Parameters employed for the CDHA synthesis.
\r\n\t
",isbn:"978-1-83969-558-2",printIsbn:"978-1-83969-557-5",pdfIsbn:"978-1-83969-559-9",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,hash:"97b6de623f15598880112f6bafedc3e1",bookSignature:"Dr. Robert M.X. Wu",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11916.jpg",keywords:"Business Models, E-commerce Marketing Strategy, E-commerce Business Models, Digital Transformation, Business Intelligence, E-business Applications, Research, Information System Management, Marketing Management, Electronic Commerce, Internet Marketing, Information Systems",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"April 26th 2022",dateEndSecondStepPublish:"May 24th 2022",dateEndThirdStepPublish:"July 23rd 2022",dateEndFourthStepPublish:"October 11th 2022",dateEndFifthStepPublish:"December 10th 2022",remainingDaysToSecondStep:"4 hours",secondStepPassed:!1,currentStepOfPublishingProcess:2,editedByType:null,kuFlag:!1,biosketch:'Dr. Wu holds a Ph.D. in e-Commerce, lectures at the School of Engineering and Technology in Australia, and is a Distinguished Professor at Shanxi Normal University, China. In 2011, Dr. Wu was recognized as a ‘Top 100 Outstanding Academic Leader for China’s Informatics’ by the China Informatics Society. He was awarded "Outstanding Contribution in Reviewing" by Q1 Journals such as Electronic Commerce Research and Applications (Elsevier).',coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"190913",title:"Dr.",name:"Robert M.X.",middleName:null,surname:"Wu",slug:"robert-m.x.-wu",fullName:"Robert M.X. Wu",profilePictureURL:"https://mts.intechopen.com/storage/users/190913/images/system/190913.jpg",biography:"Robert M.X. Wu has a diploma in Computer Science, a bachelor’s degree in Economics, and master’s and doctorate degrees in e-Commerce. He is currently lecturing e-commerce / Information Systems at Central Queensland University Australia (CQU). He has led more than ten industry-based research projects since 2012 and contributes to reviewing five A-level Australian Business Deans Council (ABDC) journals and Q1 journals.\r\nIn July 2011, Dr. Wu was recognized as a ‘Top 100 Outstanding Academic Leader for China’s Informatics’ by the China Informatics Society. In 2017 he was appointed Distinguished Professor at Shanxi Normal University, China. 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It is well known that the characteristics of the synthesis methodology have great influence on the structure, morphology, and chemical composition, as well on the mechanical, thermal, and optical properties of the resultant product. Particularly in the sol-gel synthesis of hydroxyapatite (at normal temperature and pressure conditions), the evolution of the values of the pH during the synthesis strongly affects the final structure and stoichiometry, frequently by promoting the presence of calcium vacancies, crystalline defects, and impurities in the hydroxyapatite structure, modifying the physical-chemical properties of it. While for some applications (e.g., bone replacement and development of bioactive coatings), the presence of high levels of calcium and oxygen deficiencies are undesirable, for other applications such as development luminescent probes and photocatalysts, it are well received and even propitiated [4, 5]. In the year 2006, Degirmenbasi et al. [6] reported a simple sol–gel methodology to obtain stoichiometric hydroxyapatite, by adding drop-by-drop calcium nitrite aqueous solution to sodium phosphate aqueous solution, under mechanical stirring and adjusting the pH at 10, adding sodium hydroxide to the mixture, as needed. Modifying the Degirmenbasi methodology by using a specific amount of sodium hydroxide for the synthesis, Jiménez-Flores et al. [7] reported significant differences in the crystallite size and crystalline fraction, morphology, and thermal properties between samples of calcium-deficient hydroxyapatite, synthesized by using different drip rates and stirring methods (in this case, mechanical and ultrasonic-assisted). In the aforementioned work [7], the observed differences between the synthesized samples were related to an increase in the internal energy during the synthesis—due to the different drip rates and the stirring methods. However, it is also possible that the different drip rates have caused fluctuations in the pH values, affecting the kinetics and the efficiency of the chemical reaction. To clarify the effect of the drip rate in the synthesis of hydroxyapatite, we propose to monitor the evolution of pH during the sol–gel synthesis, comparing the structural, physical, and chemical characteristics of the samples synthesized under different drip rates.
\nFor the sol-gel synthesis of calcium-deficient hydroxyapatite (CDHA), 80 ml of tetra hydrated calcium nitrate (Ca(NO3)2∙4H2O), 48 ml of sodium phosphate (Na3PO4), and 16 ml of sodium hydroxide (NaOH) aqueous solutions, at 0.1 M, were prepared at room temperature (25°C). All the chemical compounds were purchased from Sigma-Aldrich.
\nThe NaOH aqueous solution was incorporated to the Ca(NO3)2∙4H2O solution and stirred during 30 min to obtain a heterogeneous mixture, as the calcium source. This mixture was then added, drop-by-drop, to the aqueous solution of Na3PO4 under continuous stirring at 25°C. During this first stage of the synthesis (Figure 1, framed inset), the condensation and gelation of the sol particles take place. To eliminate the solvent (DI water, in this case), the obtained gel is filtered and dried, resulting into a xerogel with the appearance of small brittle glasses. Finally, such glasses were mechanically pulverized obtaining powdered samples of the synthesized compounds. In Figure 1, a schematic draw of the CDHA synthesis is shown.
\nSchematic draw of the sol–gel CDHA synthesis.
For the purposes of the present work, four different drip rates were used for the CDHA synthesis (see Table 1), considering that 20 drops are equivalent to 1 ml.
\nSample | \nStirring velocity (rpm) | \nDrip rate (μl∙s−1) | \nDrying conditions | \n
---|---|---|---|
CDHA_A | \n600 | \n≈5 | \n24 h at 80°C | \n
CDHA_B | \n≈8 | \n||
CDHA_C | \n≈10 | \n||
CDHA_D | \n≈17 | \n
Parameters employed for the CDHA synthesis.
For each sample, the evolution of the pH during the first stage of the synthesis was followed, making a comparison between the samples during the incorporation of the first 63 ml of the calcium source into the Na3PO4 solution. The results are presented in Figure 2.
\nEvolution of the pH during the synthesis of the (a) CDHA_A, (b) CDHA_B, (c) CDHA_C, and CDHA_D samples. The red line represents the best linear fit.
In all cases, the pH values decrease monotonically in time as it was expected; however, the samples exhibit different distinctive features. The shape of drip time vs. pH plots of CDHA_A and CDHA_C samples is quite similar, showing a linear region at the drip beginning (Figure 2(a) and (c)), where the pH decreases at rates of 52.2 × 10−6 and 80.8 × 10−6 s−1, respectively. After the linear region, the pH values fall down rapidly changing its concavity, approximately at 2/3 of the drip time for both samples.
\nOn the other hand, the pH values during the synthesis of the CDHA_B sample show a larger linear region than the CDHA_A and CDHA_C samples (Figure 2(b)), with a slope of 116.2 × 10−6 s−1; nevertheless, a small concavity change occurs just at the end of the drip time. Contrary to the previous samples, the drip time vs. pH plot of CDHA_D sample (Figure 2(d)) shows that the pH values decrease at a constant rate of 126.3 × 10−6 s−1. Finally, it is not worthless to mention that the final pH values (i.e., at the very end of the synthesis of each sample) were 10.04, 11.6, 11.7, and 11.86 for CDHA_A, CDHA_B, CDHA_C, and CDHA_D samples, respectively. This is an important issue to remark, since other authors report that the best conditions for the sol-gel synthesis of stoichiometric hydroxyapatite consider a pH = 10 [6, 8].
\nBy using an X-ray diffractometer (Bruker, D-8 Advance), which employs the Cu-K line (
X-ray diffraction patterns of (a) CDHA_A, (b) CDHA_B, (c) CDHA_C, and (d) CDHA_D samples.
The X-ray diffraction patterns agree well (with figure of merit up to 0.9, in all cases) with the ICDD crystallographic chart no. 00–009-0432 (from the International Centre for Diffraction Data database), corresponding to the synthetic hydroxyapatite—with chemical formula, Ca5(PO4)3(OH). For the analysis of the diffraction patterns, the principal observed diffraction peaks were considered to calculate the average crystallite size
In Eq. (2), a hexagonal 6/m-dipyramidal crystal symmetry was considered: being
Sample | \nΔ | \nΔ | \n|||
---|---|---|---|---|---|
CDHA_A | \n268.3 | \n9.412 | \n0.04 | \n6.877 | \n−0.04 | \n
CDHA_B | \n271.7 | \n9.418 | \n−0.01 | \n6.877 | \n−0.04 | \n
CDHA_C | \n275.3 | \n9.416 | \n0.01 | \n6.875 | \n−0.01 | \n
CDHA_D | \n303.3 | \n9.419 | \n−0.03 | \n6.873 | \n0.02 | \n
Average crystallite size and unitary cell parameters.
Although no significant differences were found in the values of the parameters of the unitary cell, a monotonic increase in the crystallite size is observed, as function of the drip rate. The surface morphology of the samples was studied through their corresponding micrographs, taken by a scanning electron microscope, SEM (JEOL, JSM-6390LV), employing an accelerating voltage of 20 kV and a magnification of 20,000× (see Figure 4).
\nSEM micrographs of samples: (a) CDHA_A, (b) CDHA_B, (c) CDHA_C, and (d) CDHA_D.
The SEM images show that increasing the drip rate has a discernible effect on the surface morphology of the glasses, previously to the mechanical powdering of them. The sample CDHA_A shows the most irregular surface of all (Figure 4(a)), small pores being discernible on it, while the sample CDHA_B presents a much more planar surface (Figure 4(b)) with (in appearance) larger pores on it. On the other hand, sample CDHA_C shows a less planar but smoother surface (Figure 4(c)) and, at least in appearance, a homogenous distribution of small pores on the surface. The case of CDHA_D presents a compact and granulated surface (Figure 4(d)), but still small pores are perceived.
\nIn order to determine the textural properties of the synthesized samples, the adsorption isotherms for 100 mg of powdered samples were obtained (see Figure 5) employing a Quantachrome NOVA4200e equipment, using N2 as adsorbate. The measurement temperature was kept at −196°C, using liquid nitrogen as coolant.
\nAdsorption isotherms of (a) CDHA_A, (b) CDHA_B, (c) CDHA_C, and (d) CDHA_D samples.
From the adsorption isotherms, the specific surface area was determined by the Brunauer-Emmet-Teller (BET) method, while the Barrett-Joyner-Halenda (BJH) method was for the determination of the pore size diameter [10, 11]. The textural properties of the samples have been summarized in Table 3. From their shape, the isotherms shown in Figure 5 can be classified as type V isotherm, which indicates unrestricted multilayer adsorption, characteristic of mesoporous materials. The shape of the hysteresis loops is indicative of ink-bottle-shaped pores, associated to poor network connectivity effects [12].
\nSample | \nSpecific surface area (m2∙g−1) | \nPore size diameter (Å) | \nTotal pore volume (cm3∙g−1) | \n
---|---|---|---|
CDHA_A | \n101.860 | \n203.2 | \n0.434 | \n
CDHA_B | \n91.856 | \n212.9 | \n0.464 | \n
CDHA_C | \n96.178 | \n181.9 | \n0.405 | \n
CDHA_D | \n92.403 | \n117.2 | \n0.391 | \n
Textural properties of the studied samples.
The textural properties agrees well with the SEM observations, correcting the initial visual impression on the pore size on the surface of the samples. With the exception of the CDHA_A sample, the pore radius size, as well as the total pore volume, decreases with increasing drip rate.
\nThe elemental chemical composition was determined using an energy-dispersive X-ray spectroscopy (EDS) system, integrated to the SEM equipment, which employs a Si-Li detector (Oxford Pentafet, mod. 7582). From the EDS spectra recorded for energies ranging 0.12–12 keV, the elemental quantification, as well as the Ca/P and the (Ca + O)/P ratios, has been determined and summarized in Table 4.
\nSample | \nNa (at.%) | \nC (at.%) | \nO (at.%) | \nP (at.%) | \nCa (at.%) | \nCa/P | \n(Ca + O)/P | \n
---|---|---|---|---|---|---|---|
CDHA_A | \n— | \n9.78 | \n54.58 | \n13.87 | \n21.77 | \n1.57 | \n5.50 | \n
CDHA_B | \n— | \n7.40 | \n56.91 | \n14.56 | \n21.13 | \n1.45 | \n5.36 | \n
CDHA_C | \n— | \n6.53 | \n57.69 | \n14.79 | \n20.99 | \n1.42 | \n5.32 | \n
CDHA_D | \n0.21 | \n8.59 | \n57.32 | \n14.42 | \n19.46 | \n1.35 | \n5.32 | \n
Quantification of the elemental chemical composition of the samples.
The results of the elemental quantification by EDS, together with the pH behavior during the synthesis, are indicative that the mass flow (controlled through the drip rate) significantly affects the reaction kinetics during the formation of hydroxyapatite, influencing the efficiency of ion exchange, promoting calcium and oxygen vacancies. The values of carbon content in the samples are consistent with the observed surface morphology and textural properties at different drip rates, suggesting the hypothesis that the presence of carbon in the samples could be due to the absorption of atmospheric CO2.
\nFor the identification of the functional groups present in samples, the diffuse reflectance spectra were obtained using a FTIR spectrophotometer (Shimadzu, IR Affinity-1S), operating in the attenuated total reflection mode, and the spectroscopic wave number ranging 4000 cm−1 ≤ k ≤ 650 cm−1. At next (Figure 6), the FTIR spectra are displayed identifying the detected signals.
\nFTIR spectra of samples: (a) CDHA_A, (b) CDHA_B, (c) CDHA_C, and (d) CDHA_D.
The signals centered at 958 and 1018 cm−1 are typical of asymmetric stretching of P─O bond of the PO4−3 functional group, while the signal at 875 cm−1 corresponds also to the P─O asymmetric stretch but for the HPO4−2 functional group. The signals in the neighborhood of 1408 and 1460 cm−1 correspond to stretching of the C─O bond, proper of the inorganic carbonate group. Finally, the signals at 2121 and 1988 cm−1 are related to the symmetrical stretching of the H─P bond in the HPO4−2 functional group. These results agree with the EDS elemental quantification and the X-ray diffraction patterns, confirming the formation of calcium-deficient hydroxyapatite. In addition, the presence of carbonate signals supports the hypothesis that the carbon content is due to the atmospheric CO2 absorbed during the synthesis.
\nTo investigate on the optical properties of the CDHA samples (particularly the optical band gap), two experimental techniques were employed here: the UV–Vis spectroscopy and the photoacoustic spectroscopy (PAS) techniques. The UV–Vis technique provides the diffuse reflectance, characterized by the Kubelka-Munk function F(R), as function of the wavelength (equivalent to the photon energy) of the excitation beam. Since the F(R) function depends linearly on the ratio between the optical absorption and the scattering coefficients, an empirical estimation of the band gap,
A UV–Vis spectrophotometer (Agilent, mod. Cary-100) was employed to measure the F(R) spectrum of the synthesized samples, ranging the wavelength from 200 nm ≤
Tauc plots of (a) CDHA_A, (b) CDHA_B, (c) CDHA_C, and (d) CDHA_D samples. The red line shows the extrapolation of the linear region.
To record the absorption spectra of the samples, a homemade PAS measurement system was used for such goal, for a wavelength ranging 206 nm ≤
PAS measurement system. Here,
The continuous beam, emitted by the 200 W Hg Arc lamp (Newport, Mod. 66,483) optimized for UV, passes through a monochromator (Newport, mod. Cornerstone 130 1/8 m) to obtain a quasi-monochromatic excitation beam. The continuous excitation beam was then modulated by a mechanical chopper (Stanford Research Systems, mod. SR-540), impinging into the optical window of the PAS measurement cell (MTEC, mod. 300). The PAS signal (
Tauc plots of (a) CDHA_A, (b) CDHA_B, (c) CDHA_C, and (d) CDHA_D samples. The red line shows the extrapolation of the linear region.
The optical band gap calculations, from UV–Vis and PAS measurements, are reported in Table 5, for purposes of comparison between techniques.
\nSample | \nΔ | \n||
---|---|---|---|
CDHA_A | \n5.26 | \n5.1 | \n3.14 | \n
CDHA_B | \n5.31 | \n5.18 | \n2.51 | \n
CDHA_C | \n5.33 | \n5.29 | \n0.76 | \n
CDHA_D | \n5.21 | \n5.12 | \n1.76 | \n
Optical band gap values determined from UV–Vis and PAS measurements.
From UV-Vis.
From PAS.
As can be seen from the above results, as the drip rate gets higher, the energy band gap also increases, with the one exception of the CDHA_D, and as it was expected, there is an overestimation on the optical band gap calculations from UV–Vis data. Nevertheless, in both cases (and for all samples) the empirical determination of
For the determination of the thermal response of the samples, a homemade photoacoustic detection (PA) measurement system was employed, for a modulation frequency ranging 400 Hz ≤
PA measurement system. Here,
The excitation beam wavelength was chosen to avoid the contribution of the photogenerated charge carriers to the PA signal. To perform the PA measurements in the transmission configuration [21, 22], pills of powdered samples were obtained by compacting 100 mg of powdered sample. Considering the samples as optically opaque and thermally thick, the PA signal will depend on the modulation frequency as indicated by Eq. (3):
\nIn Eq. (3),
Sample | \nSlope (mV∙s−1/2) | \nαs (× 10−7 m2∙s−1) | \n|
---|---|---|---|
CDHA_A | \n−5.75 | \n30.29 | \n1.90 | \n
CDHA_B | \n−7.78 | \n16.53 | \n1.02 | \n
CDHA_C | \n−6.75 | \n21.93 | \n2.42 | \n
CDHA_D | \n−6.49 | \n23.73 | \n2.58 | \n
Thermal diffusivity of the samples.
Although the values of the thermal diffusivities agree with the reported values for hydroxyapatite [7, 23, 24], there is no clear correlation with the synthesis drip rate nor the stoichiometry of the samples. This is because the different levels of compaction of the sample’s pills affect the effective thermal properties. The nonlinear behavior at low modulation frequencies is indicative of a transition between thermal regimes. For larger modulations frequencies, the signal-to-noise ratio becomes too small (especially for CDHA_D sample) to obtain reliable data. The previous results must be corroborated by other photothermal techniques, such as IR photothermal radiometry or lock-in thermography [25, 26].
\nThe sol–gel synthesis of calcium-deficient hydroxyapatite was successfully achieved, for four different drip rates during synthesis procedures, describing the distinctive features of the pH evolution, for each case. For the samples synthesized at drip rate values of 5, 8, 10, and 17 μl∙s−1, the structural, morphological, and textural characterizations show that the pore radius size and the total pore volume tend to decrease for a drip rate up to 5 μl∙s−1, contrary to the crystallite size, which decreases for all samples as the drip rate increases. The chemical characterizations demonstrate that increasing the drip rate promotes the presence of calcium and oxygen vacancies in the hydroxyapatite structure. From the diffuse reflectance and absorbance spectra, the energy band gap of the samples increases as the drip rate does, with the exception of the sample synthesized at 17 μl∙s−1, possible due to a combination of a larger presence of oxygen vacancies on the phosphate sites and calcium vacancies. The results of the thermal characterization allowed determining the effective thermal diffusivity of the samples, obtaining values that agree well with those reported in the literature. However, it was not possible to establish a clear correlation between the effective thermal properties and the values of the drip rate used during the synthesis. Finally, the drip rate in the hydroxyapatite sol-gel synthesis clearly governs the pH during synthesis and, therefore, has a major impact in the physical-chemical properties of the hydroxyapatite.
\nAuthors acknowledge the Instituto Politécnico Nacional from Mexico, for financial support through 1855 SIP multidisciplinary and 20170229 SIP projects. The authors wish to thank the National Energy Conversion and Storage Laboratory, CICATA U. Legaria of the Instituto Politécnico Nacional of Mexico, and the PhD student René Cabrera for helping with the acquisition and analysis of XRD data. The authors thank also the PhD student Guadalupe Romero Ortiz for helping in the acquisition of hydrogen adsorption data.
\nThe authors of this work declare no conflicts of interest of any kind.
Parkinson’s disease is the second most common neurodegenerative disease worldwide, with high annual costs of treatment. The death of dopaminergic neurons and inflammation are the main cellular processes associated with motor and cognitive dysfunctions in PD [1, 2, 3, 4]; these events can be potentiated by the loss of the brain-derived neurotrophic factor (BDNF), a key neurotropic factor in degeneration and regeneration processes.
BDNF, discovered in 1982, is a pleiotropic neurotrophin (NT). The gene encoding for
This NT is synthesized as an inactive precursor form, pre-pro-BDNF that can be cleaved to form a mature neurotrophin that is transported to the plasma membrane and then released in an unprocessed manner. The “pre” sequence is normally deleted when it translocates through the Golgi membrane, producing the pro-BDNF of 32 kDa. Small amounts of a truncated 28 kDa pro-BDNF can also be formed in the endoplasmic reticulum without interfering with the final levels of active, mature 14 kDa BDNF (m-BDNF). The N-terminal pro-domain of BDNF facilitates intracellular trafficking and regulated secretion. After cleavage of N-terminal region, the m-BDNF is released, although this does not exclude the release of the pro-BDNF form [6].
The BDNF shows affinity for two types of receptors. The first is a 75 kDa glycoprotein from the family of tumor necrosis factor receptors, represented by p75 NTR and P75 + sortilin receptors, and the second is a receptor from the protein tropomyosin receptor kinase (Trk) family, which involves the TrkA, TrkB and TrkC, whose main ligands are neuronal growth factor (NGF), BDNF/neurotrophins (NT-4 and NT-3), respectively. The p75 receptor binds to the pro-BDNF isoform and can induce apoptosis and bind non-neurotrophic ligands such as the glycoprotein of rabies virus, amyloid peptides and also other pro-neurotrophins; it can also generate neurite retraction and synaptic weakening and facilitate long-term depression [6, 7, 8]. The m-BDNF binds to TrkB receptors promoting cell survival, neurite extension and long-term synaptic potentiation and improves learning and memory; it also promotes synaptic plasticity, neurogenesis, formation of angiogenic tubes, regulation of neurotransmitter release and dendritic growth [5, 6, 9, 10, 11].
At the brain level, BDNF is produced in the hippocampus, amygdala,
Alterations of BDNF expression are implicated in the development of a variety of central nervous system (CNS) diseases, including neurodegenerative disorders, such as Alzheimer’s, Parkinson’s, Huntington’s disease and amyotrophic lateral sclerosis, and psychiatric disorders, such as depression and schizophrenia [14, 18]. However, several studies have shown that the therapeutic application of BDNF prevents neuronal degeneration after axotomy and other forms of neuronal injury [19, 20, 21, 22]. In addition, beneficial effects of BDNF have been reported in animal models of neurodegenerative diseases. Therefore, BDNF is now considered as a potential therapeutic agent for human neurodegenerative disease, for example, motor neuron disease and PD (Figure 1).
Causative and curative roles of BDNF. Schematic view of cognitive dysfunction mediated by binding of pro-BDNF to p75NTR receptor leading to apoptotic cell death. Induction of BDNF gene due to the binding of pro-BDNF to p75NTR + sortilin and mBDNF to TrkB receptors leading to cell survival mediated by NF-κB and CREB, respectively. BDNF, brain-derived neurotrophic factor; mBDNF, mature BDNF; p75NTR, p75 neurotrophin receptor; NRAGE, p75NTR interacting protein; NRIF, neurotrophin receptor interacting factor; TRAF, tumor necrosis factor receptor-associated factor; MKK7, mitogen-activated protein kinase kinase 7; ASK1, apoptotic signal-regulating kinase 1; JNK, c-Jun N-terminal kinase; IRAK, interleukin-1 receptor-associated kinase; IκB, kappa light polypeptide gene enhancer in B-cell inhibitor; NF-κB, nuclear factor kappa-light chain enhancer of B cells; TrkB, tropomyosin receptor kinase B; tPA, tissue plasminogen activator; MAPK, mitogen-activated protein kinase; ERK, extracellular signal-regulated kinase; PI3K, phosphoinositol 3-kinase; AKT, protein kinase B; PLC-γ, phospholipase C gamma; DAG, diacylglycerol; PKC, protein kinase C; IP3, inositol triphosphate; CaM, calmodulin; CaMK, calmodulin-dependent protein kinase; CREB, cyclic adenosine monophosphate response element-binding protein.
The cause of PD is linked with several molecular factors related to the survival and susceptibility of the dopaminergic neurons (DN) of the
Recently, it has been proposed that the detection of a low concentration of BDNF in serum is a biomarker of the early stages of the disease [28, 29]. The low concentration of this neurotrophic factor in serum of PD patients may be due to a low transcription of the
Currently, well-known mechanisms of microRNAs (miRNAs) play a crucial role in neurotrophin gene regulation. These miRNAs are short non-coding RNAs of ∼22 nucleotides that are coupled to the RNA-induced silencing complex (RISC) and regulate the degradation of the RNAs [32]. Several miRNAs regulate BDNF expression and could be directly involved in the survival of DN. It has been reported that miR-1 represses the levels of BDNF expression through regulatory sites in the 3′-UTR sequence of the gene [33, 34, 35]. In addition, miR-1 levels have been found to be decreased in patients with PD compared with healthy individuals [36]. The decrease in miR-1 in patients with PD may be due to an activated mechanism to increase the expression of BDNF and promote the survival of the remaining DN in the SN.
In this regard, it has also been reported that BDNF is negatively regulated by the damage induced with neurotoxin in a murine model of Parkinsonism using MPP+. The MPTP neurotoxin is converted to MPP+ by the enzyme monoamine oxidase (MAO-B), expressed by astrocytes. The MPP+ is then internalized into the DN specifically by the dopamine transporter and upon reaching toxic levels in the mitochondria and inhibits the complex I of the electron transport chain [37]. Zhang et al. [38] reported that the treatment with MPP+ led to an increased expression of miR-210-3p and decreased expression of BDNF. To corroborate the results, they performed the inhibition of miR-210-3p and observed that the levels of BDNF increased and the survival of the tyrosine hydroxylase-positive DN of the SN in mice injected with MPTP was also significantly improved. The regulation of BDNF expression has become a key strategy for the rescue of damaged DN in PD.
Another factor that alters the secretion of BDNF is the single nucleotide functional polymorphism Val66Met, whose effect has been widely studied in humans [39, 40, 41]. This polymorphism consists of a substitution of valine amino acid by methionine at position 66 of the precursor protein (pro-BDNF) causing a decrease in secretion induced by depolarization [42]. The distribution of alleles has been reported in several populations, with the Val/Val allele prevailing (from 59 to 72%), followed by Val/Met (from 25 to 38%) and with a lower prevalence of the Met/Met allele (from 2 to 4%) [43, 44, 45]. The effect of polymorphism has been studied with controversial results as some groups argue that there is an advantage of the carriers of the Met/Met allele, by showing a better cognitive performance than the individuals who presented the Val/Met allele [44]; other researchers conclude that the fact of carrying at least one 66Met allele has a high prevalence of having a greater cognitive deterioration when PD is present [43].
One of the main characteristics of PD is the formation of Lewy bodies that are composed mainly of α-synuclein protein [46]. Recently, it was found that this protein interacts with the neurotrophic receptor TrkB, inhibiting its internalization and its correct distribution. This interaction blocks BDNF signaling and results in increased death of DN induced by the MPTP [47]. In addition, α-synuclein has been shown to affect the retrograde axonal transport of BDNF and confirm the inhibition of the signaling pathway in a PD model [48]. The inhibition of this neurotrophic factor makes them susceptible to the DN of the SN and contributes to the symptoms observed in PD.
Currently, PD affects the adult population (˃65 years) and even young people [49, 50]. Although PD is multifactorial, indisputable signs of the disease include the progressive degeneration of the DN of the nigrostriatal pathway due to oxido-redox imbalance, followed by neurodegeneration, neuroinflammation, Lewy bodies’ deposits and the generalized damage of the neural circuits that control movement [24, 51, 52].
The degenerative process develops mainly in the DN. In humans, the early loss of dopaminergic neurons from the SN drastically reduces the striatal dopamine concentration [53, 54]. The origin of the motor and non-motor alterations can be sporadic due to genetic deregulation. Several genetic alterations have been described in
The Parkinson’s motor symptoms are bradykinesia, rigidity, inclined posture and tremor at rest. Neuroimaging studies suggest that the motor signs of the disease appear when 50–70% of the DN damage is present [57]. Tremor at rest is the symptom that is present in more than 70% of the patients with PD; these idiopathic tremors are more noticeable when the patient is not performing a specific movement [58]. Electrophysiological studies suggest that tremor at rest in PD is generated by multiple oscillatory circuits that are operating at the same frequencies (4 ± 6 Hz); this tremor is improved with the administration of levodopa, while orthostatic tremor, in PD, is characterized by rapid and specific tremors that affect the legs and trunk when standing. This tremor presents a frequency of 14 ± 18 Hz, where levodopa has no effect, which indicates that the pathophysiology of orthostatic tremor in PD might be different from the tremor at rest [59].
The bradykinesia or slowness of movement is manifested by the decrease in manual dexterity or the difficulty to get up from where they are sitting. Also during the progress of the disease, patients show postural instability with increased risk of falls as they take much faster and shorter steps, and postural instability has a poor response to dopamine treatments [58]. The symptoms of PD are progressive; however, the rate of progression in motor symptoms is variable according to the period of development of the disease in which they occur [60].
Other motor imbalance is the hypomimia, which is characterized by the decrease in facial expression or in the number of eye blinks, blurred vision, altered look, speech alteration, as well as the presence of dystonia or movement disorders, which causes involuntary contractions of the muscles, stooped posture, difficulty turning, kyphosis or scoliosis, which refer to an abnormal curvature of the spine, walking with the drag of the feet, or “freezing” or inability to move in patients with advanced stage of PD [59].
In functional magnetic resonance imaging studies (fMRI) of akinetic patients, changes have been observed during the performance of a complex sequential motor task, showing a reduced functional magnetic resonance signal in the rostral part of the supplementary motor area and in the right dorsolateral prefrontal cortex. In addition, these patients also showed a significant bilateral increase in the activation of the primary sensorimotor cortex, the premotor cortex lateral, the caudal part of the supplementary motor area, the inferior parietal cortex and the anterior cingulate cortex, and in other cortical motor areas [61]. It has been mentioned that during the earliest pathological stage of PD, neuronal degeneration occurs in motor nuclei of the brainstem, olfactory bulbs and limbic areas; as it proceeds, it continues to the temporal and paralimbic cortices, as well as to the thalamic nuclei, until reaching associative areas such as the prefrontal lobes, and to finally involve the first order and sensory motor areas [62, 63, 64].
However, Agosta et al. [65] found that the progression of the disease in patients with moderate and severe PD shows a small cortical atrophy compared with healthy individuals; this atrophy involves the thalamus and the prefrontal cortex; they also report that the loss of gray matter did not significantly worsen in later stages of the disease, with the thalamus showing this atrophy. They also observed that a microstructural damage of the white matter (WM) occurs with the increase in the severity of the disease, involving the brainstem, cerebellum, thalamocortical, interhemispheric and limbic pathways, as well as the extra motor association tracts. They correlate the damage in WM with the degree of cognitive deficit, considering that the damage in WM probably contributes to the more severe motor and non-motor dysfunctions that occur in patients in later stages.
Parkinson’s disease is associated with multiple cognitive deficits and an increased risk of dementia, especially in its late stage. In addition, alterations in visuospatial, attentional, executive and memory functions may occur [66]. Epidemiological studies show that cognitive impairments are present between 24 and 62% of patients with newly diagnosed PD, and in the long term about 15% of patients remain cognitively intact [67]. The incidence of dementia is approximately 100 per 100,000 patients per year among patients with PD, suggesting that people with PD have a three to six times greater risk of developing dementia than people of the same age without PD [68]. However, the pathophysiological mechanisms involved in these cognitive deficits are not yet clear.
At present, neurotrophic factors have attracted attention from both clinical and experimental levels. BDNF is one of the key molecules in the modulation of cerebral plasticity and can induce long-term potentiation (LTP) through the activation of signal transduction routes; this LTP plays a key role in the neurophysiological basis for learning and memory [69]. In experimental animal models, it has been observed that the inhibition of BDNF signaling in knockout mice can affect spatial learning and memory; on the contrary, in the general population, it has been observed that at higher levels of BDNF in the hypothalamus there is a better cognitive function, including memory [70]. Recently, it has been detected that serum levels of BDNF decrease significantly in those diseases with cognitive deficits, such as Alzheimer’s disease, mild cognitive impairment and Huntington’s disease [27, 71, 72].
At the clinical level, there has been an association between serum BDNF levels and cognitive impairment. For example, one study observed the association between the decreased levels of BDNF present in cerebrospinal fluid, which contributes to early cognitive deterioration in PD, in particular to executive-attentional dysfunction [20]. On the other hand, an increase in BDNF concentrations has been detected in the same sample type of individuals with this pathology with respect to non-diseased controls [31], which could be due to a glial activation to increase the synthesis of this neurotrophin in response to brain damage [19]. Some authors have reported the association between the Val66Met BDNF polymorphism and cognitive dysfunction in patients with PD [43, 44]; subjects with Met BDNF allele show decreased cognitive flexibility when compared to homozygous carriers of the Val BDNF allele [45] (Figure 2).
Val 66 Met/G196A BDNF polymorphism in Parkinson’s disease. Schematic representation showing the structure and location of BDNF gene and the location of single nucleotide polymorphism (SNP) that leads to the disease. BDNF, brain-derived neurotrophic factor.
In basic research, it has been observed that a higher concentration of hippocampal BDNF improves spatial memory in Morris’s water maze [73]. The hippocampus is an important nucleus for learning and memory consolidation processes, and since BDNF plays an important role in the neuroplasticity of the hippocampus, the absence of this neurotrophin might affect the processes of learning and memory in the short and long term. Also, BDNF as well as TrKB has been shown in animal models to participate in the survival of DN in the SN [74], which is one of the main populations affected in PD. Therefore, the deficiency of BDNF, as well as its TrKB receptor, could be related to the loss of DN and the progression of the disease.
In studies of patients with dopaminergic neurodegeneration, a reduction in serum BDNF levels was observed, accompanied by a loss of striatal dopamine transporter (DAT) binding, that is, a positive correlation was found between the striatal DAT junction and BDNF levels [75]. On the other hand, there are several reports showing an increase in serum BDNF levels and also improvement in cognitive performance in PD patients, who underwent cognitive rehabilitation, when compared to a placebo group. These findings suggest that serum BDNF levels may represent a biomarker for the effects of cognitive rehabilitation in PD patients affected with mild cognitive impairment [76].
Aging is another important variable that not only leads to the slow progression of PD but also hampers the medical treatment response [77]. There is aging without PD, but there is no PD without aging [78], showing decreased dopamine levels, increased sensitivity to mitochondrial dysfunction, alterations in calcium channel activity, accumulation of iron and neuromelanin, changes in protein degradation pathways [79], striatal spine retraction [80] and loss of striatal spine density [81]. With advancing age, the loss of DA neurons is fully expressed in PD genetic models in
In the brain, next to nigrostriatal pathway, hippocampus is highly sensitive to aging and BDNF is critically involved in the regulation of age-related hippocampal decline [86]. In normal striatum, BDNF maintains dendritic spine density and synapse function, whereas in aged striatum, impaired BDNF signaling is common, which is further intensified in BDNF Val66Met SNP individuals [87]. With an increase in human age, BDNF mRNA levels remained same but TrkB mRNA levels decreased in hippocampus [88], indicating that BDNF-TrkB system of hippocampus is sensitive to aging [89] and deficiency of BDNF-TrkB signaling leads to the progression of PD [74]. Recent reports in aged brain suggest a diminished capacity of aged brain to transcribe, release and/or respond to BDNF [87]. As a result, treatment with TrkB agonist activates TrkB and downstream signaling cascades in BDNF-independent manner, which is neuroprotective both
At pre-clinical level, alterations in the synthesis and presence of BDNF are related to psychiatric disorders such as anxiety and depression [91, 92]. PD patients with Val66Met BDNF and G/G-BDNF-Val66Met polymorphisms are more predisposed to develop symptoms of anxiety or depression when observed at genetic level [39]. At the protein level observation, pro-BDNF is a facilitator of hippocampal long-term depression (LTD), and Val66Met pro-BDNF impairs memory function but pro-BDNF with Met completely inhibits hippocampal LTD indicating the antagonistic activities of pro-BDNF and BDNF on hippocampal LTD [93]. A
In this context, murine models has led to demonstrate the presence of the Val66MetBDNF polymorphism associated with anxiety-like behavior and significant increase of corticosterone, the physiological stress hormone, in serum [95]. Similar to human findings, the decreased production of BDNF in the hippocampus, amygdala and prefrontal cortex [96, 97] can be reversed with antidepressant drugs [91]. Whereas Tuon et al. evaluated the anti-depressant effect of BDNF, in a 6-hydroxydopamine (6-OHDA) murine model, by replacing the pharmacological therapy with physical exercise and observed a decrease of depressive-like behavior, which was associated with the restoration of pro-BDNF, BDNF and TrkB receptor levels both in the hippocampus and the
Despite the importance of BDNF in plasticity and cellular maintenance, the serum levels of this NT have been studied [99]. Existing evidence shows that low concentration of BDNF is a risk factor to generate depression in PD patients [100].
In brain, BDNF not only mediates region-specific effects on synaptic function and neuronal morphology [8] but is also involved in various functions including aging [101], anxiety [102], chronic pain [103], deafness [104], depression [105] and long-term memory storage [9]. BDNF is proven to be the best therapeutic gene for treating metabolic syndrome [106], Friedreich’s ataxia [107], neuropsychiatric or neurocognitive disorders [108], brain ischemia [109], schizophrenia [110], glaucoma [111], epilepsy [112], spinocerebellar ataxia typ. 6 [113], Huntington’s disease [21], multiple sclerosis [114], amyotrophic lateral sclerosis [115], spinal cord injury [116], Alzheimer’s disease [22] and PD [117].
Despite encouraging and numerous researches supporting the potential therapeutic role of BDNF in non-human primate trials, no satisfactory results were found in clinical trials due to the disability to cross blood-brain barrier (BBB) and to reach degenerating neurons as such [118]. Hence, alternative methods like addition of poly ethylene glycol (PEG), either at N-terminal or at C-terminal, and vector-mediated BBB drug delivery were done to improve the BDNF distribution for use in clinical trials [119].
However, very short half-life of BDNF limits the effectiveness as a therapeutic protein, and thus, exogenous delivery methods are necessary to translate BDNF-based therapies to the clinic. In this direction, gene delivery methods through viral vectors have gained lot of attention by researchers in the beginning, but later on, it was proved that the use of viral vectors in the clinic was proven difficult due to the limited biodistribution and host immunogenicity [120]. Later on, non-viral and nanocarrier (liposome and polyplex) mediated gene delivery drew the attention as nanotechnology offers new possibilities for designing vehicles. Along with the nanotechnology, proteomics also integrated leading to the production of fusion protein vectors and mimetics (both protein and non-protein). The outline of the potential therapeutic role of BDNF in treating neurodegenerative disorders, specific focus on PD, by various researches (Table 1) and the patents related to BDNF (Table 2) are tabulated.
Animal model (toxin) | Mode of BDNF supply | Result/outcome |
---|---|---|
Mouse (MPTP) [121, 122, 123] | Intranigral | Increased cell survival |
Non-peptide mimetics of BDNF | ||
Rat (6-OHDA) [117, 124, 125, 126, 127] | Intranigral transplants of human mesenchymal stem cells (hMSC) secreting the BDNF protein | Regulated neurotrophic effect and proved vehicle for the targeted neurotrophic delivery |
Intranigral injections of recombinant human BDNF in healthy rats | Chronic BDNF did not attenuate dopaminergic parameters in either striatum or SN | |
Intra ventricular infusion | Adult brain parenchyma may recruit and/or generate new neurons | |
Intranigral neurotensin (NTS)-polyplex nanocarrier mediated gene delivery | Neurorecovery by neuritogenesis in early stage of PD | |
Intranigral recombinant adeno-associated virus (rAAV) vector-mediated gene delivery | No signs of neuroprotection | |
Rat (MPTP) [128] | Transplanting genetically engineered fibroblasts expressing BDNF protein | Axonal regeneration |
Monkey (MPTP) [129] | Intrathecal infusion | Less neuronal loss and damage was observed in SN |
Rhesus monkey [130, 131] | Stimulation of BDNF secretion by caloric restriction; physical exercise | Increased neuronal survival and locomotor activity in both SN and striatum |
Therapeutic research works using BDNF.
Assignee/s | Inventor (date) | Title |
---|---|---|
Max-Planck Gesellschaft zur Forderung der Wissenschaften, Regeneron Pharmaceuticals Inc. | Yves-Alain Barde (1989) | Brain derived neurotrophic factor |
Synergen Inc. | Frank Collins (1990) | Production of biologically active recombinant members of the NGF/BDNF family of neurotrophic proteins |
Teva Pharmaceutical Industries Ltd. | Liat Hayardeny (2009) | Treatment of BDNF-related disorders using laquinimod |
Center for research and advanced studies of the national polytechnic institute | Daniel Martinez-Fong (2012) | Compositions and methods for Parkinson’s disease treatment by BDNF-flag gene transfer through neurotensin polyplex to nigral dopamine neurons |
Curna Inc., The Scripps Research Institute | Faghini Mohammad Ali and Coito Carlos (2013) | Treatment of brain derived neurotrophic factor related diseases by inhibition of natural antisense transcript to BDNF |
VDF FutureCeuticals | Zbigniew Pietrzkowski (2013) | Compositions and methods of BDNF activation |
Meiji Co., Ltd. | Midori Natsume (2015) | Promoting the production for the composition of the brain-derived neurotrophic factor |
Zhou Yi | Zhou Xinfu (2015) | Application of brain-derived neurotrophic factor precursor protein as target for treating affective disorders |
Patents related to BDNF and its therapeutic role.
The experimental models of Parkinson give evidence of many recovery strategies to BDNF
The main objectives of experimental and clinical research include better understanding and proper diagnosis, developing new treatments and preventing them to the maximum extent. Currently, there are innumerable experimental pathology studies dedicated to solve the pathophysiology and possible treatment of PD. Based on this, clinical trials offer an excellent opportunity to help doctors and researchers to find better ways in detection, treatment or prevention in a safe way and, therefore, offer hope to people suffering from PD. Current studies include genetics, diagnostic imaging, studies that allow the identification of biomarkers of this disease, pharmacological treatment methods and various proposals for experimental therapies [132, 133]. Development and application of deep brain stimulation through implanting electrodes at specific sites to recover neuronal function is now a treatment option for some people with advanced PD when patients no longer respond to medications [134].
Having PD during aging involves rapid progression of motor impairment, altered mood and cognitive dysfunction. At the cellular level, there is a rapid loss of function and neuronal survival due to the absence of production of neurotrophic factors such as BDNF. In the preclinical phase, some experimental approaches evaluated in animal models have partially prevented the DN degeneration and neuroinflammation. However, these approaches have great challenges; the therapies should be specific to one cell population, guarantee biosafety for human use, low cost and induce a sustained therapeutic effect.
Although BDNF was found to be promising in animal models of PD, no significant results from clinical trials are reported [135], and thus, therapeutic usage of BDNF for PD in humans is not yet reported. However, as BDNF cannot pass through the BBB, intracranial administration is must and this may be overcome by delivering BDNF bound to certain molecular carriers that can cross BBB to avoid intracranial surgery-related complications and long-term effects on behavioral disorders [136]. In this aspect, researchers from University of California have combined BDNF with mesenchymal stem cells (MSC) for treating neurodegenerative diseases, but no published scientific reports exist on preclinical and clinical trials of MSC/BDNF stem cell product [137].
Brain-derived neurotropic factor is relevant to neuronal maintenance and participates in the survival of dopaminergic neurons. The deficit of this neurotrophin is the key for the pathophysiology of PD because it limits the regeneration of motor and cognitive circuits. The absence of BDNF could promote the cognitive dysfunction in vulnerable subjects. The knowledge of the synthesis and delivery routes of this neurotrophin will allow the search for better therapies focused in patients with neurodegenerative diseases.
This work was supported by Consejo Nacional de Ciencia y Tecnologia (Catedra CONACyT # 1840) for DH-B and TC-LL, the Instituto de Neuroetologia from Universidad Veracruzana (DGI-174332015137 & CA-UV025) to MJR-H, the Instituto Mexicano del Seguro Social (FIS/IMSS/PROT/G15/1480) to LMZ-F and PRODEP (UANL-PTC-908) to AV-O. AP-O received fellowship from CONACyT for postgraduate studies in Neuroethology (# 297410).
The authors declare that there are no conflicts of interest.
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\\n\\nThe Corresponding Author also warrants and represents that: (i) they have the full power to enter into this Publication Agreement on their own behalf and on behalf of each Co-Author; and (ii) they have the necessary rights and/or title in and to the Chapter to grant IntechOpen, on behalf of themselves and any Co-Author, the rights and licenses expressed to be granted in this Publication Agreement. If the Chapter was prepared jointly by the Corresponding Author and any Co-Author, the Corresponding Author warrants and represents that: (i) each Co-Author agrees to the submission, license and publication of the Chapter on the terms of this Publication Agreement; and (ii) they have the authority to enter into this Publication Agreement on behalf of and bind each Co-Author. The Corresponding Author shall: (i) ensure each Co-Author complies with all relevant provisions of this Publication Agreement, including those relating to confidentiality, performance and standards, as if a party to this Publication Agreement; and (ii) remain primarily liable for all acts and/or omissions of each such Co-Author.
\\n\\nThe Corresponding Author agrees to indemnify and hold IntechOpen harmless against all liabilities, costs, expenses, damages and losses and all reasonable legal costs and expenses suffered or incurred by IntechOpen arising out of or in connection with any breach of the aforementioned representations and warranties. This indemnity shall not cover IntechOpen to the extent that a claim under it results from IntechOpen's negligence or willful misconduct.
\\n\\n4.2 Nothing in this Publication Agreement shall have the effect of excluding or limiting any liability for death or personal injury caused by negligence or any other liability that cannot be excluded or limited by applicable law.
\\n\\n5. TERMINATION
\\n\\n5.1 IntechOpen has a right to terminate this Publication Agreement for quality, program, technical or other reasons with immediate effect, including without limitation (i) if the Corresponding Author or any Co-Author commits a material breach of this Publication Agreement; (ii) if the Corresponding Author or any Co-Author (being an individual) is the subject of a bankruptcy petition, application or order; or (iii) if the Corresponding Author or any Co-Author (being a company) commences negotiations with all or any class of its creditors with a view to rescheduling any of its debts, or makes a proposal for or enters into any compromise or arrangement with any of its creditors.
\\n\\nIn case of termination, IntechOpen will notify the Corresponding Author, in writing, of the decision.
\\n\\n6. INTECHOPEN’S DUTIES AND RIGHTS
\\n\\n6.1 Unless prevented from doing so by events outside its reasonable control, IntechOpen, in its discretion, agrees to publish the Chapter attributing it to the Corresponding Author and any Co-Author.
\\n\\n6.2 IntechOpen has the right to use the Corresponding Author’s and any Co-Author’s names and likeness in connection with scientific dissemination, retrieval, archiving, web hosting and promotion and marketing of the Chapter and has the right to contact the Corresponding Author and any Co-Author until the Chapter is publicly available on any platform owned and/or operated by IntechOpen.
\\n\\n6.3 IntechOpen is granted the authority to enforce the rights from this Publication Agreement, on behalf of the Corresponding Author and any Co-Author, against third parties (for example in cases of plagiarism or copyright infringements). In respect of any such infringement or suspected infringement of the copyright in the Chapter, IntechOpen shall have absolute discretion in addressing any such infringement which is likely to affect IntechOpen's rights under this Publication Agreement, including issuing and conducting proceedings against the suspected infringer.
\\n\\n7. MISCELLANEOUS
\\n\\n7.1 Further Assurance: The Corresponding Author shall and will ensure that any relevant third party (including any Co-Author) shall, execute and deliver whatever further documents or deeds and perform such acts as IntechOpen reasonably requires from time to time for the purpose of giving IntechOpen the full benefit of the provisions of this Publication Agreement.
\\n\\n7.2 Third Party Rights: A person who is not a party to this Publication Agreement may not enforce any of its provisions under the Contracts (Rights of Third Parties) Act 1999.
\\n\\n7.3 Entire Agreement: This Publication Agreement constitutes the entire agreement between the parties in relation to its subject matter. It replaces and extinguishes all prior agreements, draft agreements, arrangements, collateral warranties, collateral contracts, statements, assurances, representations and undertakings of any nature made by or on behalf of the parties, whether oral or written, in relation to that subject matter. Each party acknowledges that in entering into this Publication Agreement it has not relied upon any oral or written statements, collateral or other warranties, assurances, representations or undertakings which were made by or on behalf of the other party in relation to the subject matter of this Publication Agreement at any time before its signature (together "Pre-Contractual Statements"), other than those which are set out in this Publication Agreement. Each party hereby waives all rights and remedies which might otherwise be available to it in relation to such Pre-Contractual Statements. Nothing in this clause shall exclude or restrict the liability of either party arising out of its pre-contract fraudulent misrepresentation or fraudulent concealment.
\\n\\n7.4 Waiver: No failure or delay by a party to exercise any right or remedy provided under this Publication Agreement or by law shall constitute a waiver of that or any other right or remedy, nor shall it preclude or restrict the further exercise of that or any other right or remedy. No single or partial exercise of such right or remedy shall preclude or restrict the further exercise of that or any other right or remedy.
\\n\\n7.5 Variation: No variation of this Publication Agreement shall be effective unless it is in writing and signed by the parties (or their duly authorized representatives).
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\\n\\n7.7 No partnership: Nothing in this Publication Agreement is intended to, or shall be deemed to, establish or create any partnership or joint venture or the relationship of principal and agent or employer and employee between IntechOpen and the Corresponding Author or any Co-Author, nor authorize any party to make or enter into any commitments for or on behalf of any other party.
\\n\\n7.8 Governing law: This Publication Agreement and any dispute or claim (including non-contractual disputes or claims) arising out of or in connection with it or its subject matter or formation shall be governed by and construed in accordance with the law of England and Wales. The parties submit to the exclusive jurisdiction of the English courts to settle any dispute or claim arising out of or in connection with this Publication Agreement (including any non-contractual disputes or claims).
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The Corresponding Author (acting on behalf of all Authors) and INTECHOPEN LIMITED, incorporated and registered in England and Wales with company number 11086078 and a registered office at 5 Princes Gate Court, London, United Kingdom, SW7 2QJ conclude the following Agreement regarding the publication of a Book Chapter:
\n\n1. DEFINITIONS
\n\nCorresponding Author: The Author of the Chapter who serves as a Signatory to this Agreement. The Corresponding Author acts on behalf of any other Co-Author.
\n\nCo-Author: All other Authors of the Chapter besides the Corresponding Author.
\n\nIntechOpen: IntechOpen Ltd., the Publisher of the Book.
\n\nBook: The publication as a collection of chapters compiled by IntechOpen including the Chapter. Chapter: The original literary work created by Corresponding Author and any Co-Author that is the subject of this Agreement.
\n\n2. CORRESPONDING AUTHOR'S GRANT OF RIGHTS
\n\n2.1 Subject to the following Article, the Corresponding Author grants and shall ensure that each Co-Author grants, to IntechOpen, during the full term of copyright and any extensions or renewals of that term the following:
\n\nThe aforementioned licenses shall survive the expiry or termination of this Agreement for any reason.
\n\n2.2 The Corresponding Author (on their own behalf and on behalf of any Co-Author) reserves the following rights to the Chapter but agrees not to exercise them in such a way as to adversely affect IntechOpen's ability to utilize the full benefit of this Publication Agreement: (i) reprographic rights worldwide, other than those which subsist in the typographical arrangement of the Chapter as published by IntechOpen; and (ii) public lending rights arising under the Public Lending Right Act 1979, as amended from time to time, and any similar rights arising in any part of the world.
\n\nThe Corresponding Author confirms that they (and any Co-Author) are and will remain a member of any applicable licensing and collecting society and any successor to that body responsible for administering royalties for the reprographic reproduction of copyright works.
\n\nSubject to the license granted above, copyright in the Chapter and all versions of it created during IntechOpen's editing process (including the published version) is retained by the Corresponding Author and any Co-Author.
\n\nSubject to the license granted above, the Corresponding Author and any Co-Author retains patent, trademark and other intellectual property rights to the Chapter.
\n\n2.3 All rights granted to IntechOpen in this Article are assignable, sublicensable or otherwise transferrable to third parties without the Corresponding Author's or any Co-Author’s specific approval.
\n\n2.4 The Corresponding Author (on their own behalf and on behalf of each Co-Author) will not assert any rights under the Copyright, Designs and Patents Act 1988 to object to derogatory treatment of the Chapter as a consequence of IntechOpen's changes to the Chapter arising from translation of it, corrections and edits for house style, removal of problematic material and other reasonable edits.
\n\n3. CORRESPONDING AUTHOR'S DUTIES
\n\n3.1 When distributing or re-publishing the Chapter, the Corresponding Author agrees to credit the Book in which the Chapter has been published as the source of first publication, as well as IntechOpen. The Corresponding Author warrants that each Co-Author will also credit the Book in which the Chapter has been published as the source of first publication, as well as IntechOpen, when they are distributing or re-publishing the Chapter.
\n\n3.2 When submitting the Chapter, the Corresponding Author agrees to:
\n\nThe Corresponding Author will be held responsible for the payment of the Open Access Publishing Fees.
\n\nAll payments shall be due 30 days from the date of the issued invoice. The Corresponding Author or the payer on the Corresponding Author's and Co-Authors' behalf will bear all banking and similar charges incurred.
\n\n3.3 The Corresponding Author shall obtain in writing all consents necessary for the reproduction of any material in which a third-party right exists, including quotations, photographs and illustrations, in all editions of the Chapter worldwide for the full term of the above licenses, and shall provide to IntechOpen upon request the original copies of such consents for inspection (at IntechOpen's option) or photocopies of such consents.
\n\nThe Corresponding Author shall obtain written informed consent for publication from people who might recognize themselves or be identified by others (e.g. from case reports or photographs).
\n\n3.4 The Corresponding Author and any Co-Author shall respect confidentiality rights during and after the termination of this Agreement. The information contained in all correspondence and documents as part of the publishing activity between IntechOpen and the Corresponding Author and any Co-Author are confidential and are intended only for the recipient. The contents may not be disclosed publicly and are not intended for unauthorized use or distribution. Any use, disclosure, copying, or distribution is prohibited and may be unlawful.
\n\n4. CORRESPONDING AUTHOR'S WARRANTY
\n\n4.1 The Corresponding Author represents and warrants that the Chapter does not and will not breach any applicable law or the rights of any third party and, specifically, that the Chapter contains no matter that is defamatory or that infringes any literary or proprietary rights, intellectual property rights, or any rights of privacy. The Corresponding Author warrants and represents that: (i) the Chapter is the original work of themselves and any Co-Author and is not copied wholly or substantially from any other work or material or any other source; (ii) the Chapter has not been formally published in any other peer-reviewed journal or in a book or edited collection, and is not under consideration for any such publication; (iii) they themselves and any Co-Author are qualifying persons under section 154 of the Copyright, Designs and Patents Act 1988; (iv) they themselves and any Co-Author have not assigned and will not during the term of this Publication Agreement purport to assign any of the rights granted to IntechOpen under this Publication Agreement; and (v) the rights granted by this Publication Agreement are free from any security interest, option, mortgage, charge or lien.
\n\nThe Corresponding Author also warrants and represents that: (i) they have the full power to enter into this Publication Agreement on their own behalf and on behalf of each Co-Author; and (ii) they have the necessary rights and/or title in and to the Chapter to grant IntechOpen, on behalf of themselves and any Co-Author, the rights and licenses expressed to be granted in this Publication Agreement. If the Chapter was prepared jointly by the Corresponding Author and any Co-Author, the Corresponding Author warrants and represents that: (i) each Co-Author agrees to the submission, license and publication of the Chapter on the terms of this Publication Agreement; and (ii) they have the authority to enter into this Publication Agreement on behalf of and bind each Co-Author. The Corresponding Author shall: (i) ensure each Co-Author complies with all relevant provisions of this Publication Agreement, including those relating to confidentiality, performance and standards, as if a party to this Publication Agreement; and (ii) remain primarily liable for all acts and/or omissions of each such Co-Author.
\n\nThe Corresponding Author agrees to indemnify and hold IntechOpen harmless against all liabilities, costs, expenses, damages and losses and all reasonable legal costs and expenses suffered or incurred by IntechOpen arising out of or in connection with any breach of the aforementioned representations and warranties. This indemnity shall not cover IntechOpen to the extent that a claim under it results from IntechOpen's negligence or willful misconduct.
\n\n4.2 Nothing in this Publication Agreement shall have the effect of excluding or limiting any liability for death or personal injury caused by negligence or any other liability that cannot be excluded or limited by applicable law.
\n\n5. TERMINATION
\n\n5.1 IntechOpen has a right to terminate this Publication Agreement for quality, program, technical or other reasons with immediate effect, including without limitation (i) if the Corresponding Author or any Co-Author commits a material breach of this Publication Agreement; (ii) if the Corresponding Author or any Co-Author (being an individual) is the subject of a bankruptcy petition, application or order; or (iii) if the Corresponding Author or any Co-Author (being a company) commences negotiations with all or any class of its creditors with a view to rescheduling any of its debts, or makes a proposal for or enters into any compromise or arrangement with any of its creditors.
\n\nIn case of termination, IntechOpen will notify the Corresponding Author, in writing, of the decision.
\n\n6. INTECHOPEN’S DUTIES AND RIGHTS
\n\n6.1 Unless prevented from doing so by events outside its reasonable control, IntechOpen, in its discretion, agrees to publish the Chapter attributing it to the Corresponding Author and any Co-Author.
\n\n6.2 IntechOpen has the right to use the Corresponding Author’s and any Co-Author’s names and likeness in connection with scientific dissemination, retrieval, archiving, web hosting and promotion and marketing of the Chapter and has the right to contact the Corresponding Author and any Co-Author until the Chapter is publicly available on any platform owned and/or operated by IntechOpen.
\n\n6.3 IntechOpen is granted the authority to enforce the rights from this Publication Agreement, on behalf of the Corresponding Author and any Co-Author, against third parties (for example in cases of plagiarism or copyright infringements). In respect of any such infringement or suspected infringement of the copyright in the Chapter, IntechOpen shall have absolute discretion in addressing any such infringement which is likely to affect IntechOpen's rights under this Publication Agreement, including issuing and conducting proceedings against the suspected infringer.
\n\n7. MISCELLANEOUS
\n\n7.1 Further Assurance: The Corresponding Author shall and will ensure that any relevant third party (including any Co-Author) shall, execute and deliver whatever further documents or deeds and perform such acts as IntechOpen reasonably requires from time to time for the purpose of giving IntechOpen the full benefit of the provisions of this Publication Agreement.
\n\n7.2 Third Party Rights: A person who is not a party to this Publication Agreement may not enforce any of its provisions under the Contracts (Rights of Third Parties) Act 1999.
\n\n7.3 Entire Agreement: This Publication Agreement constitutes the entire agreement between the parties in relation to its subject matter. It replaces and extinguishes all prior agreements, draft agreements, arrangements, collateral warranties, collateral contracts, statements, assurances, representations and undertakings of any nature made by or on behalf of the parties, whether oral or written, in relation to that subject matter. Each party acknowledges that in entering into this Publication Agreement it has not relied upon any oral or written statements, collateral or other warranties, assurances, representations or undertakings which were made by or on behalf of the other party in relation to the subject matter of this Publication Agreement at any time before its signature (together "Pre-Contractual Statements"), other than those which are set out in this Publication Agreement. Each party hereby waives all rights and remedies which might otherwise be available to it in relation to such Pre-Contractual Statements. Nothing in this clause shall exclude or restrict the liability of either party arising out of its pre-contract fraudulent misrepresentation or fraudulent concealment.
\n\n7.4 Waiver: No failure or delay by a party to exercise any right or remedy provided under this Publication Agreement or by law shall constitute a waiver of that or any other right or remedy, nor shall it preclude or restrict the further exercise of that or any other right or remedy. No single or partial exercise of such right or remedy shall preclude or restrict the further exercise of that or any other right or remedy.
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\n\n7.6 Severance: If any provision or part-provision of this Publication Agreement is or becomes invalid, illegal or unenforceable, it shall be deemed modified to the minimum extent necessary to make it valid, legal and enforceable. If such modification is not possible, the relevant provision or part-provision shall be deemed deleted.
\n\nAny modification to or deletion of a provision or part-provision under this clause shall not affect the validity and enforceability of the rest of this Publication Agreement.
\n\n7.7 No partnership: Nothing in this Publication Agreement is intended to, or shall be deemed to, establish or create any partnership or joint venture or the relationship of principal and agent or employer and employee between IntechOpen and the Corresponding Author or any Co-Author, nor authorize any party to make or enter into any commitments for or on behalf of any other party.
\n\n7.8 Governing law: This Publication Agreement and any dispute or claim (including non-contractual disputes or claims) arising out of or in connection with it or its subject matter or formation shall be governed by and construed in accordance with the law of England and Wales. The parties submit to the exclusive jurisdiction of the English courts to settle any dispute or claim arising out of or in connection with this Publication Agreement (including any non-contractual disputes or claims).
\n\nLast updated: 2020-11-27
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Everyone must undergo this phase of life at his or her own time and pace. In the broader sense, ageing reflects all the changes taking place over the course of life. These changes start from birth—one grows, develops and attains maturity. To the young, ageing is exciting. Middle age is the time when people notice the age-related changes like greying of hair, wrinkled skin and a fair amount of physical decline. Even the healthiest, aesthetically fit cannot escape these changes. Slow and steady physical impairment and functional disability are noticed resulting in increased dependency in the period of old age. According to World Health Organization, ageing is a course of biological reality which starts at conception and ends with death. It has its own dynamics, much beyond human control. However, this process of ageing is also subject to the constructions by which each society makes sense of old age. In most of the developed countries, the age of 60 is considered equivalent to retirement age and it is said to be the beginning of old age. In this chapter, you understand the details of ageing processes and associated physiological changes.",book:{id:"6381",slug:"gerontology",title:"Gerontology",fullTitle:"Gerontology"},signatures:"Shilpa Amarya, Kalyani Singh and Manisha Sabharwal",authors:[{id:"226573",title:"Ph.D.",name:"Shilpa",middleName:null,surname:"Amarya",slug:"shilpa-amarya",fullName:"Shilpa Amarya"},{id:"226593",title:"Dr.",name:"Kalyani",middleName:null,surname:"Singh",slug:"kalyani-singh",fullName:"Kalyani Singh"},{id:"243264",title:"Dr.",name:"Manisha",middleName:null,surname:"Sabharwal",slug:"manisha-sabharwal",fullName:"Manisha Sabharwal"}]},{id:"55388",doi:"10.5772/intechopen.68944",title:"Beauty, Body Image, and the Media",slug:"beauty-body-image-and-the-media",totalDownloads:7620,totalCrossrefCites:5,totalDimensionsCites:12,abstract:"This chapter analyses the role of the mass media in people’s perceptions of beauty. We summarize the research literature on the mass media, both traditional media and online social media, and how they appear to interact with psychological factors to impact appearance concerns and body image disturbances. There is a strong support for the idea that traditional forms of media (e.g. magazines and music videos) affect perceptions of beauty and appearance concerns by leading women to internalize a very slender body type as ideal or beautiful. Rather than simply being passive recipients of unrealistic beauty ideals communicated to them via the media, a great number of individuals actually seek out idealized images in the media. Finally, we review what is known about the role of social media in impacting society’s perception of beauty and notions of idealized physical forms. Social media are more interactive than traditional media and the effects of self‐presentation strategies on perceptions of beauty have just begun to be studied. This is an emerging area of research that is of high relevance to researchers and clinicians interested in body image and appearance concerns.",book:{id:"5925",slug:"perception-of-beauty",title:"Perception of Beauty",fullTitle:"Perception of Beauty"},signatures:"Jennifer S. Mills, Amy Shannon and Jacqueline Hogue",authors:[{id:"202110",title:"Dr.",name:"Jennifer S.",middleName:null,surname:"Mills",slug:"jennifer-s.-mills",fullName:"Jennifer S. Mills"}]},{id:"59227",doi:"10.5772/intechopen.73385",title:"Differentiating Normal Cognitive Aging from Cognitive Impairment No Dementia: A Focus on Constructive and Visuospatial Abilities",slug:"differentiating-normal-cognitive-aging-from-cognitive-impairment-no-dementia-a-focus-on-constructive",totalDownloads:1317,totalCrossrefCites:2,totalDimensionsCites:5,abstract:"Constructive and visuospatial abilities in normal and in pathological aging (cognitive impairment, no dementia, CIND) are investigated. The sample includes 188 participants over 60 years of age, divided in 2 groups: healthy subjects (MMSE ≥28), without cognitive complaints, and individuals with CIND (MMSE between 24 and 27 and subjective cognitive complains). Drawing of cube and drawing of house, Benton Visual Retention Test (BVRT), and Block design are used to test the hypothesis that short visuoconstructive and visuospatial tests can distinguish normal from pathological cognitive aging in its very early stages. Results proved the discriminative sensitivity of BVRT general assessment criteria and of omissions and distortions in CIND. The diagnostic sensitivity of a modification of Moore and Wike [1984] scoring system for house and cube drawing tasks was confirmed as well. Drawing of cube and house could be used for quick screening of CIND in subjects over 60. Principal component analysis with oblimin rotation was performed to explore the different dimensions in the visuospatial and visuoconstructive abilities in old age. A four-factor structure was established, all four factors explaining 71% of the variance.",book:{id:"6381",slug:"gerontology",title:"Gerontology",fullTitle:"Gerontology"},signatures:"Radka Ivanova Massaldjieva",authors:[{id:"75907",title:"Associate Prof.",name:"Radka Ivanova",middleName:null,surname:"Massaldjieva",slug:"radka-ivanova-massaldjieva",fullName:"Radka Ivanova Massaldjieva"}]},{id:"59658",doi:"10.5772/intechopen.74748",title:"Ageing Better in the Netherlands",slug:"ageing-better-in-the-netherlands",totalDownloads:1166,totalCrossrefCites:1,totalDimensionsCites:4,abstract:"The Dutch National Care for the Elderly Programme was an initiative organized by the Netherlands Organisation for Health Research and Development (ZonMw) between 2008 and 2016. The aim of the programme was to collect knowledge about frail elderly, to assess their needs and to provide person-centred and integrated care better suited to their needs. The budget of EUR 88 million was provided by the Dutch Ministry of Health, Welfare and Sports. Putting the needs of elderly people at the heart of the programme and ensuring their active participation were key to the programme’s success. The programme outcomes included the establishment of eight geriatric networks around the medical universities with 650 organisations and the completion of 218 projects. These projects, involving 43,000 elderly people and 8500 central caregivers, resulted in the completion of 45 PhD theses and the publication of more than 400 articles and the development of 300 practice toolkits, one database and a website, www.beteroud.nl. The Dutch National Care for the Elderly Programme has since developed into a movement and continues under the consortium Ageing Better, made up of eight organisations. Through the use of ambassadors, Ageing Better promotes the message that ageing is not a disease but a new phase of life.",book:{id:"6381",slug:"gerontology",title:"Gerontology",fullTitle:"Gerontology"},signatures:"Betty Meyboom-de Jong, Klaske Wynia and Anjo Geluk-Bleumink",authors:[{id:"224997",title:"Emeritus Prof.",name:"Betty",middleName:null,surname:"Meyboom-De Jong",slug:"betty-meyboom-de-jong",fullName:"Betty Meyboom-De Jong"},{id:"232900",title:"Dr.",name:"Klaske",middleName:null,surname:"Wynia",slug:"klaske-wynia",fullName:"Klaske Wynia"},{id:"232901",title:"Mrs.",name:"Anjo",middleName:null,surname:"Geluk-Bleumink",slug:"anjo-geluk-bleumink",fullName:"Anjo Geluk-Bleumink"}]},{id:"60424",doi:"10.5772/intechopen.75435",title:"Characteristics of Hearing in Elderly People",slug:"characteristics-of-hearing-in-elderly-people",totalDownloads:1229,totalCrossrefCites:3,totalDimensionsCites:3,abstract:"The authors define the term presbycusis and discuss the prevalence of hearing loss in elderly people, its etiology, and methods of diagnostics (anamnesis, evaluation of the peripheral and central parts of the hearing system). The authors emphasize that central auditory processing disorder (CAPD) significantly impairs speech perception in elderly people and makes difficult the rehabilitation of patients with presbycusis. The possibility of improving speech intelligibility by using auditory training is considered. Improved functioning of the central auditory pathways in hearing aid (HA) users with moderate to moderately severe chronic sensorineural hearing loss (SNHL) and symptoms of CAPD was shown after the auditory training with the use of two approaches (“bottom-up” and “top-down”). The algorithm of the auditory training was designed based on distinction between nonverbal and verbal stimuli of varying complexity, as well as tasks to improve memory (e.g., memorizing poetry). The benefits of the auditory training in the rehabilitation of HA users with low speech intelligibility were demonstrated. Improvement of speech intelligibility in elderly patients with SNHL proves that plasticity of the auditory regions of the brain remains possible throughout the life. Options of the presbycusis prophylaxis are summarized.",book:{id:"6381",slug:"gerontology",title:"Gerontology",fullTitle:"Gerontology"},signatures:"Maria Boboshko, Ekaterina Zhilinskaya and Natalia Maltseva",authors:[{id:"229552",title:"Dr.",name:"Maria",middleName:null,surname:"Boboshko",slug:"maria-boboshko",fullName:"Maria Boboshko"},{id:"229568",title:"Dr.",name:"Natalia",middleName:null,surname:"Maltseva",slug:"natalia-maltseva",fullName:"Natalia Maltseva"},{id:"232968",title:"Dr.",name:"Ekaterina",middleName:null,surname:"Zhilinskaia",slug:"ekaterina-zhilinskaia",fullName:"Ekaterina Zhilinskaia"}]}],mostDownloadedChaptersLast30Days:[{id:"60564",title:"Ageing Process and Physiological Changes",slug:"ageing-process-and-physiological-changes",totalDownloads:6785,totalCrossrefCites:16,totalDimensionsCites:29,abstract:"Ageing is a natural process. Everyone must undergo this phase of life at his or her own time and pace. In the broader sense, ageing reflects all the changes taking place over the course of life. These changes start from birth—one grows, develops and attains maturity. To the young, ageing is exciting. Middle age is the time when people notice the age-related changes like greying of hair, wrinkled skin and a fair amount of physical decline. Even the healthiest, aesthetically fit cannot escape these changes. Slow and steady physical impairment and functional disability are noticed resulting in increased dependency in the period of old age. According to World Health Organization, ageing is a course of biological reality which starts at conception and ends with death. It has its own dynamics, much beyond human control. However, this process of ageing is also subject to the constructions by which each society makes sense of old age. In most of the developed countries, the age of 60 is considered equivalent to retirement age and it is said to be the beginning of old age. In this chapter, you understand the details of ageing processes and associated physiological changes.",book:{id:"6381",slug:"gerontology",title:"Gerontology",fullTitle:"Gerontology"},signatures:"Shilpa Amarya, Kalyani Singh and Manisha Sabharwal",authors:[{id:"226573",title:"Ph.D.",name:"Shilpa",middleName:null,surname:"Amarya",slug:"shilpa-amarya",fullName:"Shilpa Amarya"},{id:"226593",title:"Dr.",name:"Kalyani",middleName:null,surname:"Singh",slug:"kalyani-singh",fullName:"Kalyani Singh"},{id:"243264",title:"Dr.",name:"Manisha",middleName:null,surname:"Sabharwal",slug:"manisha-sabharwal",fullName:"Manisha Sabharwal"}]},{id:"55388",title:"Beauty, Body Image, and the Media",slug:"beauty-body-image-and-the-media",totalDownloads:7605,totalCrossrefCites:5,totalDimensionsCites:12,abstract:"This chapter analyses the role of the mass media in people’s perceptions of beauty. We summarize the research literature on the mass media, both traditional media and online social media, and how they appear to interact with psychological factors to impact appearance concerns and body image disturbances. There is a strong support for the idea that traditional forms of media (e.g. magazines and music videos) affect perceptions of beauty and appearance concerns by leading women to internalize a very slender body type as ideal or beautiful. Rather than simply being passive recipients of unrealistic beauty ideals communicated to them via the media, a great number of individuals actually seek out idealized images in the media. Finally, we review what is known about the role of social media in impacting society’s perception of beauty and notions of idealized physical forms. Social media are more interactive than traditional media and the effects of self‐presentation strategies on perceptions of beauty have just begun to be studied. This is an emerging area of research that is of high relevance to researchers and clinicians interested in body image and appearance concerns.",book:{id:"5925",slug:"perception-of-beauty",title:"Perception of Beauty",fullTitle:"Perception of Beauty"},signatures:"Jennifer S. Mills, Amy Shannon and Jacqueline Hogue",authors:[{id:"202110",title:"Dr.",name:"Jennifer S.",middleName:null,surname:"Mills",slug:"jennifer-s.-mills",fullName:"Jennifer S. Mills"}]},{id:"56505",title:"Aesthetics of the Naked Human Body: From Pornography (Sexualised Lust Object) to Iconography (Aesthetics of Human Nobility and Wisdom) in an Anthropology of Physical Beauty",slug:"aesthetics-of-the-naked-human-body-from-pornography-sexualised-lust-object-to-iconography-aesthetics",totalDownloads:2053,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"In many religious circles and philosophies of life, the human body is excluded from the realm of spirituality and meaning. Due to a dualistic approach, nudity is viewed as merely a physical and corporeal category. In social media, there is the real danger that the naked human body is exploited for commercial gain. Advertisements often leave the impression that the body, very specifically the genitals, is designed merely for physical desire and corporeal chemistry. They become easily objects for lust, excluded from the beauty of graceful existence and noble courage. It is argued that the naked human body is not designed for pornographic exploitation and promiscuous sensuality but for compassionate intimacy and nurturing care in order to instil a humane dimension in human and sexual encounters. In this regard, antiquity and the Michelangelesque perspective can contribute to a paradigm shift from abusive exploitation to the beauty of vulnerable sensitivity. In order to foster an integrative approach to theory formation in anthropology, the methodology of stereometric thinking is proposed.",book:{id:"5925",slug:"perception-of-beauty",title:"Perception of Beauty",fullTitle:"Perception of Beauty"},signatures:"Daniel J Louw",authors:[{id:"200645",title:"Prof.",name:"Daniel",middleName:"Johannes",surname:"Louw",slug:"daniel-louw",fullName:"Daniel Louw"}]},{id:"56059",title:"A Plastic Surgeon’s Perspective on Stereotyping and the Perception of Beauty",slug:"a-plastic-surgeon-s-perspective-on-stereotyping-and-the-perception-of-beauty",totalDownloads:1866,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"In the world of plastic surgery, misconceptions may lead to irrational requests or outcomes not appreciated by patients. Those who manage aesthetics should always listen and recognize the variability of cultural identities, desires, attitudes, anxieties and uncertainties of the patient. Emerging from a diversity of cultures and its transforming trends, the scope of cosmetic surgery and its practice reflect not only the individual’s personality, but also the culture as a whole. When counseling an individual, one has to recognize that even in groups of seemingly identical social or cultural standards; there are subtle differences in expectations. To illustrate the potential for inaccuracy of ethnic profiling in the field of plastic surgery authors quote their own work on Asian subjects and facial beauty and resort to experience of others. To reaffirm their opinion and to exemplify how sometimes “fine” differences in the perception of beauty exist, an original study that evaluates the preferences among selected groups of Latina women in respect to buttock aesthetics has been included. This dissertation will focus on how cultural factors influence beauty perception; strengthen the fact that beauty is in the eye of the beholder and how variable differences exist even between small subgroups.",book:{id:"5925",slug:"perception-of-beauty",title:"Perception of Beauty",fullTitle:"Perception of Beauty"},signatures:"Johanna D’Agostino and Marek Dobke",authors:[{id:"17590",title:"Dr.",name:"Marek K.",middleName:null,surname:"Dobke",slug:"marek-k.-dobke",fullName:"Marek K. Dobke"},{id:"201244",title:"Dr.",name:"Johanna",middleName:null,surname:"D'Agostino",slug:"johanna-d'agostino",fullName:"Johanna D'Agostino"}]},{id:"55690",title:"Animae Pulchrae: Depiction of Saintly Images in Byzantine Mural Painting",slug:"animae-pulchrae-depiction-of-saintly-images-in-byzantine-mural-painting",totalDownloads:1704,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"This chapter investigates the visual aspects of physical beauty of the saintly images depicted within the painterly ensembles of Byzantine art in the period between sixth and fifteenth centuries. It also examines the processes of transposition of beauty as a religious and ideological notion into the visual sphere of its iconographic and aesthetic significance. During the millennium of development of Byzantine mural painting, the different categories of saints have evolved in assemblies of respectable and influential characters with whom the believers could communicate through silent prayers, as well as through their own self-comparison. In that process of ideological interaction between the faithful and the saints as the “constitutional members” of the painted microcosmos of Christian temples, the physical appearance of the saintly images was, by all means, a strong argument in the religious discourse regarding their role in the mission for salvation of humanity. In that regard, each saintly category has received different visual concept of aesthetic values related to their specific physical attraction. Hence, different saintly categories have acquired different aesthetic codes for visual configuration of beauty in the structural design of their iconographic appearance throughout the era of Byzantine artistic production.",book:{id:"5925",slug:"perception-of-beauty",title:"Perception of Beauty",fullTitle:"Perception of Beauty"},signatures:"Elizabeta Dimitrova",authors:[{id:"201062",title:"Distinguished Prof.",name:"Elizabeta",middleName:null,surname:"Dimitrova",slug:"elizabeta-dimitrova",fullName:"Elizabeta Dimitrova"}]}],onlineFirstChaptersFilter:{topicId:"1241",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:0,limit:8,total:null},allSeries:{pteSeriesList:[],lsSeriesList:[],hsSeriesList:[],sshSeriesList:[],testimonialsList:[]},series:{item:{id:"24",title:"Sustainable Development",doi:"10.5772/intechopen.100361",issn:null,scope:"