Clinical and laboratory characteristics of children of the main and control groups.
\r\n\t(i) Quantum dots of very high-quality optical applications, Quantum dot light-emitting diodes (QD-LED) and ‘QD-White LED’, Quantum dot photodetectors (QDPs), Quantum dot solar cells (Photovoltaics).
\r\n\r\n\t(ii) Quantum Computing (quantum bits or ‘qubits’), (vii) The Future of Quantum Dots (broad range of real-time applications, magnetic quantum dots & graphene quantum dots), Superconducting Loop, Quantum Entanglement, Quantum Fingerprints.
\r\n\r\n\t(iii) Biomedical and Environmental Applications (to study intracellular processes, tumor targeting, in vivo observation of cell trafficking, diagnostics and cellular imaging at high resolutions), Bioconjugation, Cell Imaging, Photoelectrochemical Immunosensor, Membranes and Bacterial Cells, Resonance Energy-Transfer Processes, Evaluation of Drinking Water Quality, Water and Wastewater Treatment, Pollutant Control.
",isbn:"978-1-80356-594-1",printIsbn:"978-1-80356-593-4",pdfIsbn:"978-1-80356-595-8",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,isNomenclature:!1,hash:"0dd5611c62c91569bd2819e68852002a",bookSignature:"Prof. Jagannathan Thirumalai",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11756.jpg",keywords:"LED, Organic LEDs, Dyes & Pigments, Solar Cells, Laser Photonics, Electronic Switching Devices, Qubits, Josephson Junction, Bioconjugation, Cell Imaging, Photoelectrochemical Immunosensor, Membranes, and Bacterial Cells",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"March 16th 2022",dateEndSecondStepPublish:"May 27th 2022",dateEndThirdStepPublish:"July 26th 2022",dateEndFourthStepPublish:"October 14th 2022",dateEndFifthStepPublish:"December 13th 2022",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"a month",secondStepPassed:!0,areRegistrationsClosed:!1,currentStepOfPublishingProcess:3,editedByType:null,kuFlag:!1,biosketch:"Dr. J. Thirumalai received his Ph.D. from Alagappa University, Karaikudi, He was also awarded the Post-doctoral Fellowship from Pohang University of Science and Technology (POSTECH), the Republic of Korea. His research interests focus on luminescence, self-assembled nanomaterials, and thin-film optoelectronic devices. He has published more than 60 SCOPUS/ISI indexed papers and 11 book chapters, edited 4 books, and member of several national and international societies like RSC, OSA, etc. His h-index is 19.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"99242",title:"Prof.",name:"Jagannathan",middleName:null,surname:"Thirumalai",slug:"jagannathan-thirumalai",fullName:"Jagannathan Thirumalai",profilePictureURL:"https://mts.intechopen.com/storage/users/99242/images/system/99242.png",biography:"Dr. J. Thirumalai received his Ph.D. from Alagappa University, Karaikudi in 2010. He was also awarded the Post-doctoral Fellowship from Pohang University of Science and Technology (POSTECH), Republic of Korea, in 2013. He worked as Assistant Professor of Physics, B.S. Abdur Rahman University, Chennai, India (2011 to 2016). Currently, he is working as Senior Assistant Professor of Physics, Srinivasa Ramanujan Centre, SASTRA Deemed University, Kumbakonam (T.N.), India. His research interests focus on luminescence, self-assembled nanomaterials, and thin film opto-electronic devices. He has published more than 60 SCOPUS/ISI indexed papers and 11 book chapters, edited 4 books and member in several national and international societies like RSC, OSA, etc. Currently, he served as a principal investigator for a funded project towards the application of luminescence based thin film opto-electronic devices, funded by the Science and Engineering Research Board (SERB), India. As an expert in opto-electronics and nanotechnology area, he has been invited as external and internal examiners to MSc and PhD theses, invited to give talk in some forum, review papers for international and national journals.",institutionString:"SASTRA University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"10",totalChapterViews:"0",totalEditedBooks:"6",institution:null}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"17",title:"Nanotechnology and Nanomaterials",slug:"nanotechnology-and-nanomaterials"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"347258",firstName:"Marica",lastName:"Novakovic",middleName:null,title:"Ms.",imageUrl:"//cdnintech.com/web/frontend/www/assets/author.svg",email:"marica@intechopen.com",biography:null}},relatedBooks:[{type:"book",id:"5348",title:"Luminescence",subtitle:"An 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Sarria",coverURL:"https://cdn.intechopen.com/books/images_new/5884.jpg",editedByType:"Edited by",editors:[{id:"146466",title:"Prof.",name:"Andreia",surname:"Ferreira de Castro Gomes",slug:"andreia-ferreira-de-castro-gomes",fullName:"Andreia Ferreira de Castro Gomes"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7325",title:"Nanostructures in Energy Generation, Transmission and Storage",subtitle:null,isOpenForSubmission:!1,hash:"8e49924dd2c3e28c82fdc115ce04f925",slug:"nanostructures-in-energy-generation-transmission-and-storage",bookSignature:"Yanina Fedorenko",coverURL:"https://cdn.intechopen.com/books/images_new/7325.jpg",editedByType:"Edited by",editors:[{id:"199149",title:"Dr.",name:"Yanina",surname:"Fedorenko",slug:"yanina-fedorenko",fullName:"Yanina Fedorenko"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9230",title:"Smart Nanosystems for Biomedicine, Optoelectronics and Catalysis",subtitle:null,isOpenForSubmission:!1,hash:"1d1af591d87490c9ad728a1352e62d96",slug:"smart-nanosystems-for-biomedicine-optoelectronics-and-catalysis",bookSignature:"Tatyana Shabatina and Vladimir Bochenkov",coverURL:"https://cdn.intechopen.com/books/images_new/9230.jpg",editedByType:"Edited by",editors:[{id:"237988",title:"Prof.",name:"Tatyana",surname:"Shabatina",slug:"tatyana-shabatina",fullName:"Tatyana Shabatina"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9322",title:"Hybrid Nanomaterials",subtitle:"Flexible Electronics Materials",isOpenForSubmission:!1,hash:"beff6cce44f54582ee8a828759d24f19",slug:"hybrid-nanomaterials-flexible-electronics-materials",bookSignature:"Rafael Vargas-Bernal, Peng He and Shuye Zhang",coverURL:"https://cdn.intechopen.com/books/images_new/9322.jpg",editedByType:"Edited by",editors:[{id:"182114",title:"D.Sc.",name:"Rafael",surname:"Vargas-Bernal",slug:"rafael-vargas-bernal",fullName:"Rafael Vargas-Bernal"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"75148",title:"Arterial Stiffness Assessment in Children with Familial Hypercholesterolemia",doi:"10.5772/intechopen.96018",slug:"arterial-stiffness-assessment-in-children-with-familial-hypercholesterolemia",body:'Familial hypercholesterolemia (FH) is a monogenic disease with a predominantly autosomal dominant mode of inheritance, accompanied by a significant increase of the low-density lipoprotein cholesterol (LDL-C) level in the blood [1]. Patients with FH have a high risk of early development of atherosclerosis [2, 3]. The incidence of FH in the general population is estimated at about 1 per 200 persons [3], in addition, the evidence exist that in patients with established coronary heart disease, the prevalence of potential FH is up to 8.3% in men and 11.1% in women [4]. However, despite this, there is a low level of diagnosis and treatment [5, 6]. In this regard, registers of patients with FH have recently been developed for assessing the level of diagnosis, treatment and improvement in results of therapy [7, 8]. In more than 90% of cases, FH is caused by mutations in the gene encoding the LDL receptor, which reduce the cellular uptake of LDL and, therefore, significantly increase their plasma level [9]. Mutations in other genes leading to the same phenotype have also been identified: associated with apolipoprotein B, which affect the LDL-binding domain of apolipoprotein B as the most important apolipoprotein for uptake of LDL particles, and mutations in proprotein convertase subtilisin/kexin type 9 (PCSK9) [10, 11].
It is known that high plasma cholesterol level is a risk factor for the development of cardiovascular diseases [12] and may be the cause of early vascular damage. Currently, there are methods that allow registering pathological changes in blood vessels at preclinical stage. The detection of early changes in the walls of arteries by non-invasive methods, such as ultrasound duplex scanning, assessment of central aortic pressure and pulse wave velocity, has opened up new perspectives, helping to identify high-risk patients [13, 14, 15, 16, 17].
Several studies have shown that hypercholesterolemia can cause the loss of elasticity and increased stiffness of arterial vessels, leading to an increase in the pulse wave velocity due to its rapid spreading in stiff arteries [18, 19]. Arterial stiffness is considered to be a significant predictor of overall and cardiovascular mortality in patients with arterial hypertension [20, 21, 22, 23], in patients with end-stage renal failure [24, 25] and in the elderly patients [26]. In addition, it was noted that arterial stiffness is closely related to structural changes in the artery such as thickening of the intima-media complex [27]. Changes in the elastic properties of arteries may indicate a functional disorder long before the appearance of clinical symptoms. One of the indicators for assessing the stiffness of the arteries is the pulse wave velocity (PWV) measurement in aorta. It is the measurement of the speed of pulse pressure propagation along a segment of the arterial vessels [28]. It should be noted that the measurement of the arterial stiffness is quite widespread among adult patients [29, 30], while in pediatrics, despite its non-invasiveness and high informativeness, it is used much less frequently. This is probably due to the complexity of standardization, time costs and the need for additional equipment.
The aim of this study is to assess arterial stiffness in children with heterozygous familial hypercholesterolemia by measuring the pulse wave velocity in the aorta
The study involved 118 children. The control group consisted of 60 healthy children and 58 children with heterozygous familial hypercholesterolemia formed the main group (Table 1). The diagnosis of FHC was established in accordance with the British Simon Broome criteria [31]. The study included children with FH who were not taking statins. 15 patients from the main group underwent genetic testing in the Health in Code laboratory (Spain) for the detection of a monogenic mutation responsible for the development of familial hypercholesterolemia, and a positive DNA test was obtained. Exclusion criteria: secondary dyslipidemia, arterial hypertension, obesity. Written informed consent was obtained from all the participants of the study.
Control group, n = 60 | Main group, n = 58 | |
---|---|---|
Age, years (М ± σ) | 11,53 ± 4,2 | 10,92 ± 4,1 |
Gender, m/f | 40/20 | 37/21 |
Smoking, n/% | 0(0) | 0(0) |
Obesity, n/% | 0(0) | 0(0) |
Arterial hypertension, n/% | 0(0) | 0(0) |
Cutaneous xanthomas | 0(0) | 0(0) |
Corneal arch | 0(0) | 0(0) |
Thickening of the Achilles tendon | 0(0) | 0(0) |
TC, mmol/l (М ± σ) | 3,5 ± 1,2 | 7,8 ± 2,3 |
LDL, mmol/l (М ± σ) | 1,6 ± 0,8 | 6,1 ± 1,2 |
HDL, mmol/l (М ± σ) | 0,9 ± 0,1 | 1,1 ± 0,3 |
TG, mmol/l (М ± σ) | 0,8 ± 0.4 | 1,2 ± 0,3 |
Clinical and laboratory characteristics of children of the main and control groups.
Abbreviations: TC - total cholesterol; LDL - low density lipoprotein; HDL - high density lipoprotein; TG - triglycerides.
Total cholesterol, triglycerides, LDL, and high-density lipoprotein cholesterol (HDL) were measured using commercial kits (Beckman Coulter, USA) on an automatic biochemical analyzer (Au5800 Beckman Coulter, USA).
The clinical examination included a careful life history and family history taking, physical examination, and body mass index (BMI) assessment. All children underwent 24-hour blood pressure monitoring with an assessment of the pulse wave velocity in the aorta using the oscillometric method of the BPLab Vasotens system (Petr Telegin Ltd., Russia).
In the BPLab program for determining PWV in aorta the following ratio is used: PWVaorta = K × (2 × L) /RWTT, where PWVaorta is PWV in the aorta; K is the scale factor for standardizing the obtained value of the PWV; L is the length of the aortic trunk (in BPLab software, the distance from the upper edge of the sternum to the pubic bone is taken as the length of the aorta); RWTT (reflected wave transit time) [32].
Statistical analysis was carried out using the IBM SPSS Statistics v.23 software (developed by IBM Corporation, USA). The results were subjected to statistical processing using nonparametric methods in connection with the established absence of a normal distribution of quantitative indicators (testing for normal distribution was carried out using the Shapiro–Wilk test). Quantitative data were described using the values of the median (Me) and the lower and upper quartiles [Q1-Q3]. Comparison of quantitative indicators between two groups was carried out using the Mann–Whitney test, between the three groups using the Kruskal-Wallis test with an a posteriori Dunn test. Correlation analysis was carried out using the Spearman’s rank correlation coefficient; the assessment of the tightness of correlation was carried out using the Chaddock scale. Differences in indicators and identified relationships were considered statistically significant at p < 0.05.
Analysis of the values of the minimum PWV (PWVmin), mean PWV (PWVmean) and maximum PWV (PWVmax) obtained during 24-hour blood pressure monitoring revealed statistically significant differences between the main and control groups (p < 0.001) (Figure 1). The presence of FHC was accompanied by a significant increase in PWV - minimum, mean and maximum values.
Comparison of the values of the pulse wave velocity in the main and control groups. Note: *** - p < 0.001.
Taking into account the results obtained, we analyzed the degree of change in PWV depending on the age of children. For the analysis, both groups were divided into 3 age subgroups: from 5 to 7 years old, from 8 to 12 years old, from 13 to 17 years old (Table 2).
Parameter m/s | Control group | Main group | p | ||
---|---|---|---|---|---|
Me | Q1-Q3 | Me | Q1-Q3 | ||
5–7 years (n = 15) | 5–7 years (n = 16) | ||||
PWVmin | 3,0 | 2,8-3,1 | 3,05 | 2,6-3,3 | 0,19 |
PWVmean | 3,8 | 3,7-3,9 | 4,1 | 3,8-4,1 | 0,19 |
PWVmax | 4,5 | 4,3-4,8 | 4,8 | 4,1-5,3 | 0,095 |
8–12 years (n = 22) | 8–12 years (n = 21) | ||||
PWVmin | 3,6 | 3,2-4,1 | 3,5 | 3,3-3,9 | 0,052 |
PWVmean | 4,3 | 3,7-5,1 | 4,6 | 4,0-5,0 | 0,05 |
PWVmax | 4,6 | 4,45-5,05 | 5,1 | 4,7-5,8 | 0,041 |
13–17 years (n = 21) | 13–17 years (n = 23) | ||||
PWVmin | 3,9 | 3,5-4,1 | 4,7 | 4,1-5,1 | 0,009 |
PWVmean | 4,5 | 4,2-4,9 | 5,5 | 4,8-6,4 | 0,009 |
PWVmax | 5,4 | 5,05-5,6 | 6,2 | 5,7-7,55 | 0,007 |
Comparison of the values of the pulse wave velocity depending on the age of the children.
In accordance with the results obtained, in the younger age subgroup (5–7 years old), there were no statistically significant differences in PWV between the children of the main and control groups. In children aged 8–12 years, there was no statistically significant difference in the values of PWV min and mean PWV. While PWVmax was characterized by statistically significantly higher values in the main group (5.1 [4.7–5.8] m/s) relative to the control (4.6 [4.45–5.05] m/s) (p = 0.041). The most pronounced changes were found in the group of children with FHC at the age of 13–17 years. In this group were revealed statistically significant differences in the minimum, mean and maximum pulse wave velocity.
Taking into account the peculiarities of physical parameters and age periodization, we have analyzed the dynamics of changes in PWV depending on the age of children. In children of the control group, PWVmin in children 8–12 year old was statistically significantly higher than in children 5–7 year old (3.6 [3.2–4.1] m/s and 3.0 [2.8–3.1] m/s, respectively, p = 0.049). When comparing PWVmin in groups of 8–12 years old children and 13–17 years old children, no statistically significant difference was found (3.6 [3.2–4.1] m/s and 3.9 [3.5–4.1] m/s, respectively, p = 0.052). A similar dynamics of growth was observed for the mean pulse wave velocity in healthy children when compared in age subgroups 8–12 years old and 5–7 years old (4.3 [3.7–5.1] m/s and 3.8 [3.7–3.9] m/s, respectively, p = 0.026) and 8–12 years old and 13–17 years old (4.3 [3.7–5.1] m/s and 4.5 [4.2–4, 9] m/s, respectively, p = 0.114). The analysis of PWVmax showed that these indicators in the group of 5–7 years old and 8–12 years old children did not significantly differ from each other (4.5 [4.3–4.8] m/s and 4.6 [4.45–5.05] m/s, p = 0.145), while in children 13–17 years old it was significantly higher in comparison with 8–12 years old children (5.4 [5.05–5.6] m/s and 4.6 [4, 45–5.05] m/s, respectively, p = 0.022). It should be noted that there is a statistically significant difference in the values of PWVmin, mean PWV and PWVmax in children 13–17 years old relatively to 5–7 years old (Table 3).
Parameter, m/s | 5–7 years | 8–12 years | 13-17 years | Р1–2 | Р2–3 | Р1–3 |
---|---|---|---|---|---|---|
3,0 [2,8-3,1] | 3,6 [3,2-4,1] | 3,9 [3,5-4,1] | 0,052 | |||
3,8 [3,7-3,9] | 4,3 [3,7-5,1] | 4,5[4,2-4,9] | 0,114 | |||
4,5 [4,3-4,8] | 4,6 [4,45-5,05] | 5,4 [5,05-5,6] | 0,145 |
Indicators of the pulse wave velocity of children of the control group.
Note: p is the level of significance of the differences.
The study of PWV in children of the main group revealed a statistically significant difference in the increase in PWVmin, mean PWV and PWVmax indicators when compared in all main groups (Table 4).
Parameter, m/s | 5–7 years | 8–12 years | 13–17 years | Р1–2 | Р2–3 | Р1–3 |
---|---|---|---|---|---|---|
3,05[2,6-3,3] | 3,5 [3,3-3,9] | 4,7 [4,1-5,1] | ||||
4,1 [3,8-4,1] | 4,6 [4,0-5,0] | 5,5[4,8-6,4] | ||||
4,8 [4,1-5,3] | 5,1 [4,7-5,8] | 6,2 [5,7-7,55] |
Indicators of the pulse wave velocity of children of the main group.
Note: p is the level of significance of the differences.
At the same time, a more significant dynamics of increase in PWV was observed in children with FH compared with the control group in the age range of 13–17 years (Figure 2). It should be noted that the dynamics of the increase in indicators in the control group was less than in children with FH (Figure 3).
Indicators of the pulse wave velocity of the main and control groups, depending on the age of the children. Note: PWVmin - minimum pulse wave velocity, PWVmean - mean pulse wave velocity, PWVmax - maximum pulse wave velocity.
Dynamics of the increase in the mean pulse wave velocity in the main and control groups, depending on the age of the children. Note: * - p = 0.009.
Taking into account the presence of dyslipidemia in patients with FH in the form of severe hypercholesterolemia, we performed a correlation analysis of the relationship between PWV values and lipid metabolism indicators. In the main group, statistically significant direct correlations were established between PWVmin, mean PWV and PWVmax with total cholesterol level (rxy = 0.46 [95% CI: 0.227–0.644], rxy = 0.46 [95% CI: 0.229–0.642] and rxy = 0.464 [95% CI: 0.234–0.645], respectively, p < 0.001 in all cases).
In the presented study, the condition of the arterial wall was assessed by measuring the pulse wave velocity in the aorta in children with FH and healthy children of the same age. The study design differs from previous studies of PWV in the pediatric population presented in the literature [33, 34, 35, 36] in distribution of participants into age subgroups. In our opinion, such an analysis of the PWV values increases the correctness and statistical significance of the obtained results.
We found that the PWV values of children of the main group at the age of 5–7 years do not differ from those of the control group. In the 8–12-year-old subgroup in patients with FH, only the maximum PWV indicators were statistically significantly higher than in the comparison group. The identified deviations probably reflect the initial changes in the stiffness of the vascular wall in children of the main group. The most pronounced differences in the studied parameters were observed in children with FH in the age subgroup of 13–17 years old and were characterized by a statistically significant increase in PWVmin, mean PWV and PWmax relatively to the control group.
In our study, we also analyzed the dynamics of PWV growth depending on age. It was shown that PWV values increase with the age of the child both in familial hypercholesterolemia and in healthy children. This indicates that the studied indicators cannot be the same for all children and it is necessary to use age reference values in pediatrics. In addition, the increase in all three values of PWV was most pronounced in the group of 13–17 year old patients with FH, it allows us to suggest that they have a more pronounced change of properties of the vascular wall already at preclinical stages than in individuals with normal blood lipid profile.
A number of studies have revealed an increased PWV in children with hypertension [37], increased body mass index [38, 39]. In the present study, special attention was paid to patients with FH without risk factors such as smoking, obesity, and high blood pressure. Thus, the authors were able to assess the effect of hypercholesterolemia on the change in PWV precisely. The established correlation between total cholesterol level and PWV values allows us to regard an increase in total cholesterol level as a leading factor in forming the arterial stiffness in children with FH. In addition, the registration of the initial changes in PWV in the group with FH from 8–12 years old with further progression of the process in the absence of such changes in children 5–7 years old indicates a possible cumulative effect of cholesterol and its effect on the artery wall condition. This is consistent with large randomized studies showing that the effect of LDL on the development of atherosclerotic vascular disease is determined not only by the absolute level of LDL, but also by its cumulative effect on target organs [2, 40, 41].
Thus, the relationship between cholesterol level, age, and arterial stiffness indicators in familial hypercholesterolemia makes it possible to recommend the study of pulse wave velocity as a possible additional method for studying the cardiovascular risk in children with familial hypercholesterolemia and assessing the progression of the disease
We want to thank the Head of Tatarstan Republic’s Ministry of Health, the Rector of Kazan State medical University, Kazan, Russian Federation, the Head of the Children’s Republican Clinical Hospital of the Ministry of Health of the Republic of Tatarstan, Russian Federation for the help in the organization of Children’s Lipid Center, where we run our observation of children with Familial Hypercholesterolemia.
Authors declare no conflict of interest.
Management of PCOS (polycystic ovary syndrome) related to infertility, includes lifestyle changes, ovulation induction by pharmaceuticals, or assisted reproductive technology (ART) as an
Hyperandrogenism, anovulation, and ovarian morphology are the basic determinants in the diagnosis of the polycystic ovarian syndrome (PCOS) according to international guidelines. Given the different clinical presentations in patients, the criteria for the diagnosis of this condition are still discussed, as well as whether the syndrome involves several different diseases with the same clinical picture, as well as discussions about what is really a clinical picture of the polycystic ovary. Therefore, different approaches in the diagnosis and treatment of patients, have been proposed for different phenotypes of PCOS. The criteria for pre-recognition of this condition have been adopted for years by various authoritative bodies at international meetings, such as the National Institute for Health (NIH), Rotterdam consensus, Androgen Excess, and PCO Society, but there has been a constant difference over the mandatory criteria for PCOS [1]. An important starting point in the diagnosis was to exclude diseases of other endocrine glands (pituitary gland, thyroid, and adrenal gland), which give a similar clinical picture and can be confused with PCOS.
Ovulation disorder in the general population of women is estimated at 15% (12–18%) [2]. Regular menstrual cycles are not the exclusive evidence of ovulation, since in some women there is a “subclinical disorder” of ovulation that is proven only by serum values of progesterone in the middle lutein phase of the cycle (21–24.d.c. which must be >5 ng/mL). In the case of PCOS, almost 80% of patients have ovulation disorder [3].
Hyperandrogenism (hyperandrogenemia) implies clinical and/or biochemical evidence of elevated serum androgens, but the incidence in the general population of women is unknown. Hirsutism, androgenic alopecia, and acne are clinical manifestations of hyperandrogenism. The intensity of hirsutism differs ethnically and geographically, and it is desirable to develop population-specific criteria for hirsutism. Almost 70% of women with hirsutism have PCOS, 40% have severely expressed acne, and only 22% have androgenic alopecia [4]. Hyperandogenemia (biochemical hyperandrogenism) is determined by free testosterone and free androgen index (FAI—free androgen index) [5]. A total of 78% of patients with PCOS have hyperandrogenism and 40% in an unselected population of patients with BMI >25 [6].
Polycystic ovary morphology (PCOM) is evaluated by ultrasound examination based on the number of antral follicles (> of 20 per ovary) and/or on the basis of total ovarian volume (> 10 mL), where the frequency of the ultrasonic probe is an extremely important parameter. Based on these international criteria, the prevalence of PCOM in the population is 12.5% [7, 8]. Ultrasonic examination of nonselective population, based only on PCOM, significantly increase the incidence of PCOS and vice versa.
Thus, on the basis of the described criteria, four PCOS phenotypes with different prevalence in the general and separate population are defined, which are as follows [5]:
Phenotype A (hyperandrogenism, anovulation, PCOM).
Phenotype B (hyperandrogenism, anovulation).
Phenotype C (hyperandrogenism, PCOM), ovulatory PCOS.
Phenotype D (anovulation, PCOM), non-hyperandrogenemic PCOS.
Compared to phenotype C and D, patients with phenotype A and B (classical phenotype) are more often obese, with hirsutism, more likely to have insulin resistance, dyslipidemia, fatty liver, and metabolic syndrome in later life. The frequency of individual phenotype differs significantly in different populations with symptoms of PCOS and also in the general population [9]. Each of the PCOS phenotypes has its own specifics in the treatment of impaired fertility.
The first line of treatment of patients with PCOS is the induction of ovulation with clomiphene citrate or letrozole.
Gonadotropin stimulation in patients with PCOS is associated with the development of a significantly higher number of follicles in the ovaries, as well as oocytes, a significantly higher number of developed embryos and embryos in excess for cryopreservation. Ovarian stimulation in these patients lasts longer and higher doses of gonadotropin are often required, which is associated with disorders of folliculogenesis caused by hyperandrogenism. Estimating the right dose of gonadotropin is the biggest challenge in the phase of ovarian stimulation and is often insufficient. The follicles do not grow, due to hyperandrogenism, and by increasing the dose, the ovary enters in hyperstimulation, which is an extreme of the ovarian response. A newer approach to ovarian stimulation with follitropin delta, based on the patient’s body mass and AMH value, proved to be the best, especially in the PCOS patient population and has a significant reduction in the risk of ovary hyperstimulation. Patients with hyperandrogenism and polycystic ovarian morphology (phenotype A and C) have the highest risk of ovary hyperstimulation [11].
Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic complication of ovarian stimulation, and PCOS patients have the highest risk for complications during the IVF (
The protocol of choice for ovarian stimulation in patients with PCOS and risk for OHSS is an antagonistic protocol that can be fixed or flexible. In this stimulation, it is possible to achieve the final maturation of oocyte with GnRH (gonadotropin-releasing hormone) agonists, thereby avoiding the administration of hCG (human chorionic gonadotropin) injection, which is the basic molecule in the mechanism of development of OHSS in at-risk patients. In this way, the basic mechanism of vascular permeability and compromising circulation by leaking plasma from the vascular system into extracellular spaces are avoided. Those are signs of a more severe form of OHSS. Likewise, the stimulation cycle is abruptly “extinguished.” Menstrual bleeding occurs within a few days after the application of the GnRH agonist. Harvested oocytes are fertilized by IVF/ICSI procedure and developed embryos are cryopreserved, most often in the blastocyst stage, which represents the so-called “freeze-all” strategy that gives safety to the treatment of patients with PCOS. Embryo transfer is planned in the next cycle in which signs of hyperstimulation do not exist. Hormonal preparation of the endometrium, and ovarian stimulation, in this case, is not required.
Additional treatment of PCOS patients involves the use of various medications that have metabolic effects and that could significantly improve the treatment of these patients in IVF procedures by individualizing therapy. The fact is that within the PCOS population with the same PCOS phenotype, an individual woman may have a significantly different response to different types of treatments with respect to the unique hormonal/metabolic status associated with the PCOS phenotype as well. There is a large gap in the literature that indicates the need for new research and the need for an individual approach in the treatment of infertility of these patients.
Spontaneous abortions in patients with PCOS are more common compared to the general population and they are associated with insulin resistance, hyperandrogenism, and obesity. These conditions are very often associated with PCOS, but they are also separate risks for the spontaneous loss of pregnancy. Studies link spontaneous abortion to impaired endometrial receptivity and to more frequent embryo aneuploidy of patients with PCOS. In the Asian population of women with PCOS phenotypes who have hyperandrogenism (A, B, C types), a higher risk for spontaneous miscarriage after IVF procedures was observed than in phenotype D [12]. Impaired glucose and insulin metabolism at the endometrial level and excessive expression of androgen receptors in the endometrium are associated with a signal transduction disorder during the implantation process in patients with PCOS [13]. The causes of more frequent embryo aneuploidy in PCOS patients have not yet been clarified. There are assumptions that impaired glucose metabolism and steroidogenesis lead to DNA molecule instability [14].
During the stimulated IVF cycle, various indicators of quality and success of treatment are monitored. Among other things, these are the total dose of gonadotropin used for stimulation, the number of aspirated oocytes, the number of oocytes in metaphase II, the percentage of fertilization, the number of developed embryos on the 3rd day, the number of developed blastocysts on the 5th day, the number of cryopreserved embryos, the proportion of conceived pregnancies, the number of born children, etc. Since PCOS phenotypes imply hormonal and metabolic differences, the question arises whether the indicators of the course of treatment are different in patients with different PCOS phenotypes.
The results of the studies so far indicate significant differences in treatment between PCOS patients and women who do not have this syndrome and who in studies represent the usual control group. Studies most often follow PCOS patients as a single group. Different criteria for defining PCOS phenotype are associated with problems of analysis and comparison of parameters that monitor the course and outcome of the IVF procedures in different studies [15]. There are two fundamental factors that are most often analyzed and compared in patients with PCOS—hyperandrogenism and PCO morphology of the ovaries, which are clinically very important factors in decision-making during the treatment of infertility by medically assisted fertilization procedures. The role of androgens in folliculogenesis is still unclear and there are conflicting results of studies dealing with this problem. The results of studies analyzing differences in treatment outcomes among defined PCOS phenotypes indicate a negative effect of hyperandrogenism in IVF procedures, and a higher incidence of complications later in pregnancy [16]. In patients with phenotype A and B, for every 1 pg./ml increase in free testosterone concentration, the proportion of clinically confirmed pregnancies decreases by 50–60% as well as the proportion of live births [17]. According to recent findings, the differences between PCOS phenotypes refer only to the number of good embryos for transfer, which is significantly higher in patients with hyperandrogenism and ovulation disorder, but without the typical PCO morphology of the ovaries (phenotype B). The proportion of biochemical and clinically confirmed pregnancies, as well as the number of couples with born children, do not differ significantly among phenotypically different PCOS patients [17, 18]. In addition, studies indicate that the proportion of clinically confirmed pregnancies, is significantly lower in women with PCOS phenotypes A, B and C compared to control patients [17]. The number of children born does not differ in different PCOS phenotypes. In some areas of the world, certain PCOS phenotypes have not been found at all, for example, there are no phenotypes B and C among Vietnamese women with PCOS [19]. Since the anti-Müller hormone (AMH) is often elevated in patients with PCOS, it has become a powerful factor that should have prognostic value in clinically assessing the outcome of treatment with medically assisted fertilization, however, it has been proven useful only in the group of patients with phenotype B. The proportion of clinically confirmed pregnancies and the proportion of babies born increases by 1.3 times for each 1 ng/ml serum AMH concentration increase [17].
PCOS patients’ oocytes quality can be associated with the hormonal and metabolic conditions, and therefore, consequently with the quality of the embryo. Poorer oocyte quality is part of the problem of subfertility in patients with PCOS. There is evidence that oocyte quality depends on PCOS phenotype and accompanying diseases and conditions that are more common in PCOS patients. Oocyte quality is defined by the morphology and morphology of associated structures, such as zona pellucida, cumulus oophorus, and corona radiata. An ovarian microenvironment in which follicles and oocytes grow and mature is exposed to multiple hormonal abnormalities in patients with PCOS. Well-known disruptive mechanisms include elevated concentrations of LH (luteinizing hormone) and FSH (follicle-stimulating hormone), impaired ratio of these hormones, elevated AMH values, impaired insulin-like growth factor secretion, and enzymes involved in the conversion of androgens to estrogens.
Hyperandrogenism interferes with the normal feedback loop between the ovaries, pituitary gland, and hypothalamus, which leads to an increased frequency of excretion of the releasing hormone for gonadotropins, and consecutively results in premature luteinization of granulose cells and abnormal maturation of the oocytes. There is also a direct effect of hyperandrogenism on the oocyte by activating its proapoptotic mechanism [20]. Hyperandogenic ovarium microenvironment interferes with the oocyte in the continuation of meiosis, promotes mitochondrial abnormalities and oxidative stress, and interferes with lipid metabolism in the oocyte [21].
High concentrations of AMH synthesized by granulosa cells, inhibit the recruitment of follicles, and therefore, the selection of follicles that will ovulate, leading to a vicious cycle of anovulation and hyperandrogenism. In addition, by blocking the action of FSH on follicle growth and blocking the action of aromatase in charge of converting androgens synthesized in theca cells to estrogens in granulosa cells, the chronic state of hyperandrogenism is again supported. There is evidence that in patients with PCOS an increased concentration of AMH in follicular fluid exists along with oocytes of low quality. Molecular mechanisms that lead to disruption in the growth and maturation of oocytes are not known [22]. Significantly lower follicular fluid AMH levels were observed in follicles of fertilized MII oocytes than in non-fertilized non-PCOS patients [23]. Also in our non-PCOS patients with sterility and impaired fertility, gene for the AMH and androgen receptor in human cumulus cells surrounding morphologically highly graded oocytes are underexpressed [24].
Hyperinsulinemia, insulin resistance, and obesity are metabolic disorders associated with PCOS that intertwine with hormonal disorders and further worsen the conditions of oocyte microenvironments. Hyperinsulinemia reduces the synthesis of binding globulin for sex hormones (SHBG), and insulin also competes with androgens for binding sites on this carrier, which means that it promotes hyperandrogenism and all its negative effects. The direct effect of hyperinsulinemia on oocytes has been proven to disrupt the expression of genes associated with the dynamics of the division spindle and the function of centrosomes. In the case of insulin resistance, there is a change in gene expression for glucose carriers in granulose cells, and therefore, a possible decrease in energy sources for the metabolism of the oocyte itself and the processes of meiosis [25].
Based on PCOS phenotype in the population of women being treated with medically assisted reproduction procedures, no difference has been found so far in the proportion of oocytes in metaphase II, percentage of fertilization, or the evaluation of quality embryos for transfer [17, 26]. According to available data to date, patients who have a classic PCOS phenotype (A and B) associated with insulin resistance and obesity also have the highest risk for low-quality oocytes [27].
Besides poor quality oocytes, PCOS patients can have larger numbers of germinal vesicle stages – metaphase I oocyte collected from IVF, due to their elevated antral follicles count. Those are commonly maturated with unsatisfactory results. When optimized maturation procedure will serve, not only for PCOS and infertile patients but also in cancer patients for the preservation of fertility and as a more patient-friendly alternative than standard controlled ovarian stimulation. PCOS patients are not the only ones that could benefit from
The definition of phenotypes of polycystic ovarian syndrome stemmed from a diverse and complex clinical picture of this endocrine disorder. Diagnostic criteria of individual phenotype, contribute to new concepts of research into the effects of obesity, hyperandrogenism, and metabolic disorders on reproduction in humans. According to the outcomes of the treatment of infertility of patients with this disorder, significant differences in the chances of conception compared to the population of infertile women who do not have polycystic ovary syndrome have been clearly proven. Less clear is the difference in infertility treatment outcomes between women with a defined polycystic ovarian syndrome phenotype, which is the area of new research. In cases of classical phenotype polycystic ovarian syndrome (A and B) associated with obesity and insulin resistance, negative effects of this disease on gametes and embryos are possible due to cellular process disorders related to glucose and androgen metabolism.
The publication is supported by H2020: MESOC – measuring the social dimension of culture; under Grant agreement no. 870935. Uniri-biomed-18-161 project: Extracellular vesicles in human follicular fluid: content and role in oocyte maturation and embryo quality.
Authors have no conflict of interest.
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She is now a lecturer at the University of Witwatersrand, South Africa, and a principal researcher at the Health Economics and Epidemiology Research Office (HE2RO), South Africa. Dr. Moolla holds a Ph.D. in Psychology with her research being focused on mental health and resilience. In her professional work capacity, her research has further expanded into the fields of early childhood development, mental health, the HIV and TB care cascades, as well as COVID. She is also a UNESCO-trained International Bioethics Facilitator.",institutionString:"University of the Witwatersrand",institution:{name:"University of the Witwatersrand",country:{name:"South Africa"}}},{id:"419588",title:"Ph.D.",name:"Sergio",middleName:"Alexandre",surname:"Gehrke",slug:"sergio-gehrke",fullName:"Sergio Gehrke",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000038WgMKQA0/Profile_Picture_2022-06-02T11:44:20.jpg",biography:"Dr. Sergio Alexandre Gehrke is a doctorate holder in two fields. The first is a Ph.D. in Cellular and Molecular Biology from the Pontificia Catholic University, Porto Alegre, Brazil, in 2010 and the other is an International Ph.D. in Bioengineering from the Universidad Miguel Hernandez, Elche/Alicante, Spain, obtained in 2020. In 2018, he completed a postdoctoral fellowship in Materials Engineering in the NUCLEMAT of the Pontificia Catholic University, Porto Alegre, Brazil. He is currently the Director of the Postgraduate Program in Implantology of the Bioface/UCAM/PgO (Montevideo, Uruguay), Director of the Cathedra of Biotechnology of the Catholic University of Murcia (Murcia, Spain), an Extraordinary Full Professor of the Catholic University of Murcia (Murcia, Spain) as well as the Director of the private center of research Biotecnos – Technology and Science (Montevideo, Uruguay). Applied biomaterials, cellular and molecular biology, and dental implants are among his research interests. He has published several original papers in renowned journals. In addition, he is also a Collaborating Professor in several Postgraduate programs at different universities all over the world.",institutionString:null,institution:{name:"Universidad Católica San Antonio de Murcia",country:{name:"Spain"}}},{id:"342152",title:"Dr.",name:"Santo",middleName:null,surname:"Grace Umesh",slug:"santo-grace-umesh",fullName:"Santo Grace Umesh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/342152/images/16311_n.jpg",biography:null,institutionString:null,institution:{name:"SRM Dental College",country:{name:"India"}}},{id:"333647",title:"Dr.",name:"Shreya",middleName:null,surname:"Kishore",slug:"shreya-kishore",fullName:"Shreya Kishore",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/333647/images/14701_n.jpg",biography:"Dr. Shreya Kishore completed her Bachelor in Dental Surgery in Chettinad Dental College and Research Institute, Chennai, and her Master of Dental Surgery (Orthodontics) in Saveetha Dental College, Chennai. She is also Invisalign certified. She’s working as a Senior Lecturer in the Department of Orthodontics, SRM Dental College since November 2019. She is actively involved in teaching orthodontics to the undergraduates and the postgraduates. Her clinical research topics include new orthodontic brackets, fixed appliances and TADs. She’s published 4 articles in well renowned indexed journals and has a published patency of her own. Her private practice is currently limited to orthodontics and works as a consultant in various clinics.",institutionString:null,institution:{name:"SRM Dental College",country:{name:"India"}}},{id:"323731",title:"Prof.",name:"Deepak M.",middleName:"Macchindra",surname:"Vikhe",slug:"deepak-m.-vikhe",fullName:"Deepak M. Vikhe",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/323731/images/13613_n.jpg",biography:"Dr Deepak M.Vikhe .\n\n\t\n\tDr Deepak M.Vikhe , completed his Masters & PhD in Prosthodontics from Rural Dental College, Loni securing third rank in the Pravara Institute of Medical Sciences Deemed University. He was awarded Dr.G.C.DAS Memorial Award for Research on Implants at 39th IPS conference Dubai (U A E).He has two patents under his name. He has received Dr.Saraswati medal award for best research for implant study in 2017.He has received Fully funded scholarship to Spain ,university of Santiago de Compostela. He has completed fellowship in Implantlogy from Noble Biocare. \nHe has attended various conferences and CDE programmes and has national publications to his credit. His field of interest is in Implant supported prosthesis. Presently he is working as a associate professor in the Dept of Prosthodontics, Rural Dental College, Loni and maintains a successful private practice specialising in Implantology at Rahata.\n\nEmail: drdeepak_mvikhe@yahoo.com..................",institutionString:null,institution:{name:"Pravara Institute of Medical Sciences",country:{name:"India"}}},{id:"204110",title:"Dr.",name:"Ahmed A.",middleName:null,surname:"Madfa",slug:"ahmed-a.-madfa",fullName:"Ahmed A. Madfa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204110/images/system/204110.jpg",biography:"Dr. Madfa is currently Associate Professor of Endodontics at Thamar University and a visiting lecturer at Sana'a University and University of Sciences and Technology. He has more than 6 years of experience in teaching. His research interests include root canal morphology, functionally graded concept, dental biomaterials, epidemiology and dental education, biomimetic restoration, finite element analysis and endodontic regeneration. Dr. Madfa has numerous international publications, full articles, two patents, a book and a book chapter. Furthermore, he won 14 international scientific awards. Furthermore, he is involved in many academic activities ranging from editorial board member, reviewer for many international journals and postgraduate students' supervisor. Besides, I deliver many courses and training workshops at various scientific events. Dr. Madfa also regularly attends international conferences and holds administrative positions (Deputy Dean of the Faculty for Students’ & Academic Affairs and Deputy Head of Research Unit).",institutionString:"Thamar University",institution:null},{id:"210472",title:"Dr.",name:"Nermin",middleName:"Mohammed Ahmed",surname:"Yussif",slug:"nermin-yussif",fullName:"Nermin Yussif",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/210472/images/system/210472.jpg",biography:"Dr. Nermin Mohammed Ahmed Yussif is working at the Faculty of dentistry, University for October university for modern sciences and arts (MSA). Her areas of expertise include: periodontology, dental laserology, oral implantology, periodontal plastic surgeries, oral mesotherapy, nutrition, dental pharmacology. She is an editor and reviewer in numerous international journals.",institutionString:"MSA University",institution:null},{id:"204606",title:"Dr.",name:"Serdar",middleName:null,surname:"Gözler",slug:"serdar-gozler",fullName:"Serdar Gözler",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204606/images/system/204606.jpeg",biography:"Dr. Serdar Gözler has completed his undergraduate studies at the Marmara University Faculty of Dentistry in 1978, followed by an assistantship in the Prosthesis Department of Dicle University Faculty of Dentistry. Starting his PhD work on non-resilient overdentures with Assoc. Prof. Hüsnü Yavuzyılmaz, he continued his studies with Prof. Dr. Gürbüz Öztürk of Istanbul University Faculty of Dentistry Department of Prosthodontics, this time on Gnatology. He attended training programs on occlusion, neurology, neurophysiology, EMG, radiology and biostatistics. In 1982, he presented his PhD thesis \\Gerber and Lauritzen Occlusion Analysis Techniques: Diagnosis Values,\\ at Istanbul University School of Dentistry, Department of Prosthodontics. As he was also working with Prof. Senih Çalıkkocaoğlu on The Physiology of Chewing at the same time, Gözler has written a chapter in Çalıkkocaoğlu\\'s book \\Complete Prostheses\\ entitled \\The Place of Neuromuscular Mechanism in Prosthetic Dentistry.\\ The book was published five times since by the Istanbul University Publications. Having presented in various conferences about occlusion analysis until 1998, Dr. Gözler has also decided to use the T-Scan II occlusion analysis method. Having been personally trained by Dr. Robert Kerstein on this method, Dr. Gözler has been lecturing on the T-Scan Occlusion Analysis Method in conferences both in Turkey and abroad. Dr. Gözler has various articles and presentations on Digital Occlusion Analysis methods. He is now Head of the TMD Clinic at Prosthodontic Department of Faculty of Dentistry , Istanbul Aydın University , Turkey.",institutionString:"Istanbul Aydin University",institution:{name:"Istanbul Aydın University",country:{name:"Turkey"}}},{id:"240870",title:"Ph.D.",name:"Alaa Eddin Omar",middleName:null,surname:"Al Ostwani",slug:"alaa-eddin-omar-al-ostwani",fullName:"Alaa Eddin Omar Al Ostwani",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/240870/images/system/240870.jpeg",biography:"Dr. Al Ostwani Alaa Eddin Omar received his Master in dentistry from Damascus University in 2010, and his Ph.D. in Pediatric Dentistry from Damascus University in 2014. Dr. Al Ostwani is an assistant professor and faculty member at IUST University since 2014. \nDuring his academic experience, he has received several awards including the scientific research award from the Union of Arab Universities, the Syrian gold medal and the international gold medal for invention and creativity. Dr. Al Ostwani is a Member of the International Association of Dental Traumatology and the Syrian Society for Research and Preventive Dentistry since 2017. He is also a Member of the Reviewer Board of International Journal of Dental Medicine (IJDM), and the Indian Journal of Conservative and Endodontics since 2016.",institutionString:"International University for Science and Technology.",institution:{name:"Islamic University of Science and Technology",country:{name:"India"}}},{id:"42847",title:"Dr.",name:"Belma",middleName:null,surname:"Işik Aslan",slug:"belma-isik-aslan",fullName:"Belma Işik Aslan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/42847/images/system/42847.jpg",biography:"Dr. Belma IşIk Aslan was born in 1976 in Ankara-TURKEY. After graduating from TED Ankara College in 1994, she attended to Gazi University, Faculty of Dentistry in Ankara. She completed her PhD in orthodontic education at Gazi University between 1999-2005. Dr. Işık Aslan stayed at the Providence Hospital Craniofacial Institude and Reconstructive Surgery in Michigan, USA for three months as an observer. She worked as a specialist doctor at Gazi University, Dentistry Faculty, Department of Orthodontics between 2005-2014. She was appointed as associate professor in January, 2014 and as professor in 2021. Dr. Işık Aslan still works as an instructor at the same faculty. She has published a total of 35 articles, 10 book chapters, 39 conference proceedings both internationally and nationally. Also she was the academic editor of the international book 'Current Advances in Orthodontics'. She is a member of the Turkish Orthodontic Society and Turkish Cleft Lip and Palate Society. She is married and has 2 children. Her knowledge of English is at an advanced level.",institutionString:"Gazi University Dentistry Faculty Department of Orthodontics",institution:null},{id:"178412",title:"Associate Prof.",name:"Guhan",middleName:null,surname:"Dergin",slug:"guhan-dergin",fullName:"Guhan Dergin",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178412/images/6954_n.jpg",biography:"Assoc. Prof. Dr. Gühan Dergin was born in 1973 in Izmit. He graduated from Marmara University Faculty of Dentistry in 1999. He completed his specialty of OMFS surgery in Marmara University Faculty of Dentistry and obtained his PhD degree in 2006. In 2005, he was invited as a visiting doctor in the Oral and Maxillofacial Surgery Department of the University of North Carolina, USA, where he went on a scholarship. Dr. Dergin still continues his academic career as an associate professor in Marmara University Faculty of Dentistry. He has many articles in international and national scientific journals and chapters in books.",institutionString:null,institution:{name:"Marmara University",country:{name:"Turkey"}}},{id:"178414",title:"Prof.",name:"Yusuf",middleName:null,surname:"Emes",slug:"yusuf-emes",fullName:"Yusuf Emes",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178414/images/6953_n.jpg",biography:"Born in Istanbul in 1974, Dr. Emes graduated from Istanbul University Faculty of Dentistry in 1997 and completed his PhD degree in Istanbul University faculty of Dentistry Department of Oral and Maxillofacial Surgery in 2005. He has papers published in international and national scientific journals, including research articles on implantology, oroantral fistulas, odontogenic cysts, and temporomandibular disorders. Dr. Emes is currently working as a full-time academic staff in Istanbul University faculty of Dentistry Department of Oral and Maxillofacial Surgery.",institutionString:null,institution:{name:"Istanbul University",country:{name:"Turkey"}}},{id:"192229",title:"Ph.D.",name:"Ana Luiza",middleName:null,surname:"De Carvalho Felippini",slug:"ana-luiza-de-carvalho-felippini",fullName:"Ana Luiza De Carvalho Felippini",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/192229/images/system/192229.jpg",biography:null,institutionString:"University of São Paulo",institution:{name:"University of Sao Paulo",country:{name:"Brazil"}}},{id:"256851",title:"Prof.",name:"Ayşe",middleName:null,surname:"Gülşen",slug:"ayse-gulsen",fullName:"Ayşe Gülşen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/256851/images/9696_n.jpg",biography:"Dr. Ayşe Gülşen graduated in 1990 from Faculty of Dentistry, University of Ankara and did a postgraduate program at University of Gazi. \nShe worked as an observer and research assistant in Craniofacial Surgery Departments in New York, Providence Hospital in Michigan and Chang Gung Memorial Hospital in Taiwan. \nShe works as Craniofacial Orthodontist in Department of Aesthetic, Plastic and Reconstructive Surgery, Faculty of Medicine, University of Gazi, Ankara Turkey since 2004.",institutionString:"Univeristy of Gazi",institution:null},{id:"255366",title:"Prof.",name:"Tosun",middleName:null,surname:"Tosun",slug:"tosun-tosun",fullName:"Tosun Tosun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255366/images/7347_n.jpg",biography:"Graduated at the Faculty of Dentistry, University of Istanbul, Turkey in 1989;\nVisitor Assistant at the University of Padua, Italy and Branemark Osseointegration Center of Treviso, Italy between 1993-94;\nPhD thesis on oral implantology in University of Istanbul and was awarded the academic title “Dr.med.dent.”, 1997;\nHe was awarded the academic title “Doç.Dr.” (Associated Professor) in 2003;\nProficiency in Botulinum Toxin Applications, Reading-UK in 2009;\nMastership, RWTH Certificate in Laser Therapy in Dentistry, AALZ-Aachen University, Germany 2009-11;\nMaster of Science (MSc) in Laser Dentistry, University of Genoa, Italy 2013-14.\n\nDr.Tosun worked as Research Assistant in the Department of Oral Implantology, Faculty of Dentistry, University of Istanbul between 1990-2002. \nHe worked part-time as Consultant surgeon in Harvard Medical International Hospitals and John Hopkins Medicine, Istanbul between years 2007-09.\u2028He was contract Professor in the Department of Surgical and Diagnostic Sciences (DI.S.C.), Medical School, University of Genova, Italy between years 2011-16. \nSince 2015 he is visiting Professor at Medical School, University of Plovdiv, Bulgaria. \nCurrently he is Associated Prof.Dr. at the Dental School, Oral Surgery Dept., Istanbul Aydin University and since 2003 he works in his own private clinic in Istanbul, Turkey.\u2028\nDr.Tosun is reviewer in journal ‘Laser in Medical Sciences’, reviewer in journal ‘Folia Medica\\', a Fellow of the International Team for Implantology, Clinical Lecturer of DGZI German Association of Oral Implantology, Expert Lecturer of Laser&Health Academy, Country Representative of World Federation for Laser Dentistry, member of European Federation of Periodontology, member of Academy of Laser Dentistry. Dr.Tosun presents papers in international and national congresses and has scientific publications in international and national journals. He speaks english, spanish, italian and french.",institutionString:null,institution:{name:"Istanbul Aydın University",country:{name:"Turkey"}}},{id:"171887",title:"Prof.",name:"Zühre",middleName:null,surname:"Akarslan",slug:"zuhre-akarslan",fullName:"Zühre Akarslan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/171887/images/system/171887.jpg",biography:"Zühre Akarslan was born in 1977 in Cyprus. She graduated from Gazi University Faculty of Dentistry, Ankara, Turkey in 2000. \r\nLater she received her Ph.D. degree from the Oral Diagnosis and Radiology Department; which was recently renamed as Oral and Dentomaxillofacial Radiology, from the same university. \r\nShe is working as a full-time Associate Professor and is a lecturer and an academic researcher. \r\nHer expertise areas are dental caries, cancer, dental fear and anxiety, gag reflex in dentistry, oral medicine, and dentomaxillofacial radiology.",institutionString:"Gazi University",institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"256417",title:"Associate Prof.",name:"Sanaz",middleName:null,surname:"Sadry",slug:"sanaz-sadry",fullName:"Sanaz Sadry",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/256417/images/8106_n.jpg",biography:null,institutionString:null,institution:null},{id:"272237",title:"Dr.",name:"Pinar",middleName:"Kiymet",surname:"Karataban",slug:"pinar-karataban",fullName:"Pinar Karataban",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/272237/images/8911_n.png",biography:"Assist.Prof.Dr.Pınar Kıymet Karataban, DDS PhD \n\nDr.Pınar Kıymet Karataban was born in Istanbul in 1975. After her graduation from Marmara University Faculty of Dentistry in 1998 she started her PhD in Paediatric Dentistry focused on children with special needs; mainly children with Cerebral Palsy. She finished her pHD thesis entitled \\'Investigation of occlusion via cast analysis and evaluation of dental caries prevalance, periodontal status and muscle dysfunctions in children with cerebral palsy” in 2008. She got her Assist. Proffessor degree in Istanbul Aydın University Paediatric Dentistry Department in 2015-2018. ın 2019 she started her new career in Bahcesehir University, Istanbul as Head of Department of Pediatric Dentistry. In 2020 she was accepted to BAU International University, Batumi as Professor of Pediatric Dentistry. She’s a lecturer in the same university meanwhile working part-time in private practice in Ege Dental Studio (https://www.egedisklinigi.com/) a multidisciplinary dental clinic in Istanbul. Her main interests are paleodontology, ancient and contemporary dentistry, oral microbiology, cerebral palsy and special care dentistry. She has national and international publications, scientific reports and is a member of IAPO (International Association for Paleodontology), IADH (International Association of Disability and Oral Health) and EAPD (European Association of Pediatric Dentistry).",institutionString:null,institution:null},{id:"202198",title:"Dr.",name:"Buket",middleName:null,surname:"Aybar",slug:"buket-aybar",fullName:"Buket Aybar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/202198/images/6955_n.jpg",biography:"Buket Aybar, DDS, PhD, was born in 1971. She graduated from Istanbul University, Faculty of Dentistry, in 1992 and completed her PhD degree on Oral and Maxillofacial Surgery in Istanbul University in 1997.\nDr. Aybar is currently a full-time professor in Istanbul University, Faculty of Dentistry Department of Oral and Maxillofacial Surgery. She has teaching responsibilities in graduate and postgraduate programs. Her clinical practice includes mainly dentoalveolar surgery.\nHer topics of interest are biomaterials science and cell culture studies. She has many articles in international and national scientific journals and chapters in books; she also has participated in several scientific projects supported by Istanbul University Research fund.",institutionString:null,institution:null},{id:"260116",title:"Dr.",name:"Mehmet",middleName:null,surname:"Yaltirik",slug:"mehmet-yaltirik",fullName:"Mehmet Yaltirik",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/260116/images/7413_n.jpg",biography:"Birth Date 25.09.1965\r\nBirth Place Adana- Turkey\r\nSex Male\r\nMarrial Status Bachelor\r\nDriving License Acquired\r\nMother Tongue Turkish\r\n\r\nAddress:\r\nWork:University of Istanbul,Faculty of Dentistry, Department of Oral Surgery and Oral Medicine 34093 Capa,Istanbul- TURKIYE",institutionString:null,institution:null},{id:"172009",title:"Dr.",name:"Fatma Deniz",middleName:null,surname:"Uzuner",slug:"fatma-deniz-uzuner",fullName:"Fatma Deniz Uzuner",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/172009/images/7122_n.jpg",biography:"Dr. Deniz Uzuner was born in 1969 in Kocaeli-TURKEY. 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Dr. Şentürk currently works as an professor of Biochemistry in the Department of Basic Pharmacy Sciences, Faculty of Pharmacy, Ağri Ibrahim Cecen University, Turkey. \nDr. Şentürk published over 120 scientific papers, reviews, and book chapters and presented several conferences to scientists. \nHis research interests span enzyme inhibitor or activator, protein expression, purification and characterization, drug design and synthesis, toxicology, and pharmacology. \nHis research work has focused on neurodegenerative diseases and cancer treatment. 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Much of biochemistry is devoted to enzymes, proteins that catalyze chemical reactions, enzyme structures, mechanisms of action and their roles within cells. Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. This Biochemistry Series will address the current research on biomolecules and the emerging trends with great promise.",coverUrl:"https://cdn.intechopen.com/series/covers/11.jpg",latestPublicationDate:"June 29th, 2022",hasOnlineFirst:!0,numberOfOpenTopics:4,numberOfPublishedChapters:318,numberOfPublishedBooks:32,editor:{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"Blumenberg",fullName:"Miroslav Blumenberg",profilePictureURL:"https://mts.intechopen.com/storage/users/31610/images/system/31610.jpg",biography:"Miroslav Blumenberg, Ph.D., was born in Subotica and received his BSc in Belgrade, Yugoslavia. He completed his Ph.D. at MIT in Organic Chemistry; he followed up his Ph.D. with two postdoctoral study periods at Stanford University. Since 1983, he has been a faculty member of the RO Perelman Department of Dermatology, NYU School of Medicine, where he is codirector of a training grant in cutaneous biology. Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}},subseries:[{id:"14",title:"Cell and Molecular Biology",keywords:"Omics (Transcriptomics; Proteomics; Metabolomics), Molecular Biology, Cell Biology, Signal Transduction and Regulation, Cell Growth and Differentiation, Apoptosis, Necroptosis, Ferroptosis, Autophagy, Cell Cycle, Macromolecules and Complexes, Gene Expression",scope:"The Cell and Molecular Biology topic within the IntechOpen Biochemistry Series aims to rapidly publish contributions on all aspects of cell and molecular biology, including aspects related to biochemical and genetic research (not only in humans but all living beings). We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics include, but are not limited to: Advanced techniques of cellular and molecular biology (Molecular methodologies, imaging techniques, and bioinformatics); Biological activities at the molecular level; Biological processes of cell functions, cell division, senescence, maintenance, and cell death; Biomolecules interactions; Cancer; Cell biology; Chemical biology; Computational biology; Cytochemistry; Developmental biology; Disease mechanisms and therapeutics; DNA, and RNA metabolism; Gene functions, genetics, and genomics; Genetics; Immunology; Medical microbiology; Molecular biology; Molecular genetics; Molecular processes of cell and organelle dynamics; Neuroscience; Protein biosynthesis, degradation, and functions; Regulation of molecular interactions in a cell; Signalling networks and system biology; Structural biology; Virology and microbiology.",annualVolume:11410,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/14.jpg",editor:{id:"165627",title:"Dr.",name:"Rosa María",middleName:null,surname:"Martínez-Espinosa",fullName:"Rosa María Martínez-Espinosa",profilePictureURL:"https://mts.intechopen.com/storage/users/165627/images/system/165627.jpeg",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"79367",title:"Dr.",name:"Ana Isabel",middleName:null,surname:"Flores",fullName:"Ana Isabel Flores",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRpIOQA0/Profile_Picture_1632418099564",institutionString:null,institution:{name:"Hospital Universitario 12 De Octubre",institutionURL:null,country:{name:"Spain"}}},{id:"328234",title:"Ph.D.",name:"Christian",middleName:null,surname:"Palavecino",fullName:"Christian Palavecino",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000030DhEhQAK/Profile_Picture_1628835318625",institutionString:null,institution:{name:"Central University of Chile",institutionURL:null,country:{name:"Chile"}}},{id:"186585",title:"Dr.",name:"Francisco Javier",middleName:null,surname:"Martin-Romero",fullName:"Francisco Javier Martin-Romero",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSB3HQAW/Profile_Picture_1631258137641",institutionString:null,institution:{name:"University of Extremadura",institutionURL:null,country:{name:"Spain"}}}]},{id:"15",title:"Chemical Biology",keywords:"Phenolic Compounds, Essential Oils, Modification of Biomolecules, Glycobiology, Combinatorial Chemistry, Therapeutic peptides, Enzyme Inhibitors",scope:"Chemical biology spans the fields of chemistry and biology involving the application of biological and chemical molecules and techniques. In recent years, the application of chemistry to biological molecules has gained significant interest in medicinal and pharmacological studies. This topic will be devoted to understanding the interplay between biomolecules and chemical compounds, their structure and function, and their potential applications in related fields. Being a part of the biochemistry discipline, the ideas and concepts that have emerged from Chemical Biology have affected other related areas. This topic will closely deal with all emerging trends in this discipline.",annualVolume:11411,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",institutionString:null,institution:{name:"Anadolu University",institutionURL:null,country:{name:"Turkey"}}},editorTwo:{id:"13652",title:"Prof.",name:"Deniz",middleName:null,surname:"Ekinci",fullName:"Deniz Ekinci",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYLT1QAO/Profile_Picture_1634557223079",institutionString:null,institution:{name:"Ondokuz Mayıs University",institutionURL:null,country:{name:"Turkey"}}},editorThree:null,editorialBoard:[{id:"219081",title:"Dr.",name:"Abdulsamed",middleName:null,surname:"Kükürt",fullName:"Abdulsamed Kükürt",profilePictureURL:"https://mts.intechopen.com/storage/users/219081/images/system/219081.png",institutionString:null,institution:{name:"Kafkas University",institutionURL:null,country:{name:"Turkey"}}},{id:"241413",title:"Dr.",name:"Azhar",middleName:null,surname:"Rasul",fullName:"Azhar Rasul",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRT1oQAG/Profile_Picture_1635251978933",institutionString:null,institution:{name:"Government College University, Faisalabad",institutionURL:null,country:{name:"Pakistan"}}},{id:"178316",title:"Ph.D.",name:"Sergey",middleName:null,surname:"Sedykh",fullName:"Sergey Sedykh",profilePictureURL:"https://mts.intechopen.com/storage/users/178316/images/system/178316.jfif",institutionString:null,institution:{name:"Novosibirsk State University",institutionURL:null,country:{name:"Russia"}}}]},{id:"17",title:"Metabolism",keywords:"Biomolecules Metabolism, Energy Metabolism, Metabolic Pathways, Key Metabolic Enzymes, Metabolic Adaptation",scope:"Metabolism is frequently defined in biochemistry textbooks as the overall process that allows living systems to acquire and use the free energy they need for their vital functions or the chemical processes that occur within a living organism to maintain life. Behind these definitions are hidden all the aspects of normal and pathological functioning of all processes that the topic ‘Metabolism’ will cover within the Biochemistry Series. Thus all studies on metabolism will be considered for publication.",annualVolume:11413,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/17.jpg",editor:{id:"138626",title:"Dr.",name:"Yannis",middleName:null,surname:"Karamanos",fullName:"Yannis Karamanos",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002g6Jv2QAE/Profile_Picture_1629356660984",institutionString:null,institution:{name:"Artois University",institutionURL:null,country:{name:"France"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"243049",title:"Dr.",name:"Anca",middleName:null,surname:"Pantea Stoian",fullName:"Anca Pantea Stoian",profilePictureURL:"https://mts.intechopen.com/storage/users/243049/images/system/243049.jpg",institutionString:null,institution:{name:"Carol Davila University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"203824",title:"Dr.",name:"Attilio",middleName:null,surname:"Rigotti",fullName:"Attilio Rigotti",profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institutionString:null,institution:{name:"Pontifical Catholic University of Chile",institutionURL:null,country:{name:"Chile"}}},{id:"300470",title:"Dr.",name:"Yanfei (Jacob)",middleName:null,surname:"Qi",fullName:"Yanfei (Jacob) Qi",profilePictureURL:"https://mts.intechopen.com/storage/users/300470/images/system/300470.jpg",institutionString:null,institution:{name:"Centenary Institute of Cancer Medicine and Cell Biology",institutionURL:null,country:{name:"Australia"}}}]},{id:"18",title:"Proteomics",keywords:"Mono- and Two-Dimensional Gel Electrophoresis (1-and 2-DE), Liquid Chromatography (LC), Mass Spectrometry/Tandem Mass Spectrometry (MS; MS/MS), Proteins",scope:"With the recognition that the human genome cannot provide answers to the etiology of a disorder, changes in the proteins expressed by a genome became a focus in research. Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. The Proteomics topic aims to attract contributions on all aspects of MS-based proteomics that, by pushing the boundaries of MS capabilities, may address biological problems that have not been resolved yet.",annualVolume:11414,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/18.jpg",editor:{id:"200689",title:"Prof.",name:"Paolo",middleName:null,surname:"Iadarola",fullName:"Paolo Iadarola",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSCl8QAG/Profile_Picture_1623568118342",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorTwo:{id:"201414",title:"Dr.",name:"Simona",middleName:null,surname:"Viglio",fullName:"Simona Viglio",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKDHQA4/Profile_Picture_1630402531487",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorThree:null,editorialBoard:[{id:"72288",title:"Dr.",name:"Arli Aditya",middleName:null,surname:"Parikesit",fullName:"Arli Aditya Parikesit",profilePictureURL:"https://mts.intechopen.com/storage/users/72288/images/system/72288.jpg",institutionString:null,institution:{name:"Indonesia International Institute for Life Sciences",institutionURL:null,country:{name:"Indonesia"}}},{id:"40928",title:"Dr.",name:"Cesar",middleName:null,surname:"Lopez-Camarillo",fullName:"Cesar Lopez-Camarillo",profilePictureURL:"https://mts.intechopen.com/storage/users/40928/images/3884_n.png",institutionString:null,institution:{name:"Universidad Autónoma de la Ciudad de México",institutionURL:null,country:{name:"Mexico"}}},{id:"81926",title:"Dr.",name:"Shymaa",middleName:null,surname:"Enany",fullName:"Shymaa Enany",profilePictureURL:"https://mts.intechopen.com/storage/users/81926/images/system/81926.png",institutionString:"Suez Canal University",institution:{name:"Suez Canal University",institutionURL:null,country:{name:"Egypt"}}}]}]}},libraryRecommendation:{success:null,errors:{},institutions:[]},route:{name:"chapter.detail",path:"/chapters/75148",hash:"",query:{},params:{id:"75148"},fullPath:"/chapters/75148",meta:{},from:{name:null,path:"/",hash:"",query:{},params:{},fullPath:"/",meta:{}}}},function(){var e;(e=document.currentScript||document.scripts[document.scripts.length-1]).parentNode.removeChild(e)}()