\\n\\n
These books synthesize perspectives of renowned scientists from the world’s most prestigious institutions - from Fukushima Renewable Energy Institute in Japan to Stanford University in the United States, including Columbia University (US), University of Sidney (AU), University of Miami (USA), Cardiff University (UK), and many others.
\\n\\nThis collaboration embodied the true essence of Open Access by simplifying the approach to OA publishing for Academic editors and authors who contributed their research and allowed the new research to be made available free and open to anyone anywhere in the world.
\\n\\nTo celebrate the 50 books published, we have gathered them at one location - just one click away, so that you can easily browse the subjects of your interest, download the content directly, share it or read online.
\\n\\n\\n\\n\\n"}]',published:!0,mainMedia:null},components:[{type:"htmlEditorComponent",content:'
IntechOpen and Knowledge Unlatched formed a partnership to support researchers working in engineering sciences by enabling an easier approach to publishing Open Access content. Using the Knowledge Unlatched crowdfunding model to raise the publishing costs through libraries around the world, Open Access Publishing Fee (OAPF) was not required from the authors.
\n\nInitially, the partnership supported engineering research, but it soon grew to include physical and life sciences, attracting more researchers to the advantages of Open Access publishing.
\n\n\n\nThese books synthesize perspectives of renowned scientists from the world’s most prestigious institutions - from Fukushima Renewable Energy Institute in Japan to Stanford University in the United States, including Columbia University (US), University of Sidney (AU), University of Miami (USA), Cardiff University (UK), and many others.
\n\nThis collaboration embodied the true essence of Open Access by simplifying the approach to OA publishing for Academic editors and authors who contributed their research and allowed the new research to be made available free and open to anyone anywhere in the world.
\n\nTo celebrate the 50 books published, we have gathered them at one location - just one click away, so that you can easily browse the subjects of your interest, download the content directly, share it or read online.
\n\n\n\n\n'}],latestNews:[{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"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"2273",leadTitle:null,fullTitle:"Fuzzy Logic - Controls, Concepts, Theories and Applications",title:"Fuzzy Logic",subtitle:"Controls, Concepts, Theories and Applications",reviewType:"peer-reviewed",abstract:"This book introduces new concepts and theories of Fuzzy Logic Control for the application and development of robotics and intelligent machines. The book consists of nineteen chapters categorized into 1) Robotics and Electrical Machines 2) Intelligent Control Systems with various applications, and 3) New Fuzzy Logic Concepts and Theories. The intended readers of this book are engineers, researchers, and graduate students interested in fuzzy logic control systems.",isbn:null,printIsbn:"978-953-51-0396-7",pdfIsbn:"978-953-51-4314-7",doi:"10.5772/2662",price:139,priceEur:155,priceUsd:179,slug:"fuzzy-logic-controls-concepts-theories-and-applications",numberOfPages:430,isOpenForSubmission:!1,isInWos:1,isInBkci:!0,hash:"08592e2ab59a5ef109adc99aa41b2ba2",bookSignature:"Elmer P. 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Dadios obtained his Ph.D. from Loughborough University, United Kingdom. He is a Distinguished Professor and University Fellow of De La Salle University, Manila, Philippines. He is a Professorial Chairholder of the Thomas J. Lee Chair in Manufacturing Engineering Management and Victor T. Lu Chair in Production Management. He is the founder and chairman of the board of Neuronmek Inc. and Intelligent Systems Innovation Corporation. He is a top 100 scientist in the Philippines, according to the AD Scientific Index 2022. He was also listed as a top 100 scientist in 2019 by Asian Scientist Magazine. Dr. Dadios is the recipient of the 2018 Philippine Association for the Advancement of Science and Technology D. M. Consunji Award for Engineering Research; Lifetime Achievement Award from the National Research Council of the Philippines (NRCP); and the Department of Science and Technology (DOST) 50 Men and Women of Science and Technology.\n\n\tCurrently, Dr. Dadios serves as editor of the Journal of Advanced Computational Intelligence and Intelligent Informatics (JACIII) and the Journal of AI, Computer Science, and Robotics Technology. He is the editor-in-chief of the Journal of Computational Intelligence in Engineering Applications (JCIEA). He was the chair of the IEEE Philippines Section from 2010 to 2012, and the founder and chair of the IEEE Computational Intelligence Society - Philippines Chapter and the IEEE Robotics and Automation Society (RAS) - Philippines Chapter. He was also an EXCOM member of the IEEE Asia-Pacific Region from 2012 to 2020. 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As in the other biological variables, the appearance of the optic disc varies widely among healthy individuals. This fact is complicate the recognition of the pathological changes.
‘Optic Disc’ is frequently used to describe the portion of the optic nerve clinically visible on examination. This, however, may be slightly inaccurate as ‘disc’ implies a flat, 2 dimensional structure without depth, when in fact the ‘optic nerve head’ is very much a 3 dimensional structure which should ideally be viewed stereoscopically.
Posterior part of the left eye. The veins are darker in appearance than the arteries.
The optic nerve itself is a cylindrical structure of approximately 50mm in length, between the retina and the optic chiasm. This can be divided into 4 main parts:
Intraocular (the optic nerve head)
Intraorbital (between globe and optic canal)
Intracanalicular (within the optic canal)
Intracranial (between optic canal and chiasm)
The optic nerve head, or disc, is defined as the distal portion of the optic nerve extending from the myelinated portion of nerve that begins just behind the sclera, to the retinal surface. Typically, it is slightly oval with the vertical diameter being about 9% greater than the horizontal. On average the vertical disc diameter is approximately 1500 micrometers, although this may be greater in a myopic eye and less in a hypermetropic eye.
Superficial nerve fibre layer - contiguous with the nerve fibre layer of the retina
Prelaminar area - consists of nerve fibre bundles and astroglia, which form sheaths around each bundle
Laminar (Scleral) portion - contains a modification of sclera called the Lamina Cribrosa. This is made up of sheets of connective and elastic tissue, and contains fenestrations which give passage to the nerve fibre bundles and retinal blood vessels. It also serves to maintain intra-ocular pressure (IOP) against a gradient between the intra-ocular and extra-ocular spaces.
Retrolaminar portion - myelinated nerve fibres, circumscribed by leptomeninges of the CNS.1
The terminal portion of the optic nerve and its entrance into the eyeball, in horizontal section.
Schematic diagram of the human eye, with the optical disc, or blind spot, at the bottom.
When assessing a disc for glaucoma there are many subtle characteristics which should be examined. There are also various ways to examine the optic disc.
For an assessment of the optic disc, there is “the 3 Cs” rule- the cup, colour and contour.
The borders of the optic disc should be clear and well defined. If not one becomes concerned that the disc may be swollen such as in the case of papilloedema - disc swelling secondary to raised intracranial pressure. Alternatively, the disc margins may appear blurred due to presence of optic disc drusen.
Typically the optic disc looks like an orange-pink donut with a pale centre. The orange-pink appearance represents healthy, well perfused neuro-retinal tissue. There are many pathological reasons why a disc may lose this orange-pink colour and appear pale ie optic atrophy. These include advanced glaucoma, optic neuritis, arteritic or non-arteritic ischaemic optic neuropathy or a compressive lesion.
The causes of an optic neuropathy can be remembered by
The disc has an orange-pink rim with a pale centre. This pale centre is devoid of neuroretinal tissue and is called the cup. The vertical size of this cup can be estimated in relation to the disc as a whole and presented as a “cup to disc ratio”. A cup to disc ratio of 0.3 ( i.e. the cup occupies 1/3 of the height of the entire disc ) is generally considered normal, and an increased cup to disc ratio may indicate a decrease in the quantity of healthy neuro-retinal tissue and hence, glaucomatous change.
The optic disc (or optic disk optic nerve head, optic papilla or blind spot) is the location where ganglion cell axons exit the eye to form the optic nerve. There are no light sensitive rods or cones to respond to a light stimulus at this point thus it is also known as "the blind spot". A blind spot, also known as a scotoma, is an obscuration of the visual field. A particular blind spot known as the blind spot, or physiological blind spot, is the specific scotoma in the visual field that corresponds to the lack of light-detecting photoreceptor cells on the optic disc. Since there are no cells to detect light on the optic disc, a part of the field of vision is not perceived. The brain fills in with surrounding detail and with information from the other eye, so the blind spot is not normally perceived.2
Considering that the axons of the retinal ganglion cells are lost, changes occur in the structural appearance of the retinal nerve fiber layer and optic nerve head that often precede the development of visual field defects. The most important characteristics of the glaucomatous process are changes that occur in the optic nerve. Therefore, it is important for the ophthalmologist to be familiar with the characteristic signs of glaucoma in the optic disc.
The optic disc cupping has been recognized as an important characteristic of the glaucomatous process since the 19th Century. Quantification of the size of the cup and its relationship to the size of the optic disc, i.e the cup/disc (C/D) ratio, has been widely used in the differentiation of glaucomatous from normal eyes. Vertical elongation of the cup is a characteristic feature of glaucomatous optic neuropathy and the vertical C/D ratio is a simple indicator of neuroretinal rim loss that can be assessed in clinical practice without the use of sophisticated techniques or devices.1
Glaucomatous disc progression and corresponding VF defects.
The diagnosis of primary open angle glaucoma (POAG) is traditionally based on the triad of increased intraocular pressure(IOP),visual field changes and optic nerve head changes. It is well established that IOP is only a risk factor, albeit, the only risk factor that can be therapeutically manipulated. The fact that upto 50% of POAG patients can present with normal IOP2 makes it imperative that the diagnosis of POAG be made independent of IOP increase. Occurance of arcuate nerve fibre bundle visual field defects has been taken as the sine qua non for the diagnosis of POAG. Studies by Quigley et al have shown that upto 40% of the axons could be lost before a visual field defect develops on Goldmann perimetry and that 20% of axons are lost before a 5 db loss is detected on standard automated perimetry.3 The current research efforts in the early "preperimetric glaucoma" diagnosis are aimed either at psychological tests or alterations in the optic nerve head morphology as assesed by scanning laser ophthalmoscope, digital image processing of optic nerve head images or optical coherence tomography.4,5 While these advanced technologies are relevant in glaucoma diagnosis and research, they are not practical in routine clinical practice.
With some training it is possible to clinically evaluate the optic nerve head stereoscopically and detect early glaucomatous disc damage.
Cup to disc ratio greater than 0.5:1 is the most often reported sign of glaucomatous disc damage. In a given disc with a cup-disc ratio of more than 0.5:1, it is important to establish if the cup-disc ratio has been large from the onset (large physiological cup) or if it increased over a period of time. Increase in the cup-disc ratio (or enlargement of the cup) over a period of time is diagnostic of glaucomatous disc damage even in the absence of visual field defect. This definitive sign has practical limitation because one time diagnosis is not possible and followup over a period of time is neccesary. The physiological variability of the cup-disc ratio ocurs because of the large variation in the normal optic nerve head size.1
Though the normal optic nerve head size is reported to be 1.5 mm in diameter it can vary from 0.96 mm to 2.91 mm.6 As a result, the physiological cup can be as small as 0.1:1 or as large as 0.8:1.
Glaucomatous optic disc progression.
Loss of axons in glaucoma is reflected as abnormalities of the neuroretinal rim. Normally the rim is widest in the inferior temporal sector, followed by the superior temporal sector, the nasal and the temporal horizontal sector.7 Since localised field defects restricted to one hemisphere are an early sign of glaucoma, stereoscopic examination of the neuroretinal rim in the superior and inferior poles comparing carefully their thickness, pallor and notching can aid in the diagnosis of very early glaucomatous damage.
To asses the width of the neuroretinal rim, the edge of the cup has to be clearly delineated, the usual temptation is to equate the central pallor of the disc with cup, but atleast in some glaucomatous discs there is a discrepancy between the extent of central pallor (colour cup) and the site at which the vessels change their contour (contour cup). In the evaluation of glaucomatous disc damage it is the contour cup that is of relevance and not the colour cup.1
Right: Cup/Disc ratio; Left: Glaucomatous cupping, change of colour and contour.
Myopic disc can cause difficulties in glaucomatous disc evaluation either because of the oblique entry resulting in tilted disc or because of the peripapillary changes. A myopic disc the glaucomatous damage is not obvious. The inferior peripapillary atrophy results in a wrong estimation of the extent of the cup as this is mistaken for a part of the disc.
Degenerative myopic changes of the optic disc.
A myopic disc with peripapillary atrophy(arrow) which can be confused as a part of the disc, resulting in missing of the inferior notch (arrowhead) which shows the edge of the disc where the vessel is changing contour.
Careful evaluation reveals the edge of the disc to be more central with a change in vessel contour at the edge of the disc revealing the inferior notch. The corresponding superior field defect.
Superior paracentralscotoma corresponding to the disc shown on previous photo.
Acquired peripapillary atrophy has been described to be secondary to glaucomatous disc damage. Some authorities feel such changes may predispose to glaucomatous damage.
Glaucomatous cupping in a small disc. Cup size is small but the inferior notch(arrow) indicated by the change in contour of the infero-temporal vessel is typical.
The zone closer to the optic nerve head with retinal pigment epithelial (RPE) and choroidal atrophy with sclera showing through is called zone-β. The more peripheral zone with only RPE atrophy is called zone-α. Since these changes could be seen in myopia also appearance of these changes de-novo or their occurrence in small discs or non myopic eyes is more suggestive of glaucomatous disc damage. A correlation between the location of disc haemorrhage and location of peripapillary atrophy has been reported. If this is so, peripapillary atrophy could be a more reliable and permanent marker for progression than disc hemorrhages.8
NFL atrophy is associated with a high risk for field loss. Localised defects are the easiest to detect and may be very specific to differentiate early glaucoma from normal eyes. While they occur in 10 to 20% of ocular hypertensive eyes they must be looked for in every glaucoma suspect as the high specificity is clinically useful in identifying patients with impending or established perimetric loss.
Red free disc photo showing NFL loss in the inferior arcuate area (arrowheads).
A large physiological cup. If one takes care to asses the neuroretinal rim carefully and measures the optic nerve head size, one can be reasonably sure of a large physiological cup in a large disc.
Congenital colobomas of the optic nerve head are some times easy to diagnose because of the morning glory appearance or other associated colobomas. Optic nerve pit and conus of the disc can some times cause diagnostic difficulties.
Pallor disproportionate to cupping, normal intraocular pressure or unusual history of onset, progression and age should arouse suspicion of a neurological cause for the disc changes and appropriate investigations should be carried out. Photo shows cupping and pallor secondary to pituitary tumour which was mistaken for glaucoma. Also the correspoding temporal hemianopia is shown.
A Large left optic disc.
An Optic disc coloboma.
Cupping of the optic disc and pallor secondary to pituitary tumor.
Temporal hemianopsia corresponding to the disc changes shown in previous photo.
The most important points in clinical evaluation of the Optic nerve head are a stereoscopic view with magnification for proper evaluation of the neuroretinal rim changes and an estimation of the optic nerve head size.
Stereoscopic view of the optic nerve head is possible by indirect ophthalmoscopy, central part of goniolens, Hruby lens and Volk 90, 78 and 60 D lenses. Indirect ophthalmoscopy is inappropriate for assesement of the optic disc in glaucoma. I prefer the Volk lens systems. While the 78D lens provides a good balance between the field of view and magnification, the 60D lens can make measurement of optic nerve head size simple.
With one of these lenses and slitlamp with redfree light source, it is possible to asses the NFL abnormalities also, though specialised NFL photography systems are more sensitive. Use of direct ophthalmoscope in serious glaucomatous disc evaluation is to be discouraged.
Clinical estimation of optic nerve head size is possible with a Welsch Allen Ophthalmoscope or with Volk 60D lens. The smallest white round spot of the Welsch Allen ophthalmoscope usually illuminates a cone angle of 5° and casts a light of 1.5 mm in diameter on the retina.9 This retinal spot size remains constant in phakic eyes with refractive errors between -5.00 D and + 4.00 D.
The location of the originating point of the light cone does not significantly affect the retinal spot size as long as it is ± 3mm from the anterior focal point of the patient\'s eye. Since 1.5 mm is the usual size of the optic nerve head, this can be used as a yard stick for measuring disc size. Simplistically, in eyes with large physiological cups due to large discs the area illuminated is less than the area occupied by the cup.
Disc diameter can be measured by adjusting the slitlamp beam height to the edges of the disc while viewing the disc with a 60 D lens.7 This measurement is roughly equal to the measurement obtained by planimetry of disc photos with Littmann\'s correction.
A similar measurement of the vertical and horizontal disc diameter can be obtained with other lenses by multiplying the measured value with the appropriate magnification factor: Goldmann contact lens (1.26) and Volk superfield lens (1.5).7\n\t\t\t
It is useful to get habituated to a routine pattern of examination of the disc and look sequentially for findings as follows:
Overall impression of the disc
Size and shape of the disc
Evaluation of the neuroretinal rim keeping in mind the variability of its thickness in various zones mentioned in the text and also look for notch and neuroretinal rim haemorrhage.
Peripappillary atrophy
Nerve fibre layer abnormalities
Vertical cup-disc ratio and asymmetry.
Stereoscopic evaluation of the optic nerve head with emphasis on changes of the neuro retinal rim and not estimation of cup-disc ratio will aid in early diagnosis of glaucoma.
Examination of the neuroretinal rim is therefore of fundamental importance for the identification of glaucomatous damage to the optic nerve, and its changes are closely related to those occurring in the optic disc cup.1
The neuroretinal rim is the intrapapillary equivalent of the retinal nerve fiber layer, and qualitative and quantitative changes in this structure reflect the nerve fiber loss that occurs in glaucoma.
Glaucoma is a progressive optic neuropathy that is accompanied by typical changes in the visual field.2 Progressive neuroretinal rim thinning, increased excavation, and diffuse and localized loss of the retinal nerve fiber layer are all recognizable features of structural damage in the disease.3 However, their precise relationship with functional deterioration in patients with glaucoma remains largely unclear.4-8
Regulatory agencies throughout the world generally have not approved structural assessment of the optic nerve as a primary end point in clinical trials of glaucoma drugs and devices.9 The Food and Drug Administration has suggested the need to demonstrate that structural measures are predictive of clinically relevant functional outcomes in patients with glaucoma before they can reliably be used as end points in clinical trials. Currently acceptable end points according to the Food and Drug Administration include only intraocular pressure (IOP) and methods for assessment of visual function, such as standard automated perimetry (SAP). However, IOP is only a surrogate for clinically relevant outcomes in glaucoma and its relationship with disease progression is certainly imperfect.10-12 Also, although assessment of visual function is critically important for all patients with glaucoma, there is evidence to suggest that many patients may show evidence of progressive optic disc damage before functional loss is detected by SAP. Both the Ocular Hypertension Treatment Study13 and the European Glaucoma Prevention Study14 demonstrated that a substantial proportion of patients with ocular hypertension who developed glaucoma showed a change first in optic disc photographs. However, despite being included as end points for glaucoma conversion in these studies, progressive optic disc damage has not yet been demonstrated to translate into worse clinically relevant outcomes for these patients.
NFL defect in glaucoma. Left: inferior NFL wedge defect; Right: corresponding superior visual field defect.
Previous investigations have shown that cross-sectional baseline structural measurements, either by expert assessment of stereophotographs or objective imaging methods, are predictive of future development of visual field loss in those with suspected glaucoma, suggesting a potential role for these measurements in early detection of disease.15-21 However, measures of predictive ability reported in these studies have generally indicated a low accuracy of cross-sectional structural measures for predicting individual functional outcomes. This is likely due to the wide variation in the appearance of the optic nerve, which makes it difficult to identify early signs of disease at one time. Although detection of progressive optic disc change over time is likely to be a more specific indicator of the presence of structural damage from glaucoma and to correlate better with functional outcomes, the ability of progressive optic disc change in predicting functional outcomes in patients with glaucoma has not been elucidated. The purpose of this study was to evaluate the value of progressive optic disc damage detected by expert assessment of longitudinal stereophotographs in predicting future development of visual field loss in suspected glaucoma.
At times when pre-perimetric diagnosis of glaucoma is the goal, the search for the subtle signs of damage in the NFL is of utmost importance. Retinal nerve fiber layer defects have been shown to be among the earliest signs of glaucomatous damage, and they can indeed precede visual field defects.22,23 They are especially helpful for early glaucoma diagnosis and in eyes with small optic disks. The localized wedge-shaped defect of the NFL is usually seen in association with notching of the neuroretinal rim, vertical enlargement of the cup, or following disk hemorrhages. Nevertheless, in early glaucoma, bundle defects in the NFL may not be associated with neuroretinal rim thinning because the initial damaged NFL is located in the deep retinal layers. Hence, typical wedge-shaped defects can be found in disks with normal appearance.24–26 Since NFL defects are not present in normal eyes, they always indicate an abnormality. Although typically occurring in about 20% of all eyes with glaucoma, they are not pathognomonic and can also be found in other ocular diseases, such as optic disk drusen, ischemic retinopathies with cotton-wool spots, toxoplasmotic retinochoroidal scars, long-standing papilledema, or optic neuritis due to multiple sclerosis. The incidence is higher in normal-tension glaucoma than in the other forms, which makes the differential diagnosis somewhat difficult. Some authors have shown that NFL defects may be a common finding in diabetic patients with early diabetic retinopathy, and one of the risk factors is concomitant high blood pressure.27 Retinal nerve fiber layer thickness has been found to decrease with the development of diabetic retinopathy and with impairment of metabolic regulation.28 Cotton-wool spots are frequently a feature of systemic arteriolar disease, most commonly hypertension, diabetes, and collagen vascular disease; they represent infarcts at the nerve fiber layer. Cotton-wool spots have been described to be followed in some patients by localized NFL defects, with and without associated visual field defect.29,30
Glaucoma structural diagnosis has been focused on the optic disc and the peripapillary retinal nerve fiber layer (RNFL). Objective and quantitative assessment of the optic disc and the peripapillary RNFL is useful both in glaucoma diagnosis and monitoring of disease progression.1-3
Evaluation of the glaucoma optic neuropathy may be done by direct or indirect ophthalmoscopy of the optic nerve, optic nerve photography, or computerized imaging technologies. Clinical features of glaucomatous optic neuropathy include atrophy of the retinal nerve fiber layer, focal or diffuse narrowing of the neuroretinal rim, optic disc splinter haemorrhage (DH) and para papillary atrophy (PPA).4-6
Optic disc splinter haemorrhage (arrow).
α and β zones of peripapillar atrophy.
Para papillar atrophy (PPA) is a form of outer retinal atrophy that abuts the optic disc and can be divided into alpha(α) and beta(β) zones.7-9 Because this atrophy most often lies adjacent to but does not completely surround the nerve, the term parapapillary may be preferable to peripapillary atrophy, though they are used interchangeably in the literature.
In βPPA the sclera and large choroidal vessels are visible, as the retinal pigment epithelium (RPE) and most of the photoreceptors are absent.7,8 In α PPA, there is an irregular arrangement of RPE cells that can result clinically in both hypo- and hyperpigmentation. The α zone is more peripheral than the β zone when both are present.
However, there are no imaging devices to provide automated assessment of DH or PPA, which at the present time are assessed either by patient examination or by photographic interpretation. Interestingly, several studies addressing the topic have found that PPA and DH tend to occur together in eyes and, additionally, tend to occur in the same regions of the eye, leading to the possibility that PPA may be useful as an indicator of increased likelihood ofprior, present, or future disc hemorrhage.10-15 Because βPPA is present in 15%–20% of normal eyes, its presence is less specific for glaucoma than DH, which occurs only in 0.6% of healthy eyes.14,16 Given that DH is transient, lasting weeks to months, and that PPA is stable and progressive, it maybe advantageous to rely on PPA parameters for glaucoma diagnosis and monitoring.11,15
αPPA and βPPA have been evaluated in glaucoma using quantitative analysis of optic nerve photographs (morphometry) typically by manually outlining and measuring the area of PPA using a slide projector, imaging processing software, or with confocal scanning laser ophthalmoscopy.8-10,17-23 Both αPPA and βPPA are larger and occur more frequently in eyes with glaucoma than in normal eyes, though βPPA is more specific for glaucoma.8,9,17,18 Using these morphometric techniques, PPA has been reported to be helpful in differentiating between normal and glaucomatous eyes.8,9,17,18,24–27
While many morphometric investigations of PPA in glaucomatous and normal eyes have reported significant differences between these 2 groups, there is a paucity of information on how clinical evaluation of PPA may guide the clinician in the diagnosis of open-angle glaucoma (OAG). Additionally, it is difficult clinically to estimate quantitative PPA parameters, such as area of PPA, due to its heterogenous shape. Despite this, in a clinical assessment using direct ophthalmoscopy alone, information including the PPA circumferential extent and amount of neuroretinal rim narrowing increased the sensitivity and specificity for detection of glaucomatous visual field loss.4
Disc hemorrhages seem to mean different things to different clinicians. Many see them as a sign of glaucomatous progression. Some consider disc hemorrhages by themselves to represent a diagnosis of normal-tension glaucoma. Others view the hemorrhages as an indication of inadequate therapy. The development of these hemorrhages often is followed by amplification in glaucoma therapy, either adding medications or performing surgery.
Hemorrhages occur in patients with glaucoma and ocular hypertension and, rarely, in seemingly normal eyes. True glaucomatous disc hemorrhages typically occur at the superior, superior-temporal, inferior, or inferior-temporal aspect of the disc. They typically are small and reside in the retinal nerve fiber layer (RNFL), and they are contiguous with the neuroretinal rim of the optic disc. They often occur in association with notching of the neuroretinal rim or RNFL defects.
Hemorrhages that do not fit this clinical pattern are more likely caused by vascular occlusion, posterior vitreous detachment, other optic neuropathy, or blood dyscrasia such as anemia. Disc hemorrhages typically recur and in the same location on the disc. The etiology and pathogenesis of these hemorrhages remains unknown. It has been theorized that they are the result of a microvascular occlusion of the disc blood supply.
Several well-known glaucoma studies have looked at the implication of optic disc hemorrhages and virtually all indicate that the presence of one in a patient with glaucoma is a risk factor for progression. These findings themselves are not without controversy, however. For example, in the Ocular Hypertension Treatment Study (OHTS), patients with ocular hypertension who developed a disc hemorrhage during the course of the study had a nearly four-fold increased risk of progression to glaucoma compared with those who did not. The increased risk of conversion to glaucoma was about 87% of eyes that demonstrated a disc hemorrhage. That hemorrhages easily can be missed on clinical examination.
The Collaborative Normal Tension Glaucoma Study (CNTGS) found disc hemorrhages in normal-tension glaucoma to indicate the greatest risk of progression of the disease. It also discovered that reduction of IOP did not affect the outcome. Lowering IOP in patients with normal-tension glaucoma manifesting a hemorrhage did nothing to halt disease progression.
In the Early Manifest Glaucoma Treatment (EMGT) Study, disc hemorrhages, likewise, were seen as a major risk factor for disease progression. As with the CNTGS, however, IOP reduction was seen to have little benefit in altering the course of disease in eyes demonstrating disc hemorrhages. Although the hemorrhages were predictive of progression, IOP-reducing treatment was unrelated to the presence or frequency of hemorrhages. These were equally common in both the treated and untreated groups of patients in this study.
The EMGT seems to suggest that disc hemorrhages cannot be considered an indication of insufficient IOP-lowering treatment and that glaucoma progression in eyes with disc hemorrhages cannot be totally halted by IOP reduction.
It should be noted that none of the major glaucoma studies considered the development of a hemorrhage to be a clinical study endpoint for glaucoma progression or conversion to glaucoma from ocular hypertension.
Disc hemorrhages themselves are not progression but are a significant risk factor for progression
Insight of progressive glaucomatous damage to the optic disc is one of the most important aspects of glaucoma management, yet it remains largely subjective and imprecise. Progressive change in the appearance of the optic disc or retinal nerve fiber layer (RNFL) often precedes the development of visual field defects in glaucoma. Because visual field defects on standard automated perimetry may only be detected after a substantial number of nerve fibers has been lost, assessment of the optic disc and RNFL is essential for monitoring the initial stages of the disease. Before the development of visual field defects, structural changes in the optic disc or RNFL may be the only evidence for the ophthalmologist that the glaucoma is progressing and treatment needs to be intensified. Even in the presence of visual field defects, progression of optic disc damage may occur without any detectable evidence of functional deterioration.
Disc Damage Likelihood Score (
Glaucoma is defined as a process wherein there is progressive loss of retinal ganglion cells manifest clinically as loss of neuroretinal rim tissue from the optic nerve. In order to detect this, a clinician must have a method to identify these changes and distinguish them from normal. There is also a need for a system to document any change in optic nerve appearance with time in order to determine progression. The concept of cup:disc ratio(CDR) was developed by Armaly in 19671 as a standardised way of documenting disc appearance in order to address these issues. Whilst an enlarging cup:disc ratio is undoubtedly linked with glaucomatous loss, this system does not take into consideration the influence of optic disc size nor yet the focal changes seen in glaucomatous optic neuropathy. It is also well recognised that there is significant intra and inter observer error with this method.
Cup/Disc ratio progression in glaucoma.
The disc damage likelihood scale (DDLS) was devised by Spaeth et al in 2002 to incorporate the effect of disc size and focal rim width into a clinical grading scale.2 It is highly reproducible and does correlate strongly with the degree of field loss.3 The system categorises the disc as small (<1.5mm), medium(1.5-2.0mm) or large(>2.0mm). This ensures that the disc size is measured thereby reducing misclassification bias based on disc size. Disc size can be measured using a fundus lens at the slit-lamp. A slit beam is directed onto the disc and the graticule at the top used to reduce the height of the beam until it corresponds in size to the disc. The lens used will determine the correction factor. A 66D gives the exact measure from the graticule.4
60D-0.88
78D-1.2
90D-1.33
60D-1.03
90D-1.63
The next stage is to measure the width of the thinnest part of the rim. This forces the examiner to evaluate the rim throughout its entire circumference in order to identify the area of greatest thinning. The measurement is expressed in rim:disc. Where there is no rim present at the thinnest point the value is 0. The circumferential extent of rim absence is then measured in degrees. Care must be taken when evaluating a sloping rim because a sloping rim is not an absent rim.
Whilst simply documenting a CDR is quick, in the main it is of little use in either the diagnosis or longitudinal monitoring of glaucoma. The DDLS not only forces the clinician to determine the size of the disc, which by itself already is alerting the observer to which discs are big and which are small but it also formalises the evaluation of the neuroretinal rim. Because each grade is assigned a numerical value the system can then be used in research settings to determine severity or degree of progression.
Optic nerve heads come in many shapes and forms. No method of classification will fit all of these different patterns and forms. The DDLS cannot be used to evaluate certain types of discs, such as those that are congenitally anomalous. Myopic discs may be difficult to grade. Probably one of the first mental steps one takes when considering the nature of the optic disc is, “Is this an anomalous disc? Is there any system that can be used to stage or characterize this disc?” There will be those situations which the answer to that question is, “No.” It is unwise in such situations to use any of the standard systems, such as cup/disc ratio, HRT evaluations, OCT evaluations, or the DDLS.4,5
Another problem with the DDLS is that a disc may show progressive damage by having a continuing generalized narrowing of the neuroretinal rim, but not have an increase in the circumferential extent of rim absence. In such a situation the disc would unquestionably have become worse, but the DDLS score will not change. Fortunately this seems to be a rare occurrence.5
It takes some effort to learn it and initially a copy of the table should always be to hand. However, given practice and used accordingly the DDLS is an excellent tool for classifying and monitoring the optic nerve in glaucoma.
The cerebral venous system (CVS) is a wide, dynamic, and connected net of vessels developing from the encephalic parenchyma to the internal jugular veins (IJVs). As other venous system, it has three main functions: to drain blood and catabolites from the brain, to help maintaining thermic homeostasis and to refill the right-sided heart [1]. Differently from other organs, instead, intracranial veins share unique physiological features and functions. Traditionally, comprehension of CVS has been limited to descriptive anatomy and a few ranges of physiological principles.
New emerging evidences in the last years are depicting a more complex scenario, in which CVS has a pivotal role in starting and sustaining various pathological processes, from multiple sclerosis to cerebral hemorrhages, hydrocephalus, and strokes.
Primitive CVS starts differentiating from primary meninx mesenchyme as a continuous endothelial plexus connecting the dural (
Classically, first clearly identifiable parenchymal vessels are the prootic, the anterior cerebral, and the capitis lateralis and medialis veins [3].
From the 4th to the 5th months, the cortical veins net rapidly grows to sustain the hemisphere fast development. Consequently, the dural sinuses size increases with multiple series of anatomical variations and modifications from week to week. The transverse sinus balloons in response to this increasing amount of blood and to the relatively narrow diameters of jugular vein, with formation and enlargement of multiple emissary vessels for extracranial drainage to the foramen magnum and vertebral plexuses [4]. At the 35-mm stage of the embryo, drainage from the transverse sinus to the IJV can be detected [4].
After birth to the 1st year, the jugular bulb increases in size thanks to the physiological modifications of postnatal circulation, and the drainage through the emissary veins reduces its flow.
Throughout the uterine life, CVS anatomy is dynamically changing in response to the morphometric and hemodynamic adaptations of the growing organism. Progressively, from the chaotic but not homogenous primitive plexus, certain preferential routes are selected on the basis of rheologic flow parameters, while others disappear. The most suitable venous patterns are fixed, independently from our anatomical classifications, similarly to what happens for arteries but with far more variability.
In the ideal description, CVS can be distinguished in parenchymal and dural circulation. It is important to notice that intracranial veins are lacking of intraluminal valves, differently from other veins in the systemic circulation.
The deep parenchymal circulation drains blood from the deep white matter of the cerebral hemisphere, the basal ganglia, and the mesencephalon.
Dural CVS is comprised into the dural sinuses, spaces originated from the splitting of the dura derived from the ectomeninx and covered by endothelium, as above specified.
Arterial blood enters the brain through the anterior circulation, via the carotid arteries, and the posterior circulation, via the vertebral arteries. Also venous blood, or at least the major part of it, exits the brain through an anterior circulation, via the IJVs, and a posterior one, via the vertebral plexuses. Once passed the osteo-dural ring of their respective entry points inside the skull, circulatory physiology of these vessels drastically changes, given the unique physical conditions that are present in the intracranial space.
Although an exhaustive dissertation on cerebrovascular physiology is not in the focus of the present chapter; to understand CVS physiology, few mechanical, hydrostatic, and anatomical principles have to be clarified.
The skull (bone and dura together) is basically a rigid, non-expandable container, totally filled with uncompressible materials: brain parenchyma, blood and cerebrospinal fluid (CSF).
Around 1764, Alexander Monro, second of his name, published
In 1926, Harvey Cushing published “
This is an effective way to summarize the concept, but this formulation lacks the fundamental pulsating nature of cerebral flow. Blood enters the brain pulsating in the arteries; then the mechanical wave of pulsation is transmitted anisotropically through the parenchyma and CSF (fluids with different elastic properties). This wave propagation deeply affects CVS physiology: if blood enters the skull pulsating into the arteries, also it leaves from the vein pulsating.
In this balance of pressure between inflow and outflow, bridging veins have a pivotal role.
A bridging vein is defined as a cortical vessel that drains venous blood from the parenchyma to the sinuses, detaching from the cortex and crossing the subarachnoidal CSF filled and the subdural space. It has thin walls (subdural portion 10–600 μm; subarachnoid space of 50–200 μm) with loose collagen network and no muscular fibers [7]. So constituted, it acts as a perfect Starling resistor: a collapsible tube, filled with a fluid exerting pressure (P1, blood venous pressure), inside a space filled with another fluid exerting a different pressure (P2, CSF/intracranial pressure). To maintain a flow inside the tube, it is necessary that P1 > P2.
While entering, or exiting, the cerebral cortex, the superficial arteries and veins in the subarachnoid space are ensheathed in a leptomeningeal coverage, filled with CSF in a double triangle shape. These invaginations are known as Virchow-Robin spaces in their original description [8] and previously taught to be a virtual space, enlarged only in pathological processes. Further studies during the last decades reassessed the importance of these channels and prosecuted their anatomical micro description, thus renaming it perivascular spaces (PVSs).
Deeper into the parenchyma, PVS surrounds the penetrating arteries and capillaries, and it includes a real space that exists between the endothelial basement membrane (aka
This anatomical description is better defined for the arterial side of cerebral circulation, while venous PVS has not been thoroughly characterized yet.
Intracranial fluids can be divided in intracellular fluid (ICF, 60–70%), interstitial or extracellular fluid (ISF 20% 280–300 mL), blood (10%), and CSF (10% 140–150 mL). Passage of ions, solutes, and molecules between one compartment and the others is precisely regulated to maintain the different chemical composition necessary to their respective physiological role (e.g. plasma contains approximately 270 times more proteins than ISF) [10].
From 2012, a series of experiment on animals and mathematical models led to the discovery and description of the so-called “
The first evidence of an intraparenchymal bulk flow along PVS was provided by Cserr [12] in 1974 by following injected tracers.
Fluid exchanges between venular lumen and paravascular space depend primarily on transmural pressure (TMP), a fundamental hemodynamic parameter. Considering the venous wall as the exchange border for fluids, TMP is a differential pressure between internal (intravenous) pressure (IP) and external (paravascular) pressure (EP). EP is represented by the oncotic pressure of the interstitium plus the intracranial pressure (ICP). IP is the sum of blood pressure and the relative venous oncotic pressure. In turn, each of these parameters depends on several others. Of main interest is that venous pressure of parenchymal vessels depends on bridging veins (Starling resistors) function. To sustain a reabsorption flow from the parenchyma to the CVS, it is necessary that IP is lower than EP.
So, in this paradigm, a dynamic balance between CSF, ICF, ISF, and blood is continuously rearranged throughout the entire vascular, arachnoidal, and ependymal surface to maintain the physiological functions of the estimated 16–30 billion neurons of the brain.
Main driving force of this interstitial convective process is the arterial pulsation of the penetrating arteries, moving actively the CSF along the PVS [9]. Alongside, the periodical variation in ICP is generated by breathing (and similar activities that modify intrathoracic pressure) and vasomotor variations in the vascular net.
Glymphatic system function, defined as the capability of flushes toxic solutes away from the parenchyma, normally decline with aging, both in animals and humans. Proposed mechanism is a reduced CSF interstitial influx secondary to decreased pulsatility of sclerotic arteries, impaired CSF production, and reduced AQP4 expression on astrocytes end feet9. Hypertension and diabetes mellitus type 2 have also been associated with a decreased glymphatic function. Similar observations have been made in cases of stroke, subarachnoid hemorrhage, traumatic brain injury, and demyelination of various origins.
Cerebral vein thrombosis is defined as the presence, in both the cortical vessels and the dural sinuses, of clotted blood impairing physiological flow.
CVT is an uncommon form of stroke (0.5–1% of total), usually affecting young individuals with several associated risk factors (mainly related to Virchow’s triad of blood stasis):
Thrombophilia
Inflammatory bowel disease
Dehydration
Oral contraceptives
Substance abuse
Other more specific associations are made with:
Complication of epidural blood patch
Spontaneous intracranial hypotension
Lumbar puncture
An underestimated risk factor for CVT is a JV thrombosis that propagates cranially, often because of the presence of medical dispositive [13].
Exact epidemiology of CVT is unknown because clinical features are quite variable, and for this reason, cases should be classified differently [16].
Recently, cerebral venous sinus thrombosis in association with COVID-19 has been described, both as a first clinical presentation or a subsequent complication [17].
Clinical findings are related to intracranial hypertension, related to impaired venous drainage, and/or to focal brain injury from venous ischemia or hemorrhage. Obviously, clinical manifestations of CVT also depend on the location of the thrombosis.
Most frequent symptoms are
When CVT is secondary to regional infection, signs and symptom of the primary cause can be detected: toothache and odontogenic abscess; ear discharge; pain in the ear, face, or mastoid region.
In patients with suspected CVT routine, laboratory essay including complete blood count, chemistry panel, prothrombin time, and activated partial thromboplastin time should be performed [9] in order to identify pro-coagulative systemic status. D-dimer assessment makes sense in presence of low pretest probability of CVT to exclude the diagnosis, similarly to pulmonary embolism. Lumbar puncture is characterized by a high opening pressure (80% of cases) but has limited diagnostic value. It is not routinely indicated unless CNS infection is suspected.
Thirty to forty percent of patients with CVT present with an intracranial hemorrhage [18]. Progressively increasing headache over days and alterations in laboratory exams with evidence of hypercoagulability should prompt further radiological assessment for evaluating CVT. Also, at the CT exam, an ischemic/hemorragic lesion that crosses normal arterial boundaries, deep bilateral, or in close proximity to a venous sinus is suggestive of CVT.
Patients complaining of isolated headache and signs or symptoms of intracranial hypertension (papilledema or sixth nerve palsies) should be evaluated for CVT. The correct differential diagnosis between idiopathic intracranial hypertension (IIH) and CVT has therapeutic and prognostic importance. In both cases, however, clinical manifestations are related to the impaired venous outflow function, with subsequent increasing of the ISF.
In a contest of a CVT suspect case, CT without contrast may demonstrate some characteristic features, but an exact diagnosis is made complex by the intrinsic anatomic variability of the venous sinuses and cortical veins. In fact, only in 30% of CVT cases, CT scan shows some abnormalities [19].
The fundamental sign of acute CVT on a CT (without contrast) is a homogenous hyperdensity of a cortical vein or sinus. Another typical sign of the superior sagittal sinus thrombosis (posterior portion) is the filled delta sign, a dense triangle in the context of the sinus.
Only 0.5–0.8% of patients with CVT showed some signs of subarachnoid hemorrhage, often in atypical position.
The contrast-enhancing CT scan could add some clues, such as the classic “empty delta” sign: an enhancement of the dural border of the sinus with a filling defect within it due to the thrombus in a triangular shape.
This is not a precocious finding, but usually lasts for several weeks after the acute phase.
On the other hand, CT venography is much more useful in chronic follow-up because the occluded sinus cavity shows a variable density. The presence of cortical bone close to the dural sinus can produce interfering artifacts during the visualization of the enhanced dural sinus.
Classically inside the normal sinus, there is a flow void signal due to the venous stream continuously moving. Early signs of CVT can be visualized as
Meanwhile, an acute thrombus, not fully formed yet, may appear as a hypointense signal, similar to the normal flow void.
Other signs include cerebral swelling, edema, and/or hemorrhage. Diffusion-weighted imaging (DWI) sequences show hyperintense signal, meaning a reduced blood flow, with a prognostic significance: brightening sinus on DWI predict low chances of recanalization.
Magnetic resonance imaging (MRI) is particularly helpful in defining the nature and extension of parenchymal lesions, causes, or consequences of the CVT: focal edema, infarction, and infectious processes.
MRI venography is the most common CVT diagnostic technique with the use of two-dimensional time-of-flight (TOF) sequences because of its excellent sensitivity to slow flow inside the sinus.
Venous phase of cerebral angiography (4–8 s from the injections) typically, and directly, shows a filling defect in the occluded lumen. Other signs are venous congestion with dilated cortical, scalp, or facial veins, enlargement of collateral drainage, and venous flow reversal.
Although it is an invasive procedure, cerebral angiography (or venography) could help to solve undefined situations due to anatomic variations such as sinus atresia/hypoplasia, asymmetrical drainage, and normal sinus filling defects caused by arachnoid granulations or septa.
Most used therapeutic approach is based on blood anticoagulation, which aims to prevent thrombus growth, avoids development of pulmonary embolism, and promotes sinus recanalization. Different drugs and different strategies are present in literature [16], with the use of unfractionated heparin (UFH), antivitamin K molecules, low-molecular-weight heparin (LMWH), and low-dose unfractionated heparin. An effective treatment is complicated by the presence of intracranial hemorrhage or cerebral infarction at the time of the diagnosis, given the increased risk of worsening the bleeding.
The available data from RCT comparing clinical/radiological outcomes and bleeding complications support a safe and effective role for anticoagulation in the treatment of CVT, even if intracranial bleeding is present [16]. There are no data that suggest the preferential use of UFH or LMWH in CVT patients. Some data suggest that, if pulmonary embolism or deep vein thrombosis is present, LMWH have to be preferred [20].
In case of secondary CVT (infection, trauma, and other transient causes) vitamin-k antagonist should be continued for 6 months after the removal of the causative factor [16].
Otherwise, in case of primary CVT, vitamin-k antagonist should be continued for 6–12 months and further coagulative assessment should be carried on [16].
Other therapeutic options include
Cerebrospinal venous insufficiency is an emerging nosological entity collecting different conditions that shares an impaired venous outflow from the brain to the heart. Multiple central nervous system disorders, such as idiopathic intracranial hypertension (IIH), Ménière disease, transient monocular blindness, and Alzheimer’s disease, have already been reported to be associated with internal jugular vein (IJV) stenosis [22, 23]. Nowadays, different branches of medical sciences are directing their attention to the delicate balance between cerebral inflow and outflow in order to better understand CVS physiology and its correlation with several disorders. As a mechanical system, a CVS flow obstruction from any causes at any level lead to an increased pressure transmitted upward. This means an increased capillary pressure, thus an increased TMP and finally a decreased glymphatic paravascular ISF flushing and reabsorption into the CVS. Proceeding from the parenchyma to the major vessels, venous convergence reduces the possibility of alternatively restoring a fully functioning flow. Once in the IJV, collateral drainages are few and of limited caliber. So, at this level, any stenosis (intraluminal, parietal, or extraluminal) produce effects diffused at the entire CVS and to the parenchyma. In the mathematical Gadda-Ursino hemodynamic model of CVS outflow, a jugular stenosis is a significant parameter in sinus pressure regulation [24].
Over the last years, several new pathologies have been described related to IJV obstruction, and old ones received new interpretations.
Usually, patients suffering from IIH are women with elevated BMI and normal to slit cerebral ventricles [25]. Meanwhile, IIH has a strong relation with impaired CVS outflow caused by increased thoracic-abdominal or dural sinuses pressure (obesity, CVT, and superior vena cava syndrome). On the other hand, acutely dilated ventricles are related to high-pressure hydrocephalus caused by cerebrovascular pathology (infection, trauma, and hemorrhage).
Recently, an anomalous IIH case with dilated ventricle (Evans index 0.36) has been described in a woman with normal BMI complaining of headache, visual loss (Frisen grade 4 papilledema), and pulsating tinnitus. Neuroimaging did not reveal any causes of hydrocephalus from intracranial lesions, while a fluorodeoxyglucose (FDG) positron emission tomography (PET) described a diffuse hypometabolic cerebral state.
At B-mode echography of extracranial IJV, a bilateral external compression from omohyoid muscle was demonstrated, hemodynamically corresponding to blocked venous flow with scarce collateral compensation.
The patient underwent surgical bilateral resection of omohyoid muscle with ICP invasive monitoring. After transection of the muscles, a sudden drop in ICP and normalization of ICP wave were observed.
Headache and tinnitus disappeared after surgery, and papilledema progressively improved with visual acuity restoration. Serial (24 months’ follow-up) MRI documented regression of Evans index and FDG-PET showed improvement of brain metabolism.
These peculiar cases led to the description of a new clinical entity, a form of hydrocephalus that does not require CSF shunt procedures. This syndrome has been called JEDI (jugular entrapment dilated ventricles intracranial hypertension) syndrome [26]. While an extracranial obstacle to CVS is coherent with intracranial hypertension for the aforementioned principles, it is still unclear what caused ventricles dilatation in this case. More studies are needed to fully comprehend the relation between IJV obstruction, IIH, and hydrocephalus.
In 1937, the American otolaryngologist Dr. Eagle was the first to describe a clinical syndrome caused by an elongated styloid process [27]. The stylohyoid complex is composed of styloid process, stylohyoid ligament, and the lesser horn of the hyoid bone. The styloid bone starts from the inferior portion of the temporal bone, just medially to the base of mastoid process, and directs inferiorly, medially, and anteriorly, passing anteriorly and laterally to the C1 anterior arch and transverse process. These anatomical structures embriologically originate from Reichert’s cartilage of the second brachial arch.
Classic Eagle syndrome is mainly characterized by pain, dysphagia and otalgia, often exacerbated by yawning and swallowing, arising after a tonsillectomy. It is thought that postsurgical scar tissue stretches the sensory nerves ending in the peri-pharingeal region [28].
The carotid artery variant of Eagle syndrome is due to the impingement between an elongated styloid process and the carotid artery and associated nerves. It is characterized by pain and an increased risk of cerebrovascular ischemic accidents: arterial dissection, obstruction, transient ischemic attack, and stroke.
A third variant of the syndrome has been described, consisting in an IJV compressed by an elongated styloid process in the passage adjacent to the transverse process of C1. The most common involved jugular segment is J3, and in more than 50% of patients the stenosis is bilateral. It is alternatively named “
This latter form of Eagle syndrome has specific features related to an impaired CVS outflow.
Clinical presentation is frequently nonspecific. Most frequent symptoms are
More peculiar, an
It is more common in young adults (mean age of onset 38.6 years) with no prevalence between sex.
In literature, only 1/3 of patients with diagnosed Eagle jugular syndrome have an effectively elongated styloid process. This suggests that even with a normal length, an abnormally narrow space between the styloid process and C1 transverse process may lead to IJV compression [30].
Diagnosis is classically radiological, with direct evidence of impaired IJV flow (MRI venography or angiographic venography) or indirect proof of a narrowed C1-styloid space (CT scan or MRI). Few criteria have been proposed, and not diffusely shared between studies, to define a significant IJV stenosis in a setting of suspected Eagle jugular syndrome. According to Jayaraman [31], a jugular stenosis is defined as a caliber reduction >80% on axial cuts compared with the normal vein proximal to the stenosis. Ding and Bai [32] proposed other similar criteria.
More frequently, a conservative treatment is preferred with anticoagulant usage, but in most cases medical therapy has shown no effectiveness on symptoms control.
Invasive procedures are surgical (styloidectomy, C1 anterior arch removal), endovascular (ballooning or stenting), or combination of both. Styloidectomy is the most frequently performed surgical procedure, and major risks are vascular or facial nerve injuries.
On the other side, endovascular treatments are associated with stent migration or fracture, pseudoaneurysm formation, thrombosis, and cranial nerve injuries.
After an invasive approach, more than 70% of patients report an improvement in tinnitus, papilledema, and visual disturbances. Headache, the most frequent symptom, and dizziness usually do not respond to the treatment.
One of the major issues still open regarding the Eagle jugular syndrome is the lack of standardized data, especially on IJV pressure, flow velocity, and collateral pathways. Thus, a complete understanding of pathogenesis is missing.
Multiple sclerosis is a complex autoimmune demyelinating disease characterized by a chronic inflammatory response against the CNS. Many aspects of this disease are still unknown, but evidences have increased, through the last decades, pointing toward a fundamental involvement of CVS in the early development of it.
A cardinal observation is that each MS lesion is crossed and split by a central vein, that is to say that demyelination and inflammatory infiltration develop around a vein [33].
From a wider point of view, inflammatory processes in MS seem to be concentrated around venular vessels, more than capillary or arterial [34].
From these data, and others, an association has been proposed between MS and chronic cerebrospinal venous insufficiency (CCSVI), a condition of long-lasting impaired venous drainage from CVS caused by obstruction in extracranial veins. Recently, CCSVI has been associated also with other degenerative processes such as Alzheimer’s disease, Parkinson’s disease, and Meniere’s disease.
A defective valve, hypoplasia, and/or compression of the IJV or the azygos vein, as defined earlier, increase TMP and reduce the ability of glymphatic system to drain toxic catabolites from the interstitium. These peptides then accumulate at the perivenular level and may act as first inflammatory chemotactic activators and further increase oncotic pressure into the perivascular space, worsening the ISF resorption capacity. Generally, perivenular spaces are recognized as an important site of leukocyte trafficking and the potential milestones to modulate immune response.
Measuring CSF dynamic with MRI reveals interesting links between venous function and MS. In clinically isolated syndrome (CIS), conversion to clinically definite MS in the following year has been related to CSF net flow decreasing [35]. In relapsing-remitting MS, a significant reduction in CSF flow at the level of the Sylvius aqueduct was observed compared to control groups [36]. In the early and progressive form of MS, an increase in ventricular dimension has been observed during the first year. This may be related to the impaired function of glymphatic system, and there are evidences that in these patients, a therapeutic flow restoration through endovascular recanalization of IJV is linked to a significant reduction in ventricles and subarachnoid spaces dimension [37].
Moreover, CCSVI is an ultimate cause of decreased cerebral perfusion because of the propagation of retrograde hypertension. There is a linear correlation between flow into the IJV and global brain perfusion [38]. Moreover, in MS, hypoperfusion is a pathological key point that precedes plaque formation and could be a causative agent, provoking damages to the oxygen-dependent oligodendrocytes. Myelin loss and debris occur when the metabolism of these cells is altered, and this is an important inflammatory signal that attracts leukocytes. Thus, inflammation seems to be a consequence, more than a cause [39]. Subsequent BBB disruption causes microbleedings, and iron deposition, coming from hemoglobin degradation, further increases inflammatory response and microbleedings, especially around venular vessels. Consistently, cerebral tissue iron loading correlates with MS-related disability at the Expanded Disability Status Scale (EDSS) [40].
A subarachnoidal hemorrhage (SAH) not caused by vascular malformation (such as aneurysm or arteriovenous malformation (AVM) rupture) is a recognized clinical entity usually referred as
It typically presents with a pattern limited to the perimesencephalic cisterns (typical pattern), sometimes extended to the nearer basal cisterns (atypical pattern). In the majority of cases, the clinical course is benign, with a very low rate of recurrence. At the neuroimaging, no causes of bleeding are detected, neither immediately or later. Pathogenesis of na-SAH is not established, but the most shared hypothesis regards anatomic variations of CVS, particularly of the Basal Vein of Rosenthal (BVR) draining into venous systems different from the Galenic one. CVS hypertension has also been occasionally reported to influence the overall risk of na-SAH in various conditions, such as cavernous sinus thrombosis, transverse sinus thrombosis, or a bilateral jugular venous obstruction.
In a retrospective case-control study, a significant association has been made between na-SAH and the presence of an IJV stenosis (>80% of caliber reduction) at the passage through the styloid process and the arch of C1 [41]. Also, older age and diabetes were statistically linked to an increased risk of na-SAH.
This is coherent with what has been reported before: an impaired CVS outflow due to a stenosis leads to increased venular pressure, thus predisposing wall rupture and bleeding when an adjunctive pressure is applied (e.g. physical exertion). The presence of anatomic variations may be a further element that increases the risk of na-SAH, but, in the end, the way in which venous configuration of the perimesencephalic area might predispose to bleeding remains undetermined.
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It is a statically approach where we develop the mathematical models through experimental trial runs to predict the possible output on the basis of the given input data or parameters. The aim of this chapter is to stimulate the engineering community to apply Taguchi technique to experimentation, the design of experiments, and to tackle quality problems in industrial chemical processes that they deal with. Based on years of research and applications, Dr. G. Taguchi has standardized the methods for each of these DOE application steps. Thus, DOE using Taguchi approach has become a much more attractive tool to practicing engineers and scientists. And since the last four decades, there were limitations when conventional experimental design techniques were applied to industrial experimentation. And Taguchi, also known as orthogonal array design, adds a new dimension to conventional experimental design. Taguchi method is a broadly accepted method of DOE, which has proven in producing high-quality products at subsequently low cost.",book:{id:"5856",slug:"statistical-approaches-with-emphasis-on-design-of-experiments-applied-to-chemical-processes",title:"Statistical Approaches With Emphasis on Design of Experiments Applied to Chemical Processes",fullTitle:"Statistical Approaches With Emphasis on Design of Experiments Applied to Chemical Processes"},signatures:"Rahul Davis and Pretesh John",authors:[{id:"199438",title:"Mr.",name:"Rahul",middleName:null,surname:"Davis",slug:"rahul-davis",fullName:"Rahul Davis"}]},{id:"14634",doi:"10.5772/15998",title:"The Application of FT-IR Spectroscopy in Waste Management",slug:"the-application-of-ft-ir-spectroscopy-in-waste-management",totalDownloads:6635,totalCrossrefCites:18,totalDimensionsCites:34,abstract:null,book:{id:"1574",slug:"fourier-transforms-new-analytical-approaches-and-ftir-strategies",title:"Fourier Transforms",fullTitle:"Fourier Transforms - New Analytical Approaches and FTIR Strategies"},signatures:"Ena Smidt, Katharina Böhm and Manfred Schwanninger",authors:[{id:"20376",title:"Dr.",name:"Katharina",middleName:null,surname:"Böhm",slug:"katharina-bohm",fullName:"Katharina Böhm"},{id:"22840",title:"Dr.",name:"Ena",middleName:null,surname:"Smidt",slug:"ena-smidt",fullName:"Ena Smidt"},{id:"22915",title:"Dr.",name:"Manfred",middleName:null,surname:"Schwanninger",slug:"manfred-schwanninger",fullName:"Manfred Schwanninger"}]},{id:"15157",doi:"10.5772/15959",title:"Fourier Transform Mass Spectrometry for the Molecular Level Characterization of Natural Organic Matter: Instrument Capabilities, Applications, and Limitations",slug:"fourier-transform-mass-spectrometry-for-the-molecular-level-characterization-of-natural-organic-matt",totalDownloads:4331,totalCrossrefCites:6,totalDimensionsCites:33,abstract:null,book:{id:"122",slug:"fourier-transforms-approach-to-scientific-principles",title:"Fourier Transforms",fullTitle:"Fourier Transforms - Approach to Scientific Principles"},signatures:"Rachel L. Sleighter and Patrick G. Hatcher",authors:[{id:"22676",title:"Dr.",name:"Rachel L.",middleName:null,surname:"Sleighter",slug:"rachel-l.-sleighter",fullName:"Rachel L. Sleighter"},{id:"23168",title:"Dr.",name:"Patrick G.",middleName:null,surname:"Hatcher",slug:"patrick-g.-hatcher",fullName:"Patrick G. Hatcher"}]},{id:"60097",doi:"10.5772/intechopen.75381",title:"Robust Optimization: Concepts and Applications",slug:"robust-optimization-concepts-and-applications",totalDownloads:2535,totalCrossrefCites:23,totalDimensionsCites:30,abstract:"Robust optimization is an emerging area in research that allows addressing different optimization problems and specifically industrial optimization problems where there is a degree of uncertainty in some of the variables involved. There are several ways to apply robust optimization and the choice of form is typical of the problem that is being solved. In this paper, the basic concepts of robust optimization are developed, the different types of robustness are defined in detail, the main areas in which it has been applied are described and finally, the future lines of research that appear in this area are included.",book:{id:"6587",slug:"nature-inspired-methods-for-stochastic-robust-and-dynamic-optimization",title:"Nature-inspired Methods for Stochastic, Robust and Dynamic Optimization",fullTitle:"Nature-inspired Methods for Stochastic, Robust and Dynamic Optimization"},signatures:"José García and Alvaro Peña",authors:[{id:"227809",title:"Ph.D.",name:"Jose",middleName:null,surname:"Garcia",slug:"jose-garcia",fullName:"Jose Garcia"},{id:"240407",title:"Dr.",name:"Alvaro",middleName:null,surname:"Peña",slug:"alvaro-pena",fullName:"Alvaro Peña"}]}],mostDownloadedChaptersLast30Days:[{id:"59209",title:"Utilization of Response Surface Methodology in Optimization of Extraction of Plant Materials",slug:"utilization-of-response-surface-methodology-in-optimization-of-extraction-of-plant-materials",totalDownloads:5398,totalCrossrefCites:57,totalDimensionsCites:87,abstract:"Experimental design plays an important role in several areas of science and industry. Experimentation is an application of treatments applied to experimental units and is then part of a scientific method based on the measurement of one or more responses. It is necessary to observe the process and the operation of the system well. For this reason, in order to obtain a final result, an experimenter must plan and design experiments and analyzes the results. One of the most commonly used experimental designs for optimization is the response surface methodology (RSM). Because it allows evaluating the effects of multiple factors and their interactions on one or more response variables it is a useful method. In this section, recent studies have been compiled which aim to extraction of plant material in high yield and quality and determine optimum conditions for this extraction process.",book:{id:"5856",slug:"statistical-approaches-with-emphasis-on-design-of-experiments-applied-to-chemical-processes",title:"Statistical Approaches With Emphasis on Design of Experiments Applied to Chemical Processes",fullTitle:"Statistical Approaches With Emphasis on Design of Experiments Applied to Chemical Processes"},signatures:"Alev Yüksel Aydar",authors:[{id:"218870",title:"Dr.",name:"Alev Yüksel",middleName:null,surname:"Aydar",slug:"alev-yuksel-aydar",fullName:"Alev Yüksel Aydar"}]},{id:"74096",title:"Time Frequency Analysis of Wavelet and Fourier Transform",slug:"time-frequency-analysis-of-wavelet-and-fourier-transform",totalDownloads:1219,totalCrossrefCites:6,totalDimensionsCites:8,abstract:"Signal processing has long been dominated by the Fourier transform. However, there is an alternate transform that has gained popularity recently and that is the wavelet transform. The wavelet transform has a long history starting in 1910 when Alfred Haar created it as an alternative to the Fourier transform. In 1940 Norman Ricker created the first continuous wavelet and proposed the term wavelet. Work in the field has proceeded in fits and starts across many different disciplines, until the 1990’s when the discrete wavelet transform was developed by Ingrid Daubechies. While the Fourier transform creates a representation of the signal in the frequency domain, the wavelet transform creates a representation of the signal in both the time and frequency domain, thereby allowing efficient access of localized information about the signal.",book:{id:"10065",slug:"wavelet-theory",title:"Wavelet Theory",fullTitle:"Wavelet Theory"},signatures:"Karlton Wirsing",authors:[{id:"325178",title:"Dr.",name:"Karlton",middleName:null,surname:"Wirsing",slug:"karlton-wirsing",fullName:"Karlton Wirsing"}]},{id:"60864",title:"Statistical Methodology for Evaluating Business Cycles with the Conditions of Their Synchronization and Harmonization",slug:"statistical-methodology-for-evaluating-business-cycles-with-the-conditions-of-their-synchronization-",totalDownloads:1328,totalCrossrefCites:1,totalDimensionsCites:2,abstract:"The importance of the topic of business cycle research and their interaction is due to the fact that the cyclical nature of development is a universal feature of the market economy (regardless of the level of development of the country’s economy and the principles of its organization). In all cases, cyclical ups and downs depend not only on internal system cyclical processes and their factors in countries but also on the consequences of intercountry interaction. The ability to measure and predict business cycles, taking into account their mutual influence, is a prerequisite for the development of an adequate business policy of countries and their associations.",book:{id:"6703",slug:"statistics-growing-data-sets-and-growing-demand-for-statistics",title:"Statistics",fullTitle:"Statistics - Growing Data Sets and Growing Demand for Statistics"},signatures:"Elena Zarova",authors:null},{id:"54366",title:"Solution of Differential Equations with Applications to Engineering Problems",slug:"solution-of-differential-equations-with-applications-to-engineering-problems",totalDownloads:6815,totalCrossrefCites:5,totalDimensionsCites:7,abstract:"Over the last hundred years, many techniques have been developed for the solution of ordinary differential equations and partial differential equations. While quite a major portion of the techniques is only useful for academic purposes, there are some which are important in the solution of real problems arising from science and engineering. In this chapter, only very limited techniques for solving ordinary differential and partial differential equations are discussed, as it is impossible to cover all the available techniques even in a book form. The readers are then suggested to pursue further studies on this issue if necessary. After that, the readers are introduced to two major numerical methods commonly used by the engineers for the solution of real engineering problems.",book:{id:"5513",slug:"dynamical-systems-analytical-and-computational-techniques",title:"Dynamical Systems",fullTitle:"Dynamical Systems - Analytical and Computational Techniques"},signatures:"Cheng Yung Ming",authors:[{id:"191017",title:"Dr.",name:"Cheng",middleName:null,surname:"Y.M.",slug:"cheng-y.m.",fullName:"Cheng Y.M."}]},{id:"56538",title:"Stochastic Resonance and Related Topics",slug:"stochastic-resonance-and-related-topics",totalDownloads:1695,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"The stochastic resonance (SR) is the phenomenon which can emerge in nonlinear dynamic systems. In general, it is related with a bistable nonlinear system of Duffing type under additive excitation combining deterministic periodic force and Gaussian white noise. It manifests as a stable quasiperiodic interwell hopping between both stable states with a small random perturbation. Classical definition and basic features of SR are regarded. The most important methods of investigation outlined are: analytical, semi-analytical, and numerical procedures of governing physical systems or relevant Fokker-Planck equation. Stochastic simulation is mentioned and experimental way of results verification is recommended. Some areas in Engineering Dynamics related with SR are presented together with a particular demonstration observed in the aeroelastic stability. Interaction of stationary and quasiperiodic parts of the response is discussed. Some nonconventional definitions are outlined concerning alternative operators and driving processes are highlighted. The chapter shows a large potential of specific basic, applied and industrial research in SR. This strategy enables to formulate new ideas for both development of nonconventional measures for vibration damping and employment of SR in branches, where it represents an operating mode of the system itself. Weaknesses and empty areas where the research effort of SR should be oriented are indicated.",book:{id:"6128",slug:"resonance",title:"Resonance",fullTitle:"Resonance"},signatures:"Jiří Náprstek and Cyril Fischer",authors:[{id:"207472",title:"Dr.",name:"Jiri",middleName:null,surname:"Naprstek",slug:"jiri-naprstek",fullName:"Jiri Naprstek"},{id:"213311",title:"Dr.",name:"Cyril",middleName:null,surname:"Fischer",slug:"cyril-fischer",fullName:"Cyril Fischer"}]}],onlineFirstChaptersFilter:{topicId:"15",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"82432",title:"A Modern Review of Wavelet Transform in Its Spectral Analysis",slug:"a-modern-review-of-wavelet-transform-in-its-spectral-analysis",totalDownloads:0,totalDimensionsCites:0,doi:"10.5772/intechopen.105559",abstract:"The spectral analysis, in much aspects as are the wavelet transform in its numerous versions and its relation with other transforms and special functions requires a special review, since the exploration in the frequency domain to the wavelet transform is more detailed and majorly more specific in different applications. For example, the wavelet transform of special function can be very useful to create and design special signal filters or, for example, to the interphase between reception-emission devices with sensorial parts of the human body. Also the quantum wavelet transform is very useful in the spectral study of traces of particles. Likewise, in this chapter, these aspects are considered as an inherent property of the wavelet transform in the spectral exploration of some phenomena. Finally, general results to the discrete case are given, which is analyzed to the wavelet transform and its spectra.",book:{id:"11150",title:"Recent Advances of Wavelet Transform and Their Applications",coverURL:"https://cdn.intechopen.com/books/images_new/11150.jpg"},signatures:"Francisco Bulnes"},{id:"82378",title:"Covers and Properties of Families of Real Functions",slug:"covers-and-properties-of-families-of-real-functions",totalDownloads:3,totalDimensionsCites:0,doi:"10.5772/intechopen.100555",abstract:"We present results on the relationships of the covering property GΦΨ for Φ,Ψ∈OΛΩΓ and G∈S1SfinUfin of a topological space and the selection property GΦ0Ψ0 of the corresponding family of real functions. The result already published are presented without a proof, however with a citation of the corresponding paper. We present a general Theorem that covers almost all the result of this kind. Some results about hereditary properties are enclosed. We also present Scheepers Diagram of considered covering properties for uncountable covers.",book:{id:"10677",title:"Advanced Topics of Topology",coverURL:"https://cdn.intechopen.com/books/images_new/10677.jpg"},signatures:"Lev Bukovský"},{id:"82356",title:"Geometric Properties of Classical Yang-Mills Theory on Differentiable Manifolds",slug:"geometric-properties-of-classical-yang-mills-theory-on-differentiable-manifolds",totalDownloads:1,totalDimensionsCites:0,doi:"10.5772/intechopen.105399",abstract:"Gauge theories make up a class of physical theories that attempt to describe the physics of particles at a fundamental level. The purpose here is to study Yang-Mills theory at the classical level in terms of the geometry of fiber bundles and differentiable manifolds. It is shown how fundamental particles of bosonic and fermionic nature can be described mathematically. The Lagrangian for the basic interactions is presented and then put together in a unified form. Finally, some basic theorems are proved for a Yang-Mills on compact four-dimensional manifolds.",book:{id:"11502",title:"Manifolds - Recent Developments and Applications",coverURL:"https://cdn.intechopen.com/books/images_new/11502.jpg"},signatures:"Paul Bracken"},{id:"82335",title:"Straight Rectangular Waveguide for Circular Dielectric Material in the Cross Section and for Complementary Shape of the Cross Section",slug:"straight-rectangular-waveguide-for-circular-dielectric-material-in-the-cross-section-and-for-complem",totalDownloads:4,totalDimensionsCites:0,doi:"10.5772/intechopen.104815",abstract:"This chapter presents wave propagation along a straight rectangular waveguide for practical applications where there are two complementary shapes of the dielectric profile in the cross section. In the first case, the cross section consists of circular dielectric material in the center of the cross section. In the second case, the cross section consists of a circular hollow core in the center of the cross section. These examples show two discontinuous cross sections and complementary shapes that cannot be solved by analytical methods. We will explain in detail the special technique for calculating the dielectric profile for all cases. The method is based on Laplace and Fourier transforms and inverse Laplace and Fourier transform. In order to solve any inhomogeneous problem in the cross section, more than one technique can be proposed for the same mode-model method. We will explain in detail how and where the technique can be integrated into the proposed mode-model. The image method and periodic replication are needed for fulfilling the boundary condition of the metallic waveguide. The applications are useful for straight rectangular waveguides in millimeter regimes, where the circular dielectric material is located in the center of the cross section, and also for hollow waveguides, where the circular hollow core is located in the center of the cross section.",book:{id:"11150",title:"Recent Advances of Wavelet Transform and Their Applications",coverURL:"https://cdn.intechopen.com/books/images_new/11150.jpg"},signatures:"Zion Menachem"},{id:"82204",title:"Some Solvability Problems of Differential Equations in Non-standard Sobolev Spaces",slug:"some-solvability-problems-of-differential-equations-in-non-standard-sobolev-spaces",totalDownloads:6,totalDimensionsCites:0,doi:"10.5772/intechopen.104918",abstract:"In this chapter an m-th order elliptic equation is considered in Sobolev spaces generated by the norm of a grand Lebesgue space. Subspaces are determined in which the shift operator is continuous, and local solvability (in the strong sense) is established in these subspaces. It is established an interior and up-to boundary Schauder-type estimates with respect to these Sobolev spaces for m-th order elliptic operators, the trace of functions and trace operator are determined, the boundedness of trace operator and the extension theorem are proved, the properties of the Riesz potential are studied regarding these Sobolev spaces, etc. It is considered a second-order elliptic equation, and we study the Fredholmness of the Dirichlet problem in the Sobolev space generated by a separable subspace of the grand Lebesgue space. It is also considered one spectral problem for a discontinuous second-order differential operator and proved the theorem on the basicity of eigenfunctions of this operator in subspace of Morrey space, in which the infinitely differentiable functions with compact support are dense.",book:{id:"11149",title:"Differential Equations",coverURL:"https://cdn.intechopen.com/books/images_new/11149.jpg"},signatures:"Bilal Bilalov, Sabina Sadigova and Zaur Kasumov"},{id:"82011",title:"Spatial Statistics in Vector-Borne Diseases",slug:"spatial-statistics-in-vector-borne-diseases",totalDownloads:13,totalDimensionsCites:0,doi:"10.5772/intechopen.104953",abstract:"Vector-borne diseases are those caused by the bite of an infected arthropod, such as the Aedes aegypti mosquito, which can infect humans with dengue or Zika. Spatial statistics is an interesting tool that is currently implemented to predict and analyze the behavior of biological systems or natural phenomena. In this chapter, fundamental characteristics of spatial statistics are presented and its application in epidemiology is exemplified by presenting a study on the prediction of the dispersion of dengue disease in Chiapas, Mexico. A total of 573 confirmed dengue cases (CDCs) were studied over the period of January–August 2019. As part of the spatial modeling, the existence of spatial correlation in CDCs was verified with the Moran index (MI) and subsequently the spatial correlation structure was identified with the mean squarer normalized error (MSNE) criterion. A Generalized Linear Spatial Model (GLSM) was used to model the CDCs. CDCs were found to be spatially correlated, and this can be explained by a Matérn covariance function. Finally, the explanatory variables were maximum environmental temperature, altitude, average monthly rainfall, and patient age. The prediction model shows the importance of considering these variables for the prevention of future CDCs in vulnerable areas of Chiapas.",book:{id:"10678",title:"Biostatistics",coverURL:"https://cdn.intechopen.com/books/images_new/10678.jpg"},signatures:"Manuel Solís-Navarro, Susana G. Guzmán-Aquino, María Guzmán-Martínez and Jazmín García-Machorro"}],onlineFirstChaptersTotal:43},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:89,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:104,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:32,numberOfPublishedChapters:318,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:141,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:113,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:105,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:5,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:15,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. 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",coverUrl:"https://cdn.intechopen.com/series/covers/22.jpg",latestPublicationDate:"June 27th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:1,editor:{id:"356540",title:"Prof.",name:"Taufiq",middleName:null,surname:"Choudhry",slug:"taufiq-choudhry",fullName:"Taufiq Choudhry",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000036X2hvQAC/Profile_Picture_2022-03-14T08:58:03.jpg",biography:"Prof. Choudhry holds a BSc degree in Economics from the University of Iowa, as well as a Masters and Ph.D. in Applied Economics from Clemson University, USA. In January 2006, he became a Professor of Finance at the University of Southampton Business School. He was previously a Professor of Finance at the University of Bradford Management School. He has over 80 articles published in international finance and economics journals. His research interests and specialties include financial econometrics, financial economics, international economics and finance, housing markets, financial markets, among others.",institutionString:null,institution:{name:"University of Southampton",institutionURL:null,country:{name:"United Kingdom"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:5,paginationItems:[{id:"91",title:"Sustainable Economy and Fair Society",coverUrl:"https://cdn.intechopen.com/series_topics/covers/91.jpg",isOpenForSubmission:!0,editor:{id:"181603",title:"Dr.",name:"Antonella",middleName:null,surname:"Petrillo",slug:"antonella-petrillo",fullName:"Antonella Petrillo",profilePictureURL:"https://mts.intechopen.com/storage/users/181603/images/system/181603.jpg",biography:"Antonella Petrillo is a Professor at the Department of Engineering of the University of Naples “Parthenope”, Italy. She received her Ph.D. in Mechanical Engineering from the University of Cassino. Her research interests include multi-criteria decision analysis, industrial plant, logistics, manufacturing and safety. She serves as an Associate Editor for the International Journal of the Analytic Hierarchy Process. She is a member of AHP Academy and a member of several editorial boards. 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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:"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.",institutionString:"Kafkas University",institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"178366",title:"Dr.",name:"Volkan",middleName:null,surname:"Gelen",slug:"volkan-gelen",fullName:"Volkan Gelen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178366/images/system/178366.jpg",biography:"Volkan Gelen is a Physiology specialist who received his veterinary degree from Kafkas University in 2011. Between 2011-2015, he worked as an assistant at Atatürk University, Faculty of Veterinary Medicine, Department of Physiology. In 2016, he joined Kafkas University, Faculty of Veterinary Medicine, Department of Physiology as an assistant professor. Dr. Gelen has been engaged in various academic activities at Kafkas University since 2016. There he completed 5 projects and has 3 ongoing projects. He has 60 articles published in scientific journals and 20 poster presentations in scientific congresses. His research interests include physiology, endocrine system, cancer, diabetes, cardiovascular system diseases, and isolated organ bath system studies.",institutionString:"Kafkas University",institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"418963",title:"Dr.",name:"Augustine Ododo",middleName:"Augustine",surname:"Osagie",slug:"augustine-ododo-osagie",fullName:"Augustine Ododo Osagie",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/418963/images/16900_n.jpg",biography:"Born into the family of Osagie, a prince of the Benin Kingdom. I am currently an academic in the Department of Medical Biochemistry, University of Benin. Part of the duties are to teach undergraduate students and conduct academic research.",institutionString:null,institution:{name:"University of Benin",country:{name:"Nigeria"}}},{id:"192992",title:"Prof.",name:"Shagufta",middleName:null,surname:"Perveen",slug:"shagufta-perveen",fullName:"Shagufta Perveen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/192992/images/system/192992.png",biography:"Prof. Shagufta Perveen is a Distinguish Professor in the Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. Dr. Perveen has acted as the principal investigator of major research projects funded by the research unit of King Saud University. She has more than ninety original research papers in peer-reviewed journals of international repute to her credit. She is a fellow member of the Royal Society of Chemistry UK and the American Chemical Society of the United States.",institutionString:"King Saud University",institution:{name:"King Saud University",country:{name:"Saudi Arabia"}}},{id:"49848",title:"Dr.",name:"Wen-Long",middleName:null,surname:"Hu",slug:"wen-long-hu",fullName:"Wen-Long Hu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49848/images/system/49848.jpg",biography:"Wen-Long Hu is Chief of the Division of Acupuncture, Department of Chinese Medicine at Kaohsiung Chang Gung Memorial Hospital, as well as an adjunct associate professor at Fooyin University and Kaohsiung Medical University. Wen-Long is President of Taiwan Traditional Chinese Medicine Medical Association. He has 28 years of experience in clinical practice in laser acupuncture therapy and 34 years in acupuncture. He is an invited speaker for lectures and workshops in laser acupuncture at many symposiums held by medical associations. He owns the patent for herbal preparation and producing, and for the supercritical fluid-treated needle. Dr. Hu has published three books, 12 book chapters, and more than 30 papers in reputed journals, besides serving as an editorial board member of repute.",institutionString:"Kaohsiung Chang Gung Memorial Hospital",institution:{name:"Kaohsiung Chang Gung Memorial Hospital",country:{name:"Taiwan"}}},{id:"298472",title:"Prof.",name:"Andrey V.",middleName:null,surname:"Grechko",slug:"andrey-v.-grechko",fullName:"Andrey V. Grechko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/298472/images/system/298472.png",biography:"Andrey Vyacheslavovich Grechko, Ph.D., Professor, is a Corresponding Member of the Russian Academy of Sciences. He graduated from the Semashko Moscow Medical Institute (Semashko National Research Institute of Public Health) with a degree in Medicine (1998), the Clinical Department of Dermatovenerology (2000), and received a second higher education in Psychology (2009). Professor A.V. Grechko held the position of Сhief Physician of the Central Clinical Hospital in Moscow. He worked as a professor at the faculty and was engaged in scientific research at the Medical University. Starting in 2013, he has been the initiator of the creation of the Federal Scientific and Clinical Center for Intensive Care and Rehabilitology, Moscow, Russian Federation, where he also serves as Director since 2015. He has many years of experience in research and teaching in various fields of medicine, is an author/co-author of more than 200 scientific publications, 13 patents, 15 medical books/chapters, including Chapter in Book «Metabolomics», IntechOpen, 2020 «Metabolomic Discovery of Microbiota Dysfunction as the Cause of Pathology».",institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"199461",title:"Prof.",name:"Natalia V.",middleName:null,surname:"Beloborodova",slug:"natalia-v.-beloborodova",fullName:"Natalia V. Beloborodova",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/199461/images/system/199461.jpg",biography:'Natalia Vladimirovna Beloborodova was educated at the Pirogov Russian National Research Medical University, with a degree in pediatrics in 1980, a Ph.D. in 1987, and a specialization in Clinical Microbiology from First Moscow State Medical University in 2004. She has been a Professor since 1996. Currently, she is the Head of the Laboratory of Metabolism, a division of the Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Moscow, Russian Federation. N.V. Beloborodova has many years of clinical experience in the field of intensive care and surgery. She studies infectious complications and sepsis. She initiated a series of interdisciplinary clinical and experimental studies based on the concept of integrating human metabolism and its microbiota. Her scientific achievements are widely known: she is the recipient of the Marie E. Coates Award \\"Best lecturer-scientist\\" Gustafsson Fund, Karolinska Institutes, Stockholm, Sweden, and the International Sepsis Forum Award, Pasteur Institute, Paris, France (2014), etc. Professor N.V. Beloborodova wrote 210 papers, five books, 10 chapters and has edited four books.',institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"354260",title:"Ph.D.",name:"Tércio Elyan",middleName:"Azevedo",surname:"Azevedo Martins",slug:"tercio-elyan-azevedo-martins",fullName:"Tércio Elyan Azevedo Martins",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/354260/images/16241_n.jpg",biography:"Graduated in Pharmacy from the Federal University of Ceará with the modality in Industrial Pharmacy, Specialist in Production and Control of Medicines from the University of São Paulo (USP), Master in Pharmaceuticals and Medicines from the University of São Paulo (USP) and Doctor of Science in the program of Pharmaceuticals and Medicines by the University of São Paulo. Professor at Universidade Paulista (UNIP) in the areas of chemistry, cosmetology and trichology. Assistant Coordinator of the Higher Course in Aesthetic and Cosmetic Technology at Universidade Paulista Campus Chácara Santo Antônio. Experience in the Pharmacy area, with emphasis on Pharmacotechnics, Pharmaceutical Technology, Research and Development of Cosmetics, acting mainly on topics such as cosmetology, antioxidant activity, aesthetics, photoprotection, cyclodextrin and thermal analysis.",institutionString:null,institution:{name:"University of Sao Paulo",country:{name:"Brazil"}}},{id:"334285",title:"Ph.D. Student",name:"Sameer",middleName:"Kumar",surname:"Jagirdar",slug:"sameer-jagirdar",fullName:"Sameer Jagirdar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334285/images/14691_n.jpg",biography:"I\\'m a graduate student at the center for biosystems science and engineering at the Indian Institute of Science, Bangalore, India. I am interested in studying host-pathogen interactions at the biomaterial interface.",institutionString:null,institution:{name:"Indian Institute of Science Bangalore",country:{name:"India"}}},{id:"329248",title:"Dr.",name:"Md. Faheem",middleName:null,surname:"Haider",slug:"md.-faheem-haider",fullName:"Md. Faheem Haider",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329248/images/system/329248.jpg",biography:"Dr. Md. Faheem Haider completed his BPharm in 2012 at Integral University, Lucknow, India. In 2014, he completed his MPharm with specialization in Pharmaceutics at Babasaheb Bhimrao Ambedkar University, Lucknow, India. He received his Ph.D. degree from Jamia Hamdard University, New Delhi, India, in 2018. He was selected for the GPAT six times and his best All India Rank was 34. Currently, he is an assistant professor at Integral University. Previously he was an assistant professor at IIMT University, Meerut, India. He has experience teaching DPharm, Pharm.D, BPharm, and MPharm students. He has more than five publications in reputed journals to his credit. Dr. Faheem’s research area is the development and characterization of nanoformulation for the delivery of drugs to various organs.",institutionString:"Integral University",institution:{name:"Integral University",country:{name:"India"}}},{id:"329795",title:"Dr.",name:"Mohd Aftab",middleName:"Aftab",surname:"Siddiqui",slug:"mohd-aftab-siddiqui",fullName:"Mohd Aftab Siddiqui",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329795/images/15648_n.jpg",biography:"Dr. Mohd Aftab Siddiqui is currently working as Assistant Professor in the Faculty of Pharmacy, Integral University, Lucknow for the last 6 years. He has completed his Doctor in Philosophy (Pharmacology) in 2020 from Integral University, Lucknow. He completed his Bachelor in Pharmacy in 2013 and Master in Pharmacy (Pharmacology) in 2015 from Integral University, Lucknow. He is the gold medalist in Bachelor and Master degree. He qualified GPAT -2013, GPAT -2014, and GPAT 2015. His area of research is Pharmacological screening of herbal drugs/ natural products in liver and cardiac diseases. He has guided many M. Pharm. research projects. He has many national and international publications.",institutionString:"Integral University",institution:null},{id:"333824",title:"Dr.",name:"Ahmad Farouk",middleName:null,surname:"Musa",slug:"ahmad-farouk-musa",fullName:"Ahmad Farouk Musa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/333824/images/22684_n.jpg",biography:"Dato’ Dr Ahmad Farouk Musa\nMD, MMED (Surgery) (Mal), Fellowship in Cardiothoracic Surgery (Monash Health, Aust), Graduate Certificate in Higher Education (Aust), Academy of Medicine (Mal)\n\n\n\nDato’ Dr Ahmad Farouk Musa obtained his Doctor of Medicine from USM in 1992. He then obtained his Master of Medicine in Surgery from the same university in the year 2000 before subspecialising in Cardiothoracic Surgery at Institut Jantung Negara (IJN), Kuala Lumpur from 2002 until 2005. He then completed his Fellowship in Cardiothoracic Surgery at Monash Health, Melbourne, Australia in 2008. He has served in the Malaysian army as a Medical Officer with the rank of Captain upon completing his Internship before joining USM as a trainee lecturer. He is now serving as an academic and researcher at Monash University Malaysia. He is a life-member of the Malaysian Association of Thoracic & Cardiovascular Surgery (MATCVS) and a committee member of the MATCVS Database. He is also a life-member of the College of Surgeons, Academy of Medicine of Malaysia; a life-member of Malaysian Medical Association (MMA), and a life-member of Islamic Medical Association of Malaysia (IMAM). Recently he was appointed as an Interim Chairperson of Examination & Assessment Subcommittee of the UiTM-IJN Cardiothoracic Surgery Postgraduate Program. As an academic, he has published numerous research papers and book chapters. He has also been appointed to review many scientific manuscripts by established journals such as the British Medical Journal (BMJ). He has presented his research works at numerous local and international conferences such as the European Association for Cardiothoracic Surgery (EACTS) and the European Society of Cardiovascular Surgery (ESCVS), to name a few. He has also won many awards for his research presentations at meetings and conferences like the prestigious International Invention, Innovation & Technology Exhibition (ITEX); Design, Research and Innovation Exhibition, the National Conference on Medical Sciences and the Annual Scientific Meetings of the Malaysian Association for Thoracic and Cardiovascular Surgery. He was awarded the Darjah Setia Pangkuan Negeri (DSPN) by the Governor of Penang in July, 2015.",institutionString:null,institution:{name:"Monash University Malaysia",country:{name:"Malaysia"}}},{id:"30568",title:"Prof.",name:"Madhu",middleName:null,surname:"Khullar",slug:"madhu-khullar",fullName:"Madhu Khullar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/30568/images/system/30568.jpg",biography:"Dr. Madhu Khullar is a Professor of Experimental Medicine and Biotechnology at the Post Graduate Institute of Medical Education and Research, Chandigarh, India. She completed her Post Doctorate in hypertension research at the Henry Ford Hospital, Detroit, USA in 1985. She is an editor and reviewer of several international journals, and a fellow and member of several cardiovascular research societies. Dr. Khullar has a keen research interest in genetics of hypertension, and is currently studying pharmacogenetics of hypertension.",institutionString:"Post Graduate Institute of Medical Education and Research",institution:{name:"Post Graduate Institute of Medical Education and Research",country:{name:"India"}}},{id:"223233",title:"Prof.",name:"Xianquan",middleName:null,surname:"Zhan",slug:"xianquan-zhan",fullName:"Xianquan Zhan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/223233/images/system/223233.png",biography:"Xianquan Zhan received his MD and Ph.D. in Preventive Medicine at West China University of Medical Sciences. He received his post-doctoral training in oncology and cancer proteomics at the Central South University, China, and the University of Tennessee Health Science Center (UTHSC), USA. He worked at UTHSC and the Cleveland Clinic in 2001–2012 and achieved the rank of associate professor at UTHSC. Currently, he is a full professor at Central South University and Shandong First Medical University, and an advisor to MS/PhD students and postdoctoral fellows. He is also a fellow of the Royal Society of Medicine and European Association for Predictive Preventive Personalized Medicine (EPMA), a national representative of EPMA, and a member of the American Society of Clinical Oncology (ASCO) and the American Association for the Advancement of Sciences (AAAS). He is also the editor in chief of International Journal of Chronic Diseases & Therapy, an associate editor of EPMA Journal, Frontiers in Endocrinology, and BMC Medical Genomics, and a guest editor of Mass Spectrometry Reviews, Frontiers in Endocrinology, EPMA Journal, and Oxidative Medicine and Cellular Longevity. He has published more than 148 articles, 28 book chapters, 6 books, and 2 US patents in the field of clinical proteomics and biomarkers.",institutionString:"Shandong First Medical University",institution:{name:"Affiliated Hospital of Shandong Academy of Medical Sciences",country:{name:"China"}}},{id:"297507",title:"Dr.",name:"Charles",middleName:"Elias",surname:"Assmann",slug:"charles-assmann",fullName:"Charles Assmann",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/297507/images/system/297507.jpg",biography:"Charles Elias Assmann is a biologist from Federal University of Santa Maria (UFSM, Brazil), who spent some time abroad at the Ludwig-Maximilians-Universität München (LMU, Germany). He has Masters Degree in Biochemistry (UFSM), and is currently a PhD student at Biochemistry at the Department of Biochemistry and Molecular Biology of the UFSM. His areas of expertise include: Biochemistry, Molecular Biology, Enzymology, Genetics and Toxicology. He is currently working on the following subjects: Aluminium toxicity, Neuroinflammation, Oxidative stress and Purinergic system. Since 2011 he has presented more than 80 abstracts in scientific proceedings of national and international meetings. Since 2014, he has published more than 20 peer reviewed papers (including 4 reviews, 3 in Portuguese) and 2 book chapters. He has also been a reviewer of international journals and ad hoc reviewer of scientific committees from Brazilian Universities.",institutionString:"Universidade Federal de Santa Maria",institution:{name:"Universidade Federal de Santa Maria",country:{name:"Brazil"}}}]}},subseries:{item:{id:"14",type:"subseries",title:"Cell and Molecular Biology",keywords:"Omics (Transcriptomics; Proteomics; Metabolomics), Molecular Biology, Cell Biology, Signal Transduction and Regulation, Cell Growth and Differentiation, Apoptosis, Necroptosis, Ferroptosis, Autophagy, Cell Cycle, Macromolecules and Complexes, Gene Expression",scope:"The Cell and Molecular Biology topic within the IntechOpen Biochemistry Series aims to rapidly publish contributions on all aspects of cell and molecular biology, including aspects related to biochemical and genetic research (not only in humans but all living beings). 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Her research interests include archaea metabolism, enzymes purification and characterization, gene regulation, carotenoids and bioplastics production, antioxidant\ncompounds, waste water treatments, and brines bioremediation.\nRosa María’s other roles include editorial board member for several journals related\nto biochemistry, reviewer for more than 60 journals (biochemistry, molecular biology, biotechnology, chemistry and microbiology) and president of several organizing committees in international meetings related to the N-cycle or respiratory processes.",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null,series:{id:"11",title:"Biochemistry",doi:"10.5772/intechopen.72877",issn:"2632-0983"},editorialBoard:[{id:"79367",title:"Dr.",name:"Ana Isabel",middleName:null,surname:"Flores",slug:"ana-isabel-flores",fullName:"Ana Isabel Flores",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRpIOQA0/Profile_Picture_1632418099564",institutionString:null,institution:{name:"Hospital Universitario 12 De Octubre",institutionURL:null,country:{name:"Spain"}}},{id:"328234",title:"Ph.D.",name:"Christian",middleName:null,surname:"Palavecino",slug:"christian-palavecino",fullName:"Christian Palavecino",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000030DhEhQAK/Profile_Picture_1628835318625",institutionString:null,institution:{name:"Central University of Chile",institutionURL:null,country:{name:"Chile"}}},{id:"186585",title:"Dr.",name:"Francisco Javier",middleName:null,surname:"Martin-Romero",slug:"francisco-javier-martin-romero",fullName:"Francisco Javier Martin-Romero",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSB3HQAW/Profile_Picture_1631258137641",institutionString:null,institution:{name:"University of Extremadura",institutionURL:null,country:{name:"Spain"}}}]},onlineFirstChapters:{paginationCount:34,paginationItems:[{id:"81595",title:"Prosthetic Concepts in Dental Implantology",doi:"10.5772/intechopen.104725",signatures:"Ivica Pelivan",slug:"prosthetic-concepts-in-dental-implantology",totalDownloads:23,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Current Concepts in Dental Implantology - 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