Comparison among exoskeletons.
\r\n\t
",isbn:"978-1-80356-363-3",printIsbn:"978-1-80356-362-6",pdfIsbn:"978-1-80356-364-0",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,isSalesforceBook:!1,hash:"969d1c6315b04584c2f011e03dad69c2",bookSignature:"Dr. Mansoor Zoveidavianpoor",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11929.jpg",keywords:"Drilling Performance, Drilling Tools, Well Design, Drilling Procedure, Rotary Drilling, Directional Drilling, Measuring-While-Drilling, Smart Well Technology, Environment Protection, Geothermal Drilling, Sustainable Drilling Fluids, Carbon Sequestration",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"February 18th 2022",dateEndSecondStepPublish:"March 18th 2022",dateEndThirdStepPublish:"May 17th 2022",dateEndFourthStepPublish:"August 5th 2022",dateEndFifthStepPublish:"October 4th 2022",remainingDaysToSecondStep:"2 months",secondStepPassed:!0,currentStepOfPublishingProcess:4,editedByType:null,kuFlag:!1,biosketch:"Dr. Zoveidavianpoor has over 18 years of multidisciplinary oil and gas experience, built upon his technical, operational, and management roles in the industry and academia. He is a member of the Society of Petroleum Engineers (SPE), the Energy Institute, UK and is registered as a chartered petroleum engineer. He has published more than 50 publications on International peer-reviewed Journals and conferences, has contributed to 5 textbooks, and served in many scientific committees.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"92105",title:"Dr.",name:"Mansoor",middleName:null,surname:"Zoveidavianpoor",slug:"mansoor-zoveidavianpoor",fullName:"Mansoor Zoveidavianpoor",profilePictureURL:"https://mts.intechopen.com/storage/users/92105/images/system/92105.jpg",biography:"Dr. Mansoor Zoveidavianpoor has over 24 years of experience, built upon his technical, operational, and management roles in the industry and academia. Mansoor holds a BSc degree in Geology, MSc, and Ph.D. degrees both in Petroleum Engineering. He was involved in different disciplines such as project management, geology, flow assurance, piping construction, artificial intelligence, environmental engineering, drilling and production engineering, He has lectured several courses at the University Technology Malaysia (UTM), Petroleum University of Technology (PUT), and Islamic Azad University (IAU). He is a member of the Society of Petroleum Engineers (SPE) and registered as a Chartered Petroleum Engineer at Energy Institute, and EIA subject specialist at DOE Malaysia. He has published more than 50 publications on International peer-reviewed Journals and conferences, has contributed to 5 textbooks, and served in many scientific committees. Currently, he is working as an Associate Professor at UTM and involved in several consultancies in petroleum engineering and energy transition. 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Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"72",title:"Ionic Liquids",subtitle:"Theory, Properties, New Approaches",isOpenForSubmission:!1,hash:"d94ffa3cfa10505e3b1d676d46fcd3f5",slug:"ionic-liquids-theory-properties-new-approaches",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/72.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"314",title:"Regenerative Medicine and Tissue Engineering",subtitle:"Cells and Biomaterials",isOpenForSubmission:!1,hash:"bb67e80e480c86bb8315458012d65686",slug:"regenerative-medicine-and-tissue-engineering-cells-and-biomaterials",bookSignature:"Daniel Eberli",coverURL:"https://cdn.intechopen.com/books/images_new/314.jpg",editedByType:"Edited by",editors:[{id:"6495",title:"Dr.",name:"Daniel",surname:"Eberli",slug:"daniel-eberli",fullName:"Daniel Eberli"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"54940",title:"Etiology, Immunopathogenesis and Biomarkers in Behçet’s disease",doi:"10.5772/intechopen.68342",slug:"etiology-immunopathogenesis-and-biomarkers-in-beh-et-s-disease",body:'\nBehçet’s disease (BD) is a type of vasculitis characterize by recurrent inflammatory attacks causing many distinctive clinical manifestations, most commonly affecting the orogenital mucosa, skin, and the eyes [1–3]. The etiology has yet to be fully established, but it has been postulated that a genetically predisposed or susceptible population, exposed to exogenous agents, may result in the dysregulation of both autoinflammatory and autoimmune responses. It is a complex disease that has been the subject of intense research and clinical interest.
\nIn this era of precision medicine, there is a need to integrate biomarkers into clinical practice, which may serve as valuable predictive and prognostic tools to assist practicing physicians in making clinical decisions while managing complex diseases. This may also improve diagnostic capability, risk stratification, prediction of disease progression, assist in targeted therapy, and monitoring of response to treatment to improve patients’ overall clinical outcome.
\nThis review chapter will look into the most relevant articles that have defined and clarified BD over the years, as well as review the most recent publications offering new insights in order to help fill the gaps in further understanding the disease. The chapter will focus on the etiology, immunopathogenesis, recent advances in search of potential biomarkers and targets for further research.
\nWe will examine recent advances made that have shed new light on an old disease and explore the potential genetic (including genome-wide association studies (GWAS) and next-generation DNA sequencing, looking into the human leukocyte antigen (HLA) and non-HLA genetic associations) and molecular markers (including innate immune lymphoid cells and adaptive immune cells, cytokines, chemokines, other circulating biomarkers, and signaling molecules of inflammation) and their potential correlations with disease activity and therapy.
\nBD is a genetically complex and heterogeneous disease. The pursuit of gene discovery for causative genetic factors in BD spans over more than four decades since Professor Shigeaki Ohno first described the association of HL-A5 antigen observed in his Japanese BD cohort that was later renamed human leukocyte antigen (HLA)-B5 [4]. Other early evidence stems from the observation of familial clustering in BD families where more than one family member developed the disease [5–8], which provided further clues to a strong genetic predisposition to the disease.
\nThe major histocompatibility complex (MHC) has an expansive immune component including the HLA and plays a pivotal role in the genetic influences on susceptibility to autoimmunity. The ~3.5-Mb region has the highest density of genes in the human genome, the majority of which have fundamental roles in immunity [9].
\nA remarkably consistent body of evidence demonstrates association of HLA-B*51 (B*51:01 subtype) allele as the strongest genetic susceptibility gene so far among genetically predisposed BD patients. However, certain indigenous Amerindians have a high prevalence of HLA-B*51 but virtually no reported cases of BD. High level of recombination within the MHC is known to have occurred in these Eastern populations before their migration into Beringia and it was suggested that disruption of the genetic loci in linkage disequilibria with HLA-B*51 might be one reason for the absence of disease in these high HLA-B*51-bearing populations [10]. These findings emphasize the fundamental roles and interplay of both genetic and environmental components in the development of the disease.
\nThere have been conflicting views, however, on whether the disease association with HLA-B*51 is attributed to a role of MHC class I variant itself or if the association is found due to its linkage disequilibrium (LD) with another variant in the region [11].
\nThe understanding of the pathophysiology of BD is challenging, as it is at the crossroads between autoimmune and autoinflammatory syndromes [12]. A new perspective of a unifying concept of MHC-I-opathy was proposed recently comprising of BD and several clinically distinct spondyloarthropathies (such as ankylosing spondylitis and psoriasis)—all associated with MHC Class I alleles, such as HLA-B*51, HLA-B*27, and HLA-C*0602, and epistatic endoplasmic reticulum aminopeptidase 1 (ERAP-1) interactions.
\nMcGonagle et al. have proposed that the MHC-I-opathies share an immunopathogenetic basis including barrier dysfunction in environmentally exposed organs such as the skin and aberrant innate immune reactions at sites of mechanical stress. This they argue can often trigger secondary adaptive immune CD8+ T cell responses with prominent neutrophilic inflammation that culminate in the initiation and chronicity of these diseases [13]. Further research and understanding into this unifying concept of MHC I driven inflammatory response may provide further targets for disease management.
\nThe complexity and strong LD with the HLA-B*51 allele make it difficult to explore additional independent susceptibility loci within this region. Despite having the strongest genetic association, it remains unclear to this day whether disease susceptibility in BD is due to the HLA-B*51 itself or due to the genes located around the HLA which is in LD with it.
\nThe MHC Class I chain-related gene A (MICA) is located in proximity and in between the HLA-B and tumor necrosis factor (TNF) genes on the short arm of chromosome 6. It has long been considered a major genetic susceptibility gene for BD and has been studied in many different populations since the first observation of a possible association by Mizuki et al. [14]. Lee et al. conducted a meta-analysis on the associations of MICA and BD and found statistically significant association in various ethnic populations [15]. However, due to its strong LD with HLA-B*51, it has been difficult to prove MICA as a primary susceptibility gene for BD. Furthermore, different GWAS did not find an independent association between MICA and BD [16–18].
\nOmbrello et al. performed stepwise conditional analysis and found independent genetic associations for HLA-B*15 and HLA-B*27 and risk, while HLA-B*49 and HLA-A*03 were protective [19]. Montes-Cano et al. demonstrated HLA-B*57 as a marker for risk in the Spanish population [20], while Meguro et al. showed that HLA-A*26 is a risk marker in the Japanese population [16].
\nUsing a custom platform (Immunochip) that includes 8572 single nucleotide polymorphisms (SNPs) in the HLA extended region, Hughes et al. demonstrated that the robust HLA-B*51 association in BD is due to a strong association signal of an SNP rs116799036 in two independent BD cohorts (Turkish and Italian) from two ancestry groups, while also identifying two additional independent genetic associations with genome-wide significance (
It was difficult to venture beyond the MHC in the past: the tools to do so were unavailable as linkage studies were only suitable for Mendelian disorders. Intriguing new techniques have surfaced in recent times accelerating the pace for gene discovery, especially for complex diseases such as BD.
\nBeing a complex disease, BD does not follow the typical Mendelian law of inheritance, rather of a dichotomous nature conforming the “polygenic threshold model” where the phenotypic expression is resultant upon genetic variation at multiple rather than a single loci, with the majority of the cases occurring sporadically. This is the basis foundation for the development of GWAS, which was initially thought to be the “comprehensive” option designed to identify genetic variants associated with such complex disease [22].
\nThe advent of GWAS earlier in this century has dramatically improved our ability to identify and map successfully susceptibility loci associated with complex diseases such as BD, usually as single nucleotide polymorphisms (SNPs). It seems that these common genetic variants contribute to polygenic disease manifestations where phenotypic variance depends on contributions from several genetic variance.
\nFei et al. [23] performed the first GWAS study in BD in a relatively small Turkish population and identified several novel candidate genetic loci (KIAA1529, CPVL, LOC100129342, UBASH3B, and UBAC2) that are associated with increased susceptibility to BD. In the same year, Meguro et al. [16] found that the main susceptibility locus in BD Japanese population remains in the MHC itself, wherein reside two independent loci: HLA-B*51 and HLA-A*26. Two large GWAS conducted in Turkey and Japan followed in 2010: Remmers et al. confirmed the association of HLA-B*51, identified a second, independent association within the MHC Class I region and also found association at IL10 [17], while Mizuki et al. identified IL23R-IL12RB2 and IL10 as Behçet’s disease susceptibility loci [18].
\nIn 2012, GWAS performed by Kirino et al. identified novel susceptibility loci at chemokine receptors CCR1-CCR3, signal transducer and activator of transcription 4 (STAT4), killer cell lectin-like receptor K1 subfamily K, member 1 (KLRK-1), killer cell lectin-like receptor subfamily C, member 4 (KLRC4), and ERAP1 in a Turkish population [24], thus apparently supporting the emerging concept delineating common pathogenic mechanisms for BD, ankylosing spondylitis, and psoriasis. In the same year, Hou et al. also identified STAT4 as a novel susceptibility locus for BD in the Chinese population in their GWAS and functional studies [25].
\nOne of the difficulties of using GWAS in cohorts of mixed ethnicity is due to the rarity and unequal distribution of disease prevalence among different ethnic background. This was overcome by novel statistical approaches, demonstrated by Kappen et al. [26] who confirmed the central role of the HLA region in the disease and validated the association of IL2A gene by meta-analysis with previous work.
\nDespite discoveries of many unimpeachable associations with GWAS, it became apparent that the approach alone could not explain the full range of heritability or genetic susceptibilities to complex diseases [27] and at best could only identify moderate proportions of genetic variants contributing to the disease heritability. Among the growing menu of techniques, targeted next-generation sequencing is the latest promising technology in search of rare genetic variants with fewer alleles (minor-allele frequency), which likely carry a greater larger impact on disease manifestations and with larger deleterious biological effects [28, 29]. Next-generation exome sequencing has the ability to generate millions of short reads of sequence, ranging from 50 to 500 bp, in parallel. It can be targeted in key regions of the genome-to make quick discoveries [29].
\nEarly data revealing the contributory influence of non-HLA susceptibility genes came from studies in the 1990s; however, some of the associations were weak or inconclusive. In 2009, Karasneh et al. published the first systematic whole genome linkage analysis from 28 Turkish BD families, which provided evidence for non-HLA susceptibility loci with the strongest evidence seen for 12p12–13 and 6p22–24 [30].
\nThe revelation of GWAS unfolded associations with genome-wide significance (
Targeted next-generation sequencing revealed the additional involvement of rare non-synonymous variants in toll-like receptor 4 (TLR4), nucleotide-binding oligomerization domain-containing protein 2 (NOD2), and the Mediterranean Fever Gene (MEFV) [37]. Recently, Ognenovski et al. used whole exome sequencing in BD of European descent for the first time and identified and replicated two novel putative protein-damaging genetic variants within LIMK2 and NEIL1, which may influence cytoskeletal regulation and DNA repair [38].
\nThe associations with ERAP1, IL23R, IL10, and MEFV variations suggest that BD may share susceptibility genes and inflammatory pathways with spondyloarthritis [39], while the TLR and FUT polymorphisms that affect response to invasive pathogens have led to an increase interest in responses to microbiomes [40].
\nThe term “cytokine” was first introduced in 1974 by Cohen et al. [41] to describe a polypeptide mediator superfamily central in the immune system generation and regulation. An entwined network comprising of interleukins (ILs), interferons (IFNs), tumor necrosis factor (TNF), chemokines, and other mediators primed to regulate the immune system, however, due to several factors such as imbalance of its receptor expression and dysregulation of its functions, generates the pathologic systemic inflammatory and/or immune responses seen in various autoimmune and autoinflammatory disorders.
\nPro-inflammatory and anti-inflammatory cytokines have been shown to be involved in patients with BD (as discussed in more detailed below). Several studies demonstrated elevated levels of cytokines in local lesions indicating its involvement in the disease local immune responses [42–46]. Evidence from the GWASs further implicated several cytokines underlying the pathogenesis of BD [17, 18, 22–26]. Moreover, the successful use of various anti-cytokine therapies in BD patients provides additional evidence that cytokines play a crucial role in its pathogenesis [47–64]. These overall observations highlight the fundamental role of cytokines as key players in the pathogenesis of BD.
\nThere are several established cytokines that are known to be involved including IL1β, TNFα, IL6, IL10, and IL23. Various new promising candidate’s cytokines identified to be associated with BD include IL21, IL22, IL33, IL37, and several others, all of which be described as detailed below.
\nDespite the pleiotropic nature of most cytokines, this group of cytokines primarily promotes inflammation. Several pro-inflammatory cytokines have been implicated in BD.
\nAll cells of the innate immune system express and/or are affected by IL1 family members, which play a key role in the differentiation and function of polarized innate and adaptive lymphoid cells [65]. Among the 11 cytokines in the family, IL1β is the principal pro-inflammatory cytokine, leading to the expression of many chemokines and secondary mediators of inflammation and upregulating innate immunity in response to infectious agents [66]. The levels of IL1β have been shown to be elevated in several studies [45, 46, 49, 67, 68], including in synovial fluids of BD patients [45, 46]. A proof-of-concept study by Güll et al. strongly implicated IL1β and BD with significant improvement seen especially in patients with uveitis treated with IL1β-regulating antibody [47]. Recently Tugal-Tutkun et al. demonstrated rapid control of uveitis in BD patients without the need for high-dose corticosteroid in a prospective, open-label, randomized phase II trial [48] supporting several other previous studies of the proven efficacy of IL1β to induce stable clinical remission among BD patients [49–52].
\nOther pro-inflammatory cytokines in the IL1 family implicated in BD especially in the last decade include IL18 [42, 69–71], an important component of polarized Th1 cell and natural killer (NK) cell responses and of the interplay between macrophages and NK cells [65]. Identified in 2005 by Schmitz et al, IL33 was noted to have the capability to activate NF-κB and MAP kinases, and induces the expression of IL-4, IL-5, and IL-13 in vivo, leading to severe pathological changes in mucosal organs [72]. In several of his studies, Hamzaoui et al. demonstrated higher levels of IL33 in sera of active BD patients compared to BD patients in remission [73–75], and this was supported by Kim et al. [76] who found elevated IL33 in BD patients with erythema nodosum (EN) and EN-like skin lesions. Surprisingly, Koca et al. found contrasting results of lower IL33 levels in active BD Turkish patients compared to the inactive patients and healthy controls (HC) but did find significantly higher levels of IL33 among BD patients with uveitis [77].
\nAmong the 19 TNF superfamily cytokines that has so far been identified, the first member of the family, TNFα, which was the first to be discovered, is the most highly investigated. Levels have been shown to be elevated in studies from different populations [49, 69, 78–83]. Meta-analysis by Touma et al. [84] found TNF (-238A/G, -1031C/T, and -857T/C) polymorphisms are associated with susceptibility to BD, while an updated meta-analysis by Zhang et al. confirmed a significant association between the TNF−308A/G polymorphism and BD susceptibility [85]. Treatment has also been shown to be highly effective [53, 54].
\nThere is not much information about the other members of the TNF superfamily and its association with BD, but despite the limitation, isolated studies have shown several other TNF family member to be associated with BD in different ethnic populations: Cantarini et al. found significantly higher serum soluble TNFR and soluble CD40L [86], Shaker et al. demonstrated higher levels of B cell activating factor (BAFF), A proliferation producing ligand (APRIL), and B cell maturation antigen (BCMA) in BD patients [87] and Düzgün et al. found elevated soluble CD30 levels in active BD patients compared to controls [88].
\nBesides TNFα, other members of the TNF superfamily may offer options as potential targets and therapeutic candidates in BD; however, more research is needed in this field to prove its efficacy and safety profile.
\nSeveral studies have shown higher levels of serum IL6 in active BD compared to inactive BD and HC [71, 89, 90], and interestingly in neuro-BD patients, IL6 was noted to be markedly elevated in the cerebrospinal fluid (CSF), but not in the sera [91, 92]. Blockage of IL6 signaling with tocilizumab in BD patients despite looking promising in the treatment of neuro-BD [55–58] has revealed mixed results for non-neurological manifestations [58, 59, 93, 94] and is currently undergoing further evaluation in controlled clinical trials.
\nBeing the oldest cytokine discovered exactly 60 years ago, interferon-α (IFNα) has been the scope of investigation in many inflammatory diseases including BD. Despite initially thought to have mainly pro-inflammatory effects, it is becoming clearer that IFNα display a more complex function and its anti-inflammatory properties have led to its use as one of the treatment modalities in BD since the mid-1980s. Different studies by Hamzaoui, Kötter, and Pay et al. in their respective Tunisian, German and Turkish populations demonstrated higher levels of IFNα among BD patients [71, 95, 96]. In 2010, Liu et al. published their in vitro experiments demonstrating the ability of IFNα to inhibit IL17 expression and increase IL10 production by PBMCs and CD4+ T cells [97]. Successful uses of IFNα-2a and -2b as treatment modalities have been reported [60–62], and more recently, Lightman et al. reported the successful use of pegylated IFNα-2b in BD resulting significant reduction in corticosteroid use and improvement of quality of life [63]. The exact mechanism of IFNα, however, is still largely unknown.
\nThere have been remarkable advances leading to our current understanding on the lineage commitment and plasticity of helper CD4+ T cells. The “naïve” CD4+ T cells in the presence of its associated cytokines differentiates into distinct T helper (Th) cells populations-Th1, Th2, Th17 or Th22: tailoring their responses to address specific threats accordingly. On the other hand, CD4+ CD25+ regulatory T cells (Tregs), derived from the thymus or differentiation from naïve T cells, downregulate Th responses and are critical for the preservation of immune tolerance and maintaining balance in the immune system.
\nIn the early 1980s, Ohno et al. demonstrated for the first time significantly higher levels of IFNγ in Japanese BD population [98]. Ahn et al. in their case series showed that the levels of IFNγ were elevated in aqueous humor and serum in BD patients with uveitis, which was then suppressed with combined low-dose cyclosporine/prednisone treatment [99]. Many other studies similarly found elevated serum IFNγ in active BD patients [44, 71, 83, 100–106], especially in BD patients with uveitis [44, 83, 102–105].
\nOther Th1 cell-associated cytokines associated with BD include IL2 and IL12. Despite conflicting results for IL2 levels in the ocular fluid of active BD patients with uveitis [106, 107], it was found to be significantly elevated in the serum of BD patients [108] and in active disease [109]. The alpha-chain of the IL2R that is shed from the surface of T cells by proteolytic enzymes to form the soluble sIL2R, which retains affinity to IL2, is also found to be significantly higher in active BD [46, 79, 110–113] and specifically in BD patients with uveitis [112, 113]. Serum IL12 levels were also found to be elevated in BD patients with active uveitis [114–116] and other active manifestations [42, 117, 118].
\nIL23 influences Th17 cell responses but shares a common p40 subunit with IL12 [119], and like IL12 has also been shown to be elevated in BD patients with active disease [101, 105, 120, 121]. Ustekinumab, a therapeutic agent, targeting both IL12 and IL23 cytokines has been shown to be therapeutic in BD [122], and subsequently a phase 2 open-label study to evaluate the proof-of-concept of ustekinumab in BD (STELABEC) has been recently registered in France. Both IL12 and IL23 stimulates nonreceptor Janus kinase 2 (JAK2) and tyrosine kinase 2 (TYK2) activity, leading to phosphorylation of STAT family members, with IL12 particularly activating STAT4 homodimers and IL23 predominantly activating STAT3 [119, 123–125]. Tulunay et al. demonstrated that the JAK1/STAT3 signaling pathway is activated in BD, and several other studies have shown similar findings [126]. Tulunay further suggested that more direct therapies aimed at JAK/STAT-associated cytokines such as ustekinumab (anti-IL12/23) and recently the approved tofacitinib that specifically inhibits JAK1/3, may be new therapeutic options for BD [126].
\nTh17 and Th22 are the “newer” helper-T cell subsets that secrete pro-inflammatory cytokines IL17 and IL22, respectively. Both are also implicated in the pathogenesis of BD, and their levels were markedly increased in BD patients [97, 105, 127–133] including active uveitis [107, 127, 128]. Chi et al. in their study demonstrated that production of IL17 was successfully inhibited by treatment with cyclosporine [127]. Another interesting finding in one of the studies above is increased levels of CCL20, an essential potent chemoattractant for the recruitment of Th17 lymphocytes [129]. Sugita et al. established Th22-type T cell clones from ocular samples taken from BD patients with active uveitis, which produced large amounts of IL22 and TNFα [106]. Sugita also demonstrated that IL22 in the presence of retinal antigens were able to produce high levels of IL22 in mice with experimental autoimmune uveitis [106]. From the therapeutic point of view, Liu et al. demonstrated significantly higher levels of IL17 in active BD patients, and stimulation with IFNα significantly decreases this IL17 production [97].
\nIL21 is one of the more recently identified type I cytokines that has been shown to tilt the balance between Th17 cells and regulatory T cells (Tregs) [134]. Geri et al. found markedly increased IL21 in active BD patients’ sera and in the CSF of active neuro-BD patients. He further demonstrated increased Th17 and Th1 differentiation and decreased frequency of Tregs cells after stimulation of CD4+ T cells with IL21. Conversely, IL21 blockade with an IL21R-Fc restored the Th17 and Tregs homeostasis in BD patients, which might represent a potential target for novel therapy [135].
\nThe studies on Th2 cell-associated cytokines and their contribution in the pathogenesis of BD have been rather conflicting. Several studies found lower or no significant differences of the related cytokines in BD patients compared to HC [45, 106, 109, 119, 136, 137]. However, studies by Hamzaoui et al. found increased serum levels of Th2 (IL4 and IL13) cytokines, and Takeuchi et al. found elevated IL4 and IL10 in BD patients [71, 83], while studies from Raziuddin and Aridogan et al. demonstrated high levels of IL4, IL10 and IL13 in active BD patients [138, 139]. Liu et al. and Guenane et al. in separate studies found significantly higher levels of IL10 in uveitis patients with BD compared to HC and idiopathic uveitis, respectively [97, 114]. Dalghous and his colleagues observed the presence of IL4 cytokines in oral lesions only from BD patients compared to RAS patients [140], while Ben Ahmed et al. found elevated levels of IL10 comparable to the increased IFNγ levels in active lesions of BD patients [141].
\nThe possible role of Tregs in the pathogenesis of BD has gained considerable interest in recent times. Hamzaoui and Gündüz both demonstrated decreased Tregs level in clinically active BD patients [43, 142], Nanke et al. suggested that a decreased percentage of Tregs in peripheral blood of BD patients might be a predictive marker of ocular attack [143], while Sugita et al. demonstrated that Tregs level increased significantly with infliximab therapy but not with colchicine or cyclosporine in BD patients with uveitis [144]. Another subset of Tregs expresses high levels of CD52 glycoprotein [145], and together with other CD52-bearing cells (T cells, B cells, monocytes, macrophages, NK cells, dendritic cells, and granulocytes) are molecular targets of CAMPATH-1. A humanized antibody of IgG1 CAMPATH-1H/alemtuzumab has been successfully used in BD [146, 147] including in an open trial involving 18 BD patients with complete or partial remission achieved in 84% of patients [146].
\nGammadelta (γδ) T cells are innate-like lymphocytes that express a unique T cell receptor (TCR)
The relationship between γδ T cells and BD has been noted in several studies since the early 1990s. Increased γδ T cells levels were seen in BD patients compared to HC [99, 150–155] and in active BD compared to inactive BD [99, 151, 155, 156]; however conversely, several studies did not show any significant difference with HC [157–159]. Hasan et al. postulated that these discrepancies might be due to the activation status of the disease, as a reflection of local tissue inflammation compared to peripheral blood γδ T cells and such variation might be dependent on several other factors including disease severity, usage of medications such as immunomodulatory agents, and perhaps other variables, namely, age, gender, ethnicity, and/or environmental factors [149]. Their roles in the pathogenesis and potentially as therapeutic targets remain to be elucidated.
\nIL37 is part of the IL1 family (discovered in 2009 and formerly identified as IL1F7) but has emerged as an inhibitor of innate immunity [160]. It has been shown to be significantly lower in BD patients compared to HC, with pronounced inhibition in active patients, and was associated with increased production of IL1β, IL6, and TNFα in LPS-stimulated PBMCs [161, 162]. Furthermore, in vitro experiments revealed that supplementing IL37 in BD patients significantly suppresses these three pro-inflammatory cytokines [163]. There have also been suggestions of associations between BD and other cytokines such as IL15 and IL27; however, the data are still inadequate and sparse [44, 164–166].
\nThe attraction of leukocytes to tissues is essential for inflammation and is controlled by chemokines, which are chemotactic cytokines [167]. Saruhan-Direskineli et al. observed significantly higher α-chemokine CXCL10/IP10 CSF levels in neuro-BD patients compared to patients with non-inflammatory neurological disease (NIN) and multiple sclerosis, whereas CXCL8/IL8 was increased in neuro-BD compared to NIN [168]. El-Asrar et al. found higher levels of CXCL9/MIG, CXCL10/IP10 and CXCL11 in BD patients’ serum with uveitis [169], while its receptors CXCR3 expression were observed by Dalghous et al. to be higher in oral lesions biopsied form BD patients [140]. Recently, Ambrose et al. demonstrated significantly higher production of CXCL10/IP10 in blood monocytes of BD patients stimulated with IFNγ compared to HC, rheumatoid arthritis, and systemic lupus erythematosus controls [170]. There is even more robust evidence for CXCL8/IL8, a potent neutrophil chemoattractant, being implicated in BD pathogenesis, with some of the authors proposing that it could be a marker for vascular involvement and a more reliable marker for disease activity than the C-reactive protein or erythrocyte sedimentation rate [171–174].
\nIn regard to β-chemokines, Ozer et al. found significantly elevated levels of MCP1/CCL2, MIP1α/CCL3, and RANTES/CCL5 in active BD serum than in HC [175]. Similarly, Kökçam and Kim and their respective colleagues in two separate studies demonstrated high levels of MIP1α/CCL3 [176, 177] while Kaburaki et al. and Do et al. found higher levels of MCP1/CCL2 in BD patients compared to HC [178, 179]. In CSF of neuro-BD patients, Saruhan-Direskeneli et al. and Miyagishi et al. both demonstrated significantly higher levels of MIP1α/CCL3 compared to NIN [168, 180].
\nThe emerging evidence of a complex cytokine and chemokine network interplay involved in the pathogenesis of BD, the identification of candidate gene including cytokine polymorphisms and the proven potency of anti-cytokines treatment shed more light on the fundamental role of cytokines and chemokines in BD. Perhaps cytokine and/or chemokine gene therapy, which has been used in cancer therapy, though not extremely impressive but nonetheless promising, may offer a novel yet powerful approach in the treatment of BD in the future.
\nBecatti et al. demonstrated significant enhancement in leukocyte reactive oxygen species (ROS) production particularly by neutrophils in BD patients and only neutrophil-derived ROS (but not lymphocyte- or monocyte-derived ROS) showed a significant correlation with fibrinogen carbonyl content, highlighting neutrophil activation as the promoter of fibrinogen oxidation and thrombus formation in BD [181] supporting similar finding in several previous studies [182, 183]. Increasing evidence supports a role for neutrophil/lymphocyte ratio (NLR) as a cheap and simple disease activity marker in BD. NLR has been proposed as a surrogate marker for endothelial dysfunction and inflammation, and several authors have proposed the use of NLR as part of evaluation for disease activity in BD [184–187].
\nGroundbreaking studies over recent years have formally identified innate lymphoid cells (ILCs) as a distinct arm of the innate immune system, comprising of the classic cytotoxic natural killer (NK) cells, lymphoid tissue inducer cells, and non-cytotoxic ILC populations [188]. Besides controlling tissue homeostasis, it has the ability to promote inflammation at mucosal and surface barriers [188]. Yamaguchi et al. reported that NK cells are actively involved in the induction and maintenance of disease remission in BD patients, through NK2 polarization [189] while Takeno et al. from their study concluded that abnormal killer inhibitory receptor (KIR) expression of NK cells may be associated with the development of BD [190]. Furthermore, ILCs have been recently shown as an important source of cytokines production [188, 191, 192]. The recent discovery of this latest group of diverse immune cells with its many emerging diverse roles in autoimmunity and inflammation may redefine or rather perhaps reinforce our understanding of the pathogenesis of BD in the future.
\nThe inflammasome has been shown to be a key regulator of IL1β and IL18 via direct activation of caspase-1 [173–194]. Liang et al. demonstrated production of IL-1β was significantly decreased in ocular BD patients after the Nod-like receptor protein 3 (NLRP3) inflammasome was downregulated [195] while Kim et al. showed that the basal and LPS-induced expressions of NLRP3 inflammasome components were significantly increased at both mRNA and protein levels in BD patients [196]. Conversely, Türe-Özdemir and his team were not able to find any difference in DC and neutrophils of BD patients compared to HC after stimulating caspase-1 activation [197].
\nThere have been several studies implicating certain autoantibodies in BD, but all are neither non-specific nor sensitive and are of limited clinical significance. Among them the most described were anti-
The role of microbial triggers in BD has long been postulated since the disease was first described. Microbial heat shock proteins (HSPs) show significant homology with human mitochondrial HSP and molecular mimicry is suggested as the mechanism of pathology exacerbating BD when patients were exposed to these foreign antigens. While both streptococci and herpes simplex virus have garnered the most particular interest among researchers [209–214], evidence of exposure to other microbes such as staphylococci and mycobacteria has also been reported [215, 216]. Nonetheless, conflicting reports have been published and a specific pathogen has yet to be identified.
\nMicrobiome is a term first described by Lederberg in 2001 describing the microbial ecosystem [217], but it was Metchnikoff more than a centenary ago who hypothesized that the microbiota might influence the balance between pro-inflammatory and regulatory host responses and that alterations in the composition of the microbiota (a process that is known as dysbiosis) could jeopardize host immune responses [218]. Recent evidence indicates the possible contribution of the intestinal microbiota to immunological diseases outside the gut [218, 219].
\nThe advent of the 16S ribosomal RNA (16S rRNA) sequencing technology over the past quarter century has identified a comprehensive human microbiota far more comprehensive than we ever imagined. Despite the emergence of newer application such as metagenomics [220], due to the nature of the rRNA genes that are highly conserved and evolutionarily stable but differ in their hypervariable regions enables identification of species, and owing to a confluence of methodological advancements, 16S rRNA has re-emerged as a stand-alone molecular tool [221].
\nBD patients seem to exhibit specific microbiome signature. Consolandi et al. compared fecal microbiota of BD patients and HC and found significantly depleted Roseburia and Subdoligranulum genera and butyrate production in BD patients [222] while Shimizu et al. also demonstrated gut dysbiosis in BD patients with significantly increased genera Bifidobacterium and Eggerthella and decreased genera Megamonas and Prevotella compared to HC [223].
\nSeveral authors also identified salivary dysbiosis among BD patients. Seoudi et al. found in BD patients an increased colonization of
There are other possible molecular markers that have been or are still under investigations. Fecal calprotectin (FC) were demonstrated to be significantly elevated in intestinal BD in several studies [226–228], and interestingly Özşeker et al. demonstrated high fecal FC levels in asymptomatic but endoscopically proven BD patients with intestinal involvement [226]. Vascular endothelial growth factor (VEGF) levels have been observed in BD patients, particularly in active BD [229–232]. Several studies provided evidence for the increased levels of markers for endothelial activation or dysfunction such as vascular and intercellular adhesion molecules VCAM1, ICAM1, Selectins, and YKL40 in BD [233–238]. Various authors explored the association between certain genetic mutations and thrombosis in BD; however, results have been inconclusive [239–244], and current data indicate that the pathogenesis of thrombosis in BD is not due to a coagulation abnormality [245].
\nThe immunomodulatory role of vitamin D is of increasing interest, and several in vitro studies have demonstrated downregulation of inflammation by vitamin D [246–249]. Moreover, hypovitaminosis D had been implicated in various inflammatory disorders including BD [250–255]. Further investigations from different ethnic populations may provide further insights to this potentially clinically relevant knowledge of vitamin D as a potential suppressor of inflammatory response in BD.
\nEfforts to develop biomarkers in BD have been confounded by substantial impediments and challenges and the greatest is probably due to the rare nature of the disease, while others include the complex role of the susceptibility genes and related cytokines, chemokines and other signaling molecules, variability of duration and severity of the disease, as well as variations between different geographical areas and the limited number of patient samples.
\nStandardization and quality assurance are significant hurdles and collaboration between laboratories at different centers to standardize protocols and assays is essential. There are clear similarities and differences across different ethnic groups phenotypically and at a genetic or molecular level. So far, clinical data trials support the critical role of innate cytokines TNF, IL1, and IL6 in the development of inflammatory episodes of BD, and targeting T cells or B cells may provide favorable results [256]. In this era of personalized and precision medicine, collaborative efforts nationally or internationally are needed to assemble adequately powered cohorts to perform further population- or regional-based molecular and genetic studies.
\nOne possible way to move forward is broadening the classification criteria to combine objective clinical indicators and biomarkers, but despite the emergence of these candidate markers, there is still a lack of sufficient widespread evidence to support their implementation and incorporation into the contemporary classification criteria. In the meantime, it must be noted that BD remains fundamentally a clinical diagnosis.
\nMany questions remain a conundrum including (1) which patients will develop a more severe form of disease, (2) who will be resistant to certain therapy, (3) which patients with recurrent aphthous ulcers will progress to develop BD, and (4) who will benefit the most from a particular therapy. The search remains a highly scientific priority, but until we find the biomarkers, likelihood is, many of these questions will remain uncertain.
\nIt has been a long, challenging journey in search of biomarkers in Behçet’s disease. There are clear genetic and molecular similarities and variability between different ethnic populations. Collaborative efforts nationally or internationally are needed to assemble sufficiently powered sample size to perform further population- or regional-based molecular and/or genetic studies in the search for the elusive “magic bullet” as the signature marker that will revolutionize the field of BD.
\nParaplegia is the paralysis of the lower half of the body, affecting both legs; it is usually the result of spinal cord trauma [1, 2], however, it can also be caused by diseases such as ischemic events [3, 4], multiple sclerosis and amyotrophic lateral sclerosis among other neurodegenerative diseases, including Parkinson’s disease [1].
\nThe care of the patient with paraplegia must be integral, including medical, surgical, psychological treatment and finally rehabilitation by physiotherapy [5].
\nAt this last point, various therapies have been developed, including the use of exoskeletons. Studies have determined that the uses of exoskeletons include: increasing human performance, improving mobility of individuals with neurological pathologies, and providing assistive technology for people with disabilities [6]. In this chapter, different exoskeletons that are in use are presented for the rehabilitation of patients.
\nFor this chapter, a review was carried out in the search engines
Inclusion criteria: Documents published between the years 2005 to 2020 were included. The search terms were:
Subsequently, the electronic pages of the manufacturers were consulted.
\nExclusion criteria: Studies published before 2005. Studies that did not include the search terms established in the inclusion criteria, incomplete or unavailable articles.
\n\nFigure 1 shows the flow diagram of the obtaining information process.
\nFlow chart for the information selection.
The operation of exoskeletons depends on a series of biometric sensors that are activated through nerve signals sent from the brain to different muscle groups so that an exact action is developed. For the creation of exoskeletons, electrical and computer patterns are used that will allow the adaptation and generation of movement in different degrees [1].
\n5 different models of exoskeletons were found, which are discussed below. Images of the exoskeletons are shown in Figure 2.
\nExoskeletons: a) H2, b) EKSO, c) HAL, d) KINESIS y e) ReWalk (images taken from Mardomingo-Medialdea, 2018 [
It is an exoskeleton designed for the rehabilitation of adults, it is indicated for patients between 1.5 and 1.95 m in height, with a maximum body weight of 100 kg with neurological damage that prevents their motor skills [4].
\nIt was developed by the CSIC Bioengineering Group, who granted an exclusive license to Technaid S.L. for the design, manufacture and commercial exploitation of the system.
\nH2 presents an open architectural design, which allows the integration with other stimulation systems, giving it an advantage over other exoskeleton models. It has motorized joints in the hips, knees and ankles, which are powered by rechargeable batteries, and it has sensors that allow a good control to perform the desired activity, whether it is walking, getting up or sitting [7].
\nThis robotic system works through an interface that connects via Bluetooth to a smartphone; through a Wi-Fi connection, the kinetics and kinematics generated by the exoskeleton are captured and a database is formed that can be statistically analyzed [4].
\nThe interaction between the user and the exoskeleton is very important for the comfort and safety of the users in a robotic device, as the sensors must be physically placed on the human limbs and due to several issues, specifically related to safety, comfort and reliability, placement must be taken into consideration.
\nThe H2 exoskeleton is designed in such a way that there are no sensors physically attached to the human being, all the information indicates that the sensors placed on the exoskeleton are 6 potentiometers, 18 hall effect sensors and 4 foot switches that are used to determine parameters such as angular position and speed, and the force and interaction between the user’s limb and the exoskeleton. The H2 exoskeleton is equipped with industrial precision, it includes a potentiometer used as an angular position sensor, that exhibits high linearity and long rotation life. Its gear is through a steel shaft that is coupled to a toothed pulley and a belt that is used to transmit the movement of the joint avoiding slipping and therefore an absolute loss of reference. The exoskeleton platform is equipped with two foot switches based on binary resistive sensors that allow detecting the contact between the subject’s foot and the ground, these sensors are located under the heel and toe and their main objective is to detect the different phases during segmented motion [4].
\nThe main controller is based on an H2-ARM electronic board specifically designed to control usage time. The H2-ARM plate’s small size (56 x 44 mm) allows it to be placed on the exoskeleton reducing volume, as well as complexity and the difficulty of hiding wiring and connections, as well as eliminating the need for the user to carry a backpack that most lower limb exoskeletons have as a disadvantage.
\nDuring a pilot study, the H2 exoskeleton function was consistent during a clinical motion rehabilitation protocol. It was shown as a safe therapy without unwanted effects and with good tolerance by patients [8]. These results have opened the possibility of testing with a larger number of patients.
\nThis robotic exoskeleton has the ability to use motion supports, which facilitates the autonomous movement of the patient. It was developed by ReWalk Robotics Inc [9]. Its use is designed for patients who have suffered a complete spinal cord injury between C7 and T12, which puts it at an advantage over other more limiting designs in their therapeutic applications [10].
\nIt is an open architectural exoskeleton, which has a 28 V electric motor, located on the user’s back and powered by lithium batteries with autonomy of up to three hours [9].
\nA novel feature of this exoskeleton is that it has inclination sensors and a wireless communicator for its control [9].
\nThe control of the exoskeleton is given by the movements of the trunk and the movements of the center of gravity, that is, when the body moves forward, the system translates it as the beginning of the step [10].
\nThe EKSO exoskeleton, formerly known as the exoskeleton lower extremity motion system, eLEGS, was developed by Berkeley ExoWorks, a company that currently holds the name EKSO Bionics [11].
\nIt is an open structure exoskeleton, open architectural exoskeletons make it easy to connect to other types of equipment that help with the monitoring of muscle activity [7].
\nThis exoskeleton is designed to help people who have suffered strokes, multiple sclerosis, Parkinson’s disease, or spinal cord injury below C7, limiting its use for patients with higher or invasive injuries [10].
\nIts operation depends on a single engine, which is located on the patient’s back through a backpack, which makes it uncomfortable for some activities, however, the engine is highly efficient and favors motor skills, allowing the movement of 100% of the weight, lateral motion and squat position, a position not achieved with any other exoskeleton. It also allows the patient to sit up and return to the standing position. Among the advantages offered by this exoskeleton is that it favors the reduction of spasticity. Although the use of a backpack on the back is its greatest disadvantage because it makes it less comfortable than other models, it is still one of the most efficient and functional exoskeletons for patients with paraplegia caused by different diseases [10, 11].
\nThe Hybrid Assistive Limb (HAL) exoskeleton has been developed by the Japanese company CYBERDINE Inc [12].
\nIt is an exoskeleton with an open architectural structure.
\nIt has electric engines located in the lateral part of the legs and arms, making this exoskeleton one of the most comfortable of those analyzed in this chapter.
\nThe monitoring of the operation of the exoskeleton is carried out through bioelectric signal sensors located on the user’s waist, connected to an interface that allows the monitoring of motor activity [5].
\nIt is aimed at patients who have even lost all of the motor function of the lower limbs, which gives it a great advantage over other exoskeletons that are limited to the fact that the user has limited motility [10].
\nThe Kinesis exoskeleton has been developed under the auspices of the Spanish Higher Council for Scientific Research [13].
\nLike the past reviewed exoskeletons, it is an open architectural exoskeleton.
\nThis exoskeleton works with a 24 V electric engine, located on the back, a position that gives the user some discomfort, especially when changing from a standing to a sitting position [13].
\nThe user-exoskeleton interface is through functional electrical stimulation [14].
\nOne of the great advantages of this exoskeleton is that it can effectively balance robotic performance and functional electrical stimulation during motion [10].
\nHowever, a major drawback is that it is intended almost exclusively for the usage with patients with an incomplete spinal cord injury, who are capable of short movements.
\n\nTable 1 offers a comparison of the most important characteristics of the five exoskeletons analyzed.
\nNAME | \n(Hybrid Assistive Limb) | \n||||
---|---|---|---|---|---|
DEVELOPER | \nCSIC Bioengineering Group, but currently the exclusive license is for Technaid S.L. | \n||||
TARGET POPULATION | \nAdults between 1.5 and 1.95 m in height, with a maximum weight of 100 kg, with neurological damage that inhibits motor skills. | \nIt is aimed at those people with stroke, multiple sclerosis, Parkinson’s or Spinal Cord Injury up to C7. | \nAimed at people with walking problems due to neuromuscular pathologies such as Spinal Cord Injury. | \nIt is aimed at people with incomplete Spinal Cord Injury capable of making short movements. | \nIt is a lower limb exoskeleton for people with complete spinal cord injury from C7 to T12. | \n
OPEN OR CLOSED STRUCTURE | \nOPEN | \nOPEN | \nOPEN | \nOPEN | \nOPEN | \n
ENGINE AND LOCATION | \nMotorized joints in hips, knees and ankles | \nElectric engine located in the back. | \nElectric engine located on the side of the legs and arms, sensors on the waist. HAL-5. | \n24 V electric engine, located in the back. | \n28 V electric engine with lithium batteries with autonomy of 3 hours, located on the back. | \n
USER-SKELETON INTERFACE | \nInterface that connects via Bluetooth to a smartphone. | \nIndependent motor assistance. | \nBioelectric signal sensor. | \nFunctional electrical stimulation. | \nTilt sensors. Wireless communicator. | \n
ADVANTAGES AND DISADVANTAGES | \nDue to its open architecture, it can be used in combination with muscle function readers. It does not need the use of uncomfortable backpacks for the user. It can be used in patients whose paraplegia is caused by various pathologies. | \nAllows 100% weight shift, lateral movement and squatting position. Spasticity reduction. | \nIt can be used even if the person has totally lost the motor function of the lower limbs. | \nCan effectively balance robotic performance and functional electrical stimulation during movements. | \nIt is controlled thanks to the movement of the trunk and the movements of the center of gravity, when the body moves forward the system translates it as the beginning of the step. | \n
Comparison among exoskeletons.
The use of exoskeletons in the rehabilitation of patients with paraplegia shows promising results in the recovery of subjects with motor deficits [1].
\nThere are several exoskeletons developed by different companies. These exoskeletons have evolved over time to help patients who suffer from paraplegia caused by different pathologies. To get the maximum benefit from using these devices, it is necessary for the therapist to carefully choose the appropriate device for each patient. The exoskeletons presented in this chapter have proven to be excellent aids in the partial recovery of motor skills and the improvement of spasticity, although not permanently yet, with minimal pain reported by patients who have used them. However, the cost of exoskeletons is very high, as it varies among $65,000.00 and $100,000.00, which makes it prohibitive for many patients who may require it. Clinical studies in patients have different degrees of advancement, for example: the Kinesis exoskeleton has significant potential to rehabilitate walking motion of patients with incomplete spinal cord injury. The results of tests carried out with KINESIS show that the operative controller adapted to the functional deficits of the patient as well as to voluntary actions during gait, through modulating stimulation and robotic assistance, which was the objective of the controller’s design. Further developments should address the simultaneous modulation of robot stimulation and assistance based on explicit patient needs. This includes more robust methods of managing muscle fatigue. The creators foresee additional work related to various aspects of hybrid gait control: stimulation control based on estimating muscle activation, improved semi-automatic gait control, and improved muscle fatigue monitoring [15].
\nThe EXO-H2 exoskeleton is a robust and safe exoskeleton useful for patients with partial leg weakness, while using assistive devices for the upper extremities or with the help of a healthcare professional. It can be used by patients after a stroke or traumatic injury that results in difficulties while walking. There is a preliminary study of EXO-H2 in three patients with stroke-related hemiparesis. The training was well tolerated and there were no adverse events. The authors suggest that Exo-H2 opens the opportunity to study ways to optimize a rehabilitation treatment that can be customized for each patient. These results are promising and encourage future rehabilitation training with a larger cohort of patients [9].
\nOn the other hand, the HAL exoskeleton has been tested in eight patients recovering from hemiparetic strokes, in a study sponsored by the manufacturer and the Stockholm City Council, improving the ability to walk in the 10-meter walk test and in the categories of functional ambulation; it also improves torso posture and facilitates treadmill training, reporting the HAL exoskeleton as safe when used in conjunction with an inpatient rehabilitation program. In a current study between Dandeyd Hospital and the University of Tsukuba, the conventional gait training techniques are compared to the use of HAL in patients recovering from strokes, although the results are not conclusive yet.
\nThe Ekso exoskeleton in its GT model is the first exoskeleton approved by the United States Food and Drug Administration (FDA). It is currently under evaluation in many centers in the United States and Europe.
\nThe Kolakowsky-Hayner et al. [16] team found it safe to use with patients with complete thoracic spinal cord injury in a controlled environment.
\nThe team of Kressler et al. found that people with chronic complete spinal cord injury who used the Ekso for ground walking training could achieve speeds and walking distances comparable to the averages of those with incomplete motor injuries, but there was little change in the activation of the leg muscles [17].
\nEkso may help stroke patients stand longer and take more steps [9].
\nFinally, the ReWalk exoskeleton has proven to work well in patients with spinal cord injury. Outcomes of patients who have been able to walk independently have been documented. In the United States it began to be used in the middle of this decade; the United States Veterans Administration has implemented the use of ReWalk in veterans with paraplegia; and its use in patients recovering from cerebrovascular accidents and people with multiple sclerosis is currently under investigation [9].
\nThe use of robotic technology as support for the rehabilitation of patients with paraplegia is a very important tool, which should be considered as part of recovery plans, improving the quality of life of users who require them. However, it is important to note that although it has great advantages for users, the cost of these exoskeletons is so high that it becomes difficult to be provided to all those patients who need them, besides there are also some models that are in early preliminary studies to be still considered for use in regular clinical practice.
\nIn the next 10–15 years, another important area of development will be modular robotics, specifically exoskeletons made for unique joints such as the hip, knee or ankles, as well as the so-called “soft robotics” that use non-rigid materials, in custom positions to provide movement for people with different physical limitations that do not fit in the current rigid robots. An example of this type of modular robot is the Honda Strike Management Assist (SMA), which fits around a person’s waist and thighs like a belt and provides assistance to people with weakened leg muscles. Weighing approximately 2.8 kg, the SMA is much smaller and lighter than other exoskeletons. It is designed to help users regulate their walking pace and lengthen their stride, particularly for people who can walk but have mild gait deficiencies due to aging or other medical conditions. Researchers at the Chicago Rehabilitation Institute are currently evaluating the use of SMA with task-specific training, comparing it to traditional physical therapy in the outpatient setting, for people who have suffered a stroke. Additionally, soft robotics, an emerging area focused on developing systems that are lighter and more flexible to help people with weakened upper or lower limbs, is also evolving. Currently, groups such as Harvard University [18], Yale University, and ETH Zurich are working on soft material technologies that are made up of polymers, gels, and soft microfluidic electronics that exhibit significant elasticity with the potential to enhance the utility of wearable robotics. Finally, systems that combine functional electrical stimulation, pattern recognition, and brain-machine interfaces are also likely to emerge. All of these technologies have the potential to work separately or synergistically with exoskeletons, depending on a person’s level of injury and rehabilitation goals [9].
\nWe thank the National Institute of Psychiatry Ramón de la Fuente, especially to Dr. Edgar Mixcoha; and Faculty of Health Sciences of Anahuac University.
\nThe authors declare that there is no conflict of interest regarding the publication of this paper.
As an Open Access publisher, IntechOpen is dedicated to maintaining the highest ethical standards and principles in publishing. In addition, IntechOpen promotes the highest standards of integrity and ethical behavior in scientific research and peer-review. To maintain these principles IntechOpen has developed basic guidelines to facilitate the avoidance of Conflicts of Interest.
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\\n\\nA Conflict of Interest is a situation in which a person's professional judgment may be influenced by a range of factors, including financial gain, material interest, or some other personal or professional interest. For IntechOpen as a publisher, it is essential that all possible Conflicts of Interest are avoided. Each contributor, whether an Author, Editor, or Reviewer, who suspects they may have a Conflict of Interest, is obliged to declare that concern in order to make the publisher and the readership aware of any potential influence on the work being undertaken.
\\n\\nA Conflict of Interest can be identified at different phases of the publishing process.
\\n\\nIntechOpen requires:
\\n\\nCONFLICT OF INTEREST - AUTHOR
\\n\\nAll Authors are obliged to declare every existing or potential Conflict of Interest, including financial or personal factors, as well as any relationship which could influence their scientific work. Authors must declare Conflicts of Interest at the time of manuscript submission, although they may exceptionally do so at any point during manuscript review. For jointly prepared manuscripts, the corresponding Author is obliged to declare potential Conflicts of Interest of any other Authors who have contributed to the manuscript.
\\n\\nCONFLICT OF INTEREST – ACADEMIC EDITOR
\\n\\nEditors can also have Conflicts of Interest. Editors are expected to maintain the highest standards of conduct, which are outlined in our Best Practice Guidelines (templates for Best Practice Guidelines). Among other obligations, it is essential that Editors make transparent declarations of any possible Conflicts of Interest that they might have.
\\n\\nAvoidance Measures for Academic Editors of Conflicts of Interest:
\\n\\nFor manuscripts submitted by the Academic Editor (or a scientific advisor), an appropriate person will be appointed to handle and evaluate the manuscript. The appointed handling Editor's identity will not be disclosed to the Author in order to maintain impartiality and anonymity of the review.
\\n\\nIf a manuscript is submitted by an Author who is a member of an Academic Editor's family or is personally or professionally related to the Academic Editor in any way, either as a friend, colleague, student or mentor, the work will be handled by a different Academic Editor who is not in any way connected to the Author.
\\n\\nCONFLICT OF INTEREST - REVIEWER
\\n\\nAll Reviewers are required to declare possible Conflicts of Interest at the beginning of the evaluation process. If a Reviewer feels he or she might have any material, financial or any other conflict of interest with regards to the manuscript being reviewed, he or she is required to declare such concern and, if necessary, request exclusion from any further involvement in the evaluation process. A Reviewer's potential Conflicts of Interest are declared in the review report and presented to the Academic Editor, who then assesses whether or not the declared potential or actual Conflicts of Interest had, or could be perceived to have had, any significant impact on the review itself.
\\n\\nEXAMPLES OF CONFLICTS OF INTEREST:
\\n\\nFINANCIAL AND MATERIAL
\\n\\nNON-FINANCIAL
\\n\\nAuthors are required to declare all potentially relevant non-financial, financial and material Conflicts of Interest that may have had an influence on their scientific work.
\\n\\nAcademic Editors and Reviewers are required to declare any non-financial, financial and material Conflicts of Interest that could influence their fair and balanced evaluation of manuscripts. If such conflict exists with regards to a submitted manuscript, Academic Editors and Reviewers should exclude themselves from handling it.
\\n\\nAll Authors, Academic Editors, and Reviewers are required to declare all possible financial and material Conflicts of Interest in the last five years, although it is advisable to declare less recent Conflicts of Interest as well.
\\n\\nEXAMPLES:
\\n\\nAuthors should declare if they were or they still are Academic Editors of the publications in which they wish to publish their work.
\\n\\nAuthors should declare if they are board members of an organization that could benefit financially or materially from the publication of their work.
\\n\\nAcademic Editors should declare if they were coauthors or they have worked on the research project with the Author who has submitted a manuscript.
\\n\\nAcademic Editors should declare if the Author of a submitted manuscript is affiliated with the same department, faculty, institute, or company as they are.
\\n\\nPolicy last updated: 2016-06-09
\\n"}]'},components:[{type:"htmlEditorComponent",content:"In each instance of a possible Conflict of Interest, IntechOpen aims to disclose the situation in as transparent a way as possible in order to allow readers to judge whether a particular potential Conflict of Interest has influenced the Work of any individual Author, Editor, or Reviewer. IntechOpen takes all possible Conflicts of Interest into account during the review process and ensures maximum transparency in implementing its policies.
\n\nA Conflict of Interest is a situation in which a person's professional judgment may be influenced by a range of factors, including financial gain, material interest, or some other personal or professional interest. For IntechOpen as a publisher, it is essential that all possible Conflicts of Interest are avoided. Each contributor, whether an Author, Editor, or Reviewer, who suspects they may have a Conflict of Interest, is obliged to declare that concern in order to make the publisher and the readership aware of any potential influence on the work being undertaken.
\n\nA Conflict of Interest can be identified at different phases of the publishing process.
\n\nIntechOpen requires:
\n\nCONFLICT OF INTEREST - AUTHOR
\n\nAll Authors are obliged to declare every existing or potential Conflict of Interest, including financial or personal factors, as well as any relationship which could influence their scientific work. Authors must declare Conflicts of Interest at the time of manuscript submission, although they may exceptionally do so at any point during manuscript review. For jointly prepared manuscripts, the corresponding Author is obliged to declare potential Conflicts of Interest of any other Authors who have contributed to the manuscript.
\n\nCONFLICT OF INTEREST – ACADEMIC EDITOR
\n\nEditors can also have Conflicts of Interest. Editors are expected to maintain the highest standards of conduct, which are outlined in our Best Practice Guidelines (templates for Best Practice Guidelines). Among other obligations, it is essential that Editors make transparent declarations of any possible Conflicts of Interest that they might have.
\n\nAvoidance Measures for Academic Editors of Conflicts of Interest:
\n\nFor manuscripts submitted by the Academic Editor (or a scientific advisor), an appropriate person will be appointed to handle and evaluate the manuscript. The appointed handling Editor's identity will not be disclosed to the Author in order to maintain impartiality and anonymity of the review.
\n\nIf a manuscript is submitted by an Author who is a member of an Academic Editor's family or is personally or professionally related to the Academic Editor in any way, either as a friend, colleague, student or mentor, the work will be handled by a different Academic Editor who is not in any way connected to the Author.
\n\nCONFLICT OF INTEREST - REVIEWER
\n\nAll Reviewers are required to declare possible Conflicts of Interest at the beginning of the evaluation process. If a Reviewer feels he or she might have any material, financial or any other conflict of interest with regards to the manuscript being reviewed, he or she is required to declare such concern and, if necessary, request exclusion from any further involvement in the evaluation process. A Reviewer's potential Conflicts of Interest are declared in the review report and presented to the Academic Editor, who then assesses whether or not the declared potential or actual Conflicts of Interest had, or could be perceived to have had, any significant impact on the review itself.
\n\nEXAMPLES OF CONFLICTS OF INTEREST:
\n\nFINANCIAL AND MATERIAL
\n\nNON-FINANCIAL
\n\nAuthors are required to declare all potentially relevant non-financial, financial and material Conflicts of Interest that may have had an influence on their scientific work.
\n\nAcademic Editors and Reviewers are required to declare any non-financial, financial and material Conflicts of Interest that could influence their fair and balanced evaluation of manuscripts. If such conflict exists with regards to a submitted manuscript, Academic Editors and Reviewers should exclude themselves from handling it.
\n\nAll Authors, Academic Editors, and Reviewers are required to declare all possible financial and material Conflicts of Interest in the last five years, although it is advisable to declare less recent Conflicts of Interest as well.
\n\nEXAMPLES:
\n\nAuthors should declare if they were or they still are Academic Editors of the publications in which they wish to publish their work.
\n\nAuthors should declare if they are board members of an organization that could benefit financially or materially from the publication of their work.
\n\nAcademic Editors should declare if they were coauthors or they have worked on the research project with the Author who has submitted a manuscript.
\n\nAcademic Editors should declare if the Author of a submitted manuscript is affiliated with the same department, faculty, institute, or company as they are.
\n\nPolicy last updated: 2016-06-09
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In this work, we are interested in the Neuromate robot. The latter uses the procedure of stereotaxic surgery but with better planning, greater precision and simpler execution. The Neuromate robot allows in particular the registration with intraoperative images (ventriculographies, and especially angiographies) in order to perfect the planning. In this book, we focus on the contact force measurement system required for the effectiveness of the stimulation between the robot probe and the patient’s head and thus ensure the safety of the patient. A force sensor is integrated upstream of the wrist, the pressure sensor is part of a silicon matrix that has been bonded to a metal plate at 70°C. The study was carried out under the software COMSOL Multiphysics, ideally suited for the simulation of applications (Microelectromechanical systems) “MEMS”. After electromechanical stationary survey, deflection of the quadrant when the pressure difference across the membrane was 25 kPa, as expected, the deviation was expected to be greatest at the center of the membrane. The proposed sensor structure is a suitable selection for MEMS capacitive pressure sensors.",book:{id:"6865",slug:"becoming-human-with-humanoid-from-physical-interaction-to-social-intelligence",title:"Becoming Human with Humanoid",fullTitle:"Becoming Human with Humanoid - From Physical Interaction to Social Intelligence"},signatures:"Hacene Ameddah",authors:[{id:"302678",title:"Dr.",name:"Hacene",middleName:null,surname:"Ameddah",slug:"hacene-ameddah",fullName:"Hacene Ameddah"}]},{id:"70653",title:"Living and Interacting with Robots: Engaging Users in the Development of a Mobile Robot",slug:"living-and-interacting-with-robots-engaging-users-in-the-development-of-a-mobile-robot",totalDownloads:794,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Mobile robots such as Aldebaran’s humanoid Pepper currently find their way into society. Many research projects already try to match humanoid robots with humans by letting them assist, e.g., in geriatric care or simply for purposes of keeping company or entertainment. However, many of these projects deal with acceptance issues that come with a new type of interaction between humans and robots. These issues partly originate from different types of robot locomotion, limited human-like behaviour as well as limited functionalities in general. At the same time, animal-type robots—quadrupeds such as Boston Dynamic’s WildCat—and underactuated robots are on the rise and present social scientists with new challenges such as the concept of uncanny valley. The possible positive aspects of the unusual cooperations and interactions, however, are mostly pushed into the background. 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Radiotherapy and Nuclear Medicine Technology has always been my aspiration and my life. As years passed I accumulated a tremendous amount of skills and knowledge in Radiotherapy and Nuclear Medicine, Conventional Radiology, Radiation Protection, Bioinformatics Technology, PACS, Image processing, clinically and lecturing that will enable me to provide a valuable service to the community as a Researcher and Consultant in this field. My method of translating this into day to day in clinical practice is non-exhaustible and my habit of exchanging knowledge and expertise with others in those fields is the code and secret of success.",institutionString:null,institution:{name:"Majmaah University",country:{name:"Saudi Arabia"}}},{id:"313277",title:"Dr.",name:"Bartłomiej",middleName:null,surname:"Płaczek",slug:"bartlomiej-placzek",fullName:"Bartłomiej Płaczek",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/313277/images/system/313277.jpg",biography:"Bartłomiej Płaczek, MSc (2002), Ph.D. (2005), Habilitation (2016), is a professor at the University of Silesia, Institute of Computer Science, Poland, and an expert from the National Centre for Research and Development. His research interests include sensor networks, smart sensors, intelligent systems, and image processing with applications in healthcare and medicine. He is the author or co-author of more than seventy papers in peer-reviewed journals and conferences as well as the co-author of several books. He serves as a reviewer for many scientific journals, international conferences, and research foundations. Since 2010, Dr. Placzek has been a reviewer of grants and projects (including EU projects) in the field of information technologies.",institutionString:"University of Silesia",institution:{name:"University of Silesia",country:{name:"Poland"}}},{id:"35000",title:"Prof.",name:"Ulrich H.P",middleName:"H.P.",surname:"Fischer",slug:"ulrich-h.p-fischer",fullName:"Ulrich H.P Fischer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/35000/images/3052_n.jpg",biography:"Academic and Professional Background\nUlrich H. P. has Diploma and PhD degrees in Physics from the Free University Berlin, Germany. He has been working on research positions in the Heinrich-Hertz-Institute in Germany. Several international research projects has been performed with European partners from France, Netherlands, Norway and the UK. He is currently Professor of Communications Systems at the Harz University of Applied Sciences, Germany.\n\nPublications and Publishing\nHe has edited one book, a special interest book about ‘Optoelectronic Packaging’ (VDE, Berlin, Germany), and has published over 100 papers and is owner of several international patents for WDM over POF key elements.\n\nKey Research and Consulting Interests\nUlrich’s research activity has always been related to Spectroscopy and Optical Communications Technology. Specific current interests include the validation of complex instruments, and the application of VR technology to the development and testing of measurement systems. He has been reviewer for several publications of the Optical Society of America\\'s including Photonics Technology Letters and Applied Optics.\n\nPersonal Interests\nThese include motor cycling in a very relaxed manner and performing martial arts.",institutionString:null,institution:{name:"Charité",country:{name:"Germany"}}},{id:"341622",title:"Ph.D.",name:"Eduardo",middleName:null,surname:"Rojas Alvarez",slug:"eduardo-rojas-alvarez",fullName:"Eduardo Rojas Alvarez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/341622/images/15892_n.jpg",biography:null,institutionString:null,institution:{name:"University of Cuenca",country:{name:"Ecuador"}}},{id:"215610",title:"Prof.",name:"Muhammad",middleName:null,surname:"Sarfraz",slug:"muhammad-sarfraz",fullName:"Muhammad Sarfraz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/215610/images/system/215610.jpeg",biography:"Muhammad Sarfraz is a professor in the Department of Information Science, Kuwait University, Kuwait. His research interests include optimization, computer graphics, computer vision, image processing, machine learning, pattern recognition, soft computing, data science, and intelligent systems. Prof. Sarfraz has been a keynote/invited speaker at various platforms around the globe. He has advised/supervised more than 110 students for their MSc and Ph.D. theses. He has published more than 400 publications as books, journal articles, and conference papers. He has authored and/or edited around seventy books. Prof. Sarfraz is a member of various professional societies. He is a chair and member of international advisory committees and organizing committees of numerous international conferences. He is also an editor and editor in chief for various international journals.",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"32650",title:"Prof.",name:"Lukas",middleName:"Willem",surname:"Snyman",slug:"lukas-snyman",fullName:"Lukas Snyman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/32650/images/4136_n.jpg",biography:"Lukas Willem Snyman received his basic education at primary and high schools in South Africa, Eastern Cape. He enrolled at today's Nelson Metropolitan University and graduated from this university with a BSc in Physics and Mathematics, B.Sc Honors in Physics, MSc in Semiconductor Physics, and a Ph.D. in Semiconductor Physics in 1987. After his studies, he chose an academic career and devoted his energy to the teaching of physics to first, second, and third-year students. After positions as a lecturer at the University of Port Elizabeth, he accepted a position as Associate Professor at the University of Pretoria, South Africa.\r\n\r\nIn 1992, he motivates the concept of 'television and computer-based education” as means to reach large student numbers with only the best of teaching expertise and publishes an article on the concept in the SA Journal of Higher Education of 1993 (and later in 2003). The University of Pretoria subsequently approved a series of test projects on the concept with outreach to Mamelodi and Eerste Rust in 1993. In 1994, the University established a 'Unit for Telematic Education ' as a support section for multiple faculties at the University of Pretoria. In subsequent years, the concept of 'telematic education” subsequently becomes well established in academic circles in South Africa, grew in popularity, and is adopted by many universities and colleges throughout South Africa as a medium of enhancing education and training, as a method to reaching out to far out communities, and as a means to enhance study from the home environment.\r\n\r\nProfessor Snyman in subsequent years pursued research in semiconductor physics, semiconductor devices, microelectronics, and optoelectronics.\r\n\r\nIn 2000 he joined the TUT as a full professor. Here served for a period as head of the Department of Electronic Engineering. Here he makes contributions to solar energy development, microwave and optoelectronic device development, silicon photonics, as well as contributions to new mobile telecommunication systems and network planning in SA.\r\n\r\nCurrently, he teaches electronics and telecommunications at the TUT to audiences ranging from first-year students to Ph.D. level.\r\n\r\nFor his research in the field of 'Silicon Photonics” since 1990, he has published (as author and co-author) about thirty internationally reviewed articles in scientific journals, contributed to more than forty international conferences, about 25 South African provisional patents (as inventor and co-inventor), 8 PCT international patent applications until now. Of these, two USA patents applications, two European Patents, two Korean patents, and ten SA patents have been granted. A further 4 USA patents, 5 European patents, 3 Korean patents, 3 Chinese patents, and 3 Japanese patents are currently under consideration.\r\n\r\nRecently he has also published an extensive scholarly chapter in an internet open access book on 'Integrating Microphotonic Systems and MOEMS into standard Silicon CMOS Integrated circuitry”.\r\n\r\nFurthermore, Professor Snyman recently steered a new initiative at the TUT by introducing a 'Laboratory for Innovative Electronic Systems ' at the Department of Electrical Engineering. The model of this laboratory or center is to primarily combine outputs as achieved by high-level research with lower-level system development and entrepreneurship in a technical university environment. Students are allocated to projects at different levels with PhDs and Master students allocated to the generation of new knowledge and new technologies, while students at the diploma and Baccalaureus level are allocated to electronic systems development with a direct and a near application for application in industry or the commercial and public sectors in South Africa.\r\n\r\nProfessor Snyman received the WIRSAM Award of 1983 and the WIRSAM Award in 1985 in South Africa for best research papers by a young scientist at two international conferences on electron microscopy in South Africa. He subsequently received the SA Microelectronics Award for the best dissertation emanating from studies executed at a South African university in the field of Physics and Microelectronics in South Africa in 1987. In October of 2011, Professor Snyman received the prestigious Institutional Award for 'Innovator of the Year” for 2010 at the Tshwane University of Technology, South Africa. This award was based on the number of patents recognized and granted by local and international institutions as well as for his contributions concerning innovation at the TUT.",institutionString:null,institution:{name:"University of South Africa",country:{name:"South Africa"}}},{id:"317279",title:"Mr.",name:"Ali",middleName:"Usama",surname:"Syed",slug:"ali-syed",fullName:"Ali Syed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/317279/images/16024_n.png",biography:"A creative, talented, and innovative young professional who is dedicated, well organized, and capable research fellow with two years of experience in graduate-level research, published in engineering journals and book, with related expertise in Bio-robotics, equally passionate about the aesthetics of the mechanical and electronic system, obtained expertise in the use of MS Office, MATLAB, SolidWorks, LabVIEW, Proteus, Fusion 360, having a grasp on python, C++ and assembly language, possess proven ability in acquiring research grants, previous appointments with social and educational societies with experience in administration, current affiliations with IEEE and Web of Science, a confident presenter at conferences and teacher in classrooms, able to explain complex information to audiences of all levels.",institutionString:null,institution:{name:"Air University",country:{name:"Pakistan"}}},{id:"75526",title:"Ph.D.",name:"Zihni Onur",middleName:null,surname:"Uygun",slug:"zihni-onur-uygun",fullName:"Zihni Onur Uygun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/75526/images/12_n.jpg",biography:"My undergraduate education and my Master of Science educations at Ege University and at Çanakkale Onsekiz Mart University have given me a firm foundation in Biochemistry, Analytical Chemistry, Biosensors, Bioelectronics, Physical Chemistry and Medicine. After obtaining my degree as a MSc in analytical chemistry, I started working as a research assistant in Ege University Medical Faculty in 2014. In parallel, I enrolled to the MSc program at the Department of Medical Biochemistry at Ege University to gain deeper knowledge on medical and biochemical sciences as well as clinical chemistry in 2014. In my PhD I deeply researched on biosensors and bioelectronics and finished in 2020. Now I have eleven SCI-Expanded Index published papers, 6 international book chapters, referee assignments for different SCIE journals, one international patent pending, several international awards, projects and bursaries. In parallel to my research assistant position at Ege University Medical Faculty, Department of Medical Biochemistry, in April 2016, I also founded a Start-Up Company (Denosens Biotechnology LTD) by the support of The Scientific and Technological Research Council of Turkey. Currently, I am also working as a CEO in Denosens Biotechnology. The main purposes of the company, which carries out R&D as a research center, are to develop new generation biosensors and sensors for both point-of-care diagnostics; such as glucose, lactate, cholesterol and cancer biomarker detections. My specific experimental and instrumental skills are Biochemistry, Biosensor, Analytical Chemistry, Electrochemistry, Mobile phone based point-of-care diagnostic device, POCTs and Patient interface designs, HPLC, Tandem Mass Spectrometry, Spectrophotometry, ELISA.",institutionString:null,institution:{name:"Ege University",country:{name:"Turkey"}}},{id:"246502",title:"Dr.",name:"Jaya T.",middleName:"T",surname:"Varkey",slug:"jaya-t.-varkey",fullName:"Jaya T. Varkey",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/246502/images/11160_n.jpg",biography:"Jaya T. Varkey, PhD, graduated with a degree in Chemistry from Cochin University of Science and Technology, Kerala, India. She obtained a PhD in Chemistry from the School of Chemical Sciences, Mahatma Gandhi University, Kerala, India, and completed a post-doctoral fellowship at the University of Minnesota, USA. She is a research guide at Mahatma Gandhi University and Associate Professor in Chemistry, St. Teresa’s College, Kochi, Kerala, India.\nDr. Varkey received a National Young Scientist award from the Indian Science Congress (1995), a UGC Research award (2016–2018), an Indian National Science Academy (INSA) Visiting Scientist award (2018–2019), and a Best Innovative Faculty award from the All India Association for Christian Higher Education (AIACHE) (2019). She Hashas received the Sr. Mary Cecil prize for best research paper three times. She was also awarded a start-up to develop a tea bag water filter. \nDr. Varkey has published two international books and twenty-seven international journal publications. She is an editorial board member for five international journals.",institutionString:"St. Teresa’s College",institution:null},{id:"250668",title:"Dr.",name:"Ali",middleName:null,surname:"Nabipour Chakoli",slug:"ali-nabipour-chakoli",fullName:"Ali Nabipour Chakoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/250668/images/system/250668.jpg",biography:"Academic Qualification:\r\n•\tPhD in Materials Physics and Chemistry, From: Sep. 2006, to: Sep. 2010, School of Materials Science and Engineering, Harbin Institute of Technology, Thesis: Structure and Shape Memory Effect of Functionalized MWCNTs/poly (L-lactide-co-ε-caprolactone) Nanocomposites. Supervisor: Prof. Wei Cai,\r\n•\tM.Sc in Applied Physics, From: 1996, to: 1998, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Determination of Boron in Micro alloy Steels with solid state nuclear track detectors by neutron induced auto radiography, Supervisors: Dr. M. Hosseini Ashrafi and Dr. A. Hosseini.\r\n•\tB.Sc. in Applied Physics, From: 1991, to: 1996, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Design of shielding for Am-Be neutron sources for In Vivo neutron activation analysis, Supervisor: Dr. M. Hosseini Ashrafi.\r\n\r\nResearch Experiences:\r\n1.\tNanomaterials, Carbon Nanotubes, Graphene: Synthesis, Functionalization and Characterization,\r\n2.\tMWCNTs/Polymer Composites: Fabrication and Characterization, \r\n3.\tShape Memory Polymers, Biodegradable Polymers, ORC, Collagen,\r\n4.\tMaterials Analysis and Characterizations: TEM, SEM, XPS, FT-IR, Raman, DSC, DMA, TGA, XRD, GPC, Fluoroscopy, \r\n5.\tInteraction of Radiation with Mater, Nuclear Safety and Security, NDT(RT),\r\n6.\tRadiation Detectors, Calibration (SSDL),\r\n7.\tCompleted IAEA e-learning Courses:\r\nNuclear Security (15 Modules),\r\nNuclear Safety:\r\nTSA 2: Regulatory Protection in Occupational Exposure,\r\nTips & Tricks: Radiation Protection in Radiography,\r\nSafety and Quality in Radiotherapy,\r\nCourse on Sealed Radioactive Sources,\r\nCourse on Fundamentals of Environmental Remediation,\r\nCourse on Planning for Environmental Remediation,\r\nKnowledge Management Orientation Course,\r\nFood Irradiation - Technology, Applications and Good Practices,\r\nEmployment:\r\nFrom 2010 to now: Academic staff, Nuclear Science and Technology Research Institute, Kargar Shomali, Tehran, Iran, P.O. Box: 14395-836.\r\nFrom 1997 to 2006: Expert of Materials Analysis and Characterization. Research Center of Agriculture and Medicine. Rajaeeshahr, Karaj, Iran, P. O. Box: 31585-498.",institutionString:"Atomic Energy Organization of Iran",institution:{name:"Atomic Energy Organization of Iran",country:{name:"Iran"}}},{id:"248279",title:"Dr.",name:"Monika",middleName:"Elzbieta",surname:"Machoy",slug:"monika-machoy",fullName:"Monika Machoy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248279/images/system/248279.jpeg",biography:"Monika Elżbieta Machoy, MD, graduated with distinction from the Faculty of Medicine and Dentistry at the Pomeranian Medical University in 2009, defended her PhD thesis with summa cum laude in 2016 and is currently employed as a researcher at the Department of Orthodontics of the Pomeranian Medical University. She expanded her professional knowledge during a one-year scholarship program at the Ernst Moritz Arndt University in Greifswald, Germany and during a three-year internship at the Technical University in Dresden, Germany. She has been a speaker at numerous orthodontic conferences, among others, American Association of Orthodontics, European Orthodontic Symposium and numerous conferences of the Polish Orthodontic Society. She conducts research focusing on the effect of orthodontic treatment on dental and periodontal tissues and the causes of pain in orthodontic patients.",institutionString:"Pomeranian Medical University",institution:{name:"Pomeranian Medical University",country:{name:"Poland"}}},{id:"252743",title:"Prof.",name:"Aswini",middleName:"Kumar",surname:"Kar",slug:"aswini-kar",fullName:"Aswini Kar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252743/images/10381_n.jpg",biography:"uploaded in cv",institutionString:null,institution:{name:"KIIT University",country:{name:"India"}}},{id:"204256",title:"Dr.",name:"Anil",middleName:"Kumar",surname:"Kumar Sahu",slug:"anil-kumar-sahu",fullName:"Anil Kumar Sahu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204256/images/14201_n.jpg",biography:"I have nearly 11 years of research and teaching experience. I have done my master degree from University Institute of Pharmacy, Pt. Ravi Shankar Shukla University, Raipur, Chhattisgarh India. I have published 16 review and research articles in international and national journals and published 4 chapters in IntechOpen, the world’s leading publisher of Open access books. I have presented many papers at national and international conferences. I have received research award from Indian Drug Manufacturers Association in year 2015. My research interest extends from novel lymphatic drug delivery systems, oral delivery system for herbal bioactive to formulation optimization.",institutionString:null,institution:{name:"Chhattisgarh Swami Vivekanand Technical University",country:{name:"India"}}},{id:"253468",title:"Dr.",name:"Mariusz",middleName:null,surname:"Marzec",slug:"mariusz-marzec",fullName:"Mariusz Marzec",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/253468/images/system/253468.png",biography:"An assistant professor at Department of Biomedical Computer Systems, at Institute of Computer Science, Silesian University in Katowice. Scientific interests: computer analysis and processing of images, biomedical images, databases and programming languages. He is an author and co-author of scientific publications covering analysis and processing of biomedical images and development of database systems.",institutionString:"University of Silesia",institution:null},{id:"212432",title:"Prof.",name:"Hadi",middleName:null,surname:"Mohammadi",slug:"hadi-mohammadi",fullName:"Hadi Mohammadi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/212432/images/system/212432.jpeg",biography:"Dr. Hadi Mohammadi is a biomedical engineer with hands-on experience in the design and development of many engineering structures and medical devices through various projects that he has been involved in over the past twenty years. Dr. Mohammadi received his BSc. and MSc. degrees in Mechanical Engineering from Sharif University of Technology, Tehran, Iran, and his PhD. degree in Biomedical Engineering (biomaterials) from the University of Western Ontario. He was a postdoctoral trainee for almost four years at University of Calgary and Harvard Medical School. He is an industry innovator having created the technology to produce lifelike synthetic platforms that can be used for the simulation of almost all cardiovascular reconstructive surgeries. He’s been heavily involved in the design and development of cardiovascular devices and technology for the past 10 years. He is currently an Assistant Professor with the University of British Colombia, Canada.",institutionString:"University of British Columbia",institution:{name:"University of British Columbia",country:{name:"Canada"}}},{id:"254463",title:"Prof.",name:"Haisheng",middleName:null,surname:"Yang",slug:"haisheng-yang",fullName:"Haisheng Yang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/254463/images/system/254463.jpeg",biography:"Haisheng Yang, Ph.D., Professor and Director of the Department of Biomedical Engineering, College of Life Science and Bioengineering, Beijing University of Technology. He received his Ph.D. degree in Mechanics/Biomechanics from Harbin Institute of Technology (jointly with University of California, Berkeley). Afterwards, he worked as a Postdoctoral Research Associate in the Purdue Musculoskeletal Biology and Mechanics Lab at the Department of Basic Medical Sciences, Purdue University, USA. He also conducted research in the Research Centre of Shriners Hospitals for Children-Canada at McGill University, Canada. Dr. Yang has over 10 years research experience in orthopaedic biomechanics and mechanobiology of bone adaptation and regeneration. He earned an award from Beijing Overseas Talents Aggregation program in 2017 and serves as Beijing Distinguished Professor.",institutionString:"Beijing University of Technology",institution:null},{id:"255757",title:"Dr.",name:"Igor",middleName:"Victorovich",surname:"Lakhno",slug:"igor-lakhno",fullName:"Igor Lakhno",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255757/images/system/255757.jpg",biography:"Lakhno Igor Victorovich was born in 1971 in Kharkiv (Ukraine). \nMD – 1994, Kharkiv National Medical Univesity.\nOb&Gyn; – 1997, master courses in Kharkiv Medical Academy of Postgraduate Education.\nPhD – 1999, Kharkiv National Medical Univesity.\nDSc – 2019, PL Shupik National Academy of Postgraduate Education \nLakhno Igor has been graduated from an international training courses on reproductive medicine and family planning held in Debrecen University (Hungary) in 1997. Since 1998 Lakhno Igor has worked as an associate professor of the department of obstetrics and gynecology of VN Karazin National University and an associate professor of the perinatology, obstetrics and gynecology department of Kharkiv Medical Academy of Postgraduate Education. Since June 2019 he’s a professor of the department of obstetrics and gynecology of VN Karazin National University and a professor of the perinatology, obstetrics and gynecology department of Kharkiv Medical Academy of Postgraduate Education . He’s an author of about 200 printed works and there are 17 of them in Scopus or Web of Science databases. Lakhno Igor is a rewiever of Journal of Obstetrics and Gynaecology (Taylor and Francis), Informatics in Medicine Unlocked (Elsevier), The Journal of Obstetrics and Gynecology Research (Wiley), Endocrine, Metabolic & Immune Disorders-Drug Targets (Bentham Open), The Open Biomedical Engineering Journal (Bentham Open), etc. He’s defended a dissertation for DSc degree \\'Pre-eclampsia: prediction, prevention and treatment”. Lakhno Igor has participated as a speaker in several international conferences and congresses (International Conference on Biological Oscillations April 10th-14th 2016, Lancaster, UK, The 9th conference of the European Study Group on Cardiovascular Oscillations). His main scientific interests: obstetrics, women’s health, fetal medicine, cardiovascular medicine.",institutionString:"V.N. Karazin Kharkiv National University",institution:{name:"Kharkiv Medical Academy of Postgraduate Education",country:{name:"Ukraine"}}},{id:"89721",title:"Dr.",name:"Mehmet",middleName:"Cuneyt",surname:"Ozmen",slug:"mehmet-ozmen",fullName:"Mehmet Ozmen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/89721/images/7289_n.jpg",biography:null,institutionString:null,institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"243698",title:"M.D.",name:"Xiaogang",middleName:null,surname:"Wang",slug:"xiaogang-wang",fullName:"Xiaogang Wang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243698/images/system/243698.png",biography:"Dr. Xiaogang Wang, a faculty member of Shanxi Eye Hospital specializing in the treatment of cataract and retinal disease and a tutor for postgraduate students of Shanxi Medical University, worked in the COOL Lab as an international visiting scholar under the supervision of Dr. David Huang and Yali Jia from October 2012 through November 2013. Dr. Wang earned an MD from Shanxi Medical University and a Ph.D. from Shanghai Jiao Tong University. Dr. Wang was awarded two research project grants focused on multimodal optical coherence tomography imaging and deep learning in cataract and retinal disease, from the National Natural Science Foundation of China. He has published around 30 peer-reviewed journal papers and four book chapters and co-edited one book.",institutionString:"Shanxi Eye Hospital",institution:{name:"Shanxi Eye Hospital",country:{name:"China"}}},{id:"242893",title:"Ph.D. Student",name:"Joaquim",middleName:null,surname:"De Moura",slug:"joaquim-de-moura",fullName:"Joaquim De Moura",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/242893/images/7133_n.jpg",biography:"Joaquim de Moura received his degree in Computer Engineering in 2014 from the University of A Coruña (Spain). In 2016, he received his M.Sc degree in Computer Engineering from the same university. He is currently pursuing his Ph.D degree in Computer Science in a collaborative project between ophthalmology centers in Galicia and the University of A Coruña. His research interests include computer vision, machine learning algorithms and analysis and medical imaging processing of various kinds.",institutionString:null,institution:{name:"University of A Coruña",country:{name:"Spain"}}},{id:"267434",title:"Dr.",name:"Rohit",middleName:null,surname:"Raja",slug:"rohit-raja",fullName:"Rohit Raja",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRZkkQAG/Profile_Picture_2022-05-09T12:55:18.jpg",biography:null,institutionString:null,institution:null},{id:"294334",title:"B.Sc.",name:"Marc",middleName:null,surname:"Bruggeman",slug:"marc-bruggeman",fullName:"Marc Bruggeman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/294334/images/8242_n.jpg",biography:"Chemical engineer graduate, with a passion for material science and specific interest in polymers - their near infinite applications intrigue me. \n\nI plan to continue my scientific career in the field of polymeric biomaterials as I am fascinated by intelligent, bioactive and biomimetic materials for use in both consumer and medical applications.",institutionString:null,institution:null},{id:"244950",title:"Dr.",name:"Salvatore",middleName:null,surname:"Di Lauro",slug:"salvatore-di-lauro",fullName:"Salvatore Di Lauro",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0030O00002bSF1HQAW/ProfilePicture%202021-12-20%2014%3A54%3A14.482",biography:"Name:\n\tSALVATORE DI LAURO\nAddress:\n\tHospital Clínico Universitario Valladolid\nAvda Ramón y Cajal 3\n47005, Valladolid\nSpain\nPhone number: \nFax\nE-mail:\n\t+34 983420000 ext 292\n+34 983420084\nsadilauro@live.it\nDate and place of Birth:\nID Number\nMedical Licence \nLanguages\t09-05-1985. Villaricca (Italy)\n\nY1281863H\n474707061\nItalian (native language)\nSpanish (read, written, spoken)\nEnglish (read, written, spoken)\nPortuguese (read, spoken)\nFrench (read)\n\t\t\nCurrent position (title and company)\tDate (Year)\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. Private practise.\t2017-today\n\n2019-today\n\t\n\t\nEducation (High school, university and postgraduate training > 3 months)\tDate (Year)\nDegree in Medicine and Surgery. University of Neaples 'Federico II”\nResident in Opthalmology. Hospital Clinico Universitario Valladolid\nMaster in Vitreo-Retina. IOBA. University of Valladolid\nFellow of the European Board of Ophthalmology. Paris\nMaster in Research in Ophthalmology. University of Valladolid\t2003-2009\n2012-2016\n2016-2017\n2016\n2012-2013\n\t\nEmployments (company and positions)\tDate (Year)\nResident in Ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl.\nFellow in Vitreo-Retina. IOBA. University of Valladolid\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. \n\t2012-2016\n2016-2017\n2017-today\n\n2019-Today\n\n\n\t\nClinical Research Experience (tasks and role)\tDate (Year)\nAssociated investigator\n\n' FIS PI20/00740: DESARROLLO DE UNA CALCULADORA DE RIESGO DE\nAPARICION DE RETINOPATIA DIABETICA BASADA EN TECNICAS DE IMAGEN MULTIMODAL EN PACIENTES DIABETICOS TIPO 1. Grant by: Ministerio de Ciencia e Innovacion \n\n' (BIO/VA23/14) Estudio clínico multicéntrico y prospectivo para validar dos\nbiomarcadores ubicados en los genes p53 y MDM2 en la predicción de los resultados funcionales de la cirugía del desprendimiento de retina regmatógeno. Grant by: Gerencia Regional de Salud de la Junta de Castilla y León.\n' Estudio multicéntrico, aleatorizado, con enmascaramiento doble, en 2 grupos\nparalelos y de 52 semanas de duración para comparar la eficacia, seguridad e inmunogenicidad de SOK583A1 respecto a Eylea® en pacientes con degeneración macular neovascular asociada a la edad' (CSOK583A12301; N.EUDRA: 2019-004838-41; FASE III). Grant by Hexal AG\n\n' Estudio de fase III, aleatorizado, doble ciego, con grupos paralelos, multicéntrico para comparar la eficacia y la seguridad de QL1205 frente a Lucentis® en pacientes con degeneración macular neovascular asociada a la edad. (EUDRACT: 2018-004486-13). Grant by Qilu Pharmaceutical Co\n\n' Estudio NEUTON: Ensayo clinico en fase IV para evaluar la eficacia de aflibercept en pacientes Naive con Edema MacUlar secundario a Oclusion de Vena CenTral de la Retina (OVCR) en regimen de tratamientO iNdividualizado Treat and Extend (TAE)”, (2014-000975-21). Grant by Fundacion Retinaplus\n\n' Evaluación de la seguridad y bioactividad de anillos de tensión capsular en conejo. Proyecto Procusens. Grant by AJL, S.A.\n\n'Estudio epidemiológico, prospectivo, multicéntrico y abierto\\npara valorar la frecuencia de la conjuntivitis adenovírica diagnosticada mediante el test AdenoPlus®\\nTest en pacientes enfermos de conjuntivitis aguda”\\n. National, multicenter study. Grant by: NICOX.\n\nEuropean multicentric trial: 'Evaluation of clinical outcomes following the use of Systane Hydration in patients with dry eye”. Study Phase 4. Grant by: Alcon Labs'\n\nVLPs Injection and Activation in a Rabbit Model of Uveal Melanoma. Grant by Aura Bioscience\n\nUpdating and characterization of a rabbit model of uveal melanoma. Grant by Aura Bioscience\n\nEnsayo clínico en fase IV para evaluar las variantes genéticas de la vía del VEGF como biomarcadores de eficacia del tratamiento con aflibercept en pacientes con degeneración macular asociada a la edad (DMAE) neovascular. Estudio BIOIMAGE. IMO-AFLI-2013-01\n\nEstudio In-Eye:Ensayo clínico en fase IV, abierto, aleatorizado, de 2 brazos,\nmulticçentrico y de 12 meses de duración, para evaluar la eficacia y seguridad de un régimen de PRN flexible individualizado de 'esperar y extender' versus un régimen PRN según criterios de estabilización mediante evaluaciones mensuales de inyecciones intravítreas de ranibizumab 0,5 mg en pacientes naive con neovascularización coriodea secunaria a la degeneración macular relacionada con la edad. CP: CRFB002AES03T\n\nTREND: Estudio Fase IIIb multicéntrico, randomizado, de 12 meses de\nseguimiento con evaluador de la agudeza visual enmascarado, para evaluar la eficacia y la seguridad de ranibizumab 0.5mg en un régimen de tratar y extender comparado con un régimen mensual, en pacientes con degeneración macular neovascular asociada a la edad. CP: CRFB002A2411 Código Eudra CT:\n2013-002626-23\n\n\n\nPublications\t\n\n2021\n\n\n\n\n2015\n\n\n\n\n2021\n\n\n\n\n\n2021\n\n\n\n\n2015\n\n\n\n\n2015\n\n\n2014\n\n\n\n\n2015-16\n\n\n\n2015\n\n\n2014\n\n\n2014\n\n\n\n\n2014\n\n\n\n\n\n\n\n2014\n\nJose Carlos Pastor; Jimena Rojas; Salvador Pastor-Idoate; Salvatore Di Lauro; Lucia Gonzalez-Buendia; Santiago Delgado-Tirado. Proliferative vitreoretinopathy: A new concept of disease pathogenesis and practical\nconsequences. Progress in Retinal and Eye Research. 51, pp. 125 - 155. 03/2016. DOI: 10.1016/j.preteyeres.2015.07.005\n\n\nLabrador-Velandia S; Alonso-Alonso ML; Di Lauro S; García-Gutierrez MT; Srivastava GK; Pastor JC; Fernandez-Bueno I. Mesenchymal stem cells provide paracrine neuroprotective resources that delay degeneration of co-cultured organotypic neuroretinal cultures.Experimental Eye Research. 185, 17/05/2019. DOI: 10.1016/j.exer.2019.05.011\n\nSalvatore Di Lauro; Maria Teresa Garcia Gutierrez; Ivan Fernandez Bueno. Quantification of pigment epithelium-derived factor (PEDF) in an ex vivo coculture of retinal pigment epithelium cells and neuroretina.\nJournal of Allbiosolution. 2019. ISSN 2605-3535\n\nSonia Labrador Velandia; Salvatore Di Lauro; Alonso-Alonso ML; Tabera Bartolomé S; Srivastava GK; Pastor JC; Fernandez-Bueno I. Biocompatibility of intravitreal injection of human mesenchymal stem cells in immunocompetent rabbits. Graefe's archive for clinical and experimental ophthalmology. 256 - 1, pp. 125 - 134. 01/2018. DOI: 10.1007/s00417-017-3842-3\n\n\nSalvatore Di Lauro, David Rodriguez-Crespo, Manuel J Gayoso, Maria T Garcia-Gutierrez, J Carlos Pastor, Girish K Srivastava, Ivan Fernandez-Bueno. A novel coculture model of porcine central neuroretina explants and retinal pigment epithelium cells. Molecular Vision. 2016 - 22, pp. 243 - 253. 01/2016.\n\nSalvatore Di Lauro. Classifications for Proliferative Vitreoretinopathy ({PVR}): An Analysis of Their Use in Publications over the Last 15 Years. Journal of Ophthalmology. 2016, pp. 1 - 6. 01/2016. DOI: 10.1155/2016/7807596\n\nSalvatore Di Lauro; Rosa Maria Coco; Rosa Maria Sanabria; Enrique Rodriguez de la Rua; Jose Carlos Pastor. Loss of Visual Acuity after Successful Surgery for Macula-On Rhegmatogenous Retinal Detachment in a Prospective Multicentre Study. Journal of Ophthalmology. 2015:821864, 2015. DOI: 10.1155/2015/821864\n\nIvan Fernandez-Bueno; Salvatore Di Lauro; Ivan Alvarez; Jose Carlos Lopez; Maria Teresa Garcia-Gutierrez; Itziar Fernandez; Eva Larra; Jose Carlos Pastor. Safety and Biocompatibility of a New High-Density Polyethylene-Based\nSpherical Integrated Porous Orbital Implant: An Experimental Study in Rabbits. Journal of Ophthalmology. 2015:904096, 2015. DOI: 10.1155/2015/904096\n\nPastor JC; Pastor-Idoate S; Rodríguez-Hernandez I; Rojas J; Fernandez I; Gonzalez-Buendia L; Di Lauro S; Gonzalez-Sarmiento R. Genetics of PVR and RD. Ophthalmologica. 232 - Suppl 1, pp. 28 - 29. 2014\n\nRodriguez-Crespo D; Di Lauro S; Singh AK; Garcia-Gutierrez MT; Garrosa M; Pastor JC; Fernandez-Bueno I; Srivastava GK. Triple-layered mixed co-culture model of RPE cells with neuroretina for evaluating the neuroprotective effects of adipose-MSCs. Cell Tissue Res. 358 - 3, pp. 705 - 716. 2014.\nDOI: 10.1007/s00441-014-1987-5\n\nCarlo De Werra; Salvatore Condurro; Salvatore Tramontano; Mario Perone; Ivana Donzelli; Salvatore Di Lauro; Massimo Di Giuseppe; Rosa Di Micco; Annalisa Pascariello; Antonio Pastore; Giorgio Diamantis; Giuseppe Galloro. Hydatid disease of the liver: thirty years of surgical experience.Chirurgia italiana. 59 - 5, pp. 611 - 636.\n(Italia): 2007. ISSN 0009-4773\n\nChapters in books\n\t\n' Salvador Pastor Idoate; Salvatore Di Lauro; Jose Carlos Pastor Jimeno. PVR: Pathogenesis, Histopathology and Classification. Proliferative Vitreoretinopathy with Small Gauge Vitrectomy. Springer, 2018. ISBN 978-3-319-78445-8\nDOI: 10.1007/978-3-319-78446-5_2. \n\n' Salvatore Di Lauro; Maria Isabel Lopez Galvez. Quistes vítreos en una mujer joven. Problemas diagnósticos en patología retinocoroidea. Sociedad Española de Retina-Vitreo. 2018.\n\n' Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor Jimeno. iOCT in PVR management. OCT Applications in Opthalmology. pp. 1 - 8. INTECH, 2018. DOI: 10.5772/intechopen.78774.\n\n' Rosa Coco Martin; Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor. amponadores, manipuladores y tinciones en la cirugía del traumatismo ocular.Trauma Ocular. Ponencia de la SEO 2018..\n\n' LOPEZ GALVEZ; DI LAURO; CRESPO. OCT angiografia y complicaciones retinianas de la diabetes. PONENCIA SEO 2021, CAPITULO 20. (España): 2021.\n\n' Múltiples desprendimientos neurosensoriales bilaterales en paciente joven. Enfermedades Degenerativas De Retina Y Coroides. SERV 04/2016. \n' González-Buendía L; Di Lauro S; Pastor-Idoate S; Pastor Jimeno JC. Vitreorretinopatía proliferante (VRP) e inflamación: LA INFLAMACIÓN in «INMUNOMODULADORES Y ANTIINFLAMATORIOS: MÁS ALLÁ DE LOS CORTICOIDES. RELACION DE PONENCIAS DE LA SOCIEDAD ESPAÑOLA DE OFTALMOLOGIA. 10/2014.",institutionString:null,institution:null},{id:"265335",title:"Mr.",name:"Stefan",middleName:"Radnev",surname:"Stefanov",slug:"stefan-stefanov",fullName:"Stefan Stefanov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/265335/images/7562_n.jpg",biography:null,institutionString:null,institution:null},{id:"318905",title:"Prof.",name:"Elvis",middleName:"Kwason",surname:"Tiburu",slug:"elvis-tiburu",fullName:"Elvis Tiburu",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Ghana",country:{name:"Ghana"}}},{id:"336193",title:"Dr.",name:"Abdullah",middleName:null,surname:"Alamoudi",slug:"abdullah-alamoudi",fullName:"Abdullah Alamoudi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Majmaah University",country:{name:"Saudi Arabia"}}},{id:"318657",title:"MSc.",name:"Isabell",middleName:null,surname:"Steuding",slug:"isabell-steuding",fullName:"Isabell Steuding",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Harz University of Applied Sciences",country:{name:"Germany"}}},{id:"318656",title:"BSc.",name:"Peter",middleName:null,surname:"Kußmann",slug:"peter-kussmann",fullName:"Peter Kußmann",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Harz University of Applied Sciences",country:{name:"Germany"}}},{id:"338222",title:"Mrs.",name:"María José",middleName:null,surname:"Lucía Mudas",slug:"maria-jose-lucia-mudas",fullName:"María José Lucía Mudas",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Carlos III University of Madrid",country:{name:"Spain"}}},{id:"147824",title:"Mr.",name:"Pablo",middleName:null,surname:"Revuelta Sanz",slug:"pablo-revuelta-sanz",fullName:"Pablo Revuelta Sanz",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Carlos III University of Madrid",country:{name:"Spain"}}}]}},subseries:{item:{id:"39",type:"subseries",title:"Environmental Resilience and Management",keywords:"Anthropic effects, Overexploitation, Biodiversity loss, Degradation, Inadequate Management, SDGs adequate practices",scope:"\r\n\tThe environment is subject to severe anthropic effects. Among them are those associated with pollution, resource extraction and overexploitation, loss of biodiversity, soil degradation, disorderly land occupation and planning, and many others. These anthropic effects could potentially be caused by any inadequate management of the environment. However, ecosystems have a resilience that makes them react to disturbances which mitigate the negative effects. It is critical to understand how ecosystems, natural and anthropized, including urban environments, respond to actions that have a negative influence and how they are managed. It is also important to establish when the limits marked by the resilience and the breaking point are achieved and when no return is possible. The main focus for the chapters is to cover the subjects such as understanding how the environment resilience works, the mechanisms involved, and how to manage them in order to improve our interactions with the environment and promote the use of adequate management practices such as those outlined in the United Nations’ Sustainable Development Goals.
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His work is reflected in more than 230 communications presented in national and international conferences and congresses, 29 invited lectures from universities, associations and government agencies. Prof. Navarro-Pedreño is also a director of the Ph.D. Program Environment and Sustainability (2012-present) and a member of several societies among which are the Spanish Society of Soil Science, International Union of Soil Sciences, European Society for Soil Conservation, DessertNet and the Spanish Royal Society of Chemistry.",institutionString:"Miguel Hernández University of Elche, Spain",institution:null},editorTwo:null,editorThree:null,series:{id:"25",title:"Environmental Sciences",doi:"10.5772/intechopen.100362",issn:"2754-6713"},editorialBoard:[{id:"177015",title:"Prof.",name:"Elke Jurandy",middleName:null,surname:"Bran Nogueira Cardoso",slug:"elke-jurandy-bran-nogueira-cardoso",fullName:"Elke Jurandy Bran Nogueira Cardoso",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRGxzQAG/Profile_Picture_2022-03-25T08:32:33.jpg",institutionString:"Universidade de São Paulo, 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