\r\n\t1. To draw spotlight on recent studies and research concerned with the regeneration process in animal kingdom and models with emphasis on the cellular origins of regeneration. \r\n\t2. Then, we will be dealing with the reasons for the differences in the regenerative capacity of animals on many levels, including the molecular mechanism, gene expression, epigenetic regulation, common elements affecting regeneration and comparing their contributions to regeneration. \r\n\t3. To provide new insights into how to promote regeneration in mammals.
",isbn:null,printIsbn:"979-953-307-X-X",pdfIsbn:null,doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,hash:"689b9f46c48cd54a2874b8da7386549d",bookSignature:"Dr. Hussein Abdelhay Essayed Kaoud",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/8575.jpg",keywords:"Regeneration, Cellular Basis, Molecular Basis, Differentiation, Epigenetic Regulators, Regeneration Associated Genes, Autotomy, Epimorphosis, Morphallaxis, Polyphyodonty, Vertebrates, Invertebrates",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"November 17th 2020",dateEndSecondStepPublish:"December 15th 2020",dateEndThirdStepPublish:"February 13th 2021",dateEndFourthStepPublish:"May 4th 2021",dateEndFifthStepPublish:"July 3rd 2021",remainingDaysToSecondStep:"3 months",secondStepPassed:!0,currentStepOfPublishingProcess:4,editedByType:null,kuFlag:!1,biosketch:"A pioneering researcher in molecular biology, epidemiology, aquaculture toxicology, full professor of animal health and environmental pollution senior member, and holder of two registered patents and three scientific records. Veterinary fellowships in animal care and surgeons and wildlife management & conservation.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"265070",title:"Dr.",name:"Hussein Abdelhay",middleName:null,surname:"Essayed Kaoud",slug:"hussein-abdelhay-essayed-kaoud",fullName:"Hussein Abdelhay Essayed Kaoud",profilePictureURL:"https://mts.intechopen.com/storage/users/265070/images/system/265070.png",biography:"Dr. Hussein Kaoud was the Chairman of the Department of Preventive Medicine at Cairo University. He has given lectures in Molecular Epidemiology and Biotechnology at different universities and has been a member of many International Publishing Houses, Reviewer, and Editor for indexed journals. Currently, he works as Full Professor of Preventive Medicine at Cairo University, Egypt. His research interest is focused on Molecular Biology and Advanced Technology of Basic Life Sciences after he had his Ph.D. and D.Sc. He has published more than 300 publications. Dr. Hussein Kaoud has several international books, one international award (USA), 10 Cairo university International Publication awards and the Appreciation Award in Advanced Technological Sciences, from Cairo University. He supervised, examined and discussed many medical dissertations.",institutionString:"Cairo University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"4",totalChapterViews:"0",totalEditedBooks:"3",institution:{name:"Cairo University",institutionURL:null,country:{name:"Egypt"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"6",title:"Biochemistry, Genetics and Molecular Biology",slug:"biochemistry-genetics-and-molecular-biology"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"297737",firstName:"Mateo",lastName:"Pulko",middleName:null,title:"Mr.",imageUrl:"https://mts.intechopen.com/storage/users/297737/images/8492_n.png",email:"mateo.p@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:"6475",title:"Tissue Regeneration",subtitle:null,isOpenForSubmission:!1,hash:"d5ed06a80f0205146aa90d158facefd1",slug:"tissue-regeneration",bookSignature:"Hussein Abdel hay El-Sayed Kaoud",coverURL:"https://cdn.intechopen.com/books/images_new/6475.jpg",editedByType:"Edited by",editors:[{id:"265070",title:"Dr.",name:"Hussein Abdelhay",surname:"Essayed Kaoud",slug:"hussein-abdelhay-essayed-kaoud",fullName:"Hussein Abdelhay Essayed Kaoud"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5469",title:"Canine Medicine",subtitle:"Recent Topics and Advanced Research",isOpenForSubmission:!1,hash:"a7e798d88413dd09f8a4af2b2e325b82",slug:"canine-medicine-recent-topics-and-advanced-research",bookSignature:"Hussein Abdelhay Elsayed Kaoud",coverURL:"https://cdn.intechopen.com/books/images_new/5469.jpg",editedByType:"Edited by",editors:[{id:"265070",title:"Dr.",name:"Hussein Abdelhay",surname:"Essayed Kaoud",slug:"hussein-abdelhay-essayed-kaoud",fullName:"Hussein Abdelhay Essayed Kaoud"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8288",title:"Bacterial Cattle Diseases",subtitle:null,isOpenForSubmission:!1,hash:"f45b8b4974eb0d7de8719ef6b9146200",slug:"bacterial-cattle-diseases",bookSignature:"Hussein Abdel hay El-Sayed Kaoud",coverURL:"https://cdn.intechopen.com/books/images_new/8288.jpg",editedByType:"Edited by",editors:[{id:"265070",title:"Dr.",name:"Hussein Abdelhay",surname:"Essayed Kaoud",slug:"hussein-abdelhay-essayed-kaoud",fullName:"Hussein Abdelhay Essayed Kaoud"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6694",title:"New Trends in Ion Exchange Studies",subtitle:null,isOpenForSubmission:!1,hash:"3de8c8b090fd8faa7c11ec5b387c486a",slug:"new-trends-in-ion-exchange-studies",bookSignature:"Selcan Karakuş",coverURL:"https://cdn.intechopen.com/books/images_new/6694.jpg",editedByType:"Edited by",editors:[{id:"206110",title:"Dr.",name:"Selcan",surname:"Karakuş",slug:"selcan-karakus",fullName:"Selcan Karakuş"}],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:"Theophanides",surname:"Theophile",slug:"theophanides-theophile",fullName:"Theophanides Theophile"}],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:"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:"72",title:"Ionic Liquids",subtitle:"Theory, Properties, New Approaches",isOpenForSubmission:!1,hash:"d94ffa3cfa10505e3b1d676d46fcd3f5",slug:"ionic-liquids-theory-properties-new-approaches",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/72.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1373",title:"Ionic Liquids",subtitle:"Applications and Perspectives",isOpenForSubmission:!1,hash:"5e9ae5ae9167cde4b344e499a792c41c",slug:"ionic-liquids-applications-and-perspectives",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/1373.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"57",title:"Physics and Applications of Graphene",subtitle:"Experiments",isOpenForSubmission:!1,hash:"0e6622a71cf4f02f45bfdd5691e1189a",slug:"physics-and-applications-of-graphene-experiments",bookSignature:"Sergey Mikhailov",coverURL:"https://cdn.intechopen.com/books/images_new/57.jpg",editedByType:"Edited by",editors:[{id:"16042",title:"Dr.",name:"Sergey",surname:"Mikhailov",slug:"sergey-mikhailov",fullName:"Sergey Mikhailov"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"60464",title:"Influence of Glycaemic Control on Cognitive Function in Diabetic Children and Adolescents",doi:"10.5772/intechopen.75562",slug:"influence-of-glycaemic-control-on-cognitive-function-in-diabetic-children-and-adolescents",body:'
1. Introduction
Diabetes mellitus (DM) is a complex, chronic endocrine disorder of carbohydrate metabolism resulting from a defect in insulin secretion, insulin action, or both and characterised by high plasma glucose levels. Currently, it is a major contributor to morbidity and mortality and is becoming an epidemic together with obesity worldwide. In fact, according to the WHO, the number of people with diabetes has risen from 108 million in 1980 to 422 million in 2014; furthermore, WHO projects that diabetes will be the seventh leading cause of death in 2030. However, the most worrying fact is that the number of people who suffer diabetes will reach over half a billion by 2030, becoming a major public health issue [1, 2, 3, 4, 5].
Diabetes is classified into four clinical categories, T1DM, T2DM, gestational diabetes mellitus (GDM) and other specific types of diabetes due to other causes, such as genetic defects in β-cell function, genetic defects in insulin action or diseases of the exocrine pancreas, among others [6]. The two primary forms of diabetes are T1DM and T2DM. T1DM or insulin-dependent DM is an autoimmune disorder characterised by insulin deficiency (an absolute or near total loss of insulin secretion) caused by the destruction of the insulin-producing pancreatic β-cells; the onset occurs typically during childhood or early adulthood, between the ages of 8 and 12, although it could happen at early ages. This form of diabetes is fatal in the absence of insulin replacement therapy. T1DM represents approximately 5–10% of all diagnosed cases of diabetes [1, 3, 7, 8, 9], whereas T2DM or non-insulin-dependent diabetes, that accounts for 90–95% of all diagnosed cases. T2DM is characterised by decreased insulin sensitivity or insulin resistance in peripheral tissues and relative insulin deficiency; this pathology is commonly associated with other metabolic disturbances like obesity, hypercholesterolemia, hypertension and other features of the metabolic syndrome. The prevalence of this disturbance is increasing and is been diagnosed at increasingly younger ages [1, 2, 3, 7, 8, 10].
Cognitive dysfunction is a well-established consequence of diabetes. There is extensive literature which has demonstrated that diabetes, its microvascular complications (nephropathy, neuropathy and retinopathy), and its management with insulin and other drugs can induce mild to moderately severe neurocognitive dysfunction as a consequence of structural and functional changes in the central nervous system (CNS), and it will be especially harmful in infancy and childhood when it is under development. It is known that glycaemic extremes (hyper and hypoglycaemia) affect brain development. The subjects who develop diabetes early in life (6–7 years old) have an elevated risk of mild to moderately severe dysfunction that affects virtually all cognitive domains, including learning and memory. However, if the onset of the diabetes is after this critical period, the neurocognitive dysfunction will be less severe and more restricted. But, although “later onset” subjects show lower scores compared with their healthy siblings on tests of intelligence, sustained attention, visuospatial skills, psychomotor speed and executive functions, they show essentially normal learning and memory skills [9, 11]. Despite the fact that, poorly managed diabetes is associated with neurological complications [4, 12, 13].
Therefore, the primary target of diabetic treatment is to achieve a good GC measured by the glycated haemoglobin A1c (HbA1c). HbA1c reflects average glycaemia during the last 3 months and has strong predictive value for diabetes-related complications. It has to be measured every 3 months in order to determine if patients´ glycaemic targets have been reached and maintained (HbA1c < 7.5% is recommended among all paediatric age-groups according to the American Diabetes Association; a lower goal <7% is recommended if it can be achieved without excessive risk of hypoglycaemia) [4, 12, 13]. The optimal diet and macronutrient composition for diabetic children or adolescents remain controversial [14]. Initial reports support the use of the GI in diabetic management; GI is defined as ‘the incremental area under the blood glucose response curve elicited by a 50 g available carbohydrate of a test food expressed as a percentage of the response elicited by 50 g glucose in the same subject’ [15]. Recent criticisms of the GI focus on its validity, claiming that GI values are inaccurate and imprecise. Although, there are controversial results in this matter and some research groups claim that there is insufficient evidence for the beneficial effects of GI diets, several studies have demonstrated that diets promoting low GI patterns effectively improved GC by reducing the occurrence of glycaemic extremes in subjects with diabetes [2, 4, 10, 14, 15, 16, 17, 18, 19, 20].
In this chapter, we reviewed the studies published up to September 2017 about GC and cognitive development in diabetic children and adolescents. Furthermore, it has been performed a review of the nutritional approaches (Mediterranean diet, low GI diet, high-cereal fibre diet, carbohydrate exchange or low carbohydrate diets, low fat diet or diets rich in antioxidants) used for the management of diabetes, focused on low GI diets.
2. Early programming of diabetes
Recent studies highlight the importance of the intrauterine environment in women with pre-existing diabetes and obesity on the long-term health of the offspring. Thus, an intrauterine environment that exposes the foetus to excess of glucose, lipids, inflammation, growth factors, and cytokines may promote adipogenesis, alter appetite regulation, adversely affect pancreas development, and modify mitochondrial function, resulting in long-term metabolic risk to the offspring. The metabolic intrauterine environment is considered a critical risk factor for the development of adult diabetes and cardiovascular diseases [21]. As a consequence, any harm during critical developmental windows induces permanent adaptive programming in key organs, leading to persistent alterations in gene expression through epigenetic mechanisms. Nutrition constitutes the most significant environmental factor, being both a risk factor and the key in the prevention and protection against different metabolic disorders later in life [22].
In utero programming seems to create a ‘metabolic memory’, considering that physiological anomalies during the gestational period are responsible for the onset of T2DM and obesity associated with metabolic syndrome in the offspring at adulthood [23]. The periconceptional period has also been found as a critical period for nutritional effects on the ability of the foetus to respond to acute and chronic stressors, and for postnatal and adult metabolic health outcomes. It has been suggested that this period constitutes a critical time for nutritional effects on gene expression, with a potential preventive effect of postnatal risks related to prenatal maternal overconsumption and/or overweight, and DM or metabolic syndrome during pregnancy [22].
The association between poor psychosocial health, the risk of obesity and T2DM is well established. DynaHEALTH EU project hypothesises that factors determining glucose metabolism and insulin sensitivity on one hand, and the neuroendocrine response resulting from exposure to psychosocial stress on the other, should be incorporated as a single health indicator, named ‘gluco-psychosocial axis’ (GPA) [24]. It is proposed that long-term GPA status could be established during developmental windows throughout early stages of life, via programming. The metabolic and psychosocial environments in early stages of life play an important role in the structural and functional development of the GPA components. Several studies have demonstrated the importance of the prenatal environment in determining long-term health and the ageing process [24].
Epidemiological evidence suggests impaired glucose metabolism begins much earlier in life [24]. According to clinical studies pre-pregnancy diabetes or GDM, together with maternal obesity, have been associated with higher risk in the offspring of developing obesity, insulin resistance and T2DM later in life [25]. Complications in the offspring might appear even with gestational glucose levels below the thresholds of GDM; even borderline high blood glucose levels increase the risk of infants of being large for gestational age, early adiposity rebound and higher prevalence of metabolic syndrome, especially if they become obese [22]. Infants born from mothers who developed DM before pregnancy had higher risk to develop obesity, higher blood glucose and HbA1c levels, as well as lower HDL cholesterol concentrations and were more prone to DM during childhood, compared to those infants born from mothers who developed DM after pregnancy [25]. Furthermore, different studies have demonstrated that both, GDM or pre-gestational diabetes are related to delayed brain maturation, deficiencies in fine/gross motor development, cognitive deficiencies, and higher risk to develop Attention Deficit Hyperactivity Disease (ADHD) in the offspring, especially when there was a bad control of the maternal illness (HbA1c > 7.5%) during pregnancy [26, 27, 28].
T2DM burden is currently increasing in young people; higher maternal body mass index (BMI) during pregnancy is associated with higher all-cause mortality, higher cardiovascular morbidity and mortality, and increased risk of T2DM among offspring [24]. Data from PREOBE project have demonstrated that infants born from obese mothers had significantly higher birth weight and waist circumference, and those born from mothers with GDM had higher waist/height index compared to the healthy controls [29]. Maftei et al. reported that maternal pre-pregnancy BMI is related to offspring’s insulin resistance at 9–10 years old, independently of GDM, and gestational weight gain does not appear to affect insulin resistance in children [30]. Other studies, showed that both foetal hyperglycaemia and hyperinsulinaemia in GDM increase the obesity and diabetes rates in the offspring, independently of maternal genetic influence [31]. Additionally, Westermeier et al., found that maternal obesity and neonatal insulin resistance are associated with long-term development of obesity, DM, and increased global cardiovascular risk in the offspring, involving deleterious mechanisms of intrauterine programming [32].
The DynaHEALTH EU project is testing how offspring’s diseases later in life and their own GPA status is established in early life in response to metabolic and stress factors and partly related to maternal GPA status in pregnancy [24].
Nevertheless, developmental programming in humans is not limited to the in utero environment, the nutritional status during post-natal period has a considerable impact on later life health. As well, gender differences in developmental programming have been largely ignored and it has been suggested that offspring responses to the early metabolic environment are highly sexually driven. This could be due to inherent gender differences in hypothalamic development, or gender specificity of the adaptive response to environmental challenges. In fact, there is higher risk of T2DM in women who were exposed to high maternal BMI during foetal life. Thus, in the future it will be vital to take into account sex differences for the establishment of recommendations, health guidelines and in the design of new therapeutic interventions [24, 33].
Either pre-existing diabetes (T1DM/T2DM) or GDM are associated with macrosomia in the offspring. Alterations in macrosomic infants persist postnatally, leading to insulin resistance, obesity, diabetes and metabolic syndrome at adulthood [23]. Maternal programming creates a vicious cycle by which maternal diet, weight or glycaemic status can increase offspring susceptibility to metabolic disease. These offspring during their pregnancies will have their own children; also exposed to an adverse in utero environment, perpetuating the burden of such conditions to future generations (Figure 1) [25, 33].
Figure 1.
Vicious cycle of metabolic disease perpetuation to future generations and critical windows for intervention. Adapted from Dearden and Ozanne [33].
The molecular mechanisms involved in foetal programming in diabetic women are far from understood [31]. It is essential that all diabetic women receive a proper management, including preconception counselling about weight management and weight loss (if they are overweight), proper weight gain during pregnancy, the critical importance of optimising GC (HbA1c < 6.5), by self-monitoring blood glucose levels, medication (if needed), medical nutrition therapy (eating a healthy diet) and optimal individualised exercise [21, 31]. Therefore, prevention of foetal programming by tight GC will be essential in order to break the vicious cycle of obesity, diabetes and related-complications in future generations [31]. In order to develop effective intervention strategies, it is important to understand the programming effects of maternal nutrition during pregnancy and the post-natal period both separately and combined, as well as to define clearly the critical developmental periods in order to establish an appropriate time intervention [33].
3. Cognitive dysfunction related to diabetes
The negative effects of DM on retinal, renal, cardiovascular, and peripheral nervous systems are widely acknowledged, but less attention has received its effects on cognitive function and neurodevelopment. T1DM and T2DM are associated with reduced performance on numerous domains of cognitive function. The exact pathophysiology of cognitive dysfunction in diabetic patients is not well understood; nonetheless, vascular disease, hyper or hypoglycaemia, and insulin resistance seem to play significant roles [34].
Subjects with T1DM and T2DM can develop several microvascular (nephropathy, neuropathy, retinopathy) and macrovascular (coronary heart disease, peripheral arterial disease, cerebrovascular disease) complications that will contribute to cognitive dysfunction in adults; however, the major cause of mortality and morbidity in children with T1DM is the diabetic ketoacidosis, which cause cerebral injury along with haemorrhage or cerebral infarction in some cases, leading to cerebral edema (Table 1) [7, 8, 35].
Factors that contribute to the development of cognitive dysfunction in diabetic patients.
Advanced glycation end products, AGEs; cardiovascular, CV; central nervous system, CNS; high density lipoprotein cholesterol, HDL-c; hypothalamic-pituitary-adrenal, HPA; low density lipoprotein cholesterol, LDL-c. Adapted from McCrimmon RJ, Ryan CM, Frier BM. Lancet, 2012 [7].
Cognitive dysfunction in T1DM and T2DM share many similarities, but important differences do exist [7], specifically in the degree of cognitive dysfunction and in the manifestation of cognitive abnormalities [1]. Poorly managed diabetes due to chronic hyper and hypoglycaemia or elevated postprandial glucose may be common aetiological causes of the neurological complications of T1DM and T2DM or cognitive dysfunction [12, 36].
3.1. Type 1 diabetes
Different studies assessing cognition in children and adolescents with an early onset of diabetes (EOD) (6–7 years) have shown higher risk of developing more severe cognitive deficits, especially impairments in memory, learning, intelligence and verbal fluency/language [36, 37], as well as in attention, executive function [38], psychomotor speed [9], slowing of information processing, problem solving, visuoconstruction, visual perception and mental flexibility [7].
Patients with T1DM often perform within normal cognitive range; however, they may perform more poorly on some cognitive tasks compared to non-diabetic control subjects, such as executive functions, short-term memory, psychomotor efficiency and measure of mental efficiency, which predispose for more rapid deterioration of cognitive function later in life [1]. Kodl and Seaquist found different cognitive domains negatively affected in T1DM, specifically information processing*, psychomotor efficiency*, attention*, memory, learning, problem solving, motor speed, vocabulary, general intelligence, visuoconstruction*, visual perception, somatosensory examination, motor strength, mental flexibility* and executive function. According to the authors the domains marked by asterisks have strong supporting data [34].
Neuroimaging studies have found morphological abnormalities, cortical atrophy, lower grey matter volume and density in left temporal-occipital junction, white matter hyper-intensities and reduced white matter densities, concretely white matter microstructural deficits, as well as neuroanatomical changes in the hippocampal region. However, other studies did not find volumetric changes in the hippocampus [12, 36, 37]. In fact, Ho et al., have reported that measuring subfields of the hippocampus with high resolution magnetic resonance imaging may provide a way to specifically target the neurogenic regions of the hippocampus and may show different effects of diabetes on different parts of the hippocampus. It should be noted that studies carried out in rodents with T1DM have shown reductions in hippocampal cell proliferation and survival, leading to learning and memory deficits compared to control rodents (Figure 2) [3].
Figure 2.
Effect of glycaemic extremes on the development of congestive dysfunction.
Additionally, glycaemic extremes (hyper and hypoglycaemia) affect brain development. Severe hypoglycaemia during a lifetime exposure decreases lateral temporal–parietal-occipital grey matter volume, whereas after 2 years with T1DM showed a greater reduction in the regional white matter volume in the precuneus/cuneus region [11]. Furthermore, severe hypoglycaemia harms neurons in cerebral cortex, medial temporal region, including hippocampus, basal ganglia and brain stem with unknown individual consequences [36]. Hypoglycaemic episodes in T1DM children lead to significant declines in verbal abilities, memory skills and ability to organise and recall information. Severe hypoglycaemia may result in persistent electroencephalography (EEG) changes, with 80% of EEG abnormalities observed in diabetic children with history of severe hypoglycaemia compared with 30% of abnormalities in diabetic subjects without severe hypoglycaemia and 24% in healthy control children [39]. In presence of severe hypoglycaemia in T1DM, children show mildly reduced intelligence quotient (IQ), as well as adverse effects in general, verbal and performance IQ [40].
Children and adults with T1DM have worse performance in executive function, full IQ and motor speed; in presence of hyperglycaemia negative effects on memory function were observed in children. Moreover, higher HbA1c levels were associated with worse motor speed and psychomotor efficiency [41]. Additionally, chronic hyperglycaemia has been associated with reductions in grey matter volume and multiple posterior brain regions, including the cerebellum. Adolescents with three or more symptomatic hyperglycaemic episodes showed reductions in white matter integrity, specifically in superior parietal lobule, corpus callosum, posterior limb of the internal capsule, and grey matter integrity, concretely in thalamus and putamen, whereas children (4–10 years old) showed microstructural abnormalities in white matter with lower IQ scores [40]. A lifetime exposure to hyperglycaemia reduces occipital/parietal grey and matter volume; after 2 years with T1DM, a reduction in the whole brain grey matter has been observed [11]. Large effects have been observed in T1DM patients regarding visuospatial ability, motor speed, writing, sustained attention and reading [40, 42].
It is worth noting that a late onset of diabetes (LOD) entails several cognitive dysfunctions, although these impairments are less severe compared to those subjects with EOD. In subjects with a LOD, it has been found lower overall cognition, intelligence, visual learning and memory, motor speed and visual motor integration, sustained attention and executive function compared to their healthy siblings [9, 38].
Finally, several studies have shown that gender influences neurocognitive function in T1DM. In a study with children and adolescents (aged 7–16 years), boys presented decline in verbal intelligence, which was correlated with worse GC. This was not seen in girls of similar ages. It should be noted that most human studies do not distinguish between genders when describing results of neurocognitive testing [34].
3.2. Type 2 diabetes
The prevalence of childhood obesity has increased dramatically worldwide, leading to a variety of health problems, including T2DM, which previously was seen only in adults. The Centres for Disease Control (CDC) and Prevention foresee that the prevalence of T2DM in those under 20 years of age will quadruple in 40 years, assuming a 2.3% annual increase [6]. In the United States, up to 1 in 3 new cases of diabetes diagnosed in subjects younger than 18 years old is T2DM, occurring most commonly in children and adolescents between 10 and 19 years of age [43]. It is difficult to distinguish between T1DM and T2DM in children, given the current obesity epidemic worldwide. The rapid emergence of childhood T2DM means that health professionals have to treat a disease in children, which previously was encountered only in adults. This represents several challenges, because most of diabetes education materials are designed and directed to children with T1DM, but not to T2DM and probably obese patients. Another problem is that most medications used for T2DM have been tested for safety and efficacy in subjects older than 18 years old, because ethical reasons. Therefore, there is scarce scientific data for optimal management of children with T2DM [6, 43].
The comorbidities, such as obesity, hypertension and dyslipidaemia, may be present at the time of diagnosis in youth with T2DM, which contribute to the severity of the disease. The cause of diabetes-related cognitive dysfunction is difficult to establish, because of the prevalence of several comorbidities in the same individual, which might affect cognitive function [6, 7].
Lamport et al. [44], performed a systematic review in adults, concluding that T2DM is associated with cognitive impairments. In the present longitudinal review we found many studies relating an accelerated cognitive decline in adults with T2DM; however, it is difficult to conclude that these reported cognitive impairments are independently associated to abnormalities in glucose tolerance or due to the associated comorbidities present in these patients (cerebrovascular and cardiovascular diseases, obesity, hypertension and hypercholesterolemia) [44]. Some studies suggest that cognitive performance does not differ in T2DM subjects in relation to non-diabetic controls when it is taken into account the influence of age, premorbid IQ, BMI and depression [1]. Unlike the studies in T1DM patients, most studies suggest that T2DM subjects experience cognitive decline. T2DM most often is associated with deficits in cognitive domains, declarative memory, attention and executive function, alterations also seen in children and adolescents with Metabolic Syndrome or obesity and glycaemic disorders [45, 46]. The GC, the disease duration and cerebrovascular complications are considered risk factors that influence the magnitude of the cognitive decline [12]. Learning and memory deficits are the cognitive abnormalities that most clearly differentiate patients with T2DM from T1DM patients [7].
Kodl and Seaquist, established that the cognitive domains that are negatively affected in adults with T2DM are memory* (verbal memory, visual retention, working memory, immediate recall, delayed recall), psychomotor speed*, executive function*, processing speed, complex motor function, verbal fluency, attention and it seems to be related with the development of diabetes. According to the authors, the domains marked by asterisks have strong supporting data [34]. Additionally, Sweat et al., in a study carried out in 162 adolescents (aged 19.53 ± 1.53 years), found that obese adolescents showed slower processing speed maintaining equivalent executive functioning compared with their healthy siblings [46]. Whereas, a recent systematic review performed Barkin et al., showed a consistent inverse association between obesity and executive function in children and adolescents, emphasising that in future research is necessary to use a standardised method of executive function measurement in order to establish causality with obesity and develop new and more effective intervention strategies [47].
Neuroimaging studies have shown deficits in hippocampal-based cognitive performance, which may be attributed to changes in brain structure and volume, leading to deficits in attention, learning and memory [1]. T2DM subjects have similar morphological abnormalities than T1DM patients, such as cortical atrophy and white matter lesions. Moreover, it has been shown a reduction in the microstructural integrity of white matter and grey matter. The reductions in grey matter volumes have been observed in the prefrontal cortex, amygdala and hippocampus [12]. Additionally, greater cortical atrophy, more lesions in deep white matter and hippocampal (susceptible to acute metabolic changes, such as hypoglycaemia) atrophy, leading to impairments in immediate memory, have been observed (Figure 2) [7].
Hippocampal atrophy is one of the neuroanatomical characteristics that differs between people with T1DM and T2DM, both have reduced grey matter density and white matter lesions. Nevertheless, cortical atrophy is more pronounced in T2DM, possibly because the subjects are older on average. Moreover, the hippocampus is more affected in T2DM, is unclear why, because this area is susceptible to acute metabolic change, which is more prominent in T1DM. This suggests that age, sex, the associated comorbidities and the presence of macrovascular disease or insulin resistance might be important risk factors for hippocampal atrophy (Figure 2). T2DM subjects perform worse than healthy control on learning and memory tests, unlike those with T1DM, who rarely have deficits in these domains [7]. However, the results are inconclusive, because other studies have found deficits in learning and memory in T1DM patients, but Kodl and Seaquist confirmed that there is no strong evidence to suggest this [34].
4. Glycaemic index and dietetic management in diabetic children and adolescents
At present, nutritional interventions, physical activity and weight control remain the main pillars of effective diabetes management. Despite modern approaches to intensive insulin therapy and other drugs for the management of diabetes, dietary management remains as the main important action of diabetes treatment [48]. There is not an ideal nutritional intervention for the management of diabetes. A poor GC in subjects with T1DM and T2DM has been related with the onset of diabetes complications. Therefore, it is vital to develop new strategies in order to maintain a good GC. Current standards for diabetes management reflect the need to lower glucose as safely as possible, without increasing the risk or hypoglycaemic episodes. It should receive special consideration the risk of hypoglycaemia in young children (aged <6 years or EOD), because usually they are unable to recognise and/or manage the symptoms. This is called ‘hypoglycaemia unawareness’ [6].
There are different dietetic approaches aimed at the improvement of the GC in children and adolescents with T1DM and T2DM, among them it is worth noting low GI diets, diets rich in antioxidants, carbohydrate exchange diets, high-cereal fibre diet, traditional Mediterranean-style dietary pattern, low carbohydrate Mediterranean style diet, low carbohydrate diets and low fat diets.
Although there are no long-term intervention studies looking at the effects of a low GI diet on diabetes prevention, there is a large body of evidence from animal models, clinical trials and epidemiologic studies that demonstrates the benefits of a low GI diet in the prevention and management of diabetes. Low GI diets in subjects with T1DM and T2DM improve blood glucose control to a similar extent as medications, improving GC and reducing the risk of hypoglycaemic events [14].
Derdemezis and Loveg [4], reported in by a systematic review that low GI diets effectively improve GC. They observed that subjects with T2DM presented significant beneficial effects after the consumption of low GI diets; however, in some cases, a low GI diet was associated with significant weight reduction, which makes difficult to establish firm conclusions, because it is not clear if the effect on the improvement of GC is for the low GI diet per se or derived from the weight loss itself. On the other hand, in subjects with T1DM there is insufficient evidence for the beneficial effects of GI control due to different confounding factors (differences in dietary fibre intake and the values used for calculation of dietary GI and weight loss), suggesting that total carbohydrate content adjusting pre-meal insulin infusion might be more important than GI in controlling postprandial glucose levels. However, low GI diets might be used as a treatment in T1DM in order to reduce the insulin infusions. The potential of a low GI diet in preventing diabetes has not been studied to date, but low GI diet may improve GC and reduce the risk of diabetes and its complications [4].
In another study, T1DM subjects (7–17 years old) were provided with four premade test meals, which were consumed at breakfast after a minimum 10 h overnight fast [16]. The low GI test meal had a GI of 48, meanwhile the one with high-GI test meal had a GI of 84. For the measurement of blood glucose, they used a continuous glucose monitoring system. The low GI meal produced significantly lower postprandial glucose excursion (PPGE) for 30–180 minutes, lower area under the blood glucose response curve (AUC), a smaller peak blood glucose excursion, and reduced time to reach baseline blood glucose levels compared with the high GI meal when preprandial ultra-short-acting insulin was administered. Nevertheless, the effect of GI on the postprandial glucose response requires further exploration in children receiving intensive insulin therapy [16].
A systematic review performed by Thomas and Elliott [2] in T1DM and T2DM children and adults, showed that GC in people with diabetes improved significantly with a low GI diet, by decreasing hypoglycaemic episodes, compared to those on higher GI diets or measured carbohydrate exchange diets. It was observed that a low GI diet produces a decrease of 0.5% HbA1c, clinically significant, similar to the reductions produce by the medications given to newly diagnosed T2DM subjects; as a result, it has been confirmed that a low GI diet is associated with a significant reduction in the risk of microvascular complications [2].
In 2010, these authors performed a meta-analysis with evidence that low GI diets significantly improve GC, by lowering HbA1c without any increase in the rate of hypoglycaemic episodes, when compared with a measured carbohydrate exchange diet and a high-cereal fibre diet. In other studies, low GI diet improved HbA1c levels in T1DM children; in contrast, T2DM low GI group presented a significant increase in insulin sensitivity compared to the high GI group. The effect is sufficiently strong that may benefit diabetic patients by reducing or even avoiding their requirement for medication [10].
It is important to keep in mind that medications that improve blood glucose levels usually are associated with high risk of hypoglycaemia, which is the greatest barrier to achieve an optimal GC, particularly in T1DM. In people with T2DM a reduction in HbA1c levels after the consumption of low GI diets has been observed, whereas in children with T1DM, with both intensive multiple daily injection of insulin or insulin pump therapy, a reduction in postprandial glucose excursions, as well as improvements in insulin sensitivity after 3 to 4 weeks was demonstrated. However, a high GI diet worsens insulin resistance in individuals with and without diabetes and rises blood glucose levels and the need to medication in T2DM and the insulin requirements in T1DM. Therefore, the reduction of the risk of diabetes-related complications with low GI diets is similar to or greater than the diets including a high intake of fibre and whole grains [14].
A low GI diets favours slower and more gradual absorption of glucose from the gastrointestinal tract, avoiding hypoglycaemic episodes; moreover, it produces fewer stimuli for insulin release, reduces free fatty acids levels and oxidative stress, and increases insulin sensitivity [17].
According to the Canadian Diabetes Association, interventions replacing high GI carbohydrates with low GI carbohydrates in mixed meals have shown clinically significant improvements in GC over 2 weeks to 6 months in people with T1DM or T2DM; improvements were observed in cardiovascular risk factors, postprandial glycaemia and high sensitivity C-reactive protein over 1 year in people with T2DM, whereas adults and children with T1DM showed lower hypoglycaemic events over 24 to 52 weeks [20]. In addition, it has been shown that low GI diets sustain improved GC and HDL cholesterol compared with a high-cereal fibre diet over 6 months, and improved β-cell function in comparison with a low carbohydrate, high monounsaturated fat diet over 1 year in people with T2DM [20]. As it has been already mentioned, diets with lower GI result in improvements in HbA1c in the order of 0.5%. [19].
In contrast, a review carried out by Madsbad [49] in subjects with T1DM and T2DM showed different results. Dietary carbohydrate restriction as early therapy in T2DM, and as an adjunct to therapy in T1DM, effectively reduces blood glucose levels. However, longer-term studies (≥6 months) have variable results regarding the relative efficacy of low carbohydrate diets compared to low in fat or low GI diets on weight and HbA1c reductions. While recent meta-analyses suggest that low carbohydrate diets may be no more effective over the longer term than low fat or Low GI diets, in terms of weight and HbA1c changes [49].
It has been observed a reduction in the risk of diabetes with the consumption of low GI diet, whereas high dietary GI and/or glycaemic load increase the risk of T2DM [18]. Observational data suggest that replacing high GI with low GI carbohydrate reduces the risk of metabolic disturbances and T2DM. Nevertheless, some studies show inconclusive results that may be due to methodological differences and confounding parameters that can dramatically modify the post-meal metabolic response, such as the type of carbohydrate and its digestibility, quantity of carbohydrates as compared with other macronutrients, lipids, proteins and fibres [18].
Recent criticisms of the GI claim that GI methodology is not valid, and GI values are inaccurate and imprecise, and GI does not predict what foods are healthy and that whole grain and fibre are better markers of carbohydrate quality than GI. Eating a food as part of a mixed meal affects the glycaemic response, but does not alter the food’s GI, because is an intrinsic characteristic of food. However, the glycaemic response of a food or a meal is altered in the presence of other foods depending on the amount and source (GI) of carbohydrate and the amounts and types of fat and protein added. Moreover, it is important to take into account that the relative glycaemic response of a meal is determined by its calculated meal GI and the amounts of available carbohydrates, fat and protein. Therefore, GI is a valid marker of carbohydrate quality because GI methodology is accurate and precise and GI is a property of the food, and is biologically meaningful and influences outcomes in health and disease, especially in the nutritional management of diabetes. Despite the fact that the results are inconclusive, there is no evidence to suggest any negative effect of following low GI diets, which are consistent with healthy eating recommendations aimed at weight control and reducing the risk of diabetes-related complications by improving the GC in people with diabetes (Table 2) [14, 15, 17, 49].
Marsh et al. [14]; Rahelić et al. [17]; Blaak et al. [18]
Increased risk of T2DM up to 40%
Table 2.
Main effects of low and high glycaemic index diets on the nutritional management of diabetes in children and adolescents.
International Diabetes Federation.
Area under the blood glucose response curve, AUC; body mass index, BMI; cardiovascular, CV; glycated haemoglobin A1c, HbA1c; high density lipoprotein cholesterol, HDL-c; low density lipoprotein cholesterol, LDL-c; postprandial glucose excursion, PPGE; type 1 diabetes mellitus, T1DM; type 2 diabetes mellitus, T2DM
It should be noted that a traditional Mediterranean-style dietary pattern improves GC and cardiovascular risk factors, including systolic blood pressure, total cholesterol, HDL cholesterol, the total cholesterol/HDL cholesterol ratio and triglycerides in T2DM. On the other hand, a low carbohydrate Mediterranean-style diet has shown reductions in HbA1c and delays on the need for antihyperglycaemic drug therapy at 4 years of diagnosis, compared with low fat diet in overweight individuals with newly diagnosed T2DM. To sum up, traditional and low carbohydrate Mediterranean-style diets are shown to reduce HbA1c and triglycerides, whereas only the low carbohydrate Mediterranean-style diet improves LDL cholesterol and HDL cholesterol at 1 year of diagnosis in overweight subjects with T2DM [14, 20].
It has been shown that a disrupted balance between oxidative stress and antioxidant cascades contributes to neuroplasticity deficits in experimental models of diabetes; therefore, antioxidants treatments may provide excellent adjunct treatments to traditional approaches to reduce the neurological complications of diabetes. In a review carried out by Reagan, the neuroplasticity deficits were attenuated or eliminated by antioxidants, including melatonin and vitamin E, lycopene, resveratrol, dehydroepiandrosterone (DHEA) and essential fatty acids. T2DM patients supplemented with vitamin E and with increasing serum lycopene levels showed reductions in oxidative stress parameters, whereas DHEA administration showed reductions in plasma oxidative stress measures and lipid peroxidation products and increased antioxidants in T2DM subjects [12].
It is essential to take into account that the nutritional management in children and adolescents is more complex than in adults, because they do not have autonomy or the necessary knowledge to maintain a good GC. In a recent study carried out in 282 T1DM children and adolescents, a greater nutrition knowledge of parents and patients, measured by a type 1 diabetes Nutrition Knowledge Survey (NKS), was associated with both better GC and higher diet quality in their children. Therefore, it is vital an early nutritional education and the role of parents in order to achieve good nutritional management and GC during childhood [48].
The previous nutritional recommendations are aimed to achieve a good GC and nutritional management in the long-term; nonetheless, it is necessary to address the acute dietary complications, meaning the management of hypoglycaemia, because it is the most common acute complication of the treatment of T1DM. In case of hypoglycaemia (<60–70 mg/dl) it is necessary an immediate oral, rapidly absorbed, simple carbohydrate to raise blood glucose up to 100 mg/dl [39].
Finally, the exercise is indispensable in the management of diabetes, especially in T2DM children and adolescents, due to this pathology is commonly associated with obesity. The American Academy of Paediatrics recommends that health care professionals encourage children and adolescents with T2DM to practice moderate to vigorous exercise for at least 60 minutes daily and to limit non-academic ‘screen time’, such as watching television or playing computer games, to less than 2 hours per day for the reduction of BMI and the improvement of GC. Physical activity is an integral part of weight management for the prevention and treatment of T2DM. Although there is scarce available data from children and adolescents with T2DM, several well-controlled studies performed in obese children and adolescents at risk of metabolic syndrome and T2DM provide guidelines for physical activity [43].
5. Future prospects
Although, the optimal diet and macronutrient composition in diabetes remain controversial and the evidence is not sufficiently robust to recommend a low GI diet as the primary dietary strategy for GC, low GI diets are high in fibre and whole-grain products, rich in legumes, fruits and vegetables with balanced fat profile, low saturated fats and high monounsaturated fatty acids (MUFAs) and polyunsaturated fatty acids (PUFAs). Therefore, this nutritional intervention may have beneficial effects in diabetics and populations at risk, such as children with T1DM [4, 14]. Antioxidant treatments or diets rich in antioxidants may reduce the diabetes-related neurological complications, when they are used together with traditional treatments [12]. Given that there is no optimal diet for the management of GC in subjects with T1DM and T2DM, it would be interesting to study the effects of a low GI diet based in a traditional Mediterranean-diet pattern (rich in vegetables and fruits, high content in antioxidants and fibre), that had demonstrated to improve the GC in these subjects, to evaluate the power for preventing cognitive dysfunctions and to optimise the neurodevelopment in children and youth.
It is vital to perform more long-term studies in children and adolescents, especially in those with T2DM, due to the increased prevalence in this population, considering the scarce evidence for optimal management of children with T2DM [43]. On the other hand, it is essential to develop lifestyle interventions in population at risk during childhood and adolescence (individualised nutritional and exercise programmes), focused on investigating how to prevent the development of glucose tolerance impairment, and diabetes. These interventions could protect against cognitive decline, because they help to achieve GC, reducing hypo and hyperglycaemic episodes [44].
Furthermore, the clinical follow-up of T1DM children must include also a survey of neuropsychological and brain development to prevent long-lasting consequences.
6. Conclusions
Further research is needed in diabetic children and adolescents, especially well-designed long-term randomised controlled trials with larger sample size to determine the true value of low GI diets on overall quality of life, long-term GC and the prevention or management of diabetes-related complications. The results obtained up to the present moment are inconclusive due to discrepancies between the methods of analysis and the diversity in the methodology employed. Therefore, it is difficult to generalise results. It is necessary the use of validated questionnaires for the dietary assessment and standardised the GI databases in order to make the data comparable between different studies. One limitation of all observational studies published to date is that none of the food frequency questionnaires have been specifically designed to assess the GI and until recently, few were validated against another method of dietary assessment, such as 24 h recalls or diet records. Therefore, these questionnaires have poor ability to estimate carbohydrate intake, calling into question the accuracy of any GI or glycaemic load estimation [14]. On the other hand, the studies use different cognitive tests to assess cognitive domains. Therefore, it is difficult to compare results between studies. Brain imaging is becoming essential to clarify the effects of diabetes on brain development, and it will offer us new perspectives for the prevention of neurological disorders and mental health.
Covariates that could affect neurocognitive testing and should be taken into account are, age, education, sex, history of other chronic illnesses, psychiatric and neurological disorders, absence from school, socioeconomic status, and hypo/hyperglycaemia during testing. Most of the studies control for at least some of these covariates, but most fail to control all of them [34].
There is wide criticism and controversies about low GI diet. Some authors state that is easy to follow and effective, whereas other authors think GI is highly variable, not physiological and difficult to learn and follow. Despite this, GI concept is accepted by many diabetes associations around the world as an integral part of the dietary treatment of diabetes. Despite the controversy, there is substantial evidence that a low GI diet can improve the GC in subjects with diabetes. It is vital to carry out further research of the role of GI in the prevention and treatment of diabetes and its complications together with beneficial effects of a low GI diet [17]. One of the major controversies about GI is that different studies state that the GI of food change in the presence of other macronutrients, but the reality is that GI is an intrinsic characteristic of food. Therefore, the GI of food does not change in the presence of other macronutrients, such as lipids, proteins and fibre, is just the glycaemic response. It has been shown that proteins induce greater insulin secretion, while fats reduce gastric emptying and slow down the absorption of carbohydrate. It is essential to study the effects of protein, fat and fibre on the glycaemic response to a carbohydrate meal [15], especially in children and adolescents.
On the other hand, nutritional education and physical activity are essential in order to achieve a good GC of the disease. The main goal of diabetes management is to prevent long-term complications, not only cognitive dysfunction, also micro and macrovascular complications. More studies in cognitive function in diabetic children and adolescents with severe hypoglycaemia are needed, because preventing hypoglycaemia could reduce cognitive dysfunction [36], and improve healthy ageing in the diabetic patients. Long-term interventions will help also to know the impact of disease duration on cognition. More intensive diabetes medical regimes will be associated with less neurocognitive deficits, especially in patients with an EOD because they are more expose through time to glycaemic extremes (hypo and hyperglycaemias). It is vital to identify the factors that are involved in the aetiology and progression of the neurological complications, because currently the pathophysiology of cognitive dysfunction in diabetes is not well understood [1]. Therefore, it is important to understand the pathogenesis of cognitive dysfunction secondary to diabetes in order to establish more efficient treatments and prevent or reverse these cognitive alterations [34]. Thus, further well designed human studies are needed to elucidate the pathophysiology and the mechanisms of action of cognitive dysfunction through neuroimaging [3].
In conclusion, it is necessary to carry out well designed long-term intervention randomised control trials with larger sample size, detailed cognitive assessment combined with neuroimaging [7] and adequate dietetic management. Furthermore, it is essential an early dietetic intervention in order to prevent or reduce diabetes-related complications, especially in children and adolescents with an EOD, because they are exposed through time to glycaemic extremes and are more vulnerable than adults, because their CNS is developing and any damage could be irreversible. Finally, it is important to identify population at risk during early life and childhood in order to develop clear recommendations, prevent the development of diabetes and promote healthy ageing.
Acknowledgments
The authors of this chapter are participating in the DynaHEALTH project ‘Understanding the dynamic determinants of glucose homeostasis and social capability to promote healthy and active aging’. European Union’s Horizon 2020 Research and Innovation Programme under Grant Agreement No 633595.
Abbreviations
ADHD
attention deficit hyperactivity disease
AGEs
advanced glycation end products
AUC
area under the blood glucose response curve
BMI
body mass index
CDC
Centres for Disease Control
CNS
central nervous system
DHEA
dehydroepiandrosterone
DM
diabetes mellitus
EEG
electroencephalography
EOD
early onset of diabetes
GC
glycaemic control
GDM
gestational diabetes mellitus
GI
glycaemic index
GPA
gluco-psychosocial axis
HbA1c
glycated haemoglobin A1c
HDL-c
high density lipoprotein cholesterol
HPA
hypothalamic-pituitary-adrenal
IQ
intelligence quotient
LDL-c
low density lipoprotein cholesterol
LOD
late onset of diabetes
MUFAs
monounsaturated fatty acids
NKS
Nutrition Knowledge Survey
PPGE
postprandial glucose excursion
PUFAs
polyunsaturated fatty acids
T1DM
type 1 diabetes mellitus
T2DM
type 2 diabetes mellitus
WHO
World Health Organisation
\n',keywords:"diabetes, glycaemic index, blood glucose, neurodevelopment, cognitive performance, brain",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/60464.pdf",chapterXML:"https://mts.intechopen.com/source/xml/60464.xml",downloadPdfUrl:"/chapter/pdf-download/60464",previewPdfUrl:"/chapter/pdf-preview/60464",totalDownloads:646,totalViews:288,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,dateSubmitted:"May 13th 2017",dateReviewed:"February 16th 2018",datePrePublished:null,datePublished:"July 11th 2018",dateFinished:null,readingETA:"0",abstract:"According to the World Health Organisation (WHO), the number of people with diabetes has risen to 422 million in 2014. Poorly managed diabetes leads to chronic hyper and/or hypoglycaemia, which are associated with neurological complications in type 1 (T1DM) and type 2 (T2DM) diabetes mellitus. Therefore, the primary target of diabetic treatment is to achieve a good glycaemic control (GC). In this chapter, we reviewed studies published up to September 2017 about GC and cognitive development in diabetic children and adolescents, as well as the nutritional approaches used for the management of diabetes in childhood, focusing on low glycaemic index (GI) diets. According to different studies, low GI diets effectively improve GC, which may reduce the risk of diabetes-related complications, such as cognitive dysfunction; however, the evidence is not sufficiently robust and the results are inconclusive. Despite the fact that, low GI diets are consistent with healthy eating recommendations and should be encouraged in the prevention and nutritional management of diabetes. Further research is needed in diabetic children and adolescents at risk, especially well-designed long-term randomised controlled trials, with larger sample size, to determine the true value of low GI diets on long-term GC and diabetes prevention and management.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/60464",risUrl:"/chapter/ris/60464",book:{slug:"diabetes-food-plan"},signatures:"Estefanía Diéguez Castillo, Ana Nieto-Ruíz, Mireia Escudero-Marín\nand Cristina Campoy",authors:[{id:"90805",title:"Prof.",name:"Cristina",middleName:null,surname:"Campoy",fullName:"Cristina Campoy",slug:"cristina-campoy",email:"ccampoy@ugr.es",position:null,institution:{name:"University of Granada",institutionURL:null,country:{name:"Spain"}}},{id:"211059",title:"BSc.",name:"Estefanía",middleName:null,surname:"Diéguez Castillo",fullName:"Estefanía Diéguez Castillo",slug:"estefania-dieguez-castillo",email:"estefaniadieguezcastillo@gmail.com",position:null,institution:{name:"University of Granada",institutionURL:null,country:{name:"Spain"}}},{id:"233102",title:"BSc.",name:"Ana",middleName:null,surname:"Nieto",fullName:"Ana Nieto",slug:"ana-nieto",email:"ananietoruiz@gmail.com",position:null,institution:null},{id:"233103",title:"BSc.",name:"Mireia",middleName:null,surname:"Escudero",fullName:"Mireia Escudero",slug:"mireia-escudero",email:"m.escuderomarin@gmail.com",position:null,institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Early programming of diabetes",level:"1"},{id:"sec_3",title:"3. Cognitive dysfunction related to diabetes",level:"1"},{id:"sec_3_2",title:"3.1. Type 1 diabetes",level:"2"},{id:"sec_4_2",title:"3.2. Type 2 diabetes",level:"2"},{id:"sec_6",title:"4. Glycaemic index and dietetic management in diabetic children and adolescents",level:"1"},{id:"sec_7",title:"5. Future prospects",level:"1"},{id:"sec_8",title:"6. Conclusions",level:"1"},{id:"sec_9",title:"Acknowledgments",level:"1"},{id:"sec_11",title:"Abbreviations",level:"1"}],chapterReferences:[{id:"B1",body:'Wrighten SA, Piroli GG, Grillo CA, Reagan LP. A look inside the diabetic brain: Contributors to diabetes-induced brain aging. Biochimica et Biophysica Acta. 2009;1792(5):444-453'},{id:"B2",body:'Thomas D, Elliott EJ. Low glycaemic index, or low glycaemic load, diets for diabetes mellitus. Cochrane Database of Systematic Reviews. 2009;1:CD006296'},{id:"B3",body:'Ho N, Sommers MS, Lucki I. Effects of diabetes on hippocampal neurogenesis: Links to cognition and depression. Neuroscience and Biobehavioral Reviews. 2013;37(8):1346-1362'},{id:"B4",body:'Derdemezis CS, Lovegrove JA. Glycemic index, glycemic control and beyond. Current Pharmaceutical Design. 2014;20(22):3620-3630'},{id:"B5",body:'World Health Organization [website] WHO. 2017 [updated July 2017; cited September 2017]. Media Centre. Diabetes. Available from: http://www.who.int/mediacentre/factsheets/fs312/en/'},{id:"B6",body:'Association AD. 11. Children and adolescents. Diabetes Care. 2016;39(1):S86-S93'},{id:"B7",body:'McCrimmon RJ, Ryan CM, Frier BM. Diabetes and cognitive dysfunction. Lancet. 2012;379(9833):2291-2299'},{id:"B8",body:'Association AD. Standards of medical care in diabetes—2014. Diabetes Care. 2014;37(1):S14-S80'},{id:"B9",body:'Ryan CM, van Duinkerken E, Rosano C. Neurocognitive consequences of diabetes. The American Psychologist. 2016;71(7):563-576'},{id:"B10",body:'Thomas D, Elliott E. The use of low-glycaemic index diets in diabetes control. The British Journal of Nutrition. 2010;104(6):797-802'},{id:"B11",body:'Perantie DC, Koller JM, Weaver PM, Lugar HM, Black KJ, White NH, et al. Prospectively determined impact of type 1 diabetes on brain volume during development. Diabetes. 2011;60(11):3006-3014'},{id:"B12",body:'Reagan LP. Diabetes as a chronic metabolic stressor: Causes, consequences and clinical complications. Experimental Neurology. 2012;233(1):68-78'},{id:"B13",body:'Association AD. Standards of medical care in diabetes-2016. The Journal of Clinical and Applied Research and Education. 2016;39(1):S1-S2'},{id:"B14",body:'Marsh K, Barclay A, Colagiuri S, Brand-Miller J. Glycemic index and glycemic load of carbohydrates in the diabetes diet. Current Diabetes Reports. 2011;11(2):120-127'},{id:"B15",body:'Wolever T. Is glycaemic index (GI) a valid measure of carbohydrate quality? European Journal of Clinical Nutrition. 2013;67(5):522-531'},{id:"B16",body:'Ryan RL, King BR, Anderson DG, Attia JR, Collins CE, Smart CE. Influence of and optimal insulin therapy for a low–Glycemic index meal in children with type 1 diabetes receiving intensive insulin therapy. Diabetes Care. 2008;31(8):1485-1490'},{id:"B17",body:'Rahelić D, Jenkins A, Božikov V, Pavić E, Jurić K, Fairgrieve C, et al. Glycemic index in diabetes. Collegium Antropologicum. 2011;35(4):1363-1368'},{id:"B18",body:'Blaak E, Antoine JM, Benton D, Björck I, Bozzetto L, Brouns F, et al. Impact of postprandial glycaemia on health and prevention of disease. Obesity Reviews. 2012;13(10):923-984'},{id:"B19",body:'Group IDFGD. Guideline for management of postmeal glucose in diabetes. Diabetes Research and Clinical Practice. 2014;103(2):256-268'},{id:"B20",body:'Dworatzek PDAK, Gougeon R, Husein N, Sievenpiper JL, Williams SL. Nutrition therapy. Canadian Diabetes Association clinical practice guidelines expert committee. Canadian Journal of Diabetes. 2013;37(1):S45-S55'},{id:"B21",body:'Barbour LA. Changing perspectives in pre-existing diabetes and obesity in pregnancy: Maternal and infant short-and long-term outcomes. Current Opinion in Endocrinology, Diabetes, and Obesity. 2014;21(4):257-263'},{id:"B22",body:'Shapira N. Prenatal nutrition: A critical window of opportunity for mother and child. Women’s Health (London). 2008;4(6):639-656'},{id:"B23",body:'Yessoufou A, Moutairou K. Maternal diabetes in pregnancy: Early and long-term outcomes on the offspring and the concept of “metabolic memory”. Experimental Diabetes Research. 2011;2011:218598'},{id:"B24",body:'European Commission D. Grant Agreement. EU. 3.1.1: H2020'},{id:"B25",body:'Battista MC, Hivert MF, Duval K, Baillargeon JP. Intergenerational cycle of obesity and diabetes: How can we reduce the burdens of these conditions on the health of future generations? Experimental Diabetes Research. 2011;2011:596060'},{id:"B26",body:'Ratzon N, Greenbaum C, Dulitzky M, Ornoy A. Comparison of the motor development of school-age children born to mothers with and without diabetes mellitus. Physical & Occupational Therapy in Pediatrics. 2000;20(1):43-57'},{id:"B27",body:'Ornoy A. Growth and neurodevelopmental outcome of children born to mothers with pregestational and gestational diabetes. Pediatric Endocrinology Reviews. 2005;3(2):104-113'},{id:"B28",body:'Rodriguez A. Maternal pre-pregnancy obesity and risk for inattention and negative emotionality in children. Journal of Child Psychology and Psychiatry. 2010;51(2):134-143'},{id:"B29",body:'Berglund SK, García-Valdés L, Torres-Espinola FJ, Segura MT, Martínez-Zaldívar C, Aguilar MJ, et al. Maternal, fetal and perinatal alterations associated with obesity, overweight and gestational diabetes: An observational cohort study (PREOBE). BMC Public Health. 2016;16:207'},{id:"B30",body:'Maftei O, Whitrow M, Davies M, Giles L, Owens J, Moore V. Maternal body size prior to pregnancy, gestational diabetes and weight gain: Associations with insulin resistance in children at 9-10 years. Diabetic Medicine. 2015;32(2):174-180'},{id:"B31",body:'Berry DC, Boggess K, Johnson QB. Management of pregnant women with type 2 diabetes mellitus and the consequences of fetal programming in their offspring. Current Diabetes Reports. 2016;16(5):36'},{id:"B32",body:'Westermeier F, Sáez PJ, Villalobos-Labra R, Sobrevia L, Farías-Jofré M. Programming of fetal insulin resistance in pregnancies with maternal obesity by ER stress and inflammation. BioMed Research International. 2014;2014:917672'},{id:"B33",body:'Dearden L, Ozanne SE. Early life origins of metabolic disease: Developmental programming of hypothalamic pathways controlling energy homeostasis. Frontiers in Neuroendocrinology. 2015;39:3-16'},{id:"B34",body:'Kodl CT, Seaquist ER. Cognitive dysfunction and diabetes mellitus. Endocrine Reviews. 2008;29(4):494-511'},{id:"B35",body:'Glaser NS, Ghetti S, Casper TC, Dean JM, Kuppermann N. Pediatric diabetic ketoacidosis, fluid therapy, and cerebral injury: The design of a factorial randomized controlled trial. Pediatric Diabetes. 2013;14(6):435-446'},{id:"B36",body:'Blasetti A, Chiuri RM, Tocco AM, Giulio CD, Mattei PA, Ballone E, et al. The effect of recurrent severe hypoglycemia on cognitive performance in children with type 1 diabetes: A meta-analysis. Journal of Child Neurology. 2011;26(11):1383-1391'},{id:"B37",body:'Carvalho KS, Grunwald T, De Luca F. Neurological complications of endocrine disease. Seminars in Pediatric Neurology. 2017;24(1):33-42'},{id:"B38",body:'Gaudieri PA, Chen R, Greer TF, Holmes CS. Cognitive function in children with type 1 diabetes. Diabetes Care. 2008;31(9):1892-1897'},{id:"B39",body:'Clarke W, Jones T, Rewers A, Dunger D, Klingensmith GJ. Assessment and management of hypoglycemia in children and adolescents with diabetes. Pediatric Diabetes. 2009;10(12):134-145'},{id:"B40",body:'Naguib JM, Kulinskaya E, Lomax CL, Garralda ME. Neuro-cognitive performance in children with type 1 diabetes—A meta-analysis. Journal of Pediatric Psychology. 2009;34(3):271-282'},{id:"B41",body:'Tonoli C, Heyman E, Roelands B, Pattyn N, Buyse L, Piacentini MF, et al. Type 1 diabetes-associated cognitive decline: A meta-analysis and update of the current literature. Journal of Diabetes. 2014;6(6):499-513'},{id:"B42",body:'Semenkovich K, Patel P, Pollock A, Beach K, Nelson S, Masterson J, et al. Academic abilities and glycaemic control in children and young people with type 1 diabetes mellitus. Diabetic Medicine. 2016;33(5):668-673'},{id:"B43",body:'Copeland KC, Silverstein J, Moore KR, Prazar GE, Raymer T, Shiffman RN, et al. Management of newly diagnosed type 2 diabetes mellitus (T2DM) in children and adolescents. Pediatrics. 2013;131(2):364-382'},{id:"B44",body:'Lamport DJ, Lawton CL, Mansfield MW, Dye L. Impairments in glucose tolerance can have a negative impact on cognitive function: A systematic research review. Neuroscience and Biobehavioral Reviews. 2009;33(3):394-413'},{id:"B45",body:'Delgado-Rico E, Río-Valle JS, Albein-Urios N, Caracuel A, González-Jiménez E, Piqueras MJ, et al. Effects of a multicomponent behavioral intervention on impulsivity and cognitive deficits in adolescents with excess weight. Behavioural Pharmacology. 2012;23(5-6):609-615'},{id:"B46",body:'Sweat V, Yates KF, Migliaccio R, Convit A. Obese adolescents show reduced cognitive processing speed compared with healthy weight peers. Childhood Obesity. 2017;13(3):190-196'},{id:"B47",body:'Barkin SL. The relationship between executive function and obesity in children and adolescents: A systematic literature review. Journal of Obesity. 2013;2013:820956'},{id:"B48",body:'Rovner AJ, Nansel TR, Mehta SN, Higgins LA, Haynie DL, Laffel LM. Development and validation of the type 1 diabetes nutrition knowledge survey. Diabetes Care. 2012;35(8):1643-1647'},{id:"B49",body:'Madsbad S. Impact of postprandial glucose control on diabetes-related complications: How is the evidence evolving? Journal of Diabetes and its Complications. 2016;30(2):374-385'}],footnotes:[],contributors:[{corresp:null,contributorFullName:"Estefanía Diéguez Castillo",address:null,affiliation:'
Department of Paediatrics, School of Medicine, University of Granada, Spain
EURISTIKOS Excellence Centre for Paediatric Research, University of Granada, Spain
Department of Paediatrics, School of Medicine, University of Granada, Spain
EURISTIKOS Excellence Centre for Paediatric Research, University of Granada, Spain
'}],corrections:null},book:{id:"6155",title:"Diabetes Food Plan",subtitle:null,fullTitle:"Diabetes Food Plan",slug:"diabetes-food-plan",publishedDate:"July 11th 2018",bookSignature:"Viduranga Waisundara",coverURL:"https://cdn.intechopen.com/books/images_new/6155.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"194281",title:"Dr.",name:"Viduranga Yashasvi",middleName:null,surname:"Waisundara",slug:"viduranga-yashasvi-waisundara",fullName:"Viduranga Yashasvi Waisundara"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},chapters:[{id:"58954",title:"Introductory Chapter: The Need for Dietary Interventions for Diabetes",slug:"introductory-chapter-the-need-for-dietary-interventions-for-diabetes",totalDownloads:494,totalCrossrefCites:0,signatures:"Viduranga Yashasvi Waisundara",authors:[{id:"194281",title:"Dr.",name:"Viduranga Yashasvi",middleName:null,surname:"Waisundara",fullName:"Viduranga Yashasvi Waisundara",slug:"viduranga-yashasvi-waisundara"}]},{id:"61271",title:"The Microbiome and the Epigenetics of Diabetes Mellitus",slug:"the-microbiome-and-the-epigenetics-of-diabetes-mellitus",totalDownloads:895,totalCrossrefCites:3,signatures:"Lissé Angarita Dávila, Valmore Bermúdez Pirela, Waldo Díaz, Nadia\nReyna Villasmil, Silvana Cisternas León, Ma Cristina Escobar\nContreras, Kristian Buhring Bonacich, Samuel Durán Agüero, Paula\nCarrasco Vergara, Rodrigo Buhring Bonacich, Constanza Bugman,\nVirginia Céspedes, Marcell Gatica, Marion Guerrero Wyss,\nJorge González Casanova and Francisco Valdebenito",authors:[{id:"41236",title:"Dr.",name:"Valmore",middleName:null,surname:"Bermúdez",fullName:"Valmore Bermúdez",slug:"valmore-bermudez"},{id:"217192",title:"Ph.D.",name:"Lissé",middleName:null,surname:"Angarita Dávila",fullName:"Lissé Angarita Dávila",slug:"lisse-angarita-davila"},{id:"218793",title:"Dr.",name:"Nadia Reyna",middleName:null,surname:"Reyna Villasmil",fullName:"Nadia Reyna Reyna Villasmil",slug:"nadia-reyna-reyna-villasmil"},{id:"218794",title:"Dr.",name:"Samuel",middleName:null,surname:"Durán Agüero",fullName:"Samuel Durán Agüero",slug:"samuel-duran-aguero"},{id:"218795",title:"Dr.",name:"Waldo",middleName:null,surname:"Díaz",fullName:"Waldo Díaz",slug:"waldo-diaz"},{id:"218796",title:"MSc.",name:"Ma Cristina",middleName:null,surname:"Escobar Contreras",fullName:"Ma Cristina Escobar Contreras",slug:"ma-cristina-escobar-contreras"},{id:"218800",title:"MSc.",name:"Kristian",middleName:null,surname:"Bühring Bonacich",fullName:"Kristian Bühring Bonacich",slug:"kristian-buhring-bonacich"},{id:"218801",title:"MSc.",name:"Paula",middleName:null,surname:"Carrasco Vergara",fullName:"Paula Carrasco Vergara",slug:"paula-carrasco-vergara"},{id:"223462",title:"MSc.",name:"Silvana",middleName:null,surname:"Cisternas",fullName:"Silvana Cisternas",slug:"silvana-cisternas"},{id:"223468",title:"MSc.",name:"Marion",middleName:null,surname:"Guerrero Wyss",fullName:"Marion Guerrero Wyss",slug:"marion-guerrero-wyss"},{id:"223473",title:"MSc.",name:"Virginia",middleName:null,surname:"Cespedes",fullName:"Virginia Cespedes",slug:"virginia-cespedes"},{id:"223477",title:"Dr.",name:"Marcell",middleName:null,surname:"Gatica",fullName:"Marcell Gatica",slug:"marcell-gatica"},{id:"223478",title:"MSc.",name:"Rodrigo",middleName:null,surname:"Buhring",fullName:"Rodrigo Buhring",slug:"rodrigo-buhring"},{id:"223970",title:"MSc.",name:"Constanza",middleName:null,surname:"Bugmann",fullName:"Constanza Bugmann",slug:"constanza-bugmann"},{id:"239591",title:"Prof.",name:"Francisco",middleName:null,surname:"Valdebenito",fullName:"Francisco Valdebenito",slug:"francisco-valdebenito"}]},{id:"57473",title:"Dietary Recommendations for Patients with Cardiovascular Disease and Diabetes",slug:"dietary-recommendations-for-patients-with-cardiovascular-disease-and-diabetes",totalDownloads:836,totalCrossrefCites:0,signatures:"Vlad Cristina",authors:[{id:"210388",title:"Ph.D.",name:"Vlad",middleName:"I",surname:"Cristina",fullName:"Vlad Cristina",slug:"vlad-cristina"}]},{id:"58514",title:"Antidiabetic and Safety Properties of Ethanolic Leaf Extract of Corchorus olitorius in Alloxan-Induced Diabetic Rats",slug:"antidiabetic-and-safety-properties-of-ethanolic-leaf-extract-of-corchorus-olitorius-in-alloxan-induc",totalDownloads:558,totalCrossrefCites:1,signatures:"Arise Rotimi Olusanya, Bankole S. Ifeoluwa, Aboyewa Jumoke A.\nand Bobbo Khadijat",authors:[{id:"217205",title:"Dr.",name:"Rotimi",middleName:null,surname:"Arise",fullName:"Rotimi Arise",slug:"rotimi-arise"},{id:"220514",title:"Dr.",name:"Ifeoluwa",middleName:null,surname:"Bankole",fullName:"Ifeoluwa Bankole",slug:"ifeoluwa-bankole"},{id:"221006",title:"Ms.",name:"Jumoke",middleName:null,surname:"Aboyewa",fullName:"Jumoke Aboyewa",slug:"jumoke-aboyewa"},{id:"221007",title:"Ms.",name:"Khadijat",middleName:null,surname:"Bobbo",fullName:"Khadijat Bobbo",slug:"khadijat-bobbo"}]},{id:"62023",title:"Low-Carbohydrate High-Fat (LCHF) Diet: Evidence of Its Benefits",slug:"low-carbohydrate-high-fat-lchf-diet-evidence-of-its-benefits",totalDownloads:737,totalCrossrefCites:0,signatures:"Parijat De and Sagnik Mukhopadhyay",authors:[{id:"210442",title:"Dr.",name:"Parijat",middleName:null,surname:"De",fullName:"Parijat De",slug:"parijat-de"}]},{id:"57204",title:"Trace Elements Modulates Oxidative Stress in Type 2 Diabetes",slug:"trace-elements-modulates-oxidative-stress-in-type-2-diabetes",totalDownloads:547,totalCrossrefCites:0,signatures:"Ines Gouaref and Elhadj-Ahmed Koceir",authors:[{id:"217216",title:"Prof.",name:"Elhadj-Ahmed",middleName:null,surname:"Koceir",fullName:"Elhadj-Ahmed Koceir",slug:"elhadj-ahmed-koceir"},{id:"221212",title:"Dr.",name:"Ines",middleName:null,surname:"Gouaref",fullName:"Ines Gouaref",slug:"ines-gouaref"}]},{id:"61758",title:"Savior of Diabetes: Antioxidants",slug:"savior-of-diabetes-antioxidants",totalDownloads:537,totalCrossrefCites:1,signatures:"Zar Chi Thent and Azian Abd Latiff",authors:[{id:"217365",title:"Dr.",name:"Zar Chi",middleName:null,surname:"Thent",fullName:"Zar Chi Thent",slug:"zar-chi-thent"},{id:"219580",title:"Prof.",name:"Azian Abd",middleName:null,surname:"Latiff",fullName:"Azian Abd Latiff",slug:"azian-abd-latiff"}]},{id:"60464",title:"Influence of Glycaemic Control on Cognitive Function in Diabetic Children and Adolescents",slug:"influence-of-glycaemic-control-on-cognitive-function-in-diabetic-children-and-adolescents",totalDownloads:646,totalCrossrefCites:0,signatures:"Estefanía Diéguez Castillo, Ana Nieto-Ruíz, Mireia Escudero-Marín\nand Cristina Campoy",authors:[{id:"90805",title:"Prof.",name:"Cristina",middleName:null,surname:"Campoy",fullName:"Cristina Campoy",slug:"cristina-campoy"},{id:"211059",title:"BSc.",name:"Estefanía",middleName:null,surname:"Diéguez Castillo",fullName:"Estefanía Diéguez Castillo",slug:"estefania-dieguez-castillo"},{id:"233102",title:"BSc.",name:"Ana",middleName:null,surname:"Nieto",fullName:"Ana Nieto",slug:"ana-nieto"},{id:"233103",title:"BSc.",name:"Mireia",middleName:null,surname:"Escudero",fullName:"Mireia Escudero",slug:"mireia-escudero"}]},{id:"57565",title:"Medical Nutrition Therapy for Special Groups with Diabetes Mellitus",slug:"medical-nutrition-therapy-for-special-groups-with-diabetes-mellitus",totalDownloads:487,totalCrossrefCites:0,signatures:"Muhammed Kizilgul, Meltem Mermer and Bekir Ucan",authors:[{id:"210376",title:"Dr.",name:"Muhammed",middleName:null,surname:"Kizilgul",fullName:"Muhammed Kizilgul",slug:"muhammed-kizilgul"},{id:"211906",title:"Ph.D. Student",name:"Meltem",middleName:null,surname:"Mermer",fullName:"Meltem Mermer",slug:"meltem-mermer"},{id:"223836",title:"Dr.",name:"Bekir",middleName:null,surname:"Ucan",fullName:"Bekir Ucan",slug:"bekir-ucan"}]},{id:"57442",title:"Exercise and Diabetes Mellitus",slug:"exercise-and-diabetes-mellitus",totalDownloads:638,totalCrossrefCites:0,signatures:"Asmare Yitayeh Gelaw",authors:[{id:"210348",title:"Mr.",name:"Asmare Yitayeh",middleName:null,surname:"Gelaw",fullName:"Asmare Yitayeh Gelaw",slug:"asmare-yitayeh-gelaw"}]},{id:"61320",title:"New Insights into Alleviating Diabetes Mellitus: Role of Gut Microbiota and a Nutrigenomic Approach",slug:"new-insights-into-alleviating-diabetes-mellitus-role-of-gut-microbiota-and-a-nutrigenomic-approach",totalDownloads:779,totalCrossrefCites:0,signatures:"Lissé Angarita Dávila, Valmore Bermúdez Pirela, Nadia Reyna\nVillasmil, Silvana Cisternas, Waldo Díaz, Ma Cristina Escobar, Paula\nCarrasco, Samuel Durán, Kristian Buhring, Rodrigo Buhring,\nConstanza Bugman, Virginia Céspedes, Marcell Gatica, Diana Rojas,\nMarion Guerrero Wyss and Francisco Valdebenito",authors:[{id:"41236",title:"Dr.",name:"Valmore",middleName:null,surname:"Bermúdez",fullName:"Valmore Bermúdez",slug:"valmore-bermudez"},{id:"217192",title:"Ph.D.",name:"Lissé",middleName:null,surname:"Angarita Dávila",fullName:"Lissé Angarita Dávila",slug:"lisse-angarita-davila"},{id:"218793",title:"Dr.",name:"Nadia Reyna",middleName:null,surname:"Reyna Villasmil",fullName:"Nadia Reyna Reyna Villasmil",slug:"nadia-reyna-reyna-villasmil"},{id:"218794",title:"Dr.",name:"Samuel",middleName:null,surname:"Durán Agüero",fullName:"Samuel Durán Agüero",slug:"samuel-duran-aguero"},{id:"218795",title:"Dr.",name:"Waldo",middleName:null,surname:"Díaz",fullName:"Waldo Díaz",slug:"waldo-diaz"},{id:"218796",title:"MSc.",name:"Ma Cristina",middleName:null,surname:"Escobar Contreras",fullName:"Ma Cristina Escobar Contreras",slug:"ma-cristina-escobar-contreras"},{id:"218800",title:"MSc.",name:"Kristian",middleName:null,surname:"Bühring Bonacich",fullName:"Kristian Bühring Bonacich",slug:"kristian-buhring-bonacich"},{id:"218801",title:"MSc.",name:"Paula",middleName:null,surname:"Carrasco Vergara",fullName:"Paula Carrasco Vergara",slug:"paula-carrasco-vergara"},{id:"223462",title:"MSc.",name:"Silvana",middleName:null,surname:"Cisternas",fullName:"Silvana Cisternas",slug:"silvana-cisternas"},{id:"223468",title:"MSc.",name:"Marion",middleName:null,surname:"Guerrero Wyss",fullName:"Marion Guerrero Wyss",slug:"marion-guerrero-wyss"},{id:"223473",title:"MSc.",name:"Virginia",middleName:null,surname:"Cespedes",fullName:"Virginia Cespedes",slug:"virginia-cespedes"},{id:"223477",title:"Dr.",name:"Marcell",middleName:null,surname:"Gatica",fullName:"Marcell Gatica",slug:"marcell-gatica"},{id:"223478",title:"MSc.",name:"Rodrigo",middleName:null,surname:"Buhring",fullName:"Rodrigo Buhring",slug:"rodrigo-buhring"},{id:"223970",title:"MSc.",name:"Constanza",middleName:null,surname:"Bugmann",fullName:"Constanza Bugmann",slug:"constanza-bugmann"},{id:"239591",title:"Prof.",name:"Francisco",middleName:null,surname:"Valdebenito",fullName:"Francisco Valdebenito",slug:"francisco-valdebenito"},{id:"248969",title:"Dr.",name:"Diana",middleName:null,surname:"Rojas",fullName:"Diana Rojas",slug:"diana-rojas"}]}]},relatedBooks:[{type:"book",id:"8949",title:"Nutritional Value of Amaranth",subtitle:null,isOpenForSubmission:!1,hash:"2af686a663e37e1f663013cd1e3acbe0",slug:"nutritional-value-of-amaranth",bookSignature:"Viduranga Y. Waisundara",coverURL:"https://cdn.intechopen.com/books/images_new/8949.jpg",editedByType:"Edited by",editors:[{id:"194281",title:"Dr.",name:"Viduranga Yashasvi",surname:"Waisundara",slug:"viduranga-yashasvi-waisundara",fullName:"Viduranga Yashasvi Waisundara"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"},chapters:[{id:"70805",title:"Amaranth as a Pseudocereal in Modern Times: Nutrients, Taxonomy, Morphology and Cultivation",slug:"amaranth-as-a-pseudocereal-in-modern-times-nutrients-taxonomy-morphology-and-cultivation",signatures:"Asel C. Weerasekara and Viduranga Y. Waisundara",authors:[{id:"194281",title:"Dr.",name:"Viduranga Yashasvi",middleName:null,surname:"Waisundara",fullName:"Viduranga Yashasvi Waisundara",slug:"viduranga-yashasvi-waisundara"},{id:"309844",title:"Dr.",name:"Asel C.",middleName:null,surname:"Weerasekara",fullName:"Asel C. Weerasekara",slug:"asel-c.-weerasekara"}]},{id:"69525",title:"Adaptation Strategies and Microwave Drying of Amaranth Species with a High Nutritional Value to the Ecuadorian Andean Region",slug:"adaptation-strategies-and-microwave-drying-of-amaranth-species-with-a-high-nutritional-value-to-the-",signatures:"Carlos J. Torres-Miño, Rafael Hernández Maqueda and Ángel H. Moreno",authors:[{id:"305161",title:"Ph.D.",name:"Ángel",middleName:null,surname:"H. Moreno",fullName:"Ángel H. Moreno",slug:"angel-h.-moreno"},{id:"305164",title:"Dr.",name:"Rafael",middleName:null,surname:"Hernández Maqueda",fullName:"Rafael Hernández Maqueda",slug:"rafael-hernandez-maqueda"},{id:"305189",title:"Dr.",name:"Carlos J.",middleName:null,surname:"Torres-Miño",fullName:"Carlos J. Torres-Miño",slug:"carlos-j.-torres-mino"}]},{id:"69904",title:"Value of Amaranthus [L.] Species in Nigeria",slug:"value-of-em-amaranthus-em-l-species-in-nigeria",signatures:"Matthew Chidozie Ogwu",authors:[{id:"301124",title:"Dr.",name:"Matthew Chidozie",middleName:null,surname:"Ogwu",fullName:"Matthew Chidozie Ogwu",slug:"matthew-chidozie-ogwu"}]},{id:"68165",title:"Amaranth: An Ancient and High-Quality Wholesome Crop",slug:"amaranth-an-ancient-and-high-quality-wholesome-crop",signatures:"Dinesh Adhikary, Upama Khatri-Chhetri and Jan Slaski",authors:[{id:"299993",title:"Dr.",name:"Dinesh",middleName:null,surname:"Adhikary",fullName:"Dinesh Adhikary",slug:"dinesh-adhikary"},{id:"300684",title:"Ms.",name:"Upama",middleName:null,surname:"Khatri-Chhetri",fullName:"Upama Khatri-Chhetri",slug:"upama-khatri-chhetri"},{id:"308380",title:"Dr.",name:"Jan",middleName:null,surname:"Slaski",fullName:"Jan Slaski",slug:"jan-slaski"}]},{id:"70999",title:"Potential of Amaranth in Alleviating Malnutrition in Indonesia",slug:"potential-of-amaranth-in-alleviating-malnutrition-in-indonesia",signatures:"Muhammad Ikhsan Sulaiman and Rita Andini",authors:[{id:"304411",title:"Ph.D.",name:"Rita",middleName:null,surname:"Andini",fullName:"Rita Andini",slug:"rita-andini"},{id:"304416",title:"Dr.",name:"Muhammad Ikhsan",middleName:null,surname:"Sulaiman",fullName:"Muhammad Ikhsan Sulaiman",slug:"muhammad-ikhsan-sulaiman"}]},{id:"68895",title:"Functional Value of Amaranth as Applied to Sports Nutrition",slug:"functional-value-of-amaranth-as-applied-to-sports-nutrition",signatures:"Torregrosa-García Antonio and López-Román F. Javier",authors:[{id:"304203",title:"Ph.D. Student",name:"Antonio",middleName:null,surname:"Torregrosa-García",fullName:"Antonio Torregrosa-García",slug:"antonio-torregrosa-garcia"},{id:"304206",title:"Dr.",name:"Javier F.",middleName:null,surname:"López-Román",fullName:"Javier F. López-Román",slug:"javier-f.-lopez-roman"}]},{id:"67741",title:"Nutritional Functional Value and Therapeutic Utilization of Amaranth",slug:"nutritional-functional-value-and-therapeutic-utilization-of-amaranth",signatures:"Manuel Soriano-García and Isabel Saraid Aguirre-Díaz",authors:[{id:"300752",title:"Prof.",name:"Manuel",middleName:null,surname:"Soriano-García",fullName:"Manuel Soriano-García",slug:"manuel-soriano-garcia"},{id:"317538",title:"Dr.",name:"Isabel Saraid",middleName:null,surname:"Aguirre-Díaz",fullName:"Isabel Saraid Aguirre-Díaz",slug:"isabel-saraid-aguirre-diaz"}]},{id:"68642",title:"Effect of Various Process Conditions on the Nutritional and Bioactive Compounds of Amaranth",slug:"effect-of-various-process-conditions-on-the-nutritional-and-bioactive-compounds-of-amaranth",signatures:"Ofelia Marquez-Molina and Leticia Xochitl Lopez-Martinez",authors:[{id:"301437",title:"Dr.",name:"Leticia Xochitl",middleName:null,surname:"Lopez-Martinez",fullName:"Leticia Xochitl Lopez-Martinez",slug:"leticia-xochitl-lopez-martinez"},{id:"308486",title:"Dr.",name:"Ofelia",middleName:null,surname:"Marquez-Molina",fullName:"Ofelia Marquez-Molina",slug:"ofelia-marquez-molina"}]},{id:"71167",title:"Amaranth Seed Oil Composition",slug:"amaranth-seed-oil-composition",signatures:"Parisa Nasirpour-Tabrizi, Sodeif Azadmard-Damirchi, Javad Hesari and Zahra Piravi-Vanak",authors:[{id:"279804",title:"Associate Prof.",name:"Zahra",middleName:null,surname:"Piravi-Vanak",fullName:"Zahra Piravi-Vanak",slug:"zahra-piravi-vanak"},{id:"312225",title:"Prof.",name:"Sodeif",middleName:null,surname:"Azadmard-Damirchi",fullName:"Sodeif Azadmard-Damirchi",slug:"sodeif-azadmard-damirchi"},{id:"318844",title:"Dr.",name:"Parisa",middleName:null,surname:"Nasirpour-Tabrizi",fullName:"Parisa Nasirpour-Tabrizi",slug:"parisa-nasirpour-tabrizi"},{id:"318845",title:"Dr.",name:"Javad",middleName:null,surname:"Hesari",fullName:"Javad Hesari",slug:"javad-hesari"}]},{id:"68401",title:"Kinetics and Thermodynamics of Oil Extracted from Amaranth",slug:"kinetics-and-thermodynamics-of-oil-extracted-from-amaranth",signatures:"Chinedu M. Agu and Albert C. Agulanna",authors:[{id:"299277",title:"Ph.D.",name:"Chinedu M.",middleName:null,surname:"Agu",fullName:"Chinedu M. Agu",slug:"chinedu-m.-agu"},{id:"308966",title:"MSc.",name:"Albert C.",middleName:null,surname:"Agulanna",fullName:"Albert C. Agulanna",slug:"albert-c.-agulanna"}]}]}]},onlineFirst:{chapter:{type:"chapter",id:"66185",title:"Dysbiosis of the Microbiota in Anorexia Nervosa: Pathophysiological Implications",doi:"10.5772/intechopen.85253",slug:"dysbiosis-of-the-microbiota-in-anorexia-nervosa-pathophysiological-implications",body:'
1. Introduction
Anorexia nervosa (AN) is a serious and often enduring psychiatric condition. The hallmark features of AN are a phobia for weight gain, and for intake of fattening food, disturbance in body image, and often compensatory behaviors such as excessive exercise and purging, which overall leads to a reduction of energy intake relative to energy expenditure leading to low body weight. An increased risk of suicide and frequent potential life-threatening medical complications of several body organs contribute to AN having a high standardized mortality ratio of 5.2 [3.7–7.5] [1]. This is coupled with a high risk of enduring disease [2].
The weight loss is in some patients preceded by a depression, a trauma, gastrointestinal symptoms or an infection. But in a majority of patients there is no detectable psychiatric or somatic disorder preceding the weight loss. In children and adolescents with AN, family-based treatment as described by Lock and LeGrange is recommended [3] and if treatment is started shortly after debut of the disorder, the prognosis is fairly good. However, if treatment is delayed, the prognosis becomes worse [4]. In adults, individual eating-disorder-focused therapy (CBT-ED) is recommended [5]. With this treatment, drop-out rates are high and even with optimal treatment by well-trained therapists only 50% of the patients who start CBT-ED have good effect of the therapy [6, 7].
Considering the high mortality, high chronicity and lack of knowledge on the etiology of AN, there is an immense need for an improved understanding of the etiology and pathophysiology of the disease in order to find ways to better treatments. This knowledge would preferably explain both the routes into developing the disorder and mechanisms that serve to maintain it, and proposedly involve both biological and psychological factors, such that measures and biomarkers to follow the development and recovery from of the disease could be identified. Potential further benefits with biomarkers for AN may be guidance for risk stratification, treatment and target identification for novel treatments. The last few years have seen an increase in studies on the gut microbiota and its associated microbiome which might harbor trait biomarkers for AN.
The “microbiota” refers to the cumulative microorganisms, including Bacteria, Viruses, Archaea, Protists and Fungi, which populate a number of human tissues and biofluids including the skin, lungs, roal mucosa, saliva, and gastrointestinal tract, and the “microbiome” refers to the collective genomes of the present microorganisms [8]. There are more than 1000 ‘species-level’ phylotypes that coexist in a human [9], and the majority of these phylotypes are Bacteria, with Faecalibacterium prausnitzii, Roseburia intestinalis, and Bacteroides uniformis dominating in the adult microbiota found in feces samples [10]. The composition of the phylotypes is mostly consistent across individuals, albeit there may be a large variability with regard to relative composition and diversity of the included microorganisms, intra-individually depending on anatomical site and inter-individually at the same anatomical location. In addition, there are inter-individual variations at the same anatomical site.
The gut microbiota is critical for the development of the gut mucosal immunity [11, 12], and it is also involved in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis [13], serotonergic neurotransmission [14], and signaling mechanisms affecting neuronal circuits involved in motor control and anxiety in mice [15]. This pathway has been named the gut-brain axis [16].
2. The gut-brain axis
The existence of the gut-brain axis is exemplified by irritable bowel syndrome (IBS) where more than half of the patients also suffer from mood disorders and for which antidepressants is one of the more common pharmaceutical treatments [17]. In IBS and other potential gut-brain axis disorders, cognitive alterations seem to be key features of the disorders [18]. These cognitive alterations might be induced by signal transduction from gut to the brain [18]. In addition, the existence is also shown by the effects of antibiotic exposure, which may lead to altered brain function such as anxiety, panic disorder, major depression, psychosis, and delirium which are usually described as side effects of antibiotic treatment [19]. Support for the latter comes also from studies in mice which have shown that an altered composition of the gut microbiota in adult mice, and an increased exploratory behavioral including hippocampal expression of Brain Derived Nerve growth Factor (BDNF) has been found after oral administration of non-absorbable antimicrobials [20], in contrast to intraperitoneal administration, which had no effect on behavior or BDNF levels.
Another area of evidence for the gut-brain-axis stems from dietary induction of changes in gut microbiota and linked psychopathological outcomes. For example, a high fat diet has been found associated with an altered microbial diversity and diminished synaptic plasticity [21, 22] but also increased vulnerability and anxiety-like behavior in the mice [23]. In addition, a diet high in sucrose also led to an altered microbial diversity associated with impaired development of spatial bias for long term memory, short term memory, and reversal trainings [24]. Another strong evidence for the gut-brain axis comes from a study in mice exposed to a microbiome depletion and/or transplantation paradigm where microbiota, in a first step, was isolated from donors who were provided with either in high fat diet or a controlled diet, and thereafter in a second step, transfused to mice who developed significant and selective disruptions in exploratory, cognitive, and also developed the stereotypical behavior following the high fat diet [25]. However, there are also evidence from studies where alcohol exposure, smoking habits, and disruptions in diurnal rhythm all have been shown to affect the microbiota composition.
There are also other evidence pointing to a reciprocal interaction from a study where a second generation antipsychotics, olanzapine, was exposed to rats and found to affect the composition of the microbiota, which also triggered an inflammatory response and weight gain [26, 27]. Furthermore, the exposure to antibiotics seemed to attenuate these physiological effects [28].
The microbiome has also been found to have been altered in various psychiatric conditions, or to affect its clinical expression, as well altered in rodent models for these disorders [29]. One example is major depressive disorder (MDD) where, for example, in germ-free mice (mice completely void of bacterial microbiota or derived molecules), there are both changes from comparable normal mice in the hypothalamic, pituitary, adrenal stress response, as well as altered levels of monoamines concentrations or their receptors [13, 14, 15, 20, 30]. Indirect evidence in MDD also comes from an increased serum antibody level to lipopolysaccharides that stems from Gram-negative enterobacteria, which are higher in MDD compared to controls [31], and which is associated with stress associated increased gut permeability and bacterial translocation in animal models [32, 33]. In addition, depression also altered the gut microbiota in a mouse model, in which chronic depression and anxiety-like behaviors were induced by olfactory bulbectomy [34], suggesting a feedback loop between depressive states and dysbiosis.
Furthermore, a similar type of relation between dysbiosis and psychopathogenesis is found in schizophrenia [35, 36]. For example, elevated levels of serological markers of bacterial translocation have been found to be highly correlated with systemic inflammatory markers in schizophrenia [37], and, cytokine levels in schizophrenia are correlated with the severity of symptomatology [38]. From a genetic point of view, several of the strongest associations identified between genetic risk and schizophrenia stems from genes that are linked to immunological function [57, 58]. This is particularly interesting in view of the genetic association between AN and schizophrenia [39].
3. How is the effects in the gut-brain axis mediated?
The mechanism behind the gut brain axis may be multifaceted involving neural signal transduction in nervus vagus, neurotransmitters, immunological mechanisms, and mechanisms related to metabolism and energy utilization [40]. One of the strongest links from a mechanistic point of view, stems from research on serotonin and the microbiota. Enterochromaffin (EC) cells provides approximately 95% of the total body content of serotonin [41] of which the majority exists in plasma. Multiple levels of evidence links disturbances in the serotonergic system and several psychiatric disorder such as depression, anxiety, and borderline personality disorder. For example, the metabolism of tryptophan, a precursor of serotonin, is potentially regulated by the gut microbiota thereby enabling it to influence brain function [42]. Tryptophan is an essential amino acid derived from the diet [43], and tryptophan that is absorbed from the gut into the bloodstream passes the blood-brain barrier to contribute to serotonin synthesis in situ [43]. The availability of tryptophan is strongly affected by the gut microbiota, and several studies have indicated that bacteria such as streptococcus, Escherichia, enterococcus species and Bifidobacterium infantis, and especially indigenous spore-forming bacteria may modulate serotonin levels by increasing plasma tryptophan [44]. An example of this is studies in germ free mice that have found that they exhibit an increased plasma tryptophan concentration [14, 15], which after post weaning colonization can be normalized [14]. The serotonergic neurotransmission may thereby be influenced by the availability of tryptophan for serotonin production [45]. There are studies have found that a depletion of tryptophan influences mood, anxiety and borderline personality traits, for example, in AN and bulimia nervosa [46, 47, 48, 49].
There are also other evidences that link the gut microbiota with psychiatric conditions such as MDD. For examples, a recent publication by Seng et al. [50] provides three additional levels of evidences: (a) that germ free mice lacks gut microbiota and display depression like features in forced swimming test compared to conventionally raised healthy control mice; (b) that the gut microbiota composition of MDD patients differ from that of healthy controls; and (c) and that transplantation of MDD microbiota to germ free mice led to the development of depression like behaviors. In addition, Seng et al. found that mice that were harboring the microbiota from MDD patients primarily exhibited disturbances of microbiome genes and host metabolism which thereby suggests that the depression-like behavior was mediated through the host metabolism [50].
Another neurotransmitter that is produced by the microbiota and that may influence host behavior is gamma aminobutyric acid (GABA) which is the main inhibitory neurotransmitter in the CNS. GABA produced by the probiotic Lactobacillus rhamnosus was administered to mice and led to an alteration in the expression of GABA receptors in different CNS regions, associated with reduced anxiety and depression-like behaviors [51].
Another mechanism for interaction between the microbiome and the CNS is at the level of the blood-brain barrier (BBB). The vascular BBB is comprised of specialized brain endothelial cells acts as a regulatory interface between brain and blood that prevent the unrestricted transfer of molecules into the CNS. Disruption of the tight junctions of the BBB can expose the CNS, and has also been linked to CNS disorders [52]. A dysbiotic microbiome could possibly interact with the BBB in several ways: bacterial factors and immune-active molecules released from peripheral sites influenced by the microbiome can cross the BBB, alter BBB integrity or change BBB transport [53]. In germ-free mice, it has been shown that the BBB has increased permeability compared to pathogen-free mice with a normal gut flora. The increased permeability was associated with reduced expression of the tight junction proteins. Exposure of germ-free adult mice to a normal gut microbiota decreased BBB permeability and up-regulated the expression of tight junction proteins [54]. Metabolic products such as short-chain fatty acids (SCFAs) are produced through the fermentation of dietary fibers by the gut microbiota [55] and can cross the BBB to affect brain function. A low production of SCFAs could lead to increased BBB permeability and SCFAs has been shown to be able to improve a dysfunctional BBB in germ-free mice [54]. Another example is that antibiotics are able to modify barrier integrity and alter behavior in mice [56] and alterations to the microbiome composition in mice in favor of, for example, probiotic bifidobacteria spp. through food supplement with prebiotics showed impact on neuroinflammation and were accompanied with changes in the expression of tight junction proteins [57]. Furthermore, leptin, a key hormone for the control of appetite and weight gain, is normally restricted by the BBB but has been shown in mice with a deficit in leptin transport to the brain to enhance the sense of food reward [58].
4. Microbiota findings in AN studies
Dysbiosis has been proposed in AN and through the long periods of starvation associated with the core psychopathology of AN, a considerable adaptation in gut microbiota could occur in individuals with AN. A systematic review by Schwennsen et al. [59] found some evidence of dysbiosis in AN, such as the abundance of the gut microbiota in AN, which was described as either normal [60, 61], reduced [62] or altered in AN [63]. In addition, the diversity of the gut microbiota in AN was described as normal [61, 63], or reduced (alpha, i.e., within-sample diversity) [64] both in the acute stage and after weight restoration.
Common microbiota findings in the acute stages of AN were low levels of phylum Bacteroidetes [61, 64], while the phylum Firmicutes was increased in AN in three studies [61, 64, 65] however decreased in a fourth [63]. Furthermore, the genus Methanobrevibacter and specifically, the species M. smithii, has been found increased in AN patients in several studies [60, 61, 63, 65]. It is important to remember the presence or lack of a specific bacterial spp. identified by their 16rRNA gene is not the same as the presences or lack of certain metabolic functions or microbiota steady-state dynamic. The state of knowledge of the microbiota in AN is in its infancy and more studies are needed.
4.1 The microbiota and relation to clinical symptoms in AN
This systematic review [59] identified two studies describing an association between the microbiota and clinical symptoms in AN. In one study, ClpB protein concentrations were significantly correlated with several subscales on the Eating Disorder Inventory-2 (EDI-2) for patients with eating disorders and the Montgomery-Åsberg Depression Rating Scale (MADRS) total score and specifically the anhedonia score for AN patients (p < 0.05) [66]. In another study, an association between alpha diversity and depression and eating disorder psychopathology was found in AN [64]. Should further studies find further support for that the microbiota drives the symptoms of AN, this would strengthen targeting the microbiota as a primary level of treatment of AN.
5. How is the gut-brain axis involved in AN? Breakdown of organic material in the gut and its exposure in plasma
A potential mechanism through which the microbiota indirectly influences the pathophysiology and symptoms of AN is through the breakdown of organic material in the gut and the transfer of metabolites into the blood stream. One of the microbiota that has been described in AN is M. smithii, which is involved in the breakdown of polysaccharides from vegetable sources and the finding of this specific Archaeon could illustrate an adaptation to a typical diet rich in vegetables and fruits in persons with AN. In addition, methanogenic Archaea, such as M. smithii, have also been linked to constipation, a common complaint in patients with AN, which statins have been shown to alleviate by suppressing the growth of methanogens [65, 67, 68, 69]. The evidence of M. smithii in feces from constipated patients necessitate further investigation of whether this finding in AN patients is only related to constipation or also related to AN psychopathology as a potential biomarker.
The gut microbiota is involved in both weight gain and weight loss as well as with energy extraction from the diet in both humans and animals [70, 71]. Differences in the composition of the gut microbiota between obese and lean individuals have been consistently described, potentially illustrating differences in energy extraction efficiency between obese and lean individuals [72, 73], and specific gut dysbiosis could predispose to the drive toward negative energy balance in AN. With regard to the effect of weight gain on the fecal microbiota, Firmicutes has been found increased after weight restoration in two studies in AN [61, 64].
6. AN comorbid disorder as evidence of microbiota influence
Intestinal dysbiosis has previously been associated with psychological function and mental health including depression and anxiety, both of which are commonly comorbid with AN [40]. AN patients often present with comorbid anxiety (75% lifetime prevalence of anxiety disorder) [74] and depression (more than 34% lifetime prevalence of depression) [75, 76]. These findings provide further support for a role of dysbiosis in the pathophysiology of AN.
7. A leaking gut in AN?
During starvation, some of the gut bacteria will have insufficient nutrient supply for survival. Slowly growing bacteria or bacteria able to feed on the mucus lining the gut wall will survive for a longer period of time [77]. The competition between bacteria with different growth capacities to survive and proliferate in the gut has probably taken place for millions of years. Thus, it is reasonable to expect that various mechanisms for survival and proliferation have emerged among gut bacteria including the capacity to release of substances inhibiting food intake of the host. Alterations in gut permeability has been linked to a number of intestinal diseases, such as irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), but also to extraintestinal disease as depression, anxiety and autism specter disorders [78, 79]. Increased gut permeability may also facilitate signal transduction from the gut to the brain via the vagus nerve and blood [80], possibly in synergy with interaction with increased BBB permeability. In addition, in animal and human studies, the experience of stress is also linked to an increase in permeability of the intestinal barrier. This increase in permeability seems to be mediated through, among other factors, hypothalamic hormones, especially corticotropi-releasing hormone (CRH) [77]. Increased mucin degrading bacteria has been demonstrated in AN [81] indicating that decreased food intake induce overgrowth of bacteria able to feed on the mucus layer and thereby increase gut permeability.
An example of a possible biomarker species is the bacterium Akkermansia muciniphila which is abundant in humans and rodents and has been inversely correlates with body weight and is associated with metabolic syndromes and auto-immune diseases [82]. A. municiphilia is a symbiotic bacterium of the mucus layer, can utilize mucin as its sole carbon, nitrogen, and energy source and is able to produce certain SCFAs [83, 84]. In mice, it has been shown that the abundance of A. muciniphila decreased in obese and type 2 diabetic mice and that administration of the bacterium increased the intestinal levels of endocannabinoids that control inflammation, the gut barrier, and gut peptide secretion [82]. In a single AN patient case story, it has been shown that one treatment with a fecal matter transplant from a healthy donor led to weight gain and an increase in A. municiphilia and SCFAs blood levels [85]. A. municiphilia is an example of a complex interaction where the bacterium simultaneously degrade the mucin for energy, but also at the same time induces higher mucus production from the host. This could in turn improve protection of the gut wall from interaction with harmful molecules from other gut bacteria and leakage into the blood.
Furthermore, in an activity based mouse model of AN Jésus et al. demonstrated increased permeability in the colon, that is, “gut leakiness”, in anorexic mice, however the authors also found that the gut leakiness was more related to malnutrition than exercise [86]. Although there may be conflicting studies [87], yet another study examining the role of exercise on gut permeability, found that exercise increases intestinal permeability measured with the lactulose and rhamnose differential urinary excretion test [88].
Another support for a leaking gut wall in AN comes from a study by Breton et al. [66], who found an increase in ClpB protein concentrations in plasma in eating disorder patients compared to plasma of controls, and furthermore, that ClpB protein concentrations correlated positively with alpha-Melanocyte Stimulating Hormone-(alpha-MSH)-reactive IgG for all patients with eating disorders. ClpB protein is produced by Enterobacteriae such as Escherichia coli and has been found as a conformational mimetic of alpha-MSH, which is thought to be involved in satiety and anxiety [89]. The study adds evidence to the potential role of ClpB protein produced by Enterobacteriae in the gut and its impact on the brain and psychopathology in eating disorders.
The potentially altered gut permeability in AN may underlie the low-grade inflammation and increased risk of autoimmune diseases found in eating disorders [90]. Moreover, starvation has a significant impact on the gut microbiota, and a diet based on animal products used for re-nutrition, may stimulate the growth of bacteria that trigger inflammation [91].
8. A model for the pathophysiology of AN
The initial reduction of food intake induces alterations in the gut microbiota. These alterations in gut microbiota induce increased gut permeability. Due to this altered microbiota and increased gut and in addition, increased blood-brain barrier permeability, neurohormonal signals interfering with food intake are transferred to the brain, influencing brain functions, for example, cognition. This contributes in creating a vicious circle which subserves in maintaining the mechanisms associated with AN (Figure 1).
Figure 1.
The initial reduction of food intake induces alterations in the gut microbiota. These alterations in gut microbiota induce increased gut permeability. Due to this altered microbiota and increased gut and in addition, increased blood-brain barrier permeability, neurohormonal signals interfering with food intake are transferred to the brain, influencing brain functions, for example, cognition. This contributes in creating a vicious circle which subserves maintaining in the mechanisms associated with AN.
9. Conclusions
There are a lot of evidence linking dysbiosis and inflammatory and psychiatric disorders and although there are only a few studies that have examined the microbiota in AN, several of these point to a dysbiosis also in AN. The effects of this dysbiosis is mediated through the gut-brain axis, and leakage through the gut and potentially also the BBB, provide pathways for neurohormonal signals to induce and maintain psychiatric disorders such as AN. The evidence in AN will need confirmation and further clarification in larger, randomized and controlled studies. We propose a model for disease development and maintenance in AN where a dysbiosis is a key component. Future studies will need to clarify the pathophysiology of AN.
Acknowledgments
We are thankful to Psychiatric Center Ballerup and the Capitol Region of Denmark, for providing support for this study.
Conflict of interest
The authors declare no conflict of interest.
\n',keywords:"anorexia nervosa, feces, microbiota, species, biomarkers",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/66185.pdf",chapterXML:"https://mts.intechopen.com/source/xml/66185.xml",downloadPdfUrl:"/chapter/pdf-download/66185",previewPdfUrl:"/chapter/pdf-preview/66185",totalDownloads:483,totalViews:0,totalCrossrefCites:0,dateSubmitted:"November 15th 2018",dateReviewed:"February 16th 2019",datePrePublished:"March 18th 2019",datePublished:null,dateFinished:null,readingETA:"0",abstract:"Anorexia nervosa (AN) is a severe and often enduring condition of which the etiology is unknown. Studies on the gut microbiota in AN have found deviations from that of healthy individuals, which may imply a relation to pathophysiology, development and maintenance of the disorder via the gut-brain axis, which has been shown in other disorders. A narrative review of the gut microbiota studies in AN is presented. Several studies point to a dysbiosis in AN which may have implications for maintenance of a low body weight, immunological changes and a severely reduced food intake. An association may be found to clinical symptoms in AN. A pathophysiological model for disease is presented implying a role of the microbiota in maintenance of AN. Dysbiosis in AN may play an important role in the development and maintenance of AN.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/66185",risUrl:"/chapter/ris/66185",signatures:"Magnus Sjögren, Stein Frostad and Kenneth Klingenberg Barfod",book:{id:"7885",title:"Anorexia and Bulimia Nervosa",subtitle:null,fullTitle:"Anorexia and Bulimia Nervosa",slug:"anorexia-and-bulimia-nervosa",publishedDate:"October 2nd 2019",bookSignature:"Hubertus Himmerich and Ignacio Jáuregui Lobera",coverURL:"https://cdn.intechopen.com/books/images_new/7885.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"231568",title:"Dr.",name:"Hubertus",middleName:null,surname:"Himmerich",slug:"hubertus-himmerich",fullName:"Hubertus Himmerich"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:null,sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. The gut-brain axis",level:"1"},{id:"sec_3",title:"3. How is the effects in the gut-brain axis mediated?",level:"1"},{id:"sec_4",title:"4. Microbiota findings in AN studies",level:"1"},{id:"sec_4_2",title:"4.1 The microbiota and relation to clinical symptoms in AN",level:"2"},{id:"sec_6",title:"5. How is the gut-brain axis involved in AN? Breakdown of organic material in the gut and its exposure in plasma",level:"1"},{id:"sec_7",title:"6. AN comorbid disorder as evidence of microbiota influence",level:"1"},{id:"sec_8",title:"7. A leaking gut in AN?",level:"1"},{id:"sec_9",title:"8. A model for the pathophysiology of AN",level:"1"},{id:"sec_10",title:"9. Conclusions",level:"1"},{id:"sec_11",title:"Acknowledgments",level:"1"},{id:"sec_14",title:"Conflict of interest",level:"1"}],chapterReferences:[{id:"B1",body:'Keshaviah A et al. Re-examining premature mortality in anorexia nervosa: A meta-analysis redux. Comprehensive Psychiatry. 2014;55(8):1773-1784'},{id:"B2",body:'Steinhausen HC. Outcome of eating disorders. Child and Adolescent Psychiatric Clinics of North America. 2009;18(1):225-242'},{id:"B3",body:'Lock J, Le Grange D. Treatment Manual for Anorexia Nervosa: A Family-Based Approach. 2nd ed. New York; London: Guilford; 2013'},{id:"B4",body:'Treasure J, Russell G. The case for early intervention in anorexia nervosa: Theoretical exploration of maintaining factors. The British Journal of Psychiatry. 2011;199(1):5-7'},{id:"B5",body:'Eating Disorders: Recognition and treatment. Clinical Guideline, National Guideline Alliance (UK). London: National Institute for Health and Care Excellence; 2017. https://www.nice.org.uk/guidance/NG69 [Accessed 1 Mar 2019]'},{id:"B6",body:'Cooper Z, Fairburn CG. The evolution of “enhanced” cognitive behavior therapy for eating disorders: Learning from treatment nonresponse. Cognitive and Behavioral Practice. 2011;18(3):394-402'},{id:"B7",body:'Frostad S et al. Implementation of enhanced cognitive behaviour therapy (CBT-E) for adults with anorexia nervosa in an outpatient eating-disorder unit at a public hospital. Journal of Eating Disorders. 2018;6:12'},{id:"B8",body:'Quigley EMM. Gut bacteria in health and disease. Gastroenterology & Hepatology. 2013;9(9):560-569'},{id:"B9",body:'Claesson MJ et al. Comparative analysis of pyrosequencing and a phylogenetic microarray for exploring microbial community structures in the human distal intestine. PLoS One. 2009;4(8):e6669'},{id:"B10",body:'Qin J et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature. 2010;464(7285):59-65'},{id:"B11",body:'Sudo N et al. The requirement of intestinal bacterial flora for the development of an IgE production system fully susceptible to oral tolerance induction. Journal of Immunology. 1997;159(4):1739-1745'},{id:"B12",body:'Guarner F, Malagelada JR. Gut flora in health and disease. Lancet. 2003;361(9356):512-519'},{id:"B13",body:'Sudo N et al. Postnatal microbial colonization programs the hypothalamic-pituitary-adrenal system for stress response in mice. The Journal of Physiology. 2004;558(Pt 1):263-275'},{id:"B14",body:'Clarke G et al. The microbiome-gut-brain axis during early life regulates the hippocampal serotonergic system in a sex-dependent manner. Molecular Psychiatry. 2013;18(6):666-673'},{id:"B15",body:'Diaz Heijtz R et al. Normal gut microbiota modulates brain development and behavior. Proceedings of the National Academy of Sciences of the United States of America. 2011;108(7):3047-3052'},{id:"B16",body:'Cryan JF, O\'Mahony SM. The microbiome-gut-brain axis: From bowel to behavior. Neurogastroenterology and Motility. 2011;23(3):187-192'},{id:"B17",body:'Neufeld KA, Foster JA. Effects of gut microbiota on the brain: Implications for psychiatry. Journal of Psychiatry & Neuroscience. 2009;34(3):230-231'},{id:"B18",body:'Kennedy PJ et al. Irritable bowel syndrome: A microbiome-gut-brain axis disorder? World Journal of Gastroenterology. 2014;20(39):14105-14125'},{id:"B19",body:'Sternbach H, State R. Antibiotics: Neuropsychiatric effects and psychotropic interactions. Harvard Review of Psychiatry. 1997;5(4):214-226'},{id:"B20",body:'Bercik P et al. The intestinal microbiota affect central levels of brain-derived neurotropic factor and behavior in mice. Gastroenterology. 2011;141(2):599-609, 609 e1-3'},{id:"B21",body:'Liu Z et al. High-fat diet induces hepatic insulin resistance and impairment of synaptic plasticity. PLoS One. 2015;10(5):e0128274'},{id:"B22",body:'Daniel H et al. High-fat diet alters gut microbiota physiology in mice. The ISME Journal. 2014;8(2):295-308'},{id:"B23",body:'Sharma S, Fernandes MF, Fulton S. Adaptations in brain reward circuitry underlie palatable food cravings and anxiety induced by high-fat diet withdrawal. International Journal of Obesity. 2013;37(9):1183-1191'},{id:"B24",body:'Magnusson KR et al. Relationships between diet-related changes in the gut microbiome and cognitive flexibility. Neuroscience. 2015;300:128-140'},{id:"B25",body:'Bruce-Keller AJ et al. Obese-type gut microbiota induce neurobehavioral changes in the absence of obesity. Biological Psychiatry. 2015;77(7):607-615'},{id:"B26",body:'Davey KJ et al. Gender-dependent consequences of chronic olanzapine in the rat: Effects on body weight, inflammatory, metabolic and microbiota parameters. Psychopharmacology. 2012;221(1):155-169'},{id:"B27",body:'Ley RE et al. Microbial ecology: Human gut microbes associated with obesity. Nature. 2006;444(7122):1022-1023'},{id:"B28",body:'Davey KJ et al. Antipsychotics and the gut microbiome: Olanzapine-induced metabolic dysfunction is attenuated by antibiotic administration in the rat. Translational Psychiatry. 2013;3:e309'},{id:"B29",body:'Hansen AK et al. A review of applied aspects of dealing with gut microbiota impact on rodent models. ILAR Journal. 2015;56(2):250-264'},{id:"B30",body:'Neufeld KM et al. Reduced anxiety-like behavior and central neurochemical change in germ-free mice. Neurogastroenterology and Motility. 2011;23(3):255-264, e119'},{id:"B31",body:'Maes M, Kubera M, Leunis JC. The gut-brain barrier in major depression: Intestinal mucosal dysfunction with an increased translocation of LPS from gram negative enterobacteria (leaky gut) plays a role in the inflammatory pathophysiology of depression. Neuro Endocrinology Letters. 2008;29(1):117-124'},{id:"B32",body:'Bravo JA et al. Communication between gastrointestinal bacteria and the nervous system. Current Opinion in Pharmacology. 2012;12(6):667-672'},{id:"B33",body:'Ait-Belgnaoui A et al. Acute stress-induced hypersensitivity to colonic distension depends upon increase in paracellular permeability: Role of myosin light chain kinase. Pain. 2005;113(1-2):141-147'},{id:"B34",body:'Park AJ et al. Altered colonic function and microbiota profile in a mouse model of chronic depression. Neurogastroenterology and Motility. 2013;25(9):733-e575'},{id:"B35",body:'Dinan TG, Borre YE, Cryan JF. Genomics of schizophrenia: Time to consider the gut microbiome? Molecular Psychiatry. 2014;19(12):1252-1257'},{id:"B36",body:'Nemani K et al. Schizophrenia and the gut-brain axis. Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2015;56:155-160'},{id:"B37",body:'Severance EG et al. Discordant patterns of bacterial translocation markers and implications for innate immune imbalances in schizophrenia. Schizophrenia Research. 2013;148(1-3):130-137'},{id:"B38",body:'Fan X, Goff DC, Henderson DC. Inflammation and schizophrenia. Expert Review of Neurotherapeutics. 2007;7(7):789-796'},{id:"B39",body:'Duncan L et al. Significant locus and metabolic genetic correlations revealed in genome-wide association study of anorexia nervosa. The American Journal of Psychiatry. 2017;174(9):850-858'},{id:"B40",body:'Rogers GB et al. From gut dysbiosis to altered brain function and mental illness: Mechanisms and pathways. Molecular Psychiatry. 2016;21(6):738-748'},{id:"B41",body:'Erspamer V. Pharmacology of indole-alkylamines. Pharmacological Reviews. 1954;6(4):425-487'},{id:"B42",body:'O\'Mahony SM et al. Serotonin, tryptophan metabolism and the brain-gut-microbiome axis. Behavioural Brain Research. 2015;277:32-48'},{id:"B43",body:'Ruddick JP et al. Tryptophan metabolism in the central nervous system: Medical implications. Expert Reviews in Molecular Medicine. 2006;8(20):1-27'},{id:"B44",body:'Yano JM et al. Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell. 2015;161(2):264-276'},{id:"B45",body:'Ben-Ari Y. Neuropaediatric and neuroarchaeology: Understanding development to correct brain disorders. Acta Paediatrica. 2013;102(4):331-334'},{id:"B46",body:'Kaye WH et al. Anxiolytic effects of acute tryptophan depletion in anorexia nervosa. The International Journal of Eating Disorders. 2003;33(3):257-267. Discussion 268-70'},{id:"B47",body:'Kaye WH et al. Effects of acute tryptophan depletion on mood in bulimia nervosa. Biological Psychiatry. 2000;47(2):151-157'},{id:"B48",body:'Smith KA, Fairburn CG, Cowen PJ. Symptomatic relapse in bulimia nervosa following acute tryptophan depletion. Archives of General Psychiatry. 1999;56(2):171-176'},{id:"B49",body:'Weltzin TE et al. Acute tryptophan depletion and increased food intake and irritability in bulimia nervosa. The American Journal of Psychiatry. 1995;152(11):1668-1671'},{id:"B50",body:'Zheng P et al. Gut microbiome remodeling induces depressive-like behaviors through a pathway mediated by the host\'s metabolism. Molecular Psychiatry. 2016;21(6):786-796'},{id:"B51",body:'Bravo JA et al. Ingestion of lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proceedings of the National Academy of Sciences of the United States of America. 2011;108(38):16050-16055'},{id:"B52",body:'Najjar S et al. Neurovascular unit dysfunction and blood-brain barrier hyperpermeability contribute to schizophrenia neurobiology: A theoretical integration of clinical and experimental evidence. Front Psychiatry. 2017;8:83'},{id:"B53",body:'Logsdon AF et al. Gut reactions: How the blood-brain barrier connects the microbiome and the brain. Experimental Biology and Medicine (Maywood, N.J.). 2018;243(2):159-165'},{id:"B54",body:'Braniste V et al. The gut microbiota influences blood-brain barrier permeability in mice. Science Translational Medicine. 2014;6(263):263ra158'},{id:"B55",body:'Topping DL, Clifton PM. Short-chain fatty acids and human colonic function: Roles of resistant starch and nonstarch polysaccharides. Physiological Reviews. 2001;81(3):1031-1064'},{id:"B56",body:'Leclercq S et al. Low-dose penicillin in early life induces long-term changes in murine gut microbiota, brain cytokines and behavior. Nature Communications. 2017;8:15062'},{id:"B57",body:'de Cossio LF et al. Impact of prebiotics on metabolic and behavioral alterations in a mouse model of metabolic syndrome. Brain, Behavior, and Immunity. 2017;64:33-49'},{id:"B58",body:'Di Spiezio A et al. The LepR-mediated leptin transport across brain barriers controls food reward. Molecuar Metabolism. 2018;8:13-22'},{id:"B59",body:'Schwensen HF et al. A systematic review of studies on the faecal microbiota in anorexia nervosa: Future research may need to include microbiota from the small intestine. Eating and Weight Disorders. 2018;23(4):399-418'},{id:"B60",body:'Million M et al. Correlation between body mass index and gut concentrations of Lactobacillus reuteri, Bifidobacterium animalis, Methanobrevibacter smithii and Escherichia coli. International Journal of Obesity. 2013;37(11):1460-1466'},{id:"B61",body:'Mack I et al. Weight gain in anorexia nervosa does not ameliorate the faecal microbiota, branched chain fatty acid profiles, and gastrointestinal complaints. Scientific Reports. 2016;6:26752'},{id:"B62",body:'Morita C et al. Gut dysbiosis in patients with anorexia nervosa. PLoS One. 2015;10(12):e0145274'},{id:"B63",body:'Borgo F et al. Microbiota in anorexia nervosa: The triangle between bacterial species, metabolites and psychological tests. PLoS One. 2017;12(6):e0179739'},{id:"B64",body:'Kleiman SC et al. The intestinal microbiota in acute anorexia nervosa and during renourishment: Relationship to depression, anxiety, and eating disorder psychopathology. Psychosomatic Medicine. 2015;77(9):969-981'},{id:"B65",body:'Armougom F et al. Monitoring bacterial community of human gut microbiota reveals an increase in lactobacillus in obese patients and methanogens in anorexic patients. PLoS One. 2009;4(9):e7125'},{id:"B66",body:'Breton J et al. Elevated plasma concentrations of bacterial ClpB protein in patients with eating disorders. The International Journal of Eating Disorders. 2016;49(8):805-808'},{id:"B67",body:'Samuel BS, Gordon JI. A humanized gnotobiotic mouse model of host-archaeal-bacterial mutualism. Proceedings of the National Academy of Sciences of the United States of America. 2006;103(26):10011-10016'},{id:"B68",body:'Gottlieb K et al. Review article: Inhibition of methanogenic archaea by statins as a targeted management strategy for constipation and related disorders. Alimentary Pharmacology & Therapeutics. 2016;43(2):197-212'},{id:"B69",body:'Triantafyllou K, Chang C, Pimentel M. Methanogens, methane and gastrointestinal motility. Journal of Neurogastroenterology and Motility. 2014;20(1):31-40'},{id:"B70",body:'Flint HJ. Obesity and the gut microbiota. Journal of Clinical Gastroenterology. 2011;45(Suppl):S128-S132'},{id:"B71",body:'Cox LM, Blaser MJ. Pathways in microbe-induced obesity. Cell Metabolism. 2013;17(6):883-894'},{id:"B72",body:'Aguirre M et al. In vitro characterization of the impact of different substrates on metabolite production, energy extraction and composition of gut microbiota from lean and obese subjects. PLoS One. 2014;9(11):e113864'},{id:"B73",body:'Turnbaugh PJ et al. A core gut microbiome in obese and lean twins. Nature. 2009;457(7228):480-484'},{id:"B74",body:'Godart NT et al. Anxiety disorders in anorexia nervosa and bulimia nervosa: Co-morbidity and chronology of appearance. European Psychiatry. 2000;15(1):38-45'},{id:"B75",body:'Fernandez-Aranda F et al. Symptom profile of major depressive disorder in women with eating disorders. The Australian and New Zealand Journal of Psychiatry. 2007;41(1):24-31'},{id:"B76",body:'Kask J, Ekselius L, Brandt L, Kollia N, Ekbom A, and Papadopoulos FC. Mortality in women with anorexia nervosa: The role of comorbid psychiatric disorders. Psychosomatic Medicine. 2016;78(8):910-919'},{id:"B77",body:'Herpertz-Dahlmann B, Seitz J, Baines J. Food matters: How the microbiome and gut-brain interaction might impact the development and course of anorexia nervosa. European Child & Adolescent Psychiatry. 2017;26(9):1031-1041'},{id:"B78",body:'Goyette P et al. Molecular pathogenesis of inflammatory bowel disease: Genotypes, phenotypes and personalized medicine. Annals of Medicine. 2007;39(3):177-199'},{id:"B79",body:'Spiller RC. Overlap between irritable bowel syndrome and inflammatory bowel disease. Digestive Diseases. 2009;27(Suppl 1):48-54'},{id:"B80",body:'Ntranos A, Casaccia P. The microbiome-gut-behavior axis: Crosstalk between the gut microbiome and oligodendrocytes modulates behavioral responses. Neurotherapeutics. 2018;15(1):31-35'},{id:"B81",body:'Mack I et al. Is the impact of starvation on the gut microbiota specific or unspecific to anorexia nervosa? A narrative review based on a systematic literature search. Current Neuropharmacology. 2018;16(8):1131-1149'},{id:"B82",body:'Everard A et al. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proceedings of the National Academy of Sciences of the United States of America. 2013;110(22):9066-9071'},{id:"B83",body:'Derrien M et al. The Mucin degrader Akkermansia muciniphila is an abundant resident of the human intestinal tract. Applied and Environmental Microbiology. 2008;74(5):1646-1648'},{id:"B84",body:'Zhai Q et al. A next generation probiotic, Akkermansia muciniphila. Critical Reviews in Food Science and Nutrition. 2018:1-10. https://doi.org/10.1080/10408398.2018.1517725'},{id:"B85",body:'de Clercq NC, Frissen MN, Davids M, Groen AK, and Nieuwdorp M. Weight gain after fecal microbiota transplantation in a patient with recurrent underweight following clinical recovery from anorexia nervosa. Psychotherapy and Psychosomatics. 2019;88:58-60'},{id:"B86",body:'Jesus P et al. Alteration of intestinal barrier function during activity-based anorexia in mice. Clinical Nutrition. 2014;33(6):1046-1053'},{id:"B87",body:'Monteleone P et al. Intestinal permeability is decreased in anorexia nervosa. Molecular Psychiatry. 2004;9(1):76-80'},{id:"B88",body:'Pals KL et al. Effect of running intensity on intestinal permeability. Journal of Applied Physiology (Bethesda, MD: 1985). 1997;82(2):571-576'},{id:"B89",body:'Kishi T, Elmquist JK. Body weight is regulated by the brain: A link between feeding and emotion. Molecular Psychiatry. 2005;10(2):132-146'},{id:"B90",body:'Raevuori A et al. The increased risk for autoimmune diseases in patients with eating disorders. PLoS One. 2014;9(8):e104845'},{id:"B91",body:'Devkota S et al. Dietary-fat-induced taurocholic acid promotes pathobiont expansion and colitis in Il10−/− mice. Nature. 2012;487(7405):104-108'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Magnus Sjögren",address:"jan.magnus.sjoegren@regionh.dk",affiliation:'
Mental Health Center Ballerup, Denmark
Institute for Clinical Medicine, University of Copenhagen, Denmark
Department of Veterinary and Animal Sciences, Section of Experimental Animal Models, University of Copenhagen, Denmark
'}],corrections:null},book:{id:"7885",title:"Anorexia and Bulimia Nervosa",subtitle:null,fullTitle:"Anorexia and Bulimia Nervosa",slug:"anorexia-and-bulimia-nervosa",publishedDate:"October 2nd 2019",bookSignature:"Hubertus Himmerich and Ignacio Jáuregui Lobera",coverURL:"https://cdn.intechopen.com/books/images_new/7885.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"231568",title:"Dr.",name:"Hubertus",middleName:null,surname:"Himmerich",slug:"hubertus-himmerich",fullName:"Hubertus Himmerich"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}}},profile:{item:{id:"183393",title:"MSc.",name:"Sai Sunil Kumar",middleName:null,surname:"Mallineni",email:"saim@g.clemson.edu",fullName:"Sai Sunil Kumar Mallineni",slug:"sai-sunil-kumar-mallineni",position:null,biography:null,institutionString:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",totalCites:0,totalChapterViews:"0",outsideEditionCount:0,totalAuthoredChapters:"1",totalEditedBooks:"0",personalWebsiteURL:null,twitterURL:null,linkedinURL:null,institution:null},booksEdited:[],chaptersAuthored:[{title:"Defect Engineered 2D Materials for Energy Applications",slug:"defect-engineered-2d-materials-for-energy-applications",abstract:"Two-dimensional (2D) materials display unique properties that could be useful for many applications ranging from electronics and optoelectronics to catalysis and energy storage. Entropically necessary defects are inevitably present in 2D materials in the form of vacancies and grain boundaries. Additional defects, such as dopants, may be intentionally introduced to tune the electronic structure of 2D materials. While defects are often perceived as performance limiters, the presence of defects and dopants in 2D materials results in new electronic states to endow unique functionalities that are otherwise not possible in the bulk. In this chapter, we review defect-induced phenomena in 2D materials with some examples demonstrating the relevance of defects in electronic and energy applications. In particular, we present how the (i) N-dopant configuration in graphene changes the electron-phonon interactions, (ii) zigzag defects and edges in graphene increase the quantum capacitance to improve energy density of graphene-based supercapacitors, and (iii) charged grain boundaries in exfoliated Bi2Te3 preferentially scatter low-energy electrons and holes to enhance the thermoelectric performance.",signatures:"Sai Sunil Kumar Mallineni, Sriparna Bhattacharya, Fengjiao Liu,\nPooja Puneet, Apparao Rao, Anurag Srivastava and Ramakrishna\nPodila",authors:[{id:"182386",title:"Prof.",name:"Ramakrishna",surname:"Podila",fullName:"Ramakrishna Podila",slug:"ramakrishna-podila",email:"rpodila@g.clemson.edu"},{id:"183389",title:"Prof.",name:"Apparao",surname:"Rao",fullName:"Apparao Rao",slug:"apparao-rao",email:"arao@clemson.edu"},{id:"183391",title:"Dr.",name:"Pooja",surname:"Puneet",fullName:"Pooja Puneet",slug:"pooja-puneet",email:"ppuneet@clemson.edu"},{id:"183392",title:"Dr.",name:"Sriparna",surname:"Bhattacharya",fullName:"Sriparna Bhattacharya",slug:"sriparna-bhattacharya",email:"bbhatta@clemson.edu"},{id:"183393",title:"MSc.",name:"Sai Sunil Kumar",surname:"Mallineni",fullName:"Sai Sunil Kumar Mallineni",slug:"sai-sunil-kumar-mallineni",email:"saim@g.clemson.edu"},{id:"183964",title:"Prof.",name:"Anurag",surname:"Srivastava",fullName:"Anurag Srivastava",slug:"anurag-srivastava",email:"anurags@iiitm.ac.in"},{id:"191787",title:"Ms.",name:"Fengjiao",surname:"Liu",fullName:"Fengjiao Liu",slug:"fengjiao-liu",email:"fengjil@clemson.edu"}],book:{title:"Two-dimensional Materials",slug:"two-dimensional-materials-synthesis-characterization-and-potential-applications",productType:{id:"1",title:"Edited Volume"}}}],collaborators:[{id:"182114",title:"Dr.",name:"Rafael",surname:"Vargas-Bernal",slug:"rafael-vargas-bernal",fullName:"Rafael Vargas-Bernal",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/182114/images/system/182114.jpeg",biography:"Rafael Vargas-Bernal received his DSc in Electronic Engineering from the National Institute of Astrophysics, Optics and\nElectronics (INAOE), Tonantzintla, Puebla, Mexico, in 2000.\nHe was associate professor in the Department of Electronics\nEngineering from 2002 to 2010, and since 2010 he has held the\nsame position in the Materials Engineering Department at the\nInstituto Tecnológico Superior de Irapuato (ITESI), Irapuato,\nGuanajuato, Mexico. He is a level-1 researcher of the National System of Researchers from Mexico. He also belongs to the Advanced Materials Applied to Engineering\nresearch group called and has PRODEP (Program for the Professional Development\nof Teachers) desirable profile. He has been a reviewer for journals for RSC, Elsevier, and IEEE. He has published thirtten articles in indexed journals and thirty\nbook chapters. His areas of interest are nanomaterials, two-dimensional materials,\ngraphene, composites, biosensors, and gas sensors.",institutionString:"Instituto Tecnológico Superior de Irapuato",institution:{name:"Instituto Tecnológico Superior de Irapuato",institutionURL:null,country:{name:"Mexico"}}},{id:"182402",title:"Dr.",name:"Jose",surname:"Taha-Tijerina",slug:"jose-taha-tijerina",fullName:"Jose Taha-Tijerina",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:"José Jaime Taha Tijerina was born in Monterrey, Mexico, where he concluded his bachelor studies in Mechanical Engineering at Universidad de Monterrey (UdeM) in 2001. In 2004, he concluded his M.S. Degree in Mechanical Engineering at the University of Texas – Pan American (UTPA), where he was a member of Dr. Karen Lozano’s Nanotechnology research group. From 2004 to 2014 he was a member of the Applied Technology Center at GE Energy, where he performed diverse activities following the New Product Introduction (NPI) methodology. He has wide experience in leadership, planning, development and maintenance of diverse set of R&D and cost-reduction projects. In 2013, he obtained his PhD in Materials Science from the Materials Science and NanoEngineering (MSNE) department at Rice University, under Dr. Pulickel M. Ajayan advisement. From 2014 he is a member of the Advanced Structures Group in Metalsa, where he is the Materials Research Coordinator. He is an author of diverse technical papers, in congresses and specialized journals. His current research interest focusses on the synthesis and characterization of nanofluids for energy/thermal management, nanocomposites for tribology applications, materials for automotive industry.",institutionString:null,institution:{name:"University of Monterrey",institutionURL:null,country:{name:"Mexico"}}},{id:"182796",title:"Dr.",name:"Mianqi",surname:"Xue",slug:"mianqi-xue",fullName:"Mianqi Xue",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"182818",title:"Ph.D.",name:"Grzegorz",surname:"Sobon",slug:"grzegorz-sobon",fullName:"Grzegorz Sobon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Wrocław University of Technology",institutionURL:null,country:{name:"Poland"}}},{id:"183278",title:"Prof.",name:"Mercedes",surname:"Velázquez",slug:"mercedes-velazquez",fullName:"Mercedes Velázquez",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Salamanca",institutionURL:null,country:{name:"Spain"}}},{id:"183325",title:"Mr.",name:"Fengwang",surname:"Li",slug:"fengwang-li",fullName:"Fengwang Li",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"186507",title:"Dr.",name:"Teresa",surname:"Alejo",slug:"teresa-alejo",fullName:"Teresa Alejo",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"186508",title:"Dr.",name:"David",surname:"López-Diaz",slug:"david-lopez-diaz",fullName:"David López-Diaz",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"186509",title:"Dr.",name:"Beatriz",surname:"Martín-García",slug:"beatriz-martin-garcia",fullName:"Beatriz Martín-García",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/186509/images/system/186509.jpg",biography:"Jorge Martín García is Assistant Professor in the Forest Engineering and Environmental Department at the University of Extremadura (Spain). He has both experience in International and Spanish Forestry Environmental Sustainability. He has carried out research stays at the University of Aberdeen (UK), Finish Forest Research Institute (Finland), French National Institute for Agricultural Research (France) and University of San Luis (Argentina) along with some other research universities. He has also worked as a Lecturer at the college of Forestry (León, Spain) and as a Forest Manager for the Government of Spain and for some private companies. He holds a Forest Engineering Degree (Best Student Record Award) and a Master in Conservation and Sustainable Use of Forest Systems at the University of Valladolid (Spain), and his PhD Topic is “Sustainable Forest Management: in search of indicators”.",institutionString:null,institution:null},{id:"186510",title:"Prof.",name:"Maria Dolores",surname:"Merchan",slug:"maria-dolores-merchan",fullName:"Maria Dolores Merchan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Salamanca",institutionURL:null,country:{name:"Spain"}}}]},generic:{page:{slug:"our-story",title:"Our story",intro:"
The company was founded in Vienna in 2004 by Alex Lazinica and Vedran Kordic, two PhD students researching robotics. While completing our PhDs, we found it difficult to access the research we needed. So, we decided to create a new Open Access publisher. A better one, where researchers like us could find the information they needed easily. The result is IntechOpen, an Open Access publisher that puts the academic needs of the researchers before the business interests of publishers.
",metaTitle:"Our story",metaDescription:"The company was founded in Vienna in 2004 by Alex Lazinica and Vedran Kordic, two PhD students researching robotics. While completing our PhDs, we found it difficult to access the research we needed. So, we decided to create a new Open Access publisher. A better one, where researchers like us could find the information they needed easily. The result is IntechOpen, an Open Access publisher that puts the academic needs of the researchers before the business interests of publishers.",metaKeywords:null,canonicalURL:"/page/our-story",contentRaw:'[{"type":"htmlEditorComponent","content":"
We started by publishing journals and books from the fields of science we were most familiar with - AI, robotics, manufacturing and operations research. Through our growing network of institutions and authors, we soon expanded into related fields like environmental engineering, nanotechnology, computer science, renewable energy and electrical engineering, Today, we are the world’s largest Open Access publisher of scientific research, with over 4,200 books and 54,000 scientific works including peer-reviewed content from more than 116,000 scientists spanning 161 countries. Our authors range from globally-renowned Nobel Prize winners to up-and-coming researchers at the cutting edge of scientific discovery.
\\n\\n
In the same year that IntechOpen was founded, we launched what was at the time the first ever Open Access, peer-reviewed journal in its field: the International Journal of Advanced Robotic Systems (IJARS).
\\n\\n
The IntechOpen timeline
\\n\\n
2004
\\n\\n
\\n\\t
Intech Open is founded in Vienna, Austria, by Alex Lazinica and Vedran Kordic, two PhD students, and their first Open Access journals and books are published.
\\n\\t
Alex and Vedran launch the first Open Access, peer-reviewed robotics journal and IntechOpen’s flagship publication, the International Journal of Advanced Robotic Systems (IJARS).
\\n
\\n\\n
2005
\\n\\n
\\n\\t
IntechOpen publishes its first Open Access book: Cutting Edge Robotics.
\\n
\\n\\n
2006
\\n\\n
\\n\\t
IntechOpen publishes a special issue of IJARS, featuring contributions from NASA scientists regarding the Mars Exploration Rover missions.
\\n
\\n\\n
2008
\\n\\n
\\n\\t
Downloads milestone: 200,000 downloads reached
\\n
\\n\\n
2009
\\n\\n
\\n\\t
Publishing milestone: the first 100 Open Access STM books are published
\\n
\\n\\n
2010
\\n\\n
\\n\\t
Downloads milestone: one million downloads reached
\\n\\t
IntechOpen expands its book publishing into a new field: medicine.
\\n
\\n\\n
2011
\\n\\n
\\n\\t
Publishing milestone: More than five million downloads reached
\\n\\t
IntechOpen publishes 1996 Nobel Prize in Chemistry winner Harold W. Kroto’s “Strategies to Successfully Cross-Link Carbon Nanotubes”. Find it here.
\\n\\t
IntechOpen and TBI collaborate on a project to explore the changing needs of researchers and the evolving ways that they discover, publish and exchange information. The result is the survey “Author Attitudes Towards Open Access Publishing: A Market Research Program”.
\\n\\t
IntechOpen hosts SHOW - Share Open Access Worldwide; a series of lectures, debates, round-tables and events to bring people together in discussion of open source principles, intellectual property, content licensing innovations, remixed and shared culture and free knowledge.
\\n
\\n\\n
2012
\\n\\n
\\n\\t
Publishing milestone: 10 million downloads reached
\\n\\t
IntechOpen holds Interact2012, a free series of workshops held by figureheads of the scientific community including Professor Hiroshi Ishiguro, director of the Intelligent Robotics Laboratory, who took the audience through some of the most impressive human-robot interactions observed in his lab.
\\n
\\n\\n
2013
\\n\\n
\\n\\t
IntechOpen joins the Committee on Publication Ethics (COPE) as part of a commitment to guaranteeing the highest standards of publishing.
\\n
\\n\\n
2014
\\n\\n
\\n\\t
IntechOpen turns 10, with more than 30 million downloads to date.
\\n\\t
IntechOpen appoints its first Regional Representatives - members of the team situated around the world dedicated to increasing the visibility of our authors’ published work within their local scientific communities.
\\n
\\n\\n
2015
\\n\\n
\\n\\t
Downloads milestone: More than 70 million downloads reached, more than doubling since the previous year.
\\n\\t
Publishing milestone: IntechOpen publishes its 2,500th book and 40,000th Open Access chapter, reaching 20,000 citations in Thomson Reuters ISI Web of Science.
\\n\\t
40 IntechOpen authors are included in the top one per cent of the world’s most-cited researchers.
\\n\\t
Thomson Reuters’ ISI Web of Science Book Citation Index begins indexing IntechOpen’s books in its database.
\\n
\\n\\n
2016
\\n\\n
\\n\\t
IntechOpen is identified as a world leader in Simba Information’s Open Access Book Publishing 2016-2020 report and forecast. IntechOpen came in as the world’s largest Open Access book publisher by title count.
\\n
\\n\\n
2017
\\n\\n
\\n\\t
Downloads milestone: IntechOpen reaches more than 100 million downloads
\\n\\t
Publishing milestone: IntechOpen publishes its 3,000th Open Access book, making it the largest Open Access book collection in the world
We started by publishing journals and books from the fields of science we were most familiar with - AI, robotics, manufacturing and operations research. Through our growing network of institutions and authors, we soon expanded into related fields like environmental engineering, nanotechnology, computer science, renewable energy and electrical engineering, Today, we are the world’s largest Open Access publisher of scientific research, with over 4,200 books and 54,000 scientific works including peer-reviewed content from more than 116,000 scientists spanning 161 countries. Our authors range from globally-renowned Nobel Prize winners to up-and-coming researchers at the cutting edge of scientific discovery.
\n\n
In the same year that IntechOpen was founded, we launched what was at the time the first ever Open Access, peer-reviewed journal in its field: the International Journal of Advanced Robotic Systems (IJARS).
\n\n
The IntechOpen timeline
\n\n
2004
\n\n
\n\t
Intech Open is founded in Vienna, Austria, by Alex Lazinica and Vedran Kordic, two PhD students, and their first Open Access journals and books are published.
\n\t
Alex and Vedran launch the first Open Access, peer-reviewed robotics journal and IntechOpen’s flagship publication, the International Journal of Advanced Robotic Systems (IJARS).
\n
\n\n
2005
\n\n
\n\t
IntechOpen publishes its first Open Access book: Cutting Edge Robotics.
\n
\n\n
2006
\n\n
\n\t
IntechOpen publishes a special issue of IJARS, featuring contributions from NASA scientists regarding the Mars Exploration Rover missions.
\n
\n\n
2008
\n\n
\n\t
Downloads milestone: 200,000 downloads reached
\n
\n\n
2009
\n\n
\n\t
Publishing milestone: the first 100 Open Access STM books are published
\n
\n\n
2010
\n\n
\n\t
Downloads milestone: one million downloads reached
\n\t
IntechOpen expands its book publishing into a new field: medicine.
\n
\n\n
2011
\n\n
\n\t
Publishing milestone: More than five million downloads reached
\n\t
IntechOpen publishes 1996 Nobel Prize in Chemistry winner Harold W. Kroto’s “Strategies to Successfully Cross-Link Carbon Nanotubes”. Find it here.
\n\t
IntechOpen and TBI collaborate on a project to explore the changing needs of researchers and the evolving ways that they discover, publish and exchange information. The result is the survey “Author Attitudes Towards Open Access Publishing: A Market Research Program”.
\n\t
IntechOpen hosts SHOW - Share Open Access Worldwide; a series of lectures, debates, round-tables and events to bring people together in discussion of open source principles, intellectual property, content licensing innovations, remixed and shared culture and free knowledge.
\n
\n\n
2012
\n\n
\n\t
Publishing milestone: 10 million downloads reached
\n\t
IntechOpen holds Interact2012, a free series of workshops held by figureheads of the scientific community including Professor Hiroshi Ishiguro, director of the Intelligent Robotics Laboratory, who took the audience through some of the most impressive human-robot interactions observed in his lab.
\n
\n\n
2013
\n\n
\n\t
IntechOpen joins the Committee on Publication Ethics (COPE) as part of a commitment to guaranteeing the highest standards of publishing.
\n
\n\n
2014
\n\n
\n\t
IntechOpen turns 10, with more than 30 million downloads to date.
\n\t
IntechOpen appoints its first Regional Representatives - members of the team situated around the world dedicated to increasing the visibility of our authors’ published work within their local scientific communities.
\n
\n\n
2015
\n\n
\n\t
Downloads milestone: More than 70 million downloads reached, more than doubling since the previous year.
\n\t
Publishing milestone: IntechOpen publishes its 2,500th book and 40,000th Open Access chapter, reaching 20,000 citations in Thomson Reuters ISI Web of Science.
\n\t
40 IntechOpen authors are included in the top one per cent of the world’s most-cited researchers.
\n\t
Thomson Reuters’ ISI Web of Science Book Citation Index begins indexing IntechOpen’s books in its database.
\n
\n\n
2016
\n\n
\n\t
IntechOpen is identified as a world leader in Simba Information’s Open Access Book Publishing 2016-2020 report and forecast. IntechOpen came in as the world’s largest Open Access book publisher by title count.
\n
\n\n
2017
\n\n
\n\t
Downloads milestone: IntechOpen reaches more than 100 million downloads
\n\t
Publishing milestone: IntechOpen publishes its 3,000th Open Access book, making it the largest Open Access book collection in the world
\n
\n"}]},successStories:{items:[]},authorsAndEditors:{filterParams:{sort:"featured,name"},profiles:[{id:"6700",title:"Dr.",name:"Abbass A.",middleName:null,surname:"Hashim",slug:"abbass-a.-hashim",fullName:"Abbass A. Hashim",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/6700/images/1864_n.jpg",biography:"Currently I am carrying out research in several areas of interest, mainly covering work on chemical and bio-sensors, semiconductor thin film device fabrication and characterisation.\nAt the moment I have very strong interest in radiation environmental pollution and bacteriology treatment. The teams of researchers are working very hard to bring novel results in this field. I am also a member of the team in charge for the supervision of Ph.D. students in the fields of development of silicon based planar waveguide sensor devices, study of inelastic electron tunnelling in planar tunnelling nanostructures for sensing applications and development of organotellurium(IV) compounds for semiconductor applications. I am a specialist in data analysis techniques and nanosurface structure. I have served as the editor for many books, been a member of the editorial board in science journals, have published many papers and hold many patents.",institutionString:null,institution:{name:"Sheffield Hallam University",country:{name:"United Kingdom"}}},{id:"54525",title:"Prof.",name:"Abdul Latif",middleName:null,surname:"Ahmad",slug:"abdul-latif-ahmad",fullName:"Abdul Latif Ahmad",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"20567",title:"Prof.",name:"Ado",middleName:null,surname:"Jorio",slug:"ado-jorio",fullName:"Ado Jorio",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Universidade Federal de Minas Gerais",country:{name:"Brazil"}}},{id:"47940",title:"Dr.",name:"Alberto",middleName:null,surname:"Mantovani",slug:"alberto-mantovani",fullName:"Alberto Mantovani",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"12392",title:"Mr.",name:"Alex",middleName:null,surname:"Lazinica",slug:"alex-lazinica",fullName:"Alex Lazinica",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/12392/images/7282_n.png",biography:"Alex Lazinica is the founder and CEO of IntechOpen. After obtaining a Master's degree in Mechanical Engineering, he continued his PhD studies in Robotics at the Vienna University of Technology. Here he worked as a robotic researcher with the university's Intelligent Manufacturing Systems Group as well as a guest researcher at various European universities, including the Swiss Federal Institute of Technology Lausanne (EPFL). During this time he published more than 20 scientific papers, gave presentations, served as a reviewer for major robotic journals and conferences and most importantly he co-founded and built the International Journal of Advanced Robotic Systems- world's first Open Access journal in the field of robotics. Starting this journal was a pivotal point in his career, since it was a pathway to founding IntechOpen - Open Access publisher focused on addressing academic researchers needs. Alex is a personification of IntechOpen key values being trusted, open and entrepreneurial. Today his focus is on defining the growth and development strategy for the company.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"19816",title:"Prof.",name:"Alexander",middleName:null,surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/19816/images/1607_n.jpg",biography:"Alexander I. Kokorin: born: 1947, Moscow; DSc., PhD; Principal Research Fellow (Research Professor) of Department of Kinetics and Catalysis, N. Semenov Institute of Chemical Physics, Russian Academy of Sciences, Moscow.\r\nArea of research interests: physical chemistry of complex-organized molecular and nanosized systems, including polymer-metal complexes; the surface of doped oxide semiconductors. He is an expert in structural, absorptive, catalytic and photocatalytic properties, in structural organization and dynamic features of ionic liquids, in magnetic interactions between paramagnetic centers. The author or co-author of 3 books, over 200 articles and reviews in scientific journals and books. He is an actual member of the International EPR/ESR Society, European Society on Quantum Solar Energy Conversion, Moscow House of Scientists, of the Board of Moscow Physical Society.",institutionString:null,institution:{name:"Semenov Institute of Chemical Physics",country:{name:"Russia"}}},{id:"62389",title:"PhD.",name:"Ali Demir",middleName:null,surname:"Sezer",slug:"ali-demir-sezer",fullName:"Ali Demir Sezer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62389/images/3413_n.jpg",biography:"Dr. Ali Demir Sezer has a Ph.D. from Pharmaceutical Biotechnology at the Faculty of Pharmacy, University of Marmara (Turkey). He is the member of many Pharmaceutical Associations and acts as a reviewer of scientific journals and European projects under different research areas such as: drug delivery systems, nanotechnology and pharmaceutical biotechnology. Dr. Sezer is the author of many scientific publications in peer-reviewed journals and poster communications. Focus of his research activity is drug delivery, physico-chemical characterization and biological evaluation of biopolymers micro and nanoparticles as modified drug delivery system, and colloidal drug carriers (liposomes, nanoparticles etc.).",institutionString:null,institution:{name:"Marmara University",country:{name:"Turkey"}}},{id:"61051",title:"Prof.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"100762",title:"Prof.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"St David's Medical Center",country:{name:"United States of America"}}},{id:"107416",title:"Dr.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Texas Cardiac Arrhythmia",country:{name:"United States of America"}}},{id:"64434",title:"Dr.",name:"Angkoon",middleName:null,surname:"Phinyomark",slug:"angkoon-phinyomark",fullName:"Angkoon Phinyomark",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/64434/images/2619_n.jpg",biography:"My name is Angkoon Phinyomark. I received a B.Eng. degree in Computer Engineering with First Class Honors in 2008 from Prince of Songkla University, Songkhla, Thailand, where I received a Ph.D. degree in Electrical Engineering. My research interests are primarily in the area of biomedical signal processing and classification notably EMG (electromyography signal), EOG (electrooculography signal), and EEG (electroencephalography signal), image analysis notably breast cancer analysis and optical coherence tomography, and rehabilitation engineering. I became a student member of IEEE in 2008. During October 2011-March 2012, I had worked at School of Computer Science and Electronic Engineering, University of Essex, Colchester, Essex, United Kingdom. In addition, during a B.Eng. I had been a visiting research student at Faculty of Computer Science, University of Murcia, Murcia, Spain for three months.\n\nI have published over 40 papers during 5 years in refereed journals, books, and conference proceedings in the areas of electro-physiological signals processing and classification, notably EMG and EOG signals, fractal analysis, wavelet analysis, texture analysis, feature extraction and machine learning algorithms, and assistive and rehabilitative devices. I have several computer programming language certificates, i.e. Sun Certified Programmer for the Java 2 Platform 1.4 (SCJP), Microsoft Certified Professional Developer, Web Developer (MCPD), Microsoft Certified Technology Specialist, .NET Framework 2.0 Web (MCTS). I am a Reviewer for several refereed journals and international conferences, such as IEEE Transactions on Biomedical Engineering, IEEE Transactions on Industrial Electronics, Optic Letters, Measurement Science Review, and also a member of the International Advisory Committee for 2012 IEEE Business Engineering and Industrial Applications and 2012 IEEE Symposium on Business, Engineering and Industrial Applications.",institutionString:null,institution:{name:"Joseph Fourier University",country:{name:"France"}}},{id:"55578",title:"Dr.",name:"Antonio",middleName:null,surname:"Jurado-Navas",slug:"antonio-jurado-navas",fullName:"Antonio Jurado-Navas",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/55578/images/4574_n.png",biography:"Antonio Jurado-Navas received the M.S. degree (2002) and the Ph.D. degree (2009) in Telecommunication Engineering, both from the University of Málaga (Spain). He first worked as a consultant at Vodafone-Spain. From 2004 to 2011, he was a Research Assistant with the Communications Engineering Department at the University of Málaga. In 2011, he became an Assistant Professor in the same department. From 2012 to 2015, he was with Ericsson Spain, where he was working on geo-location\ntools for third generation mobile networks. Since 2015, he is a Marie-Curie fellow at the Denmark Technical University. His current research interests include the areas of mobile communication systems and channel modeling in addition to atmospheric optical communications, adaptive optics and statistics",institutionString:null,institution:{name:"University of Malaga",country:{name:"Spain"}}}],filtersByRegion:[{group:"region",caption:"North America",value:1,count:5774},{group:"region",caption:"Middle and South America",value:2,count:5240},{group:"region",caption:"Africa",value:3,count:1721},{group:"region",caption:"Asia",value:4,count:10411},{group:"region",caption:"Australia and Oceania",value:5,count:897},{group:"region",caption:"Europe",value:6,count:15812}],offset:12,limit:12,total:118381},chapterEmbeded:{data:{}},editorApplication:{success:null,errors:{}},ofsBooks:{filterParams:{hasNoEditors:"0",sort:"dateEndThirdStepPublish",topicId:"6,5"},books:[{type:"book",id:"9662",title:"Vegetation Index and Dynamics",subtitle:null,isOpenForSubmission:!0,hash:"0abf2a59ee63fc1ba4fb64d77c9b1be7",slug:null,bookSignature:"Dr. Eusebio Cano Carmona, Dr. Ricardo Quinto Canas, Dr. Ana Cano Ortiz and Dr. Carmelo Maria Musarella",coverURL:"https://cdn.intechopen.com/books/images_new/9662.jpg",editedByType:null,editors:[{id:"87846",title:"Dr.",name:"Eusebio",surname:"Cano Carmona",slug:"eusebio-cano-carmona",fullName:"Eusebio Cano Carmona"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9659",title:"Fibroblasts - Advances in Cancer, Autoimmunity and Inflammation",subtitle:null,isOpenForSubmission:!0,hash:"926fa6446f6befbd363fc74971a56de2",slug:null,bookSignature:"Ph.D. Mojca Frank Bertoncelj and Ms. Katja Lakota",coverURL:"https://cdn.intechopen.com/books/images_new/9659.jpg",editedByType:null,editors:[{id:"328755",title:"Ph.D.",name:"Mojca",surname:"Frank Bertoncelj",slug:"mojca-frank-bertoncelj",fullName:"Mojca Frank Bertoncelj"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8977",title:"Protein Kinase - New Opportunities, Challenges and Future Perspectives",subtitle:null,isOpenForSubmission:!0,hash:"6d200cc031706a565b554fdb1c478901",slug:null,bookSignature:"Dr. Rajesh Kumar Singh",coverURL:"https://cdn.intechopen.com/books/images_new/8977.jpg",editedByType:null,editors:[{id:"329385",title:"Dr.",name:"Rajesh",surname:"Singh",slug:"rajesh-singh",fullName:"Rajesh Singh"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10557",title:"Elaeis guineensis",subtitle:null,isOpenForSubmission:!0,hash:"79500ab1930271876b4e0575e2ed3966",slug:null,bookSignature:"Dr. Hesam Kamyab",coverURL:"https://cdn.intechopen.com/books/images_new/10557.jpg",editedByType:null,editors:[{id:"225957",title:"Dr.",name:"Hesam",surname:"Kamyab",slug:"hesam-kamyab",fullName:"Hesam Kamyab"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10218",title:"Flagellar Motility in Cells",subtitle:null,isOpenForSubmission:!0,hash:"5fcc15570365a82d9f2c4816f4e0ee2e",slug:null,bookSignature:"Prof. Yusuf Bozkurt",coverURL:"https://cdn.intechopen.com/books/images_new/10218.jpg",editedByType:null,editors:[{id:"90846",title:"Prof.",name:"Yusuf",surname:"Bozkurt",slug:"yusuf-bozkurt",fullName:"Yusuf Bozkurt"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10750",title:"Solanum tuberosum - a Promising Crop for Starvation Problem",subtitle:null,isOpenForSubmission:!0,hash:"516eb729eadf0d1a9d1d2e6bf31e8e9c",slug:null,bookSignature:"Prof. Mustafa Yildiz and Dr. Yasin Ozgen",coverURL:"https://cdn.intechopen.com/books/images_new/10750.jpg",editedByType:null,editors:[{id:"141637",title:"Prof.",name:"Mustafa",surname:"Yildiz",slug:"mustafa-yildiz",fullName:"Mustafa Yildiz"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10797",title:"Cell Culture",subtitle:null,isOpenForSubmission:!0,hash:"2c628f4757f9639a4450728d839a7842",slug:null,bookSignature:"Prof. Xianquan Zhan",coverURL:"https://cdn.intechopen.com/books/images_new/10797.jpg",editedByType:null,editors:[{id:"223233",title:"Prof.",name:"Xianquan",surname:"Zhan",slug:"xianquan-zhan",fullName:"Xianquan Zhan"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10772",title:"Parasitic Plants",subtitle:null,isOpenForSubmission:!0,hash:"31abd439b5674c91d18ad77dbc52500f",slug:null,bookSignature:"Dr. Ana Maria Gonzalez and Dr. Hector Sato",coverURL:"https://cdn.intechopen.com/books/images_new/10772.jpg",editedByType:null,editors:[{id:"281854",title:"Dr.",name:"Ana Maria",surname:"Gonzalez",slug:"ana-maria-gonzalez",fullName:"Ana Maria Gonzalez"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10737",title:"Equus",subtitle:null,isOpenForSubmission:!0,hash:"258ffafc92a7c9550bb85f004d7402e7",slug:null,bookSignature:"Associate Prof. Adriana Pires Neves",coverURL:"https://cdn.intechopen.com/books/images_new/10737.jpg",editedByType:null,editors:[{id:"188768",title:"Associate Prof.",name:"Adriana",surname:"Pires Neves",slug:"adriana-pires-neves",fullName:"Adriana Pires Neves"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10777",title:"Plant Reproductive Ecology - Recent Advances",subtitle:null,isOpenForSubmission:!0,hash:"3fbf391f2093649bcf3bd674f7e32189",slug:null,bookSignature:"Dr. Balkrishna Ghimire",coverURL:"https://cdn.intechopen.com/books/images_new/10777.jpg",editedByType:null,editors:[{id:"206647",title:"Dr.",name:"Balkrishna",surname:"Ghimire",slug:"balkrishna-ghimire",fullName:"Balkrishna Ghimire"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10749",title:"Legumes",subtitle:null,isOpenForSubmission:!0,hash:"49d3123cde96adbe706adadebebc5ebb",slug:null,bookSignature:"Dr. Jose Carlos Jimenez-Lopez",coverURL:"https://cdn.intechopen.com/books/images_new/10749.jpg",editedByType:null,editors:[{id:"33993",title:"Dr.",name:"Jose Carlos",surname:"Jimenez-Lopez",slug:"jose-carlos-jimenez-lopez",fullName:"Jose Carlos Jimenez-Lopez"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10751",title:"Bovine Science",subtitle:null,isOpenForSubmission:!0,hash:"9e3eb325f9fce20e6cefbce1c26d647a",slug:null,bookSignature:"Dr. Muhammad Abubakar",coverURL:"https://cdn.intechopen.com/books/images_new/10751.jpg",editedByType:null,editors:[{id:"112070",title:"Dr.",name:"Muhammad",surname:"Abubakar",slug:"muhammad-abubakar",fullName:"Muhammad Abubakar"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],filtersByTopic:[{group:"topic",caption:"Agricultural and Biological Sciences",value:5,count:19},{group:"topic",caption:"Biochemistry, Genetics and Molecular Biology",value:6,count:5},{group:"topic",caption:"Business, Management and Economics",value:7,count:2},{group:"topic",caption:"Chemistry",value:8,count:8},{group:"topic",caption:"Computer and Information Science",value:9,count:6},{group:"topic",caption:"Earth and Planetary Sciences",value:10,count:7},{group:"topic",caption:"Engineering",value:11,count:21},{group:"topic",caption:"Environmental Sciences",value:12,count:2},{group:"topic",caption:"Immunology and Microbiology",value:13,count:4},{group:"topic",caption:"Materials Science",value:14,count:6},{group:"topic",caption:"Mathematics",value:15,count:1},{group:"topic",caption:"Medicine",value:16,count:25},{group:"topic",caption:"Neuroscience",value:18,count:2},{group:"topic",caption:"Pharmacology, Toxicology and Pharmaceutical Science",value:19,count:3},{group:"topic",caption:"Physics",value:20,count:3},{group:"topic",caption:"Psychology",value:21,count:4},{group:"topic",caption:"Robotics",value:22,count:1},{group:"topic",caption:"Social Sciences",value:23,count:3},{group:"topic",caption:"Technology",value:24,count:1},{group:"topic",caption:"Veterinary Medicine and Science",value:25,count:1}],offset:12,limit:12,total:24},popularBooks:{featuredBooks:[{type:"book",id:"9521",title:"Antimicrobial Resistance",subtitle:"A One Health Perspective",isOpenForSubmission:!1,hash:"30949e78832e1afba5606634b52056ab",slug:"antimicrobial-resistance-a-one-health-perspective",bookSignature:"Mihai Mareș, Swee Hua Erin Lim, Kok-Song Lai and Romeo-Teodor Cristina",coverURL:"https://cdn.intechopen.com/books/images_new/9521.jpg",editors:[{id:"88785",title:"Prof.",name:"Mihai",middleName:null,surname:"Mares",slug:"mihai-mares",fullName:"Mihai Mares"}],equalEditorOne:{id:"190224",title:"Dr.",name:"Swee Hua Erin",middleName:null,surname:"Lim",slug:"swee-hua-erin-lim",fullName:"Swee Hua Erin Lim",profilePictureURL:"https://mts.intechopen.com/storage/users/190224/images/system/190224.png",biography:"Dr. Erin Lim is presently working as an Assistant Professor in the Division of Health Sciences, Abu Dhabi Women\\'s College, Higher Colleges of Technology in Abu Dhabi, United Arab Emirates and is affiliated as an Associate Professor to Perdana University-Royal College of Surgeons in Ireland, Selangor, Malaysia. She obtained her Ph.D. from Universiti Putra Malaysia in 2010 with a National Science Fellowship awarded from the Ministry of Science, Technology and Innovation Malaysia and has been actively involved in research ever since. Her main research interests include analysis of carriage and transmission of multidrug resistant bacteria in non-conventional settings, besides an interest in natural products for antimicrobial testing. She is heavily involved in the elucidation of mechanisms of reversal of resistance in bacteria in addition to investigating the immunological analyses of diseases, development of vaccination and treatment models in animals. She hopes her work will support the discovery of therapeutics in the clinical setting and assist in the combat against the burden of antibiotic resistance.",institutionString:"Abu Dhabi Women’s College",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Perdana University",institutionURL:null,country:{name:"Malaysia"}}},equalEditorTwo:{id:"221544",title:"Dr.",name:"Kok-Song",middleName:null,surname:"Lai",slug:"kok-song-lai",fullName:"Kok-Song Lai",profilePictureURL:"https://mts.intechopen.com/storage/users/221544/images/system/221544.jpeg",biography:"Dr. Lai Kok Song is an Assistant Professor in the Division of Health Sciences, Abu Dhabi Women\\'s College, Higher Colleges of Technology in Abu Dhabi, United Arab Emirates. He obtained his Ph.D. in Biological Sciences from Nara Institute of Science and Technology, Japan in 2012. Prior to his academic appointment, Dr. Lai worked as a Senior Scientist at the Ministry of Science, Technology and Innovation, Malaysia. His current research areas include antimicrobial resistance and plant-pathogen interaction. His particular interest lies in the study of the antimicrobial mechanism via membrane disruption of essential oils against multi-drug resistance bacteria through various biochemical, molecular and proteomic approaches. Ultimately, he hopes to uncover and determine novel biomarkers related to antibiotic resistance that can be developed into new therapeutic strategies.",institutionString:"Higher Colleges of Technology",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"8",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Higher Colleges of Technology",institutionURL:null,country:{name:"United Arab Emirates"}}},equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10020",title:"Operations Management",subtitle:"Emerging Trend in the Digital Era",isOpenForSubmission:!1,hash:"526f0dbdc7e4d85b82ce8383ab894b4c",slug:"operations-management-emerging-trend-in-the-digital-era",bookSignature:"Antonella Petrillo, Fabio De Felice, Germano Lambert-Torres and Erik Bonaldi",coverURL:"https://cdn.intechopen.com/books/images_new/10020.jpg",editors:[{id:"181603",title:"Dr.",name:"Antonella",middleName:null,surname:"Petrillo",slug:"antonella-petrillo",fullName:"Antonella Petrillo"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9560",title:"Creativity",subtitle:"A Force to Innovation",isOpenForSubmission:!1,hash:"58f740bc17807d5d88d647c525857b11",slug:"creativity-a-force-to-innovation",bookSignature:"Pooja Jain",coverURL:"https://cdn.intechopen.com/books/images_new/9560.jpg",editors:[{id:"316765",title:"Dr.",name:"Pooja",middleName:null,surname:"Jain",slug:"pooja-jain",fullName:"Pooja Jain"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9385",title:"Renewable Energy",subtitle:"Technologies and Applications",isOpenForSubmission:!1,hash:"a6b446d19166f17f313008e6c056f3d8",slug:"renewable-energy-technologies-and-applications",bookSignature:"Tolga Taner, Archana Tiwari and Taha Selim Ustun",coverURL:"https://cdn.intechopen.com/books/images_new/9385.jpg",editors:[{id:"197240",title:"Associate Prof.",name:"Tolga",middleName:null,surname:"Taner",slug:"tolga-taner",fullName:"Tolga Taner"}],equalEditorOne:{id:"186791",title:"Dr.",name:"Archana",middleName:null,surname:"Tiwari",slug:"archana-tiwari",fullName:"Archana Tiwari",profilePictureURL:"https://mts.intechopen.com/storage/users/186791/images/system/186791.jpg",biography:"Dr. Archana Tiwari is Associate Professor at Amity University, India. Her research interests include renewable sources of energy from microalgae and further utilizing the residual biomass for the generation of value-added products, bioremediation through microalgae and microbial consortium, antioxidative enzymes and stress, and nutraceuticals from microalgae. She has been working on algal biotechnology for the last two decades. She has published her research in many international journals and has authored many books and chapters with renowned publishing houses. She has also delivered talks as an invited speaker at many national and international conferences. Dr. Tiwari is the recipient of several awards including Researcher of the Year and Distinguished Scientist.",institutionString:"Amity University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Amity University",institutionURL:null,country:{name:"India"}}},equalEditorTwo:{id:"197609",title:"Prof.",name:"Taha Selim",middleName:null,surname:"Ustun",slug:"taha-selim-ustun",fullName:"Taha Selim Ustun",profilePictureURL:"https://mts.intechopen.com/storage/users/197609/images/system/197609.jpeg",biography:"Dr. Taha Selim Ustun received a Ph.D. in Electrical Engineering from Victoria University, Melbourne, Australia. He is a researcher with the Fukushima Renewable Energy Institute, AIST (FREA), where he leads the Smart Grid Cybersecurity Laboratory. Prior to that, he was a faculty member with the School of Electrical and Computer Engineering, Carnegie Mellon University, Pittsburgh, PA, USA. His current research interests include power systems protection, communication in power networks, distributed generation, microgrids, electric vehicle integration, and cybersecurity in smart grids. He serves on the editorial boards of IEEE Access, IEEE Transactions on Industrial Informatics, Energies, Electronics, Electricity, World Electric Vehicle and Information journals. Dr. Ustun is a member of the IEEE 2004 and 2800, IEC Renewable Energy Management WG 8, and IEC TC 57 WG17. He has been invited to run specialist courses in Africa, India, and China. He has delivered talks for the Qatar Foundation, the World Energy Council, the Waterloo Global Science Initiative, and the European Union Energy Initiative (EUEI). His research has attracted funding from prestigious programs in Japan, Australia, the European Union, and North America.",institutionString:"Fukushima Renewable Energy Institute, AIST (FREA)",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"National Institute of Advanced Industrial Science and Technology",institutionURL:null,country:{name:"Japan"}}},equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8985",title:"Natural Resources Management and Biological Sciences",subtitle:null,isOpenForSubmission:!1,hash:"5c2e219a6c021a40b5a20c041dea88c4",slug:"natural-resources-management-and-biological-sciences",bookSignature:"Edward R. Rhodes and Humood Naser",coverURL:"https://cdn.intechopen.com/books/images_new/8985.jpg",editors:[{id:"280886",title:"Prof.",name:"Edward R",middleName:null,surname:"Rhodes",slug:"edward-r-rhodes",fullName:"Edward R Rhodes"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10192",title:"Background and Management of Muscular Atrophy",subtitle:null,isOpenForSubmission:!1,hash:"eca24028d89912b5efea56e179dff089",slug:"background-and-management-of-muscular-atrophy",bookSignature:"Julianna Cseri",coverURL:"https://cdn.intechopen.com/books/images_new/10192.jpg",editors:[{id:"135579",title:"Dr.",name:"Julianna",middleName:null,surname:"Cseri",slug:"julianna-cseri",fullName:"Julianna Cseri"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10065",title:"Wavelet Theory",subtitle:null,isOpenForSubmission:!1,hash:"d8868e332169597ba2182d9b004d60de",slug:"wavelet-theory",bookSignature:"Somayeh Mohammady",coverURL:"https://cdn.intechopen.com/books/images_new/10065.jpg",editors:[{id:"109280",title:"Dr.",name:"Somayeh",middleName:null,surname:"Mohammady",slug:"somayeh-mohammady",fullName:"Somayeh Mohammady"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9644",title:"Glaciers and the Polar Environment",subtitle:null,isOpenForSubmission:!1,hash:"e8cfdc161794e3753ced54e6ff30873b",slug:"glaciers-and-the-polar-environment",bookSignature:"Masaki Kanao, Danilo Godone and Niccolò Dematteis",coverURL:"https://cdn.intechopen.com/books/images_new/9644.jpg",editors:[{id:"51959",title:"Dr.",name:"Masaki",middleName:null,surname:"Kanao",slug:"masaki-kanao",fullName:"Masaki Kanao"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9243",title:"Coastal Environments",subtitle:null,isOpenForSubmission:!1,hash:"8e05e5f631e935eef366980f2e28295d",slug:"coastal-environments",bookSignature:"Yuanzhi Zhang and X. San Liang",coverURL:"https://cdn.intechopen.com/books/images_new/9243.jpg",editors:[{id:"77597",title:"Prof.",name:"Yuanzhi",middleName:null,surname:"Zhang",slug:"yuanzhi-zhang",fullName:"Yuanzhi Zhang"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7847",title:"Medical Toxicology",subtitle:null,isOpenForSubmission:!1,hash:"db9b65bea093de17a0855a1b27046247",slug:"medical-toxicology",bookSignature:"Pınar Erkekoglu and Tomohisa Ogawa",coverURL:"https://cdn.intechopen.com/books/images_new/7847.jpg",editors:[{id:"109978",title:"Prof.",name:"Pınar",middleName:null,surname:"Erkekoglu",slug:"pinar-erkekoglu",fullName:"Pınar Erkekoglu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9027",title:"Human Blood Group Systems and Haemoglobinopathies",subtitle:null,isOpenForSubmission:!1,hash:"d00d8e40b11cfb2547d1122866531c7e",slug:"human-blood-group-systems-and-haemoglobinopathies",bookSignature:"Osaro Erhabor and Anjana Munshi",coverURL:"https://cdn.intechopen.com/books/images_new/9027.jpg",editors:[{id:"35140",title:null,name:"Osaro",middleName:null,surname:"Erhabor",slug:"osaro-erhabor",fullName:"Osaro Erhabor"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8558",title:"Aerodynamics",subtitle:null,isOpenForSubmission:!1,hash:"db7263fc198dfb539073ba0260a7f1aa",slug:"aerodynamics",bookSignature:"Mofid Gorji-Bandpy and Aly-Mousaad Aly",coverURL:"https://cdn.intechopen.com/books/images_new/8558.jpg",editors:[{id:"35542",title:"Prof.",name:"Mofid",middleName:null,surname:"Gorji-Bandpy",slug:"mofid-gorji-bandpy",fullName:"Mofid Gorji-Bandpy"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],offset:12,limit:12,total:5252},hotBookTopics:{hotBooks:[],offset:0,limit:12,total:null},publish:{},publishingProposal:{success:null,errors:{}},books:{featuredBooks:[{type:"book",id:"9521",title:"Antimicrobial Resistance",subtitle:"A One Health Perspective",isOpenForSubmission:!1,hash:"30949e78832e1afba5606634b52056ab",slug:"antimicrobial-resistance-a-one-health-perspective",bookSignature:"Mihai Mareș, Swee Hua Erin Lim, Kok-Song Lai and Romeo-Teodor Cristina",coverURL:"https://cdn.intechopen.com/books/images_new/9521.jpg",editors:[{id:"88785",title:"Prof.",name:"Mihai",middleName:null,surname:"Mares",slug:"mihai-mares",fullName:"Mihai Mares"}],equalEditorOne:{id:"190224",title:"Dr.",name:"Swee Hua Erin",middleName:null,surname:"Lim",slug:"swee-hua-erin-lim",fullName:"Swee Hua Erin Lim",profilePictureURL:"https://mts.intechopen.com/storage/users/190224/images/system/190224.png",biography:"Dr. Erin Lim is presently working as an Assistant Professor in the Division of Health Sciences, Abu Dhabi Women\\'s College, Higher Colleges of Technology in Abu Dhabi, United Arab Emirates and is affiliated as an Associate Professor to Perdana University-Royal College of Surgeons in Ireland, Selangor, Malaysia. She obtained her Ph.D. from Universiti Putra Malaysia in 2010 with a National Science Fellowship awarded from the Ministry of Science, Technology and Innovation Malaysia and has been actively involved in research ever since. Her main research interests include analysis of carriage and transmission of multidrug resistant bacteria in non-conventional settings, besides an interest in natural products for antimicrobial testing. She is heavily involved in the elucidation of mechanisms of reversal of resistance in bacteria in addition to investigating the immunological analyses of diseases, development of vaccination and treatment models in animals. She hopes her work will support the discovery of therapeutics in the clinical setting and assist in the combat against the burden of antibiotic resistance.",institutionString:"Abu Dhabi Women’s College",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Perdana University",institutionURL:null,country:{name:"Malaysia"}}},equalEditorTwo:{id:"221544",title:"Dr.",name:"Kok-Song",middleName:null,surname:"Lai",slug:"kok-song-lai",fullName:"Kok-Song Lai",profilePictureURL:"https://mts.intechopen.com/storage/users/221544/images/system/221544.jpeg",biography:"Dr. Lai Kok Song is an Assistant Professor in the Division of Health Sciences, Abu Dhabi Women\\'s College, Higher Colleges of Technology in Abu Dhabi, United Arab Emirates. He obtained his Ph.D. in Biological Sciences from Nara Institute of Science and Technology, Japan in 2012. Prior to his academic appointment, Dr. Lai worked as a Senior Scientist at the Ministry of Science, Technology and Innovation, Malaysia. His current research areas include antimicrobial resistance and plant-pathogen interaction. His particular interest lies in the study of the antimicrobial mechanism via membrane disruption of essential oils against multi-drug resistance bacteria through various biochemical, molecular and proteomic approaches. Ultimately, he hopes to uncover and determine novel biomarkers related to antibiotic resistance that can be developed into new therapeutic strategies.",institutionString:"Higher Colleges of Technology",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"8",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Higher Colleges of Technology",institutionURL:null,country:{name:"United Arab Emirates"}}},equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10020",title:"Operations Management",subtitle:"Emerging Trend in the Digital Era",isOpenForSubmission:!1,hash:"526f0dbdc7e4d85b82ce8383ab894b4c",slug:"operations-management-emerging-trend-in-the-digital-era",bookSignature:"Antonella Petrillo, Fabio De Felice, Germano Lambert-Torres and Erik Bonaldi",coverURL:"https://cdn.intechopen.com/books/images_new/10020.jpg",editors:[{id:"181603",title:"Dr.",name:"Antonella",middleName:null,surname:"Petrillo",slug:"antonella-petrillo",fullName:"Antonella Petrillo"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9560",title:"Creativity",subtitle:"A Force to Innovation",isOpenForSubmission:!1,hash:"58f740bc17807d5d88d647c525857b11",slug:"creativity-a-force-to-innovation",bookSignature:"Pooja Jain",coverURL:"https://cdn.intechopen.com/books/images_new/9560.jpg",editors:[{id:"316765",title:"Dr.",name:"Pooja",middleName:null,surname:"Jain",slug:"pooja-jain",fullName:"Pooja Jain"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9385",title:"Renewable Energy",subtitle:"Technologies and Applications",isOpenForSubmission:!1,hash:"a6b446d19166f17f313008e6c056f3d8",slug:"renewable-energy-technologies-and-applications",bookSignature:"Tolga Taner, Archana Tiwari and Taha Selim Ustun",coverURL:"https://cdn.intechopen.com/books/images_new/9385.jpg",editors:[{id:"197240",title:"Associate Prof.",name:"Tolga",middleName:null,surname:"Taner",slug:"tolga-taner",fullName:"Tolga Taner"}],equalEditorOne:{id:"186791",title:"Dr.",name:"Archana",middleName:null,surname:"Tiwari",slug:"archana-tiwari",fullName:"Archana Tiwari",profilePictureURL:"https://mts.intechopen.com/storage/users/186791/images/system/186791.jpg",biography:"Dr. Archana Tiwari is Associate Professor at Amity University, India. Her research interests include renewable sources of energy from microalgae and further utilizing the residual biomass for the generation of value-added products, bioremediation through microalgae and microbial consortium, antioxidative enzymes and stress, and nutraceuticals from microalgae. She has been working on algal biotechnology for the last two decades. She has published her research in many international journals and has authored many books and chapters with renowned publishing houses. She has also delivered talks as an invited speaker at many national and international conferences. Dr. Tiwari is the recipient of several awards including Researcher of the Year and Distinguished Scientist.",institutionString:"Amity University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Amity University",institutionURL:null,country:{name:"India"}}},equalEditorTwo:{id:"197609",title:"Prof.",name:"Taha Selim",middleName:null,surname:"Ustun",slug:"taha-selim-ustun",fullName:"Taha Selim Ustun",profilePictureURL:"https://mts.intechopen.com/storage/users/197609/images/system/197609.jpeg",biography:"Dr. Taha Selim Ustun received a Ph.D. in Electrical Engineering from Victoria University, Melbourne, Australia. He is a researcher with the Fukushima Renewable Energy Institute, AIST (FREA), where he leads the Smart Grid Cybersecurity Laboratory. Prior to that, he was a faculty member with the School of Electrical and Computer Engineering, Carnegie Mellon University, Pittsburgh, PA, USA. His current research interests include power systems protection, communication in power networks, distributed generation, microgrids, electric vehicle integration, and cybersecurity in smart grids. He serves on the editorial boards of IEEE Access, IEEE Transactions on Industrial Informatics, Energies, Electronics, Electricity, World Electric Vehicle and Information journals. Dr. Ustun is a member of the IEEE 2004 and 2800, IEC Renewable Energy Management WG 8, and IEC TC 57 WG17. He has been invited to run specialist courses in Africa, India, and China. He has delivered talks for the Qatar Foundation, the World Energy Council, the Waterloo Global Science Initiative, and the European Union Energy Initiative (EUEI). His research has attracted funding from prestigious programs in Japan, Australia, the European Union, and North America.",institutionString:"Fukushima Renewable Energy Institute, AIST (FREA)",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"National Institute of Advanced Industrial Science and Technology",institutionURL:null,country:{name:"Japan"}}},equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8985",title:"Natural Resources Management and Biological Sciences",subtitle:null,isOpenForSubmission:!1,hash:"5c2e219a6c021a40b5a20c041dea88c4",slug:"natural-resources-management-and-biological-sciences",bookSignature:"Edward R. Rhodes and Humood Naser",coverURL:"https://cdn.intechopen.com/books/images_new/8985.jpg",editors:[{id:"280886",title:"Prof.",name:"Edward R",middleName:null,surname:"Rhodes",slug:"edward-r-rhodes",fullName:"Edward R Rhodes"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10192",title:"Background and Management of Muscular Atrophy",subtitle:null,isOpenForSubmission:!1,hash:"eca24028d89912b5efea56e179dff089",slug:"background-and-management-of-muscular-atrophy",bookSignature:"Julianna Cseri",coverURL:"https://cdn.intechopen.com/books/images_new/10192.jpg",editors:[{id:"135579",title:"Dr.",name:"Julianna",middleName:null,surname:"Cseri",slug:"julianna-cseri",fullName:"Julianna Cseri"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10065",title:"Wavelet Theory",subtitle:null,isOpenForSubmission:!1,hash:"d8868e332169597ba2182d9b004d60de",slug:"wavelet-theory",bookSignature:"Somayeh Mohammady",coverURL:"https://cdn.intechopen.com/books/images_new/10065.jpg",editors:[{id:"109280",title:"Dr.",name:"Somayeh",middleName:null,surname:"Mohammady",slug:"somayeh-mohammady",fullName:"Somayeh Mohammady"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9243",title:"Coastal Environments",subtitle:null,isOpenForSubmission:!1,hash:"8e05e5f631e935eef366980f2e28295d",slug:"coastal-environments",bookSignature:"Yuanzhi Zhang and X. San Liang",coverURL:"https://cdn.intechopen.com/books/images_new/9243.jpg",editors:[{id:"77597",title:"Prof.",name:"Yuanzhi",middleName:null,surname:"Zhang",slug:"yuanzhi-zhang",fullName:"Yuanzhi Zhang"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9644",title:"Glaciers and the Polar Environment",subtitle:null,isOpenForSubmission:!1,hash:"e8cfdc161794e3753ced54e6ff30873b",slug:"glaciers-and-the-polar-environment",bookSignature:"Masaki Kanao, Danilo Godone and Niccolò Dematteis",coverURL:"https://cdn.intechopen.com/books/images_new/9644.jpg",editors:[{id:"51959",title:"Dr.",name:"Masaki",middleName:null,surname:"Kanao",slug:"masaki-kanao",fullName:"Masaki Kanao"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7847",title:"Medical Toxicology",subtitle:null,isOpenForSubmission:!1,hash:"db9b65bea093de17a0855a1b27046247",slug:"medical-toxicology",bookSignature:"Pınar Erkekoglu and Tomohisa Ogawa",coverURL:"https://cdn.intechopen.com/books/images_new/7847.jpg",editors:[{id:"109978",title:"Prof.",name:"Pınar",middleName:null,surname:"Erkekoglu",slug:"pinar-erkekoglu",fullName:"Pınar Erkekoglu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],latestBooks:[{type:"book",id:"9243",title:"Coastal Environments",subtitle:null,isOpenForSubmission:!1,hash:"8e05e5f631e935eef366980f2e28295d",slug:"coastal-environments",bookSignature:"Yuanzhi Zhang and X. San Liang",coverURL:"https://cdn.intechopen.com/books/images_new/9243.jpg",editedByType:"Edited by",editors:[{id:"77597",title:"Prof.",name:"Yuanzhi",middleName:null,surname:"Zhang",slug:"yuanzhi-zhang",fullName:"Yuanzhi Zhang"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10020",title:"Operations Management",subtitle:"Emerging Trend in the Digital Era",isOpenForSubmission:!1,hash:"526f0dbdc7e4d85b82ce8383ab894b4c",slug:"operations-management-emerging-trend-in-the-digital-era",bookSignature:"Antonella Petrillo, Fabio De Felice, Germano Lambert-Torres and Erik Bonaldi",coverURL:"https://cdn.intechopen.com/books/images_new/10020.jpg",editedByType:"Edited by",editors:[{id:"181603",title:"Dr.",name:"Antonella",middleName:null,surname:"Petrillo",slug:"antonella-petrillo",fullName:"Antonella Petrillo"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9521",title:"Antimicrobial Resistance",subtitle:"A One Health Perspective",isOpenForSubmission:!1,hash:"30949e78832e1afba5606634b52056ab",slug:"antimicrobial-resistance-a-one-health-perspective",bookSignature:"Mihai Mareș, Swee Hua Erin Lim, Kok-Song Lai and Romeo-Teodor Cristina",coverURL:"https://cdn.intechopen.com/books/images_new/9521.jpg",editedByType:"Edited by",editors:[{id:"88785",title:"Prof.",name:"Mihai",middleName:null,surname:"Mares",slug:"mihai-mares",fullName:"Mihai Mares"}],equalEditorOne:{id:"190224",title:"Dr.",name:"Swee Hua Erin",middleName:null,surname:"Lim",slug:"swee-hua-erin-lim",fullName:"Swee Hua Erin Lim",profilePictureURL:"https://mts.intechopen.com/storage/users/190224/images/system/190224.png",biography:"Dr. Erin Lim is presently working as an Assistant Professor in the Division of Health Sciences, Abu Dhabi Women\\'s College, Higher Colleges of Technology in Abu Dhabi, United Arab Emirates and is affiliated as an Associate Professor to Perdana University-Royal College of Surgeons in Ireland, Selangor, Malaysia. She obtained her Ph.D. from Universiti Putra Malaysia in 2010 with a National Science Fellowship awarded from the Ministry of Science, Technology and Innovation Malaysia and has been actively involved in research ever since. Her main research interests include analysis of carriage and transmission of multidrug resistant bacteria in non-conventional settings, besides an interest in natural products for antimicrobial testing. She is heavily involved in the elucidation of mechanisms of reversal of resistance in bacteria in addition to investigating the immunological analyses of diseases, development of vaccination and treatment models in animals. She hopes her work will support the discovery of therapeutics in the clinical setting and assist in the combat against the burden of antibiotic resistance.",institutionString:"Abu Dhabi Women’s College",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Perdana University",institutionURL:null,country:{name:"Malaysia"}}},equalEditorTwo:{id:"221544",title:"Dr.",name:"Kok-Song",middleName:null,surname:"Lai",slug:"kok-song-lai",fullName:"Kok-Song Lai",profilePictureURL:"https://mts.intechopen.com/storage/users/221544/images/system/221544.jpeg",biography:"Dr. Lai Kok Song is an Assistant Professor in the Division of Health Sciences, Abu Dhabi Women\\'s College, Higher Colleges of Technology in Abu Dhabi, United Arab Emirates. He obtained his Ph.D. in Biological Sciences from Nara Institute of Science and Technology, Japan in 2012. Prior to his academic appointment, Dr. Lai worked as a Senior Scientist at the Ministry of Science, Technology and Innovation, Malaysia. His current research areas include antimicrobial resistance and plant-pathogen interaction. His particular interest lies in the study of the antimicrobial mechanism via membrane disruption of essential oils against multi-drug resistance bacteria through various biochemical, molecular and proteomic approaches. Ultimately, he hopes to uncover and determine novel biomarkers related to antibiotic resistance that can be developed into new therapeutic strategies.",institutionString:"Higher Colleges of Technology",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"8",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Higher Colleges of Technology",institutionURL:null,country:{name:"United Arab Emirates"}}},equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9560",title:"Creativity",subtitle:"A Force to Innovation",isOpenForSubmission:!1,hash:"58f740bc17807d5d88d647c525857b11",slug:"creativity-a-force-to-innovation",bookSignature:"Pooja Jain",coverURL:"https://cdn.intechopen.com/books/images_new/9560.jpg",editedByType:"Edited by",editors:[{id:"316765",title:"Dr.",name:"Pooja",middleName:null,surname:"Jain",slug:"pooja-jain",fullName:"Pooja Jain"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9669",title:"Recent Advances in Rice Research",subtitle:null,isOpenForSubmission:!1,hash:"12b06cc73e89af1e104399321cc16a75",slug:"recent-advances-in-rice-research",bookSignature:"Mahmood-ur- Rahman Ansari",coverURL:"https://cdn.intechopen.com/books/images_new/9669.jpg",editedByType:"Edited by",editors:[{id:"185476",title:"Dr.",name:"Mahmood-Ur-",middleName:null,surname:"Rahman Ansari",slug:"mahmood-ur-rahman-ansari",fullName:"Mahmood-Ur- Rahman Ansari"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10192",title:"Background and Management of Muscular Atrophy",subtitle:null,isOpenForSubmission:!1,hash:"eca24028d89912b5efea56e179dff089",slug:"background-and-management-of-muscular-atrophy",bookSignature:"Julianna Cseri",coverURL:"https://cdn.intechopen.com/books/images_new/10192.jpg",editedByType:"Edited by",editors:[{id:"135579",title:"Dr.",name:"Julianna",middleName:null,surname:"Cseri",slug:"julianna-cseri",fullName:"Julianna Cseri"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9550",title:"Entrepreneurship",subtitle:"Contemporary Issues",isOpenForSubmission:!1,hash:"9b4ac1ee5b743abf6f88495452b1e5e7",slug:"entrepreneurship-contemporary-issues",bookSignature:"Mladen Turuk",coverURL:"https://cdn.intechopen.com/books/images_new/9550.jpg",editedByType:"Edited by",editors:[{id:"319755",title:"Prof.",name:"Mladen",middleName:null,surname:"Turuk",slug:"mladen-turuk",fullName:"Mladen Turuk"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10065",title:"Wavelet Theory",subtitle:null,isOpenForSubmission:!1,hash:"d8868e332169597ba2182d9b004d60de",slug:"wavelet-theory",bookSignature:"Somayeh Mohammady",coverURL:"https://cdn.intechopen.com/books/images_new/10065.jpg",editedByType:"Edited by",editors:[{id:"109280",title:"Dr.",name:"Somayeh",middleName:null,surname:"Mohammady",slug:"somayeh-mohammady",fullName:"Somayeh Mohammady"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9313",title:"Clay Science and Technology",subtitle:null,isOpenForSubmission:!1,hash:"6fa7e70396ff10620e032bb6cfa6fb72",slug:"clay-science-and-technology",bookSignature:"Gustavo Morari Do Nascimento",coverURL:"https://cdn.intechopen.com/books/images_new/9313.jpg",editedByType:"Edited by",editors:[{id:"7153",title:"Prof.",name:"Gustavo",middleName:null,surname:"Morari Do Nascimento",slug:"gustavo-morari-do-nascimento",fullName:"Gustavo Morari Do Nascimento"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9888",title:"Nuclear Power Plants",subtitle:"The Processes from the Cradle to the Grave",isOpenForSubmission:!1,hash:"c2c8773e586f62155ab8221ebb72a849",slug:"nuclear-power-plants-the-processes-from-the-cradle-to-the-grave",bookSignature:"Nasser Awwad",coverURL:"https://cdn.intechopen.com/books/images_new/9888.jpg",editedByType:"Edited by",editors:[{id:"145209",title:"Prof.",name:"Nasser",middleName:"S",surname:"Awwad",slug:"nasser-awwad",fullName:"Nasser Awwad"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},subject:{topic:{id:"16",title:"Medicine",slug:"medicine",parent:{title:"Health Sciences",slug:"health-sciences"},numberOfBooks:1511,numberOfAuthorsAndEditors:39573,numberOfWosCitations:21767,numberOfCrossrefCitations:11544,numberOfDimensionsCitations:29307,videoUrl:null,fallbackUrl:null,description:null},booksByTopicFilter:{topicSlug:"medicine",sort:"-publishedDate",limit:12,offset:0},booksByTopicCollection:[{type:"book",id:"10192",title:"Background and Management of Muscular Atrophy",subtitle:null,isOpenForSubmission:!1,hash:"eca24028d89912b5efea56e179dff089",slug:"background-and-management-of-muscular-atrophy",bookSignature:"Julianna Cseri",coverURL:"https://cdn.intechopen.com/books/images_new/10192.jpg",editedByType:"Edited by",editors:[{id:"135579",title:"Dr.",name:"Julianna",middleName:null,surname:"Cseri",slug:"julianna-cseri",fullName:"Julianna Cseri"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9027",title:"Human Blood Group Systems and Haemoglobinopathies",subtitle:null,isOpenForSubmission:!1,hash:"d00d8e40b11cfb2547d1122866531c7e",slug:"human-blood-group-systems-and-haemoglobinopathies",bookSignature:"Osaro Erhabor and Anjana Munshi",coverURL:"https://cdn.intechopen.com/books/images_new/9027.jpg",editedByType:"Edited by",editors:[{id:"35140",title:null,name:"Osaro",middleName:null,surname:"Erhabor",slug:"osaro-erhabor",fullName:"Osaro Erhabor"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9406",title:"Clinical Implementation of Bone Regeneration and Maintenance",subtitle:null,isOpenForSubmission:!1,hash:"875a140c01518fa7a9bceebd688b0147",slug:"clinical-implementation-of-bone-regeneration-and-maintenance",bookSignature:"Mike Barbeck, Nahum Rosenberg, Patrick Rider, Željka Perić Kačarević and Ole Jung",coverURL:"https://cdn.intechopen.com/books/images_new/9406.jpg",editedByType:"Edited by",editors:[{id:"204918",title:"Dr.",name:"Mike",middleName:null,surname:"Barbeck",slug:"mike-barbeck",fullName:"Mike Barbeck"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9122",title:"Cosmetic Surgery",subtitle:null,isOpenForSubmission:!1,hash:"207026ca4a4125e17038e770d00ee152",slug:"cosmetic-surgery",bookSignature:"Yueh-Bih Tang",coverURL:"https://cdn.intechopen.com/books/images_new/9122.jpg",editedByType:"Edited by",editors:[{id:"202122",title:"Prof.",name:"Yueh-Bih",middleName:null,surname:"Tang",slug:"yueh-bih-tang",fullName:"Yueh-Bih Tang"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9134",title:"Recent Advances in Digital System Diagnosis and Management of Healthcare",subtitle:null,isOpenForSubmission:!1,hash:"ff00a5718f23cb880b7337b1c36b5434",slug:"recent-advances-in-digital-system-diagnosis-and-management-of-healthcare",bookSignature:"Kamran Sartipi and Thierry Edoh",coverURL:"https://cdn.intechopen.com/books/images_new/9134.jpg",editedByType:"Edited by",editors:[{id:"29601",title:"Dr.",name:"Kamran",middleName:null,surname:"Sartipi",slug:"kamran-sartipi",fullName:"Kamran Sartipi"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9569",title:"Methods in Molecular Medicine",subtitle:null,isOpenForSubmission:!1,hash:"691d3f3c4ac25a8093414e9b270d2843",slug:"methods-in-molecular-medicine",bookSignature:"Yusuf Tutar",coverURL:"https://cdn.intechopen.com/books/images_new/9569.jpg",editedByType:"Edited by",editors:[{id:"158492",title:"Prof.",name:"Yusuf",middleName:null,surname:"Tutar",slug:"yusuf-tutar",fullName:"Yusuf Tutar"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9157",title:"Neurodegenerative Diseases",subtitle:"Molecular Mechanisms and Current Therapeutic Approaches",isOpenForSubmission:!1,hash:"bc8be577966ef88735677d7e1e92ed28",slug:"neurodegenerative-diseases-molecular-mechanisms-and-current-therapeutic-approaches",bookSignature:"Nagehan Ersoy Tunalı",coverURL:"https://cdn.intechopen.com/books/images_new/9157.jpg",editedByType:"Edited by",editors:[{id:"82778",title:"Ph.D.",name:"Nagehan",middleName:null,surname:"Ersoy Tunalı",slug:"nagehan-ersoy-tunali",fullName:"Nagehan Ersoy Tunalı"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9839",title:"Outdoor Recreation",subtitle:"Physiological and Psychological Effects on Health",isOpenForSubmission:!1,hash:"5f5a0d64267e32567daffa5b0c6a6972",slug:"outdoor-recreation-physiological-and-psychological-effects-on-health",bookSignature:"Hilde G. Nielsen",coverURL:"https://cdn.intechopen.com/books/images_new/9839.jpg",editedByType:"Edited by",editors:[{id:"158692",title:"Ph.D.",name:"Hilde G.",middleName:null,surname:"Nielsen",slug:"hilde-g.-nielsen",fullName:"Hilde G. Nielsen"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9139",title:"Topics in Primary Care Medicine",subtitle:null,isOpenForSubmission:!1,hash:"ea774a4d4c1179da92a782e0ae9cde92",slug:"topics-in-primary-care-medicine",bookSignature:"Thomas F. Heston",coverURL:"https://cdn.intechopen.com/books/images_new/9139.jpg",editedByType:"Edited by",editors:[{id:"217926",title:"Dr.",name:"Thomas F.",middleName:null,surname:"Heston",slug:"thomas-f.-heston",fullName:"Thomas F. Heston"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9785",title:"Endometriosis",subtitle:null,isOpenForSubmission:!1,hash:"f457ca61f29cf7e8bc191732c50bb0ce",slug:"endometriosis",bookSignature:"Courtney Marsh",coverURL:"https://cdn.intechopen.com/books/images_new/9785.jpg",editedByType:"Edited by",editors:[{id:"255491",title:"Dr.",name:"Courtney",middleName:null,surname:"Marsh",slug:"courtney-marsh",fullName:"Courtney Marsh"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9018",title:"Some RNA Viruses",subtitle:null,isOpenForSubmission:!1,hash:"a5cae846dbe3692495fc4add2f60fd84",slug:"some-rna-viruses",bookSignature:"Yogendra Shah and Eltayb Abuelzein",coverURL:"https://cdn.intechopen.com/books/images_new/9018.jpg",editedByType:"Edited by",editors:[{id:"278914",title:"Ph.D.",name:"Yogendra",middleName:null,surname:"Shah",slug:"yogendra-shah",fullName:"Yogendra Shah"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9523",title:"Oral and Maxillofacial Surgery",subtitle:null,isOpenForSubmission:!1,hash:"5eb6ec2db961a6c8965d11180a58d5c1",slug:"oral-and-maxillofacial-surgery",bookSignature:"Gokul Sridharan",coverURL:"https://cdn.intechopen.com/books/images_new/9523.jpg",editedByType:"Edited by",editors:[{id:"82453",title:"Dr.",name:"Gokul",middleName:null,surname:"Sridharan",slug:"gokul-sridharan",fullName:"Gokul Sridharan"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],booksByTopicTotal:1511,mostCitedChapters:[{id:"19013",doi:"10.5772/21983",title:"Cell Responses to Surface and Architecture of Tissue Engineering Scaffolds",slug:"cell-responses-to-surface-and-architecture-of-tissue-engineering-scaffolds",totalDownloads:9697,totalCrossrefCites:109,totalDimensionsCites:230,book:{slug:"regenerative-medicine-and-tissue-engineering-cells-and-biomaterials",title:"Regenerative Medicine and Tissue Engineering",fullTitle:"Regenerative Medicine and Tissue Engineering - Cells and Biomaterials"},signatures:"Hsin-I Chang and Yiwei Wang",authors:[{id:"45747",title:"Dr.",name:"Hsin-I",middleName:null,surname:"Chang",slug:"hsin-i-chang",fullName:"Hsin-I Chang"},{id:"53659",title:"Ms.",name:"Yiwei",middleName:null,surname:"Wang",slug:"yiwei-wang",fullName:"Yiwei Wang"}]},{id:"46479",doi:"10.5772/57353",title:"Floating Drug Delivery Systems for Eradication of Helicobacter pylori in Treatment of Peptic Ulcer Disease",slug:"floating-drug-delivery-systems-for-eradication-of-helicobacter-pylori-in-treatment-of-peptic-ulcer-d",totalDownloads:1995,totalCrossrefCites:79,totalDimensionsCites:180,book:{slug:"trends-in-helicobacter-pylori-infection",title:"Trends in Helicobacter pylori Infection",fullTitle:"Trends in Helicobacter pylori Infection"},signatures:"Yousef Javadzadeh and Sanaz Hamedeyazdan",authors:[{id:"94276",title:"Prof.",name:"Yousef",middleName:null,surname:"Javadzadeh",slug:"yousef-javadzadeh",fullName:"Yousef Javadzadeh"},{id:"98229",title:"Dr.",name:"Sanaz",middleName:null,surname:"Hamedeyazdan",slug:"sanaz-hamedeyazdan",fullName:"Sanaz Hamedeyazdan"}]},{id:"25512",doi:"10.5772/30872",title:"Epidemiology of Psychological Distress",slug:"epidemiology-of-psychological-distress",totalDownloads:8066,totalCrossrefCites:57,totalDimensionsCites:145,book:{slug:"mental-illnesses-understanding-prediction-and-control",title:"Mental Illnesses",fullTitle:"Mental Illnesses - Understanding, Prediction and Control"},signatures:"Aline Drapeau, Alain Marchand and Dominic Beaulieu-Prévost",authors:[{id:"84582",title:"Dr.",name:"Aline",middleName:null,surname:"Drapeau",slug:"aline-drapeau",fullName:"Aline Drapeau"},{id:"84605",title:"Dr.",name:"Alain",middleName:null,surname:"Marchand",slug:"alain-marchand",fullName:"Alain Marchand"},{id:"84606",title:"Dr.",name:"Dominic",middleName:null,surname:"Beaulieu-Prévost",slug:"dominic-beaulieu-prevost",fullName:"Dominic Beaulieu-Prévost"}]}],mostDownloadedChaptersLast30Days:[{id:"43758",title:"Anxiety Disorders in Pregnancy and the Postpartum Period",slug:"anxiety-disorders-in-pregnancy-and-the-postpartum-period",totalDownloads:39763,totalCrossrefCites:11,totalDimensionsCites:20,book:{slug:"new-insights-into-anxiety-disorders",title:"New Insights into Anxiety Disorders",fullTitle:"New Insights into Anxiety Disorders"},signatures:"Roberta Anniverno, Alessandra Bramante, Claudio Mencacci and Federico Durbano",authors:[{id:"157077",title:"Dr.",name:"Federico",middleName:null,surname:"Durbano",slug:"federico-durbano",fullName:"Federico Durbano"},{id:"166382",title:"Dr.",name:"Roberta",middleName:null,surname:"Anniverno",slug:"roberta-anniverno",fullName:"Roberta Anniverno"}]},{id:"70711",title:"Fetal Growth Restriction",slug:"fetal-growth-restriction",totalDownloads:1706,totalCrossrefCites:1,totalDimensionsCites:1,book:{slug:"growth-disorders-and-acromegaly",title:"Growth Disorders and Acromegaly",fullTitle:"Growth Disorders and Acromegaly"},signatures:"Edurne Mazarico Gallego, Ariadna Torrecillas Pujol, Alex Joan Cahuana Bartra and Maria Dolores Gómez Roig",authors:[{id:"202446",title:"Ph.D.",name:"Maria Dolores",middleName:null,surname:"Gómez Roig",slug:"maria-dolores-gomez-roig",fullName:"Maria Dolores Gómez Roig"},{id:"311835",title:"Dr.",name:"Edurne",middleName:null,surname:"Mazarico",slug:"edurne-mazarico",fullName:"Edurne Mazarico"}]},{id:"70405",title:"Hemostasis in Cardiac Surgery: How We Do it with Limited Resources",slug:"hemostasis-in-cardiac-surgery-how-we-do-it-with-limited-resources",totalDownloads:2694,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:null,title:"Contemporary Applications of Biologic Hemostatic Agents across Surgical Specialties - Volume 1",fullTitle:"Contemporary Applications of Biologic Hemostatic Agents across Surgical Specialties - Volume 1"},signatures:"Fevzi Sarper Türker",authors:null},{id:"64851",title:"Herbal Medicines in African Traditional Medicine",slug:"herbal-medicines-in-african-traditional-medicine",totalDownloads:9954,totalCrossrefCites:10,totalDimensionsCites:17,book:{slug:"herbal-medicine",title:"Herbal Medicine",fullTitle:"Herbal Medicine"},signatures:"Ezekwesili-Ofili Josephine Ozioma and Okaka Antoinette Nwamaka\nChinwe",authors:[{id:"191264",title:"Prof.",name:"Josephine",middleName:"Ozioma",surname:"Ezekwesili-Ofili",slug:"josephine-ezekwesili-ofili",fullName:"Josephine Ezekwesili-Ofili"},{id:"211585",title:"Prof.",name:"Antoinette",middleName:null,surname:"Okaka",slug:"antoinette-okaka",fullName:"Antoinette Okaka"}]},{id:"59779",title:"Effective Communication in Nursing",slug:"effective-communication-in-nursing",totalDownloads:6504,totalCrossrefCites:2,totalDimensionsCites:4,book:{slug:"nursing",title:"Nursing",fullTitle:"Nursing"},signatures:"Maureen Nokuthula Sibiya",authors:[{id:"73330",title:"Dr.",name:"Nokuthula",middleName:null,surname:"Sibiya",slug:"nokuthula-sibiya",fullName:"Nokuthula Sibiya"}]},{id:"64858",title:"The Neurobiology of Anorexia Nervosa",slug:"the-neurobiology-of-anorexia-nervosa",totalDownloads:892,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"anorexia-and-bulimia-nervosa",title:"Anorexia and Bulimia Nervosa",fullTitle:"Anorexia and Bulimia Nervosa"},signatures:"Ashley Higgins",authors:null},{id:"63771",title:"The Role of Catheter Reshaping at the Angiographic Success",slug:"the-role-of-catheter-reshaping-at-the-angiographic-success",totalDownloads:536,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"angiography",title:"Angiography",fullTitle:"Angiography"},signatures:"Yakup Balaban",authors:[{id:"252647",title:"Associate Prof.",name:"Yakup",middleName:null,surname:"Balaban",slug:"yakup-balaban",fullName:"Yakup Balaban"}]},{id:"61866",title:"Plants Secondary Metabolites: The Key Drivers of the Pharmacological Actions of Medicinal Plants",slug:"plants-secondary-metabolites-the-key-drivers-of-the-pharmacological-actions-of-medicinal-plants",totalDownloads:5564,totalCrossrefCites:13,totalDimensionsCites:32,book:{slug:"herbal-medicine",title:"Herbal Medicine",fullTitle:"Herbal Medicine"},signatures:"Rehab A. Hussein and Amira A. El-Anssary",authors:[{id:"212117",title:"Dr.",name:"Rehab",middleName:null,surname:"Hussein",slug:"rehab-hussein",fullName:"Rehab Hussein"},{id:"221140",title:"Dr.",name:"Amira",middleName:null,surname:"El-Anssary",slug:"amira-el-anssary",fullName:"Amira El-Anssary"}]},{id:"17956",title:"Sexual and Reproductive Function in Chronic Kidney Disease and Effect of Kidney Transplantation",slug:"sexual-and-reproductive-function-in-chronic-kidney-disease-and-effect-of-kidney-transplantation",totalDownloads:11790,totalCrossrefCites:1,totalDimensionsCites:1,book:{slug:"after-the-kidney-transplant-the-patients-and-their-allograft",title:"After the Kidney Transplant",fullTitle:"After the Kidney Transplant - The Patients and Their Allograft"},signatures:"Mahboob Lessan-Pezeshki and Shirin Ghazizadeh",authors:[{id:"26564",title:"Prof.",name:"Mahboob",middleName:null,surname:"Lessan Pezeshki",slug:"mahboob-lessan-pezeshki",fullName:"Mahboob Lessan Pezeshki"},{id:"26571",title:"Prof.",name:"Shirin",middleName:null,surname:"Ghazizadeh",slug:"shirin-ghazizadeh",fullName:"Shirin Ghazizadeh"}]},{id:"64747",title:"Bone Development and Growth",slug:"bone-development-and-growth",totalDownloads:3711,totalCrossrefCites:6,totalDimensionsCites:9,book:{slug:"osteogenesis-and-bone-regeneration",title:"Osteogenesis and Bone Regeneration",fullTitle:"Osteogenesis and Bone Regeneration"},signatures:"Rosy Setiawati and Paulus Rahardjo",authors:null}],onlineFirstChaptersFilter:{topicSlug:"medicine",limit:3,offset:0},onlineFirstChaptersCollection:[{id:"75604",title:"Normal Puerperium",slug:"normal-puerperium",totalDownloads:0,totalDimensionsCites:null,doi:"10.5772/intechopen.96348",book:{title:"Midwifery"},signatures:"Subrat Panda, Ananya Das, Arindam Mallik and Surajit Ray Baruah"},{id:"75596",title:"The Use of a Dynamic Elastomeric Fabric Orthotic Intervention in Adolescents and Adults with Scoliosis",slug:"the-use-of-a-dynamic-elastomeric-fabric-orthotic-intervention-in-adolescents-and-adults-with-scolios",totalDownloads:0,totalDimensionsCites:null,doi:"10.5772/intechopen.96391",book:{title:"Spinal Deformities in Adolescents, Adults and Older Adults"},signatures:"Martin Matthews and James Wynne"},{id:"75582",title:"Elimination of Plasmodium vivax Malaria: Problems and Solutions",slug:"elimination-of-plasmodium-vivax-malaria-problems-and-solutions",totalDownloads:1,totalDimensionsCites:null,doi:"10.5772/intechopen.96604",book:{title:"Current Topics and Emerging Issues in Malaria Elimination"},signatures:"Liwang Cui, Awtum Brashear, Lynette Menezes and John Adams"}],onlineFirstChaptersTotal:652},preDownload:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[{type:"book",id:"10176",title:"Microgrids and Local Energy Systems",subtitle:null,isOpenForSubmission:!0,hash:"c32b4a5351a88f263074b0d0ca813a9c",slug:null,bookSignature:"Prof. Nick Jenkins",coverURL:"https://cdn.intechopen.com/books/images_new/10176.jpg",editedByType:null,editors:[{id:"55219",title:"Prof.",name:"Nick",middleName:null,surname:"Jenkins",slug:"nick-jenkins",fullName:"Nick Jenkins"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],offset:8,limit:8,total:1},route:{name:"profile.detail",path:"/profiles/183393/sai-sunil-kumar-mallineni",hash:"",query:{},params:{id:"183393",slug:"sai-sunil-kumar-mallineni"},fullPath:"/profiles/183393/sai-sunil-kumar-mallineni",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)}()