\\n\\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\\n\\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\\n"}]',published:!0,mainMedia:{caption:"Highly Cited",originalUrl:"/media/original/117"}},components:[{type:"htmlEditorComponent",content:'IntechOpen is proud to announce that 191 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\nThroughout the years, the list has named a total of 261 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\nReleased this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"3630",leadTitle:null,fullTitle:"VLSI",title:"VLSI",subtitle:null,reviewType:"peer-reviewed",abstract:"The process of Integrated Circuits (IC) started its era of VLSI (Very Large Scale Integration) in 1970’s when thousands of transistors were integrated into one single chip. Nowadays we are able to integrate more than a billion transistors on a single chip. However, the term “VLSI” is still being used, though there was some effort to coin a new term ULSI (Ultra-Large Scale Integration) for fine distinctions many years ago. VLSI technology has brought tremendous benefits to our everyday life since its occurrence. \r\nVLSI circuits are used everywhere, real applications include microprocessors in a personal computer or workstation, chips in a graphic card, digital camera or camcorder, chips in a cell phone or a portable computing device, and embedded processors in an automobile, et al. \r\n \r\nVLSI covers many phases of design and fabrication of integrated circuits. For a commercial chip design, it involves system definition, VLSI architecture design and optimization, RTL (register transfer language) coding, (pre- and post-synthesis) simulation and verification, synthesis, place and route, timing analyses and timing closure, and multi-step semiconductor device fabrication including wafer processing, die preparation, IC packaging and testing, et al. As the process technology scales down, hundreds or even thousands of millions of transistors are integrated into one single chip. Hence, more and more complicated systems can be integrated into a single chip, the so-called System-on-chip (SoC), which brings to VLSI engineers ever increasingly challenges to master techniques in various phases of VLSI design. For modern SoC design, practical applications are usually speed hungry. For instance, Ethernet standard has evolved from 10Mbps to 10Gbps. Now the specification for 100Mbps Ethernet is on the way. On the other hand, with the popularity of wireless and portable computing devices, low power consumption has become extremely critical. To meet these contradicting requirements, VLSI designers have to perform optimizations at all levels of design. \r\n \r\nThis book is intended to cover a wide range of VLSI design topics. The book can be roughly partitioned into four parts. Part I is mainly focused on algorithmic level and architectural level VLSI design and optimization for image and video signal processing systems. Part II addresses VLSI design optimizations for cryptography and error correction coding. Part III discusses general SoC design techniques as well as other application-specific VLSI design optimizations. The last part will cover generic nano-scale circuit-level design techniques.",isbn:null,printIsbn:"978-953-307-049-0",pdfIsbn:"978-953-51-5873-8",doi:"10.5772/139",price:139,priceEur:155,priceUsd:179,slug:"vlsi",numberOfPages:466,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:null,bookSignature:"Zhongfeng Wang",publishedDate:"February 1st 2010",coverURL:"https://cdn.intechopen.com/books/images_new/3630.jpg",numberOfDownloads:59194,numberOfWosCitations:18,numberOfCrossrefCitations:17,numberOfCrossrefCitationsByBook:7,numberOfDimensionsCitations:32,numberOfDimensionsCitationsByBook:8,hasAltmetrics:1,numberOfTotalCitations:67,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:null,dateEndSecondStepPublish:null,dateEndThirdStepPublish:null,dateEndFourthStepPublish:null,dateEndFifthStepPublish:null,currentStepOfPublishingProcess:1,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"2569",title:"Dr.",name:"Zhongfeng",middleName:null,surname:"Wang",slug:"zhongfeng-wang",fullName:"Zhongfeng Wang",profilePictureURL:"https://mts.intechopen.com/storage/users/2569/images/system/2569.jpg",biography:"Dr. Zhongfeng Wang received B.S. and M.S. degrees, both from the Department of Automation at Tsinghua University, Beijing, China. He obtained the Ph.D. degree from the Department of Electrical and Computer Engineering at the University of Minnesota, Minneapolis in 2000.\n\nIn the past, he has worked for Beijing Hua-hai New Technology Development Co. (1990-95), Beijing, CHINA, Morphics Technology Inc. (now a part of Infineon Technology) (2000-02), Campbell, CA, USA, National Semiconductor Co. (2002-03), Longmont, CO. From 2003 to 2007, he worked in the School of EECS at Oregon State University (OSU), Corvallis, OR. Since June 2007, he has been working for Broadcom Corporation, Irvine, CA, as Senior Principle Scientist.\n\nDr. Wang was the recipient of the Best Student Paper award (1st prize) at the 1999 IEEE Workshop on Signal Processing Systems (SiPS '99) and the co-recipient of the IEEE Circuits and Systems (CAS) Society VLSI Transactions Best Paper Award in 2007. He is also a coauthor (and supervisor) of three (3) Best Student Paper Candidates on IEEE (ICASSP’07, APCCAS’08) and ACM (Asiloma Signal Processing and Systems Conference 2009). He has edited a book “VLSI”, published about 100 technical papers and has filed numerous U.S. patent applications. He served as Associate Editor (AE) for the IEEE Trans. on Circuits and Systems: I (TCAS-I) from 2003 to 2005. He is serving as AE for TCAS-II (2008-2009, 2010-2011) and AE for IEEE Transactions on VLSI Systems (2009-10). He has also served as technical program committee member for many IEEE and ACM conferences. He is currently in the technical committee of VLSI Systems and Applications (VTA-TC) and Circuits and Systems for Communications (CAS-COM) in the IEEE CAS Society.\n\nHis research interests include the areas of Digital Signal Processing, Digital Communications & Networking, and Low Power/High Speed VLSI Implementation. He is a member of Sigma Xi society and has been a senior member of IEEE CAS society since 2005.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"1",institution:null}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"739",title:"Electronic Circuits",slug:"electrical-and-electronic-engineering-electronic-circuits"}],chapters:[{id:"9442",title:"Discrete Wavelet Transform Structures for VLSI Architecture Design",doi:"10.5772/8239",slug:"discrete-wavelet-transform-structures-for-vlsi-architecture-design",totalDownloads:3106,totalCrossrefCites:2,totalDimensionsCites:2,hasAltmetrics:0,abstract:null,signatures:"Hannu Olkkonen and Juuso T. 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Despite their negligible mass the microbial agents, starters and non starters, play a profound role in the characterization of the fermented foods in terms of chemical and sensorial properties. In fact, fermented foods may be defined as foods processed through the activity of microorganisms. Fermentation processes take a special place in the evolution of human cuisine, by altering the taste experience of food products, as well as extending the storage period. In particular, foods fermented with lactic acid bacteria (LAB) have constituted an important part of human diet and of fermentation processes (involving various foods, including milk, meat, vegetables and fruits) [1] since ancient times. They have played an essential role in the preservation of agricultural resources and in the improvement of nutritional and organoleptic properties of human foods and animal feed. Moreover, these organisms nowadays are increasingly used as health promoting probiotics, enzyme and metabolite factories and vaccine delivery vehicles [2].
It is interesting to outline how the changes of food characteristics during the fermentation process can be described as dynamic fluctuations of the food environment itself and, at the same time, stress source for the microorganisms involved [3, 4], such as LAB. In fact, whenever autochthonous bacteria are adapted and competitive in their respective environment, the environment can be described as stressful for LAB [5, 4]. The fermentation parameters, including temperature, water activity (Aw), oxygen, pH, as well as the concentration of starter cultures, affect the regulatory mechanism and the response mechanisms of LAB, as well as their effects on the final products properties [4].
When LAB are added to food formulations, several factors that may influence the ability of those microorganisms to survive, growth and become active in the new matrix have to be considered [6]. These factors include: 1) the physiological state of the LAB used as starters (whether the cells are from the logarithmic or the stationary growth phase); 2) the physical conditions of product ripening and storage (eg. temperature); 3) the chemical composition of the matrix (eg. acidity, available carbohydrates content, nitrogen source, mineral content, water activity and oxygen concentration); 4) possible interactions of the starter cultures with probiotics and other microorganisms naturally occurring or added to the system [6].
In figure 1 the main factors affecting the viability and the responses of LAB from production to storage are described [7].
Factors affecting the viability and the responses of LAB to the various fermented foods production steps.
To better elucidate what happens to LAB during fermentation processes, we decided to use a model (defined “virtual food”) that mimics various steps occurring during processing and that can affect LAB performances or viability.
“Stress results from interactions between subjects and their environment that are perceived as straining or exceeding their adaptive capacities and threatening their well-being. The element of perception indicates that human stress responses reflect differences in personality, as well as differences in physical strength or general health” [8].
Stress has driven evolutionary changes (the development and natural selection of species over time). Thus, the species that adapted best to the causes of stress (stressors) have survived and evolved into the plant and animal kingdoms we now observe. The same evolutionary process regarded microorganisms. In fact, bacteria, irrespective of natural habitat, are exposed to constant fluctuations in their growth conditions. Consequently they have developed sophisticated responses, modulated by the re-modelling of protein complexes and by phosphorylation dependent signal transduction systems, to adapt and to survive to a variety of insults. To ensure survival to environmental adversities, bacteria may adapt to changes in their immediate vicinity by responding to the imposed stress. These responses are different and vast and depend on the microorganism nature and on the environmental stress and are accomplished by changes in the patterns of gene expression for those genes whose products are required to combat the deleterious [3]. In particular, cellular metabolic pathways are closely related to stress responses and the flux of particular metabolites to understand the hypothetically shifts and implications in the food systems has been studied in LAB [9-13, 4, 14, 15].
LAB are a functionally related group of organisms known primarily for their bioprocessing roles in food and beverages [16]. LAB play a crucial role in the development of the organoleptic and hygienic quality of fermented products. These microorganisms are used as starter cultures in many fermented products (i.e. beer, milk, dough, sausages and wine). Therefore, the reliability of starter cultures in terms of quality and functional properties (important for the development of aroma and texture), but also in terms of growth performance and robustness, has become essential for successful fermentations [17]. There have been some reports describing the physiological stress responses in LAB, particularly
LAB evolved specific mechanisms to respond and to survive to environmental stresses and changes (stress-sensing system and defences). In fact, microorganisms could have specific regulators tailored to each of their regulated genes and adapt their expression according to environment. Stress defences are good examples of such integrated regulation systems. Bacterial stress responses rely on the coordinated expression of genes that alter different cellular processes (cell division, DNA metabolism, housekeeping, membrane composition, transport, etc.) and act in concert to improve the bacterial stress tolerance. The integration of these stress responses is accomplished by networks of regulators that allow the cells to react to various and complex environmental shifts. LAB respond to stress in a very specific way dependent on the species, on the strains and on the type of stress. The best-studied stresses are acid, heat, oxidative and cold stresses, although for the latter most of the studies focused on a specific family of proteins instead of analyzing the whole response [4].
Despite the extensive use of LAB, there is a paucity of information concerning the stress-induced mechanisms studied
Heat stress response is characterized by the transient induction of general and specific proteins and by physiological changes. In every strain tested the involvement of Heat Shock Proteins (HSPs such as DnaK, GroEL and GroES during the heat stress was clear) [23-38]. The role of these stress proteins is complex; in fact, the bind substrate proteins in a transient non-covalent manner prevent premature folding and promote the attainment to the correct state
Another interesting study regarding LAB response to sub-lethal cold stress was developed by Montanari et al.[14]. These Authors separated and quantified the cell cyclopropane fatty acids lactobacillic (C19cyc11) and dehydrosterculic (C19cyc9) to study the adaptive response to sub-lethal acid and cold stresses in
When for some reasons the generation of free radicals is higher than the rate of their detoxification the cells are exposed to a constraint called “oxidative stress” [59]. For the food-associated LAB a still fragmented picture of the resistance mechanisms present emerges. Representatives of the different mechanisms have been described in different LAB [60-64]. Apart from the toxic effects of oxygen, aeration can induce important changes in the sugar metabolism of LAB. In fact, the presence of oxygen is a factor that greatly affects the outcome of a fermentation process. In general, LAB tolerate oxygen but grow better under nearly anaerobic conditions. However, in the presence of heme and oxygen LAB start respiration metabolism, by which the cell metabolism is reprogrammed so that pH, oxygen status, growth capacity and survival are markedly altered [56]. In the presence of oxygen and during the fermentation metabolism, H2O2 is formed. Numerous species of LAB contain peroxidase and/or catalase to prevent and eliminate these deleterious effects [17]. Concerning the prevention of reactive oxygen species (ROS) formation, the scope of the reactions is the eliminations of free oxygen. In a study on
General microbial interference is an effective non-specific control mechanism common to all populations and environments including foods. It represents the inhibition of the growth of certain microorganisms by other members of the habitat.
The mechanisms involved are common to all genera and include [78]:
Nutrient competition,
Generation of unfavorable environment,
Competition for attachment/adhesion sites.
Most substrates for food fermentations have a highly heterogeneous physicochemical composition, which offers the possibility for the simultaneous occupation of multiple niches by “specialized” strains, for instance, through the utilization of different carbon sources. In these substrates, coexisting strains often interact through trophic or nutritional relations via multiple mechanisms [77].
Carbon sources are often present at high concentrations in food substrates, and therefore competition concerns the rapid uptake of nutrients and conversion into biomass. In dairy fermentations nitrogen is limiting, and initially organisms compete for the free amino acids and small peptides available. While in the later stages of fermentation, they compete for the peptides released by the actions of proteolytic enzymes [77].
In a cell-density-dependent quorum-sensing system, bacteria produce extracellular signaling molecules such as peptides or post-translationally modified peptides that act as inducers for gene expression when concentrations of these molecules exceed a certain threshold value [79]. These changes might eventually lead to competitive advantages for the population, more effective adaptation and responses to changing environmental conditions, or the co-ordination of interactions between bacteria and their abiotic and biotic environments [7]. In fact, microorganisms produce diffusible chemicals for the purpose of communication and it has been reported that the stress caused by the exposure of microbial cells to their own cell free conditioned media, containing metabolites and bioactive compounds including ‘‘quorum sensing” molecules, including 2(5H)-furanones, promotes cell differentiation, autolysis and overproduction of specific metabolites [12, 80, 9, 10]. In this way the microbial cultures used in food fermentations can also contribute (by “secondary” reactions and relations) to the formation of flavor and texture [81].
In the figure 2, the steps that mainly interest food fermentation are reported. A model virtual fermented food was identified to resume the common denominator of the fermented foods dynamics, particularly focused on the reciprocal influences between environmental fluctuation and LAB fermentation.
Whatever kind of food we want to produce, fermented or not, the first step of the process is the formulation: in this phase the main raw materials (meat, milk, fruit and vegetables or their derivatives) are mixed with other ingredients, that have different roles: salts or sugars to improve taste, spices to give specific sensorial quality and as antimicrobials, additives or other substances able to affect physical and structural properties, preservatives to improve microbial stability and shelf life. The addition of those ingredients can be perceived as stress. In fermented products, proper microorganisms, mainly yeasts and LAB, are also added as starter cultures, in order to start and lead the fermentation and to obtain a stable and standard final product. As a consequence, the microorganisms, naturally occurring or added as starter cultures, have to cope with a completely different system: in particular, naturally occurring microflora have to face the changes induced by the ingredients, while the starter cultures, deriving from growth media or added as lyophilized cultures, have to adapt to a real food system, where different sources of stresses are often present.
In particular, the first sub-lethal stress, which LAB face, regards the difference between the growth medium composition and the real food. Generally, LAB lyophilized cultures can be added to the ingredients after a reactivation and subsequently added to the product. This procedure identify the presence of a stress for the LAB cells. Starter cultures are added to the raw materials in large numbers and incubated under optimal conditions, but the adaptation to substrate or raw material is always necessary [82]. It is very important to consider the physiological state of the LAB before the inoculum. This state strongly depends on the time of harvesting of the culture (whether during the logarithmic or stationary phase of growth), on the conditions leading to transition to the stationary phase, on the treatment of the culture during and after harvesting and on the chemical composition of the environment. Therefore it is important during formulation and technological processes to consider also these factors, mainly for those products where microorganisms are added as starter cultures.
Fermented food model: reciprocal influences between environmental fluctuation and lactic acid bacteria fermentation.
The interaction between the starters and the ingredients and between the starters and the naturally present microbial population can trigger few important mechanisms that will influence the quality and the characteristics of the fermented product. Analogously, many food processes and formulations have been tested for safety by challenge test inoculating pathogen bacterial cells at different growth phases, and the results proved that cells grown to the stationary phase or adapted to various stresses have greater resistance than exponential cells [83].
Other ingredients usually added to obtain safe and stable products are food preservatives, including:
Antioxidants,
Anti-browning agents
Antimicrobials.
These latter are arbitrarily classified into two groups: traditional or “regulatory approved” and naturally occurring [84]. The former includes acidifiers such as acetic acid, lactic acid and citric acid and antimicrobials such as benzoic acid and benzoates, propionate, nitrites and nitrates, sorbic acid and sorbates and sulfites. The latter includes compounds from microbial, plant and animal sources that are, for the most part, only proposed for use in foods as antimicrobials (e.g. lactoferrin, lysozyme, nisin). Throughout the ages, food antimicrobials have been used primarily to prolong shelf-life and preserve quality of foods through inhibition of spoilage microorganisms, while only few are used exclusively to control the growth of specific foodborne pathogens (e.g. nitrite, used for hundreds of years to inhibit growth and toxin production of
A good model describing the shock related to the inoculum of LAB in the raw complex material has been described during the production of fermented sausages [85]. The relatively high pH of raw meat rapidly decreases during the initial fermentation phase because organic acids, mainly lactate, are formed by LAB and the water activity is reduced during ripening, because of the addition of salt as well as drying. Furthermore, adjuvants, such as potassium or sodium nitrite and/or nitrate, are mostly added to optimize the fermentation process.
Generally strains used as starter cultures must tolerate these kinds of stresses and exhibit a high ecologic performance in the stressful food environment. Genes related to stress response are induced when
Moreover, it is important to consider that some ingredients can be also antimicrobials because of their own characteristics: in fact, if the recipe includes herbs and spices (aromatic plants, pepper), garlic and onions, an effect on microorganisms can be exerted by specific compounds characterizing these products, such as essential oils, terpenes and sulfur compounds [88].
Another essential aspect affecting the performances and metabolism of LAB are the intrinsic characteristics of raw materials that sometimes act in a synergic way with other ingredients. Considering for example fermented vegetables, the microflora of the starting fresh vegetables is typically dominated by Gram negative aerobic bacteria and yeasts, while LAB make up a minor portion of the initial population [89] and therefore they would not be able to start and lead a fermentation process. However, if anaerobic conditions are settled and salts are added, LAB can have a competitive advantage and induce spontaneous lactic acid fermentation. The growth of specific LAB is dependent on the chemical (substrate, salt concentration, pH) and physical (vegetable type, temperature) environments. As the environments change during fermentation, so can the dominant organisms, often leading to a specific and reproducible succession of bacteria.
In sauerkraut [89, 90] the presence of 1.8-2.2% of NaCl and a temperature of 18°C inhibits many strains of LAB, with the exception of
Considering olives fermentation is possible to outline the characteristics of the product affecting LAB: while the brine provides a good environment for LAB growth, with glucose, fructose and mannitol as the main source of fermentable sugars, the presence of high levels phenols (such as oleuropein) exert an antimicrobial activity, inhibiting some strains and selecting the types of organisms that predominate during the fermentation [91-93]. These LAB have to be resistant not only to phenols, but also to lye treatments and water washes, that can be performed during the processing and increase the initial pH, reducing also the nutrients content on the olive surface. The species able to face these kind of stresses usually belong to the genera
Moreover, the presence of some gases can modify the growth performances of LAB. That is also influenced by the mixing step of the ingredients in some food processes (e.g. dough mixing). In fact, in bread making process, the continuous agitation of the dough can increase the microbes exposure to oxygen, and this can be a source of oxidative stress, mainly for LAB that are usually anaerobic or facultative anaerobic. Also in these cases the bacteria can react in different ways, activating metabolic and transcriptional responses in order to detoxify ROS, as previously described.
For the fermented vegetables,above reported, the rapid consumption of oxygen due to the presence of yeasts and aerobic bacteria in the first stage of fermentation has a positive effect on LAB. In fact, they are exposed only for a short time to oxidative stress and, due to their competitive advantage, they rapidly and intensively grow in the food system.
After formulation, the technological processes involving LAB include a fermentation process.
It is reported that various beneficial phenotypic traits of LAB in food fermentations such as rapid acidification, selective proteolysis, tolerance of osmotic and stresses, resistance to ROS, and ability to thrive in nutrient poor conditions and at low temperatures are influenced by stress responses in various species of LAB [95, 96]. The knowledge of these mechanisms, and mainly of the stress responses activated by the fermentation process parameters can be useful in order to develop strains with optimal fermentation characteristics [83].
The first metabolic reaction regards the oxidation of carbohydrates (this reaction depends on the hetero-fermentative or homo-fermentative species involved) that give rise to acids, alcohols and CO2. These metabolites are directly involved in flavor, aroma and texture of the product and in a second time can influence the production and the availability of other metabolites such as vitamins and antioxidant compounds [78]. Moreover, the LAB interactions with the ingredients increase also the digestibility and decrease the glycemic index, enhancing the healthy features of the fermented foods [97].
At the same time with carbohydrates oxidation, other metabolic mechanisms interest LAB cells such as proteolysis and lipolysis. The first reaction produces polypeptides with interesting characteristics as antimicrobial compounds, salt substitutes (the oligopeptides are able to increase the palatability of the system), and amino acids deriving aromatic compounds. On the other hand lipolysis produces medium chain fatty acids, with important antimicrobial properties. All these reactions (carbohydrates oxidation, lipolysis and proteolysis) generate precursors for other mechanisms in the cells and in the food matrix that give rise to the dynamic environment characteristics of fermented foods. It is important to outline that the compounds produced by the cells, metabolizing the substrate, can modify the system, producing also compounds that can stimulate the growth of symbiotic species or inhibit the growth of antagonistic microorganisms.
The conversion of carbohydrates to metabolites as acetic acid, lactic acid or CO2 implies the acidification of the system. The contemporary pH decrease and the presence of sugar (osmotic stress) stimulate the exopolysaccharides (EPSs) production. In fact, in sourdough EPSs can be involved in acid tolerance of sourdough LAB [98]. EPSs are long-chain polysaccharides consisting of branched, repeating units of sugars or sugar derivatives. These sugar units are mainly glucose, galactose and rhamnose, in different ratios [99]. The presence of EPSs in the system can create a novel stress to the cells. The inclusion of cells within biofilm can increase their resistance to unfavorable environmental factors such as extreme temperature, low pH and osmolarity, the changes in the texture can induce in LAB also specific stress responses.
For example in yogurt production, the acidification by LAB implies proteins coagulation and thereby changes in the viscosity of the milk. In
Considering cheese, the Aw decreases during manufacture and ripening as a result of dehydration, salting, and production of water-soluble solutes from glycolysis, proteolysis, and lipolysis; the cheese Aw values range from 0.70 for extra hard cheeses to 0.99 for fresh, soft cheeses, such as cottage cheese, while semi-hard cheeses have Aw values of around 0.90. The cheese pH also decreases during manufacture and ripening [103]. The effects of different Aw and pH on
In
The ability of the target strains to dominate the fermentation is related not only to the ingredients (as above described), but also to the fermentation conditions, mainly temperature and atmosphere. If the fermentation is not performed at the optimal growth temperature for the microorganisms, they could be unable to compete with naturally occurring microflora, and consequently the whole process could be compromised. On the contrary, some microbial species have developed specific thermal resistance mechanisms, and they can easily adapt to these unfavorable conditions without implications for the fermentation processes. Moreover, the adaptation to thermal stresses often leads to tolerance to other stresses, in a mechanism usually define “cross protection”, as reported for
Other Authors with regard to different stresses reported the “cross protection” mechanism: for example the mechanisms of multiple adaptations to hops of two different strains of
Consider the atmosphere, i.e. the presence or not of oxygen, as another important variable during fermentation, it is known that oxygen can inhibit the growth of LAB, especially in the first stages. However, the food system is usually a consortium of different microorganisms: for example in bakery products and in fermented sausages the fermentation is carried out both by yeasts and LAB; the formers can therefore consume the amount of oxygen present in the mix, allowing the growth of LAB. The same thing happens for fermented vegetables, where naturally occurring Gram negative bacteria and yeast rapidly remove the oxygen, promoting the rapid predominance of Lactobacilli.
Some secondary metabolites such as bacteriocins can play a role in LAB performances and metabolism, affecting also the total population and ecology of fermented foods [107, 108]. Bacteriocins are antimicrobial peptides or proteins produced by bacteria that can be active on different microorganisms, depending on their structure. LAB belonging to the genera
Another interesting case of bacteriocin production, as a consequence of oxidative stress and carbon dioxide exposure, has been reported [110]: oxidative stress and carbon dioxide are involved in the production of a specific bacteriocin, amylovorin L, by
Another example of the influence of the process on LAB metabolism has been widely described [112]. These Authors monitored the evolution of the gene expression of
There are two main categories of factors that contribute to the optimal functioning of probiotic lactobacilli: factors that allow optimal adaptation to the new niches that they temporarily encounter in the host (adaptation factors) and factors that directly contribute to the health-promoting effects (probiotic factors) [113].
Adaptation factors include stress resistance, active metabolism adapted to the host environment, and adherence to the intestinal mucosa and mucus.
In fact, probiotic lactobacilli encounter various environmental conditions upon ingestion by the host and during transit in the gastro intestinal tract (GIT). They need to survive to: 1) the harsh conditions of the stomach secretion generating a fasting pH of 1.5, increasing to pH 3 to 5 during food intake; 2) the bile excreted by liver in small intestine represents another challenge for bacteria entering the GIT. Bile salts also seem to induce an intracellular acidification so that many resistance mechanisms are common for bile and acid stress. Indeed, the protonated form of
Sourdough fermentation dynamics. Case of possible parallel phenomena interesting acid and osmotic stress.
bile salts is thought to exhibit toxicity through intracellular acidification in a manner similar to those of organic acids like the lactic acid produced by the lactobacilli themselves. For a detailed overview of acid, bile, and other stress resistance mechanisms of lactobacilli, the reader is referred to more extensive review [113]. 3) In analogy to the stresses encountered by intestinal pathogens, they also encounter oxidative and osmotic stress in GI tract. 4) Interactions with other microbes and 5) Interactions with cells of the host immune system and the various antimicrobial products that they produce can also impose a serious threat for the probiotic microbes. Analogously to what described in food LAB, the phenomenon of cross-adaptation is often observed, i.e., that adaptation to one stress condition also protects against another stress factor, implying some common mechanisms. In this respect, also for probiotic LAB non-actively-growing stationary-phase cells are generally more resistant to various stressors than early-log-phase cells.
The different macromolecules constituting the cell membranes and cell walls of lactobacilli have been shown to contribute to maintaining cell integrity during stress to various degrees. For example, low pH caused a shift in the fatty acid composition of the cell membrane of an oral strain of
The role of EPS in acid and bile resistance is less clear. However, EPS production has not been studied in detail after exposure to bile. In fact, to our knowledge, phenotypic analyses of dedicated
A number of proteins that play a role in the protection or repair of macromolecules such as DNA and proteins also seem to be essential for acid and bile resistance. Intracellular acidification can result in a loss of purines and pyrimidines from DNA. Bile acids have also been shown to induce DNA damage and the activation of enzymes involved in DNA repair. Perhaps even more vital in the general stress response are chaperones that intervene in numerous stresses for important tasks such as protein folding, renaturation, protection of denatured proteins, and removal of damaged proteins.
Mechanisms to specifically sense the presence of certain stress factors and regulate gene expression in response to these stimuli are also crucial for bacterial survival under adverse conditions. Although these mechanisms are not well characterized for lactobacilli, they often involve two-component regulatory systems (2CRSs). 2CRSs allow bacteria to sense and respond to changes in their environment after receiving an environmental signal through transmembrane sensing domains of the histidine protein kinase (HPK).
The study of stress responses by LAB is getting closer and closer to the different "omic" fields: genomic, proteomic and metabolomic. Other traditional approaches regarding the membrane cells composition and modifications, both from a structural (cellular fatty acids composition by gas-chromatographic method) and morphological (membrane and wall modification by electronic microscopy) point of view are still used.
Genes implicated in LAB stress responses are numerous and the levels of characterization of their actual role and regulation differ widely between species. The studies concerning stress responses in LAB sometimes benefit from the knowledge already acquired in other bacteria. For example, parts of the studies on heat response have been focused on specific genes because of their major role demonstrated in other microorganisms [17]. The cheapest and easiest way to study a stress response in LAB is to follow some specific genes related to stresses such as heat shock, salts and acids [114, 115]. This type of study is useful especially if the entire genome sequence of some LAB is still unknown. However, nowadays the study of whole trascriptome (the total set of RNAs) is one of the most exhaustive ways to study modifications of gene expression as a result of a stress condition. The transcriptome of a cell contains information about the biological state of the cell and the genes that play a role under specific circumstances. The principal technique used to study the trascriptome is microarray [116].
DNA microarray technology has been used in numerous experiments to analyze gene expression: one example is the evaluation of the general stress response of
The gene expression dynamics of
The study of trascriptome is a good approach that gives a good overview of the changes that can occur inside a stressed bacterium. A limitation of this technique is that it is expensive and requires that the genome sequences of the organisms under study should be available for designing the oligonucleotides for the microarray [119].
A different but, at the same time, related point of view regards the study of proteins and proteome. The most common method to obtain this information is to extract total proteins and separate them by a sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) followed by a western blotting (in the first case) or a two dimesional electrophoresis (2D-E) analysis (in the second case). Also in this case if the study is focused on a single protein, it is necessary to know before the characteristic of the target protein to optimize the analytical conditions. 2D-Electrophoresis can provide more than 10000 detectable protein spots in a single gel run. Thus, proteins with post-translational modifications (PTMs), such as processing, phosphorylation and glycosylation, can be easily detected as separate spots. A spot separated by 2D-E theoretically consists of an almost homogeneous protein, and thus can be identified following digestion with a sequence-specific protease by peptide mass fingerprinting (PMF) approaches, typically using matrix-assisted laser desorption ionization (MALDI)- time-of-flight (TOF) mass spectrometers. The same level of automation is also available for proteomic approaches involving tandem mass spectrometry (MS-MS) analysis, extremely useful when studying organisms with incomplete or partial genomic information [120].
This kind of approach was used to investigate the cell surface proteins of a typical strain of
Due to increasingly available bacterial genomes in databases, proteomic tools have recently been used to screen proteins expressed by microorganisms in food, in order to better understand their metabolism
The global identification of stress-induced proteins in a given organism has technical limitations. Membrane proteins, for example, are rarely detected by this method. Secondly, it may be that changes in membrane proteins composition result from long-term adaptation processes, while short-term responses may primarily be accounted for the activation (and/or stabilization) of proteins already present. The latter hypothesis is valid especially in the case of transport systems, although for some of the systems studied a transcriptional induction has also been observed [17]. The use of this technique is not as widespread as that of DNA microarrays due to the challenges associated with the purification and separation of complex mixtures of proteins found in cell extracts. At the same time the study of the only transcriptome should take into consideration that a lot of post-transcriptional processes may act on RNA (ex. RNA interference, polyadenilation ecc) [125].
As reported above, the stress responses of LAB are studied also through the analysis of membrane composition, structure and integrity. Not unexpectedly, in fact, the cell membrane plays an important role in stress resistance. First of all, the membrane itself can change in adaptation to environmental conditions and these changes contribute to the protection of the bacteria [17]. The adaptive response to sub-lethal acid and cold stresses in
The last but not least approach used to study the stress response of LAB is the metabolic one. The study of the metabolites released, as a consequence of the stress exposure, can contribute to the understanding of the mechanisms that regulate the microbial interactions and the metabolic alterations induced by stress conditions. Moreover, these approaches can be exploited to identify which technological conditions induce microorganisms to produced desirable metabolites [4, 15].
With this perspective the use of GC-MS-SPME as a potent and easy tool to study the generation of volatile metabolite compounds such as flavoring molecules or aroma precursors was widely adopted [9,11-13, 15] and contributed to rationalize the process and optimize the products. In particular, the effects of HPH on different species of
Since all the techniques described above, if used alone, do not allow a total comprehension of stress responses, a lot of studies are trying to combine two or more approaches together. Combined transcriptomic and proteomic analyses were used to evaluate the glucose-limited chemo-stat in
Therefore it is possible to understand, from the references above, that techniques used to study the stress responses of LAB are taking more and more "omic" approach. This comports an accumulation of a huge number of data that it is not easy to manage and to compare. For this reason the use of new programs of data analysis is required. One of these approaches could be the use of heat maps, a technique born as a tool to understand microarray results [66]. Nowadays it could be useful also to manage the data from other fields: in fact, a heat maps was used to show the correlation between metabolites produced, the relative gene expression of specific genes and stress conditions [15]. The same useful tool, combined with other statistical analyses, has been also applied [132].
It is known that LAB can adapt to stress with different mechanisms widely studied in model and real systems. An overview of those responses has been described and reported in this chapter.
Stress not only induces changes enabling better survival, but also different performances in a system. In fermented food, the knowledge of the mechanisms that regulate LAB metabolic changes and their effects gain importance especially when those responses can be exploited in order to improve the food properties [4]. In particular, fermented foods are dynamic systems subjected to continuous evolution of their physico-chemical characteristics. The complex fluctuation of the food environment itself, during processing, is stress source for every microorganism involved and the changes that affect the fermented food habitats, can be perceived by LAB as stress.
In this chapter examples of the dynamic fluctuation effect on LAB metabolism have been described in order to outline that every reaction can cause a waterfall of metabolic events influencing the sensorial quality, the shelf-life and the bioactive compounds production of fermented foods.
The subjects of those events are LAB, indicating the importance of metabolism of these microorganisms in food. The cell physiology is crucial to ensure that cells are well suited to survival during downstream processes and that they exhibit high performances.
The production and exploitation of naturally adapted strains can be interesting for companies because of the absence of ethical and legal concerns. The adapted strains are not considered genetically modified microorganisms (GMOs) and therefore they can be applied in food processing without legal restrictions and, more important, without affecting the consumer perception, currently (in Europe) not ready to introduce in his diet foods produced with GMOs.
Individual stresses used in food processing and preservation may render probiotic LAB more resistant to further and different stresses, including those encountered in the human body, e.g. those encountered during gastro-intestinal passage (pH of the stomach, exposure to bile salts in small intestine etc.). A positive correlation has been recently observed between EPS production and resistance to bile salt and low pH stress in
This knowledge can open interesting perspectives to improve at the same time the performances of LAB, the quality of fermented food and the health-promoting properties of the LAB used.
Moreover, it will be interesting to identify the gastrointestinal tract also as a complex and dynamic system in which LAB need to adapt to adverse conditions, responding with metabolic shifts provided with interesting technological an healthy features.
The “omics” technologies could be particularly useful for identifying the mechanism leading to LAB stress responses. These approaches could also help to identify the mechanisms for cell fitness and stress adaptation that will be needed to develop more generic and science based technologies [7].
We thank Prof.ssa Maria Elisabetta Guerzoni for her enormous scientific support and Luca Vagnini for his graphic abilities (http://www.lucavagnini.com).
Tissue engineering (TE) is an interdisciplinary field whose first definition dates back to 1987. It combines the knowledge from different research areas including medicine, material science and engineering to develop engineered biological substitutes able to restore, maintain or improve tissue functions [1]. TE was introduced from the necessity of finding alternative methodologies to organ transplantations due to their increasing demand in clinical medicine. Furthermore, TE emerged as a promising approach to overcome the limitations of the conventional surgical approaches for the treatment of tissue damages caused by injuries, diseases and congenital disorders [2, 3]. These surgical procedures are based on replacing the injured tissues or organs with a healthy one harvested from the same patient (autograft), or a compatible donor (allograft). Although these approaches have been revolutionary and lifesaving, there are still some drawbacks that need to be addressed. The surgical procedures used to harvest both autografts and allografts are often invasive and painful. The risk of post-surgical limitations in the donor’s body due, for example, to infections and hematomas is, in fact, quite high. Moreover, when allografts are transplanted, the chance of inflammatory and immune responses in the patient body together with the transmission of diseases from the donor to the patient is significant [4].
TE aims at overcoming the complications associated with the conventional techniques used during organ transplantation by inducing the complete regeneration of the damaged tissues instead of replacing them [2, 3]. Several approaches to promote
Illustration of TE paradigm (figure created with
The scaffold plays an essential role in regulating the process of new tissue formation. An ideal scaffold should be biocompatible and should degrade with kinetics compatible with the rate of tissue regeneration. It should be highly porous (< 75% [7]) with adequate pore size to promote cell migration/scaffold colonization and nutrient transfer throughout the scaffold. A scaffold should mimic the features of biological tissues in terms of topological properties (e.g., shape, size), mechanical properties (e.g., stiffness), and the biochemical processes that control and regulate the functionalities of the tissues. Moreover, it should not alter the normal functions of cells, which should adhere, migrate and proliferate within the scaffold before producing new tissue [5, 6, 8, 9]. Depending on their applications, scaffolds with different shapes, compositions and properties have been developed so far.
The biomaterial formulations used to produce the scaffold strongly affect its properties [10, 11]. Thus, the selection of the proper biomaterial formulation is pivotal for inducing the regeneration of the tissue in a controlled manner avoiding any undesired side-effects (e.g., cytotoxicity, apoptosis, carcinogenicity). The most used biomaterial formulations in TE are mainly based on synthetic biopolymers, natural biopolymers and composites [12, 13]. Synthetic biopolymers, like polycaprolactone, can be produced on a large scale under controlled conditions with predictable and reproducible physicochemical properties (e.g., mechanical properties, biodegradability) [6, 14, 15]. However, many synthetic biopolymers that have been developed so far are mainly derived from petroleum and coal, which make them not compatible with the environment [16]. Natural biopolymers include animal-derived proteins (e.g., gelatin, hyaluronic acid, collagen, silk) and animal- and vegetal-derived polysaccharides (e.g., cellulose alginate, chitosan). One of the advantages of this class of biopolymers is their biological similarity to native tissues which is beneficial for supporting cell functionalities (e.g., cell adhesion). Nonetheless, the use of animal-derived biopolymers may be associated with a high risk of transmission of diseases from animal to patient [10, 17, 18]. Therefore, the use of naturally occurring biopolymers from vegetal sources represents an attractive alternative to overcome these limitations. Moreover, they represent an ecological alternative to synthetic biopolymers in the preparation of sustainable and green scaffolds.
In recent years particular attention has been paid to the adoption of methodologies to derive biopolymers from renewable sources, such as industrial by-products, such as pectin from fruit pomace produced from the fruit processing industry [19] and cellulose nanofibers obtained from paper waste [20]. The application of more ecologically viable biomaterials in TE may, in fact, strongly contribute to reduce the polluting impact of producing and using un-recyclable synthetic biopolymers. Among the renewable and natural biopolymers, pectin is gaining particular attention in TE for its advantageous properties including biocompatibility, biodegradability and non-toxicity [21, 22]. In addition, the versatility in processing pectin-based formulations allows to produce scaffolds with diverse properties and for different applications (Section 2).
This chapter aims at highlighting the applications of pectin as the building block of bidimensional (2D) and three-dimensional (3D) scaffolds for TE applications. With this aim, in Section 2 the properties of pectin as biomaterial are provided. Section 3 reports the most representative applications of pectin-based formulations for producing scaffolds for tissue regeneration in the shape of 2D films for wound healing and 3D scaffolds for tissue regeneration.
Pectin shows several remarkable properties as a biomaterial. It is biocompatible and biodegradable, and it is soluble in cytocompatible and non-toxic solvents (such as water). Pectin is a versatile biomaterial as its physical properties can be facilely tuned due to the presence of several functional groups (e.g., carboxylic groups) that can serve as binding sites for other functional groups, biomolecules and drugs [21, 22, 23]. It is a low-cost biomaterial due to its ubiquity in nature, and this can strongly reduce the costs associated with the development of engineered tissues.
Pectin can form hydrogel due to the ability of its macromolecules to absorb and retain large volumes of water. This unique property makes pectin a suitable candidate to produce a natural extracellular matrix, which naturally surrounds cells. Furthermore, due to the possibility to be processed under sterile and physiological conditions (i.e., the aqueous environment at 37°C), pectin enables to encapsulate cells within its matrix to produce cell-laden scaffolds [23, 24].
Pectin tends to dissolve under physiological conditions, therefore physicochemical approaches are required to stabilize pectin-based scaffolds. These are mainly based on the use of physicochemical crosslinking approaches which consist of the formation of a stable network of links among the pectin molecules. This network reduces the interactions of pectin molecules with water and prevents the disruption of pectin-based scaffolds. For example, the most employed approach to form water-insoluble scaffolds of low-methoxyl pectin is based on the use of divalent cations (e.g., Ca2+) that interact with the carboxylic groups of pectin forming the so-called ‘egg box’ structure [21]. Notably, the crosslinking treatments should also be cytocompatible (under specific conditions/concentrations), and should not interfere with the capability of pectin to encapsulate cells [25].
One of the major drawbacks that limit the application of pectin as a biomaterial for TE applications is its low cell adhesivity due to the lack of sites for cell adhesion (such as arg-gly-asp (RGD) sequences). Therefore, pectin is often combined/blended with other biopolymers or biomolecules to enhance its bioactivity [21, 26].
Pectin-based formulations have been processed through different fabrication approaches into scaffolds with various shapes for different applications. In particular, pectin has been mainly used for the production of 2D films for wound healing, and 3D scaffolds for tissue regeneration. Figure 2 provides a graphical overview of the main applications of pectin in TE.
Illustration of the application of pectin (derived from citrus fruits) for the production of scaffolds for TE applications (created with
One of the applications of pectin-based formulations is the preparation of 2D hydrogel patches for the treatment of wounds. These patches provide mechanical support to cells during the process of new tissue formation, and an antibacterial barrier preventing eventual infections. Moreover, the hydrophilic pectin molecules in the film can react with the fluids of the wound forming a soft gel. The presence of a gel allows to maintain a moist environment in the wound. This helps to remove or control secretions from the wounded tissue and in turn facilitates the healing process. The regeneration of the damaged tissue can be further promoted by the incorporation of bioactive molecules such as drugs (e.g., antibiotics) and/or growth factors within the pectin patches [21]. The controlled and prolonged release of these molecules directly in the damaged site can actively contribute to decreasing the risk of infections and accelerating the formation of new tissue. As mentioned in Section 2, pectin is often combined with other biopolymers to enhance its bioactivity and also to modulate the physical properties (e.g., tensile strength) of the final patch.
Pectin-based patches for wound healing reported in the literature so far are principally obtained in the shape of non-porous films and porous membranes, as detailed described in the following Sections 3.1.1 and 3.1.2, respectively.
Pectin-based films are generally 2D, non-porous and flexible substrates able to retain large volumes of water within their matrix. One of the approaches used to produce these films is the so-called ‘solvent casting’. In this approach, a pectin-based solution is initially poured into a mold, and the solvent is subsequently let to evaporate leaving a 2D non-porous film (Figure 3).
Illustration of the solvent casting approach (created with
Pectin-based patches produced with this approach support cell adhesion and proliferation and accelerate the processes occurring during the formation of new tissue [27, 28, 29, 30]. Moreover, films with high toughness and stretchability can be produced with solvent casting, and these can be potentially used as pectin-based patches for load-bearing tissues (e.g., cartilage, tendon) [28]. In addition, pectin-based patches for a controlled drug into the targeted tissue were also produced by incorporating drugs in the pectin matrix [30, 31].
Nanoporous membranes based on pectin have been mainly obtained through electrospinning. This approach allows to produce highly porous and flexible patches starting from pectin-based/polymer solutions subjected to an external electric field. A standard electrospinning apparatus is illustrated in Figure 4. It generally consists of (i) a syringe pump containing the polymer solution, (ii) a metallic needle through which the polymer solution is ejected, (iii) a high voltage power supply (in the range of tens of kVolts), and (iv) a grounded collector (usually a metal plate). When a drop of the polymer solution is extruded through the needle, the high electric forces in the space between the needle and the collector induce its stretching and the formation of fibers from a few nanometers to microns in diameters [32]. These fibers are therefore deposited and collected on the collector forming a non-woven fibrous membrane after complete evaporation of the solvent (Figure 4).
Illustration of an electrospinning setup with a magnification of the electrospun nanofibers on the collector (image obtained with scanning electron microscopy).
Pectin-based patches obtained by this approach show several advantageous properties for TE applications. The random organization of electrospun pectin fibers together with the hydrogel nature of pectin enables to mimic the nanoscale organization of the native extracellular matrix. Furthermore, the high porosity and high surface-to-volume ratio typical of electrospun patches promote cell migration and nutrient diffusion within the scaffold, which is beneficial for the process of new tissue formation [33]. Nevertheless, it is quite challenging to produce electrospun structures from pristine pectin due to some intrinsic molecular properties of pectin (such as insufficient chain entanglement) that disable the fiber formation [34]. Thus, to improve its electrospinning ability, pectin is often chemically modified [35, 36] and/or combined with other biodegradable biopolymers such as poly(ethylene oxide) [34], polyhydroxybutyrate [37] that work as carrier polymer to induce the formation of stable fibers.
Pectin-based nano-fibers find application for the preparation of films/structures that can be potentially used as patches for wound healing of soft tissues [35, 36, 37] (e.g., vascular tissue [35], retinal tissue [37]). In addition, drugs (such as antibiotics [38, 39]) and particles (such as argentum ions for antibacterial purposes [38]) can be successfully loaded in these structures obtaining patches for a local and controlled release of drugs directly into the wound.
Pectin-based formulations can be further processed to obtain 3D scaffolds able to mimic the complex architecture of biological tissues. 3D pectin-based scaffolds have been principally obtained in the shape of porous 3D sponges and 3D bioprinted scaffolds.
Sponges are comparable to foams with an interconnected network of pores. This type of architecture is beneficial for cell penetration and scaffold colonization, while ensuring adequate diffusion of nutrients to cells within the scaffold. Moreover, a highly porous scaffold with open and connected pores is of critical importance as it allows for the diffusion of nutrients and waste products through the scaffold [6, 7].
Pectin-based sponges are mainly obtained by freeze-drying, also known as lyophilization. This technique consists in freezing a polymer solution followed by the evaporation of the frozen solvent by sublimation. Thus, a solid polymer matrix with numerous and interconnected pores is obtained (Figure 5). Before freezing, polymer solutions are generally poured into molds to produce porous scaffolds with the desired shape.
Schematic of the process for obtaining cylindrical porous sponges was obtained by freeze-drying. Magnification of the porous sponges obtained by scanning electron microscopy (image created with
Pectin-based sponges have been principally used to produce scaffolds for wound healing and tissue regeneration. For example, sponges obtained with pectin-based formulations have been used as scaffolds for different types of tissues including cartilage [40, 41], skin [42], and bone [43]. The high hydrophilicity of pectin molecules and the interconnected porosity enables these sponges to entrap a large volume of water creating a 3D hydrogel-based environment that can mimic the natural extracellular matrix [40, 41]. Furthermore, this provides and stabilizes a moist environment for wounds that strongly contributes to accelerating the healing of the wounds [44].
Producing scaffolds with a customized architecture and by automated and high reproducible approaches is one of the main challenges of TE. The development of pectin-based scaffolds with patient-specific architecture may boost their clinical applications.
Pectin-based scaffolds with complex shapes have been principally obtained by extrusion-based bioprinting so far. Extrusion-based bioprinting is one of the most widely used technology in TE due to its simplicity and versatility in processing a large variety of biomaterials, cells and biomolecules. An extrusion-based bioprinter usually consists of a movable cartridge containing the biomaterial formulation (called ‘
Schematic of extrusion-based bioprinting.
The application of pectin-based inks in extrusion-based bioprinting is relatively recent compared to the other fabrication approaches described in the previous sections. Pectin solutions are often not suitable to be processed through extrusion-based bioprinting and structures with poor shape fidelity are often obtained. The first application of pectin as ink for extrusion-based bioprinting dates back to 2017. In this case, pectin was combined with another biopolymer (Pluronic F-127), and complex-shaped scaffolds were bioprinted [47, 48]. Cells were successfully loaded within this formulation and 3D bioprinted to produce living 3D constructs [24]. From that moment, other pectin-based inks have been developed and optimized to produce 3D scaffolds with high shape fidelity [49, 50, 51]. For example, pectin-based scaffolds with more complex shapes such as a human ear and nose shape for cartilage tissue regeneration were successfully obtained (Figure 6) [41].
TE represents an alternative approach to conventional surgical techniques used to treat damaged, injured or diseased tissues or organs. This approach is based on the use of tissue-mimicking and biodegradable constructs, based on the so-called ‘scaffolds’, able to restore, maintain or improve tissue functions. The physicochemical properties of the final scaffold play a key role in the process of new tissue formation. The selection of the proper biomaterial formulation is therefore essential. Recently, renewable biomaterials derived from industrial by-products are finding increasing application in TE as an alternative to petroleum-derived and unrecyclable polymers. In this regard, pectin, a polysaccharide commercially derived from citrus peel and apple pomace (both by-products of the food processing industry), is gaining attention in TE due to its biocompatibility, biodegradability and non-cytotoxicity. Diverse pectin-based formulations have been developed and employed for the fabrication of functional scaffolds for TE applications.
This chapter presented the most representative applications of pectin-based formulations for the fabrication of scaffolds for TE applications. In particular, by properly processing these formulations through specific fabrication techniques is possible to produce pectin-based scaffolds with different features: from 2D non-porous films (obtained by solvent casting) to 3D scaffolds with patient-specific shape (obtained by extrusion-based bioprinting). Although pectin shows diverse advantageous properties as biomaterial, its application in clinical practice is still under investigation. The increasing number of studies on the preparation of biocompatible pectin-based formulations may strongly boost the employment of this polysaccharide in the fabrication of sustainable scaffolds for future TE applications.
The authors wish to acknowledge the Crosslab Additive Manufacturing of the Department of Information Engineering of the University of Pisa.
The authors declare no conflict of interest.
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\n\nSljedeća terminologija odnosi se na Odredbe i uvjete, te na sve naše ugovore:
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\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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The application of this test has significantly changed the practice of medical laboratories in which it is used for detection and quantification of molecules such as hormones, peptides, antibodies, and proteins. Various technical variants of this test can detect antigen (native or foreign) or antibody, determine the intensity of the immune response whether pathological or not; the type of induced immune response as well as the innate immunity potential; and much more. These capabilities, as well as the high sensitivity and robustness of the test and a small price, make it possible to quickly and reliably diagnose diseases in most laboratories. Besides, ELISA is a test that is also used in veterinary medicine, toxicology, allergology, food industry, etc. Despite the fact that it has existed for almost 50 years, different ELISA tests with different technical solutions are still being developed, which improves and expands the application of the this exceptional test. The aim of this chapter is to empower the rider to optimize, standardize and validate an enzyme linked immunosorbent assay.",book:{id:"9850",slug:"norovirus",title:"Norovirus",fullTitle:"Norovirus"},signatures:"Rajna Minic and Irena Zivkovic",authors:[{id:"325806",title:"Ph.D.",name:"Irena",middleName:null,surname:"Zivkovic",slug:"irena-zivkovic",fullName:"Irena Zivkovic"},{id:"325839",title:"Dr.",name:"Rajna",middleName:null,surname:"Minic",slug:"rajna-minic",fullName:"Rajna Minic"}]},{id:"56750",title:"Laboratory Approach to Anemia",slug:"laboratory-approach-to-anemia",totalDownloads:6181,totalCrossrefCites:2,totalDimensionsCites:4,abstract:"Anemia is a major cause of morbidity and mortality worldwide and can be defined as a decreased quantity of circulating red blood cells (RBCs). The epidemiological studies suggested that one-third of the world’s population is affected with anemia. Anemia is not a disease, but it is instead the sign of an underlying basic pathological process. However, the sign may function as a compass in the search for the cause. Therefore, the prediagnosis revealed by thorough investigation of this sign should be supported by laboratory parameters according to the underlying pathological process. We expect that this review will provide guidance to clinicians with findings and laboratory tests that can be followed from the initial stage in the anemia search.",book:{id:"5942",slug:"current-topics-in-anemia",title:"Current Topics in Anemia",fullTitle:"Current Topics in Anemia"},signatures:"Ebru Dündar Yenilmez and Abdullah Tuli",authors:[{id:"183998",title:"Ph.D.",name:"Ebru",middleName:null,surname:"Dündar Yenilmez",slug:"ebru-dundar-yenilmez",fullName:"Ebru Dündar Yenilmez"},{id:"209103",title:"Prof.",name:"Abdullah",middleName:null,surname:"Tuli",slug:"abdullah-tuli",fullName:"Abdullah Tuli"}]},{id:"33133",title:"Waist Circumference in Children and Adolescents from Different Ethnicities",slug:"waist-circumference-in-children-and-adolescents-from-different-ethnicities",totalDownloads:8e3,totalCrossrefCites:4,totalDimensionsCites:7,abstract:null,book:{id:"642",slug:"childhood-obesity",title:"Childhood Obesity",fullTitle:"Childhood Obesity"},signatures:"Peter Schwandt and Gerda-Maria Haas",authors:[{id:"29867",title:"Prof.",name:"Peter",middleName:null,surname:"Schwandt",slug:"peter-schwandt",fullName:"Peter Schwandt"}]}],onlineFirstChaptersFilter:{topicId:"185",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"81939",title:"Translational Research on Chagas Disease: Focusing on Drug Combination and Repositioning",slug:"translational-research-on-chagas-disease-focusing-on-drug-combination-and-repositioning",totalDownloads:19,totalDimensionsCites:0,doi:"10.5772/intechopen.104231",abstract:"Chagas disease, caused by the protozoan Trypanosoma cruzi, is a major neglected disease endemic to Latin America, associated to significant morbimortality comprising a remarkable socioeconomic problem mainly for low-income tropical populations. The present chapter focuses translational research on Chagas disease, approaching drug combinations and repositioning, particularly exploiting the parasite oxidative stress by prospecting prooxidant compounds combined with antagonists of antioxidant systems, for developing low-cost and safe therapies for this infection. The pertinent literature on protozoal parasitic diseases is reviewed as well as on repurposing disulfiram aiming the combination with the Chagas disease drug of choice benznidazole. Both disulfiram and its first derivative sodium diethyldithiocarbamate (DETC) are able not only to inhibit p-glycoprotein, possibly reverting resistance phenotypes, but also to reduce toxicity of numerous other drugs, heavy metals, etc. Therefore, this innovation, presently in clinical research, may furnish a novel therapeutic for T. cruzi infections overcoming the adverse effects and refractory cases that impair the effectiveness of Chagas disease treatment.",book:{id:"11377",title:"Chagas Disease - From Cellular and Molecular Aspects of Trypanosoma cruzi-Host Interactions to the Clinical Intervention",coverURL:"https://cdn.intechopen.com/books/images_new/11377.jpg"},signatures:"Marcos André Vannier-Santos, Ana Márcia Suarez-Fontes, Juliana Almeida-Silva, Alessandra Lifsitch Viçosa, Sandra Aurora Chavez Perez, Alejandro Marcel Hasslocher-Moreno, Gabriel Parreiras Estolano da Silveira, Luciana Fernandes Portela and Roberto Magalhães Saraiva"},{id:"81702",title:"The Saga of Selenium Treatment Investigation in Chagas Disease Cardiopathy: Translational Research in a Neglected Tropical Disease in Brazil",slug:"the-saga-of-selenium-treatment-investigation-in-chagas-disease-cardiopathy-translational-research-in",totalDownloads:8,totalDimensionsCites:0,doi:"10.5772/intechopen.103772",abstract:"This chapter describes the steps from basic research to the definition of a putative public health recommendation in the clinical protocols and therapeutic guidelines for selenium (Se) supplementation for patients with Chagas disease. From 1998 to 2018, we conducted a translational research project to test the concept that chronic Chagas disease cardiopathy (CCC) severity could be associated with low levels of blood selenium (Se), and if oral Se supplementation could help to sustain the asymptomatic cardiac stage and reduce disease severity. Pre-clinical studies in mice and a clinical trial conducted in the early asymptomatic cardiac stage of CCC patients (B stage) were performed, identified as “Selenium Treatment of Chagasic Cardiopathy (STCC)” trial. The roadmap of the selenium project was/is a real saga, with important obstacles that tested team resilience and revealed Brazilian conditions of science development. We discuss the main possible mechanisms involved in the physiopathology of CCC and the lessons learned in this process. In this chapter, we also organized the timeline of the translational project and described the crucial moments of the journey, as well as the next steps driving the research teams and their international and health industry connections.",book:{id:"11377",title:"Chagas Disease - From Cellular and Molecular Aspects of Trypanosoma cruzi-Host Interactions to the Clinical Intervention",coverURL:"https://cdn.intechopen.com/books/images_new/11377.jpg"},signatures:"Tania C. de Araujo-Jorge, Anna Cristina C. Carvalho, Roberto R. Ferreira, Luciana R. Garzoni, Beatriz M.S. Gonzaga, Marcelo T. Holanda, Gilberto M. Sperandio da Silva, Maria da Gloria Bonecini-Almeida, Mauro F.F. Mediano, Roberto M. Saraiva and Alejandro M. Hasslocher-Moreno"},{id:"81938",title:"How Do Mouse Strains and Inoculation Routes Influence the Course of Experimental Trypanosoma cruzi Infection?",slug:"how-do-mouse-strains-and-inoculation-routes-influence-the-course-of-experimental-trypanosoma-cruzi-i",totalDownloads:13,totalDimensionsCites:0,doi:"10.5772/intechopen.104461",abstract:"Chagas’ disease outcomes depend on several factors including parasite and host genetics, immune response, and route of infection. In this study, we investigate the influence of inoculation route and host genetic background on the establishment and development of Chagas disease in mice, using an isolate of Trypanosoma cruzi SC2005 strain (TcII), which was obtained from an oral Chagas’ disease outbreak in Santa Catarina, Brazil. Comparative analysis of the immunopathological, histopathological, and hematological profiles of mice was performed demonstrating the influence of the route of infection in disease severity. In outbred mice, intraperitoneal (IP) infection led to higher infection and mortality rates and more severe parasitaemia, when compared with intragastric (IG) infection. Nevertheless, tissue colonization was similar, showing severe damage in the heart, with intense lymphocytic inflammatory infiltrates, regardless of the route of infection. On the other hand, in mice IG-infected, the host genetic background influences the start timing of immune response against Trypanosoma cruzi. The susceptible BALB/c inbred mouse strain presented an earlier development of a cytotoxic cellular profile, when compared with A mice. We hypothesize that the cytotoxic response mounted before the parasitaemia increase allowed for a milder manifestation of Chagas’ disease in intragastrically infected mice.",book:{id:"11377",title:"Chagas Disease - From Cellular and Molecular Aspects of Trypanosoma cruzi-Host Interactions to the Clinical Intervention",coverURL:"https://cdn.intechopen.com/books/images_new/11377.jpg"},signatures:"Flávia de Oliveira Cardoso, Carolina Salles Domingues, Tânia Zaverucha do Valle and Kátia da Silva Calabrese"},{id:"81814",title:"Evaluation of Molecular Variability of Isolates of Trypanosoma cruzi in the State of Rio de Janeiro-Brazil",slug:"evaluation-of-molecular-variability-of-isolates-of-trypanosoma-cruzi-in-the-state-of-rio-de-janeiro-",totalDownloads:11,totalDimensionsCites:0,doi:"10.5772/intechopen.104498",abstract:"Trypanosoma cruzi, the etiological agent of Chagas disease, presents considerable heterogeneity among populations of isolates within the sylvatic and domestic cycle. This study aims to evaluate the genetic diversity of 14 isolates collected from specimens of Triatoma vitticeps from Triunfo, Conceição de Macabu, and Santa Maria Madalena cities (Rio de Janeiro—Brazil). By using PCR based on the mini-exon gene, all isolates showed a profile characteristic of bands zymodeme III and with a lower intensity characteristic of TcII. To verify possible hybrids among the strains analyzed, the polymorphisms analysis of the MSH2 gene was performed. HhaI restriction enzyme digestion products resulted in characteristic TcII fragments only, demonstrating the absence of hybrids strains. In our attempt to characterize isolation in accordance with the reclassification of T. cruzi into six new groups called DTUs (“discrete typing unit”), we genotyped the mitochondrial cytochrome oxidase subunit two gene, ribosomal RNA gen (24Sα rDNA), and the spliced leader intergenic region (SL-IR). This procedure showed that TcII, TcIII, and TcIV are circulating in this area. This highlights the diversity of parasites infecting specimens of T. vitticeps, emphasizing the habit of wild type and complexity of the region epidemiological study that presents potential mixed populations.",book:{id:"11377",title:"Chagas Disease - From Cellular and Molecular Aspects of Trypanosoma cruzi-Host Interactions to the Clinical Intervention",coverURL:"https://cdn.intechopen.com/books/images_new/11377.jpg"},signatures:"Helena Keiko Toma, Luciana Reboredo de Oliveira da Silva, Teresa Cristina Monte Gonçalves, Renato da Silva Junior and Jacenir R. Santos-Mallet"},{id:"81252",title:"Modulation of Host Cell Apoptosis by Trypanosoma cruzi: Repercussions in the Development of Chronic Chagasic Cardiomyopathy",slug:"modulation-of-host-cell-apoptosis-by-trypanosoma-cruzi-repercussions-in-the-development-of-chronic-c",totalDownloads:33,totalDimensionsCites:0,doi:"10.5772/intechopen.103740",abstract:"Trypanosoma cruzi is an intracellular parasite, which causes Chagas disease, affecting millions of people throughout the world. T. cruzi can invade several cell types, among which macrophages and cardiomyocytes stand out. Chagas disease goes through two stages: acute and chronic. If it becomes chronic, its most severe form is the chagasic chronic cardiomyopathy, which accounts for most of the fatalities due to this disease. For parasites to persist for long enough in cells, they should evade several host immune responses, one of these being apoptosis. Apoptosis is a type of programmed cell death described as a well-ordered and silent collection of steps that inevitably lead cells to a noninflammatory death. Cells respond to infection by initiating their own death to combat the infection. As a result, several intracellular microorganisms have developed different strategies to overcome host cell apoptosis and persist inside cells. It has been shown that T. cruzi has the ability to inhibit host cells apoptosis and can also induce apoptosis of cells that combat the parasite such as cytotoxic T cells. The aim of this chapter is to present up-to-date information about the molecules and mechanisms engaged by T. cruzi to achieve this goal and how the modulation of apoptosis by T. cruzi reflects in the development of chronic chagasic cardiomyopathy.",book:{id:"11377",title:"Chagas Disease - From Cellular and Molecular Aspects of Trypanosoma cruzi-Host Interactions to the Clinical Intervention",coverURL:"https://cdn.intechopen.com/books/images_new/11377.jpg"},signatures:"Fiordaliso Carolina Román-Carraro, Diego Maurizio Coria-Paredes, Arturo A. Wilkins-Rodríguez and Laila Gutiérrez-Kobeh"},{id:"80917",title:"Digestive Disorders in Chagas Disease: Megaesophagus and Chagasic Megacolon",slug:"digestive-disorders-in-chagas-disease-megaesophagus-and-chagasic-megacolon",totalDownloads:25,totalDimensionsCites:0,doi:"10.5772/intechopen.102871",abstract:"Chagas disease, also known as American trypanosomiasis, caused by Trypanosoma cruzi and transmitted by hematophagous vectors, is a parasitic disease, which according to the WHO ranks fourth as a cause of loss of potential years of life due to complications that can occur in multiple body systems. According to the reports presented by the World Health Organization, there are between 16 and 18 million infected people in the world, predominantly in endemic areas of Latin America, of which only 1% receives an adequate diagnosis and full treatment, thereby that the chronic phase comes to present digestive disorders that are one of the main causes of loss in the quality of life of patients, as well as complications that can lead to life-threatening surgical emergencies.",book:{id:"11377",title:"Chagas Disease - From Cellular and Molecular Aspects of Trypanosoma cruzi-Host Interactions to the Clinical Intervention",coverURL:"https://cdn.intechopen.com/books/images_new/11377.jpg"},signatures:"Víctor Hugo García Orozco, Juan Enrique Villalvazo Navarro, Carlos Solar Aguirre, Carlos Manuel Ibarra Ocampo, César Iván Díaz Sandoval, Carlos Alejandro Ortíz Gallegos, Diego Javier Oregel Camacho and Araceli Noriega Bucio"}],onlineFirstChaptersTotal:6},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:89,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:104,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:32,numberOfPublishedChapters:318,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:141,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:113,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:106,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:5,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:15,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}}]},series:{item:{id:"6",title:"Infectious Diseases",doi:"10.5772/intechopen.71852",issn:"2631-6188",scope:"This series will provide a comprehensive overview of recent research trends in various Infectious Diseases (as per the most recent Baltimore classification). Topics will include general overviews of infections, immunopathology, diagnosis, treatment, epidemiology, etiology, and current clinical recommendations for managing infectious diseases. Ongoing issues, recent advances, and future diagnostic approaches and therapeutic strategies will also be discussed. This book series will focus on various aspects and properties of infectious diseases whose deep understanding is essential for safeguarding the human race from losing resources and economies due to pathogens.",coverUrl:"https://cdn.intechopen.com/series/covers/6.jpg",latestPublicationDate:"June 25th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:13,editor:{id:"131400",title:"Prof.",name:"Alfonso J.",middleName:null,surname:"Rodriguez-Morales",slug:"alfonso-j.-rodriguez-morales",fullName:"Alfonso J. Rodriguez-Morales",profilePictureURL:"https://mts.intechopen.com/storage/users/131400/images/system/131400.png",biography:"Dr. Rodriguez-Morales is an expert in tropical and emerging diseases, particularly zoonotic and vector-borne diseases (especially arboviral diseases). He is the president of the Travel Medicine Committee of the Pan-American Infectious Diseases Association (API), as well as the president of the Colombian Association of Infectious Diseases (ACIN). He is a member of the Committee on Tropical Medicine, Zoonoses, and Travel Medicine of ACIN. He is a vice-president of the Latin American Society for Travel Medicine (SLAMVI) and a Member of the Council of the International Society for Infectious Diseases (ISID). Since 2014, he has been recognized as a Senior Researcher, at the Ministry of Science of Colombia. He is a professor at the Faculty of Medicine of the Fundacion Universitaria Autonoma de las Americas, in Pereira, Risaralda, Colombia. He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. He is currently the Editor in Chief of the journal Travel Medicine and Infectious Diseases. His Scopus H index is 47 (Google Scholar H index, 68).",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null},editorTwo:null,editorThree:null},subseries:{paginationCount:4,paginationItems:[{id:"3",title:"Bacterial Infectious Diseases",coverUrl:"https://cdn.intechopen.com/series_topics/covers/3.jpg",isOpenForSubmission:!1,editor:null,editorTwo:null,editorThree:null},{id:"4",title:"Fungal Infectious Diseases",coverUrl:"https://cdn.intechopen.com/series_topics/covers/4.jpg",isOpenForSubmission:!0,editor:{id:"174134",title:"Dr.",name:"Yuping",middleName:null,surname:"Ran",slug:"yuping-ran",fullName:"Yuping Ran",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bS9d6QAC/Profile_Picture_1630330675373",biography:"Dr. Yuping Ran, Professor, Department of Dermatology, West China Hospital, Sichuan University, Chengdu, China. Completed the Course Medical Mycology, the Centraalbureau voor Schimmelcultures (CBS), Fungal Biodiversity Centre, Netherlands (2006). International Union of Microbiological Societies (IUMS) Fellow, and International Emerging Infectious Diseases (IEID) Fellow, Centers for Diseases Control and Prevention (CDC), Atlanta, USA. Diploma of Dermatological Scientist, Japanese Society for Investigative Dermatology. Ph.D. of Juntendo University, Japan. Bachelor’s and Master’s degree, Medicine, West China University of Medical Sciences. Chair of Sichuan Medical Association Dermatology Committee. General Secretary of The 19th Annual Meeting of Chinese Society of Dermatology and the Asia Pacific Society for Medical Mycology (2013). In charge of the Annual Medical Mycology Course over 20-years authorized by National Continue Medical Education Committee of China. Member of the board of directors of the Asia-Pacific Society for Medical Mycology (APSMM). Associate editor of Mycopathologia. Vice-chief of the editorial board of Chinses Journal of Mycology, China. Board Member and Chair of Mycology Group of Chinese Society of Dermatology.",institutionString:null,institution:{name:"Sichuan University",institutionURL:null,country:{name:"China"}}},editorTwo:null,editorThree:null},{id:"5",title:"Parasitic Infectious Diseases",coverUrl:"https://cdn.intechopen.com/series_topics/covers/5.jpg",isOpenForSubmission:!0,editor:{id:"67907",title:"Dr.",name:"Amidou",middleName:null,surname:"Samie",slug:"amidou-samie",fullName:"Amidou Samie",profilePictureURL:"https://mts.intechopen.com/storage/users/67907/images/system/67907.jpg",biography:"Dr. Amidou Samie is an Associate Professor of Microbiology at the University of Venda, in South Africa, where he graduated for his PhD in May 2008. He joined the Department of Microbiology the same year and has been giving lectures on topics covering parasitology, immunology, molecular biology and industrial microbiology. He is currently a rated researcher by the National Research Foundation of South Africa at category C2. He has published widely in the field of infectious diseases and has overseen several MSc’s and PhDs. His research activities mostly cover topics on infectious diseases from epidemiology to control. His particular interest lies in the study of intestinal protozoan parasites and opportunistic infections among HIV patients as well as the potential impact of childhood diarrhoea on growth and child development. He also conducts research on water-borne diseases and water quality and is involved in the evaluation of point-of-use water treatment technologies using silver and copper nanoparticles in collaboration with the University of Virginia, USA. He also studies the use of medicinal plants for the control of infectious diseases as well as antimicrobial drug resistance.",institutionString:null,institution:{name:"University of Venda",institutionURL:null,country:{name:"South Africa"}}},editorTwo:null,editorThree:null},{id:"6",title:"Viral Infectious Diseases",coverUrl:"https://cdn.intechopen.com/series_topics/covers/6.jpg",isOpenForSubmission:!0,editor:{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",biography:"Professor Dr. Shailendra K. Saxena is a vice dean and professor at King George's Medical University, Lucknow, India. 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He also obtained an MSc in Molecular and Genetic Medicine, and a Ph.D. in Clinical Immunology and Human Genetics from the University of Sheffield, UK. He also completed a short-term fellowship in Pediatric Clinical Immunology and Bone Marrow Transplantation at Newcastle General Hospital, England. Dr. Rezaei is a Full Professor of Immunology and Vice Dean of International Affairs and Research, at the School of Medicine, Tehran University of Medical Sciences, and the co-founder and head of the Research Center for Immunodeficiencies. He is also the founding president of the Universal Scientific Education and Research Network (USERN). Dr. Rezaei has directed more than 100 research projects and has designed and participated in several international collaborative projects. He is an editor, editorial assistant, or editorial board member of more than forty international journals. He has edited more than 50 international books, presented more than 500 lectures/posters in congresses/meetings, and published more than 1,100 scientific papers in international journals.",institutionString:"Tehran University of Medical Sciences",institution:{name:"Tehran University of Medical Sciences",country:{name:"Iran"}}},{id:"180733",title:"Dr.",name:"Jean",middleName:null,surname:"Engohang-Ndong",slug:"jean-engohang-ndong",fullName:"Jean Engohang-Ndong",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180733/images/system/180733.png",biography:"Dr. Jean Engohang-Ndong was born and raised in Gabon. After obtaining his Associate Degree of Science at the University of Science and Technology of Masuku, Gabon, he continued his education in France where he obtained his BS, MS, and Ph.D. in Medical Microbiology. He worked as a post-doctoral fellow at the Public Health Research Institute (PHRI), Newark, NJ for four years before accepting a three-year faculty position at Brigham Young University-Hawaii. Dr. Engohang-Ndong is a tenured faculty member with the academic rank of Full Professor at Kent State University, Ohio, where he teaches a wide range of biological science courses and pursues his research in medical and environmental microbiology. Recently, he expanded his research interest to epidemiology and biostatistics of chronic diseases in Gabon.",institutionString:"Kent State University",institution:{name:"Kent State University",country:{name:"United States of America"}}},{id:"188773",title:"Prof.",name:"Emmanuel",middleName:null,surname:"Drouet",slug:"emmanuel-drouet",fullName:"Emmanuel Drouet",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/188773/images/system/188773.png",biography:"Emmanuel Drouet, PharmD, is a Professor of Virology at the Faculty of Pharmacy, the University Grenoble-Alpes, France. As a head scientist at the Institute of Structural Biology in Grenoble, Dr. Drouet’s research investigates persisting viruses in humans (RNA and DNA viruses) and the balance with our host immune system. He focuses on these viruses’ effects on humans (both their impact on pathology and their symbiotic relationships in humans). He has an excellent track record in the herpesvirus field, and his group is engaged in clinical research in the field of Epstein-Barr virus diseases. He is the editor of the online Encyclopedia of Environment and he coordinates the Universal Health Coverage education program for the BioHealth Computing Schools of the European Institute of Science.",institutionString:null,institution:{name:"Grenoble Alpes University",country:{name:"France"}}},{id:"131400",title:"Prof.",name:"Alfonso J.",middleName:null,surname:"Rodriguez-Morales",slug:"alfonso-j.-rodriguez-morales",fullName:"Alfonso J. Rodriguez-Morales",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/131400/images/system/131400.png",biography:"Dr. Rodriguez-Morales is an expert in tropical and emerging diseases, particularly zoonotic and vector-borne diseases (especially arboviral diseases). He is the president of the Travel Medicine Committee of the Pan-American Infectious Diseases Association (API), as well as the president of the Colombian Association of Infectious Diseases (ACIN). He is a member of the Committee on Tropical Medicine, Zoonoses, and Travel Medicine of ACIN. He is a vice-president of the Latin American Society for Travel Medicine (SLAMVI) and a Member of the Council of the International Society for Infectious Diseases (ISID). Since 2014, he has been recognized as a Senior Researcher, at the Ministry of Science of Colombia. He is a professor at the Faculty of Medicine of the Fundacion Universitaria Autonoma de las Americas, in Pereira, Risaralda, Colombia. He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. He is currently the Editor in Chief of the journal Travel Medicine and Infectious Diseases. His Scopus H index is 47 (Google Scholar H index, 68).",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null},{id:"332819",title:"Dr.",name:"Chukwudi Michael",middleName:"Michael",surname:"Egbuche",slug:"chukwudi-michael-egbuche",fullName:"Chukwudi Michael Egbuche",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/332819/images/14624_n.jpg",biography:"I an Dr. Chukwudi Michael Egbuche. I am a Senior Lecturer in the Department of Parasitology and Entomology, Nnamdi Azikiwe University, Awka.",institutionString:null,institution:{name:"Nnamdi Azikiwe University",country:{name:"Nigeria"}}},{id:"284232",title:"Mr.",name:"Nikunj",middleName:"U",surname:"Tandel",slug:"nikunj-tandel",fullName:"Nikunj Tandel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/284232/images/8275_n.jpg",biography:'Mr. Nikunj Tandel has completed his Master\'s degree in Biotechnology from VIT University, India in the year of 2012. He is having 8 years of research experience especially in the field of malaria epidemiology, immunology, and nanoparticle-based drug delivery system against the infectious diseases, autoimmune disorders and cancer. He has worked for the NIH funded-International Center of Excellence in Malaria Research project "Center for the study of complex malaria in India (CSCMi)" in collaboration with New York University. The preliminary objectives of the study are to understand and develop the evidence-based tools and interventions for the control and prevention of malaria in different sites of the INDIA. Alongside, with the help of next-generation genomics study, the team has studied the antimalarial drug resistance in India. Further, he has extended his research in the development of Humanized mice for the study of liver-stage malaria and identification of molecular marker(s) for the Artemisinin resistance. At present, his research focuses on understanding the role of B cells in the activation of CD8+ T cells in malaria. Received the CSIR-SRF (Senior Research Fellow) award-2018, FIMSA (Federation of Immunological Societies of Asia-Oceania) Travel Bursary award to attend the IUIS-IIS-FIMSA Immunology course-2019',institutionString:"Nirma University",institution:{name:"Nirma University",country:{name:"India"}}},{id:"334383",title:"Ph.D.",name:"Simone",middleName:"Ulrich",surname:"Ulrich Picoli",slug:"simone-ulrich-picoli",fullName:"Simone Ulrich Picoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334383/images/15919_n.jpg",biography:"Graduated in Pharmacy from Universidade Luterana do Brasil (1999), Master in Agricultural and Environmental Microbiology from Federal University of Rio Grande do Sul (2002), Specialization in Clinical Microbiology from Universidade de São Paulo, USP (2007) and PhD in Sciences in Gastroenterology and Hepatology (2012). She is currently an Adjunct Professor at Feevale University in Medicine and Biomedicine courses and a permanent professor of the Academic Master\\'s Degree in Virology. She has experience in the field of Microbiology, with an emphasis on Bacteriology, working mainly on the following topics: bacteriophages, bacterial resistance, clinical microbiology and food microbiology.",institutionString:null,institution:{name:"Universidade Feevale",country:{name:"Brazil"}}},{id:"229220",title:"Dr.",name:"Amjad",middleName:"Islam",surname:"Aqib",slug:"amjad-aqib",fullName:"Amjad Aqib",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229220/images/system/229220.png",biography:"Dr. Amjad Islam Aqib obtained a DVM and MSc (Hons) from University of Agriculture Faisalabad (UAF), Pakistan, and a PhD from the University of Veterinary and Animal Sciences Lahore, Pakistan. Dr. Aqib joined the Department of Clinical Medicine and Surgery at UAF for one year as an assistant professor where he developed a research laboratory designated for pathogenic bacteria. Since 2018, he has been Assistant Professor/Officer in-charge, Department of Medicine, Manager Research Operations and Development-ORIC, and President One Health Club at Cholistan University of Veterinary and Animal Sciences, Bahawalpur, Pakistan. He has nearly 100 publications to his credit. His research interests include epidemiological patterns and molecular analysis of antimicrobial resistance and modulation and vaccine development against animal pathogens of public health concern.",institutionString:"Cholistan University of Veterinary and Animal Sciences",institution:null},{id:"62900",title:"Prof.",name:"Fethi",middleName:null,surname:"Derbel",slug:"fethi-derbel",fullName:"Fethi Derbel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62900/images/system/62900.jpeg",biography:"Professor Fethi Derbel was born in 1960 in Tunisia. He received his medical degree from the Sousse Faculty of Medicine at Sousse, University of Sousse, Tunisia. He completed his surgical residency in General Surgery at the University Hospital Farhat Hached of Sousse and was a member of the Unit of Liver Transplantation in the University of Rennes, France. He then worked in the Department of Surgery at the Sahloul University Hospital in Sousse. Professor Derbel is presently working at the Clinique les Oliviers, Sousse, Tunisia. His hospital activities are mostly concerned with laparoscopic, colorectal, pancreatic, hepatobiliary, and gastric surgery. He is also very interested in hernia surgery and performs ventral hernia repairs and inguinal hernia repairs. He has been a member of the GREPA and Tunisian Hernia Society (THS). During his residency, he managed patients suffering from diabetic foot, and he was very interested in this pathology. For this reason, he decided to coordinate a book project dealing with the diabetic foot. Professor Derbel has published many articles in journals and collaborates intensively with IntechOpen Access Publisher as an editor.",institutionString:"Clinique les Oliviers",institution:null},{id:"300144",title:"Dr.",name:"Meriem",middleName:null,surname:"Braiki",slug:"meriem-braiki",fullName:"Meriem Braiki",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/300144/images/system/300144.jpg",biography:"Dr. Meriem Braiki is a specialist in pediatric surgeon from Tunisia. She was born in 1985. She received her medical degree from the University of Medicine at Sousse, Tunisia. She achieved her surgical residency training periods in Pediatric Surgery departments at University Hospitals in Monastir, Tunis and France.\r\nShe is currently working at the Pediatric surgery department, Sidi Bouzid Hospital, Tunisia. Her hospital activities are mostly concerned with laparoscopic, parietal, urological and digestive surgery. She has published several articles in diffrent journals.",institutionString:"Sidi Bouzid Regional Hospital",institution:null},{id:"229481",title:"Dr.",name:"Erika M.",middleName:"Martins",surname:"de Carvalho",slug:"erika-m.-de-carvalho",fullName:"Erika M. de Carvalho",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229481/images/6397_n.jpg",biography:null,institutionString:null,institution:{name:"Oswaldo Cruz Foundation",country:{name:"Brazil"}}},{id:"186537",title:"Prof.",name:"Tonay",middleName:null,surname:"Inceboz",slug:"tonay-inceboz",fullName:"Tonay Inceboz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/186537/images/system/186537.jfif",biography:"I was graduated from Ege University of Medical Faculty (Turkey) in 1988 and completed his Med. PhD degree in Medical Parasitology at the same university. I became an Associate Professor in 2008 and Professor in 2014. I am currently working as a Professor at the Department of Medical Parasitology at Dokuz Eylul University, Izmir, Turkey.\n\nI have given many lectures, presentations in different academic meetings. I have more than 60 articles in peer-reviewed journals, 18 book chapters, 1 book editorship.\n\nMy research interests are Echinococcus granulosus, Echinococcus multilocularis (diagnosis, life cycle, in vitro and in vivo cultivation), and Trichomonas vaginalis (diagnosis, PCR, and in vitro cultivation).",institutionString:"Dokuz Eylül University",institution:{name:"Dokuz Eylül University",country:{name:"Turkey"}}},{id:"71812",title:"Prof.",name:"Hanem Fathy",middleName:"Fathy",surname:"Khater",slug:"hanem-fathy-khater",fullName:"Hanem Fathy Khater",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/71812/images/1167_n.jpg",biography:"Prof. Khater is a Professor of Parasitology at Benha University, Egypt. She studied for her doctoral degree, at the Department of Entomology, College of Agriculture, Food and Natural Resources, University of Missouri, Columbia, USA. She has completed her Ph.D. degrees in Parasitology in Egypt, from where she got the award for “the best scientific Ph.D. dissertation”. She worked at the School of Biological Sciences, Bristol, England, the UK in controlling insects of medical and veterinary importance as a grant from Newton Mosharafa, the British Council. Her research is focused on searching of pesticides against mosquitoes, house flies, lice, green bottle fly, camel nasal botfly, soft and hard ticks, mites, and the diamondback moth as well as control of several parasites using safe and natural materials to avoid drug resistances and environmental contamination.",institutionString:null,institution:{name:"Banha University",country:{name:"Egypt"}}},{id:"99780",title:"Prof.",name:"Omolade",middleName:"Olayinka",surname:"Okwa",slug:"omolade-okwa",fullName:"Omolade Okwa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/99780/images/system/99780.jpg",biography:"Omolade Olayinka Okwa is presently a Professor of Parasitology at Lagos State University, Nigeria. She has a PhD in Parasitology (1997), an MSc in Cellular Parasitology (1992), and a BSc (Hons) Zoology (1990) all from the University of Ibadan, Nigeria. She teaches parasitology at the undergraduate and postgraduate levels. She was a recipient of a Commonwealth fellowship supported by British Council tenable at the Centre for Entomology and Parasitology (CAEP), Keele University, United Kingdom between 2004 and 2005. She was awarded an Honorary Visiting Research Fellow at the same university from 2005 to 2007. \nShe has been an external examiner to the Department of Veterinary Microbiology and Parasitology, University of Ibadan, MSc programme between 2010 and 2012. She is a member of the Nigerian Society of Experimental Biology (NISEB), Parasitology and Public Health Society of Nigeria (PPSN), Science Association of Nigeria (SAN), Zoological Society of Nigeria (ZSN), and is Vice Chairperson of the Organisation of Women in Science (OWSG), LASU chapter. She served as Head of Department of Zoology and Environmental Biology, Lagos State University from 2007 to 2010 and 2014 to 2016. She is a reviewer for several local and international journals such as Unilag Journal of Science, Libyan Journal of Medicine, Journal of Medicine and Medical Sciences, and Annual Research and Review in Science. \nShe has authored 45 scientific research publications in local and international journals, 8 scientific reviews, 4 books, and 3 book chapters, which includes the books “Malaria Parasites” and “Malaria” which are IntechOpen access publications.",institutionString:"Lagos State University",institution:{name:"Lagos State University",country:{name:"Nigeria"}}},{id:"273100",title:"Dr.",name:"Vijay",middleName:null,surname:"Gayam",slug:"vijay-gayam",fullName:"Vijay Gayam",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/273100/images/system/273100.jpeg",biography:"Dr. Vijay Bhaskar Reddy Gayam is currently practicing as an internist at Interfaith Medical Center in Brooklyn, New York, USA. He is also a Clinical Assistant Professor at the SUNY Downstate University Hospital and Adjunct Professor of Medicine at the American University of Antigua. He is a holder of an M.B.B.S. degree bestowed to him by Osmania Medical College and received his M.D. at Interfaith Medical Center. His career goals thus far have heavily focused on direct patient care, medical education, and clinical research. He currently serves in two leadership capacities; Assistant Program Director of Medicine at Interfaith Medical Center and as a Councilor for the American\r\nFederation for Medical Research. As a true academician and researcher, he has more than 50 papers indexed in international peer-reviewed journals. He has also presented numerous papers in multiple national and international scientific conferences. His areas of research interest include general internal medicine, gastroenterology and hepatology. He serves as an editor, editorial board member and reviewer for multiple international journals. His research on Hepatitis C has been very successful and has led to multiple research awards, including the 'Equity in Prevention and Treatment Award” from the New York Department of Health Viral Hepatitis Symposium (2018) and the 'Presidential Poster Award” awarded to him by the American College of Gastroenterology (2018). He was also awarded 'Outstanding Clinician in General Medicine” by Venus International Foundation for his extensive research expertise and services, perform over and above the standard expected in the advancement of healthcare, patient safety and quality of care.",institutionString:"Interfaith Medical Center",institution:{name:"Interfaith Medical Center",country:{name:"United States of America"}}},{id:"93517",title:"Dr.",name:"Clement",middleName:"Adebajo",surname:"Meseko",slug:"clement-meseko",fullName:"Clement Meseko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/93517/images/system/93517.jpg",biography:"Dr. Clement Meseko obtained DVM and PhD degree in Veterinary Medicine and Virology respectively. He has worked for over 20 years in both private and public sectors including the academia, contributing to knowledge and control of infectious disease. Through the application of epidemiological skill, classical and molecular virological skills, he investigates viruses of economic and public health importance for the mitigation of the negative impact on people, animal and the environment in the context of Onehealth. \r\nDr. Meseko’s field experience on animal and zoonotic diseases and pathogen dynamics at the human-animal interface over the years shaped his carrier in research and scientific inquiries. He has been part of the investigation of Highly Pathogenic Avian Influenza incursions in sub Saharan Africa and monitors swine Influenza (Pandemic influenza Virus) agro-ecology and potential for interspecies transmission. He has authored and reviewed a number of journal articles and book chapters.",institutionString:"National Veterinary Research Institute",institution:{name:"National Veterinary Research Institute",country:{name:"Nigeria"}}},{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",biography:"Professor Dr. Shailendra K. Saxena is a vice dean and professor at King George's Medical University, Lucknow, India. His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. Dr. Saxena is a fellow of various international societies/academies including the Royal College of Pathologists, United Kingdom; Royal Society of Medicine, London; Royal Society of Biology, United Kingdom; Royal Society of Chemistry, London; and Academy of Translational Medicine Professionals, Austria. He was named a Global Leader in Science by The Scientist. He is also an international opinion leader/expert in vaccination for Japanese encephalitis by IPIC (UK).",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",country:{name:"India"}}},{id:"94928",title:"Dr.",name:"Takuo",middleName:null,surname:"Mizukami",slug:"takuo-mizukami",fullName:"Takuo Mizukami",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94928/images/6402_n.jpg",biography:null,institutionString:null,institution:{name:"National Institute of Infectious Diseases",country:{name:"Japan"}}},{id:"233433",title:"Dr.",name:"Yulia",middleName:null,surname:"Desheva",slug:"yulia-desheva",fullName:"Yulia Desheva",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/233433/images/system/233433.png",biography:"Dr. Yulia Desheva is a leading researcher at the Institute of Experimental Medicine, St. Petersburg, Russia. 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