IF50 values for widefield fluorescence imaging and fluorescence spectroscopy collected over time (5 h) after sample cream application on human and porcine skin model surfaces.
\\n\\n
More than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
\\n\\nOur breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
\\n\\n“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
\\n\\nAdditionally, each book published by IntechOpen contains original content and research findings.
\\n\\nWe are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
\\n\\n\\n\\n
\\n"}]',published:!0,mainMedia:{caption:"IntechOpen Maintains",originalUrl:"/media/original/113"}},components:[{type:"htmlEditorComponent",content:'
Simba Information has released its Open Access Book Publishing 2020 - 2024 report and has again identified IntechOpen as the world’s largest Open Access book publisher by title count.
\n\nSimba Information is a leading provider for market intelligence and forecasts in the media and publishing industry. The report, published every year, provides an overview and financial outlook for the global professional e-book publishing market.
\n\nIntechOpen, De Gruyter, and Frontiers are the largest OA book publishers by title count, with IntechOpen coming in at first place with 5,101 OA books published, a good 1,782 titles ahead of the nearest competitor.
\n\nSince the first Open Access Book Publishing report published in 2016, IntechOpen has held the top stop each year.
\n\n\n\nMore than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
\n\nOur breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
\n\n“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
\n\nAdditionally, each book published by IntechOpen contains original content and research findings.
\n\nWe are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
\n\n\n\n
\n'}],latestNews:[{slug:"intechopen-supports-asapbio-s-new-initiative-publish-your-reviews-20220729",title:"IntechOpen Supports ASAPbio’s New Initiative Publish Your Reviews"},{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"}]},book:{item:{type:"book",id:"4461",leadTitle:null,fullTitle:"Advanced Brain Neuroimaging Topics in Health and Disease - Methods and Applications",title:"Advanced Brain Neuroimaging Topics in Health and Disease",subtitle:"Methods and Applications",reviewType:"peer-reviewed",abstract:"The brain is the most complex computational device we know, consisting of highly interacting and redundant networks of areas, supporting specific brain functions. The rules by which these areas organize themselves to perform specific computations have only now started to be uncovered. Advances in non-invasive neuroimaging technologies have revolutionized our understanding of the functional anatomy of cortical circuits in health and disease states, which is the focus of this book. The first section of this book focuses on methodological issues, such as combining functional MRI technology with other brain imaging modalities. The second section examines the application of brain neuroimaging to understand cognitive, visual, auditory, motor and decision-making networks, as well as neurological diseases. The use of non-invasive neuroimaging technologies will continue to stimulate an exponential growth in understanding basic brain processes, largely as a result of sustained advances in neuroimaging methods and applications.",isbn:null,printIsbn:"978-953-51-1203-7",pdfIsbn:"978-953-51-7209-3",doi:"10.5772/58256",price:159,priceEur:175,priceUsd:205,slug:"advanced-brain-neuroimaging-topics-in-health-and-disease-methods-and-applications",numberOfPages:680,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"30152982950eed84faf2ad2a75f78f4e",bookSignature:"T. Dorina Papageorgiou, George I. Christopoulos and Stelios M. Smirnakis",publishedDate:"May 31st 2014",coverURL:"https://cdn.intechopen.com/books/images_new/4461.jpg",numberOfDownloads:51734,numberOfWosCitations:70,numberOfCrossrefCitations:34,numberOfCrossrefCitationsByBook:3,numberOfDimensionsCitations:104,numberOfDimensionsCitationsByBook:3,hasAltmetrics:1,numberOfTotalCitations:208,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"December 1st 2013",dateEndSecondStepPublish:"January 1st 2014",dateEndThirdStepPublish:"January 24th 2014",dateEndFourthStepPublish:"August 18th 2014",dateEndFifthStepPublish:"September 17th 2014",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"92641",title:"Dr.",name:"T. Dorina",middleName:null,surname:"Papageorgiou",slug:"t.-dorina-papageorgiou",fullName:"T. Dorina Papageorgiou",profilePictureURL:"https://mts.intechopen.com/storage/users/92641/images/system/92641.png",biography:"Dr. Papageorgiou obtained a BA in Psychology and Sociology (University of Georgia), a M.H.Sc. in Psychiatric Epidemiology (Johns Hopkins University), and a Ph.D. in the Biomedical Sciences with a focus on the neuroimaging of morphine (University of Texas - M.D. Anderson Cancer Center; MDACC). She continued with three postdoctoral fellowships: (i) neuroimaging of pain (MDACC); (ii) real-time fMRI neurofeedback of speech impairment (Baylor College of Medicine); and (ii) real-time fMRI neurofeedback of cortical blindness (BCM). As an Assistant Professor of Neurology her research focuses on cortical plasticity, and neuro-rehabilitation of cortical blindness, speech impairment and, chronic pain syndromes, as a result of neurological disorders, traumatic brain injury or, cancer-related symptoms using targeted/individualized real-time fMRI neurofeedback methods.\n~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~\nThe T. Dorina Papageorgiou - Investigational Targeted Brain Neurotherapeutics Lab has developed a novel, targeted and individualized MRI-compatible brain computer interface (BCI) based on associative learning principles that can induce neuromodulation in patients with neurological sequelae following stroke (commonly a result of a posterior cerebral artery infarct, or a middle cerebral artery infarct), traumatic brain injury or tumor resection.\n\nWe call our MRI-BCI, individualized real-time functional MRI neurofeedback (iRTfMRI nFb), which is based on promoting the reorganization of networks by bypassing lesioned pathways and capitalizing on redundant, intact but functionally associated pathways to the injured ones.\n\nThis is achieved by modulating the magnitude and spatial extent of Blood-Oxygen-Level-Dependent (BOLD) signal with the goal to recover the brain function, as a result of a neurological insult.\n\nWe apply this investigational treatment to patients with impairments of the following cortical systems:\n\nRetrochiasmal lesions downstream of the optic radiation, which result in cortical blindness.\nSupra- or infra-nuclear injury to the hypoglossal or glossopharyngeal nucleus, which result in upper motor neuron disease (lesions upstream of the medulla oblongata that can impact somatomotor, and somatosensory areas) or lower motor neuron disease (lesions downstream of the medulla oblongata).\nPain matrix network areas, which result in impaired somatosensory and somatomotor pain matrix network activity as a result of CNS- or PNS-associated pain.\nReorganization is possible by neuromodulating the spatial extent and intensity of the Blood-Oxygen-Level-Dependent (BOLD) signal to a patient's intact cortical area, which takes over in performing the function, as it has been impaired in the primary cortical areas following neurological injury.\n\nThis investigational treatment engages associative learning mechanisms that modulate the activity of intact cortical areas with the goal to improve performance in patient populations with neurological sequelae as a result of stroke, traumatic brain injury or tumor resection. Patients undergo rneurofeedback in real time to upregulate or downregulate the activity of intact cortical and/or subcortical areas in conjunction with the continuous presentation of visual stimuli inside the MRI environment with the goal to restore or reorganize lesioned pathways associated with vision, speech, or pain. The modulation in the Blood-Oxygen-Level-Dependent (BOLD) signal intensity is achieved by feeding back to the patient the magnitude of mean BOLD signal intensity of his/her intact cortical area during the presentation of a stimulus in real-time. The hypothesis is that such training engages Hebbian mechanisms that modulate the activity of intact cortical areas with the goal to improve performance.",institutionString:"Baylor College of Medicine",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Baylor College of Medicine",institutionURL:null,country:{name:"United States of America"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:{id:"123050",title:"Dr.",name:"George",middleName:null,surname:"Christopoulos",slug:"george-christopoulos",fullName:"George Christopoulos",profilePictureURL:"https://mts.intechopen.com/storage/users/123050/images/5396_n.jpg",biography:"George Christopoulos holds a Ph.D. in Cognitive Neuroscience (University of Cambridge) and has extensive post-doctoral research experience (Cambridge, Virginia Tech and Baylor College of Medicine). (By the way, he is the guy on the left in the picture). Dr. Christopoulos’ research combines game theory, behavioural economics, reinforcement learning and cognitive neuroscience in an effort to uncover the mechanisms of human decision making. His target is to help people make better decisions. Dr. Christopoulos’ \r\nenjoys multi-disciplinary work and his research has a mutual attraction with many disciplines, including culture science, organizational behaviour, psychopathology and social psychology. Dr. Christopoulos is currently an Assistant Professor at Nanyang Business School, Nanyang Technological University (Singapore) and the Research Manager of the Culture Science Institute.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Nanyang Technological University",institutionURL:null,country:{name:"Singapore"}}},coeditorTwo:{id:"113125",title:"Prof.",name:"Stelios",middleName:null,surname:"Smirnakis",slug:"stelios-smirnakis",fullName:"Stelios Smirnakis",profilePictureURL:"https://mts.intechopen.com/storage/users/113125/images/5471_n.jpg",biography:"Dr. Stelios Smirnakis was born in Iraklion, Crete, Greece. He obtained a BA in Physics and the MD/PhD in Medicine and Physics at Harvard University. After training in Neurology at the Partners Neurology Program, he specialized in Vascular Neurology and Critical Care. He served as a Research Scientist at the Max Planck Institute for Biological Cybernetics \n(Dept. Logothetis) in Tuebingen, Germany, working on a primate fMRI model of visual cortex plasticity after injury, then as Assistant Professor of Neurology at Harvard University, before moving to Baylor College of Medicine in March 2008 as an Assistant Professor of Neurology & Neuroscience. His research interests focus on studying cortical circuit function in health and disease using a range of methods including functional magnetic resonance imaging, two-photon imaging and classical electrophysiology.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Baylor College of Medicine",institutionURL:null,country:{name:"United States of America"}}},coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1059",title:"Neuroscience",slug:"mental-and-behavioural-disorders-and-diseases-of-the-nervous-system-neuroscience"}],chapters:[{id:"46092",title:"A Practical Guide to an fMRI Experiment",doi:"10.5772/58260",slug:"a-practical-guide-to-an-fmri-experiment",totalDownloads:3178,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:null,signatures:"Nasser 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He is currently an Assistant Professor - Energy Technology, School of Engineering Technology at Purdue University, USA. He is the Founder and Director of Advanced Power Units and Renewable Distributed Energy Lab (A_PURDUE). His research focuses on Modeling, Design, Multi-Objectives Optimization, Simulation, Analysis, and Control of various aspects such as Smart Nano & Micro- Grids; Electric Mobility & Transportation Electrification, Renewable Energy Systems; Wireless Charging of Electric Vehicles; Electric Vehicles; Special Purposes Electric Machines; Deep Learning Techniques; Distributed Generation Systems; Thermoelectric Generation; Special Power Electronics Converters; Power Systems; Energy Storage & Conservation; and Engineering Education. So far, He has 9 books, 5 chapters in books, 63 journal papers, 73 conference papers, and 106 other publications with his collaborators, and students related to his research interests. He has more than 20 years of working experience in academia and industry. He has experience in funding grant proposals, and He got some awards and recognitions due to his research work. He has good experience directing research for both graduate and undergraduate students for funded projects. He holds full-time academic positions at Purdue University, Georgia Southern University, the University of Illinois at Chicago, Ohio State University, USA, and Suez University, Egypt, along with some full-time and part-time positions in Egyptian companies as an electrical engineer, and consultant as a professional engineer. Additionally, He has distinguished professional training, and He is a Senior Member in the IEEE and IRED institutions along with 21 professional memberships in other societies. Finally, He served as a book editor for 4 books, and a reviewer for 8 books. He is a guest editor and editor-in-chief for three international journals. Also, He is a reviewer for other 35 international journals. Moreover, He served as invited conference sessions chair and reviewer for 31 international conferences along with other community and academic services.",institutionString:"Purdue University West Lafayette",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"4",institution:{name:"Purdue University West Lafayette",institutionURL:null,country:{name:"United States of America"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"15",title:"Mathematics",slug:"mathematics"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"347258",firstName:"Marica",lastName:"Novakovic",middleName:null,title:"Ms.",imageUrl:"//cdnintech.com/web/frontend/www/assets/author.svg",email:"marica@intechopen.com",biography:null}},relatedBooks:[{type:"book",id:"6187",title:"Advanced Applications for Artificial Neural Networks",subtitle:null,isOpenForSubmission:!1,hash:"c7fb38ad3b189551aa9a91eaa3da04d1",slug:"advanced-applications-for-artificial-neural-networks",bookSignature:"Adel El-Shahat",coverURL:"https://cdn.intechopen.com/books/images_new/6187.jpg",editedByType:"Edited by",editors:[{id:"193331",title:"Dr.",name:"Adel",surname:"El-Shahat",slug:"adel-el-shahat",fullName:"Adel El-Shahat"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5703",title:"Electrical Resistivity and Conductivity",subtitle:null,isOpenForSubmission:!1,hash:"1610778635f74a85054885a032a5554a",slug:"electrical-resistivity-and-conductivity",bookSignature:"Adel El Shahat",coverURL:"https://cdn.intechopen.com/books/images_new/5703.jpg",editedByType:"Edited by",editors:[{id:"193331",title:"Dr.",name:"Adel",surname:"El-Shahat",slug:"adel-el-shahat",fullName:"Adel El-Shahat"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7211",title:"Electric Machines for Smart Grids Applications",subtitle:"Design, Simulation and Control",isOpenForSubmission:!1,hash:"6704a769e34bd70d714b589a67565018",slug:"electric-machines-for-smart-grids-applications-design-simulation-and-control",bookSignature:"Adel El-Shahat",coverURL:"https://cdn.intechopen.com/books/images_new/7211.jpg",editedByType:"Edited by",editors:[{id:"193331",title:"Dr.",name:"Adel",surname:"El-Shahat",slug:"adel-el-shahat",fullName:"Adel El-Shahat"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9290",title:"Applied Electromechanical Devices and Machines for Electric Mobility Solutions",subtitle:null,isOpenForSubmission:!1,hash:"2e50c2d9cf3922f5f8fff01aaef1053e",slug:"applied-electromechanical-devices-and-machines-for-electric-mobility-solutions",bookSignature:"Adel El-Shahat and Mircea Ruba",coverURL:"https://cdn.intechopen.com/books/images_new/9290.jpg",editedByType:"Edited by",editors:[{id:"193331",title:"Dr.",name:"Adel",surname:"El-Shahat",slug:"adel-el-shahat",fullName:"Adel El-Shahat"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1591",title:"Infrared Spectroscopy",subtitle:"Materials Science, Engineering and Technology",isOpenForSubmission:!1,hash:"99b4b7b71a8caeb693ed762b40b017f4",slug:"infrared-spectroscopy-materials-science-engineering-and-technology",bookSignature:"Theophile Theophanides",coverURL:"https://cdn.intechopen.com/books/images_new/1591.jpg",editedByType:"Edited by",editors:[{id:"37194",title:"Dr.",name:"Theophile",surname:"Theophanides",slug:"theophile-theophanides",fullName:"Theophile Theophanides"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3161",title:"Frontiers in Guided Wave Optics and Optoelectronics",subtitle:null,isOpenForSubmission:!1,hash:"deb44e9c99f82bbce1083abea743146c",slug:"frontiers-in-guided-wave-optics-and-optoelectronics",bookSignature:"Bishnu Pal",coverURL:"https://cdn.intechopen.com/books/images_new/3161.jpg",editedByType:"Edited by",editors:[{id:"4782",title:"Prof.",name:"Bishnu",surname:"Pal",slug:"bishnu-pal",fullName:"Bishnu Pal"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"371",title:"Abiotic Stress in Plants",subtitle:"Mechanisms and Adaptations",isOpenForSubmission:!1,hash:"588466f487e307619849d72389178a74",slug:"abiotic-stress-in-plants-mechanisms-and-adaptations",bookSignature:"Arun Shanker and B. 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The photodynamic reaction comprises the interaction of a photosensitizer (PS), light (lasers, lamps, and LEDs), and oxygen present in the tissue. The photochemical process occurs when the PS absorbs light in one specific wavelength, interacts with subtracts and oxygen, and produces reactive oxygen species (ROS) and singlet oxygen (1O2), which are the main causes of PDT damage [1, 2]. Topical PDT using topical medication such as 5-aminolevulinic acid (ALA) and its methyl ester (methyl aminolevulinate [MAL]), has been widely employed to treat skin cancer, skin diseases, and aging skin [2, 3, 4]. When methyl, ethers, and other groups are added to ALA, its derivatives become more lipophilic, thereby increasing permeability through the skin [5].
ALA and MAL act as precursors of protoporphyrin IX (PPIX), an endogenous PS produced by mitochondria on cells [2]. While ALA and MAL application on PDT has the advantage of being localized and nonsystemic (transdermal application), it has some limitations as regards penetration through the skin [2, 6, 7].
ALA is a hydrophilic compound, making it difficult to cross the biological barriers of the skin, such as cell membranes. However, it has high efficiency in the production of PPIX. On the other hand, MAL has a lipophilic character allowing it to be transported by nonpolar amino acids via passive diffusion (does not require a driver) facilitating the ability to move across biological barriers reaching higher penetration in the desired tissue, and at a lesser cost than the production of PPIX [8, 9].
It is known that PPIX formation by ALA and MAL application in carcinomas is different to PPIX formation in healthy skin, thus there are few studies comparing ALA and MAL in healthy human skin. Lesar et al. compared the production efficiency of PPIX by the application of ALA and its precursors in various parts of the human body [10]. However, in our study we compared ALA, MAL, and mixtures from both on porcine and human skin models. ALA and MAL as precursors of PPIX were chosen in our study since they are used most in clinical topic PDT [11]. Many types of animal models have been suggested to replace human skin in research on transdermal permeation of molecules [8, 12], including primate, porcine, mouse, rat, guinea porcine, and snake models. Nowadays, the use of primates in research is highly constrained [8]. On the other hand, similarities between porcine skin and human skin models have been discussed in many papers [8, 13].
Animal skin differs morphologically from that of human skin with respect to epidermis and dermis thickness, hair follicles, and other characteristics. Despite their many similarities, porcine and human skin differ regarding structure, immunohistochemistry, and function. Notwithstanding, porcine appears the most suitable animal type to replace human skin in test models [14]. Indeed, porcine constitutes the nonrodent species of choice in the preclinical toxicological testing of pharmaceuticals [13].
The prospect of decreasing the number of human volunteers in studies using
Research has shown that skin barriers vary among species as regards the amount of free fatty acids and triglycerides and density of hair follicles [8]. Stratum corneum (SC) lipid composition (ceramides, free fatty acids, cholesterol, and cholesterol esters) and organization in biological membranes differ from one species to another. According to Godin, the lack of correlation in transdermal drug permeation among species or different application sites in the same animal model is mainly due to variations in skin thickness, the composition of intercellular SC lipids, and a number of skin shafts [8]. Bearing this in mind, research has shown that porcine ear skin is anatomically similar to human skin regarding lipid composition, which confirms its suitability for use as a new animal model to study adnexal glands. In addition, its anatomic and physiologic characteristics with respect to cardiovascular, urinary, integumentary, and digestive systems are similar to those of human skin [13, 16].
Many authors claim that porcine skin models constitute the most relevant animal model for human skin because porcine skin and human skin have similar histological and biochemical properties [8, 9, 15]. Porcine skin is structurally similar to human skin regarding epidermal thickness and dermal–epidermal thickness ratio; their dermis thickness is approximately 3 mm and their SC and epidermis thicknesses are in the region of 21–26 and 70 μm, respectively [8, 13]. The collagen fiber arrangement in the dermis and the SC proteins (glycosphingolipids and ceramides) present in the porcine skin are also similar to those of human skin [8].
While the vascular anatomy of human skin is superior to that of porcine skin, neonatal porcine skin has the same structure, including sweat glands and hair follicles (730 follicles/cm2), as opposed to 10 follicles/cm2 found in adult porcine skin [8, 17]. In this way, in this work we performed the tests in animals of 3–4 months of age.
Nowadays, many scientists consider porcine skin a suitable and readily available model for the human skin barrier and often employ it to test topical and transdermal pharmaceutical formulations both
Although several studies indicate similarities between porcine skin and human skin models, predictions about drug behavior in human skin based on results from tests using animal models are still under debate. Some authors believe that animal models constitute useful tools in biomedical research, but remark that effects obtained with animal models are not readily transferable to clinical settings [19].
The purpose of this work is to verify whether there is a robust correlation between porcine and human skin models and, if so, confirm that the porcine skin model is the best alternative to prediction studies with human skin volunteers using optical techniques.
In the previous study [19], porcine skin was studied, and in this chapter we can evaluate the correlation between both models. Seven different samples (ALA, MAL, and mixtures from both) were applied to human and porcine skin and their PPIX production was monitored using widefield fluorescence imaging and fluorescence spectroscopy techniques.
The PPIX precursors used in this study were ALA and MAL (final concentration of 20%), which were dissolved in different proportions in an oil-in-water (O/W) emulsion. Seven samples (ALA, MAL, and mixtures from both) were prepared in the following proportions: M1 (100% ALA), M2 (80% ALA and 20% MAL), M3 (60% ALA and 40% MAL), M4 (50% ALA and 50% MAL), M5 (40% ALA and 60% MAL), M6 (20% ALA and 80% MAL), and M7 (100% MAL). The emulsion or cream preparation was previously described [19].
Commercial ALA and MAL were obtained from PDT-PHARMA (Cravinhos, São Paulo, Brazil) and were prepared immediately prior to use without previous solubilization because the drug presents elevated solubility in the base cream used.
This study used a protocol along the lines of the procedures established by Brazil’s Human Research Ethics Committee (no. 13556713.8.0000.5504). In addition, a written informed consent was obtained from all participants. Ten female patients aged around 25 years with the clinical diagnosis of normal skin were recruited for this study. To be considered eligible, a patient had to be free of skin disorders on both arms. The volunteers were all women to decrease the variable numbers in the study.
All patients had either Fitzpatrick skin type II (50%) or III (50%). Patients with lesions on the target area or with porphyrin were excluded. Additional exclusion criteria included male volunteers, pregnant or lactating female volunteers, those allergic to ALA and MAL, and volunteers less than 20 and more than 35 years of age. The volunteer protocol followed the standardization previously described [2].
The study was performed
In human skin, the cream was applied in seven areas (a circular area of 1 cm2 each) on each volunteer’s right or left inner arm (10 woman human volunteers). Before cream application, the area was cleaned with serum. Skin autofluorescence was used as the control for each cream sample (ALA, M2, M3, M4, M5, M6, and MAL). Data were compared for each treatment group for the same volunteer and among volunteers.
In porcine skin, the cream was applied in a square area of 4 cm2 (applied on the back). To prepare the cream application it was necessary to remove the hairs from the back. Animal testing involving porcine skin models was performed as described above with seven cream samples (ALA, M2, M3, M4, M5, M6, and MAL) in triplicate (in regard to conditions as well as experiments) [19].
The areas were dressed with an occlusive mask to protect them from light. The cream was removed prior to autofluorescence collection at the skin by fluorescence spectroscopy and widefield fluorescence imaging. After collection, the same amount of cream was applied again under the same conditions at every full hour during 5 h. The experimental procedure was previously described (Figure 1) [2, 19].
Application of different cream samples (ALA, M2, M3, M4, M5, M6, and MAL) at the skin: (A) human right inner arm; (B) human left inner arm; and (C) porcine skin back.
A widefield fluorescence imaging system was used for image acquisition. It is a commercial device, produced by MM Optics, Sao Carlos, Brazil, called EVINCE. In brief, the widefield imaging system consists of a lighting device based on LEDs, emitting around 405 nm coupled to a digital camera for image acquisition [2, 19, 20]. The measurements were taken for each sample and different times of PPIX formation. The images obtained by widefield fluorescence were assessed quantitatively using a routine written in Matlab program. The program has defined an array separating the red, green, and blue (RGB) channel colors.
For pixel count analysis, standardization was obtained dividing the red channel by the green channel. This was done to avoid the effects of different shutter speeds and ISO settings for image acquisition. Finally, fluorescence (pixel count) was determined by summing the values of all red channels divided by the sum of all values of the green channel. With these data, it was possible to quantify PPIX production (which shows red fluorescence) in amount and uniformity on the skin extension [2, 19].
For fluorescence spectroscopy analysis, a system with two excitation lasers was used, emitting at 408 nm and 532 nm, respectively. The investigation fiber probe in the Y shape directs the excitation laser to the tissue, while the second arm of the Y shape collects the re-emitted light from the tissue and delivers light to a spectrophotometer. The spectrophotometer used was the USB2000 (Ocean Optics®, USA). A filter was used to remove backscattered light so that only the fluorescence was collected [2, 19, 21].
We recorded the fluorescence spectrum in contact with the tissue at five points in the area where the cream was applied, and equivalent autofluorescence collection was performed. The evaluations from spectral analysis were normalized by total area and subtracted from the autofluorescence. The spectrum evaluations were performed using an Origin 9 program as previously described in our publication [2, 19]. A spectrometer and widefield fluorescence imaging equipment collected skin fluorescence at every full hour during 5 h. At the end of the fluorescence analysis, the cream mixtures were reapplied to the treatment area and covered with an occlusive dressing.
Figure 2 shows the PPIX formation after 3 h of cream incubation for human and porcine skin obtained by widefield fluorescence imaging. Figure 3 shows the quantitative analysis of the PPIX formation by counting pixels of the images and spectroscopy collection acquired by fluorescence techniques. The result of this analysis was acquired by means of the average data collected from volunteers and animals. The results of the porcine skin model were also published previously [19]. The results in Figure 3 show that the high amount of PPIX production in human and porcine skin occurs for all cream samples (ALA, M2, M3, M4, M5, M6, and MAL) after 3 h of cream application.
Widefield fluorescence imaging after 3 h of cream sample application (ALA, M2, M3, M4, M5, M6, and MAL): (A) PPIX production in human skin (inner arm) and (B) PPIX production in porcine skin back.
Analysis of PPIX production in human and porcine skin models after 3 h of cream sample application evaluated by (a) widefield fluorescence imaging and (B) spectroscopy fluorescence.
Fluorescence imaging shows that PPIX production is heterogeneous for healthy skin in both skin models. Even so, it is possible to verify the differences in PPIX formation to ALA, MAL, and mixtures from both. The results suggest that PPIX formation is greater for ALA than for MAL for both models. In addition, PPIX formation of all sample cream mixtures from ALA and MAL (M2, M3, M4, M5, and M6) was more elevated than MAL and is similar to ALA.
In addition, it is important to mention that for porcine skin preparation it was necessary to shave the back, and for human skin preparation the area was cleaned with physiological serum. This previous skin preparation can interfere with cream sample penetration on the skin as well as PPIX production. This explains the lowest PPIX production for all samples in human skin models when compared to porcine skin models (Figure 3).
Figure 4 shows the kinetics study on human skin only, wherein the monitoring of PPIX production was carried out during 5 h, and the measurements were carried out hourly for both fluorescence techniques. From this study, it was possible to analyze which sample PPIX was produced quickest, and by means of a parameter called the index of fluorescence (IF50) it was possible to quantify the PPIX production in minutes. IF50 means 50% of maximum fluorescence value obtained for 5 h.
Kinetics of the PPIX production in human skin models by fluorescence spectroscopy and widefield fluorescence imaging evaluations for all cream samples (ALA, M2, M3, M4, M5, M6, and MAL).
Although Figure 4 presents the results of the human skin study, Table 1 shows the IF50 results for the study in human and porcine skin. We have included it here for best comparison. The graphs of the kinetics study in porcine can be observed in previously published work [19].
Samples | Widefield fluorescence imaging IF50 (min) | Fluorescence spectroscopy IF50 (min) | ||
---|---|---|---|---|
Human skin | Porcine skin | Human skin | Porcine skin | |
ALA | 103 ± 15 | 120 ± 10 | 234 ± 18 | 230 ± 7 |
M2 | 138 ± 27 | 134 ± 6 | 315 ± 13 | |
M3 | 154 ± 18 | 40 ± 60 | 312 ± 6 | 114 ± 16 |
M4 | 127 ± 14 | 128 ± 8 | 225 ± 13 | 17 ± 20 |
M5 | 122 ± 21 | 97 ± 7 | 280 ± 12 | 131 ± 17 |
M6 | 207 ± 38 | 120 ± 20 | 260 ± 15 | 187 ± 25 |
MAL | 233 ± 18 | 70 ± 5 | 388 ± 37 | 131 ± 9 |
IF50 values for widefield fluorescence imaging and fluorescence spectroscopy collected over time (5 h) after sample cream application on human and porcine skin model surfaces.
The results for the kinetics study in the human skin model show that PPIX production is faster with ALA than MAL and cream samples (M3, M4, M5, and M6) for both fluorescence analyses. However, the mixtures M3, M4, and M5 presented better results for PPIX production than MAL in the kinetics study (IF50 values). These results suggest that these differences may be due to high variability in human skin experiments. Perhaps these differences can be reduced by using a number of human volunteers.
The results for the kinetics study from Table 1 show that PPIX production in 5 h (IF50) in human skin models is faster for ALA than MAL, and the opposite occurs for porcine skin models where PPIX production is faster for MAL than ALA. This can be explained by the previous preparation for porcine skin where we can suggest that PPIX production by MAL can be optimized. The other sample creams (M3, M4, M5, and M6) show the same behavior considering the standard deviation.
The values found for IF50 through the widefield fluorescence imaging data were closer to human and porcine skin models than the IF50 values collected by fluorescence spectroscopy. We believe that this occurred because PPIX production is heterogeneous and the fluorescence spectroscopy measurements are punctual. This punctual fluorescence collection data of PPIX production can suggest false negative or false positive results. On the other hand, by using widefield fluorescence imaging, we can evaluate all PPIX production on the skin surface.
Figure 5 shows the correlation linear fitting to fluorescence measurements obtained through widefield fluorescence imaging and fluorescence spectroscopy. The fitting in Figure 5 shows that the red fluorescence signal emitted by PPIX in the porcine and human skin was measured at 3 h following application of ALA and MAL cream mixtures. These results confirm that there is a correlation between both models since the equation line factor obtained was 0.9824, bordering on 1.0, the ideal linear fitting number.
The best correlation analysis between human and porcine skin models by widefield fluorescence imaging.
The same linear fitting was performed for fluorescence collected through fluorescence spectroscopy (results not presented here). However, we do not find a correlation between both models (human and porcine skin) by this optical technique due to high variability during fluorescence spectroscopy collection.
The fitting results shown in Figure 5 indicate the best correlation between porcine and human skin models by widefield fluorescence imaging measurements. The possibility of predicting drug behavior on transdermal skin application promotes the success of clinical topical PDT treatment.
The aim of the study was to evaluate PPIX formation due to ALA, MAL, and cream sample mixtures from both (M2, M3, M4, M5, and M6) application on normal skin models (porcine and human) and then to show that there is a narrow correlation between both models. In this work we use ALA and MAL on topical application as the precursor of PPIX, since these are the most common drugs applied to clinical topical PDT. The fluorescence measurements were collected after 3 h of cream incubation time since this time is also applied to clinical PDT [19, 22].
In our group [22] the clinical PDT studies on skin cancer are done using 20% ALA and MAL cream application in 3 h of incubation time before light irradiation. During this time, PPIX production is elevated since the previous preparation was performed (curettage).
The fluorescence measurements were done using two techniques: fluorescence spectroscopy and widefield fluorescence imaging. With fluorescence spectroscopy using a 532 nm laser (green light) it is possible to evaluate the skin at greater depths (reaching the dermal papillae) when compared with widefield fluorescence imaging using a 405 nm LED (violet light) bringing images from PPIX on the superficial skin [2, 19].
In the study the choice of animal age had great influence; in agreement with the literature the thickness of porcine skin is similar to human skin at around 2 months after birth [8, 13].
PPIX formation on normal skin is not homogeneous and depends on ALA, MAL, and mixtures from both (M3, M4, M5, and M6) penetration through the skin; evaluations using images by widefield fluorescence imaging can be useful and decrease the variability on experiments. Fluorescence spectroscopy evaluation, despite being collected punctually, which can lead to erroneous measurements and high variability, reveals information about PPIX formation on the deeper skin [2, 19] and is important to understand the replacement mechanism of PPIX from deeper layers up to superficial skin layers.
As shown by Valentine et al. [23], there was no difference after increasing the amount of PPIX using ALA and MAL when analyzed by fluorescence spectroscopy using a laser emission at 405 nm (violet light). Fluorescence emission due to 405 nm illumination allows us to measure the output of PPIX on the superficial skin (stratum corneous and superior epidermis). In our work, this superficial skin analysis was performed using widefield fluorescence imaging.
There are few studies concerning the comparison of ALA and MAL in healthy human skin, but Lesar et al. [10] compared the formation efficiency of PPIX from these precursors in various parts of the human body (arm, forearm, back, and legs) with fluorescence (4–29 h) after topical application. They then observed that there were differences in PPIX production, which applied regardless of where the ALA accumulated more PPIX, but the location (back) where they applied the tape striping difference was only after 24 h.
The kinetics study observed that ALA, M4, and M5 indicated the least time of PPIX production (high PPIX production velocity) at the skin. Both studies, human and porcine skin, showed the same behavior. IF50 values acquired by widefield fluorescence imaging for both models were very close, with the exception of M3, M6, and MAL. Thereby, it is possible to appreciate the similarity of porcine skin with human skin by first performing clinical tests on porcine skin.
However, it is known that
The correlation found between human and porcine skin models measured by widefield fluorescence imaging confirms that porcine skin can be used for establishing human protocols in clinical topical PDT using ALA, MAL, and mixtures from both. The capacity of porcine skin models to predict PDT results in humans can be beneficial to clinical studies optimizing PDT treatment on patients.
The authors acknowledge the financial support of the National Council of Technological and Scientific Development (CNPq process 140370/2012-9) and São Paulo Research Foundation (FAPESP/CEPOF). Expressive thanks are extended to Ms. Michelle Requena and all the volunteers for their participation in this study.
Even for students just beginning to study biochemistry and physiology, it is immediately apparent that amino acids (AAs) are among the most important molecules in nature. Their functions are broad and varied. Indeed, protein synthesis relies on the well-known polymerization of AAs to form a peptide bond. This property is the most famous aspect of AAs. However, many AAs have specific individual functions, such as neurotransmission [1], cellular energy metabolism [2], and detoxification [3, 4]. Accumulating evidence in recent years has demonstrated that AAs also regulate both the expression of genes and the protein phosphorylation cascade. Moreover, hormones and different low-molecular-weight biologically important chemical compounds can be synthesized from AAs [5]. AAs can be divided into essential and nonessential categories. If the body cannot synthesize the carbon skeleton of an amino acid, then it is considered nutritionally essential. Indeed, the diet must contain such AAs. The dietary essentiality of other AAs (e.g., arginine, glycine, proline, and taurine) is determined by the developmental stage and species [6]. In contrast, if AAs can be synthesized de novo in a species-dependent manner, they are considered nonessential. Accumulating evidence has led to the concept of functional AAs (FAAs), which are defined as AAs that regulate key metabolic pathways to improve the health, survival, growth, development, lactation, and reproduction of organisms [7]. Since the late 1970s, researchers have generally agreed that amino acids can also function as inhibitory or excitatory neurotransmitters [8]. It should be noted that in neurochemistry, the term “neurotransmitter” is usually used synonymously with “neuromediator,” another term for a chemical participant in connections between neurons and neuroglia cells. Because these terms are exchangeable, they will both be used in the text. Based on their effects on vertebrate nerve cells, γ-aminobutyric acid (GABA), glycine, and taurine fall into the class of inhibitory amino acids, whereas glutamate and aspartate fall into the class of excitatory compounds [9]. Indeed, GABA is considered the main inhibitory neurotransmitter in the central nervous system (CNS) [10], but it is not truly a member of the AA family. Although taurine also plays a role in inhibitory neuromediation [11] and serves as an osmoeffector to regulate volume in astrocytes [12], this compound is considered a derivative of cysteine, and, similar to GABA, not a true amino acid. Thus, the remaining excitatory/inhibitory amino acid neurotransmitters are glutamate, aspartate, and glycine. The first and third are the most prominent members of the AA family. The processes that regulate glutamate and glycine in the CNS are (i) transportation, (ii) biochemical transformations in metabolic pathways, and (iii) interactions with membrane receptors. In the current chapter, the crosstalk between the processes mentioned above for both glutamate and glycine is presented because the final state of neurons seems to be a result of the balance between these excitatory and inhibitory influences.
Glutamate and glycine are nonessential amino acids; their levels differ depending on the location. The extracellular glutamate concentration around quiescent neurons is less than 1 μM, while its concentration in the cytoplasm is much higher, at approximately 2 mM [13]. The brain sequesters glycine in concentrations of 600 μM [14], with a basal concentration in the cerebrospinal fluid (CSF) of ~6 μM [15], compared to a plasma concentration of ~250 μM [16]. Because no extracellular enzymes degrade glutamate and glycine, maintaining these low extracellular concentrations requires cellular uptake of both compounds. Thus, the activity of the carriers directly regulates receptor response to neuron activation. Indeed, glutamate and glycine serve as neuromediators in the extracellular fluid because the binding site of AA receptors is exposed to the outer surface of cells. Consequently, the release of AA into the extracellular fluid controls receptor activation and active states are controlled by the removal of AAs from the extracellular fluid [17]. This uptake is catalyzed by a family of transporter proteins located on the cell surface of both astrocytes and neurons [17]. A high-affinity glutamatergic uptake system was observed in the mammalian brain in the 1970s. Subsequently, excitatory amino acid transporters (EAATs) were experimentally identified. They transport glutamate and aspartate across the plasma membrane. Notably, EAATs are part of the well-known solute carrier 1 (SLC1) family of transmembrane amino acid transporters [18]. Thus, released glutamate molecules can be removed from the synaptic cleft by the brain transporters; this process will initiate the glutamate-glutamine cycle, eventually restoring the pool of the neuromediator in synaptic vesicles [19]. Five EAAT isoforms, human EAAT1-5, have been identified; they correspond to GLAST1/GLT-1/EAAC1/EAAT4/EAAT5 in rodents, respectively [20]. In addition, the EAAT4 and EAAT5 subtypes were identified, with EAAT5 predominantly expressed in the retina. Notably, the transport cycle times of EAATs are relatively slow and their high affinity for glutamate makes it possible to sequester low glutamate concentrations from the extracellular space, preventing excitotoxicity. The slow transportation rate may in part be overcome by rapid surface diffusion and transporter tracking of EAATs upon glutamate stimulation [21]. The SLC1 family also contains two neutral amino acid transporters, alanine serine cysteine transporters 1 and 2 (ASCT1 and 2), which share high sequence homology with the EAATs [22]. EAAT1 and EAAT2 are glutamate transporters that are mostly expressed in astrocytes. These two glutamate transporters are responsible for most of the glutamate clearance in the brain. EAAT2 is widely expressed in the cerebral cortex and the hippocampus [13]. Moreover, GLT-1/EAAT2 accounts for approximately 90% of the total glutamate uptake in the brain, and thus, it is considered the most important glutamate transporter subtype in the CNS. This transporter is predominantly but not exclusively expressed in astrocytes [22]. Glutamate transporters couple glutamate uptake to the transport of inorganic ions. It is now generally accepted that 3 Na+ ions and 1 H+ ion are cotransported and 1 K+ ion is counter-transported with the uptake of each glutamate molecule. Based on this stoichiometry, glutamate transporters were calculated to concentrate glutamate up to 5 × 106-fold inside cells under physiological conditions. This glutamate transport is electrogenic [23].
The extracellular levels of glycine in inhibitory and excitatory synapses are controlled by glycine transporters (GlyTs). Both subtypes, GlyT1 and GlyT2, belong to the sodium-dependent solute carrier 6 (SLC6) family of transporters, but they have different regional and cellular expression patterns in the CNS, different stoichiometries (that is, different numbers of sodium ions that are co-transported with every glycine molecule) and varying abilities to reverse-transport glycine into the extracellular space. To date, five variants of GlyT1 (GlyT1a, GlyT1b, GlyT1c, GlyT1d, and GlyT1e) and three variants of GlyT2 (GlyT2a, GlyT2b, and GlyT2c) have been identified and occur as a result of alternative promoter usage and/or splicing, but the relative distributions of these within the CNS have not been fully characterized [21].
The essential function of membrane transporters is to accumulate neuromediators in vesicles. At presynaptic terminals, vesicular glutamate transporters (vGluTs; SLC17A7, -6, and -8) load glutamate into synaptic vesicles. The two subtypes of vGluTs, vGluT1, and vGluT2, are expressed in excitatory neurons in a complementary manner in the brain, composing two subsets of excitatory neurons [13]. Glycine also actively accumulates in synaptic vesicles through vesicular inhibitory amino acid transporter (VIAAT); currently, only one type of transporter (SLC32A1) is known to be responsible for this process [18]. The scheme of balanced neuromediator transport is represented in Figure 1.
Membrane carriers are responsible for clearance of glutamate/glycine from interstitial fluid (ISF) in the CNS. The scheme indicates two types of neurons. Some are excitatory and glutamatergic (the upper part of the scheme). Other neurons are inhibitory and glycinergic (the lower part of the scheme). Both types of neurons are interconnected with astrocytes. Moreover, glycine and glutamate are accessible for both types of cells. AA transporters (EAAT, GlyT, etc.) are found in all cell membranes but have differing isoenzyme compositions.
Remarkably, both glutamate and glycine transporters have mechanisms that include sodium ion transport. This means that neuromediator uptake is accompanied by changes in membrane potential. Moreover, the intake of both glutamate and glycine initiates several metabolic reactions in neurons and astrocytes. However, these reactions are spatially distributed, and the fate of the neuromediators is functionally determined by different cells. Interestingly, the metabolic transformations of AAs are closely related to ATP production by mitochondria and the oxidation of glucose.
As mentioned above, any example of metabolic transformation in brain tissue is tightly connected with glycolysis Therefore, glutamate/glycine participation in metabolic pathways seems to be considered correctly including the main neighbor reactions of glucose oxidation. The primary source of energy for the brain is glucose. This sugar is almost entirely oxidized under basal physiological conditions, providing nearly all the energy necessary to support brain function. However, when supplemental energy is needed, necessary energy demands may be provided by other metabolites, such as ketones, fatty acids, acetate, lactate, and certain amino acids [19]. Pyruvate, the end product of aerobic glycolysis, can enter the tricarboxylic acid (TCA) cycle by two different routes: (1) via acetyl-CoA formation, catalyzed by the pyruvate dehydrogenase complex, and (2) by the formation of oxaloacetate, catalyzed by PC [24]. However, the end metabolite of anaerobic glycolysis, lactate, also participates in the energy supply of neurons (Figure 2). Pellerin and Magistretti originally proposed the astrocyte-neuron lactate shuttle (ANLS) model, wherein lactate released from astrocytes serves as a buffer compound in response to a glutamate-induced glycolysis stimulus [25]. Then, lactate is exported to neurons, where it is converted to pyruvate to fuel oxidative phosphorylation.
A scheme of the metabolic pathways involved in general glutamate/glycine transformations. The reactions occur in various intracellular localizations and can be duplicated in different compartments. The main metabolic pathways (glycolysis and the tricarboxylic acid (TCA) cycle) are labeled. The enzyme abbreviations are as follows: GM: glutaminase; GS: glutamine synthetase; GDH: glutamate dehydrogenase; GL: glutamylcysteine ligase; GTS: glutathione synthetase; AG: asparaginase; AT: aminotransferase; PPC: phosphoenolpyruvate carboxykinase; PC: pyruvate carboxylase; PDC: pyruvate dehydrogenase complex; PK: pyruvate kinase; LDH: lactate dehydrogenase; SDH: serine dehydrogenase; STM: serine transhydroxymethylase; and GCS: the glycine cleavage system. Other abbreviations are as follows: NAD+: Nicotinamide adenine dinucleotide (oxidized); NADH: Nicotinamide adenine dinucleotide (reduced); ATP: Adenosine triphosphate; ADP: Adenosine diphosphate; and THF:Tetrahydrofolate.
Thus, the ANLS model suggests that lactate, not glucose, provides energetic support for firing neurons [26]. Glutamate and glycine are active participants in these metabolic processes. Exclusion of most blood-borne glutamate at the blood-brain barrier (BBB) and a net removal of glutamine from the brain indicate that the cerebral pools of glutamate are largely produced within the brain [27]. The stability of glutamate concentration is maintained by two main reactions. Glutamine synthetase (GS), which is found in astrocytes, is the only known enzyme to date that is capable of a reversible conversion between glutamine and glutamate and ammonia in the mammalian brain [28]. Furthermore, cells can convert glutamate to glutamine in an ATP-dependent process catalyzed by glutamine synthetase. Astrocytic uptake of glutamate and release of glutamine, together with neuronal uptake of glutamine and release of glutamate, constitute the glutamate-glutamine cycle [29]. However, much of the glutamate taken up by astrocytes is destined for oxidative degradation, which first requires conversion to the TCA cycle intermediate 2-oxoglutarate. This can take place via transamination by aminotransferase (AT) or via oxidative deamination by glutamate dehydrogenase (GDH) [30].
Once glycine passes into a cell by uptake by GlyTs, the intracellular glycine concentration can be regulated via synthesis from L-serine within the cell, which itself can be synthesized from glycolysis intermediates and L-glutamate [24]. The major pathway for the glycine catabolism involves the oxidative cleavage of glycine to CO2, NH4+, and a methylene group (–CH2–), which is accepted by tetrahydrofolate (H4folate) in a reversible reaction catalyzed by the glycine cleavage system (also called glycine synthase) [31]. The glycine cleavage system is essentially reversible but catalyzes glycine synthesis significantly only under anaerobic conditions, such as in anaerobic bacteria or anaerobic systems in vitro supplemented with NADH+H+ [32].
Taken together, all known information about the metabolic pathways suggests that glutamate and glycine self-regulate the processes of their concentration restoration and mutual transformation. Additionally, oxidative phosphorylation in the mitochondria also plays a key role in the balance of these AAs.
The neuromediator function of AAs in the CNS is performed through the activation of membrane receptors. After being released from the presynaptic membrane into a synaptic cleft, glutamate and glycine rapidly diffuse to a postsynaptic membrane, where appropriate receptors are further activated.
Glutamate receptors are divided into two groups: ionotropic glutamate receptors (iGluRs) and metabotropic glutamate receptors (mGluRs). Excitatory neurotransmission throughout the CNS is mediated by ligand-gated ion channels, including ionotropic glutamate receptors (iGluRs) [33]. Abnormalities in iGluRs lead to a wide range of neurological diseases. Glutamate, the primary neurotransmitter in almost all synapses in the CNS, is released from presynaptic terminals and diffuses to the postsynaptic membrane, where it binds to iGluRs. This process leads to the opening of ion channels, allowing cations to flow in. Thus, the transmembrane channel rapidly depolarizes the postsynaptic membrane. The decrease in membrane potential initiates signal transduction in the postsynaptic neuron. In the iGluR family, four subtypes of integral membrane proteins have been identified in vertebrates based on their pharmacological properties and sequence homologies: α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), kainate (KA), N-methyl-D-aspartate (NMDA), and δ-receptors [34]. Subsequent cloning studies have revealed that NMDARs are assembled as heteromers that differ in subunit composition. To date, seven different subunits have been identified and categorized into three subfamilies according to sequence homology [35]. Each iGluR family member exhibits specific kinetic and pharmacological properties in addition to playing a unique role in neurotransmission [36]. The iGluRs are ligand-gated ion channels that are permeable to Na+ and K+ (and Ca2+ in some instances), whereas the mGluRs are G protein-coupled receptors that trigger second messenger cascades. The early component and the late component of neurotransmission are assumed to be mediated by AMPARs and NMDARs/KARs, respectively. This assumption is based on receptor kinetics, as AMPARs are faster and NMDARs/KARs are slower. Nevertheless, acoustic signals are transferred by all of these iGluRs in a precise and reliable manner. Moreover, some auditory processing neurons have a fourth type of iGluR, the delta receptor [34]. The open, or conducting, conformation of the iGluR ion channel is nonselective for monovalent cations. Membrane excitation is often driven by channel permeability to Ca2+. This Ca2+ influx and its physiological and pathological consequences depend strongly on the specific iGluR subtype and the specific subunits in its oligomeric complex [37].
mGluRs are G protein-coupled receptors (GPCRs) that, following activation, regulate both G protein-dependent and G protein-independent signalling pathways. According to sequence homology, cell signalling activation, and agonist selectivity, the mGluRs have been divided into eight subtypes (from mGlu1 to mGlu8). These subtypes comprise three different subgroups (from I to III) [38]. Group I mGluRs (mGlu1 and mGlu5) are functionally linked to polyphosphoinositide (PI) hydrolysis and are negatively coupled with K+ channels. Both group II (mGlu2 and mGlu3) and group III (mGlu4, mGlu6, mGlu7, and mGlu8) mGluRs negatively regulate adenylate cyclase and activate mitogen-activated protein kinase (MAPK) and PI-3-kinase pathways [39]. mGluRs are usually localized on synaptic and extrasynaptic membranes in both glia and neurons. Group I mGluRs are generally postsynaptic, surrounding ionotropic receptors, and modulate depolarization and synaptic excitability. Groups II and III are mostly expressed at the presynaptic level and control the release of neurotransmitters [39, 40]. mGluRs are heavily expressed throughout the basal ganglia (BG), where they modulate neuronal excitability, transmitter release, and long-term synaptic plasticity [41]. These receptors are coupled to different G proteins and modulate slow postsynaptic neuronal responses, either through presynaptic or postsynaptic machinery or through modulation of astrocyte function [42]. mGluRs are highly and diffusely expressed in glial cells. On the one hand, this increases the options for therapeutic interventions, but on the other hand, it makes it even more difficult to selectively target single receptors to yield neuroprotection (Figure 3) [43].
A reconstruction of possible AA ionotropic receptors in the CNS. The images were created using the data collected in the Protein Data Bank (PDB) (
Glycine receptors (GlyRs), along with certain γ-aminobutyric acid receptors (GABAARs), are the principal determinants of fast inhibitory synaptic neurotransmission in the central nervous system (CNS). GlyR and GABAAR belong to the superfamily of pentameric ligand-gated ion channels (pLGICs) [33]. The two neurotransmitters (glycine and GABA) may be functionally interchangeable, and the multiple receptor subtypes with inhibitory influences provide diverse mechanisms for maintaining inhibitory homeostasis [35]. Inhibitory glycine receptors (GlyRs) are anion-selective ligand-gated ion channels (LGICs), which, together with GABAA receptors (GABAARs), nicotinic acetylcholine receptors (nAChRs), and serotonin type 3 receptors (5HT-3), form the eukaryotic Cys-loop family [36]. Several endogenous molecules, including neurotransmitters and neuromodulators (such as glutamate, Zn, and Ni), and exogenous substances, such as anaesthetics and alcohols, modulate GlyR function [40].
Despite their obvious physiological roles in protein synthesis, the cellular effects of glycine and glutamate in the CNS seem to be quite different. If glycine has been contemplated an “angel” compound, due to its generally positive effects, then glutamate has usually been considered a “demon” compound, owing to its generally negative effects. Although the last claim is far from accurate, the first is supported by many experimental findings. Indeed, the effect of glycine has always been reported as positive. It protects against oxidative stress caused by a wide variety of chemicals, drugs, and toxicants at the cellular or organ level in the liver, kidneys, intestines, and vascular system [34, 37]. Glycine is a major component of collagen molecules that is vital to stabilizing them to form a triple helix [48]. Administration of glycine attenuates diabetic complications in a streptozotocin-induced diabetic rat model [49]. Supplemental glycine effectively protects muscles in a variety of wasting models, including cancer cachexia, sepsis, and dieting [50]. Glycine may prevent ischaemia–reperfusion injury by direct cytoprotection, presumably by inhibition of the formation of plasma membrane pores and of the inflammatory response [38]. The cytoprotective and modulatory effects of glycine have been observed in many nonneuronal cell types. The action of glycine is mediated by classic or unconventional GlyRs, both inside and outside of the nervous system [51]. Glycine cytoprotection substantially overlaps with the number of agents that act on neuronal receptors with glycine as an agonist or coagonist. This observation has been confirmed by molecular pharmacology studies from multiple laboratories. The studies indicate highly constrained steric and conformational requirements for the interaction, which, along with the rapid on-off timing of the effects, is consistent with the involvement of reversible ligand-binding site interactions [52].
In contrast, glutamate is considered a toxic agent that yields excitotoxicity at overload concentrations. Indeed, the neurotoxic potential of glutamate has been recognized since the 1950s [53]. For example, a major driver of white matter demise is excitotoxicity, a consequence of the excessive glutamate released by vesicular and nonvesicular mechanisms from axons and glial cells. This excessive glutamate concentration results in overactivation of iGluRs profusely expressed by all cell compartments in white matter [54]. Generally, excitotoxicity involves a large inflow of Ca2+ and Na+ into neurons up to the conditions when Ca2+ concentrations reach critical levels, leading to cell injury or death [55]. Moreover, ambient extracellular glutamate is lower than the concentration known to trigger excitotoxicity and subsequent neurodegeneration; excitotoxicity is known to occur at extracellular glutamate concentrations as low as 2 to 5 μM, with swelling and apoptosis predominating at <20 μM glutamate and fast necrosis at >100 μM glutamate [56]. Excitotoxic neuronal death is involved in neurodegenerative diseases of the CNS, such as multiple sclerosis [57], Alzheimer’s disease [58], Parkinson’s disease [59], Huntington’s disease [60], stroke, epilepsy, alcohol withdrawal, and amyotrophic lateral sclerosis [61]. However, the role of glutamate is not only excitotoxic. The assumption that neurodegenerative disease treatments should “fight against” glutamate is incorrect given the wrong function of glutamate in the CNS. As a part of normal physiological excitation, this AA must be properly regulated, but battling with glutamate receptors or the transport system will cause serious negative consequences. Instead, the level and functional activity of glutamate may be adjusted by metabolic processes, including glycine and oxidative phosphorylation, in mitochondria.
Because glutamate is the major mediator of excitatory signals as well as of nervous system plasticity, including cell elimination, it follows that glutamate needs to be present at the right concentrations in the right places at the right time [17]. These conditions are regulated by GS, GM, and EAATs and convectional diffusion in ISF. There is evidence that extracellular glutamate is not compartmentalized by EAATs under some conditions [62]. The most obvious shift in glutamate levels is observed under high GDH and AT activity. The general activation of bioenergetics decreases the excessive glutamate concentration by stimulating the TCA cycle. Moreover, glycine can participate in this shift in a variety of ways. GlyT-1 controls glycine release and reuptake, determines glycine availability at glycine binding sites on NMDA receptors [36] and coordinates neuronal-glial interactions at glutamatergic synapses [19]. Thus, glycine assists glutamate in the activation of astrocytes and further stimulates the mitochondria according to the ANLS hypothesis. Glycine can conjugate with glutamate in the GSH synthesis pathway (Figure 1). This mechanism is essential to maintain the redox status of neurons and to prevent oxidative stress and high levels of reactive oxygen species (ROS) synthesis. Neuronal mitochondria are the target of glutamate, which attenuates succinate dehydrogenase (a key enzyme of the TCA cycle) inhibition by oxaloacetate [63], with further induction of ROS production [64]. However, glycine can prevent excessive hydrogen peroxide production induced by glutamate in brain mitochondria [65], thereby reducing the prooxidant effects of the excessive glutamate concentrations.
Interestingly, the effects of amino acids can vary depending on the species. For example, in a chick model, injections of L-glutamate, NMDA, and AMPA attenuated total distress vocalizations and induced sedation [66]. The association between glutamate and inhibition/sedation is even stronger because the brain contains a considerable level of glutamate decarboxylase, which directly catalyzes the decarboxylation of glutamate to GABA [27]. Additionally, glycine is not always associated with direct inhibition in the CNS. Indeed, in mature neurons, where there is a low intracellular Cl− concentration maintained by K+- Cl− cotransporter 2 (KCC2), activation of GlyRs elicits an influx of Cl−, leading to rapid hyperpolarization and postsynaptic inhibition [67]. In contrast, in immature neurons, activation of GlyRs results in efflux of Cl−, leading to neuronal depolarization; this opens voltage-dependent Ca2+ channels, elicits action potentials, and establishes early network activity and excitation in the developing nervous system [68].
Thus, the balance between excitation and inhibition is the result of continuous interactions among different processes involving both glutamate and glycine. It is essential that the main reactions and regulatory sites are nonhomogenously distributed in neuronal space and are time-regulated. Convective flow does not restore the homogeneity of mediator and metabolite concentrations because of the tortuosity of the system [63]. A scheme of the balanced interactions between glycinergic and glutamatergic synapses is shown in Figure 4.
The transport and activation of receptors in glycinergic and glutamatergic synapses. The transport system is tightly linked with glucose consumption. This transport system occurs in both astrocytes and neurons, but according to the ANLS model, the majority of glucose is consumed in astrocytes, with further diffusion of lactate to neurons. Lactate transport is facilitated by monocarboxylate transporters (MCTs), which have two different isoenzymes. MCT1 is expressed in astrocytes, and MCT2 is found in neurons [
The first (and obvious) clinical application of AAs is as a reference level to indicate different pathologies. This suggestion covers more AAs than those mentioned above. For decades, the biochemical analysis of AAs in body fluids has been an important diagnostic tool in the detection of congenital errors of metabolism. Significant elevations of amino acids in plasma, urine, or CSF have been the backbone of many diagnostic procedures [71]. This is because defects in amino acid catabolic pathways can be detected by the characteristic accumulation of their metabolites. Well-known examples of this are elevated plasma concentrations of phenylalanine in phenylketonuria (PKU) and increased concentrations of homocysteine in homocystinuria [71].
In addition, the properties of glutamate/glycine discussed above indicate a wide range of potential medical applications for compounds that govern transport, receptors, and metabolic systems in the CNS. A classic pharmacological approach may be based on the search for chemicals that affect the indicated processes; interactions with the target protein site or reaction must be local and precisely unidirectional and wide metabolic participation of the candidate should be avoided. There are several examples to date. Each of the three mGlu subgroups can be considered a novel target for the treatment of schizophrenia. All three symptom domains could be effectively treated by mGlu5 positive allosteric modulators, which are devoid of toxicity and seizure liability according to preclinical data. Furthermore, the potential antipsychotic and cognitive-enhancing effects of drugs targeting mGlu1 and mGlu3 were supported by recent genetic investigations of schizophrenia patients [72]. Preclinical studies have revealed that specific mGluR subtypes mediate significant neuroprotective effects that reduce toxin-induced midbrain dopaminergic neuronal death in animal models of Parkinson’s disease [41]. Additionally, mGluRs have emerged as research targets in treating Alzheimer’s disease. In particular, mGluR-based compounds producing both symptomatic and disease-modifying effects in preclinical models of the disease are of special interest [73]. G protein-coupled mGluRs expressed by tumor cells, particularly cancer stem cells, might represent new candidate drug targets for the treatment of malignant brain tumors [74]. Group III mGluR agonists have been recently identified as promising tools for managing affective symptoms, such as the pathological anxiety observed in neuropathic pain. However, the use of mGluR ligands as anxiolytics was disappointing in clinical trials. Nevertheless, there is ground for a certain amount of optimism [75].
Pharmacological modulation of glycinergic inhibition could represent a novel therapeutic strategy for a variety of diseases involving altered synaptic inhibition, primarily in the spinal cord and brain stem but possibly also at supraspinal sites [74]. Among the inhibitors of GlyT-1, two candidates have attracted the most attention. Sarcosine, a known intermediate of glycine metabolism, had positive results as a short-term treatment of major depression and for acutely ill and chronically stable schizophrenia patients. Another GlyT-1 inhibitor, bitopertin, was expected to be effective in treating negative or positive schizophrenia symptoms. However, the phase III clinical trials fell short of the primary endpoint, and the investigation was halted due to its lack of efficacy in improving negative symptoms [76]. Gelsemium, a small genus of flowering plants from the family Loganiaceae, may be used as a pain treatment and for its mechanism of action. Gelsemium and its active alkaloids may produce antinociception by activating the spinal α3 glycine/allopregnanolone pathway in inflammatory, neuropathic, and bone cancer pain without inducing antinociceptive tolerance, in contrast to morphine [75].
Another strategy is to directly use AAs for medical treatment. In this scenario, glycine is the most appropriate candidate. Glycine has a wide spectrum of protective properties against different diseases and injuries. As such, it represents a novel anti-inflammatory, immunomodulatory and cytoprotective agent [77]. Oral supplementation of glycine at a proper dose is very successful in treating several metabolic disorders in individuals with cardiovascular diseases, various inflammatory diseases, cancers, diabetes, and obesity [34]. Glycine was well tolerated at a dose of 0.8 g/kg body weight a day, resulting in significantly increased serum glycine levels and a 7% reduction in negative symptoms in patients with treatment-resistant schizophrenia [78]. An acute high dosage of glycine attenuates the neurophysiological representation of the brain’s preattentive acoustic change detection system (mismatch negativity) in healthy controls, raising the possibility that the optimal effects of glycine and other glycine agonists may depend on the integrity of the NMDA receptor system [79]. The glycine was effective in the treatment of ischaemic stroke patients. In a randomized, double-blind, placebo-controlled study on 200 patients with acute (<6 h) ischaemic stroke in the carotid artery area, 1.0–2.0 g/day of glycine was accompanied by a tendency towards decreased 30-day mortality (5.9% in the 1.0 g/day glycine and 10% in the 2.0 g/day glycine groups vs. 14% in the placebo and 14.3% in the 0.5 g/day glycine groups), an improved clinical outcome on the Orgogozo Stroke Scale (p < 0.01) and the Scandinavian Stroke Scale (p < 0.01) and a favorable functional outcome on the Barthel Index for Activities of Daily Living (p < 0.01) in the 1.0 g/day glycine group compared to those in the placebo group in patients with no or mild disability [80]. The molecular mechanism of such an effect is based on the ability of glycine to initiate stable vasodilatation of arterioles, which has been demonstrated in rat pial vessels and in mesenteric arterioles [81, 82].
According to experimental and clinical evidence, AAs are especially useful nutrients for the treatment of patients with different diseases. These nutrients not only supply a background pool for biochemical reactions, but the functions of the metabolites cover a wide range of neurochemical processes, and they are always mutually dependent. Even though some processes are decreased or increased in illnesses, it does not mean that the treatment strategy must be targeted to only correct the single altered process. A prominent example is glutamate-induced excitotoxicity in neurons. The best strategy to prevent increased glutamate concentrations is to maintain bioenergetic processes in neurons and astrocytes at high activity levels and to activate glycine-dependent processes. Moreover, it helps to assign the exceeded content of the neuromediator to a physiological range and to form stable conditions for further health development, avoiding excitotoxicity (Figure 5). Searching for exogenous antagonists of metabolic receptors seems to be an incorrect therapeutic strategy because the function of the AA-dependent system depends on the basic metabolic regulatory core of metabolic processes. Indeed, to find appropriate therapeutic methods, further fundamental and clinical investigations are necessary.
Scheme of the mutual influence of inhibition and excitation mediated by glycine and glutamate.
The author has no conflict of interest to declare.
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\\n\\nIntechOpen is committed to ensuring the long-term preservation and the availability of all scholarly research we publish. We employ a variety of means to enable us to deliver on our commitments to the scientific community. Apart from preservation by the Croatian National Library (for publications prior to April 18, 2018) and the British Library (for publications after April 18, 2018), our entire catalogue is preserved in the CLOCKSS archive.
\\n\\nOpen Science is transparent and accessible knowledge that is shared and developed through collaborative networks.
\\n\\nOpen Science is about increased rigour, accountability, and reproducibility for research. It is based on the principles of inclusion, fairness, equity, and sharing, and ultimately seeks to change the way research is done, who is involved and how it is valued. It aims to make research more open to participation, review/refutation, improvement and (re)use for the world to benefit.
\\n\\nOpen Science refers to doing traditional science with more transparency involved at various stages, for example by openly sharing code and data. It implies a growing set of practices - within different disciplines - aiming at:
\\n\\nWe aim at improving the quality and availability of scholarly communication by promoting and practicing:
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The Open Access publishing movement started in the early 2000s when academic leaders from around the world participated in the formation of the Budapest Initiative. They developed recommendations for an Open Access publishing process, “which has worked for the past decade to provide the public with unrestricted, free access to scholarly research—much of which is publicly funded. Making the research publicly available to everyone—free of charge and without most copyright and licensing restrictions—will accelerate scientific research efforts and allow authors to reach a larger number of readers” (reference: http://www.budapestopenaccessinitiative.org)
\n\nIntechOpen’s co-founders, both scientists themselves, created the company while undertaking research in robotics at Vienna University. Their goal was to spread research freely “for scientists, by scientists’ to the rest of the world via the Open Access publishing model. The company soon became a signatory of the Budapest Initiative, which currently has more than 1000 supporting organizations worldwide, ranging from universities to funders.
\n\nAt IntechOpen today, we are still as committed to working with organizations and people who care about scientific discovery, to putting the academic needs of the scientific community first, and to providing an Open Access environment where scientists can maximize their contribution to scientific advancement. By opening up access to the world’s scientific research articles and book chapters, we aim to facilitate greater opportunity for collaboration, scientific discovery and progress. We subscribe wholeheartedly to the Open Access definition:
\n\n“By “open access” to [peer-reviewed research literature], we mean its free availability on the public internet, permitting any users to read, download, copy, distribute, print, search, or link to the full texts of these articles, crawl them for indexing, pass them as data to software, or use them for any other lawful purpose, without financial, legal, or technical barriers other than those inseparable from gaining access to the internet itself. The only constraint on reproduction and distribution, and the only role for copyright in this domain, should be to give authors control over the integrity of their work and the right to be properly acknowledged and cited” (reference: http://www.budapestopenaccessinitiative.org)
\n\nOAI-PMH
\n\nAs a firm believer in the wider dissemination of knowledge, IntechOpen supports the Open Access Initiative Protocol for Metadata Harvesting (OAI-PMH Version 2.0). Read more
\n\nLicense
\n\nBook chapters published in edited volumes are distributed under the Creative Commons Attribution 3.0 Unported License (CC BY 3.0). IntechOpen upholds a very flexible Copyright Policy. There is no copyright transfer to the publisher and Authors retain exclusive copyright to their work. All Monographs/Compacts are distributed under the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). Read more
\n\nPeer Review Policies
\n\nAll scientific works are Peer Reviewed prior to publishing. Read more
\n\nOA Publishing Fees
\n\nThe Open Access publishing model employed by IntechOpen eliminates subscription charges and pay-per-view fees, enabling readers to access research at no cost. In order to sustain operations and keep our publications freely accessible we levy an Open Access Publishing Fee for manuscripts, which helps us cover the costs of editorial work and the production of books. Read more
\n\nDigital Archiving Policy
\n\nIntechOpen is committed to ensuring the long-term preservation and the availability of all scholarly research we publish. We employ a variety of means to enable us to deliver on our commitments to the scientific community. Apart from preservation by the Croatian National Library (for publications prior to April 18, 2018) and the British Library (for publications after April 18, 2018), our entire catalogue is preserved in the CLOCKSS archive.
\n\nOpen Science is transparent and accessible knowledge that is shared and developed through collaborative networks.
\n\nOpen Science is about increased rigour, accountability, and reproducibility for research. It is based on the principles of inclusion, fairness, equity, and sharing, and ultimately seeks to change the way research is done, who is involved and how it is valued. It aims to make research more open to participation, review/refutation, improvement and (re)use for the world to benefit.
\n\nOpen Science refers to doing traditional science with more transparency involved at various stages, for example by openly sharing code and data. It implies a growing set of practices - within different disciplines - aiming at:
\n\nWe aim at improving the quality and availability of scholarly communication by promoting and practicing:
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From 1985 to 1986, he was a Research Fellow in the Research Institute for Electronic Equipment, ZZU AD, Plovdiv, Bulgaria. In 1986, he joined the Department of Control Systems, Technical University of Sofia at the Plovdiv campus, where he is presently a Full Professor. He has held long-term visiting Professor/Scholar positions at various institutions in South Korea, Turkey, Mexico, Greece, Belgium, UK, and Germany. And he has coauthored one book and authored or coauthored more than 80 research papers in conference proceedings and journals. 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After finishing his P. hD degree in 1992, he served in the Industry as a Scientific Officer and continued his academic career as a visiting scholar for a number of educational institutions. In 1996 he joined National University of Science & Technology Pakistan (NUST) as an Associate Professor; NUST is one of the top few universities in Pakistan. In 1999 he joined an International Company Lineo Inc, Canada as Manager Compiler Group, where he headed the group for developing Compiler Tool Chain and Porting of Operating Systems for the BLACKfin processor. The processor development was a joint venture by Intel and Analog Devices. In 2002 Lineo Inc., was taken over by another company, so he joined Aalborg University Denmark as an Assistant Professor.\nProfessor Akbar has truly a multi-disciplined career and he continued his legacy and making progress in many areas of his interests both in teaching and research. 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This chapter will focus on usage of virtual reality in occupational therapy, history and recent developments, types of virtual reality technologic equipment, pros and cons, usage for pediatric, adult and geriatric people and recent research and articles.",book:{id:"5711",slug:"occupational-therapy-occupation-focused-holistic-practice-in-rehabilitation",title:"Occupational Therapy",fullTitle:"Occupational Therapy - Occupation Focused Holistic Practice in Rehabilitation"},signatures:"Orkun Tahir Aran, Sedef Şahin, Berkan Torpil, Tarık Demirok and\nHülya Kayıhan",authors:[{id:"172938",title:"Prof.",name:"Hulya",middleName:null,surname:"Kayihan",slug:"hulya-kayihan",fullName:"Hulya Kayihan"},{id:"183079",title:"Ph.D.",name:"Sedef",middleName:null,surname:"Şahin",slug:"sedef-sahin",fullName:"Sedef Şahin"},{id:"196848",title:"M.Sc.",name:"Orkun Tahir",middleName:null,surname:"Aran",slug:"orkun-tahir-aran",fullName:"Orkun Tahir Aran"},{id:"197159",title:"Mr.",name:"Tarık",middleName:null,surname:"Demirok",slug:"tarik-demirok",fullName:"Tarık Demirok"},{id:"197312",title:"M.Sc.",name:"Berkan",middleName:null,surname:"Torpil",slug:"berkan-torpil",fullName:"Berkan Torpil"}]},{id:"61806",doi:"10.5772/intechopen.78312",title:"Executive Functions and Neurology in Children and Adolescents",slug:"executive-functions-and-neurology-in-children-and-adolescents",totalDownloads:1759,totalCrossrefCites:3,totalDimensionsCites:5,abstract:"This chapter discusses the theoretical and methodological issues of creating a developmental perspective on executive function (EF) in childhood and adolescence. Focusing on school periods, this section outlines the development of the basic components of EF—inhibition, working memory, and attention. Cognitive and neurophysiological evaluations show that despite the emergence of EF in the first few years of life, it continues to grow significantly in childhood and adolescence. The components vary slightly according to their developmental sequence. The chapter links findings to long-standing developmental issues (i.e. developmental sequences and processes) and suggests the necessary research to establish a developmental framework covering early childhood throughout adolescence.",book:{id:"6772",slug:"occupational-therapy-therapeutic-and-creative-use-of-activity",title:"Occupational Therapy",fullTitle:"Occupational Therapy - Therapeutic and Creative Use of Activity"},signatures:"Gokcen Akyurek",authors:[{id:"197265",title:"Dr.",name:"Gokcen",middleName:null,surname:"Akyurek",slug:"gokcen-akyurek",fullName:"Gokcen Akyurek"}]},{id:"55024",doi:"10.5772/intechopen.68463",title:"Occupational Therapy in Oncology and Palliative Care",slug:"occupational-therapy-in-oncology-and-palliative-care",totalDownloads:2699,totalCrossrefCites:1,totalDimensionsCites:4,abstract:"Cancer is a chronic disease that may occur in both children and adults. Occupational therapy focuses on the activity limitations and participation problems in their life. Oncology rehabilitation involves in helping an individual with cancer to regain maximum physical, psychological, cognitive, social, and vocational functioning with the limits up to disease and its treatments in an interdisciplinary team concept. These treatment options are associated with the risk of some side effects, including fatigue, pain, cognitive problems, decrease in bone density and muscle endurance, weight loss, and stress- or anxiety-related psychosocial problems. Occupational therapy approaches are a holistic view in a client center and use training in activities of daily living, assistive technology, education of energy conservation techniques, and management of treatment-related problems, such as pain, fatigue, and nausea. In palliative and hospice care, occupational therapists support clients with cancer by minimizing the secondary symptoms related to cancer and its treatments. At the end of life, occupational therapy offers to identify the roles and activities that are meaningful and purposeful to the client with cancer and try to determine the barriers that limit their performance. Clients with cancer who have childhood cancer or adult cancer can face problems about body structure and functions, activity, and participation, which may limit their participation to their daily life.",book:{id:"5711",slug:"occupational-therapy-occupation-focused-holistic-practice-in-rehabilitation",title:"Occupational Therapy",fullTitle:"Occupational Therapy - Occupation Focused Holistic Practice in Rehabilitation"},signatures:"Sedef Şahin, Semin Akel and Meral Zarif",authors:[{id:"183079",title:"Ph.D.",name:"Sedef",middleName:null,surname:"Şahin",slug:"sedef-sahin",fullName:"Sedef Şahin"},{id:"183078",title:"Dr.",name:"Burcu Semin",middleName:null,surname:"Akel",slug:"burcu-semin-akel",fullName:"Burcu Semin Akel"},{id:"198859",title:"Dr.",name:"Meral",middleName:null,surname:"Zarif",slug:"meral-zarif",fullName:"Meral Zarif"}]},{id:"56049",doi:"10.5772/intechopen.69101",title:"Measurement of Participation: The Role Checklist Version 3: Satisfaction and Performance",slug:"measurement-of-participation-the-role-checklist-version-3-satisfaction-and-performance",totalDownloads:2823,totalCrossrefCites:3,totalDimensionsCites:4,abstract:"Participation in society is an area of interest to both clinicians and population researchers. Measurement of participation is therefore important, yet differences in definition, in terms of both content and scope, have made general agreement on one instrument tool elusive. What is recognized is the need for a theoretically based tool that captures both the insider and the outsider perspective. The outsider perspective, inclusive of the generally held views of a society, supports the utility for aggregating population data, whereas the insider perspective provides the internally held views of an individual needed for client-centered treatment planning. The Role Checklist Version 3 modifies one of the most commonly used assessment tools in occupational therapy practice, has good preliminary psychometric properties, and is theoretically consistent with both the ICF and the Model of Human Occupation. The Model of Human Occupation is the most widely used theoretical model in occupational therapy. This chapter provides an overview of the theoretical development, empirical testing, and implications for use of this participation measure by occupational therapists along with implications for population researchers.",book:{id:"5711",slug:"occupational-therapy-occupation-focused-holistic-practice-in-rehabilitation",title:"Occupational Therapy",fullTitle:"Occupational Therapy - Occupation Focused Holistic Practice in Rehabilitation"},signatures:"Patricia J. Scott, Kelsey McKinney, Jeff Perron, Emily Ruff and Jessica\nSmiley",authors:[{id:"195495",title:"Dr.",name:"Patricia J",middleName:null,surname:"Scott",slug:"patricia-j-scott",fullName:"Patricia J Scott"},{id:"208801",title:"Dr.",name:"Kelsey G.",middleName:null,surname:"McKinney",slug:"kelsey-g.-mckinney",fullName:"Kelsey G. McKinney"},{id:"208802",title:"Mr.",name:"Jeffrey M.",middleName:null,surname:"Perron",slug:"jeffrey-m.-perron",fullName:"Jeffrey M. Perron"},{id:"208803",title:"Dr.",name:"Emily G.",middleName:null,surname:"Ruff",slug:"emily-g.-ruff",fullName:"Emily G. Ruff"},{id:"208804",title:"Dr.",name:"Jessica L.",middleName:null,surname:"Smiley",slug:"jessica-l.-smiley",fullName:"Jessica L. Smiley"}]},{id:"55018",doi:"10.5772/intechopen.68315",title:"Psychomotor Therapy for Patients with Severe Mental Health Disorders",slug:"psychomotor-therapy-for-patients-with-severe-mental-health-disorders",totalDownloads:2274,totalCrossrefCites:3,totalDimensionsCites:3,abstract:"Psychomotor therapy is defined as a method of treatment based on a holistic view of the human being that is derived from the unity of body and mind. Assessments (observation and/or evaluation) are essential to achieving concrete psychosocial objectives methodically. Psychomotor therapy uses movement, body awareness and a wide range of movement activities to optimize movement behaviour as well as the cognitive, affective and relational aspects of psychomotor functioning (i.e. the relationships between physical movements and cognitive and social-affective aspects). Consequently, the approach to this type of therapy integrates the physical, cognitive and emotional aspects of functioning in relation to the capacity of being and acting in a psychosocial context in order to achieve clearly defined goals in consultation with the patients. Psychomotor therapy framework consists of three different approaches: a health-related approach, a psychosocial approach and a psychotherapeutic approach, which can be embedded in several psychotherapeutic approaches. Through the implementation of both systematically planned evaluations and individually targeted interventions in group, the psychomotor therapist strives to broaden the general action competences and specific skills and to stimulate a positive self-image and personal well-being in balanced social relationships. Today, there is sufficient evidence that psychomotor therapy has a major contribution to both well-being and mental health of patients with severe psychiatric problems. In Flemish psychiatric hospitals, psychomotor therapy is imbedded in different treatment programmes. In this chapter, the theory behind this approach and some practical examples will be provided.",book:{id:"5711",slug:"occupational-therapy-occupation-focused-holistic-practice-in-rehabilitation",title:"Occupational Therapy",fullTitle:"Occupational Therapy - Occupation Focused Holistic Practice in Rehabilitation"},signatures:"Michel Probst",authors:[{id:"196227",title:"Prof.",name:"Michel",middleName:null,surname:"Probst",slug:"michel-probst",fullName:"Michel Probst"}]}],mostDownloadedChaptersLast30Days:[{id:"55080",title:"Life Skills in Occupational Therapy",slug:"life-skills-in-occupational-therapy",totalDownloads:6076,totalCrossrefCites:4,totalDimensionsCites:1,abstract:"Occupational therapy is a health profession that uses the purposeful activities to achieve multiple and complex rehabilitation aims. The main goals of the occupational therapy are to support the reintegration of individuals in daily living skills as well as to increase their independence and autonomy. Interventions of occupational therapists have primarily focused on self-care, productivity, and leisure time activities. Since the life skills includes a wide range of abilities that enable a person to perform personal care and more complicated tasks such as traveling, shopping, community participation etc., occupational therapists provide life skills training programs to meet the needs of the clients. This chapter aims to contribute to the current understanding and practices of life skills from an occupational therapy perspective. The chapter starts with a brief discussion of the importance of life skills in occupational therapy. After this introduction, the first part takes a look at the definition of life skills and identifies core components of life skills. The second part describes assessment and interventions of life skills. The third one gives an overview about school life skills programs for children and adolescents. Finally, the last part explains some life skills programs in people with disadvantages.",book:{id:"5711",slug:"occupational-therapy-occupation-focused-holistic-practice-in-rehabilitation",title:"Occupational Therapy",fullTitle:"Occupational Therapy - Occupation Focused Holistic Practice in Rehabilitation"},signatures:"Hatice Abaoğlu, Özge Buket Cesim, Sinem Kars and Zeynep Çelik",authors:[{id:"197551",title:"Dr.",name:"Hatice",middleName:null,surname:"Abaoğlu",slug:"hatice-abaoglu",fullName:"Hatice Abaoğlu"},{id:"205199",title:"Dr.",name:"Sinem",middleName:null,surname:"Kars",slug:"sinem-kars",fullName:"Sinem Kars"},{id:"205200",title:"Dr.",name:"Zeynep",middleName:null,surname:"Celik",slug:"zeynep-celik",fullName:"Zeynep Celik"},{id:"205203",title:"Ms.",name:"Özge Buket",middleName:null,surname:"Cesim",slug:"ozge-buket-cesim",fullName:"Özge Buket Cesim"}]},{id:"62493",title:"Occupational Therapy in Forensic Settings",slug:"occupational-therapy-in-forensic-settings",totalDownloads:2543,totalCrossrefCites:2,totalDimensionsCites:2,abstract:"It is necessary for a person to comply with the expectations of society and the rules of law to which these expectations are secured. Offenders turn back to the community after the penalty was executed by isolating from society and some occupations. An occupational imbalance is seen in the individuals, during this penalty period and afterward, because of limited occupational participation. As an occupational being, this affects their physical, mental and psychological well-being. Imprisonment is an important practice in criminal law to punish criminals. This may be necessary for the protection of society from criminals, but successful integration into a community after exiting the prison is the most important factor in preventing recidivism. Occupational therapy focuses on health and well-being by using meaningful and purposeful occupations. Occupation involves any activity that people perform or participate in, such as giving care to themselves or others, working, learning, playing games, and interacting with others. From this perspective, the role of occupational therapists in forensic settings is to determine the abilities of these individuals to congregate their deprived freedoms and use them to train them for an independent and autonomous life; to provide a professional orientation, career counseling, and self-esteem; to gain some habits for physical, spiritual and moral life and to reinforce.",book:{id:"6772",slug:"occupational-therapy-therapeutic-and-creative-use-of-activity",title:"Occupational Therapy",fullTitle:"Occupational Therapy - Therapeutic and Creative Use of Activity"},signatures:"Esma Ozkan, Sümeyye Belhan, Mahmut Yaran and Meral Zarif",authors:null},{id:"70122",title:"Parkinson’s Disease Rehabilitation: Effectiveness Approaches and New Perspectives",slug:"parkinson-s-disease-rehabilitation-effectiveness-approaches-and-new-perspectives",totalDownloads:2083,totalCrossrefCites:2,totalDimensionsCites:3,abstract:"Parkinson’s disease has been considered one of the most important and common neurodegenerative diseases in the world. Its motor and nonmotor signs determine a huge functional loss, leading the individuals to lose their independence. Although the treatment requires a pharmacological approach, physical therapy has confirmed its importance in this process. Today, neurorehabilitation is indispensable to increase many of the cardinal signs of the disease. Using traditional or technological approaches, physical therapy has reached good results in improving motor and nonmotor functions, as well as the quality of life of Parkinsonians. However, it is important to develop and to fortify the physical therapy approach so that we can provide stronger evidence about our practice.",book:{id:"7543",slug:"physical-therapy-effectiveness",title:"Physical Therapy Effectiveness",fullTitle:"Physical Therapy Effectiveness"},signatures:"Luciana Auxiliadora de Paula Vasconcelos",authors:[{id:"98546",title:"Dr.",name:"Luciana Auxiliadora",middleName:null,surname:"De Paula Vasconcelos",slug:"luciana-auxiliadora-de-paula-vasconcelos",fullName:"Luciana Auxiliadora De Paula Vasconcelos"}]},{id:"62210",title:"Occupational Therapy’s Role in the Treatment of Children with Autism Spectrum Disorders",slug:"occupational-therapy-s-role-in-the-treatment-of-children-with-autism-spectrum-disorders",totalDownloads:2756,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Occupational therapists (OT) offer a wide range of therapies for individuals with ASD on the basis of specific deficits and difficulties. This chapter explores the role that OT plays, and the expertise, in relation to the interdisciplinary team. In addition, it discusses and presents empirical support for several therapeutic approaches commonly used by OTs working with individuals with ASD.",book:{id:"6772",slug:"occupational-therapy-therapeutic-and-creative-use-of-activity",title:"Occupational Therapy",fullTitle:"Occupational Therapy - Therapeutic and Creative Use of Activity"},signatures:"Bryan M. Gee, Amy Nwora and Theodore W. Peterson",authors:null},{id:"55049",title:"Community Participation in People with Disabilities",slug:"community-participation-in-people-with-disabilities",totalDownloads:2436,totalCrossrefCites:2,totalDimensionsCites:2,abstract:"Despite the fact that participation is an important building and a valuable target, the conceptualization, identification and measurement methods vary widely. This chapter tried to gain an insider’s perspective from the obstacles that summarize what meaning participation means, how to characterize it, and what prevents and supports participation. Participation is seen as a right and a responsibility attributed to and attributed to both the person and the community. Participation does not take place in a vacuum; the environment dynamically influences participation. The effects of this conceptual framework are discussed for change at the level of evaluation, research and systems to support the participation of the people with disability.",book:{id:"5711",slug:"occupational-therapy-occupation-focused-holistic-practice-in-rehabilitation",title:"Occupational Therapy",fullTitle:"Occupational Therapy - Occupation Focused Holistic Practice in Rehabilitation"},signatures:"Gokcen Akyurek and Gonca Bumin",authors:[{id:"32431",title:"Prof.",name:"Gonca",middleName:null,surname:"Bumin",slug:"gonca-bumin",fullName:"Gonca Bumin"},{id:"197265",title:"Dr.",name:"Gokcen",middleName:null,surname:"Akyurek",slug:"gokcen-akyurek",fullName:"Gokcen Akyurek"}]}],onlineFirstChaptersFilter:{topicId:"198",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:90,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:33,numberOfPublishedChapters:330,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:14,numberOfPublishedChapters:145,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:9,numberOfPublishedChapters:140,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:123,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:112,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:22,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:11,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:"2753-6580",doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. 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Much of biochemistry is devoted to enzymes, proteins that catalyze chemical reactions, enzyme structures, mechanisms of action and their roles within cells. Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. 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Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:5,paginationItems:[{id:"91",title:"Sustainable Economy and Fair Society",coverUrl:"https://cdn.intechopen.com/series_topics/covers/91.jpg",isOpenForSubmission:!0,editor:{id:"181603",title:"Dr.",name:"Antonella",middleName:null,surname:"Petrillo",slug:"antonella-petrillo",fullName:"Antonella Petrillo",profilePictureURL:"https://mts.intechopen.com/storage/users/181603/images/system/181603.jpg",biography:"Antonella Petrillo, Ph.D., is a professor in the Department of Engineering, University of Naples “Parthenope,” Italy. She received her Ph.D. in Mechanical Engineering from the University of Cassino and Southern Lazio, Italy. Her research interests include multi-criteria decision analysis, industrial plants, logistics, manufacturing, and safety. She serves as an associate editor for the International Journal of the Analytic Hierarchy Process and is an editorial board member for several other journals. 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Her focus is on quality, innovation, leadership, and personalised learning. She works primarily at the strategic and policy levels, both nationally and internationally, and with key international organisations. She is committed to promoting and improving OFDL in the context of SDG4 and the future of education. Ossiannilsson has more than 20 years of experience in her current field, but more than 40 years in the education sector. She works as a reviewer and expert for the European Commission and collaborates with the Joint Research Centre for Quality in Open Education. Ossiannilsson also collaborates with ITCILO and ICoBC (International Council on Badges and Credentials). She is a member of the ICDE Board of Directors and has previously served on the boards of EDEN and EUCEN. Ossiannilsson is a quality expert and reviewer for ICDE, EDEN and the EADTU. She chairs the ICDE OER Advocacy Committee and is a member of the ICDE Quality Network. 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She is a member of the Digital Skills and Jobs Coalition Sweden and Vice President of the Swedish Association for Distance Education. She is currently working on a government initiative on quality in distance education at the National Council for Higher Education. 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His present research includes organic synthesis, drug discovery and development, biochemistry, nanoscience, and nanotechnology.",institutionString:"Visiting Scientist at Lipid Nanostructures Laboratory, Centre for Smart Materials, School of Natural Sciences, University of Central Lancashire",institution:null},{id:"428125",title:"Dr.",name:"Vinayak",middleName:null,surname:"Adimule",slug:"vinayak-adimule",fullName:"Vinayak Adimule",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/428125/images/system/428125.jpg",biography:"Dr. Vinayak Adimule, MSc, Ph.D., is a professor and dean of R&D, Angadi Institute of Technology and Management, India. He has 15 years of research experience as a senior research scientist and associate research scientist in R&D organizations. He has published more than fifty research articles as well as several book chapters. He has two Indian patents and two international patents to his credit. Dr. Adimule has attended, chaired, and presented papers at national and international conferences. He is a guest editor for Topics in Catalysis and other journals. He is also an editorial board member, life member, and associate member for many international societies and research institutions. His research interests include nanoelectronics, material chemistry, artificial intelligence, sensors and actuators, bio-nanomaterials, and medicinal chemistry.",institutionString:"Angadi Institute of Technology and Management",institution:null},{id:"284317",title:"Prof.",name:"Kantharaju",middleName:null,surname:"Kamanna",slug:"kantharaju-kamanna",fullName:"Kantharaju Kamanna",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/284317/images/21050_n.jpg",biography:"Prof. K. Kantharaju has received Bachelor of science (PCM), master of science (Organic Chemistry) and Doctor of Philosophy in Chemistry from Bangalore University. He worked as a Executive Research & Development @ Cadila Pharmaceuticals Ltd, Ahmedabad. He received DBT-postdoc fellow @ Molecular Biophysics Unit, Indian Institute of Science, Bangalore under the supervision of Prof. P. Balaram, later he moved to NIH-postdoc researcher at Drexel University College of Medicine, Philadelphia, USA, after his return from postdoc joined NITK-Surthakal as a Adhoc faculty at department of chemistry. Since from August 2013 working as a Associate Professor, and in 2016 promoted to Profeesor in the School of Basic Sciences: Department of Chemistry and having 20 years of teaching and research experiences.",institutionString:null,institution:{name:"Rani Channamma University, Belagavi",country:{name:"India"}}},{id:"158492",title:"Prof.",name:"Yusuf",middleName:null,surname:"Tutar",slug:"yusuf-tutar",fullName:"Yusuf Tutar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/158492/images/system/158492.jpeg",biography:"Prof. Dr. Yusuf Tutar conducts his research at the Hamidiye Faculty of Pharmacy, Department of Basic Pharmaceutical Sciences, Division of Biochemistry, University of Health Sciences, Turkey. He is also a faculty member in the Molecular Oncology Program. He obtained his MSc and Ph.D. at Oregon State University and Texas Tech University, respectively. He pursued his postdoctoral studies at Rutgers University Medical School and the National Institutes of Health (NIH/NIDDK), USA. His research focuses on biochemistry, biophysics, genetics, molecular biology, and molecular medicine with specialization in the fields of drug design, protein structure-function, protein folding, prions, microRNA, pseudogenes, molecular cancer, epigenetics, metabolites, proteomics, genomics, protein expression, and characterization by spectroscopic and calorimetric methods.",institutionString:"University of Health Sciences",institution:null},{id:"180528",title:"Dr.",name:"Hiroyuki",middleName:null,surname:"Kagechika",slug:"hiroyuki-kagechika",fullName:"Hiroyuki Kagechika",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180528/images/system/180528.jpg",biography:"Hiroyuki Kagechika received his bachelor’s degree and Ph.D. in Pharmaceutical Sciences from the University of Tokyo, Japan, where he served as an associate professor until 2004. He is currently a professor at the Institute of Biomaterials and Bioengineering (IBB), Tokyo Medical and Dental University (TMDU). From 2010 to 2012, he was the dean of the Graduate School of Biomedical Science. Since 2012, he has served as the vice dean of the Graduate School of Medical and Dental Sciences. He has been the director of the IBB since 2020. Dr. Kagechika’s major research interests are the medicinal chemistry of retinoids, vitamins D/K, and nuclear receptors. He has developed various compounds including a drug for acute promyelocytic leukemia.",institutionString:"Tokyo Medical and Dental University",institution:{name:"Tokyo Medical and Dental University",country:{name:"Japan"}}},{id:"94311",title:"Prof.",name:"Martins",middleName:"Ochubiojo",surname:"Ochubiojo Emeje",slug:"martins-ochubiojo-emeje",fullName:"Martins Ochubiojo Emeje",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94311/images/system/94311.jpeg",biography:"Martins Emeje obtained a BPharm with distinction from Ahmadu Bello University, Nigeria, and an MPharm and Ph.D. from the University of Nigeria (UNN), where he received the best Ph.D. award and was enlisted as UNN’s “Face of Research.” He established the first nanomedicine center in Nigeria and was the pioneer head of the intellectual property and technology transfer as well as the technology innovation and support center. Prof. Emeje’s several international fellowships include the prestigious Raman fellowship. He has published more than 150 articles and patents. He is also the head of R&D at NIPRD and holds a visiting professor position at Nnamdi Azikiwe University, Nigeria. He has a postgraduate certificate in Project Management from Walden University, Minnesota, as well as a professional teaching certificate and a World Bank certification in Public Procurement. Prof. Emeje was a national chairman of academic pharmacists in Nigeria and the 2021 winner of the May & Baker Nigeria Plc–sponsored prize for professional service in research and innovation.",institutionString:"National Institute for Pharmaceutical Research and Development",institution:{name:"National Institute for Pharmaceutical Research and Development",country:{name:"Nigeria"}}},{id:"436430",title:"Associate Prof.",name:"Mesut",middleName:null,surname:"Işık",slug:"mesut-isik",fullName:"Mesut Işık",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/436430/images/19686_n.jpg",biography:null,institutionString:null,institution:{name:"Bilecik University",country:{name:"Turkey"}}},{id:"268659",title:"Ms.",name:"Xianquan",middleName:null,surname:"Zhan",slug:"xianquan-zhan",fullName:"Xianquan Zhan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/268659/images/8143_n.jpg",biography:"Dr. Zhan received his undergraduate and graduate training in the fields of preventive medicine and epidemiology and statistics at the West China University of Medical Sciences in China during 1989 to 1999. He received his post-doctoral training in oncology and cancer proteomics for two years at the Cancer Research Institute of Human Medical University in China. In 2001, he went to the University of Tennessee Health Science Center (UTHSC) in USA, where he was a post-doctoral researcher and focused on mass spectrometry and cancer proteomics. Then, he was appointed as an Assistant Professor of Neurology, UTHSC in 2005. He moved to the Cleveland Clinic in USA as a Project Scientist/Staff in 2006 where he focused on the studies of eye disease proteomics and biomarkers. He returned to UTHSC as an Assistant Professor of Neurology in the end of 2007, engaging in proteomics and biomarker studies of lung diseases and brain tumors, and initiating the studies of predictive, preventive, and personalized medicine (PPPM) in cancer. In 2010, he was promoted to Associate Professor of Neurology, UTHSC. Currently, he is a Professor at Xiangya Hospital of Central South University in China, Fellow of Royal Society of Medicine (FRSM), the European EPMA National Representative in China, Regular Member of American Association for the Advancement of Science (AAAS), European Cooperation of Science and Technology (e-COST) grant evaluator, Associate Editors of BMC Genomics, BMC Medical Genomics, EPMA Journal, and Frontiers in Endocrinology, Executive Editor-in-Chief of Med One. He has\npublished 116 peer-reviewed research articles, 16 book chapters, 2 books, and 2 US patents. His current main research interest focuses on the studies of cancer proteomics and biomarkers, and the use of modern omics techniques and systems biology for PPPM in cancer, and on the development and use of 2DE-LC/MS for the large-scale study of human proteoforms.",institutionString:null,institution:{name:"Xiangya Hospital Central South University",country:{name:"China"}}},{id:"40482",title:null,name:"Rizwan",middleName:null,surname:"Ahmad",slug:"rizwan-ahmad",fullName:"Rizwan Ahmad",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/40482/images/system/40482.jpeg",biography:"Dr. Rizwan Ahmad is a University Professor and Coordinator, Quality and Development, College of Medicine, Imam Abdulrahman bin Faisal University, Saudi Arabia. Previously, he was Associate Professor of Human Function, Oman Medical College, Oman, and SBS University, Dehradun. Dr. Ahmad completed his education at Aligarh Muslim University, Aligarh. He has published several articles in peer-reviewed journals, chapters, and edited books. His area of specialization is free radical biochemistry and autoimmune diseases.",institutionString:"Imam Abdulrahman Bin Faisal University",institution:{name:"Imam Abdulrahman Bin Faisal University",country:{name:"Saudi Arabia"}}},{id:"41865",title:"Prof.",name:"Farid A.",middleName:null,surname:"Badria",slug:"farid-a.-badria",fullName:"Farid A. Badria",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/41865/images/system/41865.jpg",biography:"Farid A. Badria, Ph.D., is the recipient of several awards, including The World Academy of Sciences (TWAS) Prize for Public Understanding of Science; the World Intellectual Property Organization (WIPO) Gold Medal for best invention; Outstanding Arab Scholar, Kuwait; and the Khwarizmi International Award, Iran. He has 250 publications, 12 books, 20 patents, and several marketed pharmaceutical products to his credit. He continues to lead research projects on developing new therapies for liver, skin disorders, and cancer. Dr. Badria was listed among the world’s top 2% of scientists in medicinal and biomolecular chemistry in 2019 and 2020. He is a member of the Arab Development Fund, Kuwait; International Cell Research Organization–United Nations Educational, Scientific and Cultural Organization (ICRO–UNESCO), Chile; and UNESCO Biotechnology France",institutionString:"Mansoura University",institution:{name:"Mansoura University",country:{name:"Egypt"}}},{id:"329385",title:"Dr.",name:"Rajesh K.",middleName:"Kumar",surname:"Singh",slug:"rajesh-k.-singh",fullName:"Rajesh K. Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329385/images/system/329385.png",biography:"Dr. Singh received a BPharm (2003) and MPharm (2005) from Panjab University, Chandigarh, India, and a Ph.D. (2013) from Punjab Technical University (PTU), Jalandhar, India. He has more than sixteen years of teaching experience and has supervised numerous postgraduate and Ph.D. students. He has to his credit more than seventy papers in SCI- and SCOPUS-indexed journals, fifty-five conference proceedings, four books, six Best Paper Awards, and five projects from different government agencies. He is currently an editorial board member of eight international journals and a reviewer for more than fifty scientific journals. He received Top Reviewer and Excellent Peer Reviewer Awards from Publons in 2016 and 2017, respectively. He is also on the panel of The International Reviewer for reviewing research proposals for grants from the Royal Society. He also serves as a Publons Academy mentor and Bentham brand ambassador.",institutionString:"Punjab Technical University",institution:{name:"Punjab Technical University",country:{name:"India"}}},{id:"142388",title:"Dr.",name:"Thiago",middleName:"Gomes",surname:"Gomes Heck",slug:"thiago-gomes-heck",fullName:"Thiago Gomes Heck",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/142388/images/7259_n.jpg",biography:null,institutionString:null,institution:{name:"Universidade Regional do Noroeste do Estado do Rio Grande do Sul",country:{name:"Brazil"}}},{id:"336273",title:"Assistant Prof.",name:"Janja",middleName:null,surname:"Zupan",slug:"janja-zupan",fullName:"Janja Zupan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/336273/images/14853_n.jpeg",biography:"Janja Zupan graduated in 2005 at the Department of Clinical Biochemistry (superviser prof. dr. Janja Marc) in the field of genetics of osteoporosis. Since November 2009 she is working as a Teaching Assistant at the Faculty of Pharmacy, Department of Clinical Biochemistry. In 2011 she completed part of her research and PhD work at Institute of Genetics and Molecular Medicine, University of Edinburgh. She finished her PhD entitled The influence of the proinflammatory cytokines on the RANK/RANKL/OPG in bone tissue of osteoporotic and osteoarthritic patients in 2012. From 2014-2016 she worked at the Institute of Biomedical Sciences, University of Aberdeen as a postdoctoral research fellow on UK Arthritis research project where she gained knowledge in mesenchymal stem cells and regenerative medicine. She returned back to University of Ljubljana, Faculty of Pharmacy in 2016. She is currently leading project entitled Mesenchymal stem cells-the keepers of tissue endogenous regenerative capacity facing up to aging of the musculoskeletal system funded by Slovenian Research Agency.",institutionString:null,institution:{name:"University of Ljubljana",country:{name:"Slovenia"}}},{id:"357453",title:"Dr.",name:"Radheshyam",middleName:null,surname:"Maurya",slug:"radheshyam-maurya",fullName:"Radheshyam Maurya",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/357453/images/16535_n.jpg",biography:null,institutionString:null,institution:{name:"University of Hyderabad",country:{name:"India"}}},{id:"418340",title:"Dr.",name:"Jyotirmoi",middleName:null,surname:"Aich",slug:"jyotirmoi-aich",fullName:"Jyotirmoi Aich",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000038Ugi5QAC/Profile_Picture_2022-04-15T07:48:28.png",biography:"Biotechnologist with 15 years of research including 6 years of teaching experience. Demonstrated record of scientific achievements through consistent publication record (H index = 13, with 874 citations) in high impact journals such as Nature Communications, Oncotarget, Annals of Oncology, PNAS, and AJRCCM, etc. Strong research professional with a post-doctorate from ACTREC where I gained experimental oncology experience in clinical settings and a doctorate from IGIB where I gained expertise in asthma pathophysiology. A well-trained biotechnologist with diverse experience on the bench across different research themes ranging from asthma to cancer and other infectious diseases. An individual with a strong commitment and innovative mindset. Have the ability to work on diverse projects such as regenerative and molecular medicine with an overall mindset of improving healthcare.",institutionString:"DY Patil Deemed to Be University",institution:null},{id:"349288",title:"Prof.",name:"Soumya",middleName:null,surname:"Basu",slug:"soumya-basu",fullName:"Soumya Basu",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035QxIDQA0/Profile_Picture_2022-04-15T07:47:01.jpg",biography:"Soumya Basu, Ph.D., is currently working as an Associate Professor at Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune, Maharashtra, India. With 16+ years of trans-disciplinary research experience in Drug Design, development, and pre-clinical validation; 20+ research article publications in journals of repute, 9+ years of teaching experience, trained with cross-disciplinary education, Dr. Basu is a life-long learner and always thrives for new challenges.\r\nHer research area is the design and synthesis of small molecule partial agonists of PPAR-γ in lung cancer. She is also using artificial intelligence and deep learning methods to understand the exosomal miRNA’s role in cancer metastasis. Dr. Basu is the recipient of many awards including the Early Career Research Award from the Department of Science and Technology, Govt. of India. She is a reviewer of many journals like Molecular Biology Reports, Frontiers in Oncology, RSC Advances, PLOS ONE, Journal of Biomolecular Structure & Dynamics, Journal of Molecular Graphics and Modelling, etc. She has edited and authored/co-authored 21 journal papers, 3 book chapters, and 15 abstracts. She is a Board of Studies member at her university. She is a life member of 'The Cytometry Society”-in India and 'All India Cell Biology Society”- in India.",institutionString:"Dr. D.Y. Patil Vidyapeeth, Pune",institution:{name:"Dr. D.Y. Patil Vidyapeeth, Pune",country:{name:"India"}}},{id:"354817",title:"Dr.",name:"Anubhab",middleName:null,surname:"Mukherjee",slug:"anubhab-mukherjee",fullName:"Anubhab Mukherjee",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y0000365PbRQAU/ProfilePicture%202022-04-15%2005%3A11%3A18.480",biography:"A former member of Laboratory of Nanomedicine, Brigham and Women’s Hospital, Harvard University, Boston, USA, Dr. Anubhab Mukherjee is an ardent votary of science who strives to make an impact in the lives of those afflicted with cancer and other chronic/acute ailments. He completed his Ph.D. from CSIR-Indian Institute of Chemical Technology, Hyderabad, India, having been skilled with RNAi, liposomal drug delivery, preclinical cell and animal studies. He pursued post-doctoral research at College of Pharmacy, Health Science Center, Texas A & M University and was involved in another postdoctoral research at Department of Translational Neurosciences and Neurotherapeutics, John Wayne Cancer Institute, Santa Monica, California. In 2015, he worked in Harvard-MIT Health Sciences & Technology as a visiting scientist. He has substantial experience in nanotechnology-based formulation development and successfully served various Indian organizations to develop pharmaceuticals and nutraceutical products. He is an inventor in many US patents and an author in many peer-reviewed articles, book chapters and books published in various media of international repute. Dr. Mukherjee is currently serving as Principal Scientist, R&D at Esperer Onco Nutrition (EON) Pvt. Ltd. and heads the Hyderabad R&D center of the organization.",institutionString:"Esperer Onco Nutrition Pvt Ltd.",institution:null},{id:"319365",title:"Assistant Prof.",name:"Manash K.",middleName:null,surname:"Paul",slug:"manash-k.-paul",fullName:"Manash K. Paul",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/319365/images/system/319365.png",biography:"Manash K. Paul is a Principal Investigator and Scientist at the University of California Los Angeles. He has contributed significantly to the fields of stem cell biology, regenerative medicine, and lung cancer. His research focuses on various signaling processes involved in maintaining stem cell homeostasis during the injury-repair process, deciphering lung stem cell niche, pulmonary disease modeling, immuno-oncology, and drug discovery. He is currently investigating the role of extracellular vesicles in premalignant lung cell migration and detecting the metastatic phenotype of lung cancer via machine-learning-based analyses of exosomal signatures. Dr. Paul has published in more than fifty peer-reviewed international journals and is highly cited. He is the recipient of many awards, including the UCLA Vice Chancellor’s award, a senior member of the Institute of Electrical and Electronics Engineers (IEEE), and an editorial board member for several international journals.",institutionString:"University of California Los Angeles",institution:{name:"University of California Los Angeles",country:{name:"United States of America"}}},{id:"311457",title:"Dr.",name:"Júlia",middleName:null,surname:"Scherer Santos",slug:"julia-scherer-santos",fullName:"Júlia Scherer Santos",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/311457/images/system/311457.jpg",biography:"Dr. Júlia Scherer Santos works in the areas of cosmetology, nanotechnology, pharmaceutical technology, beauty, and aesthetics. Dr. Santos also has experience as a professor of graduate courses. Graduated in Pharmacy, specialization in Cosmetology and Cosmeceuticals applied to aesthetics, specialization in Aesthetic and Cosmetic Health, and a doctorate in Pharmaceutical Nanotechnology. Teaching experience in Pharmacy and Aesthetics and Cosmetics courses. She works mainly on the following subjects: nanotechnology, cosmetology, pharmaceutical technology, aesthetics.",institutionString:"Universidade Federal de Juiz de Fora",institution:{name:"Universidade Federal de Juiz de Fora",country:{name:"Brazil"}}},{id:"219081",title:"Dr.",name:"Abdulsamed",middleName:null,surname:"Kükürt",slug:"abdulsamed-kukurt",fullName:"Abdulsamed Kükürt",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/219081/images/system/219081.png",biography:"Dr. Kükürt graduated from Uludağ University in Turkey. He started his academic career as a Research Assistant in the Department of Biochemistry at Kafkas University. In 2019, he completed his Ph.D. program in the Department of Biochemistry at the Institute of Health Sciences. He is currently working at the Department of Biochemistry, Kafkas University. He has 27 published research articles in academic journals, 11 book chapters, and 37 papers. He took part in 10 academic projects. He served as a reviewer for many articles. He still serves as a member of the review board in many academic journals. He is currently working on the protective activity of phenolic compounds in disorders associated with oxidative stress and inflammation.",institutionString:null,institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"178366",title:"Dr.",name:"Volkan",middleName:null,surname:"Gelen",slug:"volkan-gelen",fullName:"Volkan Gelen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178366/images/system/178366.jpg",biography:"Volkan Gelen is a Physiology specialist who received his veterinary degree from Kafkas University in 2011. Between 2011-2015, he worked as an assistant at Atatürk University, Faculty of Veterinary Medicine, Department of Physiology. In 2016, he joined Kafkas University, Faculty of Veterinary Medicine, Department of Physiology as an assistant professor. Dr. Gelen has been engaged in various academic activities at Kafkas University since 2016. There he completed 5 projects and has 3 ongoing projects. He has 60 articles published in scientific journals and 20 poster presentations in scientific congresses. His research interests include physiology, endocrine system, cancer, diabetes, cardiovascular system diseases, and isolated organ bath system studies.",institutionString:"Kafkas University",institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"418963",title:"Dr.",name:"Augustine Ododo",middleName:"Augustine",surname:"Osagie",slug:"augustine-ododo-osagie",fullName:"Augustine Ododo Osagie",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/418963/images/16900_n.jpg",biography:"Born into the family of Osagie, a prince of the Benin Kingdom. I am currently an academic in the Department of Medical Biochemistry, University of Benin. Part of the duties are to teach undergraduate students and conduct academic research.",institutionString:null,institution:{name:"University of Benin",country:{name:"Nigeria"}}},{id:"192992",title:"Prof.",name:"Shagufta",middleName:null,surname:"Perveen",slug:"shagufta-perveen",fullName:"Shagufta Perveen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/192992/images/system/192992.png",biography:"Prof. Shagufta Perveen is a Distinguish Professor in the Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. Dr. Perveen has acted as the principal investigator of major research projects funded by the research unit of King Saud University. She has more than ninety original research papers in peer-reviewed journals of international repute to her credit. She is a fellow member of the Royal Society of Chemistry UK and the American Chemical Society of the United States.",institutionString:"King Saud University",institution:{name:"King Saud University",country:{name:"Saudi Arabia"}}},{id:"49848",title:"Dr.",name:"Wen-Long",middleName:null,surname:"Hu",slug:"wen-long-hu",fullName:"Wen-Long Hu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49848/images/system/49848.jpg",biography:"Wen-Long Hu is Chief of the Division of Acupuncture, Department of Chinese Medicine at Kaohsiung Chang Gung Memorial Hospital, as well as an adjunct associate professor at Fooyin University and Kaohsiung Medical University. Wen-Long is President of Taiwan Traditional Chinese Medicine Medical Association. He has 28 years of experience in clinical practice in laser acupuncture therapy and 34 years in acupuncture. He is an invited speaker for lectures and workshops in laser acupuncture at many symposiums held by medical associations. He owns the patent for herbal preparation and producing, and for the supercritical fluid-treated needle. Dr. Hu has published three books, 12 book chapters, and more than 30 papers in reputed journals, besides serving as an editorial board member of repute.",institutionString:"Kaohsiung Chang Gung Memorial Hospital",institution:{name:"Kaohsiung Chang Gung Memorial Hospital",country:{name:"Taiwan"}}},{id:"298472",title:"Prof.",name:"Andrey V.",middleName:null,surname:"Grechko",slug:"andrey-v.-grechko",fullName:"Andrey V. Grechko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/298472/images/system/298472.png",biography:"Andrey Vyacheslavovich Grechko, Ph.D., Professor, is a Corresponding Member of the Russian Academy of Sciences. He graduated from the Semashko Moscow Medical Institute (Semashko National Research Institute of Public Health) with a degree in Medicine (1998), the Clinical Department of Dermatovenerology (2000), and received a second higher education in Psychology (2009). Professor A.V. Grechko held the position of Сhief Physician of the Central Clinical Hospital in Moscow. He worked as a professor at the faculty and was engaged in scientific research at the Medical University. Starting in 2013, he has been the initiator of the creation of the Federal Scientific and Clinical Center for Intensive Care and Rehabilitology, Moscow, Russian Federation, where he also serves as Director since 2015. He has many years of experience in research and teaching in various fields of medicine, is an author/co-author of more than 200 scientific publications, 13 patents, 15 medical books/chapters, including Chapter in Book «Metabolomics», IntechOpen, 2020 «Metabolomic Discovery of Microbiota Dysfunction as the Cause of Pathology».",institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"199461",title:"Prof.",name:"Natalia V.",middleName:null,surname:"Beloborodova",slug:"natalia-v.-beloborodova",fullName:"Natalia V. Beloborodova",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/199461/images/system/199461.jpg",biography:'Natalia Vladimirovna Beloborodova was educated at the Pirogov Russian National Research Medical University, with a degree in pediatrics in 1980, a Ph.D. in 1987, and a specialization in Clinical Microbiology from First Moscow State Medical University in 2004. She has been a Professor since 1996. Currently, she is the Head of the Laboratory of Metabolism, a division of the Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Moscow, Russian Federation. N.V. Beloborodova has many years of clinical experience in the field of intensive care and surgery. She studies infectious complications and sepsis. She initiated a series of interdisciplinary clinical and experimental studies based on the concept of integrating human metabolism and its microbiota. Her scientific achievements are widely known: she is the recipient of the Marie E. Coates Award \\"Best lecturer-scientist\\" Gustafsson Fund, Karolinska Institutes, Stockholm, Sweden, and the International Sepsis Forum Award, Pasteur Institute, Paris, France (2014), etc. Professor N.V. Beloborodova wrote 210 papers, five books, 10 chapters and has edited four books.',institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"354260",title:"Ph.D.",name:"Tércio Elyan",middleName:"Azevedo",surname:"Azevedo Martins",slug:"tercio-elyan-azevedo-martins",fullName:"Tércio Elyan Azevedo Martins",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/354260/images/16241_n.jpg",biography:"Graduated in Pharmacy from the Federal University of Ceará with the modality in Industrial Pharmacy, Specialist in Production and Control of Medicines from the University of São Paulo (USP), Master in Pharmaceuticals and Medicines from the University of São Paulo (USP) and Doctor of Science in the program of Pharmaceuticals and Medicines by the University of São Paulo. Professor at Universidade Paulista (UNIP) in the areas of chemistry, cosmetology and trichology. Assistant Coordinator of the Higher Course in Aesthetic and Cosmetic Technology at Universidade Paulista Campus Chácara Santo Antônio. Experience in the Pharmacy area, with emphasis on Pharmacotechnics, Pharmaceutical Technology, Research and Development of Cosmetics, acting mainly on topics such as cosmetology, antioxidant activity, aesthetics, photoprotection, cyclodextrin and thermal analysis.",institutionString:null,institution:{name:"University of Sao Paulo",country:{name:"Brazil"}}},{id:"334285",title:"Ph.D. Student",name:"Sameer",middleName:"Kumar",surname:"Jagirdar",slug:"sameer-jagirdar",fullName:"Sameer Jagirdar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334285/images/14691_n.jpg",biography:"I\\'m a graduate student at the center for biosystems science and engineering at the Indian Institute of Science, Bangalore, India. 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