Dr.",name:"Pedro",surname:"Gil",slug:"pedro-gil",fullName:"Pedro Gil"},{id:"183859",title:"Dr.",name:"Raquel",surname:"Yubero",slug:"raquel-yubero",fullName:"Raquel Yubero"}],corrections:null},{id:"52006",title:"Caring for Individuals with Dementia on a Continuum: An Interdisciplinary Approach Between Music Therapy and Nursing",doi:"10.5772/64663",slug:"caring-for-individuals-with-dementia-on-a-continuum-an-interdisciplinary-approach-between-music-ther",totalDownloads:3865,totalCrossrefCites:1,totalDimensionsCites:5,hasAltmetrics:0,abstract:"Background: Music has long been used to ease symptoms of dementia. Several studies have shown the therapeutic benefits of music therapy to decrease symptoms of agitation in people with dementia (PWD). Other research has demonstrated that the use of music during caregiving can ease agitated behaviors. However, few studies have shown the clinical benefits of using translational research in practice between music therapists and certified nursing assistants.",signatures:"Kendra Ray, Ayelet Dassa, Jan Maier, Renita Davis and Olayinka\nOgunlade",downloadPdfUrl:"/chapter/pdf-download/52006",previewPdfUrl:"/chapter/pdf-preview/52006",authors:[{id:"183246",title:"Dr.",name:"Kendra",surname:"Ray",slug:"kendra-ray",fullName:"Kendra Ray"},{id:"183915",title:"Prof.",name:"Renita",surname:"Davis",slug:"renita-davis",fullName:"Renita Davis"},{id:"183916",title:"Ms.",name:"Jan",surname:"Maier",slug:"jan-maier",fullName:"Jan Maier"},{id:"184382",title:"Dr.",name:"Ayelet",surname:"Dassa",slug:"ayelet-dassa",fullName:"Ayelet Dassa"},{id:"184383",title:"Mr.",name:"Olayinka",surname:"Ogunlade",slug:"olayinka-ogunlade",fullName:"Olayinka Ogunlade"}],corrections:null},{id:"52128",title:"Behavior and Emotion in Dementia",doi:"10.5772/64681",slug:"behavior-and-emotion-in-dementia",totalDownloads:1827,totalCrossrefCites:1,totalDimensionsCites:3,hasAltmetrics:1,abstract:"During the course of disease, the patient and caregiver face emotional and behavioral problems that may occur. Therefore, it is important to knowing how emotions and the perception of them are modified and thus to know the impact they have on mood and behavior of the patient and caregiver. Publicizing the type of pathology, both emotional and behavioral levels, in a patient with dementia can help in the development of nonpharmacological interventions that could slow the symptoms and improve the quality of life of patients.",signatures:"Teresa Mayordomo Rodríguez, Alicia Sales Galán, Rita Redondo\nFlores, Marta Torres Jordán and Javier Bendicho Montes",downloadPdfUrl:"/chapter/pdf-download/52128",previewPdfUrl:"/chapter/pdf-preview/52128",authors:[{id:"184060",title:"Dr.",name:"Teresa",surname:"Mayordomo Rodríguez",slug:"teresa-mayordomo-rodriguez",fullName:"Teresa Mayordomo Rodríguez"},{id:"370127",title:"Dr.",name:"Alicia Sales",surname:"Galán",slug:"alicia-sales-galan",fullName:"Alicia Sales Galán"},{id:"370128",title:"Dr.",name:"Rita Redondo",surname:"Flores",slug:"rita-redondo-flores",fullName:"Rita Redondo Flores"},{id:"370129",title:"Dr.",name:"Marta Torres",surname:"Jordán",slug:"marta-torres-jordan",fullName:"Marta Torres Jordán"},{id:"370130",title:"Dr.",name:"Javier Bendicho",surname:"Montes",slug:"javier-bendicho-montes",fullName:"Javier Bendicho Montes"}],corrections:null},{id:"51705",title:"Non-Pharmacological Approaches in the Treatment of Dementia",doi:"10.5772/64232",slug:"non-pharmacological-approaches-in-the-treatment-of-dementia",totalDownloads:2767,totalCrossrefCites:3,totalDimensionsCites:11,hasAltmetrics:0,abstract:"Currently, a pharmacological disease-modifying treatment for dementia is not available, but different non-pharmacological approaches appear to be useful. In this chapter, we describe traditional treatments such as cognitive and emotion-oriented interventions, sensory and multi-sensory stimulation interventions and also potentially alternative interesting options such as behavioural therapy, animal-assisted therapy, home-adaptation therapy and assistive technologies to support patient with dementia. Many non-pharmacological treatments have reported benefits in multiple research studies, but there is a need for further Randomized controlled trials (RCTs) with an adequate sample size to improve the strength of evidence in order to apply these approaches.",signatures:"Grazia D’Onofrio, Daniele Sancarlo, Davide Seripa, Francesco\nRicciardi, Francesco Giuliani, Francesco Panza and Antonio Greco",downloadPdfUrl:"/chapter/pdf-download/51705",previewPdfUrl:"/chapter/pdf-preview/51705",authors:[{id:"184079",title:"Dr.",name:"Daniele",surname:"Sancarlo",slug:"daniele-sancarlo",fullName:"Daniele Sancarlo"},{id:"184081",title:"Dr.",name:"Antonio",surname:"Greco",slug:"antonio-greco",fullName:"Antonio Greco"},{id:"272620",title:"Dr.",name:"Davide",surname:"Seripa",slug:"davide-seripa",fullName:"Davide Seripa"},{id:"272628",title:"Dr.",name:"Grazia",surname:"D'Onofrio",slug:"grazia-d'onofrio",fullName:"Grazia D'Onofrio"},{id:"368922",title:"Dr.",name:"Francesco",surname:"Ricciardi",slug:"francesco-ricciardi",fullName:"Francesco Ricciardi"},{id:"368923",title:"Dr.",name:"Francesco",surname:"Giuliani",slug:"francesco-giuliani",fullName:"Francesco Giuliani"},{id:"368924",title:"Dr.",name:"Francesco",surname:"Panza",slug:"francesco-panza",fullName:"Francesco Panza"}],corrections:null},{id:"52095",title:"Medication Management for People Living with Dementia: Development and Evaluation of a Multilingual Information Resource for Family Caregivers of People Living with Dementia",doi:"10.5772/64661",slug:"medication-management-for-people-living-with-dementia-development-and-evaluation-of-a-multilingual-i",totalDownloads:1731,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"The aim of this chapter is to describe the development and evaluation of an online multilingual information resource focused on medication management, targeting people living with dementia and their family caregivers. Maintaining effective medication management is important to allow ongoing quality of life within the community setting and avoiding medication-related preventable hospitalisations for the person living with dementia. Family caregivers are likely to assume the role of medication management on behalf of the person in their care as dementia progresses. Little training or information is available to family caregivers to assist them with this role. A pilot online information resource was developed and evaluated. Responding to the evaluation, this resource was improved, and a more extensive evaluation process was undertaken. The development and evaluation process are outlined with a view to guiding the development of similar resources, especially those targeting linguistically diverse family caregivers and those with dementia. This is especially important given that many older adults will migrate during their lifetime, often to a country where they are not familiar with the language or health services. Extra support is needed to assist older immigrants who are themselves at risk or are caring for someone with dementia.",signatures:"Robyn Gillespie, Pippa Burns, Lindsey Harrison, Amanda Baker, Khin\nWin, Victoria Traynor and Judy Mullan",downloadPdfUrl:"/chapter/pdf-download/52095",previewPdfUrl:"/chapter/pdf-preview/52095",authors:[{id:"183243",title:"Mrs.",name:"Robyn",surname:"Gillespie",slug:"robyn-gillespie",fullName:"Robyn Gillespie"},{id:"190390",title:"Dr.",name:"Pippa",surname:"Burns",slug:"pippa-burns",fullName:"Pippa Burns"},{id:"190391",title:"Dr.",name:"Judy",surname:"Mullan",slug:"judy-mullan",fullName:"Judy Mullan"},{id:"190392",title:"Dr.",name:"Lindsey",surname:"Harrison",slug:"lindsey-harrison",fullName:"Lindsey Harrison"},{id:"190393",title:"Dr.",name:"Amanda",surname:"Baker",slug:"amanda-baker",fullName:"Amanda Baker"},{id:"190394",title:"Dr.",name:"Khin",surname:"Win",slug:"khin-win",fullName:"Khin Win"},{id:"190395",title:"Dr.",name:"Victoria",surname:"Traynor",slug:"victoria-traynor",fullName:"Victoria Traynor"}],corrections:null},{id:"52044",title:"Diabetes Mellitus and Depression as Risk Factors for Dementia: SADEM Study",doi:"10.5772/64678",slug:"diabetes-mellitus-and-depression-as-risk-factors-for-dementia-sadem-study",totalDownloads:1524,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Aim: 3Evidence indicates that the comorbidity of dementia with diabetes and depression may affect most cognitive functions. Our chief interest was to examine the patterns of cognitive functioning in individuals diagnosed with dementia, diabetes, and depression as compared with dementia plus diabetes (DDM), or dementia plus depression (DD) and healthy controls.",signatures:"Juárez‐Cedillo Teresa, Hsiung Ging‐Yuek, Sepehry A. Amir, Beattie\nB. Lynn, Jacova Claudia and Escobedo de la Peña Jorge",downloadPdfUrl:"/chapter/pdf-download/52044",previewPdfUrl:"/chapter/pdf-preview/52044",authors:[{id:"183147",title:"Dr.",name:"Teresa",surname:"Juarez-Cedillo",slug:"teresa-juarez-cedillo",fullName:"Teresa Juarez-Cedillo"},{id:"187568",title:"Dr.",name:"Ging-Yuek",surname:"Hsiung",slug:"ging-yuek-hsiung",fullName:"Ging-Yuek Hsiung"},{id:"187569",title:"Dr.",name:"Amir",surname:"Sepehry",slug:"amir-sepehry",fullName:"Amir Sepehry"},{id:"187570",title:"MSc.",name:"B. Lynn",surname:"Beattie",slug:"b.-lynn-beattie",fullName:"B. Lynn Beattie"},{id:"187571",title:"Dr.",name:"Claudia",surname:"Jacova",slug:"claudia-jacova",fullName:"Claudia Jacova"},{id:"187572",title:"Dr.",name:"Jorge",surname:"Escobedo De La Peña",slug:"jorge-escobedo-de-la-pena",fullName:"Jorge Escobedo De La Peña"}],corrections:null},{id:"51311",title:"Idiopathic Normal Pressure Hydrocephalus: An Overview of Pathophysiology, Clinical Features, Diagnosis and Treatment",doi:"10.5772/64198",slug:"idiopathic-normal-pressure-hydrocephalus-an-overview-of-pathophysiology-clinical-features-diagnosis-",totalDownloads:2987,totalCrossrefCites:2,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Normal pressure hydrocephalus is characterised by the triad of gait disturbance, dementia and urinary incontinence. Although our understanding of the condition has considerably improved since it was initially described over 50 years ago, its pathophysiology is still a matter of debate. We provide an overview of the current concepts in pathophysiology and discuss the clinical features, diagnosis and treatment of this cause of dementia.",signatures:"Rubesh Gooriah and Ashok Raman",downloadPdfUrl:"/chapter/pdf-download/51311",previewPdfUrl:"/chapter/pdf-preview/51311",authors:[{id:"183615",title:"Dr.",name:"Rubesh",surname:"Gooriah",slug:"rubesh-gooriah",fullName:"Rubesh Gooriah"},{id:"367770",title:"Dr.",name:"Ashok",surname:"Raman",slug:"ashok-raman",fullName:"Ashok Raman"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"673",title:"Dyslexia",subtitle:"A Comprehensive and International Approach",isOpenForSubmission:!1,hash:"9a88d127d035ab53de96a00f9ed407ba",slug:"dyslexia-a-comprehensive-and-international-approach",bookSignature:"Taeko N. Wydell and Liory Fern-Pollak",coverURL:"https://cdn.intechopen.com/books/images_new/673.jpg",editedByType:"Edited by",editors:[{id:"87489",title:"Prof.",name:"Taeko",surname:"Wydell",slug:"taeko-wydell",fullName:"Taeko Wydell"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"2646",title:"Visual Cortex",subtitle:"Current Status and Perspectives",isOpenForSubmission:!1,hash:"8a5632344dfe9b3f0153eeee84a6ea83",slug:"visual-cortex-current-status-and-perspectives",bookSignature:"Stephane Molotchnikoff and Jean Rouat",coverURL:"https://cdn.intechopen.com/books/images_new/2646.jpg",editedByType:"Edited by",editors:[{id:"145800",title:"Prof.",name:"Stephane",surname:"Molotchnikoff",slug:"stephane-molotchnikoff",fullName:"Stephane Molotchnikoff"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"2604",title:"Basal Ganglia",subtitle:"An Integrative View",isOpenForSubmission:!1,hash:"76d19f809182eea657ce36eb4817c5b8",slug:"basal-ganglia-an-integrative-view",bookSignature:"Fernando A. Barrios and Clemens Bauer",coverURL:"https://cdn.intechopen.com/books/images_new/2604.jpg",editedByType:"Edited by",editors:[{id:"147924",title:"Dr.",name:"Fernando A.",surname:"Barrios",slug:"fernando-a.-barrios",fullName:"Fernando A. 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The tasks are meant to satisfy specific needs as desired by Man. In a most general form therefore, human needs satisfaction, requiring tasks to be done in a mechanised way, are the primary drivers of MED [2]. These needs could be anything from physical, such as moving between places ‘X’ and ‘Y’, to thermal comfort as in air-conditioning, to egoistic and futuristic as in imagining being part of a generation that sends human species out of the solar system, etc. It is evident that these need-drivers can be diverse and very complex: sometimes, they may neither be directly related to ordinary science, nor to normal expressions of art. Yet, the systems which have to do the tasks are physical. They are regulated by laws of Physics and Mathematics—whether known, or yet to be discovered. Moreover, they are expressed in artistic form to appeal to potential users and handlers. This marks the first hurdle in MED: to relate the obscure needs to as yet, inexistent systems. At engineering student level, this is perhaps the greatest challenge. We shall shortly see why this chapter symbolically refers to it as a ‘mountain’.
Physically, mechanical systems consist of materials—shaped, sized and connected in such a way that energy can be input at certain points to cause desirable changes at other points within the system [3]. ‘Desirable’ here, means the ‘changes’ at those other points positively contribute to satisfaction of needs. The simplest identifiable material in the system is called a machine element. The contribution in most systems is through several groups of connections of elements, called mechanisms, which in turn are also interconnected to form the total system, or machine. Therefore, MED has to consider selection of materials for the elements, sources of input energy, and transformations of this energy within the machines being designed. Prior education and training of mechanical engineering students tends to prepare them quite well for this part of MED. This is especially so, because MED, as a subject, is normally taught later in their studies, after they have done a fair amount of engineering science subject modules. Hence, many undergraduate MED curricula tend to focus on design of individual machine elements, as typified in Refs. [4, 5, 6], and in text books [7, 8, 9]. Necessary and convenient as this may be, it creates a mental comfort zone for students that tends to further disable them from connecting the obscure human needs to the very machine elements they may be studying. They are in one valley of comfort, while the needs are in another. An invisible mountain separates the two valleys. How do we make that mountain visible—and how do we help students ascend, and then descend it? Those are the two questions addressed in this chapter.
MED is not simply the identification of needs, and inventing or conceptualising machines to satisfy those needs. In a world of ever increasing scarcity of both materials and readily exploitable energy resources, and where many other engineering designers are competing to satisfy the same needs—possibly in different ways, MED has to include a consideration of alternative and/or complementary designs. The alternatives have to be compared with, and contrasted against, each other on well-defined criteria. Complementary designs may be necessary to extend market outreach. To the extent that these comparisons and contrasts can be modelled mathematically, and analytical optimisation procedures carried out, engineering students have little difficulty in this area. However, careful consideration of needs, gives rise to two questions. One is on extents to which the needs are likely to be met; the other is on how infrequently and for how long in a given period, they are not likely to be met. The first of these concerns, contributes to quality of the design. The second leads to reliability. These two areas are probabilistic and are less familiar to students than the physical or ‘functionality’ part of MED. Along with them, come others characterised by chaos. These include marketability, effects on and by the environment, etc. All these issues (Functionality, Quality, Reliability, Marketability, Safety and Environmental, etc.) have to be planned for in the design. Finally, the design has to be persuasively communicated.
The endpoint of MED has traditionally been sets of detailed engineering drawings [10]. Today however, it may, in addition include: a set of simulations and their results, a working physical model, a working prototype and a series of oral and written presentations. This author considers that as much as possible, mechanical engineering students should not be let to end designs at drawings alone. This is because at their stage of professional development, they have not yet mustered sufficient insights on manufacturing and assembly processes to give error-free manufacturing drawings for workshop personnel to make and assemble satisfactory machines. The author finds that—requiring and guiding them to translate their drawings into models or working prototypes, greatly helps them improve their overall design and manufacturing abilities. More importantly, drawings, and simulations, do not produce the same level of satisfaction and self-confidence building as a finished working model or a prototype. One case in this chapter illustrates the principle of ending with a working prototype while the other, builds on a similarly finished student project.
The remainder of the chapter is therefore arranged as follows: we begin with a quick description of engineering analysis, to which, most MED students and practitioners are used, and in which, they easily find a comfort zone. Then, as a point of departure, we present a sample of industry design processes as reported in the literature. In Section 3, we present two cases: one is by the author, on design evolution of a hydro mechanism he invented in 2015. The second is by a physically challenged student, building on previous work. The originality and contribution of this chapter is in demonstrating an alternative method of delivering MED courses in order to quicken nurturing of innovation and creativity among mechanical engineering undergraduates. In the conclusion section, we summarise the differences between the two delivery approaches.
In this section, we first present the current state of handling MED at undergraduate level. We show it as being biased towards engineering analysis, rather than to the more desirable engineering synthesis. In the second and third subsections, we turn to how engineers in industry do MED. In one, we debrief the reader on processes, while in the other, we describe recorded methods.
Engineering analysis works on an existing system, which may be real or virtual in form. It applies already known laws of science and engineering to check both functionality and feasibility—if virtual. By functionality is meant, a ‘YES’ to the question: does this system do what it is intended to do? Feasibility means—a high (acceptable—in the circumstances) probability that the imagined system can be made and that, after then, it will be functional. The applicable laws of science consist of the virtually ‘inviolable’ and universal principles (within limits of present knowledge) of Physics and Chemistry, usually, but not always, as explained by Mathematics. In mechanical and chemical engineering, for example, laws of motion and of thermodynamics are good examples [11, 12]. So are those of electric and magnetic circuitry, and of logic systems in electrical and electronic engineering [13], etc. The second group—i.e., of engineering—however, are not necessarily inviolable. Nor do they have to be universal. They are practice—based. These engineering practice principles distinguish the engineering professional from the physical scientist in ways similar to how a medical doctor is different from a biologist, or an agriculturalist from a botanist. In mechanical engineering, such principles include those of making parts of the system; joining and assembling into subsystems, and finally into the finished system. Then, there are principles related to system usage, e.g., legality, cost, safety, security and environmental impacts, etc. It is clear that both the making and usage principles can vary from place to place and with era, depending on levels of development and acceptability in the societies where the systems are to be made or used.
In countries like South Africa, Botswana and Kenya, where pre-university education consists of 12 years at ‘primary’ and ‘secondary’ levels [14, 15, 16], University engineering curricula tend to start off with a consolidation of physical science and mathematical principles, and are then, in mechanical engineering, followed by an introduction to ‘making’ principles. In others like Nigeria, Uganda and Zimbabwe, the consolidation starts before admission to university in a so called ‘Advanced’ level of education [17, 18, 19]. Here, the mechanical engineering student starts off at a slightly higher level, is introduced to engineering communication, and to other essential branches like electrical and materials engineering in addition to some of the ‘making’ principles. MED in either case is introduced later, with analysis of virtual systems.
Even when real systems like engines, motor vehicles, home use machines, etc. are available, they are rarely analysed as whole systems because universities tend to compartmentalise knowledge. For example, in the case of a car engine, the student would have to draw on learnings from ‘experts’ in Thermodynamics, Mechanics of Machines, Fluid Mechanics, Materials & Manufacturing Engineering, Environmental Science, Electrical/Electronics, etc. These ‘experts’ would have taught the respective ‘knowledge compartments’ most generally, often, not even mentioning the engine. For the average student, integration of these ‘compartments’ in MED can be a very difficult first step to make, up the symbolic mountain mentioned earlier.
The usage principles occasionally come superficially in some final year projects. Even then however, the current approach to MED fails to motivate creativity in part, because it deals with already existing systems, whether imaginary or not. We can accept that it can lead to innovation as when an existing system is modified substantially to perform the same function ‘better’ or to perform others it originally was not intended for. We still note however, that limitations can be imposed by an insufficient grasp of the usage principles. To summarise therefore: to the extent that current treatment of MED at universities is theoretical analysis—driven, relying on existing systems and with limited concern for usage, it stunts both innovation and creativity. The intent of this chapter is to advocate and demonstrate a reversal of that approach, and align it with the practice in industry so that on one hand, students appreciate MED better, and on the other, they can find it easier to settle in industrial practice after they leave campus. Figure 1 shows the two approaches, side by side.
(a) Current and (b) proposed teaching and learning MED approaches.
In industrial practice, design approaches have been formalised to ensure as much detail on user requirements and on limiting constraints are taken care of, to get as cost effective (or profitable) a safe and marketable product as can be achieved. Figure 2 shows some of the recommended processes in the literature. They all have the following characteristics [20, 21, 22, 23, 24, 25, 26]:
They start with a ‘needs’ identification, followed by problem formulation. This means: ‘needs’, and hence usage principles—but not analysis, drive the process.
They involve many solutions to the same problem. This means: in different circumstances, any other solution could be appropriate—much unlike in the current class room analysis driven approach.
They are highly iterative. This indicates incorporation of a trial and error methodology, quite unfamiliar to, and unappreciated by engineering students.
In the cyclic processes, there is no definite endpoint. The working product at step 8 is to be continuously improved upon, depending on emerging constraints and needs.
Four examples of formal MED processes in industry.
Nigel Cross [21] classifies engineering design methods used in the processes of Figure 2 into two major complementary groups: the creative, and the rational ones. The former are characterised by their ability to stimulate thought processes, removing mental blockages and widening areas of search for solutions to the design problem. The latter on the other hand, systematically examine different issues at each stage of the processes in Section 2.2, also eventually solving the same problem. It is reported that some creative people detest the latter approaches because of their apparent prescriptive nature. Many others however, find the rational approaches most helpful, even complementary to the creative ones. Tables 1 and 2 summarise methods in these two groups of approaches.
Method | Comments |
---|---|
Brain storming | Best in a group, where each individual can make as many suggestions as quickly come to mind, irrespective of their apparent merits/demerits. |
Synectics | Requires drawing parallels between quite unrelated events or things, preferably by people in a group discussion, to open up brain cells interconnection channels that can more easily lead to a solution. |
Search space enlargement | Redefines the spectrum in which solution is sought. This can be assisted by: questioning the basis of the problem; random actions and making parallels of their effects to the problem on hand; dialectical reasoning, etc. |
Spark of moment | Needs individual to have been thinking about the problem for some time—as in solution of plastic-latex jointing in Section 3.1 below. |
Summary of creative engineering design methods.
Process | Methods | Comments |
---|---|---|
Identifying market needs | Market research and analysis | Build product objectives tree as ordered sets of targets to be achieved, in order to satisfy market needs in the prevailing circumstances. |
Formulating product functions | Function analysis | Looks at the objectives tree, then determines overall function of the product to meet the objectives. The function is further decomposed into sub functions and then, possible mechanical components are identified to do, and, to integrate these sub functions. Limits on what can be done are imposed in form of a system boundary. |
Specifying product attributes | Performance specification | Determined from functions, independent of possible solutions—considering that different products, types and features could provide the same functions. Pahl and Beitz [27] checklist can be used to define attributes that should preferably be quantified in range form, to give a specification. |
Synthesizing alternative concepts | Brain storming | As in creative engineering methods. |
Morphological charting | Components for each sub-function in function analysis are tabulated and then, different combinations of these tried, to give different products having the same overall functionality. | |
Evaluating alternative solutions | Weighted objectives | Each feasible concept is considered for its relative position on each objective. Then summation of weighted scores guides selection. The problem however, is that ordinal scaling can result. This must be changed to interval value scaling. |
Pugh’s evaluation matrix [28] | A benchmark concept is chosen. The others are compared with it in turn for each objective on a −1, 0, +1 scale. Totals for each objective, are multiplied by a weighting factor, and then sums of scores for each concept, computed. The bench mark concept scores zero while the best one is that, scoring highest. | |
Detail design and construction | Drawings | This step involves sketches of layouts for different concepts; assembly and detailed drawings of components of the selected concept. |
Prototyping | May exist in four forms [20]: Mock-ups, Models, Prototypes, and Virtual—CAD generated systems. Experimentation is done on the first three while simulations are done on virtual ones. | |
Improving the optimized solution | Value engineering | Re-examines the selected concept with intent of either reducing delivery cost—without losing functionality, or increasing value and utility to the customer, or both. |
Summary of rational engineering design methods.
We will now illustrate two cases of using some of the above approaches in an academic—rather than—an industrial environment. The first case is by the author himself. It exemplifies the creative design approach, and addresses an issue in solar energy engineering, of maximising useful energy yields from a flat-surfaced solar energy harnessing device. The second case shows a rational design approach, as taught to students in attempt to change MED from an analysis driven course, to a synthesis driven one. It builds on student knowledge gained from designing and constructing a multispeed fluid mixing vessel. The student designs a system for essential oils extraction from African herbs.
A new hydro-mechanism for interconverting linear and rotary motion was invented—and is described in a South African patent by the Cape Peninsula University of Technology (CPUT) [29]. The primary motive of the invention was to create a mechanism that would be deployed in a novel single axis sun tracking device that relied on mechanical energy to turn a domestic home solar energy collecting surface during the day, and return it to a morning position any time before daybreak. Figure 3 shows the mechanism being used in conjunction with a photovoltaic panel.
The hydro mechanism driving a sun tracking PV panel (watch online video at:
The approach used was a slight modification of the Remo Reuben open process in Figure 2. There was branching at the stage of evaluating alternative concepts, which led to other, very different products altogether—discussed in Refs. [30, 31].
A need for a new single axis sun tracking device, suitable for sub-Saharan Africa conditions of bi-hemispherical location, low credit and disposable incomes, and an inadequate technical skill base had been established in Ref. [32].
The product design problem and its sub problems were defined as: “Design a single axis sun tracking mechanism and its coupling means to a domestic home flat solar collector, so that the latter will be able to receive more energy from the sun, and therefore through the appropriate conversion process, yield more output than when in a fixed orientation.”
The sub problems, imposed by constraints discovered during identification of the ‘Need’ were:
What would be the source(s) of energy in the mechanism?
What motion transformations would the mechanism have to effect—and by which machine elements?
How would the motion transformation be controlled, and how much energy would be required for both transformation and control?
Which materials and manufacturing/assembly methods would be used to make and install the mechanism?
What operational and maintenance tasks would be expected of the owner/user?
Many solutions were investigated. Some were tried up to manufacture stage, and then discarded. Here, only significant ones are described in chronological order up to the prototype milestone. The reasons for discarding or modifying them are given.
A STH powered, spring controlled system was envisaged as in Figure 4. A hydraulic head
Concept number 1: solar-thermal-hydraulic (STH) system.
In due course, the liquid in tank ‘
This concept required use of a low boiling point, low enthalpy of evaporation but high density liquid. The low enthalpy would give sufficient daily solar assisted evaporation rates while the high density would enable storage of enough mechanical energy to compress the spring and turn a collector whose centre of gravity would most likely be offset from the axis of rotation. Such a liquid was actually identified among the refrigerants (R140a) but it was expensive in Cape Town. Being a chloro-hydro-carbon (CH3-CCl3), it was banned in some African countries. Although there were other issues, this alone was sufficient to disqualify the concept. However, many of its elements were carried to the next concept.
After discarding the concept of using a chloro-hydrocarbon, water was considered. The immediate problem however, was that it was less dense and had a much lower vapour pressure at the envisaged working temperatures. Most importantly, its enthalpy of evaporation was an order of magnitude higher than that of R140a. These limitations were to be overcome in a series of solutions—still using STH principles (i.e., evaporate the liquid, raise it to some height and condense it there to provide a head that will reset the mechanism at the end of the day). A summary of the salient ‘solutions’ up to the time the STH system was discarded is given below.
Evacuation of the system so that the boiling point could be lowered significantly to say, below 60°C. This was in attempt to raise the vapour pressure at a working temperature of between 30 and 40°C in the evaporator tank ‘
A redesign of the evaporator ‘
A redesign of the condenser tank ‘
A redesign of the mechanical linear to rotary motion inter-conversion system. A light weight semi cylindrical rack was to be in rectilinear motion, atop a rigid stem. The stem was to be attached to the spring loaded piston. The rack would then drive a fixed axis spur gear, mounted on the solar collector’s axis of rotation (Figure 5). For locations say in the southern hemisphere, one side of the rack would be used. The other half would be used in the northern hemisphere, where the orientation of the axis and relative position of evaporator would have to be switched to still enable east to west day tracking. In this way, no internal readjustments would be necessary, if the device was moved across the equator.
The last of the STH concepts.
Figure 5 illustrates the mechanism at this stage. The mechanical valves have also been replaced with solenoid valves by now.
STH systems had been attractive mainly because they looked novel and relied entirely on ‘free’ solar energy for their operation most of the time. They had a simple backup plan of burning biomass in case of cloudy days. The evaporator, the vapour evacuation system, the cylinder-piston-spring assembly were designed and constructed. A 200 mm × 200 mm × 100 mm aluminium block for manufacture of the semi cylindrical rack was also purchased. Meanwhile, a separate experiment to verify findings of a theoretical analysis on water evaporation rate yields in an evacuated collector gave ‘unwanted’ results. Whereas water seemed to evaporate fast enough at the low pressures, most of the vapour re-condensed on the collector glazing and in the evacuation piping before reaching the condenser. It was clear that a more elaborate evacuation system would have to be used if STH were to progress further.
A second ‘unwanted’ result came from the workshop. Machining of the cylindrical rack in the CNC workshop encountered problems when the purchased block was being resized for actual machining (it had not been exactly 200 mm × 200 mm × 100 mm). These problems forced a re-examination of the ‘needs’ of Section 3.1.2. It became apparent that the manufacturing problems being encountered, together with the possibility of vacuum leaks in the field would make the product not only ‘too expensive’, but would also affect its reliability. Moreover, as seen in Figure 5, the mechanism would be bulky, and perhaps less marketable than substitutes which could come on the scene later. Thus, STH on this product was discarded. Use was however to be made of almost all components and learnings from it in this and other off shoot products.
Although STH was now out of the question, the idea of a hydraulic head provided by an oversized 100 L condenser in Figure 5 still remained attractive. The condenser had intentionally been oversized to provide sufficient heat transfer area, and also to hold reserve water in case of bad weather and inability to light a fire under the evaporator for whatever reason. The piston-cylinder assembly had been designed to discharge about 5 L a day—which would have easily been evaporated by energy incident on a 1.8 m × 1.2 m collection surface. It was therefore reasoned that with 100 L initially filled into the condenser tank (by whatever means), there could be a 20 day pumping head capacity to reset the mechanism at night. The 50 L tank of Figure 4 was also revisited to hold daily discharges from the mechanism. This would therefore hold slightly more than a week’s discharge (as it could not be filled to capacity). This, at last seemed to settle the hydraulics part—if only the cylindrical rack could be made. It was not made.
Because of manufacturing difficulties mentioned above, the aluminium rack design was reconsidered. Moreover, in absence of the evaporator, the stem sticking out of part of the cylinder looked neither a safe nor an aesthetically ‘correct’ design. Therefore, it was decided to use an ordinary straight rack-gear set completely housed within the cylinder. The rack would now be part of the piston rod, while the gear shaft axis would be fixed. The gear shaft would protrude slightly out of the cylinder to connect to the collector shaft. Minding about the ‘Needs’ in Section 3.1.2 on deployment anywhere in sub-Saharan Africa and the now user-inaccessible gearing, the gear shaft was to be standardized as horizontal, normal to the cylinder axis. Variable slope collector shaft axes for different locations were to be joined to this horizontal shaft with a Hooke coupling. Bi-hemispherical installation was to be facilitated by a double rack-gear set such as shown in Figure 6.
Reorientation of the hydro-mechanism.
This selection of elements would affect the geometry of the mechanism-collector connection of Figure 5. Either the collector would have to be lowered, or a horizontally oriented spring-piston-cylinder assembly would need to be raised. The former was considered impractical because a collector-ground clearance must be maintained during all phases of rotation of the collector. The latter was considered aesthetically unsound and required more ground space to effect. Therefore, the orientation of the cylinder was now changed to vertical as in Figure 6.
At this stage, it was supposed that the 3.5+ m high tank could be installed either on a roof or on a stand provided with properly constructed ladders for filling and inspections. In rural Africa, once about 20 days, the owner or her/his agent would have to climb up and refill it. At the university however, experimentation in the project required a safer and smarter way of filling the tank. The ‘Needs’ constraints of Section 3.1.2 specified a ‘negligible’ energy consumption by operation of the mechanism. Since tank filling would be occasional, a small 12 V DC 4 m peak head pump was acquired. Then for experiments, only one tank (‘B’ of Figure 6) would be necessary. The pump would be used to transfer water from this tank to the mechanism. In addition to being safe, this would conserve water since it could be recycled on daily basis.
The mechanism was now ready for prototyping. The machine elements and components were assembled. First attempts to run it were made in March 2015. Water leaked past the piston. To properly seal the leakage, it would be necessary to reduce clearances. A new piston with an elastomer O-ring was made. Sealing was achieved but friction was excessive. A lot of pump energy went into overcoming this friction. Then in one re assembly, a forceful push onto the piston burst the cylinder. Figure 7 shows the broken piece. It was now evident that the engineering necessary to produce an efficient and reliable piston-cylinder assembly would easily ‘violate’ the ‘cost effectiveness’ constraint in Section 3.1.2, and probably consume more than ‘negligible’ energy in operation. The assembly had to be redesigned.
Example of failure during the project.
Friction between the cylinder and the piston was the main problem in the assembly. It was therefore decided to eliminate direct contact between the piston and the cylinder. Bellows were introduced. One end of the bellow was fixed to the lower base of the cylinder while the other was fixed to a smaller diameter piston. It was supposed that water would progressively fill the bellow segments starting with the lowest, and in so doing, gradually lift the piston-spring ensemble without any significant friction with the cylinder. The first bellow tried was made from a 150 mm diameter heli-steel PVC hose. It was readily available and ‘reasonably’ priced at just below the equivalent of US$ 5.00 a meter length. It however, failed on trial. When water filled the first segments, they expanded radially before attempting to lift the piston. Even after lift-off, the expansion continued until the steel was beginning to tear out. Attempts were made on using a thicker and stronger rubber bellow made by a local rubber products moulder. It also failed. It was clear that for the bellows to be of use in this project, they would have to be restrained radially—which in the circumstances, was not feasible. They were abandoned, but lessons on need for radial restraint were to serve a breakthrough purpose soon.
Bellows failed because they were not restrained radially. Even if they had not failed, it was difficult to tell what would happen to the joints at the base in rural Africa over a prolonged period of intermittent pressurization. It was therefore decided to contain the mechanism water in a flexible liquid sac or bladder that would be completely restrained and protected by a much stiffer, though flexible covering. The active part of the bladder would be an inverted cone frustum grown on a lower normal frustum which in turn, would have grown on a cylindrical portion matching the internal surface and base of the mechanism cylinder. The cylindrical and lower cone frustum would always be with water. Pumping would only affect the upper frustum which would be closed by a permanently joined and sealed piston. The piston would carry a small bleed pipe as shown in Figure 8. The primary purpose of this pipe would be to help expel air from the system on first fill.
The prototype bladder: (a) un-protected and (b) when protected.
The bladder and its protective covers were constructed and assembled in the mechanism. The system was then test run. At long last, it was able to reach its design peak compression on 2nd July 2015. But the time to reach maximum displacement was in excess of 2 min. Also, towards that endpoint, the 10.8 W pump was drawing maximum current. The top mechanism end cap was removed so that the mechanism could be filled with water against the spring and piston weights only. It took about 20 s to reach the top dead centre position. On opening valve
This case study is about a project which started off as one of the many group projects in normal class time, intended to overcome the familiar ‘analysis-synthesis’ barrier in undergraduate MED. A group of six students had initially been tasked and guided to design and construct a variable temperature and viscosity fluids mixer for a home-cottage cosmetics factory within a period of 6 weeks. The mixer is shown in Figure 9. After the project, one of the students was involved in a serious road accident which disabled him, and prevented him from doing the normal pre graduation industrial attachment. To enable him graduate however, he was assigned a new individual design project under supervision of the author at the university. He was to use his experience in the class project, to design (not construct) a herbal oil extractor, again for a home cottage factory. Below is a summary of his design approach.
A home cottage industry ‘Two speed’ fluids mixer—as designed by MED students left—the assembled unit. Right—the counter-rotating slow speed mechanism (Watch online video at:
A machine needed to be designed for use in extraction of essential oils from African herbs. A full design with drawings (mechanical, electrical and hydraulic) was to be completed so that students could manufacture and test the machine.
Handles 200 L with 30% spare capacity.
Filtered liquid product must be extracted separately from the spent herbs.
The extraction temperature must be between 70 and 80°C.
Operates on domestic single phase 220–240 V AC power supply.
Feed herbs are received cut into pieces smaller than 10 mm in length.
Professional and pleasing appearance
Students must be able to manufacture all custom designed parts in the CPUT mechanical engineering workshop.
The student considered five concepts as shown in Figure 10. He settled for concept number 3 on account of ease of manufacture, minimal heating element corrosion risks, and maximum heat transfer area, thereby reducing heating time.
Herbal oil extraction: different heating concepts [
Having selected the mode of heating for the herbs, the student laid out the design as in Figure 11. Then he did a detailed analysis of the chosen concept in virtual form to give specifications in Table 3, followed by detailed engineering drawings of each machine element in the system.
System layout for a small scale herbal oil extractor.
Overall dimensions (mm) | Height | Length | Width | Power at 240 V AC (W) | Heater | Motor | Pump | Total |
---|---|---|---|---|---|---|---|---|
1478 | 1660 | 930 | 4000 | 180 | 260 | 4400 | ||
Motor Specs | Type | Manufacturer | Code | Power (W) | Torque (Nm) | Speed (rpm) | Output speed (rpm) | |
Worm geared | SEF | SF37DRK7154 | 180 | 70 | 1450 | 15 | ||
Heater | Power (W) | Manufacturer | Code | Pump | Head (m) | Power (W) | Max flow (L/s) | |
4000 | Thermon | UHRBC14K00350N1 | 2.75 | 260 | 2 | |||
Temperatures (°C) | Heater max. | Vessel max | Materials | Heater | Vessel | Insulation | Frame | |
90 | 70 | SS316 | SS316 | Thermalite Glass wool | MS |
Key specifications of components for a 200 L herbal oil extractor for a home cottage factory.
In this chapter, we have described and illustrated MED from both a classroom perspective and from an industrial one. In undergraduate MED, emphasis is on ability to analyse existing systems. The student is taught MED on a machine element by element basis—and most contact hours are spent that way. There is little room and time to integrate the elements in one worked example or problem. Moreover, those elements from other areas of mechanical engineering, such as in Thermo-Fluids, are normally assumed to be well covered in those subjects. They are rarely given consideration in normal MED class rooms. This is not to mention the even more critical considerations of non-science related issues which, in the first place, are often, the source of problems to be solved by engineering. It has been argued in this chapter that this treatment acclimatises the student to always be expectant of readymade systems to analyse. Even then, understanding how the systems came into being, as answers to specific human needs, can be problematic. This is a disservice to the student and to industry, because the main purpose of MED is supposed to be synthesis of mechanical systems, speaking to the needs of society.
Industry on the other hand, has no choice but to face the design challenge from a problem solution perspective. All areas of knowledge, be they from science, art, or even heuristic and intuition, are brought to bear on the problem. Market, economic, political, legal, social, aesthetic and ordinary engineering constraints are imposed on an inexistent system that is supposed to be created and made. Two largely complementary approaches of doing so were reviewed: the creative, and the rational. It was seen that the rational approach formalises the design process and tends to take care of more constraints a design may be encountering. It is thus advisable, even of creative designers to embrace it. In engineering classrooms, it is without a doubt, the recommended approach.
Two design examples were described in a university setting environment. One was primarily of creative nature, leading to an invention over a long period of time. However, whether consciously or otherwise, it was still tempered with some formality in form of a structured approach between different design stages. The main advantage of this approach seemed to be the generation of other offshoot products arising from apparent failures within the creative process. In essence, therefore, creativity can lead to many other originally unintended, but useful products. The second example was focused on the rational approach—as taught to the author’s students. A physically handicapped student was able to demonstrate that he had learned the methodology by designing a product quite related to what he had learnt—and participated in building in class, while still physically fit. Importantly, he demonstrated good understanding of the integrative nature of MED, calling on subject content from diverse areas like Fluid Mechanics, Heat transfer, Electrical Technology, Economics, etc. Moreover, the problem to be solved required him to appreciate compositions of some naturally occurring plants and means of getting useful extracts from them. Such extensive exposure is not normal in MED as commonly taught/learnt.
To conclude the chapter, it could be said that—although the traditional approach of handling MED is helpful in so far as it breaks up the subject matter into smaller, easier to learn, topics, it makes it more difficult for students, and possibly academics, to apply that knowledge to solve real life engineering design problems. This author recommends a mixed approach whereby, early on in the study of MED, the current topic-based system is used but a formalised needs-driven design approach is gradually introduced until it becomes the dominant approach by the time the student is finishing her/his MED subjects. Table 4 summarises the salient differences in approach.
Traditional | Proposed | |
---|---|---|
Content | MED as extension of Engineering Science Low involvement of issues in Humanities | MED as new body of knowledge, using GEPs*, Design codes, catalogues, standards, etc. Elements from Humanities primarily drive most of MED and even, regulate it |
Modelling | Simplified mathematical models and physical science phenomena | Mathematical and non-math models to deal with science and non-science constraints in design optimization |
Learning | Study of independent machine elements | Less time on independent elements, but more on their interdependence in an assembly |
Design process | Element to assembly design approach (down-up) | Assembly to element design approach (top-down) |
Emphasis | Engineering and scientific novelty | Problem solution as simply, safely and economically as possible |
Outputs | Engineering drawings | Working models and/or prototypes |
Summary of differences between the current and proposed MED teaching approaches.
Good engineering practice principles
It is to be understood here, that we are not talking about the final year design project, typical in many engineering schools and faculties. No—it is the timetabled MED we are referring to. The new approach not only works, but it produces tangible results as demonstrated in this chapter. It should therefore, as much as possible, be adopted.
The work in case No. 1 was funded by Cape Peninsula University of Technology Research Fund, through research account RK23.
The author’s interest in this, and other related work, is driven by an insatiable desire to make students realise that by their last year of undergraduate study, they can already have an inner ability to start contributing to make their societies live better now, and not wait for tomorrow.
The author thanks his student, Riel Haupt, for his drive and courage even after the almost fatal accident. Special thanks go to Riel’s parents for supporting him.
Chitin and chitosan belong to the polymeric materials of natural origin from the polysaccharides group. The widely used polysaccharides of natural origin also include cellulose and derivatives of hyaluronic and alginic acid. Use for the production of medical devices (contact with the patient’s body), makes them meet several requirements: they should maintain their physicochemical properties after treatment at elevated temperature during sterilization, after exposure to X-ray, detergents and aseptic. Polysaccharide biopolymers, like most polymeric materials, degrade after some time of use, so it is also important that their decomposition products do not cause inflammation, allergic or immune reactions or any other interactions with patients’ bodies.
Chitin is a polysaccharide composed of N-acetylglucosamine residues linked by β-1,4-glycosidic bonds. Chitin is the main component of the fungal walls and the shells of arthropods (crustaceans, insects, and arachnids), but is also present in sponges, corals, and mollusks. However, for laboratory and industrial purposes, it is obtained mainly from marine invertebrates such as: crabs, shrimps, lobsters and krill. The properties of chitin depend on its origin. Chitin used in the production of medical devices must come from certified, controlled fisheries and must be properly purified. The methods of isolating chitin from natural sources are strictly dependent on the choice of the organism from which it is isolated. This polysaccharide is similar in structure to cellulose. It differs in the presence of an acetyl amide group (-NHCOCH3) in place of one of the hydroxyl groups (Figure 1). The presence of this group means that there are much stronger intermolecular hydrogen bonds in chitin, which results in its greater mechanical strength compared to cellulose [1, 2].
Structural resemblance of cellulose, chitin and chitosan.
Depending on the origin source, chitin can occur in three amorphous forms: α, β and γ [2, 3]. The most widespread is α chitin found in fungi, shells of crustaceans and krill, and the skeletons of insects. The β form, which can mainly be isolated from squids, is much less common. The differences in the crystal structure of both amorphous forms of chitin affect their processing capabilities. The ordered crystal structure of chitin limits its solubility in commonly used solvents, and thus, reduces its use in industry. α-Chitin is moderately soluble in aqueous thiourea solution, aqueous alkaline urea solution, 5% LiCl/DMAC, some ionic liquids, hexafluoroacetone, hexafluoro-2-propanol, methanesulfonic acid [4, 5]. The form of β-chitin, on the other hand, swells in water (forms a suspension) and is soluble in formic acid. Chitin has no cytotoxic effect
Despite the very good biological properties of chitin, its practical use is moderate, which is related to its low solubility causing difficulties in its processing. Therefore, chitin is used as a raw material to obtain new derivatives with better performance parameters. In terms of practical use, the most important chitin derivatives are its esters and chitosan, which is a product of chitin deacetylation, which can be classified into the group of amino-polysaccharides.
The esterification of chitin hydroxyl groups allows to increase the utility potential of the polysaccharide by introducing various substituents, and thus, influencing the physical, chemical and biological properties of materials. The best known are chitin esters, in which the hydroxyl groups are esterified with one type of acylating reagent (presence of the same ester groups on both hydroxyl groups of chitin). Acetylated chitin derivatives (CH3CO- substituent) are prepared with acetic anhydride in the presence of an acid catalyst. However, the physicochemical properties conditioning the processing of chitin acetate turned out to be unsatisfactory [12]. The use of a mixture of orthophosphoric acid and trifluoroacetic acid anhydride as a catalyst allowed to obtain a variety of chitin esters derived from: butyric acid, cyclopropanecarboxylic acid, cyclobutanecarboxylic acid, cyclopentanecarboxylic acid, cyclohexanecarboxylic acid and substituted benzoic acids. In the case of chitin butyrate, the process efficiency (DS (degree of substitution) included in the range 1.9–2.38) was dependent on the excess of butyric acid anhydride use [13, 14, 15]. Di-butyrylchitin (chitin di-butyrate, DBC) is an example of a chitin derivative soluble in typical organic solvents [16]. DBC is obtained by chitin esterification with butyric anhydride. Typically, it is a two-stage process. In the first step, chitin is purified from calcium salts with 2 M hydrochloric acid. The next stage is the process of proper esterification of purified chitin. The substrates of the reaction, apart from chitin, are butyric anhydride and the catalyst, which is most often chloric (VII) acid. The reaction is carried out in a heterogeneous system by adding powdered chitin in appropriate proportions to the reaction mixture consisting of butyric anhydride and chloric (VII) acid. The classical esterification process requires the use of substrates in a molar ratio of acid anhydride to N-acetylaminoglucose unit of 10: 1. It is also crucial to carry out the reaction at a temperature of 20°C. Increasing the reaction temperature to 40°C causes a rapid lowering of the molecular weight of the modified polymer. The catalyst concentration has a direct influence on the efficiency of the esterification reaction. The yield of the reaction is the higher when more concentrated chloric (VII) acid is used. However, it should be remembered that the use of too much concentrated chloric (VII) acid results in the macromolecule degradation. The esterification process is completed by adding diethyl ether to the reaction mixture. The isolated product is then heated with water to remove residual chloric (VII) acid. The product obtained in this way is treated for 24 hours with acetone, in which only di-butyrylchitin is dissolved. Then, the solution is concentrated to 5–6%. After the desired concentration is reached, the solution is poured into deionized water to precipitate the polymer, then the product is dried to obtain solid di-butyryl chitin. The above-described process of chitin esterification allows the conversion of free hydroxyl groups on the C3 and C6 carbon of the chitin into ester groups (CH3(CH2)2CO- substituent). Di-butyrylchitin is composed of di-butyl-N-acetyl-amino-glucose units linked by 1,4-β-glycosidic bonds. The polymer is stabilized by hydrogen bonds between the polymer chains. Hydrogen bonds are formed with the participation of the hydrogen atom from the acetylamino group and the oxygen atom from the ester group. This kind of intermolecular interaction determines its good mechanical properties [12, 13, 14, 15]. Di-butyrylchitin does not dissolve and does not swell in water, but it dissolves in many organic solvents such as: acetone, methanol, ethanol, tetrahydrofuran (THF), dimethylformamide (DMF), chloroform, methylene chloride and others. Di-butyryl chitin is not easily degraded, it is resistant to γ-radiation (possibility of radiation sterilization), while enzymatic degradation under the influence of lysozyme and CE econase occurs at a slow rate, which causes a slight change in molecular weight. Di-butyrylchitin with a molecular weight above 100000 Da has film-forming and fiber-forming properties [1, 2, 12, 13, 14, 15]. Thus, obtaining DBC with the desired molecular weights directly determines its further processing capabilities (in particular electrospinning and leaching). The most important biological parameters of di-butyrylchitin are: prolongation of blood clotting time and good wettability. The use of DBC dressings has a positive effect on the granulation process (increasing the level of glycosaminoglycans in the wound), collagen cross-linking (generating more durable tissue), accelerating the wound healing process to form a healthy epidermis without scarring and protecting the wound against excessive moisture loss (optimal moist environment) [1, 2, 6, 7, 8, 9, 10, 11]. In the course of treatment, the dressing slowly bio-degrades and resorbs until it disappears completely, which eliminates the painful act of changing it. The spontaneous, anti-pain effect of the dressing was also noted. DBC does not show cytotoxicity or irritation, it is a biocompatible polymer [9]. Di-butyrylchitin fibers are obtained by two methods: wet and dry-wet. The choice of the method used determines the structure of the obtained fibers. The fibers obtained in the wet-spinning process are less regular in shape, with a greater surface development than in the case of dry-wet spinning. DBC fibers produced by wet spinning are used as a raw material for the production of nonwovens. The technique of producing nonwovens from DBC depends on cutting the fibers into 6 cm long sections, from which the fleece is produced using a mechanical method on carding machines, and then the fibers in the fleece are joined by needling and calendaring [16, 17].
The dry-wet method of forming fibers from DBC hinges on preparing a spinning solution with a concentration of 15 to 25% in ethanol, heating it to 60°C and squeezing it through a spinning die. Then, the incompletely solidified fiber is introduced into a water bath, where it is completely solidified. The fiber is then wound onto drums, stretched, and dried. A microporous DBC fiber with a linear mass of 1.7 to 5.6 g is obtained, depending on the concentration of the spinning solution used. The fibers obtained by the dry method have an elongated and curved cross-sectional shape, similar to a croissant. The degree of crystallinity of the fibers determined in X-ray examinations is similar in both methods and amounts to approx. 19%, and the transverse dimension of the crystallites approx. 23 Å. It is also easy to obtain chitin materials (the so-called regenerated chitin) from these materials without damaging their macro-structure after a mild alkaline treatment. Fibers made of regenerated chitin and di-butyrylchitin do not induce cytotoxic, haemolytic or irritating effects and cause minimal local tissue reaction after implantation [17, 18, 19]. Di-butyrylchitin and regenerated chitin fibers can be used to obtain dry dressing materials, as well as materials for other biomedical purposes. DBC-based woven dressings are biodegradable within the wound and do not need to be replaced during use [16, 17]. Chitin di-pentanoate (chitin divalerate, Di-O-Valeryl-Chitin, DVCH) is also used for the production of commercially available dressings, where chitin is esterified with two valeryl groups (CH3(CH2)3CO- substituent) at the 3 and 6 positions of N-acetylglucosamine units. The high degree of DVCH esterification was achieved by using a large excess of valeric anhydride used both as acylating agent and reaction medium, and perchloric acid as catalyst. It turned out to be optimal to conduct the reaction where the molar ratio of valeric acid anhydride to chitin was 7:1, which also facilitated thorough mixing of the components during the reaction and temperature control. The performance of the reaction under conditions of high homogeneity of the solution has a great influence on the quality of the product. Insufficient mixing of the solution during the acylation step led to a local temperature rise, uneven chitin acylation and ultimately resulted in products with varying degrees of esterification and higher polydispersity. Additionally, at elevated temperature it was observed reduction of the molecular weight of the biopolymer as a result of the acidic degradation of chitin that occurs in parallel with the acylation reaction in the presence of a strong acid. To obtain products with a high degree of esterification, 0.5 M perchloric acid was used (deacetylation of the N-acetyl group was not observed). The separation of the raw product from the reaction mixture takes place during the neutralization of the valeric acid excess with a 2.5% NaHCO3 solution. The use of sodium bicarbonate as a weak base prevents deacetylation of the N-acetyl group. Depending on the reaction time and temperature, products with different parameters are obtained. The lower temperature leads to a product with a higher molecular weight. A longer reaction time increases the yield of the reaction, but is associated with a reduction in molecular weight due to acidic degradation of the polymer. The DVCH polydispersity index ranged from 1.47 to 2.06, suggesting a low molecular weight distribution. Due to the good solubility of DVCH in organic solvents such as acetone or ethanol, it is possible to prepare thin polymer layers by casting or porous structures by salt leaching. The DVCH shows a semi-ductile behavior and breaks when it exceeds the yield point. The stretching properties of DVCH films depend on the molecular weight. The modulus, yield stress, tensile stress as well as strain at break increase continuously with increasing DVCH molecular weight. The increase in the modulus with molecular weight results in higher mechanical strength of DVCH films. The elongation at break, although slightly increases with increasing molecular weight, remains low, not exceeding 4%. As a consequence, the higher DVCH molecular weight is, it behaves like a stiff plastic that can withstand relatively high stresses but does not withstand high elongation before breakage. Using the salt leach method, it is also possible to develop porous materials from DVCH. The structure of porous DVCH-based materials consists of a unified network of interconnected channels. This structure is characterized by a high content of open pores of various sizes. Two pore populations can be distinguished: large with a size in the range 150–780 μm (average pore size approx. 435 μm ± 168 μm) and small with a size in the range of 4–22 μm (average pore size 7.7 μm ± 3.3 μm [16, 17, 18, 19]. Chitin divalerate is a technologically friendly biopolymer. The good solubility of DVCH in organic solvents (ethanol, DMAC, DMSO, acetone) due to the presence of hydrophobic valeryl groups in C-3 and C-6 positions enables its easy processing of its particles. The DVCH maintains the film-forming ability of chitin, so it can easily be used in the production of threads, films, foams and scaffolds, as well as non-woven fabrics. Biological data show that DVCH is not cytotoxic to fibroblasts and does not cause irritation or allergy to the skin of animals [20]. For the synthesis of chitin dihexanoate (DHCH) it is also possible to use appropriate acid anhydrides and methanesulfonic acid as a catalyst. In order to increase the homogeneity of the solution and better control the temperature in the process, by analogy to the synthesis of the valerate ester, an excess of acid anhydride and methanesulfonic acid are used, the mixture being the reagents and the reaction medium. Optimal methanesulfonic acid to chitin molar ratios are 16:1 and 10:1 for chitin di-hexanoate and chitin di-butyrate, respectively. This approach will result in a high degree of substitution of hydroxyl groups, equal to almost 2, and a low polydispersity. Moreover, under optimal conditions, no hydrolysis of the N-acetyl bond was observed. Good chitin solubility in methanesulfonic acid, even at low temperatures, allows the esterification process to be carried out under milder conditions. The key parameter is the intensity of agitation of the reaction suspension. Insufficient heat transfer due to poor mixing of the solution, similar to the synthesis of chitin di-pentanoate, leads to a lower degree of esterification, high polydispersity of the final product and a reduction in molecular weight. The neutralization process is carried out with a 4% sodium bicarbonate solution. The synthesis of DBC at a low temperature and short reaction time (temperature 0°C and 8°C) is ineffective due to the low reaction yields and possibly incomplete esterification of the chitin hydroxyl groups, resulting in the formation of a significant amount of insoluble gel fractions when dissolved in acetone prior to precipitation with water. For DHCH, it is preferable to use low synthesis temperatures (0°C and 8°C). The yield of DHCH synthesis was relatively high (above 70%), with the highest efficiency observed at 21°C (84 to 95%). Unfortunately, carrying out the synthesis of DHCH at 21°C resulted in a low molecular weight product. A trend analogous to that of chitin di-pentanoate was observed, indicating that the longer the reaction time, the higher the reaction performance and the lower the molecular weight of the obtained biopolymers. Although in DHCH the hydroxyl groups of chitin are substituted with longer alkyl chains than in DVCH or DBC, it has been found that DHCH retains good solubility in solvents such as ethanol, acetone, dichloromethane, 1,2-dichloroethane, N,N-dimethylformamide, N,N-dimethylacetamide and ethyl acetate and no solubility in water. Good solubility, filmogenic and fiber-forming properties of DHCH give greater possibilities of its processing (film casting, washing method, electrospinning method) compared to chitin alone. The mechanical properties of DHCH and DBC in the form of thin solid layers poured from solution were investigated in relation to their molecular weights. DHCH and DBC showed semi-continuous properties and cracked rapidly upon exceeding the plasticity point, similar to that observed for DVCH. The elongation at break was small and did not exceed 4%. For both biopolymers, their tensile properties correlate with the molecular weight. Parameters such as modulus of elasticity, stress at yield, as well as stress and strain at break, were found to increase with increasing DHCH and DBC molecular weight. Comparing the mechanical properties of DHCH, DBC and DVCH, it can be concluded that Young’s modulus decreases with increasing chain length of the acyl group of chitin diesters (a similar relationship is observed for chitin monoesters, where only one hydroxyl group is acylated). Due to the good solubility of hydrophobic chitin diesters in organic solvents and their insolubility in water, it is possible to obtain porous structures based on DHCH and DBC by using the salt leaching method. The prepared porous materials are characterized by a united network of interconnected channels and a high degree of open porosity with pores of various sizes (pore size in the range 78–421 μm, average pore size 253 μm ± 93 μm) [21, 22, 23, 24]. Due to its physic-chemical properties, DHCH can successfully replace or support materials based on di-butyrylchitin (e.g. in the form of mixtures of both biopolymers) and thus it can be used as a material for medical and pharmaceutical applications, especially in tissue engineering scaffolds and in healing wounds. The described procedure of chitin esterification to obtain products of high purity. Moreover, this method is universal (the possibility of preparation various chitin diesters) and is easy to produce and is not time-consuming [21]. Another method of chemical modification of chitin is esterification leading to carboxymethylchitin (CMCht, CM-chitin) [22, 23] or dicarboxymethylchitin using monochloroacetic or mono-chloropropionic acid followed by substitution of halogen with a hydroxyl group. This modification leads to the loss of the supramolecular structure of chitin and the formation of water-soluble derivatives [24].
The presence of two hydroxyl groups at the C-3 and C-6 positions of chitin allows the introduction of two different acyl substituents, leading to the formation of mixed esters (co-esters) of chitin. This possibility is also due to the differential reactivity of the hydroxyl groups linked to the primary and secondary carbon atoms in chitin. Thus, under ideal conditions, it is possible to obtain mixed esters containing the same molar fraction of different acyl groups in the modified material. Different ester groups (e.g., butyric and acetic acid residues) are present in mixed esters in a single polysaccharide chain. The replacement of some large bulky butyl groups with much smaller acetate groups in one polysaccharide chain causes that in a condensed state, it becomes possible to obtain favorable conditions for the formation of intermolecular bonds of the hydrogen bridge type. This effect cannot be expected when using a mixture of two different biopolymers (e.g. chitin diacetate and chitin di-butyrate). Thus, the term mixed polymers is not the same as mixed chitin esters. In order to obtain a polymer mixture, it is necessary to use at least two chemically different polymers (Figure 2). In contrast mixed ester/co-ester of chitin contains only one component. It was found that the differences between chitin mixed esters (co-esters) and a mixture of two species can be observed in NMR spectra (1H and 13C) (Figures 3 and 4). The studies used 50:50 butyryl-acetyl-chitin co-polyester (
Chemical structure of chitin di-acetate, chitin di-butyrate, butyryl-acetyl chitin co-polyester (mixture ester, co-ester).
Fragments of 13C-NMR spectra of
Fragments of 1H-NMR spectra of
A comparative analysis of the 13C-NMR spectra of the 180–150 ppm range characteristic for the chemical shifts of carbon in carboxylic acid derivatives showed that the distribution in the mixed ester of chitin
Comparative studies of 1H-NMR spectra in the range of chemical shifts 2.5 ppm to 0.5 ppm also allowed to state that in the case of butyryl-acetyl chitin co-polyesters (samples
The possibility of forming the intermolecular hydrogen bonds that stabilize butyryl-acetyl chitin co-polyester structure translates into fiber-forming properties, and thus the possibility of modulating the functional properties of the final materials and their use in the manufacture of new materials for medical use. In addition to stabilization by hydrogen bonds, it is also possible to create weak interactions based on hydrophobic interactions. The participation of such various weak interactions in the stabilization of materials may translate into their ability to interact with both hydrophobic and hydrophilic structures, which affects biological activity.
Acetate-formate mixed chitin ester was obtained using formic acid, acetic anhydride and trifluoroacetic acid as a catalyst [25]. It turned out that this ester is slightly soluble in typical organic solvents. This is one of the reasons why this derivative has not found practical use, even though its biological properties are comparable to those of chitin. A similar situation was observed in the case of trifluoroacetate-formate derivatives of chitin [26].
Attempts to obtain a mixed butyric acetic ester of chitin by reaction using acetic and butyric anhydrides and methanesulfonic acid or trifluoroacetic acid as catalysts have been unsuccessful. The final product was a mixture of chitin acetate, chitin butyrate and the expected acetate-butyrate of chitin [27, 28].
The approach to synthesize mixed chitin esters using a mixture of trifluoroacetic acid and the corresponding organic acid as catalysts also led to the formation of mixtures of chitin monoesters and mixed esters (co-polyesters) of chitin. It has been shown that carrying out the reaction at the temperature of 70°C for a short time (30 min) under homogeneous conditions allows for obtaining co-polyesters: acetate-butyrate, acetate-hexanoate, acetate-octanoate and acetate-palmitate of chitin. The final co-polyesters have molecular weights ranging from 30 to 150 kDa and the degree of esterification ranging from 1.0 to 2.0, depending on the raw materials used.
Another approach to obtain mixed butyryl-acetyl esters of chitin [29] is based on the use of butyric and acetic acid anhydrides and methanesulfonic acid as a catalyst. However, this method is not very friendly from the point of view of industrial stoppage. Thinking about the industrial synthesis of the butyryl-acetyl chitin derivative, it was necessary to establish reaction conditions that would eliminate the need to use methanesulfonic acid.
In the works on the development of a method for the production of the butyryl-acetyl chitin co-polyester on an industrial scale, it was necessary to develop, in the first stage, the conditions for the synthesis on a laboratory scale, which would later be transferred to an industrial scale. The esterification in laboratory conditions is carried out under heterogeneous conditions at 20-25°C, using chloric (VI) acid as a catalyst and a mixture of butyric and acetic acid anhydrides, used in a molar ratio of 90:10 [22, 23]. The product was obtained with a yield of 82 to 89% is soluble in DMF, DMSO and NMP, has a high molar mass (intrinsic viscosity of these products determined in DMF at the level of 2.0–2.05 dL/g) and a full degree of esterification. In the research on the development of a method of producing butyryl-acetyl chitin co-polyester in industrial conditions it was crucial to eliminate the possibility of formation an explosive mixture which may arise as a result of direct contact of acetic anhydride with perchloric acid. It turned out that the priority was to use an efficient cooling system so that the process temperature did not exceed 20°C. In laboratory conditions, it was sufficient to use an ice-water bath with NaCl (brine bath) and intensive mixing of the suspension. In laboratory conditions, diethyl ether is added to the slurry to remove excess unreacted anhydrides and formed carboxylic acids and the crude product is filtered off. The crude acetylation product is washed with water and dilute ammonia water, dried and finally dissolved in ethanol. The transfer of the conditions from the laboratory scale to the macro scale did not involve only increasing the amount of reagents and the size of the synthesizer. The key was to optimize the process conditions and the use of reagents that can be used in industrial conditions from the point of view of safety, environmental impact and economics. A reactor with a capacity of 60 dm3 with an effective cooling system was used. A 3 kg chitin input was used for the synthesis. The remaining reagents (2 dm3 of perchloric acid, 15 dm3 of butyric anhydride and 1 dm3 of acetic anhydride) were added in portions. The time required for all reagents to be introduced and for complete conversion was about 24 h. In place of diethyl ether, under industrial conditions, ethyl acetate was used to remove excess unreacted butyric and acetic anhydrides. In industrial conditions it was also necessary to replace the ammonia water to neutralize the acetic and butyric acid residues. It turned out that it is possible to use sodium carbonate for this purpose. Also, the step of separation of raw product required changes in the industrial process. In the synthesis under laboratory conditions, G4 Schott funnels were used for filtration. However, the use of this method on a large scale was ineffective. So suction filtration was used, the efficiency of which was 100 dm3 per hour. The process efficiency on an industrial scale was comparable to that of a laboratory scale synthesis. The physical and chemical properties of the final products were also comparable. The conducted research guaranteed the reproducible and required parameters of the raw material for the production of new medical materials [22, 23]. Figure 5 shows a set for the synthesis of butyryl-acetyl chitin co-polyester on an industrial scale.
Set for the synthesis of butyryl-acetyl chitin co-polyester on an industrial scale.
The development of an efficient synthesis of the butyryl-acetyl chitin co-polyester (BAC 90/10) made it possible to demonstrate that the obtained chitin derivative has the ability to form fibers from a wet solution with a strength slightly above 20 cN/tex with high porosity. Fibers with a strength at this level can be the basis for the production of 3D polymer-fiber composites. BAC 90/10 fibers show a stronger predisposition to apatite crystallization; strong sorption tendencies of fibers allowing the possibility of local supersaturation favoring the nucleation of apatite. It has been also found that BAC 90/10 fibers degrade fast under
One application of the butyryl-acetyl chitin co-polyester (BAC 90/10) is its use to produce highly porous film materials [30].
The research work began with laboratory tests during which two methods of formation of porous materials were tested: (a) pouring a 5% ethanol BAC 90/10 solution on a layer of solid inorganic salt (porophor agent), which, after solidification, was exposed to water to wash out the porophor agent, and (b) the use of porophor agent suspensions in BAC 90/10 solution, which was a mixture of solvents with a density close to the bulk density of the porophor agent. Various organic and inorganic salts (K2CO3, KHCO3, KHSO4, KNO2, (NH4)2CO3, (NH4)HCO3, (NH4)2HPO4, (NH4)2SO4, Na2CO3, NaHCO3, Na2HPO4, Na2S2O3 x 5H2O, NaCl, di-ammonium citrate, di-ammonium oxalate were tested. It was found that all tested salts can be used as porophors. However, the most optimal porophor agent, in terms of porosity (95–99%) and tensile strength of 5 cN, was NaCl.
Based on laboratory work, it was possible to start work on optimizing the production of porous dressing materials (Medisorb R, Medisorb R Ag). In the industrial method, solid NaCl as porophor agents and a 3% solution of BAC 90/10 in ethanol were used. The membrane was formed by pouring a 3% solution of BAC 90/10 onto a layer of porophor agent to produce a spongy structure. After drying, the membrane is rinsed in distilled water at 40°C until the porophor agent is washed off. The product is then dried at 80°C. After packing, the obtained membrane dressings are subjected to a process of radiation sterilization (in the case of the variant without the addition of an antibacterial substance). To obtain a silver-coated membrane, the membrane is sprayed with a suspension of metallic silver dispersed in water by means of a spray nozzle. The silver particles are evenly distributed in the suspension using an ultrasonic device. After drying and then packing, the product is subjected to radiation sterilization. The powder dressing is obtained by grinding the byturyl-acetyl chitin co-polyester, which is then sterilized by radiation [23, 31]. Figure 6 shows a scheme for the preparation of porous dressings based on butyryl-acetyl chitin co-polyester.
A scheme for the preparation of porous dressings based on butyryl-acetyl chitin co-polyester.
Dressing materials obtained by leaching salt from butyryl-acetyl chitin co-polyester (BAC 90/10) and sodium chloride with a diameter of 0.16–0.40 nm and/or microsilver were characterized by a high degree of porosity, pore size in the range of 275–305 nm and a degree of crystallinity in the range of 27.2–27.4%. SEM tests confirmed the porous structure of pores, which are negative for the crystals of the inorganic porophor agent used. In addition, the pores are open pores, which increases the effectiveness of water adsorption. Figure 7 shows microscopic picture of porous structures obtained by the porophor agent washout method.
Microscopic picture of porous structures obtained by the porophor agent washout method.
Dressings made of butyryl-acetyl chitin co-polyester (Figure 8) are intended for wounds of various etiologies, including chronic wounds, where the healing process is disturbed by comorbidities. In order to accelerate the healing of deep wounds, a dressing in the form of a backfill has been designed. Wounds are often accompanied by a bacterial infection, therefore, apart from the dressing in the form of a membrane made of chitin co-polyester only, there is also a variant containing the addition of silver, showing a bactericidal effect in the wound environment. Silver may appear in various forms, however, it has been assumed that only the ionic form of silver has a bactericidal effect. Any other form of silver must be converted to its ionic form. Hence, metallic silver with a small particle size after oxidation and hydrolysis is characterized by the highest antibacterial activity. Silver in ionic form also has the ability to interact with proteins. It has been found that the ionic form of silver has a higher protein binding capacity compared to nanoparticles [32, 33, 34, 35, 36].
Picture of porous structures obtained by the porophor agent washout method.
The presence of pores and microcapillaries in the structure of membrane dressings allows drainage of wound exudate. Dressings made on the basis of chitin co-polyesters are characterized by high biocompatibility. Biological tests confirmed the lack of cytotoxic, irritating and allergenic effects. These dressings are degraded in the subcutaneous tissue and gradually become smaller. The dressing shortens and weakens the exudative phase, drains the wound and accelerates the productive phase. The epithelialization process under the butyryl-acetyl chitin co-polyester was completed faster compared to the control sample [37].
FTIR ATR analysis was made for samples of untreated Medisorb R dressings and material treated with fresh human plasma in order to test the dressing surface degradation and protein absorption on the dressing surface. Comparing spectra of samples treated with fresh human plasma and pure material, the decreasing of intensity of the vibration band of C=O at 1733 cm−1 in relation to the amide I signal at 1659 cm−1 was observed. It confirmed the sample surface degradation, which was connected to the hydrolysis of ester BAC 90/10 groups. In the
The developed biodegradable dressings based on butyryl-acetyl chitin co-polyester were subjected to clinical evaluation using a wide range of patients. The use of dressings significantly accelerated the wound healing process caused by venous insufficiency and diabetes, also in patients whose healing process was disturbed by comorbidities. The improvement of the clinical condition of the wound depends on the individual patient and is most often observed after 30–60 days. The obtained results indicate that the tested dressings significantly reduce the time of wound healing. Medisorb R Ag is more effective than Medisorb R Membrane in the treatment of infected wounds. The powder form (Medisorb R Powder) allows the application of the dressing to deeper wounds. Thanks to their unique structure, dressings drain wound exudates beyond its environment, thus restoring the proper course of the cell reconstruction process. The ability to biodegrade in contact with the wound secretion eliminates the need to replace dressings, so the newly formed granulation tissue is not disturbed - cell reconstruction processes run smoothly [38].
Chitosan is obtained as a result of the hydrolysis of chitin N-acetylamide groups (partial deacetylation of chitin). The main advantage of chitosan is its much better solubility in aqueous acid solutions, especially organic acids. Chitin deacetylation by chemical or enzymatic methods allows for obtaining materials with various degrees of hydrolysis (Figure 9). However, it is assumed that at least 50% chitin deacetylation is necessary for the material to be classified as chitosan. The degree of deacetylation (DD) is defined as the ratio of the number of free NH2 groups to the initial number of NHCOCH3 groups present in chitin and is presented in the equation:
Chitosan formation from chitin by chitin deacetylation.
where N - the number of specific units (structural units) in the polymer.
The value of DD affects the biological and physicochemical properties of the polymer, such as solubility, swelling and stability, as well as reactivity.
Chitosan obtained by chemical (concentrated NaOH) or enzymatic (chitin deacetylase) deacetylation of chitin. The first step of preparation of chitosan is mechanical grinding of the raw chitin, and subsequent process of removing proteins, color compounds and inorganic salts takes place. The deproteinization process is usually performed with a dilute aqueous solution of sodium hydroxide at an elevated temperature [4, 5]. For protein removing also proteolytic enzymes were used [39, 40], but in the case of papain, trypsin and chymotrypsin, it was found that they did not completely remove the protein fraction. After deproteinization process, the residue is treated with dilute aqueous hydrochloric acid to dissolve the calcium carbonate. A similar effect can be obtained by using HCOOH, HNO3, H2SO4 or EDTA [5]. The decolorization process is based on extraction with ethanol, acetone or treatment with oxidizing reagents (KMnO4, NaOCl, H2O2). These activities allow to obtain chitin of required purity for its further transformation into chitosan. Chitosan from chitin obtained by chemical deacetylation is obtained at high temperature (above 100°C), under high pressure and in the presence of concentrated (40–50%) strong bases (usually NaOH). A typical industrial chitosan production process provides almost complete recovery of proteins, calcium oxide or calcium carbonate, carotenoid pigments and sodium acetate under the conditions of using sodium hydroxide as the deacetylating agent. However, this process has several disadvantages. It is not environmentally friendly as it consumes a large amount of energy and is also difficult to control leading to a heterogeneous product. The use of chitin deacetylase for the production of chitosan oligomers and polymers can potentially eliminate most of these drawbacks [41]. The advantages of enzymatic deacetylation are more pronounced in the processing of chitin oligomers, as these substrates are soluble in the aqueous medium and are therefore more susceptible to enzymes. The downside is the high cost of the enzyme and the requirement to use pre-processed chitin. The conditions of the chitin deacetylation process have a significant impact on the distribution of N-acetyl-D-glucosamine and D-glucosamine groups in the polysaccharide chain. Their location in the chain has a significant impact on the physicochemical properties of the material, such as crystallinity, solubility and susceptibility to degradation [3]. Depending on the final use, chitosan can be formed into a hydrogel, membranes, fibers, sponges and micro/nanoparticles [42].
Chitosan is a polysaccharide composed of randomly distributed acetylated and deacetylated units of D-glucosamine. Chitosan exists in five different crystal forms, four of which are hydrated and one is anhydrous. Microcrystalline chitosan is characterized by better biodegradability and bioactivity.
Most of the properties of chitosan depend on two parameters: degree of deacetylation and molecular weight distribution. Depending on the source and method of preparation, the deacetylation degree varies from 30 to 95%, and the molecular weight from 300 to over 1000 kDa [43]. The solubility of chitosan strongly depends on the deacetylation degree, which translates into the number of free amino groups. Chitosan is soluble in acidic solutions due to its susceptibility to protonation and formation of ammonium salts. It is soluble in acetic, formic, citric, lactic and hydrochloric acid and insoluble in most organic solvents. Chitosan, as a biodegradable polymer, is easily broken down by microorganisms into simple chemical compounds such as carbon dioxide (CO2) and ammonia (NH3). Like other biopolymers, it is susceptible to many chemical and physical factors leading to its degradation. The degradation process also depends on the degree of deacetylation and the molecular weight of the polymer [3, 5].
Chitosan has many valuable properties, such as: biocompatibility, biodegradability, non-toxicity, the ability to create polycations in an acidic environment, the possibility of modification, high affinity for metals, dyes and proteins, hydrophilicity, ability to create membranes and others [3, 5, 44]. These features make it applicable in medicine and pharmacy, in various industries, in environmental protection, including water treatment and separation processes. [5, 45, 46]. Chitosan also has a number of properties that limit its use in certain areas. It swells strongly in water (especially in an acidic environment), and in the swollen state it is characterized by low mechanical strength. The use of chitosan is also limited due to its high viscosity. The reduction of the viscosity of chitosan solutions can be achieved by increasing the deacetylation degree while reducing the molecular weight and increasing the temperature or ionic strength [5, 47]. The key problem with the use of chitosan is its susceptibility to external factors (humidity and temperature) and processing conditions (heating or sterilization), which can affect its structure and cause its degradation. Parameters such as molecular weight or the presence of impurities have a significant impact on the processing of chitosan [48]. This causes difficulties in maintaining the stability of chitosan (no changes in molecular weight) for a long time at room temperature [49]. The influence of many factors, such as increased temperature, the presence of strong acids, mechanical shear or radiation, on the molecular weight of chitosan was demonstrated. It is also believed that high molecular weight chitosan is more stable. The lack of reproducibility in the processing of chitosan is also due to significant differences in molecular weight, deacetylation degree and purity level depending on the source of the raw material. The level of chitosan purity may affect both biological properties, such as biodegradability or immunogenicity, as well as its solubility and stability [48, 50].
Chitosan is a non-toxic polysaccharide containing randomly distributed acetylated and deacetylated units of D-glucosamine. The results of many studies confirm the antibacterial effect of chitosan. The mechanism explaining this feature is unknown [51]. The antimicrobial activity of chitosan is strongly dependent on many factors, such as molecular weight [52], degree of deacetylation (DD), pH of the dissolving medium and its ionic strength. Stronger antibacterial activity was observed with a high degree of deacetylation [53] and a low molecular weight of chitosan [54]. The antibacterial activity of chitosan is also associated with the form of the polymer (hydrogels, membranes, dissolved form) and the presence of other compounds [55]. One of the factors responsible for the antibacterial activity of chitosan is its cationic nature. The positively charged ammonium groups of chitosan may interact with negatively charged components of the bacterial cell wall, causing damage to the cell membrane and destruction of bacterial cells (a mechanism proposed for high molecular weight chitosan) [56]. Ultimately, this causes the formation of an impermeable layer around the bacterial cell, affecting permeability and transport to the cell [57, 58]. It has been suggested that low molecular weight chitosan can penetrate bacterial cell walls and eventually enter the cytoplasm and bind to DNA affecting DNA transcription, mRNA synthesis and finally protein biosynthesis [59].
The difference in the hydrophilicity and the negative charge of the cell surface of the bacteria makes gram-negative bacteria interact more strongly with chitosan, resulting in higher antibacterial activity against them.
The antibacterial activity of chitosan or its derivatives on gram-negative bacteria has been demonstrated for various strains:
The antifungal activity of chitosan also depends on its molecular weight and degree of acetylation. It was found that chitosan shows antifungal activity against selected phytopathogenic fungi
The antiviral activity of chitosan derivatives is also suggested. The research focuses mainly on HIV. Peptide-chitosan conjugates (GlnMetTrp-chitosan and TrpMetGln-chitosan) show a protective effect on C8166 cells by counteracting the cytolytic effects of the HIV-1RF strain. These derivatives have the ability to suppress HIV-induced syncytium formation and reduce HIV load without inhibiting HIV-1 reverse transcriptase and protease
Recent studies have shown that chitosan and its derivatives exhibit anti-tumor activity in both
Various biological properties of chitosan also include good adhesion to cells, macrophage activation, stimulation of fibroblast proliferation, stimulation of cytokinin production, stimulation of type IV collagen synthesis, promoting angiogenesis processes, haemostatic properties [92, 93, 94, 95]. Moreover, it has a positive effect on granulation and epithelialization, and reduces scar formation. It is believed that many of the listed biological activities of chitosan are related to its unique feature, namely its cationic nature. Chitosan molecules with a positive charge interact with negatively charged erythrocytes and thrombocytes activating the extrinsic coagulation, effectively stopping bleeding.
Chemical modification of chitosan allows to modulate the biological activity of chitosan, for example, heparin inactivation or antiviral activity. Chitosan can be in the form of: gel, sponge, fiber or porous composition with ceramics, collagen or gelatin. Chitosan is used as a component of wound healing dressings, while in the case of scaffolds, it is usually used with other natural polymers (hyaluronic acid, alginic acid, poly-L-lactidic acid, elastin, collagen, gelatin) or additives (hydroxyapatite, calcium phosphate, ceramic components) [95, 96, 97].
Chitosan increases the inflow of phagocytic cells (segmented granulocytes and macrophages) to the site of infection, stimulates the migration and proliferation of endothelial cells and fibroblasts. The effect of chitosan on the proliferation of fibroblasts depends on the degree of deacetylation and molecular weight. Forms with a higher degree of deacetylation and lower molecular weight stimulate fibroblast proliferation to a greater extent [98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123]. Chitosan is widely researched for its use in bone and cartilage reconstruction. It has the ability to create porous structures, which makes it used in tissue engineering, orthopedics and bone regeneration. It has also been used in drug delivery systems or therapeutic substances (DNA plasmids, siRNA, nanosilver), for the production of surgical sutures, wound healing dressings and artificial internal organs [124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150].
An interesting chitosan feature is also its ability to bind with mucus and cross epithelial barriers, so that its use as an adjuvant or auxiliary adjuvant in vaccines is considered. It is also included among the auxiliary substances that enable the preparation of various forms of drugs with specific properties.
It is an excellent metal ion complexing agent. This parameter is useful due to the immobilization of metal ions with antibacterial activity and enabling their controlled release, depending on the needs [97].
Chitosan can also be an environmentally friendly agent used to obtain textiles with antibacterial properties. Attempts were made to introduce chitosan powder into cotton and polyester-cotton fabric. Chitosan was introduced after the fabric surface was activated by 20% NaOH. The performed studies confirmed that chitosan is well implemented in fabrics made of a cotton and polyester/cotton blend [151].
Due to its physicochemical and biological properties, chitosan and its derivatives are considered to be versatile biomaterials with various biological activities [152, 153, 154, 155, 156, 157, 158, 159].
Chitosan and its derivatives as materials with antimicrobial activity and low immunogenicity are widely used in wound healing. They provide a three-dimensional matrix for tissue growth, activate macrophages and stimulate cell proliferation [160]. Chitosan improves the activity of polymorphonuclear leukocytes, macrophages and fibroblasts, which increase granulation and organization of repaired tissues [161]. Its degradation to N-acetyl-β-D-glucosamine stimulates the proliferation of fibroblasts, supports regular collagen deposition, and also stimulates the synthesis of hyaluronic acid at the wound site. These properties accelerate healing and prevent scarring [162]. The development of chitosan formation in the form of nanofibers with the assumed adhesive properties allowed to obtain a material useful for the creation of dressing materials [163]. Chitosan nanofibers obtained by electrospinning method are porous, have high tensile strength, large surface area combined with an ideal rate of water vapor and oxygen transfer. They are also compatible with stem cells derived from adipose tissue, which is beneficial for wound healing [164, 165].
A characteristic feature of chitosan dressings is their ability to effectively control bleeding [166]. The most important element of hemostasis is blood clotting, which leads to the formation of a clot consisting mainly of the fibrin network and platelets embedded in it. This process prevents further loss of fluid and electrolytes from the wound and reduces contamination of the wound. There is erythema around the wound, swelling, pain and locally increased temperature. Inflammation widens local blood vessels, which facilitates the penetration of macrophage cells and fibroblasts into the wound, which cleanse the wound of tissue residues, vascular clots and pathogenic bacteria. In the next phase of healing, fibroblasts synthesize collagen and other proteins needed to build and regenerate connective tissue and rebuild damaged blood vessels. In the course of scar formation, type III collagen fibers transform into type I collagen until they reach the balance characteristic of healthy skin and are necessary to restore skin continuity. The final remodeling process leads to a significant increase in the mechanical strength of the wound. The haemostatic effect of chitosan has been clearly documented. Chitosan in the form of a non-woven fabric has a positive effect on each stage of wound healing. The unique features of chitosan include: macrophage activation, stimulation of fibroblast proliferation, absorption of growth factors, stimulation of cytokinin production, stimulation of type IV collagen synthesis, support for angiogenesis processes, antibacterial and hemostatic properties. The positive effect of chitosan on granulation tissue, epidermis and reduction of scar formation has been proven. Like chitin, chitosan is susceptible to enzymatic biodegradation which produces biologically active oligosaccharides. The positively charged chitosan molecules react with negatively charged erythrocytes and thrombocytes to activate the external clotting pathway and effectively block bleeding. At the same time, chitosan can serve as a carrier of specific medicinal substances (DNA plasmids, siRNA, nanosilver particles), which enhance its positive effect on the healing process. Chitosan has also been found to significantly increase the adhesion and aggregation of platelets in the process of hemostasis [167, 168].
Currently, there are many chitosan materials available on the market that are used to heal wounds in patients undergoing plastic surgery [169], skin grafting [170, 171] and endoscopic sinus surgery [172]. Chitosan-containing materials in the form of nonwovens, nanofibers, composites, films and sponges are: HemCon®, GuardaCare®, ChitoFlex®, ChitoGauze®, Celox™ Granules, Celox™ Gauze, Chito-Seal™, Clo-SurPLUS PAD Tegasorb™, Tegaderm™ ChiGel, ChitopackC®, and TraumaStat™ [173, 174, 175, 176].
Haemostatic dressings also include Tromboguard® - a multi-layer dressing made of three layers: semi-permeable polyurethane foil, hydrophilic polyurethane foam, and a layer containing chitosan. The film layer protects the dressing against seepage, allowing the wound environment to remain moist, ensuring optimal air permeability to its interior and creating a barrier against external factors. Polyurethane foam is a load-bearing layer and has strong absorbent properties thanks to the “pore-in-pore” structure. The polyurethane layer is responsible for storing exudate and keeping it outside the wound surface, ensuring adequate wound moisture. Additionally, it is a layer that protects the wound against mechanical damage.
The active layer, which is created by a unique composition of chitosan and alginates, activates the blood coagulation process, significantly reducing bleeding time. By reacting on the wound surface with erythro- and thrombocytes, chitosan significantly shortens the bleeding time. Calcium alginate accelerates the natural clotting process, and sodium alginate - by absorbing wound discharge - creates a layer of gel on the surface of the dressing that prevents it from sticking to the wound. Alginates are resorbable, non-toxic, non-carcinogenic, non-allergic and haemostatic [177]. When used as dressing materials, it is important that during contact with the wound, part of the alginate dressing passes in the form of a gel, which prevents the wound surface from drying out, and thus creates the possibility of creating a favorable, moist environment within the skin lesion [178]. At the same time, hemostatic properties result in a faster wound healing process and allow for more effective scarring. Patients also benefit from using these dressings to reduce pain when changing them. A significant advantage of using alginate-containing dressings is the elimination of the dressing sticking to the wound and high absorbency.
The Tromboguard® dressing (Figure 10) is used to stop bleeding in the case of: traumatic wounds, postoperative wounds, skin graft collection sites in surgery and reconstructive surgery - including combustiology, wounds requiring emergency care, gunshot and puncture wounds, wounds resulting from traffic accidents. It is characterized by a quick hemostatic effect (stops bleeding in 3 minutes), an antibacterial effect inside the product (protecting the dressing against the growth of microorganisms), and effective blood absorption even under pressure. It is not irritating, sensitizing and cytotoxic.
Tromboguard® dressing structure.
Tests of operational parameters: tensile strength, the ability to adapt to the injury site or the transmission of moisture vapors have shown that this dressing has a tensile strength (for porous materials) of min. 75 kPa (according to PN-EN ISO 1798), which corresponds to the value recommended for dressing materials, and vapor permeability (transmission of moisture vapor) of min. 400 g/m3/24h.
The results of clinical trials have demonstrated the high haemostatic efficacy of Tromboguard®. The high effectiveness and durability of the antihaemorrhagic effect was confirmed 24 hours after application, which allowed the introduction of an absorbent foam dressing [179] and a three-layer hemostatic dressing to the market [96, 97].
Chitin and its ester derivatives, as well as chitosan obtained as a result of chitin deacetylation, have many valuable chemical, physical and biological properties that determine their use in many areas, also in medicine.
The widest use of chitin and its derivatives is observed in biomedical sciences, in particular: in dressing materials (active dressings), active substance carriers (drugs and growth factors), in tissue engineering (cell scaffolds - scaffolds, mainly orthopedics) and in regenerative medicine (stem cell differentiation). Chitin accelerates the wound healing process by having a beneficial effect on processes such as angiogenesis, granulation, epithelialization and scar formation, which play a key role in the physiological wound healing process. It increases the inflow of phagocytic cells (segmented granulocytes and macrophages) to the site of infection, stimulates the migration and proliferation of endothelial cells and fibroblasts. Chitin derivative dressings are considered to be very effective medical devices in the healing of difficult-to-heal wounds [6, 7, 8, 9, 10, 11].
The results of clinical trials with dressings based on butyryl-acetyl chitin co-polyesters have also shown their high effectiveness in healing wounds of various etiologies, mainly those caused by chronic venous insufficiency and diabetes. Their use leads to a reduction in the ulcer area and its depth. These dressings were assessed as having a high safety profile [38].
On the other hand, the results of clinical trials with chitosan dressings showed high effectiveness and durability of the anti-haemorrhagic effect. These studies also confirmed the safety of the dressing [96]. The antibacterial test confirmed that the dressing is bactericidal. Thus, there are currently many different hemostatic dressings based on chitosan on the market.
This research was funded by the National Centre for Research and Development under Project POIR.04.01.02-00-0004/17.
The authors declare no conflict of interest.
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Cognitive theory of personality disorders conceptualizes personality disorder including the ASPD, according to their basic beliefs or schemas. The content of beliefs can vary in different personality disorders. Antisocial patients view themselves as loners, autonomous, and strong. Some of them see themselves as having been abused and mistreated by society and therefore justify victimizing others because they believe that they have been victimized. Their view about other people is very negative; they see others as exploitative and thus deserving of being exploited in retaliation. In this chapter, after overviewing general features of ASPD, we aim to give an explanation how cognitive behavioral therapy (CBT) conceptualizes personality disorders in general and ASPD in particular and highlight the important implementations of CBT and schema therapy.",book:{id:"5795",slug:"psychopathy-new-updates-on-an-old-phenomenon",title:"Psychopathy",fullTitle:"Psychopathy - New Updates on an Old Phenomenon"},signatures:"Ahmet Emre Sargın, Kadir Özdel and Mehmet Hakan Türkçapar",authors:[{id:"198072",title:"Prof.",name:"Mehmet Hakan",middleName:null,surname:"Turkcapar",slug:"mehmet-hakan-turkcapar",fullName:"Mehmet Hakan Turkcapar"},{id:"198073",title:"Prof.",name:"Kadir",middleName:null,surname:"Ozdel",slug:"kadir-ozdel",fullName:"Kadir Ozdel"},{id:"198074",title:"Dr.",name:"Emre",middleName:null,surname:"Sargin",slug:"emre-sargin",fullName:"Emre Sargin"}]},{id:"67355",title:"Mitochondria and Alzheimer’s Disease: An Electron Microscopy Study",slug:"mitochondria-and-alzheimer-s-disease-an-electron-microscopy-study",totalDownloads:1086,totalCrossrefCites:2,totalDimensionsCites:2,abstract:"Alzheimer’s disease is a progressive, irreversible presenile or senile neurodegenerative disorder, implicating mainly the mental faculties, characterized by decline of memory and judgment, learning impairment, loss of professional skills and verbal capacities, alterations of social behavior, decline of motor skills and eventual disarrangement of the autonomic equilibrium. Among the pathogenetic factors, oxidative stress and mitochondrial dysfunction may play an essential role. Alterations of mitochondria may enhance amyloid toxicity, which in turn may aggravate mitochondrial dysfunction. We describe ultrastructural alterations of mitochondria in the soma of neurons, in axons, dendritic profiles and synaptic terminals, in astrocytes in early cases of Alzheimer’s disease on various areas of the cerebral and the cerebellar cortex, the hippocampus, the hypothalamus, the mammillary bodies and the medial geniculate body. The morphological and morphometric study of the mitochondria revealed an impressive polymorphism at any area of the brain. The mitochondria demonstrated variation of size and shape, fragmentation of the cristae and marked changes of their structure. The most dramatic mitochondrial alterations were observed in dendritic profiles, spines and synaptic terminals. A substantial number of astrocytes demonstrated mitochondrial alterations, which coexisted with fragmentation of Golgi apparatus and dilatation of the cisternae of the smooth endoplasmic reticulum. On the basis of our observations, we feel that therapeutic strategies aiming at protecting the mitochondria might be beneficial in the treatment of early cases of AD.",book:{id:"7868",slug:"redirecting-alzheimer-strategy-tracing-memory-loss-to-self-pathology",title:"Redirecting Alzheimer Strategy",fullTitle:"Redirecting Alzheimer Strategy - Tracing Memory Loss to Self Pathology"},signatures:"Stavros J. Baloyannis",authors:[{id:"156098",title:"Emeritus Prof.",name:"Stavros J.",middleName:"J.",surname:"Baloyannis",slug:"stavros-j.-baloyannis",fullName:"Stavros J. 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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. 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Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:4,paginationItems:[{id:"14",title:"Cell and Molecular Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/14.jpg",isOpenForSubmission:!0,editor:{id:"165627",title:"Dr.",name:"Rosa María",middleName:null,surname:"Martínez-Espinosa",slug:"rosa-maria-martinez-espinosa",fullName:"Rosa María Martínez-Espinosa",profilePictureURL:"https://mts.intechopen.com/storage/users/165627/images/system/165627.jpeg",biography:"Dr. Rosa María Martínez-Espinosa has been a Spanish Full Professor since 2020 (Biochemistry and Molecular Biology) and is currently Vice-President of International Relations and Cooperation development and leader of the research group 'Applied Biochemistry” (University of Alicante, Spain). Other positions she has held at the university include Vice-Dean of Master Programs, Vice-Dean of the Degree in Biology and Vice-Dean for Mobility and Enterprise and Engagement at the Faculty of Science (University of Alicante). She received her Bachelor in Biology in 1998 (University of Alicante) and her PhD in 2003 (Biochemistry, University of Alicante). She undertook post-doctoral research at the University of East Anglia (Norwich, U.K. 2004-2005; 2007-2008).\nHer multidisciplinary research focuses on investigating archaea and their potential applications in biotechnology. She has an H-index of 21. She has authored one patent and has published more than 70 indexed papers and around 60 book chapters.\nShe has contributed to more than 150 national and international meetings during the last 15 years. Her research interests include archaea metabolism, enzymes purification and characterization, gene regulation, carotenoids and bioplastics production, antioxidant\ncompounds, waste water treatments, and brines bioremediation.\nRosa María’s other roles include editorial board member for several journals related\nto biochemistry, reviewer for more than 60 journals (biochemistry, molecular biology, biotechnology, chemistry and microbiology) and president of several organizing committees in international meetings related to the N-cycle or respiratory processes.",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"15",title:"Chemical Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",isOpenForSubmission:!0,editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",slug:"sukru-beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",biography:"Dr. Şükrü Beydemir obtained a BSc in Chemistry in 1995 from Yüzüncü Yıl University, MSc in Biochemistry in 1998, and PhD in Biochemistry in 2002 from Atatürk University, Turkey. He performed post-doctoral studies at Max-Planck Institute, Germany, and University of Florence, Italy in addition to making several scientific visits abroad. He currently works as a Full Professor of Biochemistry in the Faculty of Pharmacy, Anadolu University, Turkey. Dr. Beydemir has published over a hundred scientific papers spanning protein biochemistry, enzymology and medicinal chemistry, reviews, book chapters and presented several conferences to scientists worldwide. He has received numerous publication awards from various international scientific councils. He serves in the Editorial Board of several international journals. Dr. Beydemir is also Rector of Bilecik Şeyh Edebali University, Turkey.",institutionString:null,institution:{name:"Anadolu University",institutionURL:null,country:{name:"Turkey"}}},editorTwo:{id:"13652",title:"Prof.",name:"Deniz",middleName:null,surname:"Ekinci",slug:"deniz-ekinci",fullName:"Deniz Ekinci",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYLT1QAO/Profile_Picture_1634557223079",biography:"Dr. Deniz Ekinci obtained a BSc in Chemistry in 2004, MSc in Biochemistry in 2006, and PhD in Biochemistry in 2009 from Atatürk University, Turkey. He studied at Stetson University, USA, in 2007-2008 and at the Max Planck Institute of Molecular Cell Biology and Genetics, Germany, in 2009-2010. Dr. Ekinci currently works as a Full Professor of Biochemistry in the Faculty of Agriculture and is the Head of the Enzyme and Microbial Biotechnology Division, Ondokuz Mayıs University, Turkey. He is a member of the Turkish Biochemical Society, American Chemical Society, and German Genetics society. Dr. Ekinci published around ninety scientific papers, reviews and book chapters, and presented several conferences to scientists. He has received numerous publication awards from several scientific councils. 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He worked on the structure-function relationships of glycoconjugates and his main project was the investigations on the biological roles of the de-N-glycosylation enzymes (Endo-N-acetyl-β-D-glucosaminidase and peptide-N4-(N-acetyl-β-glucosaminyl) asparagine amidase). From 2002 he contributes to the understanding of the Blood-brain barrier functioning using proteomics approaches. He has published more than 70 papers. His teaching areas are energy metabolism and regulation, integration and organ specialization and metabolic adaptation.",institutionString:null,institution:{name:"Artois University",institutionURL:null,country:{name:"France"}}},editorTwo:null,editorThree:null},{id:"18",title:"Proteomics",coverUrl:"https://cdn.intechopen.com/series_topics/covers/18.jpg",isOpenForSubmission:!0,editor:{id:"200689",title:"Prof.",name:"Paolo",middleName:null,surname:"Iadarola",slug:"paolo-iadarola",fullName:"Paolo Iadarola",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSCl8QAG/Profile_Picture_1623568118342",biography:"Paolo Iadarola graduated with a degree in Chemistry from the University of Pavia (Italy) in July 1972. He then worked as an Assistant Professor at the Faculty of Science of the same University until 1984. In 1985, Prof. Iadarola became Associate Professor at the Department of Biology and Biotechnologies of the University of Pavia and retired in October 2017. Since then, he has been working as an Adjunct Professor in the same Department at the University of Pavia. His research activity during the first years was primarily focused on the purification and structural characterization of enzymes from animal and plant sources. During this period, Prof. Iadarola familiarized himself with the conventional techniques used in column chromatography, spectrophotometry, manual Edman degradation, and electrophoresis). Since 1995, he has been working on: i) the determination in biological fluids (serum, urine, bronchoalveolar lavage, sputum) of proteolytic activities involved in the degradation processes of connective tissue matrix, and ii) on the identification of biological markers of lung diseases. In this context, he has developed and validated new methodologies (e.g., Capillary Electrophoresis coupled to Laser-Induced Fluorescence, CE-LIF) whose application enabled him to determine both the amounts of biochemical markers (Desmosines) in urine/serum of patients affected by Chronic Obstructive Pulmonary Disease (COPD) and the activity of proteolytic enzymes (Human Neutrophil Elastase, Cathepsin G, Pseudomonas aeruginosa elastase) in sputa of these patients. More recently, Prof. Iadarola was involved in developing techniques such as two-dimensional electrophoresis coupled to liquid chromatography/mass spectrometry (2DE-LC/MS) for the proteomic analysis of biological fluids aimed at the identification of potential biomarkers of different lung diseases. He is the author of about 150 publications (According to Scopus: H-Index: 23; Total citations: 1568- According to WOS: H-Index: 20; Total Citations: 1296) of peer-reviewed international journals. He is a Consultant Reviewer for several journals, including the Journal of Chromatography A, Journal of Chromatography B, Plos ONE, Proteomes, International Journal of Molecular Science, Biotech, Electrophoresis, and others. He is also Associate Editor of Biotech.",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorTwo:{id:"201414",title:"Dr.",name:"Simona",middleName:null,surname:"Viglio",slug:"simona-viglio",fullName:"Simona Viglio",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKDHQA4/Profile_Picture_1630402531487",biography:"Simona Viglio is an Associate Professor of Biochemistry at the Department of Molecular Medicine at the University of Pavia. She has been working since 1995 on the determination of proteolytic enzymes involved in the degradation process of connective tissue matrix and on the identification of biological markers of lung diseases. She gained considerable experience in developing and validating new methodologies whose applications allowed her to determine both the amount of biomarkers (Desmosine and Isodesmosine) in the urine of patients affected by COPD, and the activity of proteolytic enzymes (HNE, Cathepsin G, Pseudomonas aeruginosa elastase) in the sputa of these patients. Simona Viglio was also involved in research dealing with the supplementation of amino acids in patients with brain injury and chronic heart failure. She is presently engaged in the development of 2-DE and LC-MS techniques for the study of proteomics in biological fluids. The aim of this research is the identification of potential biomarkers of lung diseases. 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Saxena",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",institutionURL:null,country:{name:"India"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null}]},subseriesFiltersForPublishedBooks:[{group:"subseries",caption:"Bacterial Infectious Diseases",value:3,count:2},{group:"subseries",caption:"Parasitic Infectious Diseases",value:5,count:4},{group:"subseries",caption:"Viral Infectious Diseases",value:6,count:7}],publicationYearFilters:[{group:"publicationYear",caption:"2022",value:2022,count:2},{group:"publicationYear",caption:"2021",value:2021,count:4},{group:"publicationYear",caption:"2020",value:2020,count:3},{group:"publicationYear",caption:"2019",value:2019,count:3},{group:"publicationYear",caption:"2018",value:2018,count:1}],authors:{paginationCount:148,paginationItems:[{id:"165328",title:"Dr.",name:"Vahid",middleName:null,surname:"Asadpour",slug:"vahid-asadpour",fullName:"Vahid Asadpour",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/165328/images/system/165328.jpg",biography:"Vahid Asadpour, MS, Ph.D., is currently with the Department of Research and Evaluation, Kaiser Permanente Southern California. He has both an MS and Ph.D. in Biomedical Engineering. He was previously a research scientist at the University of California Los Angeles (UCLA) and visiting professor and researcher at the University of North Dakota. He is currently working in artificial intelligence and its applications in medical signal processing. In addition, he is using digital signal processing in medical imaging and speech processing. Dr. Asadpour has developed brain-computer interfacing algorithms and has published books, book chapters, and several journal and conference papers in this field and other areas of intelligent signal processing. He has also designed medical devices, including a laser Doppler monitoring system.",institutionString:"Kaiser Permanente Southern California",institution:null},{id:"169608",title:"Prof.",name:"Marian",middleName:null,surname:"Găiceanu",slug:"marian-gaiceanu",fullName:"Marian Găiceanu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/169608/images/system/169608.png",biography:"Prof. Dr. Marian Gaiceanu graduated from the Naval and Electrical Engineering Faculty, Dunarea de Jos University of Galati, Romania, in 1997. He received a Ph.D. (Magna Cum Laude) in Electrical Engineering in 2002. Since 2017, Dr. Gaiceanu has been a Ph.D. supervisor for students in Electrical Engineering. He has been employed at Dunarea de Jos University of Galati since 1996, where he is currently a professor. Dr. Gaiceanu is a member of the National Council for Attesting Titles, Diplomas and Certificates, an expert of the Executive Agency for Higher Education, Research Funding, and a member of the Senate of the Dunarea de Jos University of Galati. He has been the head of the Integrated Energy Conversion Systems and Advanced Control of Complex Processes Research Center, Romania, since 2016. He has conducted several projects in power converter systems for electrical drives, power quality, PEM and SOFC fuel cell power converters for utilities, electric vehicles, and marine applications with the Department of Regulation and Control, SIEI S.pA. (2002–2004) and the Polytechnic University of Turin, Italy (2002–2004, 2006–2007). He is a member of the Institute of Electrical and Electronics Engineers (IEEE) and cofounder-member of the IEEE Power Electronics Romanian Chapter. He is a guest editor at Energies and an academic book editor for IntechOpen. He is also a member of the editorial boards of the Journal of Electrical Engineering, Electronics, Control and Computer Science and Sustainability. Dr. Gaiceanu has been General Chairman of the IEEE International Symposium on Electrical and Electronics Engineering in the last six editions.",institutionString:'"Dunarea de Jos" University of Galati',institution:{name:'"Dunarea de Jos" University of Galati',country:{name:"Romania"}}},{id:"4519",title:"Prof.",name:"Jaydip",middleName:null,surname:"Sen",slug:"jaydip-sen",fullName:"Jaydip Sen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/4519/images/system/4519.jpeg",biography:"Jaydip Sen is associated with Praxis Business School, Kolkata, India, as a professor in the Department of Data Science. His research areas include security and privacy issues in computing and communication, intrusion detection systems, machine learning, deep learning, and artificial intelligence in the financial domain. He has more than 200 publications in reputed international journals, refereed conference proceedings, and 20 book chapters in books published by internationally renowned publishing houses, such as Springer, CRC press, IGI Global, etc. Currently, he is serving on the editorial board of the prestigious journal Frontiers in Communications and Networks and in the technical program committees of a number of high-ranked international conferences organized by the IEEE, USA, and the ACM, USA. He has been listed among the top 2% of scientists in the world for the last three consecutive years, 2019 to 2021 as per studies conducted by the Stanford University, USA.",institutionString:"Praxis Business School",institution:null},{id:"320071",title:"Dr.",name:"Sidra",middleName:null,surname:"Mehtab",slug:"sidra-mehtab",fullName:"Sidra Mehtab",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00002v6KHoQAM/Profile_Picture_1584512086360",biography:"Sidra Mehtab has completed her BS with honors in Physics from Calcutta University, India in 2018. She has done MS in Data Science and Analytics from Maulana Abul Kalam Azad University of Technology (MAKAUT), Kolkata, India in 2020. Her research areas include Econometrics, Time Series Analysis, Machine Learning, Deep Learning, Artificial Intelligence, and Computer and Network Security with a particular focus on Cyber Security Analytics. Ms. Mehtab has published seven papers in international conferences and one of her papers has been accepted for publication in a reputable international journal. She has won the best paper awards in two prestigious international conferences – BAICONF 2019, and ICADCML 2021, organized in the Indian Institute of Management, Bangalore, India in December 2019, and SOA University, Bhubaneswar, India in January 2021. Besides, Ms. Mehtab has also published two book chapters in two books. Seven of her book chapters will be published in a volume shortly in 2021 by Cambridge Scholars’ Press, UK. Currently, she is working as the joint editor of two edited volumes on Time Series Analysis and Forecasting to be published in the first half of 2021 by an international house. Currently, she is working as a Data Scientist with an MNC in Delhi, India.",institutionString:"NSHM College of Management and Technology",institution:null},{id:"226240",title:"Dr.",name:"Andri Irfan",middleName:null,surname:"Rifai",slug:"andri-irfan-rifai",fullName:"Andri Irfan Rifai",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/226240/images/7412_n.jpg",biography:"Andri IRFAN is a Senior Lecturer of Civil Engineering and Planning. He completed the PhD at the Universitas Indonesia & Universidade do Minho with Sandwich Program Scholarship from the Directorate General of Higher Education and LPDP scholarship. He has been teaching for more than 19 years and much active to applied his knowledge in the project construction in Indonesia. His research interest ranges from pavement management system to advanced data mining techniques for transportation engineering. He has published more than 50 papers in journals and 2 books.",institutionString:null,institution:{name:"Universitas Internasional Batam",country:{name:"Indonesia"}}},{id:"314576",title:"Dr.",name:"Ibai",middleName:null,surname:"Laña",slug:"ibai-lana",fullName:"Ibai Laña",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314576/images/system/314576.jpg",biography:"Dr. Ibai Laña works at TECNALIA as a data analyst. He received his Ph.D. in Artificial Intelligence from the University of the Basque Country (UPV/EHU), Spain, in 2018. He is currently a senior researcher at TECNALIA. His research interests fall within the intersection of intelligent transportation systems, machine learning, traffic data analysis, and data science. He has dealt with urban traffic forecasting problems, applying machine learning models and evolutionary algorithms. He has experience in origin-destination matrix estimation or point of interest and trajectory detection. Working with large volumes of data has given him a good command of big data processing tools and NoSQL databases. He has also been a visiting scholar at the Knowledge Engineering and Discovery Research Institute, Auckland University of Technology.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"314575",title:"Dr.",name:"Jesus",middleName:null,surname:"L. Lobo",slug:"jesus-l.-lobo",fullName:"Jesus L. Lobo",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314575/images/system/314575.png",biography:"Dr. Jesús López is currently based in Bilbao (Spain) working at TECNALIA as Artificial Intelligence Research Scientist. In most cases, a project idea or a new research line needs to be investigated to see if it is good enough to take into production or to focus on it. That is exactly what he does, diving into Machine Learning algorithms and technologies to help TECNALIA to decide whether something is great in theory or will actually impact on the product or processes of its projects. So, he is expert at framing experiments, developing hypotheses, and proving whether they’re true or not, in order to investigate fundamental problems with a longer time horizon. He is also able to design and develop PoCs and system prototypes in simulation. He has participated in several national and internacional R&D projects.\n\nAs another relevant part of his everyday research work, he usually publishes his findings in reputed scientific refereed journals and international conferences, occasionally acting as reviewer and Programme Commitee member. Concretely, since 2018 he has published 9 JCR (8 Q1) journal papers, 9 conference papers (e.g. ECML PKDD 2021), and he has co-edited a book. He is also active in popular science writing data science stories for reputed blogs (KDNuggets, TowardsDataScience, Naukas). Besides, he has recently embarked on mentoring programmes as mentor, and has also worked as data science trainer.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"103779",title:"Prof.",name:"Yalcin",middleName:null,surname:"Isler",slug:"yalcin-isler",fullName:"Yalcin Isler",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRyQ8QAK/Profile_Picture_1628834958734",biography:"Yalcin Isler (1971 - Burdur / Turkey) received the B.Sc. degree in the Department of Electrical and Electronics Engineering from Anadolu University, Eskisehir, Turkey, in 1993, the M.Sc. degree from the Department of Electronics and Communication Engineering, Suleyman Demirel University, Isparta, Turkey, in 1996, the Ph.D. degree from the Department of Electrical and Electronics Engineering, Dokuz Eylul University, Izmir, Turkey, in 2009, and the Competence of Associate Professorship from the Turkish Interuniversity Council in 2019.\n\nHe was Lecturer at Burdur Vocational School in Suleyman Demirel University (1993-2000, Burdur / Turkey), Software Engineer (2000-2002, Izmir / Turkey), Research Assistant in Bulent Ecevit University (2002-2003, Zonguldak / Turkey), Research Assistant in Dokuz Eylul University (2003-2010, Izmir / Turkey), Assistant Professor at the Department of Electrical and Electronics Engineering in Bulent Ecevit University (2010-2012, Zonguldak / Turkey), Assistant Professor at the Department of Biomedical Engineering in Izmir Katip Celebi University (2012-2019, Izmir / Turkey). He is an Associate Professor at the Department of Biomedical Engineering at Izmir Katip Celebi University, Izmir / Turkey, since 2019. In addition to academics, he has also founded Islerya Medical and Information Technologies Company, Izmir / Turkey, since 2017.\n\nHis main research interests cover biomedical signal processing, pattern recognition, medical device design, programming, and embedded systems. He has many scientific papers and participated in several projects in these study fields. He was an IEEE Student Member (2009-2011) and IEEE Member (2011-2014) and has been IEEE Senior Member since 2014.",institutionString:null,institution:{name:"Izmir Kâtip Çelebi University",country:{name:"Turkey"}}},{id:"339677",title:"Dr.",name:"Mrinmoy",middleName:null,surname:"Roy",slug:"mrinmoy-roy",fullName:"Mrinmoy Roy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/339677/images/16768_n.jpg",biography:"An accomplished Sales & Marketing professional with 12 years of cross-functional experience in well-known organisations such as CIPLA, LUPIN, GLENMARK, ASTRAZENECA across different segment of Sales & Marketing, International Business, Institutional Business, Product Management, Strategic Marketing of HIV, Oncology, Derma, Respiratory, Anti-Diabetic, Nutraceutical & Stomatological Product Portfolio and Generic as well as Chronic Critical Care Portfolio. A First Class MBA in International Business & Strategic Marketing, B.Pharm, D.Pharm, Google Certified Digital Marketing Professional. Qualified PhD Candidate in Operations and Management with special focus on Artificial Intelligence and Machine Learning adoption, analysis and use in Healthcare, Hospital & Pharma Domain. Seasoned with diverse therapy area of Pharmaceutical Sales & Marketing ranging from generating revenue through generating prescriptions, launching new products, and making them big brands with continuous strategy execution at the Physician and Patients level. Moved from Sales to Marketing and Business Development for 3.5 years in South East Asian Market operating from Manila, Philippines. Came back to India and handled and developed Brands such as Gluconorm, Lupisulin, Supracal, Absolut Woman, Hemozink, Fabiflu (For COVID 19), and many more. In my previous assignment I used to develop and execute strategies on Sales & Marketing, Commercialization & Business Development for Institution and Corporate Hospital Business portfolio of Oncology Therapy Area for AstraZeneca Pharma India Ltd. Being a Research Scholar and Student of ‘Operations Research & Management: Artificial Intelligence’ I published several pioneer research papers and book chapters on the same in Internationally reputed journals and Books indexed in Scopus, Springer and Ei Compendex, Google Scholar etc. Currently, I am launching PGDM Pharmaceutical Management Program in IIHMR Bangalore and spearheading the course curriculum and structure of the same. I am interested in Collaboration for Healthcare Innovation, Pharma AI Innovation, Future trend in Marketing and Management with incubation on Healthcare, Healthcare IT startups, AI-ML Modelling and Healthcare Algorithm based training module development. I am also an affiliated member of the Institute of Management Consultant of India, looking forward to Healthcare, Healthcare IT and Innovation, Pharma and Hospital Management Consulting works.",institutionString:null,institution:{name:"Lovely Professional University",country:{name:"India"}}},{id:"310576",title:"Prof.",name:"Erick Giovani",middleName:null,surname:"Sperandio Nascimento",slug:"erick-giovani-sperandio-nascimento",fullName:"Erick Giovani Sperandio Nascimento",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y00002pDKxDQAW/ProfilePicture%202022-06-20%2019%3A57%3A24.788",biography:"Prof. Erick Sperandio is the Lead Researcher and professor of Artificial Intelligence (AI) at SENAI CIMATEC, Bahia, Brazil, also working with Computational Modeling (CM) and HPC. He holds a PhD in Environmental Engineering in the area of Atmospheric Computational Modeling, a Master in Informatics in the field of Computational Intelligence and Graduated in Computer Science from UFES. He currently coordinates, leads and participates in R&D projects in the areas of AI, computational modeling and supercomputing applied to different areas such as Oil and Gas, Health, Advanced Manufacturing, Renewable Energies and Atmospheric Sciences, advising undergraduate, master's and doctoral students. He is the Lead Researcher at SENAI CIMATEC's Reference Center on Artificial Intelligence. In addition, he is a Certified Instructor and University Ambassador of the NVIDIA Deep Learning Institute (DLI) in the areas of Deep Learning, Computer Vision, Natural Language Processing and Recommender Systems, and Principal Investigator of the NVIDIA/CIMATEC AI Joint Lab, the first in Latin America within the NVIDIA AI Technology Center (NVAITC) worldwide program. He also works as a researcher at the Supercomputing Center for Industrial Innovation (CS2i) and at the SENAI Institute of Innovation for Automation (ISI Automação), both from SENAI CIMATEC. He is a member and vice-coordinator of the Basic Board of Scientific-Technological Advice and Evaluation, in the area of Innovation, of the Foundation for Research Support of the State of Bahia (FAPESB). He serves as Technology Transfer Coordinator and one of the Principal Investigators at the National Applied Research Center in Artificial Intelligence (CPA-IA) of SENAI CIMATEC, focusing on Industry, being one of the six CPA-IA in Brazil approved by MCTI / FAPESP / CGI.br. He also participates as one of the representatives of Brazil in the BRICS Innovation Collaboration Working Group on HPC, ICT and AI. He is the coordinator of the Work Group of the Axis 5 - Workforce and Training - of the Brazilian Strategy for Artificial Intelligence (EBIA), and member of the MCTI/EMBRAPII AI Innovation Network Training Committee. He is the coordinator, by SENAI CIMATEC, of the Artificial Intelligence Reference Network of the State of Bahia (REDE BAH.IA). He leads the working group of experts representing Brazil in the Global Partnership on Artificial Intelligence (GPAI), on the theme \"AI and the Pandemic Response\".",institutionString:"Manufacturing and Technology Integrated Campus – SENAI CIMATEC",institution:null},{id:"1063",title:"Prof.",name:"Constantin",middleName:null,surname:"Volosencu",slug:"constantin-volosencu",fullName:"Constantin Volosencu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/1063/images/system/1063.png",biography:"Prof. Dr. Constantin Voloşencu graduated as an engineer from\nPolitehnica University of Timișoara, Romania, where he also\nobtained a doctorate degree. He is currently a full professor in\nthe Department of Automation and Applied Informatics at the\nsame university. Dr. Voloşencu is the author of ten books, seven\nbook chapters, and more than 160 papers published in journals\nand conference proceedings. He has also edited twelve books and\nhas twenty-seven patents to his name. He is a manager of research grants, editor in\nchief and member of international journal editorial boards, a former plenary speaker, a member of scientific committees, and chair at international conferences. His\nresearch is in the fields of control systems, control of electric drives, fuzzy control\nsystems, neural network applications, fault detection and diagnosis, sensor network\napplications, monitoring of distributed parameter systems, and power ultrasound\napplications. He has developed automation equipment for machine tools, spooling\nmachines, high-power ultrasound processes, and more.",institutionString:"Polytechnic University of Timişoara",institution:{name:"Polytechnic University of Timişoara",country:{name:"Romania"}}},{id:"221364",title:"Dr.",name:"Eneko",middleName:null,surname:"Osaba",slug:"eneko-osaba",fullName:"Eneko Osaba",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/221364/images/system/221364.jpg",biography:"Dr. Eneko Osaba works at TECNALIA as a senior researcher. He obtained his Ph.D. in Artificial Intelligence in 2015. He has participated in more than twenty-five local and European research projects, and in the publication of more than 130 papers. He has performed several stays at universities in the United Kingdom, Italy, and Malta. Dr. Osaba has served as a program committee member in more than forty international conferences and participated in organizing activities in more than ten international conferences. He is a member of the editorial board of the International Journal of Artificial Intelligence, Data in Brief, and Journal of Advanced Transportation. He is also a guest editor for the Journal of Computational Science, Neurocomputing, Swarm, and Evolutionary Computation and IEEE ITS Magazine.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"275829",title:"Dr.",name:"Esther",middleName:null,surname:"Villar-Rodriguez",slug:"esther-villar-rodriguez",fullName:"Esther Villar-Rodriguez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/275829/images/system/275829.jpg",biography:"Dr. Esther Villar obtained a Ph.D. in Information and Communication Technologies from the University of Alcalá, Spain, in 2015. She obtained a degree in Computer Science from the University of Deusto, Spain, in 2010, and an MSc in Computer Languages and Systems from the National University of Distance Education, Spain, in 2012. Her areas of interest and knowledge include natural language processing (NLP), detection of impersonation in social networks, semantic web, and machine learning. Dr. Esther Villar made several contributions at conferences and publishing in various journals in those fields. Currently, she is working within the OPTIMA (Optimization Modeling & Analytics) business of TECNALIA’s ICT Division as a data scientist in projects related to the prediction and optimization of management and industrial processes (resource planning, energy efficiency, etc).",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"49813",title:"Dr.",name:"Javier",middleName:null,surname:"Del Ser",slug:"javier-del-ser",fullName:"Javier Del Ser",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49813/images/system/49813.png",biography:"Prof. Dr. Javier Del Ser received his first PhD in Telecommunication Engineering (Cum Laude) from the University of Navarra, Spain, in 2006, and a second PhD in Computational Intelligence (Summa Cum Laude) from the University of Alcala, Spain, in 2013. He is currently a principal researcher in data analytics and optimisation at TECNALIA (Spain), a visiting fellow at the Basque Center for Applied Mathematics (BCAM) and a part-time lecturer at the University of the Basque Country (UPV/EHU). His research interests gravitate on the use of descriptive, prescriptive and predictive algorithms for data mining and optimization in a diverse range of application fields such as Energy, Transport, Telecommunications, Health and Industry, among others. In these fields he has published more than 240 articles, co-supervised 8 Ph.D. theses, edited 6 books, coauthored 7 patents and participated/led more than 40 research projects. He is a Senior Member of the IEEE, and a recipient of the Biscay Talent prize for his academic career.",institutionString:"Tecnalia Research & Innovation",institution:null},{id:"278948",title:"Dr.",name:"Carlos Pedro",middleName:null,surname:"Gonçalves",slug:"carlos-pedro-goncalves",fullName:"Carlos Pedro Gonçalves",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRcmyQAC/Profile_Picture_1564224512145",biography:'Carlos Pedro Gonçalves (PhD) is an Associate Professor at Lusophone University of Humanities and Technologies and a researcher on Complexity Sciences, Quantum Technologies, Artificial Intelligence, Strategic Studies, Studies in Intelligence and Security, FinTech and Financial Risk Modeling. He is also a progammer with programming experience in:\n\nA) Quantum Computing using Qiskit Python module and IBM Quantum Experience Platform, with software developed on the simulation of Quantum Artificial Neural Networks and Quantum Cybersecurity;\n\nB) Artificial Intelligence and Machine learning programming in Python;\n\nC) Artificial Intelligence, Multiagent Systems Modeling and System Dynamics Modeling in Netlogo, with models developed in the areas of Chaos Theory, Econophysics, Artificial Intelligence, Classical and Quantum Complex Systems Science, with the Econophysics models having been cited worldwide and incorporated in PhD programs by different Universities.\n\nReceived an Arctic Code Vault Contributor status by GitHub, due to having developed open source software preserved in the \\"Arctic Code Vault\\" for future generations (https://archiveprogram.github.com/arctic-vault/), with the Strategy Analyzer A.I. module for decision making support (based on his PhD thesis, used in his Classes on Decision Making and in Strategic Intelligence Consulting Activities) and QNeural Python Quantum Neural Network simulator also preserved in the \\"Arctic Code Vault\\", for access to these software modules see: https://github.com/cpgoncalves. He is also a peer reviewer with outsanding review status from Elsevier journals, including Physica A, Neurocomputing and Engineering Applications of Artificial Intelligence. Science CV available at: https://www.cienciavitae.pt//pt/8E1C-A8B3-78C5 and ORCID: https://orcid.org/0000-0002-0298-3974',institutionString:"University of Lisbon",institution:{name:"Universidade Lusófona",country:{name:"Portugal"}}},{id:"241400",title:"Prof.",name:"Mohammed",middleName:null,surname:"Bsiss",slug:"mohammed-bsiss",fullName:"Mohammed Bsiss",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/241400/images/8062_n.jpg",biography:null,institutionString:null,institution:null},{id:"276128",title:"Dr.",name:"Hira",middleName:null,surname:"Fatima",slug:"hira-fatima",fullName:"Hira Fatima",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/276128/images/14420_n.jpg",biography:"Dr. Hira Fatima\nAssistant Professor\nDepartment of Mathematics\nInstitute of Applied Science\nMangalayatan University, Aligarh\nMobile: no : 8532041179\nhirafatima2014@gmal.com\n\nDr. Hira Fatima has received his Ph.D. degree in pure Mathematics from Aligarh Muslim University, Aligarh India. Currently working as an Assistant Professor in the Department of Mathematics, Institute of Applied Science, Mangalayatan University, Aligarh. She taught so many courses of Mathematics of UG and PG level. Her research Area of Expertise is Functional Analysis & Sequence Spaces. She has been working on Ideal Convergence of double sequence. She has published 17 research papers in National and International Journals including Cogent Mathematics, Filomat, Journal of Intelligent and Fuzzy Systems, Advances in Difference Equations, Journal of Mathematical Analysis, Journal of Mathematical & Computer Science etc. She has also reviewed few research papers for the and international journals. 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