Overview of advantages and disadvantages of different types of stem cell for cell replacement therapy in Parkinson’s disease.
\r\n\t
",isbn:"978-1-80356-948-2",printIsbn:"978-1-80356-947-5",pdfIsbn:"978-1-80356-949-9",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,isNomenclature:!1,hash:"c0d1c1c93a36fd9d726445966316a373",bookSignature:"Dr. Sylvanus Gbendazhi Barnabas",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11434.jpg",keywords:"Indigenous People, Natives, First People, Minorities, United Nations, UN Declaration, Indigenous People Rights, Self-Determination, States, Independence, Struggle for Rights, Contemporary Times",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"April 7th 2022",dateEndSecondStepPublish:"May 5th 2022",dateEndThirdStepPublish:"July 4th 2022",dateEndFourthStepPublish:"September 22nd 2022",dateEndFifthStepPublish:"November 21st 2022",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"2 months",secondStepPassed:!0,areRegistrationsClosed:!1,currentStepOfPublishingProcess:3,editedByType:null,kuFlag:!1,biosketch:"Legal practitioner, consultant and a law academic with a diversity of interest in multi and intra-disciplinary scholarship on legal issues at national regional and international levels.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"293764",title:"Dr.",name:"Sylvanus",middleName:"Gbendazhi",surname:"Barnabas",slug:"sylvanus-barnabas",fullName:"Sylvanus Barnabas",profilePictureURL:"https://mts.intechopen.com/storage/users/293764/images/system/293764.jpg",biography:"Sylvanus Barnabas is a Senior Lecturer in Law at the Faculty of Law, Nile University of Nigeria where he teaches various subjects in law; he obtained the degree of Doctor of Philosophy in international human rights law from Northumbria University at Newcastle upon Tyne, United Kingdom; he has a Master of Laws degree obtained with distinction in Environmental Law and Policy from University of Kent at Canterbury, Kent, United Kingdom; he also holds a Bachelor of Laws degree from Ahmadu Bello University, Zaria, Nigeria; and he is also a qualified a barrister and solicitor of the Supreme Court of Nigeria.",institutionString:"Nigerian Turkish Nile University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Nigerian Turkish Nile University",institutionURL:null,country:{name:"Nigeria"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"21",title:"Psychology",slug:"psychology"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"440204",firstName:"Ana",lastName:"Cink",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/440204/images/20006_n.jpg",email:"ana.c@intechopen.com",biography:"As an Author Service Manager my responsibilities include monitoring and facilitating all publishing activities for authors and editors. From chapter submission and review, to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. Whether that be identifying an exceptional author and proposing an editorship collaboration, or contacting researchers who would like the opportunity to work with IntechOpen, I establish and help manage author and editor acquisition and contact."}},relatedBooks:[{type:"book",id:"6494",title:"Behavior Analysis",subtitle:null,isOpenForSubmission:!1,hash:"72a81a7163705b2765f9eb0b21dec70e",slug:"behavior-analysis",bookSignature:"Huei-Tse Hou and Carolyn S. Ryan",coverURL:"https://cdn.intechopen.com/books/images_new/6494.jpg",editedByType:"Edited by",editors:[{id:"96493",title:"Prof.",name:"Huei Tse",surname:"Hou",slug:"huei-tse-hou",fullName:"Huei Tse Hou"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9052",title:"Psychoanalysis",subtitle:"A New Overview",isOpenForSubmission:!1,hash:"69cc7a085f5417038f532cf11edee22f",slug:"psychoanalysis-a-new-overview",bookSignature:"Floriana Irtelli, Barbara Marchesi and Federico Durbano",coverURL:"https://cdn.intechopen.com/books/images_new/9052.jpg",editedByType:"Edited by",editors:[{id:"174641",title:"Dr.",name:"Floriana",surname:"Irtelli",slug:"floriana-irtelli",fullName:"Floriana Irtelli"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10981",title:"Sport Psychology in Sports, Exercise and Physical Activity",subtitle:null,isOpenForSubmission:!1,hash:"5214c44bdc42978449de0751ca364684",slug:"sport-psychology-in-sports-exercise-and-physical-activity",bookSignature:"Hilde G. Nielsen",coverURL:"https://cdn.intechopen.com/books/images_new/10981.jpg",editedByType:"Edited by",editors:[{id:"158692",title:"Ph.D.",name:"Hilde Dorthea Grindvik",surname:"Nielsen",slug:"hilde-dorthea-grindvik-nielsen",fullName:"Hilde Dorthea Grindvik Nielsen"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10211",title:"The Science of Emotional Intelligence",subtitle:null,isOpenForSubmission:!1,hash:"447fc7884303a10093bc189f4c82dd47",slug:"the-science-of-emotional-intelligence",bookSignature:"Simon George Taukeni",coverURL:"https://cdn.intechopen.com/books/images_new/10211.jpg",editedByType:"Edited by",editors:[{id:"202046",title:"Dr.",name:"Simon George",surname:"Taukeni",slug:"simon-george-taukeni",fullName:"Simon George Taukeni"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7811",title:"Beauty",subtitle:"Cosmetic Science, Cultural Issues and Creative Developments",isOpenForSubmission:!1,hash:"5f6fd59694706550db8dd1082a8e457b",slug:"beauty-cosmetic-science-cultural-issues-and-creative-developments",bookSignature:"Martha Peaslee Levine and Júlia Scherer Santos",coverURL:"https://cdn.intechopen.com/books/images_new/7811.jpg",editedByType:"Edited by",editors:[{id:"186919",title:"Dr.",name:"Martha",surname:"Peaslee Levine",slug:"martha-peaslee-levine",fullName:"Martha Peaslee Levine"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1591",title:"Infrared Spectroscopy",subtitle:"Materials Science, Engineering and Technology",isOpenForSubmission:!1,hash:"99b4b7b71a8caeb693ed762b40b017f4",slug:"infrared-spectroscopy-materials-science-engineering-and-technology",bookSignature:"Theophile Theophanides",coverURL:"https://cdn.intechopen.com/books/images_new/1591.jpg",editedByType:"Edited by",editors:[{id:"37194",title:"Dr.",name:"Theophile",surname:"Theophanides",slug:"theophile-theophanides",fullName:"Theophile Theophanides"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3161",title:"Frontiers in Guided Wave Optics and Optoelectronics",subtitle:null,isOpenForSubmission:!1,hash:"deb44e9c99f82bbce1083abea743146c",slug:"frontiers-in-guided-wave-optics-and-optoelectronics",bookSignature:"Bishnu Pal",coverURL:"https://cdn.intechopen.com/books/images_new/3161.jpg",editedByType:"Edited by",editors:[{id:"4782",title:"Prof.",name:"Bishnu",surname:"Pal",slug:"bishnu-pal",fullName:"Bishnu Pal"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3092",title:"Anopheles mosquitoes",subtitle:"New insights into malaria vectors",isOpenForSubmission:!1,hash:"c9e622485316d5e296288bf24d2b0d64",slug:"anopheles-mosquitoes-new-insights-into-malaria-vectors",bookSignature:"Sylvie Manguin",coverURL:"https://cdn.intechopen.com/books/images_new/3092.jpg",editedByType:"Edited by",editors:[{id:"50017",title:"Prof.",name:"Sylvie",surname:"Manguin",slug:"sylvie-manguin",fullName:"Sylvie Manguin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"371",title:"Abiotic Stress in Plants",subtitle:"Mechanisms and Adaptations",isOpenForSubmission:!1,hash:"588466f487e307619849d72389178a74",slug:"abiotic-stress-in-plants-mechanisms-and-adaptations",bookSignature:"Arun Shanker and B. Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"72",title:"Ionic Liquids",subtitle:"Theory, Properties, New Approaches",isOpenForSubmission:!1,hash:"d94ffa3cfa10505e3b1d676d46fcd3f5",slug:"ionic-liquids-theory-properties-new-approaches",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/72.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"22891",title:"Cell Therapy for Parkinson’s Disease: Status and Perspectives",doi:"10.5772/21203",slug:"cell-therapy-for-parkinson-s-disease-status-and-perspectives",body:'Idiopathic Parkinson’s disease (PD) is caused by progressive degeneration of melanin containing dopaminergic neurons in substantia nigra pars compacta in the upper brain stem. The loss of dopaminergic neurons results in a gradual decrease of dopaminergic input to the striatum leading to the cardinal symptoms rigidity, tremor, hypokinesia and occasionally postural instability.
One of the prospects for a curative treatment for PD is to replace the lost dopaminergic neurons by intracerebral transplantation. Grafting of fetal midbrain dopaminergic neurons into the dopamine-depleted striatum has thus emerged as an experimental therapeutic approach for PD. Preclinical and clinical trials have demonstrated that such fetal dopaminergic neurons have the potential to markedly improve motor function in animal models and PD patients. Over the last decades, approximately 400 PD patients have been grafted, and graft survival in the dopamine-depleted striatum, with substantial motor improvements, has been reported particularly in younger patients. However, looking across all the studies, where several different protocols and donor ages have been used, the symptomatic relief is inconsistent and not yet of a magnitude that would justify treatment at a large scale. Ethical concerns related to the use of human fetal brain tissue, shortage of suitable donor tissue and a poor survival of grafted dopaminergic neurons has stimulated the search for other reliable sources of donor material and development of applicable gene technological techniques for improving graft survival, differentiation and functional integration.
Expanded midbrain precursor cells, predifferentiated human embryonic stem cells or induced pluripotent stem cells as well as human neural stem cells and mesenchymal stem cells have been proposed as promising alternative sources of donor cells. In this chapter we will review current status and discuss crucial issues that remain to be resolved to develop cell replacement into an effective and safe therapy.
Conventional treatment of PD is symptomatic and includes pharmacotherapy, possibly combined with surgical deep brain stimulation (DBS). These symptomatic treatments are highly effective at managing the motor symptoms, especially in the early stages of the disease. However, they have limited capability to improve symptoms at more advanced stages, thus new therapeutic and restorative strategies, including the use of neuroprotective agents,
The observation of dopamine depletion in the striatum of PD patients (Carlsson, Lindqvist, and Magnusson 1957), led to development of the now classical L-dopa replacement therapy, with subsequent dramatic clinical benefit to virtually all patients. Medication with the dopamine precursor L-dopa results in effective improvements of motor symptoms, and it is still the most commonly used drug for treatment of PD - alone or in combination with other drugs acting primarily on the dopaminergic system. Unfortunately, L-dopa gradually loses its effect (typically after 5-7 years of L-dopa treatment) as the remaining dopaminergic neurons continue to degenerate and patients experience end-of-dose deterioration and start to fluctuate between states, where they are immobile called “off”-periods” and states where they are able to move called “on”-periods”. In addition, the treatment is coupled to further motor complications such as L-dopa-induced dyskinesias and often also psychiatric symptoms (Fahn 2006). This clearly underlines the need for development of new systemic pharmacological therapies or alternative treatment strategies.
In addition to L-dopa treatment, other drugs are used to stimulate the deteriorated dopaminergic neurotransmission, such as dopamine agonists and inhibitors of monoamine oxidase B and catechol-
Surgical procedures, such as thalamotomy or pallidotomy, and circuit inhibition by high-frequency DBS through electrodes implanted in the globus pallidus or the subthalamic nucleus have gained considerably attention as therapies for PD. In general, DBS is preferable to the prior ablative surgical methods since electrical stimulation is both reversible and programmable. Especially, stimulation in the subthalamic nucleus has shown to improve motor function and reduce dyskinesias and need for medication (Pahwa et al. 2006). Although ablative surgery and DBS eliminate or ameliorate certain symptoms of the disease, the long-term effect is not well known. DBS has been increasingly established in several clinical trials, but questions remain regarding the best timing of the procedure, the best anatomical target for stimulation, ways to avoid preoperative and postoperative adverse effects as well as which patients should be selected for the treatment (Morley and Hurtig 2010). Unfortunately, this treatment is also not restorative and cannot slow down or prevent disease progression, and most patients experience progressive worsening over time. Furthermore, DBS only treat a fairly specific set of symptoms (mostly, L-dopa induced dyskinesias and/or tremor) and has no effect on other clinical manifestations, such as postural instability.
Cell replacement therapy for treatment of PD is based on the idea that immature dopaminergic neurons, following transplantation and functional integration, can restore dopaminergic neurotransmission and exert long-lasting effects on motor symptoms. Based on data from animal experimentation, the current main focus is on elevating striatal dopamine levels rather than trying to reconstruct the relatively long nigrostriatal pathway.
Here we provide an overview of different cell types and tissues that have been used for grafting in PD - with emphasis on fetal ventral mesencephalic tissue, which has resulted in the greatest clinical benefits. This is followed by a discussion of future perspectives of cell replacement for PD, with particular focus on stem cell based strategies.
Ethical and immunological issues can be avoided by use of autografts for treatment of any disorder, including PD, making this strategy very attractive. The first clinical experiments with grafting to the brains of PD patients involved autografts of adrenal medullary tissue, which secretes dopamine among other catecholamines (Backlund et al. 1985; Lindvall et al. 1987; Drucker-Colin et al. 1988; Freed, Poltorak, and Becker 1990). These small open-label clinical trials caused initial enthusiasm, but have largely been abandoned since 1989 after failure in a number of clinical trials (Allen et al. 1989; Goetz et al. 1991). Some patients experienced modest effects for a limited period of time, and post-mortem studies showed poor survival of the grafted tissue (Hurtig et al. 1989; Kordower et al. 1991). A recent follow-up study, performed 16 years after adrenal medulla transplantation showed few surviving chromaffin cells and a complete absence of tyrosine hydroxylase (TH)-positive cells at the graft site, providing evidence of no long-term survival of adrenal medullary transplants (Kompoliti et al. 2007).
Autografts of sympathetic ganglion neurons, collected from the cervical or thoracic sympathetic chain, have also been considered as a source of donor cells for PD patients. Sympathetic ganglion neurons have been shown to express the enzymes aromatic amino acid decarboxylase and vesicular monoamine transporter 2, which are involved in production and transport of dopamine, both
A third approach has been autografts of carotid body cells, which normally secrete dopamine and divide in response to hypoxic stimuli (Espejo et al. 1998). Striatal transplantation of carotid body cells resulted in partial functional recovery in rat and primate models of PD (Espejo et al. 1998; Luquin et al. 1999). This led to a small clinical study (Arjona et al. 2003), where most patients experienced motor improvement seen as a reduction in their UPDRS “off”-score, however, there was no increase in [18F]-fluorodopa uptake in the transplanted striatum as seen by PET imaging. Furthermore, it was shown that the surviving number of dopaminergic neurons in the transplants was very low (Arjona et al. 2003). Thus, the reason for the motor improvements remains unclear.
In 1979, the first two successful attempts of transplantation with fetal ventral mesencephalic cells in animal models were reported (Perlow et al. 1979; Bjorklund and Stenevi 1979). These studies showed that rat fetal ventral mesencephalic tissue transplanted into rats with unilateral 6-hydroxydopamine (6-OHDA) lesions could reverse lesion-induced behavioral deficits. Furthermore, the grafted dopaminergic neurons innervated the striatum and were found to form synapses with host neurons. These initial and pioneering results initiated a series of studies in rodents examining the survival and functional capacity of dopaminergic neurons following grafting into different brain regions (Dunnett et al. 1983; Dunnett et al. 1981; Freund et al. 1985). Improvements were clearly seen when grafts were placed in the striatum, whereas attempts to graft into the substantia nigra, the ventral mesencephalic sub-region with dopaminergic cell body degeneration, showed survival of cells, but they did not innervate the striatum and had no significant functional effects (Dunnett et al. 1983). In 1986, human fetal ventral mesencephalic tissue was reported to survive transplantation into immunosuppressed, 6-OHDA lesioned rats and exert functional effects on motor behavior (Brundin et al. 1986; Stromberg et al. 1986). The best outcomes were seen for tissue derived from human fetuses, obtained at 5.5-8 weeks postconception. The results of these studies paved the way for the first systematic clinical transplantation trials with dopaminergic neurons to PD patients.
Since 1987, several so-called open-label trials (trials where small groups of patients receive transplants without the use of any control group or blinding procedure) have been performed. These initial trials have revealed that fetal human nigral neurons, taken at a stage of development when they have started to express their dopaminergic phenotype, can survive, integrate and function in the human brain. In 1990, the first study demonstrating survival and functional effects of grafted human ventral mesencephalic tissue in an immunosuppressed PD patient was published (Lindvall et al. 1990) and during the following years a wide number of open-label trials reported improved motor functions in the absence of medication and reduced time spend in the “off” phase (Madrazo et al. 1990; Brundin et al. 2000; Freed et al. 1992; Freed, Breeze, Rosenberg, Schneck, Wells, Barrett, Grafton, Huang et al. 1990; Freed, Breeze, Rosenberg, Schneck, Wells, Barrett, Grafton, Mazziotta et al. 1990; Lindvall et al. 1989; Lindvall et al. 1994; Peschanski et al. 1994). Furthermore, in some cases even reduced dyskinesias in the “on” state were seen (Freed, Breeze, Rosenberg, Schneck, Wells, Barrett, Grafton, Huang et al. 1990; Freed, Breeze, Rosenberg, Schneck, Wells, Barrett, Grafton, Mazziotta et al. 1990; Madrazo et al. 1990) and some patients were able to stop their antiparkinsonian medication. Imaging studies showed that the grafts gradually gave rise to improved striatal [18F]-fluorodopa uptake and few patients, who died of unrelated courses long time after surgery, had several thousand surviving dopaminergic neurons that innervated their striatum (Mendez et al. 2005; Kordower et al. 1995).
A major problem with transplantation of mesencephalic dopaminergic neurons in PD is that the outcome has varied dramatically between transplantation centers and also between patients treated at the same center essentially using the same procedure. Two main parameters are likely to be responsible for the mixed outcomes. First, differences between the PD patients regarding age, genetic background, stage of their disease, prior medication and precise neuropathological profile. The second issue is related to the surgery and post-grafting treatment such as numbers of cells being grafted, number and sites of injection, variation in surgical technique as well as tissue preparation (fresh versus stored tissue) and immunosuppression treatment (Bjorklund et al. 2003).
The greatest setback for the neural transplantation field in PD was the outcome of two double-blind placebo-controlled trials in the late 1990s (Olanow et al. 2003; Freed et al. 2001). The objective of these trials, funded by the National Institute of Health (USA), was to properly support the clinical benefits of the transplantation procedure seen in the open label trials. The first trial involved 40 PD patients between 34 and 75 years of age and with average disease duration of 14 years (Freed et al. 2001). Patients were randomly assigned to receive a transplant or undergo sham surgery. The human ventral mesencephalic donor tissue, obtained from 7-8 week old fetuses, was cultured for up to 4 weeks as “tissue strands”. Cultured tissue from two embryos was transplanted into the putamen on each side and no immunosuppression was used. Control patients received a sham-surgery with burr holes, but without penetration of the meninges. One year after transplantation there was no significant improvement in the transplant group (20% reduction in the motor part of the UPDRS as compared to the placebo group). However, when looking at the subgroup of younger patients (<60 years) a significant reduction of 30-35% was found. Though, subsequent analysis have suggested that the main determinant of this correlation was the preoperative L-dopa responsiveness rather than the age of the patient, as even older patients with good preoperative L-dopa responsiveness showed similar improvements (Bjorklund et al. 2003). Although the clinical benefits were modest and variable, PET scannings showed significant increase in [18F]-fluorodopa uptake in the putamen of the transplant as compared to the placebo group, and postmortem analysis showed dopaminergic neuronal survival and fiber outgrowth in the graft. However, the number of surviving dopaminergic neurons was lower than that reported for other patients with good clinical response to their transplants (Freed et al. 2001).
Another outcome and concern from this trial was the appearance of L-dopa-independent, graft-induced dyskinesias in 15% of the patients more than 1 year after surgery. The reasons for the limited clinical outcome and the induction of graft-induced dyskinesias remain largely unknown, but various factors have been suggested to be of critical relevance. For instance, the amount of grafted tissue was smaller than that of other more successful trials, which may explain the low recovery of dopaminergic neurons seen by postmortem analysis. Furthermore, the absence of immunosuppressive treatment may have compromised dopaminergic cell survival, as may the storage of the fetal tissue up to 4 weeks prior to transplantation.
The second double-blind placebo-controlled trial involved 34 patients with advanced PD, aged between 30 and 75 years (Olanow et al. 2003). Patients were randomly assigned to receive bilateral transplantation with either 1 or 4 donors per side or sham surgery. Solid ventral mesencephalic tissue was obtained from 6-9 week old fetuses and stored for 2 days prior to transplantation. All patients received immunosuppression (cyclosporine A) starting 2 weeks before the transplantation and continuing for up to 6 month after surgery. Two years after transplantation, no significant treatment effects were assessed by the motor component of the UPDRS in the “off” medication, but there was a tendency for an improved motor score for the 4-donor group. Moreover, no differences between groups in terms of the change in time spend in “on” without dyskinesias and in required L-dopa dose was found. However, subsequent analysis based on disease severity showed that patients in the 4-donor group with preoperative less severe disease did display significant improvements in their UPDRS motor scores. Also patients both in the 1 and 4-donor groups showed significant motor improvements compared to placebo at 6 and 9 month after transplantation, but this effect declined thereafter, which may be related to the withdrawal of the immunosuppressive therapy at this time point. In fact, the initial improvements were similar to that reported for some of the previous open label trials. PET scannings showed significant bilateral increase in striatal [18F]-fluorodopa uptake in both transplant groups as compared to the placebo group, with the 4-donor group displaying the greatest increase. Postmortem analysis also revealed good survival of dopaminergic neurons with relatively good innervations of the striatum, again with the 4-donor group showing the best results. However, as in the study by Freed et al. (2001), development of significant off-medication graft-induced dyskinesias were observed in 56% of the grafted patients 6 to 12 month after transplantation.
Thus, the results of these two double-blind placebo-controlled trials raised serious concerns about the utility and safety of fetal ventral mesencephalic transplants in PD patients. The main concerns related to the moderate efficacy of the transplants compared to previous open-label trials and to the development of graft-induced dyskinesias in a significant number of patients. The differences in the study design between the open-label trials and the placebo-controlled trials may contribute the the poor outcome of the placebo-controlled studies. However, the specific reasons remain largely unresolved as further discussed in the next section.
Several issues have been suggested as explanations for the inconsistencies of the transplantation trials using fetal ventral mesencephalic tissue, such as patient selection, tissue preparation, graft placement and the need for immunosuppressive treatment. So far there is no clear consensus as to whether one or all of these factors contribute. As a consequence of all these possible confounders a re-evaluation of the field of neural grafting for PD has been undertaken. First, the indications that patient selection may be an important factor come from the observations that the best results in the double-blind placebo-controlled trials were seen for patients with less severe disease and good preoperative response to L-dopa. Furthermore, there is also some evidence that older patients generally do less well (Winkler, Kirik, and Bjorklund 2005). Second, parameters such as the number and age of donor fetuses, surgical techniques applied and graft placement may all have affected the survival and functional integration of the grafted dopaminergic neurons. In the study by Freed et al. (2001) the method involved less tissue, stored for longer times, while the Olanow et al. (2003) study used tissue pieces, stored for a short period of time. Several studies have shown that a variety of issues in the preparation process are critical for the optimization of dopaminergic cell survival in the transplants and some of the factors used in the protocols from these trials may have had harmful effects on dopaminergic cell survival after transplantation. Third, immunosuppression is an issue. Even though the brain is considered an immunologically privileged site, the host immunesystem can respond to the graft. Previous animal experiments have shown that intracerebral allografts of fetal ventral mesencephalic tissue can survive for prolonged periods in the absence of any immunosuppression (Head and Griffin 1985). However, in cases where the donor and host differ immunologically on both major and minor histocompatibility antigens, the graft is likely to induce a long-lasting inflammatory response, accompanied by upregulation of class I and class II antigens on the grafted cells, sustained expression of immunological markers, and macrophage and microglial activation at the graft site (Hudson et al. 1994; Shinoda et al. 1995, 1996). The intensity of the immune reaction can increase over time, indicating that the immune cells observed in the brain after grafting are not stationary and inactive but rather provide an ongoing inflammatory process (Shinoda et al. 1995). Nonetheless, the major clinical transplantation centers have in some cases chosen not to immunosuppres the PD patients (Freed et al. 2001) or to use a mild treatment for only 6 month (Olanow et al. 2003). Lastly, the mechanisms behind the development of graft-induced dyskinesias are not fully understood. These dyskinesias differ in nature compared to the typical L-dopa-induced dyskinesias. The severity tend to correlate negatively with the [18F]-fluorodopa uptake in the striatum prior to transplantation, but it does not correlate with improvement in the UPDSC scores or daily medication needs after transplantation. Moreover, their appearance does not seem to relate to the severity of the preoperative L-dopa induced dyskinesias or the change in these after transplantation. Several factors have been suggested to cause the graft induced dyskinesias, such as inhomogeneous dopaminergic reinnervation of the host putamen (Ma et al. 2002), the presence of cells other than A9 dopaminergic neurons within the grafts, especially serotonergic neurons included in the grafts (Carlsson et al. 2007; Carta et al. 2007) and the graft size and placement in the striatum (Lane et al. 2006).
Thus, increased understanding of possible mechanism behind the disappointing results of the two double-blind placebo-controlled trials has led to initiation of a new clinical trial using fetal transplants for PD. This exciting project, called TRANSEURO, is funded by the 7th Framework Program of the European Commission and is a major collaboration between leading experts as clinicians, scientists, industrial partners, ethicists and patients’ representative in this field (http://www.transeuro.org.uk/index.html). The main goals of the project are to show that consistency and efficacy of dopaminergic cell replacement in PD can be improved by careful attention to tissue preparation and delivery, patient selection and immunosuppressive treatment as discussed above. Moreover, to show that dopaminergic cell replacement can be clinically efficacious in the absence of any troublesome graft induced dyskinesias in patients with mild PD and to develop a protocol that can serve as a template for all future clinical trials in the cell therapy field, including expected future stem cell-based therapies. The first patients are to be transplanted in the beginning of 2012. After that, a double-blind placebo-controlled trial will be performed at several centers in Europe and USA. The general idea is to try to push the field ahead, while techniques for development of suitable cells from human stem cells are being conducted (Holden 2009).
Recent post-mortem studies have shown that grafted dopaminergic neurons survive for up to 16 years in the brains of PD patients after transplantation (Mendez et al. 2008; Li et al. 2008; Kordower et al. 2008). These studies include in total 6 patients with long-term survival (9-16 years) after transplantation and all had experienced clinical benefits, though to a variable degree. In general, the grafts contained numerous TH-positive dopaminergic neurons with fibers innervating the host striatum. The grafts largely resembled those in patients who died 1.5-4 years after transplantation (Mendez et al. 2005; Kordower et al. 1996), though with lower numbers of TH-positive cells. Thus, these studies provide the first evidence of long-term survival of grafted dopaminergic neurons in PD. However, in two of these studies Lewy bodies and -synuclein aggregates were found in few of the grafted cells (Kordower et al. 2008; Li et al. 2008). Low levels of dopamine transporter was also found in some of the grafted cells, which had not been seen for patients who died 1.5 year after transplantation (Kordower et al. 2008). Thus, these observations suggest that the pathogenetic process in PD can affect the transplanted neurons. At the moment, it is unclear what the functional significance of these findings is, but it is important to note that the majority of the grafted cells appeared normal and healthy and even if the graft may start to degenerate after 10 years or more due to host to graft disease propagation, the therapeutic window for cell transplantation would still be wide enough to allow a significant clinical intervention.
Xenografting is transplantation of tissue between different species. Fetal porcine neural tissue has been considered the most suitable alternative source for transplantation into the human brain due to the ease of breeding and the similarity in brain size combined with a protracted gestational period, which may provide the basis for long-distance axonal growth after grafting. Another interesting perspective has been the potential development of non-immunogenic transgenic donor pigs. The ability of xenografted ventral mesencephalic tissue to survive and mediate functional benefits in animal models of PD (Brevig et al. 2001; Galpern et al. 1996; Huffaker et al. 1989) led to a clinical safety trial, where 12 PD patients received unilateral striatal transplants of porcine ventral mesencephalic tissue suspensions (Schumacher et al. 2000; Deacon et al. 1997). A significant reduction in UPDRS was reported for some patients, but there was no increase in [18F]-fluorodopa uptake at the transplant site, and a postmortem study of a patient who died of unrelated causes 8 month after transplantation showed that only around 650 TH-positive neurons out of 12 million transplanted cells had survived. This finding suggests a lack of trophic support of the grafted tissue. Furthermore, some lymphocyte infiltration into and around the graft was found even though the patient was immunosupressed with cyclosporine A (Deacon et al. 1997). A second double-blind placebo controlled trial involving 18 patients caused only moderate improvements in UPDRS scores in both transplant and sham surgery groups. However, these results have only been published in a press release in March 2001 (Wijeyekoon and Barker 2009).
Due to these disappointing results the clinical use of this approach is considered doubtful, especially as the use of xenogenic tissue deals with some additional issues as compared to allogenic grafts. First, there are the problems of increased graft rejection and second, there is the risk of spreading infection across the species barrier by porcine endogenous retroviruses (Sayles, Jain, and Barker 2004). Thus, further work will be required to decide if fetal porcine tissue is of clinical relevance.
Stem cells are defined as undifferentiated cells without mature, tissue-specific characteristics that are able to reproduce themselves by division into identical daughter cells. Moreover, in response to proper stimuli stem cells are able to produce more specific progenitor cells that can further differentiate into one or more functional cell types. Stem cells are considered to represent a very promising source of cells cell replacement therapy in a number of diseases, including PD, due to these key properties, namely, self-renewal and multipotentiality as well as the possibility to manipulate these cells
Dopaminergic neurons can be generated from stem cells of different sources (Fig. 1). Embryonic stem cells (ESCs) are isolated from the inner cell mass of the preimplantation blastocyst, and they have unlimited self-renewal capacity and are pluripotent, since they are
Illustration of different types of stem cells considered for cell replacement therapy in Parkinson’s disease.
able to generate cells of all three germ layers. Somatic or tissue-derived stem cells can be isolated from developing tissues of the fetus or in the newborn, juvenile or adult organism. Somatic stem cells have a more limited proliferation capacity than ESCs and are termed multipotent, typically being able to differentiate into the different cell types of one germ layer. Potential groups of stem cells for cell therapy for PD include ESCs, neural stem cells (NSCs), mesenchymal stem cells (MSCs) and more recently induced pluripotent stem (iPS) cells, which all will be discussed separately in this section.
The most important question, using stem cells as a therapy for PD, remains whether it is possible to generate a large number of cells with the capacity to survive and function as dopaminergic neurons following transplantation and to be sure that these stem cell derived grafts do not show adverse effects such as tumor formation or immune rejection (Table 1).
Generally, human ESCs are considered the most promising source of stem cells for cell therapy in PD as well as other diseases, since they have several advantages to somatic stem cells. First, most somatic stem cells are difficult to isolate and propagate, whereas ESCs are easily derived and are able to grow almost indefinitely in culture. Second, ESCs can be genetically manipulated by homologous recombination to correct a genetic defect, whereas somatic stem cells only can be genetically manipulated through the introduction of viral transgenes. Third, ESCs can be guided into becoming any type of cell in the body through specific culture conditions, whereas the differentiation potential of somatic stem cells is much more restricted. The major limitation is ethical issues regarding the use of fertilized eggs for derivation of ESCs.
The challenges in providing cells for replacement therapy for PD both lie in stimulating ESCs to form neurons and, afterwards to make these neurons differentiate into functional dopaminergic cells. Thus, several strategies have been used to differentiate ESCs into dopaminergic neurons in vitro. In 2000, two reports for the first time described the generation of midbrain dopaminergic neurons from mouse ESCs (Kawasaki et al. 2000; Lee et al. 2000). Kawasaki et al. (2000) used a co-culture strategy in which the ESCs were grown on a layer of bone marrow stromal cells (PA6) to induce neural differentiation and the generation of dopaminergic neurons. They named this neural inducing effect as stromal cell-derived inducing activity (SDIA). The study by Lee et al. (2000) was based on a five-stage protocol, based on the generation, and later differentiation of spherical aggregate structures called embryoid bodies and addition of different combinations of factors known to promote dopaminergic differentiation such as fibroblast growth factor 8 (FGF8), sonic hedgehog (Shh) and ascorbic acid. The co-culture system resulted in a yield of approximately 16% TH-positive cells (Kawasaki et al. 2000), whereas the five-stage protocol only resulted in around 5% TH-positive cells (Lee et al. 2000). In 2002, Kim et al. reported that 78% TH-positive cells could be generated
Human ESCs can also be induced to become dopaminergic neurons both in vitro and in vivo. As for the mouse ESCs the most promising strategy for the generation of dopaminergic neurons has been co-culture systems (Perrier et al. 2004; Zeng et al. 2004) as compared to the multiple-stage method (Carpenter et al. 2001; Zhang et al. 2001). In 2004, Perrier et al. reported a very successful protocol for the generation of dopaminergic neurons from human ESCs. In this protocol the human ESCs were co-cultured with bone marrow stromal cells and treated in a sequential manner with patterning and differentiation molecules, including FGF8, Shh, FGF2, brain-derived neurotrophic factor (BDNF), glial cell line derived neuroptrophic factor (GDNF), transforming growth factor (TGF)-β3, dibutyryl-cAMP, and ascorbic acid. This treatment resulted in a yield of 65-80% TH-positive cells out of total neurons. Moreover, the dopaminergic neurons expressed several midbrain dopaminergic markers, released dopamine, had TH-positive synaptic terminals, and showed the presence of depolarization-induced and tetrodotoxin sensitive actions potentials, indicating that these cells were truly functional midbrain dopaminergic neurons (Perrier et al. 2004). More recently, great efforts have been put into defining chemical conditions that enhance dopaminergic differentiation in order to get rid of feeder layers and co-culture that compromise clinical use (Iacovitti et al. 2007; Song et al. 2008). Interestingly, a study by Vazin et al. (2009) identified four factors secreted from mouse stromal PA6 cells that are often used as feeder cells in the co-culture system, and these factors greatly enhanced the generation of neurons including the dopaminergic phenotype from human ESCs when added to the medium.
Dopaminergic neurons derived from human ESCs have also been transplanted into rodent models of PD, but the number of surviving TH-positive cells has been very low, and many of the transplants have shown evidence of proliferating cells and teratoma formation (Ben-Hur et al. 2004; Park et al. 2005; Zeng et al. 2004). Hence, improving the survival of the grafted human ESCs is a major challenge that has to be overcome before clinical application of the cells is possible. Interestingly, Roy et al. 2006 found a significant improved generation of TH-positive cells (up to 67% of total cells counted), when the human ESCs were cultured according to a feeder-based protocol in which human midbrain astrocytes were used to induce dopaminergic differentiation. These cells induced a significant behavioural recovery when transplanted into the striatum of parkinsonian rats. The dopaminergic neurons were reported to survive for 8 weeks, however neural tissue overgrowth and neuroepithelial tumors were found (Roy et al. 2006). More recent studies, using longer differentiation periods have produced larger numbers of dopaminergic neurons in the transplants (Yang et al. 2008).
As described above, the use, growth and differentiation of ESCs are not without disadvantages, and the use of fertilized eggs raise ethical concerns and limitations. In order to use human ESCs in the clinic it is important to culture the ESCs in xeno-free systems, which have not been the case for several existing protocols. However, as discussed above this issue has started to be resolved by production of chemically defined medias. Other problems that need to be solved before clinical use are the low survival and maintenance of the transplanted human ESC-derived dopaminergic neurons, and in addition the high risk of teratoma formations or other kinds of uncontrolled cell growth such as tumors by residual undifferentiated cells. Moreover, the risk of immune rejection questions the safety of clinical application of human ESCs.
NSCs are multipotent stem cells derived from neural tissues, which have the ability to self-renew and give rise to cells restricted to the neuronal and glial lineages, namely neurons, astrocytes and oligodendrocytes. Such NSCs are found in the developing nervous system and in certain regions of the adult brain. One advantage of NSCs as compared to ESCs is that they are less likely to form tumors after transplantation, since they are not pluripotent and capable of unlimited proliferation, and they seem to be more genomically stable than ESCs (Maitra et al. 2005; Draper et al. 2004). Both ESCs and fetal or adult NSCs represent potential cell sources for therapy, which and will be described and discussed in the following paragraphs (Fig. 2).
A)
NSCs from the developing central nervous system proliferate in response to similar growth factors regardless of which part of the brain they originate. However, they are not equivalent to each other and seem to maintain certain region-specific properties, even after they have been cultured
As previously described (section 2.2.2), PD patients have been successfully transplanted with ventral mesencephalic tissue from embryos at different stages. However, tissue from several human embryos is required for each patient due to the poor survival of the grafted neurons, thus resulting in practical-logistic problems. To overcome this problem several groups have focused on the idea of expanding ventral mesencephalic tissue to reduce the number of fetuses required for transplantation of one patient. In 1998, Studer et al. isolated neural precursor cells from the rat ventral mesecephalon and successfully expanded these cells by use of the mitogen FGF2, resulting in a 10-fold increase in the total number of cells and a 3-fold increase in the number of dopaminergic neurons. When transplanted into the striatum of 6-OHDA-lesioned rats the cells induced functional recovery. However, despite these promising results the general survival of grafted dopaminergic neurons was only around 3-5% (Studer, Tabar, and McKay 1998). Subsequently, the proportion of TH-positive cells generated by this method was further increased by culturing the cells at physiologically low oxygen tension (Studer et al. 2000). Carvey et al. 2001 reported a generation of 20-25% TH-positive cells from rat embryonic ventral mesencephalic precursor cells by using a combination of the cytokines IL-1 and IL-11, leukemia inhibitory factor and GDNF. They further expanded these cells and found clones containing up to 98% TH-positive cells and these were selected for transplantation into the striatum of 6-OHDA lesioned rats. The grafts completely reversed the rotational asymmetry, however, as seen in the study by Studer et al. (1998), the survival of the differentiated cells was very poor (Carvey et al. 2001).
In order to enhance the generation of midbrain specific dopaminergic neurons as well as increase the survival of these cells after transplantation genetic modification is an attractive strategy. In an early study, overexpression of Nurr1 in an immortalized NSC line originally derived from the mouse cerebellum showed a robust generation of dopaminergic neurons when these cells were co-cultured with astrocytes of mesencephalic origin (Wagner et al. 1999). Rat forebrain precursors have been reported to differentiate into dopaminergic neurons after genetic modification to co-express Nurr1, Shh and Bcl-xL or Nurr1 and Mash1, and these cells also showed behavioral benefits after transplantation into 6-OHDA- lesioned rats (Park et al. 2006). Overexpression of Nurr1 in NSCs derived from the rat ventral mesencephalon have been shown to result in 5% TH-positive neurons (Kim et al. 2007), whereas co-expression of Nurr1 and Neurogenin 2, another transcription factor important for development of mesencephalic dopaminergic neurons, did not mediate additional positive effect on the yield of TH-positive cells, but increased maturation of the dopaminergic phenotype (Andersson et al. 2007). In contrast, another study did not find increased generation of dopaminergic neurons after retroviral induction of rat mesencephalic derived NSCs with Lmx1a, Msx1, Neurogenin 2 and Pitx3 (Roybon et al. 2008). Single expression of each of these genes was not enough to promote dopaminergic differentiation and dual overexpression of Lmx1a and one of the other transcription factors also failed to generate dopaminergic neurons. The authors suggest that NSC harvested from this rather late (embryonic day 14.5) stage of development have lost their potential to be driven into a specific neuronal phenotype, thus NSC from a earlier time point or ESC may be better candidates for generation of dopaminergic neurons (Roybon et al. 2008).
Initial attempts to expand human NSCs from the developing mesencephalon only generated low numbers of dopaminergic neurons, which was also seen after transplantation into 6-OHDA-lesioned rats (Svendsen et al. 1997). Subsequently, an increased yield of dopaminergic neurons was found by culturing the human NSCs at low oxygen tension with further induction of differentiation by IL-1, IL-11, leukemia inhibitory factor and GDNF, but survival and possible
Another approach to obtain large numbers of human dopaminergic neurons for transplantation is to generate immortalized cell lines by genetic modification, thus such cell lines offer a theoretically unlimited source of specific NSCs. Some NSC lines have shown to generate around 20% TH-positive cells (Paul et al. 2007; Lotharius et al. 2002), but when these cells were transplanted into immunosuppressed 6-OHDA-lesioned rats they either died or loose TH expression (Paul et al. 2007). In order to enhance dopaminergic survival further genetic modifications can be added, such as overexpression of Bcl-xL, an anti-apoptotic protein stimulating commitment and survival of dopaminergic neurons (Liste, Garcia-Garcia, and Martinez-Serrano 2004; Krabbe et al. 2009). Such immortalized cells serve as important model cell lines or tools for basic stem cell research, but several safety issues have to be resolved if such cell lines should be considered for clinical use.
The human brain is traditionally classified as a non-renewable organ unable to replace damaged or degenerated cells. Neurogenesis in the adult rat brain was first described in the early 1960s by Joseph Altman (Altman and Das 1965), but general acceptance of this neurogenesis was not made until the early 1990s (Reynolds and Weiss 1992). One major advantage of using NSCs from the adult brain compared to those from the embryonic brain is that it would abolish all ethical concerns regarding the use of embryonic tissue.
In the adult mammalian brain NSCs are mainly found in the subventricular zone (SVZ) of the lateral ventricles (Lois and Alvarez-Buylla 1994; Morshead et al. 1994) and the subgranular zone of the hippocampal dentate gyrus (Bayer, Yackel, and Puri 1982; Palmer, Ray, and Gage 1995). From the SVZ, neuroblasts migrate a long distance anteriorly, through the rostral migratory stream, to their final destination in the olfactory bulb, where they mature into local interneurons as reported both in rodents (Lois and Alvarez-Buylla 1994) and in humans (Curtis et al. 2007). Newly generated cells in the subgranular zone migrate to the granular layer of the dentate gyrus, where they replace degenerated neurons and extend projections to the CA3 area of the hippocampus (Bayer, Yackel, and Puri 1982). Several studies have shown that neurogenesis also occur, although at much lower levels, in other areas of the adult mammalian nervous system, such as the cerebral cortex (Palmer et al. 1999), hypothalamus (Markakis et al. 2004), septum (Palmer, Ray, and Gage 1995), retina (Tropepe et al. 2000), optic nerve (Palmer et al. 1999), spinal cord (Weiss et al. 1996), and more debatable in the substantia nigra harbouring the dopaminergic neurons that degenerate in PD (Zhao et al. 2003). As indicated, some controversy remains in relation to the substantia nigra since other research groups have not been able to replicate some of these results (Lie et al. 2002; Frielingsdorf et al. 2004). Lie et al. (2002) found no evidence of either newly generated dopaminergic in the adult rat substantia nigra or neurons of any type
So far, attempts to develop dopaminergic neurons from NSCs from adult tissue have only been moderately successful both
An alternative strategy is to stimulate endogenous NSCs to differentiate into dopaminergic neurons either in the striatum or the substantia nigra. So far attempts to stimulate the development of new neurons in the 6-OHDA-lesioned rats striatum have not been successful. Some studies have shown that TGF can stimulate neurogenesis and migration to the striatum, but none of these cells were of dopaminergic or other neuronal phenotypes (Cooper and Isacson 2004; de Chevigny et al. 2008). Ideally, stimulation of neurogenesis in the substantia nigra could reconnect the basal ganglia circuitry and hence increase functional recovery in PD. However, although there might be NSCs in the adult substantia nigra (Zhao et al. 2003) it is only a very small pool of cells insufficient to replace the dopaminergic neuron loss during progressive PD. Moreover, even if it is possible to stimulate neurogenesis in the substantia nigra lack of long-distance axonal growth, along the degenerated nigrostriatal projections, remains a very challenging problem.
From an immunological and ethical prospective it would be ideal if stem cells could be harvested from, for instance, the patient’s own bone marrow and then be used to generate neurons for transplantation. The adult bone marrow contains at least two kinds of stem cell populations: hematopoietic stem cells and mesenchymal stem cells (MSCs) also called bone marrow stromal cells. Hematopoietic stem cells continually repopulate the circulation by differentiating into erythroid, myeloid, and lymphoid lineages, whereas MSCs give rise to mesenchymal derivatives, including osteocytes, chondrocytes, adipocytes and myocytes (Pittenger et al. 1999). MSCs are found only in low numbers in the bone marrow (around 1 MSC per 100 mononuclear marrow cells). They can be purified, from other cells in the bone marrow, on the basis of their ability to adhere to plastic surfaces (Reyes et al. 2001). MSCs are like other stem cells capable of self-renewal, but it has been proposed that self-renewal is less crucial for the physiology of mesenchymal tissue as are multipotentiality and phenotypic flexibility, which indicates that commitment and differentiation are reversible in response to environmental cues. MSCs display the ability of interconversion from one cell type to another at a later differentiation stage than that of other multipotent stem cells (Park, Oreffo, and Triffitt 1999; Beresford et al. 1992). One reason for this potential could be that it is necessary for bone modelling and remodelling (Bianchi et al. 2001).
Several studies provide evidence that MSCs can be induced to overcome their mesenchymal fate and break the barrier of germ layer commitment by transdifferentiation into cell types of other germ layers (Krabbe, Zimmer, and Meyer 2005). In fact, it has been proposed that MSCs have a neural predisposition, since they express neural markers such as neuron specific-enolase, neuronal nuclei, nestin, glial acidic fibrillary protein and TH at basal levels (Blondheim et al. 2006). However, both the transdifferentiation potential of MSCs and the indication that these cells should be biological neurons are controversial. Evidence of a “neuronal” MSC is considered weak and what seems to be transdifferentiation may be explained by a stress response causing a rapid disruption of the actin cytoskeleton with cell shrinkage as a result (Neuhuber et al. 2004) or by cell fusion, in which MSCs have fused with other cell types rather than switching lineage identity (Lu, Blesch, and Tuszynski 2004; Terada et al. 2002).
Nevertheless, efforts are still being made to generate functional neuronal cells from MSCs, and at the beginning of the millennium several research groups have reported that it was possible to induce both human, rat and mouse MSCs to differentiate into neuron-like cells
If MSCs are going to be used as a cell source for cell therapy of PD it is important to differentiate these cells into functional dopaminergic neurons, which have been investigated by different strategies. Several groups have induced MSCs by adding cocktails of extrinsic factors to the culture medium (Barzilay et al. 2008; Hermann, Maisel, and Storch 2006; Tatard et al. 2007; Trzaska, Kuzhikandathil, and Rameshwar 2007; Trzaska et al. 2009), others by co-culturing of the MSCs with specific cell types (Jiang et al. 2003), or by genetic manipulation of the cells (Dezawa et al. 2004). From a therapeutically point of view the first mentioned strategy has some advantages, since the cells are not transformed or co-cultured with other cell-types making the cell transplantation more safe. In 2007, Trazska et al. found an effective protocol for dopaminergic differentiation of MSCs in which a cocktail of FGF8, Shh and bFGF were added to the medium. About 67% of the cells expressed the dopaminergic marker TH along with other dopaminergic markers. Moreover, the cells secreted dopamine, but without showing further evidence of being functional mature dopaminergic neurons, and hence they were called dopaminergic progenitors (Trzaska, Kuzhikandathil, and Rameshwar 2007). These results were supported by Barzilay et al. (2008), who tested 20 different protocols for dopaminergic induction of MSCs. They found that the most significant upregulation of TH expression was obtained using BDNF either alone or in combination with GDNF, TGF-β3 and retinoic acid. However, as described by Trzaska et al. (2007), the TH-positive cells did not show mature functional dopaminergic neuron characteristics (Barzilay et al. 2008). In 2009, Trzaska et al. investigated potentially factors that could stimulate the dopaminergic maturation of the cells and found that the MSC-derived neuronal cells showed robust upregulation of tropomyosin-receptor-kinase B beginning at day 9 of the induction. One factor which is known to be involved in the maturation of dopaminergic neurons and which binds to this receptor is BDNF (Baquet, Bickford, and Jones 2005). Hence, they added BDNF to the medium after 9 days of induction and found generation of cells that elicited spontaneous post-synaptic current and secreted dopamine in response to Ca2+-dependent depolarization. These findings show that the MSC-derived dopaminergic neurons can mimic the physiology of native neurons. Moreover, BDNF treatment resulted in KCl-induced depolarization and enhanced dopamine release. They also investigated whether the BDNF-treated cells responded to neurotransmitters such as GABA, acetylcholine and glutamate and found that the BDNF-treated cells responded to both acetylcholine and GABA, but not glutamate. However, the way they responded to GABA and the lack of response to glutamate indicates that these cells were still developing and not fully mature (Trzaska et al. 2009).
All the studies mentioned above indicate that generation of dopaminergic neurons from MSCs may be possible, but to candidate as donor cells for PD, it still remains to be elucidated if the cells contain the entire dopaminergic machinery present in functional dopaminergic neurons
For a long time ESCs have been considered the most promising source of cells for future cell replacement therapy in PD. However, ethical concerns regarding the use of human embryos and the possibility of immune rejection due to immunological incompatibility between patient and donor ESCs may limit their use. To overcome these problems scientists have worked on the development of pluripotent stem cells from adult somatic cells, involving genetic changes (reprogramming) of the somatic cell nucleus. Until recently, reprogramming of cells involved cloning of cells by somatic cell nuclear transfer, where the nucleus in an oocyte is replaced with the nucleus from an adult somatic cell (Wilmut et al. 1997) or by fusion of an adult somatic cell with an ESC (Cowan et al. 2005). However, besides being both time consuming and technical difficult this kind of reprogramming still requires the use of human oocytes or ESCs and hence do not solve the ethical problems.
In 2006, Takahashi and Yamanaka reported for the first time that it was possible to reprogram adult mouse fibroblasts to pluripotent stem cells by retroviral transduction with the four transcription factors Oct3/4, Sox2, c-Myc and Klf4, which are highly expressed in ESCs (Takahashi and Yamanaka 2006). The resulting so-called induced pluripotent stem (iPS) cells share several properties with ESCs, including morphology, growth properties and pluripotency, defined by their ability to form teratomas
The similarities of iPS cells to ESCs, and the fact that these cells can be generated from the patient’s own cells, make them very attractive candidates for cell-based therapy. However, before iPS cells can be used in the clinic there are several issues that need to be resolved. First, it is extremely important to optimize the procedure for reprogramming of the somatic cells. As described above, many groups have generated iPS cells by use of retroviral vectors. Since retrovirus integrates randomly in the DNA it may alter the differentiation potential or even induce malignant transformation of the iPS cells. Moreover, most research groups have used c-Myc as one of the reprogramming factors and since c-Myc is a proto-oncogene, its reactivation could give rise to transgene-derived tumor formation. In one study 20% out of 121 mice derived from an iPS cell line developed tumors. In these tumors, retroviral expression of c-Myc, but not Oct3/4, Sox2, or Klf4 was reactivated (Okita, Ichisaka, and Yamanaka 2007). Hence, recent studies have focused on developing safer reprogramming strategies, for example, by generation of iPS cells without using the c-Myc oncogene. In 2008, Nakagawa et al. generated iPS cell lines from both mouse and human fibroblasts without the use of c-Myc. They found that it was possible to generate cells expressing ESC markers, and that the induction of the fibroblasts to iPS cells was more specific, since a lower number of non-iPS cells were generated. However, efficiency of the generation process was substantially reduced with the omission of c-Myc. They also examined the tumourigenicity in mice derived from these cells and found that omission of the c-Myc retrovirus significantly reduced the risk of tumorigenicity in chimeras (Nakagawa et al. 2008). Other studies have also examined different combinations of transcription factors, and of the original four transcription factors, Oct3/4 is the only one that cannot be replaced by other transcription family members and have been required in every reprogramming strategy in both mouse and human cells. Other strategies have been to generate iPS cells using integration systems such as plasmids (Kaji et al. 2009) and transposons (Woltjen et al. 2009), which allow removal of these systems after reprogramming. Moreover, iPS cells have also been generated without genomic integration using nonintegrative adenoviral vectors (Zhou and Freed 2009; Stadtfeld et al. 2008), repeated plasmid transfection with or without the use of small molecules (Okita et al. 2010; Okita et al. 2008; Yu et al. 2009) and just addition of recombinant proteins (Zhou et al. 2009; Kim et al. 2009). Although, these methods are not yet as efficient as the retroviral approach, they have clearly shown that random DNA mutagenesis is not a requirement for reprogramming and give hope for the development of clinically applicable iPS cells free of viruses and transgenic integration.
Interestingly, a recent publication have shown a method for direct reprogramming of fibroblasts into neurons, avoiding generation of undifferentiated cells and their following differentiation (Vierbuchen et al. 2010). They started from a pool of nineteen neural-lineage specific transcription factors and identified a combination of only three factors (Mash1, Brn2 and Myt1l) that were sufficient to convert mouse fibroblasts into functional neurons in vitro. Such induced neurons clearly have some advantages to iPS cells, since they avoid generation of pluripotent cells that can give rise to tumors. In this study the induced neurons mainly gave rise to GABAergic neurons after differentiation, but their regional identity is still unclear (Vierbuchen et al. 2010). This strategy offers new perspectives to the reprogramming field and future studies need to determine if certain cell types are more useful in generation of specific cells for replacement strategies and if it is necessary to reprogram cells all the way back to pluripotent stem cells.
Advantages | Disadvantages | |
ESCs | Unlimited proliferation capacity Potential to generate any cell type (pluripotent) Generation of stem cell banks | Risk of teratomas (heterogenous composition) Time demanding/complex differentiation into dopaminergic neurons Risk of immune rejection Ethical issues |
NSCs | Restricted differentiation potential (multipotent) Low risk of tumor formation | Limited proliferation capacity Reduced neuronal differentiation capacity following long-term proliferation Risk of immune rejection Ethical issues (fetal NSCs) |
MSCs | Easily harvested Possibility of generating patient specific cells No ethical concerns | Differentiation into “truly” functional dopaminergic neuron still uncertain |
iPS cells | Unlimited proliferation Potential to generate any cell type (pluripotent) Generation of stem cell banks Possibility of generating patient specific cells No risk of immune rejection No ethical concerns | Risk of teratoma (heterogenous composition) Risk of tumor formation (viral transduction) Time demanding/complex differentiation into dopaminergic neurons Expensive procedure |
Overview of advantages and disadvantages of different types of stem cell for cell replacement therapy in Parkinson’s disease.
The therapeutic potential of human iPS cells for cell-based therapy of PD relies on efficient differentiation of iPS cells into functional midbrain dopaminergic neurons. Several groups have worked on generation of dopaminergic neurons from iPS cells
Interestingly, the iPS cell technology also provides the basis for development new disease models, since they can be generated from patients with specific diseases. Although, iPS cells can be used for both sporadic and genetic diseases, they might be of particular advantage for diseases with a solid genetic background and/or which occur early in development. Some studies have generated iPS cells from patients suffering from sporadic PD (Park et al. 2008; Soldner et al. 2009). Soldner et al. (2009) developed dopaminergic neurons from iPS cells derived from patients with PD as efficiently as iPS cells from healthy individuals and did not report any phenotypic differences, thus the disease derived cells did not show any specific features of PD
Instead of acting as a source of cells for neuronal replacement an alternative use of stem cells for transplantation is as so-called “cell factories” releasing neurotrophic and neuroprotective factors. Several neurotrophic factors have been shown to stimulate survival and/or differentiation of nigral dopaminergic neurons
NSCs are considered very suitable for
Another way to overcome problems of host immunoresponses when using allografts, is the development of new materials to encapsulate transplanted cells, thereby serving as a biological shield to prevent immune rejection and eliminate the need for immunosuppression. The encapsulating material should allow inward diffusion of nutrients to the transplanted cells and at the same time permit outward secretion of trophic factors. Besides protection from the host immune system, these capsules have the advantage that they can be removed for safety reasons or for renewal of cells. Several studies have reported successful delivery of GDNF from encapsulated cells (Kishima et al. 2004; Tseng et al. 1997; Sagot et al. 1996; Ahn et al. 2005). Kishima et al. (2004) found a transient recovery in motor function after intraventricular infusion of encapsulated GDNF-producing cells in MPTP lesioned baboons, however no neuroprotection against the toxin was found. The lack of neuroprotective effect may be due to the intraventricular placement of the capsules resulting in inefficient passage of GDNF to the striatum, thus better graft sites should be used. Furthermore, they reported GDNF release and survival of encapsulated cells for more than 1 year after transplantation (Kishima et al. 2004).
Delivery of neurotrophic factors by co-grafted genetically modified stem cells or cell lines may also serve as a useful tool for stimulation of functional integration and protection of grafted dopaminergic neurons from any source. In one study, Ahn et al. (2005) tested such a strategy by co-grafting an encapsulated cell line overexpressing GDNF with human fetal mesencepahlic tissue into 6-OHDA lesioned rats, leading to increased fiber outgrowth in areas between the capsules and the grafts. This result indicates that continuous delivery of GDNF or other important neurotrophic factors via encapsulated genetically modified cells could further optimize neural transplantation as a therapy for PD.
Neural transplantation has emerged as a potential therapy for Parkinson\'s disease (PD). In experimental studies based on animal models and PD patients, various sources and types of donor cells have been investigated for their potential applicability. Clinical studies performed during the 1980s and 1990s, where dopaminergic neurons derived from human fetal brain tissue were transplanted into striatum of patients with PD, provided proof-of-concept that long-lasting therapeutic benefits can be achieved. Subsequent studies, in particular two double-blind placebo-controlled trials, showed variable and mostly disappointing results. They also revealed that some patients develop graft-induced dyskinesias as side effects. Thus, while nigral transplants clearly work well in certain PD patients, the technique needs refinement before it can successfully be applied on a large series of patients. This optimization includes patient selection (age, medical history, response to L-dopa), trial design, origin and preparation of donor cells, immunosuppression, and surgical techniques for successful functional outcome and avoiding unwanted side effects. Hopefully, the TRANSEURO project will provide some of this essential knowledge and as such contribute to the development of a standardized, efficient and safe protocol that can serve as a template for clinical trials, including expected future stem cell-based trials for PD. However, before such a stem cell therapy can be initiated, also a number fundamental biological issues need to be taken into consideration. Embryonic stem cells (ESCs) and the newly developed induced pluripotent stem (iPS) cells seem to have the greatest potential to generate large numbers of dopaminergic neurons, but the use of these cell types is associated with a risk of tumor formation due to potentially remaining undifferentiated cells in the donor cell preparations. Moreover, using ESCs are related to ethical and immunological concerns. IPS cells and mesenchymal stem cells have the prospect of being made patient specific overcoming the risk of immune rejection, and they are not affiliated with ethical problems. So far it has been difficult to generate large numbers of dopaminergic neurons from neural stem cells, but these cells have a more straightforward differentiation pathway to form midbrain specific dopaminergic neurons, and they are not tumorigenic. Independent of the type of stem cell in question, it will be challenging to develop a differentiation protocol leading to “truly” functional dopaminergic projection neurons with midbrain characteristics without still having undifferentiated cells in the preparation.
BDNF, brain-derived neurotrophic factor; DBS, Deep brain stimulation; ESC, embryonic stem cell; FACS, Fluorescence-activated cell sorting; FGF, fibroblast growth factor; GDNF, glial-derived neurotrophic factor; 6-OHDA, 6-hydroxydopamine; iPS, induced pluripotent stem cell; MPTP, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; MSC, mesenchymal stem cell; NSC, neural stem cell; SDIA, stromal cell-derived inducing activity; PD, Parkinson’s disease, PET; Positron Emmision Tomography; Shh, sonic hedgehog; SVZ, subventricular zone; TGF, transforming growth factor; UPDRS, unified Parkinson’s disease rating scale.
Globally, there is an increase in the prevalence of non-communicable diseases such as Type 2 Diabetes Mellitus, cancer, hypertension, other cardiovascular diseases and stroke. Most of these illnesses are related to a modification in the lifestyle worldwide costs of healthcare leading to morbidity and mortality are diseases linked to environmental factors and lifestyle modification [1]. There has been a steady increase worldwide in the prevalence of non-communicable diseases to an alarming rate including diabetes mellitus which is becoming an epidemic [2, 3, 4] as this increase has been on for the past 20 years [5, 6, 7]. According to the International Diabetes Federation (IDF), it is estimated that 387 million adults are diabetic with either type 1 or type 2 diabetes mellitus [3] and this number is predicted to rise to 392 million by 2035 [3, 8]. This predicted increase is due to globalization and urbanization [2]. Urbanization is affected by modifications in lifestyle with physical inactivity and sedentary lifestyle from various epidemiological and interventional studies have revealed that the majority of chronic illnesses such as diseases that affect the cardiovascular system such as hypertension, cancer and Type 2 Diabetes Mellitus result due to lifestyle behavior and habits that are caused by improper eating habits, eating unhealthy foods, and lack of physical activity [9, 10, 11]. In primary and specialist health facilities, the majority of the consultations are related to highly preventable lifestyle.
Lifestyle modification is the first line of treatment in the management of non-communicable diseases [12, 13]. The commonest form of diabetes mellitus affecting 90% of diabetics is Type 2 Diabetes Mellitus. Diabetes mellitus is an economic and health burden to the sufferer and health systems as it also affects the quality of life especially when complications occur [2, 4, 8, 9, 14].
Diabetes mellitus is a risk factor for cardiovascular disease, a common cause of blindness due to diabetic retinopathy, amputation of the lower limb following diabetic neuropathy and diabetic foot ulcer and other life-threatening complications such as end-stage kidney disease (ESKD) [9, 15, 16]. Globally, diabetes mellitus is the second leading cause of blindness and renal disease [17]. Therefore it is important to prevent diabetes mellitus as it causes loss of working hours due to the impact they have on the economy and the individual. This is worst in the low and middle-income countries with the poor healthcare system and lack of health insurance for the entire populace where people have to pay out of pocket when seeking healthcare.
Diabetes mellitus is a chronic non-communicable metabolic disease in which the plasma glucose is elevated [12], characterized by insulin resistance and deficiency in insulin secretion and it may be acquired or hereditary [17, 18]. Obesity and overweight are risk factors for diabetes mellitus [17]. This is because insulin resistance and metabolic syndrome are promoted by obesity and overweight [8, 17]. For the primary prevention of diabetes mellitus, a 5-10 kg weight loss is recommended [6, 8].
Sensitivity to insulin and glycaemic control is improved by engaging in moderate weight loss and increased physical activity [6]. Obesity is a risk factor for diabetes mellitus [6]. Ignoring lifestyle medicine leads to an increased workload on the healthcare system. Globalization and adaptation of the Western lifestyle are some of the reasons for the increasing numbers of chronic diseases including Type 2 Diabetes Mellitus. Making good choices in lifestyle can significantly help in lowering the risk of these chronic diseases as most of the risk factors for these diseases are related to lifestyle behavior [2].
The history of lifestyle is very important in history taking [7]. The component of lifestyle medicine which promotes weight loss and prevents obesity is essential in the management and prevention of diabetes mellitus [8, 19, 20]. Therefore diabetes mellitus can be prevented by maintaining an ideal weight, therefore, modification in lifestyle does not only prevent diabetes mellitus but also prevents other non-communicable diseases [3, 8, 21].
This is review article on the role of lifestyle medicine in the management of Type 2 Diabetes Mellitus. A search was done using Google scholar, and PubMed using the key words lifestyle medicine and diabetes, the role of the pillars of lifestyle and management of Type 2 Diabetes Mellitus. Articles that highlighted the management of Type 2 Diabetes Mellitus using hypoglycaemic agents were excluded in this study.
Lifestyle medicine is a relatively new medical specialty yet to be established in most countries. Lifestyle medicine has been defined by various scholars. Lifestyle medicine is the use of interventions and integration of lifestyle practices within conventional medicine to lower the risk of disease. It serves as an adjunct to the management of illnesses [22, 23]. The practice of lifestyle medicine is evidence-based in scientific research and it addresses the root and underlying causes of diseases by empowering individuals with life skills and knowledge through a behavioral change in making healthy choices [24]. In this new medical discipline, it uses daily habits and practice impacts on both the prevention and treatment of diseases to improve the overall health of the individual in conjunction with both pharmaceutical and surgical therapy [3, 25]. All pharmaceutical agents have side effects as most drugs are metabolized in the liver and excreted by the kidneys. Hence it is very important to prevent them like diabetes mellitus. The Canadian Academy of Lifestyle Medicine defines lifestyle medicine as an evidence-based branch of medicine in which there is a comprehensive change in lifestyle including nutrition, physical activity, stress management, social connectedness and exposure to harmful environmental factors [26]. Lifestyle medicine is used to prevent and treat lifestyle-related diseases but it does not tell patients to abandon and stop their medications.
Lifestyle-related diseases (LRD) are illnesses in which lifestyle factors significantly influence the pathophysiology of the disease as there can be a significant improvement in the prevention and treatment of the disease following a change in the aetiological factors. Travel medicine and sports medicine, lifestyle medicine is a novel branch in the clinical practice of medicine [8] but it is gaining grounds due to its benefits. The prevention and reversal of chronic diseases linked to lifestyle can be done using evidence-based lifestyle therapeutic approaches. Lifestyle interventions affect physical and mental health positively, including a better quality of life [13]. The focus of lifestyle medicine programmes in the management of diabetes mellitus is to change the eating habits and physical activity behavior, especially in obese patients with type 2 diabetes mellitus is very important to control symptoms and it reduces the risk of cardiovascular-related morbidity and diabetic complications [27].
The components of lifestyle medicine are interventions that when they are practised lead to improvement in health and overall wellbeing. The modalities of lifestyle medicine are (Figure 1) [3, 13, 28]:
Increased physical activity and exercise.
Stress management.
Healthy eating by promoting consumption of whole plant-based diet.
Adequate sleep and good sleep hygiene.
Avoid consumption of tobacco and alcohol.
Increased mental and emotional wellbeing by having good social connectedness.
Courtesy American College of Lifestyle Medicine.
All the components of lifestyle medicine are important and play necessary roles in the prevention of Type 2 Diabetes Mellitus and management of Type 1 & 2 Diabetes Mellitus. This is because Type 1 Diabetes Mellitus has a strong relationship with genetics but lifestyle modification guides its management in the long-term to prevent diabetic complications such as diabetic neuropathy, retinopathy including diabetic foot ulcer. This is very important as it affects the overall wellbeing of the individual especially in developing countries where amputees are shamed and have general poor wellbeing and economic power. Type 2 Diabetes Mellitus can be prevented through modification in lifestyle by healthy living on a whole plant-based diet, prevention of obesity by weight control, having good sleep hygiene and avoiding unnecessary stress as much as possible [8, 12, 19]. This is because the risk factors of diabetes mellitus are related to modifiable lifestyle such as obesity [14]. The practice of lifestyle medicine is cost-effective in the management and prevention of diabetes mellitus because no special equipment is really necessary as what is involved is to be disciplined which has to be enforced by individuals on themselves [14]. Good healthy eating of a whole plant-based diet and increased physical activity is aimed at increasing energy uptake, reducing energy intake in food thereby preventing overweight and obesity which is a key risk factor for Type 2 Diabetes Mellitus and gestational diabetes mellitus [6]. Evidence from research has shown that remission of Type 2 Diabetes Mellitus with bariatric surgery can occur following intensive interventions in lifestyle but with few untoward adverse effects [11].
According to the American College of Lifestyle Medicine [11]:
Significant clinical improvement in patients with type 2 diabetes mellitus can occur following adequate intensive interventions in modifications of lifestyle.
Consumption of a whole plant-based diet in addition to participating in moderate exercise can lead to remission of diabetes mellitus and should be added to the optimal treatment of diabetes mellitus.
Lifestyle modification is also important in the prevention of pre-diabetes Mellitus before it progresses to diabetes mellitus [3]. In the Heart of New Ulm (HONU) Project, the heart screening programme showed that a decline in lifestyle modification especially increased body weight (overweight and obesity) and consumption of alcohol as well as a reduction in the consumption of fruits and vegetables over two years is associated with a higher incidence of metabolic syndrome including diabetes mellitus [11].
The result of this project showed a strong association between body mass index and metabolic syndrome [11]. In another study conducted in Nepal, there was a statistical relationship between type 2 diabetes mellitus and hypertension, dyslipidaemia, alcohol and tobacco use [14]. All these are diseases related to harmful healthy habits which can be prevented by modification in lifestyle. Evidence from other research has shown that remission of type 2 diabetes mellitus is possible with non-pharmacological interventions which include lifestyle modification that translates to the practice of lifestyle medicine [8, 11], increasing physical activity in the form of exercise and engaging in healthy dietary habits and reduction in weight is the primary goal of prevention of Type 2 Diabetes Mellitus [11].
Modification in lifestyle is the first line of management of diabetes mellitus. Weight loss is necessary for Type 2 Diabetes Mellitus and hypertension related to obesity. Exercise and healthy eating are necessary to lose weight and there are some of the pillars lifestyle medicine [29]. The reduction in weight is important as a preventive measure of cardiovascular disease and non-communicable disease as obesity serves as a risk factor for these diseases. The modification in lifestyle required for the management of diabetes mellitus are Medical Nutrition Therapy (MNT), Diabetes Self-Management Education and Support (DSMES), physical activity, cessation of the use of tobacco and counseling [30]. The results of the study conducted by Johansen et al. [31] in which 98 participants were randomized. There was a change in the level of glycosylated hemoglobin (HbA1c) from 6.65 to 6.34% in the group where there was an intervention in the modification of their lifestyle, there was a reduction in the dose of oral hypoglycaemic agents in 73.5% of the study participants [31].
Stress management is one of the pillars of lifestyle medicine. Stress can be defined as the response the body makes to any demand that is made on it. Being a diabetic is stressful already and diabetes mellitus is also stressful to the body; the worst is when there are diabetic complications. During stress, several hormones are released such as cortisol and other hormones that mobilized energy [32]. These hormones lead to hyperglycaemia as stress affects the endocrine system leading to changes in the mechanism of metabolism of glucose. Chronic exposure to stress has several deleterious effects on the body [33]. The rise in the blood glucose following stress is not associated with physical stress alone but with any form of stress including emotional and psychosocial stress [34], which may be experienced daily.
There is an undiagnosed and underestimated incidence of depression, anxiety, the stress in diabetics [32], and there is a correlation between these mental problems with non-communicable diseases including diabetes mellitus. Some diabetics have co-morbid mental health disorders that are not recognized by the physician hence they are not diagnosed [32]. In a case–control study conducted by Krishna [34] among Type 2 diabetics on depression, anxiety and stress, there was a lower level of depression, anxiety and stress in the healthy controls compared to those diagnosed with diabetes mellitus as the diabetics had a higher incidence of depression, anxiety and stress. Hence, stress management is key in diabetes mellitus management.
Emotional problems are common in diabetics and diabetics are at risk of various emotional and psychological problems such as depression, anxiety and diabetes-specific distress [35]. One of the sources of distress in diabetes is the lifelong treatment which is required [36]. Faridah et al. [36] in their study on the relationship between emotional distress and quality of life of patients with Type 2 Diabetes Mellitus used the diabetes distress scale for their study. In this study, a significant relationship was observed using linear regression between emotional distress characteristics p-value >0.05 [36]. There was a positive relationship between glycaemic control and emotional distress in another study conducted by Strandberg et al. (2019) [37] where 319 adults with Type 1 diabetes mellitus were studied. This study proposed that during every clinical consultation with a diabetic, depression and diabetes specific emotional distress should be watched out for [37].
In a South African cohort study conducted to investigate distress related to diabetes mellitus in patients with Type 2 Diabetes Mellitus, diabetes distress scale was used for this study. Distress was seen in 44% of the study participants [38]. This study recommends that attention should be paid to the psychological requirements of the patients as it has a great impact on the outcome of the disease [38]. In a randomized trial of Type 2 Diabetes Mellitus by Survit et al. [39], a significant reduction in HbA1c occurred following education on stress management (0.5%). There was a lower level of the HbA1c after one year in subjects who were educated on stress management [39].
Sleep is important for good health and adequate sleep is important for the management of sleep. Sleep may be defined as a state of unconsciousness in which the body rejuvenates itself and the soul is also nourished [15]. During sleep there is a healing of the physical body leading to the enhancement of health. The prescribed amount of sleep required daily is eight hours within 24 hours and at least 30 minutes of nap in the afternoon [15]. When sleeping, stress reduces including regaining energy and strength after tiredness as there is a reduction in the levels of hormones released during stress such as cortisol. Poor sleep or insufficient sleep can cause deleterious effects on the body, especially mental and physical health. Sleep is necessary for the regulation of several physiologic functions and processes. Some of these processes are related to the regulation of metabolism including the metabolism of glucose in the body [40]. The human mind and body need sleep to function healthily [41]. Several factors affect sleep including stress. In the management of diabetes mellitus, adequate sleep is important [42] as it is required for the effective maintenance of good glycaemic control [33]. In Type 2 diabetes mellitus, there is a correlation between glycaemic control and disturbances. In sleep, as evidenced by epidemiologic studies, although the extent remains unclear [42]. Results of some studies have shown that loss of sleep causes an increase in calorie intake within 24 hours [40]. Although there is a novel discovery that insufficient sleep has been associated as an important risk factor for the development of diabetes mellitus, these studies are not yet conclusive [40].
Some other studies have investigated the association between diabetes mellitus and sleep apnoea, have revealed that autonomic neuropathy may be the reason for a dysfunction in the central respiration control of the diaphragm and also a decrease in the upper airway [16]. Also sleep apnoea in diabetes mellitus may also be related to obesity, as obesity is a risk factor for diabetes mellitus and sleep apnoea in a study by Bing-Qian et al. [33] on the impact of the quality of sleep on glycaemic control on patients with Type 2 Diabetes Mellitus, there was no significant relationship seen between the sleep efficiency and glycaemic control [1] although the researchers acknowledged that good sleep is necessary for improving the quality of life of diabetics. In a systematic review and meta-analysis on the impact of the amount of sleep and quality of sleep on glycaemic control in Type 2 Diabetes Mellitus, there was not enough evidence to conclude to relate the quality of sleep and the level of glycosylated hemoglobin although it was found that higher levels of glycosylated hemoglobin were seen in diabetics with sleep disturbances the glycosylated hemoglobin was not affected by disturbed sleep [42]. However glycaemic control in patients with Type 2 Diabetes Mellitus is disrupted with too much or too little sleep.
According to Surani et al. [41], there is a disruption in the glycaemic control following impaired quality of sleep which may have some deleterious effects on the body and the quality of life [42] as poor sleep leads to impaired decision making, loss of concentration. This will affect taking decisions on healthy food choices hence patients will choose unhealthy habits that will worsen the glycaemic control and overall management of the patients. In diabetics, there is speculation that reduced quality and duration of sleep can affect glucose control negatively [41, 43]. Also poor sleep in diabetics may be due to poor glycaemic control leading to poor quality of sleep which is required for the general wellbeing of every human being [43]. Hence for good glycaemic control, good sleep hygiene is necessary [15]. As sometimes disturbance of sleep may be an unrecognized health issue in diabetics.
Physical inactivity and sedentary lifestyle are one of the risk factors for non-communicable diseases and obesity and obesity is a risk factor for diabetes mellitus. There are short and long term advantages of physical activity including exercise and this cause a reduction of illnesses with obesity and physical inactivity as its predisposing factors including diabetes mellitus [24]. According to the results of several meta-analytical epidemiological studies on physical exercise including the Diabetes Prevention Programme (DPP) in the United States, diet and exercise and other components of lifestyle medicine causes a reduction in the progression of impaired glucose tolerance (IGT) in Type 2 Diabetes Mellitus [44].
During physical activity and exercise, it acts as physical stress on the body thereby leading to changes in the transportation of glucose thereby satisfying the increased energy demand that occurs during exercise [8]. Hence among the core components of lifestyle medicine in the management of diabetes mellitus [12]. Results of some observational studies have revealed that one of the non-invasive therapies for the prevention and management of diabetes mellitus is exercise; this extends to pregnant women, hence exercise also serves as a preventive measure and for management of gestational diabetes mellitus [45] low impact exercises can be done by pregnant women.
In diabetes mellitus, there is an inadequate amount of insulin and hyperglycaemia also results from increased insulin resistance [19]. Insulin resistance is promoted by obesity and physical inactivity. In the muscles that are not exercised, deposition of visceral fat and also deposition of fat in the liver and muscle occurs by the sequestration of glucose transporter 4 (GLUT-4) [8]. This deposition of fat increases obesity and also worsens insulin resistance. Exercise burns off deposited fat which will definitely in turn positively affect insulin resistance. Improvement of the tolerance of glucose, reduction of insulin resistance and improvement in the lipid profile occurs during exercise thereby increasing and improving cardiovascular and cardiopulmonary function [10]. This improves the sensitivity of insulin and also helps in weight loss, which in turn improves the overall wellbeing of the diabetic and also serves as a preventive measure of other non-communicable diseases [5, 10, 45]. It also stimulates the uptake of glucose. In a study conducted by Miyauch et al. [46], the levels of glycosylated hemoglobin were decreased was seen in patients who engage in an exercise regimen [46]. The aims of exercise in both the prevention and management of Type 2 Diabetes Mellitus are to achieve good metabolic control of diabetes mellitus, weight reduction, increased physical activity, improvement of the cardiovascular function, improvement in dyslipidaemia by reduction of the blood lipids and the general sense of wellbeing and quality of life [10]. Exercise is also necessary for the management of Type 1 Diabetes Mellitus.
Mechanism of improvement of blood glucose through exercise therapy [18]:
Increased intake of glucose
Increased utilization of glucose
Improved insulin sensitivity
Protection of the function of beta cells of the pancreas
The recommended international guidelines for exercise for adults 18 years and above is to engage in an exercise of moderate intensity for 150 minutes or aerobic exercise and physical activity of vigorous activity for 15 minutes weekly. This can be done as episodes of ten minutes including exercises that strengthen the body involving the major groups of muscles performed on two or more days per week [8]. An exercise regimen begins with a warm-up exercise to stimulate the muscles followed by the conditioning phase and ending with the cooling-down phase. All the phases of exercise are important to prevent injury and muscle soreness. Exercise can act as medicine to the body but diabetics should still be counseled on taking their medications and not to avoid regular check-ups. Diabetics should avoid high impact and vigorous exercises except under the guidance of a physician. Diabetics who should not participate in exercises:
Diabetics with retinopathy
Diabetics with neuropathy
Recurrent hypoglycaemia
Recurrent hyperglycaemia
Exercise is very important in the prevention of Type 2 Diabetes Mellitus, it is also important in the management of Type 1, 2 and gestational diabetes mellitus [10, 18, 38].
Eating a whole plant-based diet involves eating meals composed of plants and removing processed meals, animal and animal products, high salt, sugar and fat. This is because they are all risk factors for non-communicable diseases and diabetes mellitus. These meals are referred to as unhealthy foods because of the negative effects. Consumption of a whole plant-based diet involves eating food rich in fruits, vegetables, and legumes. Fruits, vegetables and legumes are available globally and should be encouraged. Good nutrition is very important in any lifestyle intervention [24]. In whole food plant-based diet, consumption of fruits, legumes, whole grains, including nuts and seeds are emphasized. Also, the consumption of animal products and unhealthy foods such as red and white meat, poultry, fish, eggs, dairy products, refined and processed meal, added sugars and oils are minimized and if possible eliminated from the diet [11]. It has been shown that vegetarians who do not eat any animal product have a low prevalence of diabetes mellitus 2.9% with omnivores having a prevalence of 7.6%. Various data have shown between the consumption of processed meat such as bacon, sausage, and hot dog including consumption of eggs and diabetes mellitus [9]. Counseling patients on nutrition is very important in the management of diabetes mellitus. Every diabetic should always have a counseling session during their follow-up visit which should include diet from food available in the locality. The etiology of a wide range of diseases is linked to diet. One of the fundamental determinants of human health is the amount and type of food consumed [5].
It is very important to balance calorie intake and physical activity as a strategy to maintain an ideal weight and preventing overweight obesity and chronic diseases [3]. To fill up the satiety while consuming low calories, complex carbohydrates with a low glycaemic index should be consumed. Other dietary restrictions such as fasting improve the blood glucose but it should be done under the supervision of a physician preferably an endocrinologist and a diabetologist if available to avoid rebound hyperglycaemia which can lead to non-diabetic ketoacidosis and hyperglycemic hyperosmolar state. Intermittent fasting can be practised by diabetics as it is effective but not strict fasting [11].
Decreased consumption of fruits and vegetables is associated with metabolic syndrome [11]. Nutrition is very important in the practice of lifestyle medicine, various guidelines on nutrition for diabetes mellitus have recommended diets lows in red and processed meat, refined grains, added sugar, food sweetened with sugar and salts and saturated and trans-fat [3].
Lifestyle medicine promotes the eating of whole plant based diet which is one of the pillars of lifestyle medicine. There are various other diets plans that has been found to be beneficial in the management of diabetes mellitus such as the low glycaemic diet, dietary approaches to stop hypertension diet (DASH) and the Mediterranean diet.
In a study conducted by Paula et al. [47], they found out when the DASH diet was combined with walking, the result is a reduction in the ambulatory blood pressure monitoring in hypertensive patients with diabetes mellitus [47].
Diabetes mellitus is a non-communicable disease that can be prevented and managed using lifestyle modification which involves eating a diet that is rich in complex carbohydrates and roughage. People with a family history of diabetes mellitus can prevent it from manifesting in them by modifying it. Good glycaemic control in diabetics can be achieved through good dietary control. This is because of financial commitment to diabetic management in patients without access to health insurance. It also helps to eliminate the psychosocial aspect diabetics go through having to take drugs throughout their lifetime.
As a company committed to the wider dissemination of knowledge, IntechOpen supports the OAI Metadata Harvesting Protocol (OAI-PMH Version 2.0).
',metaTitle:"OAI-PMH",metaDescription:"As a firm believer in the wider dissemination of knowledge, IntechOpen supports the OAI Metadata Harvesting Protocol (OAI-PMH Version 2.0).",metaKeywords:null,canonicalURL:"/page/oai-pmh",contentRaw:'[{"type":"htmlEditorComponent","content":"The OAI-PMH (Open Archives Initiative Protocol for Metadata Harvesting) is used to govern the collection of metadata descriptions and enables other archives to access our database. The Protocol has been developed by the Open Archives Initiative, based on ensuring interoperability standards in order to ease and promote broader and more efficient dissemination of information within the scientific community.
\\n\\nWe have adopted the Protocol to increase the number of readers of our publications. All our Works are more widely accessible, with resulting benefits for scholars, researchers, students, libraries, universities and other academic institutions. Through this method of exposing metadata, IntechOpen enables citation indexes, scientific search engines, scholarly databases, and scientific literature collections to gather metadata from our repository and make our publications available to a broader academic audience.
\\n\\nAs a Registered Data Provider, metadata for published Books and Chapters are available via our interface at the base URL: http://mts.intechopen.com/oai/index.php
\\n\\nREQUESTS
\\n\\nYou can find out more about the Protocol by visiting the Open Archives website. For additional questions please contact us at ai@intechopen.com.
\\n\\nDATABASES
\\n\\nDatabases, repositories and search engines that provide services based on metadata harvested using the OAI metadata harvesting protocol include:
\\n\\nBASE - Bielefeld Academic Search Engine
\\n\\nOne of the world's most powerful search engines, used primarily for academic Open Access web resources.
\\n\\n\\n\\nA search engine for online catalogues of publications from all over the world.
\\n"}]'},components:[{type:"htmlEditorComponent",content:'The OAI-PMH (Open Archives Initiative Protocol for Metadata Harvesting) is used to govern the collection of metadata descriptions and enables other archives to access our database. The Protocol has been developed by the Open Archives Initiative, based on ensuring interoperability standards in order to ease and promote broader and more efficient dissemination of information within the scientific community.
\n\nWe have adopted the Protocol to increase the number of readers of our publications. All our Works are more widely accessible, with resulting benefits for scholars, researchers, students, libraries, universities and other academic institutions. Through this method of exposing metadata, IntechOpen enables citation indexes, scientific search engines, scholarly databases, and scientific literature collections to gather metadata from our repository and make our publications available to a broader academic audience.
\n\nAs a Registered Data Provider, metadata for published Books and Chapters are available via our interface at the base URL: http://mts.intechopen.com/oai/index.php
\n\nREQUESTS
\n\nYou can find out more about the Protocol by visiting the Open Archives website. For additional questions please contact us at ai@intechopen.com.
\n\nDATABASES
\n\nDatabases, repositories and search engines that provide services based on metadata harvested using the OAI metadata harvesting protocol include:
\n\nBASE - Bielefeld Academic Search Engine
\n\nOne of the world's most powerful search engines, used primarily for academic Open Access web resources.
\n\n\n\nA search engine for online catalogues of publications from all over the world.
\n'}]},successStories:{items:[]},authorsAndEditors:{filterParams:{},profiles:[{id:"396",title:"Dr.",name:"Vedran",middleName:null,surname:"Kordic",slug:"vedran-kordic",fullName:"Vedran Kordic",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/396/images/7281_n.png",biography:"After obtaining his Master's degree in Mechanical Engineering he continued his education at the Vienna University of Technology where he obtained his PhD degree in 2004. He worked as a researcher at the Automation and Control Institute, Faculty of Electrical Engineering, Vienna University of Technology until 2008. His studies in robotics lead him not only to a PhD degree but also inspired him to co-found and build the International Journal of Advanced Robotic Systems - world's first Open Access journal in the field of robotics.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"441",title:"Ph.D.",name:"Jaekyu",middleName:null,surname:"Park",slug:"jaekyu-park",fullName:"Jaekyu Park",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/441/images/1881_n.jpg",biography:null,institutionString:null,institution:{name:"LG Corporation (South Korea)",country:{name:"Korea, South"}}},{id:"465",title:"Dr",name:"Christian",middleName:null,surname:"Martens",slug:"christian-martens",fullName:"Christian Martens",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"479",title:"Dr.",name:"Valentina",middleName:null,surname:"Colla",slug:"valentina-colla",fullName:"Valentina Colla",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/479/images/358_n.jpg",biography:null,institutionString:null,institution:{name:"Sant'Anna School of Advanced Studies",country:{name:"Italy"}}},{id:"494",title:"PhD",name:"Loris",middleName:null,surname:"Nanni",slug:"loris-nanni",fullName:"Loris Nanni",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/494/images/system/494.jpg",biography:"Loris Nanni received his Master Degree cum laude on June-2002 from the University of Bologna, and the April 26th 2006 he received his Ph.D. in Computer Engineering at DEIS, University of Bologna. On September, 29th 2006 he has won a post PhD fellowship from the university of Bologna (from October 2006 to October 2008), at the competitive examination he was ranked first in the industrial engineering area. He extensively served as referee for several international journals. He is author/coauthor of more than 100 research papers. He has been involved in some projects supported by MURST and European Community. His research interests include pattern recognition, bioinformatics, and biometric systems (fingerprint classification and recognition, signature verification, face recognition).",institutionString:null,institution:null},{id:"496",title:"Dr.",name:"Carlos",middleName:null,surname:"Leon",slug:"carlos-leon",fullName:"Carlos Leon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Seville",country:{name:"Spain"}}},{id:"512",title:"Dr.",name:"Dayang",middleName:null,surname:"Jawawi",slug:"dayang-jawawi",fullName:"Dayang Jawawi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Technology Malaysia",country:{name:"Malaysia"}}},{id:"528",title:"Dr.",name:"Kresimir",middleName:null,surname:"Delac",slug:"kresimir-delac",fullName:"Kresimir Delac",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/528/images/system/528.jpg",biography:"K. Delac received his B.Sc.E.E. degree in 2003 and is currentlypursuing a Ph.D. degree at the University of Zagreb, Faculty of Electrical Engineering andComputing. His current research interests are digital image analysis, pattern recognition andbiometrics.",institutionString:null,institution:{name:"University of Zagreb",country:{name:"Croatia"}}},{id:"557",title:"Dr.",name:"Andon",middleName:"Venelinov",surname:"Topalov",slug:"andon-topalov",fullName:"Andon Topalov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/557/images/1927_n.jpg",biography:"Dr. Andon V. Topalov received the MSc degree in Control Engineering from the Faculty of Information Systems, Technologies, and Automation at Moscow State University of Civil Engineering (MGGU) in 1979. He then received his PhD degree in Control Engineering from the Department of Automation and Remote Control at Moscow State Mining University (MGSU), Moscow, in 1984. From 1985 to 1986, he was a Research Fellow in the Research Institute for Electronic Equipment, ZZU AD, Plovdiv, Bulgaria. In 1986, he joined the Department of Control Systems, Technical University of Sofia at the Plovdiv campus, where he is presently a Full Professor. He has held long-term visiting Professor/Scholar positions at various institutions in South Korea, Turkey, Mexico, Greece, Belgium, UK, and Germany. And he has coauthored one book and authored or coauthored more than 80 research papers in conference proceedings and journals. His current research interests are in the fields of intelligent control and robotics.",institutionString:null,institution:{name:"Technical University of Sofia",country:{name:"Bulgaria"}}},{id:"585",title:"Prof.",name:"Munir",middleName:null,surname:"Merdan",slug:"munir-merdan",fullName:"Munir Merdan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/585/images/system/585.jpg",biography:"Munir Merdan received the M.Sc. degree in mechanical engineering from the Technical University of Sarajevo, Bosnia and Herzegovina, in 2001, and the Ph.D. degree in electrical engineering from the Vienna University of Technology, Vienna, Austria, in 2009.Since 2005, he has been at the Automation and Control Institute, Vienna University of Technology, where he is currently a Senior Researcher. His research interests include the application of agent technology for achieving agile control in the manufacturing environment.",institutionString:null,institution:null},{id:"605",title:"Prof",name:"Dil",middleName:null,surname:"Hussain",slug:"dil-hussain",fullName:"Dil Hussain",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/605/images/system/605.jpg",biography:"Dr. Dil Muhammad Akbar Hussain is a professor of Electronics Engineering & Computer Science at the Department of Energy Technology, Aalborg University Denmark. Professor Akbar has a Master degree in Digital Electronics from Govt. College University, Lahore Pakistan and a P-hD degree in Control Engineering from the School of Engineering and Applied Sciences, University of Sussex United Kingdom. Aalborg University has Two Satellite Campuses, one in Copenhagen (Aalborg University Copenhagen) and the other in Esbjerg (Aalborg University Esbjerg).\n· He is a member of prestigious IEEE (Institute of Electrical and Electronics Engineers), and IAENG (International Association of Engineers) organizations. \n· He is the chief Editor of the Journal of Software Engineering.\n· He is the member of the Editorial Board of International Journal of Computer Science and Software Technology (IJCSST) and International Journal of Computer Engineering and Information Technology. \n· He is also the Editor of Communication in Computer and Information Science CCIS-20 by Springer.\n· Reviewer For Many Conferences\nHe is the lead person in making collaboration agreements between Aalborg University and many universities of Pakistan, for which the MOU’s (Memorandum of Understanding) have been signed.\nProfessor Akbar is working in Academia since 1990, he started his career as a Lab demonstrator/TA at the University of Sussex. After finishing his P. hD degree in 1992, he served in the Industry as a Scientific Officer and continued his academic career as a visiting scholar for a number of educational institutions. In 1996 he joined National University of Science & Technology Pakistan (NUST) as an Associate Professor; NUST is one of the top few universities in Pakistan. In 1999 he joined an International Company Lineo Inc, Canada as Manager Compiler Group, where he headed the group for developing Compiler Tool Chain and Porting of Operating Systems for the BLACKfin processor. The processor development was a joint venture by Intel and Analog Devices. In 2002 Lineo Inc., was taken over by another company, so he joined Aalborg University Denmark as an Assistant Professor.\nProfessor Akbar has truly a multi-disciplined career and he continued his legacy and making progress in many areas of his interests both in teaching and research. He has contributed in stochastic estimation of control area especially, in the Multiple Target Tracking and Interactive Multiple Model (IMM) research, Ball & Beam Control Problem, Robotics, Levitation Control. He has contributed in developing Algorithms for Fingerprint Matching, Computer Vision and Face Recognition. He has been supervising Pattern Recognition, Formal Languages and Distributed Processing projects for several years. He has reviewed many books on Management, Computer Science. Currently, he is an active and permanent reviewer for many international conferences and symposia and the program committee member for many international conferences.\nIn teaching he has taught the core computer science subjects like, Digital Design, Real Time Embedded System Programming, Operating Systems, Software Engineering, Data Structures, Databases, Compiler Construction. In the Engineering side, Digital Signal Processing, Computer Architecture, Electronics Devices, Digital Filtering and Engineering Management.\nApart from his Academic Interest and activities he loves sport especially, Cricket, Football, Snooker and Squash. He plays cricket for Esbjerg city in the second division team as an opener wicket keeper batsman. He is a very good player of squash but has not played squash since his arrival in Denmark.",institutionString:null,institution:null},{id:"611",title:"Prof.",name:"T",middleName:null,surname:"Nagarajan",slug:"t-nagarajan",fullName:"T Nagarajan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Universiti Teknologi Petronas",country:{name:"Malaysia"}}}],filtersByRegion:[{group:"region",caption:"North America",value:1,count:6669},{group:"region",caption:"Middle and South America",value:2,count:5955},{group:"region",caption:"Africa",value:3,count:2457},{group:"region",caption:"Asia",value:4,count:12710},{group:"region",caption:"Australia and Oceania",value:5,count:1016},{group:"region",caption:"Europe",value:6,count:17716}],offset:12,limit:12,total:134176},chapterEmbeded:{data:{}},editorApplication:{success:null,errors:{}},ofsBooks:{filterParams:{topicId:"8"},books:[{type:"book",id:"11559",title:"Photocatalysts - New Perspectives",subtitle:null,isOpenForSubmission:!0,hash:"fc9a28dbceaeccb8991b24aec1decd32",slug:null,bookSignature:"Prof. Nasser S Awwad, Dr. Saleh S. Alarfaji and Dr. Ahmed Alomary",coverURL:"https://cdn.intechopen.com/books/images_new/11559.jpg",editedByType:null,editors:[{id:"145209",title:"Prof.",name:"Nasser",surname:"Awwad",slug:"nasser-awwad",fullName:"Nasser Awwad"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11560",title:"Piezoelectric Materials - New Opportunities to Energy Harvesting Devices",subtitle:null,isOpenForSubmission:!0,hash:"ef99895997e3b7c308813218cd6f61e7",slug:null,bookSignature:"D.Sc. Rafael Vargas-Bernal",coverURL:"https://cdn.intechopen.com/books/images_new/11560.jpg",editedByType:null,editors:[{id:"182114",title:"D.Sc.",name:"Rafael",surname:"Vargas-Bernal",slug:"rafael-vargas-bernal",fullName:"Rafael Vargas-Bernal"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11561",title:"Zeolite From Wastes - New Perspectives on Innovative Resources and Their Valorization Process",subtitle:null,isOpenForSubmission:!0,hash:"3ed0dfd842de9cd1143212415903e6ad",slug:null,bookSignature:"Dr. Claudia Belviso",coverURL:"https://cdn.intechopen.com/books/images_new/11561.jpg",editedByType:null,editors:[{id:"61457",title:"Dr.",name:"Claudia",surname:"Belviso",slug:"claudia-belviso",fullName:"Claudia Belviso"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11562",title:"Chemistry with Pyridine Derivatives",subtitle:null,isOpenForSubmission:!0,hash:"3fc5963720fa7ae08c9e31bdec4f7cc2",slug:null,bookSignature:"Dr. Satyanarayan Pal",coverURL:"https://cdn.intechopen.com/books/images_new/11562.jpg",editedByType:null,editors:[{id:"230561",title:"Dr.",name:"Satyanarayan",surname:"Pal",slug:"satyanarayan-pal",fullName:"Satyanarayan Pal"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11563",title:"A Comprehensive Review of the Versatile Dehydration Processes",subtitle:null,isOpenForSubmission:!0,hash:"91d7853d4e74d161d7a8f5913626cf94",slug:null,bookSignature:"Ph.D. Jelena Jovanovic",coverURL:"https://cdn.intechopen.com/books/images_new/11563.jpg",editedByType:null,editors:[{id:"447810",title:"Ph.D.",name:"Jelena",surname:"Jovanovic",slug:"jelena-jovanovic",fullName:"Jelena Jovanovic"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11895",title:"Sonochemistry - Recent Advances, New Perspectives, and Advanced Applications",subtitle:null,isOpenForSubmission:!0,hash:"a3bb7281ab6a6ce27a0d69cddedc05fd",slug:null,bookSignature:"Prof. Mohammed Khalid",coverURL:"https://cdn.intechopen.com/books/images_new/11895.jpg",editedByType:null,editors:[{id:"137240",title:"Prof.",name:"Mohammed",surname:"Khalid",slug:"mohammed-khalid",fullName:"Mohammed Khalid"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11897",title:"Applications of Isotope Sciences and Technologies in Supporting Life Sustainability",subtitle:null,isOpenForSubmission:!0,hash:"d751173a15d5437ee71c7352bf93b1f7",slug:null,bookSignature:"Prof. Rehab O. O. Abdel Rahman",coverURL:"https://cdn.intechopen.com/books/images_new/11897.jpg",editedByType:null,editors:[{id:"92718",title:"Prof.",name:"Rehab O.",surname:"Abdel Rahman",slug:"rehab-o.-abdel-rahman",fullName:"Rehab O. Abdel Rahman"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11898",title:"Glycerol - Current Catalytic and Biochemical Processes for Sustainability",subtitle:null,isOpenForSubmission:!0,hash:"f4b04aa4b82f5a8f2de916212b20da55",slug:null,bookSignature:"Ph.D. Israel Pala-Rosas, Dr. Jose Salmones and Prof. Jose Luis Contreras Larios",coverURL:"https://cdn.intechopen.com/books/images_new/11898.jpg",editedByType:null,editors:[{id:"284261",title:"Ph.D.",name:"Israel",surname:"Pala-Rosas",slug:"israel-pala-rosas",fullName:"Israel Pala-Rosas"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11899",title:"Ethanol Chemistry - Production, Modelling, Applications, and Technological Aspects",subtitle:null,isOpenForSubmission:!0,hash:"bee828f72f44f58c6bcb10453b91c3e9",slug:null,bookSignature:"Assistant Prof. Rampal Pandey",coverURL:"https://cdn.intechopen.com/books/images_new/11899.jpg",editedByType:null,editors:[{id:"338234",title:"Assistant Prof.",name:"Rampal",surname:"Pandey",slug:"rampal-pandey",fullName:"Rampal Pandey"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11900",title:"Chirality - New Insights",subtitle:null,isOpenForSubmission:!0,hash:"5d72254042e1414658194eb8f9fc7067",slug:null,bookSignature:"Dr. Takashiro Akitsu",coverURL:"https://cdn.intechopen.com/books/images_new/11900.jpg",editedByType:null,editors:[{id:"147861",title:"Dr.",name:"Takashiro",surname:"Akitsu",slug:"takashiro-akitsu",fullName:"Takashiro Akitsu"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11902",title:"Lignin - Chemistry, Structure, and Application",subtitle:null,isOpenForSubmission:!0,hash:"4c3ccf3ce961d9c60aeb9774034eeb87",slug:null,bookSignature:"Associate Prof. Arpit Sand and Dr. Jaya Tuteja",coverURL:"https://cdn.intechopen.com/books/images_new/11902.jpg",editedByType:null,editors:[{id:"287032",title:"Associate Prof.",name:"Arpit",surname:"Sand",slug:"arpit-sand",fullName:"Arpit Sand"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11903",title:"Covalent Organic Frameworks",subtitle:null,isOpenForSubmission:!0,hash:"8125f3f415f5d2fa9583abde0143602d",slug:null,bookSignature:"Prof. Yanan Gao and Dr. Fei Lu",coverURL:"https://cdn.intechopen.com/books/images_new/11903.jpg",editedByType:null,editors:[{id:"171387",title:"Prof.",name:"Yanan",surname:"Gao",slug:"yanan-gao",fullName:"Yanan Gao"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],filtersByTopic:[{group:"topic",caption:"Agricultural and Biological Sciences",value:5,count:38},{group:"topic",caption:"Biochemistry, Genetics and Molecular Biology",value:6,count:13},{group:"topic",caption:"Business, Management and Economics",value:7,count:7},{group:"topic",caption:"Chemistry",value:8,count:23},{group:"topic",caption:"Computer and Information Science",value:9,count:24},{group:"topic",caption:"Earth and Planetary Sciences",value:10,count:15},{group:"topic",caption:"Engineering",value:11,count:65},{group:"topic",caption:"Environmental Sciences",value:12,count:10},{group:"topic",caption:"Immunology and Microbiology",value:13,count:16},{group:"topic",caption:"Materials Science",value:14,count:25},{group:"topic",caption:"Mathematics",value:15,count:11},{group:"topic",caption:"Medicine",value:16,count:116},{group:"topic",caption:"Nanotechnology and Nanomaterials",value:17,count:6},{group:"topic",caption:"Neuroscience",value:18,count:4},{group:"topic",caption:"Pharmacology, Toxicology and Pharmaceutical Science",value:19,count:9},{group:"topic",caption:"Physics",value:20,count:9},{group:"topic",caption:"Psychology",value:21,count:10},{group:"topic",caption:"Robotics",value:22,count:2},{group:"topic",caption:"Social Sciences",value:23,count:9},{group:"topic",caption:"Veterinary Medicine and Science",value:25,count:4}],offset:12,limit:12,total:37},popularBooks:{featuredBooks:[{type:"book",id:"10858",title:"MOOC (Massive Open Online Courses)",subtitle:null,isOpenForSubmission:!1,hash:"d32f86793bc72dde32532f509b1ec5b0",slug:"mooc-massive-open-online-courses-",bookSignature:"Dragan Cvetković",coverURL:"https://cdn.intechopen.com/books/images_new/10858.jpg",editors:[{id:"101330",title:"Dr.",name:"Dragan",middleName:"Mladen",surname:"Cvetković",slug:"dragan-cvetkovic",fullName:"Dragan Cvetković"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10195",title:"Serotonin and the CNS",subtitle:"New Developments in Pharmacology and Therapeutics",isOpenForSubmission:!1,hash:"7ed9d96da98233a885bd2869a8056c36",slug:"serotonin-and-the-cns-new-developments-in-pharmacology-and-therapeutics",bookSignature:"Berend Olivier",coverURL:"https://cdn.intechopen.com/books/images_new/10195.jpg",editors:[{id:"71579",title:"Prof.",name:"Berend",middleName:null,surname:"Olivier",slug:"berend-olivier",fullName:"Berend Olivier"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10755",title:"Corporate Governance",subtitle:"Recent Advances and Perspectives",isOpenForSubmission:!1,hash:"ffe06d1d5c4bf0fc2e63511825fe1257",slug:"corporate-governance-recent-advances-and-perspectives",bookSignature:"Okechukwu Lawrence Emeagwali and Feyza Bhatti",coverURL:"https://cdn.intechopen.com/books/images_new/10755.jpg",editors:[{id:"196317",title:"Associate Prof.",name:"Okechukwu Lawrence",middleName:null,surname:"Emeagwali",slug:"okechukwu-lawrence-emeagwali",fullName:"Okechukwu Lawrence Emeagwali"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"11120",title:"Environmental Impact and Remediation of Heavy Metals",subtitle:null,isOpenForSubmission:!1,hash:"9e77514288e7394f1e6cd13481af3509",slug:"environmental-impact-and-remediation-of-heavy-metals",bookSignature:"Hosam M. Saleh and Amal I. Hassan",coverURL:"https://cdn.intechopen.com/books/images_new/11120.jpg",editors:[{id:"144691",title:"Prof.",name:"Hosam M.",middleName:null,surname:"Saleh",slug:"hosam-m.-saleh",fullName:"Hosam M. Saleh"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10901",title:"Grapes and Wine",subtitle:null,isOpenForSubmission:!1,hash:"5d7f2aa74874444bc6986e613ccebd7c",slug:"grapes-and-wine",bookSignature:"Antonio Morata, Iris Loira and Carmen González",coverURL:"https://cdn.intechopen.com/books/images_new/10901.jpg",editors:[{id:"180952",title:"Prof.",name:"Antonio",middleName:null,surname:"Morata",slug:"antonio-morata",fullName:"Antonio Morata"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"11080",title:"Engineering Principles",subtitle:"Welding and Residual Stresses",isOpenForSubmission:!1,hash:"6c07a13a113bce94174b40096f30fb5e",slug:"engineering-principles-welding-and-residual-stresses",bookSignature:"Kavian Omar Cooke and Ronaldo Câmara Cozza",coverURL:"https://cdn.intechopen.com/books/images_new/11080.jpg",editors:[{id:"138778",title:"Dr.",name:"Kavian",middleName:"Omar",surname:"Cooke",slug:"kavian-cooke",fullName:"Kavian Cooke"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"11332",title:"Essential Oils",subtitle:"Advances in Extractions and Biological Applications",isOpenForSubmission:!1,hash:"742e6cae3a35686f975edc8d7f9afa94",slug:"essential-oils-advances-in-extractions-and-biological-applications",bookSignature:"Mozaniel Santana de Oliveira and Eloisa Helena de Aguiar Andrade",coverURL:"https://cdn.intechopen.com/books/images_new/11332.jpg",editors:[{id:"195290",title:"Ph.D.",name:"Mozaniel",middleName:null,surname:"Santana De Oliveira",slug:"mozaniel-santana-de-oliveira",fullName:"Mozaniel Santana De Oliveira"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"11029",title:"Hepatitis B",subtitle:null,isOpenForSubmission:!1,hash:"609701f502efc3538c112ff47a2c2119",slug:"hepatitis-b",bookSignature:"Luis Rodrigo",coverURL:"https://cdn.intechopen.com/books/images_new/11029.jpg",editors:[{id:"73208",title:"Prof.",name:"Luis",middleName:null,surname:"Rodrigo",slug:"luis-rodrigo",fullName:"Luis Rodrigo"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9537",title:"Human Rights in the Contemporary World",subtitle:null,isOpenForSubmission:!1,hash:"54f05b93812fd434f3962956d6413a6b",slug:"human-rights-in-the-contemporary-world",bookSignature:"Trudy Corrigan",coverURL:"https://cdn.intechopen.com/books/images_new/9537.jpg",editors:[{id:"197557",title:"Dr.",name:"Trudy",middleName:null,surname:"Corrigan",slug:"trudy-corrigan",fullName:"Trudy Corrigan"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"11371",title:"Cerebral Circulation",subtitle:"Updates on Models, Diagnostics and Treatments of Related Diseases",isOpenForSubmission:!1,hash:"e2d3335445d2852d0b906bb9750e939f",slug:"cerebral-circulation-updates-on-models-diagnostics-and-treatments-of-related-diseases",bookSignature:"Alba Scerrati, Luca Ricciardi and Flavia Dones",coverURL:"https://cdn.intechopen.com/books/images_new/11371.jpg",editors:[{id:"182614",title:"Dr.",name:"Alba",middleName:null,surname:"Scerrati",slug:"alba-scerrati",fullName:"Alba Scerrati"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"11012",title:"Radiopharmaceuticals",subtitle:"Current Research for Better Diagnosis and Therapy",isOpenForSubmission:!1,hash:"f9046d6f96148b285e776f384991120d",slug:"radiopharmaceuticals-current-research-for-better-diagnosis-and-therapy",bookSignature:"Farid A. Badria",coverURL:"https://cdn.intechopen.com/books/images_new/11012.jpg",editors:[{id:"41865",title:"Prof.",name:"Farid A.",middleName:null,surname:"Badria",slug:"farid-a.-badria",fullName:"Farid A. Badria"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9974",title:"E-Learning and Digital Education in the Twenty-First Century",subtitle:null,isOpenForSubmission:!1,hash:"88b58d66e975df20425fc1dfd22d53aa",slug:"e-learning-and-digital-education-in-the-twenty-first-century",bookSignature:"M. Mahruf C. Shohel",coverURL:"https://cdn.intechopen.com/books/images_new/9974.jpg",editors:[{id:"94099",title:"Dr.",name:"M. Mahruf C.",middleName:null,surname:"Shohel",slug:"m.-mahruf-c.-shohel",fullName:"M. Mahruf C. Shohel"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],offset:12,limit:12,total:4428},hotBookTopics:{hotBooks:[],offset:0,limit:12,total:null},publish:{},publishingProposal:{success:null,errors:{}},books:{featuredBooks:[{type:"book",id:"10858",title:"MOOC (Massive Open Online Courses)",subtitle:null,isOpenForSubmission:!1,hash:"d32f86793bc72dde32532f509b1ec5b0",slug:"mooc-massive-open-online-courses-",bookSignature:"Dragan Cvetković",coverURL:"https://cdn.intechopen.com/books/images_new/10858.jpg",publishedDate:"June 23rd 2022",numberOfDownloads:1677,editors:[{id:"101330",title:"Dr.",name:"Dragan",middleName:"Mladen",surname:"Cvetković",slug:"dragan-cvetkovic",fullName:"Dragan Cvetković"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10195",title:"Serotonin and the CNS",subtitle:"New Developments in Pharmacology and Therapeutics",isOpenForSubmission:!1,hash:"7ed9d96da98233a885bd2869a8056c36",slug:"serotonin-and-the-cns-new-developments-in-pharmacology-and-therapeutics",bookSignature:"Berend Olivier",coverURL:"https://cdn.intechopen.com/books/images_new/10195.jpg",publishedDate:"June 23rd 2022",numberOfDownloads:1337,editors:[{id:"71579",title:"Prof.",name:"Berend",middleName:null,surname:"Olivier",slug:"berend-olivier",fullName:"Berend Olivier"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10755",title:"Corporate Governance",subtitle:"Recent Advances and Perspectives",isOpenForSubmission:!1,hash:"ffe06d1d5c4bf0fc2e63511825fe1257",slug:"corporate-governance-recent-advances-and-perspectives",bookSignature:"Okechukwu Lawrence Emeagwali and Feyza Bhatti",coverURL:"https://cdn.intechopen.com/books/images_new/10755.jpg",publishedDate:"June 23rd 2022",numberOfDownloads:1309,editors:[{id:"196317",title:"Associate Prof.",name:"Okechukwu Lawrence",middleName:null,surname:"Emeagwali",slug:"okechukwu-lawrence-emeagwali",fullName:"Okechukwu Lawrence Emeagwali"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"11120",title:"Environmental Impact and Remediation of Heavy Metals",subtitle:null,isOpenForSubmission:!1,hash:"9e77514288e7394f1e6cd13481af3509",slug:"environmental-impact-and-remediation-of-heavy-metals",bookSignature:"Hosam M. Saleh and Amal I. Hassan",coverURL:"https://cdn.intechopen.com/books/images_new/11120.jpg",publishedDate:"June 23rd 2022",numberOfDownloads:847,editors:[{id:"144691",title:"Prof.",name:"Hosam M.",middleName:null,surname:"Saleh",slug:"hosam-m.-saleh",fullName:"Hosam M. Saleh"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10901",title:"Grapes and Wine",subtitle:null,isOpenForSubmission:!1,hash:"5d7f2aa74874444bc6986e613ccebd7c",slug:"grapes-and-wine",bookSignature:"Antonio Morata, Iris Loira and Carmen González",coverURL:"https://cdn.intechopen.com/books/images_new/10901.jpg",publishedDate:"June 15th 2022",numberOfDownloads:2273,editors:[{id:"180952",title:"Prof.",name:"Antonio",middleName:null,surname:"Morata",slug:"antonio-morata",fullName:"Antonio Morata"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"11080",title:"Engineering Principles",subtitle:"Welding and Residual Stresses",isOpenForSubmission:!1,hash:"6c07a13a113bce94174b40096f30fb5e",slug:"engineering-principles-welding-and-residual-stresses",bookSignature:"Kavian Omar Cooke and Ronaldo Câmara Cozza",coverURL:"https://cdn.intechopen.com/books/images_new/11080.jpg",publishedDate:"June 23rd 2022",numberOfDownloads:591,editors:[{id:"138778",title:"Dr.",name:"Kavian",middleName:"Omar",surname:"Cooke",slug:"kavian-cooke",fullName:"Kavian Cooke"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"11332",title:"Essential Oils",subtitle:"Advances in Extractions and Biological Applications",isOpenForSubmission:!1,hash:"742e6cae3a35686f975edc8d7f9afa94",slug:"essential-oils-advances-in-extractions-and-biological-applications",bookSignature:"Mozaniel Santana de Oliveira and Eloisa Helena de Aguiar Andrade",coverURL:"https://cdn.intechopen.com/books/images_new/11332.jpg",publishedDate:"June 23rd 2022",numberOfDownloads:515,editors:[{id:"195290",title:"Ph.D.",name:"Mozaniel",middleName:null,surname:"Santana De Oliveira",slug:"mozaniel-santana-de-oliveira",fullName:"Mozaniel Santana De Oliveira"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"11029",title:"Hepatitis B",subtitle:null,isOpenForSubmission:!1,hash:"609701f502efc3538c112ff47a2c2119",slug:"hepatitis-b",bookSignature:"Luis Rodrigo",coverURL:"https://cdn.intechopen.com/books/images_new/11029.jpg",publishedDate:"June 23rd 2022",numberOfDownloads:413,editors:[{id:"73208",title:"Prof.",name:"Luis",middleName:null,surname:"Rodrigo",slug:"luis-rodrigo",fullName:"Luis Rodrigo"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9537",title:"Human Rights in the Contemporary World",subtitle:null,isOpenForSubmission:!1,hash:"54f05b93812fd434f3962956d6413a6b",slug:"human-rights-in-the-contemporary-world",bookSignature:"Trudy Corrigan",coverURL:"https://cdn.intechopen.com/books/images_new/9537.jpg",publishedDate:"June 8th 2022",numberOfDownloads:2194,editors:[{id:"197557",title:"Dr.",name:"Trudy",middleName:null,surname:"Corrigan",slug:"trudy-corrigan",fullName:"Trudy Corrigan"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"11371",title:"Cerebral Circulation",subtitle:"Updates on Models, Diagnostics and Treatments of Related Diseases",isOpenForSubmission:!1,hash:"e2d3335445d2852d0b906bb9750e939f",slug:"cerebral-circulation-updates-on-models-diagnostics-and-treatments-of-related-diseases",bookSignature:"Alba Scerrati, Luca Ricciardi and Flavia Dones",coverURL:"https://cdn.intechopen.com/books/images_new/11371.jpg",publishedDate:"June 23rd 2022",numberOfDownloads:341,editors:[{id:"182614",title:"Dr.",name:"Alba",middleName:null,surname:"Scerrati",slug:"alba-scerrati",fullName:"Alba Scerrati"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],latestBooks:[{type:"book",id:"11043",title:"Endometriosis",subtitle:"Recent Advances, New Perspectives and Treatments",isOpenForSubmission:!1,hash:"7baf1c70b11d41400bb9302ae9411ca4",slug:"endometriosis-recent-advances-new-perspectives-and-treatments",bookSignature:"Giovana Ap. Gonçalves",coverURL:"https://cdn.intechopen.com/books/images_new/11043.jpg",editedByType:"Edited by",publishedDate:"June 28th 2022",editors:[{id:"185930",title:"Associate Prof.",name:"Giovana",middleName:null,surname:"Gonçalves",slug:"giovana-goncalves",fullName:"Giovana Gonçalves"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10536",title:"Campylobacter",subtitle:null,isOpenForSubmission:!1,hash:"c4b132b741dd0a2ed539b824ab63965f",slug:"campylobacter",bookSignature:"Guillermo Tellez-Isaias and Saeed El-Ashram",coverURL:"https://cdn.intechopen.com/books/images_new/10536.jpg",editedByType:"Edited by",publishedDate:"June 28th 2022",editors:[{id:"73465",title:"Dr.",name:"Guillermo",middleName:null,surname:"Téllez",slug:"guillermo-tellez",fullName:"Guillermo Téllez"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10798",title:"Starch",subtitle:"Evolution and Recent Advances",isOpenForSubmission:!1,hash:"f197f6062c1574a9a90e50a369271bcf",slug:"starch-evolution-and-recent-advances",bookSignature:"Martins Ochubiojo Emeje",coverURL:"https://cdn.intechopen.com/books/images_new/10798.jpg",editedByType:"Edited by",publishedDate:"June 28th 2022",editors:[{id:"94311",title:"Prof.",name:"Martins",middleName:"Ochubiojo",surname:"Ochubiojo Emeje",slug:"martins-ochubiojo-emeje",fullName:"Martins Ochubiojo Emeje"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11083",title:"Hazardous Waste Management",subtitle:null,isOpenForSubmission:!1,hash:"d553bd4f6f1c4b115ca69bd19faac7dc",slug:"hazardous-waste-management",bookSignature:"Rajesh Banu Jeyakumar, Kavitha Sankarapandian and Yukesh Kannah Ravi",coverURL:"https://cdn.intechopen.com/books/images_new/11083.jpg",editedByType:"Edited by",publishedDate:"June 28th 2022",editors:[{id:"218539",title:"Dr.",name:"Rajesh Banu",middleName:null,surname:"Jeyakumar",slug:"rajesh-banu-jeyakumar",fullName:"Rajesh Banu Jeyakumar"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10848",title:"Tribology of Machine Elements",subtitle:"Fundamentals and Applications",isOpenForSubmission:!1,hash:"3c4ca4c4692ca8d4fa749b4ae81ec1fa",slug:"tribology-of-machine-elements-fundamentals-and-applications",bookSignature:"Giuseppe Pintaude, Tiago Cousseau and Anna Rudawska",coverURL:"https://cdn.intechopen.com/books/images_new/10848.jpg",editedByType:"Edited by",publishedDate:"June 28th 2022",editors:[{id:"18347",title:"Prof.",name:"Giuseppe",middleName:null,surname:"Pintaude",slug:"giuseppe-pintaude",fullName:"Giuseppe Pintaude"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10856",title:"Crude Oil",subtitle:"New Technologies and Recent Approaches",isOpenForSubmission:!1,hash:"8d0a7ca35b3de95b295dc4eab39a087e",slug:"crude-oil-new-technologies-and-recent-approaches",bookSignature:"Manar Elsayed Abdel-Raouf and Mohamed Hasan El-Keshawy",coverURL:"https://cdn.intechopen.com/books/images_new/10856.jpg",editedByType:"Edited by",publishedDate:"June 28th 2022",editors:[{id:"102626",title:"Prof.",name:"Manar",middleName:null,surname:"Elsayed Abdel-Raouf",slug:"manar-elsayed-abdel-raouf",fullName:"Manar Elsayed Abdel-Raouf"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9625",title:"Spinocerebellar Ataxia",subtitle:"Concepts, Particularities and Generalities",isOpenForSubmission:!1,hash:"365a7025fd46eb45de2549bdd9d50b98",slug:"spinocerebellar-ataxia-concepts-particularities-and-generalities",bookSignature:"Patricia Bozzetto Ambrosi",coverURL:"https://cdn.intechopen.com/books/images_new/9625.jpg",editedByType:"Edited by",publishedDate:"June 28th 2022",editors:[{id:"221787",title:"Dr.",name:"Patricia",middleName:null,surname:"Bozzetto Ambrosi",slug:"patricia-bozzetto-ambrosi",fullName:"Patricia Bozzetto Ambrosi"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10905",title:"Plant Defense Mechanisms",subtitle:null,isOpenForSubmission:!1,hash:"84ad5b27dde5f01dc76087d0fd6fa834",slug:"plant-defense-mechanisms",bookSignature:"Josphert Ngui Kimatu",coverURL:"https://cdn.intechopen.com/books/images_new/10905.jpg",editedByType:"Edited by",publishedDate:"June 28th 2022",editors:[{id:"224171",title:"Prof.",name:"Josphert N.",middleName:null,surname:"Kimatu",slug:"josphert-n.-kimatu",fullName:"Josphert N. Kimatu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10686",title:"Natural Gas",subtitle:"New Perspectives and Future Developments",isOpenForSubmission:!1,hash:"581763788a6a59e653a9d1d9b5a42d79",slug:"natural-gas-new-perspectives-and-future-developments",bookSignature:"Maryam Takht Ravanchi",coverURL:"https://cdn.intechopen.com/books/images_new/10686.jpg",editedByType:"Edited by",publishedDate:"June 28th 2022",editors:[{id:"2416",title:"Dr.",name:"Maryam",middleName:null,surname:"Takht Ravanchi",slug:"maryam-takht-ravanchi",fullName:"Maryam Takht Ravanchi"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10988",title:"Railway Transport Planning and Manageme",subtitle:null,isOpenForSubmission:!1,hash:"5cb54cc53caedad9ec78372563c82e2c",slug:"railway-transport-planning-and-management",bookSignature:"Stefano de Luca, Roberta Di Pace and Chiara Fiori",coverURL:"https://cdn.intechopen.com/books/images_new/10988.jpg",editedByType:"Edited by",publishedDate:"June 28th 2022",editors:[{id:"271061",title:"Prof.",name:"Stefano",middleName:null,surname:"de Luca",slug:"stefano-de-luca",fullName:"Stefano de Luca"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},subject:{topic:{id:"629",title:"Remote Sensing",slug:"atmospheric-sciences-remote-sensing",parent:{id:"99",title:"Atmospheric Sciences",slug:"atmospheric-sciences"},numberOfBooks:1,numberOfSeries:0,numberOfAuthorsAndEditors:32,numberOfWosCitations:23,numberOfCrossrefCitations:24,numberOfDimensionsCitations:42,videoUrl:null,fallbackUrl:null,description:null},booksByTopicFilter:{topicId:"629",sort:"-publishedDate",limit:12,offset:0},booksByTopicCollection:[{type:"book",id:"5180",title:"Tropical Cyclone Dynamics, Prediction, and Detection",subtitle:"Recent Developments in",isOpenForSubmission:!1,hash:"25b2b97da73e831dff9b60bf4cc3e027",slug:"recent-developments-in-tropical-cyclone-dynamics-prediction-and-detection",bookSignature:"Anthony R. Lupo",coverURL:"https://cdn.intechopen.com/books/images_new/5180.jpg",editedByType:"Edited by",editors:[{id:"18289",title:"Prof.",name:"Anthony",middleName:"Rocco",surname:"Lupo",slug:"anthony-lupo",fullName:"Anthony Lupo"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],booksByTopicTotal:1,seriesByTopicCollection:[],seriesByTopicTotal:0,mostCitedChapters:[{id:"51496",doi:"10.5772/64333",title:"Progress in Tropical Cyclone Predictability and Present Status in the North Indian Ocean Region",slug:"progress-in-tropical-cyclone-predictability-and-present-status-in-the-north-indian-ocean-region",totalDownloads:3326,totalCrossrefCites:13,totalDimensionsCites:19,abstract:"Tropical cyclone (TC) is an important research area since it has a significant impact on human life, properties and environment. The researchers all over the world have been studying fundamental and advanced processes to better understand and thereby predict the genesis and evolution of TCs. This review chapter provides a brief overview on TC climatology, their basic characteristics, movement and intensification, research on structure analysis and prediction of these fascinating storms, with primary emphasis to North Indian Ocean (NIO). The role of ocean and atmosphere in determining the genesis and intensification of TCs is discussed. This chapter reviews the past and current research activities including inter-annual and intra-seasonal changes in TCs, current status of TC research using numerical weather prediction, gaps identified and relevant measures taken by the meteorological and government agencies in this direction, along with future directions in order to improve the understanding and predictability over the NIO region.",book:{id:"5180",slug:"recent-developments-in-tropical-cyclone-dynamics-prediction-and-detection",title:"Tropical Cyclone Dynamics, Prediction, and Detection",fullTitle:"Recent Developments in Tropical Cyclone Dynamics, Prediction, and Detection"},signatures:"Kasturi Singh, Jagabandhu Panda, Krishna K. Osuri and Naresh\nKrishna Vissa",authors:[{id:"178828",title:"Dr.",name:"Naresh",middleName:null,surname:"Vissa",slug:"naresh-vissa",fullName:"Naresh Vissa"},{id:"178872",title:"Dr.",name:"Jagabandhu",middleName:null,surname:"Panda",slug:"jagabandhu-panda",fullName:"Jagabandhu Panda"},{id:"180613",title:"Ms.",name:"Kasturi",middleName:null,surname:"Singh",slug:"kasturi-singh",fullName:"Kasturi Singh"},{id:"180614",title:"Dr.",name:"Krishna K.",middleName:null,surname:"Osuri",slug:"krishna-k.-osuri",fullName:"Krishna K. Osuri"}]},{id:"51981",doi:"10.5772/64859",title:"An Operational Statistical Scheme for Tropical Cyclone-Induced Rainfall Forecast",slug:"an-operational-statistical-scheme-for-tropical-cyclone-induced-rainfall-forecast",totalDownloads:1691,totalCrossrefCites:2,totalDimensionsCites:10,abstract:"Nonparametric methods are used in this study to analyze and predict short-term rainfall due to tropical cyclones (TCs) in a coastal meteorological station. All 427 TCs during 1953–2011, which made landfall along the Southeast China coast with a distance less than 700 km to a certain meteorological station, Shenzhen, are analyzed and grouped according to their landfalling direction, distance, and intensity. The corresponding daily rainfall records at Shenzhen Meteorological Station (SMS) during TCs landfalling period (a couple of days before and after TC landfall) are collected. The maximum daily rainfall (R24) and maximum 3-day accumulative rainfall (R72) records at SMS for each TC category are analyzed by a nonparametric statistical method, percentile estimation. The results are plotted by statistical boxplot, expressing in the probability of precipitation. The performance of the statistical boxplots was evaluated to forecast the short-term rainfall at SMS during the TC seasons in 2012 and 2013. The results show that the boxplot scheme can be used as a valuable reference to predict the short-term rainfall at SMS due to TCs landfalling along the Southeast China coast.",book:{id:"5180",slug:"recent-developments-in-tropical-cyclone-dynamics-prediction-and-detection",title:"Tropical Cyclone Dynamics, Prediction, and Detection",fullTitle:"Recent Developments in Tropical Cyclone Dynamics, Prediction, and Detection"},signatures:"Qinglan Li, Hongping Lan, Johnny C.L. Chan, Chunyan Cao, Cheng Li\nand Xingbao Wang",authors:[{id:"179370",title:"Dr.",name:"Qinglan",middleName:null,surname:"Li",slug:"qinglan-li",fullName:"Qinglan Li"},{id:"185562",title:"Prof.",name:"Hongping",middleName:null,surname:"Lan",slug:"hongping-lan",fullName:"Hongping Lan"},{id:"185563",title:"Prof.",name:"Johnny C.L.",middleName:null,surname:"Chan",slug:"johnny-c.l.-chan",fullName:"Johnny C.L. Chan"},{id:"185564",title:"Ms.",name:"Chunyan",middleName:null,surname:"Cao",slug:"chunyan-cao",fullName:"Chunyan Cao"},{id:"185565",title:"Mr.",name:"Cheng",middleName:null,surname:"Li",slug:"cheng-li",fullName:"Cheng Li"},{id:"185566",title:"Dr.",name:"Xingbao",middleName:null,surname:"Wang",slug:"xingbao-wang",fullName:"Xingbao Wang"}]},{id:"50973",doi:"10.5772/64009",title:"Influence of Tropical Cyclones in the Western North Pacific",slug:"influence-of-tropical-cyclones-in-the-western-north-pacific",totalDownloads:2291,totalCrossrefCites:0,totalDimensionsCites:4,abstract:"The Western North Pacific (WNP) is the most favorable area in the world for the generation of tropical cyclones (TCs). As the most intense weather system, TCs play an important role in the change of ocean environment in the WNP. Based on many investigations published in the literature, we obtained a collective and systematic understanding of the influence of TCs on ocean components in the WNP, including sea temperature, ocean currents, mesoscale eddies, storm surges, phytoplankton (indicated by chlorophyll a). Some ocean responses to TCs are unique in the WNP because of the existence of the Kuroshio and special geographical configurations such as the South China Sea.",book:{id:"5180",slug:"recent-developments-in-tropical-cyclone-dynamics-prediction-and-detection",title:"Tropical Cyclone Dynamics, Prediction, and Detection",fullTitle:"Recent Developments in Tropical Cyclone Dynamics, Prediction, and Detection"},signatures:"Wen-Zhou Zhang, Sheng Lin and Xue-Min Jiang",authors:[{id:"179513",title:"Dr.",name:"Wen-Zhou",middleName:null,surname:"Zhang",slug:"wen-zhou-zhang",fullName:"Wen-Zhou Zhang"},{id:"180488",title:"BSc.",name:"Sheng",middleName:null,surname:"Lin",slug:"sheng-lin",fullName:"Sheng Lin"},{id:"180491",title:"BSc.",name:"Xue-Min",middleName:null,surname:"Jiang",slug:"xue-min-jiang",fullName:"Xue-Min Jiang"}]},{id:"51916",doi:"10.5772/64114",title:"Satellite Remote Sensing of Tropical Cyclones",slug:"satellite-remote-sensing-of-tropical-cyclones",totalDownloads:2547,totalCrossrefCites:4,totalDimensionsCites:3,abstract:"This chapter provides a review on satellite remote sensing of tropical cyclones (TCs). Applications of satellite remote sensing from geostationary (GEO) and low earth orbital (LEO) platforms, especially from passive microwave (PMW) sensors, are focused on TC detection, structure, and intensity analysis as well as precipitation patterns. The impacts of satellite remote sensing on TC forecasts are discussed with respect to helping reduce the TC's track and intensity forecast errors. Finally, the multi‐satellite‐sensor data fusion technique is explained as the best way to automatically monitor and track the global TC's position, structure, and intensity.",book:{id:"5180",slug:"recent-developments-in-tropical-cyclone-dynamics-prediction-and-detection",title:"Tropical Cyclone Dynamics, Prediction, and Detection",fullTitle:"Recent Developments in Tropical Cyclone Dynamics, Prediction, and Detection"},signatures:"Song Yang and Joshua Cossuth",authors:[{id:"178744",title:"Dr.",name:"Song",middleName:null,surname:"Yang",slug:"song-yang",fullName:"Song Yang"},{id:"179320",title:"Dr.",name:"Joshua",middleName:null,surname:"Cossuth",slug:"joshua-cossuth",fullName:"Joshua Cossuth"}]},{id:"51689",doi:"10.5772/64029",title:"Climate Risk Early Warning System for Island Nations: Tropical Cyclones",slug:"climate-risk-early-warning-system-for-island-nations-tropical-cyclones",totalDownloads:1653,totalCrossrefCites:2,totalDimensionsCites:2,abstract:"Tropical cyclones (TCs) frequently affect coastal areas of Australia and islands in the tropical Indian and Pacific oceans. Multi-hazards associated with TCs (destructive winds, storm surges and torrential rain) have dramatic impact on population and infrastructure. Accurate forecasting of TC seasonal activity is an important part of a Climate Risk Early Warning System (CREWS) for improving resilience of the society to potentially destructive impacts of TCs. Currently, a statistical model-based prediction of TC activity in the coming season is used for operational seasonal forecasting in the Australian region and the South Pacific Ocean. In this chapter, a possibility of improving the accuracy of seasonal TC prediction using advanced statistical model-based approaches is demonstrated. It is also demonstrated that an alternative approach—dynamical (physics-based) climate modelling—is promising for skilful seasonal TC forecasting. Using improved statistical and dynamical model-based methodologies for TC seasonal prediction as an integral part of the CREWS will provide valuable information about TC seasonal variability and will assist with decision making, responses and adaptation in island countries.",book:{id:"5180",slug:"recent-developments-in-tropical-cyclone-dynamics-prediction-and-detection",title:"Tropical Cyclone Dynamics, Prediction, and Detection",fullTitle:"Recent Developments in Tropical Cyclone Dynamics, Prediction, and Detection"},signatures:"Yuriy Kuleshov",authors:[{id:"102903",title:"Prof.",name:"Yuriy",middleName:null,surname:"Kuleshov",slug:"yuriy-kuleshov",fullName:"Yuriy Kuleshov"}]}],mostDownloadedChaptersLast30Days:[{id:"51652",title:"Satellite Climatology of Tropical Cyclone with Concentric Eyewalls",slug:"satellite-climatology-of-tropical-cyclone-with-concentric-eyewalls",totalDownloads:1502,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"An objective method is developed to identify concentric eyewalls (CEs) for tropical cyclones (TCs) using passive microwave satellite imagery from 1997 to 2014 in the western North Pacific (WNP) and Atlantic (ATL) basin. There are 91 (33) TCs and 113 (50) cases with CE identified in the WNP (ATL). Three CE structural change types are classified as follows: a CE with the inner eyewall dissipated in an eyewall replacement cycle (ERC, 51 and 56% in the WNP and ATL), a CE with the outer eyewall dissipated first and the no eyewall replacement cycle (NRC, 27 and 29% in the WNP and ATL), and a CE structure that is maintained for an extended period (CEM, 23 and 15% in the WNP and ATL). The moat size and outer eyewall width in the WNP (ATL) basin are approximately 20–50% (15–25%) larger in the CEM cases than that in the ERC and NRC cases. Our analysis suggests that the ERC cases are more likely dominated by the internal dynamics, whereas the NRC cases are heavily influenced by the environment condition, and both the internal and environmental conditions are important in the CEM cases. A good correlation of the annual CE TC number and the Oceanic Niño index is found (0.77) in WNP basin, with most of the CE TCs occurring in the warm episodes. In contrast, the El Niño/Southern Oscillation (ENSO) may not influence on the CE formation in the ATL basin. After the CE formation, however, the unfavorable environment that is created by ENSO may reduce the TC intensity quickly during warm episode. The variabilities of structural changes in the WNP basin are larger than that in the ATL basin.",book:{id:"5180",slug:"recent-developments-in-tropical-cyclone-dynamics-prediction-and-detection",title:"Tropical Cyclone Dynamics, Prediction, and Detection",fullTitle:"Recent Developments in Tropical Cyclone Dynamics, Prediction, and Detection"},signatures:"Yi-Ting Yang, Hung-Chi Kuo, Eric A. Hendricks and Melinda S. Peng",authors:[{id:"24152",title:"Dr.",name:"Melinda",middleName:null,surname:"Peng",slug:"melinda-peng",fullName:"Melinda Peng"},{id:"24153",title:"Prof.",name:"Hung-Chi",middleName:null,surname:"Kuo",slug:"hung-chi-kuo",fullName:"Hung-Chi Kuo"},{id:"179607",title:"Dr.",name:"Yi-Ting",middleName:null,surname:"Yang",slug:"yi-ting-yang",fullName:"Yi-Ting Yang"},{id:"180632",title:"Prof.",name:"Eric",middleName:null,surname:"Hendricks",slug:"eric-hendricks",fullName:"Eric Hendricks"}]},{id:"51981",title:"An Operational Statistical Scheme for Tropical Cyclone-Induced Rainfall Forecast",slug:"an-operational-statistical-scheme-for-tropical-cyclone-induced-rainfall-forecast",totalDownloads:1691,totalCrossrefCites:2,totalDimensionsCites:10,abstract:"Nonparametric methods are used in this study to analyze and predict short-term rainfall due to tropical cyclones (TCs) in a coastal meteorological station. All 427 TCs during 1953–2011, which made landfall along the Southeast China coast with a distance less than 700 km to a certain meteorological station, Shenzhen, are analyzed and grouped according to their landfalling direction, distance, and intensity. The corresponding daily rainfall records at Shenzhen Meteorological Station (SMS) during TCs landfalling period (a couple of days before and after TC landfall) are collected. The maximum daily rainfall (R24) and maximum 3-day accumulative rainfall (R72) records at SMS for each TC category are analyzed by a nonparametric statistical method, percentile estimation. The results are plotted by statistical boxplot, expressing in the probability of precipitation. The performance of the statistical boxplots was evaluated to forecast the short-term rainfall at SMS during the TC seasons in 2012 and 2013. The results show that the boxplot scheme can be used as a valuable reference to predict the short-term rainfall at SMS due to TCs landfalling along the Southeast China coast.",book:{id:"5180",slug:"recent-developments-in-tropical-cyclone-dynamics-prediction-and-detection",title:"Tropical Cyclone Dynamics, Prediction, and Detection",fullTitle:"Recent Developments in Tropical Cyclone Dynamics, Prediction, and Detection"},signatures:"Qinglan Li, Hongping Lan, Johnny C.L. Chan, Chunyan Cao, Cheng Li\nand Xingbao Wang",authors:[{id:"179370",title:"Dr.",name:"Qinglan",middleName:null,surname:"Li",slug:"qinglan-li",fullName:"Qinglan Li"},{id:"185562",title:"Prof.",name:"Hongping",middleName:null,surname:"Lan",slug:"hongping-lan",fullName:"Hongping Lan"},{id:"185563",title:"Prof.",name:"Johnny C.L.",middleName:null,surname:"Chan",slug:"johnny-c.l.-chan",fullName:"Johnny C.L. Chan"},{id:"185564",title:"Ms.",name:"Chunyan",middleName:null,surname:"Cao",slug:"chunyan-cao",fullName:"Chunyan Cao"},{id:"185565",title:"Mr.",name:"Cheng",middleName:null,surname:"Li",slug:"cheng-li",fullName:"Cheng Li"},{id:"185566",title:"Dr.",name:"Xingbao",middleName:null,surname:"Wang",slug:"xingbao-wang",fullName:"Xingbao Wang"}]},{id:"51916",title:"Satellite Remote Sensing of Tropical Cyclones",slug:"satellite-remote-sensing-of-tropical-cyclones",totalDownloads:2547,totalCrossrefCites:4,totalDimensionsCites:3,abstract:"This chapter provides a review on satellite remote sensing of tropical cyclones (TCs). Applications of satellite remote sensing from geostationary (GEO) and low earth orbital (LEO) platforms, especially from passive microwave (PMW) sensors, are focused on TC detection, structure, and intensity analysis as well as precipitation patterns. The impacts of satellite remote sensing on TC forecasts are discussed with respect to helping reduce the TC's track and intensity forecast errors. Finally, the multi‐satellite‐sensor data fusion technique is explained as the best way to automatically monitor and track the global TC's position, structure, and intensity.",book:{id:"5180",slug:"recent-developments-in-tropical-cyclone-dynamics-prediction-and-detection",title:"Tropical Cyclone Dynamics, Prediction, and Detection",fullTitle:"Recent Developments in Tropical Cyclone Dynamics, Prediction, and Detection"},signatures:"Song Yang and Joshua Cossuth",authors:[{id:"178744",title:"Dr.",name:"Song",middleName:null,surname:"Yang",slug:"song-yang",fullName:"Song Yang"},{id:"179320",title:"Dr.",name:"Joshua",middleName:null,surname:"Cossuth",slug:"joshua-cossuth",fullName:"Joshua Cossuth"}]},{id:"51496",title:"Progress in Tropical Cyclone Predictability and Present Status in the North Indian Ocean Region",slug:"progress-in-tropical-cyclone-predictability-and-present-status-in-the-north-indian-ocean-region",totalDownloads:3326,totalCrossrefCites:13,totalDimensionsCites:19,abstract:"Tropical cyclone (TC) is an important research area since it has a significant impact on human life, properties and environment. The researchers all over the world have been studying fundamental and advanced processes to better understand and thereby predict the genesis and evolution of TCs. This review chapter provides a brief overview on TC climatology, their basic characteristics, movement and intensification, research on structure analysis and prediction of these fascinating storms, with primary emphasis to North Indian Ocean (NIO). The role of ocean and atmosphere in determining the genesis and intensification of TCs is discussed. This chapter reviews the past and current research activities including inter-annual and intra-seasonal changes in TCs, current status of TC research using numerical weather prediction, gaps identified and relevant measures taken by the meteorological and government agencies in this direction, along with future directions in order to improve the understanding and predictability over the NIO region.",book:{id:"5180",slug:"recent-developments-in-tropical-cyclone-dynamics-prediction-and-detection",title:"Tropical Cyclone Dynamics, Prediction, and Detection",fullTitle:"Recent Developments in Tropical Cyclone Dynamics, Prediction, and Detection"},signatures:"Kasturi Singh, Jagabandhu Panda, Krishna K. Osuri and Naresh\nKrishna Vissa",authors:[{id:"178828",title:"Dr.",name:"Naresh",middleName:null,surname:"Vissa",slug:"naresh-vissa",fullName:"Naresh Vissa"},{id:"178872",title:"Dr.",name:"Jagabandhu",middleName:null,surname:"Panda",slug:"jagabandhu-panda",fullName:"Jagabandhu Panda"},{id:"180613",title:"Ms.",name:"Kasturi",middleName:null,surname:"Singh",slug:"kasturi-singh",fullName:"Kasturi Singh"},{id:"180614",title:"Dr.",name:"Krishna K.",middleName:null,surname:"Osuri",slug:"krishna-k.-osuri",fullName:"Krishna K. Osuri"}]},{id:"50973",title:"Influence of Tropical Cyclones in the Western North Pacific",slug:"influence-of-tropical-cyclones-in-the-western-north-pacific",totalDownloads:2291,totalCrossrefCites:0,totalDimensionsCites:4,abstract:"The Western North Pacific (WNP) is the most favorable area in the world for the generation of tropical cyclones (TCs). As the most intense weather system, TCs play an important role in the change of ocean environment in the WNP. Based on many investigations published in the literature, we obtained a collective and systematic understanding of the influence of TCs on ocean components in the WNP, including sea temperature, ocean currents, mesoscale eddies, storm surges, phytoplankton (indicated by chlorophyll a). Some ocean responses to TCs are unique in the WNP because of the existence of the Kuroshio and special geographical configurations such as the South China Sea.",book:{id:"5180",slug:"recent-developments-in-tropical-cyclone-dynamics-prediction-and-detection",title:"Tropical Cyclone Dynamics, Prediction, and Detection",fullTitle:"Recent Developments in Tropical Cyclone Dynamics, Prediction, and Detection"},signatures:"Wen-Zhou Zhang, Sheng Lin and Xue-Min Jiang",authors:[{id:"179513",title:"Dr.",name:"Wen-Zhou",middleName:null,surname:"Zhang",slug:"wen-zhou-zhang",fullName:"Wen-Zhou Zhang"},{id:"180488",title:"BSc.",name:"Sheng",middleName:null,surname:"Lin",slug:"sheng-lin",fullName:"Sheng Lin"},{id:"180491",title:"BSc.",name:"Xue-Min",middleName:null,surname:"Jiang",slug:"xue-min-jiang",fullName:"Xue-Min Jiang"}]}],onlineFirstChaptersFilter:{topicId:"629",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:0,limit:8,total:null},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:89,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:104,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:32,numberOfPublishedChapters:318,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:141,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:113,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:105,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:5,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:15,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"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:"3",title:"Dentistry",doi:"10.5772/intechopen.71199",issn:"2631-6218",scope:"\r\n\tThis book series will offer a comprehensive overview of recent research trends as well as clinical applications within different specialties of dentistry. Topics will include overviews of the health of the oral cavity, from prevention and care to different treatments for the rehabilitation of problems that may affect the organs and/or tissues present. The different areas of dentistry will be explored, with the aim of disseminating knowledge and providing readers with new tools for the comprehensive treatment of their patients with greater safety and with current techniques. Ongoing issues, recent advances, and future diagnostic approaches and therapeutic strategies will also be discussed. This series of books will focus on various aspects of the properties and results obtained by the various treatments available, whether preventive or curative.
",coverUrl:"https://cdn.intechopen.com/series/covers/3.jpg",latestPublicationDate:"May 13th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:8,editor:{id:"419588",title:"Ph.D.",name:"Sergio",middleName:"Alexandre",surname:"Gehrke",slug:"sergio-gehrke",fullName:"Sergio Gehrke",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000038WgMKQA0/Profile_Picture_2022-06-02T11:44:20.jpg",biography:"Dr. Sergio Alexandre Gehrke is a doctorate holder in two fields. The first is a Ph.D. in Cellular and Molecular Biology from the Pontificia Catholic University, Porto Alegre, Brazil, in 2010 and the other is an International Ph.D. in Bioengineering from the Universidad Miguel Hernandez, Elche/Alicante, Spain, obtained in 2020. In 2018, he completed a postdoctoral fellowship in Materials Engineering in the NUCLEMAT of the Pontificia Catholic University, Porto Alegre, Brazil. He is currently the Director of the Postgraduate Program in Implantology of the Bioface/UCAM/PgO (Montevideo, Uruguay), Director of the Cathedra of Biotechnology of the Catholic University of Murcia (Murcia, Spain), an Extraordinary Full Professor of the Catholic University of Murcia (Murcia, Spain) as well as the Director of the private center of research Biotecnos – Technology and Science (Montevideo, Uruguay). Applied biomaterials, cellular and molecular biology, and dental implants are among his research interests. He has published several original papers in renowned journals. In addition, he is also a Collaborating Professor in several Postgraduate programs at different universities all over the world.",institutionString:null,institution:{name:"Universidad Católica San Antonio de Murcia",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:2,paginationItems:[{id:"1",title:"Oral Health",coverUrl:"https://cdn.intechopen.com/series_topics/covers/1.jpg",isOpenForSubmission:!0,annualVolume:11397,editor:{id:"173955",title:"Prof.",name:"Sandra",middleName:null,surname:"Marinho",slug:"sandra-marinho",fullName:"Sandra Marinho",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRGYMQA4/Profile_Picture_2022-06-01T13:22:41.png",biography:"Dr. Sandra A. Marinho is an Associate Professor and Brazilian researcher at the State University of Paraíba (Universidade Estadual da Paraíba- UEPB), Campus VIII, located in Araruna, state of Paraíba since 2011. She holds a degree in Dentistry from the Federal University of Alfenas (UNIFAL), while her specialization and professional improvement in Stomatology took place at Hospital Heliopolis (São Paulo, SP). Her qualifications are: a specialist in Dental Imaging and Radiology, Master in Dentistry (Periodontics) from the University of São Paulo (FORP-USP, Ribeirão Preto, SP), and Doctor (Ph.D.) in Dentistry (Stomatology Clinic) from Hospital São Lucas of the Pontifical Catholic University of Rio Grande do Sul (HSL-PUCRS, Porto Alegre, RS). She held a postdoctoral internship at the Federal University from Jequitinhonha and Mucuri Valleys (UFVJM, Diamantina, MG). She is currently a member of the Brazilian Society for Dental Research (SBPqO) and the Brazilian Society of Stomatology and Pathology (SOBEP). Dr. Marinho's experience in Dentistry mainly covers the following subjects: oral diagnosis, oral radiology; oral medicine; lesions and oral infections; oral pathology, laser therapy and epidemiological studies.",institutionString:null,institution:{name:"State University of Paraíba",institutionURL:null,country:{name:"Brazil"}}},editorTwo:null,editorThree:null},{id:"2",title:"Prosthodontics and Implant Dentistry",coverUrl:"https://cdn.intechopen.com/series_topics/covers/2.jpg",isOpenForSubmission:!0,annualVolume:11398,editor:{id:"179568",title:"Associate Prof.",name:"Wen Lin",middleName:null,surname:"Chai",slug:"wen-lin-chai",fullName:"Wen Lin Chai",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRHGAQA4/Profile_Picture_2022-05-23T14:31:12.png",biography:"Professor Dr. Chai Wen Lin is currently a lecturer at the Department of Restorative Dentistry, Faculty of Dentistry of the University of Malaya. She obtained a Master of Dental Science in 2006 and a Ph.D. in 2011. Her Ph.D. research work on the soft tissue-implant interface at the University of Sheffield has yielded several important publications in the key implant journals. She was awarded an Excellent Exchange Award by the University of Sheffield which gave her the opportunity to work at the famous Faculty of Dentistry of the University of Gothenburg, Sweden, under the tutelage of Prof. Peter Thomsen. In 2016, she was appointed as a visiting scholar at UCLA, USA, with attachment in Hospital Dentistry, and involvement in research work related to zirconia implant. In 2016, her contribution to dentistry was recognized by the Royal College of Surgeon of Edinburgh with her being awarded a Fellowship in Dental Surgery. She has authored numerous papers published both in local and international journals. She was the Editor of the Malaysian Dental Journal for several years. Her main research interests are implant-soft tissue interface, zirconia implant, photofunctionalization, 3D-oral mucosal model and pulpal regeneration.",institutionString:null,institution:{name:"University of Malaya",institutionURL:null,country:{name:"Malaysia"}}},editorTwo:{id:"479686",title:"Dr.",name:"Ghee Seong",middleName:null,surname:"Lim",slug:"ghee-seong-lim",fullName:"Ghee Seong Lim",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003ScjLZQAZ/Profile_Picture_2022-06-08T14:17:06.png",biography:"Assoc. Prof Dr. Lim Ghee Seong graduated with a Bachelor of Dental Surgery from University of Malaya, Kuala Lumpur in 2008. He then pursued his Master in Clinical Dentistry, specializing in Restorative Dentistry at Newcastle University, Newcastle, UK, where he graduated with distinction. He has also been awarded the International Training Fellowship (Restorative Dentistry) from the Royal College of Surgeons. His passion for teaching then led him to join the faculty of dentistry at University Malaya and he has since became a valuable lecturer and clinical specialist in the Department of Restorative Dentistry. He is currently the removable prosthodontic undergraduate year 3 coordinator, head of the undergraduate module on occlusion and a member of the multidisciplinary team for the TMD clinic. He has previous membership in the British Society for Restorative Dentistry, the Malaysian Association of Aesthetic Dentistry and he is currently a lifetime member of the Malaysian Association for Prosthodontics. Currently, he is also the examiner for the Restorative Specialty Membership Examinations, Royal College of Surgeons, England. He has authored and co-authored handful of both local and international journal articles. His main interest is in prosthodontics, dental material, TMD and regenerative dentistry.",institutionString:null,institution:{name:"University of Malaya",institutionURL:null,country:{name:"Malaysia"}}},editorThree:null}]},overviewPageOFChapters:{paginationCount:15,paginationItems:[{id:"82427",title:"Our Globalization Era among Success, Obstacles and Doubts",doi:"10.5772/intechopen.105545",signatures:"Arnaldo Canziani, Annalisa Baldissera and Ahmad Kahwaji",slug:"our-globalization-era-among-success-obstacles-and-doubts",totalDownloads:5,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Globalization and Sustainability - Recent Advances, New Perspectives and Emerging Issues",coverURL:"https://cdn.intechopen.com/books/images_new/11476.jpg",subseries:{id:"91",title:"Sustainable Economy and Fair Society"}}},{id:"82248",title:"Sustainability and Excellence: Pillars for Business Survival",doi:"10.5772/intechopen.105420",signatures:"Irina Severin, Maria Cristina Dijmarescu and Mihai Caramihai",slug:"sustainability-and-excellence-pillars-for-business-survival",totalDownloads:5,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Globalization and Sustainability - Recent Advances, New Perspectives and Emerging Issues",coverURL:"https://cdn.intechopen.com/books/images_new/11476.jpg",subseries:{id:"91",title:"Sustainable Economy and Fair Society"}}},{id:"82124",title:"Assessment of Diversity, Growth Characteristics and Aboveground Biomass of Tree Species in Selected Urban Green Areas of Osogbo, Osun State",doi:"10.5772/intechopen.104982",signatures:"Omolara Aremu, Olusola O. Adetoro and Olusegun Awotoye",slug:"assessment-of-diversity-growth-characteristics-and-aboveground-biomass-of-tree-species-in-selected-u",totalDownloads:5,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Forest Degradation Under Global Change",coverURL:"https://cdn.intechopen.com/books/images_new/11457.jpg",subseries:{id:"94",title:"Climate Change and Environmental Sustainability"}}},{id:"81975",title:"Self-Sustained Communities: Food Security in Times of Crisis",doi:"10.5772/intechopen.104425",signatures:"Kriengsak Chareonwongsak",slug:"self-sustained-communities-food-security-in-times-of-crisis",totalDownloads:11,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Food Systems Resilience",coverURL:"https://cdn.intechopen.com/books/images_new/10897.jpg",subseries:{id:"91",title:"Sustainable Economy and Fair Society"}}}]},overviewPagePublishedBooks:{paginationCount:0,paginationItems:[]},openForSubmissionBooks:{paginationCount:0,paginationItems:[]},onlineFirstChapters:{paginationCount:13,paginationItems:[{id:"82285",title:"Parvovirus Vectors: The Future of Gene Therapy",doi:"10.5772/intechopen.105085",signatures:"Megha Gupta",slug:"parvovirus-vectors-the-future-of-gene-therapy",totalDownloads:4,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Recent Advances in Canine Medicine",coverURL:"https://cdn.intechopen.com/books/images_new/11580.jpg",subseries:{id:"19",title:"Animal Science"}}},{id:"81793",title:"Canine parvovirus-2: An Emerging Threat to Young Pets",doi:"10.5772/intechopen.104846",signatures:"Mithilesh Singh, Rajendran Manikandan, Ujjwal Kumar De, Vishal Chander, Babul Rudra Paul, Saravanan Ramakrishnan and Darshini Maramreddy",slug:"canine-parvovirus-2-an-emerging-threat-to-young-pets",totalDownloads:16,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Recent Advances in Canine Medicine",coverURL:"https://cdn.intechopen.com/books/images_new/11580.jpg",subseries:{id:"19",title:"Animal Science"}}},{id:"81271",title:"The Diversity of Parvovirus Telomeres",doi:"10.5772/intechopen.102684",signatures:"Marianne Laugel, Emilie Lecomte, Eduard Ayuso, Oumeya Adjali, Mathieu Mével and Magalie Penaud-Budloo",slug:"the-diversity-of-parvovirus-telomeres",totalDownloads:38,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Recent Advances in Canine Medicine",coverURL:"https://cdn.intechopen.com/books/images_new/11580.jpg",subseries:{id:"19",title:"Animal Science"}}},{id:"79209",title:"Virtual Physiology: A Tool for the 21st Century",doi:"10.5772/intechopen.99671",signatures:"Carmen Nóbrega, Maria Aires Pereira, Catarina Coelho, Isabel Brás, Ana Cristina Mega, Carla Santos, Fernando Esteves, Rita Cruz, Ana I. Faustino-Rocha, Paula A. Oliveira, João Mesquita and Helena Vala",slug:"virtual-physiology-a-tool-for-the-21st-century",totalDownloads:153,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Updates on Veterinary Anatomy and Physiology",coverURL:"https://cdn.intechopen.com/books/images_new/10665.jpg",subseries:{id:"19",title:"Animal Science"}}},{id:"78849",title:"Application of Vermicompost Fertilizer in Aquaculture Nutrition: Review",doi:"10.5772/intechopen.100326",signatures:"Sonnia Nzilani Musyoka and Rita Nairuti",slug:"application-of-vermicompost-fertilizer-in-aquaculture-nutrition-review",totalDownloads:71,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Animal Nutrition - Annual Volume 2022",coverURL:"https://cdn.intechopen.com/books/images_new/11416.jpg",subseries:{id:"20",title:"Animal Nutrition"}}},{id:"78543",title:"Pulmonary Vein: Embryology, Anatomy, Function and Disease",doi:"10.5772/intechopen.100051",signatures:"Chan I-Ping and Hsueh Tung",slug:"pulmonary-vein-embryology-anatomy-function-and-disease",totalDownloads:182,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Updates on Veterinary Anatomy and Physiology",coverURL:"https://cdn.intechopen.com/books/images_new/10665.jpg",subseries:{id:"19",title:"Animal Science"}}},{id:"78564",title:"Anatomy of the Rhesus Monkey (Macaca mulatta): The Essentials for the Biomedical Researcher",doi:"10.5772/intechopen.99067",signatures:"Christophe Casteleyn and Jaco Bakker",slug:"anatomy-of-the-rhesus-monkey-macaca-mulatta-the-essentials-for-the-biomedical-researcher",totalDownloads:348,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Updates on Veterinary Anatomy and Physiology",coverURL:"https://cdn.intechopen.com/books/images_new/10665.jpg",subseries:{id:"19",title:"Animal Science"}}},{id:"77999",title:"Bronchus-Associated Lymphoid Tissue (BALT) Histology and Its Role in Various Pathologies",doi:"10.5772/intechopen.99366",signatures:"Tuba Parlak Ak",slug:"bronchus-associated-lymphoid-tissue-balt-histology-and-its-role-in-various-pathologies",totalDownloads:212,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Updates on Veterinary Anatomy and Physiology",coverURL:"https://cdn.intechopen.com/books/images_new/10665.jpg",subseries:{id:"19",title:"Animal Science"}}},{id:"78242",title:"Genomic Instability and Cyto-Genotoxic Damage in Animal Species",doi:"10.5772/intechopen.99685",signatures:"María Evarista Arellano-García, Olivia Torres-Bugarín, Maritza Roxana García-García, Daniel García-Flores, Yanis Toledano-Magaña, Cinthya Sofia Sanabria-Mora, Sandra Castro-Gamboa and Juan Carlos García-Ramos",slug:"genomic-instability-and-cyto-genotoxic-damage-in-animal-species",totalDownloads:150,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Updates on Veterinary Anatomy and Physiology",coverURL:"https://cdn.intechopen.com/books/images_new/10665.jpg",subseries:{id:"19",title:"Animal Science"}}},{id:"78503",title:"Biomechanics of the Canine Elbow Joint",doi:"10.5772/intechopen.99569",signatures:"Thomas Rohwedder",slug:"biomechanics-of-the-canine-elbow-joint",totalDownloads:179,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Updates on Veterinary Anatomy and Physiology",coverURL:"https://cdn.intechopen.com/books/images_new/10665.jpg",subseries:{id:"19",title:"Animal Science"}}}]},subseriesFiltersForOFChapters:[{caption:"Animal Nutrition",value:20,count:1,group:"subseries"},{caption:"Animal Science",value:19,count:12,group:"subseries"}],publishedBooks:{paginationCount:11,paginationItems:[{type:"book",id:"10664",title:"Animal Reproduction",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/10664.jpg",slug:"animal-reproduction",publishedDate:"May 25th 2022",editedByType:"Edited by",bookSignature:"Yusuf Bozkurt and Mustafa Numan Bucak",hash:"2d66af42fb17d0a6556bb9ef28e273c7",volumeInSeries:11,fullTitle:"Animal Reproduction",editors:[{id:"90846",title:"Prof.",name:"Yusuf",middleName:null,surname:"Bozkurt",slug:"yusuf-bozkurt",fullName:"Yusuf Bozkurt",profilePictureURL:"https://mts.intechopen.com/storage/users/90846/images/system/90846.jpg",institutionString:"İskenderun Technical University",institution:{name:"İskenderun Technical University",institutionURL:null,country:{name:"Turkey"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"10830",title:"Animal Feed Science and Nutrition",subtitle:"Production, Health and Environment",coverURL:"https://cdn.intechopen.com/books/images_new/10830.jpg",slug:"animal-feed-science-and-nutrition-production-health-and-environment",publishedDate:"May 18th 2022",editedByType:"Edited by",bookSignature:"Amlan Kumar Patra",hash:"79944fc8fbbaa329aed6fde388154832",volumeInSeries:10,fullTitle:"Animal Feed Science and Nutrition - Production, Health and Environment",editors:[{id:"310962",title:"Dr.",name:"Amlan",middleName:"Kumar",surname:"Patra",slug:"amlan-patra",fullName:"Amlan Patra",profilePictureURL:"https://mts.intechopen.com/storage/users/310962/images/system/310962.jpg",institutionString:null,institution:{name:"West Bengal University of Animal and Fishery Sciences",institutionURL:null,country:{name:"India"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"8737",title:"Rabies Virus at the Beginning of 21st Century",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/8737.jpg",slug:"rabies-virus-at-the-beginning-of-21st-century",publishedDate:"May 11th 2022",editedByType:"Edited by",bookSignature:"Sergey Tkachev",hash:"49cce3f548da548c718c865feb343509",volumeInSeries:9,fullTitle:"Rabies Virus at the Beginning of 21st Century",editors:[{id:"61139",title:"Dr.",name:"Sergey",middleName:null,surname:"Tkachev",slug:"sergey-tkachev",fullName:"Sergey Tkachev",profilePictureURL:"https://mts.intechopen.com/storage/users/61139/images/system/61139.png",institutionString:"Russian Academy of Sciences",institution:{name:"Russian Academy of Sciences",institutionURL:null,country:{name:"Russia"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"10496",title:"Advanced Studies in the 21st Century Animal Nutrition",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/10496.jpg",slug:"advanced-studies-in-the-21st-century-animal-nutrition",publishedDate:"December 8th 2021",editedByType:"Edited by",bookSignature:"László Babinszky, Juliana Oliveira and Edson Mauro Santos",hash:"8ffe43a82ac48b309abc3632bbf3efd0",volumeInSeries:8,fullTitle:"Advanced Studies in the 21st Century Animal Nutrition",editors:[{id:"53998",title:"Prof.",name:"László",middleName:null,surname:"Babinszky",slug:"laszlo-babinszky",fullName:"László Babinszky",profilePictureURL:"https://mts.intechopen.com/storage/users/53998/images/system/53998.png",institutionString:"University of Debrecen",institution:{name:"University of Debrecen",institutionURL:null,country:{name:"Hungary"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"10497",title:"Canine Genetics, Health and Medicine",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/10497.jpg",slug:"canine-genetics-health-and-medicine",publishedDate:"June 2nd 2021",editedByType:"Edited by",bookSignature:"Catrin Rutland",hash:"b91512e31ce34032e560362e6cbccc1c",volumeInSeries:7,fullTitle:"Canine Genetics, Health and Medicine",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:"8545",title:"Animal Reproduction in Veterinary Medicine",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/8545.jpg",slug:"animal-reproduction-in-veterinary-medicine",publishedDate:"January 20th 2021",editedByType:"Edited by",bookSignature:"Faruk Aral, Rita Payan-Carreira and Miguel Quaresma",hash:"13aaddf5fdbbc78387e77a7da2388bf6",volumeInSeries:6,fullTitle:"Animal Reproduction in Veterinary Medicine",editors:[{id:"25600",title:"Prof.",name:"Faruk",middleName:null,surname:"Aral",slug:"faruk-aral",fullName:"Faruk Aral",profilePictureURL:"https://mts.intechopen.com/storage/users/25600/images/system/25600.jpg",institutionString:"Independent Researcher",institution:{name:"Harran University",institutionURL:null,country:{name:"Turkey"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"9081",title:"Equine Science",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/9081.jpg",slug:"equine-science",publishedDate:"September 23rd 2020",editedByType:"Edited by",bookSignature:"Catrin Rutland and Albert Rizvanov",hash:"ac415ef2f5450fa80fdb9cf6cf32cd2d",volumeInSeries:5,fullTitle:"Equine Science",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:"8460",title:"Reproductive Biology and Technology in Animals",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/8460.jpg",slug:"reproductive-biology-and-technology-in-animals",publishedDate:"April 15th 2020",editedByType:"Edited by",bookSignature:"Juan Carlos Gardón Poggi and Katy Satué Ambrojo",hash:"32ef5fe73998dd723d308225d756fa1e",volumeInSeries:4,fullTitle:"Reproductive Biology and Technology in Animals",editors:[{id:"251314",title:"Dr.",name:"Juan Carlos",middleName:null,surname:"Gardón",slug:"juan-carlos-gardon",fullName:"Juan Carlos Gardón",profilePictureURL:"https://mts.intechopen.com/storage/users/251314/images/system/251314.jpeg",institutionString:"Catholic University of Valencia San Vicente Mártir, Spain",institution:null}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"8524",title:"Lactation in Farm Animals",subtitle:"Biology, Physiological Basis, Nutritional Requirements, and Modelization",coverURL:"https://cdn.intechopen.com/books/images_new/8524.jpg",slug:"lactation-in-farm-animals-biology-physiological-basis-nutritional-requirements-and-modelization",publishedDate:"January 22nd 2020",editedByType:"Edited by",bookSignature:"Naceur M'Hamdi",hash:"2aa2a9a0ec13040bbf0455e34625504e",volumeInSeries:3,fullTitle:"Lactation in Farm Animals - Biology, Physiological Basis, Nutritional Requirements, and Modelization",editors:[{id:"73376",title:"Dr.",name:"Naceur",middleName:null,surname:"M'Hamdi",slug:"naceur-m'hamdi",fullName:"Naceur M'Hamdi",profilePictureURL:"https://mts.intechopen.com/storage/users/73376/images/system/73376.jpg",institutionString:null,institution:null}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"7144",title:"Veterinary Anatomy and Physiology",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7144.jpg",slug:"veterinary-anatomy-and-physiology",publishedDate:"March 13th 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:"Prof.",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:4},{group:"subseries",caption:"Animal Science",value:19,count:5}],publicationYearFilters:[{group:"publicationYear",caption:"2022",value:2022,count:3},{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:25,paginationItems:[{id:"429683",title:"Dr.",name:"Bilal",middleName:null,surname:"Khalid",slug:"bilal-khalid",fullName:"Bilal Khalid",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/429683/images/system/429683.png",biography:"Dr. Bilal Khalid received a Ph.D. in Industrial Business Administration from KMITL Business School, Bangkok, in 2021, and a master’s in International Business Management from Stamford International University, Bangkok, in 2017. Dr. Khalid\\'s research interests include leadership and negotiations, digital transformations, gamification, eLearning, blockchain, Big Data, and management of information technology. Dr. Bilal Khalid also serves as an academic editor at Education Research International and a reviewer for international journals.",institutionString:"KMITL Business School",institution:{name:"King Mongkut's Institute of Technology Ladkrabang",country:{name:"Thailand"}}},{id:"418514",title:"Dr.",name:"Muhammad",middleName:null,surname:"Mohiuddin",slug:"muhammad-mohiuddin",fullName:"Muhammad Mohiuddin",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000038UqSfQAK/Profile_Picture_2022-05-13T10:39:03.jpg",biography:"Dr. Muhammad Mohiuddin is an Associate Professor of International Business at Laval University, Canada. He has taught at Thompson Rivers University, Canada; University of Paris-Est, France; Osnabruck University of Applied Science, Germany; and Shanghai Institute of Technology and Tianjin University of Technology, China. He has published research in Research Policy, Applied Economics, Review of Economic Philosophy, Strategic Change, International Journal of Logistics, Sustainability, Journal of Environmental Management, Journal of Global Information Management, Journal of Cleaner Production, M@N@GEMENT, and more. He is a member of CEDIMES Institut (France), Academy of International Business (AIB), Strategic Management Society (SMS), Academy of Management (AOM), Administrative Science Association of Canada (ASAC), and Canadian council of small business and entrepreneurship (CCSBE). He is currently the director of the Research Group on Contemporary Asia (GERAC) at Laval University. He is also co-managing editor of Transnational Corporations Review and a guest editor for Electronic Commerce Research and Journal of Internet Technology.",institutionString:"Université Laval",institution:{name:"Université Laval",country:{name:"Canada"}}},{id:"189147",title:"Dr.",name:"Hailan",middleName:null,surname:"Salamun",slug:"hailan-salamun",fullName:"Hailan Salamun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/189147/images/19274_n.jpeg",biography:"Hailan Salamun, (Dr.) was born in Selangor, Malaysia and graduated from Tunku Ampuan Jamaah Religious High School at Shah Alam. Obtained a degree from the International Islamic University (UIA), Gombak in the field of Islamic Revealed Knowledge and Heritage. Next, I furthered my studies to the professional level to obtain a Diploma in Education at UIA. After serving for several years in school, I furthered my studies to the Master of Dakwah and Leadership at Universiti Kebangsaan Malaysia (UKM), Bangi. I graduated with a Doctor of Philosophy in Principalship Leadership from the University of Malaya (UM) in 2010. I am currently a senior lecturer in the Department of Nationalism and Civilization, Center for Basic and Continuing Education, Universiti Malaysia Terengganu. Prior to that, I had served in several educational institutions such as schools, the Institute of Teacher Education (IPG), and also the University of Malaya. I am also actively involved in paper presentation, writing and publishing. My research interests are focused on leadership, education, society and Islamic civilization. This area of research requires a detailed understanding of Islamic studies and research studies in leadership. Another research interest that I have explored recently is the politics of the Malay community and also the leadership of the mosque.",institutionString:null,institution:{name:"Universiti Malaysia Terengganu",country:{name:"Malaysia"}}},{id:"442081",title:"Dr.",name:"Audrey",middleName:null,surname:"Addy",slug:"audrey-addy",fullName:"Audrey Addy",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Kwame Nkrumah University of Science and Technology",country:{name:"Ghana"}}},{id:"437993",title:"Mr.",name:"Job",middleName:null,surname:"Jackson",slug:"job-jackson",fullName:"Job Jackson",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Management College of Southern Africa",country:{name:"South Africa"}}},{id:"428495",title:"Prof.",name:"Asyraf",middleName:null,surname:"Ab Rahman",slug:"asyraf-ab-rahman",fullName:"Asyraf Ab Rahman",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Universiti Malaysia Terengganu",country:{name:"Malaysia"}}},{id:"429650",title:"Dr.",name:"Jacqueline",middleName:null,surname:"Kareem",slug:"jacqueline-kareem",fullName:"Jacqueline Kareem",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Christ University",country:{name:"India"}}},{id:"421041",title:"Dr.",name:"Sunil",middleName:null,surname:"Kumar Ramdas",slug:"sunil-kumar-ramdas",fullName:"Sunil Kumar Ramdas",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Jain University",country:{name:"India"}}},{id:"421833",title:"Mr.",name:"Eugene",middleName:null,surname:"Owusu-Acheampong",slug:"eugene-owusu-acheampong",fullName:"Eugene Owusu-Acheampong",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Ghana",country:{name:"Ghana"}}},{id:"239876",title:"Ph.D.",name:"Luciana",middleName:null,surname:"Mourão",slug:"luciana-mourao",fullName:"Luciana Mourão",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Universidade Salgado de Oliveira",country:{name:"Brazil"}}},{id:"421735",title:"Dr.",name:"elizabeth",middleName:null,surname:"addy",slug:"elizabeth-addy",fullName:"elizabeth addy",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"442083",title:"Dr.",name:"James",middleName:null,surname:"Addy",slug:"james-addy",fullName:"James Addy",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"437991",title:"Prof.",name:"Muhammad",middleName:null,surname:"Hoque",slug:"muhammad-hoque",fullName:"Muhammad Hoque",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"421006",title:"Dr.",name:"Anna",middleName:null,surname:"Uster",slug:"anna-uster",fullName:"Anna Uster",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"470243",title:"Dr.",name:"Md Samim",middleName:null,surname:"Al Azad",slug:"md-samim-al-azad",fullName:"Md Samim Al Azad",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"470244",title:"Dr.",name:"Slimane",middleName:null,surname:"Ed-dafali",slug:"slimane-ed-dafali",fullName:"Slimane Ed-dafali",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"421011",title:"Dr.",name:"Afatakpa",middleName:null,surname:"Fortune",slug:"afatakpa-fortune",fullName:"Afatakpa Fortune",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"446057",title:"Mr.",name:"Okedare",middleName:null,surname:"David Olubukunmi",slug:"okedare-david-olubukunmi",fullName:"Okedare David Olubukunmi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"421778",title:"Dr.",name:"Fatimah",middleName:"Saeed",surname:"AlAhmari",slug:"fatimah-alahmari",fullName:"Fatimah AlAhmari",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"421024",title:"Prof.",name:"Harold Andrew",middleName:null,surname:"Patrick",slug:"harold-andrew-patrick",fullName:"Harold Andrew Patrick",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"421065",title:"Ms.",name:"Euzália",middleName:null,surname:"do Rosário Botelho Tomé",slug:"euzalia-do-rosario-botelho-tome",fullName:"Euzália do Rosário Botelho Tomé",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"421053",title:"Associate Prof.",name:"Ken",middleName:null,surname:"Kalala Ndalamba",slug:"ken-kalala-ndalamba",fullName:"Ken Kalala Ndalamba",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"421826",title:"Dr.",name:"Inusah",middleName:null,surname:"Salifu",slug:"inusah-salifu",fullName:"Inusah Salifu",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"420823",title:"Prof.",name:"Gardênia da Silva",middleName:null,surname:"Abbad",slug:"gardenia-da-silva-abbad",fullName:"Gardênia da Silva Abbad",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"437613",title:"MSc.",name:"Juliana",middleName:null,surname:"Legentil",slug:"juliana-legentil",fullName:"Juliana Legentil",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null}]}},subseries:{item:{id:"20",type:"subseries",title:"Animal Nutrition",keywords:"Sustainable Animal Diets, Carbon Footprint, Meta Analyses",scope:"An essential part of animal production is nutrition. Animals need to receive a properly balanced diet. One of the new challenges we are now faced with is sustainable animal diets (STAND) that involve the 3 P’s (People, Planet, and Profitability). We must develop animal feed that does not compete with human food, use antibiotics, and explore new growth promoters options, such as plant extracts or compounds that promote feed efficiency (e.g., monensin, oils, enzymes, probiotics). These new feed options must also be environmentally friendly, reducing the Carbon footprint, CH4, N, and P emissions to the environment, with an adequate formulation of nutrients.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/20.jpg",hasOnlineFirst:!0,hasPublishedBooks:!0,annualVolume:11416,editor:{id:"175967",title:"Dr.",name:"Manuel",middleName:null,surname:"Gonzalez Ronquillo",slug:"manuel-gonzalez-ronquillo",fullName:"Manuel Gonzalez Ronquillo",profilePictureURL:"https://mts.intechopen.com/storage/users/175967/images/system/175967.png",biography:"Dr. Manuel González Ronquillo obtained his doctorate degree from the University of Zaragoza, Spain, in 2001. He is a research professor at the Faculty of Veterinary Medicine and Animal Husbandry, Autonomous University of the State of Mexico. He is also a level-2 researcher. He received a Fulbright-Garcia Robles fellowship for a postdoctoral stay at the US Dairy Forage Research Center, Madison, Wisconsin, USA in 2008–2009. He received grants from Alianza del Pacifico for a stay at the University of Magallanes, Chile, in 2014, and from Consejo Nacional de Ciencia y Tecnología (CONACyT) to work in the Food and Agriculture Organization’s Animal Production and Health Division (AGA), Rome, Italy, in 2014–2015. He has collaborated with researchers from different countries and published ninety-eight journal articles. He teaches various degree courses in zootechnics, sheep production, and agricultural sciences and natural resources.\n\nDr. Ronquillo’s research focuses on the evaluation of sustainable animal diets (StAnD), using native resources of the region, decreasing carbon footprint, and applying meta-analysis and mathematical models for a better understanding of animal production.",institutionString:null,institution:{name:"Universidad Autónoma del Estado de México",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null,series:{id:"13",title:"Veterinary Medicine and Science",doi:"10.5772/intechopen.73681",issn:"2632-0517"},editorialBoard:[{id:"175762",title:"Dr.",name:"Alfredo J.",middleName:null,surname:"Escribano",slug:"alfredo-j.-escribano",fullName:"Alfredo J. Escribano",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRGnzQAG/Profile_Picture_1633076636544",institutionString:"Consultant and Independent Researcher in Industry Sector, Spain",institution:null},{id:"310962",title:"Dr.",name:"Amlan",middleName:"Kumar",surname:"Patra",slug:"amlan-patra",fullName:"Amlan Patra",profilePictureURL:"https://mts.intechopen.com/storage/users/310962/images/system/310962.jpg",institutionString:null,institution:{name:"West Bengal University of Animal and Fishery Sciences",institutionURL:null,country:{name:"India"}}},{id:"216995",title:"Prof.",name:"Figen",middleName:null,surname:"Kırkpınar",slug:"figen-kirkpinar",fullName:"Figen Kırkpınar",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRMzxQAG/Profile_Picture_1625722918145",institutionString:null,institution:{name:"Ege University",institutionURL:null,country:{name:"Turkey"}}}]},onlineFirstChapters:{paginationCount:2,paginationItems:[{id:"82392",title:"Nanomaterials as Novel Biomarkers for Cancer Nanotheranostics: State of the Art",doi:"10.5772/intechopen.105700",signatures:"Hao Yu, Zhihai Han, Cunrong Chen and Leisheng Zhang",slug:"nanomaterials-as-novel-biomarkers-for-cancer-nanotheranostics-state-of-the-art",totalDownloads:2,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Biotechnology - Biosensors, Biomaterials and Tissue Engineering - Annual Volume 2022",coverURL:"https://cdn.intechopen.com/books/images_new/11405.jpg",subseries:{id:"9",title:"Biotechnology - Biosensors, Biomaterials and Tissue Engineering"}}},{id:"81778",title:"Influence of Mechanical Properties of Biomaterials on the Reconstruction of Biomedical Parts via Additive Manufacturing Techniques: An Overview",doi:"10.5772/intechopen.104465",signatures:"Babatunde Olamide Omiyale, Akeem Abiodun Rasheed, Robinson Omoboyode Akinnusi and Temitope Olumide Olugbade",slug:"influence-of-mechanical-properties-of-biomaterials-on-the-reconstruction-of-biomedical-parts-via-add",totalDownloads:9,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Biotechnology - Biosensors, Biomaterials and Tissue Engineering - Annual Volume 2022",coverURL:"https://cdn.intechopen.com/books/images_new/11405.jpg",subseries:{id:"9",title:"Biotechnology - Biosensors, Biomaterials and Tissue Engineering"}}}]},publishedBooks:{paginationCount:1,paginationItems:[{type:"book",id:"7437",title:"Nanomedicines",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7437.jpg",slug:"nanomedicines",publishedDate:"February 13th 2019",editedByType:"Edited by",bookSignature:"Muhammad Akhyar Farrukh",hash:"0e1f5f6258f074c533976c4f4d248568",volumeInSeries:5,fullTitle:"Nanomedicines",editors:[{id:"63182",title:"Dr.",name:"Muhammad Akhyar",middleName:null,surname:"Farrukh",slug:"muhammad-akhyar-farrukh",fullName:"Muhammad Akhyar Farrukh",profilePictureURL:"https://mts.intechopen.com/storage/users/63182/images/system/63182.png",institutionString:"Forman Christian College",institution:{name:"Forman Christian College",institutionURL:null,country:{name:"Pakistan"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null}]},testimonialsList:[{id:"18",text:"It was great publishing with IntechOpen, the process was straightforward and I had support all along.",author:{id:"71579",name:"Berend",surname:"Olivier",institutionString:"Utrecht University",profilePictureURL:"https://mts.intechopen.com/storage/users/71579/images/system/71579.png",slug:"berend-olivier",institution:{id:"253",name:"Utrecht University",country:{id:null,name:"Netherlands"}}}},{id:"8",text:"I work with IntechOpen for a number of reasons: their professionalism, their mission in support of Open Access publishing, and the quality of their peer-reviewed publications, but also because they believe in equality.",author:{id:"202192",name:"Catrin",surname:"Rutland",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/202192/images/system/202192.png",slug:"catrin-rutland",institution:{id:"134",name:"University of Nottingham",country:{id:null,name:"United Kingdom"}}}},{id:"27",text:"The opportunity to work with a prestigious publisher allows for the possibility to collaborate with more research groups interested in animal nutrition, leading to the development of new feeding strategies and food valuation while being more sustainable with the environment, allowing more readers to learn about the subject.",author:{id:"175967",name:"Manuel",surname:"Gonzalez Ronquillo",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/175967/images/system/175967.png",slug:"manuel-gonzalez-ronquillo",institution:{id:"6221",name:"Universidad Autónoma del Estado de México",country:{id:null,name:"Mexico"}}}}]},submityourwork:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:89,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:104,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:32,numberOfPublishedChapters:318,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:141,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:113,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:105,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:5,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:15,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],subseriesList:[],annualVolumeBook:{},thematicCollection:[],selectedSeries:null,selectedSubseries:null},seriesLanding:{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:"June 29th, 2022",hasOnlineFirst:!0,numberOfOpenTopics:4,numberOfPublishedChapters:318,numberOfPublishedBooks:32,editor:{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"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"}}},subseries:[{id:"14",title:"Cell and Molecular Biology",keywords:"Omics (Transcriptomics; Proteomics; Metabolomics), Molecular Biology, Cell Biology, Signal Transduction and Regulation, Cell Growth and Differentiation, Apoptosis, Necroptosis, Ferroptosis, Autophagy, Cell Cycle, Macromolecules and Complexes, Gene Expression",scope:"The Cell and Molecular Biology topic within the IntechOpen Biochemistry Series aims to rapidly publish contributions on all aspects of cell and molecular biology, including aspects related to biochemical and genetic research (not only in humans but all living beings). We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics include, but are not limited to: Advanced techniques of cellular and molecular biology (Molecular methodologies, imaging techniques, and bioinformatics); Biological activities at the molecular level; Biological processes of cell functions, cell division, senescence, maintenance, and cell death; Biomolecules interactions; Cancer; Cell biology; Chemical biology; Computational biology; Cytochemistry; Developmental biology; Disease mechanisms and therapeutics; DNA, and RNA metabolism; Gene functions, genetics, and genomics; Genetics; Immunology; Medical microbiology; Molecular biology; Molecular genetics; Molecular processes of cell and organelle dynamics; Neuroscience; Protein biosynthesis, degradation, and functions; Regulation of molecular interactions in a cell; Signalling networks and system biology; Structural biology; Virology and microbiology.",annualVolume:11410,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/14.jpg",editor:{id:"165627",title:"Dr.",name:"Rosa María",middleName:null,surname:"Martínez-Espinosa",fullName:"Rosa María Martínez-Espinosa",profilePictureURL:"https://mts.intechopen.com/storage/users/165627/images/system/165627.jpeg",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",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",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",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",keywords:"Phenolic Compounds, Essential Oils, Modification of Biomolecules, Glycobiology, Combinatorial Chemistry, Therapeutic peptides, Enzyme Inhibitors",scope:"Chemical biology spans the fields of chemistry and biology involving the application of biological and chemical molecules and techniques. In recent years, the application of chemistry to biological molecules has gained significant interest in medicinal and pharmacological studies. This topic will be devoted to understanding the interplay between biomolecules and chemical compounds, their structure and function, and their potential applications in related fields. Being a part of the biochemistry discipline, the ideas and concepts that have emerged from Chemical Biology have affected other related areas. This topic will closely deal with all emerging trends in this discipline.",annualVolume:11411,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",institutionString:null,institution:{name:"Anadolu University",institutionURL:null,country:{name:"Turkey"}}},editorTwo:{id:"13652",title:"Prof.",name:"Deniz",middleName:null,surname:"Ekinci",fullName:"Deniz Ekinci",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYLT1QAO/Profile_Picture_1634557223079",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",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",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",keywords:"Biomolecules Metabolism, Energy Metabolism, Metabolic Pathways, Key Metabolic Enzymes, Metabolic Adaptation",scope:"Metabolism is frequently defined in biochemistry textbooks as the overall process that allows living systems to acquire and use the free energy they need for their vital functions or the chemical processes that occur within a living organism to maintain life. Behind these definitions are hidden all the aspects of normal and pathological functioning of all processes that the topic ‘Metabolism’ will cover within the Biochemistry Series. Thus all studies on metabolism will be considered for publication.",annualVolume:11413,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/17.jpg",editor:{id:"138626",title:"Dr.",name:"Yannis",middleName:null,surname:"Karamanos",fullName:"Yannis Karamanos",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002g6Jv2QAE/Profile_Picture_1629356660984",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",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",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",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",keywords:"Mono- and Two-Dimensional Gel Electrophoresis (1-and 2-DE), Liquid Chromatography (LC), Mass Spectrometry/Tandem Mass Spectrometry (MS; MS/MS), Proteins",scope:"With the recognition that the human genome cannot provide answers to the etiology of a disorder, changes in the proteins expressed by a genome became a focus in research. Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. The Proteomics topic aims to attract contributions on all aspects of MS-based proteomics that, by pushing the boundaries of MS capabilities, may address biological problems that have not been resolved yet.",annualVolume:11414,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/18.jpg",editor:{id:"200689",title:"Prof.",name:"Paolo",middleName:null,surname:"Iadarola",fullName:"Paolo Iadarola",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSCl8QAG/Profile_Picture_1623568118342",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorTwo:{id:"201414",title:"Dr.",name:"Simona",middleName:null,surname:"Viglio",fullName:"Simona Viglio",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKDHQA4/Profile_Picture_1630402531487",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorThree:null,editorialBoard:[{id:"72288",title:"Dr.",name:"Arli Aditya",middleName:null,surname:"Parikesit",fullName:"Arli Aditya Parikesit",profilePictureURL:"https://mts.intechopen.com/storage/users/72288/images/system/72288.jpg",institutionString:null,institution:{name:"Indonesia International Institute for Life Sciences",institutionURL:null,country:{name:"Indonesia"}}},{id:"40928",title:"Dr.",name:"Cesar",middleName:null,surname:"Lopez-Camarillo",fullName:"Cesar Lopez-Camarillo",profilePictureURL:"https://mts.intechopen.com/storage/users/40928/images/3884_n.png",institutionString:null,institution:{name:"Universidad Autónoma de la Ciudad de México",institutionURL:null,country:{name:"Mexico"}}},{id:"81926",title:"Dr.",name:"Shymaa",middleName:null,surname:"Enany",fullName:"Shymaa Enany",profilePictureURL:"https://mts.intechopen.com/storage/users/81926/images/system/81926.png",institutionString:"Suez Canal University",institution:{name:"Suez Canal University",institutionURL:null,country:{name:"Egypt"}}}]}]}},libraryRecommendation:{success:null,errors:{},institutions:[]},route:{name:"profile.detail",path:"/profiles/169014",hash:"",query:{},params:{id:"169014"},fullPath:"/profiles/169014",meta:{},from:{name:null,path:"/",hash:"",query:{},params:{},fullPath:"/",meta:{}}}},function(){var e;(e=document.currentScript||document.scripts[document.scripts.length-1]).parentNode.removeChild(e)}()