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\n
1. Introduction
\n
The interest in flow control in the fluid dynamic domain has showed a quick growth in last 15 years [1] due to rapid development of sensors and actuators technologies. Even though passive control techniques are still attractive since they do not require an energy input, active control strategies have recently received more attention since they can be used in a selective way and can be operated only when it is effectively requested. Among different active techniques, plasma aerodynamic actuators are attractive because they present high dynamic responses due to the absence of moving parts, are characterized by low weight, are easy to build, are backward compatible with existing aerodynamic surfaces, and generate negligible aerodynamics interferences when they are switched off. When actuated, they can significantly modify the status of the boundary layer developing on the body surfaces. For this reason, they have been extensively studied for aeronautical applications to prevent flow separation enhancing lift and reducing drag [2, 3]. More recently, they have been used also to control friction drag by delaying transition [4, 5] or by oscillating the flow in spanwise direction [6], and to control global instabilities of the flow [2, 3, 7]. Due to these characteristics, the potential of plasma actuators has been extended to many other applications like for instance tip clearance flow control of turbines [8, 9], and wind turbine blades and holder [10, 11].
\n
This brief review about DBD aerodynamic actuators is all but exhaustive. The main goals of this work are to give to the reader some basic knowledge about the physics of plasma actuators and to show most important applications of these devices into the active flow control domain.
\n
\n
\n
2. DBD aerodynamic actuators: basic principles
\n
Plasma aerodynamic actuators are based on the electrohydrodynamic (EHD) interaction generated by the so-called ionic wind. High electric fields can locally ionize the air. The produced heavy-charged species are accelerated by the applied electric field and, by means of collisions, they can yield momentum to the surrounding neutral gas. The force f per unit volume within the discharge can be yield by the following expression:
\n
f=ni−neE¯E1
\n
where E is the electric filed and ni and ne are ion and electron number density respectively.
\n
First studies were conducted by using direct current (DC) corona discharges [2]. Main disadvantages of these actuators are low flexibility in electrodes configuration and in the supply system, and the transition into spark regime producing irreversible damage of the actuator itself.
\n
Nowadays, the largest part of plasma aerodynamic actuators is based on the surface dielectric barrier discharge (SDBD). This typology of discharge allows to use several electrodes geometry, different supply voltage waveforms, and it prevents the transition into the arc regime due to the presence of the dielectric material. DBD actuators generate non-thermal plasmas [12], limiting power consumption and allowing their use over heat sensitive surfaces.
\n
A classical DBD aerodynamic plasma actuator is constituted by a dissymmetric electrode pair separated by a dielectric slab (Figure 1). When high voltages (typically 10–50 kV at 1–100 kHz) are applied to the electrodes, a surface discharge is produced (Figure 2). Discharge appears to be macroscopically homogeneous to the unaided eye, but it is constituted by a sequence of micro-discharges [13] lasting typically for tens of nanoseconds with a repetition rate of several hundreds of megahertz. Fast ignition and quenching of the discharge can be inferred by voltage-current time behavior reported in Figure 3.
\n
Figure 1.
Schematic of a SDBD actuator for flow control.
\n
Figure 2.
Top view image of SDBD discharge [14].
\n
Figure 3.
Voltage-current time behavior of a SDBD [15].
\n
The presence of the plasma and the particular electrode configuration induce a jet tangential to the actuator wall, similar to a classic blowing technique [13]. These jets can modify the aerodynamic boundary layer, increasing flow momentum, at least in the near-wall region above the surface. A large number of experimental [14–25] and numerical [26–47] works have been done in last decade to understand basic physical phenomena involved in the EHD interaction.
\n
A typical velocity profile induced by the tangential wall jet is shown in Figure 4. Measurements have been carried out by a glass Pitot tube positioned 2 mm downstream with respect plasma extension and moved parallel to the actuator surface. Maximum velocity of about 5–6 m/s are usually reached.
\n
Figure 4.
Typical pitot velocity profile of a DBD plasma actuator (red line). Blue lines represent standard deviation [48].
\n
Fast dynamics of these actuators is underlined in Figure 5 where Schlieren images of the induced jet developing during ignition of the discharge are shown. Steady state (d) is typically reached after 400 ms after discharge ignition.
\n
Figure 5.
Schlieren images of induced wall jet during ignition phase of the discharge (a, b, and c) and steady state operation (d) [48].
\n
As already introduced [26–47], EHD interaction produced by DBD plasma actuators has been numerically investigated a well. Main issues are related to the simulation of the discharge and its interaction with surrounding gas. A ‘realistic’ simulation of a DBD streamer should take into account gas ionization, plasma chemistry, thermal fluxes, diffusion of neutral and charged species, and charge deposition over dielectric surfaces. Time steps of about tens of picoseconds and mesh size in the order of few micrometers are usually required to reproduce the formation of a plasma filament lasting for tens of nanoseconds and featured with characteristic length of about few millimeters. Several coefficients related to diffusion, secondary electrons emission, reaction rates, and electrons attachment are often not easy to estimate or to recover from existing literature. The numerical model leads to the temporal/spatial evolution of the body force produced by the discharge. The second step is the coupling between the discharge and the surrounding gas. This is another numerical challenge because characteristic times and lengths of the discharge are several orders of magnitude smaller with respect those related to the fluid-dynamic domain. Several authors [26–36] followed this computational strategy obtaining interesting results in good agreement with experimental fluid-dynamic effects. In Figure 6a, integrated horizontal body force as a function of the applied voltage is shown [36]. The two half periods produce different force dynamics and magnitude. In Figure 6b, the time-averaged horizontal force distribution above the actuator surface is depicted [33]. Highest values have been obtained close to plasma end.
\n
Figure 6.
Time evolution of the EHD body force (a) [36], and spatial distribution of the average horizontal force (b) [33].
\n
A simpler approach is to estimate the electron number density [37–42], on the basis of experimental measurements or theoretical calculations, and to evaluate EHD body force using Equation 1. This force is subsequently utilized as input parameter in the Navier-Stokes equation solver. A spatial/temporal average value of the body force can also be obtained by means of experimental results [43–47]. This method allows to use standard fluid-dynamic solvers avoiding difficulties arising from the couple between plasma and surrounding gas.
\n
Both numerical and experimental works demonstrated the capability of plasma actuators to produce a thrust able to move surrounding gas in a desired direction. In order to increase both induced speed and region in which the actuator manifests its influence, a series of DBD actuators can be manufactured (Figure 7). Each actuator of this multi-electrode arrangement contributes to increase the induced speed.
\n
Figure 7.
Horizontal velocity profile (y = 0.5 mm) above four DBD actuators in series [13].
\n
On a parallel plane, voltage waveform shape (arbitrary or nanopulsed signals) can enhance thrust of the induced jet, increasing effectiveness of actuators [15, 49–56]. The use of arbitrary waveforms can enhance plasma ignition phases in which induced thrust is higher. In this way, induced speed (Figure 8) and efficiency (Figure 9) can be both increased [15]. Nanopulsed discharges are able to generate energetic plasmas lasting for few nanoseconds. During the ignition of the discharge, a high amount of energy is deposited within the gas inducing local shock waves able to significantly modify the boundary layer of an incoming flow [56].
\n
Figure 8.
Pitot velocity profiles obtained close to plasma extension for different supplying voltage waveforms [15].
\n
Figure 9.
Electric into kinetic conversion efficiency for a DBD actuator driven with different voltage waveforms [15].
\n
Another possibility to increase actuator performance is the adoption of a third exposed electrode supplied with high-voltage DC fields. In this way, a sliding DBD is generated. Depending on the sign of the DC field, it is possible to modify the morphology of the induced ionic wind [57, 58].
\n
DBD actuators can be arranged to produce normal or vectorized jets, too. These devices can be used to mimic classical synthetic jets and are usually called plasma synthetic jet actuators (PSJA). Typical geometries are annular and linear one [48, 59–62]. In both cases, tangential wall jets collide merging in a unique-induced jet able to generate perturbations far away from the actuator surface (Figures 10 and 11). When the linear configuration is adopted, by supplying exposed electrodes with different voltages, it is possible to produce an induced jet with an arbitrary inclination. Three-dimensional flows can be also produced by using a classical DBD actuator, but with an exposed electrode characterized with serpentine or serrated geometries, instead of the usual linear one [63, 64]. This particular electrode geometry generates small tangential jets that collide and propagate downstream pushed by the EHD interaction body force.
\n
Figure 10.
Induced normal jet of linear (left-hand side) and annular (right-hand side) PSJA.
\n
Figure 11.
Schlieren images of PSJAs of linear (a) and annular (b) geometries. Electrode distance (a) and diameter (b) is 30 mm.
\n
\n
\n
3. DBD aerodynamic actuators: flow manipulation
\n
In the last decade, DBD aerodynamic actuators have been extensively studied in the active flow control domain. Position and actuation strategies of these devices are key points in their effectiveness in flow control over aerodynamic surfaces. Many studies have been accomplished over airfoils [65–72], diffusers [73, 74], and wind [10, 11 and 75] and turbine [8, 9] blades, in order to enhance fluid-dynamic performance. Moreover, the adoption of these devices over landing gears and trailing edge surfaces have demonstrated the possibility to obtain a noise reduction effect [76–78].
\n
DBD actuators can be usually positioned over aerodynamic surfaces in spanwise and streamwise directions. In the former, the induced body force is in the same direction as the incoming flow. In the latter, induced thrust is perpendicular to the free stream direction. In this case, the composition of these two flows produces vorticities propagating in the downstream direction.
\n
In Figure 12, a NACA 0015 airfoil equipped with four spanwise DBD plasma actuators is shown. The four plasma regions are clearly visible in the figure as bluish strips. In this configuration, actuators produce a tangential wall jet directed downstream. The effect of this plasma device in the recovery of stall condition is depicted in Figure 13, where smoke visualization is reported. Experiments show how the most effective actuator is the one positioned on the airfoil leading edge, just before the region where separation occurs [66, 67, 79, 80].
\n
Figure 12.
Airfoil equipped with four spanwise plasma actuators [65].
\n
Figure 13.
Flow structure around NACA0015 airfoil at Re = 15000 without (left-hand side) and with (right-hand side) plasma actuation [65].
\n
When DBD actuators are streamwise mounted, induced and incoming flows combine together producing vorticities propagating in the downstream direction (Figure 14). Such a device can be used as a plasma vortex generator (PVG)
\n
Figure 14.
Vortex formation mechanism induced by a streamwise plasma actuator [8].
\n
Changes in drag coefficient (CD) and lift coefficient (CL) by using a PVG are reported in Figure 15. At low Reynolds numbers, actuator effectiveness is very pronounced, leading to noticeable CD reduction with a parallel increment in the stall angle.
\n
Figure 15.
Drag (a) and lift coefficient enhancement (b) with counter-rotating PVGs on a NACA 4418 airfoil [8].
\n
Figure 16.
Pressure coefficient contours with streamlines over an airfoil with 15° angle of attack: plasma actuator off (a) and on (b) [47].
\n
Figure 17.
Lift recovery in percentage for different actuators location with a free stream velocity of 11 m/s: steady operation (a) and duty cycle operation (b) [66].
\n
Effectiveness in flow control by means plasma actuators has been demonstrated by numerical works, too [47, 81–87]. In Figure 16, pressure coefficient contours with streamlines obtained over an airfoil with a 15° angle of attack are displayed. In Figure 16a, plasma actuator is switched off, and separation occurs. When the plasma device is activated, reattachment of the flow is achieved (Figure 16b).
\n
Plasma actuators have demonstrated to strongly improve their ability in flow manipulation when operated with a duty cycle strategy [47, 66, 71, 72, 88]. With this approach, the DBD device is turned on and off with intermittence by following a particular duty cycle frequency. This frequency is usually chosen in the range 5–100 Hz and it is strictly related to natural vorticities developing over the aerodynamic surface. The percentage ratio between the period in which discharge is fed and the whole duty cycle period is called duty cycle percentage. If it is fixed to 50%, it means that discharge is ignited half of the time. On a parallel plane, this actuation strategy leads to lower power consumption.
\n
Figure 17 shows lift recovery in percentage of a stalled NACA0015 airfoil equipped with spanwise vectorized actuators located in different airfoil positions [66]. Jet 5 is generated by a DBD actuator located in the leading edge. When actuators are continuously operated, lift increments are limited to about 15%. When operated with a duty cycle strategy, lift increments are close to 50%.
\n
Plasma actuators can also be used to reduce noise induced by aerodynamic surfaces, especially by landing gears and trailing edges [76–78]. Studies on bluff bodies have demonstrated the ability of DBD actuators to reduce downstream turbulence, leading to the suppression of particular tones or to an overall noise mitigation up to 4 dB.
\n
\n
\n
4. Conclusion
\n
Studies carried out in the last decades have demonstrated the possibility to use DBD aerodynamic actuators for active flow control purposes. In this last section, main advantages and disadvantages in the use of these plasma devices will be summarized.
\n
Pros
Possibility to locate these actuators in different positions on a surface and over existing aerodynamic bodies.
Negligible aerodynamic interferences when they are not active.
Fast actuation times.
Low power consumption.
Possibility to tune the on/off actuation strategy depending on the particular fluid dynamic condition.
\n
Cons
Induced velocity below 10 m/s.
Low electric into kinetic conversion efficiency.
Use of potentially hazardous high voltages and electromagnetic noise generation.
Effectiveness in flow control for Reynolds numbers typically below few hundred thousand.
\n
Disadvantages already introduced will be overcome only when a more detailed knowledge of basic interactions between discharge a neutral gas will be achieved. When higher induced speeds will be available, new and more effective flow control strategies will be developed.
\n
\n\n',keywords:"Active flow control, Dielectric barrier discharge, Electrohydrodynamic interaction, Plasma physics, Noise mitigation",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/50409.pdf",chapterXML:"https://mts.intechopen.com/source/xml/50409.xml",downloadPdfUrl:"/chapter/pdf-download/50409",previewPdfUrl:"/chapter/pdf-preview/50409",totalDownloads:2878,totalViews:948,totalCrossrefCites:7,totalDimensionsCites:9,totalAltmetricsMentions:10,impactScore:3,impactScorePercentile:87,impactScoreQuartile:4,hasAltmetrics:1,dateSubmitted:"September 30th 2015",dateReviewed:"February 25th 2016",datePrePublished:null,datePublished:"September 8th 2016",dateFinished:"April 22nd 2016",readingETA:"0",abstract:"Active flow control has recently received an increasing attention since it allows to directly manipulate the flow-field around a surface only when it is effectively requested. Aerodynamic plasma actuators supplied by a dielectric barrier discharge (DBD) can be used for this purpose. Usually, sinusoidal voltages in the range 5–50 kV peak and frequencies between 1 and 100 kHz are utilized to ignite this plasma typology. The surface discharge produced by these devices is able to tangentially accelerate the flow field by means of the electrohydrodynamic (EHD) interaction. DBDs generate non-thermal plasmas characterized by low input energies and limited temperature increments. Plasma actuators can be easily designed by following the shape of the aerodynamic body and can be used over heat-sensitive surfaces. These aerodynamic devices have demonstrated to produce boundary layer modifications with induced speeds up to 10 m/s. Their use over airfoils, flaps, and blades have shown the possibility to delay the transition between laminar to turbulent regime, to prevent flow separation enhancing lift and reducing drag. Moreover, the adoption of these actuators over landing gears and trailing edges may induce a noise reduction effect. Dielectric materials, electrodes configuration, and supplying waveforms are most relevant parameters to be considered to enhance actuator performance. On a parallel plane, on/off actuation strategy is a key point in the use of these devices when utilized over aerodynamic surfaces impinged within an external flow.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/50409",risUrl:"/chapter/ris/50409",book:{id:"5136",slug:"recent-progress-in-some-aircraft-technologies"},signatures:"Gabriele Neretti",authors:[{id:"178403",title:"Dr.",name:"Gabriele",middleName:null,surname:"Neretti",fullName:"Gabriele Neretti",slug:"gabriele-neretti",email:"gabriele.neretti@unibo.it",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178403/images/5665_n.jpg",institution:{name:"University of Bologna",institutionURL:null,country:{name:"Italy"}}}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. DBD aerodynamic actuators: basic principles",level:"1"},{id:"sec_3",title:"3. DBD aerodynamic actuators: flow manipulation",level:"1"},{id:"sec_4",title:"4. Conclusion",level:"1"}],chapterReferences:[{id:"B1",body:'\nM. Gad-El-Hak. Flow Control. Cambrige: Cambrige University Press; 2000.\n'},{id:"B2",body:'\nE. Moreau. Airflow control by non-thermal plasma actuator. J. Phys. D: Appl Phys. 2007;40:605. DOI: 10.1088/0022-3727/40/3/S01\n'},{id:"B3",body:'\nJ.J. Wang, K. Choi, L. Feng, T. N. Jukes, R. D. Whalley. Recent developments in DBD plasma flow control. Progress in Aerospace Sciences. 2013;62:52–78. DOI:10.1016/j.paerosci.2013.05.003\n'},{id:"B4",body:'\nS, Grundmann, C. Tropea. Experimental transition delay using glow-discharge plasma actuators. Exp. Fluids. 2007;42:653–657.\n'},{id:"B5",body:'\nS. Grundmann, C. Tropea. Active cancellation of artificially introduced Tollmien-Schlichting waves using plasma actuators. Exp. Fluids. 2008;44:795–806.\n'},{id:"B6",body:'\nS.P. Wilkinson. Investigation of an oscillating surface plasma for turbulent drag reduction. In: Proceedings of the 41st aerospace sciences meeting and exhibit; Reno, USA. AIAA; 2003. AIAA 2003–1023\n'},{id:"B7",body:'\nG. Touchard. Plasma actuators for aeronautical applications-state of art review. International Journal of Plasma Environmental Science and Technology. 2008;2(1):1–25.\n'},{id:"B8",body:'\nChoi, K.–S., Jukes, T.N., Whalley, R.D., Feng, L.H., Wang, J.J., Matsunuma, T. and Segawa, T.. Plasma Virtual Actuators for Flow Control. Journal of Flow Control, Measurement & Visualization. 2005;3:22–34. DOI:10.4236/jfcmv.2015.31003.\n'},{id:"B9",body:'\nThomas C. Corke, Flint O. Thomas, and Junhui Huang. Documentation and Control of Flow Separation on a Low Pressure Turbine Linear Cascade of Pak-B Blades Using Plasma Actuators. In: NASA/CR-2007–214677, editor. University of Notre Dame, Aerospace and Mechanical Engineering Department, . 2007.\n'},{id:"B10",body:'\nRobert C. 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AIAA 2008-3763.\n'},{id:"B63",body:'\nR Joussot, A Leroy, R Weber, H Rabat, S Loyer and D Hong. Plasma morphology and induced airflow characterization of a DBD actuator with serrated electrode. J. Phys. D: Appl. Phys. 2013; 46(125204); 12pp. DOI: 10.1088/0022-3727/46/12/125204.\n'},{id:"B64",body:'\nR J Durscher and S Roy. Three-dimensional flow measurements induced from serpentine plasma actuators in quiescent air. J. Phys. D: Appl. Phys. 2012; 45 (035202);9pp. DOI:10.1088/0022-3727/45/3/035202.\n'},{id:"B65",body:'\nY.E. Akansu, F. Karakaya, and A. Şanlısoy. Active Control of Flow around NACA 0015 Airfoil by Using DBD Plasma Actuator. EPJ Web of Conferences. 2013; 45(01008): 7pp. DOI: 10.1051/epjconf/20134501008.\n'},{id:"B66",body:'\nC.A. Borghi, A. Cristofolini, G, Neretti, P. Seri, A. Talamelli, and A. Rossetti. Wind Tunnel Experiments on a NACA0015 Airfoil Equipped with Vectorizable\n'},{id:"B67",body:'\nM.L. Post and T.C. Corke. Separation Control on High Angle of Attack Airfoil Using Plasma Actuators. AIAA Journal. 2004; 42: pp. 2177-2184.\n'},{id:"B68",body:'\nC. He, T.C. Corke, and M.P. Patel. Plasma Flaps and Slats: An Application of Weakly Ionized Plasma Actuators. J. Aircraft. 2009; 46; pp. 864-873. DOI: 10.2514/1.38232.\n'},{id:"B69",body:'\nD.P. Rizzetta and M.R. Visbal. Numerical Investigation of Plasma-Based Control for Low-Reynolds-Number Airfoil Flows. AIAA Journal. 2011; 49: pp. 411-425. DOI: 10.2514/1.J050755.\n'},{id:"B70",body:'\nMark Riherd and Subrata Roy. Serpentine geometry plasma actuators for flow control. J. of Appl. Physics D. 2013; 114(083303). DOI: 10.1063/1.4818622\n'},{id:"B71",body:'\nK. Inaoka, T. Mori, M. Yamaguchi, and M. Senda. Feedback flow control of a low-Re airfoil by flap actuators. Journal of Fluids and Structures. 2015; 58: 319-330. DOI: 10.1016/j.jfluidstructs.2015.08.011.\n'},{id:"B72",body:'\nT. C. Corke, P.O. Bowles, C. He, and E. Matlis. Sensing and control of flow separation using plasma actuators. Phil. Trans. R. Soc. A. 2011; 369: 1459-1475. DOI: 10.1098/rsta.2010.0356\n'},{id:"B73",body:'\nMaden, R. Maduta, S. Jakirlic, S. Grundmann, C. Tropea, and J.K. Eaton. Plasma-Based\n'},{id:"B74",body:'\nS. Grundmann, E. L. Sayles, and J. K. Eaton. Sensitivity of an asymmetric 3D diffuser to plasma-actuator induced inlet condition perturbations. Experiments in Fluids. 2010; 50(1):217–23. DOI: 10.1007/s00348-010-0922-0.\n'},{id:"B75",body:'\nPotočar, E., Širok, B., Hočevar, M., and Eberlinc, M. Control of Separation Flow over a Wind Turbine Blade with Plasma Actuators. Journal of Mechanical Engineering. 2012; 58(1): 37-45. DOI: 10.5545/sv-jme.2011.016.\n'},{id:"B76",body:'\nYong Li, Xin Zhang, and Xun Huang. The use of plasma actuators for bluff body broadband noise control. Experiments in Fluids. 2010; 49(2); 367-377. DOI: 10.1007/s00348-009-0806-3.\n'},{id:"B77",body:'\nF. O. Thomas, A. Kozlov, and T. C. Corke. Plasma Actuators for Cylinder Flow Control and Noise Reduction. AIAA Journal. 2008; 46(8): pp. 1921-1931.\n'},{id:"B78",body:'\nXun Huang, and Xin Zhang. Plasma actuators for noise control. International Journal of Aeroacoustics. 2010; 9(4 & 5): pages 679-704.\n'},{id:"B79",body:'\nC. L. Kelley, P. O. Bowles, J. Cooney, C. He, T.C. Corke, B. A. Osborne, J.S. Silkey, and J. Zehnle. Leading-Edge Separation Control Using Alternating-Current and Nanosecond-Pulse Plasma Actuators. AIAA Journal. 2014; 52(9): 1871-1884.doi: 10.2514/1.J052708\n'},{id:"B80",body:'\nY. Bouremela, J.M. Lia, Z. Zhaob, and M. Debiasia. Effects of AC Dielectric Barrier Discharge Plasma Actuator Location on Flow Separation and Airfoil Performance. Procedia Engineering. 2013; 67: 270-278. DOI: 10.1016/j.proeng.2013.12.026.\n'},{id:"B81",body:'\nHikaru Aono, Taku Nonomura, Aiko Yakeno, Kozo Fujii and Koichi Okada. Plasma Flow Control Simulation of an Airfoil of Wind Turbine at an Intermediate Reynolds Number. In: 8th Symposium on Flow Manipulation and Active Control: Theory, Experiments and Implementation; July 7-11, 2013; Nevada, USA, . 2013. DOI: 978-0-7918-5555-3.\n'},{id:"B82",body:'\nMiguel Visbal, Datta Gaitonde, and Subrata Roy. Control of Transitional and Turbulent Flows Using Plasma-Based Actuators. In: 36th AIAA Fluid Dynamics Conference and Exhibit, Fluid Dynamics and Co-located Conferences; 5-8 June, 2006; San Francisco, California. 2006. AIAA-2006-3230. DOI: 10.2514/6.2006-3230 .\n'},{id:"B83",body:'\nA. N. M. M. I. Mukut, H. Mizunuma, O. Hiromichi, T. Segawa. Winglet type dielectric barrier discharge plasma actuators: performance characterization and numerical comparison. Procedia Engineering. 2015; 105: 250-257. DOI: http://dx.doi.org/10.1016/j.proeng.2015.05.104.\n'},{id:"B84",body:'\nXiaohu Zhao, Yinghong LI, Yun Wu, Tao Zhu, Yiwen Li. Numerical Investigation of Flow Separation Control on a Highly Loaded Compressor Cascade by Plasma Aerodynamic Actuation . 2012;25(3):349–360. DOI: 10.1016/S1000-9361(11)60396-8\n'},{id:"B85",body:'\nPhilipp C. Dörr, Markus, J. Kloker. Transition Control in a Three-dimensional Boundary-layer Flow Using Plasma Actuators. Procedia IUTAM. 2015;14:469–478. DOI: 10.1016/j.piutam.2015.03.075.\n'},{id:"B86",body:'\nI. Maden, R. Maduta, J. Kriegseis, S. Jakirlič, C. Schwarz, S. Grundmann, C. Tropea. Experimental and computational study of the flow induced by a plasma actuator. International Journal of Heat and Fluid Flow. 2013;41:80–89. DOI: 10.1016/j.ijheatfluidflow.2013.02.013\n'},{id:"B87",body:'\nE. Peersa, Z. Ma, X. Huang . A numerical model of plasma effects in flow control. Physics Letters A. 2010;374(13-14):1501–1504. DOI: 10.1016/j.physleta.2009.08.046\n'},{id:"B88",body:'\nA. Kurz, S. Grundmann, C. Tropea, M. Forte, A. Seraudie, O. Vermeersch, D. Arnal, N. Goldin, R. King. Boundary Layer Transition Control using DBD Plasma Actuators. Journal Aerospace Lab. 2013; 6: AL-06-02. ISSN: 2107-6596.\n'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Gabriele Neretti",address:"gabriele.neretti@unibo.it",affiliation:'
Electrical, Electronic Engineering Department Guglielmo Marconi, University of Bologna, Bologna, Italy
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1. Introduction
Thyroid dysfunction as well as polycystic ovary syndrome (PCOS) are very common endocrine disorders among the general population. Although, thyroid dysfunction and PCOS have completely different etiopathogenesis, but have various common features. In primary hypothyroidism, an increased ovarian volume and cystic changes in ovaries have been reported. It is also increasingly recognized that thyroid dysfunction is more common in females with PCOS as compared to the healthy individuals [1, 2]. This is may be due to some common considerations as well as pathophysiological connection between PCOS and thyroid disorders leading an individual towards both the disorders. Considering the high prevalence of Hashimoto’s thyroiditis (HT) and the high prevalence of PCOS in women in the reproductive period, the emphasis will lie on the possible etiological and clinical connections between HT and PCOS.
2. Endocrine system
The endocrine system is a network of glands that produce and secrete hormones to regulate many physiological processes [3]. The endocrine system is comprised of hypothalamus, pituitary gland, pancreas, adrenal gland, ovaries, testes, pineal gland, thyroid gland, parathyroid gland and thymus gland [4]. These glands communicate with each other through different pathways called axis. Major endocrine pathways include hypothalamic-pituitary-thyroid axis (HPTA), hypothalamic-pituitary-gonadal axis, hypothalamic-pituitary-adrenal-axis, renin-angiotensin-aldosterone axis and hypothalamic-pituitary-adipose axis [5]. Endocrine glands are also closely linked with stress system, gut microbial flora and immune system [6].
2.1 Endocrine feedback system
Hormones are required for maintaining homeostasis and optimum body functions. Adequate secretion of hormones is ensured through biological feedback system that aims to provide hormones in a specific physiological range. Feedback system, is combination of several axis, that regulates endocrine and neural responses after any external or internal stimuli [7]. There are two types of feedback systems; positive feedback mechanism and negative feedback mechanism. Thyroid hormones exert both positive and negative feedback mechanism, which controls the release of both thyrotropin-releasing hormone (TRH) from hypothalamus and thyroid stimulating hormone (TSH) from anterior pituitary gland [8].
2.2 Endocrine dysfunction
Endocrine dysfunction is characterized by abnormal production and secretion of hormones from particular glands. Endocrine dysfunction can be categorized into following types; endocrine hyposecretion (deficiency of hormones), endocrine hypersecretion (excess of hormones), altered tissue response (hormone insensitivity irrespective of circulating hormone) and endocrine tumors [3, 9].
3. Thyroid gland
The thyroid gland is, morphologically, a butterfly-shaped organ, located anterior to the trachea, just inferior to the larynx. It is flanked by wing-shaped left and right lobes and the medial region called isthmus [3, 10]. The thyroid gland produces thyroid hormones, mainly triiodothyronine (T3) and thyroxine (T4). Multiple thyroid hormone receptor isoforms, derived from two distinct genes, mediate the action of thyroid hormones. The thyroid hormone receptors belong to a nuclear receptor superfamily. Thyroid hormone receptors bind to specific thyroid hormone-responsive sequences in promoters of target genes by regulating transcription. However, hypothalamic-pituitary-thyroid axis regulates thyroid hormones [7, 11].
3.1 Hypothalamic-pituitary-thyroid (HPT) axis
The hypothalamic-pituitary-thyroid axis is the part of neuroendocrine system consisting of hypothalamus, pituitary gland and thyroid gland. The hypothalamus is directly connected to the pituitary gland [12]. Hypothalamus secretes TRH which stimulates pituitary gland to produce and secrete TSH. TSH then acts on thyroid gland to produce and secrete thyroxine (T4) and triiodothyronine (T3). T4 is converted into T3 by deidonination controlled by various hormones like TSH, vasopressin and catecholamines in the peripheral organs (liver, adipose tissues, glia and skeletal muscles). T4 and T3 control the secretion of TRH and TSH by negative feedback mechanism to maintain normal levels of the hormones of HPT axis into the blood stream. Reduced levels of circulating TH result in increased TRH and TSH production and vice versa [13].
3.2 Thyroid dysfunction
Thyroid disease is very common worldwide affecting 5–15% of general population. Women are 3–4 times more susceptible to experience any type of thyroid disease. Thyroid dysfunction can be due to overproduction or under production of thyroid hormones. Thyroid disorders can lead to enlargement of thyroid gland as well as thyroid cancer. Abnormal production of thyroid hormones can lead to following pathological conditions; hypothyroidism (under production of thyroid hormones) and hyperthyroidism (overproduction of thyroid hormones) [3, 14]. There are a few drugs, classically associated with thyroid dysfunction, including lithium, amiodarone, interferon alfa, interleukin-2 and tyrosine kinase inhibitors [15].
3.2.1 Hypothyroidism
Hypothyroidism is described as the thyroid gland’s inability to produce enough thyroid hormone to meet the body’s metabolic demands. Hypertension, dyslipidemia, cognitive impairment, infertility and neuromuscular dysfunction are associated with untreated hypothyroidism. Hypothyroidism is more prevalent in women than men and increases with age. Primary thyroid gland failure or insufficient gland stimulation by the hypothalamus or pituitary gland may lead to hypothyroidism. Primary gland failure can be resulted from congenital abnormalities, iodine deficiency, autoimmune destruction (Hashimoto disease) and infiltrative diseases. Iatrogenic hypothyroidism occurs after radioiodine therapy, thyroid surgery and neck irradiation. Disorders generally associated with transient hypothyroidism include postpartum thyroiditis, silent thyroiditis, subacute thyroiditis and thyroiditis associated with thyroid stimulating hormone (TSH) and receptor-blocking antibodies. Basic causes of hypothyroidism are generally found with other manifestations of hypothalamic or pituitary dysfunction, and, are characterized by decreased levels of TSH relative to inadequate thyroid hormone.
3.2.2 Hyperthyroidism
Hyperthyroidism is defined as “the excessive production and secretion of thyroid hormones from the thyroid gland” and is characterized by weight loss, tachycardia, palpitation, arrhythmia, tremor, nervousness, irritability, anxiety, heat intolerance, sweating, increased thirst and appetite, fatigue, hyperdefecation, diffused goiter, warm and moist skin and disturbances in menstrual cycle [14, 16]. Hyperthyroidism can be caused by graves’ disease, painless thyroiditis or postpartum thyroiditis, painful subacute thyroiditis, toxic multinodular goiter or toxic adenoma and exogenous thyroid hormone excess [3]. Menstrual disturbances are common in hyperthyroidism. Thyrotoxicosis may cause delay in sexual maturation and onset of menstrual cycle, oligomenorrhea, polymenorrhea and increased concentrations of sex hormone binding globulin (SHBG). Progesterone (P4) and follicle-stimulating hormone (FSH) significantly increase and, luteinizing hormone (LH) as well as estradiol (E2) significantly decrease in hyperthyroidism [17].
4. Ovary
Ovaries are the female pelvic reproductive organs that house the ova and are also responsible for the production of sex hormones. Ovaries are paired organs located on both sides of the uterus within the broad ligament beneath the uterine (fallopian) tubes. The ovary within the ovarian fossa is a space that is bound by the external iliac vessels, obliterated umbilical artery and the ureter. The ovaries house and release ova or eggs, needed for reproduction. A female has approximately 1–2 million eggs at the time of birth but only 300 of these eggs will become mature and released for fertilization [18].
4.1 Polycystic ovary syndrome (PCOS)
PCOS is the common endocrine disorder among females. It is estimated that 6–10% of women are affected by PCOS in reproductive years of their life. 1 out of 10 women experiences its symptoms in her fertile age. The multifaceted nature of PCOS makes it difficult to define. This clinically heterogenous endocrine syndrome is infertility to gynecologist, hirsutism to a dermatologist, menstrual irregularity to a physician and pseudo-Cushing’s disease to an internist. Considering all the the symptoms collectively, it can be defined by hyperandrogenism, oligomenorrhea and multiple cystic follicles in ovaries. Disturbed pulsatile release of GnRH leads to excessive LH, contributing to hyperandrogenism and polycystic morphology. Genetic and epigenetic reasons of these changes have also been investigated [19, 20].
4.2 Hypothalamic-pituitary-ovarian (HPO) axis
Reproductive activity is regulated by the hypothalamic-pituitary-ovarian (HPO) axis which secretes hormones necessary for reproduction. HPO is comprised of three main components. Hypothalamus is located at the base of the brain, just above the brainstem. Along with homeostasis, the hypothalamus also secretes certain hormones, including gonadotropin-releasing hormone (GnRH). Pituitary gland is located below the hypothalamus, in the base of the skull. This gland secretes a variety of hormones, including luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in response to GnRH. Ovaries are located in the woman’s pelvis, and secrete estrogen and progesterone [21].
5. PCOS and hypothalamic-pitutary-thyroid axis
HPO axis and HPT axis are physiologically related. Thyroid receptors in ovaries control female reproductive functions and estrogen affects HPT axis. This link designates subclinical hypothyroidism as a determinant of PCOS. The high prevalence of hypothyroidism among PCOS patients also indicates a strong relation. Thyroid levels are more frequently disturbed in PCOS patients and are more commonly associated with anovulation. Insulin resistance is also a common feature of both the diseases. Incidence of subclinical hypothyroidism among PCOS women augments insulin resistance and hyperandrogenism [22, 23].
6. Prevalence
The autoimmune thyroid disease (AITD) is found more prevalent in females with PCOS than the females without PCOS. Many systematic prospective studies were carried out to observe the levels of thyroglobulin (Tg) antibodies and thyroid peroxidase (TPO), distinctive for hashimoto thyroiditis (HT) in females with PCOS. It was observed that TPO and Tg levels were elevated in PCOS patients than the healthy females. Moreover, in thyroid ultrasound, hypoechoic pattern which is typical of Hashimoto thyroiditis (HT) was also found more prevalent in PCOS patients. Increased level of thyroid antibodies and hypoechoic thyroid ultrasound pattern revealed the prevalence of HT in PCOS patients and found to be increased by threefold when compared with controls [24, 25]. In Asia, recently cross-sectional studies, revealed higher prevalence of TPO-positive autoimmune thyroiditis with increased mean TSH levels, increased prevalence of goiter and frequently a hypoechoic thyroid ultrasound pattern in patients with PCOS aged between 13 and 45 years, than in control [1, 26, 27]. Recent meta-analysis included most of the studies, which confirmed higher prevalence of AITD, higher TSH levels and positive TPO and TG antibodies in PCOS patients than in controls [28].
The possibility of having Graves’ disease along with PCOS could be higher. In this regard, no broad epidemiological data was found as of recently with the exception of the case reports [1, 2, 29].
In girls of age 13–18 years with HT, a study showed highly significant prevalence of PCOS than in girls without HT, who were negative for TPO antibodies [30]. From the majority of studies, this can be concluded that HT and PCOS frequently occur together.
7. Etiology and pathogenesis
The etiology of HT is complicated and involves mainly genetic along with gender-associated and environmental factors like iodine supply, drugs, chemicals and infections [31]. Similarly, genetic, ovarian-related as well as other hormonal and metabolic factors such as hyperinsulinemia were supposed to involve in the etiology of PCOS [32].
Genetic susceptibility for HT has been confirmed by family and twin studies [33, 34]. Similarly, genetic susceptibility and familial aggregation were also found in PCOS patients [35, 36]. Various susceptibility genes have already been proposed for HT as well as PCOS [37, 38]. Although, a common genetic background still has not been established. Polymorphism of susceptibility genes in HT may influence the occurrence and characteristics of PCOS. Such possible connections will be discussed in more detail. Furthermore, HT is the most prevalent autoimmune disorder [37]. Possible role of autoimmune phenomena in the etiology of PCOS has been suggested [30, 39]. Therefore, supposed genetic and causal factors related to autoimmunity in both the disorders will be explained along with the role of polymorphism of susceptibility genes, alter growth factor beta (TGFβ), regulatory T cells (Tregs), the thymus and variations of sex hormones.
7.1 Susceptibility and candidate genes
In HT, family and twin studies recognized strong genetic susceptibility. The risk of developing HT is increased by 32 and 21 fold in children and siblings of patients with HT respectively, where females were more prone to be affected than males [33]. Various genes are said to be associated with the disease occurrence, progression and severity such as human leukocyte antigen (HLA-DR), cytotoxic T-lymphocyte-associated protein 4 (CTLA4), CD40, interleukin 2 receptor, protein tyrosine phosphatase 22 (PTPN22), alpha (IL2RA), vitamin D receptor (VDR) and thyroid-specific gene thyroglobulin (Tg) [31, 40, 41].
Familial clustering is well established in PCOS. An increased prevalence of PCOS has been documented in first-degree relatives of females with PCOS [38, 42, 43]. Several candidate genes have been studied for PCOS, such as those coding for fibrillin 3 (FBN3), insulin (INS), INS receptor substrate 1, transcription factor 7-like 2, calpain 10, the fat mass and obesity associated protein [44, 45], sex hormone binding globulin (SHBG) [38] and VDR [46]. Recently, in an Asian as well as European population, the DENND1A gene, which encodes a protein participating in the endosomal membrane transport, was recognized by genome-wide association studies (GWAS) as a true PCOS susceptibility gene [47, 48]. However, the found results of a large number of candidate gene studies were mostly inconclusive.
7.2 Genetic polymorphism
FBN3 gene polymorphisms may play a role in the etiology of PCOS and HT by influencing the activity of TGF, which is regulated by FBNs. The FBN3 gene, like FBN1 and FBN2, is likely to encode FBNs, which are microfibril networks in the extracellular matrix that provide binding opportunities for TGF sequestration [49, 50]. Polymorphisms in the FBN3 gene, which impact the activity of TGF, which is regulated by FBNs, may play a role in the etiology of PCOS and HT. FBN3 is likely to encode FBNs, which are a component of extracellular matrix microfibril networks that provide binding opportunities for TGF sequestration, similar to FBN1 and FBN2 [47, 50, 51, 52]. Activins, inhibins, and anti-Mullerian hormone, all members of the TGF superfamily, are thought to play a role in the etiology of PCOS. However, genome wide association studies (GWAS) have found no members of the TGF signaling pathway to be among the top signals for PCOS. Changes in TGF have been linked to the etiology of PCOS in terms of prenatal origins, metabolic abnormalities, and reproductive abnormalities [50]. FBN3 is abundant in fetal organs, including the ovaries [53, 54]. FBN3 expression in the stromal compartments of fetal ovaries disappears after the first trimester. As a result, FBN3 has an effect on the activity of TGF, which is involved in the regulation of stromal formation and function throughout fetal development, confirming notions about PCOS having a fetal origin [54]. Recent genetic studies have also reported that polymorphism of the FBN3 gene has been shown to be associated with the levels of TGFβ. Allele 8 (A8) of D19S884, a dinucleotide repeat polymorphism in intron 55 of the fibrillin-3 gene, is linked to polycystic ovary syndrome [55]. Similarly, in HT, lower levels of serum TGFβ1 were found when compared with healthy controls. Moreover, levels of serum TGFβ1 did not increase after treatment with levothyroxine (l-T4), indicating the interrelation between TGFβ1 and HT [56]. TGF stimulates the production of the transcription factor forkhead box P3 (FOXP3) and the creation of Tregs in the establishment of immunological tolerance, and it works as a fundamental regulator of immune tolerance by promoting suppressive Tregs and blocking T cell differentiation [31, 57].
As a result, TGF could play a role in the development of autoimmune diseases like HT. Given this context, it’s possible that PCOS women with allele 8 of the D19S884 gene in the FBN3 gene, and hence lower TGF1 levels, are more likely to develop HT than PCOS women without allele 8, but this has yet to be researched.
There has recently been evidence of a link between the three prime untranslated region (3′-UTR) mutation rs1038426 of the gonadotropin-releasing hormone receptor (GnRHR) and INS production in PCOS, as well as a link between serum TSH, serum INS levels, and INS sensitivity. This could point to a significant role for GnRHR genetic variants in INS secretion and INS resistance in PCOS, as well as a link to thyroid function [58].
Finally, the CYP1B1 gene, which codes for an enzyme that converts E2 to 4-hydroxyestradiol, is linked to PCOS. The CYP1B1 L432V (rs1056836) polymorphism was linked to serum thyroxine (T4), free T3 (fT3), and free T4 (fT4) levels [59]. This discovery could point to a third genetic relationship between thyroid function and PCOS.
7.3 Thymus
The importance of the thymus gland in immune system modulation and autoimmune development is well understood. Two processes permit the maintenance of self-tolerance and prevention of autoimmunity; the central immunological tolerance, which is enabled by the thymic deletion of autoreactive T cells during fetal development, and peripheral immune tolerance, in which Tregs play the key role [37, 60]. These cells are attained from the thymus as well as peripheral T cells. Tregs suppress the immune system and prevent an overabundance of immunological responses [61]. As previously established, lower TGF1 levels in the blood have been linked to HT [56].
In animal models, estrogen-induced immunological disruption has been demonstrated to play a role in the development of PCOS. Anovulation and follicular cysts were generated in female mice when estrogen was given before 10 days of age, when the thymus was in the latter stages of development [62]. The effect of estrogen on the thymus was investigated in estrogen-injected female mice with intact thymus, had follicular cysts in their ovaries; however, no cysts were found in mice who were thymectomized before estrogen injections and then reconstituted with adult thymocytes. Ovulation occurred and follicular cysts did not arise when estrogen was unable to exert influence upon the thymus during its development when adult thymic cells were given later. In addition, estrogen-injected animals with an intact thymus had a lower number of thymocytes than controls. The absence of Tregs due to an estrogen-affected thymus was thought to be a needed for the production of estrogen-induced cysts, supporting the autoimmune etiology of PCOS [63]. Similarly, the highest prevalence of infertility was seen in women prenatally exposed to diethylstilbestrol (DES), a strong synthetic estrogen that was given in the United States from 1940 to 1971, when they were exposed to DES from 9 to 12 gestational weeks [64]. This is also the period during which the thymus develops at its most rapidly [65]. A higher frequency of autoimmune disorders has been found in DES-exposed women [66]. Phytoestrogens, which are found in flax seeds and soy bean products, may expose modern pregnant women to higher doses of estrogen. In addition to estrogens, adrenal steroids like corticosterone have been demonstrated to reduce thymic weight and number, resulting in anovulation and the production of ovarian cysts in mice [67].
To summarize, different variables such as excessive estrogen levels or severe stress with increased adrenal hormones may be responsible for changes in the fetal thymus, resulting in changes in immunological tolerance and the occurrence of HT and PCOS in predisposed individuals in adulthood.
7.4 Sex hormones
The sex hormones play an important role as females are significantly more often affected by autoimmune disorders than males. Autoimmune disease autoimmune affects 5% of the world’s population and 78% of those affects women [68]. A doubled chromosome X and a low androgen-to-estrogen ratio were thought to play a role in the etiology of autoimmune disorders even in Klinefelter’s syndrome [69]. The onset of autoimmune disorders in women is earlier than in males, and it frequently correlates with elevated levels of the female hormone progesterone [68]. As a result, when comparing pre-pubertal children with chronic autoimmune thyroiditis to pubertal adolescents or adults, the female-to-male ratio was shown to be considerably lower in pre-pubertal children with chronic autoimmune thyroiditis [70]. Similarly, estrogen usage was linked negatively with the presence of TPO antibodies [71]. During the menstrual cycle, higher levels of estrogens during the follicular phase and lower levels of estrogens during menstruation and luteal phase, lead to a shift from Th1 to Th2 mediated immunity, respectively [72]. As a result, throughout the typical menstrual cycle, levels of the Th2 cytokine interleukin 6 (IL6) were adversely linked with progesterone levels in young women. IL6 levels were lowest during the luteal phase and highest during the follicular phase [73]. The activation of FOXP3 and the generation of Tregs was inhibited by IL6 [62]. On the other hand estrogens have been shown to promote Treg development [72].
As a result, it was observed that the number of Tregs decreases during the luteal phase and increases during the late follicular phase [74]. Pregnancy causes several changes in the immune system in order to tolerate the fetus, the most notable of which is a shift from Th1 to Th2 cytokine profile [75, 76]. This is most likely due to Treg expansion generated by estrogen, which suppresses both Th1 and Th2 immune responses, while the latter are less vulnerable to Tregs and thus prevail. After delivery, a decrease in Tregs alters the cytokine profile from Th2 to Th1, causing autoimmunity to exacerbate or worsen [76] A connection between the number of deliveries and the risk of AITD was found in a few retrospective studies [77, 78].
Sex hormones regulate in vitro and in vivo immune system [79]. Estrogens have been linked to a hyperactivity of T cells and a hypoactivity of B cells in animal studies [80]. The generation of autoantibodies was higher in female mice than in male mice [81]. Estrogens have been shown to decrease T suppressor cell function, enhance B cell activity, boost the release of the Th2 cytokine IL6, and shift the immune response to Th2 and antibody generation [38, 68]. In comparison to men, women have a greater CD4+/CD8+ ratio, higher CD4+ levels, and more antibodies [75]. Androgens suppress most immune system components, increase the activity of T suppressor cells, and increase the Th1 response and CD8+ cell activation [74, 82]. Progesterone inhibits macrophage growth, IL6 generation, and peripheral antibody production [82]. Oscillations in progesterone levels during pregnancy and the ovulatory cycle are thought to be linked to reversible immune system alterations [83].
Women with PCOS have lower progesterone and higher testosterone levels than women without PCOS [2]. Menstrual irregularity in women suffering from PCOS and several anovulatory cycles may have no or very low progesterone, resulting in an elevated estrogen-to-progesterone ratio for long duration. As a result, their vulnerability to autoimmune diseases may increases because of a stimulating effect of estrogens on the immune system [39, 49]. On the other hand, autoimmune disease could be prevented by androgens. However, their impact on the immune system and levels in PCOS are unlikely to be sufficient to avoid autoimmunity. As a result, an imbalance in progesterone, estrogen, and androgens may contribute to the development of HT. Taking this idea into account, as well as the three PCOS phenotypes that have been postulated [84], the increased prevalence of HT would be expected in women with PCOS and chronic anovulation as well as without hyperandrogenism, followed by classic PCOS with hyperandrogenism and anovulation, while the decreased incidence would be supposed to expect in ovulatory PCOS with hyperandrogenism. However, this hypothesis is yet to be confirmed.
8. Conclusions
Almost unanimously, prevalence studies report on a frequent joint appearance of PCOS and HT in women within the reproductive age. Therefore, the above discussion, may conclude that thyroid disorders and PCOS are undoubtedly associated with each other, with respect to their etiology, pathogenesis and clinical consequences. However, this chapter provides scientific ground to further investigate the connection between thyroid dysfunction and PCOS.
Conflict of interest
The authors declare no conflict of interest.
Acronyms and abbreviations
AITD
autoimmune thyroid disease
CTLA
cytotoxic T-lymphocyte-associated protein
E
estradiol
FBN
fibrillin
FSH
follicle stimulating hormone
GnRH
gonadotropin releasing hormone
GWAS
genome wide association studies
HPOA
hypothalamic-pituitary-ovarian axis
HPTA
hypothalamic-pituitary-thyroid axis
HT
Hashimoto’s thyroiditis
HLA
human leukocyte antigen
IL
interleukin
IL2RA
interleukin 2 receptor alpha
INS
insulin
LH
luteinizing hormone
PCOS
polycystic ovary syndrome
PTPN
protein tyrosine phosphate non-receptor
P
progesterone
SBGH
sex hormone binding globulin
Tg
thyroglobulin
TGFβ
growth factor beta
Th
T helper cell
TH
thyroid hormone
TPO
thyroid peroxidase
TRN
thyrotropin releasing hormone
Tregs
regulatory T cells
TSH
thyroid stimulating hormone
T3
triiodothyronine
T4
thyroxine
UTR
untranslated region
VDR
vitamin D receptor
\n',keywords:"thyroid dysfunction, hypothyroidism, hyperthyroidism, PCOS, HPTA",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/80385.pdf",chapterXML:"https://mts.intechopen.com/source/xml/80385.xml",downloadPdfUrl:"/chapter/pdf-download/80385",previewPdfUrl:"/chapter/pdf-preview/80385",totalDownloads:40,totalViews:0,totalCrossrefCites:0,dateSubmitted:"December 4th 2021",dateReviewed:"January 5th 2022",datePrePublished:"February 21st 2022",datePublished:null,dateFinished:"February 7th 2022",readingETA:"0",abstract:"As the prevalence of endocrine dysfunction is increasing and is associated with many complications including polycystic ovary syndrome (PCOS) which, itself is a risk factor of thyroid dysfunction. Although the causality of this association is uncertain, the two conditions share a bidirectional relationship. Both syndromes share certain common characteristics, risk factors and pathophysiological abnormalities, which can be managed by lifestyle changes as well as pharmacological treatment. Polycystic appearing ovaries are a clinical feature of hypothyroidism as well as hyperthyroidism in a few case studies. Adiposity, evidence of deranged autoimmunity, increased insulin resistance and disturbed leptin levels are present in both the disease states, seeming to play a complex role in connecting these two disorders. Major endocrine pathways including hypothalamic-pituitary-thyroid axis (HPTA) and HP-gonadal axis are involved in parallel relationship of PCOS and thyroid dysfunction. This chapter helps to explore all the dimensions of the relationship between PCOS and thyroid dysfunction.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/80385",risUrl:"/chapter/ris/80385",signatures:"Mariya Anwaar and Qaiser Jabeen",book:{id:"11085",type:"book",title:"Polycystic Ovary Syndrome",subtitle:null,fullTitle:"Polycystic Ovary Syndrome",slug:null,publishedDate:null,bookSignature:"Dr. Zhengchao Wang",coverURL:"https://cdn.intechopen.com/books/images_new/11085.jpg",licenceType:"CC BY 3.0",editedByType:null,isbn:"978-1-80355-382-5",printIsbn:"978-1-80355-381-8",pdfIsbn:"978-1-80355-383-2",isAvailableForWebshopOrdering:!0,editors:[{id:"204883",title:"Dr.",name:"Zhengchao",middleName:null,surname:"Wang",slug:"zhengchao-wang",fullName:"Zhengchao Wang"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:null,sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Endocrine system",level:"1"},{id:"sec_2_2",title:"2.1 Endocrine feedback system",level:"2"},{id:"sec_3_2",title:"2.2 Endocrine dysfunction",level:"2"},{id:"sec_5",title:"3. Thyroid gland",level:"1"},{id:"sec_5_2",title:"3.1 Hypothalamic-pituitary-thyroid (HPT) axis",level:"2"},{id:"sec_6_2",title:"3.2 Thyroid dysfunction",level:"2"},{id:"sec_6_3",title:"3.2.1 Hypothyroidism",level:"3"},{id:"sec_7_3",title:"3.2.2 Hyperthyroidism",level:"3"},{id:"sec_10",title:"4. Ovary",level:"1"},{id:"sec_10_2",title:"4.1 Polycystic ovary syndrome (PCOS)",level:"2"},{id:"sec_11_2",title:"4.2 Hypothalamic-pituitary-ovarian (HPO) axis",level:"2"},{id:"sec_13",title:"5. PCOS and hypothalamic-pitutary-thyroid axis",level:"1"},{id:"sec_14",title:"6. Prevalence",level:"1"},{id:"sec_15",title:"7. Etiology and pathogenesis",level:"1"},{id:"sec_15_2",title:"7.1 Susceptibility and candidate genes",level:"2"},{id:"sec_16_2",title:"7.2 Genetic polymorphism",level:"2"},{id:"sec_17_2",title:"7.3 Thymus",level:"2"},{id:"sec_18_2",title:"7.4 Sex hormones",level:"2"},{id:"sec_20",title:"8. Conclusions",level:"1"},{id:"sec_24",title:"Conflict of interest",level:"1"},{id:"sec_21",title:"Acronyms and abbreviations",level:"1"}],chapterReferences:[{id:"B1",body:'Sinha U et al. Thyroid disorders in polycystic ovarian syndrome subjects: A tertiary hospital based cross-sectional study from Eastern India. Indian Journal of Endocrinology and Metabolism. 2013;17(2):304-309'},{id:"B2",body:'Janssen OE et al. High prevalence of autoimmune thyroiditis in patients with polycystic ovary syndrome. European Journal of Endocrinology. 2004;150(3):363-369'},{id:"B3",body:'Anwaar M, Rasheed HMF, Jabeen Q. Insight into therapeutic role of plant-derived medicines in thyroid dysfunction. 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Increased occurrence of autoimmune disease among women exposed in utero to diethylstilbestrol. Fertility and Sterility. 1988;49(6):1080'},{id:"B67",body:'Chapman JC et al. The administration of cortisone to female B6A mice during their immune adaptive period causes anovulation and the formation of ovarian cysts. American Journal of Reproductive Immunology. 2002;48(3):184-189'},{id:"B68",body:'Quintero OL et al. Autoimmune disease and gender: Plausible mechanisms for the female predominance of autoimmunity. Journal of Autoimmunity. 2012;38(2):J109-J119'},{id:"B69",body:'Rovenský J. Rheumatic diseases and Klinefelter\'s syndrome. Autoimmunity Reviews. 2006;6(1):33-36'},{id:"B70",body:'Mariotti S et al. Puberty is associated with a marked increase of the female sex predominance in chronic autoimmune thyroiditis. Hormone Research in Pædiatrics. 2009;72(1):52-56'},{id:"B71",body:'Strieder TGA et al. Risk factors for and prevalence of thyroid disorders in a cross-sectional study among healthy female relatives of patients with autoimmune thyroid disease. Clinical Endocrinology. 2003;59(3):396-401'},{id:"B72",body:'Pennell LM, Galligan CL, Fish EN. Sex affects immunity. Journal of Autoimmunity. 2012;38(2):J282-J291'},{id:"B73",body:'Angstwurm MWA, Gärtner R, Ziegler-Heitbrock HWL. Cyclic plasma il-6 levels during normal menstrual cycle. Cytokine. 1997;9(5):370-374'},{id:"B74",body:'Arruvito L et al. Expansion of CD4+CD25+and FOXP3+ regulatory T cells during the follicular phase of the menstrual cycle: Implications for human reproduction. The Journal of Immunology. 2007;178(4):2572-2578'},{id:"B75",body:'Wegmann TG et al. Bidirectional cytokine interactions in the maternal-fetal relationship: Is successful pregnancy a TH2 phenomenon? Immunology Today. 1993;14(7):353-356'},{id:"B76",body:'Gaberšček S, Zaletel K. Thyroid physiology and autoimmunity in pregnancy and after delivery. Expert Review of Clinical Immunology. 2011;7(5):697-707'},{id:"B77",body:'Jørgensen KT et al. Childbirths and risk of female predominant and other autoimmune diseases in a population-based Danish cohort. Journal of Autoimmunity. 2012;38(2):J81-J87'},{id:"B78",body:'Friedrich N et al. Association between parity and autoimmune thyroiditis in a general female population. Autoimmunity. 2008;41(2):174-180'},{id:"B79",body:'Paavonen T. Hormonal Regulation of Immune Responses. Annals of Medicine. 1994;26(4):255-258'},{id:"B80",body:'Ahmed SA et al. Gender and risk of autoimmune diseases: Possible role of estrogenic compounds. Environmental Health Perspectives. 1999;107(Suppl. 5):681-686'},{id:"B81",body:'Törnwall J et al. Estrogen in autoimmunity: Expression of estrogen receptors in thymic and autoimmune T cells. The Journal of Gender Specific Medicine. 1999;2(5):33-40'},{id:"B82",body:'Seli E, Arici A. Sex steroids and the immune system. 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This is not only worrying for critical tasks such as those performed by surgical, or military robots but also for household robots such as vacuum cleaners or for teleconference robots compromise privacy and safety of their owners. What will happen if these robots are hacked? This study presents a survey on the cybersecurity attacks associated with service robots, and as a result, a taxonomy that classifies the risks faced by users when using service robots, distinguishing between security and safety threads, is presented. We also present the robot software development phase as one the most relevant ones for the security of robots.",book:{id:"6003",slug:"robotics-legal-ethical-and-socioeconomic-impacts",title:"Robotics",fullTitle:"Robotics - Legal, Ethical and Socioeconomic Impacts"},signatures:"Francisco J. Rodríguez Lera, Camino Fernández Llamas, Ángel\nManuel Guerrero and Vicente Matellán Olivera",authors:[{id:"124522",title:"Dr.",name:"Vicente",middleName:null,surname:"Matellan",slug:"vicente-matellan",fullName:"Vicente Matellan"},{id:"211294",title:"Prof.",name:"Camino",middleName:null,surname:"Fernández-Llamas",slug:"camino-fernandez-llamas",fullName:"Camino Fernández-Llamas"},{id:"211295",title:"MSc.",name:"Ángel Manuel",middleName:null,surname:"Guerrero-Higueras",slug:"angel-manuel-guerrero-higueras",fullName:"Ángel Manuel Guerrero-Higueras"},{id:"211296",title:"Dr.",name:"Francisco Javier",middleName:null,surname:"Rodríguez-Lera",slug:"francisco-javier-rodriguez-lera",fullName:"Francisco Javier Rodríguez-Lera"}]},{id:"53439",doi:"10.5772/65765",title:"Rethinking Autonomy and Consent in Healthcare Ethics",slug:"rethinking-autonomy-and-consent-in-healthcare-ethics",totalDownloads:2503,totalCrossrefCites:5,totalDimensionsCites:5,abstract:"In healthcare ethics, autonomy has arguably become the ‘principal principle’. As a principle that can be readily turned into a process, the giving of ‘informed consent’ by a patient has become the surrogate measure of whether medical interventions are ethically acceptable. While ‘informed consent’ processes in medical care are presumed to be robust, research confirms that most patients do not adequately understand the medical purpose, limitations or potential ethical implications of the many medical procedures to which they consent. In this chapter, we argue that the founding tenets of autonomy and informed consent which presume people to be detached autonomous individuals who act rationally from self‐interest does not authentically capture the essence of human ‘being’. Furthermore, such assumptions do not acknowledge the deeply relational and embedded reality of the human condition which inevitably shape decision making. We contend that within healthcare organisations, the current processes of operationalising informed consent predominantly serve legal and administrative needs, while unwittingly disempowering patients, and silencing key aspects of their experience of illness. Rather than rational self‐interest, we argue that vulnerability, interdependence and trust lie at the core of ethical decision making in healthcare. Re‐framing autonomy in a way that deliberately considers the unique moral frameworks, relationships, and cultures of individuals can provide a more ethically sensitive and respectful basis for decision making in healthcare. As interdependence is an integral consideration in decision making, it must be deliberately acknowledged and incorporated into healthcare practices. Embracing a narrative approach within a shared decision making framework allows the vulnerabilities, fears and aspirations of stakeholders to be heard, creating a more effective and authentic way to meet the ethical goal of respecting those who seek care.",book:{id:"5418",slug:"bioethics-medical-ethical-and-legal-perspectives",title:"Bioethics",fullTitle:"Bioethics - Medical, Ethical and Legal Perspectives"},signatures:"Eleanor Milligan and Jennifer Jones",authors:[{id:"187831",title:"Prof.",name:"Eleanor",middleName:null,surname:"Milligan",slug:"eleanor-milligan",fullName:"Eleanor Milligan"}]},{id:"52563",doi:"10.5772/65089",title:"Medical Ethics and Bedside Rationing in Low‐Income Countries: Challenges and Opportunities",slug:"medical-ethics-and-bedside-rationing-in-low-income-countries-challenges-and-opportunities",totalDownloads:2102,totalCrossrefCites:0,totalDimensionsCites:3,abstract:"There’s evidence that implementing the four medical ethics principles may be challenging especially in low income country contexts with extreme resource scarcity and limited capacity to facilitate deliberations on the different ethical dilemmas. These challenges can partly be explained by the social, economic, and political contexts in which the decisions are made, as well as the limited time, training and guidance to facilitate ethical decision making. Based on current literature, and using the example of bedside rationing; this chapter synthesizes the challenges clinicians face when operationalizing the four principle; identifying the opportunities to address them. We suggest that clinicians’ ability to implement the four principles are constrained by meso‐ and macro‐level decision making as well as their lack of training, explicit guidelines, and peer support. To ameliorate this situation, current efforts to strengthen the clinicians’ capacity to make ethical decisions should be complimented with developing of context relevant guidelines for ethical clinical decision making. The renewed global commitment to the sustainable development goals and universal healthcare coverage should be recognized as an opportunity to leverage resources and champion the integration of equity and justice as a core value in resource allocation at the bedside, meso-, macro- and global levels.",book:{id:"5418",slug:"bioethics-medical-ethical-and-legal-perspectives",title:"Bioethics",fullTitle:"Bioethics - Medical, Ethical and Legal Perspectives"},signatures:"Lydia Kapiriri",authors:[{id:"189068",title:"Associate Prof.",name:"Lydia",middleName:null,surname:"Kapiriri",slug:"lydia-kapiriri",fullName:"Lydia Kapiriri"}]},{id:"56170",doi:"10.5772/intechopen.69768",title:"Ethic Reflections about Service Robotics, from Human Protection to Enhancement: Case Study on Cultural Heritage",slug:"ethic-reflections-about-service-robotics-from-human-protection-to-enhancement-case-study-on-cultural",totalDownloads:1601,totalCrossrefCites:0,totalDimensionsCites:2,abstract:"In a vision of future implications of human‐robot interactions, it is vital to investigate how computer ethics and specifically roboethics could help to enhance human’s life. In this chapter, the role of design expertise will be emphasized by setting multiple disciplines into a constructive dialogue. The reflections will take into consideration different themes, such as acceptability and aesthetics, but above all the ability to generate value and meaning in different contexts. These contexts could find a description in the concept of human enhancement, connected through each other with the skills of the design research. The methodology of the design research will find applicability in the case study of Virgil, where a roboethic approach is contextualized into a cultural heritage field. In this field, it is shown how the ethical approach will bring a benefit to local communities, but at large to any social and cultural strategies involved in the stakeholders’ network.",book:{id:"6003",slug:"robotics-legal-ethical-and-socioeconomic-impacts",title:"Robotics",fullTitle:"Robotics - Legal, Ethical and Socioeconomic Impacts"},signatures:"Luca Giuliano, Maria Luce Lupetti, Sara Khan and Claudio Germak",authors:[{id:"203858",title:"Dr.",name:"Claudio",middleName:null,surname:"Germak",slug:"claudio-germak",fullName:"Claudio Germak"},{id:"203861",title:"Dr.",name:"Luca",middleName:null,surname:"Giuliano",slug:"luca-giuliano",fullName:"Luca Giuliano"},{id:"203862",title:"Dr.",name:"Maria Luce",middleName:null,surname:"Lupetti",slug:"maria-luce-lupetti",fullName:"Maria Luce Lupetti"},{id:"211018",title:"Dr.",name:"Sara",middleName:null,surname:"Khan",slug:"sara-khan",fullName:"Sara Khan"}]},{id:"52100",doi:"10.5772/64947",title:"Ethical Publications in Medical Research",slug:"ethical-publications-in-medical-research",totalDownloads:1868,totalCrossrefCites:2,totalDimensionsCites:2,abstract:"Ethics in medical sciences research may not always translate into ethical publications. Unfortunately due to lack of regulatory bodies, publication misconduct is now a global menace for the scientific community. Publication misconducts are not only restricted to research fraud or data manipulations alone but also seriously include plagiarism, duplicate publications especially on figures and tables, authorship disputes and conflict of interests. As global scientific research is expanding particularly in the field of health sciences hence possibilities of more rise of unethical practices from research to publications are very high, authors suggest a strong peer-reviewing system, use latest technological support, strong publication ethics policies, active monitoring, protection of whistle blowers and more liaisons between journals and research institutions or universities possibly to prevent publication misconduct effectively. This chapter discusses how medical publications might have abused various ethical norms not only while conducting research but also during the publication process. The review also discusses the possible preventive measures against unethical practices of research publications.",book:{id:"5418",slug:"bioethics-medical-ethical-and-legal-perspectives",title:"Bioethics",fullTitle:"Bioethics - Medical, Ethical and Legal Perspectives"},signatures:"Kusal K. Das and Mallanagoud S. Biradar",authors:[{id:"187859",title:"Prof.",name:"Kusal",middleName:"K.",surname:"Das",slug:"kusal-das",fullName:"Kusal Das"},{id:"188854",title:"Prof.",name:"M.S.",middleName:null,surname:"Biradar",slug:"m.s.-biradar",fullName:"M.S. Biradar"}]}],mostDownloadedChaptersLast30Days:[{id:"52101",title:"Ethical Issues in Organ Procurement and Transplantation",slug:"ethical-issues-in-organ-procurement-and-transplantation",totalDownloads:4749,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"The Ciba Foundation held the first international, interdisciplinary conference on ethical and legal issues in transplantation in March 1966. Many of the ethical issues discussed at that conference remain with us today. Organ procurement and transplantation have forced the medical community and society at large to ask such fundamental questions as when are we dead, how can death be declared so that any life‐support measures can be discontinued? Is it ethical to remove an organ or part of an organ from a living person? Since there is such a shortage of organ and people on transplant waiting lists die for lack of an organ, what types of incentives, if any, can be used to increase the organ supply? Transplant centers face additional ethical issues. How can a limited supply of organs be fairly allocated to a large number of patients on the waiting list? Are the methods of putting patients on the waiting list appropriate? Transplant centers are regulated by a variety of governmental organizations. These organizations may have performance criteria. Do these performance criteria lead transplant centers to modify which organs they will accept or which patients they will list? As long as a shortage of organs remains, these ethical issues are likely to persist.",book:{id:"5418",slug:"bioethics-medical-ethical-and-legal-perspectives",title:"Bioethics",fullTitle:"Bioethics - Medical, Ethical and Legal Perspectives"},signatures:"Richard J. Howard and Danielle L. Cornell",authors:[{id:"188201",title:"M.D.",name:"Richard",middleName:null,surname:"Howard",slug:"richard-howard",fullName:"Richard Howard"},{id:"194143",title:"Ms.",name:"Danielle",middleName:null,surname:"Cornell",slug:"danielle-cornell",fullName:"Danielle Cornell"}]},{id:"56170",title:"Ethic Reflections about Service Robotics, from Human Protection to Enhancement: Case Study on Cultural Heritage",slug:"ethic-reflections-about-service-robotics-from-human-protection-to-enhancement-case-study-on-cultural",totalDownloads:1603,totalCrossrefCites:0,totalDimensionsCites:2,abstract:"In a vision of future implications of human‐robot interactions, it is vital to investigate how computer ethics and specifically roboethics could help to enhance human’s life. In this chapter, the role of design expertise will be emphasized by setting multiple disciplines into a constructive dialogue. The reflections will take into consideration different themes, such as acceptability and aesthetics, but above all the ability to generate value and meaning in different contexts. These contexts could find a description in the concept of human enhancement, connected through each other with the skills of the design research. The methodology of the design research will find applicability in the case study of Virgil, where a roboethic approach is contextualized into a cultural heritage field. In this field, it is shown how the ethical approach will bring a benefit to local communities, but at large to any social and cultural strategies involved in the stakeholders’ network.",book:{id:"6003",slug:"robotics-legal-ethical-and-socioeconomic-impacts",title:"Robotics",fullTitle:"Robotics - Legal, Ethical and Socioeconomic Impacts"},signatures:"Luca Giuliano, Maria Luce Lupetti, Sara Khan and Claudio Germak",authors:[{id:"203858",title:"Dr.",name:"Claudio",middleName:null,surname:"Germak",slug:"claudio-germak",fullName:"Claudio Germak"},{id:"203861",title:"Dr.",name:"Luca",middleName:null,surname:"Giuliano",slug:"luca-giuliano",fullName:"Luca Giuliano"},{id:"203862",title:"Dr.",name:"Maria Luce",middleName:null,surname:"Lupetti",slug:"maria-luce-lupetti",fullName:"Maria Luce Lupetti"},{id:"211018",title:"Dr.",name:"Sara",middleName:null,surname:"Khan",slug:"sara-khan",fullName:"Sara Khan"}]},{id:"52100",title:"Ethical Publications in Medical Research",slug:"ethical-publications-in-medical-research",totalDownloads:1871,totalCrossrefCites:2,totalDimensionsCites:2,abstract:"Ethics in medical sciences research may not always translate into ethical publications. Unfortunately due to lack of regulatory bodies, publication misconduct is now a global menace for the scientific community. Publication misconducts are not only restricted to research fraud or data manipulations alone but also seriously include plagiarism, duplicate publications especially on figures and tables, authorship disputes and conflict of interests. As global scientific research is expanding particularly in the field of health sciences hence possibilities of more rise of unethical practices from research to publications are very high, authors suggest a strong peer-reviewing system, use latest technological support, strong publication ethics policies, active monitoring, protection of whistle blowers and more liaisons between journals and research institutions or universities possibly to prevent publication misconduct effectively. This chapter discusses how medical publications might have abused various ethical norms not only while conducting research but also during the publication process. The review also discusses the possible preventive measures against unethical practices of research publications.",book:{id:"5418",slug:"bioethics-medical-ethical-and-legal-perspectives",title:"Bioethics",fullTitle:"Bioethics - Medical, Ethical and Legal Perspectives"},signatures:"Kusal K. Das and Mallanagoud S. Biradar",authors:[{id:"187859",title:"Prof.",name:"Kusal",middleName:"K.",surname:"Das",slug:"kusal-das",fullName:"Kusal Das"},{id:"188854",title:"Prof.",name:"M.S.",middleName:null,surname:"Biradar",slug:"m.s.-biradar",fullName:"M.S. Biradar"}]},{id:"52301",title:"Pharmacy Ethics and the Spirit of Capitalism: A Review of the Literature",slug:"pharmacy-ethics-and-the-spirit-of-capitalism-a-review-of-the-literature",totalDownloads:2260,totalCrossrefCites:0,totalDimensionsCites:2,abstract:"This chapter explores the issue of the conflict (real or potential) between the ethical imperatives that should guide the pharmacist in the typical practicing of the profession (i.e. within a pharmacy) and the economic constraints derived from the business dimension of the pharmacy. Marrying service and business in a single profession, pharmacy is supposed to balance harmoniously its two sides, if not to subject business demands to the higher societal, ethical requirements. However, such a balancing exercise is rather like dancing on a rope, and ethics may be trumped by economics, a phenomenon deplored sometimes by pharmacy academics or hospital pharmacists, and by a part of community pharmacists as well. Economics may prevail over ethics in rough forms such as selling health risk products (as it was in the past for tobacco or alcohol) or in more elusive ones, such as longer work hours and shorter counselling times, promoting or dispensing needless or ineffective products (food supplements, cosmetics, etc.), silently refusing to provide or recommend lower cost generics, etc. Ethical research in the field of pharmacy has generally been scarce, and numerous knowledge gaps remain to be filled by future investigations.",book:{id:"5418",slug:"bioethics-medical-ethical-and-legal-perspectives",title:"Bioethics",fullTitle:"Bioethics - Medical, Ethical and Legal Perspectives"},signatures:"Robert Ancuceanu and Ioana-Laura Bogdan",authors:[{id:"189717",title:"Associate Prof.",name:"Robert",middleName:null,surname:"Ancuceanu",slug:"robert-ancuceanu",fullName:"Robert Ancuceanu"}]},{id:"53299",title:"‘Assisted Dying’: A View of the Legal, Social, Ethical and Clinical Perspectives",slug:"-assisted-dying-a-view-of-the-legal-social-ethical-and-clinical-perspectives",totalDownloads:1672,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Discussion of legislation of physician-assisted suicide and euthanasia, often euphemistically called ‘assisted dying’, frequently focuses on individual cases promoted by campaigners as the reason that the law to licence doctors to supply lethal drugs to patients requesting them should change under certain conditions. But such legislation has wider consequences that simply for a handful of cases, as the relentlessly increasing numbers of such deaths have shown.",book:{id:"5418",slug:"bioethics-medical-ethical-and-legal-perspectives",title:"Bioethics",fullTitle:"Bioethics - Medical, Ethical and Legal Perspectives"},signatures:"Ilora Gillian Finlay of Llandaff",authors:[{id:"191502",title:"Prof.",name:"Ilora Gillian",middleName:null,surname:"Finlay of Llandaff",slug:"ilora-gillian-finlay-of-llandaff",fullName:"Ilora Gillian Finlay of Llandaff"}]}],onlineFirstChaptersFilter:{topicId:"267",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:87,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:98,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:27,numberOfPublishedChapters:287,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:139,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:0,numberOfUpcomingTopics:2,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!1},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:10,numberOfPublishedChapters:103,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:12,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:0,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!1},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:10,numberOfOpenTopics:4,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}}]},series:{item:{id:"11",title:"Biochemistry",doi:"10.5772/intechopen.72877",issn:"2632-0983",scope:"Biochemistry, the study of chemical transformations occurring within living organisms, impacts all areas of life sciences, from molecular crystallography and genetics to ecology, medicine, and population biology. Biochemistry examines macromolecules - proteins, nucleic acids, carbohydrates, and lipids – and their building blocks, structures, functions, and interactions. Much of biochemistry is devoted to enzymes, proteins that catalyze chemical reactions, enzyme structures, mechanisms of action and their roles within cells. Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. 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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"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:3,paginationItems:[{id:"7",title:"Bioinformatics and Medical Informatics",coverUrl:"https://cdn.intechopen.com/series_topics/covers/7.jpg",isOpenForSubmission:!0,editor:{id:"351533",title:"Dr.",name:"Slawomir",middleName:null,surname:"Wilczynski",slug:"slawomir-wilczynski",fullName:"Slawomir Wilczynski",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035U1loQAC/Profile_Picture_1630074514792",biography:"Professor Sławomir Wilczyński, Head of the Chair of Department of Basic Biomedical Sciences, Faculty of Pharmaceutical Sciences, Medical University of Silesia in Katowice, Poland. His research interests are focused on modern imaging methods used in medicine and pharmacy, including in particular hyperspectral imaging, dynamic thermovision analysis, high-resolution ultrasound, as well as other techniques such as EPR, NMR and hemispheric directional reflectance. Author of over 100 scientific works, patents and industrial designs. Expert of the Polish National Center for Research and Development, Member of the Investment Committee in the Bridge Alfa NCBiR program, expert of the Polish Ministry of Funds and Regional Policy, Polish Medical Research Agency. Editor-in-chief of the journal in the field of aesthetic medicine and dermatology - Aesthetica.",institutionString:null,institution:{name:"Medical University of Silesia",institutionURL:null,country:{name:"Poland"}}},editorTwo:null,editorThree:null},{id:"8",title:"Bioinspired Technology and Biomechanics",coverUrl:"https://cdn.intechopen.com/series_topics/covers/8.jpg",isOpenForSubmission:!0,editor:{id:"144937",title:"Prof.",name:"Adriano",middleName:"De Oliveira",surname:"Andrade",slug:"adriano-andrade",fullName:"Adriano Andrade",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRC8QQAW/Profile_Picture_1625219101815",biography:"Dr. Adriano de Oliveira Andrade graduated in Electrical Engineering at the Federal University of Goiás (Brazil) in 1997. He received his MSc and PhD in Biomedical Engineering respectively from the Federal University of Uberlândia (UFU, Brazil) in 2000 and from the University of Reading (UK) in 2005. He completed a one-year Post-Doctoral Fellowship awarded by the DFAIT (Foreign Affairs and International Trade Canada) at the Institute of Biomedical Engineering of the University of New Brunswick (Canada) in 2010. Currently, he is Professor in the Faculty of Electrical Engineering (UFU). He has authored and co-authored more than 200 peer-reviewed publications in Biomedical Engineering. He has been a researcher of The National Council for Scientific and Technological Development (CNPq-Brazil) since 2009. He has served as an ad-hoc consultant for CNPq, CAPES (Coordination for the Improvement of Higher Education Personnel), FINEP (Brazilian Innovation Agency), and other funding bodies on several occasions. He was the Secretary of the Brazilian Society of Biomedical Engineering (SBEB) from 2015 to 2016, President of SBEB (2017-2018) and Vice-President of SBEB (2019-2020). He was the head of the undergraduate program in Biomedical Engineering of the Federal University of Uberlândia (2015 - June/2019) and the head of the Centre for Innovation and Technology Assessment in Health (NIATS/UFU) since 2010. He is the head of the Postgraduate Program in Biomedical Engineering (UFU, July/2019 - to date). He was the secretary of the Parkinson's Disease Association of Uberlândia (2018-2019). Dr. Andrade's primary area of research is focused towards getting information from the neuromuscular system to understand its strategies of organization, adaptation and controlling in the context of motor neuron diseases. His research interests include Biomedical Signal Processing and Modelling, Assistive Technology, Rehabilitation Engineering, Neuroengineering and Parkinson's Disease.",institutionString:null,institution:{name:"Federal University of Uberlândia",institutionURL:null,country:{name:"Brazil"}}},editorTwo:null,editorThree:null},{id:"9",title:"Biotechnology - Biosensors, Biomaterials and Tissue Engineering",coverUrl:"https://cdn.intechopen.com/series_topics/covers/9.jpg",isOpenForSubmission:!0,editor:{id:"126286",title:"Dr.",name:"Luis",middleName:"Jesús",surname:"Villarreal-Gómez",slug:"luis-villarreal-gomez",fullName:"Luis Villarreal-Gómez",profilePictureURL:"https://mts.intechopen.com/storage/users/126286/images/system/126286.jpg",biography:"Dr. Luis Villarreal is a research professor from the Facultad de Ciencias de la Ingeniería y Tecnología, Universidad Autónoma de Baja California, Tijuana, Baja California, México. Dr. Villarreal is the editor in chief and founder of the Revista de Ciencias Tecnológicas (RECIT) (https://recit.uabc.mx/) and is a member of several editorial and reviewer boards for numerous international journals. He has published more than thirty international papers and reviewed more than ninety-two manuscripts. His research interests include biomaterials, nanomaterials, bioengineering, biosensors, drug delivery systems, and tissue engineering.",institutionString:null,institution:{name:"Autonomous University of Baja California",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null}]},overviewPageOFChapters:{paginationCount:17,paginationItems:[{id:"81751",title:"NanoBioSensors: From Electrochemical Sensors Improvement to Theranostic Applications",doi:"10.5772/intechopen.102552",signatures:"Anielle C.A. Silva, Eliete A. Alvin, Lais S. de Jesus, Caio C.L. de França, Marílya P.G. da Silva, Samaysa L. Lins, Diógenes Meneses, Marcela R. Lemes, Rhanoica O. Guerra, Marcos V. da Silva, Carlo J.F. de Oliveira, Virmondes Rodrigues Junior, Renata M. Etchebehere, Fabiane C. de Abreu, Bruno G. Lucca, Sanívia A.L. Pereira, Rodrigo C. Rosa and Noelio O. 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For 20 years, he has studied the analysis and processing of biomedical images, emphasizing the full automation of measurement for a large inter-individual variability of patients. Dr. Koprowski has authored more than a hundred research papers with dozens in impact factor (IF) journals and has authored or co-authored six books. Additionally, he is the author of several national and international patents in the field of biomedical devices and imaging. Since 2011, he has been a reviewer of grants and projects (including EU projects) in biomedical engineering.",institutionString:null,institution:{name:"University of Silesia",institutionURL:null,country:{name:"Poland"}}}]},{type:"book",id:"7218",title:"OCT",subtitle:"Applications in Ophthalmology",coverURL:"https://cdn.intechopen.com/books/images_new/7218.jpg",slug:"oct-applications-in-ophthalmology",publishedDate:"September 19th 2018",editedByType:"Edited by",bookSignature:"Michele Lanza",hash:"e3a3430cdfd6999caccac933e4613885",volumeInSeries:2,fullTitle:"OCT - Applications in Ophthalmology",editors:[{id:"240088",title:"Prof.",name:"Michele",middleName:null,surname:"Lanza",slug:"michele-lanza",fullName:"Michele Lanza",profilePictureURL:"https://mts.intechopen.com/storage/users/240088/images/system/240088.png",biography:"Michele Lanza is Associate Professor of Ophthalmology at Università della Campania, Luigi Vanvitelli, Napoli, Italy. His fields of interest are anterior segment disease, keratoconus, glaucoma, corneal dystrophies, and cataracts. His research topics include\nintraocular lens power calculation, eye modification induced by refractive surgery, glaucoma progression, and validation of new diagnostic devices in ophthalmology. \nHe has published more than 100 papers in international and Italian scientific journals, more than 60 in journals with impact factors, and chapters in international and Italian books. He has also edited two international books and authored more than 150 communications or posters for the most important international and Italian ophthalmology conferences.",institutionString:'University of Campania "Luigi Vanvitelli"',institution:{name:'University of Campania "Luigi Vanvitelli"',institutionURL:null,country:{name:"Italy"}}}]},{type:"book",id:"7560",title:"Non-Invasive Diagnostic Methods",subtitle:"Image Processing",coverURL:"https://cdn.intechopen.com/books/images_new/7560.jpg",slug:"non-invasive-diagnostic-methods-image-processing",publishedDate:"December 19th 2018",editedByType:"Edited by",bookSignature:"Mariusz Marzec and Robert Koprowski",hash:"d92fd8cf5a90a47f2b8a310837a5600e",volumeInSeries:3,fullTitle:"Non-Invasive Diagnostic Methods - Image Processing",editors:[{id:"253468",title:"Dr.",name:"Mariusz",middleName:null,surname:"Marzec",slug:"mariusz-marzec",fullName:"Mariusz Marzec",profilePictureURL:"https://mts.intechopen.com/storage/users/253468/images/system/253468.png",biography:"An assistant professor at Department of Biomedical Computer Systems, at Institute of Computer Science, Silesian University in Katowice. Scientific interests: computer analysis and processing of images, biomedical images, databases and programming languages. 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