Peptides proposed to affect appetite regulation. adapted from Burrage and McCandless, 2007
\r\n\tThe fifth topic is “complications and drug side effects in the treatment of pigmentation disorders”. These include drug allergies, hyper- and hypopigmentation, persistent skin depigmentation, scars, skin burns, and the potential for skin cancer and skin lymphoma. The last topic is called “coping and support along with skin pigmentation diseases”. Increase the quality of life, psychotherapy, team therapy, and asking for understanding and support from family members.
",isbn:"978-1-80356-900-0",printIsbn:"978-1-80356-899-7",pdfIsbn:"978-1-80356-901-7",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,isSalesforceBook:!1,isNomenclature:!1,hash:"2ac6c9f424eec37ed85232c2c97ef6f6",bookSignature:"Associate Prof. Shahin Aghaei",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11698.jpg",keywords:"Melanoma, Post-inflammatory Hyperpigmentation, Albinism, Piebaldism, Vitiligo, Pityriasis Alba, Laser Therapy, Cosmetic Coverage, Drug Reactions, Skin Sensitivity, Quality of Life, Team Therapy",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"April 5th 2022",dateEndSecondStepPublish:"June 14th 2022",dateEndThirdStepPublish:"August 13th 2022",dateEndFourthStepPublish:"November 1st 2022",dateEndFifthStepPublish:"December 31st 2022",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"2 months",secondStepPassed:!0,areRegistrationsClosed:!0,currentStepOfPublishingProcess:4,editedByType:null,kuFlag:!1,biosketch:"Associate Professor of Clinical Dermatology and Dermatologic Surgery, lead author or contributor to nearly 60 articles published in international dermatology journals, and editor-in-chief of the Journal of Surgical Dermatology in Singapore.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"64024",title:"Associate Prof.",name:"Shahin",middleName:null,surname:"Aghaei",slug:"shahin-aghaei",fullName:"Shahin Aghaei",profilePictureURL:"https://mts.intechopen.com/storage/users/64024/images/system/64024.jpg",biography:"Shahin Aghaei, MD, graduated from Shiraz University of Medical Sciences, Iran, in 2004. He was awarded a fellowship from the International Society of Dermatopathology (ISD) from Charles University, Czech Republic, in 2008 and a fellowship in Dermatologic Surgery from the Medical University of Graz, Austria, in 2010. He is currently editor in chief of the Journal of Surgical Dermatology in Singapore and Associate Professor of Dermatology and Dermatologic Surgery at Iran University of Medical Sciences, School of Medicine. 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The increase in obesity prevalence among children is particularly alarming because obesity-related complications, including obesity-associated sleep apnea,[5] non-alcoholic fatty liver disease [6], and type 2 diabetes,[7] are increasingly diagnosed in pediatric patients. Excess weight in children may increase the likelihood of heart disease in adulthood as a result of the early establishment of risk factors [8]. Pediatric obesity has been shown to have a tremendous impact on later health [8], even independent of adult weight [9]. Additionally, childhood obesity is linked with important psychosocial consequences and poor general quality of life [10].
\n\t\t\tIn order to create the best management programs and determine novel therapeutic targets, it becomes essential to understand the factors causing today’s rising epidemic of childhood obesity.
\n\t\t\tObesity develops as a result of dietary and lifestyle factors, but studies also suggest a genetic influence on obesity [11]. Obesity is highly influenced by genetics; available data suggest that 40% to 77% of the observed variance in human body weight can be accounted for, by inherited factors [12–14]. Obesity, also just as clearly has environmental causes; our genetic endowments have changed minimally during the last 40 years, yet the prevalence of childhood obesity has tripled in US [15] and significantly increased worldwide [16], an observation that can only be explained by changes in external factors affecting children’s energetic balance.
\n\t\t\tThis chapter provides an overview of the current knowledge on genetic factors implicated in the obesity epidemic.
\n\t\t\t\n\t\t\t\t\n\t\t\t\t\t
This review chapter has been developed using an evidence-based approach. Data from clinical and observational studies, review articles and twin studies were all considered when shaping this review. Literature searches for topics relating to genetic obesity were carried out in PubMed and EMBASE between 10 June and 10 August 2012, using Medical Subject Heading Terms and relevant keywords. To ensure relevance to the modern day clinical setting, literature searches were limited to articles published since 1 January 2000. Older, historically significant, articles identified by the authors were also included. Only articles from the peer-reviewed literature were included in the literature search. Articles in a non-English language were not included. Abstracts from industry-sponsored meetings were not included.
\n\t\tCurrently, there are quite a few theories that intend to explain the etiology of human obesity: the thrifty gene hypothesis, the fetal programming hypothesis, the predation release hypothesis, the sedentary lifestyle hypothesis, the ethnic shift hypothesis, the increased reproductive fitness hypothesis, the assortative mating hypothesis, and the complex hypothesis [17]. However, an acceptable consensus in the field is still lacking, probably due to the fact that the development of obesity comes from highly complex interactions. The vast majority of genetic factors are presumed to affect body weight enough to cause obesity, only when specific environmental conditions pertain.
\n\t\t\t\n\t\t\t\t
A growing body of empirical evidence suggests the concept of
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The
The
The
The
The
Genes can favor fat accumulation in a given environment by increased desire to overeat; the tendency to be sedentary; a diminished ability to utilize dietary fats as fuel; an enlarged, easily stimulated capacity to store body fat. The variation in how people respond to the same environmental conditions is an additional indication that genes play an important role in the development of obesity [40]. This is also consistent with the notion that obesity results from genetic variation interacting with shifting environmental conditions. The influence of genes ranges from polygenic genetic predisposition with impact on appetite, metabolism, and the deposition of fat, to rare monogenic disorders where obesity is the primary feature. Arduous efforts have been made by the scientific society to better understand the physiological basis of obesity. Crucial to this research is the inquiry of how does our body control ingestion, digestion, absorption, and metabolism and how nutrients are distributed among various tissues, organs, and systems [41]. Simultaneously, there is a growing interest regarding the role of genetics in further explaining feeding regulatory systems [14].
\n\t\tThe genetic contribution to common obesity has been established initially through family, twin, and adoption studies. Twin studies have shown a relatively high heritability ranging from 40%-77% [12–14]. However, the search for obesity susceptibility genes has been an arduous task. Gene identification for the last 15 years has been based on two broad genetic epidemiological approaches (candidate gene and genome-wide linkage methods). Recently, genome-wide association studies have brought great information on obesity related genes.
\n\t\t\t\n\t\t\t\t
The candidacy of a gene for obesity is based on the following resources: animal models using gene knockout and transgenic approaches; cellular model systems showing their role in metabolic pathways involved in glucose metabolism; linkage and positional cloning studies using extreme cases. This approach emphasizes on an association between a variant or mutation within or near the candidate gene and a trait of interest (such as obesity). Candidate gene approach needs to be on a large scale and well powered, in order to detect the expected small effects of genetic variants involved in common traits and disease [42].
\n\t\t\tThe latest update of the Human Obesity Gene Map reported 127 candidate genes for obesity-related traits. Results of large-scale studies suggest that obesity is strongly associated with genetic variants in the melanocortin-4 receptor (MC4R) gene, leptin gene, adrenergic
\n\t\t\t\t
Genome-wide linkage studies, through surveying the whole genome, aim to identify new, unanticipated genetic variants associated with a disease or trait of interest. Genome-wide linkage studies rely on the relatedness of study participants and test whether certain chromosomal regions cosegregate with a disease or trait across generations [42]. The latest Human Obesity Gene Map update reported 253 loci from 61 genome-wide linkage scans, of which 15 loci have been replicated in at least three studies [45]. Yet, none of these replicated loci could be narrowed down sufficiently to pinpoint the genes or variants that underline the linkage signal.
\n\t\t\t\n\t\t\t\t
Genome-wide association studies are used in genetics research to look for associations between many (typically hundreds of thousands) of specific genetic variations (most commonly, single nucleotide polymorphisms -SNP) and particular diseases or traits. Similar to genome-wide linkage, the genome-wide association approach sweeps the entire genome, unrestricted by prior assumptions. Genome-wide association studies screen the whole genome at higher resolution levels than genome-wide linkage studies and are capable to narrow down the associated locus more accurately. The genome-wide association approach has effectively replaced genome-wide linkage approach for common disease [42].
\n\t\t\tRecent success of genome-wide association studies has drawn a lot of attention. High-density multistage genome-wide association analyses have so far discovered ~30 loci consistently associated with BMI and obesity-related traits. The strongest signal remains the association with variants within FTO (the fat-mass and obesity-related gene). Other signals near BDNF, SH2B1, and NEGR1 (all implicated in aspects of neuronal function),further support the idea that obesity is a disorder of hypothalamic function [42].
\n\t\tThe strongest risk factor for childhood and adolescent obesity is parental obesity [46]. The risk becomes especially elevated if both parents are obese [47]. However, obesity inheritance does not usually follow classic Mendelian patterns. A combination of gene mutations, deletions and single nucleotide polymorphisms are all known to contribute to obesity. Most cases are polygenic, the result of multiple genes interacting with a shifting environment. Each “obesity gene” only makes a small contribution to phenotype, but collectively, inherited genetic variations play a major role in determining body mass and how the body maintains a balance between physical activity and nutrition. While obesity is most commonly associated with polygenic inheritance, there are other instances in which the cause is monogenic or syndromic. Monogenic obesity typically is caused by a single gene mutation with severe obesity as the main symptom. Syndromic obesity, on the other hand, has many characteristics, of which obesity is one symptom [48].
\n\t\t\t\n\t\t\t\t
\n\t\t\t\t
\n\t\t\t\t
\n\t\t\t\t
A “monogene” is by textbook definition, a gene with a strong effect on the phenotype (Mendelian traits or Mendelian - single gene conditions), giving rise to a one-on-one relationship between genotype and phenotype. A “major gene” is defined as a gene harboring, a variant which is associated with a high lifetime risk for a disease. Modifier genes and environmental factors additionally play a role in the etiology of the respective diseases [50].
\n\t\t\t\n\t\t\t\t
Leptin is an adipocyte-derived hormone that is secreted proportionally to body fat content, it crosses the blood–brain barrier, and stimulates a subset of neurons in the hypothalamus to produce peptides that reduce feeding and promote increased energy expenditure (leptin–melanocortin pathway). Additionally, leptin inhibits hypothalamic neurons that produce peptides promoting feeding and decreased energy expenditure.
\n\t\t\tAttention has focused on identifying the molecular events that lie downstream of the leptin receptor in hypothalamic target neurons. In particular, neurons within the hypothalamus act as primary sensors of alterations in energy stores to control appetite and energy homeostasis. Pro-opiomelanocortin (POMC) neurons produce the
\n\t\t\t\t\t\t\t | \n\t\t\t\t\t|
\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t\n\t\t\t\t\t\t\t | \n\t\t\t\t\t
Neuropeptide Y | \n\t\t\t\t\t\tGhrelin | \n\t\t\t\t\t
Melanin-concentrating hormone (MCH) | \n\t\t\t\t\t\t\n\t\t\t\t\t |
Orexins/hypocretins | \n\t\t\t\t\t\t\n\t\t\t\t\t |
Agouti-related peptide (AGRP) | \n\t\t\t\t\t\t\n\t\t\t\t\t |
Galanin | \n\t\t\t\t\t\t\n\t\t\t\t\t |
Endogenous opioids | \n\t\t\t\t\t\t\n\t\t\t\t\t |
Endocannabinoids | \n\t\t\t\t\t\t\n\t\t\t\t\t |
\n\t\t\t\t\t\t\t | \n\t\t\t\t\t|
\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t\n\t\t\t\t\t\t\t | \n\t\t\t\t\t
Cocaine- and amphetamine- related transcript (CART) | \n\t\t\t\t\t\tLeptin | \n\t\t\t\t\t
Melanocortins (POMC) | \n\t\t\t\t\t\tPeptide YY | \n\t\t\t\t\t
Corticotropin-releasing factor (CRF) | \n\t\t\t\t\t\tCholecystokinin (CCK) | \n\t\t\t\t\t
Insulin | \n\t\t\t\t\t\tInsulin | \n\t\t\t\t\t
Serotonin | \n\t\t\t\t\t\tAmylin | \n\t\t\t\t\t
Glucagon-like peptides | \n\t\t\t\t\t\tGlucagon-like peptides | \n\t\t\t\t\t
Neurotensin | \n\t\t\t\t\t\tBombesin | \n\t\t\t\t\t
Peptides proposed to affect appetite regulation. adapted from Burrage and McCandless, 2007
The cumulative prevalence of monogenic obesity among children with severe obesity is about 5% [44]. Several monogenic disorders resulting from disruption of the leptin–melanocortin pathway have been identified. In these disorders, severe obesity of early onset is itself the predominant presenting feature, although often accompanied by characteristic patterns of neuroendocrine dysfunction. Mutations in the melanocortin-4 receptor gene (
\n\t\t\t\t
In 1997 two severely obese cousins were reported from a highly consanguineous family of Pakistani origin [53]. Despite their severe obesity, both children had undetectable levels of serum leptin and a mutation in the gene encoding leptin. Leptin deficiency is associated with hyperphagia and increased energy intake. Other phenotypic features include hypogonadotropic hypogonadism, elevated plasma insulin, T-cell abnormalities, and advanced bone age [54].
\n\t\t\tThe role of leptin in some monogenic forms of obesity was further supported by the striking effect of leptin replacement in an extremely obese child with congenital leptin deficiency. In a 9-year-old boy with congenital leptin deficiency, daily subcutaneous injection of recombinant human leptin for a year, led to a complete reversal of obesity, with sustained fat-mass loss. Moreover, partial leptin deficiency in 13 Pakistani subjects, due to a heterozygous frame shift mutation in the leptin gene, was found to be associated with increased body fat [55,56]. However, only a handful of families with extreme forms of obesity in early infancy have mutations in these genes [57].
\n\t\t\t\n\t\t\t\t
Shortly after leptin deficiency was discovered, a similar phenotype, but with elevated plasma leptin levels, was identified [58]. The cause was a homozygous mutation in the leptin receptor. A later study suggested that approximately 3% of severe morbid obesity in a population including both non-consanguineous and consanguineous families could be explained by mutations in the leptin receptor [59].
\n\t\t\t\n\t\t\t\t
Mutations in another component of the leptin–melanocortin pathway melanocortin-4 receptor have also been associated with obesity. MC4R deficiency represents the most common monogenic obesity disorder that has been identified so far. It is present in about 5-6% of obese individuals from different ethnic groups, with a higher prevalence in cases with increased severity and earlier age of onset [60,61]. Affected subjects exhibit hyperphagia, but this is not as severe as that seen in leptin deficiency, although it often starts in the first year of life. Alongside the increase in fat mass, MC4R-deficient subjects also have an increase in lean mass, that is not seen in leptin deficiency and a marked increase in bone mineral density. The accelerated linear growth is apparently not related to a dysfunction of the GH axis and may be a consequence of the disproportionate early hyperinsulinaemia. Interestingly, both heterozygous and homozygous mutations in MC4R have been implicated in obesity, but extreme obesity is incompletely penetrant in heterozygous patients. In other words, some individuals with a single copy of the mutation are obese, whereas others are not obese [51].
\n\t\t\tCurrently, there is no specific therapy for MC4R deficiency, however, it is highly likely that these subjects would respond well to pharmacotherapy that overcame the reduction in the hypothalamic melanocortinergic tone that exists in these patients [12].
\n\t\t\t\n\t\t\t\t
Small numbers of patients have been described with mutations in the gene encoding pro-opiomelanocortin, which is involved in the leptin-melanocortin pathway [62,63]. In neonatal life, these patients present with adrenal crisis due to ACTH deficiency (POMC is a precursor of ACTH in the pituitary), also, the children have pale skin and red hair due to the lack of MSH action at melanocortin-1 receptors in the skin and hair follicles. POMC deficiency results in hyperphagia and early-onset obesity due to loss of melanocortin signaling at the melanocortin-4 receptor (MC4R) [12].
\n\t\t\t\n\t\t\t\t
Jackson et al described a woman with severe early-onset obesity, hypogonadotropic hypogonadism, postprandial hypoglycaemia, hypocortisolemia, and evidence of impaired processing of POMC and proinsulin who was a compound heterozygote for prohormone convertase-1 mutations [63].
\n\t\t\tAlthough great hope was invested in the studies of patients with early-onset severe obesity, they have revealed the identity of very few genes associated with obesity. Interestingly, the few gene mutations associated with morbid obesity appear to influence body weight primarily by altering appetite. Some of the molecules may also impact activity, but this has not yet been shown to be a significant contributor to obesity. A significant limitation of the strategy of focusing on morbid obesity is that mutations or genetic variants in these genes may not be associated with more common forms of the condition [51].
\n\t\t\t\n\t\t\t\t
Syndromic obesity is represented by at least 20 rare syndromes (shown in Table 2), that are caused by discrete genetic defects or chromosomal abnormalities, both autosomal and X-linked, that are characterized by obesity. Most of these obesity syndromes associate mental retardation.
\n\t\t\tIt was expected that the syndromic forms of obesity could help unravel novel genes relevant for idiopathic obesity. However, although the genes for several of the syndromic forms have been detected, the relevance of these genes for general obesity is still unclear [45,57].
\n\t\t\t1 | \n\t\t\t\t\t\tAchondroplasia | \n\t\t\t\t\t
2 | \n\t\t\t\t\t\tAlström Syndrome | \n\t\t\t\t\t
3 | \n\t\t\t\t\t\tBannayan-Riley-Ruvalcaba Syndrome | \n\t\t\t\t\t
4 | \n\t\t\t\t\t\tBeckwith-Wiedemann Syndrome | \n\t\t\t\t\t
5 | \n\t\t\t\t\t\tBiedl Bardet Syndrome | \n\t\t\t\t\t
6 | \n\t\t\t\t\t\tBorjeson-Forssman-Lehmann Syndrome | \n\t\t\t\t\t
7 | \n\t\t\t\t\t\tCarpenter syndrome | \n\t\t\t\t\t
8 | \n\t\t\t\t\t\tCDG 1a | \n\t\t\t\t\t
9 | \n\t\t\t\t\t\tCohen Syndrome | \n\t\t\t\t\t
10 | \n\t\t\t\t\t\tFragile X Syndrome | \n\t\t\t\t\t
11 | \n\t\t\t\t\t\tMehmo Syndrome | \n\t\t\t\t\t
12 | \n\t\t\t\t\t\tMeningomyelocoele | \n\t\t\t\t\t
13 | \n\t\t\t\t\t\tPrader Willi Syndrome | \n\t\t\t\t\t
14 | \n\t\t\t\t\t\tPsdeuohypoparathyroidism 1a | \n\t\t\t\t\t
15 | \n\t\t\t\t\t\tSimpson-Golabi-Behmel Syndrome | \n\t\t\t\t\t
16 | \n\t\t\t\t\t\tSmith-Magenis Syndrome | \n\t\t\t\t\t
17 | \n\t\t\t\t\t\tSotos Syndrome | \n\t\t\t\t\t
18 | \n\t\t\t\t\t\tWilson-Turner Syndrome | \n\t\t\t\t\t
19 | \n\t\t\t\t\t\tUlnar-Mammary Schinzel Syndrome | \n\t\t\t\t\t
20 | \n\t\t\t\t\t\tWeaver Syndrome | \n\t\t\t\t\t
Syndromes characterized by obesity.
\n\t\t\t\t
Prader–Willi syndrome (PWS) is the most frequent of these syndromes (1 in 25,000 births). It is an autosomal-dominant disorder, characterized by obesity, hyperphagia, muscular hypotonia, mental retardation, short stature and hypogonadotropic hypogonadism. It is usually caused by a paternally inherited deletion at the chromosomal region 15q11.2–q12, and less frequently by maternal uniparental disomy (Orphanet). The cause of hyperphagia in PWS is not proven, although PWS phenotypes are consistent with a combined hypothalamic impairment, causing several endocrine abnormalities. Also, it was suggested that the elevated production of the stomach secreted peptide ghrelin seen in PWS might increase appetite by interacting with the POMC/CART and NPY hypothalamic neurons [57].
\n\t\t\t\n\t\t\t\t
The loss of the single minded homologue 1 (SIM1) gene has also been associated with hyperphagia in syndromic obesity. This gene encodes a transcription factor that has a pivotal role in neurogenesis. In humans, deletion or disruption of the SIM1 region results in either a “Prader–Willi-like” phenotype or a form of early-onset obesity, associated with excessive food intake [64].
\n\t\t\t\n\t\t\t\t
The WAGR syndrome (Wilms tumor, aniridia, genitourinary anomalies and mental retardation syndrome and obesity) is caused by heterozygous contiguous gene deletions that involve at least two genes,
\n\t\t\t\t
PHP1A syndrome is due to a maternally transmitted mutation in GNAS1, which encodes the α-subunit of the Gs protein. Food-intake abnormalities in patients with this syndrome might be due to the expression of the resulting variant Gs protein in the hypothalamic circuitry that controls energy balance, which involves many G-protein coupled receptors [66].
\n\t\t\t\n\t\t\t\t
Bardet–Biedl syndrome is characterized by six main features: Rod-Cone Dystrophy (the most frequent phenotype), polydactyly, learning disabilities, hypogonadism in males, renal abnormalities and obesity. In BBS patients, obesity has early onset, usually arising within the first few years of life. However, one study of post-pubertal BBS patients found that only 52% were clinically obese; therefore, this syndrome can present with a heterogeneous phenotype [67].
\n\t\t\t\n\t\t\t\t
Albright’s hereditary osteodystrophy describes a constellation of physical features, including short adult stature, obesity, brachydactyly, and ectopic ossifications. It is an autosomal dominant disorder due to germline mutations in GNAS1, which encodes for a-subunit of the stimulatory G protein (Gsa) [68].
\n\t\t\t\n\t\t\t\t
Fragile X syndrome is characterized by moderate to severe mental retardation, macroorchidism, large ears, macrocephaly, prominent jaw (mandibular prognathism), high-pitched jocular speech and obesity. Fragile X syndrome is an X-linked, single gene disorder caused by dysfunction in the transcription of the
\n\t\t\t\t
Borjeson, Forssman and Lehmann described a syndrome characterized by moderate to severe mental retardation, epilepsy, hypogonadism, and obesity with marked gynecomastia [70]. Mutations in a novel, widely expressed zinc-finger gene plant homeodomain (PHD)-like finger (PHF6) have been identified in affected families, although the functional properties of this protein remain unclear [71].
\n\t\t\t\n\t\t\t\t
Alstrom syndrome is a homogeneous autosomal recessive disorder that is characterized by childhood obesity associated with hyperinsulinaemia, chronic hyperglycemia and neurosensory deficits. Subsets of affected individuals present with additional features such as dilated cardiomyopathy, hepatic dysfunction, hypothyroidism, male hypogonadism, short stature and mild to moderate developmental delay. Symptoms first appear in infancy and progressive development of multi-organ pathology leads to a reduced life expectancy. Variability in age of onset and severity of clinical symptoms, even within families, is likely due to genetic background. Mutations in a single gene, ALMS1, have been found to be responsible for all cases of Alstrom syndrome [72].
\n\t\t\t\n\t\t\t\t
Complex polygenic obesity represents the end result of behavioral, environmental, and genetic factors that may influence individual responses to diet and physical activity. Changes in our environment over the last decades, in particular the unlimited supply of cheap, highly palatable, energy-dense foods; plus a sedentary lifestyle, the so called “obesogenic” environment together with a genetic susceptibility are the culprits for today’s obesity epidemic [73].
\n\t\t\tCompared with obesity syndromes or single-gene obesity, the recent rapid increase in prevalence of childhood obesity suggests that environmental factors most likely have a larger impact on body weight in common obesity patients, although individual responses to these environmental factors are influenced by genetic factors -“susceptibility genes”.
\n\t\t\tSome traits can be due to simultaneous presence of DNA variation in multiple genes. Any of a group of alleles, at distinct gene loci that collectively control the inheritance of a quantitative phenotype or modify the expression of a qualitative character, are termed “polygenic” variants. It is generally assumed that for quantitative traits, each allele has a small effect, but the allelic effects can be additive or non-additive. Potentially, many such polygenic variants play a role in body weight regulation. It is estimated that the total number of genes with a small effect most likely exceeds 100 [50].
\n\t\t\trs2815752 | \n\t\t\t\t\t\t1 | \n\t\t\t\t\t\t72,524,461 | \n\t\t\t\t\t\tNEGR1 | \n\t\t\t\t\t\t32,387 | \n\t\t\t\t\t\t62% (A) | \n\t\t\t\t\t\t+0.10 kg/m2 per A alleleb\n\t\t\t\t\t\t | \n\t\t\t\t\t
rs2568958 | \n\t\t\t\t\t\t1 | \n\t\t\t\t\t\t72,537,704 | \n\t\t\t\t\t\tNEGR1 | \n\t\t\t\t\t\t25,344 | \n\t\t\t\t\t\t58% (A) | \n\t\t\t\t\t\t+0.43 kg/m2 for AA genotypec\n\t\t\t\t\t\t | \n\t\t\t\t\t
rs10913469 | \n\t\t\t\t\t\t1 | \n\t\t\t\t\t\t176,180,142 | \n\t\t\t\t\t\tSEC16B,RASAL2 | \n\t\t\t\t\t\t25,344 | \n\t\t\t\t\t\t20% (C) | \n\t\t\t\t\t\t+0.50 kg/m2 for CC genotypec\n\t\t\t\t\t\t | \n\t\t\t\t\t
rs6548238 | \n\t\t\t\t\t\t2 | \n\t\t\t\t\t\t624,905 | \n\t\t\t\t\t\tTMEM18 | \n\t\t\t\t\t\t32,387 | \n\t\t\t\t\t\t84% (C) | \n\t\t\t\t\t\t+0.26 kg/m2 per C alleleb\n\t\t\t\t\t\t | \n\t\t\t\t\t
rs7561317 | \n\t\t\t\t\t\t2 | \n\t\t\t\t\t\t634,953 | \n\t\t\t\t\t\tTMEM18 | \n\t\t\t\t\t\t25,344 | \n\t\t\t\t\t\t84% (G) | \n\t\t\t\t\t\t+0.70 kg/m2 for GG genotypec\n\t\t\t\t\t\t | \n\t\t\t\t\t
rs7566605 | \n\t\t\t\t\t\t2 | \n\t\t\t\t\t\t118,552,495 | \n\t\t\t\t\t\tINSIG2 | \n\t\t\t\t\t\t9,881 | \n\t\t\t\t\t\t37% (C) | \n\t\t\t\t\t\t+1.00 kg/m2 for CC genotype | \n\t\t\t\t\t
rs7647305 | \n\t\t\t\t\t\t3 | \n\t\t\t\t\t\t187,316,984 | \n\t\t\t\t\t\tSFRS10, ETV5, DGKG | \n\t\t\t\t\t\t25,344 | \n\t\t\t\t\t\t77% (C) | \n\t\t\t\t\t\t+0.54 kg/m2 for CC genotypec\n\t\t\t\t\t\t | \n\t\t\t\t\t
rs10938397 | \n\t\t\t\t\t\t4 | \n\t\t\t\t\t\t45,023,455 | \n\t\t\t\t\t\tGNPDA2 | \n\t\t\t\t\t\t32,387 | \n\t\t\t\t\t\t48% (G) | \n\t\t\t\t\t\t+0.19 kg/m2 per G alleleb\n\t\t\t\t\t\t | \n\t\t\t\t\t
rs4712652 | \n\t\t\t\t\t\t6 | \n\t\t\t\t\t\t22,186,593 | \n\t\t\t\t\t\tPRL | \n\t\t\t\t\t\t2,796 | \n\t\t\t\t\t\t41% (A) | \n\t\t\t\t\t\t+0.031 kg/m2 per A allele in childrend\n\t\t\t\t\t\t | \n\t\t\t\t\t
rs10508503 | \n\t\t\t\t\t\t10 | \n\t\t\t\t\t\t16,339,956 | \n\t\t\t\t\t\tPTER | \n\t\t\t\t\t\t2,796 | \n\t\t\t\t\t\t8.5% (C) | \n\t\t\t\t\t\t+0.144 kg/m2 per C allele in childrend\n\t\t\t\t\t\t | \n\t\t\t\t\t
rs6265 (V66M) | \n\t\t\t\t\t\t11 | \n\t\t\t\t\t\t27,636,492 | \n\t\t\t\t\t\tBDNF | \n\t\t\t\t\t\t25,344 | \n\t\t\t\t\t\t85% (G) | \n\t\t\t\t\t\t+0.67 kg/m2 for GG genotypec\n\t\t\t\t\t\t | \n\t\t\t\t\t
rs10838738 | \n\t\t\t\t\t\t11 | \n\t\t\t\t\t\t47,619,625 | \n\t\t\t\t\t\tMTCH2 | \n\t\t\t\t\t\t32,387 | \n\t\t\t\t\t\t34% (G) | \n\t\t\t\t\t\t+0.07 kg/m2 per G alleleb\n\t\t\t\t\t\t | \n\t\t\t\t\t
rs7138803 | \n\t\t\t\t\t\t12 | \n\t\t\t\t\t\t48,533,735 | \n\t\t\t\t\t\tBCDIN3D, FAIM2 | \n\t\t\t\t\t\t25,344 | \n\t\t\t\t\t\t37% (A) | \n\t\t\t\t\t\t+0.54 kg/m2 for AA genotypec\n\t\t\t\t\t\t | \n\t\t\t\t\t
rs7498665 | \n\t\t\t\t\t\t16 | \n\t\t\t\t\t\t28,790,742 | \n\t\t\t\t\t\tSH2B1 | \n\t\t\t\t\t\t32,387 | \n\t\t\t\t\t\t41% (G) | \n\t\t\t\t\t\t+0.15 kg/m2 per G alleleb\n\t\t\t\t\t\t | \n\t\t\t\t\t
rs7498665 | \n\t\t\t\t\t\t16 | \n\t\t\t\t\t\t28,790,742 | \n\t\t\t\t\t\tSH2B1, ATP2A1 | \n\t\t\t\t\t\t25,344 | \n\t\t\t\t\t\t44% (G) | \n\t\t\t\t\t\t+0.45 kg/m2 for GG genotypec\n\t\t\t\t\t\t | \n\t\t\t\t\t
rs8050136 | \n\t\t\t\t\t\t16 | \n\t\t\t\t\t\t52,373,776 | \n\t\t\t\t\t\tFTO | \n\t\t\t\t\t\t25,344 | \n\t\t\t\t\t\t41% (A) | \n\t\t\t\t\t\t+1.07 kg/m2 for AA genotypec\n\t\t\t\t\t\t | \n\t\t\t\t\t
rs9939609 | \n\t\t\t\t\t\t16 | \n\t\t\t\t\t\t52,378,028 | \n\t\t\t\t\t\tFTO | \n\t\t\t\t\t\t38,759 | \n\t\t\t\t\t\t40% (A) | \n\t\t\t\t\t\t+0.40 kg/m2 per A allele | \n\t\t\t\t\t
rs9939609 | \n\t\t\t\t\t\t16 | \n\t\t\t\t\t\t52,378,028 | \n\t\t\t\t\t\tFTO | \n\t\t\t\t\t\t32,387 | \n\t\t\t\t\t\t41% (A) | \n\t\t\t\t\t\t+0.33 kg/m2 per A alleleb\n\t\t\t\t\t\t | \n\t\t\t\t\t
rs1421085 | \n\t\t\t\t\t\t16 | \n\t\t\t\t\t\t52,358,455 | \n\t\t\t\t\t\tFTO | \n\t\t\t\t\t\t2,796 | \n\t\t\t\t\t\t40% (C) | \n\t\t\t\t\t\t+0.112 kg/m2 per C alleled\n\t\t\t\t\t\t | \n\t\t\t\t\t
rs1424233 | \n\t\t\t\t\t\t16 | \n\t\t\t\t\t\t78,240,251 | \n\t\t\t\t\t\tMAF | \n\t\t\t\t\t\t2,796 | \n\t\t\t\t\t\t43% (A) | \n\t\t\t\t\t\t+0.091 kg/m2 per A allele in childrend\n\t\t\t\t\t\t | \n\t\t\t\t\t
rs1805081 | \n\t\t\t\t\t\t18 | \n\t\t\t\t\t\t19,394,429 | \n\t\t\t\t\t\tNPC1 | \n\t\t\t\t\t\t2,796 | \n\t\t\t\t\t\t44% (A) | \n\t\t\t\t\t\t-0.087 kg/m2 per A allele in childrend\n\t\t\t\t\t\t | \n\t\t\t\t\t
rs17782313 | \n\t\t\t\t\t\t18 | \n\t\t\t\t\t\t56,002,077 | \n\t\t\t\t\t\tMC4R | \n\t\t\t\t\t\t16,876 | \n\t\t\t\t\t\t24% (C) | \n\t\t\t\t\t\t+0.22 kg/m2 per C allele | \n\t\t\t\t\t
rs17782313 | \n\t\t\t\t\t\t18 | \n\t\t\t\t\t\t56,002,077 | \n\t\t\t\t\t\tMC4R | \n\t\t\t\t\t\t32,387 | \n\t\t\t\t\t\t22% (C) | \n\t\t\t\t\t\t+0.22 kg/m2 per C alleleb\n\t\t\t\t\t\t | \n\t\t\t\t\t
rs17782313 | \n\t\t\t\t\t\t18 | \n\t\t\t\t\t\t56,002,077 | \n\t\t\t\t\t\tMC4R | \n\t\t\t\t\t\t2,796 | \n\t\t\t\t\t\t17,5% (C) | \n\t\t\t\t\t\t+0.097 kg/m2 per C alleled | \n\t\t\t\t\t
rs12970134 | \n\t\t\t\t\t\t18 | \n\t\t\t\t\t\t56,035,730 | \n\t\t\t\t\t\tMC4R | \n\t\t\t\t\t\t25,344 | \n\t\t\t\t\t\t30% (A) | \n\t\t\t\t\t\t+0.36 kg/m2 for AA genotypec | \n\t\t\t\t\t
rs52820871 (I251L) | \n\t\t\t\t\t\t18 | \n\t\t\t\t\t\t56,189,806 | \n\t\t\t\t\t\tMC4R | \n\t\t\t\t\t\t16,797 | \n\t\t\t\t\t\t0.75% (251L) | \n\t\t\t\t\t\t-0.35 SD of their BMI Z-score/251L allele | \n\t\t\t\t\t
rs2229616 (V103I) | \n\t\t\t\t\t\t18 | \n\t\t\t\t\t\t56,190,256 | \n\t\t\t\t\t\tMC4R | \n\t\t\t\t\t\t7,713 | \n\t\t\t\t\t\t2% (103I) | \n\t\t\t\t\t\t-0.48 kg/m2 per 103I allele | \n\t\t\t\t\t
rs29941 | \n\t\t\t\t\t\t19 | \n\t\t\t\t\t\t39,001,372 | \n\t\t\t\t\t\tCHST8,KCTD15 | \n\t\t\t\t\t\t25,344 | \n\t\t\t\t\t\t70% (C) | \n\t\t\t\t\t\t+0.46 kg/m2 for CC genotypec\n\t\t\t\t\t\t | \n\t\t\t\t\t
rs11084753 | \n\t\t\t\t\t\t19 | \n\t\t\t\t\t\t39,013,977 | \n\t\t\t\t\t\tKCTD15 | \n\t\t\t\t\t\t32,387 | \n\t\t\t\t\t\t67% (G) | \n\t\t\t\t\t\t+0.06 kg/m2 per G alleleb\n\t\t\t\t\t\t | \n\t\t\t\t\t
\n\t\t\t\t\t\ta Either in the GWAS or the initial sample
\n\t\t\t\t\t\tb Reported in the population-based cohorts EPIC, FINRISK97, BPPP and METSIM (N = 18,812)
\n\t\t\t\t\t\tc Reported for the Islandic sample (N = 25,344)
\n\t\t\t\t\t\td Reported for children from the Northern Finland Birth Cohort (N = 5,291)
NEGR1: neuronal growth factor regulator 1; SEC16B; cerevisiae, homolog of, B; RASAL2: RAS protein activator like 2; TMEM18: transmembrane protein 18, INSIG2: insulin induced gene 2, SFRS10: splicing factor, arginine/serine-rich, 10; ETV5:etsvariant 5; DGKG diacylglycerol kinase, gamma, 90kD, GNPDA2: glucosamine-6-phosphate deaminase 2; PRL: prolactin; PTER: phosphotriesterase related; BDNF: brain derived neurotrophic factor; MTCH2: mitochondrial carrier homolog 2 (C. elegans); BCDIN3D: BCDIN3 domain containing; FAIM2: Fas apoptotic inhibitory molecule 2; SH2B1: SH2B adaptor protein 1; ATP2A1: ATPase, Ca++ transporting, cardiac muscle, fast twitch 1; FTO: fat mass and obesity associated; MAF: v-maf musculoaponeurotic fibrosarcoma oncogene homolog (avian); NPC1: Niemann-Pick disease, type C1; MC4R: melanocortin 4 receptor; CHST8: carbohydrate (N-acetylgalactosamine 4-0) sulfotransferase 8; KCTD15: potassium channel tetramerisation domain containing 15
Genetic variants with a polygenic effect on body weight in humans [50]
A large number of candidate gene association studies, of variable power, have been searched in obesity and related phenotypes. By far the most strongly replicated candidate gene from these analyses is melanocortin 4 receptor, but other replicated associations include those with adipokine and adipokine receptor genes. Further confirming the central role of behavioral stimuli in obesity, alleles of genes encoding dopamine, serotonin, and cannabinoid receptors (DRD2, HTR2C, and CBI) [74–76] are also reported to be associated with feeding behavior and related traits.
\n\t\t\tGenome-wide association studies have led to the identification of new candidate genes in obesity, most notably the “fat mass and obesity associated” gene (FTO). Rodent studies indicate that FTO mRNA is highly expressed in brain areas important for regulation of energy- and reward driven consumption. Food deprivation alters FTO expression in the hypothalamus in rats and mice. The contribution of the FTO variant is fairly modest, with adult homozygotes for the risk allele having only a 2- to 3-kg increase in weight [77], but the obesity high-risk allele is common in Caucasian populations and its effects begin early in life. Higher fat mass is observable from the age of 2 weeks, and carriage of the allele is associated with higher BMI and reduced satiety in children [11,50].
\n\t\t\tOther loci detected in genome wide association studies were identified in large study groups and via meta-analyses. Genome wide association studies (GWAS) reported novel obesity genes with small effects on human body weight. A total of more than 150,000 individuals was analyzed. Hinney et al. made a comprehensive review of these new loci in their paper published in 2010 in European Child Adolescent Psychiatry, see Table 3-adapted from Hinney et al [50].
\n\t\t\tAlternatively, the missing heritability may be accounted for by other genetic factors like genomic copy number variation and epigenetic modifications.
\n\t\t\t\n\t\tSome people have a different response of to environmental conditions and this may be the result of genetic variation alone, but there is increasing recognition that genetic expression related to disease risk may be modified by the environment during development. The “epigenetic changes” include methylation and alterations to histone proteins that alter the likelihood that specific genes are transcribed. Epigenetic changes usually occur during prenatal development or the early postnatal period. Maternal nutrition is a major factor leading to epigenetic changes. Thus, the levels of vitamins consumed in pregnancy, such as folate, methionine, and vitamin B12, which affect methylation become very important [78]. Undernutrition during prenatal development has been suggested to lead to postnatal consumption of a fatty diet. On the other hand, overnutrition of the mother is just as influential. The most convincingly shown factor is glycemic status during pregnancy. Hyperglycemia clearly affects infants’ birth weight but, beyond its effects on body weight, may increase the risk for subsequent development of insulin resistance and obesity. Nutritional signals reaching the developing hypothalamus during pregnancy may influence the sensitivity of these neurons to respond to similar signals postnatally. Infant nutrition in the neonatal period may also potentially affect future risk for obesity and its complications [79].
\n\t\tIn order to establish the diagnosis of overweight or obese in a child, the clinician must evaluate the BMI and compare it to the standardized reference chart, appropriate for the age and sex of the child. According to World Health Organization the definition of overweight and obesity in children is established at the following cut-offs [80]:
\n\t\t\tOverweight: >+1Standard Deviations (equivalent to BMI 25 kg/m2 at 19 years)
\n\t\t\tObesity: >+2 Standard Deviations (equivalent to BMI 30 kg/m2 at 19 years).
\n\t\t\tThe cumulative prevalence of monogenic obesity among children with severe obesity is about 5%. There are a lot of genes implicated in obesity and too many obese patients in the world to perform molecular study for everyone. Most genetic and hormonal causes of obesity are rare. The decision to test for these abnormalities should depend upon the presence of particular phenotypes and clinical features suggesting the possibility of a diagnosable disorder [table 4). The presence of severe obesity in a young child (<5 yr old) associated to extreme hyperphagia, severe insulin resistance disproportionate for the degree of obesity and a positive family history of early-onset obesity may support a genetic analysis.
\n\t\t\t\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t\n\t\t\t\t\t\t\t | \n\t\t\t\t\t
Early onset (!!! 5 years of age) | \n\t\t\t\t\t\tgenetic disorders | \n\t\t\t\t\t
Visual impairment and deafness | \n\t\t\t\t\t\tgenetic disorders | \n\t\t\t\t\t
Primary hypogonadotropic hypogonadism or hypogenitalism | \n\t\t\t\t\t\tgenetic disorders | \n\t\t\t\t\t
Family history: consanguineous relationships, other children affected | \n\t\t\t\t\t\tgenetic disorders | \n\t\t\t\t\t
Hyperphagia-often denied, ask specific questions such as waking at night to eat, demanding food very soon after a meal | \n\t\t\t\t\t\tif severe, suggests a genetic cause for obesity | \n\t\t\t\t\t
Mood disturbance and central obesity | \n\t\t\t\t\t\tCushing’s syndrome | \n\t\t\t\t\t
Frequent infections and fatigue | \n\t\t\t\t\t\tACTH deficiency due to POMC mutations | \n\t\t\t\t\t
Dry skin, constipation, intolerance to cold, or fatigue | \n\t\t\t\t\t\thypothyroidism | \n\t\t\t\t\t
Developmental delay | \n\t\t\t\t\t\tbehavioral disorders | \n\t\t\t\t\t
Short duration of obesity | \n\t\t\t\t\t\tendocrine or central cause | \n\t\t\t\t\t
Onset and tempo of pubertal development | \n\t\t\t\t\t\tendocrine disorders | \n\t\t\t\t\t
Damage to the CNS (e.g. infection, trauma, hemorrhage, radiation therapy, seizures) | \n\t\t\t\t\t\thypothalamic obesity, pituitary GH deficiency or pituitary hypothyroidism | \n\t\t\t\t\t
Morning headaches, vomiting, visual disturbances, excessive urination or drinking | \n\t\t\t\t\t\ttumor or mass in the hypothalamus | \n\t\t\t\t\t
Treatment with certain drugs or medications known to promote weight gain | \n\t\t\t\t\t\tobesity related to drugs | \n\t\t\t\t\t
\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t\n\t\t\t\t\t\t\t | \n\t\t\t\t\t
Dysmorphic features or skeletal dysplasia | \n\t\t\t\t\t\tgenetic disorders | \n\t\t\t\t\t
Red hair (if not familial) | \n\t\t\t\t\t\tmutations in POMC in white Caucasians | \n\t\t\t\t\t
Tall stature (on the upper centiles) | \n\t\t\t\t\t\tcommon obesity, but also MC4R deficiency | \n\t\t\t\t\t
Selective fat deposition (60%) | \n\t\t\t\t\t\tleptin and leptin receptor deficiency | \n\t\t\t\t\t
Short stature or a reduced rate of linear growth | \n\t\t\t\t\t\tGH deficiency, hypothyroidism, cortisol excess, pseudohypoparathyroidism, or a genetic syndrome such as Prader–Willi | \n\t\t\t\t\t
Central body fat distribution with purple striae | \n\t\t\t\t\t\tCushing’s syndrome | \n\t\t\t\t\t
Diminished growth rate and pubertal development | \n\t\t\t\t\t\tgrowth hormone deficiency, hypothyroidism, cortisol excess, and genetic syndromes | \n\t\t\t\t\t
Accelerated growth rate and pubertal development | \n\t\t\t\t\t\tprecocious puberty and some girls with PCOS | \n\t\t\t\t\t
Acanthosis nigricans | \n\t\t\t\t\t\tinsulin resistance | \n\t\t\t\t\t
\n\t\t\t\t\t\t\t | \n\t\t\t\t\t|
- Fasting and 2-hour glucose and insulin levels - Proinsulin if PC-1 deficiency considered - Fasting lipid panel - Thyroid function tests - Serum leptin - Karyotype, DNA for molecular diagnosis - Bone age, Growth hormone (GH) secretion and function tests, when indicated - Assessment of reproductive hormones, when indicated - Serum calcium, phosphorus, and parathyroid hormone levels to evaluate for suspected pseudohypoparathyroidism - MRI scan of the brain with focus on the hypothalamus and pituitary - ACTH, adrenocorticotropic hormone; - POMC, pro-opiomelanocortin; MAOI, monoamine oxidase inhibitor; MC4R, melanocortin-4 receptor; PC-1, prohormone convertase-1. | \n\t\t\t\t\t
Assessment of the obese child.
Obesity is caused by complex interactions between environment, behavior and genetic predisposition. The increased heath risk that obesity brings is well established by now. There is growing evidence that genetic predisposition presents a cornerstone role in the development of obesity. Nevertheless, despite the enormous success of genetic studies, there are still important gaps in knowledge. Obesity-specific gene expression pattern may help in understanding the pathogenic mechanisms of obesity and its associated metabolic diseases. Recent advances in identifying genetic risk factors for obesity have contributed to understanding disease pathology, which, in term, may lead to development of new therapeutic strategies, including personalized medicine. In the everyday practice of a clinician, when facing a patient with obesity, it is important to identify particular phenotypes and clinical features that can help to recognize the children who need genetic screening.
\n\t\tMany epidemiologic studies report an increase in incidence and prevalence of Crohn’s disease [CD] and Ulcerative Colitis (UC) in a global proportion. It is more evident in countries that going through an industrialization process, e.g., Asia, South America and Middle East [1, 2, 3]. The incidence follows the country industrialization and people living in urban areas has a greater incidence of IBD [4, 5]. The global prevalence of IBD has increased from 79.5 to 84.3 per 100,000 persons in recent years. IBD has been considered a disease of high-income regions. The USA had the highest age-standardized prevalence rate globally; approximately a quarter of total global patients with IBD living there in 2017. The UK had the highest age-standardized prevalence in Europe. The prevalence of IBD range from 252 to 439 cases per 100 000 population in the USA and 373 per 100 000 population in UK [6].
The complete mechanism of pathogenesis of IBD still unclear. IBD has a complex immune-mediated inflammatory disease that affects primarily the digestive tube. Those individuals with a genetic predisposition when exposed to different environmental factors may initiate an inflammatory response that is influenced by gut microbiome (Figure 1) [7]. The process is characterized by chronic relapsing and remitting inflammation for life.
Pathogenesis of IBD.
Many diet components were reported to be protective factors to IBD as fiber, short-chain fatty acids, wheat, gluten, zinc, vitamin D. On the other hand some kind of food may worsen the disease: FODMAPs, red meat, emulsifiers and sugar [8].
The interaction of diet components with the microbiome is not so simple: more fiber, less flares. Some patients complain worsening of symptoms with fibers consumption. One hypothesis is that altered microbiome may produce incomplete fermentation and then, originating pro-inflammatory byproducts as succinate [9].
The microbiome is the group of all organisms found in the whole gut and includes bacteria, fungi, viruses and protozoa. Most of them are found in the colon. Many studies showed that IBD patients have altered microbiome and pro-inflammatory bacteria. When you treat a patient with Crohn disease and make an ostomy avoid intestinal transit in affected bowel segment it result in decreased inflammation [10, 11, 12, 13].
Another evidence of environmental factor is the impairment in Peroxisome proliferator-activated receptors-γ (PPARγ) activity. Environmental pollutants can block the PPARy signaling pathway while mesalazine enhances its expression [14].
The Hippo pathway is an evolutionarily conserved pathway that controls organ size and homoeostasis through modulating cell proliferation, survival, apoptosis, and stemness. Hippo pathway is involved in the IBD pathogenesis, including intestinal cell regeneration, gut microbiota, and angio- genesis of the intestines [15, 16].
Crohn disease (CD) and Ulcerative Colitis (UC) are grouped as inflammatory bowel diseases but each one has distinct clinical characteristics (Table 1). These differences have to be in mind when a bowel resection and anastomosis is done in a patient with Crohn disease.
Differences | Crohn disease | Ulcerative colites |
---|---|---|
Full thickness inflammation of bowel wall | Compromise mucosa | |
All gastrointestinal segments; Generally ilium and colon; Non-continuous pattern. | Rectum and/or entire colon; Continuous pattern. | |
Abscesses, fistulas, strictures. | Bleeding, perforation, toxic megacolon. |
Characteristics of n disease (CD) and Ulcerative Colites (UC).
Clinically CD may be classified into three phenotypes: inflammatory, penetrating (fistulizing) and stricturing [17]. During the diagnosis evaluation 10% may be in the stricturing group and one decade later up to one third of patients may present stricturing Figure 2 [18, 19].
Natural progression of Crohn disease. (From Jacques Cosnes et al. [
The treatment of strictures may be done by endoscopy (endoscopic balloon dilatation, strictureplasty or surgical resection of bowel segment.
According to Cosnes et al. [18] the site of lesions is the most important factor to determine the disease behavior and progression to complication:
Small bowel and anoperineal > stricture and penetrating complications;
Esphagogastroduodenal and colon > inflammation.
In general, 75% of patients with strictures may require surgery once during lifetime but it may range from 70–90%. Right timing in indication of surgery for CD may reduce complication rates, diminish operative technical difficulties and stoma indication, less emergency surgeries and also better mortality rates [18, 20, 21].
As CD does not have cure, surgery has a well-defined hole in therapeutic armamentarium. The aim of surgery is to treat complications, control symptoms, to try to preserve bowel length and keep to bowel function (Table 2).
|
Indications for surgery in CD.
Endoscopy may confirm the IBD diagnosis in most cases up to 90% of patients with Crohn disease or Ulcerative colitis. It allows a detailed examination of the mucosa of terminal ilium, colon and rectum. It is considered the gold standard exam for IBD diagnosis. Enteroscopy is indicated in patients with normal colonoscopy and gastroscopy but present suspection of Crohn disease. Enteroscpy may be diagnostic or therapeutic with dilation of strictures areas (Figure 3) [22].
Enteroscopy showing lesions in the jejunum and normal ileum.
Both radiological methods CT or MR Enterography have been the best non-invasive exams to evaluate the small bowel in Crohn disease. Enterography may identify affected segments, disease activity and complications (abscess and fistula). Enterography may help to differentiate inflammatory or fibrotic areas of stenosis (Figure 4–6). Stricture is defined as a bowel segment with luminal narrowing and unequivocal upstream bowel dilation (Table 3) [23].
Axial contrast- enhanced CT enterography: homogeneous mural hyperenhancement (long arrow) and stratified mural hyperenhacement (short arrow).
A – Coronal T2 sequence MR enterography: homogeneous small bowel wall thickening and sacculations (arrow); B - Coronal T2 sequence MR enterography: small bowel wall thickening with stratified (bilaminar) mural hyperenhancement (arrow).
A – Coronal T2 sequence MR enterography: homogeneous small bowel wall thickening (arrow); B - Coronal contrast-enhanced fat-suppressed T1-weighted MR enterography: small bowel wall thickening with stratified (bilaminar) mural hyperenhancement (arrow).
Segmental mural hyperenhancement |
|
Wall thickening |
|
Stricture |
|
Radiological findings in CT or MR enterography in Crohn disease.
The primary approach is to resect the small bowel stricture. Resection is associated to lower rates of recurrence. Patients submitted do strictureplasty alone may present a higher rate of disease recurrence [24]. The patient should have a small length stricture and no prior resection (Table 4).
Crohn’s disease is a panintestinal disease, with intermittent activity and the potential of focal exacerbations throughout the patient’s life |
It is impossible to cure Crohn’s disease by excision. The surgeon is required only to treat the complications |
The essence of surgical treatment is to make the operation as safeas possible. If the operation becomes safe and patients survive, they will inevitably have recurrences and so repeated operations may be required. |
Therefore, it is important to conserve as much gut as possible All diseased bowels need not be excised, only that part with complications |
If only stenotic complications are being treated, perhaps the stenosis can be simply widened by strictureplasty or dilatation |
Five “Golden Rules” of surgical management of Crohn’s disease.
Surgery may be done by laparotomy or laparoscopy with same good results and 2 cm margins of normal tissue is advised to make an anastomosis. Both anastomosis may be used: hand-sewn or stapled.
When a ileocolic resection is done the mesentery should be removed. When mesentery is left it is associated with higher recurrence rates and reoperations [25].
Bypass surgery has been rarely employed due to the risk of neoplasia in the excluded segment [26, 27]. It may be an option to treat duodenal disease. There are two types of bypass: simples bypass and exclusion bypass [28]. Exclusion bypass is used when you cannot remove the affected segment because adherences to the retroperitoneum (Figure 7).
Bypass surgery: simples bypass (A) and exclusion bypass (B).
Strictureplasty is indicated to prevent small bowel syndrome in those patients after repeated resections or extensive bowel resections. Strictures are identified by palpation of the small bowel or alternatively introducing a 20 mm ball into the intestine and locating those points where the ball stops. The type of surgery is chosen according to the size of stricture (Table 5). The most used techniques are Heineke-Mikulicz 81%, Finney 10%, side-to-side isoperistaltic 5%, others 4%. The segments more affected are jejunum and/or ileum (94%), previous ileocolonic or ileorectal anastomosis (IRA) (4%), duodenum (1%), and colon (1%) [29, 30].
Size of stricture | Techniques |
---|---|
Short-length (<10 cm) | Heineke-Mikulicz |
Moskel-Walske-Neumayer | |
Judd | |
Medium-length (10–20 cm) | Finney |
Jaboulay | |
Long-length (>20 cm) | Michelassi |
Poggioli | |
Sasaki | |
Hotokezaka |
Techniques of strictureplasty.
Strictureplasty should be used in those patients with concern for development of short bowel syndrome [31, 32].
Diffuse involvement of the small bowel with multiple strictures.
Non phlegmonous fibrotic stricture.
Rapid recurrence of Crohn’s disease manifested as obstruction.
Stricture(s) in a patient who had undergone previous major resection(s) of small bowel (>100 cm).
Stricture in a patient with intestinal failure or short bowel syndrome.
Strictureplasty has some contraindications [29, 32]:
Colonic strictures.
Free or contained perforation of the small bowel.
Hypoalbuminemia (<2.0 g/dL).
Multiple strictures within a short segment.
Phlegmonous inflammation involving the affected site.
Stricture in close proximity to a site chosen for resection.
The technique of Heineke-Mikulicz [33, 34] (Figure 8) is the most used one and is similar to that used for pyloroplasty. A small incision over the stricture is extended to 2 cm in normal tissue. The incision is closed transversally: 1 or 2 layers with absorbable suture and continuous or separate stitch. The Moskel-Walske-Neumayer technique (Figure 9) is used when you have a great difference in the width of bowel to anastomosis. If you have a fistula in the stricture the Judd (Figure 10) technique is preferable to remove the fistula tract and repair the stenosis.
The Heineke-Mikulicz technique. A - Longitudinal incision; B - transverse suture; C - final aspect.
The Moskel-Walske-Neumayer technique. A-Stenosis between segments with different diameters; B - It is made an Y shape incision; C - A free-tension suture is made.
The Judd technique. A- stenosis with fistula; B - the fistula is removed; C - end-to-end anastomosis.
The Jaboulay technique requires 2 incisions in normal segments avoiding the center of the stenosis (Figure 11).
The Jaboulay technique (1): two incisions in normal segments. A1 - the diseased segment is escluded fron the incision; B1 - Posterior and C1 - anterior sutures are made. The Finney technique (2): A2- one incision including the deseased segment is made; B2 and C2 show the posterior and anterior sutures.
The Finney technique (Figure 11) consist in one incision along the stenosis reaching up the normal tissue and them the bowel is folded in a U shape to be closed.
In the Michelassi technique [35] the stenotic segment is divided in the middle and a longitudinal incision is made in both segments. A restoring anastomosis is made with the overlapping of both diseased segments (Figure 12). The Sasaki technique is a modification of Michelassi technique with the use of nonspatulated bowel ends to create an additional Heineke-Mikulicz strictureplasty on both ends [36] (Figure 12).
The Michelassi technique (1): A1 - anastomosis of two stenotic segments B1 - the edges of bowel can be trimmed to allow better approximation; C1 - latero-lateral anastomosis; D1- final aspect. The variation is the Sasaki technique (2): A2 - anastomosis of two diseased segments; B2 - the edges of bowels are mantained; C2 - the end of the anastomosis is then transversely closed; D2 - final aspect.
The Poggioli technique [37] is a modification of Michelassi technique and the difference is that we overlap a diseased segment with a non-diseased segment (Figure 13).
The Poggioli technique. A - long diseased segment; B - the diseased segment is separated from normal segment; C - a longitudinal incision is made in both segments; D - lateral enterostomy with overlap of affected and normal segments.
A combination of resection and enterostomy was described by Hotokezaka [38] (Figure 14). The bowel segment with severe stenosis is removed. The remaining segment with stenosis is divide in the midpoint. A side-to-side antimesenteric enterostomy with the 2 bowel segments are made and them and end-to-end anastomosis are made between the strictureplasty and the resection site.
The Hotokezaka technique. A - cecum and terminal ilium are resectes; B - a less affected segment is used to strictureplasty; C - Diseased segment is divide at the midle; D - side-to-side antimesenteric enterostomy with the 2 bowel segments is made; E - final aspect.
Results Strictureplasty vs. Resection.
The rate of complication for strictureplasty is about 4% to abscess, fistula and leakage [31]. Bowel resection is associated with lower recurrence rate (25.1%) compared to structureplasty (35.9%; p = 0.04). Recurrence-free survival was longer for bowel resection vs. strictureplasty (p = 0.02) [39, 40].
Surgical recurrence was higher for bowel resection (29.4%) vs. strictureplasty (39.7%; p = 0.002). No difference was observed for medical recurrence for bowel resection (12.4%) vs. strictureplasty (18.0%; p = 0.82) and also for overall morbidity between bowel resection (18.1%) vs. strictureplasty (10.7%; p = 0.65) [39, 40].
In fact, most cases a combination of techniques are used: resection for the severe lesion and plasty for the other. This approach seems to have the same rate of complications. This approach may decrease the risk of intestinal failure because patients may need future interventions and additional resection. Young age may be a risk for recurrent stricture. The 5-year reoperation rate for recurrent obstruction was 22% for resection alone, 30% for strictureplasty alone and 42% for strictureplasty and resection (P = 0.038) [39, 40].
Kono et al. [41] reported a new technique of anchored anastomosis that could prevent recurrence. After resection of a severe stenosis with linear staple both end are put together with suture and a Jaboulay like side-to-side anastomosis is performed [42] (Figure 15).
Kono-S anastomosis: A - stenosis is removed; B - the ends of both segments are closed; C - both ends are put send-to-end; D - longitudinal incisions are made in both segments; E - the suture column beside the laterallateral anastomosis may sustain the lumen open and prevent stenosis; F - final aspect.
The use of fecal diversion is not common but in some clinical conditions may be indicated [31]:
long-term and/or high-dose steroid use,
recent use of biologics,
malnutrition with hypoalbumenia (<2 g/dL).
Colonic Crohn disease may be treated by segmental or total colectomy with ileo-rectal anastomosis. Total proctocolectomy with definitive ileostomy are indicated in those patients with severe perineal disease. Ileal pouch–anal anastomosis is less indicated due to pouch complications.
Strictureplasty should not be used in large bowel because the risk of malignization. Chronic inflammation is a risk factor for colon cancer and dysplasia is considered to be the precursor of most colorectal cancer in IBD patients [43].
Due to its anatomical characteristics duodenal stricture may require different therapeutic alternatives: endoscopic dilatation, bypass, resection or strictureplasty. The incidence of duodenal or upper gastrointestinal tract by Crohn disease varies according to age: adults 0.3 to 5%, adolescents 28% and 43% in pediatric patients with CD [44]. Patients with duodenal CD may present more aggressive evolution with high rates of recurrence and needs for surgical treatments [45].
Clinically patient complain: Epigastric pain, nausea, anorexia, early satiety, blation and belching, weight, Less common symptoms are: anemia, diarrhea, feculent vominiting, hematemesis or melena [46].
Surgical treatment indication: outlet obstruction (83%), refractory pain (11%), and bleeding (5%) [47]. Surgical options are: resection, gastrojejunostomy, duodeno- jejunostomy, gastroduodenostomy and by-pass.
Ulcerative colitis (UC) is a chronic inflammatory condition of the colon and rectum. Initial therapeutic approach is based in different classes of medicine: anti-inflammatory, immunosuppressant (aminosalicylates, corticosteroids, thiopurines) and biological treatment as anti-tumor necrosis factor (anti-TNF), anti-integrins, anti-jak and other. However, most patients have successful clinical control and good evolution approximately 20–30% of patients will require surgery during their life [48].
However, surgery is a curative treatment for UC, the decision about an elective surgery is preference-sensitive. Generally, the indications for surgery are: medically refractory disease, dysplasia and carcinoma.
The surgery basically is total proctocolectomy with anastomosis or end ileostomy. The proctocolectomy with anastomosis is the ileal pouch–anal anastomosis (IPAA).
Total abdominal colectomy with ileorectal anastomosis is not indicated to patients with UC. The reasons are: half of patients will have a worsen disease in the rectum that will need protectomy and the risk of rectal cancer is 7–8% [49].
Proctocolectomy and ileal pouch–anal anastomosis (IPAA)
IPAA procedure may be done in stages:
Three-stage operation: (1) total colectomy with end ileostomy and rectal stump, (2) proctectomy with IPAA and loop ileostomy, and (3) ileostomy closure;
Two-stage operation: (1) total proctocolectomy with IPAA and loop ileostomy and (2) ileostomy tclosure;
One-stage operation: total proctocolectomy with IPAA and no diversion.
There are different types of pouch and most surgeons favor the J pouch due to the simplicity to construct and good outcomes. The procedure may be done by laparotomy, laparoscopy, robotic or associated approaches.
It is indicated for those patients who does not meet the criteria for IPAA. It is contraindicated in obese patients. The patient has to be able to handle the ostomy and do self-intubation.
Surgery for bowel Crohn disease is not curative and procedures hat to be as less aggressive as possible. Surgery is indicated only in those cases with complication as obstruction and fistula. Resection approach is preferable to patients without risk to develop short bowel syndrome. Strictureplasty may be used to preserve bowel integrity. Different techniques are used depend upon the length of the stenosis. Bowel Resection is associated with lower recurrence rate and longer recurrence-free survival.
Dr. Carlos Alberto Ximenes Filho for providing CT and MR figures.
The authors declare no conflict of interest.
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This chapter dwells on the sources and reactivity of phenolic compounds in water, their toxic effects on humans, and methods of their removal from water. Specific emphasis is placed on the techniques of their removal from water with attention on both conventional and advanced methods. Among these methods are ozonation, adsorption, extraction, photocatalytic degradation, biological, electro‐Fenton, adsorption and ion exchange and membrane‐based separation.",book:{id:"6029",slug:"phenolic-compounds-natural-sources-importance-and-applications",title:"Phenolic Compounds",fullTitle:"Phenolic Compounds - Natural Sources, Importance and Applications"},signatures:"William W. Anku, Messai A. Mamo and Penny P. 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In addition, the postharvest conditions may modify several phytochemical substances. Phenolic compounds are referred to as phytochemicals found in a large number of foods and beverages. The relative high diversity of these molecules produced by plants must be taken into account when methods of preparation are employed to obtain industrial or homemade products. Phenolic compounds comprise one (phenolic acids) or more (polyphenols) aromatic rings with attached hydroxyl groups in their structures. Their antioxidant capacities are related to these hydroxyl groups and phenolic rings. Despite the antioxidant activity, they have many other beneficial effects on human health. However, before attributing health benefits to these compounds, absorption, distribution, and metabolism of each phenolic compound in the body are important points that should be considered.",book:{id:"5609",slug:"phenolic-compounds-biological-activity",title:"Phenolic Compounds",fullTitle:"Phenolic Compounds - Biological Activity"},signatures:"Igor Otavio Minatel, Cristine Vanz Borges, Maria Izabela Ferreira,\nHector Alonzo Gomez Gomez, Chung-Yen Oliver Chen and\nGiuseppina Pace Pereira Lima",authors:[{id:"146379",title:"Dr.",name:"Giuseppina",middleName:null,surname:"Lima",slug:"giuseppina-lima",fullName:"Giuseppina Lima"},{id:"194002",title:"MSc.",name:"Cristine",middleName:null,surname:"Vanz Borges",slug:"cristine-vanz-borges",fullName:"Cristine Vanz Borges"},{id:"194003",title:"Prof.",name:"Igor Otavio",middleName:null,surname:"Minatel",slug:"igor-otavio-minatel",fullName:"Igor Otavio Minatel"},{id:"194004",title:"Dr.",name:"Maria Izabela",middleName:null,surname:"Ferreira",slug:"maria-izabela-ferreira",fullName:"Maria Izabela Ferreira"},{id:"194005",title:"Prof.",name:"Hector",middleName:null,surname:"Gomez-Gomez",slug:"hector-gomez-gomez",fullName:"Hector Gomez-Gomez"},{id:"194006",title:"Prof.",name:"Chung-Yen Oliver",middleName:null,surname:"Chen",slug:"chung-yen-oliver-chen",fullName:"Chung-Yen Oliver Chen"}]}],mostDownloadedChaptersLast30Days:[{id:"55500",title:"Interpretation of Mass Spectra",slug:"interpretation-of-mass-spectra",totalDownloads:12503,totalCrossrefCites:12,totalDimensionsCites:25,abstract:"The chapter includes an introduction to the main ionisation techniques in mass spectrometry and the way the resulting fragments can be analysed. First, the fundamental notions of mass spectrometry are explained, so that the reader can easily cover this chapter (graphs, main pick, molecular ion, illogical pick, nitrogen rule, etc.). Isotopic percentage and nominal mass calculation are also explained along with fragmentation mechanism. A paragraph emphasises the ionisation energy issues, the basics of ionisation voltage, the developing potential and the energy balance. A frame time of the main theoretical milestones in both theory and experimental mass spectrometry is highlighted here. In the second part of the chapter, the molecular fragmentation for alkanes, iso-alkanes, cycloalkanes, halogen, alcohols, phenols, ethers, carbonyl compounds, carboxylic acids and functional derivatives, nitrogen compounds (amines, nitro compounds), sulphur compounds, heterocycles and biomolecules (amino acids, steroids, triglycerides) is explained. Fragmentation schemes are followed by the simplified spectra, which help the understanding of such complex phenomena. At the end of the chapter, acquisition of mass spectrum is discussed. The chapter presented here is an introduction to mass spectrometry, which, we think, helps the understanding of the mechanism of fragmentation corroborating spectral data and molecular structures.",book:{id:"5735",slug:"mass-spectrometry",title:"Mass Spectrometry",fullTitle:"Mass Spectrometry"},signatures:"Teodor Octavian Nicolescu",authors:[{id:"196775",title:"Dr.",name:"Teodor Octavian",middleName:"Octavian",surname:"Nicolescu",slug:"teodor-octavian-nicolescu",fullName:"Teodor Octavian Nicolescu"}]},{id:"57909",title:"Validation of Analytical Methods",slug:"validation-of-analytical-methods",totalDownloads:6989,totalCrossrefCites:13,totalDimensionsCites:21,abstract:"Method validation is a key element in the establishment of reference methods and within the assessment of a laboratory’s competence in generating dependable analytical records. Validation has been placed within the context of the procedure, generating chemical data. Analytical method validation, thinking about the maximum relevant processes for checking the best parameters of analytical methods, using numerous relevant overall performance indicators inclusive of selectivity, specificity, accuracy, precision, linearity, range, limit of detection (LOD), limit of quantification (LOQ), ruggedness, and robustness are severely discussed in an effort to prevent their misguided utilization and ensure scientific correctness and consistency among publications.",book:{id:"6379",slug:"calibration-and-validation-of-analytical-methods-a-sampling-of-current-approaches",title:"Calibration and Validation of Analytical Methods",fullTitle:"Calibration and Validation of Analytical Methods - A Sampling of Current Approaches"},signatures:"Tentu Nageswara Rao",authors:[{id:"220824",title:"Dr.",name:"Tentu",middleName:null,surname:"Nageswara Rao",slug:"tentu-nageswara-rao",fullName:"Tentu Nageswara Rao"}]},{id:"55440",title:"Solubility Products and Solubility Concepts",slug:"solubility-products-and-solubility-concepts",totalDownloads:3090,totalCrossrefCites:6,totalDimensionsCites:7,abstract:"The chapter refers to a general concept of solubility product Ksp of sparingly soluble hydroxides and different salts and calculation of solubility of some hydroxides, oxides, and different salts in aqueous media. A (criticized) conventional approach, based on stoichiometry of a reaction notation and the solubility product of a precipitate, is compared with the unconventional/correct approach based on charge and concentration balances and a detailed physicochemical knowledge on the system considered, and calculations realized according to generalized approach to electrolytic systems (GATES) principles. An indisputable advantage of the latter approach is proved in simulation of static or dynamic, two-phase nonredox or redox systems.",book:{id:"5891",slug:"descriptive-inorganic-chemistry-researches-of-metal-compounds",title:"Descriptive Inorganic Chemistry Researches of Metal Compounds",fullTitle:"Descriptive Inorganic Chemistry Researches of Metal Compounds"},signatures:"Anna Maria Michałowska-Kaczmarczyk, Aneta Spórna-Kucab and\nTadeusz Michałowski",authors:[{id:"35273",title:"Prof.",name:"Tadeusz",middleName:null,surname:"Michalowski",slug:"tadeusz-michalowski",fullName:"Tadeusz Michalowski"},{id:"203867",title:"Dr.",name:"Anna Maria",middleName:null,surname:"Michałowska-Kaczmarczyk",slug:"anna-maria-michalowska-kaczmarczyk",fullName:"Anna Maria Michałowska-Kaczmarczyk"},{id:"203868",title:"Dr.",name:"Aneta",middleName:null,surname:"Spórna-Kucab",slug:"aneta-sporna-kucab",fullName:"Aneta Spórna-Kucab"}]},{id:"62736",title:"Radioisotope: Applications, Effects, and Occupational Protection",slug:"radioisotope-applications-effects-and-occupational-protection",totalDownloads:4543,totalCrossrefCites:10,totalDimensionsCites:17,abstract:"This chapter presents a brief introduction to radioisotopes, sources and types of radiation, applications, effects, and occupational protection. The natural and artificial sources of radiations are discussed with special reference to natural radioactive decay series and artificial radioisotopes. Applications have played significant role in improving the quality of human life. The application of radioisotopes in tracing, radiography, food preservation and sterilization, eradication of insects and pests, medical diagnosis and therapy, and new variety of crops in agricultural field is briefly described. Radiation interacts with matter to produce excitation and ionization of an atom or molecule; as a result physical and biological effects are produced. These effects and mechanisms are discussed. The dosimetric quantities used in radiological protection are described. Radiological protections and the control of occupational and medical exposures are briefly described.",book:{id:"5903",slug:"principles-and-applications-in-nuclear-engineering-radiation-effects-thermal-hydraulics-radionuclide-migration-in-the-environment",title:"Principles and Applications in Nuclear Engineering",fullTitle:"Principles and Applications in Nuclear Engineering - Radiation Effects, Thermal Hydraulics, Radionuclide Migration in the Environment"},signatures:"Sannappa Jadiyappa",authors:[{id:"239626",title:"Dr.",name:null,middleName:null,surname:"Sannappa J.",slug:"sannappa-j.",fullName:"Sannappa J."}]},{id:"58596",title:"Linearity of Calibration Curves for Analytical Methods: A Review of Criteria for Assessment of Method Reliability",slug:"linearity-of-calibration-curves-for-analytical-methods-a-review-of-criteria-for-assessment-of-method",totalDownloads:8095,totalCrossrefCites:19,totalDimensionsCites:44,abstract:"Calibration curve is a regression model used to predict the unknown concentrations of analytes of interest based on the response of the instrument to the known standards. Some statistical analyses are required to choose the best model fitting to the experimental data and also evaluate the linearity and homoscedasticity of the calibration curve. Using an internal standard corrects for the loss of analyte during sample preparation and analysis provided that it is selected appropriately. After the best regression model is selected, the analytical method needs to be validated using quality control (QC) samples prepared and stored in the same temperature as intended for the study samples. Most of the international guidelines require that the parameters, including linearity, specificity, selectivity, accuracy, precision, lower limit of quantification (LLOQ), matrix effect and stability, be assessed during validation. Despite the highly regulated area, some challenges still exist regarding the validation of some analytical methods including methods when no analyte-free matrix is available.",book:{id:"6379",slug:"calibration-and-validation-of-analytical-methods-a-sampling-of-current-approaches",title:"Calibration and Validation of Analytical Methods",fullTitle:"Calibration and Validation of Analytical Methods - A Sampling of Current Approaches"},signatures:"Seyed Mojtaba Moosavi and Sussan Ghassabian",authors:[{id:"216099",title:"Dr.",name:"Sussan",middleName:null,surname:"Ghassabian",slug:"sussan-ghassabian",fullName:"Sussan Ghassabian"},{id:"216101",title:"Mr.",name:"Seyed Mojtaba",middleName:null,surname:"Moosavi",slug:"seyed-mojtaba-moosavi",fullName:"Seyed Mojtaba Moosavi"}]}],onlineFirstChaptersFilter:{topicId:"8",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"83005",title:"Catalytic Behavior of Extended π-Conjugation in the Kinetics of Sensitizer-Mediator Interaction",slug:"catalytic-behavior-of-extended-conjugation-in-the-kinetics-of-sensitizer-mediator-interaction",totalDownloads:3,totalDimensionsCites:0,doi:"10.5772/intechopen.106511",abstract:"This chapter discusses the catalytic effect of extended π-conjugation on the electron transfer process between ferricyphen-ferrocyanide and ferricypyr-ferrocyanide in an aqueous medium. Ferricyphen and ferricypyr may be feasible options for the sensitizer in dye-sensitized solar cells due to their high reduction potential, stability, capability as an outer-sphere oxidant, and photosensitivity. Meanwhile, ferrocyanide could be used as a mediator in DSSCs instead of iodide to avoid iodate production and achieve a similar reduction potential and stability. This chapter compared the ability of competent putative sensitizers to oxidize the likely mediator in water. In contrast to the 2,2′-dipyridyl chelate, the extended π-conjugation in 1,10-phenanthroline accelerated the redox process by increasing the electron affinity of ferricyphen as compared to ferricypyr. The reactions had the same kinetics but different rate constants, indicating that the ferricyphen-ferrocyanide reaction was several times faster than the ferricypyr-ferrocyanide reaction, revealing and confirming the catalytic influence of extended π-conjugation on the redox process.",book:{id:"11217",title:"Recent Advances in Chemical Kinetics",coverURL:"https://cdn.intechopen.com/books/images_new/11217.jpg"},signatures:"Rozina Khattak"},{id:"83004",title:"Pyridine Heterocycles in the Therapy of Oncological Diseases",slug:"pyridine-heterocycles-in-the-therapy-of-oncological-diseases",totalDownloads:1,totalDimensionsCites:0,doi:"10.5772/intechopen.106406",abstract:"Oncological diseases pose a major challenge for modern medicine. Heterocyclic compounds play a vital role in modern medical and pharmaceutical science as most medicinal substances incorporate them. Nitrogen-containing heterocycles serve as the basis of numerous drugs and, therefore, are deeply involved in the design and synthesis of promising new therapeutic agents. Pyridine or pyrimidine scaffolds, with a number of substituents attached, comprise a large portion of FDA-approved drugs. They are chemically stable in the human body, manifest an affinity for DNA via hydrogen bonding, and present an opportunity for the development of novel anticancer agents. A large number of pyridine-based molecules are synthesized and tested for anticancer activity each year. The present chapter aims to introduce the most current synthetic approaches, published in scientific literature, and would also elaborate on structure-activity relationships described therein.",book:{id:"11562",title:"Chemistry with Pyridine Derivatives",coverURL:"https://cdn.intechopen.com/books/images_new/11562.jpg"},signatures:"Lozan T. Todorov and Irena P. Kostova"},{id:"82969",title:"Utilizing Photocatalysts in Reducing Moisture Absorption in Composites of Natural Fibers",slug:"utilizing-photocatalysts-in-reducing-moisture-absorption-in-composites-of-natural-fibers",totalDownloads:3,totalDimensionsCites:0,doi:"10.5772/intechopen.106543",abstract:"Due to growing environmental consciousness and the depletion of oil supplies, numerous efforts have been made to replace synthetic fibers in fiber-reinforced composites with natural fibers (NFr). The low cost and abundance of NFr and its biodegradability and low density have encouraged researchers worldwide to study their potential applications in several industrial sectors. However, NFr has several disadvantages: excessive moisture absorption and subsequent swelling and degradation, low chemical and fire resistance, and insufficient interfacial interactions with polymers. Consequently, there is great interest in modifying the surface of NFr using a variety of methods. This chapter presents an overview of the NFr, its characterization, the problems associated with adding NFr to polymer composites. This literature survey suggests an in-depth review of photocatalysis by utilizing photocatalysts nanoparticle (PHNPs) aimed at increasing the hydrophobicity and interfacial bonding between the NFr and the matrix Using a photo-induced oxidation mechanism to disassemble water molecules, pollutants, and bacteria in a wet environment. Additionally, we reviewed the effects of these PHNPs on the moisture absorption, mechanical characteristics, and dimensional stability of NFr composites. As a result, this review article may make a valuable contribution to researchers interested in coating and treating NFr to further enhance their surface characteristics.",book:{id:"11559",title:"Photocatalysts - New Perspectives",coverURL:"https://cdn.intechopen.com/books/images_new/11559.jpg"},signatures:"Mohammed Mohammed and Rozyanty Rahman"},{id:"82853",title:"Revealing Retention Mechanisms in Liquid Chromatography: QSRR Approach",slug:"revealing-retention-mechanisms-in-liquid-chromatography-qsrr-approach",totalDownloads:9,totalDimensionsCites:0,doi:"10.5772/intechopen.106245",abstract:"One-factor-at-a-time experimentation was used for a long time as gold-standard optimization for liquid chromatographic (LC) method development. This approach has two downsides as it requires a needlessly great number of experimental runs and it is unable to identify possible factor interactions. At the end of the last century, however, this problem could be solved with the introduction of new chemometric strategies. This chapter aims at presenting quantitative structure–retention relationship (QSRR) models with structuring possibilities, from the point of feature selection through various machine learning algorithms that can be used in model building, for internal and external validation of the proposed models. The presented strategies of QSRR model can be a good starting point for analysts to use and adopt them as a good practice for their applications. QSRR models can be used in predicting the retention behavior of compounds, to point out the molecular features governing the retention, and consequently to gain insight into the retention mechanisms. In terms of these applications, special attention was drawn to modified chromatographic systems, characterized by mobile or stationary phase modifications. Although chromatographic methods are applied in a wide variety of fields, the greatest attention has been devoted to the analysis of pharmaceuticals.",book:{id:"11557",title:"Chemometrics - Recent Advances, New Perspectives and Applications",coverURL:"https://cdn.intechopen.com/books/images_new/11557.jpg"},signatures:"Jovana Krmar, Bojana Svrkota, Nevena Đajić, Jevrem Stojanović, Ana Protić and Biljana Otašević"},{id:"82796",title:"A Revisit of the Underlying Fundamentals in the Laser Emission from BODIPYs",slug:"a-revisit-of-the-underlying-fundamentals-in-the-laser-emission-from-bodipys",totalDownloads:15,totalDimensionsCites:0,doi:"10.5772/intechopen.106334",abstract:"This chapter aims to provide a comprehensive assessment of the laser performance of commercially available laser dyes based on the boron-dipyrromethene (BODIPY) chromophore in a liquid state, as well as to remark the main underlying photophysical signatures triggering such photonic behavior. First, we describe their light absorption and fluorescence properties in solution. This spectroscopic study is supplemented with quantum mechanics calculations and electrochemical measurements. Afterward, the dyes are tested as active media of tunable lasers under transversal pumping. The recorded laser efficiencies and photostabilities are correlated with the registered photophysical properties identifying the main structural guidelines and photonic parameters, which rule the laser bands’ position, intensity, and stability. As a result, we provide a comparative dataset of the laser performance, not available hitherto. Besides, the unraveling of the complex molecular structure-photophysics-laser relationship should help in the rational design of new tunable dye lasers with an improved photonic response along the entire visible region and reaching eventually the near infrared.",book:{id:"12081",title:"Dyes and Pigments - Insights and Applications",coverURL:"https://cdn.intechopen.com/books/images_new/12081.jpg"},signatures:"Alaitz Peñafiel, Ainhoa Oliden-Sánchez, Edurne Avellanal-Zaballa, Leire Gartzia-Rivero, Rebeca Sola-Llano and Jorge Bañuelos"},{id:"82706",title:"Applications of Near-Infrared Spectroscopy (NIRS) in Fish Value Chain",slug:"applications-of-near-infrared-spectroscopy-nirs-in-fish-value-chain",totalDownloads:18,totalDimensionsCites:0,doi:"10.5772/intechopen.105736",abstract:"Near-infrared spectroscopy (NIRS) has undergone a significant evolution in the last years due to the numerous scientific studies that revealed its potential for industrial applications, attracting a growing interest in the food sector. Furthermore, new advances have allowed the reduction in size and cost of the NIR devices, making them appropriate for on-site determinations. The complex structure of the fish value chain, combined to its high market value, makes this sector particularly vulnerable to fraud and adulteration practices. Also, the perishable nature of fish and fish products, as well as the lack of traceability, arises the urgent need for a fast, reliable and portable tool capable of precisely characterizing the quality and authenticity of the product while also ensuring its safety. In this chapter, the capabilities of NIRS combined to several chemometric techniques for quality, authenticity and safety applications are presented through an extensive review of the most recent research works.",book:{id:"11564",title:"Infrared Spectroscopy - Perspectives and Applications",coverURL:"https://cdn.intechopen.com/books/images_new/11564.jpg"},signatures:"Sonia Nieto-Ortega, Rebeca Lara, Giuseppe Foti, Ángela Melado-Herreros and Idoia Olabarrieta"}],onlineFirstChaptersTotal:58},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:90,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:108,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:33,numberOfPublishedChapters:330,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:14,numberOfPublishedChapters:145,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:9,numberOfPublishedChapters:141,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:123,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:112,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:22,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:11,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:"2753-6580",doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}}]},series:{item:{id:"7",title:"Biomedical Engineering",doi:"10.5772/intechopen.71985",issn:"2631-5343",scope:"Biomedical Engineering is one of the fastest-growing interdisciplinary branches of science and industry. The combination of electronics and computer science with biology and medicine has improved patient diagnosis, reduced rehabilitation time, and helped to facilitate a better quality of life. Nowadays, all medical imaging devices, medical instruments, or new laboratory techniques result from the cooperation of specialists in various fields. The series of Biomedical Engineering books covers such areas of knowledge as chemistry, physics, electronics, medicine, and biology. This series is intended for doctors, engineers, and scientists involved in biomedical engineering or those wanting to start working in this field.",coverUrl:"https://cdn.intechopen.com/series/covers/7.jpg",latestPublicationDate:"August 14th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:12,editor:{id:"50150",title:"Prof.",name:"Robert",middleName:null,surname:"Koprowski",slug:"robert-koprowski",fullName:"Robert Koprowski",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYTYNQA4/Profile_Picture_1630478535317",biography:"Robert Koprowski, MD (1997), PhD (2003), Habilitation (2015), is an employee of the University of Silesia, Poland, Institute of Computer Science, Department of Biomedical Computer Systems. For 20 years, he has studied the analysis and processing of biomedical images, emphasizing the full automation of measurement for a large inter-individual variability of patients. Dr. Koprowski has authored more than a hundred research papers with dozens in impact factor (IF) journals and has authored or co-authored six books. Additionally, he is the author of several national and international patents in the field of biomedical devices and imaging. Since 2011, he has been a reviewer of grants and projects (including EU projects) in biomedical engineering.",institutionString:null,institution:{name:"University of Silesia",institutionURL:null,country:{name:"Poland"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:4,paginationItems:[{id:"14",title:"Cell and Molecular Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/14.jpg",isOpenForSubmission:!0,editor:{id:"165627",title:"Dr.",name:"Rosa María",middleName:null,surname:"Martínez-Espinosa",slug:"rosa-maria-martinez-espinosa",fullName:"Rosa María Martínez-Espinosa",profilePictureURL:"https://mts.intechopen.com/storage/users/165627/images/system/165627.jpeg",biography:"Dr. Rosa María Martínez-Espinosa has been a Spanish Full Professor since 2020 (Biochemistry and Molecular Biology) and is currently Vice-President of International Relations and Cooperation development and leader of the research group 'Applied Biochemistry” (University of Alicante, Spain). Other positions she has held at the university include Vice-Dean of Master Programs, Vice-Dean of the Degree in Biology and Vice-Dean for Mobility and Enterprise and Engagement at the Faculty of Science (University of Alicante). She received her Bachelor in Biology in 1998 (University of Alicante) and her PhD in 2003 (Biochemistry, University of Alicante). She undertook post-doctoral research at the University of East Anglia (Norwich, U.K. 2004-2005; 2007-2008).\nHer multidisciplinary research focuses on investigating archaea and their potential applications in biotechnology. She has an H-index of 21. She has authored one patent and has published more than 70 indexed papers and around 60 book chapters.\nShe has contributed to more than 150 national and international meetings during the last 15 years. Her research interests include archaea metabolism, enzymes purification and characterization, gene regulation, carotenoids and bioplastics production, antioxidant\ncompounds, waste water treatments, and brines bioremediation.\nRosa María’s other roles include editorial board member for several journals related\nto biochemistry, reviewer for more than 60 journals (biochemistry, molecular biology, biotechnology, chemistry and microbiology) and president of several organizing committees in international meetings related to the N-cycle or respiratory processes.",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"15",title:"Chemical Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",isOpenForSubmission:!0,editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",slug:"sukru-beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",biography:"Dr. Şükrü Beydemir obtained a BSc in Chemistry in 1995 from Yüzüncü Yıl University, MSc in Biochemistry in 1998, and PhD in Biochemistry in 2002 from Atatürk University, Turkey. He performed post-doctoral studies at Max-Planck Institute, Germany, and University of Florence, Italy in addition to making several scientific visits abroad. He currently works as a Full Professor of Biochemistry in the Faculty of Pharmacy, Anadolu University, Turkey. Dr. Beydemir has published over a hundred scientific papers spanning protein biochemistry, enzymology and medicinal chemistry, reviews, book chapters and presented several conferences to scientists worldwide. He has received numerous publication awards from various international scientific councils. He serves in the Editorial Board of several international journals. Dr. Beydemir is also Rector of Bilecik Şeyh Edebali University, Turkey.",institutionString:null,institution:{name:"Anadolu University",institutionURL:null,country:{name:"Turkey"}}},editorTwo:{id:"13652",title:"Prof.",name:"Deniz",middleName:null,surname:"Ekinci",slug:"deniz-ekinci",fullName:"Deniz Ekinci",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYLT1QAO/Profile_Picture_1634557223079",biography:"Dr. Deniz Ekinci obtained a BSc in Chemistry in 2004, MSc in Biochemistry in 2006, and PhD in Biochemistry in 2009 from Atatürk University, Turkey. He studied at Stetson University, USA, in 2007-2008 and at the Max Planck Institute of Molecular Cell Biology and Genetics, Germany, in 2009-2010. Dr. Ekinci currently works as a Full Professor of Biochemistry in the Faculty of Agriculture and is the Head of the Enzyme and Microbial Biotechnology Division, Ondokuz Mayıs University, Turkey. He is a member of the Turkish Biochemical Society, American Chemical Society, and German Genetics society. Dr. Ekinci published around ninety scientific papers, reviews and book chapters, and presented several conferences to scientists. He has received numerous publication awards from several scientific councils. Dr. Ekinci serves as the Editor in Chief of four international books and is involved in the Editorial Board of several international journals.",institutionString:null,institution:{name:"Ondokuz Mayıs University",institutionURL:null,country:{name:"Turkey"}}},editorThree:null},{id:"17",title:"Metabolism",coverUrl:"https://cdn.intechopen.com/series_topics/covers/17.jpg",isOpenForSubmission:!0,editor:{id:"138626",title:"Dr.",name:"Yannis",middleName:null,surname:"Karamanos",slug:"yannis-karamanos",fullName:"Yannis Karamanos",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002g6Jv2QAE/Profile_Picture_1629356660984",biography:"Yannis Karamanos, born in Greece in 1953, completed his pre-graduate studies at the Université Pierre et Marie Curie, Paris, then his Masters and Doctoral degree at the Université de Lille (1983). He was associate professor at the University of Limoges (1987) before becoming full professor of biochemistry at the Université d’Artois (1996). He worked on the structure-function relationships of glycoconjugates and his main project was the investigations on the biological roles of the de-N-glycosylation enzymes (Endo-N-acetyl-β-D-glucosaminidase and peptide-N4-(N-acetyl-β-glucosaminyl) asparagine amidase). From 2002 he contributes to the understanding of the Blood-brain barrier functioning using proteomics approaches. He has published more than 70 papers. His teaching areas are energy metabolism and regulation, integration and organ specialization and metabolic adaptation.",institutionString:null,institution:{name:"Artois University",institutionURL:null,country:{name:"France"}}},editorTwo:null,editorThree:null},{id:"18",title:"Proteomics",coverUrl:"https://cdn.intechopen.com/series_topics/covers/18.jpg",isOpenForSubmission:!0,editor:{id:"200689",title:"Prof.",name:"Paolo",middleName:null,surname:"Iadarola",slug:"paolo-iadarola",fullName:"Paolo Iadarola",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSCl8QAG/Profile_Picture_1623568118342",biography:"Paolo Iadarola graduated with a degree in Chemistry from the University of Pavia (Italy) in July 1972. He then worked as an Assistant Professor at the Faculty of Science of the same University until 1984. In 1985, Prof. Iadarola became Associate Professor at the Department of Biology and Biotechnologies of the University of Pavia and retired in October 2017. Since then, he has been working as an Adjunct Professor in the same Department at the University of Pavia. His research activity during the first years was primarily focused on the purification and structural characterization of enzymes from animal and plant sources. During this period, Prof. Iadarola familiarized himself with the conventional techniques used in column chromatography, spectrophotometry, manual Edman degradation, and electrophoresis). Since 1995, he has been working on: i) the determination in biological fluids (serum, urine, bronchoalveolar lavage, sputum) of proteolytic activities involved in the degradation processes of connective tissue matrix, and ii) on the identification of biological markers of lung diseases. In this context, he has developed and validated new methodologies (e.g., Capillary Electrophoresis coupled to Laser-Induced Fluorescence, CE-LIF) whose application enabled him to determine both the amounts of biochemical markers (Desmosines) in urine/serum of patients affected by Chronic Obstructive Pulmonary Disease (COPD) and the activity of proteolytic enzymes (Human Neutrophil Elastase, Cathepsin G, Pseudomonas aeruginosa elastase) in sputa of these patients. More recently, Prof. Iadarola was involved in developing techniques such as two-dimensional electrophoresis coupled to liquid chromatography/mass spectrometry (2DE-LC/MS) for the proteomic analysis of biological fluids aimed at the identification of potential biomarkers of different lung diseases. He is the author of about 150 publications (According to Scopus: H-Index: 23; Total citations: 1568- According to WOS: H-Index: 20; Total Citations: 1296) of peer-reviewed international journals. He is a Consultant Reviewer for several journals, including the Journal of Chromatography A, Journal of Chromatography B, Plos ONE, Proteomes, International Journal of Molecular Science, Biotech, Electrophoresis, and others. He is also Associate Editor of Biotech.",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorTwo:{id:"201414",title:"Dr.",name:"Simona",middleName:null,surname:"Viglio",slug:"simona-viglio",fullName:"Simona Viglio",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKDHQA4/Profile_Picture_1630402531487",biography:"Simona Viglio is an Associate Professor of Biochemistry at the Department of Molecular Medicine at the University of Pavia. She has been working since 1995 on the determination of proteolytic enzymes involved in the degradation process of connective tissue matrix and on the identification of biological markers of lung diseases. She gained considerable experience in developing and validating new methodologies whose applications allowed her to determine both the amount of biomarkers (Desmosine and Isodesmosine) in the urine of patients affected by COPD, and the activity of proteolytic enzymes (HNE, Cathepsin G, Pseudomonas aeruginosa elastase) in the sputa of these patients. Simona Viglio was also involved in research dealing with the supplementation of amino acids in patients with brain injury and chronic heart failure. She is presently engaged in the development of 2-DE and LC-MS techniques for the study of proteomics in biological fluids. The aim of this research is the identification of potential biomarkers of lung diseases. She is an author of about 90 publications (According to Scopus: H-Index: 23; According to WOS: H-Index: 20) on peer-reviewed journals, a member of the “Società Italiana di Biochimica e Biologia Molecolare,“ and a Consultant Reviewer for International Journal of Molecular Science, Journal of Chromatography A, COPD, Plos ONE and Nutritional Neuroscience.",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorThree:null}]},overviewPageOFChapters:{paginationCount:42,paginationItems:[{id:"82914",title:"Glance on the Critical Role of IL-23 Receptor Gene Variations in Inflammation-Induced Carcinogenesis",doi:"10.5772/intechopen.105049",signatures:"Mohammed El-Gedamy",slug:"glance-on-the-critical-role-of-il-23-receptor-gene-variations-in-inflammation-induced-carcinogenesis",totalDownloads:12,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Chemokines Updates",coverURL:"https://cdn.intechopen.com/books/images_new/11672.jpg",subseries:{id:"18",title:"Proteomics"}}},{id:"82875",title:"Lipidomics as a Tool in the Diagnosis and Clinical Therapy",doi:"10.5772/intechopen.105857",signatures:"María Elizbeth Alvarez Sánchez, Erick Nolasco Ontiveros, Rodrigo Arreola, Adriana Montserrat Espinosa González, Ana María García Bores, Roberto Eduardo López Urrutia, Ignacio Peñalosa Castro, María del Socorro Sánchez Correa and Edgar Antonio Estrella Parra",slug:"lipidomics-as-a-tool-in-the-diagnosis-and-clinical-therapy",totalDownloads:7,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Fatty Acids - Recent Advances",coverURL:"https://cdn.intechopen.com/books/images_new/11669.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"82440",title:"Lipid Metabolism and Associated Molecular Signaling Events in Autoimmune Disease",doi:"10.5772/intechopen.105746",signatures:"Mohan Vanditha, Sonu Das and Mathew John",slug:"lipid-metabolism-and-associated-molecular-signaling-events-in-autoimmune-disease",totalDownloads:17,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Fatty Acids - Recent Advances",coverURL:"https://cdn.intechopen.com/books/images_new/11669.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"82483",title:"Oxidative Stress in Cardiovascular Diseases",doi:"10.5772/intechopen.105891",signatures:"Laura Mourino-Alvarez, Tamara Sastre-Oliva, Nerea Corbacho-Alonso and Maria G. 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She is also the Global Harmonization Initiative (GHI)",institutionString:"Australian College of Business & Technology",institution:{name:"Kobe College",institutionURL:null,country:{name:"Japan"}}}]},{type:"book",id:"6820",title:"Keratin",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/6820.jpg",slug:"keratin",publishedDate:"December 19th 2018",editedByType:"Edited by",bookSignature:"Miroslav Blumenberg",hash:"6def75cd4b6b5324a02b6dc0359896d0",volumeInSeries:2,fullTitle:"Keratin",editors:[{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"Blumenberg",slug:"miroslav-blumenberg",fullName:"Miroslav Blumenberg",profilePictureURL:"https://mts.intechopen.com/storage/users/31610/images/system/31610.jpg",biography:"Miroslav Blumenberg, Ph.D., was born in Subotica and received his BSc in Belgrade, Yugoslavia. He completed his Ph.D. at MIT in Organic Chemistry; he followed up his Ph.D. with two postdoctoral study periods at Stanford University. 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Évora",institutionURL:null,country:{name:"Portugal"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null}]},subseriesFiltersForPublishedBooks:[{group:"subseries",caption:"Animal Nutrition",value:20,count:2},{group:"subseries",caption:"Animal Reproductive Biology and Technology",value:28,count:4},{group:"subseries",caption:"Animal Science",value:19,count:5}],publicationYearFilters:[{group:"publicationYear",caption:"2022",value:2022,count:3},{group:"publicationYear",caption:"2021",value:2021,count:3},{group:"publicationYear",caption:"2020",value:2020,count:3},{group:"publicationYear",caption:"2019",value:2019,count:1},{group:"publicationYear",caption:"2018",value:2018,count:1}],authors:{paginationCount:148,paginationItems:[{id:"165328",title:"Dr.",name:"Vahid",middleName:null,surname:"Asadpour",slug:"vahid-asadpour",fullName:"Vahid Asadpour",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/165328/images/system/165328.jpg",biography:"Vahid Asadpour, MS, Ph.D., is currently with the Department of Research and Evaluation, Kaiser Permanente Southern California. He has both an MS and Ph.D. in Biomedical Engineering. He was previously a research scientist at the University of California Los Angeles (UCLA) and visiting professor and researcher at the University of North Dakota. He is currently working in artificial intelligence and its applications in medical signal processing. In addition, he is using digital signal processing in medical imaging and speech processing. Dr. Asadpour has developed brain-computer interfacing algorithms and has published books, book chapters, and several journal and conference papers in this field and other areas of intelligent signal processing. He has also designed medical devices, including a laser Doppler monitoring system.",institutionString:"Kaiser Permanente Southern California",institution:null},{id:"169608",title:"Prof.",name:"Marian",middleName:null,surname:"Găiceanu",slug:"marian-gaiceanu",fullName:"Marian Găiceanu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/169608/images/system/169608.png",biography:"Prof. Dr. Marian Gaiceanu graduated from the Naval and Electrical Engineering Faculty, Dunarea de Jos University of Galati, Romania, in 1997. He received a Ph.D. (Magna Cum Laude) in Electrical Engineering in 2002. Since 2017, Dr. Gaiceanu has been a Ph.D. supervisor for students in Electrical Engineering. He has been employed at Dunarea de Jos University of Galati since 1996, where he is currently a professor. Dr. Gaiceanu is a member of the National Council for Attesting Titles, Diplomas and Certificates, an expert of the Executive Agency for Higher Education, Research Funding, and a member of the Senate of the Dunarea de Jos University of Galati. He has been the head of the Integrated Energy Conversion Systems and Advanced Control of Complex Processes Research Center, Romania, since 2016. He has conducted several projects in power converter systems for electrical drives, power quality, PEM and SOFC fuel cell power converters for utilities, electric vehicles, and marine applications with the Department of Regulation and Control, SIEI S.pA. (2002–2004) and the Polytechnic University of Turin, Italy (2002–2004, 2006–2007). He is a member of the Institute of Electrical and Electronics Engineers (IEEE) and cofounder-member of the IEEE Power Electronics Romanian Chapter. He is a guest editor at Energies and an academic book editor for IntechOpen. He is also a member of the editorial boards of the Journal of Electrical Engineering, Electronics, Control and Computer Science and Sustainability. Dr. Gaiceanu has been General Chairman of the IEEE International Symposium on Electrical and Electronics Engineering in the last six editions.",institutionString:'"Dunarea de Jos" University of Galati',institution:{name:'"Dunarea de Jos" University of Galati',country:{name:"Romania"}}},{id:"4519",title:"Prof.",name:"Jaydip",middleName:null,surname:"Sen",slug:"jaydip-sen",fullName:"Jaydip Sen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/4519/images/system/4519.jpeg",biography:"Jaydip Sen is associated with Praxis Business School, Kolkata, India, as a professor in the Department of Data Science. His research areas include security and privacy issues in computing and communication, intrusion detection systems, machine learning, deep learning, and artificial intelligence in the financial domain. He has more than 200 publications in reputed international journals, refereed conference proceedings, and 20 book chapters in books published by internationally renowned publishing houses, such as Springer, CRC press, IGI Global, etc. Currently, he is serving on the editorial board of the prestigious journal Frontiers in Communications and Networks and in the technical program committees of a number of high-ranked international conferences organized by the IEEE, USA, and the ACM, USA. He has been listed among the top 2% of scientists in the world for the last three consecutive years, 2019 to 2021 as per studies conducted by the Stanford University, USA.",institutionString:"Praxis Business School",institution:null},{id:"320071",title:"Dr.",name:"Sidra",middleName:null,surname:"Mehtab",slug:"sidra-mehtab",fullName:"Sidra Mehtab",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00002v6KHoQAM/Profile_Picture_1584512086360",biography:"Sidra Mehtab has completed her BS with honors in Physics from Calcutta University, India in 2018. She has done MS in Data Science and Analytics from Maulana Abul Kalam Azad University of Technology (MAKAUT), Kolkata, India in 2020. Her research areas include Econometrics, Time Series Analysis, Machine Learning, Deep Learning, Artificial Intelligence, and Computer and Network Security with a particular focus on Cyber Security Analytics. Ms. Mehtab has published seven papers in international conferences and one of her papers has been accepted for publication in a reputable international journal. She has won the best paper awards in two prestigious international conferences – BAICONF 2019, and ICADCML 2021, organized in the Indian Institute of Management, Bangalore, India in December 2019, and SOA University, Bhubaneswar, India in January 2021. Besides, Ms. Mehtab has also published two book chapters in two books. Seven of her book chapters will be published in a volume shortly in 2021 by Cambridge Scholars’ Press, UK. Currently, she is working as the joint editor of two edited volumes on Time Series Analysis and Forecasting to be published in the first half of 2021 by an international house. Currently, she is working as a Data Scientist with an MNC in Delhi, India.",institutionString:"NSHM College of Management and Technology",institution:{name:"Association for Computing Machinery",country:{name:"United States of America"}}},{id:"226240",title:"Dr.",name:"Andri Irfan",middleName:null,surname:"Rifai",slug:"andri-irfan-rifai",fullName:"Andri Irfan Rifai",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/226240/images/7412_n.jpg",biography:"Andri IRFAN is a Senior Lecturer of Civil Engineering and Planning. He completed the PhD at the Universitas Indonesia & Universidade do Minho with Sandwich Program Scholarship from the Directorate General of Higher Education and LPDP scholarship. He has been teaching for more than 19 years and much active to applied his knowledge in the project construction in Indonesia. His research interest ranges from pavement management system to advanced data mining techniques for transportation engineering. He has published more than 50 papers in journals and 2 books.",institutionString:null,institution:{name:"Universitas Internasional Batam",country:{name:"Indonesia"}}},{id:"314576",title:"Dr.",name:"Ibai",middleName:null,surname:"Laña",slug:"ibai-lana",fullName:"Ibai Laña",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314576/images/system/314576.jpg",biography:"Dr. Ibai Laña works at TECNALIA as a data analyst. He received his Ph.D. in Artificial Intelligence from the University of the Basque Country (UPV/EHU), Spain, in 2018. He is currently a senior researcher at TECNALIA. His research interests fall within the intersection of intelligent transportation systems, machine learning, traffic data analysis, and data science. He has dealt with urban traffic forecasting problems, applying machine learning models and evolutionary algorithms. He has experience in origin-destination matrix estimation or point of interest and trajectory detection. Working with large volumes of data has given him a good command of big data processing tools and NoSQL databases. He has also been a visiting scholar at the Knowledge Engineering and Discovery Research Institute, Auckland University of Technology.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"314575",title:"Dr.",name:"Jesus",middleName:null,surname:"L. Lobo",slug:"jesus-l.-lobo",fullName:"Jesus L. Lobo",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314575/images/system/314575.png",biography:"Dr. Jesús López is currently based in Bilbao (Spain) working at TECNALIA as Artificial Intelligence Research Scientist. In most cases, a project idea or a new research line needs to be investigated to see if it is good enough to take into production or to focus on it. That is exactly what he does, diving into Machine Learning algorithms and technologies to help TECNALIA to decide whether something is great in theory or will actually impact on the product or processes of its projects. So, he is expert at framing experiments, developing hypotheses, and proving whether they’re true or not, in order to investigate fundamental problems with a longer time horizon. He is also able to design and develop PoCs and system prototypes in simulation. He has participated in several national and internacional R&D projects.\n\nAs another relevant part of his everyday research work, he usually publishes his findings in reputed scientific refereed journals and international conferences, occasionally acting as reviewer and Programme Commitee member. Concretely, since 2018 he has published 9 JCR (8 Q1) journal papers, 9 conference papers (e.g. ECML PKDD 2021), and he has co-edited a book. He is also active in popular science writing data science stories for reputed blogs (KDNuggets, TowardsDataScience, Naukas). Besides, he has recently embarked on mentoring programmes as mentor, and has also worked as data science trainer.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"103779",title:"Prof.",name:"Yalcin",middleName:null,surname:"Isler",slug:"yalcin-isler",fullName:"Yalcin Isler",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRyQ8QAK/Profile_Picture_1628834958734",biography:"Yalcin Isler (1971 - Burdur / Turkey) received the B.Sc. degree in the Department of Electrical and Electronics Engineering from Anadolu University, Eskisehir, Turkey, in 1993, the M.Sc. degree from the Department of Electronics and Communication Engineering, Suleyman Demirel University, Isparta, Turkey, in 1996, the Ph.D. degree from the Department of Electrical and Electronics Engineering, Dokuz Eylul University, Izmir, Turkey, in 2009, and the Competence of Associate Professorship from the Turkish Interuniversity Council in 2019.\n\nHe was Lecturer at Burdur Vocational School in Suleyman Demirel University (1993-2000, Burdur / Turkey), Software Engineer (2000-2002, Izmir / Turkey), Research Assistant in Bulent Ecevit University (2002-2003, Zonguldak / Turkey), Research Assistant in Dokuz Eylul University (2003-2010, Izmir / Turkey), Assistant Professor at the Department of Electrical and Electronics Engineering in Bulent Ecevit University (2010-2012, Zonguldak / Turkey), Assistant Professor at the Department of Biomedical Engineering in Izmir Katip Celebi University (2012-2019, Izmir / Turkey). He is an Associate Professor at the Department of Biomedical Engineering at Izmir Katip Celebi University, Izmir / Turkey, since 2019. In addition to academics, he has also founded Islerya Medical and Information Technologies Company, Izmir / Turkey, since 2017.\n\nHis main research interests cover biomedical signal processing, pattern recognition, medical device design, programming, and embedded systems. He has many scientific papers and participated in several projects in these study fields. He was an IEEE Student Member (2009-2011) and IEEE Member (2011-2014) and has been IEEE Senior Member since 2014.",institutionString:null,institution:{name:"Izmir Kâtip Çelebi University",country:{name:"Turkey"}}},{id:"339677",title:"Dr.",name:"Mrinmoy",middleName:null,surname:"Roy",slug:"mrinmoy-roy",fullName:"Mrinmoy Roy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/339677/images/16768_n.jpg",biography:"An accomplished Sales & Marketing professional with 12 years of cross-functional experience in well-known organisations such as CIPLA, LUPIN, GLENMARK, ASTRAZENECA across different segment of Sales & Marketing, International Business, Institutional Business, Product Management, Strategic Marketing of HIV, Oncology, Derma, Respiratory, Anti-Diabetic, Nutraceutical & Stomatological Product Portfolio and Generic as well as Chronic Critical Care Portfolio. A First Class MBA in International Business & Strategic Marketing, B.Pharm, D.Pharm, Google Certified Digital Marketing Professional. Qualified PhD Candidate in Operations and Management with special focus on Artificial Intelligence and Machine Learning adoption, analysis and use in Healthcare, Hospital & Pharma Domain. Seasoned with diverse therapy area of Pharmaceutical Sales & Marketing ranging from generating revenue through generating prescriptions, launching new products, and making them big brands with continuous strategy execution at the Physician and Patients level. Moved from Sales to Marketing and Business Development for 3.5 years in South East Asian Market operating from Manila, Philippines. Came back to India and handled and developed Brands such as Gluconorm, Lupisulin, Supracal, Absolut Woman, Hemozink, Fabiflu (For COVID 19), and many more. In my previous assignment I used to develop and execute strategies on Sales & Marketing, Commercialization & Business Development for Institution and Corporate Hospital Business portfolio of Oncology Therapy Area for AstraZeneca Pharma India Ltd. Being a Research Scholar and Student of ‘Operations Research & Management: Artificial Intelligence’ I published several pioneer research papers and book chapters on the same in Internationally reputed journals and Books indexed in Scopus, Springer and Ei Compendex, Google Scholar etc. Currently, I am launching PGDM Pharmaceutical Management Program in IIHMR Bangalore and spearheading the course curriculum and structure of the same. I am interested in Collaboration for Healthcare Innovation, Pharma AI Innovation, Future trend in Marketing and Management with incubation on Healthcare, Healthcare IT startups, AI-ML Modelling and Healthcare Algorithm based training module development. I am also an affiliated member of the Institute of Management Consultant of India, looking forward to Healthcare, Healthcare IT and Innovation, Pharma and Hospital Management Consulting works.",institutionString:null,institution:{name:"Lovely Professional University",country:{name:"India"}}},{id:"310576",title:"Prof.",name:"Erick Giovani",middleName:null,surname:"Sperandio Nascimento",slug:"erick-giovani-sperandio-nascimento",fullName:"Erick Giovani Sperandio Nascimento",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y00002pDKxDQAW/ProfilePicture%202022-06-20%2019%3A57%3A24.788",biography:"Prof. Erick Sperandio is the Lead Researcher and professor of Artificial Intelligence (AI) at SENAI CIMATEC, Bahia, Brazil, also working with Computational Modeling (CM) and HPC. He holds a PhD in Environmental Engineering in the area of Atmospheric Computational Modeling, a Master in Informatics in the field of Computational Intelligence and Graduated in Computer Science from UFES. He currently coordinates, leads and participates in R&D projects in the areas of AI, computational modeling and supercomputing applied to different areas such as Oil and Gas, Health, Advanced Manufacturing, Renewable Energies and Atmospheric Sciences, advising undergraduate, master's and doctoral students. He is the Lead Researcher at SENAI CIMATEC's Reference Center on Artificial Intelligence. In addition, he is a Certified Instructor and University Ambassador of the NVIDIA Deep Learning Institute (DLI) in the areas of Deep Learning, Computer Vision, Natural Language Processing and Recommender Systems, and Principal Investigator of the NVIDIA/CIMATEC AI Joint Lab, the first in Latin America within the NVIDIA AI Technology Center (NVAITC) worldwide program. He also works as a researcher at the Supercomputing Center for Industrial Innovation (CS2i) and at the SENAI Institute of Innovation for Automation (ISI Automação), both from SENAI CIMATEC. He is a member and vice-coordinator of the Basic Board of Scientific-Technological Advice and Evaluation, in the area of Innovation, of the Foundation for Research Support of the State of Bahia (FAPESB). He serves as Technology Transfer Coordinator and one of the Principal Investigators at the National Applied Research Center in Artificial Intelligence (CPA-IA) of SENAI CIMATEC, focusing on Industry, being one of the six CPA-IA in Brazil approved by MCTI / FAPESP / CGI.br. He also participates as one of the representatives of Brazil in the BRICS Innovation Collaboration Working Group on HPC, ICT and AI. He is the coordinator of the Work Group of the Axis 5 - Workforce and Training - of the Brazilian Strategy for Artificial Intelligence (EBIA), and member of the MCTI/EMBRAPII AI Innovation Network Training Committee. He is the coordinator, by SENAI CIMATEC, of the Artificial Intelligence Reference Network of the State of Bahia (REDE BAH.IA). He leads the working group of experts representing Brazil in the Global Partnership on Artificial Intelligence (GPAI), on the theme \"AI and the Pandemic Response\".",institutionString:"Manufacturing and Technology Integrated Campus – SENAI CIMATEC",institution:null},{id:"1063",title:"Prof.",name:"Constantin",middleName:null,surname:"Volosencu",slug:"constantin-volosencu",fullName:"Constantin Volosencu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/1063/images/system/1063.png",biography:"Prof. Dr. Constantin Voloşencu graduated as an engineer from\nPolitehnica University of Timișoara, Romania, where he also\nobtained a doctorate degree. He is currently a full professor in\nthe Department of Automation and Applied Informatics at the\nsame university. Dr. Voloşencu is the author of ten books, seven\nbook chapters, and more than 160 papers published in journals\nand conference proceedings. He has also edited twelve books and\nhas twenty-seven patents to his name. He is a manager of research grants, editor in\nchief and member of international journal editorial boards, a former plenary speaker, a member of scientific committees, and chair at international conferences. His\nresearch is in the fields of control systems, control of electric drives, fuzzy control\nsystems, neural network applications, fault detection and diagnosis, sensor network\napplications, monitoring of distributed parameter systems, and power ultrasound\napplications. He has developed automation equipment for machine tools, spooling\nmachines, high-power ultrasound processes, and more.",institutionString:'"Politechnica" University Timişoara',institution:null},{id:"221364",title:"Dr.",name:"Eneko",middleName:null,surname:"Osaba",slug:"eneko-osaba",fullName:"Eneko Osaba",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/221364/images/system/221364.jpg",biography:"Dr. Eneko Osaba works at TECNALIA as a senior researcher. He obtained his Ph.D. in Artificial Intelligence in 2015. He has participated in more than twenty-five local and European research projects, and in the publication of more than 130 papers. He has performed several stays at universities in the United Kingdom, Italy, and Malta. Dr. Osaba has served as a program committee member in more than forty international conferences and participated in organizing activities in more than ten international conferences. He is a member of the editorial board of the International Journal of Artificial Intelligence, Data in Brief, and Journal of Advanced Transportation. He is also a guest editor for the Journal of Computational Science, Neurocomputing, Swarm, and Evolutionary Computation and IEEE ITS Magazine.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"275829",title:"Dr.",name:"Esther",middleName:null,surname:"Villar-Rodriguez",slug:"esther-villar-rodriguez",fullName:"Esther Villar-Rodriguez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/275829/images/system/275829.jpg",biography:"Dr. Esther Villar obtained a Ph.D. in Information and Communication Technologies from the University of Alcalá, Spain, in 2015. She obtained a degree in Computer Science from the University of Deusto, Spain, in 2010, and an MSc in Computer Languages and Systems from the National University of Distance Education, Spain, in 2012. Her areas of interest and knowledge include natural language processing (NLP), detection of impersonation in social networks, semantic web, and machine learning. Dr. Esther Villar made several contributions at conferences and publishing in various journals in those fields. Currently, she is working within the OPTIMA (Optimization Modeling & Analytics) business of TECNALIA’s ICT Division as a data scientist in projects related to the prediction and optimization of management and industrial processes (resource planning, energy efficiency, etc).",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"49813",title:"Dr.",name:"Javier",middleName:null,surname:"Del Ser",slug:"javier-del-ser",fullName:"Javier Del Ser",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49813/images/system/49813.png",biography:"Prof. Dr. Javier Del Ser received his first PhD in Telecommunication Engineering (Cum Laude) from the University of Navarra, Spain, in 2006, and a second PhD in Computational Intelligence (Summa Cum Laude) from the University of Alcala, Spain, in 2013. He is currently a principal researcher in data analytics and optimisation at TECNALIA (Spain), a visiting fellow at the Basque Center for Applied Mathematics (BCAM) and a part-time lecturer at the University of the Basque Country (UPV/EHU). His research interests gravitate on the use of descriptive, prescriptive and predictive algorithms for data mining and optimization in a diverse range of application fields such as Energy, Transport, Telecommunications, Health and Industry, among others. In these fields he has published more than 240 articles, co-supervised 8 Ph.D. theses, edited 6 books, coauthored 7 patents and participated/led more than 40 research projects. He is a Senior Member of the IEEE, and a recipient of the Biscay Talent prize for his academic career.",institutionString:"Tecnalia Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"278948",title:"Dr.",name:"Carlos Pedro",middleName:null,surname:"Gonçalves",slug:"carlos-pedro-goncalves",fullName:"Carlos Pedro Gonçalves",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRcmyQAC/Profile_Picture_1564224512145",biography:'Carlos Pedro Gonçalves (PhD) is an Associate Professor at Lusophone University of Humanities and Technologies and a researcher on Complexity Sciences, Quantum Technologies, Artificial Intelligence, Strategic Studies, Studies in Intelligence and Security, FinTech and Financial Risk Modeling. He is also a progammer with programming experience in:\n\nA) Quantum Computing using Qiskit Python module and IBM Quantum Experience Platform, with software developed on the simulation of Quantum Artificial Neural Networks and Quantum Cybersecurity;\n\nB) Artificial Intelligence and Machine learning programming in Python;\n\nC) Artificial Intelligence, Multiagent Systems Modeling and System Dynamics Modeling in Netlogo, with models developed in the areas of Chaos Theory, Econophysics, Artificial Intelligence, Classical and Quantum Complex Systems Science, with the Econophysics models having been cited worldwide and incorporated in PhD programs by different Universities.\n\nReceived an Arctic Code Vault Contributor status by GitHub, due to having developed open source software preserved in the \\"Arctic Code Vault\\" for future generations (https://archiveprogram.github.com/arctic-vault/), with the Strategy Analyzer A.I. module for decision making support (based on his PhD thesis, used in his Classes on Decision Making and in Strategic Intelligence Consulting Activities) and QNeural Python Quantum Neural Network simulator also preserved in the \\"Arctic Code Vault\\", for access to these software modules see: https://github.com/cpgoncalves. He is also a peer reviewer with outsanding review status from Elsevier journals, including Physica A, Neurocomputing and Engineering Applications of Artificial Intelligence. Science CV available at: https://www.cienciavitae.pt//pt/8E1C-A8B3-78C5 and ORCID: https://orcid.org/0000-0002-0298-3974',institutionString:"University of Lisbon",institution:{name:"Universidade Lusófona",country:{name:"Portugal"}}},{id:"241400",title:"Prof.",name:"Mohammed",middleName:null,surname:"Bsiss",slug:"mohammed-bsiss",fullName:"Mohammed Bsiss",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/241400/images/8062_n.jpg",biography:null,institutionString:null,institution:null},{id:"276128",title:"Dr.",name:"Hira",middleName:null,surname:"Fatima",slug:"hira-fatima",fullName:"Hira Fatima",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/276128/images/14420_n.jpg",biography:"Dr. Hira Fatima\nAssistant Professor\nDepartment of Mathematics\nInstitute of Applied Science\nMangalayatan University, Aligarh\nMobile: no : 8532041179\nhirafatima2014@gmal.com\n\nDr. Hira Fatima has received his Ph.D. degree in pure Mathematics from Aligarh Muslim University, Aligarh India. Currently working as an Assistant Professor in the Department of Mathematics, Institute of Applied Science, Mangalayatan University, Aligarh. She taught so many courses of Mathematics of UG and PG level. Her research Area of Expertise is Functional Analysis & Sequence Spaces. She has been working on Ideal Convergence of double sequence. She has published 17 research papers in National and International Journals including Cogent Mathematics, Filomat, Journal of Intelligent and Fuzzy Systems, Advances in Difference Equations, Journal of Mathematical Analysis, Journal of Mathematical & Computer Science etc. She has also reviewed few research papers for the and international journals. 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We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics can include but are not limited to: Biotechnology such as biotechnological products and process engineering; Biotechnologically relevant enzymes and proteins; Bioenergy and biofuels; Applied genetics and molecular biotechnology; Genomics, transcriptomics, proteomics; Applied microbial and cell physiology; Environmental biotechnology; Methods and protocols. Moreover, topics in biosensor technology, like sensors that incorporate enzymes, antibodies, nucleic acids, whole cells, tissues and organelles, and other biological or biologically inspired components will be considered, and topics exploring transducers, including those based on electrochemical and optical piezoelectric, thermal, magnetic, and micromechanical elements. Chapters exploring biomaterial approaches such as polymer synthesis and characterization, drug and gene vector design, biocompatibility, immunology and toxicology, and self-assembly at the nanoscale, are welcome. Finally, the tissue engineering subcategory will support topics such as the fundamentals of stem cells and progenitor cells and their proliferation, differentiation, bioreactors for three-dimensional culture and studies of phenotypic changes, stem and progenitor cells, both short and long term, ex vivo and in vivo implantation both in preclinical models and also in clinical trials.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/9.jpg",keywords:"Biotechnology, Biosensors, Biomaterials, Tissue Engineering"}],annualVolumeBook:{},thematicCollection:[],selectedSeries:null,selectedSubseries:null},seriesLanding:{item:{id:"7",title:"Biomedical Engineering",doi:"10.5772/intechopen.71985",issn:"2631-5343",scope:"Biomedical Engineering is one of the fastest-growing interdisciplinary branches of science and industry. The combination of electronics and computer science with biology and medicine has improved patient diagnosis, reduced rehabilitation time, and helped to facilitate a better quality of life. Nowadays, all medical imaging devices, medical instruments, or new laboratory techniques result from the cooperation of specialists in various fields. The series of Biomedical Engineering books covers such areas of knowledge as chemistry, physics, electronics, medicine, and biology. 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Dr. Koprowski has authored more than a hundred research papers with dozens in impact factor (IF) journals and has authored or co-authored six books. Additionally, he is the author of several national and international patents in the field of biomedical devices and imaging. Since 2011, he has been a reviewer of grants and projects (including EU projects) in biomedical engineering.",institutionString:null,institution:{name:"University of Silesia",institutionURL:null,country:{name:"Poland"}}},subseries:[{id:"7",title:"Bioinformatics and Medical Informatics",keywords:"Biomedical Data, Drug Discovery, Clinical Diagnostics, Decoding Human Genome, AI in Personalized Medicine, Disease-prevention Strategies, Big Data Analysis in Medicine",scope:"Bioinformatics aims to help understand the functioning of the mechanisms of living organisms through the construction and use of quantitative tools. The applications of this research cover many related fields, such as biotechnology and medicine, where, for example, Bioinformatics contributes to faster drug design, DNA analysis in forensics, and DNA sequence analysis in the field of personalized medicine. Personalized medicine is a type of medical care in which treatment is customized individually for each patient. Personalized medicine enables more effective therapy, reduces the costs of therapy and clinical trials, and also minimizes the risk of side effects. Nevertheless, advances in personalized medicine would not have been possible without bioinformatics, which can analyze the human genome and other vast amounts of biomedical data, especially in genetics. The rapid growth of information technology enabled the development of new tools to decode human genomes, large-scale studies of genetic variations and medical informatics. The considerable development of technology, including the computing power of computers, is also conducive to the development of bioinformatics, including personalized medicine. In an era of rapidly growing data volumes and ever lower costs of generating, storing and computing data, personalized medicine holds great promises. Modern computational methods used as bioinformatics tools can integrate multi-scale, multi-modal and longitudinal patient data to create even more effective and safer therapy and disease prevention methods. 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Possible contributions can address (but are not limited to) the following research topics: Bioinspired design and control of exoskeletons, orthoses, and prostheses; Experimental evaluation of the effect of assistive devices (e.g., influence on gait, balance, and neuromuscular system); Bioinspired technologies for rehabilitation, including clinical studies reporting evaluations; Application of neuromuscular and biomechanical models to the development of bioinspired technology.',annualVolume:11404,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/8.jpg",editor:{id:"144937",title:"Prof.",name:"Adriano",middleName:"De Oliveira",surname:"Andrade",fullName:"Adriano Andrade",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRC8QQAW/Profile_Picture_1625219101815",institutionString:null,institution:{name:"Federal University of Uberlândia",institutionURL:null,country:{name:"Brazil"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"49517",title:"Prof.",name:"Hitoshi",middleName:null,surname:"Tsunashima",fullName:"Hitoshi Tsunashima",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYTP4QAO/Profile_Picture_1625819726528",institutionString:null,institution:{name:"Nihon University",institutionURL:null,country:{name:"Japan"}}},{id:"425354",title:"Dr.",name:"Marcus",middleName:"Fraga",surname:"Vieira",fullName:"Marcus Vieira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003BJSgIQAX/Profile_Picture_1627904687309",institutionString:null,institution:{name:"Universidade Federal de Goiás",institutionURL:null,country:{name:"Brazil"}}},{id:"196746",title:"Dr.",name:"Ramana",middleName:null,surname:"Vinjamuri",fullName:"Ramana Vinjamuri",profilePictureURL:"https://mts.intechopen.com/storage/users/196746/images/system/196746.jpeg",institutionString:"University of Maryland, Baltimore County",institution:{name:"University of Maryland, Baltimore County",institutionURL:null,country:{name:"United States of America"}}}]},{id:"9",title:"Biotechnology - Biosensors, Biomaterials and Tissue Engineering",keywords:"Biotechnology, Biosensors, Biomaterials, Tissue Engineering",scope:"The Biotechnology - Biosensors, Biomaterials and Tissue Engineering topic within the Biomedical Engineering Series aims to rapidly publish contributions on all aspects of biotechnology, biosensors, biomaterial and tissue engineering. We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics can include but are not limited to: Biotechnology such as biotechnological products and process engineering; Biotechnologically relevant enzymes and proteins; Bioenergy and biofuels; Applied genetics and molecular biotechnology; Genomics, transcriptomics, proteomics; Applied microbial and cell physiology; Environmental biotechnology; Methods and protocols. Moreover, topics in biosensor technology, like sensors that incorporate enzymes, antibodies, nucleic acids, whole cells, tissues and organelles, and other biological or biologically inspired components will be considered, and topics exploring transducers, including those based on electrochemical and optical piezoelectric, thermal, magnetic, and micromechanical elements. 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