",isbn:"978-1-83969-070-9",printIsbn:"978-1-83969-069-3",pdfIsbn:"978-1-83969-071-6",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,hash:"6504dee75dbbfd7792308293a8f1a27f",bookSignature:"Prof. Moulay Tahar Lamchich",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11520.jpg",keywords:"Optimal Method, Intelligent Technique, Torque Control, Speed Control, Electrical Machine, Hybrid Vehicle, Renewable Energy System, Embedded System, Electrical Vehicle, Electrical Generator, Machine's Noise, Special Machine",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"April 19th 2022",dateEndSecondStepPublish:"May 17th 2022",dateEndThirdStepPublish:"July 16th 2022",dateEndFourthStepPublish:"October 4th 2022",dateEndFifthStepPublish:"December 3rd 2022",remainingDaysToSecondStep:"5 days",secondStepPassed:!0,currentStepOfPublishingProcess:3,editedByType:null,kuFlag:!1,biosketch:"Dr. Moulay Tahar Lamchich is a pioneering researcher in the management, supervision, and control of multi-source energy conversion systems and electrical machines. He completed his thesis in electromechanics in September 1991 and received his Ph.D. in July 2001. Dr. Lamchich is currently a Professor at the Faculty of Sciences Semlalia at Marrakech (Morocco). He has published over fifty technical papers in reviews and international conferences. His main activity is based on short-circuit mechanical effects.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"21932",title:"Prof.",name:"Moulay Tahar",middleName:null,surname:"Lamchich",slug:"moulay-tahar-lamchich",fullName:"Moulay Tahar Lamchich",profilePictureURL:"https://mts.intechopen.com/storage/users/21932/images/system/21932.png",biography:"Moulay Tahar Lamchich is a Professor at the Faculty of Sciences Semlalia, Cadi Ayyad University at Marrakech (Morocco). He completed his thesis in electromechanics in September 1991 and received his Ph.D. in July 2001. His main activity is based on short-circuit mechanical effects in substation structures, control of different types of machine drives, static converters, active power filters. For more than tweenty years, his research interests have included renewable energies, particularly the control and supervision of hybrid and multiple source systems for decentralized energy production, and intelligent management of energy. He has published more than fifty technical papers in reviews and international conferences. With IntechOpen, he has published two chapters and was editor of the books 'Torque Control” and 'Harmonic Analysis”. 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1. Introduction
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With the progress of tissue engineering technology in the last decade, many kinds of engineered cardiac tissues (ECTs) have been developed and reported. These tissues possess striated myofibers which recapitulate unique contractile function of heart tissues. Takahashi, Yamanaka, and colleagues developed iPSCs from mice in 2006 and from human next year [1, 2]. Human iPS cells (hiPSCs) have the potential to differentiate into cardiomyocytes and other cardiac lineage cells. Recently, the efficiency of cardiac differentiation has rapidly improved, which makes it possible to robustly induce cardiac lineage cells [3, 4, 5, 6]. By using cardiac cells derived from hiPSCs as a cell source for ECT generation, the potential of ECTs has expanded. The present chapter overviews the current status of ECT technology and its possible application.
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2. Methods for generating engineered cardiac tissues
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2.1. Cell sheet technology
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Okano, Shimizu and colleagues have developed a culture surface grafted with temperature-responsive polymer, poly(N-isopropyl acrylamide) (PIPAAm) [7]. This system enables confluent cells to detach themselves from the surface while maintaining a sheet structure simply by reducing the culture temperature. The cell sheets are fabricated without the use of exogenous matrices. It has endogenous matrix layer at the bottom side, and it secures biological attachment to the recipient heart surface within 30 min [8]. This scaffold-free tissue is a thin sheet, and three-dimensional thicker structure can be obtained by stacking several sheets. However, stacking more than three layers (approximately 80 μm thickness) triggers cell death at the center due to hypoxia [9]. At our lab, we overcame this limit by stacking cell sheets with gelatin hydrogel microspheres (GHM) [10]. Five-layered cell sheets with GHM displayed better cell viability in vitro compared with the control cell sheet without GHM. Furthermore, cell sheet modification with GHM improved the retention of grafted cell sheets on the rat heart epicardial surface after myocardial infarction. We succeeded in generating over 1 mm thick constructs from 15 sheets using this technology.
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2.2. Biomaterials
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Cardiomyocytes and other cells are embedded in biomaterials, such as collagen I, matrigel, and/or fibrin in a casting mold. Exogenous gel matrix promotes self-assembly of cells leading to form a tissue structure. The first successful cardiac tissue fabrication by this method was reported in the year 1997 [11]. Fixed anchors in these molds generate static strain, which enhances the cell alignment and contractile function. The geometry of mold controls the final tissue architecture, and a variety of tissue shapes have been formulated, including linear [12, 13, 14, 15, 16], circular [17], and mesh structures (Figure 1) [18, 19, 20]. By applying engineering manufacturing methods, it may be possible to automate the process of generating small-sized ECTs, leading to the development of high throughput in vitro analysis systems [21, 22]. In fact, recently, 3D bio-printing technology has been applied and provided the possibility of creating more complicated structures reproducibly by printing both scaffold matrix and living cells [23].
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Figure 1.
Generation of a mesh ECT by biomaterial-based technique. (a) Schematic diagram for a mesh ECT generation. Cardiomyocytes (CM), endothelial cells (EC), and mural cells (MC) are induced from human iPS cells (h-iPSCs) using two different protocols. Cells and collagen-based matrix were combined and poured into custom polydimethylsiloxane (PDMS) molds at day 0 and cultured for 14 days. (b) Representative image of a PDMS mold (left) and a mesh ECT (right). Scale bar: 10 mm. (Reproduced from Ref. [20] with permission).
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2.3. Prefabricated matrix
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Biomaterials provide a ‘soft’ environment for the cells to grow in. On the other hand, synthetic microporous (‘spongy’) scaffolds made from alginate, collagen, and gelatin or other stiffer materials, such as polystyrene, PLLA (Poly-L-Lactide Acid), PLGA (Poly(lactic-co-glycolic acid)) and PCL (Polycaprolactone), have also been tested [24, 25]. The advantage of this method is that these rigid scaffolds contribute to engineering any desired structure and size with mechanical stability. However, the maturation of various mesodermal cells is matrix stiffness dependent, and therefore both the biomaterial gel and the supporting mold may impact cell maturation and survival [26].
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2.4. Decellularized tissue
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Deccllurization of a whole heart is achieved by the treatment with sodium dodecyl sulfate (SDS) and Triton X-100 under Langendorf perfusion [27]. The decellularized tissue maintains most of the tissue contents and function of the extracellular matrix. Hence, decellularized tissue provides a native scaffold which can support repopulation by mesoderm lineage cells. These decellularized tissues may be advantageous in the generation of in vitro cardiac tissues [28, 29].
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3. Maturation of the tissue
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3.1. Cellular contents
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A heart tissue is composed of multiple cell types including cardiomyocytes, fibroblasts, endothelial cells, and smooth muscle cells. In human hearts, cardiomyocytes account for 25-50% of total cells, occupying around 70% of the whole volume [30]. Many reports have demonstrated that non-myocytes support the maturation of cardiomyocytes and play a significant role in both myocardial structure and function [13, 16, 19].
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We induced cardiomyocytes (CM), endothelial cells (EC), and vascular mural cells (MC) from hiPSCs, and generated ECTs from several formulations of cardiomyocytes and non-myocytes, such as CM+EC, CM+MC, and CM+EC+MC [16]. According to in vitro force measurement, CM+EC+MC ECTs showed most advanced electrophysiological properties. Furthermore, histological analysis revealed CM+EC+MC possessed more unidirectionally aligned myofiber with mature sarcomeric structures (Figure 2).
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Figure 2.
Electromechanical properties and structural maturation of hiPSC-ECTs. (a) Schematic diagrams for generationg 3 types of ECTs containing cardiomyocytes (CM), endothelial cells (EC), and/or mural cells (MC) (upper) and the proportions of each cell type (lower) [n = 8 (CM+ EC), 7 (CM+ MC), and 12 (CM+ EC+ MC). (b–d) Results of contractile force measurements [n = 8 (CM+ EC), 7 (CM+ MC), and 12 (CM+ EC+ MC)]. (b) Maximum capture rate (left), relaxation time (center) and excitation threshold voltage (right) (c) Relationship between active force and pacing frequency (2Hz to 3.5Hz). (d) Young’s modulus of ECTs. NS, not significant; *P < 0.05,**P < 0.01, ***P < 0.001. (e) Representative alignment analysis using cTnT-stained images after 2-dimensional (2D) and 3-dimensional (3D) culture for 3 types of ECTs (left). Calculated concentration parameter (κ ) (right) [n =3 (2D) and 5 (each 3D)]. Larger values of κ represent greater alignment to a single direction. cTnT, cardiac troponin T; Deg, degree. (f) Representative transmission electron microscopic images for each type of ECT cultured for 4 weeks. Arrows indicate myofibers. N, nucleus; Mt, mitochondria; I, I-band; A, A-band; Z, Z-line. (Reproduced from Ref. [16] with permission).
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The mechanism for the improvement of tissue maturation as the result of a more complex lineage mixture is still unknown. Evidence is emerging that cardiomyocytes and fibroblasts are electrically coupled, which may modulate electrophysiologic function [31]. Direct interaction of different cell types or paracrine effects can be considered. It is reported that extracellular matrix derived from cardiac fibroblast supported the proliferation in vitro and indicated the usefulness of the coculture [32].
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3.2. Effects of extended culture duration on CM and ECT maturation and function
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Cardiomyocytes derived from pluripotent stem cells mature early in culture but are arrested at the late embryonic stage under 2-dimensional (2D) culture condition [33]. Meanwhile, it is widely recognized that cardiomyocytes in a 3-dimensional (3D) cardiac tissue acquire a more mature phenotype than those in 2D culture [25, 34].
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In our study, we prolonged culture duration of mesh ECTs from 14 to 28days [20]. Long-cultured constructs showed the tendency to augment the active contractile force along with the increase of beating frequency from 1.5Hz to 2.5Hz and maintained greater force compared to 14-day constructs. The shift from a negative to a neutral force-frequency relationship in 28-day constructs represents sustained functional maturation as well as more rapid force generation and relaxation cycle, and the ability to capture higher pacing frequency. Additional culture duration enhanced myofiber alignment along with the expression of several genes related to ion channels and gap junction (Figure 3).
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Figure 3.
Effects of extended culture duration on mesh ECT maturation. (a) Averaged normalized active force-time curves for mesh ECT cultured for either 14 (blue, D14) or 28 (red, D28) (n = 6) days under 2 Hz electrical stimulation. Contraction time (CT) or relaxation time (RT) represents the time of 90% increase or decrease of force respectively. Comparison of (b) contraction time 90% (n = 6; ***P < 0.01), (c) relaxation time 90% (***P < 0.001) at 2 Hz pacing, (d) maximum capture rate (n = 6; ***P < 0.001), (e) force-frequency relationship (n = 6; *P < 0.05 to ***P < 0.001 vs. D14), and (f) cardiomyocyte alignment concentration (κ), [n = 4 (D14) and n = 3 (D28); ***P < 0.001]. (g), (h) Q-PCR analysis (n = 3; *P < 0.05 to ***P < 0.001). cTnT level was lower in D28, and other genes were normalized to the value of cTnT expression. (Reproduced from Ref. [20] with permission).
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3.3. Impact of culture condition on ECT maturation and function
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In order to expand the dimension of ECTs, it is necessary to improve the distribution of oxygen and nutrient throughout tissues. Direct perfusion of culture medium reduces the gradients associated with diffusional mass transport between the construct surfaces and the inner phase and improves the microenvironmental conditions within ECTs. [35, 36, 37]. In addition to the increase of cellularity at the center of ECTs, perfusion system contributes to the maturation of cardiomyocytes and the tissue structure. It is reported that even the simple rocking dynamic culture yields engineered myocardium with near-adult functional output [38]. The system accelerates force generation and conduction velocity probably due to the activation of mTOR signaling.
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For generating ECTs, especially from biomaterial-based technique, materials from other sources, such as collagen derived from rat or matrigel, have been widely used with xeno-serum containing culture medium. Tiburcy and colleagues modified their methods toward clinical application and developed a formulation for generating ECTs by using medical grade bovine collagen and maintaining them under serum-free defined condition [19]. This modification provided a proof-of-concept for a universally applicable technology for the engineering cardiac tissue. In addition, ECTs generated by this condition displayed advanced cardiomyocyte maturation compared to the conventional methods [19].
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3.4. Role of mechanical loading on ECT maturation and function.
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Several in vitro ECT studies revealed the impact of uniaxial mechanical loading on the alignment of cardiomyocytes and functional maturation. The simplest system for that is the two fixed anchors which generate static strain on the tissue between them. Furthermore, cyclic stress conditioning markedly increases cardiomyocyte hypertrophy and proliferation rates versus unconditioned constructs [13]. We demonstrated that ECTs displayed a broad spectrum of altered gene expression in response to cyclic stretch, reflecting a complex regulation of proliferation, differentiation, and architectural alignment of cardiomyocytes and non-cardiomyocytes within ECTs [39].
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Electrical stimulation is considered to be another important cue for further maturation of tissues [40]. Nunes and colleagues subjected their engineered tissues, named biowires, on electrical stimulation at up to 6 Hz [41]. Biowires subjected to electrical stimulation had markedly increased myofibril ultrastructural organization, elevated conduction velocity and improved both electrophysiological and Ca2+ handling properties compared to non-stimulated controls. These changes were in agreement with cardiomyocyte maturation and were dependent on the stimulation frequency.
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Another group created a system which applied combined electromechanical stimulation mimicking isovolumic contraction and confirmed the improvement of functional properties over electrical or mechanical stimulation alone. In the report, the timing of the combined stimulation greatly affected the electrophysiological properties of ECTs [42].
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4. Applications of ECTs
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4.1. Drug screening
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Cardiotoxicity is one of the main causes of drug withdrawal from the market [43, 44]. To evaluate the safety and effectiveness of drugs, several kinds of pre-clinical studies are performed using non-human models. However, these models occasionally show incorrect results, such as pseudo-negative, due to the difference of electrophysiology in other species [45]. By using hiPSC technology, effects to humans can be examined from the early stage [46]. Moreover, hiPSC-derived ECTs are expected to be more specific and sensitive platforms for drug screening [14].
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We have developed a 3D cardiac tissue model which reproduces Torsade de Pointes (TdP) showing both a typical polymorphic extracellular field potential and meandering spiral wave re-entry upon treatment with IKr channel blockers [47]. It is generated from hiPSC-derived cardiomyocytes and mesenchymal cells using the cell sheet technology. The appearance of TdP-like waveforms was significantly higher in this 3D model compared with 2D monolayer conditions indicating that the multilayered 3D structure is an essential factor for this arrhythmia along with the coexistence of non-cardiomyocytes.
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Many groups have developed various high throughput screening formats, such as strip format [48] and heart-on-chip [21, 49], and confirmed the similarity of hiPSC-derived engineered tissues with native heart tissues [14, 50, 51, 52]. Video optical recording system set up in a usual CO2 incubator is also useful to continuously monitor contractile abilities of tissues [48].
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Cardiomyocytes from hiPSCs are at the premature stage, and even ECTs generated to date remain immature compared to native adult myocardium. Hence, further cues for maturation as described above is necessary to imitate native tissues more precisely [51].
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4.2. Disease modeling
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iPS cells derived from a patient with a known genetic mutation for the disease can provide the disease model, which may offer a useful strategy for understanding the mechanism of the disease and exploring a new treatment modality.
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Cardio-facio-cutaneous syndrome (CFCS) is one of the RASopathies, and cardiac abnormalities are the most common findings among CFCS, including hypertrophic cardiomyopathy (HCM) in approximately 40% of patients. Nearly 75% of patients with CFCS exhibit mutations in BRAF, which encodes a serine/threonine kinase and a direct effector of Ras. Cashman and colleagues created 3D human engineered cardiac tissue model of HCM using human cardiomyocytes yielded by directed differentiation of iPSCs established from a patient with CFCS carrying an activated BRAF mutation [53].
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Chronic catecholamine overstimulation contributes to heart failure progression. Overstimulation of ECTs with norepinephrine provides a simulation of a human heart failure phenotype [19]. Tissues responded to chronic catecholamine toxicity with contractile dysfunction, cardiomyocyte hypertrophy, cardiomyocyte death, and NT-proBNP release, which are classical hallmarks of heart failure. Notably, the pathological phenotype could be partially or fully prevented by β1- or α1-adrenoreceptor blockade, demonstrating the applicability of ECTs in the in vitro simulation of heart failure and its prevention by pharmacological means.
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4.3. Transplantation therapy
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HiPSCs are now one of the most promising cell sources for cardiac regenerative cell therapy [54, 55, 56]. There are major methods of cell delivery, including intracoronary or intramuscular injection of dispersed cells and epicardial transplantation of engineered tissues [57]. It is possible to deliver a large number of differentiated cells with organized architecture by ECT implantation. The grafted tissues survive and support the heart wall, which overcomes the problem of poor retention rate following cell injection [34].
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A variety of studies has revealed the efficacy of ECT implantation for myocardial structural and functional recovery in injured hearts of several animal models [6, 10, 58, 59]. We implanted ECTs in an athymic nude rat myocardial infarction model. ECTs with vascular cells displayed the invasion of vasculature from the host heart to the tissue and their perfusion. Survived ECTs replaced the ventricular wall in the injured area and prevented the scar formation after myocardial infarction and improved cardiac function (Figure 4). ECTs survived during 4-week follow-up period [16, 20]. However, further work is required to identify the underlying mechanism for the functional recovery. Meanwhile, the first transplantation of cardiac progenitor patch derived from human embryonic stem cells in a severe heart failure patient was performed in France, offering an encouraging result [60].
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Figure 4.
Therapeutic effects of hiPSC-mesh ECT implantation in a rat myocardial infarction model. (a) Schematic timeline of surgery. A mesh ECT matured in vitro for 14 days (or sham suture) is implanted in a nude rat (week 0) 1 week after the induction of myocardial infarction by ligating left anterior descending artery (LAD). Echocardiogram (Echo) is performed prior to LAD ligation at week-1 (W-1), prior to implantation at week 0 (W0), then week 2 (W2) and week 4 (W4). (b) Grafted mesh ECT on the heart surface covering infarction site. (c) Representative Masson’s trichrome staining images of sham treated (left) and mesh ECT implanted (right) rat hearts at W4. Scale bar: 2 mm. Red dotted line indicates engrafted area. (d) Comparison of scar area (% of LV area) at W4 (n=5, *P<0.05 Implant versus Sham). (e-g) Results of echocardiogram [n=5 (Implant, red solid line) and 5 (Sham, blue dotted line)]. (e) Left ventricular end diastolic area (LVAd; mm2), (f) ejection fraction, EF (%), and (g) cardiac index, CI (mL/min/kg) (*P<0.05 Implant versus Sham at W4). (Reproduced from Ref. [20] with permission).
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5. Conclusion
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In this chapter, we have reviewed several aspects of current cardiac tissue engineering technologies and presented the possible applications of these tissues for in vitro drug toxicity testing, human disease modeling, and paradigms for myocardial recovery with muscle replacement following injury. This rapidly evolving new field is now incorporating manufacturing process to expand the scalability and reduce the cost of generating these novel engineered in vitro myocardial tissues.
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Conflict of interest
None.
\n',keywords:"iPS cell, engineered cardiac tissue, tissue engineering, drug screening, disease modeling, cardiac regeneration",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/57430.pdf",chapterXML:"https://mts.intechopen.com/source/xml/57430.xml",downloadPdfUrl:"/chapter/pdf-download/57430",previewPdfUrl:"/chapter/pdf-preview/57430",totalDownloads:1155,totalViews:188,totalCrossrefCites:0,totalDimensionsCites:0,totalAltmetricsMentions:0,impactScore:0,impactScorePercentile:13,impactScoreQuartile:1,hasAltmetrics:0,dateSubmitted:"September 5th 2017",dateReviewed:"October 11th 2017",datePrePublished:"December 20th 2017",datePublished:"May 2nd 2018",dateFinished:"November 2nd 2017",readingETA:"0",abstract:"By combining tissue engineering techniques with human-induced pluripotent stem cell (hiPSC) technology, human-derived engineered cardiac tissues (ECTs) have been developed using several cell lineage compositions and 3-dimensional geometries. Although hiPSC ECTs are relatively immature compared with native adult heart tissues, they have promising potential as a platform technology for drug-screening and disease modeling, and as grafts for hiPSC-based regenerative heart therapy. This chapter provides the focused overview of the current status of cardiac tissue engineering technology and its possible application.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/57430",risUrl:"/chapter/ris/57430",book:{id:"5907",slug:"stem-cells-in-clinical-practice-and-tissue-engineering"},signatures:"Takeichiro Nakane, Hidetoshi Masumoto and Bradley B. Keller",authors:[{id:"158126",title:"Prof.",name:"Hidetoshi",middleName:null,surname:"Masumoto",fullName:"Hidetoshi Masumoto",slug:"hidetoshi-masumoto",email:"masumoto@kuhp.kyoto-u.ac.jp",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Kyoto University",institutionURL:null,country:{name:"Japan"}}},{id:"221131",title:"M.D.",name:"Takeichiro",middleName:null,surname:"Nakane",fullName:"Takeichiro Nakane",slug:"takeichiro-nakane",email:"nakanet@kuhp.kyoto-u.ac.jp",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Kyoto University",institutionURL:null,country:{name:"Japan"}}},{id:"221144",title:"Prof.",name:"Bradley",middleName:null,surname:"Keller",fullName:"Bradley Keller",slug:"bradley-keller",email:"Brad.Keller@louisville.edu",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"University of Louisville",institutionURL:null,country:{name:"United States of America"}}}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Methods for generating engineered cardiac tissues",level:"1"},{id:"sec_2_2",title:"2.1. Cell sheet technology",level:"2"},{id:"sec_3_2",title:"2.2. Biomaterials",level:"2"},{id:"sec_4_2",title:"2.3. Prefabricated matrix",level:"2"},{id:"sec_5_2",title:"2.4. Decellularized tissue",level:"2"},{id:"sec_7",title:"3. Maturation of the tissue",level:"1"},{id:"sec_7_2",title:"3.1. Cellular contents",level:"2"},{id:"sec_8_2",title:"3.2. Effects of extended culture duration on CM and ECT maturation and function",level:"2"},{id:"sec_9_2",title:"3.3. Impact of culture condition on ECT maturation and function",level:"2"},{id:"sec_10_2",title:"3.4. Role of mechanical loading on ECT maturation and function.",level:"2"},{id:"sec_12",title:"4. Applications of ECTs",level:"1"},{id:"sec_12_2",title:"4.1. Drug screening",level:"2"},{id:"sec_13_2",title:"4.2. Disease modeling",level:"2"},{id:"sec_14_2",title:"4.3. Transplantation therapy",level:"2"},{id:"sec_16",title:"5. Conclusion",level:"1"},{id:"sec_20",title:"Conflict of interest",level:"1"}],chapterReferences:[{id:"B1",body:'Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006;126:663-676'},{id:"B2",body:'Takahashi K, Tanabe K, Ohnuki M, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 2007;131:861-872'},{id:"B3",body:'Laflamme MA, Chen KY, Naumova AV, et al. Cardiomyocytes derived from human embryonic stem cells in pro-survival factors enhance function of infarcted rat hearts. Nature Biotechnology. 2007;25:1015-1024'},{id:"B4",body:'Kattman SJ, Witty AD, Gagliardi M, et al. Stage-specific optimization of activin/nodal and BMP signaling promotes cardiac differentiation of mouse and human pluripotent stem cell lines. 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I-Wire Heart-on-a-Chip II: Biomechanical analysis of contractile, three-dimensional cardiomyocyte tissue constructs. Acta Bio-materialia. 2017;48:79-87'},{id:"B23",body:'Gaetani R, Feyen DAM, Verhage V, et al. Epicardial application of cardiac progenitor cells in a 3D-printed gelatin/hyaluronic acid patch preserves cardiac function after myocardial infarction. Biomaterials. 2015;61:339-348'},{id:"B24",body:'Asthana A, Kisaalita WS. Biophysical microenvironment and 3D culture physiological relevance. Drug Discovery Today. 2013;18:533-540'},{id:"B25",body:'Hirt MN, Hansen A, Eschenhagen T. Cardiac tissue engineering: State of the art. Circulation Research. 2014;114:354-367'},{id:"B26",body:'Young JL, Engler AJ. Hydrogles with time-dependent material properties enhance cardiomyocyte differentiation in-vitro. Biomaterials. 2011;32:1002-1009'},{id:"B27",body:'Ott HC, Matthiesen TS, Goh S-K, et al. Perfusion-decellularized matrix: using nature’s platform to engineer a bioartificial heart. Nature Medicine. 2008;14:213-221'},{id:"B28",body:'Guyette JP, Charest J, Mills RW, et al. Bioengineering human myocardium on native extracellular matrix. Circulation Research. 2015 CIRCRESAHA.115.306874'},{id:"B29",body:'Blazeski A, Kostecki GM, Tung L. Engineered heart slices for electrophysiological and contractile studies. Biomaterials. 2015;55:119-128'},{id:"B30",body:'Jugdutt BI. Ventricular remodeling after infarction and the extracellular collagen matrix: When is enough enough? Circulation. 2003;108:1395-1403'},{id:"B31",body:'Quinn TA, Camelliti P, Rog-Zielinska EA, et al. Electrotonic coupling of excitable and nonexcitable cells in the heart revealed by optogenetics. Proceedings of the National Academy of Sciences. 2016;113:14852-14857'},{id:"B32",body:'Zeng Q, Guo Y, Liu L, et al. Cardiac fibroblast-derived extracellular matrix produced in vitro stimulates growth and metabolism of cultured ventricular cells. 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Dynamic culture yields engineered myocardium with near-adult functional output. Biomaterials. 2016;111:66-79'},{id:"B39",body:'Ye F, Yuan F, Li X, et al. Gene expression profiles in engineered cardiac tissues respond to mechanical loading and inhibition of tyrosine kinases. Physiological Reports. 2013;1:e00078'},{id:"B40",body:'Korolj A, Wang EY, Civitarese RA, et al. Biophysical stimulation for in vitro engineering of functional cardiac tissues. Clinical Science. 2017;131http://www.clinsci.org/content/131/13/1393 [Accessed 5 September 2017]'},{id:"B41",body:'Nunes SS, Miklas JW, Liu J, et al. Biowire: A platform for maturation of human pluripotent stem cell-derived cardiomyocytes. Nature Methods. 2013;10:781-787'},{id:"B42",body:'Morgan KY, Black LD. Mimicking isovolumic contraction with combined electromechanical stimulation improves the development of engineered cardiac constructs. Tissue Engineering. Part A. 2014;20:1654-1667'},{id:"B43",body:'Ferri N, Siegl P, Corsini A, et al. Drug attrition during pre-clinical and clinical development: Understanding and managing drug-induced cardiotoxicity. Pharmacology & Therapeutics. 2013;138:470-484'},{id:"B44",body:'Li X, Zhang R, Zhao B, et al. Cardiotoxicity screening: A review of rapid-throughput in vitro approaches. Archives of Toxicology. 2016;90:1803-1816'},{id:"B45",body:'Gintant G. An evaluation of hERG current assay performance: Translating preclinical safety studies to clinical QT prolongation. Pharmacology & Therapeutics. 2011;129:109-119'},{id:"B46",body:'Navarrete EG, Liang P, Lan F, et al. Screening drug-induced arrhythmia events using human induced pluripotent stem cell-derived cardiomyocytes and low-impedance microelectrode arrays. Circulation. 2013;128:S3-13. DOI: 10.1161/CIRCULATIONAHA.112.000570'},{id:"B47",body:'Kawatou M, Masumoto H, Fukushima H, et al. Modelling Torsade de Pointes arrhythmias in vitro in 3D human iPS cell-engineered heart tissue. Nature Communications. 2017;8:1078'},{id:"B48",body:'Hansen A, Eder A, Bönstrup M, et al. Development of a drug screening platform based on engineered heart tissue. Circulation Research. 2010;107:35-44'},{id:"B49",body:'Grosberg A, Alford PW, McCain ML, et al. Ensembles of engineered cardiac tissues for physiological and pharmacological study: Heart on a chip. Lab on a Chip. 2011;11:4165-4173'},{id:"B50",body:'Tzatzalos E, Abilez OJ, Shukla P, et al. Engineered heart tissues and induced pluripotent stem cells: Macro- and microstructures for disease modeling, drug screening, and translational studies. Advanced Drug Delivery Reviews. 2015:1-11'},{id:"B51",body:'Feric NT, Radisic M. Towards adult-like human engineered cardiac tissue: Maturing human pluripotent stem cell-derived cardiomyocytes in human engineered cardiac tissues. Advanced drug delivery reviews. 2016;96:110-134. DOI: 10.1016/j.addr.2015.04.019'},{id:"B52",body:'Mannhardt I, Breckwoldt K, Letuffe-Brenière D, et al. Human engineered heart tissue: Analysis of contractile force. Stem Cell Reports. 2016;7:29-42'},{id:"B53",body:'Cashman TJ, Josowitz R, Johnson BV, et al. Human engineered cardiac tissues created using induced pluripotent stem cells reveal functional characteristics of BRAF-mediated hypertrophic cardiomyopathy. PLoS One. 2016;11:1-17'},{id:"B54",body:'Yamashita JK. ES and iPS cell research for cardiovascular regeneration. Experimental Cell Research. 2010;316:2555-2559'},{id:"B55",body:'Masumoto H, Sakata R. Cardiovascular surgery for realization of regenerative medicine. General Thoracic and Cardiovascular Surgery. 2012;60:744-755'},{id:"B56",body:'Masumoto H, Yamashita JK. Pluripotent Stem Cells for Cardiac Cell Therapy: The Application of Cell Sheet Technology, Pluripotent Stem Cells, Dr. Deepa Bhartiya (Ed.), InTech; 2013. DOI: 10.5772/56326. Available from: https://www.intechopen.com/books/pluripotent-stem-cells/pluripotent-stem-cells-for-cardiac-cell-therapy-the-application-of-cell-sheet-technology'},{id:"B57",body:'Lalit PA, Hei DJ, Raval AN, et al. Induced pluripotent stem cells for post-myocardial infarction repair: Remarkable opportunities and challenges. Circulation Research. 2014;114:1328-1345'},{id:"B58",body:'Kawamura M, Miyagawa S, Miki K, et al. Feasibility, safety, and therapeutic efficacy of human induced pluripotent stem cell-derived cardiomyocyte sheets in a porcine ischemic cardiomyopathy model. Circulation. 2012;126:29-37'},{id:"B59",body:'Weinberger F, Breckwoldt K, Pecha S, et al. Cardiac repair in guinea pigs with human engineered heart tissue from induced pluripotent stem cells. Science Translational Medicine. 2016;8:363ra148-363ra148'},{id:"B60",body:'Menasché P, Vanneaux V, Hagège A, et al. Human embryonic stem cell-derived cardiac progenitors for severe heart failure treatment: First clinical case report: Figure 1. European Heart Journal. 2015;36:2011-2017'}],footnotes:[],contributors:[{corresp:null,contributorFullName:"Takeichiro Nakane",address:null,affiliation:'
Department of Cardiovascular Surgery, Kyoto University Graduate School of Medicine, Japan
Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application (CiRA), Kyoto University, Japan
Kosair Charities Pediatric Heart Research Program, Cardiovascular Innovation Institute, University of Louisville, The United States of America
Chiropractic Biophysics® (CBP®) technique is a full-spine and posture correcting method that incorporates engineering and mathematical principles into a unique approach in the treatment of spine disorders [1, 2, 3, 4, 5]. CBP technique is best described as a ‘structural’ rehabilitation approach as opposed to ‘functional’ rehabilitation that typically encompasses physiotherapeutic modalities, stretching and exercises to regain function. The goal in structural rehabilitation is to restore the spine alignment and posture to as near normal as possible.
CBP operates on three main premises: 1. There is a normal/ideal static spinal configuration; 2. Abnormal alterations of the spine/posture result in abnormal function disrupting homeostatic balance; 3. Altered static spine/postural alignment results in abnormal dynamics [1]. The contemporary spine literature supports all three of these premises (See Section 4). CBP technique has published research on many facets of the technique including defining what normal/ideal spine alignment is, how to measure spine alignment parameters with reliable and repeatable methods, how to correct/re-align spinal displacements, and evidence proving correcting spine and postural displacements correlates with improvements in pain, disability and quality of life (QOL) measures (These studies are detailed later).
Herein, an overview is given of the scientific approach to treating spine disorders (i.e. subluxation) by the unique approach of CBP technique. A review will be given of the historical beginnings of CBP, rotations and translations of posture, the Harrison normal spinal model, radiographic analysis, posture and spinal coupling, the CBP protocol, clinical evidence of efficacy as well as the safety of the use of X-rays (The term ‘X-rays’ imply the use of plain radiographs throughout this chapter).
2. Historical beginnings
Donald D. Harrison, who had a Master’s degree in Mechanical Engineering and a Doctorate degree in Applied Mathematics developed a devote urgency to bring contemporary science to chiropractic. In the late 1970s, Harrison was the main instructor for the chiropractic technique named ‘Pettibon.’ Dissatisfied with the failure to produce spinal correction, he often incorporated his own methods in certain cases to better attain spine and posture improvements. It was in the treatment of one particular case (circa 1980) where he discovered that the body must be treated using the principles of mathematics; the term ‘mirror image®’ adjusting he later coined to describe these new approaches [1].
A 1974 paper by Panjabi et al. describes a Cartesian coordinate system for use in the description and study of joint biomechanics (Figure 1) [6]. Harrison was the first to apply this system of analysis to upright human posture (Figures 2 and 3). Harrison began discovering the rotations and translations of human posture in 1980. During the early 1980s, the analysis system evolved to incorporate a full spine analysis of the head, rib cage and pelvis in three-dimensions. The technique methods continued to evolve with intellectual contributions from early practitioners of CBP including among others, Drs. DeGeorge, Gambale, Pope and Deed Harrison (founder’s son).
Figure 1.
A vertebra described in terms of rotations about and translations along the x, y, and z-axes on a cartesian coordinate system as proposed by Panjabi (courtesy CBP seminars).
Figure 2.
If the head, thoracic cage, and pelvis are considered rigid bodies, then the possible rotations in three-dimensions are illustrated. Flexion and extension are rotations on the x-axis, axial rotation is about the y-axis, and lateral flexion is rotation about the z-axis (courtesy CBP seminars).
Figure 3.
If the head, thoracic cage, and pelvis are considered rigid bodies, then the possible translations in three-dimensions are illustrated. Lateral translations occur along the x-axis, vertical translations occur along the y-axis, and anterior–posterior translations (protraction-retraction) occurs along the z-axis (courtesy CBP seminars).
One of the unique methods within CBP is the use of ‘extension traction’ to restore the normal cervical or lumbar lordosis (Figures 4 and 5). The first cervical extension traction was with use of an inclined bench that utilized a camlock and pulley system to hyperextend the neck by pulling on the forehead [7]. This is the traction used in the first CBP non-randomized controlled clinical trial (nRCT) that showed that no traction either by no treatment or only cervical manipulation but no traction resulted in no improved alignment, while the traction group (also receiving cervical spinal manipulation) achieved improved lordosis [7].
Further development in cervical traction involved the addition of a posterior-to-anterior (PA) pull through the mid cervical spine with simultaneous extension and distraction of the head while sitting in a chair, so-called ‘Pope’s 2-way’ traction (Figure 4) [8]. A slight modification of this traction involves the use of a chin-forehead strap to add weight directly to the patients head as an extension-compression 2-way traction (Figure 4) [9]. More recently, a cervical extension orthotic (Denneroll) has been shown to be effective at increasing cervical lordosis (Figure 4).
In the mid 1990s, Deed Harrison helped to develop precision vectors for lumbar extension traction (Figure 5), where the first nRCT showing lumbar curve restoration was published in the Archives of Physical Medicine and Rehabilitation in 2002 and concluded: “This new method of lumbar extension traction is the first nonsurgical rehabilitative procedure to show increases in lumbar lordosis in chronic LBP (low back pain) subjects with hypolordosis” [10]. A lumbar extension orthotic device by Denneroll is also used for lumbar extension traction (Figure 5).
CBP technique is one of the most scientifically based posture and spine correcting techniques. There are many randomized controlled trials (RCTs), nRCTs, and well over 100 case reports/series documenting the improvement of diverse spine deformity patterns with concomitant reduction of pain, disability and increased QOL measures [11].
3. Rotations and translations of posture
The main strength of CBP technique is its fundamental underpinnings in engineering and mathematics [1]. It is a general theorem that any object can be decomposed as a rotation, a translation and a deformation [12]. Acknowledging that deformation of living tissues occurs, as in compressing of discs, ligaments, muscles etc., we divert attention to rotations and translations of posture. The main masses of the body, namely the head, thorax and pelvis can be described in relation to the body mass below within a Cartesian coordinate system (Figures 2 and 3). That is, the head is described in relation to the thorax, the thorax in relation to the pelvis, and the pelvis in relation to the feet [1, 13].
Any rotations or translations of the body masses as seen in neutral posture via external observation or internally by X-ray is acknowledged as abnormal. Therefore, no offset of the masses equates to the normal postural alignment (i.e. un-subluxated position). It is important to note that in the assessment of a patient, it is the presence of a rotation or translation in the neutral standing position that is abnormal. When Harrison first applied this method of analysis, the treatment became apparent with the postural diagnosis. That is, for any rotation or translation apparent in neutral standing posture, the opposite position would need to be the treatment as applied during exercises, spinal traction or spinal adjustments, as this is the mathematical solution, “the exact reversing of the patient’s abnormal posture.” [1] In fact, because the soft tissues require a significant magnitude of stress and strains to attempt to correct the spinal position via mirror image methods, Harrison suggested that postural reflections (i.e. ‘mirror image’ adjustments) need to be applied in “twice the negative of the translation distances and rotation angles.” [1].
It should be noted when Harrison finally developed the full spine analysis of rotations and translations of posture in the mid 1980s, he discovered that virtually 50% of all human movements had never been studied (except forward head posture). Thus, the Harrison research group performed several studies to evaluate the normal range of motion for several translation postures including lateral head and thoracic postures as well as anterior and posterior thoracic translation postures (Discussed in Section 6). [2, 3] Clinically, the spinal coupling patterns as discovered to be associated with these common postural positions are of utmost importance in the treatment of these spinal disorders.
Importance of the study of these never previously studied translation postures can be highlighted in the distinction between true scoliosis and ‘pseudo-scoliosis’ (Figure 6) [14] Pseudo-scoliosis is a lateral thoracic translation posture that characteristically features little to no vertebral rotation (simple to correct) [15, 16], whereas, true scoliosis characteristically features significant vertebral rotation (and is typically much more difficult to treat). X-ray screening of the spine is the only way to differentiate true scoliosis from pseudo-scoliosis.
Figure 6.
Posture image and antero-posterior lumbar radiographs depicting a left lateral thoracic translation (side shift). Both patients in the radiographs have a 20 mm left lateral shift of T10 off midline. Left patient has a pure left lateral thoracic translation posture, aka ‘pseudo-scoliosis.’ Right patient has a true left lumbar scoliosis (vertebral rotation). Green line is vertical; red line highlights patient alignment (courtesy CBP seminars).
As mentioned, the absence of rotations and translations of the body masses in standing posture is normal. However, the shape of the spine position, particularly in the sagittal plane has traditionally been debated.
4. The Harrison normal spine model
In the mid 1990s to the mid 2000s, the Harrison research team performed a series of spine modeling studies of the sagittal spinal curves (Figure 7) [17, 18, 19, 20, 21, 22, 23, 24]. To this day, this seminal work serves as the treatment outcome goal (i.e. gold standard) for providing structural rehabilitation by CBP methods (Figure 8). In a series of systematic studies, elliptical shape modeling of the path of the posterior longitudinal ligament was performed as it could be easily compared to the posterior vertebral body margins on X-rays, the same anatomical region used for measuring the sagittal spinal curves (i.e. Harrison posterior tangents (Figure 9) [25, 26, 27, 28]).
Figure 7.
The Harrison normal sagittal spine model as the path of the posterior longitudinal ligament. The cervical, thoracic and lumbar curves are all portions of an elliptical curve having a unique minor-to-major axis ratio. The cervical curve is circular meaning the minor and major axes are equal (courtesy CBP seminars).
Figure 8.
Three patients demonstrating dramatically different spine alignment patterns. Left: excessive lumbar hyperlordosis, L4 anterolisthesis, and excessive anterior sagittal balance in a mid-aged female with disabling low back pain; middle: excessive thoracolumbar kyphosis and early degenerative changes in a mid-aged male; right: excessive thoracic hyperkyphosis in a young male with Scheuermann’s disease. Red line is contiguous with posterior vertebral body margins; green line represents Harrison normal spinal model (courtesy PAO).
Figure 9.
Harrison posterior tangent method involves lines drawn contiguous with the posterior vertebral body margins. Intersegmental as well as regional sagittal curves are easily quantified having a standard error of measurement within about 2° (courtesy CBP seminars).
Computer iterations of spine shape modeling were applied to determine the best-fit geometric spinal shapes by fitting ellipses of varying minor-to-major axis ratios to the digitized data points from the posterior vertebral body corners from X-ray samples for each of the three regions of the spine (cervical [17, 18, 19], thoracic [20, 21], and lumbar spine [22, 23, 24]). As shown in Figure 7, the Harrison normal spinal model features a circular cervical lordosis, an elliptical thoracic curve featuring greater curvature cephalad with a straightened thoraco-lumbar junction and an elliptical lumbar lordosis showing a greater distal lumbar curvature. The spine is assumed to be vertical in the front view.
Although some have attempted to criticize the Harrison normal spinal model, it is important to acknowledge that it has been validated in several ways. Simple analysis of alignment data on samples of normal, asymptomatic populations have been done [17, 18, 19, 20, 21, 22, 23, 24]. Comparison studies between normal samples to symptomatic samples have been performed [17, 29]. Comparisons between normal samples to theoretical ideal models have been done [17, 18, 20, 23]. Statistical differentiation of asymptomatic subjects from symptomatic pain group patients based on alignment data has been performed [19, 24].
In subsequent biomechanical modeling studies, the Harrison group used a validated postural loading model to verify that sagittal spinal balance and the sagittal curves of the spine are critical biomechanical parameters for maintaining postural load balance in healthy subjects [30]. Keller et al. [30] stated “because the pattern of [intervertebral disc] IVD postural stresses mirrored the sagittal curvatures and sagittal displacement of the spine, a failure of the IVD’s hydrostatic mechanism under these sustained loads could occur”. In a similar biomechanical modeling study, Harrison et al. determined that anterior sagittal thoracic posture (anterior thorax translation relative to the pelvis) resulted in significant increases in disc loads and stresses for all vertebral levels below T9 and that the extensor muscle loads required to maintain static equilibrium in upright anterior posture increased almost five times that of normal [31]. In another study Keller et al. [32] determined that “postural forces are responsible for initiation of osteoporotic spinal deformity in elderly subjects”.
The Harrison group also used an elliptical shell model to evaluate the loads and bending moments on the cervical vertebrae in varying cervical spine deformity alignments [33, 34]. They found that in normal lordosis the anterior and posterior vertebral body stresses are nearly uniform and minimal, whereas, in cervical deformity configurations having kyphosis (S-shape kyphosis high or low, total kyphosis), the vertebral body stresses are ‘very large’ and opposite in direction compared to normal lordosis [33]. They concluded “This analysis provides the basis for the formation of osteophytes (Wolff’s Law) on the anterior margins of vertebrae in kyphotic regions of the sagittal cervical curve. This indicates that any kyphosis is an undesirable configuration in the cervical spine” [33]. Anterior head translation and a ‘military’ neck also displayed significantly increased vertebral body stresses that are reverse in direction from C5-T1 and are also proven to be “undesirable configurations in the cervical spine” [34].
5. Radiographic analysis
All radiographs should be taken in the ‘neutral’ standing position with the feet positioned with the heels at hips width apart. This is to avoid any induced postural deviations due to foot position. Also, to ensure a reproducible neutral (i.e. natural) body position, the subject should close their eyes and nod the head back and forth a couple times to where the subject should stop in their preferred position and then open their eyes while maintaining this adopted stance. Any postural misalignments seen in the subject should not be corrected. The lower body mass on the particular view being taken should be centered to the bucky. All X-rays should be taken without footwear.
It should be mentioned that the measurement of different sagittal spinal contours including regional curves or absolute rotation angles (ARAs) (i.e. cervical/lumbar lordosis; thoracic kyphosis) and intersegmental relative rotation angles (RRAs) between adjacent vertebrae can be easily quantified by use of the Harrison posterior tangent (HPT) lines (Figure 9) [25, 26, 27, 28]. The HPT method is preferred for three main reasons, 1. The posterior margins of the vertebral bodies are less affected by osteoarthritic changes as compared to the anterior margins which makes anatomical measurements more reliable and valid; 2. The posterior tangents are contiguous with the slope of the spinal curves and represent the first derivative in an engineering analysis and therefore, their intersection accurately depicts the sagittal configuration; 3. The HPT method has a small standard error of measurement (SEM) of approximately 2° versus higher SEMs with the Cobb (4.5–10°) [25, 26, 27]. This is why the HPT method is superior to other methods of sagittal spine mensuration including the popular Cobb method.
Generally, the global curves are measured as C2-C7, T1-T12, and L1-L5, however since the inflection of the cervical lordosis to thoracic kyphosis occurs at T1, some clinicians prefer to measure the cervical curve from C1-T1, and the thoracic curve from T2-T11 or T3-T10. Anterior sagittal translation distances are simply measured by the horizontal displacement offset between comparison vertebrae such as C2-S1, C2-C7 or T1, T1-T12, etc.
The anterior-to-posterior (AP) or PA X-rays are taken using the same postural positioning. The modified Risser-Ferguson method is employed to measure coronal plane alignment (Figure 10) [28]. On the AP/PA cervicothoracic view an upper angle is created as the angle between the best fit line of the upper cervical segments and intersection with the bite line, and a lower angle is formed between the best fit lines of the upper to lower spine segments [28]. The Rz angle is the angle formed by a vertical axis line (VAL) drawn from T4 and the lower cervicothoracic best fit line. Normal upper angle, lower angle and Rz cervicothoracic angles are 90°, 0° and 0°, respectively. The AP/PA thoracic view may show an angle. The lumbo-pelvic view has an upper angle, the angle between the best fit line of the upper versus lower lumbar segments, and a lower angle, the angle between the best fit line between the lower segments and the horizontal pelvic line [28]. The upper angle and lower angle should be 0° and 90°, respectively. Any regional or full-spine coronal balance offset (i.e. imbalance) can be easily quantified as the horizontal distance between the uppermost segment to the lowermost segment (e.g. C2-T2, T1-T12, T12-S1, C2-S1).
Figure 10.
AP radiographic line drawing by modified Risser-Ferguson method.
6. Posture and spinal coupling
Postural rotations and translations as described by Harrison (Figures 2 and 3) are understood as ‘main motions’ and the corresponding spinal displacements to accommodate the postural positions are termed ‘coupled motions’ [2, 3, 35, 36, 37, 38]. In CBP, a considerable clinical significance is placed on the correlation between the patient’s three-dimensional postural presentation (posture displacement in terms of rotations and translations) and the two-dimensional X-ray coupled motion (spinal rotations and translations) [2, 3, 38].
Of prime importance is the appreciation that unless there is buckling, anomalies or ligament damage, standing neutral postural rotation and translation displacements of the head or thorax cause the vertebral spinal coupling patterns as seen on X-ray. If a patient’s rotations and/or translations of posture ‘match’ the associated spinal coupling pattern as expected (i.e. normal coupling), then it is considered an ‘easy’ or typical case and the intuitive mirror image application of CBP methods would apply. When the patient’s rotations and/or translations of posture do not match the expected spine coupling pattern (i.e. spinal coupling does not match postural displacement), then it is considered an atypical case where the clinician needs to consider alternative (i.e. more complicated) strategies for spine rehabilitation.
A classic demonstration of the ‘matching’ versus ‘mismatching’ of rotations and translations of posture and spine coupling patterns can be illustrated with forward head posture, aka, anterior head translation (AHT) (Figure 11). The natural and expected spine coupling with a forward translated head posture involves lower cervical spine flexion and upper cervical spine extension. As seen in Figure 11, many spine different vertebral coupling patterns are possible including hyperlordosis, hypolordosis, or kyphosis and accordingly, each cervical configuration requires its own unique application of CBP methods for its ideal correction.
Figure 11.
Forward head translation as shown in posture and in three unique lateral cervical radiographs. All three X-ray images have about 25 mm of forward head translation. Left: hyperlordosis; middle: hypolordosis; right: kyphosis. Green line is normal alignment; red line highlights patient alignment.
These cervical spine patterns have been termed harmonics and their presence can only be determined by radiography [2, 39]. Importantly, in CBP treatment approaches, each cervical spine coupling pattern (harmonic) requires its own unique treatment protocol. This is why many manual therapy approaches (e.g. Mackenzie head retractions) are inadequate at correcting posture and spine alignment as these are prescribed universally (i.e. ‘blackbox treatment’) resulting in many patients receiving treatment protocols that are contraindicated. A patient with a hyperlordotic cervical spine should never be prescribed neck extension exercises as this would dynamically hyperextend the cervical joints. A patient with a complete cervical kyphosis should never be prescribed head retraction exercises as this often ‘buckles’ the spine into further kyphosis.
Also, as mentioned and illustrated in Figure 6, ‘pseudo-scoliosis’ or pure lateral translations of the thorax (or head) must be distinguished from true scoliosis by examination of the spinal coupling patterns [14]. If there is minimal or no vertebral rotation then this represents a typical case requiring CBP mirror image postural correction [3]. If there is vertebral rotation then it is considered true scoliosis and a completely different application of CBP methods (i.e. non-commutative properties of finite rotation angles [40, 41]). Case examples of the special application of CBP methods in the treatment of scoliosis is described later.
7. CBP protocol
The CBP patient management protocol [2, 3, 4] involves all typical initial patient examination procedures including the consultation, examination as well as pain, disability and quality of life questionnaires (Figure 12). In addition, CBP treatment consideration requires, without exception, a full-spine posture assessment as well as full-spine AP and lateral standing radiographs. Posture needs to be either qualitatively, but ideally quantitatively assessed as rotations and translations of the head, thorax and pelvis in three-dimensions (Figures 2 and 3). The X-rays need to be digitized and quantified, ideally with the Harrison posterior tangent method for the sagittal images and with the modified Risser-Ferguson on the AP images.
Figure 12.
CBP protocol treatment algorithm.
As seen in Figure 12, if appropriate, a new patient should be treated for their acute pain that is distinct and separate from CBP methods. It is recommended that the acute ‘pain care’ treatment include spinal manipulation, stretching (e.g. proprioceptive neuromuscular facilitation (PNF), Yoga, etc.), heat/ice, soft tissue myofascial therapy (e.g. transverse friction, Nimmo-receptor tonus technique, etc.). Once the patient experiences some initial pain relief (e.g. 6–12 treatments) they can be re-assessed and graduated to CBP structural rehabilitation. The decision to first treat a new patient with ‘acute’ pain care is a clinical decision that is mainly for patients that have either never seen a chiropractor previously or they have not been previously treated for their acute condition. For patients who have received recent previous treatment without relief, CBP rehabilitation care is recommended from the start of treatment [2, 3, 4].
CBP structural rehabilitation is suggested as either three times per week for 12-weeks (36 treatments) or four times per week for 9-weeks (36 treatments), however, the controlled trial data support treatment blocks of 30–40 treatment sessions [7, 8, 9, 10, 15, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55]. An initial patient who has acute or chronic pains and who has not been treated recently or at all for their current spine issue should be treated for an initial 6–12 sessions to provide pain relief. After signs of relief have occurred, a progress exam should be performed and the patient should be transitioned or ‘graduated’ to CBP corrective care.
CBP treatment occurs in ‘blocks of care.’ Numerous CBP controlled clinical trials (RCTs [43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55] and nRCTs [7, 8, 9, 10, 15, 42]) provide evidence for spine altering changes to occur in the range of 30–40 treatment sessions; thus, it is the practitioners’ choice to set their protocol within this range (i.e. treatment blocks). The end of each ‘block’ of CBP care requires a progress exam which includes all of the typical assessment procedures as well as a posture and X-ray assessment. Exam results may either dictate the need for further CBP treatment or the recommendation for ‘supportive’ or maintenance care. An initial block of CBP structural rehabilitation will include any acute care provided in the first 2–4 weeks. It is always recommended that ongoing ‘progress exams’ be performed regularly, at either 4-week or 12 treatment intervals, or as frequently as recommended by each practitioner’s regional regulatory board requirements.
CBP does not specifically support ‘long-term’ care plans. However, based on the data, an adult typically needs 6-months of corrective care (e.g. 72 treatments over 6-months at 3x/week) which is an evidence-based recommendation. Although, any given patient may require a shorted (i.e. 3-month) or longer treatment program based on their initial presenting postural parameters—approximate treatment extrapolations can be made by studying Tables 1–3. There is also support for supportive/maintenance care at a frequency of approximately 2×/month [8, 9, 10].
Study
Journal
Traction method
Traction time
Number of treatments
Change (*)
Change/txt (*)
Theoretical treatment extrapolation
Hypolordotic -20°
No curve 0°
Kyphotic +20°
RCTs
Moustafa
Sci Reports
Denneroll
20m
30
13.9
0.46
32
76
119
Moustafa
Heliyon
Denneroll
15–20m
30
13.4
0.45
34
78
123
Moustafa
J Athl Train
Denneroll
20m
30
14.7
0.49
31
71
112
Moustafa
APMR
Denneroll
20m
30
13.1
0.44
34
80
126
Moustafa
EJPRM
Denneroll
20m
30
13.7
0.46
33
77
120
Moustafa
BFPTCU
Denneroll
20m
36
12.8
0.36
42
98
155
nRCTs
Harrison
JMPT
Pope 2-way
20m
38
17.9
0.47
32
74
117
Harrison
APMR
2way
20m
35
14.2
0.41
37
86
136
Harrison
JMPT
Ext-comp
10m
60
13.2
022
68
159
250
Table 1.
Summary of cervical lordosis improvement by number of treatments, magnitude correction/treatment and the extrapolation to typical sagittal cervical curve subluxation types and the theoretical treatment number required for their correction to -35° C2-7 ARA.
*Note: Correction is estimated to achieve -35 of cervical lordosis.
Study
Journal
Traction method
Traction time
Number of treatments
Change (*)
Change/ txt (*)
Theoretical treatment extrapolation
Hypolordotic -30°
Hypolordotic -15°
No curve 0°
RCTs
Moustafa
JBMR/JMPT
LET
20m
30
6.2
0.21
48
121
194
Moustafa
Clin Rehab
LET
20m
30
8.7
0.29
34
86
138
nRCTs
Harrison
APMR
LET
20m
36
11.3
0.31
32
80
127
Table 2.
Summary of lumbar lordosis improvement by number of treatments, magnitude correction/treatment and the extrapolation to typical sagittal lumbar curve subluxation types and the theoretical treatment number required for their correction to -40° L1-5 ARA.
*Note: Correction is estimated to achieve -40 of lumbar lordosis.
Study
Journal
Traction method
Traction time
Number of treatments
Change (mm)
Change/txt (mm)
Theoretical treatment extrapolation
Mild offset ±10mm
Moderate offset ±20mm
Severe offset ±30mm
nRCTs
Head trans Harrison
JRRD
Lat trans
20 m
37
6.9
0.19
54
107
161
Thorax trans Harrison
Eur Sp J
Lat trans
20 m
36
7.7
0.21
47
94
140
Table 3.
Summary of AP head and thorax lateral translation reduction by number of treatments, magnitude correction/treatment and the extrapolation to larger coronal plane offset subluxations and the theoretical treatment number required for their correction.
Note: Correction is estimated to achieve 0mm of offset.
8. Clinical evidence of efficacy
As mentioned, CBP technique has an abundance of clinical evidence supporting its effectiveness in correcting spine deformity and posture [7, 8, 9, 10, 15, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55]. Recently, systematic reviews have summarized the clinical evidence as reported in the published controlled trials on these methods [56, 57]. We summarize the evidence here in four parts: cervical lordosis, lumbar lordosis, lateral translation (pseudo-scoliosis) postures of the head and thorax, and finally, evolving evidence from case reports/series on other important spine deformities including lumbar spondylolisthesis, cervical spondylolisthesis, thoracic hyperkyphosis, thoraco-lumbar junctional kyphosis, thoracic hypokyphosis (straight back syndrome), anterior sagittal balance, lumbar kyphosis (flat back syndrome), lumbar hyperlordosis, post-surgical cervical spine fusion and scoliosis.
8.1 Cervical lordosis
A recent systematic review found that of the RCTs and nRCTs on CBP extension traction methods, a 12–18° improvement in cervical lordosis can be achieved in 10–15 weeks after 30–36 treatment sessions [57]. Most RCTs have used the cervical Denneroll [43, 44, 45, 46, 47, 49, 50], and the three nRCTs all used different CET methods (Table 1) [7, 8, 9].
Table 1 shows the improvement in degrees per treatment as well as theoretical numbers of treatments for various presenting cervical spine subluxations. On average, there appears to be just less than a half degree improvement per treatment session; obviously, there are patients that will have both more correction and less correction than this. Using this estimation as an initial guideline, evidence-based treatment numbers can be predicted. For example, a patient presenting with a cervical kyphosis of 20° would require over 100 treatments to restore the neck to a curve of 35°.
Figures 13 and 14 show the long-term outcomes in patients receiving cervical extension traction versus comparative groups not receiving the traction. The patients restoring lordosis via CBP traction methods show improved cervical alignment which is maintained at a years’ follow-up (Figure 13) whereas, comparative groups receiving various physiotherapeutic treatments less the extension traction do not experience cervical improvement (Figure 13) and also show that any initial pain relief regresses back towards baseline levels after the cessation of treatment (Figure 14). Patient’s with improved lordosis retain their initial pain relief a year later (Figure 14). This is alarming as it shows patients receiving various physiotherapeutic treatments who do not improve their cervical lordosis (in hypolordotic patients) will have a future regression of symptoms post-treatment and may be misled by ‘apparent treatment efficacy’ [5, 57].
Figure 13.
Data from five RCTs demonstrates patients achieving cervical lordosis improvement (via extension traction) as well as conventional treatments have lordosis improvements that are sustained for 1 year after stopping treatment versus the cervical curve of comparative groups (controls not achieving lordosis improvement) remain unaffected by conventional treatments (weighted averages from five RCTs [44, 45, 47, 49, 50]). * indicates a significant group difference as specified in each of the five trials; brackets represent weighted standard deviation.
Figure 14.
Data from five RCTs demonstrates patients achieving cervical lordosis improvement (via extension traction) as well as conventional treatments have pain reductions that are sustained for 1 year after stopping treatment versus comparative groups (controls not achieving lordosis improvement) who show a regression (increase) of pain intensity towards baseline after stopping treatment (weighted averages from five RCTs [45, 46, 47, 49, 50]). * indicates a significant group difference as specified in each of the five trials; brackets represent weighted standard deviation.
8.2 Lumbar lordosis
A recent systematic review found “Limited but good quality evidence substantiates that the use of extension traction methods in rehabilitation programs definitively increases lumbar hypolordosis” [56]. The authors further stated: “Preliminarily, these studies indicate these methods provide longer-term relief to patients with low back disorders versus conventional rehabilitation approaches tested” [56]. On average, a 7–11° increase in lordosis can be achieved over 10–12 weeks after 30–36 treatment sessions (Table 2).
It must be mentioned that lumbar extension traction is necessary to increase the lumbar lordosis. Importantly, using the data from published trials [10, 53, 54, 55], one can extrapolate approximate treatment duration (Table 2). As seen, a mild hypolordotic lumbar spine of 30° (L1-L5 ARA) may only require 32–48 treatments, whereas, a flat lumbar curve would require 127–194 treatments to achieve a normal 40° lordosis.
The same trend as observed in patients receiving cervical lordosis correction versus comparative groups not receiving lordosis improvement is seen in the trials on the lumbar spine [5, 56]. Lordosis increase in patients receiving lumbar extension traction is achieved and maintained at 6-months follow-up (Figure 15); these patients also retain their initial pain relief whereas, comparative patient groups not receiving lordosis improvement (Figure 15) lose their initial pain relief by 6-months after cessation of treatment (Figure 16). Again, this is alarming and shows how active low back treatment, although offering transient pain relief, will likely regress after treatment if not receiving concurrent lordosis correction in those suffering from hypolordotic-related LBP [5, 56].
Figure 15.
Data from two RCTs demonstrates patients achieving lumbar lordosis improvement (via extension traction) as well as conventional treatments have lordosis improvements that are sustained for 6-months after stopping treatment versus the lumbar curve of comparative groups (controls not achieving lordosis improvement) remain unaffected by conventional treatments (weighted averages from two RCTs [53, 54]). * indicates a significant group difference as specified in each of the two trials; brackets represent weighted standard deviation.
Figure 16.
Data from two RCTs demonstrates patients achieving lumbar lordosis improvement (via extension traction) as well as conventional treatments have pain reductions that are sustained for 6-months after stopping treatment versus comparative groups (controls not achieving lordosis improvement) who show a regression (increase) of pain intensity towards baseline after stopping treatment (weighted averages from two RCTs [53, 54]). * indicates a significant group difference as specified in each of the two trials; brackets represent weighted standard deviation.
8.3 AP head and thorax postures
Coronal plane lateral translations of the head and thorax also referred to as ‘pseudo-scoliosis’ each has an nRCT published [15, 42] and many case reports demonstrating its reduction [16, 58, 59, 60, 61, 62, 63]. As discussed earlier, the differentiation from true scoliosis is that the involved vertebrae have minimal to no rotation, whereas, true scoliosis has substantial vertebral rotation (Figure 6). Also, the spinal coupling pattern of a laterally translated body mass (head or thorax) will demonstrate the lower involved spinal region to laterally flex towards the side of the translation and the upper involved spinal region to laterally flex back towards the vertical [35, 36].
Based on the data, a laterally translated body mass can be reduced about 7–8 mm after about 35 treatments. On average, correction of a laterally translated head or thorax can be corrected at about 0.2 mm per treatment, or about 1 mm per five treatments. Extrapolations of treatment numbers to patient subluxation presentation are shown in Table 3. From the data in each of the nRCTs, an approximate 50% reduction of the initial laterally translated head and thorax postures occurred; therefore, an average patient having an approximate 15 mm translation posture (head or rib cage) requires 6-months of corrective care (approximately 72 treatments). It must also be mentioned that many case reports have demonstrated larger lateral translation postural corrections/reductions with CBP methods in similar time frames [16, 58, 59, 60, 61, 62, 63], thus, these serve as approximate treatment extrapolations.
8.4 Other spine deformities
It is known that the science for manual therapies is lacking [64]. Therefore, lesser forms of evidence must be considered when evaluating various treatment approaches used to treat various spinal conditions by manual therapists [65, 66]; this includes treatment utilizing CBP methods. We now highlight more recent case studies and series showing structural spinal correction for a variety of relatively common disorders.
8.4.1 Lumbar spondylolisthesis
Fedorchuk et al. [67] reported on an 11 mm reduction (13.3–2.4 mm) of an L4 anterolisthesis in a 69-year old suffering from LBP and leg cramping. Pain relief was achieved after 60 treatments over 45 weeks. This was the first documented report of a reduction of a Grade 2 lumbar spondylolisthesis by CBP methods, as well as any other non-surgical method.
Oakley and Harrison reported on the reduction of multiple retrolistheses from L1-L4 ranging from 4.5 to 5.9 mm in a 32-year old male with LBP [68]. These were all reduced to within normal (<4.5 mm) after approximately 36 treatments over 14-weeks. A 13-month follow-up indicated the patient remained well and reported no back pain and the corrections had remained stable.
Fedorchuk et al. [69] reported on the reduction of L1 (−6.6 to −1.7 mm) and L2 (−6.1 to −2.0 mm) retrolistheses and an L5 anterolisthesis (+6.8 to −2.5 mm) in a 63-year old female bodybuilder with severe LBP and osteoarthritis. Thirty treatments were given over 10-weeks which resulted in normalizing all spondylolistheses as well as a dramatic reduction in pain and an ability to leg press 60 more pounds in the gym.
Fedorchuk et al. reported the complete reduction of an L3 retrolisthesis and L4 anterolisthesis after 50 treatments over a 7-month period [70]. The patient was 57-years old with severe LBP and sciatica. The L3 retrolisthesis reduced from −5.3 to −1.7 and the L4 anterolisthesis reduced from +5.4 to +1.0 mm. After treatment the patient was able to return to playing hockey and experienced full resolution of the back pain which had forced him to retire from sport. A 1-year follow-up showed the patient had remained well and maintained the corrections.
8.4.2 Cervical spondylolisthesis
Recently, Fedorchuk et al. present a case series of eight female patients with concomitant cervical hypolordosis, forward head translation and spondylolistheses [71]. All were in motor vehicle collisions, each having at least one, and at most four simultaneous cervical vertebral spondylolistheses ranging in magnitude from >2 mm up to 4.5 mm. All cases experienced a reduction in translational offset of the spondylolistheses, and increase in cervical lordosis and a decrease in forward head translation as well as an increase in spinal canal diameter at the location of the spondylolisthesis after 30 treatment sessions that included cervical extension traction over a duration of 12-weeks. On average, the spondylolistheses reduced by 2.6 mm and there was an average drop in neck disability by 30%.
In another case, Fedorchuk et al. presented a single case of a 52-year old with chronic neck pain [72]. The patient had a C4 anterolisthesis of 2.4 mm which was reduced to 0.7 mm as well as an increase in cervical lordosis and reduction in forward head translation after 30 treatments over 12-weeks. The patient reported a resolution of their neck pain and stiffness.
8.4.3 Thoracic hyperkyphosis
Thoracic hyperkyphosis is a relatively common subluxation pattern in the aging. Although there is one RCT on CBP methods showing reduction of the deformity, it is yet to be formally published [52]. A systematic review of CBP methods used to reduce thoracic hyperkyphosis was published [73] and summarized the outcomes of several case reports and series [74, 75, 76, 77, 78, 79]. In Table 2 of the Oakley and Harrison review an average 12° reduction in thoracic kyphosis occurred after 32 treatments over 14.5 weeks from a total of 17 patients [52]. The improved posture correlated with reduced pain, disability and improved QOL [52]. Figures 17 and 18 show various CBP mirror image spinal exercises and traction, respectively.
Figure 17.
CBP recommended mirror image exercises for patients with thoracic hyper-kyphosis.
Figure 18.
CBP mirror image traction for patients with thoracic hyper-kyphosis.
8.4.4 Thoracolumbar junctional kyphosis
Thoracolumbar kyphosis is the forward angled spine at the junction of the thoracic and lumbar spine and is associated with chronic LBP (CLBP). Gubbels et al. presented a case of the minimization of pain in a 16-year old female after a 22° reduction of thoracolumbar kyphosis, a 48 mm reduction of posterior sagittal balance, an 11° increase in lumbar lordosis and a 10° increase in sacral inclination [80]. Twenty-four in office treatments were given over an 8-week period with daily home traction resulting in a minimization of back pains.
8.4.5 Thoracic hypokyphosis (straight back syndrome)
Thoracic spine hypolordosis is termed straight back syndrome (SBS) and is associated with back pains and exertional dyspnea. Fortner et al. [81] reported on an 18-year old male suffering from back pains and exertional dyspnea. Twenty-four treatments over a 9-week period resulted in a 15° increase in thoracic kyphosis, a decrease in pain and improved exertional dyspnea symptoms. A 4-month follow-up showed the patient remained well.
Betz et al. [82] reported the improvement in a 19-year old male who suffered from exertional dyspnea and back pain. Over 12-weeks a 14° increase in thoracic curve was achieved resulting in relief of exertional dyspnea and pain, as well as increases in both the antero-posterior thoracic diameter and the ratio of antero-posterior to transthoracic diameter, both measures critical to the wellbeing of patients with SBS. A 2.75-year follow-up showed the patient remained well.
Fedorchuk et al. [83] reported on a 13° increased thoracic curve in a 26-year old male with back pains and type 1 diabetes. Treatment over 7-weeks included 36 sessions. Back pains reduced and importantly, there was also improvement in blood glucose immediately following the onset of each visit. An improvement in blood glucose averages, percentage of time of blood glucose in a healthy target range, and glycosylated hemoglobin occurred and the patient was able to reduce their basal insulin need by approximately half after the 7-weeks of care.
Mitchel et al. [84] reported a 10° increase in thoracic curve over 16-weeks in a 33-year old male suffering from exertional dyspnea and back pains. The measured lung capacity improved by 2L, the back pain diminished and the exertional dyspnea resolved. A 7-month follow-up indicated the patient remained well.
8.4.6 Anterior sagittal balance
Anterior sagittal balance (ASB) is the forward displacement of the upper body over the pelvis. Haas et al. reported on the dramatic 110 mm reduction in ASB in an 87-year old female with CLBP and sciatica [85]. Treatment consisted of 24 in office sessions over an 8-week period. The patient achieved a dramatic reduction of symptoms, improvements in flexibility and orthopedic testing.
Anderson et al. [86] reported on a 91 mm reduction in ASB in a 59-year old male patient suffering from a variety of symptoms associated with Parkinson’s disease. Initial treatment involved 38 treatments over 5 months. The patient experienced significant improvements in multiple postural parameters, gait, balance, hand tremors, low back and knee pains and SF-36 values. A 21-month follow-up showed the patient remained essentially well and most of the initial postural improvements were maintained.
8.4.7 Lumbar kyphosis (flat back syndrome)
Flat back syndrome (FBS) is the anterior translation of the upper body and gross loss (or kyphosis) of the lumbar spine and is associated with high pain and disability. In a case series, Harrison and Oakley describe the significant restoration of lumbar lordosis in two patients suffering from debilitating CLBP from flat back syndrome [87]. One patient had a 50° lordosis improvement in 100 treatments over 20 weeks, the other had a 26° lordosis improvement in 70 treatments over 16.5 weeks. In the discussion section of the report, it was calculated that the treatment costs of the patients receiving CBP treatment versus the projected costs for the surgical procedures recommended to the two patients equated to only 1–8%; the authors stated “at first 70 or 100 treatments may be criticized as ‘over-treatment,’ however, considering the overall cost-effectiveness and positive patient outcomes, it certainly is not” [87].
8.4.8 Lumbar hyperlordosis
Although lumbar hypolordosis is the most common lumbar misalignment in those presenting with chronic LBP [10], lumbar hyperlordosis is also seen clinically. CBP methods can be directed at decreasing lumbar lordosis and its typically associated anteriorly rotated pelvis. In a recent case, Oakley et al. [88] presented a case demonstrating the relief of CLBP and hip pains after an 8° reduction in lumbar hyperlordosis, a 5° reduction in pelvic tilt and an accompanying 17 mm reduction of forward sagittal balance. This occurred over a period of 13 months and 73 total treatments.
8.4.9 Post-surgical cervical spine fusion
Post-surgical cervical spine intervertebral fusion is not a common finding in clinical practice however, it is occasionally encountered. Many of these patients continue to suffer years after the intervention. Harrison et al. [89] presented a case showing improvement in sagittal postural parameters which corresponded with improved clinical outcome in a 52-year old male. Over a 6-month period, a 6° increase in cervical lordosis was achieved as well as a 13 mm reduction in anterior head translation (AHT). These improvements were maintained at a 2.5-year follow-up.
Fedorchuk et al. [90] also presented a successful outcome in a 43-year old with a C5-6 intersegmental fusion. After 36 treatments over 3-months, there was a 13° increase in cervical lordosis, a 9 mm decrease in AHT and a 5 mm reduction in lateral head translation.
8.4.10 Scoliosis
Although too large of a topic to address in this chapter, CBP technique has a unique approach in the treatment of scoliosis [3]. CBP methods incorporates the ‘non-commutative property of finite rotation angles under addition’ to ascertain the order of postural movements to be prescribed in the mirror image treatment of this disorder. Harrison and Oakley described reductions in curve magnitude in five lumbar or thoracolumbar scoliosis patients ranging from 5° to 24° after 18–84 treatments [40]. All patients were female and ranged in age from 19 to 45 years.
Haggard et al. reported a 19° reduction in a thoracolumbar curve in a 15-year old female patient after 24 office treatments over 15-weeks. The patient also performed 45 at home spine blocking sessions as prescribed by the attending chiropractor [41]. The patients LBP and headaches were dramatically improved, and the curve was reduced to 8°.
9. Use of X-ray
Use of X-ray for spine analysis is essential for treating spine deformities, including with CBP technique methods. Historically, there has been concerns of carcinogenicity associated with X-ray use. Recently, however, new evidence has come to light showing that anti-X-ray sentiment stemming from the supposed carcinogenicity is based on flawed science [91, 92, 93]. The bottom line is the linear no-threshold (LNT) model used to support radiation risk analysis is not scientific as it is not consistent with current radiobiological data [94, 95, 96, 97, 98].
X-rays and CT scans deliver low-dose radiation doses (<200 mGy), and because of this they cannot cause cancer. This is because low-dose (versus high-dose) radiation exposures stimulate the adaptive repair systems of the body to repair any damage done [99, 100, 101]. Although this topic is important, it is a much larger issue than the scope of this chapter but many recent reviews have found that X-rays (and CT scans) are not harmful [103]. In fact, after a substantial and critical review of higher quality studies on radiation exposure, Schultz et al. concluded: “The evidence suggests that exposure to multiple CT scans and other sources of low-dose radiation with a cumulative dose up to 100 mSv (approximately 10 scans), and possibly as high as 200 mSv (approximately 20 scans), does not increase cancer risk.” Thus, there should be no hesitation or misunderstanding surrounding X-ray risks. Doctors and patients need to become updated on X-ray safety and not succumb to the traditional carcinogenicity misinformation.
10. Conclusion
CBP technique is a well-studied approach to the structural improvement of spinal disorders. Many spinal disorders with associated pain and functional syndromes have either well characterized or evolving evidence for their treatment by the mirror image approach that underpins CBP methods. The correlation of the spine alignment and postural rotations and translations of posture are of critical importance and unique in the CBP approach.
Acknowledgments
We acknowledge the pioneering work of Dr. Donald D. Harrison.
Conflict of interest
D.E.H. teaches spine rehabilitation methods and sells products related to the treatment of spine deformities; P.A.O. is a paid consultant to CBP.
Nomenclature
AHT
anterior head translation
ASB
anterior sagittal balance
AP
anterior-to-posterior
ARA
absolute rotation angle
CBP
Chiropractic BioPhysics®
CLBP
chronic low back pain
HPT
Harrison posterior tangent
IVD
intervertebral disc
LBP
low back pain
LNT
linear no-threshold
nRCT
non-randomized controlled trial
QOL
quality of life
PA
posterior-to-anterior
PNF
proprioceptive neuromuscular facilitation
RCT
randomized controlled trial
RRA
relative rotation angle
SEM
standard error of measurement
SBS
straight back syndrome
\n',keywords:"spine deformity, structural rehabilitation, traction, exercise, chiropractic",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/81876.pdf",chapterXML:"https://mts.intechopen.com/source/xml/81876.xml",downloadPdfUrl:"/chapter/pdf-download/81876",previewPdfUrl:"/chapter/pdf-preview/81876",totalDownloads:11,totalViews:0,totalCrossrefCites:0,dateSubmitted:"October 13th 2021",dateReviewed:"January 16th 2022",datePrePublished:"May 19th 2022",datePublished:null,dateFinished:"May 19th 2022",readingETA:"0",abstract:"Chiropractic Biophysics® (CBP®) technique is a full-spine and posture correcting method that incorporates mathematical principles into a unique approach to treat spinal disorders. It considers that the identification of postural rotations and translations of human postures are first evaluated and compared to the radiographic assessment of the spine alignment. Mirror image® postural positions and movements are utilized including spinal extension positions to improve the spine and posture towards a normal/ideal alignment. Specifically, corrective exercises, corrective traction and chiropractic adjustments are performed encompassing a multimodal rehabilitation program with the goal of improving the posture and spine alignment. CBP Rehabilitation programs are typically performed in-office with supportive at-home measures. Repeat assessment including radiographs are used to quantify and monitor structural improvements. CBP technique is an evidence-based approach to treat spine deformities and is supported by all forms of clinical evidence including systematic literature reviews, randomized controlled trials, non-randomized controlled trials, case reports/series as well as is supported by biomechanical posture-spine coupling validity, radiographic and posture analysis reliability/repeatability and use of a validated biomechanical spinal model as the outcome goal of care. CBP technique is a proven method to improve pain, disability and quality of life in those with structural deformities.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/81876",risUrl:"/chapter/ris/81876",signatures:"Deed E. Harrison and Paul A. Oakley",book:{id:"11042",type:"book",title:"Complementary Therapies",subtitle:null,fullTitle:"Complementary Therapies",slug:null,publishedDate:null,bookSignature:"Prof. Mario Bernardo-Filho, Prof. Redha Taiar, Danúbia Da Cunha De Sá-Caputo and Dr. Adérito Seixas",coverURL:"https://cdn.intechopen.com/books/images_new/11042.jpg",licenceType:"CC BY 3.0",editedByType:null,isbn:"978-1-83969-012-9",printIsbn:"978-1-83969-011-2",pdfIsbn:"978-1-83969-013-6",isAvailableForWebshopOrdering:!0,editors:[{id:"157376",title:"Prof.",name:"Mario",middleName:null,surname:"Bernardo-Filho",slug:"mario-bernardo-filho",fullName:"Mario Bernardo-Filho"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"308067",title:"Dr.",name:"Paul A.",middleName:null,surname:"Oakley",fullName:"Paul A. Oakley",slug:"paul-a.-oakley",email:"docoakley.icc@gmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"308068",title:"Dr.",name:"Deed E.",middleName:null,surname:"Harrison",fullName:"Deed E. Harrison",slug:"deed-e.-harrison",email:"drdeedharrison@gmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Historical beginnings",level:"1"},{id:"sec_3",title:"3. Rotations and translations of posture",level:"1"},{id:"sec_4",title:"4. The Harrison normal spine model",level:"1"},{id:"sec_5",title:"5. Radiographic analysis",level:"1"},{id:"sec_6",title:"6. Posture and spinal coupling",level:"1"},{id:"sec_7",title:"7. CBP protocol",level:"1"},{id:"sec_8",title:"8. Clinical evidence of efficacy",level:"1"},{id:"sec_8_2",title:"8.1 Cervical lordosis",level:"2"},{id:"sec_9_2",title:"8.2 Lumbar lordosis",level:"2"},{id:"sec_10_2",title:"8.3 AP head and thorax postures",level:"2"},{id:"sec_11_2",title:"8.4 Other spine deformities",level:"2"},{id:"sec_11_3",title:"8.4.1 Lumbar spondylolisthesis",level:"3"},{id:"sec_12_3",title:"8.4.2 Cervical spondylolisthesis",level:"3"},{id:"sec_13_3",title:"8.4.3 Thoracic hyperkyphosis",level:"3"},{id:"sec_14_3",title:"8.4.4 Thoracolumbar junctional kyphosis",level:"3"},{id:"sec_15_3",title:"8.4.5 Thoracic hypokyphosis (straight back syndrome)",level:"3"},{id:"sec_16_3",title:"8.4.6 Anterior sagittal balance",level:"3"},{id:"sec_17_3",title:"8.4.7 Lumbar kyphosis (flat back syndrome)",level:"3"},{id:"sec_18_3",title:"8.4.8 Lumbar hyperlordosis",level:"3"},{id:"sec_19_3",title:"8.4.9 Post-surgical cervical spine fusion",level:"3"},{id:"sec_20_3",title:"8.4.10 Scoliosis",level:"3"},{id:"sec_23",title:"9. Use of X-ray",level:"1"},{id:"sec_24",title:"10. Conclusion",level:"1"},{id:"sec_25",title:"Acknowledgments",level:"1"},{id:"sec_28",title:"Conflict of interest",level:"1"},{id:"sec_27",title:"Nomenclature",level:"1"}],chapterReferences:[{id:"B1",body:'Harrison DD, Janik TJ, Harrison GR, Troyanovich S, Harrison DE, Harrison SO. Chiropractic biophysics technique: A linear algebra approach to posture in chiropractic. Journal of Manipulative and Physiological Therapeutics. 1996;19(8):525-535'},{id:"B2",body:'Harrison DE, Harrison DD, Haas JW. Structural Rehabilitation of the Cervical Spine. Evanston, WY: Harrison CBP® Seminars, Inc.; 2002'},{id:"B3",body:'Harrison DE, Betz JW, Harrison DD, et al. CBP Structural Rehabilitation of the Lumbar Spine. Eagle, ID, USA: Harrison Chiropractic Biophysics Seminars; 2007'},{id:"B4",body:'Oakley PA, Harrison DD, Harrison DE, Haas JW. Evidence-based protocol for structural rehabilitation of the spine and posture: Review of clinical biomechanics of posture (CBP) publications. Journal of the Canadian Chiropractic Association. 2005;49(4):270-296'},{id:"B5",body:'Oakley PA, Moustafa IM, Harrison DE. Restoration of Cervical and Lumbar Lordosis: CBP® Methods Overview. In: Bettany-Saltikov J, Kandasamy G, editors. Spinal Deformities in Adolescents, Adults and Older Adults [Internet]. London: IntechOpen; 2019 [cited 2022 Apr 26]. DOI: 10.5772/intechopen.90713'},{id:"B6",body:'Panjabi MM, White AA 3rd, Brand RA Jr. A note on defining body parts configurations. Journal of Biomechanics. 1974;7(4):385-387'},{id:"B7",body:'Harrison DD, Jackson BL, Troyanovich S, Robertson G, de George D, Barker WF. The efficacy of cervical extension-compression traction combined with diversified manipulation and drop table adjustments in the rehabilitation of cervical lordosis: A pilot study. Journal of Manipulative and Physiological Therapeutics. 1994;17(7):454-464'},{id:"B8",body:'Harrison DE, Cailliet R, Harrison DD, Janik TJ, Holland B. A new 3-point bending traction method for restoring cervical lordosis and cervical manipulation: A nonrandomized clinical controlled trial. Archives of Physical Medicine and Rehabilitation. 2002;83(4):447-453'},{id:"B9",body:'Harrison DE, Harrison DD, Betz JJ, Janik TJ, Holland B, Colloca CJ, et al. Increasing the cervical lordosis with chiropractic biophysics seated combined extension-compression and transverse load cervical traction with cervical manipulation: Nonrandomized clinical control trial. Journal of Manipulative and Physiological Therapeutics. 2003;26(3):139-151'},{id:"B10",body:'Harrison DE, Cailliet R, Harrison DD, Janik TJ, Holland B. Changes in sagittal lumbar configuration with a new method of extension traction: Nonrandomized clinical controlled trial. Archives of Physical Medicine and Rehabilitation. 2002;83(11):1585-1591'},{id:"B11",body:'CBP NonProfit. www.cbpnonprofit.com'},{id:"B12",body:'Beer FP, Johnston ER. Vector Mechanics for Engineers: Statics and Dynamics. 4th ed. New York: McGraw-Hill; 1984. p. 95'},{id:"B13",body:'Harrison DD. Abnormal postural permutations calculated as rotations and translations from an ideal normal upright static spine. In: Sweere J, editor. Chiropractic Family Practice. Gaitherburg, MD: Aspen Publishers; 1992'},{id:"B14",body:'Harrison DE, Betz JW, Cailliet R, Colloca CJ, Harrison DD, Haas JW, et al. Radiographic pseudoscoliosis in healthy male subjects following voluntary lateral translation (side glide) of the thoracic spine. Archives of Physical Medicine and Rehabilitation. 2006;87(1):117-122'},{id:"B15",body:'Harrison DE, Cailliet R, Betz JW, Harrison DD, Colloca CJ, Haas JW, et al. A non-randomized clinical control trial of Harrison mirror image methods for correcting trunk list (lateral translations of the thoracic cage) in patients with chronic low back pain. European Spine Journal. 2005;14(2):155-162'},{id:"B16",body:'Henshaw M, Oakley PA, Harrison DE. Correction of pseudoscoliosis (lateral thoracic translation posture) for the treatment of low back pain: A CBP® case report. Journal of Physical Therapy Science. 2018;30(9):1202-1205'},{id:"B17",body:'Harrison DD, Janik TJ, Troyanovich SJ, Holland B. Comparisons of lordotic cervical spine curvatures to a theoretical ideal model of the static sagittal cervical spine. Spine. 1996;21(6):667-675'},{id:"B18",body:'Harrison DD, Janik TJ, Troyanovich SJ, Harrison DE, Colloca CJ. Evaluations of the assumptions used to derive an ideal normal cervical spine model. Journal of Manipulative and Physiological Therapeutics. 1997;20(4):246-256'},{id:"B19",body:'Harrison DD, Harrison DE, Janik TJ, Cailliet R, Haas JW, Ferrantelli J, et al. Modeling of the sagittal cervical spine as a method to discriminate hypolordosis: Results of elliptical and circular modeling in 72 asymptomatic subjects, 52 acute neck pain subjects, and 70 chronic neck pain subjects. Spine. 2004;29:2485-2492'},{id:"B20",body:'Harrison DE, Janik TJ, Harrison DD, Cailliet R, Harmon S. Can the thoracic kyphosis be modeled with a simple geometric shape? The results of circular and elliptical modeling in 80 asymptomatic subjects. Journal of Spinal Disorders. 2002;15(3):213-220'},{id:"B21",body:'Harrison DE, Harrison DD, Janik TJ, Cailliet R, Haas JW. Do alterations in vertebral and disc dimensions affect an elliptical model of the thoracic kyphosis? Spine. 2003;28(5):463-469'},{id:"B22",body:'Troyanovich SJ, Cailliet R, Janik TJ, Harrison DD, Harrison DE. Radiographic mensuration characteristics of the sagittal lumbar spine from a normal population with a method to synthesize prior studies of lordosis. Journal of Spinal Disorders. 1997;10(5):380-386'},{id:"B23",body:'Janik TJ, Harrison DD, Cailliet R, Troyanovich SJ, Harrison DE. Can the sagittal lumbar curvature be closely approximated by an ellipse? Journal of Orthopaedic Research. 1998;16(6):766-770'},{id:"B24",body:'Harrison DD, Cailliet R, Janik TJ, Troyanovich SJ, Harrison DE, Holland B. Elliptical modeling of the sagittal lumbar lordosis and segmental rotation angles as a method to discriminate between normal and low back pain subjects. Journal of Spinal Disorders. 1998;11(5):430-439'},{id:"B25",body:'Harrison DE, Harrison DD, Cailliet R, et al. Cobb method or Harrison posterior tangent method: which to choose for lateral cervical radiographic analysis. Spine. 2000;25:2072-2078'},{id:"B26",body:'Harrison DE, Cailliet R, Harrison DD, et al. Reliability of centroid, Cobb, and Harrison posterior tangent methods: Which to choose for analysis of thoracic kyphosis. Spine. 2001;26:E227-E234'},{id:"B27",body:'Harrison DE, Harrison DD, Cailliet R, et al. Radiographic analysis of lumbar lordosis: Centroid, Cobb, TRALL, and Harrison posterior tangent methods. Spine. 2001;26:E235-E242'},{id:"B28",body:'Harrison DE, Holland B, Harrison DD, et al. Further reliability analysis of the Harrison radiographic line drawing methods: Crossed ICCs for lateral posterior tangents and AP modified-Risser Ferguson. Journal of Manipulative and Physiological Therapeutics. 2002;25:93-98'},{id:"B29",body:'McAviney J, Schulz D, Bock R, Harrison DE, Holland B. Determining the relationship between cervical lordosis and neck complaints. Journal of Manipulative and Physiological Therapeutics. 2005;28(3):187-193'},{id:"B30",body:'Keller TS, Colloca CJ, Harrison DE, Harrison DD, Janik TJ. Influence of spine morphology on intervertebral disc loads and stresses in asymptomatic adults: Implications for the ideal spine. The Spine Journal. 2005;5(3):297-309'},{id:"B31",body:'Harrison DE, Colloca CJ, Harrison DD, Janik TJ, Haas JW, Keller TS. Anterior thoracic posture increases thoracolumbar disc loading. European Spine Journal. 2005;14(3):234-242'},{id:"B32",body:'Keller TS, Harrison DE, Colloca CJ, Harrison DD, Janik TJ. Prediction of osteoporotic spinal deformity. Spine. 2003;28(5):455-462'},{id:"B33",body:'Harrison DE, Harrison DD, Janik TJ, William Jones E, Cailliet R, Normand M. Comparison of axial and flexural stresses in lordosis and three buckled configurations of the cervical spine. Clinical Biomechanics. 2001;16(4):276-284'},{id:"B34",body:'Harrison DE, Jones EW, Janik TJ, Harrison DD. Evaluation of axial and flexural stresses in the vertebral body cortex and trabecular bone in lordosis and two sagittal cervical translation configurations with an elliptical shell model. Journal of Manipulative and Physiological Therapeutics. 2002;25(6):391-401'},{id:"B35",body:'Harrison DE, Harrison DD, Cailliet R, Janik TJ, Troyanovich SJ. Cervical coupling during lateral head translations creates an S-configuration. Clinical Biomechanics (Bristol, Avon). 2000;15(6):436-440'},{id:"B36",body:'Harrison DE, Cailliet R, Harrison DD, Janik TJ, Troyanovich SJ, Coleman RR. Lumbar coupling during lateral translations of the thoracic cage relative to a fixed pelvis. Clinical Biomechanics (Bristol, Avon). 1999;14(10):704-709'},{id:"B37",body:'Harrison DE, Cailliet R, Harrison DD, Janik TJ. How do anterior/posterior translations of the thoracic cage affect the sagittal lumbar spine, pelvic tilt, and thoracic kyphosis? European Spine Journal. 2002;11(3):287-293'},{id:"B38",body:'Harrison DE, Harrison DD, Haas JW, Oakley PA. Spinal Biomechanics for Clinicians. Vol. I. Evanston, WY: Harrison Chiropractic Biophysics Seminars, Inc.; 2003'},{id:"B39",body:'Oakley PA, Cuttler JM, Harrison DE. X-ray imaging is essential for contemporary chiropractic and manual therapy spinal rehabilitation: Radiography increases benefits and reduces risks. Dose-Response. 2018;16(2):1559325818781437'},{id:"B40",body:'Harrison DE, Oakley PA. Scoliosis deformity reduction in adults: A CBP® Mirror image® case series incorporating the \'non-commutative property of finite rotation angles under addition\' in five patients with lumbar and thoraco-lumbar scoliosis. Journal of Physical Therapy Science. 2017;29(11):2044-2050'},{id:"B41",body:'Haggard JS, Haggard JB, Oakley PA, Harrison DE. Reduction of progressive thoracolumbar adolescent idiopathic scoliosis by chiropractic biophysics® (CBP®) mirror image® methods following failed traditional chiropractic treatment: A case report. Journal of Physical Therapy Science. 2017;29(11):2062-2067'},{id:"B42",body:'Harrison DE, Cailliet R, Betz J, Haas JW, Harrison DD, Janik TJ, et al. Conservative methods for reducing lateral translation postures of the head: A nonrandomized clinical control trial. Journal of Rehabilitation Research and Development. 2004;41(4):631-639'},{id:"B43",body:'Moustafa IM, Diab AA, Hegazy F, Harrison DE. Demonstration of central conduction time and neuroplastic changes after cervical lordosis rehabilitation in asymptomatic subjects: A randomized, placebo-controlled trial. Scientific Reports. 2021;11(1):15379'},{id:"B44",body:'Moustafa IM, Diab A, Shousha T, Harrison DE. Does restoration of sagittal cervical alignment improve cervicogenic headache pain and disability: A 2-year pilot randomized controlled trial. Heliyon. 2021;7(3):e06467'},{id:"B45",body:'Moustafa I, Youssef ASA, Ahbouch A, Harrison DE. Demonstration of autonomic nervous function and cervical sensorimotor control after cervical lordosis rehabilitation: A randomized controlled trial. Journal of Athletic Training. 2021;56(3):10'},{id:"B46",body:'Moustafa IM, Diab AA, Hegazy F, Harrison DE. Does improvement towards a normal cervical sagittal configuration aid in the management of cervical myofascial pain syndrome: A 1-year randomized controlled trial. BMC Musculoskeletal Disorders. 2018;19(1):396'},{id:"B47",body:'Moustafa IM, Diab AA, Harrison DE. The effect of normalizing the sagittal cervical configuration on dizziness, neck pain, and cervicocephalic kinesthetic sensibility: A 1-year randomized controlled study. European Journal of Physical and Rehabilitation Medicine. 2017;53(1):57-71'},{id:"B48",body:'Moustafa IM, Diab AAM, Hegazy FA, Harrison DE. Does rehabilitation of cervical lordosis influence sagittal cervical spine flexion extension kinematics in cervical spondylotic radiculopathy subjects? Journal of Back and Musculoskeletal Rehabilitation. 2017;30(4):937-941'},{id:"B49",body:'Moustafa IM, Diab AA, Taha S, Harrison DE. Addition of a sagittal cervical posture corrective orthotic device to a multimodal rehabilitation program improves short- and long-term outcomes in patients with discogenic cervical radiculopathy. Archives of Physical Medicine and Rehabilitation. 2016;97(12):2034-2044'},{id:"B50",body:'Moustafa IM. Does improvement towards a normal cervical configuration aid in the management of fibromyalgia. A randomized controlled trial. Bulletin of Faculty of Pharmacy, Cairo University. 2013;18(2):29-41'},{id:"B51",body:'Moustafa IM, Diab AM, Ahmed A, Harrison DE. The efficacy of cervical lordosis rehabilitation for nerve root function, pain, and segmental motion in cervical spondylotic radiculopathy. Physiotherapy. 2011;97(supplment):846-847'},{id:"B52",body:'Moustafa IM, Walton LM, Raigangir V, Shousha TM, Harrison D. Reduction of posture hyperkyphosis improves short- and long-term outcomes in patients with neck pain. Abstract: International Journal of Orthopaedic & Sports Physical Therapy. 2020;50(1):CSM143'},{id:"B53",body:'Diab AAM, Moustafa IM. The efficacy of lumbar extension traction for sagittal alignment in mechanical low back pain: A randomized trial. Journal of Back and Musculoskeletal Rehabilitation. 2013;26(2):213-220'},{id:"B54",body:'Moustafa IM, Diab AA. Extension traction treatment for patients with discogenic lumbosacral radiculopathy: A randomized controlled trial. Clinical Rehabilitation. 2012;27(1):51-62'},{id:"B55",body:'Diab AA, Moustafa IM. Lumbar lordosis rehabilitation for pain and lumbar segmental motion in chronic mechanical low back pain: A randomized trial. Journal of Manipulative and Physiological Therapeutics. 2012;35(4):246-253'},{id:"B56",body:'Oakley PA, Ehsani NN, Moustafa IM, Harrison DE. Restoring lumbar lordosis: A systematic review of controlled trials utilizing Chiropractic Bio Physics® (CBP®) non-surgical approach to increasing lumbar lordosis in the treatment of low back disorders. Journal of Physical Therapy Science. 2020;32(9):601-610'},{id:"B57",body:'Oakley PA, Ehsani NN, Moustafa IM, Harrison DE. Restoring cervical lordosis by cervical extension traction methods in the treatment of cervical spine disorders: A systematic review of controlled trials. Journal of Physical Therapy Science. 2021;33(10):784-794'},{id:"B58",body:'Haas JW, Oakley PA, Harrison DE. Cervical pseudo-scoliosis reduction and alleviation of dystonia symptoms using chiropractic BioPhysics® (CBP®) technique: A case report with a 1.5-year follow-up. The Journal of Contemporary Chiropractic. 2019;2:131-137'},{id:"B59",body:'Jaeger JO, Oakley PA, Moore RR, Ruggeroli EP, Harrison DE. Resolution of temporomandibular joint dysfunction (TMJD) by correcting a lateral head translation posture following previous failed traditional chiropractic therapy: A CBP® case report. Journal of Physical Therapy Science. 2018;30(1):103-107'},{id:"B60",body:'Oakley PA, Harrison DE. Alleviation of pain and disability in a post-surgical C4-C7 total fusion patient after reducing a lateral head translation (side shift) posture: A CBP® case report with a 14 year follow-up. Journal of Physical Therapy Science. 2018;30(7):952-957'},{id:"B61",body:'Berry RH, Oakley P, Harrison D. Alleviation of radiculopathy by structural rehabilitation of the cervical spine by correcting a lateral head translation posture (-TxH) using Berry translation traction as a part of CBP methods: A case report. The Chiropractic Journal of Australia. 2017;45(1):63-72'},{id:"B62",body:'Berry RH, Oakley PA, Harrison DE. Alleviation of chronic headaches by correcting lateral head translation posture (-TxH) using Chiropractic Biophysics & Berry Translation Traction. Annals of Vertebral Subluxation Research. 2017;(1-2):87-92'},{id:"B63",body:'Oakley PA, Berry RH, Harrison DE. A structural approach to the postsurgical laminectomy case. Journal of Vertebral Subluxation Research. 2007;(March 19):1-7'},{id:"B64",body:'Nuckols TK, Lim YW, Wynn BO, et al. Rigorous development does not ensure that guidelines are acceptable to a panel of knowledgeable providers. Journal of General Internal Medicine. 2008;23(1):37-44'},{id:"B65",body:'Rome P, Waterhouse JD. An evidence-based narrative of the evidence-base concept. Asia-Pacific Chiropractic Journal. 2020;1:004. https://doi.org/10.46323/2021004'},{id:"B66",body:'Ebrall P, Doyle M. The value of case reports as clinical evidence. The Chiropractic Journal of Australia. 2020;47(1):29-43'},{id:"B67",body:'Fedorchuk C, Lightstone DF, McRae C, Kaczor D. Correction of grade 2 spondylolisthesis following a non-surgical structural spinal rehabilitation protocol using lumbar traction: A case study and selective review of literature. Journal of Radiology Case Reports. 2017;11(5):13-26'},{id:"B68",body:'Oakley PA, Harrison DE. Correction of multilevel lumbar retrolistheses by non-surgical extension traction procedures in a patient with congenital fusion of L5-S1: A CBP® case report with a 13-month follow-up. The Journal of Contemporary Chiropractic. 2020;3(1):137-142'},{id:"B69",body:'Fedorchuk C, Haugen H. Reduction in three levels of lumbar degenerative spondylolisthesis following chiropractic care: A case report & review of the literature. Annals of Vertebral Subluxation Research. 2020;(Dec. 3):165-170'},{id:"B70",body:'Fedorchuk CA, Lightstone DF, Oakley PA, Harrison DE. Correction of a double spondylolisthesis of the lumbar spine utilizing chiropractic biophysics® technique: A case report with 1-year follow-up. Journal of Physical Therapy Science. 2021;33(1):89-93'},{id:"B71",body:'Fedorchuk C, Lightstone DF, DeVon CR, Katz E, Wilcox J. Improvements in cervical spinal canal diameter and neck disability following correction of cervical lordosis and cervical spondylolistheses using chiropractic BioPhysics technique: A case series. Journal of Radiology Case Reports. 2020;14(4):21-37'},{id:"B72",body:'Fedorchuk C, Lightstone D. Reduction in cervical anterolisthesis & pain in a 52-year-old female using chiropractic biophysics® technique: A case study and selective review of literature. Annals of Vertebral Subluxation Research. 2016;3:118-124'},{id:"B73",body:'Oakley PA, Harrison DE. Reducing thoracic Hyperkyphosis subluxation deformity: A systematic review of chiropractic BioPhysics® methods employed in its structural improvement. The Journal of Contemporary Chiropractic. 2018;1(1):59-66'},{id:"B74",body:'Fortner MO, Oakley PA, Harrison DE. Alleviation of chronic spine pain and headaches by reducing forward head posture and thoracic hyperkyphosis: A CBP® case report. Journal of Physical Therapy Science. 2018;30(8):1117-1123'},{id:"B75",body:'Oakley PA, Jaeger JO, Brown JE, Polatis TA, Clarke JG, Whittler CD, et al. The CBP® mirror image® approach to reducing thoracic hyperkyphosis: A retrospective case series of 10 patients. Journal of Physical Therapy Science. 2018;30(8):1039-1045'},{id:"B76",body:'Fortner MO, Oakley PA, Harrison DE. Treating \'slouchy\' (hyperkyphosis) posture with chiropractic biophysics®: A case report utilizing a multimodal mirror image® rehabilitation program. Journal of Physical Therapy Science. 2017;29(8):1475-1480'},{id:"B77",body:'Miller JE, Oakley PA, Levin SB, Harrison DE. Reversing thoracic hyperkyphosis: A case report featuring mirror image® thoracic extension rehabilitation. Journal of Physical Therapy Science. 2017;29(7):1264-1267'},{id:"B78",body:'Fedorchuk C, Snow E. Reduction in thoracic hyperkyphosis with increased peak expiratory flow (PEF), forced expiratory volume (FEV) and SF-36 scores following CBP protocols in asymptomatic patients: A case series. Annals of Vertebral Subluxation Research. 2017;(Oct. 12):189-200'},{id:"B79",body:'Jaeger JO, Oakley PA, Colloca CJ, et al. Non-surgical reduction of thoracic hyper-kyphosis in a 24-year old music teacher utilizing chiropractic biophysics® technique. British Journal of Medicine and Medical Research. 2016;11:1-9'},{id:"B80",body:'Gubbels CM, Werner JT, Oakley PA, Harrison DE. Reduction of thoraco-lumbar junctional kyphosis, posterior sagittal balance, and increase of lumbar lordosis and sacral inclination by chiropractic BioPhysics® methods in an adolescent with back pain: A case report. Journal of Physical Therapy Science. 2019;31(10):839-843'},{id:"B81",body:'Fortner MO, Oakley PA, Harrison DE. Chiropractic biophysics management of straight back syndrome and exertional dyspnea: A case report with follow-up. The Journal of Contemporary Chiropractic. 2019;2:115-122'},{id:"B82",body:'Betz JW, Oakley PA, Harrison DE. Relief of exertional dyspnea and spinal pains by increasing the thoracic kyphosis in straight back syndrome (thoracic hypo-kyphosis) using CBP® methods: A case report with long-term follow-up. Journal of Physical Therapy Science. 2018;30(1):185-189'},{id:"B83",body:'Fedorchuk C, Lightstone DF, Comer RD, Weiner MT, McCoy M. Improved glycosylated hemoglobin, hyperglycemia, and quality of life following thoracic hypokyphosis vertebral subluxation correction using Chiropractic BioPhysics®: A prospective case report. Journal of Diabetes & Metabolism. 2018;9(10):1-10'},{id:"B84",body:'Mitchell JR, Oakley PA, Harrison DE. Nonsurgical correction of straight back syndrome (thoracic hypokyphosis), increased lung capacity and resolution of exertional dyspnea by thoracic hyperkyphosis mirror image® traction: A CBP® case report. Journal of Physical Therapy Science. 2017;29(11):2058-2061'},{id:"B85",body:'Haas JW, Harrison DE, Oakley PA. Non-surgical reduction in anterior sagittal balance subluxation and improvement in overall posture in a geriatric suffering from low back pain and sciatica: A CBP® case report. The Journal of Contemporary Chiropractic. 2020;3(1):45-50'},{id:"B86",body:'Anderson JM, Oakley PA, Harrison DE. Improving posture to reduce the symptoms of Parkinson’s: A CBP® case report with a 21 month follow-up. Journal of Physical Therapy Science. 2019;31(2):153-158'},{id:"B87",body:'Harrison DE, Oakley PA. Non-operative correction of flat back syndrome using lumbar extension traction: A CBP® case series of two. Journal of Physical Therapy Science. 2018;30(8):1131-1137'},{id:"B88",body:'Oakley PA, Ehsani NN, Harrison DE. Non-surgical reduction of lumbar hyperlordosis, forward sagittal balance and sacral tilt to relieve low back pain by Chiropractic BioPhysics® methods: A case report. Journal of Physical Therapy Science. 2019;31(10):860-864'},{id:"B89",body:'Harrison DE, Oakley PA, Betz JW. Anterior head translation following cervical fusion-a probable cause of post-surgical pain and impairment: A CBP® case report. Journal of Physical Therapy Science. 2018;30(2):271-276'},{id:"B90",body:'Fedorchuk C, Lightstone DF, Andino H. Failed neck surgery: Improvement in neck pain, migraines, energy levels, and performance of activities of daily living following subluxation correction using Chiropractic Biophysics® Technique: A case study. Annals of Vertebral Subluxation Research. 2017;(May 18):93-100'},{id:"B91",body:'Calabrese EJ. Cancer risk assessment foundation unraveling: New historical evidence reveals that the US National Academy of Sciences (US NAS), biological effects of atomic radiation (BEAR) committee genetics panel falsified the research record to promote acceptance of the LNT. Archives of Toxicology. 2015;89(4):649-650'},{id:"B92",body:'Calabrese EJ. An abuse of risk assessment: How regulatory agencies improperly adopted LNT for cancer risk assessment. Archives of Toxicology. 2015;89(4):647-648'},{id:"B93",body:'Calabrese EJ. On the origins of the linear no-threshold (LNT) dogma by means of untruths, artful dodges and blind faith. Environmental Research. 2015;142:432-442'},{id:"B94",body:'Scott BR, Sanders CL, Mitchel REJ, Boreham DR. CT scans may reduce rather than increase risk of cancer. The Journal of the American Physicians and Surgeons. 2008;13(1):8-11'},{id:"B95",body:'Lemon JA, Phan N, Boreham DR. Single CT scan prolongs survival by extending cancer latency in Trp53 heterozygous mice. Radiation Research. 2017;188(4.2):505-511'},{id:"B96",body:'Lemon JA, Phan N, Boreham DR. Multiple CT scans extend lifespan by delaying cancer progression in cancer-prone mice. Radiation Research. 2017;188(4.2):495-504'},{id:"B97",body:'Cuttler JM. Application of low doses of ionizing radiation in medical therapies. Dose-Response. 2020;18(1):1559325819895739'},{id:"B98",body:'Calabrese EJ, Dhawan G, Kapoor R, Kozumbo WJ. Radiotherapy treatment of human inflammatory diseases and conditions: Optimal dose. Human & Experimental Toxicology. 2019;38(8):888-898'},{id:"B99",body:'Pollycove M, Feinendegen LE. Radiation-induced versus endogenous DNA damage: Possible effect of inducible protective responses in mitigating endogenous damage. Human and Experimental Toxicology. 2003;22(6):290-306'},{id:"B100",body:'Pollycove M. Radiobiological basis of low-dose irradiation in prevention and therapy of cancer. Dose-Response. 2006;5(1):26-38'},{id:"B101",body:'Feinendegen LE, Cuttler JM. Biological effects from low doses and dose rates of ionizing radiation: Science in the service of protecting humans, a synopsis. Health Physics. 2018;114(6):623-626'}],footnotes:[],contributors:[{corresp:null,contributorFullName:"Deed E. Harrison",address:null,affiliation:'
CBP NonProfit, Inc., USA
'},{corresp:"yes",contributorFullName:"Paul A. Oakley",address:"docoakley.icc@gmail.com",affiliation:'
Private Practice, Canada
'}],corrections:null},book:{id:"11042",type:"book",title:"Complementary Therapies",subtitle:null,fullTitle:"Complementary Therapies",slug:null,publishedDate:null,bookSignature:"Prof. Mario Bernardo-Filho, Prof. Redha Taiar, Danúbia Da Cunha De Sá-Caputo and Dr. Adérito Seixas",coverURL:"https://cdn.intechopen.com/books/images_new/11042.jpg",licenceType:"CC BY 3.0",editedByType:null,isbn:"978-1-83969-012-9",printIsbn:"978-1-83969-011-2",pdfIsbn:"978-1-83969-013-6",isAvailableForWebshopOrdering:!0,editors:[{id:"157376",title:"Prof.",name:"Mario",middleName:null,surname:"Bernardo-Filho",slug:"mario-bernardo-filho",fullName:"Mario Bernardo-Filho"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}}},profile:{item:{id:"345906",title:"Dr.",name:"Sekhane",middleName:null,surname:"Hocine",email:"docsekhoc@gmail.com",fullName:"Sekhane Hocine",slug:"sekhane-hocine",position:null,biography:null,institutionString:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",totalCites:0,totalChapterViews:"0",outsideEditionCount:0,totalAuthoredChapters:"1",totalEditedBooks:"0",personalWebsiteURL:null,twitterURL:null,linkedinURL:null,institution:null},booksEdited:[],chaptersAuthored:[{id:"79375",title:"An Overview Study of Micro-Grids for Self-Production in Renewable Energies",slug:"an-overview-study-of-micro-grids-for-self-production-in-renewable-energies",abstract:"Micro-grids (μ-grids) are small-scale power grids, specially designed to provide low voltage (LV) power supply to a small number of consumers. These networks include: different production units (energy resources), storage devices and local controllable loads, which have the possibility of being controlled. In this chapter, we will study in detail the constitution of an electrical micro-grid, their two operating modes (connected mode and islanded mode), and their controls. On the other hand, we will also discuss on hybrid micro-grids and their advantages. We will also discuss for the monitoring and data logging products used in micro-grids and hybrid micro-grids. Finally, at the end of this chapter we will ended with the importance of micro-grids systems.",signatures:"Hocine Sekhane",authors:[{id:"345906",title:"Dr.",name:"Sekhane",surname:"Hocine",fullName:"Sekhane Hocine",slug:"sekhane-hocine",email:"docsekhoc@gmail.com"}],book:{id:"10377",title:"Electric Power Conversion and Micro-Grids",slug:"electric-power-conversion-and-micro-grids",productType:{id:"1",title:"Edited Volume"}}}],collaborators:[{id:"344676",title:"Dr.",name:"Mohamed A.",surname:"Ebrahim",slug:"mohamed-a.-ebrahim",fullName:"Mohamed A. Ebrahim",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"344677",title:"Prof.",name:"Ebtisam M.",surname:"Saied",slug:"ebtisam-m.-saied",fullName:"Ebtisam M. 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Abdel Fattah",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Electronics Research Institute",institutionURL:null,country:{name:"Egypt"}}},{id:"344680",title:"Prof.",name:"Hisham",surname:"El Khashab",slug:"hisham-el-khashab",fullName:"Hisham El Khashab",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"344716",title:"Dr.",name:"Emmanuel",surname:"Hernandez Mayoral",slug:"emmanuel-hernandez-mayoral",fullName:"Emmanuel Hernandez Mayoral",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"345292",title:"Ph.D.",name:"Borys",surname:"Pleskach",slug:"borys-pleskach",fullName:"Borys Pleskach",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"352041",title:"Mr.",name:"Carlos",surname:"D. 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Ove Odredbe i uvjeti ističu pravila i regulacije u svezi korištenja IntechOpenove stranice www.intechopen.com i svih poddomena u vlasništvu IntechOpena, tvrtke sa sjedištem u 5 Princes Gate Court, London, SW7 2QJ, Ujedinjeno Kraljevstvo.
',metaTitle:"Odredbe i uvjeti",metaDescription:"Ove Odredbe i uvjeti ističu pravila i regulacije u svezi korištenja IntechOpenove stranice www.intechopen.com i svih poddomena u vlasništvu IntechOpena, tvrtke sa sjedištem u 5 Princes Gate Court, London, SW7 2QJ, Ujedinjeno Kraljevstvo.",metaKeywords:null,canonicalURL:"/page/cro-terms-and-conditions",contentRaw:'[{"type":"htmlEditorComponent","content":"
1. Odredbe
\\n\\n
Pristupom na stranicu www.intechopen.com slažete se s ovim odredbama, sa svim primjenjivim zakonskim odredbama, te se slažete s poštovanjem svih lokalnih zakona. Korištenje i/ili pristup ovoj stranici temelji se na potpunom prihvaćanju ovih odredbi. Svi materijali na ovoj stranici zaštićeni su primjenjivim zakonima o autorskim pravima i žigu.
\\n\\n
Sljedeća terminologija odnosi se na Odredbe i uvjete, te na sve naše ugovore:
\\n\\n
Klijent, stranka, vi, vaš odnosi se na vas, osobu koja pristupa ovoj stranici i prihvaća IntechOpenove Odredbe i uvjete;
\\n\\n
Kompanija, tvrtka, mi, naše odnosi se na tvrtku IntechOpen;
\\n\\n
Stranke, strane odnosi se na klijenta i na nas, ili samo na klijenta ili nas.
\\n\\n
Sve odredbe koje se odnose na ponudu, prihvat ili razmatranje plaćanja, a za koja mi pružamo asistenciju klijentu, bilo na ugovoreni ili fiksni način, a s ciljem da se ostvare potrebe i želje klijenta u svezi s našim uslugama, su podložne zakonskim odredbama Ujedinjenog Kraljevstva.
\\n\\n
2. Licenca
\\n\\n
Osim ako nije suprotno navedeno, IntechOpen i/ili svi davatelji licence vlasnici su intelektualnog vlasništva nad svim materijalima na www.intechopen.com. Sva prava intelektualnog vlasništva su pridržana. Stranice sa www.intechopen.com možete gledati, preuzimati, dijeliti, dijeliti poveznice i printati za osobnu uporabu, a temeljem pravila sadržanih u ovim Odredbama i uvjetima.
\\n\\n
3. Kolačići
\\n\\n
Mi koristimo kolačiće. Korištenjem IntechOpenove stranice slažete se s korištenjem kolačića u skladu s IntechOpenovom Politikom privatnosti. Većina modernih, interaktivnih stranica koristi kolačiće kako bi omogućila ponovno pronalaženje korisničkih detalja kod svakog posjeta. Na našoj stranici kolačići se uglavnom koriste kako bi omogućili funkcionalnost i olakšali posjetiteljima korištenje stranice.
\\n\\n
4. Ograničenja odgovornosti
\\n\\n
IntechOpen ili njegovi suradnici niti u jednom slučaju neće biti odgovorni za štete (štete uključuju gubitak podataka ili profita, druge poslovne prekide, te sve ostale štete) koje nastanu zbog korištenja materijala na IntechOpenovoj stranici ili nemogućnosti da se iste koriste, čak i ako je IntechOpen ili njegov predstavnik o takvoj šteti obaviješten pismenim ili usmenim putem. Neke jurisdikcije ne dozvoljavaju ograničenja garancija ili ograničenja obveza za posljedične ili slučajne štete pa se u tom slučaju ova ograničenja možda ne odnose na vas.
\\n\\n
5. Točnost materijala
\\n\\n
Materijali koji se pojavljuju na IntechOpenovoj stranici mogu sadržavati manje greške, tipfelere ili fotografske greške. IntechOpen može napraviti promjene na bilo kojem materijalu koji se nalazi na stranici u bilo koje vrijeme.
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6. Poveznice
\\n\\n
IntechOpen nije formalno povezan niti s jednom vanjskom stranicom čije poveznice vode na www.intechopen.com, osim ako to nije izravno navedeno. Iz tog razloga IntechOpen nije odgovoran za sadržaj koji se pojavljuje na takvim stranicama. Poveznica na IntechOpenovu stranicu ne implicira povezanost sa IntechOpenom. Korištenje takvih poveznica isključiva je odgovornost korisnika.
\\n\\n
Zadržavamo pravo vlasništva nad cjelokupnom stranicom www.intechopen.com i nad svim materijalom na toj stranici. Koristeći se našim uslugama, slažete se da maknete sve poveznice na našu stranicu odmah nakon što to od vas zatražimo. Također, zadržavamo pravo da ove Odredbe i uvjete, i politiku o poveznicama izmjenimo u bilo koje vrijeme. Koristeći se poveznicama na naše stranice slažete se s ovim Odredbama i uvjetima.
\\n\\n
Ako smatrate da je bilo koja poveznica na našoj stranici sumnjiva iz bilo kojeg razloga, molimo vas da nas kontaktirate. U tom slučaju razmotrit ćemo micanje poveznice s naše stranice, iako nismo obvezni to napraviti.
\\n\\n
7. Okviri (Frames)
\\n\\n
Bez prethodne privole i izričite pisane dozvole, ne možete stvarati okvire oko naših stranica ili koristiti druge tehnike koje na bilo koji način mogu promijeniti prezentaciju ili izgled naše stranice.
\\n\\n
8. Promjene
\\n\\n
IntechOpen može ove Odredbe izmijeniti u bilo koje vrijeme i bez prethodne obavijesti. Koristeći ovu stranicu vi se slažete s trenutnim Odredbama i uvjetima koje su na snazi.
\\n\\n
9. Nadležno pravo
\\n\\n
Ove Odredbe i uvjeti su sastavljeni u skladu s odredbama prava Ujedinjenog Kraljevstva, a za sve sporove nadležan je sud u Londonu, Ujedinjeno Kraljevstvo.
Pristupom na stranicu www.intechopen.com slažete se s ovim odredbama, sa svim primjenjivim zakonskim odredbama, te se slažete s poštovanjem svih lokalnih zakona. Korištenje i/ili pristup ovoj stranici temelji se na potpunom prihvaćanju ovih odredbi. Svi materijali na ovoj stranici zaštićeni su primjenjivim zakonima o autorskim pravima i žigu.
\n\n
Sljedeća terminologija odnosi se na Odredbe i uvjete, te na sve naše ugovore:
\n\n
Klijent, stranka, vi, vaš odnosi se na vas, osobu koja pristupa ovoj stranici i prihvaća IntechOpenove Odredbe i uvjete;
\n\n
Kompanija, tvrtka, mi, naše odnosi se na tvrtku IntechOpen;
\n\n
Stranke, strane odnosi se na klijenta i na nas, ili samo na klijenta ili nas.
\n\n
Sve odredbe koje se odnose na ponudu, prihvat ili razmatranje plaćanja, a za koja mi pružamo asistenciju klijentu, bilo na ugovoreni ili fiksni način, a s ciljem da se ostvare potrebe i želje klijenta u svezi s našim uslugama, su podložne zakonskim odredbama Ujedinjenog Kraljevstva.
\n\n
2. Licenca
\n\n
Osim ako nije suprotno navedeno, IntechOpen i/ili svi davatelji licence vlasnici su intelektualnog vlasništva nad svim materijalima na www.intechopen.com. Sva prava intelektualnog vlasništva su pridržana. Stranice sa www.intechopen.com možete gledati, preuzimati, dijeliti, dijeliti poveznice i printati za osobnu uporabu, a temeljem pravila sadržanih u ovim Odredbama i uvjetima.
\n\n
3. Kolačići
\n\n
Mi koristimo kolačiće. Korištenjem IntechOpenove stranice slažete se s korištenjem kolačića u skladu s IntechOpenovom Politikom privatnosti. Većina modernih, interaktivnih stranica koristi kolačiće kako bi omogućila ponovno pronalaženje korisničkih detalja kod svakog posjeta. Na našoj stranici kolačići se uglavnom koriste kako bi omogućili funkcionalnost i olakšali posjetiteljima korištenje stranice.
\n\n
4. Ograničenja odgovornosti
\n\n
IntechOpen ili njegovi suradnici niti u jednom slučaju neće biti odgovorni za štete (štete uključuju gubitak podataka ili profita, druge poslovne prekide, te sve ostale štete) koje nastanu zbog korištenja materijala na IntechOpenovoj stranici ili nemogućnosti da se iste koriste, čak i ako je IntechOpen ili njegov predstavnik o takvoj šteti obaviješten pismenim ili usmenim putem. Neke jurisdikcije ne dozvoljavaju ograničenja garancija ili ograničenja obveza za posljedične ili slučajne štete pa se u tom slučaju ova ograničenja možda ne odnose na vas.
\n\n
5. Točnost materijala
\n\n
Materijali koji se pojavljuju na IntechOpenovoj stranici mogu sadržavati manje greške, tipfelere ili fotografske greške. IntechOpen može napraviti promjene na bilo kojem materijalu koji se nalazi na stranici u bilo koje vrijeme.
\n\n
6. Poveznice
\n\n
IntechOpen nije formalno povezan niti s jednom vanjskom stranicom čije poveznice vode na www.intechopen.com, osim ako to nije izravno navedeno. Iz tog razloga IntechOpen nije odgovoran za sadržaj koji se pojavljuje na takvim stranicama. Poveznica na IntechOpenovu stranicu ne implicira povezanost sa IntechOpenom. Korištenje takvih poveznica isključiva je odgovornost korisnika.
\n\n
Zadržavamo pravo vlasništva nad cjelokupnom stranicom www.intechopen.com i nad svim materijalom na toj stranici. Koristeći se našim uslugama, slažete se da maknete sve poveznice na našu stranicu odmah nakon što to od vas zatražimo. Također, zadržavamo pravo da ove Odredbe i uvjete, i politiku o poveznicama izmjenimo u bilo koje vrijeme. Koristeći se poveznicama na naše stranice slažete se s ovim Odredbama i uvjetima.
\n\n
Ako smatrate da je bilo koja poveznica na našoj stranici sumnjiva iz bilo kojeg razloga, molimo vas da nas kontaktirate. U tom slučaju razmotrit ćemo micanje poveznice s naše stranice, iako nismo obvezni to napraviti.
\n\n
7. Okviri (Frames)
\n\n
Bez prethodne privole i izričite pisane dozvole, ne možete stvarati okvire oko naših stranica ili koristiti druge tehnike koje na bilo koji način mogu promijeniti prezentaciju ili izgled naše stranice.
\n\n
8. Promjene
\n\n
IntechOpen može ove Odredbe izmijeniti u bilo koje vrijeme i bez prethodne obavijesti. Koristeći ovu stranicu vi se slažete s trenutnim Odredbama i uvjetima koje su na snazi.
\n\n
9. Nadležno pravo
\n\n
Ove Odredbe i uvjeti su sastavljeni u skladu s odredbama prava Ujedinjenog Kraljevstva, a za sve sporove nadležan je sud u Londonu, Ujedinjeno Kraljevstvo.
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Also, these results show that proposed methods will estimate the rotor position and speed with high precision for all speeds from near zero speeds up to rated speed. These procedures have the advantages of simple implementation on the every switched reluctance motor drive without extra hardware, low cost, high reliability, low vibration, and excellent performance at long term.",book:{id:"5127",slug:"new-applications-of-artificial-intelligence",title:"New Applications of Artificial Intelligence",fullTitle:"New Applications of Artificial Intelligence"},signatures:"M. Divandari and B. 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The current paper describes the basic characteristics of hardware ANNs that generate the gait for multilegged robots. The pulses emitted by the hardware ANN generate oscillating patterns of electrical activity. The pulse-type hardware ANN model has the basic features of a class II neuron model, which behaves like a resonator. Thus, gait generation by the hardware ANNs mimics the synchronization phenomena in biological neural networks. Consequently, our constructed hardware ANNs can generate multilegged robot gaits without requiring software programs.",book:{id:"6187",slug:"advanced-applications-for-artificial-neural-networks",title:"Advanced Applications for Artificial Neural Networks",fullTitle:"Advanced Applications for Artificial Neural Networks"},signatures:"Ken Saito, Masaya Ohara, Mizuki Abe, Minami Kaneko and Fumio\nUchikoba",authors:[{id:"157327",title:"Dr.",name:"Ken",middleName:null,surname:"Saito",slug:"ken-saito",fullName:"Ken Saito"},{id:"157328",title:"Dr.",name:"Minami",middleName:null,surname:"Kaneko",slug:"minami-kaneko",fullName:"Minami Kaneko"},{id:"157330",title:"Prof.",name:"Fumio",middleName:null,surname:"Uchikoba",slug:"fumio-uchikoba",fullName:"Fumio Uchikoba"},{id:"219934",title:"Mr.",name:"Masaya",middleName:null,surname:"Ohara",slug:"masaya-ohara",fullName:"Masaya Ohara"},{id:"219935",title:"BSc.",name:"Mizuki",middleName:null,surname:"Abe",slug:"mizuki-abe",fullName:"Mizuki Abe"}]},{id:"67472",title:"Object Re-Identification Based on Deep Learning",slug:"object-re-identification-based-on-deep-learning",totalDownloads:1352,totalCrossrefCites:1,totalDimensionsCites:3,abstract:"With the explosive growth of video data and the rapid development of computer vision technology, more and more relevant technologies are applied in our real life, one of which is object re-identification (Re-ID) technology. Object Re-ID is currently concentrated in the field of person Re-ID and vehicle Re-ID, which is mainly used to realize the cross-vision tracking of person/vehicle and trajectory prediction. This chapter combines theory and practice to explain why the deep network can re-identify the object. To introduce the main technical route of object Re-ID, the examples of person/vehicle Re-ID are given, and the improvement points of existing object Re-ID research are described separately.",book:{id:"8725",slug:"visual-object-tracking-with-deep-neural-networks",title:"Visual Object Tracking with Deep Neural Networks",fullTitle:"Visual Object Tracking with Deep Neural Networks"},signatures:"Xiying Li and Zhihao Zhou",authors:null},{id:"56981",title:"Advanced Process Control",slug:"advanced-process-control",totalDownloads:1359,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"The debutanizer column is an important unit operation in petroleum refining industries. The top product is liquefied petroleum gas and the bottom product is light naphtha. This system is difficult to handle. This is because due to its non-linear behavior, multivariable interaction and existence of numerous constraints on its manipulated variable. Neural network techniques have been increasingly used for a wide variety of applications. In this book, equation-based multi-input multi-output (MIMO) neural network has been proposed for multivariable control strategy to control the top and bottom temperatures of the column. The manipulated variables for column are reflux and reboiler flow rates, respectively. This neural network model are based on multivariable equation, instead of the normal black box structure. It has the advantage of being robust in nature while being easier to interpret in terms of its input-output variables. It has been employed for set point changes and disturbance changes. The results show that the neural network equation-based model for direct inverse and internal model approach performs better than the conventional proportional, integral and derivative (PID) controller.",book:{id:"6187",slug:"advanced-applications-for-artificial-neural-networks",title:"Advanced Applications for Artificial Neural Networks",fullTitle:"Advanced Applications for Artificial Neural Networks"},signatures:"Nasser Mohamed Ramli",authors:[{id:"209483",title:"Dr.",name:"Nasser",middleName:null,surname:"Mohamed Ramli",slug:"nasser-mohamed-ramli",fullName:"Nasser Mohamed Ramli"}]}],onlineFirstChaptersFilter:{topicId:"522",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:87,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:98,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:27,numberOfPublishedChapters:287,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:139,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:0,numberOfUpcomingTopics:2,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!1},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:10,numberOfPublishedChapters:103,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:0,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!1},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:10,numberOfOpenTopics:4,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}},{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}}]},series:{item:{id:"11",title:"Biochemistry",doi:"10.5772/intechopen.72877",issn:"2632-0983",scope:"Biochemistry, the study of chemical transformations occurring within living organisms, impacts all areas of life sciences, from molecular crystallography and genetics to ecology, medicine, and population biology. Biochemistry examines macromolecules - proteins, nucleic acids, carbohydrates, and lipids – and their building blocks, structures, functions, and interactions. Much of biochemistry is devoted to enzymes, proteins that catalyze chemical reactions, enzyme structures, mechanisms of action and their roles within cells. Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. This Biochemistry Series will address the current research on biomolecules and the emerging trends with great promise.",coverUrl:"https://cdn.intechopen.com/series/covers/11.jpg",latestPublicationDate:"May 18th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:27,editor:{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"Blumenberg",slug:"miroslav-blumenberg",fullName:"Miroslav Blumenberg",profilePictureURL:"https://mts.intechopen.com/storage/users/31610/images/system/31610.jpg",biography:"Miroslav Blumenberg, Ph.D., was born in Subotica and received his BSc in Belgrade, Yugoslavia. He completed his Ph.D. at MIT in Organic Chemistry; he followed up his Ph.D. with two postdoctoral study periods at Stanford University. Since 1983, he has been a faculty member of the RO Perelman Department of Dermatology, NYU School of Medicine, where he is codirector of a training grant in cutaneous biology. Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:9,paginationItems:[{id:"14",title:"Cell and Molecular Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/14.jpg",editor:{id:"165627",title:"Dr.",name:"Rosa María",middleName:null,surname:"Martínez-Espinosa",slug:"rosa-maria-martinez-espinosa",fullName:"Rosa María Martínez-Espinosa",profilePictureURL:"https://mts.intechopen.com/storage/users/165627/images/system/165627.jpeg",biography:"Dr. Rosa María Martínez-Espinosa has been a Spanish Full Professor since 2020 (Biochemistry and Molecular Biology) and is currently Vice-President of International Relations and Cooperation development and leader of the research group 'Applied Biochemistry” (University of Alicante, Spain). Other positions she has held at the university include Vice-Dean of Master Programs, Vice-Dean of the Degree in Biology and Vice-Dean for Mobility and Enterprise and Engagement at the Faculty of Science (University of Alicante). She received her Bachelor in Biology in 1998 (University of Alicante) and her PhD in 2003 (Biochemistry, University of Alicante). She undertook post-doctoral research at the University of East Anglia (Norwich, U.K. 2004-2005; 2007-2008).\nHer multidisciplinary research focuses on investigating archaea and their potential applications in biotechnology. She has an H-index of 21. She has authored one patent and has published more than 70 indexed papers and around 60 book chapters.\nShe has contributed to more than 150 national and international meetings during the last 15 years. Her research interests include archaea metabolism, enzymes purification and characterization, gene regulation, carotenoids and bioplastics production, antioxidant\ncompounds, waste water treatments, and brines bioremediation.\nRosa María’s other roles include editorial board member for several journals related\nto biochemistry, reviewer for more than 60 journals (biochemistry, molecular biology, biotechnology, chemistry and microbiology) and president of several organizing committees in international meetings related to the N-cycle or respiratory processes.",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"79367",title:"Dr.",name:"Ana Isabel",middleName:null,surname:"Flores",slug:"ana-isabel-flores",fullName:"Ana Isabel Flores",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRpIOQA0/Profile_Picture_1632418099564",institutionString:null,institution:{name:"Hospital Universitario 12 De Octubre",institutionURL:null,country:{name:"Spain"}}},{id:"328234",title:"Ph.D.",name:"Christian",middleName:null,surname:"Palavecino",slug:"christian-palavecino",fullName:"Christian Palavecino",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000030DhEhQAK/Profile_Picture_1628835318625",institutionString:null,institution:{name:"Central University of Chile",institutionURL:null,country:{name:"Chile"}}},{id:"186585",title:"Dr.",name:"Francisco Javier",middleName:null,surname:"Martin-Romero",slug:"francisco-javier-martin-romero",fullName:"Francisco Javier Martin-Romero",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSB3HQAW/Profile_Picture_1631258137641",institutionString:null,institution:{name:"University of Extremadura",institutionURL:null,country:{name:"Spain"}}}]},{id:"15",title:"Chemical Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",slug:"sukru-beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",biography:"Dr. Şükrü Beydemir obtained a BSc in Chemistry in 1995 from Yüzüncü Yıl University, MSc in Biochemistry in 1998, and PhD in Biochemistry in 2002 from Atatürk University, Turkey. He performed post-doctoral studies at Max-Planck Institute, Germany, and University of Florence, Italy in addition to making several scientific visits abroad. He currently works as a Full Professor of Biochemistry in the Faculty of Pharmacy, Anadolu University, Turkey. Dr. Beydemir has published over a hundred scientific papers spanning protein biochemistry, enzymology and medicinal chemistry, reviews, book chapters and presented several conferences to scientists worldwide. He has received numerous publication awards from various international scientific councils. He serves in the Editorial Board of several international journals. Dr. Beydemir is also Rector of Bilecik Şeyh Edebali University, Turkey.",institutionString:null,institution:{name:"Anadolu University",institutionURL:null,country:{name:"Turkey"}}},editorTwo:{id:"13652",title:"Prof.",name:"Deniz",middleName:null,surname:"Ekinci",slug:"deniz-ekinci",fullName:"Deniz Ekinci",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYLT1QAO/Profile_Picture_1634557223079",biography:"Dr. Deniz Ekinci obtained a BSc in Chemistry in 2004, MSc in Biochemistry in 2006, and PhD in Biochemistry in 2009 from Atatürk University, Turkey. He studied at Stetson University, USA, in 2007-2008 and at the Max Planck Institute of Molecular Cell Biology and Genetics, Germany, in 2009-2010. Dr. Ekinci currently works as a Full Professor of Biochemistry in the Faculty of Agriculture and is the Head of the Enzyme and Microbial Biotechnology Division, Ondokuz Mayıs University, Turkey. He is a member of the Turkish Biochemical Society, American Chemical Society, and German Genetics society. Dr. Ekinci published around ninety scientific papers, reviews and book chapters, and presented several conferences to scientists. He has received numerous publication awards from several scientific councils. Dr. Ekinci serves as the Editor in Chief of four international books and is involved in the Editorial Board of several international journals.",institutionString:null,institution:{name:"Ondokuz Mayıs University",institutionURL:null,country:{name:"Turkey"}}},editorThree:null,editorialBoard:[{id:"241413",title:"Dr.",name:"Azhar",middleName:null,surname:"Rasul",slug:"azhar-rasul",fullName:"Azhar Rasul",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRT1oQAG/Profile_Picture_1635251978933",institutionString:null,institution:{name:"Government College University, Faisalabad",institutionURL:null,country:{name:"Pakistan"}}},{id:"178316",title:"Ph.D.",name:"Sergey",middleName:null,surname:"Sedykh",slug:"sergey-sedykh",fullName:"Sergey Sedykh",profilePictureURL:"https://mts.intechopen.com/storage/users/178316/images/system/178316.jfif",institutionString:null,institution:{name:"Novosibirsk State University",institutionURL:null,country:{name:"Russia"}}}]},{id:"17",title:"Metabolism",coverUrl:"https://cdn.intechopen.com/series_topics/covers/17.jpg",editor:{id:"138626",title:"Dr.",name:"Yannis",middleName:null,surname:"Karamanos",slug:"yannis-karamanos",fullName:"Yannis Karamanos",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002g6Jv2QAE/Profile_Picture_1629356660984",biography:"Yannis Karamanos, born in Greece in 1953, completed his pre-graduate studies at the Université Pierre et Marie Curie, Paris, then his Masters and Doctoral degree at the Université de Lille (1983). He was associate professor at the University of Limoges (1987) before becoming full professor of biochemistry at the Université d’Artois (1996). He worked on the structure-function relationships of glycoconjugates and his main project was the investigations on the biological roles of the de-N-glycosylation enzymes (Endo-N-acetyl-β-D-glucosaminidase and peptide-N4-(N-acetyl-β-glucosaminyl) asparagine amidase). From 2002 he contributes to the understanding of the Blood-brain barrier functioning using proteomics approaches. He has published more than 70 papers. His teaching areas are energy metabolism and regulation, integration and organ specialization and metabolic adaptation.",institutionString:null,institution:{name:"Artois University",institutionURL:null,country:{name:"France"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"243049",title:"Dr.",name:"Anca",middleName:null,surname:"Pantea Stoian",slug:"anca-pantea-stoian",fullName:"Anca Pantea Stoian",profilePictureURL:"https://mts.intechopen.com/storage/users/243049/images/system/243049.jpg",institutionString:null,institution:{name:"Carol Davila University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"203824",title:"Dr.",name:"Attilio",middleName:null,surname:"Rigotti",slug:"attilio-rigotti",fullName:"Attilio Rigotti",profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institutionString:null,institution:{name:"Pontifical Catholic University of Chile",institutionURL:null,country:{name:"Chile"}}},{id:"300470",title:"Dr.",name:"Yanfei (Jacob)",middleName:null,surname:"Qi",slug:"yanfei-(jacob)-qi",fullName:"Yanfei (Jacob) Qi",profilePictureURL:"https://mts.intechopen.com/storage/users/300470/images/system/300470.jpg",institutionString:null,institution:{name:"Centenary Institute of Cancer Medicine and Cell Biology",institutionURL:null,country:{name:"Australia"}}}]},{id:"18",title:"Proteomics",coverUrl:"https://cdn.intechopen.com/series_topics/covers/18.jpg",editor:{id:"200689",title:"Prof.",name:"Paolo",middleName:null,surname:"Iadarola",slug:"paolo-iadarola",fullName:"Paolo Iadarola",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSCl8QAG/Profile_Picture_1623568118342",biography:"Paolo Iadarola graduated with a degree in Chemistry from the University of Pavia (Italy) in July 1972. He then worked as an Assistant Professor at the Faculty of Science of the same University until 1984. In 1985, Prof. Iadarola became Associate Professor at the Department of Biology and Biotechnologies of the University of Pavia and retired in October 2017. Since then, he has been working as an Adjunct Professor in the same Department at the University of Pavia. His research activity during the first years was primarily focused on the purification and structural characterization of enzymes from animal and plant sources. During this period, Prof. Iadarola familiarized himself with the conventional techniques used in column chromatography, spectrophotometry, manual Edman degradation, and electrophoresis). Since 1995, he has been working on: i) the determination in biological fluids (serum, urine, bronchoalveolar lavage, sputum) of proteolytic activities involved in the degradation processes of connective tissue matrix, and ii) on the identification of biological markers of lung diseases. In this context, he has developed and validated new methodologies (e.g., Capillary Electrophoresis coupled to Laser-Induced Fluorescence, CE-LIF) whose application enabled him to determine both the amounts of biochemical markers (Desmosines) in urine/serum of patients affected by Chronic Obstructive Pulmonary Disease (COPD) and the activity of proteolytic enzymes (Human Neutrophil Elastase, Cathepsin G, Pseudomonas aeruginosa elastase) in sputa of these patients. More recently, Prof. Iadarola was involved in developing techniques such as two-dimensional electrophoresis coupled to liquid chromatography/mass spectrometry (2DE-LC/MS) for the proteomic analysis of biological fluids aimed at the identification of potential biomarkers of different lung diseases. He is the author of about 150 publications (According to Scopus: H-Index: 23; Total citations: 1568- According to WOS: H-Index: 20; Total Citations: 1296) of peer-reviewed international journals. He is a Consultant Reviewer for several journals, including the Journal of Chromatography A, Journal of Chromatography B, Plos ONE, Proteomes, International Journal of Molecular Science, Biotech, Electrophoresis, and others. He is also Associate Editor of Biotech.",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorTwo:{id:"201414",title:"Dr.",name:"Simona",middleName:null,surname:"Viglio",slug:"simona-viglio",fullName:"Simona Viglio",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKDHQA4/Profile_Picture_1630402531487",biography:"Simona Viglio is an Associate Professor of Biochemistry at the Department of Molecular Medicine at the University of Pavia. She has been working since 1995 on the determination of proteolytic enzymes involved in the degradation process of connective tissue matrix and on the identification of biological markers of lung diseases. She gained considerable experience in developing and validating new methodologies whose applications allowed her to determine both the amount of biomarkers (Desmosine and Isodesmosine) in the urine of patients affected by COPD, and the activity of proteolytic enzymes (HNE, Cathepsin G, Pseudomonas aeruginosa elastase) in the sputa of these patients. Simona Viglio was also involved in research dealing with the supplementation of amino acids in patients with brain injury and chronic heart failure. She is presently engaged in the development of 2-DE and LC-MS techniques for the study of proteomics in biological fluids. The aim of this research is the identification of potential biomarkers of lung diseases. 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2019",editedByType:"Edited by",bookSignature:"Catrin Sian Rutland and Valentina Kubale",hash:"75cdacb570e0e6d15a5f6e69640d87c9",volumeInSeries:2,fullTitle:"Veterinary Anatomy and Physiology",editors:[{id:"202192",title:"Dr.",name:"Catrin",middleName:null,surname:"Rutland",slug:"catrin-rutland",fullName:"Catrin Rutland",profilePictureURL:"https://mts.intechopen.com/storage/users/202192/images/system/202192.png",institutionString:null,institution:{name:"University of Nottingham",institutionURL:null,country:{name:"United Kingdom"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"7233",title:"New Insights into Theriogenology",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7233.jpg",slug:"new-insights-into-theriogenology",publishedDate:"December 5th 2018",editedByType:"Edited by",bookSignature:"Rita Payan-Carreira",hash:"74f4147e3fb214dd050e5edd3aaf53bc",volumeInSeries:1,fullTitle:"New Insights into Theriogenology",editors:[{id:"38652",title:"Dr.",name:"Rita",middleName:null,surname:"Payan-Carreira",slug:"rita-payan-carreira",fullName:"Rita Payan-Carreira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRiFPQA0/Profile_Picture_1614601496313",institutionString:null,institution:{name:"University of Évora",institutionURL:null,country:{name:"Portugal"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null}]},subseriesFiltersForPublishedBooks:[{group:"subseries",caption:"Animal Nutrition",value:20,count:2},{group:"subseries",caption:"Animal Reproductive Biology and Technology",value:28,count:3},{group:"subseries",caption:"Animal Science",value:19,count:5}],publicationYearFilters:[{group:"publicationYear",caption:"2022",value:2022,count:2},{group:"publicationYear",caption:"2021",value:2021,count:3},{group:"publicationYear",caption:"2020",value:2020,count:3},{group:"publicationYear",caption:"2019",value:2019,count:1},{group:"publicationYear",caption:"2018",value:2018,count:1}],authors:{paginationCount:302,paginationItems:[{id:"198499",title:"Dr.",name:"Daniel",middleName:null,surname:"Glossman-Mitnik",slug:"daniel-glossman-mitnik",fullName:"Daniel Glossman-Mitnik",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/198499/images/system/198499.jpeg",biography:"Dr. Daniel Glossman-Mitnik is currently a Titular Researcher at the Centro de Investigación en Materiales Avanzados (CIMAV), Chihuahua, Mexico, as well as a National Researcher of Level III at the Consejo Nacional de Ciencia y Tecnología, Mexico. His research interest focuses on computational chemistry and molecular modeling of diverse systems of pharmacological, food, and alternative energy interests by resorting to DFT and Conceptual DFT. He has authored a coauthored more than 255 peer-reviewed papers, 32 book chapters, and 2 edited books. He has delivered speeches at many international and domestic conferences. He serves as a reviewer for more than eighty international journals, books, and research proposals as well as an editor for special issues of renowned scientific journals.",institutionString:"Centro de Investigación en Materiales Avanzados",institution:{name:"Centro de Investigación en Materiales Avanzados",country:{name:"Mexico"}}},{id:"76477",title:"Prof.",name:"Mirza",middleName:null,surname:"Hasanuzzaman",slug:"mirza-hasanuzzaman",fullName:"Mirza Hasanuzzaman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/76477/images/system/76477.png",biography:"Dr. Mirza Hasanuzzaman is a Professor of Agronomy at Sher-e-Bangla Agricultural University, Bangladesh. He received his Ph.D. in Plant Stress Physiology and Antioxidant Metabolism from Ehime University, Japan, with a scholarship from the Japanese Government (MEXT). Later, he completed his postdoctoral research at the Center of Molecular Biosciences, University of the Ryukyus, Japan, as a recipient of the Japan Society for the Promotion of Science (JSPS) postdoctoral fellowship. He was also the recipient of the Australian Government Endeavour Research Fellowship for postdoctoral research as an adjunct senior researcher at the University of Tasmania, Australia. Dr. Hasanuzzaman’s current work is focused on the physiological and molecular mechanisms of environmental stress tolerance. Dr. Hasanuzzaman has published more than 150 articles in peer-reviewed journals. He has edited ten books and written more than forty book chapters on important aspects of plant physiology, plant stress tolerance, and crop production. According to Scopus, Dr. Hasanuzzaman’s publications have received more than 10,500 citations with an h-index of 53. He has been named a Highly Cited Researcher by Clarivate. He is an editor and reviewer for more than fifty peer-reviewed international journals and was a recipient of the “Publons Peer Review Award” in 2017, 2018, and 2019. He has been honored by different authorities for his outstanding performance in various fields like research and education, and he has received the World Academy of Science Young Scientist Award (2014) and the University Grants Commission (UGC) Award 2018. He is a fellow of the Bangladesh Academy of Sciences (BAS) and the Royal Society of Biology.",institutionString:"Sher-e-Bangla Agricultural University",institution:{name:"Sher-e-Bangla Agricultural University",country:{name:"Bangladesh"}}},{id:"187859",title:"Prof.",name:"Kusal",middleName:"K.",surname:"Das",slug:"kusal-das",fullName:"Kusal Das",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSBDeQAO/Profile_Picture_1623411145568",biography:"Kusal K. Das is a Distinguished Chair Professor of Physiology, Shri B. M. Patil Medical College and Director, Centre for Advanced Medical Research (CAMR), BLDE (Deemed to be University), Vijayapur, Karnataka, India. Dr. Das did his M.S. and Ph.D. in Human Physiology from the University of Calcutta, Kolkata. His area of research is focused on understanding of molecular mechanisms of heavy metal activated low oxygen sensing pathways in vascular pathophysiology. He has invented a new method of estimation of serum vitamin E. His expertise in critical experimental protocols on vascular functions in experimental animals was well documented by his quality of publications. He was a Visiting Professor of Medicine at University of Leeds, United Kingdom (2014-2016) and Tulane University, New Orleans, USA (2017). For his immense contribution in medical research Ministry of Science and Technology, Government of India conferred him 'G.P. Chatterjee Memorial Research Prize-2019” and he is also the recipient of 'Dr.Raja Ramanna State Scientist Award 2015” by Government of Karnataka. He is a Fellow of the Royal Society of Biology (FRSB), London and Honorary Fellow of Karnataka Science and Technology Academy, Department of Science and Technology, Government of Karnataka.",institutionString:"BLDE (Deemed to be University), India",institution:null},{id:"243660",title:"Dr.",name:"Mallanagouda Shivanagouda",middleName:null,surname:"Biradar",slug:"mallanagouda-shivanagouda-biradar",fullName:"Mallanagouda Shivanagouda Biradar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243660/images/system/243660.jpeg",biography:"M. S. Biradar is Vice Chancellor and Professor of Medicine of\nBLDE (Deemed to be University), Vijayapura, Karnataka, India.\nHe obtained his MD with a gold medal in General Medicine and\nhas devoted himself to medical teaching, research, and administrations. He has also immensely contributed to medical research\non vascular medicine, which is reflected by his numerous publications including books and book chapters. Professor Biradar was\nalso Visiting Professor at Tulane University School of Medicine, New Orleans, USA.",institutionString:"BLDE (Deemed to be University)",institution:{name:"BLDE University",country:{name:"India"}}},{id:"289796",title:"Dr.",name:"Swastika",middleName:null,surname:"Das",slug:"swastika-das",fullName:"Swastika Das",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/289796/images/system/289796.jpeg",biography:"Swastika N. Das is Professor of Chemistry at the V. P. Dr. P. G.\nHalakatti College of Engineering and Technology, BLDE (Deemed\nto be University), Vijayapura, Karnataka, India. She obtained an\nMSc, MPhil, and PhD in Chemistry from Sambalpur University,\nOdisha, India. Her areas of research interest are medicinal chemistry, chemical kinetics, and free radical chemistry. She is a member\nof the investigators who invented a new modified method of estimation of serum vitamin E. She has authored numerous publications including book\nchapters and is a mentor of doctoral curriculum at her university.",institutionString:"BLDEA’s V.P.Dr.P.G.Halakatti College of Engineering & Technology",institution:{name:"BLDE University",country:{name:"India"}}},{id:"248459",title:"Dr.",name:"Akikazu",middleName:null,surname:"Takada",slug:"akikazu-takada",fullName:"Akikazu Takada",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248459/images/system/248459.png",biography:"Akikazu Takada was born in Japan, 1935. After graduation from\nKeio University School of Medicine and finishing his post-graduate studies, he worked at Roswell Park Memorial Institute NY,\nUSA. He then took a professorship at Hamamatsu University\nSchool of Medicine. In thrombosis studies, he found the SK\npotentiator that enhances plasminogen activation by streptokinase. He is very much interested in simultaneous measurements\nof fatty acids, amino acids, and tryptophan degradation products. By using fatty\nacid analyses, he indicated that plasma levels of trans-fatty acids of old men were\nfar higher in the US than Japanese men. . He also showed that eicosapentaenoic acid\n(EPA) and docosahexaenoic acid (DHA) levels are higher, and arachidonic acid\nlevels are lower in Japanese than US people. By using simultaneous LC/MS analyses\nof plasma levels of tryptophan metabolites, he recently found that plasma levels of\nserotonin, kynurenine, or 5-HIAA were higher in patients of mono- and bipolar\ndepression, which are significantly different from observations reported before. In\nview of recent reports that plasma tryptophan metabolites are mainly produced by\nmicrobiota. He is now working on the relationships between microbiota and depression or autism.",institutionString:"Hamamatsu University School of Medicine",institution:{name:"Hamamatsu University School of Medicine",country:{name:"Japan"}}},{id:"137240",title:"Prof.",name:"Mohammed",middleName:null,surname:"Khalid",slug:"mohammed-khalid",fullName:"Mohammed Khalid",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/137240/images/system/137240.png",biography:"Mohammed Khalid received his B.S. degree in chemistry in 2000 and Ph.D. degree in physical chemistry in 2007 from the University of Khartoum, Sudan. He moved to School of Chemistry, Faculty of Science, University of Sydney, Australia in 2009 and joined Dr. Ron Clarke as a postdoctoral fellow where he worked on the interaction of ATP with the phosphoenzyme of the Na+/K+-ATPase and dual mechanisms of allosteric acceleration of the Na+/K+-ATPase by ATP; then he went back to Department of Chemistry, University of Khartoum as an assistant professor, and in 2014 he was promoted as an associate professor. In 2011, he joined the staff of Department of Chemistry at Taif University, Saudi Arabia, where he is currently an assistant professor. His research interests include the following: P-Type ATPase enzyme kinetics and mechanisms, kinetics and mechanisms of redox reactions, autocatalytic reactions, computational enzyme kinetics, allosteric acceleration of P-type ATPases by ATP, exploring of allosteric sites of ATPases, and interaction of ATP with ATPases located in cell membranes.",institutionString:"Taif University",institution:{name:"Taif University",country:{name:"Saudi Arabia"}}},{id:"63810",title:"Prof.",name:"Jorge",middleName:null,surname:"Morales-Montor",slug:"jorge-morales-montor",fullName:"Jorge Morales-Montor",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/63810/images/system/63810.png",biography:"Dr. Jorge Morales-Montor was recognized with the Lola and Igo Flisser PUIS Award for best graduate thesis at the national level in the field of parasitology. He received a fellowship from the Fogarty Foundation to perform postdoctoral research stay at the University of Georgia. He has 153 journal articles to his credit. He has also edited several books and published more than fifty-five book chapters. He is a member of the Mexican Academy of Sciences, Latin American Academy of Sciences, and the National Academy of Medicine. He has received more than thirty-five awards and has supervised numerous bachelor’s, master’s, and Ph.D. students. Dr. Morales-Montor is the past president of the Mexican Society of Parasitology.",institutionString:"National Autonomous University of Mexico",institution:{name:"National Autonomous University of Mexico",country:{name:"Mexico"}}},{id:"217215",title:"Dr.",name:"Palash",middleName:null,surname:"Mandal",slug:"palash-mandal",fullName:"Palash Mandal",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/217215/images/system/217215.jpeg",biography:null,institutionString:"Charusat University",institution:null},{id:"49739",title:"Dr.",name:"Leszek",middleName:null,surname:"Szablewski",slug:"leszek-szablewski",fullName:"Leszek Szablewski",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49739/images/system/49739.jpg",biography:"Leszek Szablewski is a professor of medical sciences. He received his M.S. in the Faculty of Biology from the University of Warsaw and his PhD degree from the Institute of Experimental Biology Polish Academy of Sciences. He habilitated in the Medical University of Warsaw, and he obtained his degree of Professor from the President of Poland. Professor Szablewski is the Head of Chair and Department of General Biology and Parasitology, Medical University of Warsaw. Professor Szablewski has published over 80 peer-reviewed papers in journals such as Journal of Alzheimer’s Disease, Biochim. Biophys. Acta Reviews of Cancer, Biol. Chem., J. Biomed. Sci., and Diabetes/Metabol. Res. Rev, Endocrine. He is the author of two books and four book chapters. He has edited four books, written 15 scripts for students, is the ad hoc reviewer of over 30 peer-reviewed journals, and editorial member of peer-reviewed journals. Prof. Szablewski’s research focuses on cell physiology, genetics, and pathophysiology. He works on the damage caused by lack of glucose homeostasis and changes in the expression and/or function of glucose transporters due to various diseases. He has given lectures, seminars, and exercises for students at the Medical University.",institutionString:"Medical University of Warsaw",institution:{name:"Medical University of Warsaw",country:{name:"Poland"}}},{id:"173123",title:"Dr.",name:"Maitham",middleName:null,surname:"Khajah",slug:"maitham-khajah",fullName:"Maitham Khajah",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/173123/images/system/173123.jpeg",biography:"Dr. Maitham A. Khajah received his degree in Pharmacy from Faculty of Pharmacy, Kuwait University, in 2003 and obtained his PhD degree in December 2009 from the University of Calgary, Canada (Gastrointestinal Science and Immunology). Since January 2010 he has been assistant professor in Kuwait University, Faculty of Pharmacy, Department of Pharmacology and Therapeutics. His research interest are molecular targets for the treatment of inflammatory bowel disease (IBD) and the mechanisms responsible for immune cell chemotaxis. He cosupervised many students for the MSc Molecular Biology Program, College of Graduate Studies, Kuwait University. Ever since joining Kuwait University in 2010, he got various grants as PI and Co-I. He was awarded the Best Young Researcher Award by Kuwait University, Research Sector, for the Year 2013–2014. He was a member in the organizing committee for three conferences organized by Kuwait University, Faculty of Pharmacy, as cochair and a member in the scientific committee (the 3rd, 4th, and 5th Kuwait International Pharmacy Conference).",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"195136",title:"Dr.",name:"Aya",middleName:null,surname:"Adel",slug:"aya-adel",fullName:"Aya Adel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/195136/images/system/195136.jpg",biography:"Dr. Adel works as an Assistant Lecturer in the unit of Phoniatrics, Department of Otolaryngology, Ain Shams University in Cairo, Egypt. Dr. Adel is especially interested in joint attention and its impairment in autism spectrum disorder",institutionString:"Ain Shams University",institution:{name:"Ain Shams University",country:{name:"Egypt"}}},{id:"94911",title:"Dr.",name:"Boulenouar",middleName:null,surname:"Mesraoua",slug:"boulenouar-mesraoua",fullName:"Boulenouar Mesraoua",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94911/images/system/94911.png",biography:"Dr Boulenouar Mesraoua is the Associate Professor of Clinical Neurology at Weill Cornell Medical College-Qatar and a Consultant Neurologist at Hamad Medical Corporation at the Neuroscience Department; He graduated as a Medical Doctor from the University of Oran, Algeria; he then moved to Belgium, the City of Liege, for a Residency in Internal Medicine and Neurology at Liege University; after getting the Belgian Board of Neurology (with high marks), he went to the National Hospital for Nervous Diseases, Queen Square, London, United Kingdom for a fellowship in Clinical Neurophysiology, under Pr Willison ; Dr Mesraoua had also further training in Epilepsy and Continuous EEG Monitoring for two years (from 2001-2003) in the Neurophysiology department of Zurich University, Switzerland, under late Pr Hans Gregor Wieser ,an internationally known epileptologist expert. \n\nDr B. Mesraoua is the Director of the Neurology Fellowship Program at the Neurology Section and an active member of the newly created Comprehensive Epilepsy Program at Hamad General Hospital, Doha, Qatar; he is also Assistant Director of the Residency Program at the Qatar Medical School. \nDr B. Mesraoua's main interests are Epilepsy, Multiple Sclerosis, and Clinical Neurology; He is the Chairman and the Organizer of the well known Qatar Epilepsy Symposium, he is running yearly for the past 14 years and which is considered a landmark in the Gulf region; He has also started last year , together with other epileptologists from Qatar, the region and elsewhere, a yearly International Epilepsy School Course, which was attended by many neurologists from the Area.\n\nInternationally, Dr Mesraoua is an active and elected member of the Commission on Eastern Mediterranean Region (EMR ) , a regional branch of the International League Against Epilepsy (ILAE), where he represents the Middle East and North Africa(MENA ) and where he holds the position of chief of the Epilepsy Epidemiology Section; Dr Mesraoua is a member of the American Academy of Neurology, the Europeen Academy of Neurology and the American Epilepsy Society.\n\nDr Mesraoua's main objectives are to encourage frequent gathering of the epileptologists/neurologists from the MENA region and the rest of the world, promote Epilepsy Teaching in the MENA Region, and encourage multicenter studies involving neurologists and epileptologists in the MENA region, particularly epilepsy epidemiological studies. \n\nDr. Mesraoua is the recipient of two research Grants, as the Lead Principal Investigator (750.000 USD and 250.000 USD) from the Qatar National Research Fund (QNRF) and the Hamad Hospital Internal Research Grant (IRGC), on the following topics : “Continuous EEG Monitoring in the ICU “ and on “Alpha-lactoalbumin , proof of concept in the treatment of epilepsy” .Dr Mesraoua is a reviewer for the journal \"seizures\" (Europeen Epilepsy Journal ) as well as dove journals ; Dr Mesraoua is the author and co-author of many peer reviewed publications and four book chapters in the field of Epilepsy and Clinical Neurology",institutionString:"Weill Cornell Medical College in Qatar",institution:{name:"Weill Cornell Medical College in Qatar",country:{name:"Qatar"}}},{id:"282429",title:"Prof.",name:"Covanis",middleName:null,surname:"Athanasios",slug:"covanis-athanasios",fullName:"Covanis Athanasios",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/282429/images/system/282429.jpg",biography:null,institutionString:"Neurology-Neurophysiology Department of the Children Hospital Agia Sophia",institution:null},{id:"190980",title:"Prof.",name:"Marwa",middleName:null,surname:"Mahmoud Saleh",slug:"marwa-mahmoud-saleh",fullName:"Marwa Mahmoud Saleh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/190980/images/system/190980.jpg",biography:"Professor Marwa Mahmoud Saleh is a doctor of medicine and currently works in the unit of Phoniatrics, Department of Otolaryngology, Ain Shams University in Cairo, Egypt. She got her doctoral degree in 1991 and her doctoral thesis was accomplished in the University of Iowa, United States. Her publications covered a multitude of topics as videokymography, cochlear implants, stuttering, and dysphagia. She has lectured Egyptian phonology for many years. Her recent research interest is joint attention in autism.",institutionString:"Ain Shams University",institution:{name:"Ain Shams University",country:{name:"Egypt"}}},{id:"259190",title:"Dr.",name:"Syed Ali Raza",middleName:null,surname:"Naqvi",slug:"syed-ali-raza-naqvi",fullName:"Syed Ali Raza Naqvi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259190/images/system/259190.png",biography:"Dr. Naqvi is a radioanalytical chemist and is working as an associate professor of analytical chemistry in the Department of Chemistry, Government College University, Faisalabad, Pakistan. Advance separation techniques, nuclear analytical techniques and radiopharmaceutical analysis are the main courses that he is teaching to graduate and post-graduate students. In the research area, he is focusing on the development of organic- and biomolecule-based radiopharmaceuticals for diagnosis and therapy of infectious and cancerous diseases. Under the supervision of Dr. Naqvi, three students have completed their Ph.D. degrees and 41 students have completed their MS degrees. He has completed three research projects and is currently working on 2 projects entitled “Radiolabeling of fluoroquinolone derivatives for the diagnosis of deep-seated bacterial infections” and “Radiolabeled minigastrin peptides for diagnosis and therapy of NETs”. He has published about 100 research articles in international reputed journals and 7 book chapters. Pakistan Institute of Nuclear Science & Technology (PINSTECH) Islamabad, Punjab Institute of Nuclear Medicine (PINM), Faisalabad and Institute of Nuclear Medicine and Radiology (INOR) Abbottabad are the main collaborating institutes.",institutionString:"Government College University",institution:{name:"Government College University, Faisalabad",country:{name:"Pakistan"}}},{id:"58390",title:"Dr.",name:"Gyula",middleName:null,surname:"Mozsik",slug:"gyula-mozsik",fullName:"Gyula Mozsik",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/58390/images/system/58390.png",biography:"Gyula Mózsik MD, Ph.D., ScD (med), is an emeritus professor of Medicine at the First Department of Medicine, Univesity of Pécs, Hungary. He was head of this department from 1993 to 2003. His specializations are medicine, gastroenterology, clinical pharmacology, clinical nutrition, and dietetics. His research fields are biochemical pharmacological examinations in the human gastrointestinal (GI) mucosa, mechanisms of retinoids, drugs, capsaicin-sensitive afferent nerves, and innovative pharmacological, pharmaceutical, and nutritional (dietary) research in humans. He has published about 360 peer-reviewed papers, 197 book chapters, 692 abstracts, 19 monographs, and has edited 37 books. He has given about 1120 regular and review lectures. He has organized thirty-eight national and international congresses and symposia. He is the founder of the International Conference on Ulcer Research (ICUR); International Union of Pharmacology, Gastrointestinal Section (IUPHAR-GI); Brain-Gut Society symposiums, and gastrointestinal cytoprotective symposiums. He received the Andre Robert Award from IUPHAR-GI in 2014. Fifteen of his students have been appointed as full professors in Egypt, Cuba, and Hungary.",institutionString:"University of Pécs",institution:{name:"University of Pecs",country:{name:"Hungary"}}},{id:"277367",title:"M.Sc.",name:"Daniel",middleName:"Martin",surname:"Márquez López",slug:"daniel-marquez-lopez",fullName:"Daniel Márquez López",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/277367/images/7909_n.jpg",biography:"Msc Daniel Martin Márquez López has a bachelor degree in Industrial Chemical Engineering, a Master of science degree in the same área and he is a PhD candidate for the Instituto Politécnico Nacional. His Works are realted to the Green chemistry field, biolubricants, biodiesel, transesterification reactions for biodiesel production and the manipulation of oils for therapeutic purposes.",institutionString:null,institution:{name:"Instituto Politécnico Nacional",country:{name:"Mexico"}}},{id:"196544",title:"Prof.",name:"Angel",middleName:null,surname:"Catala",slug:"angel-catala",fullName:"Angel Catala",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/196544/images/system/196544.jpg",biography:"Angel Catalá studied chemistry at Universidad Nacional de La Plata, Argentina, where he received a Ph.D. in Chemistry (Biological Branch) in 1965. From 1964 to 1974, he worked as an Assistant in Biochemistry at the School of Medicine at the same university. From 1974 to 1976, he was a fellow of the National Institutes of Health (NIH) at the University of Connecticut, Health Center, USA. From 1985 to 2004, he served as a Full Professor of Biochemistry at the Universidad Nacional de La Plata. He is a member of the National Research Council (CONICET), Argentina, and the Argentine Society for Biochemistry and Molecular Biology (SAIB). His laboratory has been interested for many years in the lipid peroxidation of biological membranes from various tissues and different species. Dr. Catalá has directed twelve doctoral theses, published more than 100 papers in peer-reviewed journals, several chapters in books, and edited twelve books. He received awards at the 40th International Conference Biochemistry of Lipids 1999 in Dijon, France. He is the winner of the Bimbo Pan-American Nutrition, Food Science and Technology Award 2006 and 2012, South America, Human Nutrition, Professional Category. In 2006, he won the Bernardo Houssay award in pharmacology, in recognition of his meritorious works of research. Dr. Catalá belongs to the editorial board of several journals including Journal of Lipids; International Review of Biophysical Chemistry; Frontiers in Membrane Physiology and Biophysics; World Journal of Experimental Medicine and Biochemistry Research International; World Journal of Biological Chemistry, Diabetes, and the Pancreas; International Journal of Chronic Diseases & Therapy; and International Journal of Nutrition. He is the co-editor of The Open Biology Journal and associate editor for Oxidative Medicine and Cellular Longevity.",institutionString:"Universidad Nacional de La Plata",institution:{name:"National University of La Plata",country:{name:"Argentina"}}},{id:"186585",title:"Dr.",name:"Francisco Javier",middleName:null,surname:"Martin-Romero",slug:"francisco-javier-martin-romero",fullName:"Francisco Javier Martin-Romero",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSB3HQAW/Profile_Picture_1631258137641",biography:"Francisco Javier Martín-Romero (Javier) is a Professor of Biochemistry and Molecular Biology at the University of Extremadura, Spain. He is also a group leader at the Biomarkers Institute of Molecular Pathology. Javier received his Ph.D. in 1998 in Biochemistry and Biophysics. At the National Cancer Institute (National Institute of Health, Bethesda, MD) he worked as a research associate on the molecular biology of selenium and its role in health and disease. After postdoctoral collaborations with Carlos Gutierrez-Merino (University of Extremadura, Spain) and Dario Alessi (University of Dundee, UK), he established his own laboratory in 2008. The interest of Javier's lab is the study of cell signaling with a special focus on Ca2+ signaling, and how Ca2+ transport modulates the cytoskeleton, migration, differentiation, cell death, etc. He is especially interested in the study of Ca2+ channels, and the role of STIM1 in the initiation of pathological events.",institutionString:null,institution:{name:"University of Extremadura",country:{name:"Spain"}}},{id:"217323",title:"Prof.",name:"Guang-Jer",middleName:null,surname:"Wu",slug:"guang-jer-wu",fullName:"Guang-Jer Wu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/217323/images/8027_n.jpg",biography:null,institutionString:null,institution:null},{id:"148546",title:"Dr.",name:"Norma Francenia",middleName:null,surname:"Santos-Sánchez",slug:"norma-francenia-santos-sanchez",fullName:"Norma Francenia Santos-Sánchez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/148546/images/4640_n.jpg",biography:null,institutionString:null,institution:null},{id:"272889",title:"Dr.",name:"Narendra",middleName:null,surname:"Maddu",slug:"narendra-maddu",fullName:"Narendra Maddu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/272889/images/10758_n.jpg",biography:null,institutionString:null,institution:null},{id:"242491",title:"Prof.",name:"Angelica",middleName:null,surname:"Rueda",slug:"angelica-rueda",fullName:"Angelica Rueda",position:"Investigador Cinvestav 3B",profilePictureURL:"https://mts.intechopen.com/storage/users/242491/images/6765_n.jpg",biography:null,institutionString:null,institution:null},{id:"88631",title:"Dr.",name:"Ivan",middleName:null,surname:"Petyaev",slug:"ivan-petyaev",fullName:"Ivan Petyaev",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Lycotec (United Kingdom)",country:{name:"United Kingdom"}}},{id:"423869",title:"Ms.",name:"Smita",middleName:null,surname:"Rai",slug:"smita-rai",fullName:"Smita Rai",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Integral University",country:{name:"India"}}},{id:"424024",title:"Prof.",name:"Swati",middleName:null,surname:"Sharma",slug:"swati-sharma",fullName:"Swati Sharma",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Integral University",country:{name:"India"}}},{id:"439112",title:"MSc.",name:"Touseef",middleName:null,surname:"Fatima",slug:"touseef-fatima",fullName:"Touseef Fatima",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Integral University",country:{name:"India"}}},{id:"424836",title:"Dr.",name:"Orsolya",middleName:null,surname:"Borsai",slug:"orsolya-borsai",fullName:"Orsolya Borsai",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Agricultural Sciences and Veterinary Medicine of Cluj-Napoca",country:{name:"Romania"}}},{id:"422262",title:"Ph.D.",name:"Paola Andrea",middleName:null,surname:"Palmeros-Suárez",slug:"paola-andrea-palmeros-suarez",fullName:"Paola Andrea Palmeros-Suárez",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Guadalajara",country:{name:"Mexico"}}}]}},subseries:{item:{id:"27",type:"subseries",title:"Multi-Agent Systems",keywords:"Collaborative Intelligence, Learning, Distributed Control System, Swarm Robotics, Decision Science, Software Engineering",scope:"Multi-agent systems are recognised as a state of the art field in Artificial Intelligence studies, which is popular due to the usefulness in facilitation capabilities to handle real-world problem-solving in a distributed fashion. The area covers many techniques that offer solutions to emerging problems in robotics and enterprise-level software systems. Collaborative intelligence is highly and effectively achieved with multi-agent systems. Areas of application include swarms of robots, flocks of UAVs, collaborative software management. Given the level of technological enhancements, the popularity of machine learning in use has opened a new chapter in multi-agent studies alongside the practical challenges and long-lasting collaboration issues in the field. It has increased the urgency and the need for further studies in this field. We welcome chapters presenting research on the many applications of multi-agent studies including, but not limited to, the following key areas: machine learning for multi-agent systems; modeling swarms robots and flocks of UAVs with multi-agent systems; decision science and multi-agent systems; software engineering for and with multi-agent systems; tools and technologies of multi-agent systems.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/27.jpg",hasOnlineFirst:!1,hasPublishedBooks:!1,annualVolume:11423,editor:{id:"148497",title:"Dr.",name:"Mehmet",middleName:"Emin",surname:"Aydin",slug:"mehmet-aydin",fullName:"Mehmet Aydin",profilePictureURL:"https://mts.intechopen.com/storage/users/148497/images/system/148497.jpg",biography:"Dr. Mehmet Emin Aydin is a Senior Lecturer with the Department of Computer Science and Creative Technology, the University of the West of England, Bristol, UK. 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