WHO classification of endometrial hyperplasia [33]
\r\n\tThis book intends to provide the reader with a comprehensive overview of the current state-of-the-art novel imaging techniques by focusing on the most important evidence-based developments in this area.
",isbn:null,printIsbn:null,pdfIsbn:null,doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,isNomenclature:!1,hash:"d9159ce31733bf78cc2a79b18c225994",bookSignature:"Dr. Gabriel Cismaru",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11867.jpg",keywords:"Hypertrophic Cardiomyopathy, Dilated Cardiomyopathy, Restrictive Cardiomyopathy, Transesophageal Echocardiography, Intracardiac Echocardiography, 3-Dimensional Echocardiography, Adult Congenital Heart Disease, Tetralogy of Fallot, Transposition of the Great Vessels, Coronary Artery Disease, Risk Stratification, Revascularization",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"April 21st 2022",dateEndSecondStepPublish:"May 19th 2022",dateEndThirdStepPublish:"July 18th 2022",dateEndFourthStepPublish:"October 6th 2022",dateEndFifthStepPublish:"December 5th 2022",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"3 months",secondStepPassed:!0,areRegistrationsClosed:!0,currentStepOfPublishingProcess:4,editedByType:null,kuFlag:!1,biosketch:"Dr. Cismaru Gabriel is an Assistant Professor at the University of Medicine and Pharmacy Cluj-Napoca, certified in Cardiology. After completing his certification in cardiology, Dr. Cismaru began his electrophysiology fellowship at the Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu. He has authored or co-authored peer-reviewed articles and book chapters in the field of cardiac pacing, defibrillation, electrophysiological study, and catheter ablation.",coeditorOneBiosketch:"Raluca Tomoaia is an MD, Ph.D. in novel techniques in Echocardiography at the University of Medicine and Pharmacy in Cluj-Napoca, Romania., assistant professor, and a researcher in echocardiography and cardiovascular imaging.",coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"191888",title:"Dr.",name:"Gabriel",middleName:null,surname:"Cismaru",slug:"gabriel-cismaru",fullName:"Gabriel Cismaru",profilePictureURL:"https://mts.intechopen.com/storage/users/191888/images/system/191888.png",biography:"Dr. Cismaru Gabriel is an assistant professor at the Cluj-Napoca University of Medicine and Pharmacy, Romania, where he has been qualified in cardiology since 2011. He obtained his Ph.D. in medicine with a research thesis on electrophysiology and pro-arrhythmic drugs in 2016. Dr. Cismaru began his electrophysiology fellowship at the Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu, France, after finishing his cardiology certification with stages in Clermont-Ferrand and Dinan, France. He began working at the Rehabilitation Hospital\\'s Electrophysiology Laboratory in Cluj-Napoca in 2011. He is an experienced operator who can implant pacemakers, CRTs, and ICDs, as well as perform catheter ablation of supraventricular and ventricular arrhythmias such as ventricular tachycardia and ventricular fibrillation. He has been qualified in pediatric cardiology since 2022, and he regularly performs device implantation and catheter ablation in children. Dr. Cismaru has authored or co-authored peer-reviewed publications and book chapters on cardiac pacing, defibrillation, electrophysiological studies, and catheter ablation.",institutionString:"Iuliu Hațieganu University of Medicine and Pharmacy",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"7",totalChapterViews:"0",totalEditedBooks:"2",institution:{name:"Iuliu Hațieganu University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"16",title:"Medicine",slug:"medicine"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:null},relatedBooks:[{type:"book",id:"5970",title:"Bedside Procedures",subtitle:null,isOpenForSubmission:!1,hash:"ba56d3036ac823a7155f40e4a02c030d",slug:"bedside-procedures",bookSignature:"Gabriel Cismaru",coverURL:"https://cdn.intechopen.com/books/images_new/5970.jpg",editedByType:"Edited by",editors:[{id:"191888",title:"Dr.",name:"Gabriel",surname:"Cismaru",slug:"gabriel-cismaru",fullName:"Gabriel Cismaru"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9064",title:"Epidemiology and Treatment of Atrial Fibrillation",subtitle:null,isOpenForSubmission:!1,hash:"1cd6bf2b3181eb82446347fbe478a2bc",slug:"epidemiology-and-treatment-of-atrial-fibrillation",bookSignature:"Gabriel Cismaru and Keith Andrew Chan",coverURL:"https://cdn.intechopen.com/books/images_new/9064.jpg",editedByType:"Edited by",editors:[{id:"191888",title:"Dr.",name:"Gabriel",surname:"Cismaru",slug:"gabriel-cismaru",fullName:"Gabriel Cismaru"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6550",title:"Cohort Studies in Health Sciences",subtitle:null,isOpenForSubmission:!1,hash:"01df5aba4fff1a84b37a2fdafa809660",slug:"cohort-studies-in-health-sciences",bookSignature:"R. 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The lower, narrow part, which builds on top of the vaginal opening, was marked as
The reproductive axis consists of the hypothalamus, pituitary, and ovaries. The gonadotropin-releasing hormone (GnRH) acts on the anterior pituitary by regulating the synthesis and storage of gonadotropins, follicle-stimulating hormone (FSH), and luteinizing hormone (LH). GnRH also regulates the movement of gonadotropins from the reserve pool to a readily released point and their secretion. This action requires pulsatile GnRH release [1]. The secretion of FSH and LH takes place in a coordinated manner so as to regulate the growth of ovarian follicles, ovulation, and the maintenance of the corpus luteum and requires constant pulsatile release of LHRH from the hypothalamus [2]. Both estrogens and progestins help regulate the release of gonadotropins, acting through both the hypothalamus and anterior pituitary. High/low levels of either progestins or a combination of progestins and estrogens, as well as the length of exposure to these hormones, inhibit/stimulate the release of GnRH, FSH, and LH from the anterior pituitary – a negative/positive feedback control, respectively [3].
In the reproductive age of women, 17β-estradiol (E2) is a major circulating estrogen that is produced by the granulosa cells of the ovary prior to ovulation and by corpus luteum following ovulation. Almost 95 % of circulating Es in premenopausal women consists of 17β-estradiol and the remaining 5 % originates from the peripheral conversion of the estrone (E1) to estradiol [4]. Although a small amount of estrone, the second most important estrogen, is secreted directly from the ovaries and adrenal glands, its main quantity derives from conversion of androstenedione in adipose tissue [5]. The estrogenic potency of estrone is lesser than estradiol, and both, E2 and E1, are biologically equivalent with subtle structural differences and metabolized by the same pathways. Once a woman has reached menopause and ovaries lose their function, estrone becomes a predominant form of estrogen [6]. Studies have shown the trend to higher mortality rate from coronary heart disease in women with lower estrone level, while patients with higher estrone level had lower body weight, less frequent hypertension and diabetes mellitus, and also a lower triglyceride level [7].
During normal ovulatory cycle, the level of E2 varies individually within the range defined for the follicular phase, mid-cycle, and luteal phase. Most of E2 in the circulation is bound to sex hormone-binding globulin (SHBG) and to a lesser extent, to other serum proteins, such as albumin. Only a very small fraction of this hormone is free and is located in the conjugated form [8,9].
During a normal menstrual cycle, E2 secretion is biphasic, and the highest concentration is recorded just prior to ovulation. This growth affects the pituitary gland secretion of FSH and LH by a positive feedback. After ovulation, E2 level rapidly decreases and luteal cells, by their activities, cause mild, subsequent rise and a plateau of E2 during the luteal phase [2]. During pregnancy, the level of E2 in serum increases to much higher values than recorded in the preovulatory peak, and it is maintained during pregnancy [10].
Progesterone (P) belongs to a group of steroid hormones called progestogens, and it is secreted by the
The transition from the reproductive period to the menopause is a gradual process that takes place over many years and is referred to as perimenopause. It starts with the first symptoms of changes in the cyclic occurrence of menstruation and/or bleeding, which may be accompanied by physical and psychological symptoms and ends with the last menstruation. In terms of morphology, this phase is characterized by a sudden drop in the number of primordial follicles in the ovaries, as well as extreme fluctuations in hormone levels [16], so that the frequency of normal ovulatory cycles decreases [2].
It has been shown that some women experience an increase in serum FSH concentrations before the age of 40, especially during the mid-follicular and early luteal phase [17]. Similar increase of FSH was also detected through regular cycles, although there were no clinical manifestations of approaching menopause [18].
Generally, a significant increase in the concentration of FSH is observed approximately 5 years before the onset of menopause and it is positively correlated with age [19,20]. With the onset of menopause, there is an additional increase in FSH levels in serum for about six months, and the peak concentration is detected 3–4 years after menopause. After this period, a slight decline in serum FSH was detected. However, compared with fertile women, levels of gonadotropins remained at elevated levels even 10 years after menopause [19]. Besides FSH, the LH concentration also changes during this period. It has been shown that serum LH increases slightly during 4–5 years of perimenopause in women who still regularly cycled [17]. During the first six months from the onset of menopause, there is an increase in serum concentrations of LH, and the highest level is recorded during the first year of menopause. Over the next 8 years, there is a continuous fall, but as in the case of FSH, the LH level remained elevated compared with fertile period [19]. These data represent the results which should not be generalized and considered as absolute parameters that apply to the period of perimenopause and menopause, since clear markers still have to be identified. In addition, they cannot be reliably interpreted since ovulatory (potentially fertile) cycles can normally take place immediately after the detection of postmenopausal levels of FSH. Both estradiol and inhibin are important regulators of the negative feedback loop of circulating FSH [21-23].
As a consequence of declined follicular function during menopause, the concentration of Es in circulation also decreases. The level of estradiol in the serum of postmenopausal women is less than 15 pg/ml, and the level of estrone is about 30 pg/ml, so that the ratio E1/E2 is 2:1 [11,24]. The main source of E1, which is the principal form of the postmenopausal estrogen, derives from androstenedione in peripheral adipose tissue and liver [2]. In this period, 95 % of the total synthesis of androstenedione occurs in the adrenal glands and only 5 % in the ovaries [25,26]. Increased conversion of androstenedione to estrone is proportional to the increase of body weight, and it consequently increases the amount of estrogen in the bloodstream [2,26]. The main source of E2 in postmenopausal women originates from the peripheral conversion of E1. During and after menopause, the concentration of E1 decreases as well as the concentration of E2, so that both forms of estrogen are strongly correlated [27,28]. The concentration of estrone sulfate, which is a metabolite of those estrogens, shows a similar trend of decline in menopausal women. Although it does not belong to the active Es, it can be activated by hydrolysis of the sulfate group [27]. Since premenopause leads to inadequate luteal function or anovulation, progesterone is also lowered in the serum. The level of P is further reduced during the aging process, so it is very low in postmenopausal women [19]. Statistically, approximately 2 % to 3 % of women will develop uterine cancer during lifetime. About 97 % of all uterine cancers originate from endometrial glands and represent endometrial carcinomas [29]. Endometrial carcinoma is the fourth common cancer after breast, bowel, and lung carcinoma [30].
Endometrial proliferation is a normal part of the menstrual cycle that occurs during the follicular/estrogen phase of the cycle [31]. If the endometrium is exposed to continuous endogenous or exogenous estrogen in the absence of progesterone, simple proliferation can advance to endometrial hyperplasia, which is the most common precursor of endometrioid adenocarcinoma. Generally, endometrial hyperplasia is the abnormal proliferation of the glands and the stroma characterized by the presence of architectural and cytological changes [32].
As an attempt to correlate morphological features with clinical outcome, the World Health Organization (WHO) classified endometrial hyperplasia:
Nonatypical hyperplasias (typical) | \n\t\t
Simple hyperplasia without atypia | \n\t\t
Complex hyperplasia without atypia (syn. adenomatous hyperplasia without atypia) | \n\t\t
Atypical hyperplasias | \n\t\t
Simple atypical hyperplasia | \n\t\t
Complex atypical hyperplasia (syn. atypical adenomatous hyperplasia) | \n\t\t
WHO classification of endometrial hyperplasia [33]
The normal proliferative endometrium is characterized by no crowding of glands within the stroma. Morphological features of all endometrial hyperplasia forms include an increase in the gland-stroma ratio, irregularities in gland shape, and variation in gland size. Regardless of the presence of atypia, simple and complex forms of hyperplasia are distinguished by architectural alterations characterized by glandular complexity and the amount of stroma separating the glands [34]. Hyperplasia generally involves much of the whole endometrium, but sometimes it may be present as a localized lesion and might be associated within an endometrial polyp. Most endometrial hyperplasias are estrogen driven and related to type 1 endometrial carcinoma, the endometrioid endometrial adenocarcinoma [35].
Thus, the WHO classification also includes lesions termed
There is a discussion to replace the WHO classification of type 1 endometrial carcinoma precursors with the endometrial intraepithelial neoplasia classification system. This system was proposed in 2000 by an international group of gynecologic pathologists, and it defines two classes of endometrial changes, endometrial hyperplasia (EH) and endometrial intraepithelial neoplasia (EIN) [43]. In this classification, endometrial hyperplasia refers to changes observed with anovulation or other etiologies of prolonged estrogen exposure. Morphologically, EH varies from proliferative endometrium with a few cysts to endometria with many dilated glands. This type is also known as cystic glandular hyperplasia, mild hyperplasia, or simple hyperplasia [44]. The term EIN represents monoclonal endometrial preinvasive glandular proliferation as the immediate precursor of endometrial type 1 adenocarcinoma. In EIN, the proliferation of endometrial glands exceeds the stroma (gland/stroma >1) [45]. EIN categories do not correspond directly to the WHO system of classification. Most simple and some complex hyperplasias fall into EH category and many complex hyperplasias with or without atypia are in the EIN category.
A well-documented study regarding the epidemiology of endometrial hyperplasia included women aged 18 to 90 over the 18-year period. The diagnosis was mostly made in women aged 50–54 years and rarely was found in women under the age of 30. The incidence of simple and complex hyperplasia was 142 and 213 per 100,000 women-years, respectively. The rate of atypical hyperplasia was highest in older women aged 60–64 years, and it was 56 per 100,000 women-years. This rate seems to correlate with age of peak incidence for endometrial cancer [46,47]. Age-specific cancer incidence was demonstrated for the pancreas, bladder, stomach, lung, prostate, ovary, colorectal, and uterine endometrium. One explanation for increased cancer incidence with age is the latency period required for damage to occur and cancer to develop, including the time necessary for accumulation of carcinogen-induced genetic mutations like in oncogenes and tumor suppressor genes but also as a maladaptive response to replicative senescence due to telomere shortening. Also, a deterioration of the innate and the adaptive immune response with aging, referred to as immunosenescence, must be considered [48].
Symptoms of endometrial hyperplasia include heavy or prolonged menstrual periods, intermenstrual bleeding, and prolonged amenorrhea. Postmenopausal women with hyperplasia may experience vaginal bleeding or spotting. However, only minority of women with abnormal uterine bleeding (AUB) are subsequently diagnosed with endometrial hyperplasia [49].
The risk factors for endometrial hyperplasia are the same as for endometrial carcinoma. Most of them include exposure of endometrium to continuous estrogen unopposed by progestin. Unopposed estrogen may be of various sources like early menarche (beginning menstruation before age 12), hormone replacement therapy (HRT) with exogenous estrogen, late menopause (after 52 years of age), estrogen-secreting tumor (some breast cancer types), and nulliparity or low parity. Medical conditions such as diabetes mellitus, polycystic ovary syndrome, or thyroid diseases also increase the risk for hyperplasia and cancer of the uterus. Endometrial hyperplasia is also more likely to occur in women with personal history of breast, colorectal, or ovarian cancer and in women of white race. Endometrial cancer and hyperplasia are more common in Caucasian women, while uterine sarcoma is more common in African American women [50,51].
Although the findings suggest that there are certain molecular characteristics which distinguish types and degrees of endometrial cancer, the molecular mechanisms that underlie the endometrial carcinogenesis are still unclear. Cell changes can begin with genetic aberrations and continue with uncontrolled growth stimulated by tumor promoters.
Endometrial tissue is the target tissue for steroid hormones produced by ovaries. Both epithelium and stroma contain receptors for Es and Ps, and ovarian steroids have a fundamental role in the regulation of growth and differentiation of endometrial cells [2]. It seems this influence is partly preserved in well-differentiated tumors of the lower grade, as suggested by data which showed that these tumors are frequently receptor positive than the advanced tumors [52]. Growth factors are, among other influences, regulated by steroid hormones, and they are involved in a paracrine and autocrine regulation of endometrial proliferation. The most often mentioned are the epidermal growth factor (EGF) and transforming growth factor-α (TGF-α). Both factors are single-chain peptides that exert their effect through the EGF receptor. They were shown to be expressed in normal endometrial tissue [53] and to stimulate growth of cultured endometrial cancer cells [54]. In addition to these two factors, it is considered that the transforming growth factor-β (TGF-β) is also involved in the carcinogenesis. This factor is expressed in normal human endometrium and certain endometrial cancer cell lines. In some of these cell lines, like RL95-2, SPEC-2, and KLE, the TGF-β inhibits their growth [55]. Among the other growth factors which affect endometrial carcinogenesis, the basic fibroblast growth factor (bFGF) and insulin-like growth factor I (IGF-I) should also be mentioned [56].
The most frequently altered oncogenes in endometrial cancer are the point-mutational activation of K-ras. Point mutations of K-ras were found in approximately 10–30 % of endometrial cancers [57]. Also, K-ras mutations have been identified in endometrial hyperplasia and more frequently in complex atypical hyperplasia, suggesting that K-ras mutations may be an early event in endometrial carcinogenesis [58].
In addition to this oncogene, the amplification and overexpressed HER-2/neu (c-erb B-2) was found in about 10–20 % of sporadic endometrial carcinoma cases [59-61]. HER-2/neu gene encodes a membrane receptor protein which is structurally similar to the receptor for epidermal growth factor (EGF-R). In some endometrial carcinomas, the overexpression of oncogenes Myb, Fos, Myc, and fms, as well as their correlation with advanced stages of carcinogenesis and poor prognosis of the outcome of survival, was recorded [57, 62]. Results of some endometrial carcinoma studies detected the overexpression of oncogenes Myb, Fos, Myc, and fms, as well as their correlation with advanced stages of carcinogenesis and poor prognosis of the outcome of survival [57, 62].
Until now, it is observed that mutations in PTEN (phosphatase and tenzin homologue deletion on chromosome 10) tumor suppressor gene, also known as MMAC1 and TEP1, are detected in approximately 50 % of endometrial cancers [63], as well as in 20 % of endometrial hyperplasias, suggesting that these mutations occur relatively early in pathogenesis of this cancer type [64, 65]. PTEN is a dual-specificity protein phosphatase which dephosphorylates tyrosine-, serine- and threonine-phosphorylated proteins. Acting as lipid phosphatase, which is critical for its tumor suppressor function, it removes the phosphate in the D3 position of the inositol ring from phosphatidylinositol 3,4,5-trisphosphate; phosphatidylinositol 3,4-diphosphate; phosphatidylinositol 3-phosphate; and inositol 1,3,4,5-tetrakisphosphate. PTEN is crucial in the control of PI3K-AKT/PKB signaling pathway by dephosphorylating phosphoinositides and thereby modulating cell cycle progression and cell survival [66, 67]. There is a wide spectrum of PTEN mutations in endometrial cancer, which occur in exons 3, 4, 5, 7, and 8 and targeting the phosphatase domain and regions that control the stability and localization of proteins. The consequence of these mutations is reduced or completely absent expression of PTEN [68]. It was shown that progesterone treatment of cultured endometrial stromal cells induces an increase in PTEN levels, while estradiol induces the PTEN phosphorylation. This indicates an outstanding role of PTEN in the development and/or progression of endometrial cancer [69]. Although loss of PTEN function was implicated in the pathogenesis of many different tumors [70], it is believed that the altered expression of PTEN can be a diagnostic marker for the early precancerous conditions of the endometrium [43].
Mutations of the p53 tumor suppressor gene have been found in approximately 10–20 % of all endometrial cancers, with the greatest frequency in the high-grade tumors. Approximately 50 % of grade III tumors type 1 and the rare tumors of type 2 contain mutations in p53, but they have not been reliably detected within the tumor of grade I or hyperplasia [68, 71, 72], so it is considered that they occur in the late stages of endometrial carcinogenesis [56, 68]. The partial role of the p53 in the cell cycle regulation is mediated through the transcriptional activation of other genes, such as p21, followed by inhibition of the cyclin-dependent kinases [73]. Thus, inactivation of p21 could potentially lead to tumor progression. Studies have shown that in approximately 15–40 % of endometrial cancer cases, a loss of p21 gene expression can be detected [74-76]. In addition to p53 and p21, the alterations of p16INK4a (CDKN2A) tumor suppressor gene were also observed. This gene encodes the p16 protein that specifically binds to CDK4 cyclin-dependent kinases, thereby inhibiting the catalytic activity of the CDK4-cyclin D complexes. Until now, it is observed that methylation, mutations, and deletions of p16INK4a gene are rare, and they were detected in approximately 2–6 % of endometrial cancer cases [56, 77], while the loss of expression was found in 20–70 % of cases [78-80].
Endothelins (ETs), ET-1, ET-2, and ET-3, are potent vasoconstricting peptides involved in the pathophysiology of many human malignancies by activating G protein-coupled receptor (GPCR) subtypes, ETA and ETB [81]. Expression of ET-1 was detected in normal human endometrium and in endometrial adenocarcinoma. Also, ETAR and ETBR expression was decreased in endometrial cancer tissue compared with that of normal endometrium [82].The ET-1-ETRA axis is frequently dysfunctional in numerous types of carcinomas and contributes to the promotion of cell growth and migration [83].
In addition to mutations of the PTEN gene, microsatellite instability (MSI) is often detected in type 1 of endometrial cancer. MSI was first demonstrated in patients with hereditary nonpolyposis colorectal carcinoma (HNPCC), in which endometrial cancer is often an associated phenomenon. Additional studies have shown that MSI is detected in approximately 25 % of sporadic cases of endometrial cancer [84] or by other studies in 9–45 % of cases [56]. Unlike hereditary forms of nonpolyposis colorectal carcinoma, where subjects with this type of cancer carry mutations of one of the DNA mismatch repair genes, hMLH1, hMSH2, and hMSH6 [85, 86], promoter hypermethylation of the gene hMLH1 represents the predominant cause of MSI only in sporadic cases [87]. There are also data on the hypermethylation of this gene promoter in hyperplasia and in the absence of cancer, which suggests that inactivation of mismatch repair genes precedes the formation of MSI [88].
Oxygen may be a source of reactive oxygen species (ROS) due to its incomplete reduction mostly by the oxidoreductase complex I and III of the mitochondrial respiratory chain [89], forming the superoxide anion radical (O2\n\t\t\t\t•-). ROS molecules are characterized by a higher reactivity than oxygen in its ground state. The ROS include free radicals (a term that refers to molecules with one unpaired electron in the outer orbital), like superoxide anion radical (O2\n\t\t\t\t•-), hydroxyl radical (•OH), peroxyl radical (ROO• ), as well as reactive nonradical molecules such as singlet oxygen (1O2), peroxynitrite (ONOO-), or hydrogen peroxide (H2O2). Their half-life varies from a few nanoseconds for the most reactive molecules up to a few seconds or hours for stable radicals [90].
There are a few major sources of O2\n\t\t\t\t•- in the cell: the respiratory chain in mitochondria, endoplasmic reticulum cytochromes (cytochrome P-450-dependent oxygenase, NADPH-cytochrome P-450 reductase), as well as the oxidase contained in the cell cytoplasm and membranes (NADPH oxidase of polymorphonuclear leucocytes, macrophages, and endothelial cells) [91, 92]. The resulting O2\n\t\t\t\t•- may be converted to H2O2 by spontaneous dismutation, as well as by the enzyme superoxide dismutase (SOD). In addition, the H2O2 may originate from the monoamine oxidase activity [93] or from the beta-oxidation of fatty acids in peroxisomes [94]. Its reduction is carried out by the enzyme catalase (CAT) and glutathione peroxidase (GPx), which can be considered as the main way of detoxification. H2O2 may also be reduced by the neutrophil myeloperoxidase which catalyzes the conversion of H2O2 and Cl- to hypochlorous acid (HOCl) and in the presence of transition metals (Fe2+ or Cu+), producing •OH [95]. The hydroxyl radical is a highly reactive oxidant that reacts almost instantaneously with the surrounding molecules abstracting the hydrogen atom (RH). The resulting free radical (R•) is more stable and therefore has usually longer half-life compared to the •OH [96]. Peroxyl radicals have a relatively long half-life, and they are formed in the process of lipid peroxidation, which begins with removal of the hydrogen atom of polyunsaturated fatty acids [97]. Lipid peroxidation in cell membranes can significantly damage their function due to the formation of irreversible disturbance of fluidity and elasticity, which can lead to impairment of cellular homeostasis.
ROS are constantly produced in the body as a result of normal metabolic processes, but there is also a significant influence of external factors. Many chemical and biological agents which are prooxidants under certain conditions can lead to increased production of free radicals. If their production exceeds the capacity of the antioxidant defense, the oxidative stress occurs [96]. ROS can react with any molecules in the cell, thus causing considerable damage which results in cellular dysfunction. These processes are increasingly studied today in the framework of the mechanisms of etiopathogenesis of various diseases. Also, their role in cell signaling, proliferation, differentiation, and programmed cell death – apoptosis – is intensively examined.
The term antioxidant refers to a substance that, when present in small amounts compared with the substrate to be oxidized, inhibits or prevents its oxidation. The antioxidant system can be divided into two categories: nonenzymatic antioxidants, which include various compounds of low molecular weight (vitamin E, vitamin C, carotenoids, polyphenols, ubiquinone, and glutathione), and the AO enzyme system [98].
Vitamin E (tocopherol-OH, vitamin E) is a generic name for a group of compounds known as the tocopherols and tocotrienols, and it includes all forms which exhibit biological activity of natural vitamin E (d-alpha-tocopherol) [98]. Vitamin C (ascorbic acid) is the most important hydrophilic antioxidant. Their main function is to prevent peroxidation of lipids in the membrane and, consequently, cell damage. The carotenoids are the vitamin A, which also possess antioxidant properties. Beta-carotene is one of the most studied forms, and its antioxidant function is based on its attribute to quench the singlet oxygen and remove free radicals, thus protecting the cell membrane lipids from oxidative degradation. Polyphenols are a group of compounds with antioxidant capacity to prevent formation of ROS production through inhibition of the enzyme, as well as trace elements, involved in their formation [99]. Ubiquinone prevents lipid peroxidation in liposomes, lipid emulsions, phospholipids, and LDL particles [100]. Glutathione (GSH) is a tripeptide consisting of L-glutamine, L-cysteine, and L-glycine. In addition to its role as a substrate of GSH redox cycles, it also removes the hydroxyl radicals and singlet oxygen and maintains the enzymes and other cellular components in a reduced state [98].
In mammals, three types of SODs have been identified, depending on the cellular localization and prosthetic groups. In the cytoplasm, the predominant form is copper-zinc-superoxide dismutase (CuZnSOD, SOD1), which represents a stable dimeric protein with molecular mass of 32 kDa. It contains copper and zinc in its active site. Copper is considered necessary for the catalytic activity of this enzyme, whereas zinc contributes to its stability [101]. CuZnSOD is also located in the extracellular matrix, and this form is known as the extracellular superoxide dismutase (EC-SOD, SOD3). This form of CuZnSOD is a tetrameric protein with molecular mass of 135 kDa, and it possesses a heparin-binding domain that affects its extracellular distribution [102]. Manganese superoxide dismutase (MnSOD SOD2) is a tetramer enzyme with molecular weight of 88 kDa, containing manganese atom in the active sites and it is located in the mitochondria.
CAT is homo-tetramer enzyme with molecular weight of 240 kDa, with each subunit containing the heme prosthetic group and also the attached NADPH that protects the enzyme from oxidative damage. CAT has a function to decompose H2O2 to O2 and H2O [103].
GPx family can be divided into two groups: selenium-independent peroxidase presented glutathione S-transferase (GST) and selenium-dependent peroxidases (GPx).
Glutathione S-transferase belongs to the so-called phase II detoxifying enzymes that are involved in conjugation reactions of a wide range of electrophilic xenobiotics (including carcinogens and mutagens). Several selenoprotein glutathione peroxidases are present in human tissues, cell GPx (GPx-1, CGP-x), gastrointestinal GPx (GPx-2, giGPx), plasma (extracellular) GPx (GPx-3, eGPx), and phospholipid hydroperoxide GPx (GPx-4, PHGPx) and GPx-6, which is only expressed in the epithelium of the olfactory system [104]. With the exception of PHGPx which is a monomer (19 kDa), other forms of GPx are composed of four identical subunits of a molecular weight of 19–25 kDa. Each subunit in its active site contains a selenocysteine (CysSe). The enzyme uses a reduced GSH as a source of reducing equivalents (electrons) to regenerate CysSe to the reduced state [105]. Glutathione reductase (GR) is an enzyme that catalyzes the reduction of oxidized glutathione GSSG to GSH and it is essential for the GSH redox cycle [106].
Because of their high reactivity, elevated ROS concentrations represent a great danger for biomolecules. At physiological concentrations, these molecules are often necessary for normal functioning of cells as second messengers in the transduction of the cell signaling [107]. They can be activated in such a way as to prevent or potentiate the cell death. Many signaling pathways in the cell can be activated in both directions (cell survival or apoptosis), which depends on the type and duration of oxidative stress or cell types. Also, some of these pathways can affect the activation or suppression of other signaling pathways in the cell.
It is difficult to determine which type of ROS activates signaling pathways, because of their extremely rapid conversion to other forms or due to the conversion of acid conjugates or complexes with transition metals [108]. It is believed that H2O2 is highly suitable as a secondary messenger because it does not randomly react with all of the molecules like other forms of ROS, but tends to oxidize the -SH group of cysteine (Cys), which is then reduced by GSH [109].
In this way, by redox cycling of Cys, many transcription factors are regulated, such as activating protein 1 (AP-1) [110], nuclear factor NF-IL6 [111], and proteins important in cell signaling and cancerogenesis: protein kinase C (PKC), Ca2+-ATPase, collagenases, and SRC tyrosine kinase [108]. It is known that ROS are critical molecules in regulation not only of the AP-1 but also AP-2 [112] and of nuclear factor NF-kappaB [113] transcription families, which have a decisive role in cell proliferation, differentiation, and morphogenesis.
Other processes induced by hydrogen peroxide included activation of the stress-activated protein kinase/c-Jun N-terminal kinases (SAPK/JNK), the increased c-Jun phosphorylation, activation of caspase 3 (CPP32), and decomposition of poly(ADP-ribose) polymerase (PARP), which are associated with the apoptosis process [114]. Besides regulating the activity of cell proteins, H2O2 also induces the expression of many genes [115]. In addition, these molecules are responsible for the disruption of cell signaling and regular patterns of gene expression [116], which can lead to a number of pathological processes including carcinogenesis. The process of carcinogenesis is complex and consists of a series of changes at the cellular and molecular levels and in at least three stages: initiation, promotion, and malignant conversion, i.e., progression [117].
In relation to carcinogenesis, it is known that the AO system has a role in preventing its occurrence and promotion. The studies AO status in tumor tissues have not yet yielded results that could lead to general conclusions about AO defense in tumor tissues. Since the carcinogenesis occurs in several stages, it is likely that the antioxidant defense depends on the type of cell and tissue [118]. Mammalian cells and tissues differ significantly in the generation of ROS. They also vary in antioxidant activity, induction capability, and cell repair capacities which altogether results in a different susceptibility of mammalian tissues for tumor induction [119-121].
Our earlier studies indicated a significant role of oxidative-induced injury in the breast carcinogenesis, particularly during the later stages of aging [122]. It was also observed that chemotherapy and radiotherapy promote further oxidative shift, which potentiates already existing chronic oxidative stress linked to breast cancer [123]. It is believed that the high antioxidant capacity protects DNA from oxidative damage and mutagenesis but also can protect the cells in the stage of initiation of increased oxidative toxicity, thus favoring their clonal expansion and tumor progression [124]. It has long been known that oxidizing agents may be cytotoxic, although under certain circumstances, can promote cell growth and facilitate the clonal expansion of the initiated cells in carcinogenesis [125].
Some previous studies have shown that compared to healthy people, women with benign and malignant changes in the genital tract have increased level of lipid peroxidation and altered activity of AO enzymes in peripheral blood and tissue. Chiou and Hu [126] have detected that the activity of SOD in plasma and erythrocytes of patients with cervicitis and uterine myoma was lower compared to that of healthy women. At the same time, patients with cervicitis had an increased level of CAT and GPx activity, while their activity in patients with uterine fibroids (leiomyoma) was reduced. Similar results regarding the activities of SOD, CAT, and GPx in erythrocytes of patients with cervicitis were obtained by Manoharan et al. [127]. These authors also found that the activity of these enzymes was lower in patients with cervical cancer. Research of Kolanjiappan et al. [128] and Manoharan et al. [127] showed that the level of lipid peroxidation increased and the concentration of the antioxidant GSH, vitamin E, and CAT decreased in erythrocytes of patients with cervical cancer. These patients had altered activity of Na+K+-ATPase in erythrocytes compared to healthy persons. Our previous results showed that AO status in blood of gynecological patients varies with diagnosis and the enzyme type. Generally, both reduction in antioxidants and elevation of lipid peroxidation were observed. Lipid hydroperoxide level was negatively correlated to SOD and GPx activities and concurrently positively correlated with CAT activity. In addition, the lipid hydroperoxides/glutathione peroxidase ratio increased, according to the type of uterine disorder [129-131]. The perturbation of antioxidant status was more pronounced in blood of patients with hyperplastic and adenocarcinoma lesions compared to those with benign uterine changes such as polypus and myoma. Our results of AO status in endometrial tissue showed significant decrease of SOD activity in women with hyperplasia and adenocarcinoma. In both types of hyperplasia, activities of GPx and GR were increased to 60 % and 100 % on average, while in adenocarcinoma patients, only GR activity was elevated to 100 %. CAT activity was significantly decreased in adenocarcinoma patients (47 %). Lipid hydroperoxides level was negatively correlated to SOD and CAT activities and positively correlated to GPx and GR activities [132]. Since association of different clinical risk factors and various types of gynecologic pathologies is still not fully known as well as their influence on AO status, in our latest study, we evaluated the influence of diagnostic categories, age, and reproductive factors on AO status in blood of gynecological patients [133].The obtained results showed that reproductive and other factors may be associated, at least partially, with AO capacity and ability to defend against the oxidative damage in gynecological patients.
The AO status and hormone influence were studied during the menstrual cycle and postmenopause in healthy women and those with gynecologic disorders. The SOD was found to have a role in maintaining luteal cell integrity and steroidogenic capacity in fertile women [134]. An increase in the GPx activity was observed during the menstrual cycle, from the late follicular to the early luteal phase. The rise in GPx activity is related to increased ovarian production of estrogen that occurs in that particular period of menstrual cycle [135]. Decrease in GPx activity has been noted in the endometrium and blood in late-menopausal women [136]. Menopause is accompanied by hormone imbalance. A significant fall of the estrogen serum level with rise of follicle-stimulating hormone (FSH) has been recorded in postmenopausal women compared to premenopausal women [137]. Hormone replacement therapy (HRT) shows protective antioxidant role by reduction of lipid peroxide (LOOH) serum levels [138]. It is also found that HRT positively correlates with SOD activity in postmenopausal women [139].
We have shown that AO enzyme activity and lipid hydroperoxide level in patients with endometrial polyps are influenced by the changes in sex hormones during the menstrual cycle and in menopause [140]. In this study, we aimed to examine the AO status in menstrual cycle and postmenopause of women with endometrial hyperplasia simplex as well as the relationship between sex hormones and AO parameters.
Venous blood samples were collected into heparinized tubes on the same day of uterine biopsy and aliquoted immediately. For SOD assay (OxisResearch™), blood was centrifuged at 2500 g for 5 min. Plasma was discarded and pellet was resuspended in 4 packed-cell volume of ice-cold demineralized ultrapure water (MilliQ reagent grade water system, Millipore Corp., Bedford, MA, USA). After addition of ethanol/chloroform extraction reagent (62.5/37.5 vol/vol) to remove hemoglobin interference, samples were centrifuged at 3000 g for 10 min (Eppendorf centrifuge 5417, Eppendorf AG, Hamburg, Germany). Upper aqueous layer was collected and kept at -70 ºC until assay.
Fresh endometrial tissue samples were washed in saline solution and homogenized in phosphate buffer containing 0.05M KH2PO4 and 1 mM EDTA, pH 7.8 (1 g tissue per 2 ml buffer) in a Teflon/glass homogenizer (Spindler & Hoyer, Göttingen, Germany) and frozen at -70 ºC for 20 h in order to disrupt cell membranes. For SOD assay (OxisResearch™), thawed homogenates were vortexed 1 min and centrifuged at 8600 g, for 20 min at 4 ºC (Eppendorf centrifuge 5417, Eppendorf AG, Hamburg, Germany). According to manufacturer’s recommendation, after addition of ethanol/chloroform extraction reagent (62.5/37.5 vol/vol) to completely remove hemoglobin interference, samples were centrifuged at 6000 g for 20 min, at 4 ºC (Beckman centrifuge J2-21, Beckman Instruments Inc., Palo Alto, CA, USA). Upper aqueous layer was collected and kept at -70 ºC until assay. The enzyme activities and lipid hydroperoxide (LOOH) concentration were monitored spectrophotometrically (Perkin Elmer Spectrophotometer, Lambda 25, Perkin Elmer Instruments, Norwalk, CT,USA).
The specific enzyme activities were expressed as Units (U) or mU per milligram of total cell protein (U or mU/mg protein), and LOOH concentration was expressed as nmol/mg protein. Protein concentration in tissue homogenates was performed by the method of Lowry et al. [141] and expressed as mg/ml. Plasma follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E), and progesterone (P) levels were analyzed using standard radioimmunoassay (RIA) methods by the hormone analysis laboratory.
The phase-related concentrations of gonadotropins and sex hormones are reported in Table 2. Significant changes were observed in FSH (H=12.75, p<0.01, Kruskal-Wallis), LH (H=8.98, p<0.01, Kruskal-Wallis), and estradiol (H=7.93, p<0.05, Kruskal-Wallis) concentrations.
\n\t\t\t | \n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t
FSH (U/L)** Median (Min/max) | \n\t\t\t14.30±3.51 11.50 (7.50–31.50) | \n\t\t\t13.20±2.21 10.80 (0.1–31.50) | \n\t\t\t38.88±7.88 32.15 (14.30–75.00) | \n\t\t
LH (U/L)** Median (Min/max) | \n\t\t\t3.33±1.70 2.50 (0.60–9.40) | \n\t\t\t3.93±0.96 3.10 (0.60–11.20) | \n\t\t\t11.88±2.47 11.25 (1.30–24.00) | \n\t\t
Estradiol (pg/ml)* Median (Min/max) | \n\t\t\t39.30±7.59 48.80 (12.60–57.20) | \n\t\t\t71.41±14.07 56.50 (10.00–208.10) | \n\t\t\t5.16±1.16 3.80 (0.70–11.40) | \n\t\t
Progesterone (nmol/L) Median (Min/max) | \n\t\t\t7.40±1.09 6.30 (5.20–12.10) | \n\t\t\t8.83±2.68 5.30 (1.30–41.60) | \n\t\t\t5.16±1.16 3.80 (0.70–11.40) | \n\t\t
Changes in hormone levels during follicular phase, luteal phase, and in postmenopause (data are expressed as mean ± SEM; * p<0.05, **p<0.01)
Figure 1 shows the phase-related changes of LOOH concentrations and AO enzyme activities in the blood of examined patients. The significant change with respect to the phase was observed in LOOH concentrations (H=5.76, p<0.05, Kruskal-Wallis). In the follicular phase, it was significantly lower than in the postmenopause (p<0.05, Dunn test). There were no significant changes of AO enzymes in the examined phases.
The linear regression analysis of individual hormonal variables against antioxidant parameters in blood (Figure 2) showed a significant negative correlation between FSH concentrations and GR activity (r=-0.42, p<0.05), as well as a significant positive correlation between LH and LOOH concentrations (r=0.38, p<0.05). No significant correlations were found between other hormones and antioxidant variables.
Changes in blood LOOH concentrations and AO enzyme activities in follicular phase (F), luteal phase (L), and postmenopause (PM) in blood of patients with hyperplasia simplex. Data are shown as mean ± SEM.
Linear regression line and 95 % CI to study the relationship between log FSH and GR activity; log LH and LOOH concentration in the blood of patients with hyperplasia simplex
The phase-related changes of LOOH concentrations and AO enzyme activities in hyperplasia simplex tissue are shown in Figure 3. The LOOH concentration significantly differed with respect to the phase (H=7.74, p<0.05, Kruskal-Wallis), and it was significantly elevated in luteal phase and in postmenopause, in comparison to the follicular phase (p<0.05, Dunn test).
Unlike blood, where no changes in AO enzyme activities were recorded, we found significant phase-related changes of SOD (H=9.11, p=0.01, Kruskal-Wallis) and CAT activity H=7.60, p<0.05, Kruskal-Wallis). Both enzymes had similar activity pattern, which was higher in luteal phase and in postmenopause, compared to follicular phase (p<0.05, Dunn test). The phase-related activity of GPx and GR did not show any statistical difference.
The linear regression analysis of hormone levels on the examined AO parameters in hyperplasia simplex tissue showed a negative correlation between progesterone and GR activity (Figure 4) (r=-0.36, p<0.05).
Changes in endometrial LOOH concentrations and AO enzyme activities in follicular phase (F), luteal phase (L), and postmenopause (PM) in hyperplasia simplex tissue. Data are shown as mean ± SEM.
Linear regression line and 95 % CI to study the relationship between log Pr and GR activity in hyperplasia simplex tissue.
Studies have shown a different AO status and sex hormone influence during menstrual cycle and postmenopause in healthy women and those with ovarian disorders [143-146], but we found no data regarding that relation in patients with endometrial hyperplasia simplex.
In the blood of these patients, we detected a lower level of LOOH in the F phase in comparison to the postmenopause. In hyperplastic tissue, LOOH level was lower in the F phase than in L phase and postmenopause. The activities of SOD and CAT were also lower in F phase when compared to the L phase and postmenopause. There was a negative correlation between FSH/P concentrations and GR activity in the blood and hyperplastic tissue, respectively. Positive correlation between LH and LOOH concentrations was recorded in the blood.
Similar pattern of LOOH concentration and SOD activity in endometrium of healthy women throughout the menstrual cycle was also observed in [134]. They found that LOOH concentration increased from early proliferative phase to mid-late proliferative phase and further increased in the late secretory phase. The SOD activity increased from early proliferative phase to mid-late proliferative phase, further increased in the mid-secretory phase, and then decreased in the late secretory phase. Previous investigations of immunohistochemical distribution of SOD in human endometrium during menstrual cycle also showed that surface and glandular epithelia contain SOD during proliferative and secretory phases except just prior to the menstruation [147].
The study of Ota et al. [148] regarding SOD expression in endometrium during the menstrual cycle of healthy fertile women and women with diagnosed endometriosis and adenomyosis have shown the phase-dependent changes of SODs in glandular and surface epithelia in healthy women. Specifically, the expression of copper, zinc SOD was lowest during the early and mid-proliferative phases and then gradually increased and was most pronounced in the early and mid-secretory phases. The expression of manganese SOD reached a peak in the late secretory phase. In women with endometriosis and adenomyosis, the expression of both SODs was constantly elevated compared to healthy women throughout the menstrual cycle, which suggested a key role of superoxide in infertility caused by endometriosis and adenomyosis [148]. Our recent findings in women with endometrial polyp showed the opposite pattern of LOOH concentration and SOD activity in blood and polyp tissue than in women with hyperplasia simplex. Both parameters were higher in the proliferative phase compared to the secretory phase or postmenopause in blood and endometrium of the examined women [140].
Regarding CAT, in [149], it was found that CAT expression in healthy women fluctuated greatly during the menstrual cycle and the surface epithelium showed a similar pattern to that in the glandular epithelium. The expression was the lowest during the early proliferative phase, increased during the mid-proliferative phase, and peaked in the late secretory phase. In patients with endometriosis, the CAT expression did not fluctuate during the cycle, but it was consistently elevated throughout the menstrual cycle when compared to healthy women. Likewise, in women with adenomyosis, the CAT expression did not vary during the cycle in comparison to healthy ones, and it was significantly higher than in patients with endometriosis [149]. In women with endometrial polyp, we found no significant change of CAT activity in different phases [140]. In this study, however, the CAT activity in endometrium of patients with simple hyperplasia was also similar to the healthy women.
Studies in women with gynecologic disorders indicate a different AO status, as one of the possible factors contributing to the development of oxidative stress [150]. There are also studies which investigated the role of oxidative stress and hormones in development of gynecologic pathologies. For example, in [151], it was found that FSH, LH, and estrogen could induce ROS production at different levels in ovarian epithelial carcinoma and may therefore participate in cancer development process. FSH was found to increase cell proliferation in ovarian epithelial carcinoma (OEC) [152], and LH may also be involved in OEC development under pathological conditions [151].
Simple hyperplasia is the most common type of endometrial hyperplasia and the type most likely to spontaneously regress, and it rarely progresses to endometrial cancer [42, 51, 153]. The LOOH concentrations and AO enzyme activities in this study which were similar to the healthy women point to the preserved cellular AO status in these patients. Endometrial hyperplasias are generally considered as precancerous lesions and are treated either conservatively or surgically. The regression of hyperplastic to normal endometrium is the main purpose of any conservative treatment. It is based on the administration of agents, like progestogens [154], which have an indirect antiestrogenic action and also a direct antiproliferative effect on the endometrium [155]. Also, therapeutic application of gonadotropin-releasing hormone analogue (GnRHa) in women with hyperplasia was associated with high regression rates. The regression to normal endometrium is considered to be due to decreased gonadotropin levels as a result of pituitary downregulation or to the decreased ovarian steroidogenesis following low gonadotropin levels [156, 157]. The results of this study also showed that gonadotropins and progesterone influenced oxidant/antioxidant parameters in hyperplastic patients. Although we found no significant changes of GR activity among the menstrual cycle phases, FSH/P was negatively correlated with GR activity in the blood and hyperplastic tissue, while positive correlation between LH and LOOH concentrations was recorded in the blood. Our previous study in women with endometrial polyp also showed the influence of gonadotropins on AO status. In these patients, we observed a negative correlation between FSH/LH and GPx activity and also between LH and SOD activity [140].
The role of gonadotropins in gynecological diseases in not fully clarified. In ovarian epithelial cancer (OEC), gonadotropin theory proposes that elevated serum FSH and LH levels contribute significantly to its development [158]. FSH generally acts through its membrane-bound receptor which activates the intracellular signaling cascade, starting with cyclic AMP/protein kinase A (cAMP/PKA) that is followed by phosphorylation of specific transcriptional factors, like cAMP-response element-binding protein (CRE), or p38 MAPK, which controls other kinase cascades. The FSH receptor can also activate extracellular signal-regulated protein kinases (ERK-s) [159].
It was shown that synthesis of antioxidants, such as glutathione in the ovary, is regulated by gonadotropins, but exact mechanisms are still unknown [160]. One of the mechanisms behind FSH and antioxidants interaction is through activation of transcriptional factors, like Nrf2. The induced Nrf2 binds to the antioxidant-response element (ARE), thus coordinately regulates the expression of AO genes [161].
The pathogenesis of endometrial hyperplasia is still not fully understood. Prolonged estrogen stimulation is considered as one of the factors related to the etiology. This study showed that patients with endometrial hyperplasia simplex have similar AO status like healthy women, and it also demonstrated the relation of hormones and prooxidant/antioxidant parameters in this gynecologic disorder. Since simple hyperplasia may spontaneously regress, these results point to the preserved AO capacity as a potentially important factor in the regression mechanisms. However, the role of ROS production as a risk factor for endometrial hyperplasia still needs to be clarified as well as the role of AO status in response to gonadotropins and sex steroids.
This work was financially supported by the Ministry of Education, Science and Technological Development, Republic of Serbia (Grants 41027, 41022, 173041).
Forests provide important protection against rockfall in steep mountain terrain [1]. Thanks to this so-called nature-based solution, maintenance and installation costs of technical protection measures, such as dams or nets, are financially bearable or can even be avoided at many places due to the reduction of rockfall rebound heights and impact energies by previous impacts on trees [2]. Furthermore, protection forests fulfill additional functions in terms of wood production, biodiversity or water filtration [3]. Knowing the value of the protection service of mountain forests is key to efficiently allocate financial resources in forest and natural hazard management. A realistic valuation of the protective function of forests, however, can only be guaranteed if long-term costs and benefits are considered [4]. Often, the value of the protective function of forests is only qualitatively assessed or estimated based on general costs of replacing [5]. However, such approaches, only indirectly quantify the effect of forests on natural hazards and do not account for the potential damage prevented by the forest. A risk-based approach, on the other hand, allows for a translation of the physical effect of trees on the natural hazard process into monetary terms and thus a direct quantification of the avoided costs [6]. The latter are defined as the difference in risk with and without the protective effect of the forest [7]. To support decisions on risk prevention measures, including protection forest management or combinations of different types of measures, a cost–benefit analysis (CBA) is a method that provides standardized and quantified information on the efficacy and efficiency of the analyzed measures [8]. For a realistic long-term economic assessment of risk reduction measures, all costs and benefits must be adjusted to a common point of time, which can be done by calculating the Net Present Value (NPV), being the sum of all future expected benefits and costs discounted to today [9].
Valuing the protection service of the forest can facilitate the prioritization of protection forest management at local, regional and national scale. At local (e.g. slope) scale, a detailed quantification of the protective effect of a protection forest complex (i.e. one or multiple forest stands that protect against a natural hazard process) is required i) for the planning and comparison of risk prevention measures and ii) as basis for an efficient forest management. A valuation of the forest’s protective effect at regional (e.g., valley) scale is important for the large-scale planning and prioritization of forest management measures.
In this chapter, we quantify the protective effect of forests against rockfall at local and regional scale using a risk-based approach. We present a simple method to estimate risk and the risk reduction provided by forest at regional scale and then do a profound economic valuation of a single protection forest complex based on a cost–benefit analysis and compare it to technical protection measures. The methodological approaches are presented based on a case study region along the Gotthard highway in Switzerland, where rockfall events frequently end up on the mountain side driving lanes.
As a basis for prioritization of regional protection forest planning, we determined rockfall risk under the current forest conditions for a case study region along the Gotthard highway based on a simple risk approach. We subsequently used a statistical model to determine the risk reduction potential of the forest in monetary terms (Figure 1). The study region comprises a section of the Gotthard highway A2 in Switzerland between Gurtnellen and Wassen with a length of ~5.5 km (canton Uri; Figure 2). This highway section is continuously endangered by rockfall from cliff faces that stretch stepwise from approx. 750 to 2000 m a.s.l. There are several sections (in total ~2.2 km) that are protected by galleries from rockfall and other natural hazard processes.
Flow chart of the methodology for the risk-based evaluation of the protective effect of forests at regional scale.
Study region along the A2 Gotthard highway with protection forest complexes and release area and the local case study site in Meitschlingen.
Rockfall release areas were determined using a slope threshold angle of 50°. We estimated rockfall runout zones based on the energy line principle, using the ELine tool [10], which calculates potential runout cones for each rockfall start cell. In case of multiple start cells, overlaying runout cones allow for a quantification of the reach probability of blocks in a specific cell. Based on these modeled reach probabilities, we calculated a relative reach probability along the highway by defining three probability classes (“low”, “medium”, “high”). We assumed an energy line angle of 30° for the total study area and additionally calculated runout zones with an angle of 35°, which did not result in changing reach probability classes. The runout zones were determined for a block volume of 2 m3, which regularly reaches the highway. The occurrence frequency of blocks >= 2 m3 on the highway was determined based on inventory data from the national road office [11]. The catalog contained 31 events of one or several blocks that reached the highway or stopped in nets just above in 30 years. We therefore assumed in this study an occurrence frequency of 1 rockfall event (>= 2 m3) per year reaching the highway (galleries excluded). This frequency was then weighted for different highway sectors according to the calculated reach probability classes. We then calculated the yearly rockfall risk (CHF.yr.−1) for each section based on [11] and accounted for the damage types “direct impact” (only for regular fluid traffic conditions), “collision” (with rock deposits on the road or other vehicles), “infrastructure damage” and “road closure after a hazard event” (see also [12] for a detailed description of risk calculation). The variable values used for the risk calculation are presented in Table 1. Sectors with galleries were not considered in the risk analysis. We used vulnerability values for objects and persons for the intensity classes according to [11]. The monetary value of the element at risk was calculated as the sum of the standardized object value [11] and the monetized value of persons (given as 6,600,000 CHF person−1 in Switzerland; [14]).
Variable | Value | Unit | Source |
---|---|---|---|
Mean daily traffic (MDT) | 22,500 | vehicles.day−1 | www.astra.admin.ch |
Indicated maximum speed on the highway section | 100 | km.h−1 | Field observation |
Forest intervention costs (harvesting + preparation, road maintenance) | 110 | CHF.m−3 | [13] |
Revenue from wood sales | 75 | CHF.m−3 | idem. |
Net installation costs (200 kJ) | 1,200 | CHF.m−1 | [4] |
Net installation costs (500 kJ) | 1,500 | CHF.m−1 | idem. |
Net installation costs (5000 kJ) | 4,500 | CHF.m−1 | idem. |
Discount rate (mean value last 30 years in CH) | 2 | % | idem. |
Road closure costs | 87,000 | CHF.day−1 | [11] |
Costs of human life | 6,6 Mio | CHF | [14] |
Values and their sources of variables used for the calculation of risks and the NPV.
In order to estimate the risk for the unforested slope, we determined the risk reduction potential of the current forest based on a statistical approach proposed by [13]. The model calculates the relative reduction (in percent) of the rockfall frequency and intensity depending on the basal area of the forest, the forested slope length, the block volume and the horizontal forest structure (e.g., gaps, clustered, …). We applied it to homogenous forest areas determined based on the forested slope length. Since no regional data on forest structure (e.g. cantonal forest inventory) was available, we assumed a basal area of 15 (“bad forest condition”) and 30 (“good forest condition”) m2.ha−1, respectively, covering a realistic range determined based on the forest data available from the local case study (see subchapter 3). We only calculated frequency reduction, since we used intensity classes in the risk analysis and a direct translation of the forest effect is not applicable. Based on the derived risk without forest, we were able to assess the risk reduction provided by the forest per road section in monetary terms (CHF.yr.−1).
The risk on the total section for the current situation with forest amounts to ~330,000 CHF.yr.−1 (Table 2). More than two thirds stem from direct impacts and 25% from road closure after hazard events. In other words, one fatality due to direct impacts is expected every 30 years on average. The risk reduction provided by the forest varies between 15 and 55% under good forest conditions and 0 and 30% under relatively bad forest conditions (i.e., regarding rockfall protection), respectively (Table 2). This results in a yearly risk reduction between 800 and 2,500 CHF and 0 and 1,000 CHF, respectively, per ha protection forest (Figure 3). Based on the calculated risk reduction, the total risk would increase to ~470,000 CHF.yr.−1 without forest.
Section | Total risk with forest [CHF.yr.−1] | Risk reduction forest (range) [%] | Total risk without forest (range) [CHF.yr.−1] |
---|---|---|---|
1 | 13,800 | 0 | 13,800 |
3 | 19,000 | 0–15 | 19,000–22,300 |
5 | 52,200 | 0–16 | 52,200–62,400 |
7 | 113,700 | 30–55 | 157,000–208,700 |
9 | 90,300 | 0–21 | 90,300–114,600 |
10 | 40,800 | 0–15 | 40,800–48,100 |
Calculated total risk with and without forest for the road sections (see Figure 3; without galleries) and risk reduction provided by the forest (reported as range for a forest with a basal area of 15 or 30 m2.Ha−1).
Total risk with the current forest along the considered highway section, and risk reduction provided by the protection forest complexes.
As a basis for comprehensive forest management at local scale, we economically assessed the performance of a particular protection forest complex in the study region and compared it to structural protective measures and a combined approach (Figure 4). The chosen site is the Gotthard highway section between Meitschligen and Stotzigwald (Figure 2).
Flow chart of the methodology for the economic evaluation of a protection forest at local scale based on the calculation of the net present value (NPV).
We determined the net present value (NPV) of the current forest with a management scenario of gap cuttings that aims at promoting regeneration (variant 1) and compared it to i) a combination of variant 1 and the currently installed flexible nets (variant 2), and ii) only currently installed flexible nets, without trees (variant 3). To determine the benefit (i.e., risk reduction), we compared the risk with a given protection measure variant with the situation without protective measures (no trees and no nets). This is the “baseline” variant.
To calculate the risk for a given protection measure, we modeled the propagation of single rectangular blocks with a maximum volume of 1, 2 and 15 m3 with the three-dimensional rockfall trajectory software RockyFor3D [15]. The topography was defined by a digital elevation model (DEM) with a resolution of 2 x 2 m and soil types and roughness were mapped in the field. Forest stands were delineated with orthophotos and field inventory plots. For each stand, we measured trees with a stem diameter at breast height (DBH) larger than 8 cm in randomly sampled plots of 20 by 20 meters. All trees were recorded. Subsequently, the mean DBH, the standard deviation of the DBH, the number of stems per hectare and the proportion of coniferous trees were calculated for each stand. RockyFor3D uses this data to create a forest model consisting of individual trees with their position and DBH. We assumed that every 20 years, 25% of the total standing volume would be removed by using cable crane lines and lateral regeneration gap cuttings of 20 by 30 m. We removed the trees in the intervention gaps from the generated forest model and simulated rockfall trajectories and calculated the change in risk reduction after a forest intervention. The current mean standing volume per ha is 575 m3 (i.e., almost 6000 m3 on 10.4 ha). The net costs of a single forest intervention add up to 165,808 CHF (intervention costs) – 113,098 CHF (revenue of wood sales) = 57,710 CHF.
The rock type is gneiss and we defined its density as 2700 kg.m−3. The used block volumes were defined by a geological engineering consulting firm commissioned by the Swiss Federal Roads Office FEDRO for a hazard analysis in 2010. The attributed onset probabilities (detachment probability at the rockfall cliffs) were 0.067 (10-year recurrence interval – 1 m3), 0.023 (30-year recurrence interval – 2 m3), 0.007 (100-year recurrence interval – 15 m3) and 0.003 (300-year recurrence interval – 15 m3). The difference between the 100- and 300-year recurrence interval was determined by the number of individual blocks that descend the slope, which was randomly set to 2 to 5 blocks for the 100- and 4 to 8 blocks for the 300-year recurrence interval. The 10-year recurrence interval was a fixed single block scenario, while the 30-year recurrence interval was a randomized 1 to 3 block(s) scenario.
Upslope along the highway we placed a virtual control screen allowing for recording all relevant data for the risk calculation (number of passed rocks, energy distribution, passing height distribution). For each defined block volume and variant, we simulated 1000 trajectories per release cell.
As for the large-scale study, our risk calculation was based on [10] and accounted for the same damage types. We then calculated the NPV, based on the defined recurrence intervals, following:
Where I(w) = revenue from wood sales (CHF); I(rr) = risk reduction (CHF); O(n): costs for installing flexible nets (CHF); O(m) = Operation and maintenance costs for the flexible nets (CHF); O(f) = Costs for forest interventions (CHF); i = discount rate; t = year.
Values for the variables we used for the calculation of risks and the NPV, are presented in Table 1. We here focused on the risk calculation on the highway only.
The total risk per year (sum of the risk for the four defined rockfall recurrence intervals) for both the baseline and protection forest variant is given in Table 3. The current forest (without nets) provides a risk reduction of 5,154 CHF.yr.−1. In combination with nets, the risk reduction is increased up to 10,900 CHF.yr.−1. However, only the NPV of variant 1 (current forest without nets) is positive. All variants with nets have a distinctly negative NPV due to the high investment and maintenance costs of the rockfall nets.
Variant | Total risk [CHF.yr.−1] | Difference with baseline variant [CHF.yr.−1] | NPV [1000 CHF] | Benefit–cost ratio [−] |
---|---|---|---|---|
“Baseline” (no trees, no nets) | 30,647 | — | — | — |
1 (current forest/no nets) | 25,493 | 5,154 | 110 | 1.79 |
2 (variant 1 + current nets) | 23,464 | 7,182 | -1,314 | 0.24 |
3 (variant 1 + maximum nets) | 19,743 | 10,904 | −10,814 | 0.05 |
4 (current nets, no trees) | 29,690 | 956 | −1,469 | 0.04 |
Total risk per year, risk reduction (difference to baseline variant), NPV and benefit–cost ratio per protection measure variant for the case study site in Meitschligen.
The here presented large-scale risk assessment evinced a substantial risk reduction between 500 and 5000 CHF.(ha.yr)−1 of the current protection forest along the Gotthard highway. Without the forest, risk would increase up to 150%. When additionally considering the reduction of rockfall intensity (and not only rockfall frequency), risk could even increase more. The proposed methodology allows for a simple estimation of risk and the protective effect of the forest and thus serves as an ideal basis for a rough prioritization of protection forest management at regional scale. Assuming that silvicultural interventions in a protection forest complex are required approximately once per 20 to 30 years and that they cost 12,500 CHF per hectare and intervention (maximum federal contribution to protection forest intervention in Switzerland; [16]), protection forest management is with yearly costs of ~500 CHF highly efficient. For this, however, a basal area of minimum 30 m2.ha−1 is required. How much a forest reduces risk depends strongly on its structure and state. A low tree density and a short forested slope length can critically reduce the protective capacity [13, 17]. Thus, spatial data on forest structure are required to satisfactorily predict the risk reduction of the forest. In this study, such data was partially missing why we calculated risk reduction for a range of the basal area. Furthermore, the block volume strongly influences the protective effect of forests. This effect was greatly simplified by considering rockfall risk generalized for block volumes >= 2 m3.
For a risk-based planning of protection forest management at local scale, a more detailed approach is necessary. The calculation of the NPV of a protection forest complex based on its risk reduction allowed for a long-term economic valuation of the protection service and a comparison to technical measures and combined approaches. Although the variant forest + nets provides the highest risk reduction, its NPV is highly negative (−1 million CHF over a period of 100 years) and its benefit–cost ratio is 0.05. Variant 1 (forest with management and no nets) is the only one with a positive NPV. This variant is also the only one with a benefit–cost ratio larger than 1. Comparing variant 1 to variant 4 (nets without forest) shows a substantial increase of the efficacy of the forest-nets combination with an increased risk reduction of more than 400%. Hence, combining forests and nets can significantly increase the risk mitigation capacity of nets.
Finally, the results from the regional study are in good agreement with the detailed analysis on local scale (i.e., the Gotthard highway section between Meitschligen and Stotzigwald used for the local scale study corresponds to 60% of the highway section nr. 10 in the regional study). On regional scale, we calculated a risk of 40,800 CHF.yr.−1 and a risk reduction of the forest of 7,200 CHF.yr.−1 for a forest with a basal area of 30 m2.ha−1 in the respective section. In the local study, we revealed a risk of 25,400 CHF.yr.−1 and a risk reduction of 5,200 CHF.yr.−1. This indicates that the on large scale estimated risk reduction of the forest covers a realistic range.
The presented methods allow for a differentiated procedure for protection forest planning at different scales. At regional scale, the combination of a simple risk approach and a statistical model enables practitioners to determine the risk reducing effect of the forest as basis for prioritization of forest management measures. Currently, prioritization is mainly done on the basis of Eisenhower’s Urgency/Importance principle, where urgency is determined by the state of the protection forest and importance on the provided protection. The latter however, is based on a rapid qualitative expert appraisal, which can be more objective based on the method proposed in this chapter. The method requires mainly i) elevation and land cover data for a rough estimation of rockfall runout and intensities; ii) basic data on the damage potential; and iii) spatial data on forest cover (i.e. basal area and forested slope length). At local scale, more detailed data on rockfall frequency and runout as well as on forest structure and the costs and benefits of protection forest interventions are necessary to conduct a detailed economic evaluation of the protection forest service. Such an evaluation allows practitioners for planning efficient (both economically reasonable and sufficiently effective) protective measure variants that take protection forests, including the required silvicultural interventions, into account. For additional risk-based evaluation approaches of forests’ protective effects against gravitational natural hazards see chapters [18, 19, 20] of this book.
The authors declare no conflict of interest.
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Flawed sample preparations can undermine the quality of results and lead to false conclusions. Thus, the aim of this chapter is to equip researchers, post graduate students and technicians with essential knowledge required to prepare samples for scanning electron microscopy (SEM) investigations in the life sciences.",book:{id:"5075",slug:"modern-electron-microscopy-in-physical-and-life-sciences",title:"Modern Electron Microscopy in Physical and Life Sciences",fullTitle:"Modern Electron Microscopy in Physical and Life Sciences"},signatures:"Mogana Das Murtey and Patchamuthu Ramasamy",authors:[{id:"176330",title:"Dr.",name:"Mogana",middleName:"Das",surname:"Murtey",slug:"mogana-murtey",fullName:"Mogana Murtey"},{id:"181159",title:"Mr.",name:"Patchamuthu",middleName:null,surname:"Ramasamy",slug:"patchamuthu-ramasamy",fullName:"Patchamuthu Ramasamy"}]},{id:"26791",doi:"10.5772/28067",title:"Optical Vortices in a Fiber: Mode Division Multiplexing and Multimode Self-Imaging",slug:"optical-vortices-in-a-fiber-mode-division-multiplexing-and-multimode-self-reproducing",totalDownloads:4552,totalCrossrefCites:30,totalDimensionsCites:49,abstract:null,book:{id:"2018",slug:"recent-progress-in-optical-fiber-research",title:"Recent Progress in Optical Fiber Research",fullTitle:"Recent Progress in Optical Fiber Research"},signatures:"S.N. 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The possible interferences of atomic or molecular species are used to specify organic, inorganic or biological materials which allows critical applications in defense (landmines, explosive, forensic (trace of explosive or organic materials), public health (toxic substances pharmaceutical products), or environment (organic wastes). Laser induced plasma for organic material potentially provide fast sensor systems for explosive trace and pathogen biological agent detection and analysis. The laser ablation process starts with electronic energy absorption (~fs) and ends at particle recondensation (~ms). Then, the ablation process can be governed by thermal, non-thermal processes or a combination of both. There are several types of models, i.e., thermal, mechanical, photophysical, photochemical and defect models, which describe the ablation process by one dominant mechanism only. Plasma ignition process includes bond breaking and plasma shielding during the laser pulse. 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During first microsecond after the laser pulse, plume expansion is adiabatic afterwards line radiation becomes the dominant mechanism of energy loss.",book:{id:"5093",slug:"plasma-science-and-technology-progress-in-physical-states-and-chemical-reactions",title:"Plasma Science and Technology",fullTitle:"Plasma Science and Technology - Progress in Physical States and Chemical Reactions"},signatures:"Kashif Chaudhary, Syed Zuhaib Haider Rizvi and Jalil Ali",authors:[{id:"176684",title:"Dr.",name:"Kashif Tufail",middleName:null,surname:"Chaudhary",slug:"kashif-tufail-chaudhary",fullName:"Kashif Tufail Chaudhary"},{id:"176867",title:"Dr.",name:"Syed Zuhaib",middleName:null,surname:"Haider Rizivi",slug:"syed-zuhaib-haider-rizivi",fullName:"Syed Zuhaib Haider Rizivi"},{id:"176868",title:"Prof.",name:"Jalil",middleName:null,surname:"Ali",slug:"jalil-ali",fullName:"Jalil Ali"}]},{id:"52164",title:"An Overview on Quantum Cascade Lasers: Origins and Development",slug:"an-overview-on-quantum-cascade-lasers-origins-and-development",totalDownloads:3262,totalCrossrefCites:3,totalDimensionsCites:11,abstract:"This chapter presents an introductory review on quantum cascade lasers (QCLs). 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Furthermore, a number of state-of-the-art applications are described in different fields, and finally a brief assessment of the possibilities of volume production and the overall state of the art in QCLs research are elaborated.",book:{id:"5389",slug:"quantum-cascade-lasers",title:"Quantum Cascade Lasers",fullTitle:"Quantum Cascade Lasers"},signatures:"Raúl Pecharromán-Gallego",authors:[{id:"188866",title:"Dr.",name:"Raúl",middleName:null,surname:"Pecharromán-Gallego",slug:"raul-pecharroman-gallego",fullName:"Raúl Pecharromán-Gallego"}]},{id:"49526",title:"Focused Ion Beams (FIB) — Novel Methodologies and Recent Applications for Multidisciplinary Sciences",slug:"focused-ion-beams-fib-novel-methodologies-and-recent-applications-for-multidisciplinary-sciences",totalDownloads:4330,totalCrossrefCites:5,totalDimensionsCites:11,abstract:"Considered as the newest field of electron microscopy, focused ion beam (FIB) technologies are used in many fields of science for site-specific analysis, imaging, milling, deposition, micromachining, and manipulation. Dual-beam platforms, combining a high-resolution scanning electron microscope (HR-SEM) and an FIB column, additionally equipped with precursor-based gas injection systems (GIS), micromanipulators, and chemical analysis tools (such as energy-dispersive spectra (EDS) or wavelength-dispersive spectra (WDS)), serve as multifunctional tools for direct lithography in terms of nano-machining and nano-prototyping, while advanced specimen preparation for transmission electron microscopy (TEM) can practically be carried out with ultrahigh precision. Especially, when hard materials and material systems with hard substrates are concerned, FIB is the only technique for site-specific micro- and nanostructuring. Moreover, FIB sectioning and sampling techniques are frequently used for revealing the structural and morphological distribution of material systems with three-dimensional (3D) network at micro-/nanoscale.This book chapter includes many examples on conventional and novel processes of FIB technologies, ranging from analysis of semiconductors to electron tomography-based imaging of hard materials such as nanoporous ceramics and composites. 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In addition, the colloidal nanoparticles produced by laser ablation have very high purity—they are free from surfactants and reaction products or by-products. In this chapter, nanosecond, picosecond and femtosecond laser pulse durations are compared in laser material processing. Due to the unique properties of the short and ultra-short laser pulse durations in material processing, they are more apparent in the production of precision material processing and generation of nanoparticles in liquid environments.",book:{id:"5236",slug:"high-energy-and-short-pulse-lasers",title:"High Energy and Short Pulse Lasers",fullTitle:"High Energy and Short Pulse Lasers"},signatures:"Abubaker Hassan Hamad",authors:[{id:"183494",title:"Dr.",name:"Abubaker",middleName:"Hassan",surname:"Hamad",slug:"abubaker-hamad",fullName:"Abubaker Hamad"}]},{id:"49537",title:"Electron Diffraction",slug:"electron-diffraction",totalDownloads:10164,totalCrossrefCites:12,totalDimensionsCites:32,abstract:"Electron microscopes are usually supplied with equipment for obtaining diffraction patterns and micrographs from the same area of a specimen and the best results are attained if the complete use is to be made of these combined facilities. Electron diffraction patterns are used to obtain quantitative data including phase identification, orientation relationship and crystal defects in materials, etc. At first, a general introduction including a geometrical and quantitative approach to electron diffraction from a crystalline specimen, the reciprocal lattice and electron diffraction in the electron microscope are presented. The scattering process by an individual atom as well as a crystal, the Bragg law, Laue conditions and structure factor are also discussed. Types of diffraction patterns such as ring pattern, spot pattern and Kikuchi pattern, and general and unique indexing diffraction patterns are explained. The procedure for indexing simple, complicated and imperfect patterns as well as Kikuchi lines and a combination of Kikuchi lines and spots is outlined. The known and unknown materials are identified by indexing patterns. Practical comparisons between various methods of analysing diffraction patterns are also described. The basic diffraction patterns and the fine structure in the patterns including specimen tilting experiments, orientation relationship determination, phase identification, twinning, second phases, crystallographic information, dislocation, preferred orientation and texture, extra spots and streaks are described in detail. Finally, electron diffraction patterns of new materials are investigated.",book:{id:"5075",slug:"modern-electron-microscopy-in-physical-and-life-sciences",title:"Modern Electron Microscopy in Physical and Life Sciences",fullTitle:"Modern Electron Microscopy in Physical and Life Sciences"},signatures:"Mohsen Asadi Asadabad and Mohammad Jafari Eskandari",authors:[{id:"176352",title:"Dr.",name:"Mohsen",middleName:null,surname:"Asadi Asadabad",slug:"mohsen-asadi-asadabad",fullName:"Mohsen Asadi Asadabad"},{id:"177600",title:"Dr.",name:"Mohammad",middleName:null,surname:"Jafari Eskandari",slug:"mohammad-jafari-eskandari",fullName:"Mohammad Jafari Eskandari"}]}],onlineFirstChaptersFilter:{topicId:"20",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"83166",title:"General Drag Correlations for Particle-Fluid System",slug:"general-drag-correlations-for-particle-fluid-system",totalDownloads:0,totalDimensionsCites:null,doi:"10.5772/intechopen.106427",abstract:"Particle-fluid flows are commonly encountered in industrial applications. It is of great importance to understand the fundamentals governing the behavior of such a flow system for better process design, control, and optimization. Generally, the particle-fluid flow behavior is strongly influenced by the interaction forces between fluid and particles. Among the various kinds of particle-fluid interaction forces, the drag force is the most essential. This chapter reviews the modeling of drag force for particle-fluid systems: from single particle to multiple particles, monosize to multisize, spherical to nonspherical, and Newtonian fluid to non-Newtonian fluid. Typical drag correlations in the literature are compared and assessed in terms of physical meaning, consistency, and generality.",book:{id:"11498",title:"Boundary Layer Flows - Modelling, Computation, and Applications of Laminar, Turbulent Incompressible and Compressible Flows",coverURL:"https://cdn.intechopen.com/books/images_new/11498.jpg"},signatures:"Zheng Qi, Shibo Kuang, Liangwan Rong, Kejun Dong and Aibing Yu"},{id:"83137",title:"Synthesis of Nano-Optical Elements for Forming 3D Images at Zero Diffraction Order",slug:"synthesis-of-nano-optical-elements-for-forming-3d-images-at-zero-diffraction-order",totalDownloads:1,totalDimensionsCites:0,doi:"10.5772/intechopen.106145",abstract:"A method is proposed to compute and synthesize a nano-optical element to produce a new visual effect: a 3D image formed in the vicinity of zero diffraction order. Usual relief rainbow holograms or OVDs can form 3D effect, but at +1 or − 1 diffraction order only and they provide 3D parallax in left/right direction only, and after rotation/inclination of an element, a 3D image changes its color and further disappears completely. The new visual effect provides with full 3D parallax. Moreover, a 3D zero-order image is well visible when an optical element is rotated through 360 degrees; the color of 3D image does not depend on the viewing angle. A synthesis technology is developed incorporating the computation of scattering patterns in elementary areas, computation of the phase function of the entire optical element, and the formation of its microrelief by using e-beam lithography. The microrelief consists of multilevel kinoforms with an accuracy of 10 nm in terms of depth. It was demonstrated by experimental results that the new visual effect is easy for visual perception under white light illumination. A sample of nano-optical element is manufactured, which when illuminated by white light, forms a 3D image in the vicinity of zero-order of diffraction (video available at: https://bit.ly/3QtzxbI).",book:{id:"11860",title:"Holography - Recent Advances and Applications",coverURL:"https://cdn.intechopen.com/books/images_new/11860.jpg"},signatures:"Anton Goncharsky and Svyatoslav Durlevich"},{id:"83061",title:"Dipole Solitons in a Nonlocal Nonlinear Medium with Self-Focusing and Self-Defocusing Quintic Nonlinear Responses",slug:"dipole-solitons-in-a-nonlocal-nonlinear-medium-with-self-focusing-and-self-defocusing-quintic-nonlin",totalDownloads:17,totalDimensionsCites:0,doi:"10.5772/intechopen.106207",abstract:"Stability dynamics of dipole solitons have been numerically investigated in a nonlocal nonlinear medium with self-focusing and self-defocusing quintic nonlinearity by the squared-operator method. It has been demonstrated that solitons can stay nonlinearly stable for a wide range of each parameter, and two nonlinearly stable regions have been found for dipole solitons in the gap domain. Moreover, it has been observed that instability of dipole solitons can be improved or suppressed by modification of the potential depth and strong anisotropy coefficient.",book:{id:"10958",title:"Vortex Dynamics - From Physical to Mathematical Aspects",coverURL:"https://cdn.intechopen.com/books/images_new/10958.jpg"},signatures:"Mahmut Bağcı, Melis Turgut, Nalan Antar and İlkay Bakırtaş"},{id:"82984",title:"Feedback Linearization Control of Interleaved Boost Converter Fed by PV Array",slug:"feedback-linearization-control-of-interleaved-boost-converter-fed-by-pv-array",totalDownloads:2,totalDimensionsCites:0,doi:"10.5772/intechopen.106355",abstract:"One of the powerful methods of nonlinear control is the feedback linearization technique. This technique consists of input state and input-output linearization methods. In this chapter, the feedback linearization technique, including input state and input-output linearization methods, is described. Then, input-output linearization method is used for output voltage control of interleaved boost converter. Firstly, mathematical model of the interleaved boost converter is derived after that the method is applied. Besides, the interleaved boost converter is fed by a PV array under irradiation level and ambient temperature change. As a result of the simulation study, output voltage control of interleaved boost converter under reference voltage change is realized as desired.",book:{id:"11499",title:"Nonlinear Systems - Recent Developments and Advances",coverURL:"https://cdn.intechopen.com/books/images_new/11499.jpg"},signatures:"Erdal Şehirli"},{id:"82973",title:"Compact Incoherent Multidimensional Imaging Systems Using Static Diffractive Coded Apertures",slug:"compact-incoherent-multidimensional-imaging-systems-using-static-diffractive-coded-apertures",totalDownloads:8,totalDimensionsCites:0,doi:"10.5772/intechopen.105864",abstract:"Incoherent holographic imaging technologies, in general, involve multiple optical components for beam splitting—combining and shaping—and in most cases, require an active optical device such as a spatial light modulator (SLM) for generating multiple phase-shifted holograms in time. The above requirements made the realization of holography-based products expensive, heavy, large, and slow. To successfully transfer the holography capabilities discussed in research articles to products, it is necessary to find methods to simplify holography architectures. In this book chapter, two important incoherent holography techniques, namely interference-based Fresnel incoherent correlation holography (FINCH) and interferenceless coded aperture correlation holography (I-COACH), have been successfully simplified in space and time using advanced manufacturing methods and nonlinear reconstruction, respectively. Both techniques have been realized in compact optical architectures using a single static diffractive optical element manufactured using lithography technologies. Randomly multiplexed diffractive lenses were manufactured using electron beam lithography for FINCH. A quasi-random lens and a mask containing a quasi-random array of pinholes were manufactured using electron beam lithography and photolithography, respectively, for I-COACH. In both cases, the compactification has been achieved without sacrificing the performances. The design, fabrication, and experiments of FINCH and I-COACH with static diffractive optical elements are presented in details.",book:{id:"11860",title:"Holography - Recent Advances and Applications",coverURL:"https://cdn.intechopen.com/books/images_new/11860.jpg"},signatures:"Vijayakumar Anand, Soon Hock Ng, Tomas Katkus, Daniel Smith, Vinoth Balasubramani, Denver P. Linklater, Pierre J. Magistretti, Christian Depeursinge, Elena P. Ivanova and Saulius Juodkazis"},{id:"82958",title:"Electromagnetic Relations between Materials and Fields for Microwave Chemistry",slug:"electromagnetic-relations-between-materials-and-fields-for-microwave-chemistry",totalDownloads:8,totalDimensionsCites:0,doi:"10.5772/intechopen.106257",abstract:"We consider the application of microwave energy to a material. The effects of the electromagnetic field on the material and of the material on the electromagnetic field will be described, focusing on the dielectric relaxation phenomenon of the liquid. The dielectric permittivity of mixtures is discussed by extending Debye relaxation to explain how the material behaves with respect to an electric field. We will also consider the energy that the electric field imparts to the material, both thermally and nonthermally. We will develop this relation and describe what form it should take if there is a nonthermal effect in the chemical reaction field under microwave irradiation.",book:{id:"11494",title:"Electric Field in Advancing Science and Technology",coverURL:"https://cdn.intechopen.com/books/images_new/11494.jpg"},signatures:"Sugiyama Jun-ichi, Sugiyama Hayato, Sato Chika and Morizumi Maki"}],onlineFirstChaptersTotal:37},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:11,numberOfPublishedChapters:91,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:333,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:11,numberOfPublishedChapters:144,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:126,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:113,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:23,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:13,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:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}},{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}}]},series:{item:{id:"13",title:"Veterinary Medicine and Science",doi:"10.5772/intechopen.73681",issn:"2632-0517",scope:"Paralleling similar advances in the medical field, astounding advances occurred in Veterinary Medicine and Science in recent decades. These advances have helped foster better support for animal health, more humane animal production, and a better understanding of the physiology of endangered species to improve the assisted reproductive technologies or the pathogenesis of certain diseases, where animals can be used as models for human diseases (like cancer, degenerative diseases or fertility), and even as a guarantee of public health. Bridging Human, Animal, and Environmental health, the holistic and integrative “One Health” concept intimately associates the developments within those fields, projecting its advancements into practice. This book series aims to tackle various animal-related medicine and sciences fields, providing thematic volumes consisting of high-quality significant research directed to researchers and postgraduates. It aims to give us a glimpse into the new accomplishments in the Veterinary Medicine and Science field. 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After almost 32 years of teaching at the University of Trás-os-Montes and Alto Douro, she recently moved to the University of Évora, Department of Veterinary Medicine, where she teaches in the field of Animal Reproduction and Clinics. Her primary research areas include the molecular markers of the endometrial cycle and the embryo–maternal interaction, including oxidative stress and the reproductive physiology and disorders of sexual development, besides the molecular determinants of male and female fertility. She often supervises students preparing their master's or doctoral theses. She is also a frequent referee for various journals.",institutionString:null,institution:{name:"University of Évora",institutionURL:null,country:{name:"Portugal"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:3,paginationItems:[{id:"19",title:"Animal Science",coverUrl:"https://cdn.intechopen.com/series_topics/covers/19.jpg",isOpenForSubmission:!0,editor:{id:"259298",title:"Dr.",name:"Edward",middleName:null,surname:"Narayan",slug:"edward-narayan",fullName:"Edward Narayan",profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",biography:"Dr. Edward Narayan graduated with Ph.D. degree in Biology from the University of the South Pacific and pioneered non-invasive reproductive and stress endocrinology tools for amphibians - the novel development and validation of non-invasive enzyme immunoassays for the evaluation of reproductive hormonal cycle and stress hormone responses to environmental stressors. \nDr. Narayan leads the Stress Lab (Comparative Physiology and Endocrinology) at the University of Queensland. A dynamic career research platform which is based on the thematic areas of comparative vertebrate physiology, stress endocrinology, reproductive endocrinology, animal health and welfare, and conservation biology. \nEdward has supervised 40 research students and published over 60 peer reviewed research.",institutionString:null,institution:{name:"University of Queensland",institutionURL:null,country:{name:"Australia"}}},editorTwo:null,editorThree:null},{id:"20",title:"Animal Nutrition",coverUrl:"https://cdn.intechopen.com/series_topics/covers/20.jpg",isOpenForSubmission:!0,editor:{id:"175967",title:"Dr.",name:"Manuel",middleName:null,surname:"Gonzalez Ronquillo",slug:"manuel-gonzalez-ronquillo",fullName:"Manuel Gonzalez Ronquillo",profilePictureURL:"https://mts.intechopen.com/storage/users/175967/images/system/175967.png",biography:"Dr. Manuel González Ronquillo obtained his doctorate degree from the University of Zaragoza, Spain, in 2001. He is a research professor at the Faculty of Veterinary Medicine and Animal Husbandry, Autonomous University of the State of Mexico. He is also a level-2 researcher. He received a Fulbright-Garcia Robles fellowship for a postdoctoral stay at the US Dairy Forage Research Center, Madison, Wisconsin, USA in 2008–2009. He received grants from Alianza del Pacifico for a stay at the University of Magallanes, Chile, in 2014, and from Consejo Nacional de Ciencia y Tecnología (CONACyT) to work in the Food and Agriculture Organization’s Animal Production and Health Division (AGA), Rome, Italy, in 2014–2015. He has collaborated with researchers from different countries and published ninety-eight journal articles. He teaches various degree courses in zootechnics, sheep production, and agricultural sciences and natural resources.\n\nDr. Ronquillo’s research focuses on the evaluation of sustainable animal diets (StAnD), using native resources of the region, decreasing carbon footprint, and applying meta-analysis and mathematical models for a better understanding of animal production.",institutionString:null,institution:{name:"Universidad Autónoma del Estado de México",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null},{id:"28",title:"Animal Reproductive Biology and Technology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/28.jpg",isOpenForSubmission:!0,editor:{id:"177225",title:"Prof.",name:"Rosa Maria Lino Neto",middleName:null,surname:"Pereira",slug:"rosa-maria-lino-neto-pereira",fullName:"Rosa Maria Lino Neto Pereira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bS9wkQAC/Profile_Picture_1624519982291",biography:"Rosa Maria Lino Neto Pereira (DVM, MsC, PhD and) is currently a researcher at the Genetic Resources and Biotechnology Unit of the National Institute of Agrarian and Veterinarian Research (INIAV, Portugal). She is the head of the Reproduction and Embryology Laboratories and was lecturer of Reproduction and Reproductive Biotechnologies at Veterinary Medicine Faculty. She has over 25 years of experience working in reproductive biology and biotechnology areas with a special emphasis on embryo and gamete cryopreservation, for research and animal genetic resources conservation, leading research projects with several peer-reviewed papers. Rosa Pereira is member of the ERFP-FAO Ex situ Working Group and of the Management Commission of the Portuguese Animal Germplasm Bank.",institutionString:"The National Institute for Agricultural and Veterinary Research. Portugal",institution:null},editorTwo:null,editorThree:null}]},overviewPageOFChapters:{paginationCount:21,paginationItems:[{id:"83115",title:"Fungi and Oomycetes–Allies in Eliminating Environmental Pathogens",doi:"10.5772/intechopen.106498",signatures:"Iasmina Luca",slug:"fungi-and-oomycetes-allies-in-eliminating-environmental-pathogens",totalDownloads:0,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Animal Welfare - New Insights",coverURL:"https://cdn.intechopen.com/books/images_new/11579.jpg",subseries:{id:"19",title:"Animal Science"}}},{id:"82991",title:"Diseases of the Canine Prostate Gland",doi:"10.5772/intechopen.105835",signatures:"Sabine Schäfer-Somi",slug:"diseases-of-the-canine-prostate-gland",totalDownloads:8,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Recent Advances in Canine Medicine",coverURL:"https://cdn.intechopen.com/books/images_new/11580.jpg",subseries:{id:"19",title:"Animal Science"}}},{id:"82956",title:"Potential Substitutes of Antibiotics for Swine and Poultry Production",doi:"10.5772/intechopen.106081",signatures:"Ho Trung Thong, Le Nu Anh Thu and Ho Viet Duc",slug:"potential-substitutes-of-antibiotics-for-swine-and-poultry-production",totalDownloads:4,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Antibiotics and Probiotics in Animal Food - Impact and Regulation",coverURL:"https://cdn.intechopen.com/books/images_new/11578.jpg",subseries:{id:"20",title:"Animal Nutrition"}}},{id:"82905",title:"A Review of Application Strategies and Efficacy of Probiotics in Pet Food",doi:"10.5772/intechopen.105829",signatures:"Heather Acuff and Charles G. Aldrich",slug:"a-review-of-application-strategies-and-efficacy-of-probiotics-in-pet-food",totalDownloads:16,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Antibiotics and Probiotics in Animal Food - Impact and Regulation",coverURL:"https://cdn.intechopen.com/books/images_new/11578.jpg",subseries:{id:"20",title:"Animal Nutrition"}}}]},overviewPagePublishedBooks:{paginationCount:11,paginationItems:[{type:"book",id:"7233",title:"New Insights into Theriogenology",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7233.jpg",slug:"new-insights-into-theriogenology",publishedDate:"December 5th 2018",editedByType:"Edited by",bookSignature:"Rita Payan-Carreira",hash:"74f4147e3fb214dd050e5edd3aaf53bc",volumeInSeries:1,fullTitle:"New Insights into Theriogenology",editors:[{id:"38652",title:"Prof.",name:"Rita",middleName:null,surname:"Payan-Carreira",slug:"rita-payan-carreira",fullName:"Rita Payan-Carreira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRiFPQA0/Profile_Picture_1614601496313",biography:"Rita Payan Carreira earned her Veterinary Degree from the Faculty of Veterinary Medicine in Lisbon, Portugal, in 1985. She obtained her Ph.D. in Veterinary Sciences from the University of Trás-os-Montes e Alto Douro, Portugal. After almost 32 years of teaching at the University of Trás-os-Montes and Alto Douro, she recently moved to the University of Évora, Department of Veterinary Medicine, where she teaches in the field of Animal Reproduction and Clinics. Her primary research areas include the molecular markers of the endometrial cycle and the embryo–maternal interaction, including oxidative stress and the reproductive physiology and disorders of sexual development, besides the molecular determinants of male and female fertility. She often supervises students preparing their master's or doctoral theses. She is also a frequent referee for various journals.",institutionString:null,institution:{name:"University of Évora",institutionURL:null,country:{name:"Portugal"}}}]},{type:"book",id:"7144",title:"Veterinary Anatomy and Physiology",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7144.jpg",slug:"veterinary-anatomy-and-physiology",publishedDate:"March 13th 2019",editedByType:"Edited by",bookSignature:"Catrin Sian Rutland and Valentina Kubale",hash:"75cdacb570e0e6d15a5f6e69640d87c9",volumeInSeries:2,fullTitle:"Veterinary Anatomy and Physiology",editors:[{id:"202192",title:"Dr.",name:"Catrin",middleName:null,surname:"Rutland",slug:"catrin-rutland",fullName:"Catrin Rutland",profilePictureURL:"https://mts.intechopen.com/storage/users/202192/images/system/202192.png",biography:"Catrin Rutland is an Associate Professor of Anatomy and Developmental Genetics at the University of Nottingham, UK. She obtained a BSc from the University of Derby, England, a master’s degree from Technische Universität München, Germany, and a Ph.D. from the University of Nottingham. She undertook a post-doctoral research fellowship in the School of Medicine before accepting tenure in Veterinary Medicine and Science. Dr. Rutland also obtained an MMedSci (Medical Education) and a Postgraduate Certificate in Higher Education (PGCHE). She is the author of more than sixty peer-reviewed journal articles, twelve books/book chapters, and more than 100 research abstracts in cardiovascular biology and oncology. She is a board member of the European Association of Veterinary Anatomists, Fellow of the Anatomical Society, and Senior Fellow of the Higher Education Academy. Dr. Rutland has also written popular science books for the public. https://orcid.org/0000-0002-2009-4898. www.nottingham.ac.uk/vet/people/catrin.rutland",institutionString:null,institution:{name:"University of Nottingham",institutionURL:null,country:{name:"United Kingdom"}}}]},{type:"book",id:"8524",title:"Lactation in Farm Animals",subtitle:"Biology, Physiological Basis, Nutritional Requirements, and Modelization",coverURL:"https://cdn.intechopen.com/books/images_new/8524.jpg",slug:"lactation-in-farm-animals-biology-physiological-basis-nutritional-requirements-and-modelization",publishedDate:"January 22nd 2020",editedByType:"Edited by",bookSignature:"Naceur M'Hamdi",hash:"2aa2a9a0ec13040bbf0455e34625504e",volumeInSeries:3,fullTitle:"Lactation in Farm Animals - Biology, Physiological Basis, Nutritional Requirements, and Modelization",editors:[{id:"73376",title:"Dr.",name:"Naceur",middleName:null,surname:"M'Hamdi",slug:"naceur-m'hamdi",fullName:"Naceur M'Hamdi",profilePictureURL:"https://mts.intechopen.com/storage/users/73376/images/system/73376.jpg",biography:"Naceur M’HAMDI is Associate Professor at the National Agronomic Institute of Tunisia, University of Carthage. He is also Member of the Laboratory of genetic, animal and feed resource and member of Animal science Department of INAT. He graduated from Higher School of Agriculture of Mateur, University of Carthage, in 2002 and completed his masters in 2006. Dr. M’HAMDI completed his PhD thesis in Genetic welfare indicators of dairy cattle at Higher Institute of Agronomy of Chott-Meriem, University of Sousse, in 2011. 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He has developed various compounds including a drug for acute promyelocytic leukemia.",institutionString:"Tokyo Medical and Dental University",institution:{name:"Tokyo Medical and Dental University",country:{name:"Japan"}}},{id:"94311",title:"Prof.",name:"Martins",middleName:"Ochubiojo",surname:"Ochubiojo Emeje",slug:"martins-ochubiojo-emeje",fullName:"Martins Ochubiojo Emeje",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94311/images/system/94311.jpeg",biography:"Martins Emeje obtained a BPharm with distinction from Ahmadu Bello University, Nigeria, and an MPharm and Ph.D. from the University of Nigeria (UNN), where he received the best Ph.D. award and was enlisted as UNN’s “Face of Research.” He established the first nanomedicine center in Nigeria and was the pioneer head of the intellectual property and technology transfer as well as the technology innovation and support center. Prof. Emeje’s several international fellowships include the prestigious Raman fellowship. He has published more than 150 articles and patents. He is also the head of R&D at NIPRD and holds a visiting professor position at Nnamdi Azikiwe University, Nigeria. He has a postgraduate certificate in Project Management from Walden University, Minnesota, as well as a professional teaching certificate and a World Bank certification in Public Procurement. Prof. Emeje was a national chairman of academic pharmacists in Nigeria and the 2021 winner of the May & Baker Nigeria Plc–sponsored prize for professional service in research and innovation.",institutionString:"National Institute for Pharmaceutical Research and Development",institution:{name:"National Institute for Pharmaceutical Research and Development",country:{name:"Nigeria"}}},{id:"436430",title:"Associate Prof.",name:"Mesut",middleName:null,surname:"Işık",slug:"mesut-isik",fullName:"Mesut Işık",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/436430/images/19686_n.jpg",biography:null,institutionString:null,institution:{name:"Bilecik University",country:{name:"Turkey"}}},{id:"268659",title:"Ms.",name:"Xianquan",middleName:null,surname:"Zhan",slug:"xianquan-zhan",fullName:"Xianquan Zhan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/268659/images/8143_n.jpg",biography:"Dr. Zhan received his undergraduate and graduate training in the fields of preventive medicine and epidemiology and statistics at the West China University of Medical Sciences in China during 1989 to 1999. He received his post-doctoral training in oncology and cancer proteomics for two years at the Cancer Research Institute of Human Medical University in China. In 2001, he went to the University of Tennessee Health Science Center (UTHSC) in USA, where he was a post-doctoral researcher and focused on mass spectrometry and cancer proteomics. Then, he was appointed as an Assistant Professor of Neurology, UTHSC in 2005. He moved to the Cleveland Clinic in USA as a Project Scientist/Staff in 2006 where he focused on the studies of eye disease proteomics and biomarkers. He returned to UTHSC as an Assistant Professor of Neurology in the end of 2007, engaging in proteomics and biomarker studies of lung diseases and brain tumors, and initiating the studies of predictive, preventive, and personalized medicine (PPPM) in cancer. In 2010, he was promoted to Associate Professor of Neurology, UTHSC. Currently, he is a Professor at Xiangya Hospital of Central South University in China, Fellow of Royal Society of Medicine (FRSM), the European EPMA National Representative in China, Regular Member of American Association for the Advancement of Science (AAAS), European Cooperation of Science and Technology (e-COST) grant evaluator, Associate Editors of BMC Genomics, BMC Medical Genomics, EPMA Journal, and Frontiers in Endocrinology, Executive Editor-in-Chief of Med One. He has\npublished 116 peer-reviewed research articles, 16 book chapters, 2 books, and 2 US patents. His current main research interest focuses on the studies of cancer proteomics and biomarkers, and the use of modern omics techniques and systems biology for PPPM in cancer, and on the development and use of 2DE-LC/MS for the large-scale study of human proteoforms.",institutionString:null,institution:{name:"Xiangya Hospital Central South University",country:{name:"China"}}},{id:"40482",title:null,name:"Rizwan",middleName:null,surname:"Ahmad",slug:"rizwan-ahmad",fullName:"Rizwan Ahmad",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/40482/images/system/40482.jpeg",biography:"Dr. Rizwan Ahmad is a University Professor and Coordinator, Quality and Development, College of Medicine, Imam Abdulrahman bin Faisal University, Saudi Arabia. Previously, he was Associate Professor of Human Function, Oman Medical College, Oman, and SBS University, Dehradun. Dr. Ahmad completed his education at Aligarh Muslim University, Aligarh. He has published several articles in peer-reviewed journals, chapters, and edited books. His area of specialization is free radical biochemistry and autoimmune diseases.",institutionString:"Imam Abdulrahman Bin Faisal University",institution:{name:"Imam Abdulrahman Bin Faisal University",country:{name:"Saudi Arabia"}}},{id:"41865",title:"Prof.",name:"Farid A.",middleName:null,surname:"Badria",slug:"farid-a.-badria",fullName:"Farid A. Badria",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/41865/images/system/41865.jpg",biography:"Farid A. Badria, Ph.D., is the recipient of several awards, including The World Academy of Sciences (TWAS) Prize for Public Understanding of Science; the World Intellectual Property Organization (WIPO) Gold Medal for best invention; Outstanding Arab Scholar, Kuwait; and the Khwarizmi International Award, Iran. He has 250 publications, 12 books, 20 patents, and several marketed pharmaceutical products to his credit. He continues to lead research projects on developing new therapies for liver, skin disorders, and cancer. Dr. Badria was listed among the world’s top 2% of scientists in medicinal and biomolecular chemistry in 2019 and 2020. He is a member of the Arab Development Fund, Kuwait; International Cell Research Organization–United Nations Educational, Scientific and Cultural Organization (ICRO–UNESCO), Chile; and UNESCO Biotechnology France",institutionString:"Mansoura University",institution:{name:"Mansoura University",country:{name:"Egypt"}}},{id:"329385",title:"Dr.",name:"Rajesh K.",middleName:"Kumar",surname:"Singh",slug:"rajesh-k.-singh",fullName:"Rajesh K. Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329385/images/system/329385.png",biography:"Dr. Singh received a BPharm (2003) and MPharm (2005) from Panjab University, Chandigarh, India, and a Ph.D. (2013) from Punjab Technical University (PTU), Jalandhar, India. He has more than sixteen years of teaching experience and has supervised numerous postgraduate and Ph.D. students. He has to his credit more than seventy papers in SCI- and SCOPUS-indexed journals, fifty-five conference proceedings, four books, six Best Paper Awards, and five projects from different government agencies. He is currently an editorial board member of eight international journals and a reviewer for more than fifty scientific journals. He received Top Reviewer and Excellent Peer Reviewer Awards from Publons in 2016 and 2017, respectively. He is also on the panel of The International Reviewer for reviewing research proposals for grants from the Royal Society. He also serves as a Publons Academy mentor and Bentham brand ambassador.",institutionString:"Punjab Technical University",institution:{name:"Punjab Technical University",country:{name:"India"}}},{id:"142388",title:"Dr.",name:"Thiago",middleName:"Gomes",surname:"Gomes Heck",slug:"thiago-gomes-heck",fullName:"Thiago Gomes Heck",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/142388/images/7259_n.jpg",biography:null,institutionString:null,institution:{name:"Universidade Regional do Noroeste do Estado do Rio Grande do Sul",country:{name:"Brazil"}}},{id:"336273",title:"Assistant Prof.",name:"Janja",middleName:null,surname:"Zupan",slug:"janja-zupan",fullName:"Janja Zupan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/336273/images/14853_n.jpeg",biography:"Janja Zupan graduated in 2005 at the Department of Clinical Biochemistry (superviser prof. dr. Janja Marc) in the field of genetics of osteoporosis. Since November 2009 she is working as a Teaching Assistant at the Faculty of Pharmacy, Department of Clinical Biochemistry. In 2011 she completed part of her research and PhD work at Institute of Genetics and Molecular Medicine, University of Edinburgh. She finished her PhD entitled The influence of the proinflammatory cytokines on the RANK/RANKL/OPG in bone tissue of osteoporotic and osteoarthritic patients in 2012. From 2014-2016 she worked at the Institute of Biomedical Sciences, University of Aberdeen as a postdoctoral research fellow on UK Arthritis research project where she gained knowledge in mesenchymal stem cells and regenerative medicine. She returned back to University of Ljubljana, Faculty of Pharmacy in 2016. She is currently leading project entitled Mesenchymal stem cells-the keepers of tissue endogenous regenerative capacity facing up to aging of the musculoskeletal system funded by Slovenian Research Agency.",institutionString:null,institution:{name:"University of Ljubljana",country:{name:"Slovenia"}}},{id:"357453",title:"Dr.",name:"Radheshyam",middleName:null,surname:"Maurya",slug:"radheshyam-maurya",fullName:"Radheshyam Maurya",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/357453/images/16535_n.jpg",biography:null,institutionString:null,institution:{name:"University of Hyderabad",country:{name:"India"}}},{id:"418340",title:"Dr.",name:"Jyotirmoi",middleName:null,surname:"Aich",slug:"jyotirmoi-aich",fullName:"Jyotirmoi Aich",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000038Ugi5QAC/Profile_Picture_2022-04-15T07:48:28.png",biography:"Biotechnologist with 15 years of research including 6 years of teaching experience. Demonstrated record of scientific achievements through consistent publication record (H index = 13, with 874 citations) in high impact journals such as Nature Communications, Oncotarget, Annals of Oncology, PNAS, and AJRCCM, etc. Strong research professional with a post-doctorate from ACTREC where I gained experimental oncology experience in clinical settings and a doctorate from IGIB where I gained expertise in asthma pathophysiology. A well-trained biotechnologist with diverse experience on the bench across different research themes ranging from asthma to cancer and other infectious diseases. An individual with a strong commitment and innovative mindset. Have the ability to work on diverse projects such as regenerative and molecular medicine with an overall mindset of improving healthcare.",institutionString:"DY Patil Deemed to Be University",institution:null},{id:"349288",title:"Prof.",name:"Soumya",middleName:null,surname:"Basu",slug:"soumya-basu",fullName:"Soumya Basu",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035QxIDQA0/Profile_Picture_2022-04-15T07:47:01.jpg",biography:"Soumya Basu, Ph.D., is currently working as an Associate Professor at Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune, Maharashtra, India. With 16+ years of trans-disciplinary research experience in Drug Design, development, and pre-clinical validation; 20+ research article publications in journals of repute, 9+ years of teaching experience, trained with cross-disciplinary education, Dr. Basu is a life-long learner and always thrives for new challenges.\r\nHer research area is the design and synthesis of small molecule partial agonists of PPAR-γ in lung cancer. She is also using artificial intelligence and deep learning methods to understand the exosomal miRNA’s role in cancer metastasis. Dr. Basu is the recipient of many awards including the Early Career Research Award from the Department of Science and Technology, Govt. of India. She is a reviewer of many journals like Molecular Biology Reports, Frontiers in Oncology, RSC Advances, PLOS ONE, Journal of Biomolecular Structure & Dynamics, Journal of Molecular Graphics and Modelling, etc. She has edited and authored/co-authored 21 journal papers, 3 book chapters, and 15 abstracts. She is a Board of Studies member at her university. She is a life member of 'The Cytometry Society”-in India and 'All India Cell Biology Society”- in India.",institutionString:"Dr. D.Y. Patil Vidyapeeth, Pune",institution:{name:"Dr. D.Y. Patil Vidyapeeth, Pune",country:{name:"India"}}},{id:"354817",title:"Dr.",name:"Anubhab",middleName:null,surname:"Mukherjee",slug:"anubhab-mukherjee",fullName:"Anubhab Mukherjee",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y0000365PbRQAU/ProfilePicture%202022-04-15%2005%3A11%3A18.480",biography:"A former member of Laboratory of Nanomedicine, Brigham and Women’s Hospital, Harvard University, Boston, USA, Dr. Anubhab Mukherjee is an ardent votary of science who strives to make an impact in the lives of those afflicted with cancer and other chronic/acute ailments. He completed his Ph.D. from CSIR-Indian Institute of Chemical Technology, Hyderabad, India, having been skilled with RNAi, liposomal drug delivery, preclinical cell and animal studies. He pursued post-doctoral research at College of Pharmacy, Health Science Center, Texas A & M University and was involved in another postdoctoral research at Department of Translational Neurosciences and Neurotherapeutics, John Wayne Cancer Institute, Santa Monica, California. In 2015, he worked in Harvard-MIT Health Sciences & Technology as a visiting scientist. He has substantial experience in nanotechnology-based formulation development and successfully served various Indian organizations to develop pharmaceuticals and nutraceutical products. He is an inventor in many US patents and an author in many peer-reviewed articles, book chapters and books published in various media of international repute. Dr. Mukherjee is currently serving as Principal Scientist, R&D at Esperer Onco Nutrition (EON) Pvt. Ltd. and heads the Hyderabad R&D center of the organization.",institutionString:"Esperer Onco Nutrition Pvt Ltd.",institution:null},{id:"319365",title:"Assistant Prof.",name:"Manash K.",middleName:null,surname:"Paul",slug:"manash-k.-paul",fullName:"Manash K. Paul",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/319365/images/system/319365.png",biography:"Manash K. Paul is a scientist and Principal Investigator at the University of California Los Angeles. He has contributed significantly to the fields of stem cell biology, regenerative medicine, and lung cancer. His research focuses on various signaling processes involved in maintaining stem cell homeostasis during the injury-repair process, deciphering the lung stem cell niche, pulmonary disease modeling, immuno-oncology, and drug discovery. He is currently investigating the role of extracellular vesicles in premalignant lung cell migration and detecting the metastatic phenotype of lung cancer via artificial intelligence-based analyses of exosomal Raman signatures. Dr. Paul also works on spatial multiplex immunofluorescence-based tissue mapping to understand the immune repertoire in lung cancer. Dr. Paul has published in more than sixty-five peer-reviewed international journals and is highly cited. He is the recipient of many awards, including the UCLA Vice Chancellor’s award and the 2022 AAISCR-R Vijayalaxmi Award for Innovative Cancer Research. He is a senior member of the Institute of Electrical and Electronics Engineers (IEEE) and an editorial board member for several international journals.",institutionString:"University of California Los Angeles",institution:{name:"University of California Los Angeles",country:{name:"United States of America"}}},{id:"311457",title:"Dr.",name:"Júlia",middleName:null,surname:"Scherer Santos",slug:"julia-scherer-santos",fullName:"Júlia Scherer Santos",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/311457/images/system/311457.jpg",biography:"Dr. Júlia Scherer Santos works in the areas of cosmetology, nanotechnology, pharmaceutical technology, beauty, and aesthetics. Dr. Santos also has experience as a professor of graduate courses. Graduated in Pharmacy, specialization in Cosmetology and Cosmeceuticals applied to aesthetics, specialization in Aesthetic and Cosmetic Health, and a doctorate in Pharmaceutical Nanotechnology. Teaching experience in Pharmacy and Aesthetics and Cosmetics courses. She works mainly on the following subjects: nanotechnology, cosmetology, pharmaceutical technology, aesthetics.",institutionString:"Universidade Federal de Juiz de Fora",institution:{name:"Universidade Federal de Juiz de Fora",country:{name:"Brazil"}}},{id:"219081",title:"Dr.",name:"Abdulsamed",middleName:null,surname:"Kükürt",slug:"abdulsamed-kukurt",fullName:"Abdulsamed Kükürt",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/219081/images/system/219081.png",biography:"Dr. Kükürt graduated from Uludağ University in Turkey. He started his academic career as a Research Assistant in the Department of Biochemistry at Kafkas University. In 2019, he completed his Ph.D. program in the Department of Biochemistry at the Institute of Health Sciences. He is currently working at the Department of Biochemistry, Kafkas University. He has 27 published research articles in academic journals, 11 book chapters, and 37 papers. He took part in 10 academic projects. He served as a reviewer for many articles. He still serves as a member of the review board in many academic journals. He is currently working on the protective activity of phenolic compounds in disorders associated with oxidative stress and inflammation.",institutionString:null,institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"178366",title:"Dr.",name:"Volkan",middleName:null,surname:"Gelen",slug:"volkan-gelen",fullName:"Volkan Gelen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178366/images/system/178366.jpg",biography:"Volkan Gelen is a Physiology specialist who received his veterinary degree from Kafkas University in 2011. Between 2011-2015, he worked as an assistant at Atatürk University, Faculty of Veterinary Medicine, Department of Physiology. In 2016, he joined Kafkas University, Faculty of Veterinary Medicine, Department of Physiology as an assistant professor. Dr. Gelen has been engaged in various academic activities at Kafkas University since 2016. There he completed 5 projects and has 3 ongoing projects. He has 60 articles published in scientific journals and 20 poster presentations in scientific congresses. His research interests include physiology, endocrine system, cancer, diabetes, cardiovascular system diseases, and isolated organ bath system studies.",institutionString:"Kafkas University",institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"418963",title:"Dr.",name:"Augustine Ododo",middleName:"Augustine",surname:"Osagie",slug:"augustine-ododo-osagie",fullName:"Augustine Ododo Osagie",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/418963/images/16900_n.jpg",biography:"Born into the family of Osagie, a prince of the Benin Kingdom. I am currently an academic in the Department of Medical Biochemistry, University of Benin. Part of the duties are to teach undergraduate students and conduct academic research.",institutionString:null,institution:{name:"University of Benin",country:{name:"Nigeria"}}},{id:"192992",title:"Prof.",name:"Shagufta",middleName:null,surname:"Perveen",slug:"shagufta-perveen",fullName:"Shagufta Perveen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/192992/images/system/192992.png",biography:"Prof. Shagufta Perveen is a Distinguish Professor in the Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. Dr. Perveen has acted as the principal investigator of major research projects funded by the research unit of King Saud University. She has more than ninety original research papers in peer-reviewed journals of international repute to her credit. She is a fellow member of the Royal Society of Chemistry UK and the American Chemical Society of the United States.",institutionString:"King Saud University",institution:{name:"King Saud University",country:{name:"Saudi Arabia"}}},{id:"49848",title:"Dr.",name:"Wen-Long",middleName:null,surname:"Hu",slug:"wen-long-hu",fullName:"Wen-Long Hu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49848/images/system/49848.jpg",biography:"Wen-Long Hu is Chief of the Division of Acupuncture, Department of Chinese Medicine at Kaohsiung Chang Gung Memorial Hospital, as well as an adjunct associate professor at Fooyin University and Kaohsiung Medical University. Wen-Long is President of Taiwan Traditional Chinese Medicine Medical Association. He has 28 years of experience in clinical practice in laser acupuncture therapy and 34 years in acupuncture. He is an invited speaker for lectures and workshops in laser acupuncture at many symposiums held by medical associations. He owns the patent for herbal preparation and producing, and for the supercritical fluid-treated needle. Dr. Hu has published three books, 12 book chapters, and more than 30 papers in reputed journals, besides serving as an editorial board member of repute.",institutionString:"Kaohsiung Chang Gung Memorial Hospital",institution:{name:"Kaohsiung Chang Gung Memorial Hospital",country:{name:"Taiwan"}}},{id:"298472",title:"Prof.",name:"Andrey V.",middleName:null,surname:"Grechko",slug:"andrey-v.-grechko",fullName:"Andrey V. Grechko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/298472/images/system/298472.png",biography:"Andrey Vyacheslavovich Grechko, Ph.D., Professor, is a Corresponding Member of the Russian Academy of Sciences. He graduated from the Semashko Moscow Medical Institute (Semashko National Research Institute of Public Health) with a degree in Medicine (1998), the Clinical Department of Dermatovenerology (2000), and received a second higher education in Psychology (2009). Professor A.V. Grechko held the position of Сhief Physician of the Central Clinical Hospital in Moscow. He worked as a professor at the faculty and was engaged in scientific research at the Medical University. Starting in 2013, he has been the initiator of the creation of the Federal Scientific and Clinical Center for Intensive Care and Rehabilitology, Moscow, Russian Federation, where he also serves as Director since 2015. He has many years of experience in research and teaching in various fields of medicine, is an author/co-author of more than 200 scientific publications, 13 patents, 15 medical books/chapters, including Chapter in Book «Metabolomics», IntechOpen, 2020 «Metabolomic Discovery of Microbiota Dysfunction as the Cause of Pathology».",institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"199461",title:"Prof.",name:"Natalia V.",middleName:null,surname:"Beloborodova",slug:"natalia-v.-beloborodova",fullName:"Natalia V. Beloborodova",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/199461/images/system/199461.jpg",biography:'Natalia Vladimirovna Beloborodova was educated at the Pirogov Russian National Research Medical University, with a degree in pediatrics in 1980, a Ph.D. in 1987, and a specialization in Clinical Microbiology from First Moscow State Medical University in 2004. She has been a Professor since 1996. Currently, she is the Head of the Laboratory of Metabolism, a division of the Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Moscow, Russian Federation. N.V. Beloborodova has many years of clinical experience in the field of intensive care and surgery. She studies infectious complications and sepsis. She initiated a series of interdisciplinary clinical and experimental studies based on the concept of integrating human metabolism and its microbiota. Her scientific achievements are widely known: she is the recipient of the Marie E. Coates Award \\"Best lecturer-scientist\\" Gustafsson Fund, Karolinska Institutes, Stockholm, Sweden, and the International Sepsis Forum Award, Pasteur Institute, Paris, France (2014), etc. Professor N.V. Beloborodova wrote 210 papers, five books, 10 chapters and has edited four books.',institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"354260",title:"Ph.D.",name:"Tércio Elyan",middleName:"Azevedo",surname:"Azevedo Martins",slug:"tercio-elyan-azevedo-martins",fullName:"Tércio Elyan Azevedo Martins",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/354260/images/16241_n.jpg",biography:"Graduated in Pharmacy from the Federal University of Ceará with the modality in Industrial Pharmacy, Specialist in Production and Control of Medicines from the University of São Paulo (USP), Master in Pharmaceuticals and Medicines from the University of São Paulo (USP) and Doctor of Science in the program of Pharmaceuticals and Medicines by the University of São Paulo. Professor at Universidade Paulista (UNIP) in the areas of chemistry, cosmetology and trichology. Assistant Coordinator of the Higher Course in Aesthetic and Cosmetic Technology at Universidade Paulista Campus Chácara Santo Antônio. Experience in the Pharmacy area, with emphasis on Pharmacotechnics, Pharmaceutical Technology, Research and Development of Cosmetics, acting mainly on topics such as cosmetology, antioxidant activity, aesthetics, photoprotection, cyclodextrin and thermal analysis.",institutionString:null,institution:{name:"University of Sao Paulo",country:{name:"Brazil"}}},{id:"334285",title:"Ph.D. Student",name:"Sameer",middleName:"Kumar",surname:"Jagirdar",slug:"sameer-jagirdar",fullName:"Sameer Jagirdar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334285/images/14691_n.jpg",biography:"I\\'m a graduate student at the center for biosystems science and engineering at the Indian Institute of Science, Bangalore, India. I am interested in studying host-pathogen interactions at the biomaterial interface.",institutionString:null,institution:{name:"Indian Institute of Science Bangalore",country:{name:"India"}}},{id:"329248",title:"Dr.",name:"Md. Faheem",middleName:null,surname:"Haider",slug:"md.-faheem-haider",fullName:"Md. Faheem Haider",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329248/images/system/329248.jpg",biography:"Dr. Md. Faheem Haider completed his BPharm in 2012 at Integral University, Lucknow, India. In 2014, he completed his MPharm with specialization in Pharmaceutics at Babasaheb Bhimrao Ambedkar University, Lucknow, India. He received his Ph.D. degree from Jamia Hamdard University, New Delhi, India, in 2018. He was selected for the GPAT six times and his best All India Rank was 34. Currently, he is an assistant professor at Integral University. Previously he was an assistant professor at IIMT University, Meerut, India. He has experience teaching DPharm, Pharm.D, BPharm, and MPharm students. He has more than five publications in reputed journals to his credit. Dr. Faheem’s research area is the development and characterization of nanoformulation for the delivery of drugs to various organs.",institutionString:"Integral University",institution:{name:"Integral University",country:{name:"India"}}},{id:"329795",title:"Dr.",name:"Mohd Aftab",middleName:"Aftab",surname:"Siddiqui",slug:"mohd-aftab-siddiqui",fullName:"Mohd Aftab Siddiqui",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329795/images/system/329795.png",biography:"Dr. Mohd Aftab Siddiqui is an assistant professor in the Faculty of Pharmacy, Integral University, Lucknow, India, where he obtained a Ph.D. in Pharmacology in 2020. He also obtained a BPharm and MPharm from the same university in 2013 and 2015, respectively. His area of research is the pharmacological screening of herbal drugs/natural products in liver cancer and cardiac diseases. He is a member of many professional bodies and has guided many MPharm and PharmD research projects. Dr. Siddiqui has many national and international publications and one German patent to his credit.",institutionString:"Integral University",institution:null}]}},subseries:{item:{id:"86",type:"subseries",title:"Business and Management",keywords:"Demographic Shifts, Innovation, Technology, Next-gen Leaders, Worldwide Environmental Issues and Clean Technology, Uncertainty and Political Risks, Radical Adjacency, Emergence of New Business Ecosystem Type, Emergence of Different Leader and Leader Values Types, Universal Connector, Elastic Enterprise, Business Platform, Supply Chain Complexity",scope:"