IntechOpen was founded by scientists, for scientists, in order to make book publishing accessible around the globe. Over the last two decades, this has driven Open Access (OA) book publishing whilst levelling the playing field for global academics. Through our innovative publishing model and the support of the research community, we have now published over 5,700 Open Access books and are visited online by over three million academics every month. These researchers are increasingly working in broad technology-based subjects, driving multidisciplinary academic endeavours into human health, environment, and technology.
\\n\\n
By listening to our community, and in order to serve these rapidly growing areas which lie at the core of IntechOpen's expertise, we are launching a portfolio of Open Science journals:
All three journals will publish under an Open Access model and embrace Open Science policies to help support the changing needs of academics in these fast-moving research areas. There will be direct links to preprint servers and data repositories, allowing full reproducibility and rapid dissemination of published papers to help accelerate the pace of research. Each journal has renowned Editors in Chief who will work alongside a global Editorial Board, delivering robust single-blind peer review. Supported by our internal editorial teams, this will ensure our authors will receive a quick, user-friendly, and personalised publishing experience.
\\n\\n
"By launching our journals portfolio we are introducing new, dedicated homes for interdisciplinary technology-focused researchers to publish their work, whilst embracing Open Science and creating a unique global home for academics to disseminate their work. We are taking a leap toward Open Science continuing and expanding our fundamental commitment to openly sharing scientific research across the world, making it available for the benefit of all." Dr. Sara Uhac, IntechOpen CEO
\\n\\n
"Our aim is to promote and create better science for a better world by increasing access to information and the latest scientific developments to all scientists, innovators, entrepreneurs and students and give them the opportunity to learn, observe and contribute to knowledge creation. Open Science promotes a swifter path from research to innovation to produce new products and services." Alex Lazinica, IntechOpen founder
\\n\\n
In conclusion, Natalia Reinic Babic, Head of Journal Publishing and Open Science at IntechOpen adds:
\\n\\n
“On behalf of the journal team I’d like to thank all our Editors in Chief, Editorial Boards, internal supporting teams, and our scientific community for their continuous support in making this portfolio a reality - we couldn’t have done it without you! With your support in place, we are confident these journals will become as impactful and successful as our book publishing program and bring us closer to a more open (science) future.”
\\n\\n
We invite you to visit the journals homepage and learn more about the journal’s Editorial Boards, scope and vision as all three journals are now open for submissions.
\\n\\n
Feel free to share this news on social media and help us mark this memorable moment!
After years of being acknowledged as the world's leading publisher of Open Access books, today, we are proud to announce we’ve successfully launched a portfolio of Open Science journals covering rapidly expanding areas of interdisciplinary research.
\n\n\n\n
IntechOpen was founded by scientists, for scientists, in order to make book publishing accessible around the globe. Over the last two decades, this has driven Open Access (OA) book publishing whilst levelling the playing field for global academics. Through our innovative publishing model and the support of the research community, we have now published over 5,700 Open Access books and are visited online by over three million academics every month. These researchers are increasingly working in broad technology-based subjects, driving multidisciplinary academic endeavours into human health, environment, and technology.
\n\n
By listening to our community, and in order to serve these rapidly growing areas which lie at the core of IntechOpen's expertise, we are launching a portfolio of Open Science journals:
All three journals will publish under an Open Access model and embrace Open Science policies to help support the changing needs of academics in these fast-moving research areas. There will be direct links to preprint servers and data repositories, allowing full reproducibility and rapid dissemination of published papers to help accelerate the pace of research. Each journal has renowned Editors in Chief who will work alongside a global Editorial Board, delivering robust single-blind peer review. Supported by our internal editorial teams, this will ensure our authors will receive a quick, user-friendly, and personalised publishing experience.
\n\n
"By launching our journals portfolio we are introducing new, dedicated homes for interdisciplinary technology-focused researchers to publish their work, whilst embracing Open Science and creating a unique global home for academics to disseminate their work. We are taking a leap toward Open Science continuing and expanding our fundamental commitment to openly sharing scientific research across the world, making it available for the benefit of all." Dr. Sara Uhac, IntechOpen CEO
\n\n
"Our aim is to promote and create better science for a better world by increasing access to information and the latest scientific developments to all scientists, innovators, entrepreneurs and students and give them the opportunity to learn, observe and contribute to knowledge creation. Open Science promotes a swifter path from research to innovation to produce new products and services." Alex Lazinica, IntechOpen founder
\n\n
In conclusion, Natalia Reinic Babic, Head of Journal Publishing and Open Science at IntechOpen adds:
\n\n
“On behalf of the journal team I’d like to thank all our Editors in Chief, Editorial Boards, internal supporting teams, and our scientific community for their continuous support in making this portfolio a reality - we couldn’t have done it without you! With your support in place, we are confident these journals will become as impactful and successful as our book publishing program and bring us closer to a more open (science) future.”
\n\n
We invite you to visit the journals homepage and learn more about the journal’s Editorial Boards, scope and vision as all three journals are now open for submissions.
\n\n
Feel free to share this news on social media and help us mark this memorable moment!
\n\n
\n'}],latestNews:[{slug:"intechopen-supports-asapbio-s-new-initiative-publish-your-reviews-20220729",title:"IntechOpen Supports ASAPbio’s New Initiative Publish Your Reviews"},{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"}]},book:{item:{type:"book",id:"4520",leadTitle:null,fullTitle:"Osteoarthritis - Progress in Basic Research and Treatment",title:"Osteoarthritis",subtitle:"Progress in Basic Research and Treatment",reviewType:"peer-reviewed",abstract:"The most common form of arthritis is osteoarthritis (OA), which most often affects the hip, knee, foot and hand. 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\n
1. Introduction
\n
Functionally gradient materials (FGMs) make a composite material by varying the microstructure from one material to another material with a specific gradient. It can be designed for specific function and applications. If it is for thermal or corrosive resistance or malleability and toughness, both strengths of the material may be used to avoid corrosion, fatigue, fracture, and stress corrosion cracking. FGMs are usually made into several structures, such as beams [1, 2, 3, 4], plates [5, 6, 7, 8], and shells [9, 10, 11, 12]. In this area, the variation of material properties in functionally graded beams may be oriented in transverse (thickness) direction or/and longitudinal/axial (length) direction.
\n
For functionally graded beams with thickness-wise gradient variation, there have been many studies devoted to this topic. Lee et al. [13] establish an accurate transfer matrix method to analyze the free vibration characteristics of FGM beams whose Young’s modulus and density vary continuously with the height of the beam section through power law distribution. Su et al. [14] developed the dynamic stiffness method to investigate the free vibration behavior of FGM beams. Jing et al. [15] introduced a new approach by combining the cell-centered finite volume method and Timoshenko beam theory to analyze static and free vibration of FGM beams. Ait Atmane et al. [16] investigated the free vibration of a nonuniform FGM beams with exponentially varying width and material properties. Sina et al. [17] studied the free vibration of FGM beams by analytical method based on the traditional first-order shear deformation theory. Sharma [18] investigated the computational characteristics of harmonic differential quadrature method for free vibration of functionally graded piezoelectric material beam, which the material properties are assumed to have a power law or sigmoid law variation across the depth. Li et al. [19] proposed a high-order shear theory for free vibration of FGM beams with continuously varying material properties under different boundary conditions. Celebi et al. [20] employed the complementary function method to investigate the free vibration analysis of simply supported FGM beams, which the material properties change arbitrarily in the thickness direction. Chen et al. [21] studied the nonlinear free vibration behavior of shear deformable sandwich porous FGM beam based on the von kármán type geometric nonlinearity and Ritz method. Nazemnezhad and Hosseini-Hashemi [22] examined the nonlinear free vibration of FGM nanobeams with immovable ends using the multiple scale method.
\n
As the FGMs are good for severe conditions, thermal-mechanical effect on FGM structures has attracted broad attention. In this field, Farzad Ebrahimi and Erfan Salari obtained outstanding achievements. Considering the thermal-mechanical effect and size-dependent thermo-electric effect, the buckling and vibration behavior of FGM nanobeams are studied [23, 24, 25, 26]. Considering the concept of neutral axis, they [27] studied the free buckling and vibration of FGM nanobeams using semi-analytical differential transformation method. To discuss the effect of the shear stress, Reddy’s higher-order shear deformation beam theory is introduced to study the vibration of the FGM structures [28, 29, 30]. Ebrahimi et al. [31, 32, 33] also studied vibration characteristics of FGM beams with porosities. Based on nonlocal elasticity theory, the nonlocal temperature-dependent vibration of FGM nanobeams were studied in thermal environment [34, 35, 36].
\n
Another significant class of functionally graded beams is those with lengthwise varying material properties. It is difficult to obtain precise solutions for axially functionally graded (AFG) beams because of the variable coefficients of the governing equation. To solve this problem, a great deal of methods has been used to analyze the vibration characteristics of AFG beams. By assuming that the material constituents vary throughout the longitudinal directions according to a simple power law, Alshorbagy et al. [37] developed a two-node, six-degree-of-freedom finite element method (FEM) in conjunction with Euler-Bernoulli beam theory to detect the free vibration characteristics of a functionally graded beam. Shahba et al. [38, 39] used the FEM to study the free vibration of an AFG-tapered beam based on Euler-Bernoulli and Timoshenko beam theory. Shahba and Rajasekaran [40] studied the free vibration analysis of AFG-tapered Euler-Bernoulli beams employing the differential transform element method. Liu et al. [41] applied the spline finite point method to investigate the same problems. Rajasekaran [42] researched the free bending vibration of rotating AFG-tapered Euler-Bernoulli beams with different boundary conditions using the differential transformation method and differential quadrature element method. Rajasekaran and Tochaei [43] carried out the free vibration analysis of AFG Timoshenko beams using the same method. Huang and Li [44] studied the free vibration of variable cross-sectional AFG beams. The differential equation with variable coefficients is combined with the boundary conditions and transformed into Fredholm integral equation. By solving Fredholm integral equation, the natural frequencies of AFG beams can be obtained. Huang et al. [45] proposed a new approach for investigating the vibration behaviors of AFG Timoshenko beams with nonuniform cross section by introducing an auxiliary function. Huang and Rong [46] introduced a simple approach to deal with the free vibration of nonuniform AFG Euler-Bernoulli beams based on the polynomial expansion and integral technique. Hein and Feklistova [47] solved the vibration problems of AFG beams with various boundary conditions and varying cross sections via the Haar wavelet series. Xie et al. [48] presented a spectral collocation approach based on integrated polynomials combined with the domain decomposition technique for free vibration analyses of beams with axially variable cross sections, moduli of elasticity, and mass densities. Kukla and Rychlewska [49] proposed a new approach to study the free vibration analysis of an AFG beam; the approach relies on replacing functions characterizing functionally graded beams with piecewise exponential functions. Zhao et al. [50] introduced a new approach based on Chebyshev polynomial theory to investigate the free vibration of AFG Euler-Bernoulli and Timoshenko beams with nonuniform cross sections. Fang and Zhou [51, 52] researched the modal analysis of rotating AFG-tapered Euler-Bernoulli and Timoshenko beams with various boundary conditions employing the Chebyshev-Ritz method. Li et al. [53, 54] obtained the exact solutions for the free vibration of FGM beams with material profiles and cross-sectional parameters varying exponentially in the axial direction, where assumptions of Euler-Bernoulli and Timoshenko beam theories have been applied, respectively. Sarkar and Ganguli [55] studied the free vibration of AFG Timoshenko beams with different boundary conditions and uniform cross sections. Akgöz and Civalek [56] examined the free vibrations of AFG-tapered Euler-Bernoulli microbeams based on Bernoulli-Euler beam and modified couple stress theory. Yuan et al. [57] proposed a novel method to simplify the governing equations for the free vibration of Timoshenko beams with both geometrical nonuniformity and material inhomogeneity along the beam axis, and a series of exact analytical solutions are derived from the reduced equations for the first time. Yilmaz and Evran [58] investigated the free vibration of axially layered FGM short beams using experimental and FEM simulation, which the beams are manufactured by using the powder metallurgy technique using different weight fractions of aluminum and silicon carbide powders.
\n
Till now, there also are plenty of literatures devoted to the free vibration for nonuniform beams. Boiangiu et al. [59] obtained the exact solutions for free bending vibrations of straight beams with variable cross section using Bessel’s functions and proposed a transfer matrix method to determine the natural frequencies of a complex structure of conical and cylindrical beams. Garijo [60] analyzed the free vibration of Euler-Bernoulli beams of variable cross section employing a collocation technique based on Bernstein polynomials. Arndt et al. [61] presented an adaptive generalized FEM to determine the natural frequencies of nonuniform Euler-Bernoulli beams. The spline-method of degree 5 defect 1 is proposed by Zhernakov et al. [62] to determine the natural frequencies of beam with variable cross section. Wang [63] studied the vibration of a cantilever beam with constant thickness and linearly tapered sides by means of a novel accurate, efficient initial value numerical method. Silva and Daqaq [64] solved the linear eigenvalue problem exactly of a slender cantilever beam of constant thickness and linearly varying width using the Meijer G-function approach. Rajasekaran and Khaniki [65] applied the FEM to research the vibration behavior of nonuniform small-scale beams in the framework of nonlocal strain gradient theory. Çalım [66] investigated the dynamic behavior of nonuniform composite beams employing an efficient method of analysis in the Laplace domain. Yang et al. [67] applied the power series method to investigate the natural frequencies and the corresponding complex mode functions of a rotating tapered cantilever Timoshenko beam. Clementi [68] analytically determined the frequency response curves of a nonuniform beam undergoing nonlinear oscillations by the multiple time scale method. Wang [69] proposed the differential quadrature element method for the natural frequencies of multiple-stepped beams with an aligned neutral axis. Abdelghany [70] utilized the differential transformation method to examine the free vibration of nonuniform circular beam.
\n
The asymptotic development method, which is a kind of perturbation analysis method, is always used to solve nonlinear vibration equations. For example, Chen et al. [71, 72] studied the nonlinear dynamic behavior of axially accelerated viscoelastic beams and strings based on the asymptotic perturbation method. Ding et al. [73, 74] studied the influence of natural frequency of transverse vibration of axially moving viscoelastic beams and the steady-state periodic response of forced vibration of dynamic viscoelastic beams based on the multi-scale method. Chen [75] used the asymptotic perturbation method to analyze the finite deformation of prestressing hyperelastic compression plates. Hao et al. [76] employed the asymptotic perturbation method to obtain the nonlinear dynamic responses of a cantilever FGM rectangular plate subjected to the transversal excitation in thermal environment. Andrianov and Danishevs’kyy [77] proposed an asymptotic method for solving periodic solutions of nonlinear vibration problems of continuous structures. Based on the asymptotic expansion method of Poincaré-Lindstedt version [78], the longitudinal vibration of a bar and the transverse vibration of a beam under the action of a nonlinear restoring force are studied. The asymptotic development method is applied to obtain an approximate analytical expression of the natural frequencies of nonuniform cables and beams [79, 80]. Cao et al. [81, 82] applied the asymptotic development method to analyze the free vibration of nonuniform axially functionally graded (AFG) beams. Tarnopolskaya et al. [83] gave the first comprehensive study of the mode transition phenomenon in vibration of beams with arbitrarily varying curvature and cross section on the basis of asymptotic analysis.
\n
The present topic focus on the free vibration of AFG beams with uniform or nonuniform cross sections using analytical method: the asymptotic perturbation method (APM) and Meijer G-function. First, the governing differential equation for free vibration of nonuniform AFG beam is summarized and rewritten in a form of a dimensionless equation based on Euler-Bernoulli beam theory. Second, the analytic equations are then derived in detail in Sections 3 and 4, respectively, where the nature frequencies are obtained and compared with the results of the finite element method and the published references. Finally, the conclusions are presented.
\n
\n
\n
2. Governing equation of the AFG beam
\n
This studied free vibration of the axially functionally graded beam, which is a nonuniform and nonhomogeneous structure because of the variable width and height, as shown in Figure 1. Based on Euler-Bernoulli beam theory, the governing differential equation of the beam can be written as
\n
Figure 1.
The geometry and coordinate system of an AFG beam.
where \n\nw\n\nx\nt\n\n\n is the transverse deflection at position x and time t; \n\nL\n\n is the length of the beams; \n\nE\n\nx\n\nI\n\nx\n\n\n is the bending stiffness, which is determined by Young’s modulus \n\nE\n\nx\n\n\n and the area moment of inertia \n\nI\n\nx\n\n\n; and \n\nρ\n\nx\n\nA\n\nx\n\n\n is the unit mass length of beam, which is determined by volume mass density \n\nρ\n\nx\n\n\n and variable cross-sectional area \n\nA\n\nx\n\n\n.
\n
Because of the particularity of AFG beam, bending stiffness \n\nE\n\nx\n\nI\n\nx\n\n\n and unit mass \n\nρ\n\nx\n\nA\n\nx\n\n\n will change with the axis coordinates, which makes the original constant coefficient differential equation become variable coefficient differential equation and to some extent increases the difficulty of solving. In order to facilitate calculation, we simplify the calculation process by introducing dimensionless parameters. Reference flexural stiffness \n\n\nEI\n0\n\n\n and reference mass \n\nρ\n\nA\n0\n\n\n are introduced, and the above two dimensionless parameters are invariant. Suppose \n\nE\n\nx\n\nI\n\nx\n\n=\n\nEI\n0\n\n+\n\n\nE\n\nx\n\nI\n\nx\n\n\n¯\n\n\n and \n\nρ\n\nx\n\nA\n\nx\n\n=\nρ\n\nA\n0\n\n+\n\n\nρ\n\nx\n\nA\n\nx\n\n\n¯\n\n\n, where \n\n\nEI\n0\n\n\n and \n\nρ\n\nA\n0\n\n\n are the invariant parts and \n\n\n\nE\n\nx\n\nI\n\nx\n\n\n¯\n\n\n and \n\n\n\nρ\n\nx\n\nA\n\nx\n\n\n¯\n\n\n represent flexural stiffness and mass per unit length, respectively, and vary with the axial coordinates. Here, we introduce a dimensionless space variable \n\nξ\n=\nx\n/\nL\n\n and a dimensionless time variable \n\nτ\n=\n\nt\n\nL\n2\n\n\n\n\n\nEI\n0\n\n\nρ\n\nA\n0\n\n\n\n\n\n; Eq. (1) can be rewritten in the dimensionless form:
are the nondimensional varying parts of the flexural stiffness and of the mass per unit length, respectively.
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\n
\n
3. Asymptotic perturbation method
\n
\n
3.1 Equation deriving
\n
In this section, the APM is introduced to obtain a simple proximate formula for the nature frequency of the AFG beam. Firstly, we assume that
\n
\n\nw\n\nξ\nτ\n\n=\nW\n\nξ\n\nsin\n\nωτ\n\n\nE4
\n
where \n\nW\n\nξ\n\n\n is the amplitude of vibration and \n\nω\n\n is the circular frequency of vibration. We obtain the following equation by substituting Eq. (4) with Eq. (2):
Substituting these expressions with governing Eq. (5) and then expanding the expressions into a \n\nε\n\n-series, Eqs. (8) and (9) are obtained by equating the coefficients of \n\n\nε\n0\n\n\n and \n\n\nε\n1\n\n\n to zero, yielding a sequence of problems for the unknowns \n\n\nω\ni\n\n\n and \n\n\nW\ni\n\n\nξ\n\n\n:
Now, the solution of the first-order equation is analyzed. In Eq. (9), both \n\n\nh\n1\n\n\nξ\n\n\n and \n\n\nW\n1\n\n\n are linearly correlated with \n\n\nW\n0\n\n\n. Based on the theory of ordinary differential equations [84], the solvability conditions of linear differential equations can be expressed by the orthogonality of solutions of homogeneous systems of equations. At the same time, according to the orthogonality of modal vibration theory, the solution of Eq. (9) exists under the condition of the solvability of differential equation:
Because \n\n\nh\n1\n\n\nξ\n\n\n is linearly correlated with \n\n\nW\n0\n\n\n, the former equations indicate that the arbitrary amplitude of \n\n\nW\n0\n\n\n does not impact \n\n\nω\n1\n\n\n. This finding yields the first-order correction of the natural frequency \n\n\nω\n0\n\n\n corresponding to a nonuniform and homogeneous beam.
we have \n\n\n\n\n\n\n\ndf\n1\n\ndξ\n\n\n\n\nd\n2\n\n\nW\n0\n\n\n\nd\n\nξ\n2\n\n\n\n\nW\n0\n\n+\n\nf\n1\n\n\n\n\nd\n3\n\n\nW\n0\n\n\n\nd\n\nξ\n3\n\n\n\n\nW\n0\n\n−\n\nf\n1\n\n\n\n\nd\n2\n\n\nW\n0\n\n\n\nd\n\nξ\n2\n\n\n\n\n\ndW\n0\n\ndξ\n\n\n\n\n0\n1\n\n+\n\n∫\n0\n1\n\n\nf\n1\n\n\n\n\n\n\nd\n2\n\n\nW\n0\n\n\n\nd\n\nξ\n2\n\n\n\n\n2\n\ndξ\n=\n0\n\n.
giving \n\n\n∫\n0\n1\n\n\nf\n2\n\n\nW\n0\n2\n\ndξ\n=\n0\n\n. Then, we obtain \n\n\nω\n1\n\n=\n0\n\n. These values are the properties of the equivalent homogeneous beam having the same frequency (at least up to the first order) as the given nonuniform AFG beam.
\n
The nth natural circular frequency of the AFG beam can be derived as
Each order of frequency of \n\n\nω\n0\n\n\n can be determined by Eq. (16) (in turn, positive numbers from small to large). The required variables have been computed by the above expression. Eq. (25) is an approximate formula for the natural frequencies of variable cross-sectional AFG beams.
\n
In order to show the applicability of this method, we study other supporting conditions, and we can easily get the corresponding boundary conditions of Eqs. (13) and (14). Due to the limited space, the detailed derivation process is omitted, and the final results are shown in Table 1.
Frequency equations and mode shapes for various beams.
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\n
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3.2 Numerical results and discussion
\n
Based on the above analysis, four kinds of AFG beams with various taper ratios are considered, as shown in Figure 2. The numerical simulations are carried out, and the results are compared with the published literature results to verify the validity of the proposed method.
\n
Figure 2.
Geometry and coordinate system of an AFG beam for different taper ratios: (a) case 1, \n\n\nc\nb\n\n=\n\nc\nh\n\n=\n0\n\n; (b) case 2, \n\n\nc\nh\n\n=\n0\n,\n\nc\nb\n\n≠\n0\n\n; (c) case 3, \n\n\nc\nb\n\n=\n0\n,\n\nc\nh\n\n≠\n0\n\n; and (d) case 4, \n\n\nc\nb\n\n≠\n0\n,\n\nc\nh\n\n≠\n0\n\n.
\n
In Figure 2, \n\n\nB\nL\n\n\n and \n\n\nB\nR\n\n\n are the width of the left and right ends of the beams, respectively, and \n\n\nH\nL\n\n\n and \n\n\nH\nR\n\n\n are the height of the left and right ends of the beams, respectively. Here, we assume that the geometric characteristics of AFG beams vary linearly along the longitudinal direction. Therefore, the variation of cross-sectional area \n\nA\n\nx\n\n\n and moment of inertia \n\nI\n\nx\n\n\n along the beam axis can be clearly expressed as follows:
where \n\n\nc\nb\n\n=\n1\n−\n\n\nB\nR\n\n\nB\nL\n\n\n\n and \n\n\nc\nh\n\n=\n1\n−\n\n\nH\nR\n\n\nH\nL\n\n\n\n are the breadth and height taper ratios, respectively. \n\n\nA\nL\n\n\n and \n\n\nI\nL\n\n\n are cross-sectional area and area moment of inertia of the beam left sides, respectively. It is instructive to remember that if \n\n\nc\nb\n\n=\n\nc\nh\n\n=\n0\n\n, the beam would be uniform; if \n\n\nc\nh\n\n=\n0\n,\n\nc\nb\n\n≠\n0\n\n, the beam would be tapered with constant height; if \n\n\nc\nb\n\n=\n0\n,\n\nc\nh\n\n≠\n0\n\n, the beam would be tapered with constant width; and if \n\n\nc\nb\n\n≠\n0\n,\n\nc\nh\n\n≠\n0\n\n, the beam would be double tapered. These four cases are corresponding to Figure 2(a)–(d), respectively. Moreover, the material properties such as Young’s modulus \n\nE\n\nx\n\n\n and mass density \n\nρ\n\nx\n\n\n along the beam axis are assumed as
where \n\n\nE\nL\n\n\n and \n\n\nρ\nL\n\n\n are Young’s modulus and mass density of the beam left sides, respectively.
\n
Based on the introduced analytical equation, the first third-order nondimensional natural frequencies (\n\n\nΩ\nn\n\n=\n\nλ\nn\n\n\nL\n2\n\n\n\n\nρ\nL\n\n\nA\nL\n\n/\n\nE\nL\n\n\nI\nL\n\n\n\n\n) of the four cases of nonuniform AFG beams with different boundary configurations were obtained. The results were listed in Tables 2–7, respectively, and it also was compared with those of published work by Shahba et al. [38].
Nondimensional natural frequencies of the AFG double-tapered beam (case 4); boundary conditions: C-C.
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Table 2 shows the first third-order natural frequencies of the AFG beam, case of Figure 2(a), which is uniform but nonhomogeneous. It can be clearly seen that the analytical results obtained from the asymptotic development method are in good agreement with those given by Ref. [38].
\n
As can be seen from Tables 3 and 4, the first third-order dimensionless natural frequencies of AFG conical beams with only varying width or height are studied, respectively. It is easy to find the following conclusions. This method has higher accuracy on the equal height AFG-tapered beam. When the height changes, there is a certain fractional error in the AFG-tapered beam.
\n
According to Figure 2(d), when the height and width of AFG beams change simultaneously, we can see that AFG beams are not uniform. The natural frequencies of three boundary conditions (free clamping, simply supported, and clamping) are studied in Tables 5, 6, 7. From the data in the table, it can be clearly found that the natural frequencies of AFG beams at low order are in good agreement with Ref. [38], while at high order, there are some errors in the natural frequencies.
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\n
\n
\n
4. The method of Meijer G-function
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\n
4.1 Equation deriving
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In this section, the Meijer G-function is introduced to obtain the formula of the nature frequency of the AFG beam. Here, a special case of AFG beam is considered, where the cross section is uniform. Thus, in Eq. (1), Young’s modulus \n\nE\n\nx\n\n\n and material mass density \n\nρ\n\nx\n\n\n are variable parameters, and the area moment of inertia \n\nI\n\n and the cross-sectional area \n\nA\n\n are invariant. To solve the governing equation, two parameters are firstly introduced to depict the functional gradient parameter equation:
where \n\n\nf\nE\n\n=\n1\n−\n\n\nE\nR\n\n\nE\nL\n\n\n\n, \n\n\nρ\nE\n\n=\n1\n−\n\n\nρ\nR\n\n\nρ\nL\n\n\n\n. \n\n\nE\nL\n\n\n and \n\n\nE\nR\n\n\n are Young’s modulus at the left/right end of the beam, and \n\n\nρ\nL\n\n\n and \n\n\nρ\nR\n\n\n are the mass density at the left/right end of the beam. Eq. (2) is then rewritten as
Based on the vibration theory, we assume \n\nw\n\nx\nt\n\n=\nϕ\n\nx\n\nq\n\nt\n\n\n, where \n\n\nq\nn\n\n\nt\n\n=\n\nA\nn\n\ncos\n\n\nβ\nn\n\n2\n\nt\n+\n\nB\nn\n\nsin\n\n\nβ\nn\n\n2\n\nt\n\n and \n\n\n\nβ\nn\n\n2\n\n\n is the modal frequency for dimensionless. The governing equation is then derived as
Next, Meijer G-function will be used to solve the linear partial differential equation. The general expression of Meijer G-function differential equation is written as
where \n\nm\n,\nn\n,\np\n\n and \n\nq\n\n are integers satisfying \n\n0\n≤\nm\n≤\nq\n,\n0\n≤\nn\n≤\np\n\n, G is the dependent variable also known as the Meijer G-function, z is the independent variable, and \n\n\na\nl\n\n\n and \n\n\nb\nk\n\n\n are real numbers.
\n
A definition of the Meijer G-function is given by the following path integral in the complex plane, called the Mellin-Barnes type:
where an empty product is interpreted as 1, \n\n0\n≤\nm\n≤\nq\n,\n0\n≤\nn\n≤\np\n\n, and the parameters are such that none of the poles of \n\nΓ\n\n\n\nb\nj\n\n−\nξ\n\n\n,\n\n\n\nj\n=\n1\n…\nm\n\n\n\n coincides with the poles of \n\nΓ\n\n\n1\n−\n\na\nj\n\n+\nξ\n\n\n,\n\n\nj\n=\n1\n…\nn\n\n\n\n. Where \n\ni\n\n is a complex number such that i2\n\n=\n\n −1.
\n
A special case of Eq. (31) can be expanded by assuming \n\nn\n=\np\n=\n0\n\n and \n\nq\n=\n4\n\n. We can get that
Because of the difficulty of solving the differential equation with variable coefficients, we can simplify Eq. (35). Let \n\n1\n−\n\nf\nE\n\nx\n=\n1\n−\n\nf\nρ\n\nx\n=\n1\n−\nFx\n\n; it can be rewritten as
In order to solve the above equation, the coefficients of the ordinary differential Eqs. (33) and (36) are the same, so we can calculate the corresponding values, as shown in Table 8.
\n
\n
\n
\n
\n
\n
\n\n
\n
Case
\n
\n\n\n\nb\n1\n\n\n\n
\n
\n\n\n\nb\n2\n\n\n\n
\n
\n\n\n\nb\n3\n\n\n\n
\n
\n\n\n\nb\n4\n\n\n\n
\n
\n\n\n
\n
1
\n
1/2
\n
1/4
\n
0
\n
1/4
\n
\n
\n
2
\n
1/4
\n
1/4
\n
0
\n
1/2
\n
\n
\n
3
\n
0
\n
1/4
\n
1/2
\n
1/4
\n
\n
\n
4
\n
1/2
\n
0
\n
1/4
\n
1/4
\n
\n
\n
5
\n
0
\n
1/2
\n
1/4
\n
1/4
\n
\n
\n
6
\n
0
\n
1/4
\n
1/4
\n
1/2
\n
\n
\n
7
\n
1/4
\n
0
\n
1/4
\n
1/2
\n
\n
\n
8
\n
1/4
\n
1/2
\n
0
\n
1/4
\n
\n
\n
9
\n
1/4
\n
0
\n
1/2
\n
1/4
\n
\n\n
Table 8.
Possible case of unknown constant \n\n\nb\nk\n\n\n of Meijer G-function equation.
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One set of data can be selected from Table 8 and expressed in the form of closed solutions of Meijer G-function:
Based on the above analysis, the natural frequencies of beams under different boundary conditions can be solved. Meanwhile, the results of finite element method are also conducted to verify the accuracy of the analytical results. Here, we use the power law gradient of the existing AFG beams [44], and the material properties of AFG beams change continuously along the axial direction. Therefore, the expressions of Young’s modulus \n\nE\n\nx\n\n\n and mass density \n\nρ\n\nx\n\n\n are listed in detail:
where \n\n\nY\nL\n\n\n and \n\n\nY\nR\n\n\n denote the corresponding material properties of the left and right sides of the beam, respectively. \n\nα\n\n is the gradient parameter describing the volume fraction change of both constituents involved. When gradient parameter \n\nα\n\n is equal and less than zero, Young’s modulus and mass density at the left end are less than those at the right end. When \n\nα\n\n equals zero, the beam is equivalent to a uniform Euler-Bernoulli beam, and Young’s modulus and mass density of the beam do not change with the length direction of the beam.
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The variation of \n\nY\n\nx\n\n\n along the axis direction of the beam can be shown in Figure 3 for \n\n\nY\nR\n\n=\n3\n\nY\nL\n\n\n. In order to show the practicability of this method, we choose the existing materials to study. The materials of AFG beams are composed of aluminum (\n\nAl\n\n) and zirconia (\n\n\nZrO\n2\n\n\n).The left and right ends of the beam are pure aluminum and pure zirconia, respectively. The material properties of AFG beams are given in detail in Table 9. We choose the sizes of commonly used beams which are L = 0.2 m, B = 0.02 m, and H = 0.001 m.
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Figure 3.
Variation of the material properties defined by Eq. (46) with \n\n\nY\nR\n\n=\n3\n\nY\nL\n\n\n.
In order to verify the correctness of this method, some finite element simulation software is used to verify its correctness. In this paper, we analyze the natural frequencies of uniform AFG beams under different boundary conditions. In the process of finite element analysis, the AFG beam is transformed into a finite length model by using the delamination method [85]. At the same time, the AFG beam is delaminated along the axial direction. As shown in Figure 4, the material properties change along the axial direction, and the material properties of the adjacent layers are different. In order to analyze the performance of the beam, the uniform element is used to mesh each layer. In order to make the natural frequencies of AFG beams more precise, we can increase the number of layers and refine the finite element meshes.
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Figure 4.
Finite segment model of the AFG beam.
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In the Meijer G-function method, in order to solve the linear natural frequencies of beams under different boundary conditions, the determinant of the coefficient matrix of Eqs. (42)–(45) is equal to zero. Finally, linear natural frequencies of beams with different boundary conditions of the first four orders are listed in Table 10.
\n
\n
\n
\n
\n
\n
\n
\n
\n
\n
\n
\n\n
\n
F
\n
Order
\n
C-F
\n
C-P
\n
S-S
\n
C-C
\n
\n
\n
Present
\n
FEM
\n
Present
\n
FEM
\n
Present
\n
FEM
\n
Present
\n
FEM
\n
\n\n\n
\n
\n\n\nα\n=\n0.9\n\n\n
\n
1
\n
2.4641
\n
2.4651
\n
4.0787
\n
4.0789
\n
3.0888
\n
3.0891
\n
4.5585
\n
4.5579
\n
\n
\n
2
\n
5.2251
\n
5.2265
\n
7.1520
\n
7.1516
\n
6.2895
\n
6.2893
\n
7.6920
\n
7.6908
\n
\n
\n
3
\n
8.2540
\n
8.2560
\n
10.2762
\n
10.2778
\n
9.4410
\n
9.4420
\n
10.8549
\n
10.8560
\n
\n
\n
4
\n
11.3209
\n
11.324
\n
13.4075
\n
13.4092
\n
12.5854
\n
12.5869
\n
14.0136
\n
14.0148
\n
\n
\n
\n\n\nα\n=\n0.5\n\n\n
\n
1
\n
2.0774
\n
2.0772
\n
4.0055
\n
4.0056
\n
3.1344
\n
3.1344
\n
4.7098
\n
4.7096
\n
\n
\n
2
\n
4.8497
\n
4.8491
\n
7.1104
\n
7.1100
\n
6.2859
\n
6.2861
\n
7.8364
\n
7.8360
\n
\n
\n
3
\n
7.9496
\n
7.9501
\n
10.2396
\n
10.2409
\n
9.4278
\n
9.4294
\n
10.9827
\n
10.9836
\n
\n
\n
4
\n
11.0455
\n
11.0652
\n
13.3748
\n
13.3760
\n
12.5668
\n
12.5707
\n
14.1256
\n
14.1273
\n
\n
\n
\n\n\nα\n=\n1.7\n\n\n
\n
1
\n
1.6098
\n
1.6104
\n
3.7738
\n
3.7738
\n
3.1279
\n
3.1277
\n
4.6896
\n
4.6897
\n
\n
\n
2
\n
4.4786
\n
4.4792
\n
6.9816
\n
6.9816
\n
6.2887
\n
6.2884
\n
7.8189
\n
7.8187
\n
\n
\n
3
\n
7.7326
\n
7.7332
\n
10.1477
\n
10.1490
\n
9.4315
\n
9.4325
\n
10.9679
\n
10.9696
\n
\n
\n
4
\n
10.9067
\n
10.9079
\n
13.3045
\n
13.3042
\n
12.5726
\n
12.5737
\n
14.1139
\n
14.1158
\n
\n
\n
\n\n\nα\n=\n2.7\n\n\n
\n
1
\n
1.5370
\n
1.5377
\n
3.7214
\n
3.7217
\n
3.1188
\n
3.1212
\n
4.6629
\n
4.6630
\n
\n
\n
2
\n
4.4142
\n
4.4142
\n
6.9470
\n
6.9471
\n
6.2907
\n
6.2904
\n
7.7947
\n
7.7948
\n
\n
\n
3
\n
7.6920
\n
7.6931
\n
10.1207
\n
10.1222
\n
9.4350
\n
9.4360
\n
10.9482
\n
10.9497
\n
\n
\n
4
\n
10.8759
\n
108,772
\n
13.2807
\n
13.2823
\n
12.5762
\n
12.5774
\n
14.0972
\n
14.0988
\n
\n\n
Table 10.
Comparisons between FEM and numerical calculation of linear dimensionless natural frequencies of AFG beams with different boundary conditions.
\n
From Table 10, we can see that the results of finite element method are similar to those of Meijer G-function and the error is small. This can prove the accuracy of the method in frequency calculation on the one hand. In Figure 5, we can find that the first third-order dimensionless natural frequencies of C-F beams are in good agreement with FEM and numerical calculation. With the gradual increase of gradient parameter F, the dimensionless natural frequency of C-F beam increases gradually, and the change speed is accelerated. At the same time, the FEM and numerical simulation errors are very small, so the precise linear natural frequencies can be obtained.
\n
Figure 5.
Dimensionless natural frequencies of C-F beams vary with parameter F: (a) fundamental frequencies, (b) second-order frequencies, and (c) third-order frequencies.
\n
\n
\n
\n
5. Conclusions
\n
FGMs are innovative materials and are very important in engineering and other applications. Despite the variety of methods and approaches for numerical and analytical investigation of nonuniform FG beams, no simple and fast analytical method applicable for such beams with different boundary conditions and varying cross-sectional area was proposed. In this topic, two analytical approaches, the asymptotic perturbation and the Meijer G-function method, were described to analyze the free vibration of the AFG beams.
\n
Based on the Euler-Bernoulli beam theory, the governing differential equations and related boundary conditions are described, which is more complicated because of the partial differential equation with variable coefficients. For both the asymptotic perturbation and the Meijer G-function method, the variable flexural rigidity and mass density are divided into invariant parts and variable parts firstly. Different analytical processes are then carried out to deal with the variable parts applying perturbation theory and the Meijer G-function, respectively. Finally, the simple formulas are derived for solving the nature frequencies of the AFG beams with C-F boundary conditions followed with C-C, C-S, and C-P conditions, respectively. It is observed that natural frequency increases gradually with the increase of the gradient parameter.
\n
Accuracy of the results is also examined using the available data in the published literature and the finite element method. In fact, it can be clearly found that result of the APM is more accurate in low-order mode, which is caused by the defect of the perturbation theory. However, the APM is simple and easily comprehensible, while the Meijer G-function method is more complex and unintelligible for engineers. In general, the results show that the proposed two analytical methods are efficient and can be used to analyze the free vibration of AFG beams.
\n
\n
Acknowledgments
\n
The authors gratefully acknowledge the support of the National Natural Science Foundation of China (Grant Nos. 11672008, 11702188, and 11272016).
\n
\n',keywords:"axially functionally graded beams, free vibration, natural frequency, asymptotic perturbation method, Meijer G-function, finite segment model",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/66810.pdf",chapterXML:"https://mts.intechopen.com/source/xml/66810.xml",downloadPdfUrl:"/chapter/pdf-download/66810",previewPdfUrl:"/chapter/pdf-preview/66810",totalDownloads:1190,totalViews:0,totalCrossrefCites:1,totalDimensionsCites:1,totalAltmetricsMentions:0,introChapter:null,impactScore:0,impactScorePercentile:41,impactScoreQuartile:2,hasAltmetrics:0,dateSubmitted:"November 6th 2018",dateReviewed:"March 14th 2019",datePrePublished:"April 22nd 2019",datePublished:"January 8th 2020",dateFinished:"April 22nd 2019",readingETA:"0",abstract:"Axially functionally graded (AFG) beam is a special kind of nonhomogeneous functionally gradient material structure, whose material properties vary continuously along the axial direction of the beam by a given distribution form. There are several numerical methods that have been used to analyze the vibration characteristics of AFG beams, but it is difficult to obtain precise solutions for AFG beams because of the variable coefficients of the governing equation. In this topic, the free vibration of AFG beam using analytical method based on the perturbation theory and Meijer G-Function are studied, respectively. First, a detailed review of the existing literatures is summarized. Then, based on the governing equation of the AFG Euler-Bernoulli beam, the detailed analytic equations are derived on basis of the perturbation theory and Meijer G-function, where the nature frequencies are demonstrated. Subsequently, the numerical results are calculated and compared, meanwhile, the analytical results are also confirmed by finite element method and the published references. The results show that the proposed two analytical methods are simple and efficient and can be used to conveniently analyze free vibration of AFG beam.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/66810",risUrl:"/chapter/ris/66810",book:{id:"8844",slug:"mechanics-of-functionally-graded-materials-and-structures"},signatures:"Dongxing Cao, Bin Wang, Wenhua Hu and Yanhui Gao",authors:[{id:"283678",title:"Prof.",name:"Dongxing",middleName:null,surname:"Cao",fullName:"Dongxing Cao",slug:"dongxing-cao",email:"caostar@bjut.edu.cn",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"295692",title:"Mr.",name:"Bin",middleName:null,surname:"Wang",fullName:"Bin Wang",slug:"bin-wang",email:"bjutwangbin@163.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Beijing University of Technology",institutionURL:null,country:{name:"China"}}},{id:"295693",title:"Dr.",name:"Wenhua",middleName:null,surname:"Hu",fullName:"Wenhua Hu",slug:"wenhua-hu",email:"huwenhua@tjut.edu.cn",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Tianjin University of Technology",institutionURL:null,country:{name:"China"}}},{id:"295694",title:"Mr.",name:"Yanhui",middleName:null,surname:"Gao",fullName:"Yanhui Gao",slug:"yanhui-gao",email:"gyhhxs@163.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Beijing University of Technology",institutionURL:null,country:{name:"China"}}}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Governing equation of the AFG beam",level:"1"},{id:"sec_3",title:"3. Asymptotic perturbation method",level:"1"},{id:"sec_3_2",title:"3.1 Equation deriving",level:"2"},{id:"sec_4_2",title:"3.2 Numerical results and discussion",level:"2"},{id:"sec_6",title:"4. The method of Meijer G-function",level:"1"},{id:"sec_6_2",title:"4.1 Equation deriving",level:"2"},{id:"sec_7_2",title:"4.2 Numerical results and discussion",level:"2"},{id:"sec_9",title:"5. Conclusions",level:"1"},{id:"sec_10",title:"Acknowledgments",level:"1"}],chapterReferences:[{id:"B1",body:'Nie GJ, Zhong Z, Chen S. Analytical solution for a functionally graded beam with arbitrary graded material properties. Composites Part B: Engineering. 2013;44(1):274-282. DOI: 10.1016/j.compositesb.2012.05.029'},{id:"B2",body:'Nguyen DK. Large displacement response of tapered cantilever beams made of axially functionally graded material. Composites Part B: Engineering. 2013;55(9):298-305. 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College of Mechanical Engineering, Beijing University of Technology, China
Beijing Key Laboratory of Nonlinear Vibrations and Strength of Mechanical Structures, China
College of Mechanical Engineering, Beijing University of Technology, China
Beijing Key Laboratory of Nonlinear Vibrations and Strength of Mechanical Structures, China
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1. Introduction
Nodding syndrome (NS) is a devastating childhood neurological disorder of uncertain nosology [1]. The syndrome is characterized by atonic seizures, head nodding, cognitive decline, muscle weakness, school dropout, thermal dysfunction, internal displacement, food insecurity, wasting, stunted growth, exposures to infectious diseases, contaminated environment and with a number of repetitive behavioral abnormalities [1, 2]. It occurs in clusters in three Eastern African countries (Uganda, Tanzania and South Sudan) and has spatial temporality and clustered in time (during IDP period), space (clustered on either sides of the two main rivers of Aswa and Pager) and person (mainly at 5–15 years of age at onset) particularly in Northern Uganda [3]. The syndrome was first described in 1st scientific meeting organized by the Ugandan Ministry of Health (MOH) and World Health Organization (WHO) in Sheraton, Kampala, Uganda in 2012 [4]. The outcome of the meeting was the agreed WHO epidemiological and surveillance case definition of probable nodding syndrome [5, 6]. It states, “Probable NS cases should meet the following criteria:
Reported head nodding in a previously normal person who have been observed and recorded by a trained healthcare worker.
Head nodding is defined as repetitive, involuntary drops of the head to the chest on two or more occasions.
Age at onset of nodding between 3 and 18 years old.
Frequency of nodding 5 to 20 per minute.
Plus at least one of the following criteria:
Other neurological abnormalities (cognitive decline, school dropout due to cognitive/behavioral problems, other seizures or neurological abnormalities).
Clustering in space or time with similar cases.
Triggered by food and/or cold weather.
Stunting or wasting.
Delayed sexual or physical development.
Psychiatric symptoms.”
In addition, it has been observed that nodding episodes were stimulated by sights of local food, starvation, exposure to cold weather/temperatures, cold water, stress, physical exercises and there was an association with high anion gap and that most NS began in the internally Displaced Peoples camps (IDPs) or immediately after resettlement into the satellite camps and eventually to their original villages [1, 2, 3, 4, 5]. Researchers propose that NS is an emerging neurological disorder in Eastern Africa likely due to factors that were experienced during the IDPs [1, 3, 4, 5] and that no new NS cases have been reported since 2012 by the Ugandan Ministry of Health (MOH) and WHO after the IDP camps were disbanded and the affected communities resettled in their villages [1, 3, 5].
Some authors have suggested that nodding syndrome may perhaps be similar to a psychogenic disease (psychogenic illness) in which physical illnesses that are believed to arise from emotional or mental stressors or from psychological or psychiatric disorders may have resulted from the 20 year old civil war that occurred in Northern Uganda. Psychogenic diseases are most commonly applied to illnesses where there is a physical abnormality and other biomarker has not yet been identified as observed in children with NS. Interestingly, the onset of NS perhaps has some similarities to a mass psychogenic illness which involves rapid spread of illness, signs and symptoms affecting a cohesive group originating from a nervous system disturbance involving seizures, loss/reduction of cognitive function with emotional and behavioral abnormalities.
However, findings in NS children contrasts greatly from epidemic hysteria, psychogenic contagion, imitation as perhaps observed among some NS families where two or more children in the same family were affected with the syndrome. Important to note was that all the children that developed NS in the same family did not show evidence of hysterical behavior but physical signs and symptoms that seems to arise from a common experience during the IDPs. Each NS child’s presentation vary from each other and perhaps reflecting the spectrum nature of NS occurrence from the most severe to mild form. It was also noted that the course of the NS illness was greatly altered and improved by early initiation of medical intervention on the affected NS child.
The most recent findings through an extensive histoimmunochemistry of brains of deceased nodding syndrome children have revealed that Nodding Syndrome is a tauopathy [7]. This draws more attention to the possibility of diet and environmental exposures of NS children as the likely source of the pathology [3].
Interestingly, all communities where NS occur at epidemic proportion experienced some degree of internal displacement before the onset of NS [2, 3, 5]. In addition, there is a widely held belief among the affected communities in Northern Uganda that NS had possibly originated from contaminated relief food provided during IDPs or exposure to war munitions/chemicals during the protracted 20 year old war in Northern Uganda between the rebel, Lord’s Resistance Army (LRA) and the Government of Uganda where 90% of the population in Acholi were displaced into IDPs [8, 9]. Some studies have reported consumption of spoiled relief foods by NS children while in IDPs but there are no mentions of the proportions of NS children that ate it [10, 11, 12, 13, 14]. Furthermore, Researchers have extensively investigated cause(s) of NS due to infectious agents but with no single cause that have so far been confirmed [1, 10]. In particular, studies from Northern Uganda have identified high Anion gap metabolic acidosis among NS children compared to their sex and age matched controls [1, 6, 10, 15]. These findings suggested perhaps that NS could be secondary to a metabolic disorder and perhaps a mitochondrial disorder [1, 6, 10, 15]. In addition, researchers observed that nodding episodes were precipitated by sights of local food, starvation, exposure to cold weather/temperatures or cold water, stress, excess physical exercises and there was a statistically significant association with high anion gap [1, 6, 10, 15]. Other researchers suggested that since the IDPs were disbanded, no new NS cases were reported when the affected communities resettled in their villages and feed on their home grown foods [2, 6, 8, 15] an indication that perhaps the factors that led to the onset of the syndrome were removed by moving the communities from the agents that may have been involved in its etiology.
In a recent case control study, researchers found a statistically significant association between NS and biotinidase and acetyl carnitine deficiencies [16]. In addition, other studies had previously observed a deficiency in Vitamin B6 [15] and Vitamin D in NS children [17, 18]. All these findings may suggest perhaps that NS could be secondary to a metabolic disorder and perhaps a mitochondrial disorder may be one of the factors [1, 3, 4, 5, 6, 10, 16]. Interestingly, recent data on NS children in a study conducted by a team of researchers from the US funded by National Institute of Health (NIH) suggested an association between NS with cerebrospinal fluid (CSF) VGKC antibodies [19] and serum leiomidin-1 antibody, suggesting a neuroinflammatory cause [20]. All these findings give credence to an emerging neurological disorder which is devastating the lives of many young people in Eastern Africa and that there is no single identifiable marker and that management and prevention strategies have remained elusive.
On the other hand, autism spectrum disorders (ASD) is a group of behaviorally defined neurodevelopmental disorders with lifelong consequences [21]. They are defined by impairments in communication and social interaction along with restrictive and repetitive behaviors [21]. Autism spectrum disorder is now estimated to affect 1 out of 68 individuals in the United States with approximately four times more males than females being affected [22]. Although ASD is behaviorally defined, children with ASD also have many co-occurring medical conditions such as gastrointestinal abnormalities [23], seizures and epilepsy [24], attention deficits [25], anxiety disorders [26] and allergies [27]. It is reported that one of the most significant co morbidities associated with ASD that causes significant disability is epilepsy [28] and a number of studies have suggested that epilepsy affects a high proportion of individuals with ASD [28]. In addition, a number of risk factors for autism can be categorized as risk factors for inflammation or indicators of inflammation [28] which seems to be similar to the factors suggested in the etiology of nodding syndrome.
2. Nodding syndrome and displacement into IDP camps
Several epidemiological studies in Uganda show NS clustered in time (IDP camp period); space (Geographically located on either side of two major rivers (Aswa & Pager) and in person (NS onset is mainly between ages of 5–15 years) [2, 3, 29]. There is an association between life in the IDP camps and onset of NS [2, 3, 4, 29]. Historically from 1986 to 2007/2008, Northern Uganda experienced a civil war between the Ugandan Army and rebel groups [2, 30]. Starting in mid-1990s, IDP camps were established in some parts of Northern Uganda with the goal of protecting the population and with an estimated 285,000 people from Kitgum District displaced into IDPs [2, 31, 32]. In the period before displacement into IDPs, there were no reported cases of NS [2]. Similarly in 2001, another community of Aromowanglobo in Awere sub county, Gulu District were moved into IDPs where many of them became dependent on food rations supplied by the relief agencies [3, 33]. IDP camps became associated with malnutrition, social norm breakdown, rising incidence of alcoholism, mental health disorders, suicidal tendencies, increasing prevalence of HIV, Cholera, Hepatitis B & E and other infectious diseases, neglect and waste of the youths [2, 3, 4, 29]. The IDPs began to be disbanded in late 2006 when the LRA retreated to South Sudan but during the height of the insurgency in 2002 over 1.5 million people were displaced in the Acholi sub region and thus accounting for over 90% of the population [31, 32]. After 2007, the Government began returning the displaced people into their homes in a phase-wise approach from the main IDPs to satellite camps near their villages [2, 31, 32]. Eventually by 2010, the communities were returned to their original homes in their farmland where the returnees were to settle and rebuild their lives [2, 3, 4, 31, 32].
In 2009, the Ugandan Ministry of Health (MOH) identified NS in communities in Northern Uganda and later on established NS screening and rehabilitation centers in 2012 where NS children were treated with anticonvulsants, multivitamins and nutritional supplements [3, 5, 6, 10, 19, 29]. The consistency of supplies and rehabilitation processes faced challenges including irregular supply of anticonvulsants and food for NS children and the vulnerable families [2, 8, 9, 31, 32]. In the same period, there was an apparent relationship between the peaks of NS cases in Kitgum District and earlier peak influxes of households into IDPs [2] which was similarly observed in Awere Sub County in Gulu district [3]. Important to note was that the 1997 peak influx of IDPs in Kitgum District was followed 7 years later by an elevated number of new NS cases in 2004 (2003–2005) and similarly in the 2003 large influx of households had a larger peak in new NS cases 5 years later in 2008 [2]. This was similarly observed in Awere in Gulu where the 2001–2002 influxes were followed with increased incidences of NS, 7 years later in 2008–2009 [3]. The peaks of reported NS onset correlated with peaks of household displacement and food insecurity, where residents were heavily dependent on food aid from relief agencies [2, 3, 29, 31, 32, 33, 34]. The IDP camps were exceptionally poor, insecure, unsanitary, with overcrowding, violence, food insecurity and squalid, and morbidity and mortality rates were high [2, 35].
In 2005, a Government survey of Kitgum district estimated an IDP population of 310,111 persons; 21% of whom were children under 5 years [2]. At the time of the survey, over 66% of children were reported to have been ill sometime in the previous 2 weeks and the crude mortality rates were reported to be 2 deaths per 10,000 per day and double that rate for children under the age of 5 years [2, 29, 35]. In addition, the top self-reported causes of death in IDPs were malaria/fever (34.7%), AIDS (15.1%) and violence (10.5%) [2] and water was obtained from protected sources but water intake was low and the waiting time was high and the infant feeding practices were poor [2]. It is reported that for children under the age of 5 years, the traditional disease concept of “Two Lango” or “Gin pa Omiru” which was a combination of oral thrush, malnutrition and diarrhea was the second most commonly reported causes of death [2, 34]. These findings were thorough analysis of the events in all IDPs across the Acholi and Lango sub regions where NS occurred at epidemic proportions.
3. Epidemiological, environmental and dietary findings on nodding syndrome children
Studies show that NS in Awere, Gulu district, Northern Uganda was first noted in 2002 which corresponded with 1 year stay in IDPs [3]. The month of peak incidence of NS onset was April and October [3]. These peaks corresponded fairly with the peaks of monthly average rainfall for 1st and 2nd rainy seasons [3] and related to scarcity of food as observed by Landis et al. [2]. The factors around the syndrome onset could have perhaps been in IDPs since all NS children were in IDPs before onset of nodding [2, 3, 29]. The other reason could perhaps be that NS children who were born before IDPs, had developed NS earlier except, the condition was not detected or overtly manifested but that the IDP camp conditions precipitated its overt manifestation perhaps coupled with other stressor factors such as Onchocerca Volvulus (OV) infection; malnutrition, war trauma and febrile illnesses [1, 2, 3, 4, 5, 29]. In addition, most NS children were in 1st, 2nd and 3rd birth orders in descending orders respectively [3, 5] and all of them experienced IDP life which peaked at 5 years of IDP stay [3]. Additionally, most NS children have other siblings with NS and its occurrence in siblings mirrored NS children’s birth orders [3]. This finding, perhaps point towards a possibility of an acquired disease which was overtly manifested possibly as a result of family/household factors such as; poor storage of food leading to contamination and/or infection with OV or stress which made the syndrome perhaps manifestly overt on exposure to these factors [3, 5]. Perhaps the perfect examples of such could be seen in deficiencies of metabolites in acquired diseases whose disease occurrence becomes overtly expressed in circumstances of stress [36]. That could perhaps explain why there are no new NS cases since 2012 when the communities were resettled in their villages and feed on their own home grown foods [3, 19, 29, 37].
In general, the information provided by parents of NS children show that NS children were all reported to have been born normal and that the developmental milestones were normal until NS began [1, 3, 5, 29, 37, 38]. Before onset of nodding, food listed in [3, 5] were the supplementary and weaning foods that were supplied by relief agencies and eaten by the IDPs residents including NS children [31]. The quantity and duration of these food ration eaten by each NS child could however, not be determined but report on it was provided by the World Food Program (WFP) [31, 32].
Interestingly in 2012 when some NS children were examined before admission to the Hope for HumaNs (HfH) centre for NS rehabilitation, they were diagnosed mostly with Severe Acute Malnutrition (SAM) and a few with Moderate Acute Malnutrition (MAM) respectively on the basis of their z-scores [38]. Upon enrolment for a multidisciplinary and syndromic treatment with anticonvulsants, multivitamins, local food supplements, and psychosocial support; their health conditions greatly improved, seizure frequency reduced, mental health status improved, cognitive impairment improved, they gained weight and height and by 2014 when the author re-assessed these NS children in a longitudinal study, most of them had improved and categorized as MAM and healthy nutritionally [5, 29, 38, 39]. This observation was perhaps due to good feeding program at the HfH centre and adequate rehabilitation processes accorded to NS children. However, much as they had improved and some had returned to school, none of them could be declared cured because they still experienced sporadic episodes of nodding, emotional and perceptual disturbances and some cognitive impairment [5, 10, 29, 38, 39].
4. Biotinidase and acetyl carnitine deficiency, nodding syndrome and metabolic disorder
In one of the pilot studies conducted on NS children in Northern Uganda, it was observed that most NS children demonstrated a deficiency of biotinidase enzyme activity ranging from 0 to 100% [16]. The average percentage deficiency was 78% (78 SD ± 13.362), an indication that this enzymatic deficiency was a spectrum which varied considerably from one NS child to another depending on the percentage deficiency of biotinidase activity [40, 41, 42, 43] just like the severity and clinical presentations of NS varied from one child to another [5]. Biotinidase deficiency has commonly been classified as partial or profound deficiency whereby the clinical presentations and occurrence depended on the percentage deficiency and the presence of stressor factors [40, 41, 42, 43]. It is reported that partial biotinidase deficiency is a milder form of this condition in which without treatment with biotin, the affected child may experience hypotonia, skin rashes and hair loss, but these problems may appear only during illness, infections, or other times of stress [40, 41, 42, 43]. These authors suggest that NS occurs as a spectrum similarly to biotinidase deficiency and that for NS children that had partial biotinidase deficiency, they experienced severe stress (Malnutrition, psychological stress and OV infection) that resulted into the overt presentation of NS [16]. The stressors in this case could have perhaps been the IDP camp life, where there was inadequate food for consumption (with resultant malnutrition) [31, 32, 35] or infection with Onchocerca volvulus which afflicted nearly 80% of NS children or psychological stress [1, 4, 17]. Other stressors could have been severe illnesses such as malaria, meningitis, cholera and others which were common in the IDP camps and affected a large number of IDP residents [2, 35, 44]. On the other hand profound biotinidase deficiency is a more severe and can cause seizures, weak muscle tone (hypotonia), breathing problems, hearing and vision loss, problems with movement and balance (ataxia), skin rashes, hair loss (alopecia) and fungal infection particularly candidiasis [40, 41, 42, 43]. The affected children with biotinidase deficiency also have delayed development miles stones [40, 41, 42, 43]. Most of these symptoms and signs were similarly observed in NS children in Northern Uganda.
The clinical presentations of NS children examined in 2012 and repeated in 2014 as part of a longitudinal study are similar to the clinical presentations of biotinidase deficiency [39]. However, hearing and vision loss which are typically seen in profound biotinidase deficiency were not observed in 2014 perhaps due to 2 years of rehabilitation where it is suspected that the symptoms and signs which were akin to profound biotinidase activity deficiency could not all be observed [39]. It is important to note that biotinidase functions by recycling the vitamin biotin which is also known as vitamin B7 and it is bound to amino groups of lysine residues of apoenzymes [41, 42, 43, 45]. If levels of serum biotinidase are low then biotin cannot be broken down and released from proteins into the diet [41, 42, 43, 45]. In addition, biotin serves as a coenzyme for four carboxylases enzymes; propionyl-CoA carboylases & β-methyl crotonyl-CoA carboxylases, which are important in protein catabolism; pyruvate carboxylases, which are essential for gluconeogenesis and acetyl CoA carboxylases, which are involved in the first step in fatty acid synthesis [42, 45]. Similarly, the majority of the NS children had deficiency of the acetyl carnitine, a metabolite responsible for the transfer of short chain fatty acids into the mitochondrium for metabolism and this perhaps represented the view that at the time of stress, NS children were unable to utilize the short chain fatty acids and perhaps with the resultant observed clinical features. Similarly, a previous study had noted a near significant association between NS and pyridoxine deficiency (Bunga’s study (p = 0.06)) [11].This finding was very important as seizures are normally associated with abnormal pyridoxine metabolism [11].
In the same study, the levels of serum urate were overall unremarkable, demonstrating that NS wasn’t perhaps associated with abnormalities involving purine or pyrimidine metabolism [16]. The urate/creatinine ratio levels were lower than normal range, suggesting that NS was not probably associated with rhabdomyolysis [16]. In addition, it was previously observed by another author that NS was associated with vitamin D deficiency in which 7 out of 8 NS cases had reported vitamin D deficiency [17]. Furthermore, findings from other studies indicate that the levels of organic acid in urine were generally high and this was consistent with other findings of high anion gap metabolic acidosis seen in NS patients in a case control study [1]; case series [17]; case reports [10, 15] and clinical studies [39].
Therefore, NS in South Sudan & Northern Uganda represents an emerging neurological disorder where investigations searching for potential environmental toxins have not yet been fully conducted [4, 29, 46]. It is reported that thousands of pesticides, solvents and other industrial chemicals have not been tested for neurodevelopmental toxicity in the community where NS occurs at epidemic proportions [46]. Historically, it has taken several decades of scrutiny to confirm developmental neurotoxicity secondary to industrial chemicals following initial clinical diagnosis of poisoning [47]. In South Sudan in 2011, CDC study collected urine and blood and did analysis for heavy metals; however the preliminary analysis of blood and urine results remains unpublished [48]. Bunga’s (2011) Sudanese unpublished study mentioned in Dowell et al.’s study, found no abnormality detected in the urine for mercury, thiocyanate and arsenic [11]. Foltz et al., tested serum for copper and urine for homocysteine & thiocyanate levels [49]; Sevjar et al. reported to have had an unremarkable toxin analysis (data not shown) [50]. The vast majority of investigations into possible neurotoxic causes to NS children came from information regarding diet, collected via questionnaires from NS caregivers [14, 18, 46, 51, 52, 53, 54]. There have been associations that have been demonstrated between eating red sorghum and NS in a South Sudan study [46]. It has also been further reported that there is an unidentified associated with mycotoxins which was suggested as a likely putative agent [4, 29, 46]. Interestingly to date, there is no published laboratory microbiological or neurotoxicological analysis of food that was eaten in the IDPs camps to confirm these hypotheses. Further to this, NS in South Sudan and Northern Uganda is suspected to be caused by a chemical neurotoxin from war munitions used during the civil wars [8, 9, 46]. However, there are no published studies investigating quantifiable war munitions and/or chemicals as possible cause(s), despite several case control studies demonstrating a positive association with exposure to war munitions and gun raids [11, 46, 49]. However, a recent case series in Northern Uganda found that all NS children had been exposed to either severe war-related psychological and physical trauma and that most of those interviewed in an observational study laid blame on war munitions/chemicals [8, 55]. These findings showed that the environmental exposures of the affected communities were reported although not proven but still forms a basis for hypothesis that it could be a factor that could not be ignored in the epidemiology of NS in Northern and South Sudan.
5. Experience of treatment and rehabilitation of children with nodding syndrome
The treatment and rehabilitation responses of NS children in Northern Uganda by Hope for HumaNs (HfH) has registered positive outcome with improved mid upper arm circumference (MUAC), height, weight and hematological indices [39]. The comprehensive rehabilitation approach (correcting protein-energy using MAMA nutritional food supplements and vitamin-related malnutrition, de-worming, oral fungicide, anti-seizure medications (sodium valproate with/or without Carbamazepine); close monitoring; tailored dosing and adjustments; special needs education program; counseling) pioneered by HfH at Odek rehabilitation centre has proven clinically transformative (steady growth, improved emotional and marked seizure reduction status—though greater among males than females for unknown reasons) [3, 4, 38]. It was still noted though that cognitive, behavioral problems and social difficulties still confronted these NS children even 9 months after rehabilitation at the HfH centre [39].
6. Nodding syndrome (NS), biotinidase and acetyl carnitine deficiency and autism spectrum disorder (ASD)
Although autism spectrum disorder (ASD) was originally thought to be a static, inheritable neurodevelopmental disorder, its understanding is currently undergoing a major shift [45]. It is now emerging as a dynamic system of metabolic and immune anomalies involving many organ systems, including the brain and environmental exposures [45, 56]. The initial detailed observation and inquiry on patients with ASD and related conditions, the histories of their caregivers and families have been providing important information [45]. To date, it is not yet clear how gastrointestinal (GI) factors are related to ASD [45, 56] however, many patients with ASD have a history of previous antibiotic exposure or hospitalization, GI symptoms, abnormal food cravings and unique intestinal bacterial populations, which have been proposed to relate to variable symptom severity [45, 57]. An author recently recommended that new approaches would be required to examine the diverse symptoms and co morbidities of this growing family of neurodevelopmental disorders known as autism spectrum disorder [45]. It is reported that neurochemical changes which is consistent and predictive with findings in ASD patients, including neuroinflammation, increased oxidative stress, mitochondrial dysfunction, glutathione depletion and altered phospholipids/acylcarnitine profiles, have been observed [45, 57]. In addition, propionic acid have been reported to have bioactive effects on; neurotransmitter systems; intracellular acidification and calcium release; fatty acid metabolism; gap junction gating; immune function and alteration of gene expression that warrant further exploration [45]. Furthermore, other authors have proposed that traditional scientific experimentation was required to verify the hypothesis that enteric short-chain fatty acids may be a potential environmental trigger in some forms of ASD [45, 56, 58]. Interestingly, the collaborative developments in systems biology particularly examining the role of microbiome and its effects on host metabolism, immune and mitochondrial function and gene expression, is reported to hold a great promise in investigation on ASD [23, 45, 58, 59, 60, 61]. It is further suggested that the microbiome produces an array of bioactive metabolic products capable of entering systemic circulation [23, 45, 61]. Other authors have suggested that enteric microbiome and its metabolic products were dynamic and could be altered throughout an individual’s life cycle, particularly during the first 18 months of life [57, 58, 59, 60, 62]. In addition, it was reported that the metabolic products from the GI tract microbiome could have profound and dynamic effects on host metabolism, immune functions and gene expressions which happens in many organ systems including the CNS [58]. Furthermore, other authors recommended that it was important to consider the effects of infant formula versus breastfeeding, a high-calorie Western diet and exposure to antibiotics and disinfectants in human beings, animals and plants on the alteration of the human microbiome and its metabolites [45, 54, 56, 63, 64]. These should be considered a possible source of environmental triggers of many diseases of increasing incidence including ASD [45]. This was particularly evident from human populations who migrated to Western societies, such as the Somalis in the diaspora, who appeared to have a much higher incidence of ASD than it existed in their country of origin [45, 65].
Furthermore, there are examples of this experience in biology to show that it may be possible that GI biome could alter the behaviors of animals [45, 66, 67, 68]. Examples; Rabies and Bornavirus infect the CNS in animals and induce aggression that spreads the virus in the saliva from one animal to another through biting behaviors [45]; Cordyceps (Ophiocordyceps unilateralis) is a fungal infection that affects the behavior of ants, causing them to climb to the top of plants before they die [45]. The resulting fruiting bodies of the fungus then sprout out of the dead insect to spread spores [45]; in addition, Toxoplasmosis causes rodents to act without an appropriate fear response, leading to transmission of the infectious agent through cats via predation and ultimately on to humans [45]; Furthermore, Mundane acts such as sneezing with a common cold or increased gastric motility leading to nausea and vomiting in viral gastroenteritis are said to be in the best interest of spreading the infectious agent [45]. The researcher then ponders whether similar things that happen such as carbohydrate craving, diarrhea and fecal smearing in ASD helps to feed and spread bacteria? [45]. It was observed that families of ASD children just like NS children often become more alienated when they are told about their children’s regression condition and that there was not much that could be done [45] and they were often encouraged to use medications to partially reduce aggressive behavior and to wait for their turn for the under-funded behavioral intervention programs that take years to begin and years to complete [45, 56]. The strain and stress of dealing with these children can destroy families and end productive careers, leading desperate and vulnerable parents to turn to unproven controversial treatments that can be costly, potentially dangerous and without confirmed effectiveness [45]. This has been observed in parents of children with NS who have in their helplessness resorted to the use of traditional medicines including and not limited to the use of crashed roots, traditional medicines, witchcrafts, prayers, visits to shrines and animal sacrifices as remedies for the treatment of this syndrome [10, 15, 46, 50]. In addition, there are new interesting issues to learn about some observations of bizarre food cravings, GI symptoms, epilepsy, infectious processes and metabolic disturbances in children affected with ASD [45, 68, 69, 70] just like for the NS children. However, there were reports that some ASD children appeared to improve, either spontaneously, after certain broad spectrum antibiotics, or possibly by altering their diet [45]. This particular scenario has been observed in NS children at the HfH rehabilitation centre in which NS children whose feeding pattern (using a locally prepare MAMA food supplement) and symptomatic treatment have made them improve physically but still confronted with cognitive, emotional and perceptual difficulties [3, 4, 38, 39]. A researcher wonders whether there might be a common digestive system link to these findings even if current understanding in conventional western medicine could do little for these ASD and NS children. The mitochondrial disorders observed in ASD—studied extensively by Dan Rossignol, Rossignol Medical Center, Irvine, California, and Richard Frye, University of Arkansas, appeared to occur largely through environmental and not inherited means [45, 71, 72]. It is reported that these disorders observed might be caused by or at least worsened by enteric short-chain fatty acids including propionic acid from GI tract bacteria [45, 57, 71, 72]. This is similarly a suggestion being advanced on NS children seen in Northern Uganda and South Sudan because first, they were made to feed on food provided by the relief agencies which were not their usual diet during IDPs period (plumpy nuts, powdered milk, soya beans, red sorghum, cooking oil which were sometimes of uncertain composition, rice, yellow posho and other food substances that were made available to them) [3]. Secondly, there have been consistent observation in case control studies, case series, case reports and clinical and biochemical studies that NS children do have high anion gap metabolic acidosis with depleted bicarbonate levels and one author proposed that the cause of this syndrome may perhaps be due to mitochondrial disorders, a factor which may be common to ASD and NS [1, 2, 10, 15, 50]. The cooking oil supplied and consumed by the IDP residents provided by the relief agencies were not common to their GI microbiome but may have perhaps been those of short chain fatty acids [1, 2, 3, 5].
Furthermore, the reported collaborative work of Dr. Frye, who reviewed his ASD patient population and found a large subset with the lipid (acylcarnitine) and biochemical (citric acid, glutathione) findings predicted by the propionic rodent model was another breakthrough in the advancement of science of ASD [45, 71, 72, 73, 74]. His finding in June 2012, that there was an absence of genetic abnormalities to explain these changes in ASD, suggesting that the biochemical findings stemmed from environmental factors and were not inherited [45, 73, 74]. These similar findings were observed in NS children in Northern Uganda where there have been observed acetyl carnitine and biotinidase deficiency in a pilot study conducted on NS children undergoing rehabilitation at the HfH centre [5].
In addition, a recently work with Bistra Nankova, from New York Medical College, found that short chain fatty acids, including propionic acid are histone deacetylase inhibitors and thus were switchers for genes particularly those involved in the metabolism of catecholamines and was important in anxiety, arousal, movement disorders, aggression and cravings [45]. This brings to mind a thought that potentially bacteria can control and tinker with our metabolisms and even human genes [45]. Additionally, some researchers now argue that these bacteria, through natural selection, may be controlling or modulating our behavior and they may serve the host well until environmental factors such as the Western diet or overuse of antibiotics reset the microbiome to produce alterations of this behavior—the obsessions, perseverations, food fixations and tics but also at times enhanced memory associated with ASD [45, 75, 76, 77, 78, 79, 80].
The author argued that it was important to note that propionic acid affects multiple systems at different developmental periods in a complex manner and that the evidence of increased propionic acid or other short-chain enteric fatty acids involved in the pathophysiology of ASD, although compelling, was still circumstantial [45, 77, 78, 79]. These researchers further reported that propionic and related short-chain fatty acids could elicit behaviors that are anxiety-like, perseverative, repetitive, ritualistic and antisocial [80, 81, 82, 83, 84]. These behaviors were reported to be common to many other neuropsychiatric conditions (obsessive compulsive, mood, anxiety, attention deficit/hyperactive and eating disorders, irritable bowel syndrome, and schizophrenia) where infectious agents have been proposed [45, 81, 84]. In addition, the researchers argued that there was a growing incidence of ASD and ASD-related conditions, coupled with the observed alterations in the human microbiome secondary to dietary, medical and agricultural factors and their potential effects on human and animal behavior should be examined further [45, 58, 60, 81, 85, 86]. Professor Jared Diamond contended in his book Guns, Germs, and Steel that the impact of human migration and urbanization, domestication of plants and animals and resultant human diseases shaping cultures was not trivial [87]. He further stated that, it was not so far-fetched to say that Western society has altered human microbial populations, which in turn may be altering human behavior and culture [87]. The similarities in the clinical presentations and the biochemical findings in children with NS and ASD draws the attention of these researchers to perhaps an understanding that NS may perhaps be a condition akin to autism spectrum disorder (ASD); a disease spectrum that is not well understood but continues to ravage the lives of many young people and families in developing and developed world akin to the experience of NS in the East Africa. Nodding syndrome were seen only in children who were born normal, lived in the IDP camps, were from poor families, all ate food ration from relief agencies foreign to their GIT and that all the children who developed NS were IDP resident at some stage in their lives [2, 3, 4, 5]. The relief agencies distributed various forms of cereals (Plumpy nuts, Beans, soya, red sorghum, yellow posho, and maize) and cooking oil which were perhaps foreign to their GI microbiome of the affected communities and the communities ate them, they provided cooking oil whose constituents were foreign to the population and they consumed them [2, 3, 33, 34]. In addition, NS children have been found to have deficiency of Vitamin B6, Vitamin D, Acetyl carnitine and biotinidase [5]. These factors point to the changes in the diet of the children and adults in these communities where NS occurs at epidemic proportions during and after the war and/or IDPs camp life which may have perhaps been partly responsible for the syndrome that we have been investigating without finding the cause [2, 3, 5]. Important to note was that the Ugandan Ministry of Health and World Health organization have since 2012 reported no new cases of NS in Northern Uganda since the IDP camps were disbanded and communities returned to their farmland and feed on their locally grown foods [2, 3, 4, 5]. Therefore autism spectrum disorder, nodding syndrome, biotinidase and acetyl carnitine deficiency [1, 2, 3, 5, 88] may be conditions that share many things in common and this may be the right moment to think of considering them as similar/common entities.
7. Conclusion
Nodding syndrome (NS) is a childhood neurological disorder that occurs in clusters in Eastern Africa and of uncertain nosology. However, studies have demonstrated biotinidase and acetyl carnitine deficiency, Vitamin B6 deficiency, high anion gap metabolic acidosis and Vitamin D deficiency. In addition, NS children experienced internal displacement, fed on IDP diets which were mainly foreign to their GI microbiome and other environmental exposures, exposure to wartime situations and infectious diseases at childhood. Rehabilitated of NS children using home grown food supplement (MAMA supplement plus other symptomatic remedies), their conditions improved tremendously and some have returned to school although there is no clear evidence that they have been completely cured. Furthermore, there are no new cases of NS as reported by the Ugandan Ministry of Health (MOH) and World Health Organization (WHO) since 2012 when the IDP camps were disbanded and communities resettled in their own communities and feed on their own home grown foods. Although these findings are inconclusive at this stage, perhaps NS observed in this region may be akin to autism spectrum disorder (ASD).
Acknowledgments
The authors acknowledge the support of Hope for HumaNs (HfH), an NGO which contributed tremendously towards the rehabilitation of NS children for over 5 years. Gulu University, an academic institution which has provided logistical and administrative support to the authors for this book chapter.
Conflict of interest
All authors declare no conflict of interest.
\n',keywords:"nodding syndrome, autism spectrum disorder, Gulu, Uganda",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/65105.pdf",chapterXML:"https://mts.intechopen.com/source/xml/65105.xml",downloadPdfUrl:"/chapter/pdf-download/65105",previewPdfUrl:"/chapter/pdf-preview/65105",totalDownloads:926,totalViews:0,totalCrossrefCites:0,dateSubmitted:"September 25th 2018",dateReviewed:"December 13th 2018",datePrePublished:"April 3rd 2019",datePublished:"October 9th 2019",dateFinished:"January 9th 2019",readingETA:"0",abstract:"Nodding syndrome (NS) is a devastating childhood neurological disorder seen in clusters in Eastern Africa but of uncertain nosology. It is characterized by repetitive head nodding, atonic seizures, cognitive decline, and school dropout, wasting and stunted growth and it occurs in children subject to internal displacement, food insecurity, and exposure to infectious diseases, contaminated environment and with a number of repetitive behavioral abnormalities. On the other hand autism spectrum disorders (ASD) is a group of behaviorally defined neurodevelopmental disorders with lifelong consequences. They are defined by impairments in communication and social interaction along with restrictive and repetitive behaviors. It is a complex disorder associated with a wide range of disparate and seemingly unrelated factors such as; maternal exposure to various chemical substances, maternal exposure to child abuse, maternal evidence of Diabetes, autoimmune diseases, age of either parents at conception, exposure of infants to various chemical substances, low vitamin D levels of the infant at birth, gender of the infant and a large number of genetic factors. There are a number of similarities in the clinical, biochemical and behavioral findings in children with NS and ASD.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/65105",risUrl:"/chapter/ris/65105",signatures:"David Lagoro Kitara, Denis Anywar Arony and Suzanne Gazda",book:{id:"7835",type:"book",title:"Autism Spectrum Disorders",subtitle:"Advances at the End of the Second Decade of the 21st Century",fullTitle:"Autism Spectrum Disorders - Advances at the End of the Second Decade of the 21st Century",slug:"autism-spectrum-disorders-advances-at-the-end-of-the-second-decade-of-the-21st-century",publishedDate:"October 9th 2019",bookSignature:"Michael Fitzgerald",coverURL:"https://cdn.intechopen.com/books/images_new/7835.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",isbn:"978-1-78984-022-3",printIsbn:"978-1-78984-021-6",pdfIsbn:"978-1-83962-273-1",isAvailableForWebshopOrdering:!0,editors:[{id:"205005",title:"Dr.",name:"Michael",middleName:null,surname:"Fitzgerald",slug:"michael-fitzgerald",fullName:"Michael Fitzgerald"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"277395",title:"Prof.",name:"David",middleName:null,surname:"Kitara Lagoro",fullName:"David Kitara Lagoro",slug:"david-kitara-lagoro",email:"klagoro@gmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"310269",title:"Dr.",name:"Denis",middleName:null,surname:"Anywar Arony",fullName:"Denis Anywar Arony",slug:"denis-anywar-arony",email:"denisjoel@gmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"310270",title:"Dr.",name:"Suzanne",middleName:null,surname:"Gazda",fullName:"Suzanne Gazda",slug:"suzanne-gazda",email:"suzannegazda@gmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Nodding syndrome and displacement into IDP camps",level:"1"},{id:"sec_3",title:"3. Epidemiological, environmental and dietary findings on nodding syndrome children",level:"1"},{id:"sec_4",title:"4. Biotinidase and acetyl carnitine deficiency, nodding syndrome and metabolic disorder",level:"1"},{id:"sec_5",title:"5. Experience of treatment and rehabilitation of children with nodding syndrome",level:"1"},{id:"sec_6",title:"6. Nodding syndrome (NS), biotinidase and acetyl carnitine deficiency and autism spectrum disorder (ASD)",level:"1"},{id:"sec_7",title:"7. Conclusion",level:"1"},{id:"sec_8",title:"Acknowledgments",level:"1"},{id:"sec_11",title:"Conflict of interest",level:"1"}],chapterReferences:[{id:"B1",body:'Kitara DL, Anywar AD, Mwaka AD, Uwonda G, Abwang B, Kigonya E. Nodding syndrome in northern Uganda: A probable metabolic disorder. 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The World Journal of Biological Psychiatry. 2009;10(4 Pt 2):648-657'},{id:"B85",body:'Cho I, Yamanishi S, Cox L. Antibiotics in early life alter the murine colonic microbiome and adiposity. Nature. 2012;488(7413):621-626'},{id:"B86",body:'Petrof EO, Claud EC, Gloor GB, Allen-Vercoe E. Microbial ecosystems therapeutics: A new paradigm in medicine? Beneficial Microbes. 2013;4(1):53-65'},{id:"B87",body:'Diamond J. Guns, Germs, and Steel. New York, NY: W.W. Norton & Company, Inc; 1997'},{id:"B88",body:'Hoffman TL, Simon EM, Ficicioglu C. Biotinidase deficiency: The importance of adequate follow-up for an inconclusive newborn screening result. European Journal of Pediatrics. 2005;164:298-301'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"David Lagoro Kitara",address:"klagoro@gmail.com",affiliation:'
Department of Surgery, Faculty of Medicine, Gulu University, Uganda
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IntechOpen’s Academic Editors and Authors have received funding for their work through many well-known funders, including: the European Commission, Bill and Melinda Gates Foundation, Wellcome Trust, Chinese Academy of Sciences, Natural Science Foundation of China (NSFC), CGIAR Consortium of International Agricultural Research Centers, National Institute of Health (NIH), National Science Foundation (NSF), National Aeronautics and Space Administration (NASA), National Institute of Standards and Technology (NIST), German Research Foundation (DFG), Research Councils United Kingdom (RCUK), Oswaldo Cruz Foundation, Austrian Science Fund (FWF), Foundation for Science and Technology (FCT), Australian Research Council (ARC).
Open Access publication costs can often be designated directly in the grants or in specific budgets allocated for that purpose. Many of the most important funding organisations encourage, and even request, that the projects they fund are made available at no cost to the wider public. IntechOpen strives to maintain excellent relationships with these funders and ensures compliance with mandates.
\\n\\n
In order to help Authors identify appropriate funding agencies and institutions, we have created a list, based on extensive research on various OA resources (including ROARMAP and SHERPA/JULIET) of organizations that have funds available. Before consulting our list we encourage you to petition your own institution or organization for Open Access funds or check the specifications of your grant with your funder to ascertain if publication costs are included. Where you are in receipt of a grant you should clarify:
\\n\\n
\\n\\t
Does your institution already have a budget for covering Open Access publication costs?
\\n\\t
Does your grant list Open Access publication fees as legitimate direct/indirect costs?
\\n
\\n\\n
If you are associated with any of the institutions in our list below, you can apply to receive OA publication funds by following the instructions provided in the links. Please consult the Open Access policies or grant Terms and Conditions of any institution with which you are linked to explore ways to cover your publication costs (also accessible by clicking on the link in their title).
\\n\\n
Please note that this list is not a definitive one and is updated regularly. To suggest possible modifications or the inclusion of your institution/funder, please contact us at funders@intechopen.com
\\n\\n
Please be aware that you must be a member, or grantee, of the institutions/funders listed in order to apply for their Open Access publication funds.
Open Access publication costs can often be designated directly in the grants or in specific budgets allocated for that purpose. Many of the most important funding organisations encourage, and even request, that the projects they fund are made available at no cost to the wider public. IntechOpen strives to maintain excellent relationships with these funders and ensures compliance with mandates.
\n\n
In order to help Authors identify appropriate funding agencies and institutions, we have created a list, based on extensive research on various OA resources (including ROARMAP and SHERPA/JULIET) of organizations that have funds available. Before consulting our list we encourage you to petition your own institution or organization for Open Access funds or check the specifications of your grant with your funder to ascertain if publication costs are included. Where you are in receipt of a grant you should clarify:
\n\n
\n\t
Does your institution already have a budget for covering Open Access publication costs?
\n\t
Does your grant list Open Access publication fees as legitimate direct/indirect costs?
\n
\n\n
If you are associated with any of the institutions in our list below, you can apply to receive OA publication funds by following the instructions provided in the links. Please consult the Open Access policies or grant Terms and Conditions of any institution with which you are linked to explore ways to cover your publication costs (also accessible by clicking on the link in their title).
\n\n
Please note that this list is not a definitive one and is updated regularly. To suggest possible modifications or the inclusion of your institution/funder, please contact us at funders@intechopen.com
\n\n
Please be aware that you must be a member, or grantee, of the institutions/funders listed in order to apply for their Open Access publication funds.
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He previously worked as a post-doctoral fellow at the Ben-Gurion University of Negev, Israel; University of the Free State, South Africa; and Central University of Technology Bloemfontein, South Africa. He obtained his Ph.D. in Organic Chemistry from Nagaoka University of Technology, Japan. He has published more than seventy-four journal articles and attended several national and international conferences as speaker and chair. Dr. Kendrekar has received many international awards. He has several funded projects, namely, anti-malaria drug development, MRSA, and SARS-CoV-2 activity of curcumin and its formulations. He has filed four patents in collaboration with the University of Central Lancashire and Mayo Clinic Infectious Diseases. His present research includes organic synthesis, drug discovery and development, biochemistry, nanoscience, and nanotechnology.",institutionString:"Visiting Scientist at Lipid Nanostructures Laboratory, Centre for Smart Materials, School of Natural Sciences, University of Central Lancashire",institution:null},{id:"428125",title:"Dr.",name:"Vinayak",middleName:null,surname:"Adimule",slug:"vinayak-adimule",fullName:"Vinayak Adimule",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/428125/images/system/428125.jpg",biography:"Dr. Vinayak Adimule, MSc, Ph.D., is a professor and dean of R&D, Angadi Institute of Technology and Management, India. He has 15 years of research experience as a senior research scientist and associate research scientist in R&D organizations. He has published more than fifty research articles as well as several book chapters. He has two Indian patents and two international patents to his credit. Dr. Adimule has attended, chaired, and presented papers at national and international conferences. He is a guest editor for Topics in Catalysis and other journals. He is also an editorial board member, life member, and associate member for many international societies and research institutions. His research interests include nanoelectronics, material chemistry, artificial intelligence, sensors and actuators, bio-nanomaterials, and medicinal chemistry.",institutionString:"Angadi Institute of Technology and Management",institution:null},{id:"284317",title:"Prof.",name:"Kantharaju",middleName:null,surname:"Kamanna",slug:"kantharaju-kamanna",fullName:"Kantharaju Kamanna",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/284317/images/21050_n.jpg",biography:"Prof. K. Kantharaju has received Bachelor of science (PCM), master of science (Organic Chemistry) and Doctor of Philosophy in Chemistry from Bangalore University. He worked as a Executive Research & Development @ Cadila Pharmaceuticals Ltd, Ahmedabad. He received DBT-postdoc fellow @ Molecular Biophysics Unit, Indian Institute of Science, Bangalore under the supervision of Prof. P. Balaram, later he moved to NIH-postdoc researcher at Drexel University College of Medicine, Philadelphia, USA, after his return from postdoc joined NITK-Surthakal as a Adhoc faculty at department of chemistry. Since from August 2013 working as a Associate Professor, and in 2016 promoted to Profeesor in the School of Basic Sciences: Department of Chemistry and having 20 years of teaching and research experiences.",institutionString:null,institution:{name:"Rani Channamma University, Belagavi",country:{name:"India"}}},{id:"158492",title:"Prof.",name:"Yusuf",middleName:null,surname:"Tutar",slug:"yusuf-tutar",fullName:"Yusuf Tutar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/158492/images/system/158492.jpeg",biography:"Prof. Dr. Yusuf Tutar conducts his research at the Hamidiye Faculty of Pharmacy, Department of Basic Pharmaceutical Sciences, Division of Biochemistry, University of Health Sciences, Turkey. He is also a faculty member in the Molecular Oncology Program. He obtained his MSc and Ph.D. at Oregon State University and Texas Tech University, respectively. He pursued his postdoctoral studies at Rutgers University Medical School and the National Institutes of Health (NIH/NIDDK), USA. His research focuses on biochemistry, biophysics, genetics, molecular biology, and molecular medicine with specialization in the fields of drug design, protein structure-function, protein folding, prions, microRNA, pseudogenes, molecular cancer, epigenetics, metabolites, proteomics, genomics, protein expression, and characterization by spectroscopic and calorimetric methods.",institutionString:"University of Health Sciences",institution:null},{id:"180528",title:"Dr.",name:"Hiroyuki",middleName:null,surname:"Kagechika",slug:"hiroyuki-kagechika",fullName:"Hiroyuki Kagechika",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180528/images/system/180528.jpg",biography:"Hiroyuki Kagechika received his bachelor’s degree and Ph.D. in Pharmaceutical Sciences from the University of Tokyo, Japan, where he served as an associate professor until 2004. He is currently a professor at the Institute of Biomaterials and Bioengineering (IBB), Tokyo Medical and Dental University (TMDU). From 2010 to 2012, he was the dean of the Graduate School of Biomedical Science. Since 2012, he has served as the vice dean of the Graduate School of Medical and Dental Sciences. He has been the director of the IBB since 2020. Dr. Kagechika’s major research interests are the medicinal chemistry of retinoids, vitamins D/K, and nuclear receptors. He has developed various compounds including a drug for acute promyelocytic leukemia.",institutionString:"Tokyo Medical and Dental University",institution:{name:"Tokyo Medical and Dental University",country:{name:"Japan"}}},{id:"94311",title:"Prof.",name:"Martins",middleName:"Ochubiojo",surname:"Ochubiojo Emeje",slug:"martins-ochubiojo-emeje",fullName:"Martins Ochubiojo Emeje",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94311/images/system/94311.jpeg",biography:"Martins Emeje obtained a BPharm with distinction from Ahmadu Bello University, Nigeria, and an MPharm and Ph.D. from the University of Nigeria (UNN), where he received the best Ph.D. award and was enlisted as UNN’s “Face of Research.” He established the first nanomedicine center in Nigeria and was the pioneer head of the intellectual property and technology transfer as well as the technology innovation and support center. Prof. Emeje’s several international fellowships include the prestigious Raman fellowship. He has published more than 150 articles and patents. He is also the head of R&D at NIPRD and holds a visiting professor position at Nnamdi Azikiwe University, Nigeria. He has a postgraduate certificate in Project Management from Walden University, Minnesota, as well as a professional teaching certificate and a World Bank certification in Public Procurement. Prof. Emeje was a national chairman of academic pharmacists in Nigeria and the 2021 winner of the May & Baker Nigeria Plc–sponsored prize for professional service in research and innovation.",institutionString:"National Institute for Pharmaceutical Research and Development",institution:{name:"National Institute for Pharmaceutical Research and Development",country:{name:"Nigeria"}}},{id:"436430",title:"Associate Prof.",name:"Mesut",middleName:null,surname:"Işık",slug:"mesut-isik",fullName:"Mesut Işık",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/436430/images/19686_n.jpg",biography:null,institutionString:null,institution:{name:"Bilecik University",country:{name:"Turkey"}}},{id:"268659",title:"Ms.",name:"Xianquan",middleName:null,surname:"Zhan",slug:"xianquan-zhan",fullName:"Xianquan Zhan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/268659/images/8143_n.jpg",biography:"Dr. Zhan received his undergraduate and graduate training in the fields of preventive medicine and epidemiology and statistics at the West China University of Medical Sciences in China during 1989 to 1999. He received his post-doctoral training in oncology and cancer proteomics for two years at the Cancer Research Institute of Human Medical University in China. In 2001, he went to the University of Tennessee Health Science Center (UTHSC) in USA, where he was a post-doctoral researcher and focused on mass spectrometry and cancer proteomics. Then, he was appointed as an Assistant Professor of Neurology, UTHSC in 2005. He moved to the Cleveland Clinic in USA as a Project Scientist/Staff in 2006 where he focused on the studies of eye disease proteomics and biomarkers. He returned to UTHSC as an Assistant Professor of Neurology in the end of 2007, engaging in proteomics and biomarker studies of lung diseases and brain tumors, and initiating the studies of predictive, preventive, and personalized medicine (PPPM) in cancer. In 2010, he was promoted to Associate Professor of Neurology, UTHSC. Currently, he is a Professor at Xiangya Hospital of Central South University in China, Fellow of Royal Society of Medicine (FRSM), the European EPMA National Representative in China, Regular Member of American Association for the Advancement of Science (AAAS), European Cooperation of Science and Technology (e-COST) grant evaluator, Associate Editors of BMC Genomics, BMC Medical Genomics, EPMA Journal, and Frontiers in Endocrinology, Executive Editor-in-Chief of Med One. He has\npublished 116 peer-reviewed research articles, 16 book chapters, 2 books, and 2 US patents. His current main research interest focuses on the studies of cancer proteomics and biomarkers, and the use of modern omics techniques and systems biology for PPPM in cancer, and on the development and use of 2DE-LC/MS for the large-scale study of human proteoforms.",institutionString:null,institution:{name:"Xiangya Hospital Central South University",country:{name:"China"}}},{id:"40482",title:null,name:"Rizwan",middleName:null,surname:"Ahmad",slug:"rizwan-ahmad",fullName:"Rizwan Ahmad",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/40482/images/system/40482.jpeg",biography:"Dr. Rizwan Ahmad is a University Professor and Coordinator, Quality and Development, College of Medicine, Imam Abdulrahman bin Faisal University, Saudi Arabia. Previously, he was Associate Professor of Human Function, Oman Medical College, Oman, and SBS University, Dehradun. Dr. Ahmad completed his education at Aligarh Muslim University, Aligarh. He has published several articles in peer-reviewed journals, chapters, and edited books. His area of specialization is free radical biochemistry and autoimmune diseases.",institutionString:"Imam Abdulrahman Bin Faisal University",institution:{name:"Imam Abdulrahman Bin Faisal University",country:{name:"Saudi Arabia"}}},{id:"41865",title:"Prof.",name:"Farid A.",middleName:null,surname:"Badria",slug:"farid-a.-badria",fullName:"Farid A. Badria",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/41865/images/system/41865.jpg",biography:"Farid A. Badria, Ph.D., is the recipient of several awards, including The World Academy of Sciences (TWAS) Prize for Public Understanding of Science; the World Intellectual Property Organization (WIPO) Gold Medal for best invention; Outstanding Arab Scholar, Kuwait; and the Khwarizmi International Award, Iran. He has 250 publications, 12 books, 20 patents, and several marketed pharmaceutical products to his credit. He continues to lead research projects on developing new therapies for liver, skin disorders, and cancer. Dr. Badria was listed among the world’s top 2% of scientists in medicinal and biomolecular chemistry in 2019 and 2020. He is a member of the Arab Development Fund, Kuwait; International Cell Research Organization–United Nations Educational, Scientific and Cultural Organization (ICRO–UNESCO), Chile; and UNESCO Biotechnology France",institutionString:"Mansoura University",institution:{name:"Mansoura University",country:{name:"Egypt"}}},{id:"329385",title:"Dr.",name:"Rajesh K.",middleName:"Kumar",surname:"Singh",slug:"rajesh-k.-singh",fullName:"Rajesh K. Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329385/images/system/329385.png",biography:"Dr. Singh received a BPharm (2003) and MPharm (2005) from Panjab University, Chandigarh, India, and a Ph.D. (2013) from Punjab Technical University (PTU), Jalandhar, India. He has more than sixteen years of teaching experience and has supervised numerous postgraduate and Ph.D. students. He has to his credit more than seventy papers in SCI- and SCOPUS-indexed journals, fifty-five conference proceedings, four books, six Best Paper Awards, and five projects from different government agencies. He is currently an editorial board member of eight international journals and a reviewer for more than fifty scientific journals. He received Top Reviewer and Excellent Peer Reviewer Awards from Publons in 2016 and 2017, respectively. He is also on the panel of The International Reviewer for reviewing research proposals for grants from the Royal Society. He also serves as a Publons Academy mentor and Bentham brand ambassador.",institutionString:"Punjab Technical University",institution:{name:"Punjab Technical University",country:{name:"India"}}},{id:"142388",title:"Dr.",name:"Thiago",middleName:"Gomes",surname:"Gomes Heck",slug:"thiago-gomes-heck",fullName:"Thiago Gomes Heck",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/142388/images/7259_n.jpg",biography:null,institutionString:null,institution:{name:"Universidade Regional do Noroeste do Estado do Rio Grande do Sul",country:{name:"Brazil"}}},{id:"336273",title:"Assistant Prof.",name:"Janja",middleName:null,surname:"Zupan",slug:"janja-zupan",fullName:"Janja Zupan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/336273/images/14853_n.jpeg",biography:"Janja Zupan graduated in 2005 at the Department of Clinical Biochemistry (superviser prof. dr. Janja Marc) in the field of genetics of osteoporosis. Since November 2009 she is working as a Teaching Assistant at the Faculty of Pharmacy, Department of Clinical Biochemistry. In 2011 she completed part of her research and PhD work at Institute of Genetics and Molecular Medicine, University of Edinburgh. She finished her PhD entitled The influence of the proinflammatory cytokines on the RANK/RANKL/OPG in bone tissue of osteoporotic and osteoarthritic patients in 2012. From 2014-2016 she worked at the Institute of Biomedical Sciences, University of Aberdeen as a postdoctoral research fellow on UK Arthritis research project where she gained knowledge in mesenchymal stem cells and regenerative medicine. She returned back to University of Ljubljana, Faculty of Pharmacy in 2016. She is currently leading project entitled Mesenchymal stem cells-the keepers of tissue endogenous regenerative capacity facing up to aging of the musculoskeletal system funded by Slovenian Research Agency.",institutionString:null,institution:{name:"University of Ljubljana",country:{name:"Slovenia"}}},{id:"357453",title:"Dr.",name:"Radheshyam",middleName:null,surname:"Maurya",slug:"radheshyam-maurya",fullName:"Radheshyam Maurya",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/357453/images/16535_n.jpg",biography:null,institutionString:null,institution:{name:"University of Hyderabad",country:{name:"India"}}},{id:"418340",title:"Dr.",name:"Jyotirmoi",middleName:null,surname:"Aich",slug:"jyotirmoi-aich",fullName:"Jyotirmoi Aich",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000038Ugi5QAC/Profile_Picture_2022-04-15T07:48:28.png",biography:"Biotechnologist with 15 years of research including 6 years of teaching experience. Demonstrated record of scientific achievements through consistent publication record (H index = 13, with 874 citations) in high impact journals such as Nature Communications, Oncotarget, Annals of Oncology, PNAS, and AJRCCM, etc. Strong research professional with a post-doctorate from ACTREC where I gained experimental oncology experience in clinical settings and a doctorate from IGIB where I gained expertise in asthma pathophysiology. A well-trained biotechnologist with diverse experience on the bench across different research themes ranging from asthma to cancer and other infectious diseases. An individual with a strong commitment and innovative mindset. Have the ability to work on diverse projects such as regenerative and molecular medicine with an overall mindset of improving healthcare.",institutionString:"DY Patil Deemed to Be University",institution:null},{id:"349288",title:"Prof.",name:"Soumya",middleName:null,surname:"Basu",slug:"soumya-basu",fullName:"Soumya Basu",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035QxIDQA0/Profile_Picture_2022-04-15T07:47:01.jpg",biography:"Soumya Basu, Ph.D., is currently working as an Associate Professor at Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune, Maharashtra, India. With 16+ years of trans-disciplinary research experience in Drug Design, development, and pre-clinical validation; 20+ research article publications in journals of repute, 9+ years of teaching experience, trained with cross-disciplinary education, Dr. Basu is a life-long learner and always thrives for new challenges.\r\nHer research area is the design and synthesis of small molecule partial agonists of PPAR-γ in lung cancer. She is also using artificial intelligence and deep learning methods to understand the exosomal miRNA’s role in cancer metastasis. Dr. Basu is the recipient of many awards including the Early Career Research Award from the Department of Science and Technology, Govt. of India. She is a reviewer of many journals like Molecular Biology Reports, Frontiers in Oncology, RSC Advances, PLOS ONE, Journal of Biomolecular Structure & Dynamics, Journal of Molecular Graphics and Modelling, etc. She has edited and authored/co-authored 21 journal papers, 3 book chapters, and 15 abstracts. She is a Board of Studies member at her university. She is a life member of 'The Cytometry Society”-in India and 'All India Cell Biology Society”- in India.",institutionString:"Dr. D.Y. Patil Vidyapeeth, Pune",institution:{name:"Dr. D.Y. Patil Vidyapeeth, Pune",country:{name:"India"}}},{id:"354817",title:"Dr.",name:"Anubhab",middleName:null,surname:"Mukherjee",slug:"anubhab-mukherjee",fullName:"Anubhab Mukherjee",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y0000365PbRQAU/ProfilePicture%202022-04-15%2005%3A11%3A18.480",biography:"A former member of Laboratory of Nanomedicine, Brigham and Women’s Hospital, Harvard University, Boston, USA, Dr. Anubhab Mukherjee is an ardent votary of science who strives to make an impact in the lives of those afflicted with cancer and other chronic/acute ailments. He completed his Ph.D. from CSIR-Indian Institute of Chemical Technology, Hyderabad, India, having been skilled with RNAi, liposomal drug delivery, preclinical cell and animal studies. He pursued post-doctoral research at College of Pharmacy, Health Science Center, Texas A & M University and was involved in another postdoctoral research at Department of Translational Neurosciences and Neurotherapeutics, John Wayne Cancer Institute, Santa Monica, California. In 2015, he worked in Harvard-MIT Health Sciences & Technology as a visiting scientist. He has substantial experience in nanotechnology-based formulation development and successfully served various Indian organizations to develop pharmaceuticals and nutraceutical products. He is an inventor in many US patents and an author in many peer-reviewed articles, book chapters and books published in various media of international repute. Dr. Mukherjee is currently serving as Principal Scientist, R&D at Esperer Onco Nutrition (EON) Pvt. Ltd. and heads the Hyderabad R&D center of the organization.",institutionString:"Esperer Onco Nutrition Pvt Ltd.",institution:null},{id:"319365",title:"Assistant Prof.",name:"Manash K.",middleName:null,surname:"Paul",slug:"manash-k.-paul",fullName:"Manash K. Paul",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/319365/images/system/319365.png",biography:"Manash K. Paul is a Principal Investigator and Scientist at the University of California Los Angeles. He has contributed significantly to the fields of stem cell biology, regenerative medicine, and lung cancer. His research focuses on various signaling processes involved in maintaining stem cell homeostasis during the injury-repair process, deciphering lung stem cell niche, pulmonary disease modeling, immuno-oncology, and drug discovery. He is currently investigating the role of extracellular vesicles in premalignant lung cell migration and detecting the metastatic phenotype of lung cancer via machine-learning-based analyses of exosomal signatures. Dr. Paul has published in more than fifty peer-reviewed international journals and is highly cited. He is the recipient of many awards, including the UCLA Vice Chancellor’s award, a senior member of the Institute of Electrical and Electronics Engineers (IEEE), and an editorial board member for several international journals.",institutionString:"University of California Los Angeles",institution:{name:"University of California Los Angeles",country:{name:"United States of America"}}},{id:"311457",title:"Dr.",name:"Júlia",middleName:null,surname:"Scherer Santos",slug:"julia-scherer-santos",fullName:"Júlia Scherer Santos",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/311457/images/system/311457.jpg",biography:"Dr. Júlia Scherer Santos works in the areas of cosmetology, nanotechnology, pharmaceutical technology, beauty, and aesthetics. Dr. Santos also has experience as a professor of graduate courses. Graduated in Pharmacy, specialization in Cosmetology and Cosmeceuticals applied to aesthetics, specialization in Aesthetic and Cosmetic Health, and a doctorate in Pharmaceutical Nanotechnology. Teaching experience in Pharmacy and Aesthetics and Cosmetics courses. She works mainly on the following subjects: nanotechnology, cosmetology, pharmaceutical technology, aesthetics.",institutionString:"Universidade Federal de Juiz de Fora",institution:{name:"Universidade Federal de Juiz de Fora",country:{name:"Brazil"}}},{id:"219081",title:"Dr.",name:"Abdulsamed",middleName:null,surname:"Kükürt",slug:"abdulsamed-kukurt",fullName:"Abdulsamed Kükürt",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/219081/images/system/219081.png",biography:"Dr. Kükürt graduated from Uludağ University in Turkey. He started his academic career as a Research Assistant in the Department of Biochemistry at Kafkas University. In 2019, he completed his Ph.D. program in the Department of Biochemistry at the Institute of Health Sciences. He is currently working at the Department of Biochemistry, Kafkas University. He has 27 published research articles in academic journals, 11 book chapters, and 37 papers. He took part in 10 academic projects. He served as a reviewer for many articles. He still serves as a member of the review board in many academic journals. He is currently working on the protective activity of phenolic compounds in disorders associated with oxidative stress and inflammation.",institutionString:null,institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"178366",title:"Dr.",name:"Volkan",middleName:null,surname:"Gelen",slug:"volkan-gelen",fullName:"Volkan Gelen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178366/images/system/178366.jpg",biography:"Volkan Gelen is a Physiology specialist who received his veterinary degree from Kafkas University in 2011. Between 2011-2015, he worked as an assistant at Atatürk University, Faculty of Veterinary Medicine, Department of Physiology. In 2016, he joined Kafkas University, Faculty of Veterinary Medicine, Department of Physiology as an assistant professor. Dr. Gelen has been engaged in various academic activities at Kafkas University since 2016. There he completed 5 projects and has 3 ongoing projects. He has 60 articles published in scientific journals and 20 poster presentations in scientific congresses. His research interests include physiology, endocrine system, cancer, diabetes, cardiovascular system diseases, and isolated organ bath system studies.",institutionString:"Kafkas University",institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"418963",title:"Dr.",name:"Augustine Ododo",middleName:"Augustine",surname:"Osagie",slug:"augustine-ododo-osagie",fullName:"Augustine Ododo Osagie",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/418963/images/16900_n.jpg",biography:"Born into the family of Osagie, a prince of the Benin Kingdom. I am currently an academic in the Department of Medical Biochemistry, University of Benin. Part of the duties are to teach undergraduate students and conduct academic research.",institutionString:null,institution:{name:"University of Benin",country:{name:"Nigeria"}}},{id:"192992",title:"Prof.",name:"Shagufta",middleName:null,surname:"Perveen",slug:"shagufta-perveen",fullName:"Shagufta Perveen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/192992/images/system/192992.png",biography:"Prof. Shagufta Perveen is a Distinguish Professor in the Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. Dr. Perveen has acted as the principal investigator of major research projects funded by the research unit of King Saud University. She has more than ninety original research papers in peer-reviewed journals of international repute to her credit. She is a fellow member of the Royal Society of Chemistry UK and the American Chemical Society of the United States.",institutionString:"King Saud University",institution:{name:"King Saud University",country:{name:"Saudi Arabia"}}},{id:"49848",title:"Dr.",name:"Wen-Long",middleName:null,surname:"Hu",slug:"wen-long-hu",fullName:"Wen-Long Hu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49848/images/system/49848.jpg",biography:"Wen-Long Hu is Chief of the Division of Acupuncture, Department of Chinese Medicine at Kaohsiung Chang Gung Memorial Hospital, as well as an adjunct associate professor at Fooyin University and Kaohsiung Medical University. Wen-Long is President of Taiwan Traditional Chinese Medicine Medical Association. He has 28 years of experience in clinical practice in laser acupuncture therapy and 34 years in acupuncture. He is an invited speaker for lectures and workshops in laser acupuncture at many symposiums held by medical associations. He owns the patent for herbal preparation and producing, and for the supercritical fluid-treated needle. Dr. Hu has published three books, 12 book chapters, and more than 30 papers in reputed journals, besides serving as an editorial board member of repute.",institutionString:"Kaohsiung Chang Gung Memorial Hospital",institution:{name:"Kaohsiung Chang Gung Memorial Hospital",country:{name:"Taiwan"}}},{id:"298472",title:"Prof.",name:"Andrey V.",middleName:null,surname:"Grechko",slug:"andrey-v.-grechko",fullName:"Andrey V. Grechko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/298472/images/system/298472.png",biography:"Andrey Vyacheslavovich Grechko, Ph.D., Professor, is a Corresponding Member of the Russian Academy of Sciences. He graduated from the Semashko Moscow Medical Institute (Semashko National Research Institute of Public Health) with a degree in Medicine (1998), the Clinical Department of Dermatovenerology (2000), and received a second higher education in Psychology (2009). Professor A.V. Grechko held the position of Сhief Physician of the Central Clinical Hospital in Moscow. He worked as a professor at the faculty and was engaged in scientific research at the Medical University. Starting in 2013, he has been the initiator of the creation of the Federal Scientific and Clinical Center for Intensive Care and Rehabilitology, Moscow, Russian Federation, where he also serves as Director since 2015. He has many years of experience in research and teaching in various fields of medicine, is an author/co-author of more than 200 scientific publications, 13 patents, 15 medical books/chapters, including Chapter in Book «Metabolomics», IntechOpen, 2020 «Metabolomic Discovery of Microbiota Dysfunction as the Cause of Pathology».",institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"199461",title:"Prof.",name:"Natalia V.",middleName:null,surname:"Beloborodova",slug:"natalia-v.-beloborodova",fullName:"Natalia V. Beloborodova",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/199461/images/system/199461.jpg",biography:'Natalia Vladimirovna Beloborodova was educated at the Pirogov Russian National Research Medical University, with a degree in pediatrics in 1980, a Ph.D. in 1987, and a specialization in Clinical Microbiology from First Moscow State Medical University in 2004. She has been a Professor since 1996. Currently, she is the Head of the Laboratory of Metabolism, a division of the Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Moscow, Russian Federation. N.V. Beloborodova has many years of clinical experience in the field of intensive care and surgery. She studies infectious complications and sepsis. She initiated a series of interdisciplinary clinical and experimental studies based on the concept of integrating human metabolism and its microbiota. Her scientific achievements are widely known: she is the recipient of the Marie E. Coates Award \\"Best lecturer-scientist\\" Gustafsson Fund, Karolinska Institutes, Stockholm, Sweden, and the International Sepsis Forum Award, Pasteur Institute, Paris, France (2014), etc. Professor N.V. Beloborodova wrote 210 papers, five books, 10 chapters and has edited four books.',institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"354260",title:"Ph.D.",name:"Tércio Elyan",middleName:"Azevedo",surname:"Azevedo Martins",slug:"tercio-elyan-azevedo-martins",fullName:"Tércio Elyan Azevedo Martins",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/354260/images/16241_n.jpg",biography:"Graduated in Pharmacy from the Federal University of Ceará with the modality in Industrial Pharmacy, Specialist in Production and Control of Medicines from the University of São Paulo (USP), Master in Pharmaceuticals and Medicines from the University of São Paulo (USP) and Doctor of Science in the program of Pharmaceuticals and Medicines by the University of São Paulo. Professor at Universidade Paulista (UNIP) in the areas of chemistry, cosmetology and trichology. Assistant Coordinator of the Higher Course in Aesthetic and Cosmetic Technology at Universidade Paulista Campus Chácara Santo Antônio. Experience in the Pharmacy area, with emphasis on Pharmacotechnics, Pharmaceutical Technology, Research and Development of Cosmetics, acting mainly on topics such as cosmetology, antioxidant activity, aesthetics, photoprotection, cyclodextrin and thermal analysis.",institutionString:null,institution:{name:"University of Sao Paulo",country:{name:"Brazil"}}},{id:"334285",title:"Ph.D. Student",name:"Sameer",middleName:"Kumar",surname:"Jagirdar",slug:"sameer-jagirdar",fullName:"Sameer Jagirdar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334285/images/14691_n.jpg",biography:"I\\'m a graduate student at the center for biosystems science and engineering at the Indian Institute of Science, Bangalore, India. 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