\\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:"intechopen-supports-asapbio-s-new-initiative-publish-your-reviews-20220729",title:"IntechOpen Supports ASAPbio’s New Initiative Publish Your Reviews"},{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"}]},book:{item:{type:"book",id:"390",leadTitle:null,fullTitle:"Sarcoidosis Diagnosis and Management",title:"Sarcoidosis",subtitle:"Diagnosis and Management",reviewType:"peer-reviewed",abstract:"Sarcoidosis is a type of inflammation that occurs in various locations of the body for no known reason. Normally, when foreign substances or organisms enter the body, the immune system will fight back by activating an immune response. Inflammation is a normal part of this immune response, but it should subside once the foreign antigen is gone. In sarcoidosis, the inflammation persists, and some of the immune cells form abnormal clumps of tissue called granulomas. The disease can affect any organ in the body, but it is most likely to occur in the lungs. It can also affect the skin, eyes, liver, or lymph nodes. Although the cause of sarcoidosis is not known, research suggests that it may be due to an extreme immune response or extreme sensitivity to certain substances. It also seems to have a genetic component as well, and tends to run in families. Sarcoidosis most commonly develops in people between 20 and 50 years of age. African Americans are somewhat more likely to develop sarcoidosis than Caucasians, and females are somewhat more likely to develop sarcoidosis than males. The symptoms of sarcoidosis depend on the organ involved. This book deals with the diagnosis and treatment of this mysterious disease of unknown etiology.",isbn:null,printIsbn:"978-953-307-414-6",pdfIsbn:"978-953-51-6526-2",doi:"10.5772/909",price:119,priceEur:129,priceUsd:155,slug:"sarcoidosis-diagnosis-and-management",numberOfPages:292,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"6f65cbeeb961a79c37a7fc9ed5cb7e8d",bookSignature:"Mohammad Hosein Kalantar Motamedi",publishedDate:"October 21st 2011",coverURL:"https://cdn.intechopen.com/books/images_new/390.jpg",numberOfDownloads:69231,numberOfWosCitations:9,numberOfCrossrefCitations:4,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:8,numberOfDimensionsCitationsByBook:0,hasAltmetrics:0,numberOfTotalCitations:21,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"November 22nd 2010",dateEndSecondStepPublish:"December 20th 2010",dateEndThirdStepPublish:"April 26th 2011",dateEndFourthStepPublish:"May 26th 2011",dateEndFifthStepPublish:"July 25th 2011",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"90148",title:"Dr.",name:"Mohammad Hosein",middleName:"Kalantar",surname:"Motamedi",slug:"mohammad-hosein-motamedi",fullName:"Mohammad Hosein Motamedi",profilePictureURL:"https://mts.intechopen.com/storage/users/90148/images/system/90148.jpg",biography:"Dr. Mohammad Hosein Kalantar Motamedi is a Professor of Oral and Maxillofacial Surgery at the Trauma Research Center, BMSU, and attending faculty of OMF Surgery at the Azad University of Medical Sciences, Tehran. He received his American Diploma from Pennington High School, in Pennington, VA, USA (honor student) and his Iranian Diploma from Hurr High School in Tehran (honor student). After graduation he was accepted at the University of Houston, Texas, USA where he studied predent. Two years later he transferred to the University of Tehran College of dentistry where he received his Doctorate of Dental Surgery Degree (DDS). He completed his Residency in Oral and Maxillofacial Surgery at SBUMS from 1987-1991, and was valedictorian of the National Board Exams in 1991. In 1995 he completed his fellowship at the University of Basel, Switzerland; he obtained full Professorship in 2007. He has published 25 books, 61 international conferences proceedings, supervised 63 doctorate dissertations, and published 185 papers indexed in PUBMED with an h-index of 21. He is Editor-in-Chief of TRAUMA MONTHLY journal and one of the founders of the BMSU Trauma Research Center and more recently the Craniomaxillofacial Research Center. He was granted 1st place prize at the Bagher Alum National Research Festival in 2010 and awarded 2nd Place Prize at the 16th International Razi Research Festival on Medical Sciences. The Iranian Society of OMF Surgeons awarded him “Most Published” in 2009 and 2010, and he was chosen for membership in the National Elite Foundation. In 2013 he was accepted in the Academy of Medical Sciences and he is listed in the Marquis Book \\'Who’s Who in the World” (1999-2020).",institutionString:"BMSU and AUMS",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"7",totalChapterViews:"0",totalEditedBooks:"5",institution:{name:"Baqiyatallah University of Medical Sciences",institutionURL:null,country:{name:"Iran"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1047",title:"Pulmonology",slug:"pulmonology"}],chapters:[{id:"22108",title:"Immunopathogenesis of Sarcoidosis",doi:"10.5772/24401",slug:"immunopathogenesis-of-sarcoidosis",totalDownloads:2914,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:null,signatures:"Giorgos A. Margaritopoulos, Foteini N. Economidou, Nikos M. Siafakas and Katerina M. 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Nowadays, suitable technologies have already been developed for a diverse range of target functionalities of entomocomposting, namely:
The treatment of polluting organic waste for safe disposal, from the point of view of environmental safety;
The production of insects (in the larval, pupal or imaginal stage), from the perspective of food and feed security;
and the production of an organic fertilizer, from the perspective of rationalizing sustained agricultural production and reducing to minimum the environmental impact of agricultural activity, without prejudice of the optimum levels of the potential production in each “soil-climate-culture” interaction process.
Whatever the main objective is, the entomocompost will always provide invaluable added value (as produced or, possibly, after suitable treatment) for safeguarding food security and the environment, due to its potential in the immediate and deferred fertilization of agricultural soils, so as in the recovery of exhausted soils and even in the inclusion of new unproductive land, as, for example, in the case of abandoned mining sites.
But when we talk about entomocompost we are referring to a product with a very diversified physical, chemical and microbiological composition, depending on the nature of the substrate to be digested and the species used to produce it; thus, the option to obtain an organic fertilizer by entomocomposting for pre-defined main purposes, requires taking the following into consideration, as regards the elements of the above mentioned “substrate-insect” interaction: On the one hand, knowledge of the nature of the substrates to be biodigested and the more adequate species to do the job; on the other hand, the eventual treatment of the substrate that may enhance more efficient bio-digestion and/or specific qualities of the frass, and the choice of the best insect species (or genotype within the elected species) in order to obtain most efficiently the entomocompost that is more suitable for fertilizing the soil and the crop for which it is intended.
This would be ideal, and to some extent feasible, at rural level, however, the production of entomocompost for crop fertilization is still in short supply, even counting on the compost obtained in a different context.
Organic bio-digestion by insects for the production of entomocompost also requires the choice of technology to be adopted, both for industrial production and for medium-scale production in rural areas (either at cooperative scale or at farm level), and in the case of agricultural and livestock holdings, it evokes the choice of a circular economy system.
This chapter deals with the knowledge that informs the decision to be taken for all the aforementioned options, by the some other, concluding with a compilation of the experimental results that we consider most relevant with regard to the relative fertilizing potential (immediate and deferred) for specific situations of the “soil–plant-fertilizer” triad interaction. Some notes on insects regarding food and feed are anticipated, as they are inextricably linked to the production of the entomocompost.
The present COVID-19 pandemic has shown how Europe is hostage of the international feed market, and as far as nutrition is concerned, protein is a huge problem to be solved. However, society continues to waste food products, contributing to a very inefficient agriculture vale chain in which more than 25% of food products can be lost.
Based on a one hundred percent circular economy-based approach, vegetable by-products can be converted into high valuable nutrient sources for both animals and plants. Insects can be the key for the transformation of this otherwise lost nutrients into new nutritional solutions not only for both humans and animals, but also for plants.
In a very short period, insects can convert a very large range low value by-products into high value insect protein and oil for animal and human nutrition and insect frass, and organic fertilizer for plants. With this process, now completely industrialized and at a full-scale level, it is possible to reduce the Europe dependency from the international feed and food markets, contributing to a local and more sustainable food production.
As mentioned, nowadays, feed producers face several significant global challenges to find suitable resources to produce compound feed for livestock, aquaculture, and pets. On the one hand, the growing demand for animal products, and thus for animal feed, associated with the need to find resources with reduced environmental impact, has led to the development of novel feed ingredients, and moves to decrease dependency on common resources, such as soybean meal, maize and fishmeal. The current use of these resources is assessed as being unsustainable therefore driving the need for alternative ingredients to maintain the balance between food, feed and biofuel industries. Land degradation, water deprivation and drastic climate change are additional challenges impacting on livestock production, aquaculture and the pet food industry.
On the other hand, recent events have illustrated the need to reduce our dependency on imported resources, specifically from other continents, strengthened by consumer opinion exerting pressure to provide more ‘natural’ food production for humans, livestock and pets. Accordingly, the development of novel sustainable raw materials plus improved efficiency of resource use play, and will continue to play, a vital role in ensuring the sustainability of feed manufacture.
Significant relevance is now placed on the development of new feed resources based on environmentally friendly approaches, circular economy solutions, and the use of natural resources. However, it is not likely in the near future to be feasible to completely replace existing feed ingredients with novel ones, leading to a focus in the sector on improving efficient use of existing ingredients, thus decreasing demand.
Some novel food and feed ingredients have the significant advantage of making use of available agri-food co-products and transforming them locally into new nutrient sources. Insects are one such ingredient that has the capability to convert low value vegetal co-products into a high value nutritional solution, while also aligning with the environmental drivers that are prompting the food and feed revolution.
It has been estimated that food waste accounts for 23% of arable land and 24% of freshwater resources used for crop production [2]. Thus, it is relevant to evaluate the use of insects in feed from a circular economy point of view. Insect rearing can potentially be used to upgrade low-value organic food waste streams increasing the efficiency of natural resource use and animal production.
Several livestock production companies in the world operate vertically, producing feed for the animals, raising and processing them before market. Co-products include manure and other animal and vegetable co-products as well as former foodstuffs. Insects could be an invaluable tool for such organizations, as they can provide a perfect link between nutrient loss in vegetable co-products, and the protein supplement needed for animal feed.
Therefore, insects have a perfect spot in certain value chains, where, more than creating value, they contribute to natural resource use efficiency through nutrient bioconversion. This might be the greatest contribution of insects to the food value chain, as they have the capability to be integrated perfectly in present day market chains, whilst also converting wastes and less desirable co-products into high value nutrient resources. When applied with the right infrastructure, such systems could contribute to animal production efficiency, environmental sustainability, and supply chain profitability. Furthermore, insects, as for other novel food and feed ingredients, offer the potential to decrease dependency upon foreign products imports, creating new local products, and thus helping to shorten supply chains.
Thus, there is growing interest regarding the use of insects as an alternative ingredient source for both food and feed production. The use of alternative ingredients in animal diets can be optimized in terms of their nutritional characterization, their safety and technological quality, in order to achieve better performance as well as facing the challenges of increased feed demand in volume as well as quality and sustainability factors.
Insects can supplement traditional feed sources such as soy, maize, grain and fishmeal, with several different species of insects considered for use as a partial or total substitute of traditional feed sources [3, 4, 5, 6]. Many trials have been conducted with different animal species, both terrestrial and marine, with the challenges associated with the use of insects in these animals changing, dependent not only on the animal species being fed, but also on the insect species being used, and the rearing substrate on which it was grown. However, it has also been demonstrated that different organic substrates can be used to rear insects, such as Black Soldier Fly (BSF), without significantly affecting its amino acid composition, the profile of which has been shown to be similar to that of fish meal and soybean meal [3, 7]. By contrast, when considering fat and ash composition, both can differ substantially according to the rearing substrate [8]. Thus, insect nutritional and technological properties are linked to the species, rearing system adopted and especially to the substrate used [8].
On the other hand, the so produced novel plant nutritional source, entomocompost, can contribute to a wide range of soil solutions, from drought resistance and plant nutrition to even pest control and sprouting promotion.
However, this novel sector still faces several challenges, from legal to consumer acceptance and to industrialization and growth. Although the legal framework is changing and adapting to this new reality, consumers still have to prepare for it, and insect producers have a lot to learn from other livestock and industrial sectors. Besides that, the use of insects as a tool to other applications is still in its infancy, as insects can be used from bioremediation in garbage disposal systems, to the production of new plastic solutions.
If initially the use of uncontrolled composting of organic agricultural wastes may have been motivated by obtaining a fertilizer for crops, as in the case of the use for this purpose of animal bedding and manure slurry, the fact is that subsequently, with the exponential growing production of industrial and urban organic waste, the emphasis has shifted to the disposal of polluting waste.
Within this last context, controlled composting methods have been developed [9], including in its motivation for the production of arthropods and worms for food and feed, and not least for the production of organic fertilizers; in fact, food security is no less relevant, and to this end the resilience of agricultural soil fertility, the restoration of depleted soils and even the acariation for agricultural production of infertile soils hitherto ignored for this purpose, without compromising environmental security, is urgently needed.
But fertility is an ambiguous concept when applied in relation to the productive capacity of agricultural soils. Actually, boosting the full productive capacity of a given plant species (or even of a given genotype of the same species), depends on rigorously reconciling its physical and chemical requirements with the soil and climate conditions in which it is located, and these can be very diverse – in poor soil conditions, a primitive variety has more yield potential than a variety improved for yield capacity [10, 11].
However, that above-mentioned objective, of full productive capacity, will not always be the most appropriate if it is not based on economic, environmental and ethical considerations, because maximizing production does not always lead to greater financial return, it frequently translates into an environmental burden and it often forgets the responsibility of the agricultural sector in the context of global food security.
With regard to soil fertilization, which underlies the subject of this Communication, the above considerations are also valid: Soil fertilizers should be required to provide an advantageous cost–benefit balance, to cooperate in protecting the environment, and to increase the resilience of soil fertility as a basis for long-term food security. According to these requirements there seems to be difficult to find a perfect type of fertilizer.
As with the majority of organic fertilizers, the main virtue of entomocompost lies in their action in correcting the physical, chemical and microbiological properties of soils (a fundamental factor in their deferred fertility) and in supplying the mineral elements necessary for each crop, in each specific situation (an important factor for their immediate fertility) [12]. Furthermore, entomocomposting can be a relevant factor in recycling exhaustible plant nutrient resources; an example of this is mentioned by Zhang
Any entomocompost is, however, more than the frass obtained from a given substrate; apart from the frass, it contains the remainder of the substrate and residues from the metamorphosis of pupae into adults (if not the pupae themselves). This is not entirely true in the case of biological digestion by the BSF larvae, which evidences the unique behavior of abandoning the compost at the pre-pupa stage, a phenomenon with obvious advantages in pupal harvesting and which is referred to in the bibliography as self-harvesting. For this reason, for the entomocompost obtained from BSF was proposed [14] the acronym CASH (Compost After Self Harvesting).
But the constraints on the more generalized use of entomocomposts are not limited to those mentioned above. They range from lack of definition of the exact formulation of their composition, to lack of knowledge of the mineralization rate (for formulations of its fertilizing elements that can be directly assimilated by the plants) in the soil and climate situations in question, to logistical and scale limitations to supply. In reference to this latter setback, Timsina [15] states that “considering the current organic sources of nutrients in developing countries, organic nutrients alone are not enough to increase crop yields to meet global food demand”.
Through bio-digestion by insects, the formulation of the substrate is largely altered in its physical, chemical and microbiological composition, with decisive consequences on the fertilizing potential of the entomocompost; it, therefore, plays a relevant role in the quality of the compost. As referred by Poveda
As an extreme situation, regarding the nature of the substrate, Koh
An entomocompost of a substrate of agroindustry origin, or of remnants and residues from agricultural production, is not seen as a threat of chemical or microbiological contamination of agricultural soil. On the other hand, a compost obtained by insect bio-digestion in industrial urban waste plants, requires analysis and possible remediation if chemical and microbiological substances harmful to soil fertility are found to be present, as for instance in the case of houseflies, with high levels of lead and arsenic in the frass [18].
Entomocompost derived from manure and slurry does not normally pose the danger of soil contamination of any kind, however, in the context of insect production for feed or for food, is not at all suitable, and is subject to severe restrictions. To overcome these constraints, which are mainly dictated by the nature of the substrates, some progress has already been made.
Thus, although the use of unsafe wastes as substrate for entomocomposting can be done with efficiency, as this technic is mainly applied for food and feed purposes, it is quite uncommon to see full-scale insect rearing units using such substrates. In fact, the majority of entomocomposting units, or insect farms, are using vegetable coproducts as substrates for insect production, being its main purpose the production of insects as a protein source and the insect frass a co-product of this process. Nevertheless, and as previously demonstrated, entomocompost is a high valuable product with very good effects in soil fertility and plant health.
This way, entomocomposting should not only be considered as a process to produce food and feed, but also to produce the entomocompost as a main objective, opening the use of other, unsafe, wastes that cannot be used when the produced insects are intended for the food chain. However, such approach will require studies to evaluate food safety concerns in a one health approach, evaluating from environmental impacts and benefits, to possible impacts in the soil and plants. The so produced insects cannot be intended for the food cahin but might well find an economic value as a raw material for biorefineries such as fuel and plastic, or to be also used as fertilizers.
The use of entomocomposting technics to convert unsafe substrates such as urban organic wastes, manure or sewer sludge, is being tried in several R&D projects. Such is the case of NETA project (POCI-01-0247-FEDER-046959), a project in which a new manure and sewer water is being treated with a novel process and the sludge is being tested as a substrate for entomocomposting. This produced insect frass is being tested in vegetable and olive oil production, while the larvae are being evaluated in terms of safety, evaluating both chemical and microbiological contaminants, and being used for industrial purposes.
In order to be possible to produce insects for food and feed purposes with organic wastes as substrate, what would unlock the entomocomposting potential as a bioremediation tool, one should first show if such approach is safe. However, before proving its safety, one of the main challenges in entomocomposting organic wastes is that if we used the same insect species as for the production of food and feed, it will not be possible to differentiate insect products produced with safe or unsafe substrates. Thus, one possibility would be to develop the entomocomposting process of unsafe substrates, such as organic wastes, manure and sewer sludge, with insect species not being used for food and feed purposes. That would allow to differentiate the obtained insect product with DNA testing and would unlock a very beneficial tool for the treatment of high environmental impact organic wastes, transforming them into novel products and returning lost value to the value chain, while contributing to both economic growth and sustainability in a 100% circular economy approach.
Thus, it should be highlighted that using insects for nutrient production is not a goal in itself but can be an instrument to achieve goals in biowaste reduction and conversion, improving sustainability and optimizing the food value chain. Insects should be evaluated as a tool to increase the efficiency of resources use and to increase income, and thus, one must evaluate them beyond their nutrient value as a feed ingredient.
For example, BSF are a rich source of lipids which can be industrially extracted to obtain a pure oil with several different potential uses, from feed and food, to biodiesel and cosmetics. It has been shown that BSF fat could be a useful alternative for other commonly used fats, with specific technological properties in common with palm and coconut oils, which are increasingly associated with negative environmental impacts. In particular, the melting and crystallization behavior of BSF larval fat seems to allow replacement for traditional fats [19].
In addition, the insect exoskeleton can be processed to obtain chitin and chitosan, and its industrial scale production could offer a potential source of prebiotic oligosaccharides for pet, animal, and human nutrition [20]. Applications for chitin and chitosan go beyond nutrition, as chitosan is characterized by non-toxicity, biodegradability, film-forming capacity, antimicrobial and antioxidant properties and good barrier properties of packaging films against oxygen [21, 22, 23]. Thus, the potential for the use of insect derived chitosan to produce biodegradable plastics is being evaluated for a variety of applications, ranging from agriculture to food packaging.
Chitin-derived products have also been shown to be toxic to plant pests and pathogens, inducing plant defenses and stimulating the growth and activity of beneficial microbes. Chitin-based treatments augment and amplify the action of beneficial chitinolytic microbes [24]. Such properties prompted the development of novel crop fertilizer and crop protection products, which can be used in conjunction with one of the main insect products, the insect frass. In natural conditions, it is well known that frass deposition to soil has a great impact on soil fertility due to its high nutrient and labile carbon content and, therefore, several companies have already started to sell frass as a fertilizer [25].
With all the economic and environmental advantages in the search for agricultural production that is compatible, in a sustainable way, with global demand, entomocomposts have been affirming themselves as an important alternative for reducing (if not replacing, in some cases) synthetic mineral fertilizers. To this end, several insect species have been evaluated for their proficiency in composting organic substrates.
In a careful literature review, Poveda [26] presents two thorough lists of studies on the use of insect frass as fertilizers, indicating, for each case, the plants, the benefits and the mechanisms by which these benefits were expressed.
In addition to providing the necessary mineral nutrient elements for plants, the benefits provided by adding insect frass to the soil are diverse in nature, such as: increased germination, sprouting, growth and nutritional content of plants; increased tolerance to abiotic stress; activation of the plant’s defense mechanisms against pathogens and pests; increased nitrogen in plant tissue; reduced oviposition of pest insects and; increased microbial activity in soils.
However, these advantages are not all concentrated in a single species so, although frass from various species may have a relevant role as a complementary fertilizer in specific situations, few species have shown the potential to produce an entomocompost with the potential to be an alternative to avoid completely mineral fertilization in all situations. One of this specie contradicts the thesis of Lardé [27], supported by Smetana
But if the possibility of biotic associations or of physical or chemical corrections of entomocompost for preferential purposes (within the versatility of its benefits in crop nutrition and soil fertility resilience) is a proven reality in the experimental and commercial field, in the field of genetic enhancement of insect species for entomocomposting only the first steps have been taken.
Advances in this field are predictable and particularly desirable, notably when it comes to insects with the ability to adapt to a wide diversity of substrates. This is the case of BSF, which is able to efficiently biodigest manure from various livestock species (from polygastric, monogastric or fish species) as well as residues and remnants from crops or from agroindustry.
The methodologies for this could be very diverse, but the simple continuous selection of pupae fed on the digestion of specific substrates can lead (as it has happened with the generality of animal and plant species already submitted to human-induced selection) to the differentiation of specialist genotypes more competent than generalists, probably because it should be anchored in an evolution towards more targeted physiological mechanisms that are necessarily less energy-demanding; this option, which would certainly not meet with the disagreement of the detractors of transgenics, would only require, as an additional effort, the separation of breeding facilities for flies, even though it may be slower in results, but “constant dripping wears the rock away”.
Insect production has grown a lot in the last decade. This new sector emerged with the support of FAO-UN who first referred to this field in the beginning of the decade and started an insect rush in several countries, with the development of new business. However, by then, both the business and the process where not mature yet and it took several years of development to see the first full-scale insect rearing unit being built by a handful of companies. However, the legal framework had not grown at the same rhythm, what promoted a lower growth. At this point, different companies have developed their entomocomposting technics in parallel, and even using the same insect species and substrates the processes can follow completely different approaches.
Besides that, although several approached have been made to create technologies to produce insects, and entomocompost, at a small scale, and although it can be applied at the farm level, it is only economically relevant at a large and controlled scale, ensuring both food safety and traceability.
Large scale insect production is an industrial sector in which several tons of vegetable by-products are converted by insects every day. Contrary to most composting technologies, insect production generally does not use piles of by-products. It processes them into controlled mixes of raw-materials ready to be digested. This raw material processing allows a steady rhythm of conversion and production. In most cases insects are thus reared inside plastic boxes of different sizes in large controlled environment warehouses. The time needed for composting and the number of insects to be used to convert each ton of by-products change from insect specie to insect specie and between companies. The main insect species to be used for food and feed are
Therefore, insect production has not only to achieve economically viable production at scale, investing in new full-scale insect production units, but it must also be standardized, to obtain a steady production and uniform product. Standardization is key not only in relation to a single production unit, but also between different producers. Insects as a food and feed resource, and also as a plant nutrition source, would greatly benefit from standard quality and nutritional values when considering the same insect species and product. This would increase farmers trust in this novel fertilizer. However, different insect producers may use different insect species and rearing substrates, as well as different production and processing techniques. This results in different products, with different nutritional values and properties, entering the market.
Nevertheless, as the insect rearing industry is only in its infancy, we believe that in the future the production and processing of insects and frass will tend to be more similar between operators, as different production processes and technologies attain relevance in the sector. One opportunity to increase standardization and quality of insect products might be technology transfer between companies, enabling rapid growth of this novel sector and allowing investors and new operators to enter the market without the need to invest in the development of processing technologies. Technology transfer from other companies and research institutes that have spent recent years in R&D will have processes providing the most suitable solutions, avoiding the need for new producers to start from scratch, costing time and money as well as decreasing the chances of success for new businesses.
For Zink & Geyer [35] “the proponents of the circular economy have tended to look at the world purely as an engineering system and have neglected the economic part of the circular economy”; to this assertion, the facts have been demonstrating, convincingly anchored in science, that the linear economy alternative, in turn, blatantly belittles the environmental part.
The circular economy is “a new economic model operating in closed circuits, catalyzed by innovation throughout the value chain” [36], and, within the agrarian economy, whether in plant or animal production, entomocomposting is an innovative alternative, more efficient than traditional composting, to reduce the import of feed and fertilizers and energy losses, with added advantages in terms of safeguarding the environment.
This is how the entomocomposting of crop remains and residues, so as livestock production wastes, is a multifaceted pivotal factor of the greatest relevance to different circularities within farms, as shown in Figure 1.
Multiple circularities driven by BSF on farms.
The circularities represented in the diagram are multiple and interlinked and are not necessarily closed. In fact, there will always be a need for outsourcing, both for supplementation of feed and fertilizer, in quantities compatible with optimizing the efficiency of the entomocompost and the feed value derived from pupae.
The protagonist in this diagram is BSF, for the peculiarities that distinguish it, in a positive way, from the other composting agents, namely:
High prolificacy;
High proficiency and speed in biodigestion;
Widespread range of organic substrates that have the potential to digest;
Efficiency in the elimination of potentially harmful microorganisms;
The ability to drastically eliminate housefly multiplication during digestion processes;
Capacity to provide the presence of plant growth factors in the CASH.
But beyond these, two singularities, particularly relevant in agricultural and livestock holdings, distinguish them from other insects:
Self-harvesting and;
The fact that the adult does not have a developed mouth apparatus, feeding on the copious reserves accumulated in the larval stage, and thus does not bother (or even transmit diseases to) humans and animals.
Finally, and following the results reported by Yildirim-Aksoy
Notwithstanding the fact that entomocomposting by BSF has already proven to be highly efficient in recycling and reuse capacity in the plant and animal production circuit, the deficit generated in the export of plant and animal products to the market means that feed and fertilizers have to be imported. To this end, in rural areas, initiatives (possibly of a cooperative nature) for the production, on an industrial scale, of entomocomposts and larvae (or pupae) for soil fertilization and feed, allow the circularity of the production system to be extrapolated from the individual sphere to the community sphere; With this type of initiative, the agroindustry will play a relevant role, with additional advantages in terms of capacity and fluidity of the system, broadening the scope of circularity at regional level.
Most of the research on the role of insects in soil fertility has focused on specific aspects of the benefits of their frass, not necessarily obtained through the technological composting of organic waste but through their metabolism as part of the soil entomological fauna; with this last aim, numerous studies have been published, as it can be seen in the comprehensive listing by Poveda [26].
These
When it comes to the use of a compost derived from off-site insect digestion of organic waste, a more objective assessment of its fertilizing potential, although guided by scientifically well-founded theoretical considerations, should be further informed by evaluation in preliminary production trials in a conditioned environment, in accordance with the pre-defined end goal.
The fact that seldom these trials showed a decrease in production - as was reported by Alattar
Some pot tests have shown the potential of entomocompost, obtained from substrates of various kinds, to reduce mineral fertilization in several crops, as for instance: With mealworm (
Also testing the potential fertilizer value of BSF frass from several origins and for different plant species, in pot experiment, comparing either with other organic composts or with commercial substrates, the results found by Newton
Although these results are encouraging, the conclusive proof, which is specific to the conditions that characterize the experimental situations, can only be given in the light of the results of the field test. Trials of this nature are still scarce and will never allow abusive extrapolations, but they constitute the most valuable information on the fertilizing potential of entomocompounds in relation to mineral fertilization.
Notwithstanding the fact that Temple
These results support the thesis that in the experimental situations tested to date, the percentage of CASH capable of competing with mineral fertilization alone, in what concerns the immediate fertilization for crops, is between 10% and 40% in volume. More optimistic results were seen, for example, in a demonstration field [56] with potato (
The arguments mentioned so far, based on experimental results endorsed in the literature, justify promising perspectives regarding the role of insects in the production of organic fertilizers capable of allowing a reduction of mineral fertilizers as far as the immediate fertilization of crops is concerned; nevertheless, more important than the immediate fertilization of crops is the deferred fertility of soils, both in the resilience or increase of their fertility and in the acariation of soils rendered unproductive by anthropogenic or climatic effects.
In any case, the medium- and long-term promotion and resilience of the fertility of the soils, which should be fostered by insect frass, would be translated, as for the generality of organic fertilizers, by the improvement of the structure of the soils and its capacity to retain water and crop nutrients and as well as by symbiotic interaction with the soil microbial flora and with the plant. Many knowledge within this perspective is still needed, but also a lot have been accumulated, allowing for hopeful evidences, such as: better use efficiency of P and K [57]; improved soil fertility and defense against pathogens [58]; suppression against
These data augur well, but medium and long-term field trials are indispensable for continued soil fertility management, since organic matter resilience is not its greatest virtue, particularly in tropical and sub-tropical climates.
Despite being still at the beginning of its career as a biodigester, for the production of organic fertilizers, and beyond the benefits of the utmost relevance in the perspective of safeguarding the environmental balance and food safety, research and experimental development has already given concrete proof of its potential as an indispensable partner in the resilience and recuperation of soils for agricultural production.
The role of insects in the biological digestion of organic substrates, with a view to the fertilizing potential of entomocomposts, has raised a growing commitment from the scientific and technical community in the field of agriculture and environmental protection; however, despite the accumulation of positive results from the application of this type of fertilizer, significant progress is still expected in this sector, with the improvement of the genetic capacity of insects, of the pre-treatment of substrates and of the entomocomposting technology, so as the adequacy of fertilization techniques.
In the context of the organic fertilizers, entomocomposting takes precedence over other composting methods, mainly because of the speed of the organic waste digestion process, drastically reducing composting time and thus the risk of environmental pollution, besides advantages such as soil health, pest control, sprouting and germination potential.
Various insects have been tested for their potential in digesting substrates of a very different nature, giving rise to entomocomposts with positive results, in reduce mineral fertilizers, in crop production, or as correctors of certain chemical and/or microbiological deficiencies, not to mention physical soil deficiencies, for which any organic fertilizer is capable of dealing with.
Nevertheless, more results are expected with further research into entomocomposting technology, with the discovery of new insect species and their genetic improvement for the biodigestion of different organic substrates, and with new techniques for the enhancement of the fertilizing effect of composts, in order to make available suitable formulations for different “soil x plant x fertilizer” interaction situations.
Until now, as shown in the tests presented in this analysis, the greatest success in the contentious debate “organic vs. mineral” has been achieved in situations of compromise, where the organic fertilizer has the complementary role, by its relatively low and unbalanced nutrient content, notwithstanding its biological interaction with plant and soil microrganisms, its action in improving the soil’s physical properties and its capacity to retain water and nutrients – so, as advocated by Ronald and Adamchak [62] or Amman K. [63], and as Saint Tomas d’Aquino said so well, ‘
Furthermore, although growing exponentially, increased production of organic waste for entomocomposting is unlikely to be sufficient to ensure global food security on its own, as it is a direct function of population growth; suggestions based on success rates reported in the literature for insect frass - ranging from 10 to 40% by volume - may be realistic to be expected, at least in the medium term. In fact, if the potential of the triple valence of entomocomposting (protection of the environment, food security and resilient soil fertility) can already be categorically stated, the use of entomocompost as a fertilizer still faces the major constraint of the lack of scale of its production.
Considering all these possibilities, insects must be recognized not only as a nutrient source but also as a tool. The value of insects can surpass the production of nutrients and the use of its by/co-products to increase its profitability. In the near future insects could be used in manure and household waste treatment approaches, decreasing the environmental impact of livestock production and landfill volumes [5, 64, 65]. This approach would open a completely new opportunity for insect rearing, that is distinct from insect production for animal nutrition which must comply with safety and hygiene regulations.
Increased sustainability of animal and food production can be delivered by insect use, not only through the development of new feed resources but also by contributing to the reduction and conversion of wastes into novel raw materials for bioindustry and biorefinery approaches.
There is still much to do in this regard but, in rural areas, the proposal of a circular economy system in the management of agricultural, livestock and forestry production, with circularities within private farms to be extrapolated (cooperatively) to the regional level with agroindustry and an industrial entomocomposting unit, deserved to be weighed up.
This chapter was performed under the scope of the NETA project: New Strategies in Wastewater Treatment (POCI-01-0247- FEDER-046959) funded by PORTUGAL2020.
Decontamination is a fundamental requirement for research facilities where pathogen elimination is critical, and laboratory facility managers routinely employ various methods of fumigation or fogging disinfection in the never-ending battle against contamination. Historically, technologies such as chlorine dioxide and formaldehyde gas systems have been applied in these areas for pathogen disinfection. Likewise, high concentration vaporized hydrogen peroxide has also been relied on to achieve similar outcomes. A large percentage of these methods follow a familiar pattern of solution injection, dwell (contact time), evacuation, and validation; however, not every system delivers the same functionality or efficacy. Differences in formula and design influence personnel hours, material compatibility, and risk management.
While effective, these high concentration solutions come with inherent risks to health and safety. A recent innovation significantly lowers the risk of exposure to high-concentration chemicals— an HHP™ system which combines a 7% hydrogen peroxide solution with a calibrated fogging device to deliver a mixture of gaseous and micro aerosolized particles. Studies performed with this technology demonstrate high level pathogen disinfection across a variety of tested viruses, bacteria, and substrates. This chapter will provide readers with a deeper understanding of essential components and considerations when implementing systems for viral decontamination. This chapter introduces the latest evolution in hydrogen peroxide disinfection of viral pathogens to address these challenges: an HHP system using patented Pulse™ technology.
A dichotomy of virology work is the need for both viral presence within the confines of research and the equally consistent need to establish pathogen-free research spaces. Throughout the world, contagious disease through viral contamination is an ever-present concern, and SARS-CoV-2 has brought the need to decontaminate to the forefront of virtually every industry. Scientific industries performing research, manufacturing pharmaceuticals, or providing healthcare services, all employ protocols for the disinfection of their environments in order for safe, successful, timely work to take place. These industries depend upon disinfection chemicals, and perhaps just as importantly the chemical delivery systems, that ensure the integrity of their work, personnel safety, and efficient transition from one research project or product type to the next.
Today, a number of distinct categories are used to classify and understand disinfection methods. Disinfection chemicals are tested with established protocols and classified according to their relative success at eliminating specific pathogens. The
Decontamination | The use of physical and/or chemical means to remove, inactivate, or destroy microbial pathogens (e.g., bloodborne or aerosolized) on a surface or item to the point where they are no longer capable of transmitting infectious particles and the item or surface is rendered safe to handle: however, this definition has been broadened by infection control specialists to include all pathogens and physical spaces (e.g., patient rooms, laboratories, buildings). |
Disinfectant | A substance, or mixture of substances, that destroys or irreversibly inactivates bacteria, fungi, and viruses, but not necessarily bacterial spores or prions, in the inanimate environment. |
Disinfection | A process that destroys pathogens and other microorganisms, except prions, by physical or chemical means. |
High-Level Disinfection | A lethaI process utilizing a sterilant under less than sterilizing conditions (e.g., 10–30 min contact time instead of 6–10 h needed for sterilization). The process kills all forms of microbiaI life except for large numbers of bacterial spores. |
lnactivation | A procedure to render a pathogen non-viable, viral nucleic acid sequences non-infectious, or a toxin non-toxic whiIe retaining characteristic(s) of interest for future use. Methods targeting tropism may be host-specific. |
Sterilization | A physical or chemical process that kills or inactivates all microbial life forms including highly resistant bacterial spores. |
Sterilant | A substance or mixture of substances that destroys or eliminates all forms of microbial life in the inanimate environment including all forms of vegetative bacteria, bacterial spores, fungi, fungal spores, and viruses. |
Validation | Establishment of the performance characteristics of a method and provision of objective evidence that the performance requirements for a specified intended use are fulfilled. |
Aerosol | Particulate matter, solid or liquid, larger than a molecule but small enough to remain suspended in the atmosphere [4]. |
Gas | A substance or matter in a state in which it will expand freely to fill the whole of a container, having no fixed shape (unlike a solid) and no fixed volume (unlike a liquid) [5]. |
Hybrid H2O2 | A mixture of gaseous and micro aerosolized substance which remain suspended in the air to fill the whole container [6] |
Vapor | A substance diffused or suspended in the air, especially one normally Iiquid or solid [7]. |
One growing understanding is that the application method of a disinfectant plays a critical role in the success of the disinfection results. While some of the most common spray and wipe surface disinfectants have been in use for decades, there are challenges to their application which can result in inconsistent or ineffective results. Adequate distribution and required contact time are difficult to achieve on a consistent basis by hand application methods, especially in large spaces with high ceilings and complex surface profiles. These accessibility issues and failures may result in inconsistent and incomplete elimination of surface contamination [13]. To address inherent inconsistencies in manual disinfection and to provide alternative methods of delivery, various technologies have been applied. Those technologies include fumigation with formaldehyde, chlorine dioxide gas, fogging of hydrogen peroxide as vapor, silver hydrogen peroxide systems, and hybrid hydrogen peroxide systems. Their gaseous and vaporous form allows access to, and contact with, surfaces that spray and wipe methods alone often cannot access. Automated systems have taken these chemicals with known disinfectant action and paired them with dispersion devices, aiming to deliver an appropriate contact time and maximize surface exposure. These systems automate much of the disinfection process, helping to remove human error and mitigate safety concerns from contact with potentially caustic chemicals. In particular, H2O2-based systems have become a front-runner among automated high-level disinfection technologies due to H2O2’s effectiveness, material compatibilities, lack of chemical residues, and increased safety over other technologies such as formaldehyde or chlorine dioxide gas [14, 15, 16, 17, 18]. When applied in multiple life science environments, H2O2 fogging is well documented to have efficacy against numerous viral pathogens and has seen a rise in use in environments where thorough efficacy and decontamination of a room and its contents are needed [19, 20, 21, 22].
Anyone who has skinned their knee and poured hydrogen peroxide on the wound to stave off infection is familiar with the use of H2O2 as an antiseptic and anti-bacterial agent. Indeed, hydrogen peroxide is produced naturally in the body, acting as a beacon triggering the accumulation of white blood cells of the immune response [23]. Hydrogen Peroxide was first discovered in 1818 by Louis Jacque Theénard, who described it as ‘eau oxygénéé or water oxygen for its composition containing one more oxygen atom than water [24]. This single oxygen–oxygen or peroxide bond is naturally unstable and prone to decomposition with or without the presence of a catalyst [25]. During decomposition, the active oxygen atom cleaves off, releasing energy and resulting in water and oxygen molecules [26]. The oxidizing activity, resulting from the presence of the extra oxygen atom, is what makes hydrogen peroxide an effective disinfectant. It is the reactive formulation of hydrogen peroxide which causes destruction of pathogens by breaking apart structures, interrupting key functions, causing damage to DNA, and eliminating infectious particles.
One of the biggest challenges to any disinfectant application is ensuring a thorough and consistent disinfectant exposure to contaminated surfaces for an effective contact time. To achieve success, fogging technologies must perform a complicated dance between the amount of chemical injected, temperature, humidity, dew point, and method, all of which can affect efficacy from one application to the next. To answer this need, CURIS System designed and patented the concept of replenishing any naturally decomposing solution and called it Pulse technology, simplifying the complicated balance of a successful disinfection. Combining a 7% hydrogen peroxide solution with a calibrated fogging device, this HHP system delivers hybrid hydrogen peroxide, a mixture of gaseous and micro aerosol particles. While effective in a liquid solution, fogging with hydrogen peroxide in this hybrid form increases the availability of each H2O2 molecule, maximizing oxidation opportunities and leading to the destruction of pathogens on surfaces. Beyond just inactivating pathogens, this oxidation causes a physical destructive action of pathogen components, which further delineates this substance as a decontaminant as defined by the BMBL.
A fundamental distinction of this system is its ability to disperse a lower concentration of 7% hydrogen peroxide at calibrated intervals, maximizing contact time while using less H2O2 to achieve microbicidal efficacy. The HHP device operates by delivering the HHP mixture in a two-part process. First, it fills an enclosure with disinfecting fog to an optimal level for killing pathogens. Second, it maintains the fog at the optimal level without oversaturation by periodically injecting more solution into the space being treated, and thereby prolonging the active contact time of the H2O2 (Figure 1). This not only helps to keep surfaces dry, it also reduces sensitivity to variations in temperature and other factors. One might consider this similar to cruise control in a vehicle—the initial phase continuously revs the engine to get the vehicle up to speed, while the second phase uses the engine just enough to keep it at the cruising speed without exceeding the limit. In the case of disinfection, it means keeping the fog concentration at the optimum “kill” level to achieve efficacy in a relatively short time, yet without exceeding this optimum level to the point where the fog condenses on surfaces in the treatment area.
With a concentration of 7% H2O2, the solution, known as CURoxide™, is below the 8% hazard threshold [27, 28]. Being below the threshold means special shipping considerations are not required. Moreover, this enables safer handling for personnel than the 35–59% H2O2 solutions traditionally employed for fogging applications [18, 29, 30, 31]. Likewise, the 7% solution is safer for laboratory materials than the 28.1–52% concentration of corrosive industrial strength grade hydrogen peroxide [27, 32]. This material safety (compatibility) is perhaps most evident when considering how the hydrogen peroxide concentration of a solution will evolve when the solution transitions through states of matter. Hydrogen peroxide is more resistant to leaving the liquid state and more likely to return to it than the water in the solution. When transitioning from vapor back into liquid, this can result in surface condensation at more than double the initial liquid concentration (Figure 2). At 7% H2O2, the HHP solution remains below the 45% known level of material incompatibility [33].
The levels of particle concentration used in typical high-level disinfection are of particular concern to facility managers. These concerns may be lessened by employing lower particle-producing products. Technologies utilizing formaldehyde, chlorine dioxide, and high concentration H2O2 operate at concentrations as high as 1,400 parts per million (ppm) [34, 35, 36]. By contrast, the HHP 7% solution has a lower operating concentration of approximately 138 ppm [37]. Traditional vaporized approaches require a concentration that is up to 10× higher than the lower 7% H2O2 concentration enables, which accordingly may result in a greater risk to personnel from leakage with typical high concentration systems [38]. This is particularly important because, according to the National Library of Medicine, “Inhalation of vapors from concentrated (greater than 10%) solutions may result in severe pulmonary irritation” [39]. This may be why there is a substantial safety concern among facility managers when it comes to typical fogging approaches, as these approaches utilize caustic chemicals at very high concentrations which are known to penetrate through gaps as small as a keyhole [38, 40].
Roughly the size of a small suitcase, the 36-pound (16 kg) HHP system fogs enclosures from an adjustable stainless-steel nozzle at the top of the unit. It can be wheeled or carried throughout a facility to disinfect a wide variety of spaces, large or small, and its Rotomold design provides durability for long-term use and sturdiness during transport. A push-button design allows users to input area dimensions through the device’s manual digital interface, or users may operate the device remotely via a tablet for touchless disinfection from outside the treatment space. The system self-calculates the cubic footage of the space to be fogged to determine the amount of disinfectant needed, and an indicator light shows users when the appropriate amount of solution has been added to the reservoir. An electronically sequenced A/C electrical outlet provides optional connection for any desired additional equipment.
In a world where everything is documented to defend, reinforce, train, and track information, technologies with the ability to employ these methods are invaluable to present and future decontamination applications. The HHP system incorporates patented smart technology, allowing operation not only from a device interface but also remotely through its control app for phones and tablets (Figure 3). For larger spaces, multiple devices may simultaneously work together via wireless communication to combine their capacities to fill the larger volume without the added complications of cables. Whether used alone or in a network, the fogging device(s) self-calculates the dosage required for a space once dimensions are provided. For each disinfection cycle, a job report is wirelessly generated and saved into a secure data system, providing the facility with trackable records in support of risk management protocols. On-demand training, reference materials, and technical support are also available through this secure data storage system, which includes security codes, usernames, and password protection against unauthorized operation and modifications. These smart technology components give laboratory personnel the ability to remotely operate and monitor the system, lessening concerns affiliated with exposure to high concentrations of H2O2.
The HHP device offers the ability to decontaminate enclosed spaces as large as 14,000 ft3 (396 m3) by itself or wirelessly pair up to 25 devices together to treat spaces as large as 350,000 ft3 (9,911 m3) at once. Although the EPA approvals are for 3,682 ft3 (103 m3) due to the size limitation of the testing laboratory, efficacy of bacterial spores are documented in much larger spaces [41]. The small, compact design also reaches tall ceilings efficaciously, as noted in studies where 6-log10 reductions of
Since many life science facilities are made up of diversely sized spaces and needs, the next generation of Pulse technology device was developed. Retaining the core fogging unit’s design, the new attachment model offers the ability to fog, hand spray, or port in, all from the same unit. This fogging model can disinfect large open spaces with a hand sprayer (with proper personal protective equipment). The device can also port into enclosed spaces, such as labs or mobile equipment, with extension nozzles, or it can connect to various enclosures found within laboratories.
To enable decontamination of small enclosures, the HHP system pairs with a mobile cart designed to attach to biological safety cabinets, isolators, incubators, filters, and filter housings (Figure 4a) [42]. This modular pairing delivers low concentration H2O2 solution to the closed system environment, extracts vapor once decontamination has been achieved, and conditions the space to return it to its normal operating environment. No disassembly of lab equipment is required. The system achieves decontamination of the entire chamber, including filters, and contents. The rolling cart weighs approximately 50 pounds (22 kg) and includes a pullout tray to house the HHP fogging device. For scalable applications, the fogging device can fog a whole laboratory or be coupled to the mobile cart as needed for smaller enclosures.
The HHP system also enables integration with a laboratory or stand-alone chamber. This modular design allows for custom installation into facilities—including integrated nozzles and touchscreen operation—to provide decontamination to these essential spaces (Figure 4b). For facilities requiring unified operation of environmental or electronic controls, the HHP system works in tandem with smart integration technology to provide remote operation, automation, and mounted disinfection for one or more enclosed spaces at a time. Decontamination chamber or washer integration includes cycles of less than 120 minutes, including aeration. This chamber integration enables users to operate the entire chamber from one common point, the display screen. It is suitable for coupling with chambers from a variety of manufacturers.
During the 2020–2021 COVID-19 pandemic, the HHP system was approved by the EPA for use against SARS-CoV-2 through the Emerging Viral Pathogen designation due to its sporicidal efficacy [37]. As a result, the HHP system was used in many different environments as a tool for mitigating risk to personnel, research, and equipment. Healthcare facilities faced with shortages of personal protective equipment (PPE) employed the system to decontaminate and safely reuse PPE until the supply could be reestablished. Life science facilities incorporated the HHP system for decontaminating manufacturing spaces where vaccine work was taking place. The HHP system was also instrumental in multiple military applications, significantly aided by the portable design and accessible use. Some prior and ongoing uses include disinfection of manufacturing facilities with a need for sterilization, sterile processing facilities, drug manufacturing facilities, vivariums, laboratory contents, laboratories with interstitial spaces, laboratory filter housings, compounding pharmacies, surgical suites, healthcare patient rooms, ambulances, equipment for service providers, biological safety cabinets, isolator filters, and gnotobiotics.
Studies performed with Pulse technology demonstrate high-level pathogen disinfection across a variety of tested viruses, bacteria, and bacterial spores. The data presented here include a mixture of peer-reviewed studies, Good Laboratory Practice (GLP)-regulated testing, and real-world applications where disinfection can be further complicated by condition-dependent factors such as biofilms, soil loads, and surface type (porous/non-porous), all of which can protect and harbor infectious pathogens [13, 43]. Across the body of this work, the target of high-level disinfection is not only to reduce the present contamination, but to reduce it sufficiently to prevent an infectious dose or the potential for colony regrowth. The work presented here demonstrates the HHP system’s ability to decontaminate, destroying microbial pathogens. This complete decontamination is critical as any surviving pathogens have the potential to interfere with or invalidate research, contaminate sterile products, and cause health hazards.
When targeting pathogens invisible to the eye, there must be some way to measure the efficacy of disinfection. Employing validation tools gives the ability to verify a disinfection process using living organisms and giving results rooted in science. Though several types of chemical and pH indicators exist, indicators of
Recognizing a disinfectant’s ability to kill less susceptible pathogens as an indicator of broader effectiveness, the EPA offers a variety of specific designations a chemical or system can claim. In 2018, the HHP system was approved for sporicidal classification by the EPA for a 6-log10 reduction of
Norovirus, a single stranded non-enveloped virus of the Caliciviridae family, is a leading cause of acute gastroenteritis in humans. The most common genogroup GII is responsible for 95% of infections, which can have severe and even fatal outcomes in at-risk populations such as young children or the elderly. Norovirus, once present, can become a pervasive problem due to the environmental stability of the virus, low infectious dose, resistance to alcohol and chlorine-based disinfectants, and the potential for prolonged asymptomatic shedding of infected individuals. Norovirus is also used as a target organism for testing, as it is considered to be a non-enveloped virus with relatively low susceptibility to disinfectants [48].
In 2018, a 1,600-bed assisted living facility had a norovirus outbreak affecting 1/4 of the residents within a 2-week period with an average of 40 new cases a day, despite protective measures such as the quarantine of afflicted individuals. A bio-decontamination company employing HHP technology was brought into the facility for outbreak response and control. HHP fogging was implemented as part of a 5-point process including continued quarantine and enhanced staff education. After a four-day implementation period, no new cases were reported, effectively ending the outbreak [49].
The HHP system was also tested under GLP conditions for efficacy against the norovirus testing surrogate feline calicivirus [20]. In this testing, 21 inoculated glass agar carrier plates were placed throughout the test room, ranging from floor level to 12 feet (3.6 m) in height, and exposed to the HHP fogging protocols. There was no recovered virus from the challenged plates for an overall reduction of 7.6 log10 (Table 1). Interestingly, efficacious results were also noted in GLP compliant testing when a carrier plate lid was accidentally left on during the HHP fogging cycle. This protocol deviation allowed for the observation that, even under these challenging conditions, the HHP fog migrated underneath the lid and achieved inactivation of viral particles [20].
HHP Efficacy | ||||
---|---|---|---|---|
Pathogen [reference] | Characteristics | Strain/Source | Carrier Type | Results |
Gram-positive, rod-shaped, endospore formation | 19615 | Dacron suture loop Porcelain Penicylinders (50% Tyvek/Tyvek) | 75 of 77 carriers negative 5.2 log10 reduction (Penicylinder) 6.2 log10 reduction (suture) | |
Gram-positive, rod-shaped, endospore formation | 3584 | Dacron suture loop Porcelain Penicylinders (50% Tyvek/Tyvek) | 73 of 74 carriers negative 6.1 log10 reduction (Penicylinder) 6.3 log10 reduction (suture) | |
Gram-positive, rod-shaped, endospore formation | ATCC 7953 | Tyvek/Tyvek stainless steel coupon | 206 carriers negative 6.2 log10 reduction | |
Gram-positive, rod-shaped, endospore formation | ATCC 43598 | Stainless Steel Disk | 90 carriers negative 6.6 log10 reduction | |
Enveloped, icosahedral | phi 6 | Porous N95 Mask | 36 of 37 ≥ 6.0 log10 reduction* | |
Non-enveloped, icosahedral | Unknown | Wild type | 100% reduction of cases | |
Non-enveloped, icosahedral | Strain F-9, ATCC VF-782 | Glass Petri Dish | 40 of 40 plates ≥7.58 log10 reduction | |
Enveloped, icosahedral | Strain F | Porous N95 Mask | 64 of 65 ≥ 5 log10 reduction* | |
Non-enveloped (naked), icosahedral | Strain B3 | Porous N95 Mask | 6o of 63 ≥ 4.3 log10 reduction* | |
Enveloped, no icosahedral capsid | Isolate USA-WA1/2020 | Porous N95 Mask | 48 of 48 reduced below LOD |
The combination of these two studies demonstrates that the HHP system effectively disinfects complex spaces contaminated with norovirus or its surrogates in both laboratory and real-world conditions. Though the assisted living facility case study did not measure a numerical reduction of viral burden, the effective outbreak control of 100% reduction in new cases leads to the conclusion that norovirus was reduced to levels less than the infectious dose.
In the spring/summer of 2020, the COVID-19 pandemic triggered a scarcity, and subsequent shortage of personal protective equipment (PPE) used by hospitals and other healthcare facilities. In an attempt to find ways to mitigate this emergency, researchers at Pennsylvania State University (Penn State) employed HHP to disinfect expired N95 respirators to assess the applicability of the HHP system for this use. Respirators were tested both for any physical degradation effects of the treatment on the respirator material and for efficacy of disinfection of respirator components via inoculation with three viral pathogens and one bacteriophage. Viral work performed at the Eva J Pell Biosafety Level 3 laboratory at Penn State used viruses of different characteristics, as well as a bacteriophage, to represent the range of physical characteristics of pathogens to which healthcare workers may be exposed (Table 1) [19]. Three viruses: herpes simplex virus (HSV-1; enveloped virus; family Herpesviridae), coxsackievirus (CVB3; non-enveloped virus; family Picornaviridae), and SARS-CoV-2 (isolate USA-WA1/2020; enveloped virus; family Coronaviridae), as well as pseudomonas bacteriophage (phi6; enveloped), were chosen for testing (Figure 6). The inside, outside, and strap materials of the respirators were used as inoculation sites. While the majority of these surfaces are made up of porous materials, at least one type of respirator had an outer layer of hydrophobic material which caused the inoculation droplet to dry into a ‘coffee ring’ pattern on the respirator. This testing of porous materials is significant because it presents a more difficult challenge to disinfection than non-porous surfaces, since the materials which absorb the pathogen may also provide a degree of protection, at least temporarily [51]. Disinfectant efficacy testing is commonly done on non-porous surfaces, which does not reflect the difficulty and variables that porous surfaces present.
Testing performed at Penn State also included the use of biological indicators as validation of the protocol for a successful HHP cycle. For each HHP cycle, 6 to 12 biological indicators (
The EPA and the Centers for Disease Control and Prevention (CDC) recognize that certain microorganisms can be ranked with respect to their tolerance to chemical disinfectants [7]. As a result, efficacy against less susceptible bacterial spores can be extrapolated to indicate efficacy against more susceptible microorganisms, including enveloped and non-enveloped viruses [8, 9, 52].
To assess efficacy within various Biosafety Level 3 Agricultural (BSL-3Ag) environments, Kansas State University challenged the HHP system within their Biosecurity Research Institute, a BSL-3Ag facility. Testing was performed in three laboratories representing a range of sizes: 2,281 ft3 (65 m3), 4,668 ft3 (132 m3), and 44,212 ft3 (1,252 m3). Each of the two smaller laboratories were tested over a series of three disinfection cycles with biological indicators of
Within the largest space tested, the 44,212 ft3 (1,252 m3) necropsy laboratory, four HHP devices were used for the disinfection cycle. The smart technology of the HHP system automated the connection of multiple Pulse fogging devices for a synchronized, custom-calibrated, HHP cycle. A total of 206 biological indicators were tested over two HHP cycles in locations throughout the laboratory, including at the 21-ft (6.4 m) ceiling height, soft-sided anteroom, walk-in cooler, and change rooms. All 206 challenged indicators were negative for spore growth, demonstrating a greater than 6-log10 reduction of
The BMBL (6th edition) defines sterilization as; “a physical or chemical process that kills or inactivates all microbial life forms including highly resistant bacterial spores.” The importance of sterilization is well understood in life science, pharmaceutical, and healthcare industries. Through the process of sterilization, researchers and physicians alike establish the basis for reliable and safe protocols and procedures. Standards for fogging sterilization testing are developed by the Association of Official Analytical Chemists (AOAC International), a globally recognized, third party not-for-profit, that provides education and facilitates the development of test methods and standards.
The HHP system was challenged with the Fogging Devices Sterilant Test (OCSPP 810.2100) for efficacy against
Formaldehyde is a naturally occurring compound consisting of hydrogen, oxygen, and carbon which is used as a disinfectant in both its liquid and gaseous states [55]. Used as a laboratory fumigant since the late 19th century, formaldehyde has remained in use due to its efficacy and low cost [56, 57]. For use as a disinfectant, formalin, the aqueous form of formaldehyde, is heated into a vapor producing formaldehyde gas [58]. When encountering microbes, this gas causes a cross-linking of molecules leading to protein clumping and loss of structure [59]. While an effective sterilant, formaldehyde must be handled with extreme care as exposure can cause asthma-like respiratory problems, cancer, or even be fatal to humans [55]. In gaseous form, formaldehyde is used at 8,000–10,000 ppm concentration and leaves behind a residue which must be removed through manual cleaning [56, 60]. Due to the potential health hazards and the required labor-intensive clean-up of residue, formaldehyde use is declining in favor of less hazardous and faster solutions. Indeed, the European Union lists formaldehyde as a substance of very high concern and has issued regulation calling for the progressive substitution when suitable alternatives have been identified [61]. While generally compatible with laboratory materials, formaldehyde can be absorbed into porous materials such as HEPA filters, off-gassing slowly and extending the time needed for safe re-entry [56, 62]. Formaldehyde production equipment ranges from as small as an electric fry pan requiring timers or externally controlled circuits to larger automated devices roughly the size of a household refrigerator and weighing approximately 396 pounds (180 kg) [63].
Chlorine dioxide (ClO2) is a synthetic, green-colored gas that gives off a bleach-like odor. Despite the familiar scent, chlorine dioxide gas is toxic and must be carefully contained when employed as a fumigant [64]. Consisting of unstable chlorine (Cl2) and oxygen molecules (O2), ClO2 disassociates when heated into chloride (Cl-), chlorite (ClO-) and chlorate ions (ClO3-). Some formulations can leave residues of sodium chlorite or inert salts, such as sodium chloride, on surfaces [65]. The disinfection cycle for ClO2 commonly consists of five steps: pre-conditioning, conditioning, charge (gas injection), exposure (contact time), and aeration [66]. The cycle is humidity-dependent, requiring a dosage increase of approximately 500 ppm for each 10% change in humidity, leading to an operating concentration range of 600–1550 ppm [66]. Similar to formaldehyde, ClO2 can be absorbed into porous surfaces and thus take longer to aerate than non-porous materials [65]. One consideration for system use is material compatibility with laboratory equipment. Some device manufacturers recommend that the ClO2-generating equipment remain outside the space being disinfected to prevent repeated exposure [34]. Instable in solution, chlorine dioxide must be mixed on-site by laboratory personnel. The effectiveness of ClO2 in penetrating treated spaces may also cause concern for personnel safety, as it can migrate out of seemingly enclosed spaces [38, 40]. As a result, facilities employing ClO2 systems must carefully monitor the disinfection cycle to ensure safety [64]. Roughly the size of an office bookcase and weighing approximately 230 pounds (104 kg), one system can treat up to 70,000 ft3 (2,000 m3) which may maximize the treatment space per device compared to other systems. ClO2 can also be dispensed from smaller devices which fit into a biological safety cabinet to treat that equipment [67, 68].
High concentration H2O2 devices are roughly the size of a medium file cabinet, wheeled around facilities on four castors and can be very heavy, weighing up to 500 pounds (227 kg). They are operated via touchscreen displays and the range of treatment area is between 8,800 to 20,000 ft3 (249 to 566 m3), depending on the device. One system can connect up to 10 devices via ethernet cables linking one device to another and enabling the treatment of larger spaces. Validation of these vaporous systems is determined using chemical and biological indicators, often
High concentration vaporous H2O2 systems traditionally employ a 35–59% H2O2 liquid solution, heated to a vaporous state [29]. These chemicals must be handled with care, since human contact with the liquid or vapor can be harmful and has been known to result in second- and third-degree burns [29, 30, 31]. Once heated, these chemicals are delivered to the treatment space, where vapor concentrations can reach peak levels of up to 1,400 ppm H2O2 [36], often necessitating precise operating conditions and continuous monitoring of the treatment cycle by the operator(s). A myriad of sensors precisely measures peak concentrations and these aid in delivering a specific combination of conditions to result in efficacy. These systems can be highly complex, accompanied by user manuals nearing a hundred pages of instructions. The four-part fogging process—dehumidification, conditioning, decontamination, and aeration—may require a technician to be present during the entire cycle of several hours [34, 69]. One reason for this vigilant monitoring may be to respond quickly should the system over or under deliver the high concentrations of H2O2 required. Another reason for persistent oversight may be a valid fear of escaped H2O2 vapor, which could migrate out of the treated space at high concentrations and affect personnel [38, 40].
Chemical solutions, even within the range of H2O2 technologies, differ not only in concentration, but also in their formulation. Some available H2O2 solutions contain additional active ingredients, such as the heavy metal silver nitrate [70]. Although silver has a long history of use in wound care, it is also known to cause a permanent retention of silver once in the body [71]. Silver ions are one of the most toxic known forms of heavy metal [70]. Accidental ingestion of these invisible silver residues can cause problems for the microbiome of the human digestive system, since these metals lack the ability to differentiate beneficial bacteria from pathogenic bacteria [72]. Silver persists not only in the body, but also in the environment, where it remains toxic and can be lethal to organisms [70]. As a result of a growing understanding of these unintended negative consequences, the use of silver for disinfection is regulated by the European Union (BPR, Regulation (EU) 528/2012) which states that “It may unnecessarily expose humans, animals and the environment to biocidal active substance, generate health and/or environmental risks and impacts, and may also contribute to the development of resistance to biocides leading to other health and/or environmental issues” [73]. Likewise the EPA acknowledges the potential health hazards related to exposure to silver, and has issued cautionary documents to this effect [74]. Due to the high level of potential exposure during residue cleanup, and the resulting inhalation or dermal absorption of this heavy metal, proper protocols and control should be always employed [74]. Devices for aerosolizing H2O2 with silver vary in size from toolbox-sized fixed systems in mobile transportation to large, stand-alone portable systems. Some of these systems spray in a mist, while others use a more wet delivery method which may impede the generation of floating aerosols [75].
There are several key elements to consider when deciding on a decontamination system. An ideal anti-microbial disinfectant should have the following characteristics: (1) is destructive to the greatest variety of pathogens, including bacterial spores, bacteria, viruses, molds, and fungi; (2) minimizes risks to personnel; (3) is non-corrosive and compatible with materials under normal application conditions; (4) is easy to implement; (5) imparts no harmful residue to the laboratory space or equipment; and (6) provides affordable decontamination. When comparing various disinfection systems, consider the most pertinent aspects below:
First and foremost, it is important for the system to not only be efficacious against more susceptible organisms, but efficacious against less susceptible organisms to the degree necessary to confidently implement the system as a regular component of the research cycle. Commensurate with the definitions of disinfection and decontamination [1], disinfection inactivates pathogens, while decontamination goes to the further degree of inactivating and denaturing them. In industries where pathogen-free environments form the foundational block for successful research, only decontamination will suffice. A detail-conscious manager should not only look for a decontaminant but select one which can demonstrate proof of efficacy with both porous and non-porous surfaces, most accurately representing the array found within life science sectors. Further supporting efficacy, laboratories should be able to validate their chosen system using biological indicators in adherence to international standards [44]. In support of risk management, the system should enable validation of sterilization through a 6-log10 sporicidal reduction that can be tracked and recorded [2]. With only the most efficacious systems under consideration, facility managers should evaluate each system’s impact on personnel safety, ideal laboratory operation, equipment material compatibility, and integrity of research.
Even more important than the safety of materials is the safety of personnel, which should be a top priority when implementing a decontamination system. Safety should be considered from the perspective of normal operation as well as in the event of an accidental exposure. Under normal conditions, devices which can be operated remotely create a layer of isolation between the decontamination system and the human operator, allowing for implementation without direct contact for personnel. In the unlikely event of an accidental exposure, higher concentration solutions may come with risks for exposure to high-consequence chemicals either from contact or inhalation [39]. Choosing a product with lower operating concentrations may likewise decrease the potential for risks associated with accidental exposure caused by unintended fog leakage [38, 40]. As with most gaseous systems, the Occupational Safety and Health Administration (OSHA) has defined a minimum reoccupation level, Permissible Exposure Limit (PEL), which must be considered: ClO2 = 0.1 ppm; H2O2 = 1 ppm; and formaldehyde = 0.75 ppm. Technologies employing lower operational ppm may reach reoccupation levels more quickly due to a lower peak threshold [15, 16, 76].
Decontamination within facilities is a recurring need, so both the physical devices as well as the chemicals or solutions used in them should be reviewed for the consequences of regular use. Devices with instructions requiring the operating machinery to remain outside of the room being disinfected may call into question the safety of exposed laboratory equipment within this space [34]. Likewise, systems with operating concentrations that can condense at levels beyond known material compatibility, such as 45% hydrogen peroxide, may also damage laboratory equipment [33].
Decision makers should critically examine the number of parts necessary for implementing a system. Multiple components may appear to create value but instead may only introduce complication and risks. Hosing laying on the floor add contamination risk in two ways: (1) hoses may impede a complete disinfection of any surfaces they touch and (2) those same hoses may contribute to cross contamination as they are moved throughout the facility. Additionally, a system with many components also comes with many opportunities to misplace or damage a critical element, potentially disrupting scheduled disinfection cycles. Quality and durability of the equipment is paramount as well.
While not strictly required, the degree of support available also contributes to the ease of use of a system. Whether creating new protocols, training personnel, or troubleshooting unique challenges, ensuring there is a commitment from the vendor to provide support can mean the difference between a quick phone call or time spent deciphering a 100-page manual.
Besides providing ease of use, the optimal disinfectant will also be free of byproducts which can leave precipitates or residues behind on the treated surfaces, or damage those surfaces [56, 65, 73, 74]. Additives such as metals are often marketed as beneficial catalysts, yet any benefit imparted can be overshadowed by what is left behind. Any disinfection system should benefit the facility by controlling contaminants, rather than introducing them to sensitive laboratory environments. It is essential for the integrity of research that no residual components be left in a space perceived sterile which can interfere with, invalidate, or otherwise impact the scientific work taking place.
As cost-cutting measures within laboratory spaces continue to be important, one way to save money is to choose a system that can readily be operated in-house by personnel who feel safe doing so. Outsourcing can be associated with significantly higher costs. Systems that are safer, scalable, trackable, easy to use, and modular can be employed for more than one application, resulting in even more cost savings.
When striving to meet strict viral disinfection requirements yet achieve balance with ease of use, timeliness, and safety requirements, facility managers should assess the disinfection needs of individual laboratory environments and the facility as a whole. Ideal disinfection systems should include technologies that have the ability to achieve validated decontamination with the lowest risk to equipment and personnel. We believe that the Hybrid Hydrogen Peroxide system introduced and discussed in detail here merits consideration as a versatile tool for viral disinfection. Pulse technology provides an unexpected efficacy with a 7% H2O2 solution equaling the best commercially available high-concentration H2O2 systems. The simplicity of one portable device with optional accessories and integration capabilities offers intriguing possibilities for reaching and decontaminating viral pathogens that may be found in the myriad of spaces within laboratory environments. Although conceived with sterilization efficacy in mind, its simplicity of use and safer operation enabled widespread adoption into multiple markets such as education and the military, with applicators ranging from entry level technicians to experienced personnel. As research continues to venture into unknown territories, awareness of potential viral threats has increased as well. Current adoption into the life sciences field is robust and underscores the value which can be added through implementing a targeted yet versatile system for facility decontamination. This chapter provides encouragement that innovations in disinfection technology, such as the HHP system, continue to keep pace with these viral threats with fact-based, science-driven results.
The authors would like to thank Jodi Woodson and Alyssa DeLotte for their invaluable contributions to this chapter.
Ove Odredbe i uvjeti ističu pravila i regulacije u svezi korištenja IntechOpenove stranice www.intechopen.com i svih poddomena u vlasništvu IntechOpena, tvrtke sa sjedištem u 5 Princes Gate Court, London, SW7 2QJ, Ujedinjeno Kraljevstvo.
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\\n\\nSljedeća terminologija odnosi se na Odredbe i uvjete, te na sve naše ugovore:
\\n\\nKlijent, stranka, vi, vaš odnosi se na vas, osobu koja pristupa ovoj stranici i prihvaća IntechOpenove Odredbe i uvjete;
\\n\\nKompanija, tvrtka, mi, naše odnosi se na tvrtku IntechOpen;
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\\n\\nMi koristimo kolačiće. Korištenjem IntechOpenove stranice slažete se s korištenjem kolačića u skladu s IntechOpenovom Politikom privatnosti. Većina modernih, interaktivnih stranica koristi kolačiće kako bi omogućila ponovno pronalaženje korisničkih detalja kod svakog posjeta. Na našoj stranici kolačići se uglavnom koriste kako bi omogućili funkcionalnost i olakšali posjetiteljima korištenje stranice.
\\n\\nIntechOpen ili njegovi suradnici niti u jednom slučaju neće biti odgovorni za štete (štete uključuju gubitak podataka ili profita, druge poslovne prekide, te sve ostale štete) koje nastanu zbog korištenja materijala na IntechOpenovoj stranici ili nemogućnosti da se iste koriste, čak i ako je IntechOpen ili njegov predstavnik o takvoj šteti obaviješten pismenim ili usmenim putem. Neke jurisdikcije ne dozvoljavaju ograničenja garancija ili ograničenja obveza za posljedične ili slučajne štete pa se u tom slučaju ova ograničenja možda ne odnose na vas.
\\n\\nMaterijali koji se pojavljuju na IntechOpenovoj stranici mogu sadržavati manje greške, tipfelere ili fotografske greške. IntechOpen može napraviti promjene na bilo kojem materijalu koji se nalazi na stranici u bilo koje vrijeme.
\\n\\nIntechOpen nije formalno povezan niti s jednom vanjskom stranicom čije poveznice vode na www.intechopen.com, osim ako to nije izravno navedeno. Iz tog razloga IntechOpen nije odgovoran za sadržaj koji se pojavljuje na takvim stranicama. Poveznica na IntechOpenovu stranicu ne implicira povezanost sa IntechOpenom. Korištenje takvih poveznica isključiva je odgovornost korisnika.
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\\n\\nIntechOpen može ove Odredbe izmijeniti u bilo koje vrijeme i bez prethodne obavijesti. Koristeći ovu stranicu vi se slažete s trenutnim Odredbama i uvjetima koje su na snazi.
\\n\\nOve Odredbe i uvjeti su sastavljeni u skladu s odredbama prava Ujedinjenog Kraljevstva, a za sve sporove nadležan je sud u Londonu, Ujedinjeno Kraljevstvo.
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\n\nSljedeća terminologija odnosi se na Odredbe i uvjete, te na sve naše ugovore:
\n\nKlijent, stranka, vi, vaš odnosi se na vas, osobu koja pristupa ovoj stranici i prihvaća IntechOpenove Odredbe i uvjete;
\n\nKompanija, tvrtka, mi, naše odnosi se na tvrtku IntechOpen;
\n\nStranke, strane odnosi se na klijenta i na nas, ili samo na klijenta ili nas.
\n\nSve odredbe koje se odnose na ponudu, prihvat ili razmatranje plaćanja, a za koja mi pružamo asistenciju klijentu, bilo na ugovoreni ili fiksni način, a s ciljem da se ostvare potrebe i želje klijenta u svezi s našim uslugama, su podložne zakonskim odredbama Ujedinjenog Kraljevstva.
\n\nOsim ako nije suprotno navedeno, IntechOpen i/ili svi davatelji licence vlasnici su intelektualnog vlasništva nad svim materijalima na www.intechopen.com. Sva prava intelektualnog vlasništva su pridržana. Stranice sa www.intechopen.com možete gledati, preuzimati, dijeliti, dijeliti poveznice i printati za osobnu uporabu, a temeljem pravila sadržanih u ovim Odredbama i uvjetima.
\n\nMi koristimo kolačiće. Korištenjem IntechOpenove stranice slažete se s korištenjem kolačića u skladu s IntechOpenovom Politikom privatnosti. Većina modernih, interaktivnih stranica koristi kolačiće kako bi omogućila ponovno pronalaženje korisničkih detalja kod svakog posjeta. Na našoj stranici kolačići se uglavnom koriste kako bi omogućili funkcionalnost i olakšali posjetiteljima korištenje stranice.
\n\nIntechOpen ili njegovi suradnici niti u jednom slučaju neće biti odgovorni za štete (štete uključuju gubitak podataka ili profita, druge poslovne prekide, te sve ostale štete) koje nastanu zbog korištenja materijala na IntechOpenovoj stranici ili nemogućnosti da se iste koriste, čak i ako je IntechOpen ili njegov predstavnik o takvoj šteti obaviješten pismenim ili usmenim putem. Neke jurisdikcije ne dozvoljavaju ograničenja garancija ili ograničenja obveza za posljedične ili slučajne štete pa se u tom slučaju ova ograničenja možda ne odnose na vas.
\n\nMaterijali koji se pojavljuju na IntechOpenovoj stranici mogu sadržavati manje greške, tipfelere ili fotografske greške. IntechOpen može napraviti promjene na bilo kojem materijalu koji se nalazi na stranici u bilo koje vrijeme.
\n\nIntechOpen nije formalno povezan niti s jednom vanjskom stranicom čije poveznice vode na www.intechopen.com, osim ako to nije izravno navedeno. Iz tog razloga IntechOpen nije odgovoran za sadržaj koji se pojavljuje na takvim stranicama. Poveznica na IntechOpenovu stranicu ne implicira povezanost sa IntechOpenom. Korištenje takvih poveznica isključiva je odgovornost korisnika.
\n\nZadržavamo pravo vlasništva nad cjelokupnom stranicom www.intechopen.com i nad svim materijalom na toj stranici. Koristeći se našim uslugama, slažete se da maknete sve poveznice na našu stranicu odmah nakon što to od vas zatražimo. Također, zadržavamo pravo da ove Odredbe i uvjete, i politiku o poveznicama izmjenimo u bilo koje vrijeme. Koristeći se poveznicama na naše stranice slažete se s ovim Odredbama i uvjetima.
\n\nAko smatrate da je bilo koja poveznica na našoj stranici sumnjiva iz bilo kojeg razloga, molimo vas da nas kontaktirate. U tom slučaju razmotrit ćemo micanje poveznice s naše stranice, iako nismo obvezni to napraviti.
\n\nBez prethodne privole i izričite pisane dozvole, ne možete stvarati okvire oko naših stranica ili koristiti druge tehnike koje na bilo koji način mogu promijeniti prezentaciju ili izgled naše stranice.
\n\nIntechOpen može ove Odredbe izmijeniti u bilo koje vrijeme i bez prethodne obavijesti. Koristeći ovu stranicu vi se slažete s trenutnim Odredbama i uvjetima koje su na snazi.
\n\nOve Odredbe i uvjeti su sastavljeni u skladu s odredbama prava Ujedinjenog Kraljevstva, a za sve sporove nadležan je sud u Londonu, Ujedinjeno Kraljevstvo.
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MS pathogenesis is not clear. Destruction of myelin by inflammation caused by autoimmune reactions has been proposed. Interestingly, healthy humans usually do not develop abzymes (Abzs). It was shown that DNase and MBP-hydrolyzing Abzs are easily detectable at the beginning of autoimmune diseases (ADs) including MS, when concentrations of antibodies to autoantigens are not yet significantly increased and correspond to levels in healthy donors. In addition, the relative enzymatic activity of antibodies from cerebrospinal fluid (CSF) is ~50-fold higher than that from the sera of the same MS patients. Experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice, a model mimicking relevant aspects of human MS was used. During development of spontaneous and MOG35-55-induced EAE in C57BL/6 mice, a specific reorganization of the immune system of mice was observed. It leads to a condition which was associated with the generation of catalytically active IgGs-hydrolyzing DNA, myelin basic protein (MBP), and MOG. Production of Abzs was associated with increased proteinuria, leading changes in differentiation of mice bone marrow hematopoietic stem cells (HSCs) and an increase in proliferation of lymphocytes in bone marrow, spleen, and thymus as well as a significant suppression of cell apoptosis in these organs. Treatment of control non-autoimmune CBA mice with MOG led to the different differentiation and proliferation of HSCs comparing with EAE C57BL/6 mice. The treatment of EAE mice with cuprizone inducing demyelination lead to a significant decrease in the size of the brain corpus callosum, but do not significantly change the differentiation profile of HSCs differentiation when compared with untreated mice. It indicates that cuprizone treatment is associated with demyelination, but not autoimmune reactivity. The possible differences in immune system reorganizations during preclinical phases of the disease, acute and late EAE, leading to production of different autoantibodies and Abzs as well other changes are discussed.",book:{id:"5156",slug:"trending-topics-in-multiple-sclerosis",title:"Trending Topics in Multiple Sclerosis",fullTitle:"Trending Topics in Multiple Sclerosis"},signatures:"Georgy A. Nevinsky",authors:[{id:"47119",title:"Dr.",name:"Georgy",middleName:null,surname:"Nevinsky",slug:"georgy-nevinsky",fullName:"Georgy Nevinsky"}]},{id:"21744",doi:"10.5772/19010",title:"Hallmarks in the History of Epilepsy: From Antiquity Till the Twentieth Century",slug:"hallmarks-in-the-history-of-epilepsy-from-antiquity-till-the-twentieth-century",totalDownloads:9305,totalCrossrefCites:6,totalDimensionsCites:27,abstract:null,book:{id:"627",slug:"novel-aspects-on-epilepsy",title:"Novel Aspects on Epilepsy",fullTitle:"Novel Aspects on Epilepsy"},signatures:"Emmanouil Magiorkinis, Kalliopi Sidiropoulou and Aristidis Diamantis",authors:[{id:"33300",title:"Dr.",name:"Emmanouil",middleName:null,surname:"Magiorkinis",slug:"emmanouil-magiorkinis",fullName:"Emmanouil Magiorkinis"},{id:"33563",title:"Ms.",name:"Kalliopi",middleName:null,surname:"Sidiropoulou",slug:"kalliopi-sidiropoulou",fullName:"Kalliopi Sidiropoulou"},{id:"33564",title:"Dr.",name:"Aristidis",middleName:null,surname:"Diamantis",slug:"aristidis-diamantis",fullName:"Aristidis Diamantis"}]},{id:"24857",doi:"10.5772/28930",title:"Hormonal Signaling Systems of the Brain in Diabetes Mellitus",slug:"hormonal-signaling-systems-of-the-brain-in-diabetes-mellitus",totalDownloads:1993,totalCrossrefCites:3,totalDimensionsCites:25,abstract:null,book:{id:"745",slug:"neurodegenerative-diseases-processes-prevention-protection-and-monitoring",title:"Neurodegenerative Diseases",fullTitle:"Neurodegenerative Diseases - Processes, Prevention, Protection and Monitoring"},signatures:"Alexander Shpakov, Oksana Chistyakova, Kira Derkach and Vera Bondareva",authors:[{id:"75886",title:"Dr",name:"Vera",middleName:null,surname:"Bondareva",slug:"vera-bondareva",fullName:"Vera Bondareva"},{id:"75888",title:"Dr.",name:"Alexander",middleName:null,surname:"Shpakov",slug:"alexander-shpakov",fullName:"Alexander Shpakov"},{id:"81684",title:"Dr",name:"Oksana",middleName:null,surname:"Chistyakova",slug:"oksana-chistyakova",fullName:"Oksana Chistyakova"},{id:"81685",title:"Dr.",name:"Kira",middleName:null,surname:"Derkach",slug:"kira-derkach",fullName:"Kira Derkach"}]},{id:"19739",doi:"10.5772/18469",title:"Antiepileptic Medicinal Plants used in Traditional Medicine to Treat Epilepsy",slug:"antiepileptic-medicinal-plants-used-in-traditional-medicine-to-treat-epilepsy",totalDownloads:9699,totalCrossrefCites:7,totalDimensionsCites:23,abstract:null,book:{id:"628",slug:"clinical-and-genetic-aspects-of-epilepsy",title:"Clinical and Genetic Aspects of Epilepsy",fullTitle:"Clinical and Genetic Aspects of Epilepsy"},signatures:"E. Ngo Bum, G.S. Taiwe, F.C.O. Moto, G.T. Ngoupaye, R.R.N. Vougat, V.D. Sakoue, C. Gwa, E.R. Ayissi, C. Dong, A. Rakotonirina and S.V. Rakotonirina",authors:[{id:"31580",title:"Prof.",name:"Elisabeth",middleName:null,surname:"Ngo Bum",slug:"elisabeth-ngo-bum",fullName:"Elisabeth Ngo Bum"},{id:"46671",title:"Dr.",name:"Germain",middleName:"Sotoing",surname:"Taïwe",slug:"germain-taiwe",fullName:"Germain Taïwe"},{id:"46672",title:"MSc.",name:"Fleur",middleName:null,surname:"Moto",slug:"fleur-moto",fullName:"Fleur Moto"},{id:"46673",title:"Prof.",name:"Gwladys",middleName:"Temkou",surname:"Ngoupaye",slug:"gwladys-ngoupaye",fullName:"Gwladys Ngoupaye"},{id:"46674",title:"MSc.",name:"Espoir",middleName:null,surname:"Ayissi",slug:"espoir-ayissi",fullName:"Espoir Ayissi"},{id:"46675",title:"MSc.",name:"Christian",middleName:null,surname:"Dong",slug:"christian-dong",fullName:"Christian Dong"},{id:"46676",title:"MSc.",name:"Frédéric",middleName:null,surname:"Maidawa",slug:"frederic-maidawa",fullName:"Frédéric Maidawa"},{id:"46677",title:"MSc.",name:"Gildas",middleName:null,surname:"Djafsia",slug:"gildas-djafsia",fullName:"Gildas Djafsia"},{id:"46678",title:"MSc.",name:"Leopold",middleName:null,surname:"Nanga",slug:"leopold-nanga",fullName:"Leopold Nanga"},{id:"46679",title:"MSc.",name:"Saleh",middleName:null,surname:"Soudi",slug:"saleh-soudi",fullName:"Saleh Soudi"},{id:"46680",title:"Dr.",name:"Alice",middleName:null,surname:"Rakotonirina",slug:"alice-rakotonirina",fullName:"Alice Rakotonirina"},{id:"46681",title:"Dr.",name:"Silvère",middleName:null,surname:"Rakotonirina",slug:"silvere-rakotonirina",fullName:"Silvère Rakotonirina"}]},{id:"44560",doi:"10.5772/54744",title:"The Role of Epigenetics in Neurodegenerative Diseases",slug:"the-role-of-epigenetics-in-neurodegenerative-diseases",totalDownloads:4012,totalCrossrefCites:10,totalDimensionsCites:18,abstract:null,book:{id:"3278",slug:"neurodegenerative-diseases",title:"Neurodegenerative Diseases",fullTitle:"Neurodegenerative Diseases"},signatures:"Luca Lovrečić, Aleš Maver, Maja Zadel and Borut Peterlin",authors:[{id:"75615",title:"Dr.",name:"Luca",middleName:null,surname:"Lovrecic",slug:"luca-lovrecic",fullName:"Luca Lovrecic"}]}],mostDownloadedChaptersLast30Days:[{id:"44555",title:"Pharmacological Treatment of Acute Ischemic Stroke",slug:"pharmacological-treatment-of-acute-ischemic-stroke",totalDownloads:3670,totalCrossrefCites:6,totalDimensionsCites:9,abstract:null,book:{id:"3278",slug:"neurodegenerative-diseases",title:"Neurodegenerative Diseases",fullTitle:"Neurodegenerative Diseases"},signatures:"Humberto Mestre, Yael Cohen-Minian, Daniel Zajarias-Fainsod and\nAntonio Ibarra",authors:[{id:"72488",title:"Dr.",name:"José Juan Antonio",middleName:null,surname:"Ibarra Arias",slug:"jose-juan-antonio-ibarra-arias",fullName:"José Juan Antonio Ibarra Arias"},{id:"120571",title:"Mr.",name:"Humberto",middleName:null,surname:"Mestre",slug:"humberto-mestre",fullName:"Humberto Mestre"},{id:"165904",title:"Dr.",name:"Daniel",middleName:null,surname:"Zajarias-Fainsod",slug:"daniel-zajarias-fainsod",fullName:"Daniel Zajarias-Fainsod"},{id:"165905",title:"Mrs.",name:"Yael",middleName:null,surname:"Cohen-Minian",slug:"yael-cohen-minian",fullName:"Yael Cohen-Minian"}]},{id:"60608",title:"Mucuna and Parkinson’s Disease: Treatment with Natural Levodopa",slug:"mucuna-and-parkinson-s-disease-treatment-with-natural-levodopa",totalDownloads:4661,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"Mucuna pruriens is a tropical bean containing large amounts of levodopa and is the most important natural remedy for Parkinson’s disease. Famous neurologists have patented methods of extraction for its advantages over the synthetic forms, Sinemet and Madopar. This natural levodopa is less toxic and has a faster and more lasting effect and can delay the need for pharmaceuticals and combination therapies. Currently, there are many patients with Parkinson’s disease who take Mucuna and spontaneously reduce the dose of conventional drugs and do so behind their doctors’ backs. Mucuna should always be taken under medical supervision.",book:{id:"6406",slug:"parkinson-s-disease-understanding-pathophysiology-and-developing-therapeutic-strategies",title:"Parkinson's Disease",fullTitle:"Parkinson's Disease - Understanding Pathophysiology and Developing Therapeutic Strategies"},signatures:"Rafael González Maldonado",authors:[{id:"214658",title:"Dr.",name:"Rafael",middleName:null,surname:"Gonzalez-Maldonado",slug:"rafael-gonzalez-maldonado",fullName:"Rafael Gonzalez-Maldonado"}]},{id:"19700",title:"Physiotherapy for Children with Cerebral Palsy",slug:"physiotherapy-for-children-with-cerebral-palsy",totalDownloads:21769,totalCrossrefCites:1,totalDimensionsCites:3,abstract:null,book:{id:"630",slug:"epilepsy-in-children-clinical-and-social-aspects",title:"Epilepsy in Children",fullTitle:"Epilepsy in Children - Clinical and Social Aspects"},signatures:"Mintaze Kerem Günel",authors:[{id:"38412",title:"Prof.",name:"Mintaze",middleName:null,surname:"Kerem Günel",slug:"mintaze-kerem-gunel",fullName:"Mintaze Kerem Günel"}]},{id:"51151",title:"Association Between Multiple Sclerosis Risk and Human Immunodeficiency Virus Infection: Insights and Challenges",slug:"association-between-multiple-sclerosis-risk-and-human-immunodeficiency-virus-infection-insights-and-",totalDownloads:2044,totalCrossrefCites:0,totalDimensionsCites:1,abstract:"Multiple sclerosis (MS) is a convoluted autoimmune and inflammatory disease of the central nervous system (CNS) in which the protective myelin sheath is eroded and the underlying nerve fibers are damaged. There is no conclusive knowledge on the role played by different etiological factors in its development, and studies have shown that it primarily results due to complex interactions between the genetic, geographic and infectious components. Among the risk factors reported to have a possible role in MS development, retroviruses also appear to influence it. Studies suggest human immunodeficiency virus (HIV) infection to be inversely related to MS risk, but to date, the association between the two remains enigmatic. This protective inverse association has become an area of active research and the most plausible explanations for this may be immune suppression and/or antiretroviral medications. The purpose of writing this chapter is to provide background information on the unfathomable relationship between HIV infection and the risk of developing MS while at the same time providing description of the insights garnered from recent studies. While highlighting the application of ART (antiretroviral therapy) as budding future alternative for MS management, this chapter provides momentum for further studies.",book:{id:"5156",slug:"trending-topics-in-multiple-sclerosis",title:"Trending Topics in Multiple Sclerosis",fullTitle:"Trending Topics in Multiple Sclerosis"},signatures:"Ehtishamul Haq, Insha Zahoor and Mushfiquddin Khan",authors:[{id:"181077",title:"Dr.",name:"Ehtishamul",middleName:null,surname:"Haq",slug:"ehtishamul-haq",fullName:"Ehtishamul Haq"},{id:"185233",title:"Dr.",name:"Insha",middleName:null,surname:"Zahoor",slug:"insha-zahoor",fullName:"Insha Zahoor"},{id:"185234",title:"Dr.",name:"Mushfiquddin",middleName:null,surname:"Khan",slug:"mushfiquddin-khan",fullName:"Mushfiquddin Khan"}]},{id:"63824",title:"Plasmapheresis in Treatment of Myasthenia Gravis",slug:"plasmapheresis-in-treatment-of-myasthenia-gravis",totalDownloads:1349,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"Treatment of myasthenia gravis is still a rather difficult task, since there is no single tactic to use different drugs (corticosteroids, rituximab, immunoglobulins), especially since it is associated with a number of side effects. They are not able to remove the accumulating autoantibodies and immune complexes, the large size of which does not allow them to be excreted by the kidneys as well. Special problems of treatment arise when myasthenic crises develop associated with respiratory failure requiring artificial lungs ventilation. Plasmapheresis can help to solve this for it is possible to remove antibodies and other pathological metabolites. In addition, regular plasmapheresis is able not only to prevent exacerbations but also to reduce doses of the maintenance therapy with less risk of their side effects, which is confirmed by our own experience.",book:{id:"7160",slug:"selected-topics-in-myasthenia-gravis",title:"Selected Topics in Myasthenia Gravis",fullTitle:"Selected Topics in Myasthenia Gravis"},signatures:"Valerii Voinov",authors:null}],onlineFirstChaptersFilter:{topicId:"1056",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"81721",title:"Atrial Fibrillation and Stroke",slug:"atrial-fibrillation-and-stroke",totalDownloads:5,totalDimensionsCites:0,doi:"10.5772/intechopen.104619",abstract:"Atrial fibrillation (AF) represents a major cause of morbidity and mortality in adults, especially for its strong association with thromboembolism and stroke. In this chapter, we aim to provide an overview on this cardiac arrhythmia, addressing several important questions. Particularly, we faced the possible mechanisms leading to an increased risk of embolism in AF, emphasizing how Virchow’s triad for thrombogenesis is unable to fully explain this risk. Disentangling the risk of stroke caused by AF and by other associated vascular conditions is extremely challenging, and risk stratification of patients with AF into those at high and low risk of thromboembolism has become a crucial determinant of optimal antithrombotic prophylaxis. Moreover, we discuss the typical clinical and radiological characteristics of cardioembolic strokes, addressing acute, time-dependent reperfusional therapies in case of ischemic stroke. The role of anticoagulation in AF is also fully analyzed; the benefit of oral anticoagulation generally outweighs the risk of bleeding in AF patients, and a variety of scoring systems have been developed to improve clinical decision-making when initiating anticoagulation. With their predictable pharmacokinetic profiles, wide therapeutic windows, fewer drug–drug and drug-food interactions, and the non-vitamin K antagonist (VKA) oral anticoagulants (NOACs) have changed the landscape of thromboprophylaxis for AF patients, offering the opportunity to use effective anticoagulants without the need for intensive therapeutic drug monitoring.",book:{id:"10782",title:"Cerebrovascular Diseases - Elucidating Key Principles",coverURL:"https://cdn.intechopen.com/books/images_new/10782.jpg"},signatures:"Francesca Spagnolo, Vincenza Pinto and Augusto Maria Rini"},{id:"81639",title:"Atrial Cardiopathy and Cryptogenic Stroke",slug:"atrial-cardiopathy-and-cryptogenic-stroke",totalDownloads:24,totalDimensionsCites:0,doi:"10.5772/intechopen.103736",abstract:"Cryptogenic stroke (CS) is defined as the presence of cerebral infarcts, the cause which has not been identified despite an appropriate diagnostic evaluation, and it accounts for approximately 30–40% of all ischemic strokes. There is a certain subgroup of CS with embolic characteristics on neuroimaging studies and no evidence of atrial fibrillation alternative or any alternative cause. Recent data suggest that disorders of the atrium, even without atrial fibrillation, could increase thromboembolic risk. The pathological atrial substrate, or atrial cardiopathy (AC), may be an important and underrecognized cause of cryptogenic strokes. This chapter will review the information on the rationale and data behind the concept of atrial cardiopathy, its pathophysiology, proposed biomarkers of atrial cardiopathy, and therapeutic implications.",book:{id:"10782",title:"Cerebrovascular Diseases - Elucidating Key Principles",coverURL:"https://cdn.intechopen.com/books/images_new/10782.jpg"},signatures:"Marianela López Armaretti, Natalia Romina Balian and María Cristina Zurrú"},{id:"81011",title:"Amino Acids as Neurotransmitters. The Balance between Excitation and Inhibition as a Background for Future Clinical Applications",slug:"amino-acids-as-neurotransmitters-the-balance-between-excitation-and-inhibition-as-a-background-for-f",totalDownloads:32,totalDimensionsCites:0,doi:"10.5772/intechopen.103760",abstract:"For more than 30 years, amino acids have been well-known (and essential) participants in neurotransmission. They act as both neuromediators and metabolites in nervous tissue. Glycine and glutamic acid (glutamate) are prominent examples. These amino acids are agonists of inhibitory and excitatory membrane receptors, respectively. Moreover, they play essential roles in metabolic pathways and energy transformation in neurons and astrocytes. Despite their obvious effects on the brain, their potential role in therapeutic methods remains uncertain in clinical practice. In the current chapter, a comparison of the crosstalk between these two systems, which are responsible for excitation and inhibition in neurons, is presented. The interactions are discussed at the metabolic, receptor, and transport levels. Reaction-diffusion and a convectional flow into the interstitial fluid create a balanced distribution of glycine and glutamate. Indeed, the neurons’ final physiological state is a result of a balance between the excitatory and inhibitory influences. However, changes to the glycine and/or glutamate pools under pathological conditions can alter the state of nervous tissue. Thus, new therapies for various diseases may be developed on the basis of amino acid medication.",book:{id:"10890",title:"COVID-19, Neuroimmunology and Neural Function",coverURL:"https://cdn.intechopen.com/books/images_new/10890.jpg"},signatures:"Yaroslav R. Nartsissov"},{id:"80821",title:"Neuroimmunology and Neurological Manifestations of COVID-19",slug:"neuroimmunology-and-neurological-manifestations-of-covid-19",totalDownloads:59,totalDimensionsCites:0,doi:"10.5772/intechopen.103026",abstract:"Infection with SARS-CoV-2 is causing coronavirus disease in 2019 (COVID-19). Besides respiratory symptoms due to an attack on the broncho-alveolar system, COVID-19, among others, can be accompanied by neurological symptoms because of the affection of the nervous system. These can be caused by intrusion by SARS-CoV-2 of the central nervous system (CNS) and peripheral nervous system (PNS) and direct infection of local cells. In addition, neurological deterioration mediated by molecular mimicry to virus antigens or bystander activation in the context of immunological anti-virus defense can lead to tissue damage in the CNS and PNS. In addition, cytokine storm caused by SARS-CoV-2 infection in COVID-19 can lead to nervous system related symptoms. Endotheliitis of CNS vessels can lead to vessel occlusion and stroke. COVID-19 can also result in cerebral hemorrhage and sinus thrombosis possibly related to changes in clotting behavior. Vaccination is most important to prevent COVID-19 in the nervous system. There are symptomatic or/and curative therapeutic approaches to combat COVID-19 related nervous system damage that are partly still under study.",book:{id:"10890",title:"COVID-19, Neuroimmunology and Neural Function",coverURL:"https://cdn.intechopen.com/books/images_new/10890.jpg"},signatures:"Robert Weissert"},{id:"80005",title:"Infarct Stroke and Blood Glucose Associated with Food Consumption in Indonesia",slug:"infarct-stroke-and-blood-glucose-associated-with-food-consumption-in-indonesia",totalDownloads:62,totalDimensionsCites:0,doi:"10.5772/intechopen.101548",abstract:"Stroke is the primary cause of death in adults. It is predicted that the death caused by stroke will increase twice in the next 30 years. In Indonesia, stroke is one of the diseases of the circulatory system, which has been taking the first place of causing death since 2007. Indonesia has rice as the main type of daily food consumed, which has higher glycemic index than other sources. This study aims to find the risk of blood glucose level that determines the incidence of infarct stroke. There were 164 patients enrolled in this study, 82 patients in each stroke and not stroke group. The blood examination is using the enzymatic method, which is the hexokinase method. The results of research revealed that indicators of high blood glucose level were found in infract stroke incidence, including casual blood glucose, fasting blood glucose, 2-h postprandial blood glucose, and glycated hemoglobin. These four indicators were found in a higher level in the infarct stroke than the non-stroke group. Other epidemiological studies have shown that diabetes is a risk factor for stroke. Therefore, education about food selection should be a priority in the effort to prevent infarct stroke and diabetes mellitus in Indonesia.",book:{id:"10782",title:"Cerebrovascular Diseases - Elucidating Key Principles",coverURL:"https://cdn.intechopen.com/books/images_new/10782.jpg"},signatures:"Santi Martini, Hermina Novida and Kuntoro"},{id:"80391",title:"COVID-19 and Seizures",slug:"covid-19-and-seizures",totalDownloads:59,totalDimensionsCites:0,doi:"10.5772/intechopen.102540",abstract:"The past two years were deeply marked by the emergence of a global pandemic caused by the worldwide spread of the virus severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection. The plethora of repercussions on the health of those affected is extensive, ranging from asymptomatic individuals, mild flu-like disease, and severe respiratory failure, eventually leading to death. Despite this predilection for the respiratory system, the virus is responsible for multisystemic manifestations and soon became clear that neurological involvement was a frequent issue of coronavirus disease 2019 (COVID-19). Much have been pointed out about the neurotropic nature of the virus, the ways by which it invades and targets specific structures of the central nervous system, and the physiopathology behind the neurologic manifestations associated with it (namely encephalomyelitis, Guillain-Barré syndrome, lacunar infarcts, and vascular dysfunction, just to list a few). 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He is a full professor of signal processing and pattern recognition and is head of the Signals and Communications Department at ULPGC, teaching from 2001 on subjects on signal processing and learning theory. His research lines are biometrics, biomedical signals and images, data mining, classification system, signal and image processing, machine learning, and environmental intelligence. He has researched in 52 international and Spanish research projects, some of them as head researcher. He is co-author of 4 books, co-editor of 27 proceedings books, guest editor for 8 JCR-ISI international journals, and up to 24 book chapters. He has over 450 papers published in international journals and conferences (81 of them indexed on JCR – ISI - Web of Science). He has published seven patents in the Spanish Patent and Trademark Office. He has been a supervisor on 8 Ph.D. theses (11 more are under supervision), and 130 master theses. 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His research interests include computer/machine vision, machine learning, pattern recognition, computational intelligence. \nDr. Papakostas served as a reviewer in numerous journals, as a program\ncommittee member in international conferences and he is a member of the IAENG, MIR Labs, EUCogIII, INSTICC and the Technical Chamber of Greece (TEE).",institutionString:null,institution:{name:"International Hellenic University",institutionURL:null,country:{name:"Greece"}}},editorTwo:null,editorThree:null},{id:"25",title:"Evolutionary Computation",coverUrl:"https://cdn.intechopen.com/series_topics/covers/25.jpg",isOpenForSubmission:!0,editor:{id:"136112",title:"Dr.",name:"Sebastian",middleName:null,surname:"Ventura Soto",slug:"sebastian-ventura-soto",fullName:"Sebastian Ventura Soto",profilePictureURL:"https://mts.intechopen.com/storage/users/136112/images/system/136112.png",biography:"Sebastian Ventura is a Spanish researcher, a full professor with the Department of Computer Science and Numerical Analysis, University of Córdoba. 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He is currently a principal researcher in data analytics and optimisation at TECNALIA (Spain), a visiting fellow at the Basque Center for Applied Mathematics (BCAM) and a part-time lecturer at the University of the Basque Country (UPV/EHU). His research interests gravitate on the use of descriptive, prescriptive and predictive algorithms for data mining and optimization in a diverse range of application fields such as Energy, Transport, Telecommunications, Health and Industry, among others. In these fields he has published more than 240 articles, co-supervised 8 Ph.D. theses, edited 6 books, coauthored 7 patents and participated/led more than 40 research projects. 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He is currently a full professor in\nthe Department of Automation and Applied Informatics at the\nsame university. Dr. Voloşencu is the author of ten books, seven\nbook chapters, and more than 160 papers published in journals\nand conference proceedings. He has also edited twelve books and\nhas twenty-seven patents to his name. He is a manager of research grants, editor in\nchief and member of international journal editorial boards, a former plenary speaker, a member of scientific committees, and chair at international conferences. His\nresearch is in the fields of control systems, control of electric drives, fuzzy control\nsystems, neural network applications, fault detection and diagnosis, sensor network\napplications, monitoring of distributed parameter systems, and power ultrasound\napplications. 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Gharieb",profilePictureURL:"https://mts.intechopen.com/storage/users/225387/images/system/225387.jpg",institutionString:"Assiut University",institution:{name:"Assiut University",institutionURL:null,country:{name:"Egypt"}}}]},{id:"8",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.',annualVolume:11404,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/8.jpg",editor:{id:"144937",title:"Prof.",name:"Adriano",middleName:"De Oliveira",surname:"Andrade",fullName:"Adriano Andrade",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRC8QQAW/Profile_Picture_1625219101815",institutionString:null,institution:{name:"Federal University of Uberlândia",institutionURL:null,country:{name:"Brazil"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"49517",title:"Prof.",name:"Hitoshi",middleName:null,surname:"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",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",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"}}}]},{id:"9",title:"Biotechnology - Biosensors, Biomaterials and Tissue Engineering",keywords:"Biotechnology, Biosensors, Biomaterials, Tissue Engineering",scope:"The Biotechnology - Biosensors, Biomaterials and Tissue Engineering topic within the Biomedical Engineering Series aims to rapidly publish contributions on all aspects of biotechnology, biosensors, biomaterial and tissue engineering. We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics can include but are not limited to: Biotechnology such as biotechnological products and process engineering; Biotechnologically relevant enzymes and proteins; Bioenergy and biofuels; Applied genetics and molecular biotechnology; Genomics, transcriptomics, proteomics; Applied microbial and cell physiology; Environmental biotechnology; Methods and protocols. Moreover, topics in biosensor technology, like sensors that incorporate enzymes, antibodies, nucleic acids, whole cells, tissues and organelles, and other biological or biologically inspired components will be considered, and topics exploring transducers, including those based on electrochemical and optical piezoelectric, thermal, magnetic, and micromechanical elements. Chapters exploring biomaterial approaches such as polymer synthesis and characterization, drug and gene vector design, biocompatibility, immunology and toxicology, and self-assembly at the nanoscale, are welcome. Finally, the tissue engineering subcategory will support topics such as the fundamentals of stem cells and progenitor cells and their proliferation, differentiation, bioreactors for three-dimensional culture and studies of phenotypic changes, stem and progenitor cells, both short and long term, ex vivo and in vivo implantation both in preclinical models and also in clinical trials.",annualVolume:11405,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/9.jpg",editor:{id:"126286",title:"Dr.",name:"Luis",middleName:"Jesús",surname:"Villarreal-Gómez",fullName:"Luis Villarreal-Gómez",profilePictureURL:"https://mts.intechopen.com/storage/users/126286/images/system/126286.jpg",institutionString:null,institution:{name:"Autonomous University of Baja California",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"35539",title:"Dr.",name:"Cecilia",middleName:null,surname:"Cristea",fullName:"Cecilia Cristea",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYQ65QAG/Profile_Picture_1621007741527",institutionString:null,institution:{name:"Iuliu Hațieganu University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"40735",title:"Dr.",name:"Gil",middleName:"Alberto Batista",surname:"Gonçalves",fullName:"Gil Gonçalves",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYRLGQA4/Profile_Picture_1628492612759",institutionString:null,institution:{name:"University of Aveiro",institutionURL:null,country:{name:"Portugal"}}},{id:"211725",title:"Associate Prof.",name:"Johann F.",middleName:null,surname:"Osma",fullName:"Johann F. 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