Some collaborations took place both locally or outside your country in helping capacity building but help will also be needed in some aspect.
\\n\\n
IntechOpen Book Series will also publish a program of research-driven Thematic Edited Volumes that focus on specific areas and allow for a more in-depth overview of a particular subject.
\\n\\nIntechOpen Book Series will be launching regularly to offer our authors and editors exciting opportunities to publish their research Open Access. We will begin by relaunching some of our existing Book Series in this innovative book format, and will expand in 2022 into rapidly growing research fields that are driving and advancing society.
\\n\\nLaunching 2021
\\n\\nArtificial Intelligence, ISSN 2633-1403
\\n\\nVeterinary Medicine and Science, ISSN 2632-0517
\\n\\nBiochemistry, ISSN 2632-0983
\\n\\nBiomedical Engineering, ISSN 2631-5343
\\n\\nInfectious Diseases, ISSN 2631-6188
\\n\\nPhysiology (Coming Soon)
\\n\\nDentistry (Coming Soon)
\\n\\nWe invite you to explore our IntechOpen Book Series, find the right publishing program for you and reach your desired audience in record time.
\\n\\nNote: Edited in October 2021
\\n"}]',published:!0,mainMedia:{caption:"",originalUrl:"/media/original/132"}},components:[{type:"htmlEditorComponent",content:'With the desire to make book publishing more relevant for the digital age and offer innovative Open Access publishing options, we are thrilled to announce the launch of our new publishing format: IntechOpen Book Series.
\n\nDesigned to cover fast-moving research fields in rapidly expanding areas, our Book Series feature a Topic structure allowing us to present the most relevant sub-disciplines. Book Series are headed by Series Editors, and a team of Topic Editors supported by international Editorial Board members. Topics are always open for submissions, with an Annual Volume published each calendar year.
\n\nAfter a robust peer-review process, accepted works are published quickly, thanks to Online First, ensuring research is made available to the scientific community without delay.
\n\nOur innovative Book Series format brings you:
\n\nIntechOpen Book Series will also publish a program of research-driven Thematic Edited Volumes that focus on specific areas and allow for a more in-depth overview of a particular subject.
\n\nIntechOpen Book Series will be launching regularly to offer our authors and editors exciting opportunities to publish their research Open Access. We will begin by relaunching some of our existing Book Series in this innovative book format, and will expand in 2022 into rapidly growing research fields that are driving and advancing society.
\n\nLaunching 2021
\n\nArtificial Intelligence, ISSN 2633-1403
\n\nVeterinary Medicine and Science, ISSN 2632-0517
\n\nBiochemistry, ISSN 2632-0983
\n\nBiomedical Engineering, ISSN 2631-5343
\n\nInfectious Diseases, ISSN 2631-6188
\n\nPhysiology (Coming Soon)
\n\nDentistry (Coming Soon)
\n\nWe invite you to explore our IntechOpen Book Series, find the right publishing program for you and reach your desired audience in record time.
\n\nNote: Edited in October 2021
\n'}],latestNews:[{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"},{slug:"intechopen-identified-as-one-of-the-most-significant-contributor-to-oa-book-growth-in-doab-20210809",title:"IntechOpen Identified as One of the Most Significant Contributors to OA Book Growth in DOAB"}]},book:{item:{type:"book",id:"7960",leadTitle:null,fullTitle:"Assorted Dimensional Reconfigurable Materials",title:"Assorted Dimensional Reconfigurable Materials",subtitle:null,reviewType:"peer-reviewed",abstract:"This book outlines assorted dimensional materials acquired through reconfiguration of potentially applicable physical properties and functions of some multifunctional matrixes, composites, hybrids, and blends. As the frontiers of Science and Technology become widened, many multifunctional materials are created via physico-chemically reconfigured alterations to cater for remarkable applications in this era of modernization. Today, material for sustainable and green development in S&T draws noteworthy global interest in industry and technology such as polymer-based sensors/markers, thermal conductors, metal-alloys, piezo-energy harvesters, and thermoelectrics. Chapters of this book explain practicable methodologies and viable applications in the diverse areas of material chemistry, physics, and modern engineering. All skeletal reconfigured matrixes are promising due to augmented new functionality that offers novel and advanced utilities to the resultant matrixes, composites, blends, gels, and hybrids.",isbn:"978-1-78985-514-2",printIsbn:"978-1-78985-513-5",pdfIsbn:"978-1-83968-193-6",doi:"10.5772/intechopen.77790",price:119,priceEur:129,priceUsd:155,slug:"assorted-dimensional-reconfigurable-materials",numberOfPages:140,isOpenForSubmission:!1,isInWos:1,isInBkci:!1,hash:"bc49969c3a4e2fc8f65d4722cc4d95a5",bookSignature:"Rajendra Sukhjadeorao Dongre and Dilip Rankrishna Peshwe",publishedDate:"September 9th 2020",coverURL:"https://cdn.intechopen.com/books/images_new/7960.jpg",numberOfDownloads:3346,numberOfWosCitations:8,numberOfCrossrefCitations:5,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:12,numberOfDimensionsCitationsByBook:0,hasAltmetrics:0,numberOfTotalCitations:25,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"January 31st 2019",dateEndSecondStepPublish:"May 23rd 2019",dateEndThirdStepPublish:"July 22nd 2019",dateEndFourthStepPublish:"October 10th 2019",dateEndFifthStepPublish:"December 9th 2019",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"188286",title:"Associate Prof.",name:"Rajendra",middleName:"Sukhadeorao",surname:"Dongre",slug:"rajendra-dongre",fullName:"Rajendra Dongre",profilePictureURL:"https://mts.intechopen.com/storage/users/188286/images/system/188286.jpg",biography:"Rajendra S. Dongre received his M.Sc. from the Department of Chemistry, R.T.M., Nagpur University in 1996 (Gold Medalist) and his PhD in 2010. His research work includes organic synthesis, chitosan bio-composite, assorted dimensional matrix, and remediation of water pollution de-fluoridation; nitrate, chromium, and phosphate lead (II). He has worked as a Scientist-B in the CSIR-LAB, National Environmental Engineering Research Institute (NEERI) Nagpur M.S., India. Overall, he has 25 years of experience in research and development and 18 years of post-graduate teaching experience, which has resulted in 70 international research paper publications. He has guided four research students to pursue their PhD. He received the 6th National Award (runner-up) for Technology Innovation in Petrochemicals and Downstream Plastics Processing Industry, for research in the field of polymer science and technology, handed by the Honorable Ananth Kumar, Petrochemical & Fertilizers Minister of Government of India in 2016. He received the 5th National Science & Technology Award for research contribution in the field of developing science in 2017, by EET-CRS, Noida, India.",institutionString:"RTM Nagpur University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"10",totalChapterViews:"0",totalEditedBooks:"2",institution:null}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:{id:"289232",title:"Dr.",name:"Dilip R.",middleName:null,surname:"Peshwe",slug:"dilip-r.-peshwe",fullName:"Dilip R. Peshwe",profilePictureURL:"https://mts.intechopen.com/storage/users/289232/images/system/289232.jpg",biography:"Dr. Dilip R. Peshwe is a HAG Professor of Metallurgical and Materials Engineering and Dean (Faculty Welfare), Visvesvaraya National Institute of Technology (VNIT), Nagpur India. His areas of research interest include physical metallurgy, the welding and casting process, tribology, polymers, composites and wear of engineering materials. Eighteen students have completed their PhD under his guidance. He has published more than 150 research papers in international peer-reviewed journals and is the author of four books and six patents. He is the recipient of various prestigious awards such as the Jawaharlal Nehru Memorial Trust Award, Best S&T Innovation Award of Khadi & Industries Commission, and the IIM-SAIL Gold Medal of Indian Institute of Metals.",institutionString:"Visvesvaraya National Institute of Technology",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:null},coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"14",title:"Materials Science",slug:"materials-science"}],chapters:[{id:"72831",title:"Introductory Chapter: Assorted Dimensional Reconfigurable Materials",doi:"10.5772/intechopen.93243",slug:"introductory-chapter-assorted-dimensional-reconfigurable-materials",totalDownloads:510,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:null,signatures:"Rajendra Sukhjadeorao Dongre and Dilip R. Peshwe",downloadPdfUrl:"/chapter/pdf-download/72831",previewPdfUrl:"/chapter/pdf-preview/72831",authors:[{id:"188286",title:"Associate Prof.",name:"Rajendra",surname:"Dongre",slug:"rajendra-dongre",fullName:"Rajendra Dongre"},{id:"289232",title:"Dr.",name:"Dilip R.",surname:"Peshwe",slug:"dilip-r.-peshwe",fullName:"Dilip R. Peshwe"}],corrections:null},{id:"68998",title:"Graphene/Metal Oxide Nanocomposite Usage as Photoanode in Dye-Sensitized and Perovskite Solar Cells",doi:"10.5772/intechopen.88971",slug:"graphene-metal-oxide-nanocomposite-usage-as-photoanode-in-dye-sensitized-and-perovskite-solar-cells",totalDownloads:668,totalCrossrefCites:2,totalDimensionsCites:5,hasAltmetrics:0,abstract:"Global energy shortage will be one of the most critical challenges in the next 50 years. Currently, over 80% of energy consumed is produced from fossil fuels, which is directly linked to global warming and environmental pollution issues. Environment-friendly renewable energy is rapidly gaining importance for the existence of human civilization. A leading source of renewable energy is the solar energy, which is inexhaustible and abundantly available. Solar cells that convert solar energy directly into electricity are drawing considerable attention as a potential turnkey solution to address these challenges. Several approaches have been made in this respect, including the development of better materials and the designs of new solar cell configuration and architecture. Among the innovative materials with potential application in emerging 3G solar cells, graphene and its derivatives such as GO, rGO and G/nanocomposite have been widely explored as transparent conducting electrodes, electron donor or acceptor materials and counter electrodes (CE). In this chapter, the use of graphene nanocomposites has been explored as an electrode material in DSSCs and PSCs. Recently, graphene/metal oxide nanocomposites have been widely used in DSSCs and PSCs and played a significant role in increasing charge transport, reducing charge recombination and thus enhancing the performance of solar cell.",signatures:"Tahira Mahmood, Madeeha Aslam and Abdul Naeem",downloadPdfUrl:"/chapter/pdf-download/68998",previewPdfUrl:"/chapter/pdf-preview/68998",authors:[{id:"305971",title:"Prof.",name:"Tahira",surname:"Mahmood",slug:"tahira-mahmood",fullName:"Tahira Mahmood"},{id:"305974",title:"Ms.",name:"Madeeha",surname:"Aslam",slug:"madeeha-aslam",fullName:"Madeeha Aslam"}],corrections:null},{id:"72004",title:"Titanium Dioxide Versatile Solid Crystalline: An Overview",doi:"10.5772/intechopen.92056",slug:"titanium-dioxide-versatile-solid-crystalline-an-overview",totalDownloads:832,totalCrossrefCites:2,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Among the several choices, titanium dioxide (TiO2) is the most efficient material and has attracted great attention because of its certain specific properties like high permittivity, refractive index, efficiency, low cost, chemical inertness, non-toxicity, photocatalytic activity, photostability and capability of decomposing a wide variety of organic compounds. In the field of dental, orthopedic and osteosynthesis applications, the titanium and its native oxide (titanium dioxide) are used as an implant material. TiO2 is used in an extremely wide range of commercial applications and research areas including: (i) TiO2 powder: as a white pigment in paint, plastic, inks, paper and cosmetics; in washing powder, toothpaste, sunscreen, foodstuffs, pharmaceuticals, photographic plates, for creating synthetic gemstones; and as a catalyst. (ii) TiO2 thin films: for ultra-thin capacitors and MOSFETs due to its extremely high dielectric constant; as humidity and oxygen sensor due to the dependence of its electrical conductance on the gases present; as an optical coating and a material for waveguides due to its high refractive index; as a protective coating and corrosion-resistant barrier; and as a photoanode in solar cells due its photoelectric activity.",signatures:"Lourduraj Stephen",downloadPdfUrl:"/chapter/pdf-download/72004",previewPdfUrl:"/chapter/pdf-preview/72004",authors:[{id:"293490",title:"Dr.",name:"Lourduraj",surname:"Stephen",slug:"lourduraj-stephen",fullName:"Lourduraj Stephen"}],corrections:null},{id:"72670",title:"An Overview of Anodic Oxides Derived Advanced Nanocomposites Substrate for Surface Enhance Raman Spectroscopy",doi:"10.5772/intechopen.92811",slug:"an-overview-of-anodic-oxides-derived-advanced-nanocomposites-substrate-for-surface-enhance-raman-spe",totalDownloads:399,totalCrossrefCites:1,totalDimensionsCites:4,hasAltmetrics:0,abstract:"Surface-enhanced Raman spectroscopy (SERS) is an analytical technique, which allows to identify traces of chemical or biological substances in many field, like pharmaceutical and food industries, homeland security, nanosensors, or environmental protection. The analytes are identified based on their vibrational spectra, unique for a given compound. The advantage of SERS is effective qualitative analysis of trace amounts of analyte, but the disadvantages are stability of substrate and repeatability of measurements. The challenge is to improve SERS substrates to minimize these drawbacks. Nowadays high-precision electron beam lithography or focused ion beam is used in SERS substrate fabrication, which is impractical for large-scale production. In recent years, researchers’ attention has focused on porous anodic oxides, with inexpensive and scalable production method, as potential materials for SERS substrates. This chapter will discuss the progress of anodic oxides used as a SERS substrate, and the brief description of conventional SERS substrate fabrication methods will be presented.",signatures:"Marta Michalska-Domańska",downloadPdfUrl:"/chapter/pdf-download/72670",previewPdfUrl:"/chapter/pdf-preview/72670",authors:[{id:"303858",title:"Dr.",name:"Marta",surname:"Michalska-Domanska",slug:"marta-michalska-domanska",fullName:"Marta Michalska-Domanska"}],corrections:null},{id:"71968",title:"An Experimental Investigation of Al2O3-40% TiO2 Powder Amalgamated via Atmospheric Plasma Spray Coating onto SS316 Substrate and Parameter Optimization Using TLBO Algorithm",doi:"10.5772/intechopen.92175",slug:"an-experimental-investigation-of-al-sub-2-sub-o-sub-3-sub-40-tio-sub-2-sub-powder-amalgamated-via-at",totalDownloads:351,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"SS316 is a commercial stainless steel. MTBF (Mean Time Between Failure) of SS 316 wear prone areas can be effectively increased by ceramic coating. The coating thickness, surface roughness, coating microhardness, abrasion rate, and coating porosity decides the quality and durability in ceramic coating. The current research work explains an experimental investigation to optimize the Atmosphere Plasma Spray process input parameters of Al2O3-40%TiO2 ceramic coatings. Three-level L18 Orthogonal Array (OA) design of Experiments (DoE) is used to conduct the current work. The main input parameters considered in the current study are nozzle distance, substrate speed, arc current, carrier gas flow, and coating powder flow rate. The output parameters considered are coating thickness, surface roughness, coating microhardness, abrasion rate, and percentage of porosity. Mathematical models are generated for individual output parameters. AHP (Analytical Hierarchy Process) is effectively used to find out weights for individual output parameters treating them as objective functions, and a combined objective function is generated.",signatures:"Thankam Sreekumar Rajesh",downloadPdfUrl:"/chapter/pdf-download/71968",previewPdfUrl:"/chapter/pdf-preview/71968",authors:[{id:"301820",title:"Dr.",name:"Rajesh",surname:"Sreekumar",slug:"rajesh-sreekumar",fullName:"Rajesh Sreekumar"}],corrections:null},{id:"71360",title:"LDH Ternary Nanocomposites: g-C3N4 Intercalated ZnO\\Mg-Al for Superior Photocatalytic Activity towards Dye Degradation",doi:"10.5772/intechopen.89325",slug:"ldh-ternary-nanocomposites-g-c-sub-3-sub-n-sub-4-sub-intercalated-zno-mg-al-for-superior-photocataly",totalDownloads:588,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Photocatalytic dye degradation has received more attention as an affordable and effective way to treat the dye polluted water. In the present chapter, we are going to discuss; (i) the preparation and photophysical characterization of g-C3N4 intercalated ZnO\\\\Mg-Al LDH, a novel ternary nanocomposite, and (ii) its visible light photocatalytic degradation activity against the methylene blue dye. LDHs are 2D materials composed of “brucite-like” cationic layers where an inclusion of trivalent cations presents an overall positive charge to the nanosheets. g-C3N4 is one of the organic semiconductor photocatalyst which active for several types of reactions such as CO2 reduction, water splitting, and degradation because of its stable, non-toxic, and earth-abundant nature. Mainly, the development of numerous 2D g-C3N4 nanosheets has been extensively used in the field of photocatalyst. By the combination heterojunction with 2D/2D interface can effectively improve the photocatalytic activity. The nitrogen-rich g-C3N4 intercalated ZnO\\\\Mg-Al LDH ternary nanocomposite formation could follow the direct dye degradation process and results enhance the visible light absorption. The enhanced photocatalytic activity is mainly due to the improved charge separation rate and high number of photogenerated electrons. 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This search for the democratization of access to scientific knowledge finds support in the model of dissemination of information through Open Access publications, especially through the digital format through the Internet. The current accessibility by the most diverse social classes in the most diverse countries is due in large part to scientific development in semiconductors.
\r\n\r\n\tSemiconductor research goes much further than the development of electronic devices, because it has a multidisciplinary character, with contributions from basic sciences, such as Chemistry, Physics, and Mathematics, as well as from the frontier of knowledge, such as nanotechnology. This multidisciplinarity allows that in addition to important technological advances in electronic devices, such as diodes and transistors, integrated circuits, lasers, solar and photovoltaic cells, sensors, memory devices, among many others, there are also positive impacts for the production of new scientific knowledge.
\r\n\r\n\tIt is within this context that this book project is inserted, aiming to gather recent and unpublished discoveries, conclusive reviews and other methodological and conceptual approaches on the subject of semiconductors. The idea is to contribute so that authors can disseminate their work both to other groups of researchers in their fields of study around the world, but also to a society in general, showing how semiconductor research positively changes our lives.
\r\n\r\n\tThe "New Advances in Semiconductors" book will cover the main themes of the area but will be limited to these, such as unpublished experimental data, description of synthesis methods and processing techniques, characterizations of traditional or new semiconductor materials, statistical and mathematical treatments, modeling and other theoretical approaches. Articles with alternative discussions will also be welcome, whether on materials, properties, or applications, or the economic and social implications in the field of semiconductors. Thus, this book project aims to gather articles with technical-scientific information and also with general views on the topic of Semiconductors."
",isbn:"978-1-80355-682-6",printIsbn:"978-1-80355-681-9",pdfIsbn:"978-1-80355-683-3",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,isSalesforceBook:!1,hash:"238b808626f765e883b9bff8b62eae18",bookSignature:"Dr. Alberto Adriano Cavalheiro",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11158.jpg",keywords:"Doping Mechanisms, Anomalous Effects, Prediction of Properties, Crystallinity, Phase Transitions, Heterojunctions, Amorphous Materials, Applications and Performance, Composition, Multifunctional Materials, Theoretical Approaches, Early History",numberOfDownloads:114,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfDimensionsCitations:0,numberOfTotalCitations:0,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"October 5th 2021",dateEndSecondStepPublish:"November 2nd 2021",dateEndThirdStepPublish:"January 1st 2022",dateEndFourthStepPublish:"March 22nd 2022",dateEndFifthStepPublish:"May 21st 2022",remainingDaysToSecondStep:"7 months",secondStepPassed:!0,currentStepOfPublishingProcess:5,editedByType:null,kuFlag:!1,biosketch:"A researcher recognized for his work in the structural elucidation of crystalline semiconductor materials, head of the Interdisciplinary Laboratory of Advanced Materials of Navirai (LIMAN), and Area Coordinator at UEMS in the PIBID program, the largest and most important Teaching Initiation Program in Brazil.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"201848",title:"Dr.",name:"Alberto Adriano",middleName:null,surname:"Cavalheiro",slug:"alberto-adriano-cavalheiro",fullName:"Alberto Adriano Cavalheiro",profilePictureURL:"https://mts.intechopen.com/storage/users/201848/images/system/201848.jpg",biography:"Alberto Adriano Cavalheiro is an associate professor at the State University of Mato Grosso do Sul (UEMS), Brazil, where he works as a permanent lecturer in the Graduate Program in Natural Resources and coordinates the LIMAN materials laboratory. He holds a bachelor\\'s, master’s, and a doctorate in Chemistry and a Licentiate of Science. He completed two postdocs with research in semiconductors and catalysts. He works in teaching, research, and extension, with a focus on chemistry and material and environmental sciences. He also coordinates the chemistry area of the Teaching Initiation Program at UEMS. He has numerous funded projects, articles in peer-reviewed journals, and book chapters to his credit. 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In addition, PUFAs are precursors of an almost infinite variety of metabolites, and endocannabinoids are part of them. In particular, anandamide and 2-arachidonoylglycerol (2-AG), the two major endocannabinoids in the brain, are directly derived from arachidonic acid (ARA), the more abundant ω-6 PUFA in the brain. Interestingly, other endocannabinoids are derived from ω-3 PUFA, but their role in the brain remains elusive.
\nAmount of ω-3 and ω-6 PUFAs provided by food has direct consequences on their bioavailability and it has been established that the ideal ratio in the diet is of about 5:1 of ω-6:ω-3 PUFAs precursors. However, our modern diet is hugely unbalanced with an estimated average ratio of 20:1 [1]. The dietary deficit in ω-3 PUFAs has been associated with numerous diseases, and it becomes evident that imbalance of ω-3/ω-6 PUFAs in the brain is linked to several neurological and neuropsychiatric disorders [2, 3].
\nOne possible mechanism for the involvement of dietary PUFAs in brain health is its role in modulating the endocannabinoid system. Indeed, bioavailability of ω-6 and ω-3 PUFAs modulates brain endocannabinoids: an increase in dietary ω-6 PUFAs is associated with increased levels of anandamide and 2-AG [4–6]. In this context, our group recently demonstrated that developmental ω-3 PUFA deficiency in mice abolishes the endocannabinoid-dependent synaptic plasticity and associated signaling pathways [7, 8]. This was the first evidence that a change in dietary precursors can have a strong impact on the outcome of the endocannabinoid system. Endocannabinoids are thus in a unique position to link food lipids and synaptic activity and our working hypothesis is that the effects of dietary ω-6/ω-3 PUFAs on brain function are mediated by their modulatory actions on the endocannabinoid system.
\nIn this chapter, PUFAs entry in the brain and metabolism linking PUFAs to endocannabinoids production will be described. Then, how dietary ω-6/ω-3 PUFAs impact on the functioning of endocannabinoid system will be reviewed. In the third part, what is known about the interactions between PUFAs and endocannabinoids in neurological and neuropsychiatric disorders will be described. Finally, we will conclude on the possible implications of the interactions between PUFAs and endocannabinoids in the brain.
\nThe main PUFAs present in the brain are arachidonic acid (ARA, 20:4n-6) and docosahexaenoic acid (DHA, 22:6n-3). These two long-chain PUFAs can be directly provided by food, or metabolized from dietary precursors in the liver (Figure 1). Blood ARA and DHA enter the brain, probably by a free diffusion across the cell membranes of the blood–brain barrier, even active transporters may exist [3, 9–12] (Figure 1). Once in the brain, active processes preserve ARA and DHA in high concentrations and degrade or recycle the other types of PUFAs [13]. Some evidence also suggest active transporters with specificity for some PUFAs to regulate the levels of each PUFA in the brain [14–18].
\nPUFAs are constituent of plasma membranes and they accumulate into brain cells phospholipids predominantly during brain development [19]. This means that the PUFA composition of membranes in the brain is predominantly determined during cerebral development, which raises the importance of adequate ARA and DHA dietary supply during perinatal periods. At adult age, ARA and DHA supply in the brain is mainly to recycle existing pools used for PUFA metabolites and it is estimated that in humans half-life of ARA is five months, compared to two years for DHA [20]. Accordingly, it has been estimated that the brain needs 18 mg/day of ARA and 4 mg/day of DHA. Even if the developmental period is crucial for PUFAs accretion in brain membranes and therefore composition, changes in the diet or in the metabolism of PUFAs can alter the ratio between ARA and DHA at adulthood. This is particularly true in some neurological disorders such as depression, schizophrenia, Alzheimer disease or Parkinson’s disease [3, 21], where the organism is not able to buffer PUFAs concentrations. In regard to the endocannabinoid system, dietary PUFAs levels have profound consequences because PUFAs are the precursors of brain endocannabinoids (Figure 2). In animal models fed three to four months with a diet deficient in ω-3 PUFAs, the amount of DHA in the brain is reduced by 30% [7, 8, 22–26], with a consequence on endocannabinoid system (see part 3b and Figure 3).
\nOnce into the brain PUFAs do not stay free in the medium, they are immediately esterified to phospholipids by specific enzymes (Figure 1). When associated to phospholipids, PUFAs play important role in the structure of membranes, by determining its curveting and flexibility [27, 28]. More importantly, PUFAs can be released by phospholipase enzymes to be metabolized by cyclooxygenase (COX) / lipoxygenase (LOX) pathways in a huge variety of derivates [3, 29–31] (Figure 1). These derivates are mainly involved in neuroinflammatory processes and the classical picture is that derivates from ω-6 PUFAs, in particular ARA, are pro-inflammatory whereas ω-3 PUFAs derivates, mainly EPA (ecosapentaenoic acid) and DHA, are anti-inflammatory and pro-resolutive factors. The main enzymes involved in these processes are COX, LOX and cytochrome P450 [3, 29–31]. In the brain, it is still unclear whether neurons and/or glial cells are the main cellular type involved in the production of PUFA derivates with pro or anti-inflammatory activities. Apart of inflammatory derivates, PUFAs are also precursors of endocannabinoids and this is the object of the present review (see part 2c).
\nThere are various means by which PUFAs can influence synaptic function. First, as structural elements of plasma membranes, PUFAs can modulate the dynamic of membranes [27, 28, 32] and thus the functionality and traffic of transmembrane and membrane-associated proteins. These proteins are very numerous at both pre- and post-synapses (receptors, transporters, ion channels …) and are essential for the function of the synapse. Second, PUFAs and/or their derivates are agonists of receptors with synaptic functions. This mode of action of PUFAs is very complex and hardly understood, therefore still being an intense research topic [3]. Third, PUFAs are precursors of endocannabinoids, which are lipid mediators with essential functions in neurotransmission and synaptic plasticity [33]. This will be largely developed in parts 3 and 4.
\nDHA has positive effects on neuronal survival and neurogenesis [34, 35]. However, underlying mechanisms remain poorly understood. Interestingly, it has been recently discovered that synaptamide, an endocannabinoid derivate of DHA, play an important role in cellular growing and differentiation in the brain during development [36]. Neuroprotectin D1 (NPD1) is another derivate from DHA that protects against neuronal death by triggering the synthesis of anti-apoptotic proteins [37, 38]. It is also known that DHA stimulates neuronal survival by inducing the synthesis of BDNF (brain-derived neurotrophic factor) [39]. These positive effects could explain the potential benefit of DHA supplementation in neurodegenerative disorders [21, 40], but this needs to be further explored.
\nAs previously mentioned, PUFAs are precursors of an infinite variety of derivates, preferentially pro-inflammatory for ARA derivates and anti-inflammatory for DHA and EPA derivates (Figure 1). As a consequence, a diet rich in DHA in humans is associated with a decreased risk of developing neurological disorders with an inflammatory component, such as Alzheimer’s disease or depression [41–43]. In animal models, our laboratory demonstrated that neuroinflammatory processes are over-activated in the brain of mice fed a diet deficient for ω-3 PUFAs [26, 44]. Conversely, ω-3 PUFA brain enrichment protects against deleterious effects of inflammation on cognitive performances [24, 45, 46]
\nEndocannabinoids are defined as endogenous lipids able to activate CB1 or CB2 cannabinoid receptors. The two major endocannabinoids described in the organism are 2-AG and anandamide (AEA). They are part of two families of endocannabinoids, 2-acylglycerols for 2-AG, and ethanolamides for AEA (Figure 2), but all species in these families are not ligand of cannabinoid receptors. AEA and 2-AG are the two species with the highest affinity for CB1 and CB2, and their role in neuronal plasticity has been thoroughly demonstrated [33, 47]. These two canonical endocannabinoids are derived from the ω-6 PUFA ARA and most of studies have focused on these endocannabinoids. However, more and more studies are highlighting the role of ω-3-derived endocannabinoids. These species are agonists of CB1 and CB2 receptors, but their role in neuroplasticity is yet to be unraveled.
\nBriefly, there is a two-step process to form endocannabinoids from phospholipids. Endocannabinoids are made on-demand and they are rapidly degraded, back into PUFAs or oxydized into active metabolites. Interestingly, degradation enzymes are more numerous and more active than production enzymes of endocannabinoids, suggesting that endocannabinoids are highly regulated and never stay for long at the synapse [48]. This may be explained by the fast desensitization of CB1 receptor. Endocannabinoid system thus appears as a highly dynamic and regulated system.
\nHere, we will describe the canonical pathways for endocannabinoids production and degradation at the synapse. However, these canonical are still under debate, especially because the importance of secondary pathways is unknown [49].
\nThe first step of 2-AG formation is the hydrolysis by a phospholipase C (PLC) enzyme of a phosphatidylinositol (PI) containing an ARA PUFA. In postsynaptic neurons, it is mainly the PLCβ that is involved in this process because it is activated by Gq/11-coupled receptors, such as group I metabotropic glutamate receptors or acetylcholine receptors [48, 50–52]. The product of this reaction is ARA-containing diacylglycerol (DAG). This DAG is then the substrate of a DAG-lipase enzyme (DAGL) that hydrolyzes the DAG into 2-AG (removal of the acyl group) (Figure 2). DAGL enzyme has two isoforms, DAGLα and DAGLβ and it is likely that DAGLα is the main enzyme responsible for the formation of 2-AG in the brain. Indeed, DAGLα is spatially close to PLCβ, and DAGLα-deficient but not DAGLβ-deficient mice display a strong reduction in 2-AG brain levels [53, 54].
\nOnce it is formed, 2-AG exerts its action by targeting CB1 receptors on presynaptic neurons or CB2 receptors on glial cells surrounding the synapse (microglia and astrocyte). 2-AG is thus a retrograde messenger that is released from the post-synapse into the synaptic cleft. The question of an active transporter for 2-AG has been densely investigated but up to now, there is no identified transporter for 2-AG [55]. The most likely hypothesis at present is that DAGL enzyme is responsible for release of 2-AG in the synaptic cleft.
\nOnce 2-AG binds to CB1 and/or CB2 receptors, it is rapidly processed for degradation by the enzyme MAGL (monoacylglycerol lipase) (Figure 2). The MAGL enzyme is present in postsynaptic astro-glial compartments [56–58] and it hydrolyzes 2-AG to form ARA and glycerol. There is some redundancy in degradation enzymes for 2-AG because ABHD6 (Abhydrolase domain containe protein 6) and ABHD12 can also hydrolyze 2-AG [48, 56]. Degradation of 2-AG can also be performed by its oxygenation with COX and LOX enzymes, which produces PUFA derivates with bioactive functions [59–61] (Figure 2).
\nMetabolism of AEA follows a similar process as 2-AG. First, the N-acyltransferase enzyme (NAT) uses the ARA of a phosphatidylcholine (PC) and a phosphatidylethanolamine (PE) to form a N-acyl-phosphatidylethanolamine product (NAPE) (Figure 2). Anandamide production is triggered by calcium entry into the cell, since the NAT enzyme is activated by calcium [62]. Sources of calcium can be diverse, mainly NMDA receptor and voltage-gated calcium channels, or alternatively release from intracellular stores. Interestingly this calcium-dependent NAT remains molecularly uncharacterized [48], which reflects the gaps in the literature that exist concerning the endocannabinoid system. The NAPE formed is then hydrolyzed in AEA by a NAPE-phospholipase D enzyme (NAPE-PLD) (Figure 2). Here again, this enzyme is not well characterized and many questions remain about its activity, regulation and localization [48].
\nTransport of AEA is better characterized than 2-AG transport, but it is still largely under debate. A FLAT transporter (fatty acid amide hydrolase-like anandamide transporter) has been discovered recently for intracellular transport of AEA [63], but a study published one year later contradicts its putative role [64]. It is thus too soon to conclude clearly on this point [49, 55]. In addition, recent studies revealed that the preferred target of AEA in the brain may be postsynaptic TRPV1 (transient receptor potential vallinoid 1) channels and not necessarily presynaptic receptors. It is thus possible that AEA does not need to travel the synaptic cleft but may act directly by travelling through the plasma membrane to activate intracellular postsynaptic TRPV1 receptors. TRPV channels are vallinoid receptors involved in nociception that are primarily activated by capsaicin [65–67]. In the brain, AEA appears as a potent agonist of TRPV1 and its role in endocannabinoid-dependent synaptic plasticity has been demonstrated [33, 68–70].
\nThe main enzyme responsible for degradation of AEA is FAAH (fatty acid amide hydrolase) which produces an ethanolamine and an ARA PUFA (Figure 2). FAAH is situated in the intracellular compartment and is bound to membranes, which can modulate the access of AEA to its degradation enzyme [71]. Drugs targeting the FAAH enzyme have been extensively studied for the treatment of endocannabinoids-related disorders, such as anxiety, depression, inflammation or neuropathic pain [72]. However, pharmaceutics are struggling to find a compound with high efficiency and low side effects, which may be due to chronic effects of FAAH inhibition that differ from acute effects [73, 74] (Figure 2).
\nContrarily to 2-AG, there is no known other enzyme for degradation of AEA, except COX and LOX enzymes that can oxygenate the ARA group of AEA to form bioactive derivates of ARA [59–61].
\nOne of the reasons for the complexity of the endocannabinoid system and its study is the existence of multiple alternative enzymatic pathways. Transgenic mice constitute a good tool to investigate the redundancy of a protein. Mice deficient for DAGLα have a strong decrease in 2-AG levels, while mice deficient for MAGL display very high levels of 2-AG [48, 53, 75]. This suggests that redundancy for 2-AG synthesis and degradation is not the majority. Conversely, mice deficient for NAPE-PLD have elevated levels of NAPE, but there is almost no change in AEA levels [48, 76, 77]. This suggests that NAPE-PLD is the main pathway to hydrolyze NAPE but that robust redundant mechanisms do exist to form AEA. However, these secondary mechanisms have not yet been discovered. Apart from these studies, other pathways have been described to form and degrade endocannabinoids [49]. For example, 2-AG can be formed by hydrolysis of lyso-PI by phospholipase 1 enzyme [48]. However, the physiological significance of these secondary pathways has yet to be unraveled.
\nIn the brain, 2-AG and AEA are the canonical endocannabinoids but other bioactive lipids derived from ω-3 PUFAs are ligand of CB1 and CB2 receptors. The two main ω-3 PUFAs described in the literature are ethanolamides derived from DHA, called DHEA (N-Docosahexaenoyl ethanolamine), and from EPA, called EPEA (N-Eicosapentaenoyl ethanolamine). Endocannabinoids EPEA and DHEA are present in the brain in concentrations about two fold higher compared to AEA [78], but their binding affinity for CB1 and CB2 receptors is probably lower [79, 80]. EPEA and DHEA share the exact same pathways of production as AEA, except that NAT enzyme uses respectively the EPA or the DHA group of a phosphatidylethanolamine to form the NAPE product (Figure 2). The ω-3-derived endocannabinoids also follow the degradation pathways of AEA, with FAAH as the main degradation enzyme, and there is the possibility for DHEA and EPEA to be oxidized by COX and LOX enzymes (Figure 2).
\nAs discussed in parts 4 and 5, dietary ω-6/ω-3 ratio directly modulates the proportion of ethanolamides derived from ω-6 and ω-3, but the role of ω-3 derived endocannabinoids remains elusive. One issue that faces researchers to study the role of ω-3-derived endocannabinoids is that they share exactly the same enzymatic pathways as AEA. It is thus currently not possible to precisely target their synthesis or degradation.
\nSo far, the role of DHEA has been demonstrated in neuronal development and synaptogenesis [36, 81, 82], but its effect is likely independent of activation of cannabinoid receptors. It exists other ethanolamides derived from monounsaturated fatty acids (such as N-oleoyl amide derived from oleic acid). They don’t bind to CB1 or CB2 receptors, but they can have cannabimimetic activities. It has been suggested that these ethanolamides could serve as ‘entourage molecules’ to modulate the signaling of AEA [59]. Finally the ω-3 derived endocannabinoid 2-docosahexanoylglycerol (2-DHG) is sometimes evoked in the literature [83, 84], but there is a crucial lack of data about the enzymatic pathways and the binding affinity of this bioactive lipid (Figure 2).
\nAt the periphery, endocannabinoids receptors are mostly present in adipose tissue, immune system, musculoskeletal system, gonads and cardiovascular system. All of these compartments are also regulated by dietary PUFAs. Because PUFAs are precursors of endocannabinoids, the effect of dietary PUFAs on endocannabinoids in these compartments has been relatively well documented [85–92]. Consistently, it appears that increasing dietary ω-6 PUFAs does increase levels of ARA-derived endocannabinoids in the organism (Figure 3). Conversely, diets enriched in ω-3 decreases ARA-derived endocannabinoids (AEA and 2-AG) while it increases levels of endocannabinoids derived from ω-3 PUFAs, namely DHEA and EPEA (Figure 3). However, studies have rarely investigated the functional consequences of this link between dietary PUFAs and levels of endocannabinoids. There is a strong hypothesis that beneficial effects of ω-3 supplementation pass through an effect on the endocannabinoid system, but it has never been directly tested.
\nIn details, the impact of dietary PUFA on endocannabinoids has been investigated in the context of obesity. Indeed, activation of CB1 receptors in adipose tissue increases food intake and increases the creation of new adipocytes [93]. Endocannabinoids are thus a target to treat obesity [94]. Rimonabant, an antagonist of CB1 receptors, has been used in overweighed patients to reduce their food intake, with very positive results. However, strong side effects on mood for some patients lead to the withdrawal of rimonabant from the market. In this context, dietary PUFAs appeared as homeostatic regulators of endocannabinoids [95], encouraging researchers to investigate the effect of ω-3 rich diet on obesity. It has been shown that a diet rich in ω-3 leads to weight loss, in parallel to a decrease of AEA and 2-AG [88, 93]. Interestingly, a high fat diet rich in ω-3 does not induce weight gain, while a low fat diet rich in ω-6 increases weight gain [89, 90, 96]. These evidence suggest that dietary PUFAs act on fat formation and thus on weight gain
Inflammation is another component of obesity that can be modulated by endocannabinoids and PUFAs. Endocannabinoids are homeostatic regulator of the immune system and their oxydized metabolites (directly derived from PUFAs) can have a direct role in inflammation [97]. In parallel, the role of PUFAs on inflammation is well documented [98, 99]. Globally, we can summarize that ω-6 PUFAs, such as ARA, are metabolized in pro-inflammatory derivates while ω-3 PUFAs, such as DHA and EPA, are metabolized in anti-inflammatory and pro-resolution derivates [3, 29–31]. PUFAs play thus a central role in the immune response of the organism. However, very little is known about the interactions between PUFAs and endocannabinoids in the peripheral immune system.
\nConcerning the musculoskeletal compartment, evidence exists for a correlation between dietary ω-6/ω-3 ratio and levels of ARA- and ω-3-derived endocannabinoids [91, 100, 101]. More interestingly, addition of free ω-3 in the culture medium of osteoblastes changes the level of proteins of the endocannabinoid system: CB2 receptors and NAPE-PLD [101]. Moreover, a diet enriched with DHA for 2 to 4 months increases expression of CB1 and CB2 receptors in muscles, and it favors glucose uptake by the muscle and not by the adipose tissue [91]. It thus appears that in the musculoskeletal system, dietary PUFAs could affect not only endocannabinoid levels, but also the regulation of the proteins of the endocannabinoid system.
\nIn the field of cardiovascular health, it is recognized that both endocannabinoids and ω-3 PUFAs have beneficial effects [102, 103], but the link between endocannabinoids and PUFAs has never been investigated to our knowledge. Of note, we found one review paper suggesting that ω-3-derived endocannabinoids could be beneficial for heart function [102], but this hypothesis remain to be tested.
\nFinally, there is an emerging role of endocannabinoids in gonadic function and more largely in the control of fertility [104–106]. Endocannabinoids and associated receptors are present in female and male gonads and they play a role of fertility signal in the reproduction cycle. In addition, endocannabinoids can regulate gonadic hormones [106]. As a consequence, an aberrant endocannabinoid signaling impairs fertility at all stages [104]. In parallel, PUFAs also play important role in fertility and especially in function of spermatozoa. Indeed, testis and sperm are very rich in DHA and the high concentration of PUFAs —DHA in particular— is necessary for optimal motility and thus fertility of germ cells [92, 107, 108]. It is suggested that PUFAs are necessary to sperm function due to their role in membrane fluidity, however, the hypothesis that PUFAs play a role in sperm fertility
Generally, we can conclude from these studies that modulating dietary PUFAs inevitably modulates levels of endocannabinoids in the organism. In addition, it often emerges from these studies the idea that it exists ‘good endocannabinoids’ and ‘bad endocannabinoids’. In this concept, ARA-derived endocannabinoids need to be down-regulated in pathological states (obesity, inflammation, etc.), and a diet rich in ω-3 decreases the levels of ARA-derived endocannabinoids (the ‘bad’ one), in favor to ω-3-derived endocannabinoids (the ‘good’ one). This appealing hypothesis needs to be studied because the presence of ω-3-derived endocannabinoids in the organism is known, but their function remains to be fully investigated.
\nSimilar to studies at the periphery, dietary ω-6 PUFAs increases levels of 2-AG and AEA in the brain (is this where levels are increased?), while dietary ω-3 PUFAs increases levels of ω-3-derived endocannabinoids (Figure 3). Specifically in the brain, a first study in 2001 compared diets with or without PUFAs on ethanolamides, without distinguishing ω-3 and ω-6 [4]. In this study, three weeks of diet deficient for PUFAs was enough to reduce levels of ethanolamides in piglet brains. Interestingly, levels of ethanolamides were strongly affected in brainstem, cerebellum, visual cortex and striatum, while they were unaffected in visual cortex and hippocampus. Two years later, another study focused on ω-3 PUFAs content of the diet and its impact on 2-AG in mouse brain [5]. In this study, analysis was done on mice fed with one or the other diet for two generations. As expected, brain levels of 2-AG were increased by a diet rich in ω-6 and they were decreased by a diet rich in ω-3. More interestingly, DHA brain levels were modified by the diet, while ARA, the precursor of 2-AG remained perfectly stable. Indeed, consistently in the literature, ARA levels are hardly modified by PUFAs content of the diet, while DHA brain levels are easily correlated to dietary ω-6/ω-3. This suggests that ARA levels in the brain are highly controlled to maintain homeostasis and increase in 2-AG and AEA following ω-6 rich diet could be one way of buffering ARA concentrations. More recently, a dietary experiment has been conducted on rats with only one week of diet at adult age and no difference has been found compared to the control diet [6]. Another study with two weeks of DHA-rich diet showed increased levels of DHEA and decreased levels of AEA, without changes on 2-AG levels [78].
\nThese studies confirm that dietary PUFAs modulate levels of endocannabinoids in the brain, as well as in the periphery. However, the function of the endocannabinoid system in the brain depends also on the ability of the signaling machinery to trigger the appropriate production of endocannabinoids, on the functionality of the receptors, and on the function of degradation enzymes.
\nVery little is known about modifications of the endocannabinoid system in the brain due to dietary PUFAs. A recent study examined the impact of ω-3 deficient diet on enzymes implicated in the metabolism of PUFAs, but not concerning directly the endocannabinoid system [22]. In this study, 15 weeks of ω-3 deficient diet modified the levels of phospholipases A2 and COX enzymes, to favor degradation of ARA and reduce the metabolism of DHA. This suggests that imbalanced PUFAs content in the diet are compensated by enzymatic processes in the brain, but the question remains open for enzymes of the endocannabinoid system. One study reported that DHA supplementation increases levels of CB1 and TRPV1, in terms of mRNA expression and protein levels [109] (Figure 3). Recently, our laboratory demonstrated that a dietary ω-3 deficiency from gestation induces a desensitization of the CB1 receptor [7, 8] (Figure 3). We hypothesize that this is due to high levels of 2-AG and AEA produced by developmental ω-3 deficiency, but this remains to be fully investigated. Our results have been reinforced by a recent study showing that a diet with 5% krill oil (rich in EPA and DHA) given for six weeks to adult mice enhanced the activity of CB1 receptor [110]. It is known that the CB1 receptor can be easily desensitized and internalized by its ligand [111]. This has been particularly studied in the context of chronic cannabinoid consumption to decipher the mechanisms of addiction. Mechanisms of desensitization and downregulation are not totally elucidated but they probably involve phosphorylation of the receptor and transcription of immediate early genes [112, 113]. Interestingly, CB1 receptors do not desensitize at the same rate, depending on the brain structure [113]. Studies on the role of dietary PUFAs on CB1 receptors demonstrate that dietary PUFAs can constitute another powerful mechanism for regulation of the functionality of the CB1 receptor.
\nIn the brain, synaptic plasticity is the main measurable outcome of the functionality of the endocannabinoid system. Indeed, endocannabinoids act to reduce the synaptic efficacy, at very short, medium, or long periods of time, depending on the signaling pathways that trigger endocannabinoid production. As we described above, endocannabinoids are produced on-demand
Some studies have investigated the link between dietary PUFAs and synaptic plasticity [44, 82, 117, 118]. It appears that ω-3 PUFA dietary deficiency impairs glutamatergic synaptic transmission and plasticity [44, 82, 117, 119, 120], whereas DHA-rich diet can prevent loss of synaptic plasticity induced by prenatal ethanol exposure [118] (Figure 3). Apart from these studies, only one study from our laboratory precisely investigated the impact of dietary PUFAs on the endocannabinoid-dependent synaptic plasticity [7]. This study demonstrated that developmental dietary ω-3 PUFA deficiency abolishes the endocannabinoid-dependent synaptic plasticity in the prefrontal cortex and in the nucleus accumbens [7]. This is the first evidence that a change in dietary precursors can have a strong impact on the outcome of the endocannabinoid system. Following this study, we investigated the impact of developmental dietary ω-3 PUFA deficiency on endocannabinoid-dependent synaptic plasticity in the hippocampus. We demonstrated that ω-3 PUFA deficiency strongly impaired the endocannabinoid-dependent heterosynaptic plasticity at GABAergic synapses, which prevents the induction of plasticity at glutamatergic synapses (Thomazeau, Bosch-Bouju, Manzoni and Layé, article accepted at Cerebral Cortex). Conversely, another ongoing study from our team shows that ω-3 PUFA-rich diet maintains endocannabinoid-dependent Hebbian plasticity in the nucleus accumbens following a chronic social defeat stress. Mechanistically, it is still unclear how dietary PUFAs impact on endocannabinoid plasticity. As evoked above, dietary PUFAs can change levels of endocannabinoids. This could impact on the endocannabinoid system and notably on the CB1 receptor that easily desensitizes. Along with this hypothesis, we demonstrated in our recent study that the loss of plasticity following ω-3 PUFA deficiency was due to a loss of functionality of the CB1 receptor, by its uncoupling from the Gi protein [7, 8] (Figure 3).
\nOther hypotheses need to be explored to better understand the impact of dietary PUFAs on endocannabinoid plasticity. Notably, it is suggested that endocannabinoid signaling is sensitive to the lipid environment, namely, the levels of lipid rafts in the membrane [121–123]. Lipid rafts are high density domains rich in sphingolipids and cholesterol [124]. It has been proposed that synapses are especially enriched in lipid rafts and that these microdomains are necessary to maintain synapses and allow protein trafficking [125]. At the opposite of lipid rafts are DHA-rich domains; they are thin, ‘leaky’, dynamic and flexible [126]. This is notably due to the high flexibility of DHA. High density lipid rafts and low-density DHA-domains are competing permanently. It is suggested that lipid rafts are initially small nanodomains that organize together to form bigger domains, of the microscale. In this configuration, the organization of lipid rafts would be controlled by DHA, which aggregates nanodomains together or conversely disrupt large lipid rafts [126–128]. We can thus hypothesize that dietary PUFAs modulate the endocannabinoid plasticity in the brain by playing on the fine structure of plasma membranes.
\nStudying the impact of dietary PUFAs on brain endocannabinoids is of interest in the context of brain disorders. It exists dense literature about the role of dietary PUFAs on brain health, and endocannabinoids are implicated in numerous brain diseases. However, the link between dietary PUFAs and endocannabinoids in the context of brain disorders has been only rarely investigated.
\nOn one hand, dietary PUFAs appear to be determinant for the regulation of mood and anxiety disorders. In humans, the risk of developing depression is associated with low content of ω-3 in the diet [129], and patients with mood and/or anxiety disorders have lower levels of ω-3 in the blood and in the brain, compared to healthy subjects [3, 130–132] (Figure 4). Supplementation of food supply with ω-3 PUFAs constitutes thus an interesting strategy for the prevention and treatment of mood and anxiety disorders, in particular because of the low side effects expected compared to pharmacological agents. Several trials have been conducted in this context, however, meta-analyses reported mitigated outcomes so far [129, 133]. Some trials showed no convincing effect while others demonstrated that ω-3 supplementation for 8-12 weeks have significant positive effects, notably because it improves the efficiency of antidepressants and thus increases the proportion of remission [134]. The lack of clear effect of ω-3 supplementation to treat mood and anxiety disorders in humans can be explained by the complexity of neuropsychiatric disorders and the heterogeneity of methods in the different studies. As an example, a recent study highlighted the positive effect of EPA treatment in patients suffering from major depression homogenized on the basis of their inflammatory status [43]. The clinical studies are corroborated by preclinical studies. Dietary ω-3 deficiency in rodents induces strong anxiety- and depressive-like behaviors [7–9, 135–137]. Conversely, ω-3 supplementation given beforehand a protocol of acute or chronic stress plays a protective role against anxiety- and depressive-like behaviors [136, 138, 139].
\nOn the other hand, the role of endocannabinoids system in the regulation of mood and anxiety disorders has recently raised much interest in preclinical studies. The first evidence came from behavioral studies showing that mice lacking the gene for CB1 receptor display strong depressive and anxiety-like behaviors, which can be reproduced in control mice with CB1 receptor antagonists [140, 141]. Inversely, depressive- and anxiety-like behaviors induced by acute or chronic stress are associated with alteration of AEA and 2-AG levels [142, 143], CB1 receptor desensitization [144, 145] and impairment of endocannabinoid-dependent synaptic plasticity [144, 146, 147]. Recently, we conducted a study in this context demonstrating that a chronic social defeat stress in mice totally abolished spike-timing endocannabinoid-dependent synaptic plasticity. In humans, it is established that patients suffering from mood and anxiety disorders have lower levels of endocannabinoids in blood [148]. Even if cannabis has been used for decades as a self-medication to dampen stress and anxiety, only few clinical studies so far have tried enhancement of endocannabinoid signaling as a potential therapeutics to treat mood and anxiety disorders [149, 150]. This may be due to the potential side effects of directly targeting the endocannabinoid system, and in this context dietary PUFAs, as homeostatic regulators of endocannabinoids [95], could constitute a very interesting and promising therapeutic candidate to target the endocannabinoid system.
\nFrom these studies, it thus appears that both dietary PUFAs and endocannabinoids play a role in mood and anxiety disorders and the link between both has been made only in our laboratory in preclinical studies. We demonstrated that an ω-3 deficient diet from the first gestational stage greatly impairs endocannabinoid signaling, which is associated to anxiety and depressive-like behaviors in mice [7, 136]. Currently, our ongoing studies tend to demonstrate that DHA-rich diet protects mice from deleterious effects of a chronic social defeat stress on anxiety- and depressive-like behaviors and on endocannabinoid-dependent synaptic plasticity. At long-term, we believe these studies will constitute a solid argument to investigate the effect of ω-3 supplementation to normalize endocannabinoid levels in patients suffering from anxiety or depressive disorders.
\nIn the investigation of the interactions between endocannabinoids and dietary PUFAs in mood and anxiety disorders, we also need to consider the HPA (hypothalamus-pituitary-adrenal) axis. Indeed, dietary PUFAs are powerful modulators of the HPA axis, and function of endocannabinoids is also tightly related to the HPA axis. Our studies demonstrated that variations in dietary ω-3 PUFAs impact on the HPA axis [136, 151]: mice fed with an ω-3 PUFA deficient diet exhibit higher levels of corticosterone while mice fed with a DHA rich diet display control levels of corticosterone, and these levels are not affected by social defeat stress. In parallel, interactions between endocannabinoids and the HPA axis are reciprocal. Studies have shown that glucocorticoids can activate the release of endocannabinoids, AEA and 2-AG [152]. Conversely, endocannabinoids act efficiently to regulate stress response, partly by modulating the glucocorticoid system [150, 153]. For future studies, it is thus crucial to consider the HPA axis as a potential intermediate between dietary PUFAs and endocannabinoids in the context of depressive and anxiety disorders.
\nIn Parkinson’s disease, endocannabinoids seem to play a protective role by decreasing the oxidative stress [154]. Similarly, ω-3 rich diet improves survival of dopaminergic neurons in rodent models of the disease with MPTP (1-méthyl-4-phényl-1,2,3,6-tétrahydropyridine) injections or α-synuclein transgenic mice [155–159] (Figure 4). In patients, levels of AEA in the cerebrospinal fluid are increased, and the risk for Parkinson’s disease is increased by ω-6 rich diet, and decreased by ω-3 rich diet [42, 160]. However, clinical trials with either dietary PUFAs or with drugs targeting the endocannabinoid system have shown inconsistent results [154]. In this pathology too, it would be interesting to investigate if endocannabinoids derived from ω-3 are of potential interest to protect neurons from degeneration and improve quality of life of patients (Figure 4).
\nIn Alzheimer’s disease, implication of both endocannabinoids and dietary PUFAs are not central in the study of the physiopathology, still, there are interesting ways to investigate. In animal models, ω-3 PUFA supplementation clearly improves cognition and associated neurobiological markers [21, 45, 46, 161, 162] (Figure 4). However, clinical trials did not provide convincing results and further investigation are thus needed [3, 21, 163]. Endocannabinoids are also trialed as potential therapeutics to treat Alzheimer’s disease, because they can act on multiple aspects of the disease, but no strong result has emerged from these trials yet.
\nFrom our perspective it is interesting to note that both PUFAs and endocannabinoids could interfere with the development of the disease by dampening neuroinflammation and oxidative stress. We thus believe these are the two neurobiological aspects of the disease that have to be studied to determine if dietary PUFAs can act
The role of endocannabinoids in neuropathic and physical pain has been clearly established [164, 165]. Indeed, endocannabinoids have the ability to lower the excitability of nociceptors and thus reduce the intensity of the nociceptive information [165]. A recent study interestingly demonstrated that ω-3 rich diet was able to reduce physical pain and that this relief was significantly correlated to an increase in DHEA and 2-DHG, the two DHA-derived endocannabinoids [84] (Figure 4). This reinforces the hypothesis that ω-3 dietary PUFAs favor ‘good’ endocannabinoids, derived from ω-3 PUFAs (Figure 4). As proposed by Piomelli et al., [165], the links between endocannabinoids and dietary PUFAs in the context of pain are probably related to inflammatory processes and this is another way to explore.
\nIn 1996, a study demonstrated that lithium, a mood stabilizer used for bipolar disorders, decreases recycling of ARA, COX2 activity and levels of prostaglandins [166]. Similar effects have been reported with other mood stabilizers and antipsychotic molecules. Metabolism of ARA could thus serve as a marker for the development of new molecules for the treatment of mood and anxiety disorders.
\nAs we mentioned above, supplementation with ω-3 PUFAs in the treatment of mood and anxiety disorders have provided mitigated results, but this could be due to the low turnover of PUFAs in the brain [20]. A possibility to bypass this issue would be to accelerate the bioavailability of PUFAs to the brain, by direct injection of free or esterified PUFAs into the brain. A preclinical study in rat demonstrated that an injection of DHA can reduce seizure score within one hour or one day, where three months are needed to reach the same result through the diet [167–169]. These promising results could be applied in the future to humans to reduce damages following stroke or reduce seizure events, but further investigations are needed before such clinical trials.
\nAnother field that needs to be explored to our opinion is the role of dietary PUFAs on endocannabinoids during brain development. As mentioned in this chapter, PUFA accretion in the brain occurs largely during brain development and our laboratory published many articles on the effects of imbalanced dietary PUFA during development on the adult brain [3, 7, 26]. In parallel, increasing evidence highlights that endocannabinoid signaling is essential for brain wiring [170, 171]. Notably, endocannabinoids and CB1 receptors serve as guidance signals for axon cone growth [171]. The link between dietary PUFA and endocannabinoids is not yet clearly established, but it is very likely that effects of imbalanced PUFAs during development has strong consequences on the role of endocannabinoid as guidance molecules during brain wiring. This can have strong implication for brain disorders with developmental origin, such as schizophrenia.
\nIn conclusion, dietary ω-6/ω-3 PUFAs appears as potent modulators and homeostatic regulators of endocannabinoids in the brain. The consequences of this modulation need to be investigated to understand its putative role in brain health and diseases (in particular those with endocannabinoid impairment) and develop future therapeutics to target the endocannabinoid system through dietary ω-6/ω-3 PUFAs. The most promising hypothesis that needs to be explored to our opinion is that dietary PUFAs could switch the system from ‘bad’ (ω-6-derived) endocannabinoids to ‘good’ (ω-3-derived) endocannabinoids.
\nThis research was financially supported by INRA, Agence Nationale de la Recherche (ANR-MoodFood) and the Region Aquitaine. CBB had fellowships from the Agence Nationale de la Recherche and the European Agreenskills program (COFUND FP7-267196).
\nUnlike in developed countries, the delivery of cardiovascular services to children born with congenital heart defects in Nigeria is inadequate. There are problems at both pediatric and adult ages with high morbidity and mortality on account of inadequate surgical care. The country initially lacked both manpower and infrastructure so that many souls of congenital pediatric patients departed their bodies with their pathologies undiagnosed and untreated. Pioneers of cardiac surgery in Nigeria were not decisive of separate pediatric cardiac program while they engaged the government. Presently, with many trained personnel, there is a need for structured pediatric cardiac team with requisite infrastructure to work. This will bring the desired success.
In Nigeria, a foreign cardiac team with a local team performed the first open heart surgery in our institution, University of Nigeria Teaching Hospital (UNTH), Enugu, in 1974. UNTH is the teaching hospital for the Federal Government of Nigeria and is affiliated to University of Nigeria, Nsukka. Foreign cardiac team was led by a British-Egyptian Surgeon, Sir (Dr) Magdi Yacoub, and indigenous team was led by late Professor Fabian Udekwu. This singular act added to many others attracted the attention of the Federal Military Government of Nigeria, which designated it the National Cardiothoracic Center of Excellence (NCTCE) in 1984.
Adult cardiac surgery was the main focus of the program. The hospital stood by her deeds and was able to establish itself, as the leader in open heart surgery not only in Nigeria but also in West African subregion [1]. Afterward, the center’s activities decreased due to poor military governance and corruption. The near total neglect of healthcare system (HCS) in the country led to the collapse of the center due to brain drain and inadequate facilities such that between 1974 and 2000, only a total of 102 open heart operations were carried out, mainly by local team [1].
With return to civilian rule in Nigeria in 1999, efforts were made to improve the center through Foreign Cardiac Mission Model. The first mission was by International Children Heart Foundation (ICHF) in 2003 under the sponsorship of Kanu Heart Foundation. Incidentally, that mission was the first pediatric mission, and William Novick (International Cardiac Foundation) was the lead surgeon. The team visited once and performed mainly pediatric cases for the first time at the center. Other international cardiac missions started visiting 10 years later and became regular with more frequent visits every year [2]. Options considered toward sustenance of pediatric cardiac surgery were staff training and equipment procurement. One way to achieve the desired training in emerging country like ours is by regular and frequent visits to centers such as NCTCE by foreign cardiac teams and performing the surgery alongside the local team (cardiac mission model) [3, 4, 5]. Other options include sending the local team to established centers, for example, India for hands-on training for a period not less than 2 years. Furthermore, members of the local team individually went for training abroad on their personal arrangement at different times and in different established centers.
The cardiac mission model would not even have been possible without the aids from some agencies of the Federal Government of Nigeria, Nigerians in Diaspora, public spirited individuals, and foreign organizations as shown in Table 1. Most of the countries in West African subregion are very poor, and a study by Edwin F et al. showed that no existing cardiac center in the subregion came into being without huge governmental support [6].
S/N | Name of organization | Local or foreign | Aid provided |
---|---|---|---|
1 | Federal Ministry of Health (FMOH) | Local | Payment of salaries and allowances of local team members. Provided infrastructure |
2 | UNTH | Local | When UNTH moved to new site, a ward was restructured for cardiac surgery and ICU. Sponsorship for both foreign and local training of local team. Also, provided air tickets, local transportation, feeding and security for foreign cardiac teams as well as sourcing for disposables. |
3 | TET fund (University of Nigeria) | Local | Equipment (Cath Lab, six ventilators, two theater tables, two theater lights, eight ICU beds, six monitors, etc.) |
4 | Kanu Heart foundation (KHF) | Local | Sponsorship of International Children Heart Foundation (ICHF) visit in 2003. Brought equipment and disposables |
5 | Enugu State Government | Local | Logistics for foreign team and fees for some patients |
6 | Innova Hospital, Hyderabad, India in 2009 | Foreign | UNTH sent two cardiac anesthetists, two cardiothoracic surgeons, two medical laboratory scientists for perfusion, two pediatric cardiologists, three nurses, two physiotherapists, and a technician for training as staff build up to her restart of open-heart surgery in 2013. It was tuition-free |
7 | VOOM Foundation from 2013 | Diaspora (USA) | Foreign team, equipment, and disposables severally |
8 | Save-a-Heart Nigeria started with VOOM but separated later. | Diaspora (UK) | Foreign team, equipment, and disposables severally |
9 | Rotary Club of Nigeria | Local | Payment of surgical fees for some patients |
10 | Opubic of Italy | Foreign | Free pediatric cardiac surgery with disposables severally |
11 | Novic Cardiac Alliance of USA with VOOM Foundation | Foreign | Foreign team, equipment, and disposables |
12 | Cardiostat of USA with VOOM Foundation | Foreign | Foreign team, equipment, and disposables |
13 | Public spirited individuals, businesses | Local | Payment of surgical fees and blood donation |
14 | Bigard Seminary, Enugu (Seminarians were donors) | Local | Free blood donation severally |
15 | Santarina of India | Foreign | |
16 | UNEC medical students | Free blood donations |
Some collaborations took place both locally or outside your country in helping capacity building but help will also be needed in some aspect.
Good things that go for foreign mission team include high technical skill and team work in contrast to what is obtainable on the ground. Treating patients locally in this method is cheaper and serves as workshop and training session for different categories of workers at minimal cost to the institution. However, model of cardiac missions is not a sustainable one because a lot of effort and expenditure are allocated toward surgery on a few patients [7].
The adoption of cardiac mission model by developing countries such as Nigeria as a way of helping indigent patients with both congenital and acquired heart diseases is good. However, that method is like giving someone a fish anytime he demands it. The best way is to incorporate teaching the person how to fish, that is, developing and equipping local team. It is only in this way will establishing pediatric cardiac center across the low- and middle-income countries become sustainable.
Pediatric cardiology and pediatric cardiac surgery practices in Nigeria are taxing [8, 9]. Getting all the requirements to cater for the surgical needs of a very large number of children with congenital heart defects with its attendant financial constraints, poor funding from the government is really a huge task.
Pediatric cardiology and pediatric cardiac surgery training in Nigeria involve the management of different cardiac diseases in children. This covers children with both congenital and acquired heart disease [10]. This also includes arrhythmias and coronary heart diseases. Besides, interventional cardiology practice is really at the primordial phase with less than three teaching hospitals providing the skills and competences all over the country [10].
Even the foreign missions that come occasionally could not provide the necessary skills of all the surgical intervention as they spend few days and may not inculcate such skills to the local surgeons within few days of stay.
Pediatric cardiac surgery program requires enormous resources and commitment to establish. Training of cardiac anesthetist like every other personnel in the team requires enormous funds. This is because the training is done abroad. [11].
Training and retraining are also necessary in order to prevent attrition. Attrition therefore constitutes a big problem as the volume of cardiac surgery carried out in Nigeria is very small compared with the burden of pediatric cardiac disease in the country. Training or upgrading the education of the pediatric cardiac team, massive training of core personnel for pediatric cardiac surgery and pediatric cardiologist will enable the work to be self-sustaining as their services will be patronized by both locals and foreigners. Funds will be generated as is done in other heart centers in India, America, etc.
There are three main methods of acquiring training. It could be by an institution sending a team to undergo training in another institution. The second option involves inviting experts to come and train the local personnel on the job while the third option is for individuals to scout for training positions anywhere by themselves.
Another good alternative is to engage a cardiac team from a good cardiac center to work with the locals on continuous basis until skill transfer is achieved. This will be cost-effective, and more patients will receive care while skill acquisition will take place smoothly. [11].
Monitoring in cardiac anesthesia is pivotal to the success of cardiac surgery [12]. Monitoring equipment is expensive, and for a country such as Nigeria, acquisition of these equipment is difficult to come by. This equipment ranges from anesthesia work station, ultrasound, transesophageal echocardiography, multiparameter monitor, cardiac output monitor, I-Stat machine for point of care test in the operation theater, and intensive care unit. Other equipment include syringe pump, infusion pumps, blood warmer, etc.
Procurements through competitive bidding: The prices are usually overinflated owing to the fact that contractors are owed for a period between 1 and 2 years. This adds to the high cost of pediatric cardiac surgery in Nigeria. Some cardiac missions such as Cardiostart International, William Novick cardiac Alliance, VOOMF, Save-a-heart Nigeria, ICHF/Kanu Heart foundation brought consumables during visits. These are, however, not usually enough.
NCTCE has some challenges emanating from poor funding, incomplete treatment of patients, and late presentation by patients as well as poor equipment maintenance. It is thought that successful creation of Nigeria Cardiac Foundation where every Nigerian contributes 0.20–0.25% monthly salary will impact significantly in funding cardiac surgery. Another alternative is to incorporate pediatric cardiac surgery into National Health Insurance (NHIS). This will also address the challenges of late presentation. As can be seen, the Cardiac Surgery Intersociety Alliance (CSIA) or any other body can assist our center in providing appropriate training for pediatric cardiac surgeons, anesthetists, perfusionists, nurses, etc., among other helps that are needed. Donation of consumables and equipment will be of immense benefit to the program. CSIA model is what NCTCE needs at this time in addition to what others may offer.
These initial efforts were not sustained owing to the following factors: poor funding and total neglect of health sector, brain drain syndrome, reliance on medical tourism, and competing double burden of diseases as well as corruption, nepotism. Other issues were poor social infrastructures such as public power and water supply, poor remuneration of health workers with incessant strike actions, and insecurity in the land and inter-professional conflicts [1].
Low government health spending over the last two decades has limited the expansion of highly cost-effective interventions, stunted health outcomes and exposing large shares of the population to catastrophic health expenditures. Nigeria spends less on health than nearly every country in the world. In 2016, government health spending was 0.6% as a share of GDP or just $US11 per capita. As a result, Nigeria significantly underperforms on key health outcomes. Maternal mortality at 576 deaths per 100,000 live births is one of the highest in the world (2.6 times the global average); one in eight children dies before reaching their fifth birthday; and 25% of households spend more than 10% of their household consumption on health [13].
The migration of health professionals from Nigeria to high-income countries—medical brain drain, deserves critical attention due to its adverse effects on the healthcare system (HCS) for developing nations, which indirectly impacts population health outcomes and creates greater inequity among vulnerable populations. This international migration of medical doctors (MDs) has created a great challenge for public health systems; it worsens already weak healthcare systems, which widens the health inequalities gap worldwide. Globally, Nigeria ranks among the worst countries in regard to maternal health outcomes. Although it represents 2% of the global population, it disproportionately contributes to nearly 10% of global maternal deaths [14]. With the current new world order, where the world is a global village, it is very easy and fashionable for members of the team to migrate and work in other parts of the world. With the skill, training, exposure, vigor, endurance, and other qualities, the tested professional can easily leave the service and country and comfortably settle and earn hard currency. The attraction to brain drain is always there for members of this team, and this has adversely affected the growth of pediatric cardiac surgery and other programs in UNTH, in particular, and Nigeria in general. Unless something urgent is done, this trend will continue, and Nigeria will be the loser.
Political instability in the country and frequent widespread violence combine to limit the number of foreign agencies that participate in the surgical management of heart disease in Nigeria. Some of these charities have personnel and equipment. Some foreign physicians want experience in treating types of heart disease that are no longer common in their countries. However, even charitable organizations cannot take their safety for granted. Furthermore, political decisions that affect the treatment of heart disease vary with each political leader, and these leaders change very often. Their successors do not maintain continuity. Some emphasize primary health care to the detriment of the treatment of heart disease.
It is important to note that lack of facilities for sustainable pediatric cardiac services and pediatric cardiology practice in Nigeria results in preventable deaths and suffering. Regrettably, about 15 million children are noted to have died and had some morbidities from potentially treatable cardiac diseases [15].
The practice of pediatric cardiac surgery had been ignored for long, as this has now evoked major concern to governmental and nongovernmental organizations and cardiovascular specialists [1]. In some areas in West African province, it is noted that only 20% of the parents of children who are less than 15 years and who needed pediatric surgical intervention are able to finance the operation within 12 months of diagnosis [1, 16].
Early diagnosis and treatment are very necessary to enhance the survival of children with cardiac disease [1]. This can be achieved by the provision of affordable human resources, diagnostic and surgical as well as other interventional facilities at each level of care in the country.
The practice of pediatric cardiology and pediatric cardiac services in Nigeria is faced with several challenges. The cost of pediatric cardiac services is very exorbitant and unaffordable for most developing nations. Nigeria gives priority to other disease burdens other than cardiac disease during budget allocations. The current COVID-19 pandemic, HIV/AIDS pandemic, poor health infrastructure and referral systems, malaria, pneumonias, and malnutrition have made the situation worse and dampen the importance of pediatric cardiac service.
The population of children with uncorrected congenital heart disease in Nigeria in particular and Africa in general is considerable. This is due to the fact that most pediatric services are centered on diagnosis and management of infectious diseases, shortage of trained personnel who diagnose congenital heart defects, resulting in late diagnosis and referral. Besides, the number of facilities for pediatric cardiac surgery is meager with attendant paucity of pediatric cardiac surgeons [16].
In Africa, pediatric cardiac surgery is usually performed in adults than in younger children, due to lack of manpower [17, 18]. The country no longer completely lacks facility and skills in carrying out stage procedures for cyanotic congenital cardiac disease or palliative surgery such as pulmonary artery banding or systemic-pulmonary shunt as earlier reported [19].
The challenges encountered in the establishment of pediatric surgery for cardiovascular diseases in African could be resolved through capacity building and inculcating expertise in the diagnosis and management of congenital heart diseases; training and retraining of local pediatric cardiologist and pediatric cardiac surgeon in the management of cardiac disease tailored to our sociocultural background; getting state-of-the-art equipment and facilities that will enhance the management of cardiovascular diseases in children; public enlightenment and campaign on preventive measures on emerging and reemerging cardiac disease, creating endowment funds and financial support where there will be community participation; making policies that establish pediatric cardiac training in Nigeria that will be sustainable and achievable; reinforcement of skills in terms of professional competences, exchange program, knowledge, innovative surgical techniques, new technologies, equipment, and human resources; granting financial aid to take care of the poorest of the poor by public, governmental, or private initiatives; establishment of number of centers of excellence dedicated to training, retraining, research, and clinical care in pediatric heart surgery in sub-Saharan Africa; developing international cooperation through foundations and nongovernmental organizations, and through banking firms and grants; and seeking the support of pharmaceutical industries and medical equipment [20, 21, 22].
In short, we want to outline and describe what it took to overcome some of the obstacles we faced in developing or expanding pediatric cardiac care.
After the ICHF/KHF mission in our center in 2003, pediatric cardiology and surgery activities in our center dwindled owing to dilapidated equipment, poor workers’ remuneration, and brain drain as well as poor leadership, coupled with government directive to move UNTH to the permanent site without any building for pediatric cardiac surgery activities. In 2007, UNTH moved to the permanent site and then came a change in the leadership of NCTCE. Through continuous appropriate dialog and advocacy, NCTCE benefitted from TETFUND program. With advice from Prof. Tom Pezzella of ICHF, USA, a training center was found in India (ICHH, Hyderabad India), with institutional collaboration. With this development, pediatric cardiac anesthetists and intensivists, technicians, ICU and perioperative nurses including pediatric cardiologists got training within periods ranging from 6 months to 2 years.
There was the arrangement for pediatric cardiac surgeons to do 1 year training at the Indian center with the Indian team coming to our center to see a smooth takeoff of sustainable pediatric cardiac surgery program. However, that arrangement did not materialize because cardiac mission model was adopted. This cardiac mission model started in February 2013 and ended in October 2019. During the period, William Global Cardiac Alliance, Vincent Ohaju Memorial Foundation, Save-A-Heart-Nigeria, Cardiostart International, O’Pobic, Santarina all visited our center and performed operations in 113 in pediatric patients over 7 year period [23, 24].
Currently, our cardiologists can adequately handle all echocardiographic investigations. In addition, our adult cardiologists are able to handle all forms of cardiac pacemaker insertions, coronary angiography, and some coronary artery stenting and angioplasties. Our cardiothoracic surgeons with anesthesiologists and other theater staff can handle all non-open heart surgical procedures and some open-heart surgical procedures such as repair of atrial septal defects (ASD), repair of some ventricular septal defects (VSD), excision of some types of intracardiac tumors, and replacement of the mitral valve. We are still not able to do intracardiac repair for the blue babies in addition to some other types of congenital cardiac anomalies as well as some types of valve repair/replacement and coronary artery bypass procedures.
The COVID-19 pandemic has slowed the engagement of a resident foreign pediatric cardiac surgeon (GhanianModerl–ref) at NCTCE by the present UNTH/NCTCE management to equip the local surgeon with adequate skills that will make the program very sustainable.
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She obtained a BSc from the University of Derby, England, a master’s degree from Technische Universität München, Germany, and a Ph.D. from the University of Nottingham. She undertook a post-doctoral research fellowship in the School of Medicine before accepting tenure in Veterinary Medicine and Science. Dr. Rutland also obtained an MMedSci (Medical Education) and a Postgraduate Certificate in Higher Education (PGCHE). She is the author of more than sixty peer-reviewed journal articles, twelve books/book chapters, and more than 100 research abstracts in cardiovascular biology and oncology. She is a board member of the European Association of Veterinary Anatomists, Fellow of the Anatomical Society, and Senior Fellow of the Higher Education Academy. 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He studied \r\nchemistry at the Universidad Nacional de La Plata, Argentina, where received aPh.D. degree in chemistry (Biological Branch) in 1965. From\r\n1964 to 1974, he worked as Assistant in Biochemistry at the School of MedicineUniversidad Nacional de La Plata, Argentina. From 1974 to 1976, he was a Fellowof the National Institutes of Health (NIH) at the University of Connecticut, Health Center, USA. From 1985 to 2004, he served as a Full Professor oBiochemistry at the Universidad Nacional de La Plata, Argentina. He is Member ofthe National Research Council (CONICET), Argentina, and Argentine Society foBiochemistry and Molecular Biology (SAIB). His laboratory has been interested for manyears in the lipid peroxidation of biological membranes from various tissues and different species. Professor Catalá has directed twelve doctoral theses, publishedover 100 papers in peer reviewed journals, several chapters in books andtwelve edited books. 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Angel Catalá belongto the Editorial Board of Journal of lipids, International Review of Biophysical ChemistryFrontiers in Membrane Physiology and Biophysics, World Journal oExperimental Medicine and Biochemistry Research International, W orld Journal oBiological Chemistry, Oxidative Medicine and Cellular Longevity, Diabetes and thePancreas, International Journal of Chronic Diseases & Therapy, International Journal oNutrition, Co-Editor of The Open Biology Journal.",institutionString:null,institution:{name:"National University of La Plata",institutionURL:null,country:{name:"Argentina"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"186048",title:"Prof.",name:"Ines",middleName:null,surname:"Drenjančević",slug:"ines-drenjancevic",fullName:"Ines Drenjančević",profilePictureURL:"https://mts.intechopen.com/storage/users/186048/images/5818_n.jpg",institutionString:null,institution:{name:"University of Osijek",institutionURL:null,country:{name:"Croatia"}}},{id:"187859",title:"Prof.",name:"Kusal",middleName:"K.",surname:"Das",slug:"kusal-das",fullName:"Kusal Das",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSBDeQAO/Profile_Picture_1623411145568",institutionString:"BLDE (Deemed to be University), India",institution:null},{id:"79615",title:"Dr.",name:"Robson",middleName:null,surname:"Faria",slug:"robson-faria",fullName:"Robson Faria",profilePictureURL:"https://mts.intechopen.com/storage/users/79615/images/system/79615.png",institutionString:null,institution:{name:"Oswaldo Cruz Foundation",institutionURL:null,country:{name:"Brazil"}}},{id:"84459",title:"Prof.",name:"Valerie",middleName:null,surname:"Chappe",slug:"valerie-chappe",fullName:"Valerie Chappe",profilePictureURL:"https://mts.intechopen.com/storage/users/84459/images/system/84459.jpg",institutionString:null,institution:{name:"Dalhousie University",institutionURL:null,country:{name:"Canada"}}}]},{id:"12",title:"Human Physiology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/12.jpg",editor:{id:"195829",title:"Prof.",name:"Kunihiro",middleName:null,surname:"Sakuma",slug:"kunihiro-sakuma",fullName:"Kunihiro Sakuma",profilePictureURL:"https://mts.intechopen.com/storage/users/195829/images/system/195829.jpg",biography:"Professor Kunihiro Sakuma, Ph.D., currently works in the Institute for Liberal Arts at the Tokyo Institute of Technology. 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His research interest focuses on computational chemistry and molecular modeling of diverse systems of pharmacological, food, and alternative energy interests by resorting to DFT and Conceptual DFT. He has authored a coauthored more than 255 peer-reviewed papers, 32 book chapters, and 2 edited books. He has delivered speeches at many international and domestic conferences. He serves as a reviewer for more than eighty international journals, books, and research proposals as well as an editor for special issues of renowned scientific journals.",institutionString:"Centro de Investigación en Materiales Avanzados",institution:{name:"Centro de Investigación en Materiales Avanzados",country:{name:"Mexico"}}},{id:"76477",title:"Prof.",name:"Mirza",middleName:null,surname:"Hasanuzzaman",slug:"mirza-hasanuzzaman",fullName:"Mirza Hasanuzzaman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/76477/images/system/76477.png",biography:"Dr. Mirza Hasanuzzaman is a Professor of Agronomy at Sher-e-Bangla Agricultural University, Bangladesh. He received his Ph.D. in Plant Stress Physiology and Antioxidant Metabolism from Ehime University, Japan, with a scholarship from the Japanese Government (MEXT). Later, he completed his postdoctoral research at the Center of Molecular Biosciences, University of the Ryukyus, Japan, as a recipient of the Japan Society for the Promotion of Science (JSPS) postdoctoral fellowship. He was also the recipient of the Australian Government Endeavour Research Fellowship for postdoctoral research as an adjunct senior researcher at the University of Tasmania, Australia. Dr. Hasanuzzaman’s current work is focused on the physiological and molecular mechanisms of environmental stress tolerance. Dr. Hasanuzzaman has published more than 150 articles in peer-reviewed journals. He has edited ten books and written more than forty book chapters on important aspects of plant physiology, plant stress tolerance, and crop production. According to Scopus, Dr. Hasanuzzaman’s publications have received more than 10,500 citations with an h-index of 53. He has been named a Highly Cited Researcher by Clarivate. He is an editor and reviewer for more than fifty peer-reviewed international journals and was a recipient of the “Publons Peer Review Award” in 2017, 2018, and 2019. He has been honored by different authorities for his outstanding performance in various fields like research and education, and he has received the World Academy of Science Young Scientist Award (2014) and the University Grants Commission (UGC) Award 2018. He is a fellow of the Bangladesh Academy of Sciences (BAS) and the Royal Society of Biology.",institutionString:"Sher-e-Bangla Agricultural University",institution:{name:"Sher-e-Bangla Agricultural University",country:{name:"Bangladesh"}}},{id:"187859",title:"Prof.",name:"Kusal",middleName:"K.",surname:"Das",slug:"kusal-das",fullName:"Kusal Das",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSBDeQAO/Profile_Picture_1623411145568",biography:"Kusal K. Das is a Distinguished Chair Professor of Physiology, Shri B. M. Patil Medical College and Director, Centre for Advanced Medical Research (CAMR), BLDE (Deemed to be University), Vijayapur, Karnataka, India. Dr. Das did his M.S. and Ph.D. in Human Physiology from the University of Calcutta, Kolkata. His area of research is focused on understanding of molecular mechanisms of heavy metal activated low oxygen sensing pathways in vascular pathophysiology. He has invented a new method of estimation of serum vitamin E. His expertise in critical experimental protocols on vascular functions in experimental animals was well documented by his quality of publications. He was a Visiting Professor of Medicine at University of Leeds, United Kingdom (2014-2016) and Tulane University, New Orleans, USA (2017). For his immense contribution in medical research Ministry of Science and Technology, Government of India conferred him 'G.P. Chatterjee Memorial Research Prize-2019” and he is also the recipient of 'Dr.Raja Ramanna State Scientist Award 2015” by Government of Karnataka. He is a Fellow of the Royal Society of Biology (FRSB), London and Honorary Fellow of Karnataka Science and Technology Academy, Department of Science and Technology, Government of Karnataka.",institutionString:"BLDE (Deemed to be University), India",institution:null},{id:"243660",title:"Dr.",name:"Mallanagouda Shivanagouda",middleName:null,surname:"Biradar",slug:"mallanagouda-shivanagouda-biradar",fullName:"Mallanagouda Shivanagouda Biradar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243660/images/system/243660.jpeg",biography:"M. S. Biradar is Vice Chancellor and Professor of Medicine of\nBLDE (Deemed to be University), Vijayapura, Karnataka, India.\nHe obtained his MD with a gold medal in General Medicine and\nhas devoted himself to medical teaching, research, and administrations. He has also immensely contributed to medical research\non vascular medicine, which is reflected by his numerous publications including books and book chapters. Professor Biradar was\nalso Visiting Professor at Tulane University School of Medicine, New Orleans, USA.",institutionString:"BLDE (Deemed to be University)",institution:{name:"BLDE University",country:{name:"India"}}},{id:"289796",title:"Dr.",name:"Swastika",middleName:null,surname:"Das",slug:"swastika-das",fullName:"Swastika Das",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/289796/images/system/289796.jpeg",biography:"Swastika N. Das is Professor of Chemistry at the V. P. Dr. P. G.\nHalakatti College of Engineering and Technology, BLDE (Deemed\nto be University), Vijayapura, Karnataka, India. She obtained an\nMSc, MPhil, and PhD in Chemistry from Sambalpur University,\nOdisha, India. Her areas of research interest are medicinal chemistry, chemical kinetics, and free radical chemistry. She is a member\nof the investigators who invented a new modified method of estimation of serum vitamin E. She has authored numerous publications including book\nchapters and is a mentor of doctoral curriculum at her university.",institutionString:"BLDEA’s V.P.Dr.P.G.Halakatti College of Engineering & Technology",institution:{name:"BLDE University",country:{name:"India"}}},{id:"248459",title:"Dr.",name:"Akikazu",middleName:null,surname:"Takada",slug:"akikazu-takada",fullName:"Akikazu Takada",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248459/images/system/248459.png",biography:"Akikazu Takada was born in Japan, 1935. After graduation from\nKeio University School of Medicine and finishing his post-graduate studies, he worked at Roswell Park Memorial Institute NY,\nUSA. He then took a professorship at Hamamatsu University\nSchool of Medicine. In thrombosis studies, he found the SK\npotentiator that enhances plasminogen activation by streptokinase. He is very much interested in simultaneous measurements\nof fatty acids, amino acids, and tryptophan degradation products. By using fatty\nacid analyses, he indicated that plasma levels of trans-fatty acids of old men were\nfar higher in the US than Japanese men. . He also showed that eicosapentaenoic acid\n(EPA) and docosahexaenoic acid (DHA) levels are higher, and arachidonic acid\nlevels are lower in Japanese than US people. By using simultaneous LC/MS analyses\nof plasma levels of tryptophan metabolites, he recently found that plasma levels of\nserotonin, kynurenine, or 5-HIAA were higher in patients of mono- and bipolar\ndepression, which are significantly different from observations reported before. In\nview of recent reports that plasma tryptophan metabolites are mainly produced by\nmicrobiota. He is now working on the relationships between microbiota and depression or autism.",institutionString:"Hamamatsu University School of Medicine",institution:{name:"Hamamatsu University School of Medicine",country:{name:"Japan"}}},{id:"137240",title:"Prof.",name:"Mohammed",middleName:null,surname:"Khalid",slug:"mohammed-khalid",fullName:"Mohammed Khalid",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/137240/images/system/137240.png",biography:"Mohammed Khalid received his B.S. degree in chemistry in 2000 and Ph.D. degree in physical chemistry in 2007 from the University of Khartoum, Sudan. He moved to School of Chemistry, Faculty of Science, University of Sydney, Australia in 2009 and joined Dr. Ron Clarke as a postdoctoral fellow where he worked on the interaction of ATP with the phosphoenzyme of the Na+/K+-ATPase and dual mechanisms of allosteric acceleration of the Na+/K+-ATPase by ATP; then he went back to Department of Chemistry, University of Khartoum as an assistant professor, and in 2014 he was promoted as an associate professor. In 2011, he joined the staff of Department of Chemistry at Taif University, Saudi Arabia, where he is currently an assistant professor. His research interests include the following: P-Type ATPase enzyme kinetics and mechanisms, kinetics and mechanisms of redox reactions, autocatalytic reactions, computational enzyme kinetics, allosteric acceleration of P-type ATPases by ATP, exploring of allosteric sites of ATPases, and interaction of ATP with ATPases located in cell membranes.",institutionString:"Taif University",institution:{name:"Taif University",country:{name:"Saudi Arabia"}}},{id:"63810",title:"Prof.",name:"Jorge",middleName:null,surname:"Morales-Montor",slug:"jorge-morales-montor",fullName:"Jorge Morales-Montor",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/63810/images/system/63810.png",biography:"Dr. Jorge Morales-Montor was recognized with the Lola and Igo Flisser PUIS Award for best graduate thesis at the national level in the field of parasitology. He received a fellowship from the Fogarty Foundation to perform postdoctoral research stay at the University of Georgia. He has 153 journal articles to his credit. He has also edited several books and published more than fifty-five book chapters. He is a member of the Mexican Academy of Sciences, Latin American Academy of Sciences, and the National Academy of Medicine. He has received more than thirty-five awards and has supervised numerous bachelor’s, master’s, and Ph.D. students. Dr. Morales-Montor is the past president of the Mexican Society of Parasitology.",institutionString:"National Autonomous University of Mexico",institution:{name:"National Autonomous University of Mexico",country:{name:"Mexico"}}},{id:"217215",title:"Dr.",name:"Palash",middleName:null,surname:"Mandal",slug:"palash-mandal",fullName:"Palash Mandal",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/217215/images/system/217215.jpeg",biography:null,institutionString:"Charusat University",institution:null},{id:"49739",title:"Dr.",name:"Leszek",middleName:null,surname:"Szablewski",slug:"leszek-szablewski",fullName:"Leszek Szablewski",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49739/images/system/49739.jpg",biography:"Leszek Szablewski is a professor of medical sciences. He received his M.S. in the Faculty of Biology from the University of Warsaw and his PhD degree from the Institute of Experimental Biology Polish Academy of Sciences. He habilitated in the Medical University of Warsaw, and he obtained his degree of Professor from the President of Poland. Professor Szablewski is the Head of Chair and Department of General Biology and Parasitology, Medical University of Warsaw. Professor Szablewski has published over 80 peer-reviewed papers in journals such as Journal of Alzheimer’s Disease, Biochim. Biophys. Acta Reviews of Cancer, Biol. Chem., J. Biomed. Sci., and Diabetes/Metabol. Res. Rev, Endocrine. He is the author of two books and four book chapters. He has edited four books, written 15 scripts for students, is the ad hoc reviewer of over 30 peer-reviewed journals, and editorial member of peer-reviewed journals. Prof. Szablewski’s research focuses on cell physiology, genetics, and pathophysiology. He works on the damage caused by lack of glucose homeostasis and changes in the expression and/or function of glucose transporters due to various diseases. He has given lectures, seminars, and exercises for students at the Medical University.",institutionString:"Medical University of Warsaw",institution:{name:"Medical University of Warsaw",country:{name:"Poland"}}},{id:"173123",title:"Dr.",name:"Maitham",middleName:null,surname:"Khajah",slug:"maitham-khajah",fullName:"Maitham Khajah",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/173123/images/system/173123.jpeg",biography:"Dr. Maitham A. Khajah received his degree in Pharmacy from Faculty of Pharmacy, Kuwait University, in 2003 and obtained his PhD degree in December 2009 from the University of Calgary, Canada (Gastrointestinal Science and Immunology). Since January 2010 he has been assistant professor in Kuwait University, Faculty of Pharmacy, Department of Pharmacology and Therapeutics. His research interest are molecular targets for the treatment of inflammatory bowel disease (IBD) and the mechanisms responsible for immune cell chemotaxis. He cosupervised many students for the MSc Molecular Biology Program, College of Graduate Studies, Kuwait University. Ever since joining Kuwait University in 2010, he got various grants as PI and Co-I. He was awarded the Best Young Researcher Award by Kuwait University, Research Sector, for the Year 2013–2014. He was a member in the organizing committee for three conferences organized by Kuwait University, Faculty of Pharmacy, as cochair and a member in the scientific committee (the 3rd, 4th, and 5th Kuwait International Pharmacy Conference).",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"195136",title:"Dr.",name:"Aya",middleName:null,surname:"Adel",slug:"aya-adel",fullName:"Aya Adel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/195136/images/system/195136.jpg",biography:"Dr. Adel works as an Assistant Lecturer in the unit of Phoniatrics, Department of Otolaryngology, Ain Shams University in Cairo, Egypt. Dr. Adel is especially interested in joint attention and its impairment in autism spectrum disorder",institutionString:"Ain Shams University",institution:{name:"Ain Shams University",country:{name:"Egypt"}}},{id:"94911",title:"Dr.",name:"Boulenouar",middleName:null,surname:"Mesraoua",slug:"boulenouar-mesraoua",fullName:"Boulenouar Mesraoua",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94911/images/system/94911.png",biography:"Dr Boulenouar Mesraoua is the Associate Professor of Clinical Neurology at Weill Cornell Medical College-Qatar and a Consultant Neurologist at Hamad Medical Corporation at the Neuroscience Department; He graduated as a Medical Doctor from the University of Oran, Algeria; he then moved to Belgium, the City of Liege, for a Residency in Internal Medicine and Neurology at Liege University; after getting the Belgian Board of Neurology (with high marks), he went to the National Hospital for Nervous Diseases, Queen Square, London, United Kingdom for a fellowship in Clinical Neurophysiology, under Pr Willison ; Dr Mesraoua had also further training in Epilepsy and Continuous EEG Monitoring for two years (from 2001-2003) in the Neurophysiology department of Zurich University, Switzerland, under late Pr Hans Gregor Wieser ,an internationally known epileptologist expert. \n\nDr B. Mesraoua is the Director of the Neurology Fellowship Program at the Neurology Section and an active member of the newly created Comprehensive Epilepsy Program at Hamad General Hospital, Doha, Qatar; he is also Assistant Director of the Residency Program at the Qatar Medical School. \nDr B. Mesraoua's main interests are Epilepsy, Multiple Sclerosis, and Clinical Neurology; He is the Chairman and the Organizer of the well known Qatar Epilepsy Symposium, he is running yearly for the past 14 years and which is considered a landmark in the Gulf region; He has also started last year , together with other epileptologists from Qatar, the region and elsewhere, a yearly International Epilepsy School Course, which was attended by many neurologists from the Area.\n\nInternationally, Dr Mesraoua is an active and elected member of the Commission on Eastern Mediterranean Region (EMR ) , a regional branch of the International League Against Epilepsy (ILAE), where he represents the Middle East and North Africa(MENA ) and where he holds the position of chief of the Epilepsy Epidemiology Section; Dr Mesraoua is a member of the American Academy of Neurology, the Europeen Academy of Neurology and the American Epilepsy Society.\n\nDr Mesraoua's main objectives are to encourage frequent gathering of the epileptologists/neurologists from the MENA region and the rest of the world, promote Epilepsy Teaching in the MENA Region, and encourage multicenter studies involving neurologists and epileptologists in the MENA region, particularly epilepsy epidemiological studies. \n\nDr. Mesraoua is the recipient of two research Grants, as the Lead Principal Investigator (750.000 USD and 250.000 USD) from the Qatar National Research Fund (QNRF) and the Hamad Hospital Internal Research Grant (IRGC), on the following topics : “Continuous EEG Monitoring in the ICU “ and on “Alpha-lactoalbumin , proof of concept in the treatment of epilepsy” .Dr Mesraoua is a reviewer for the journal \"seizures\" (Europeen Epilepsy Journal ) as well as dove journals ; Dr Mesraoua is the author and co-author of many peer reviewed publications and four book chapters in the field of Epilepsy and Clinical Neurology",institutionString:"Weill Cornell Medical College in Qatar",institution:{name:"Weill Cornell Medical College in Qatar",country:{name:"Qatar"}}},{id:"282429",title:"Prof.",name:"Covanis",middleName:null,surname:"Athanasios",slug:"covanis-athanasios",fullName:"Covanis Athanasios",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/282429/images/system/282429.jpg",biography:null,institutionString:"Neurology-Neurophysiology Department of the Children Hospital Agia Sophia",institution:null},{id:"190980",title:"Prof.",name:"Marwa",middleName:null,surname:"Mahmoud Saleh",slug:"marwa-mahmoud-saleh",fullName:"Marwa Mahmoud Saleh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/190980/images/system/190980.jpg",biography:"Professor Marwa Mahmoud Saleh is a doctor of medicine and currently works in the unit of Phoniatrics, Department of Otolaryngology, Ain Shams University in Cairo, Egypt. She got her doctoral degree in 1991 and her doctoral thesis was accomplished in the University of Iowa, United States. Her publications covered a multitude of topics as videokymography, cochlear implants, stuttering, and dysphagia. She has lectured Egyptian phonology for many years. Her recent research interest is joint attention in autism.",institutionString:"Ain Shams University",institution:{name:"Ain Shams University",country:{name:"Egypt"}}},{id:"259190",title:"Dr.",name:"Syed Ali Raza",middleName:null,surname:"Naqvi",slug:"syed-ali-raza-naqvi",fullName:"Syed Ali Raza Naqvi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259190/images/system/259190.png",biography:"Dr. Naqvi is a radioanalytical chemist and is working as an associate professor of analytical chemistry in the Department of Chemistry, Government College University, Faisalabad, Pakistan. Advance separation techniques, nuclear analytical techniques and radiopharmaceutical analysis are the main courses that he is teaching to graduate and post-graduate students. In the research area, he is focusing on the development of organic- and biomolecule-based radiopharmaceuticals for diagnosis and therapy of infectious and cancerous diseases. Under the supervision of Dr. Naqvi, three students have completed their Ph.D. degrees and 41 students have completed their MS degrees. He has completed three research projects and is currently working on 2 projects entitled “Radiolabeling of fluoroquinolone derivatives for the diagnosis of deep-seated bacterial infections” and “Radiolabeled minigastrin peptides for diagnosis and therapy of NETs”. He has published about 100 research articles in international reputed journals and 7 book chapters. Pakistan Institute of Nuclear Science & Technology (PINSTECH) Islamabad, Punjab Institute of Nuclear Medicine (PINM), Faisalabad and Institute of Nuclear Medicine and Radiology (INOR) Abbottabad are the main collaborating institutes.",institutionString:"Government College University",institution:{name:"Government College University, Faisalabad",country:{name:"Pakistan"}}},{id:"58390",title:"Dr.",name:"Gyula",middleName:null,surname:"Mozsik",slug:"gyula-mozsik",fullName:"Gyula Mozsik",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/58390/images/system/58390.png",biography:"Gyula Mózsik MD, Ph.D., ScD (med), is an emeritus professor of Medicine at the First Department of Medicine, Univesity of Pécs, Hungary. He was head of this department from 1993 to 2003. His specializations are medicine, gastroenterology, clinical pharmacology, clinical nutrition, and dietetics. His research fields are biochemical pharmacological examinations in the human gastrointestinal (GI) mucosa, mechanisms of retinoids, drugs, capsaicin-sensitive afferent nerves, and innovative pharmacological, pharmaceutical, and nutritional (dietary) research in humans. He has published about 360 peer-reviewed papers, 197 book chapters, 692 abstracts, 19 monographs, and has edited 37 books. He has given about 1120 regular and review lectures. He has organized thirty-eight national and international congresses and symposia. He is the founder of the International Conference on Ulcer Research (ICUR); International Union of Pharmacology, Gastrointestinal Section (IUPHAR-GI); Brain-Gut Society symposiums, and gastrointestinal cytoprotective symposiums. He received the Andre Robert Award from IUPHAR-GI in 2014. Fifteen of his students have been appointed as full professors in Egypt, Cuba, and Hungary.",institutionString:"University of Pécs",institution:{name:"University of Pecs",country:{name:"Hungary"}}},{id:"277367",title:"M.Sc.",name:"Daniel",middleName:"Martin",surname:"Márquez López",slug:"daniel-marquez-lopez",fullName:"Daniel Márquez López",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/277367/images/7909_n.jpg",biography:"Msc Daniel Martin Márquez López has a bachelor degree in Industrial Chemical Engineering, a Master of science degree in the same área and he is a PhD candidate for the Instituto Politécnico Nacional. His Works are realted to the Green chemistry field, biolubricants, biodiesel, transesterification reactions for biodiesel production and the manipulation of oils for therapeutic purposes.",institutionString:null,institution:{name:"Instituto Politécnico Nacional",country:{name:"Mexico"}}},{id:"196544",title:"Prof.",name:"Angel",middleName:null,surname:"Catala",slug:"angel-catala",fullName:"Angel Catala",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/196544/images/system/196544.jpg",biography:"Angel Catalá studied chemistry at Universidad Nacional de La Plata, Argentina, where he received a Ph.D. in Chemistry (Biological Branch) in 1965. From 1964 to 1974, he worked as an Assistant in Biochemistry at the School of Medicine at the same university. From 1974 to 1976, he was a fellow of the National Institutes of Health (NIH) at the University of Connecticut, Health Center, USA. From 1985 to 2004, he served as a Full Professor of Biochemistry at the Universidad Nacional de La Plata. He is a member of the National Research Council (CONICET), Argentina, and the Argentine Society for Biochemistry and Molecular Biology (SAIB). His laboratory has been interested for many years in the lipid peroxidation of biological membranes from various tissues and different species. Dr. Catalá has directed twelve doctoral theses, published more than 100 papers in peer-reviewed journals, several chapters in books, and edited twelve books. He received awards at the 40th International Conference Biochemistry of Lipids 1999 in Dijon, France. He is the winner of the Bimbo Pan-American Nutrition, Food Science and Technology Award 2006 and 2012, South America, Human Nutrition, Professional Category. In 2006, he won the Bernardo Houssay award in pharmacology, in recognition of his meritorious works of research. Dr. Catalá belongs to the editorial board of several journals including Journal of Lipids; International Review of Biophysical Chemistry; Frontiers in Membrane Physiology and Biophysics; World Journal of Experimental Medicine and Biochemistry Research International; World Journal of Biological Chemistry, Diabetes, and the Pancreas; International Journal of Chronic Diseases & Therapy; and International Journal of Nutrition. He is the co-editor of The Open Biology Journal and associate editor for Oxidative Medicine and Cellular Longevity.",institutionString:"Universidad Nacional de La Plata",institution:{name:"National University of La Plata",country:{name:"Argentina"}}},{id:"186585",title:"Dr.",name:"Francisco Javier",middleName:null,surname:"Martin-Romero",slug:"francisco-javier-martin-romero",fullName:"Francisco Javier Martin-Romero",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSB3HQAW/Profile_Picture_1631258137641",biography:"Francisco Javier Martín-Romero (Javier) is a Professor of Biochemistry and Molecular Biology at the University of Extremadura, Spain. He is also a group leader at the Biomarkers Institute of Molecular Pathology. Javier received his Ph.D. in 1998 in Biochemistry and Biophysics. At the National Cancer Institute (National Institute of Health, Bethesda, MD) he worked as a research associate on the molecular biology of selenium and its role in health and disease. After postdoctoral collaborations with Carlos Gutierrez-Merino (University of Extremadura, Spain) and Dario Alessi (University of Dundee, UK), he established his own laboratory in 2008. The interest of Javier's lab is the study of cell signaling with a special focus on Ca2+ signaling, and how Ca2+ transport modulates the cytoskeleton, migration, differentiation, cell death, etc. He is especially interested in the study of Ca2+ channels, and the role of STIM1 in the initiation of pathological events.",institutionString:null,institution:{name:"University of Extremadura",country:{name:"Spain"}}},{id:"217323",title:"Prof.",name:"Guang-Jer",middleName:null,surname:"Wu",slug:"guang-jer-wu",fullName:"Guang-Jer Wu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/217323/images/8027_n.jpg",biography:null,institutionString:null,institution:null},{id:"148546",title:"Dr.",name:"Norma Francenia",middleName:null,surname:"Santos-Sánchez",slug:"norma-francenia-santos-sanchez",fullName:"Norma Francenia Santos-Sánchez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/148546/images/4640_n.jpg",biography:null,institutionString:null,institution:null},{id:"272889",title:"Dr.",name:"Narendra",middleName:null,surname:"Maddu",slug:"narendra-maddu",fullName:"Narendra Maddu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/272889/images/10758_n.jpg",biography:null,institutionString:null,institution:null},{id:"242491",title:"Prof.",name:"Angelica",middleName:null,surname:"Rueda",slug:"angelica-rueda",fullName:"Angelica Rueda",position:"Investigador Cinvestav 3B",profilePictureURL:"https://mts.intechopen.com/storage/users/242491/images/6765_n.jpg",biography:null,institutionString:null,institution:null},{id:"88631",title:"Dr.",name:"Ivan",middleName:null,surname:"Petyaev",slug:"ivan-petyaev",fullName:"Ivan Petyaev",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Lycotec (United Kingdom)",country:{name:"United Kingdom"}}},{id:"423869",title:"Ms.",name:"Smita",middleName:null,surname:"Rai",slug:"smita-rai",fullName:"Smita Rai",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Integral University",country:{name:"India"}}},{id:"424024",title:"Prof.",name:"Swati",middleName:null,surname:"Sharma",slug:"swati-sharma",fullName:"Swati Sharma",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Integral University",country:{name:"India"}}},{id:"439112",title:"MSc.",name:"Touseef",middleName:null,surname:"Fatima",slug:"touseef-fatima",fullName:"Touseef Fatima",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Integral University",country:{name:"India"}}},{id:"424836",title:"Dr.",name:"Orsolya",middleName:null,surname:"Borsai",slug:"orsolya-borsai",fullName:"Orsolya Borsai",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Agricultural Sciences and Veterinary Medicine of Cluj-Napoca",country:{name:"Romania"}}},{id:"422262",title:"Ph.D.",name:"Paola Andrea",middleName:null,surname:"Palmeros-Suárez",slug:"paola-andrea-palmeros-suarez",fullName:"Paola Andrea Palmeros-Suárez",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Guadalajara",country:{name:"Mexico"}}}]}},subseries:{item:{id:"8",type:"subseries",title:"Bioinspired Technology and Biomechanics",keywords:"Bioinspired Systems, Biomechanics, Assistive Technology, Rehabilitation",scope:'Bioinspired technologies take advantage of understanding the actual biological system to provide solutions to problems in several areas. Recently, bioinspired systems have been successfully employing biomechanics to develop and improve assistive technology and rehabilitation devices. The research topic "Bioinspired Technology and Biomechanics" welcomes studies reporting recent advances in bioinspired technologies that contribute to individuals\' health, inclusion, and rehabilitation. Possible contributions can address (but are not limited to) the following research topics: Bioinspired design and control of exoskeletons, orthoses, and prostheses; Experimental evaluation of the effect of assistive devices (e.g., influence on gait, balance, and neuromuscular system); Bioinspired technologies for rehabilitation, including clinical studies reporting evaluations; Application of neuromuscular and biomechanical models to the development of bioinspired technology.',coverUrl:"https://cdn.intechopen.com/series_topics/covers/8.jpg",hasOnlineFirst:!1,hasPublishedBooks:!0,annualVolume:11404,editor:{id:"144937",title:"Prof.",name:"Adriano",middleName:"De Oliveira",surname:"Andrade",slug:"adriano-andrade",fullName:"Adriano Andrade",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRC8QQAW/Profile_Picture_1625219101815",biography:"Dr. Adriano de Oliveira Andrade graduated in Electrical Engineering at the Federal University of Goiás (Brazil) in 1997. He received his MSc and PhD in Biomedical Engineering respectively from the Federal University of Uberlândia (UFU, Brazil) in 2000 and from the University of Reading (UK) in 2005. He completed a one-year Post-Doctoral Fellowship awarded by the DFAIT (Foreign Affairs and International Trade Canada) at the Institute of Biomedical Engineering of the University of New Brunswick (Canada) in 2010. Currently, he is Professor in the Faculty of Electrical Engineering (UFU). He has authored and co-authored more than 200 peer-reviewed publications in Biomedical Engineering. He has been a researcher of The National Council for Scientific and Technological Development (CNPq-Brazil) since 2009. He has served as an ad-hoc consultant for CNPq, CAPES (Coordination for the Improvement of Higher Education Personnel), FINEP (Brazilian Innovation Agency), and other funding bodies on several occasions. He was the Secretary of the Brazilian Society of Biomedical Engineering (SBEB) from 2015 to 2016, President of SBEB (2017-2018) and Vice-President of SBEB (2019-2020). He was the head of the undergraduate program in Biomedical Engineering of the Federal University of Uberlândia (2015 - June/2019) and the head of the Centre for Innovation and Technology Assessment in Health (NIATS/UFU) since 2010. He is the head of the Postgraduate Program in Biomedical Engineering (UFU, July/2019 - to date). He was the secretary of the Parkinson's Disease Association of Uberlândia (2018-2019). Dr. Andrade's primary area of research is focused towards getting information from the neuromuscular system to understand its strategies of organization, adaptation and controlling in the context of motor neuron diseases. His research interests include Biomedical Signal Processing and Modelling, Assistive Technology, Rehabilitation Engineering, Neuroengineering and Parkinson's Disease.",institutionString:null,institution:{name:"Federal University of Uberlândia",institutionURL:null,country:{name:"Brazil"}}},editorTwo:null,editorThree:null,series:{id:"7",title:"Biomedical Engineering",doi:"10.5772/intechopen.71985",issn:"2631-5343"},editorialBoard:[{id:"49517",title:"Prof.",name:"Hitoshi",middleName:null,surname:"Tsunashima",slug:"hitoshi-tsunashima",fullName:"Hitoshi Tsunashima",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYTP4QAO/Profile_Picture_1625819726528",institutionString:null,institution:{name:"Nihon University",institutionURL:null,country:{name:"Japan"}}},{id:"425354",title:"Dr.",name:"Marcus",middleName:"Fraga",surname:"Vieira",slug:"marcus-vieira",fullName:"Marcus Vieira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003BJSgIQAX/Profile_Picture_1627904687309",institutionString:null,institution:{name:"Universidade Federal de Goiás",institutionURL:null,country:{name:"Brazil"}}},{id:"196746",title:"Dr.",name:"Ramana",middleName:null,surname:"Vinjamuri",slug:"ramana-vinjamuri",fullName:"Ramana Vinjamuri",profilePictureURL:"https://mts.intechopen.com/storage/users/196746/images/system/196746.jpeg",institutionString:"University of Maryland, Baltimore County",institution:{name:"University of Maryland, Baltimore County",institutionURL:null,country:{name:"United States of America"}}}]},onlineFirstChapters:{paginationCount:0,paginationItems:[]},publishedBooks:{paginationCount:6,paginationItems:[{type:"book",id:"9008",title:"Vitamin K",subtitle:"Recent Topics on the Biology and Chemistry",coverURL:"https://cdn.intechopen.com/books/images_new/9008.jpg",slug:"vitamin-k-recent-topics-on-the-biology-and-chemistry",publishedDate:"March 23rd 2022",editedByType:"Edited by",bookSignature:"Hiroyuki Kagechika and Hitoshi Shirakawa",hash:"8b43add5389ba85743e0a9491e4b9943",volumeInSeries:27,fullTitle:"Vitamin K - Recent Topics on the Biology and Chemistry",editors:[{id:"180528",title:"Dr.",name:"Hiroyuki",middleName:null,surname:"Kagechika",slug:"hiroyuki-kagechika",fullName:"Hiroyuki Kagechika",profilePictureURL:"https://mts.intechopen.com/storage/users/180528/images/system/180528.jpg",institutionString:"Tokyo Medical and Dental University",institution:{name:"Tokyo Medical and Dental University",institutionURL:null,country:{name:"Japan"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"9759",title:"Vitamin E in Health and Disease",subtitle:"Interactions, Diseases and Health Aspects",coverURL:"https://cdn.intechopen.com/books/images_new/9759.jpg",slug:"vitamin-e-in-health-and-disease-interactions-diseases-and-health-aspects",publishedDate:"October 6th 2021",editedByType:"Edited by",bookSignature:"Pınar Erkekoglu and Júlia Scherer Santos",hash:"6c3ddcc13626110de289b57f2516ac8f",volumeInSeries:22,fullTitle:"Vitamin E in Health and Disease - Interactions, Diseases and Health Aspects",editors:[{id:"109978",title:"Prof.",name:"Pınar",middleName:null,surname:"Erkekoğlu",slug:"pinar-erkekoglu",fullName:"Pınar Erkekoğlu",profilePictureURL:"https://mts.intechopen.com/storage/users/109978/images/system/109978.jpg",institutionString:"Hacettepe University",institution:{name:"Hacettepe University",institutionURL:null,country:{name:"Turkey"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"7004",title:"Metabolomics",subtitle:"New Insights into Biology and Medicine",coverURL:"https://cdn.intechopen.com/books/images_new/7004.jpg",slug:"metabolomics-new-insights-into-biology-and-medicine",publishedDate:"July 1st 2020",editedByType:"Edited by",bookSignature:"Wael N. 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Behind these definitions are hidden all the aspects of normal and pathological functioning of all processes that the topic ‘Metabolism’ will cover within the Biochemistry Series. 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Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. 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