ASIA scale.
\r\n\tIt has been established that energy/nutrient depletion, calcium flux injury, or oxidative stress disrupt endoplasmic reticulum homeostasis and even induce accumulation of misfolded/unfolded proteins leading to endoplasmic reticulum stress. Under endoplasmic reticulum stress conditions, an adaptive mechanism of coordinated signaling pathways, defined unfolded protein response (UPR), is activated to return the endoplasmic reticulum to its healthy functioning state. The aging causes a decrease of the protective adaptive response of the UPR and an increase of the pro-apoptotic pathway together with endoplasmic reticulum ultrastructural injury. Controlling endoplasmic reticulum stress response, maintaining the appropriate endoplasmic reticulum ultrastructure and homeostasis, and retaining mitochondria interplay are crucial aspects for cellular health.
\r\n\r\n\tThis book presents a comprehensive overview of endoplasmic reticulum, including, but not limited to, endoplasmic reticulum ultrastructural anatomy, MAMs, endoplasmic reticulum stress, and their implication in health and diseases. Additionally, identifying perturbations in the endoplasmic reticulum stress response could lead to early detection of age-related disease and may help develop therapeutic approaches.
",isbn:"978-1-80356-228-5",printIsbn:"978-1-80356-227-8",pdfIsbn:"978-1-80356-229-2",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,hash:"5d7d49bd80f53dad3761f78de4a862c6",bookSignature:"Dr. Gaia Favero",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11674.jpg",keywords:"Metabolism, Aging, Neurodegenerative Diseases, Endoplasmic Reticulum, Microscopy, Metabolic Stress, Ultrastructural Anatomy, Cellular Stress, Contactology, Mitochondria, Cellular Stress, Endoplasmic Reticulum Response",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"February 9th 2022",dateEndSecondStepPublish:"May 6th 2022",dateEndThirdStepPublish:"July 5th 2022",dateEndFourthStepPublish:"September 23rd 2022",dateEndFifthStepPublish:"November 22nd 2022",remainingDaysToSecondStep:"13 days",secondStepPassed:!0,currentStepOfPublishingProcess:3,editedByType:null,kuFlag:!1,biosketch:"Human anatomy researcher involved in crucial topics on morphology, anatomy, and molecular medicine - working on innovative approaches to aging-related pathopsychological processes at the University of Brescia.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"238047",title:"Dr.",name:"Gaia",middleName:null,surname:"Favero",slug:"gaia-favero",fullName:"Gaia Favero",profilePictureURL:"https://mts.intechopen.com/storage/users/238047/images/system/238047.jpg",biography:'Dr. Gaia Favero is a prominent scientist in the field of life sciences. She is currently engaged as a researcher for the Scientific-Disciplinary Sector BIO/16 Human Anatomy at the Anatomy and Pathophysiology Division, Department of Clinical and Experimental Sciences, University of Brescia (Italy).\r\nDr. Favero focuses on aging-related morphological dysfunctions as the prelude to various pathophysiological processes in her research programs. The central hypothesis is that natural antioxidants and, in particular, melatonin may act as molecular "switches" that modulate cells and tissues by suppressing, at various levels, oxidative stress and inflammatory signalling cascades. These research approaches represent powerful tools for developing innovative preventive strategies and identifying novel prognostic biomarkers for several diseases. The above-reported research activity determined more than 120 scientific publications and an h-index of 25.',institutionString:"University of Brescia",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"University of Brescia",institutionURL:null,country:{name:"Italy"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"6",title:"Biochemistry, Genetics and Molecular Biology",slug:"biochemistry-genetics-and-molecular-biology"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"278926",firstName:"Ivana",lastName:"Barac",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/278926/images/8058_n.jpg",email:"ivana.b@intechopen.com",biography:"As an Author Service Manager my responsibilities include monitoring and facilitating all publishing activities for authors and editors. From chapter submission and review, to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. 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Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"72",title:"Ionic Liquids",subtitle:"Theory, Properties, New Approaches",isOpenForSubmission:!1,hash:"d94ffa3cfa10505e3b1d676d46fcd3f5",slug:"ionic-liquids-theory-properties-new-approaches",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/72.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"314",title:"Regenerative Medicine and Tissue Engineering",subtitle:"Cells and Biomaterials",isOpenForSubmission:!1,hash:"bb67e80e480c86bb8315458012d65686",slug:"regenerative-medicine-and-tissue-engineering-cells-and-biomaterials",bookSignature:"Daniel Eberli",coverURL:"https://cdn.intechopen.com/books/images_new/314.jpg",editedByType:"Edited by",editors:[{id:"6495",title:"Dr.",name:"Daniel",surname:"Eberli",slug:"daniel-eberli",fullName:"Daniel Eberli"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"57",title:"Physics and Applications of Graphene",subtitle:"Experiments",isOpenForSubmission:!1,hash:"0e6622a71cf4f02f45bfdd5691e1189a",slug:"physics-and-applications-of-graphene-experiments",bookSignature:"Sergey Mikhailov",coverURL:"https://cdn.intechopen.com/books/images_new/57.jpg",editedByType:"Edited by",editors:[{id:"16042",title:"Dr.",name:"Sergey",surname:"Mikhailov",slug:"sergey-mikhailov",fullName:"Sergey Mikhailov"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1373",title:"Ionic Liquids",subtitle:"Applications and Perspectives",isOpenForSubmission:!1,hash:"5e9ae5ae9167cde4b344e499a792c41c",slug:"ionic-liquids-applications-and-perspectives",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/1373.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"2270",title:"Fourier Transform",subtitle:"Materials Analysis",isOpenForSubmission:!1,hash:"5e094b066da527193e878e160b4772af",slug:"fourier-transform-materials-analysis",bookSignature:"Salih Mohammed Salih",coverURL:"https://cdn.intechopen.com/books/images_new/2270.jpg",editedByType:"Edited by",editors:[{id:"111691",title:"Dr.Ing.",name:"Salih",surname:"Salih",slug:"salih-salih",fullName:"Salih Salih"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"72439",title:"Rehabilitation Therapies in Spinal Cord Injury Patients",doi:"10.5772/intechopen.92825",slug:"rehabilitation-therapies-in-spinal-cord-injury-patients",body:'\nSpinal cord injury (SCI) is attributable to trauma caused by accidents like car crashes, falls or sports such as diving or gymnastics, and violent causes like gunshots or injuries by cold weapon [1] and also caused by nontraumatic causes like primary or metastatic tumors, compressive myelopathy such as cervical spondylotic myelopathy, neurodegenerative diseases such as motor neuron disease, autoimmune diseases like multiple sclerosis, infections such as epidural abscess, and vascular diseases such as medullary infarction, as well as genetic causes, for example, spinal muscular atrophy [2] that affect spinal cord motor and sensory function, also causing neurogenic bladder or bowel.
\nThe global prevalence rate, including both traumatic and nontraumatic causes, is 40–80 cases per million people; however 90% of cases are due to traumatic causes, with a male-to-female ratio of 2:1, respectively [3], presenting with a bimodal age peak of young people and 60-year-old people [4]. To estimate the economic burden, the first year after injury treatment cost is estimated to be $334,170 USD rising to $1,023,924 USD [5]. The main causes of SCI are vehicle accidents, falls, violence [6], compressive myelopathy, tumors, and multiple sclerosis [2]. Most damaged anatomical regions are the lower cervical spine, cervicothoracic union, and thoracic-lumbar union [6]. Prognosis depends on the level of injury [4].
\nTo the present day, there are no medical or surgical procedures to reverse neurological damage in SCI patients; therefore new rehabilitation strategies have been designed to avoid deterioration in many patient scopes. This process has to be coordinated by a multidisciplinary SCI expert team so that biopsychosocial impact on patients is reduced.
\nThere are several tools to assess the patient with SCI; some of them are the following, ASIA scale, Spinal Cord Independence Measure (SCIM) scale, Walking Index for Spinal Cord Injury II (WISCI II) scale, and Short-Form Health Survey (SF-36) quality of life test, which will be discussed in detail below. These are very useful instruments that ease decision-making on treatment and rehabilitation, taking into consideration patient capacity and expectations to integrate into society.
\nThis scale developed by the American Spinal Injury Association is considered the gold standard for SCI clinical evaluation. The scale significance relies on its capacity to determine the level of injury, whether it is a complete or incomplete injury, predict prognosis, and serve as guidance for treatment.
\nIt consists of the examination of dermatomes and myotomes. For evaluation of sensory function, 28 key dermatomes are explored using a piece of cotton and a monofilament. For motor examination, five upper and five lower key muscle groups are evaluated. S4 and S5 dermatome evaluation is useful to determine if the injury is complete or incomplete by looking for external anal sphincter contraction and anal pressure sense.
\nPatients are classified from A, which means an injury is complete, to E, where patients have normal functionality (Table 1). This tool provides a long-term reliable prognosis, but it does not take into account pain and spasticity [7, 8].
\nComplete | \nNo motor and sensory function | \n|
Incomplete | \nSensory function preserved. No motor function below the level of injury, including S4-S5 level | \n|
Incomplete | \nMotor function preserved below the level of injury and more than half of the key muscles below the level of injury with less than 3/5 strength | \n|
Incomplete | \nMotor function preserved below the level of injury and at least half of key muscles with strength more than 3/5 | \n|
Normal | \nNormal sensory and motor function | \n
ASIA scale.
According to this scale, an accurate prognosis can be established if a 72-h post-injury evaluation is made. 80% of patients with an A-type injury will remain in this classification; meanwhile, 10% will convert into a B-type injury and the 10% remaining will convert into a C-type injury; from the conversion percentage, only 14% of the patients will gain some aided gait capacity. Patients with B-type injury are considered to gain 33% of gait capacity, C-type injury patients will gain approximately 75% of gait capacity, and D-type injury patients will have a very good prognosis since most of them will be able to walk in 1-year post-injury [9, 10].
\nThe Spinal Cord Independence Measure is a tool that assesses an SCI patient capacity to perform daily life activities. This instrument evaluates 19 areas and contains 4 subscales: self-caring (0–20 points), breathing and sphincter control (0–40 points), room and bathroom mobility (0–10 points), and interior and exterior mobility (0–30 points). Besides these subscales, feeding, bed mobility, pressure ulcer prevention, and transfer from wheelchair to the car and floor are included [11].
\nThe maximum score to obtain is 100 points; a high score means that the patient is independent for daily life activities. This is a self-assessment tool, so there is no need for qualified personnel to evaluate it [12].
\nThe Walking Index for Spinal Cord Injury II is a reliable and trustworthy tool to measure walking improvement in SCI patients [13]. It comprises 21 levels that evaluate gait, considering the use of walking aids. It goes from 0 (the patient is not able to walk) to 20 (the patient walks at least 10 m without crutches or assistance) [14].
\nThe Short-Form Health Survey questionnaire is a nonspecific generic test broadly used to evaluate the quality of life, considering both positive and negative subjects, in patients with chronic conditions and mobility diseases [15]. It is easy to answer and takes approximately 5 to 10 min.
\nThe test comprises 36 items, divided into 8 subscales that evaluate the following areas: physical function (10 items), role limitations due to physical issues (4 items), pain (2 items), general health appreciation (5 items), vitality (4 items), social function (2 items), role limitations due to emotional issues (3 items), mental health (5 items), and an additional item that compares actual health with previous year perception of health [16]. Many studies have found with this instrument that SCI has a negative influence on the quality of life of patients [17].
\nSCI is a neurological condition that demands a long rehabilitation period, coordinated by a multidisciplinary team because of the damage that it entails. To avoid complications as much as possible, to improve function, and to achieve the most independence, numerous rehabilitation strategies have been shown in many studies to have an impact in patient recovery; some of them are the following: strength, range of movement and stretching exercises, functional electrical stimulation (FES), epidural electrical stimulation (EES) of the spinal cord, occupational therapy, dry needling, and exoskeleton.
\nRange of movement refers to the normal movement of a joint; hence range of movement exercises are those that promote joint mobility and flexibility.
\nStudies have observed that these exercises improve function for daily life activities [18], prevent contractures, protect tenodesis effect [19], strengthen paralyzed muscles, promote nerve and cerebral remodeling, and improve spinal microenvironment and functional prognosis [20]. For protection of the joint structure and preservation of muscle tone, sandbags, pillows, or orthotics are usually used. Exercise is important for strengthening the muscles of the upper limbs, emphasizing on rotation of the shoulders for the use of crutches or wheelchair. These exercises will help in the mobilization and independence in daily life activities. In patients with incomplete SCI, walking potential is high, so sitting, parallel bars, and balance exercises should be done [19].
\nFunctional electrical stimulation is a technique that artificially activates sensory-motor systems through electrical current pulses, producing action potentials in afferent and efferent neural pathways to stimulate muscles and generate movement [21]. This procedure is added to other therapies to increase mobility, sensory feedback, and muscle activity to decrease atrophy. It also provides cardiorespiratory fitness; improves posture and trunk stability [22]; prevents contractures, pressure ulcers, and orthostatic hypotension [23]; promotes nerve restoration; and prevents peripheral nerve deterioration [24].
\nFunctional electrical stimulation is a technique that artificially activates sensory-motor systems through electrical current pulses, producing action potentials in afferent and efferent neural pathways to stimulate muscles and generate movement [21]. The main elements of a FES system are the battery, an electronic stimulator, control unit, wiring, and electrodes. The controller can work through a switch, joystick, or voice. There are different types of electrodes, superficial, intramuscular percutaneous, implantable, and epimysial; however the commercially available are the superficial ones, which should be placed over the skin above the nerves to be stimulated; the rest of the electrodes are for research purpose only. The electrodes must be of low-impedance, flexible, and easy to don and doff [22]. The electrical parameters of these systems are waveforms, amplitude, pulse width, reciprocity, ramp, and duration; all of these are combined to generate an electrical current and must be adjusted to achieve the desired response [22, 23].
\nIt is important to evaluate the patient to determine if he or she is a candidate for this therapy. Some exclusion criteria for FES are the following: if the patient has an electrical implantable device, history of cancer, osteomyelitis, epilepsy, and thrombosis [23].
\nFES systems can be applied to different sites. In patients with cervical SCI, hand function recovery is the main priority, so there are FES systems developed for the upper limb that work through neuroprosthetics with a stimulator for forearm and hand muscles; patients with injuries at C5-C6 level can benefit with this therapy. The only commercially available systems for the upper limb are NESSH200 and Compex. NESSH200 consists of an adjustable wrist prosthetic with five electrodes for finger flexors and extensors, allowing handgrip [24, 25]. There are FES systems for lower limbs that allow sitting and mobility. The best candidates for this therapy are patients with injuries at T4-T12 level, which have more impact in patients with incomplete injuries. The FES neuroprosthetics for the lower limbs stimulate the knees and hips [24]. A commercially available FES system in the USA is the Parastep, which works through 4–6 channels to stimulate the quadriceps and gluteal muscles. Battery is placed on the waist and controls are over a walker [25]. FES cycling systems are also commercially available; one of them is developed by Restorative Therapies, Inc. [24] and the other one, ERGYS, developed by Therapeutic Technologies, Inc. which has six electrodes to stimulate the quadriceps, hamstrings, and gluteal muscles [22].
\nThis procedure is added to other therapies to increase mobility, sensory feedback, and muscle activity to decrease atrophy. It also provides cardiorespiratory fitness; improves posture and trunk stability [26]; prevents contractures, pressure ulcers, and orthostatic hypotension [27]; promotes nerve restoration; and prevents peripheral nerve deterioration [28].
\nThis strategy requires a device to be implanted through a laminectomy over the dura mater of the spinal cord [25]. The device delivers a rhythmical afferent electrical current to posterior nerve roots to activate central circuits that regulate movement, pain, and the cardiorespiratory system [22].
\nIt is believed that EES activates two pathways: The first one stimulates afferent dorsal pathways that synapse with motor neurons; the second pathway directly stimulates motor neurons through stimulation of efferent motor nerves [26].
\nStudies in SCI patients have shown that this strategy decreases fatigue [25], improves cardiovascular and respiratory fitness, increases lean body mass, and improves bladder voiding [26]. The main disadvantage of EES is that it requires surgery for device insertion, which implicates the risk of infection, hematoma, or injury because of the device [25].
\nThis experimental strategy requires a device to be implanted through a laminectomy over the dura mater of the spinal cord [29]. The device delivers a rhythmical afferent electrical current to posterior nerve roots to activate central circuits that regulate movement, pain, and the cardiorespiratory system [26].
\nIt is believed that EES activates two pathways: The first one stimulates afferent dorsal pathways that synapse with motor neurons; the second pathway directly stimulates motor neurons through stimulation of efferent motor nerves [30].
\nStudies in SCI patients have shown that this strategy decreases fatigue [29], improves cardiovascular and respiratory fitness, increases lean body mass, and improves bladder voiding [30]. The main disadvantages of EES are that it requires surgery for device insertion, which implicates the risk of infection, hematoma, or injury because of the device [29], it is expensive, and it does not yet establish a standard number of sessions and parameter configurations since multiple studies have shown that outcomes vary in each patient due to SCI heterogeneity [30].
\nIt is worth mentioning that this technique is used merely for research purpose only and it is not approved by health authorities. The evidence that exists to date is not enough to justify its use, since it has been studied only in specific small cohorts of patients or single patients with SCI and there are no clinical trials with this method [29, 30].
\nTENS is a high- and low-frequency electrical current therapy. It is used for pain management, but many other benefits have been observed, such as balance and proprioception improvement and spasticity decrease [31]. To date, its mechanism of action is unknown; however, different theories assume it works by modulating inhibitory spinal circuits, by activating afferent neurons, or by inducing central nervous system plasticity [32]. When applying it, it is necessary to consider electrode positioning, frequency, and pulse intensity; though, there is not a consensus on how long sessions should last and how much frequency has to be applied. The main advantages of this therapy are that it is low cost, it is easy to apply since the patient can do it by himself/herself, and there are no side effects reported yet [31, 33].
\nOccupational therapy is a crucial process in rehabilitation since it eases societal role finding [19]. It focuses on enhancing daily life activity execution and fine movement, by searching for total independence or performing compensatory strategies to adapt [34, 35, 36] as well as patient’s environment adaption (home, transportation, or workplace) to achieve total inclusion with its remaining abilities.
\nIt demands equipment and techniques for transferring from one surface to another, dressing, bathing, grooming, feeding, cooking, respiratory exercises, and vesical and intestinal control. Besides, it also trains on wheelchair use and provides counseling for house modification like ramp addition, bath chair incorporation, and current insulation [34, 37].
\nDry needling is an invasive procedure that consists of reaching muscle myofascial trigger points (MTPs) with a needle [38]. MTPs are small, tense muscle nodules that cause pain, cause weakness, and limit range of motion [39].
\nIt is considered that dry needling stimulation inhibits spontaneous electrical activity in MTPs by diminishing the availability of acetylcholine in the motor end plate (it is believed that MTP originates here); consequently, muscle fiber relaxes, promoting pain and spasticity reduction and improving gait speed and stability in patients with incomplete injury [39, 40]. It is worth mentioning that more studies have to be made to set the frequency, duration, and intensity of sessions to obtain desirable outcomes [41].
\nExoskeletons are battery-powered robotic devices that adjust to the patients’ limbs; it can be operated with manual or oral control or micromovement detector to ease mobility and gait [26, 34].
\nTwo main objectives of exoskeletons are promoting recovery through repeated movements to increase neural plasticity and assist mobility [42]. ReWalk™ and Indego™ are two community use exoskeletons [43] that enable walking, sitting, and climbing stairs up and down [44, 45]. Their use has shown improvements in quality of life, body composition, bone density, neuropathic pain, and spasticity [42] and an increase in gait speed [43], number of steps, and distance test before and after 90 days of training [34]. Restraints for certain users are height, weight, articular rigidity, and high cost ($80,000 USD) [43].
\nElectrical stimulation outcome measurement can be performed through different methods, depending on the evaluated function. After FES, cycling outcomes can be measured by tridimensional analysis of the gait, estimation of oxygen consumption by indirect calorimetry, and muscle tone evaluation with Modified Ashworth Scale [46]. To evaluate outcomes after EES, the following methods can be applied: Motor activity can be evaluated by electromyography and motor tasks, the cardiovascular status might be evaluated by blood pressure measurement after tilt table testing; sexual performance can be assessed by the achievement of orgasm, and for bladder control evaluation, the Neurogenic Bladder Symptom Score (NBSS) can be applied, or post-void residual volume and voluntary urination capacity can be evaluated [47]. In other studies, the outcomes have been measured through motor task performance such as sitting and balance, body fat mass measurement, and respiratory function or inspiratory function by coughing; all cases are compared before and after therapy application [30].
\nCardiovascular rehabilitation is critical because daily life activities are not enough to preserve cardiovascular health. It is estimated that the prevalence of cardiovascular diseases in patients with SCI is 60–70% and these represent, just as in able population, the main cause of death [48]. Besides, if the level of injury is higher, so will be the sedentarism and risk [49]. Another detail to consider is that SCI patients have a higher risk of complications such as thromboembolism, autonomic dysreflexia (AD), orthostatic hypotension, pain, and cardiac atrophy [34].
\nFor cardiovascular status enhancement in the SCI patient, it is suggested to: (1) do body weight-supported training for it has advantageous effects on cardiac rhythm and blood pressure; (2) do upper limb exercise with moderate to strenuous intensity 3 days a week for at least 6 weeks; and (3) train with functional electrical stimulation 3 days a week for at least 2 months. This kind of training improves the patient lipid profile because it reduces triglycerides and LDL cholesterol [48].
\nAfter a long resting period, patients may suffer orthostatic hypotension. Training with a tilt table can be useful to get patients used to a vertical position, with a gradual beginning until tolerance of position is achieved. Afterward, patients should sit on the border of the bed by their own 3 or 4 times a day to keep balance. This is important because the position is needed for wheelchair use [19].
\nFor optimal glycemic control, aerobic exercise and EES 30 min a day for at least 3 times a week for 8 weeks is recommended [48].
\nAutonomic dysreflexia consists of a sudden blood pressure elevation caused by stimuli such as bladder overdistension or lack of bowel voiding, tight clothes, or pressure ulcers.
\nAD is considered when systolic blood pressure increases to 20–40 mmHg over the baseline. This usually occurs in patients with injuries in or over T6 level. AD happens because the previously mentioned stimuli start an uncontrolled adrenergic response due to an abnormal supraspinal regulatory signal, causing blood pressure elevation and bradycardia as a compensatory response.
\nAD is an emergency since it can cause serious complications such as hypertensive encephalopathy, seizures, cardiac arrest, or even death. To prevent patients from AD, stimuli should be avoided. Some pharmacological treatments used are nitrates, nifedipine, prazosin, capsaicin, and botulinum toxin for refractory cases [50, 51].
\nPulmonary rehabilitation is critical in the acute and chronic phases of SCI, particularly in patients with high-level injuries because there are respiratory muscle paralysis limiting thoracic expansion, low pulmonary volumes, and weak cough [52]. Previously mentioned issues cause hypoventilation, mucus plugs, surfactant decrease, pneumonia, atelectasis, or respiratory failure that may result in death if not properly cared [53].
\nAdditionally, due to respiratory mechanics compromise, certain voice characteristics are affected such as less syllable production per breathing, less volume, and more roughness [54].
\nThe next section discusses the strategies to improve pulmonary function: (1) postural changes and early mobilization; (2) breathing techniques, spontaneous cough, and cough aid; (3) secretion management and respiratory muscle training [19, 34, 53]; and (4) pulmonary percussion and vibration therapy [26].
\nNeurofacilitation techniques are frequently used in patients who suffered a stroke but these can also be applied to patients with SCI. It consists of a group of techniques whose main objectives are functionality recovering through noninvasive neuropsychological stimulation, promoting nerve regeneration, and neural systems reorganization [55]. Some of these techniques are mentioned below.
\nIt is useful for upper limb rehabilitation. It consists of repeatedly training the limb mobility; meanwhile the contralateral limb is immobilized. However, there has to be some mobility remaining to be applied [55].
\nThis is a functional movement training in which the patient stands over a treadmill with a harness, aided by therapists to move the legs and keep balance. It can be beneficial since it is an aerobic exercise [55].
\nBobath method consists of a group of complex, specific, and individualized techniques based on postural control and task execution, taking advantage of neuromuscular plasticity to achieve problem-solving in people with movement disorders. It is possible to control posture, reduce spasticity, increase muscle tone, and improve standing ability through this method [56, 57].
\nUp to 80% of patients with SCI suffer neurogenic bladder as a result of detrusor hyperactivity disorder, sphincter dyssynergia, or detrusor areflexia; they have an increased risk of urinary incontinence, recurrent infections, vesicoureteral reflux, and renal and bladder lithiasis [58].
\nMost of the patients will need management for dry, incomplete voiding, to ensure the low-pressure reservoir function of the bladder. This management begins with anticholinergic medication and intermittent catheterization; patients who failed these treatments need more invasive treatments such as sphincterotomy, botulinum toxin applications, and stent insertion [59].
\nImaging and urodynamic studies should be performed for the initial evaluation of the patient [60]. Catheterization techniques are detailed below.
\nThis is the most used method for bladder drainage without the need for a permanent catheter. A catheter is inserted in an interval of 4–6 h. It prevents complications such as hydronephrosis and kidney and bladder stones. It must be done by patients who have enough manual ability (writing and feeding) or a caregiver willing to do it [60].
\nIt consists of the insertion of a suprapubic or urethral catheter. This catheterization is suggested for patients with poor manual ability, cognitive deficits, and limited assistance [60].
\nIt is the application of suprapubic pressure for drainage of the bladder. It is used when the bladder is flaccid or when it is necessary to increase the contraction; the Valsalva method is also used to drain the bladder [60].
\nTransurethral sphincterotomy, stent colocation, or ileocystoplasty can be done.
\nNeurogenic bowel dysfunction occurs 95% of the time as constipation and 75% as fecal incontinence. Hemorrhoids, abdominal pain, prolapse, rectal bleeding, and anal fissures also occur and can trigger episodes of autonomic dysreflexia.
\nThe management of this dysfunction requires a history of bowel habits in addition to a complete physical examination [61]. It is recommended to establish a schedule to defecate in a comfortable position, implementing changes in diet and lifestyle before using laxatives or suppositories. The caregiver must perform an examination or digital stimulation; manual removal of feces is also preferable [60, 61]. Enemas are another treatment [62].
\nAfter SCI, sexual function is affected since it alters the motor, sensory, and autonomous functionality, and its importance relies in the fact that the number of patients with SCI is young in a childbearing age. There is damage to male fertility, vaginal lubrication, erection, and ejaculation [63].
\nThe causes of sexual dysfunction are multifactorial: altered sensitivity, erectile dysfunction, and side effects of medical therapy.
\nIn men with SCI, some dysfunctions can present as a delayed orgasm, erectile or ejaculatory disorder, seminal abnormalities such as hypomotility, or low sperm viability [64].
\nIt is a questionnaire designed to assess the sexual function and satisfaction in men. This instrument includes 10 questions where physical and emotional aspects are considered; scores go from 0 to 100 points [65].
\nAdministration of phosphodiesterase-5 inhibitors is helpful in inhibition of guanosine monophosphate degradation causing smooth muscle relaxation. Other methods are intracavernous application of phentolamine, papaverine, and alprostadil or intraurethral application of alprostadil [64].
\nVibratory stimulation can be done until antegrade ejaculation is achieved. Another method is electroejaculation, which electrically stimulates prostatic nerves and muscles and seminal vesicles; if retrograde ejaculation occurs, a catheter is needed to collect residual semen from the bladder [64].
\nIn women, sexual function after SCI has not been sufficiently studied as in male dysfunction. Sexual rehabilitation in women focuses on psychological matters and sphincter control during sexual activities. In addition, vaginal lubrication depends on neurological factors and vascular factors [66, 67].
\nSCI causes an alteration in the microenvironment of the skin, causing excessive sweating, thinning, onychogryphosis, paronychia, tinea, seborrheic dermatitis, and cellulitis [68, 69]; besides, keeping the same position for a long time damages the integrity causing pressure ulcers [70].
\nPressure ulcers are the result of applying pressure to tissue over a bone prominence, exceeding the 12–32 mmHg capillary pressure collapsing the capillaries and causing ischemia. Pressure ulcers represent a major problem for patients with SCI in the acute and chronic stages, also considering the cost involved in treatment [71]. For correct management, pressure must be decreased, and special mattresses, heel protectors, and turns and transfers are recommended. Regarding turns, these must be done in intervals of 2–4 h. Lateral positioning should be limited to minimize pressure on bony prominences. When the patient is in supine position, the bed must incline less than 30° or the limbs must be elevated. Patients using a wheelchair should be trained to distribute pressure by tilting at intervals of 15–30 min [62].
\nSince life expectancy in patients with SCI has been prolonged, the incidence of metabolic syndrome, diabetes, cardiovascular diseases, but also malnutrition has increased substantially; therefore, it is important to make a nutritional plan.
\nThere are no nutritional guidelines for patients with SCI; however, the following general measures are suggested:
Abundant consumption of fruits and vegetables to obtain fiber and avoid constipation; it is recommended to adjust the amount of it to avoid bloating and diarrhea.
Plenty intake of water (minimum 1.5 l).
Protein consumption of 0.8 g/kg per day is recommended, and if a pressure ulcer is present, this amount can be 1.2 g/kg, rising up to 2 g/kg if the ulcers are grade III or IV. The purpose of increasing protein consumption is to decrease the negative nitrogen balance, which is greater in acute stages of the disease; it is also helpful in preserving muscle mass and avoiding glucose intolerance. Liquid protein supplements that contain leucine may be recommended.
High-fat diets should be avoided since the patient lipid profile is altered and predisposes to metabolic syndrome.
Omega-3 is recommended because of its neuro- and cardioprotective effects; however more studies are required.
Micronutrients such as vitamins A, B5, D, E, and C and biotin and minerals such as calcium, chlorine, magnesium, and potassium are usually low consumed, so their intake should increase to improve glucose metabolism.
Nutritional plans must be individualized according to the objectives, the age of the patient, and the level of the injury [72, 73].
\nPsychological management after SCI is essential for the patient in order to return to activities of daily living. After an injury, there are many psychological stages in the readjustment process: shock and denial, depression, anxiety, anger, negotiation, and adaptation.
\nPsychological rehabilitation should start in the intensive care unit because the patient can experience disorientation, depression, anxiety, and sensory and sleep deprivation.
\nPsychotherapy groups are helpful to provide emotional support, educate in the development of new skills, and minimize social aversion. Similarly, family psychotherapy groups make it easier for the family to adjust to the new situation since similar emotional reactions also occur in them [74].
\nThis rehabilitation begins since the patient is admitted to the hospital until the stabilization. It can be a period of 6–12 weeks, depending on the existence of complications. Rehabilitation in the acute phase is important to increase the patient strength and stability for postural adaptation and orthostatic hypotension [19, 28]. Passive exercises have been observed to decrease the risk of spasticity [43]. Other early interventions in rehabilitation are bed mobility with rotation at 2–3-h intervals to prevent pressure ulcers [19, 34].
\nThis rehabilitation is focused on the patient capacity to reintegrate into society. The goals are aimed to develop motor skills such as walking, transferring using the upper limbs, and wheelchair use [28], restore psychological status as much as possible, and perform occupational therapy [19].
\nDespite the fact that most of the patients with SCI want to be able to walk again, the goals of rehabilitation are mainly focused on restoring quality of life [75], and these should be individualized according to the ASIA classification.
\nThe following functional goals can be considered in the first 5 months according to the level of injury (time may vary depending on the patient ASIA classification he/she has):
C4: independence with a motorized wheelchair, partial or assisted ventilation, and dependence on activities of daily living.
C5: independence with a motorized wheelchair with hand control; may require extra respiratory care, performance of some activities of daily living, adapted driving is possible.
C6: independence with a manual wheelchair, assistance in transfer with a sliding table, control of supporting points, can do certain activities of daily life; extension of the wrist is possible; adapted driving is possible.
C7: this is a key level for wheelchair mobility, independent transfers without sliding board support.
C8-L2: advanced wheelchair skills, independent daily life activities, driving with adaptations.
L3 and lower: home and community ambulation with aid devices, independence in daily life activities [19, 34].
SCI is a relevant health issue because of the impact it has on the patient, his/her family, and health system. Even though there is active research for treatment development, being surgical or medical, in order to achieve motor recovery, in the present time, there are only treatments to reduce the damage after SCI and prevent future damage so none of this therapies are curative; one of this treatments is rehabilitation, which must be coordinated by a multidisciplinary team to reduce possible complications that may arise.
\nTo achieve better outcomes at clinical level, it is recommended to perform an integral rehabilitation therapy that combines different strategies, for example, functional, transcutaneous, or epidural electrical stimulation in addition to musculoskeletal rehabilitation exercises to decrease complications associated with this pathology. It is important to emphasize that some rehabilitation strategies have not yet been approved by health authorities for commercial use and to date have only shown results in very small populations with very particular characteristics, which impede their general application in patients with SCI, in addition to the heterogeneity of spinal cord injuries due to the level of injury, age, treatments used before, or time since injury.
\nThe ultimate goal of these interventions is to achieve patient’s societal reintegration and become independent in most of the activities according to the severity of their condition; therefore improving and updating these strategies create opportunities for novel innovative research, as well as implementing rehabilitation strategies as a complement for regenerative pharmacological and non-pharmacological strategies for the SCI patient.
\nDCs represent an important link between innate and adaptive immunity. DCs are heterogeneous population of antigen-presenting cells that are crucial to initiate and polarize the immune response. Although, all DCs are capable of capturing, processing, and presenting antigens to T cells, DCs subtypes differ in origin, location, migration patterns, and specialized immunological roles [1]. All the DCs are continuously renewed by hematopoietic stem cell progenitor cell located in bone marrow, except of Langerhans cells (LCs) that develop from embryonic macrophages in the yolk sac and fetal liver, that are recruited in the epidermis during embryonic life. The process is not clearly, but hematopoietic stem cell is differentiated into granulocyte-macrophage progenitors (GMP) and multilymphoid progenitors (MLP), that have the potential to differentiate into macrophage-dendritic precursor (MPD) or common dendritic cell progenitor (CDP) like progenitor. These progenitors are subsequently differentiated into common monocyte progenitor (cMoPs), plasmacytoid dendritic cells (pDCs) and human equivalent of pre-DC, those are the most important to differentiate all subsets of DCs. cMoPs develop into blood monocytes, which differentiate into monocyte-derived DCs (MoDCs) in inflamed tissues, and fully mature pDCs along with unmatured pre-DCs migrate through the blood tissue. Immature human pre-DCs differentiate either in the bloodstream or in tissues following migration, developing thus in different DCs subsets (Figure 1) [2, 3, 4].
Dendritic cell lineage development. The hematopoietic stem cell located in bone morrow is the progenitor of all DCs. Here the differentiation in multi-lymphoid progenitor and granulocyte-macrophage can become the human equivalent of macrophage-dendritic precursor (MPD) or dendritic cell progenitor (CDP). From this cell arise three important progenitor cells (cMoPs), pDCs and pre-DC, these last cells migrate to bloodstream or target tissue/organ to maturate and differentiate to become one of the different subsets of DCs. Explanation in the text. Figure modified by the authors from reference [
The DCs are present in lymph organs and non-lymphoid organs, also in blood stream, afferent lymph, and mucous membranes. There are different ways to classify DCs, by its linage, as mentioned above there are cMoPs and pDCs. The cMocPs express typical myeloid antigens as CD11c, but lack of CD14 or CD16 and may be split in CD1c + and CD141+ fractions. While pDCs have expression of CD123, CD303 and CD304, with high or low expression of CD123, CD303 or CD304; the cluster of differentiation is determined in the differentiation of their precursor. These cells cMoPs and pDCs are classified into blood DCs [5, 6].
Inflammatory DCs derived from classical CD14+ blood monocytes, using granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-4. Monocytes are highly plastic, and they differentiate into DCs or different forms of macrophages (M1/M2). Human inflammatory exudates contain distinct inflammatory DC-like and macrophage-like cells and transcriptional profiling suggests a common monocyte origin. Key features of these cells are the expression of CD1c, CD1a, CD206, FcεR1, Sirpα but lack of CD16 and CD209. Non-classical monocytes and antigen 6-Sulpho LacNac DCs are a heterogeneous population and CD16+ monocytes possess distinct characteristics including higher major histocompatibility complex (MHC) class II and co-stimulatory antigen expression, classify as a type of blood DCs [5].
The functional-anatomical classification of DCs is widely vast, the classification of DCs are dependent of anatomical location or function, for example, DCs in heart are known as interstitial cells, in ganglia are known as interdigitating cells, but when DCs are in the afferent lymph are called veiled cells. Also, the function of these are different but sequential [5, 6]. Intestinal DCs are found in small intestine, lamina propia and gut associated lymphoid tissue. This DCs express CD103 and Sirpα in three different ways, such as CD103 + Sirpα- DCs, The CD103 + Sirpα+ DCs and CD103- Sirpα+ DCs. Most of these cells are located deeper into lamina propia, and express CD45, human leukocyte antigen-DR isotype (HLA-DR), CD14, CD64 and high levels of CX3C chemokine receptor 1(CX3CR1), and since these cells do not migrate to the lymph nodes, they have been depicted as intestinal macrophages. In the mesenteric lymph node DCs are a mixture of cells found in the peripheral blood. Such as peripheral blood, where soluble food bioactives may also be directly available for internalization by DCs in the draining lymph nodes
LCs and microglia are two specialized self-renewing DCs, found them in stratified squamous epithelium and parenchyma of the brain, respectively. The LCs differentiate into migratory DCs, whereas microglia are considered as a type of specialized macrophage. There are DCs found in tissues and lymph nodes with marker CD14+, a subset of CD11c+, found in interstitial DCs; but they are more monocyte-like or macrophage-like, that may arise from classical monocytes [5].
Immatures and matures DCs have different morphologic, immatures DCs monocyte-derived are spherical, irregular shape, with little cytoplasmatic projections, also abundant phase-dense granules (birbeck’s granules or bodies) and irregular nucleus with small nucleoli. Once the DCs maturates shows stellate process, giving veiled appearance, with more extended dendrites projecting in many directions from the body cell [6, 8].
The DCs have 3 stages precursor, immature and mature stage, but some authors do not count the precursor phase [6, 9]. Precursor phase course with any of the principal precursor as cMoPs, pDCs or Human equivalent of pre-DCs. It migrates from bone morrow to specific tissue or area, process leaded by chemokine chemoreceptors such as C-C chemokine receptor type 1 (CCR1), CCR5 and CCR6 and by adhesion molecules CD26P ligand. When the cell arrives to the corresponding tissue or place, it becomes immature DC. The immature DC express CCR1 and CCR3, where its ligand is in endothelium and inflammatory cells, promoting its migration to different organs and inflammatory tissues. This immature DC is capable of capture antigens by different receptors like Fc receptor, integrins, type C lectin and scavenger receptors such as lectin-type oxidized LDL receptor 1 (LOX-1) and CD91. Immature DC is characterized for various amounts of chemokines, so it can be extravasated to inflammatory tissue [6].
Once the DC has captured the antigen, this one is degraded to peptides that will get bind to MHC class I or class II. The endogenous antigens are processed by MHC class I, while exogenous antigens are processed by MHC class II. The lipidic antigens are presented by different molecules CD1(a-d) to T cell receptor (TCR) or natural killer T (NKT) cell. The differentiation process of immature DC to mature DC needs different signals to complete the process. To the immature DC gets mature, needs to stimulate T lymphocyte. This is possible when the antigen is presented to T lymphocyte by MHC class I or class II to TCR receptor and interaction of costimulatory molecules (CD28, CD40, CD54, CD58, CD80, CD83 and CD86) to activate T lymphocyte. Other molecules like adhesion (CD58, CD54) danger signal (CD40 ligand, tumor necrosis factor (TNF)-α, IL-1, IL-6, Interferon (INF)-α and Toll-like receptors (TLRs) agonist) [6, 8]. When the DC becomes mature, decreases the chemokine receptor expression of CCR1 and CCR5, whereas CCR7 increases. The CCR7 ligand is in ganglia walls and ganglionic paracortical zone. There, the mature DC secretes chemokines such as thymus and activation-regulated chemokine (TARC), macrophage-derived chemokine (MDC) or interferon gamma-induced protein 10 (IP-10), which recruits different types of T lymphocytes, monocytes, regulated on activation, normal T cell expressed and secreted (RANTES), macrophage inflammatory protein (MIP)-1α and MIP-β, to the local microenvironment [6].
DCs cells have many functions, but these can be globed within three functions. The first one is the main function as antigen presentation and activation of T lymphocytes as inducing adaptative immunity, with important release of cytokines for example IL-12 to differentiate T lymphocytes in T helper cell or cytotoxic lymphocytes. DCs have a wide range of properties including potent stimulation of native CD4+ T cells, cross-presentation to CD8+ T cells and production of pro-inflammatory cytokines IL-1, IL-6, TNF-α, IL-12 and IL-23 [5, 9, 10]. The second function to induce tolerance. There are 2 types of tolerance central and peripheral. Central tolerance develops in thymus where a tolerance upon our own antigens occurs, and the reactive T lymphocytes to those antigens are destroyed, this also happen in bone morrow for B lymphocytes. The peripheral tolerance occurs when costimulatory molecules, last step of antigen presentation is not complete, there is a failure in activation of T lymphocyte, so the T lymphocyte become tolerogenic [6, 9, 10]. The third function to maintain immune memory in tandem with B cells. As mentioned before, there are population of DCs in ganglia, in the germinal center are found the follicular DCs which seems to be a reservoir of antigen and antibody complexes, that last an exceptionally long time up to months or years. This allows a constant stimulation of B cells to maintain memory [9].
There are others important functions of DCs, as their role in innate immunity, the DCs have pattern recognition receptor (PRR) and pathogen-associated molecular pattern (PAMPs) [10]. These receptor patterns activate TLR pathways, type C lectins and release pro-inflammatory cytokines to activate innate immunity system [8]. Also, DCs have been related to B lymphocytes proliferation and induction of T lymphocytes to suppress the immune response by missing of costimulatory molecules without IL-12, inducing T lymphocytes to secrete IL-10 and transforming growth factor (TGF)-β [6, 9].
Since the discovery of DCs [11], the knowledge of the innate and adaptive immune response has been increasing significantly. At present, DCs are considered a key cell in immune response activation with multiple functions including the virus recognition, processing of viral antigen and as antigen-presenting cells to cells of specific immune response, serving as a bridge between innate and adaptive response [12]. DCs are bone marrow-derived cells and they can be found in different parts of the organism including mucous membrane, the skin, and lymphoid tissue [13]. Depending on surface markers, DCs can be classified as immature or mature myeloid DCs and plasmacytoid DCs [14, 15].
Immature DCs are inactive cell with high capacity to capture viral antigen. They are present in virtually all tissue with high probability to capture invading viruses. Immature DCs lack the capacity of antigen presentation. On the other hand, mature MDC is generated by an immature DC that was activated when recognized and processed viral antigen. Mature DCs function as antigen presenting cells (APCs). They express MHC-II molecules and different co-stimulators surface molecules that give them the antigen presentation capacity. Mature DCs also produce different cytokines to initiate antiviral immune response [16].
Likewise, plasmacytoid DCs also sense viral pathogen. They are called plasmacytoid DCs by its high resemblance to plasma cells. Although pDC has the ability of antigen-presenting, this function is low compared with MDC. However, pDCs contribute to both inflammatory process and antiviral state. They are specialized DCs that produce proinflammatory cytokines and high levels of IFN type I [17]. Both MDC and pDCs are present in lymphatic nodes where they are capable to present viral antigen to naïve T cell [18, 19].
Immature DCs are considered the sentinels of the immune response. These cells are distributed in practically all the body where they have the capacity of interact with the invading virus. They carry out the function against viral infection by different mechanisms. They can be infected by viruses or they can respond to molecules produced and secreted by other virus infected cells. When they are infected, DCs can respond in various ways, firstly, DCs have different receptors distributed on cell surface, cytoplasm, and specialized endosomes. TLRs and C-type lectins receptors (CLRs) are present in cell surface and some TLRs in endosomes, while retinoic acid-inducible gene (RIG), melanoma differentiation-associated protein 5 (MDA5) and nucleotide-binding oligomerization domain 2 (NOD2) are only present in cytosol [20, 21, 22]. TLRs have N-terminal ectodomains (ECDs) which recognize molecules of viruses. This ECDs are constructed by a tandem motif of leucine-rich repeats (LRRs) and forms a horseshoe structures [23]. Binding of TLRs with their ligand depends on these structures [24]. However, diverse receptors respond to an extensive repertoire of viral PAMPs. These viral PAMPs can be glycoproteins present on the viral external surface, viral genome, or replication intermediates formed during viral replication [25].
Depending on the activated receptor, DCs can produce proinflammatory cytokines or IFN. During maturation process DCs interact with the antigen and upregulate MHC-II to present antigen to naïve CD4+T cells. In addition, DCs produce diverse surface molecules such as CCR7 which is necessary in trafficking into lymphatic nodes and CD40, CD80, and CD86 which are co-stimulatory surface factors that enable them to activate T naïve cell to initiate the adaptive immune responses [26, 27].
DCs is the main cell used to establish an effective immune response. At present, four subsets with different functions have been identify in human. Each subset of DC has different markers and a functional distinction that enable them to participate in different states to orchestrate an antiviral immune response. Each type of DC expresses different receptors that can be membrane-associated molecules or free in the cytoplasm. Activation of these receptors ends in different cytokine-proinflammatory production and interferon. Depending on cytokine produced, naïve CD4+T cells is differentiated into T helper effector cell [14].
Myeloid DCs, called classical or conventional DCs (cDCs) detect viral proteins through expression of membrane surface receptors such TLR-4 and DC-specific intercellular adhesion molecule 3 (ICAM3)-grabbing non-integrin (DC-SIGN) (see Figure 2) [28]. DC-SIGN support the initial immune response between T cells and DCs, but when DC-SIGN have contact with viral glycoproteins results in activation of signal transduction pathways than cause modulation of immune responses [29]. The signaling pathway triggered by DC-SIGN recruits Ras and the subsequent phosphorylation of the kinase RAF1 which is mediated by p21-activated kinases (PAKs) and Src Kinases. The activation of RAF1 induces phosphorylation of nuclear factor (NF)-κB increasing the transcriptional activation from IL-18, IL-10 and IL-12 promoter [29, 30].
Signaling pathway and cytokines production of DCs during viral infection. (A) Myeloid DCs and (B) Plasmacytoid DCs. Description in the text (figure created by Muñoz-Carrillo
The association of viral proteins through concave surface of TLR4-ECD induces two different pathways [31]. Myeloid differentiation primary response 88 (MyD88)-Dependent Pathway initiates with the recruitment of MyD88 adapter and subsequent activation of tumor necrosis factor receptor (TNFR)-associated factor 6 (TRAF6). Then TRAF6 activates the NF-κB essential modulator (NEMO), which is the regulatory subunit IKK complex and activates NF-κB causing its translocation to the nucleus, where induces gene expression such as IL-6 and IL-12 [21]. MyD88-Independent pathway recruits TIR-domain-containing adapter-inducing interferon-β (TRIF) [32]. TRIF activates TRAF3 and finally induce interferon regulatory transcription factor (IRF-3) activation and the subsequent IFN-β expression [21].
In addition to membrane surface receptors cDCs also have endosomal TLRs such as TLR-3 and TLR-7/TLR-8 which sense dsRNA and ssRNA respectively. Each receptor has a specific signaling pathways [14]. TLR-3 sense viral dsRNA through its largely uniform and flat horseshoe structure of TLR-ECD [33]. TLR3 has the same MyD88-Independent pathway with the activation of TRAF3 and subsequent IFN-β expression [32]. Viral ssRNA are sense by TLR-7 and TLR-8, these receptors activate MyD88 pathway with the recruitment of TRAF6 and TRAF3. Finally, activation of IRF-3 and IRF-7 induces IFN-β and IFN-α expression respectively (see Figure 2A) [21, 34].
In addition to DC-SIGN and TLRs, the viral genome can be exposed in the cytoplasm during the replicative processes or during direct penetration into the cell. NOD2 and RNA helicases such melanoma differentiation-associated protein 5 (MDA5) and RIG-1 detect dsRNA in the cytoplasm [35]. Interferon promoter stimulator-1 (IPS-1) interacts with MDA5, RIG-1 and NOD2
On the other hand, pDCs not express DC-SIGN but express CD4 that can sense glycoproteins of viruses as human immunodeficiency virus (HIV). The viruses can enter through direct fusion with the cell membrane or through receptor-mediated endocytosis and activates different signaling pathways (see Figure 2B) [40, 41]. The endosomal receptors TLR-7 and TLR-9 are selectively express in pDCs and sense RNA or DNA respectively. This engage activates downstream signaling pathway [42]. TLR-9 and TLR-7 activates IRF-3 and IRF-7 like in cDCs signaling with final IFN-β and IFN-α expression respectively [43]. TLR-9 signaling pathways include the recruitment of Interleukin-1 receptor-associated kinase 4 (IRAK4) through its death domain. Activated IRAK4 interacts with IRAK2. This complex associates with TRAF6 to final activation and nucleus translocation of NF-κB and leads TNF-α and IL-6 production [17, 44, 45]. pDCs can also be infected by direct penetration of virus and the viral genome can be sense by RIG-1, MDA5 and NOD2. The signaling in the pDCs is through IPS-1 pathways as the same way that on cDCs [20, 22]. This pathway activates NFκB, IRF-3 and IRF-7 to express IL-12, IFN-β and IFN-α respectively [38, 39].
Other subsets of DCs are the LCs and Interstitial DCs (IDCs), these kinds of DCs are commonly the first DCs that have contact with some virus [46]. LCs are localized in mucosal stratified squamous epithelium and skin epidermis. LCs express different CLR: CD207 or Langerin. Moreover, LC has a low expression of TLR4 and expression of TLR-3, −7 and − 8 [14, 47]. LCs activated finally express IL-8, IL-6, TNF-α [48]. On the other hand, the IDCs are localized in the epidermis and express similar receptors that cDCs like DC-SIGN and TLR-3, -4, -7 and -8 and have similar signaling pathways [14].
Activation of the antiviral response generated by immune system depends largely on the activation of dendritic cells. Each subtype of this family of antigen-presenting cells have an important role by processing viral antigens that trigger different signaling pathways through their distinct receptors. The consequence of this signaling pathway results in the expression of various cytokines involved in the activation of immune cells. For this reason, a better knowledge about how different immune cells subtypes can induce distinct pathways is required for a better vision of whole antiviral response.
In parasitic infections is difficult to generalize about the mechanisms of antiparasitic immunity because there is a great variety of different parasites that have different morphology and reside in different locations of tissues and hosts during their life cycles [49]. For this reason, we will talk about the role of dendritic cells in protozoa and helminths infection, two of the main parasites of medical importance for human health.
DCs have the capacity to recognize different molecules in the surface of parasites and are efficient phagocytes; thus, several intracellular parasites reside inside DCs. Once DCs phagocytose intracellular parasites, they can exert their microbicidal capacities, although it has been shown that they are not as efficient in the destruction of microorganisms as other phagocytes such as macrophages and neutrophils. Once internalized, DCs process antigens for presentation to T cells [50].
Protozoan parasites are pathogens that have developed additional and sophisticated strategies to escape the immune attack of the host. This is because their life cycles generally involve several stages of specific antigenicity, which facilitates their survival and propagation within different cells, tissues, and hosts [51]. Frequently, the host is unable to eliminate protozoan infections, which often results in chronic disease or irreparable infections, in which the host continues to act as a reservoir of parasites, a cause of great concern due to their prevalence, morbidity and mortality [52, 53]. This host resistance to protozoa infections depends mainly on the development of a T helper type 1 (Th1) response and on the production of IL-12 by APCs [54]. Therefore, the classical reaction of the host to infections by protozoan parasites is the maturation of different subsets of DC, and in some cases, the activity of these cells leads to a response that is effective in controlling the infection [55].
Among the most important protozoan parasites are those that living in human blood and tissues, which can cause fatal diseases. The immune response against protozoan infections involves a strong innate immune response followed by predominantly a Th1 response. The innate immune system is comprised of several cell types, including DCs. Recognition of pathogens by these cell types leads to phagocytosis in some cases, and the production of pro-inflammatory cytokines, which assist in shaping the subsequent adaptive immune response (see Figure 3) [56].
Role of DCs in protozoan infections. Polarization of Th1 response through interactions between PAMPs and PRRs (TLR-2, -4, -9, -11 and -12), which in a signal-dependent manner (involving the activation of MAPKs p38/JNK and MyD88) induce the expression of Th1 cytokines such as IL-12, Il-6, IFN-γ and TNF-α. the PRRs from protozoa induce the presentation of antigens, the co-stimulation, and the expression of the cytokine IL-12, IFN-γ production by DCs during Ag presentation, by signaling pathway STAT-4. Description in the text. (figure created by Muñoz-Carrillo
During the parasitic protozoan infections different PRRs present in DCs are involved in the recognition PAMPs of parasites. In trypanosomiasis, the glycoinositolophospholipids (GIPLs) and glucosylphosphatidylinositol (GPI) anchors from Trypanosoma cruzi are recognized by TLR-4 and TLR-2, respectively, inducing the inflammatory cytokines production [57, 58]. Likewise, the DNA of
Helminth parasites, like protozoan parasites, have significant differences in their biological life cycles, which are reflected in the differences in clinical outcomes seen among helminth parasites. Pathological consequences of most helminth infections have been associated with both with the parasite intensity (or burden) and the relative acuteness or chronicity of the infection, because the helminth parasites modulate/regulate the host response to themselves (parasite-specific immunoregulation) [84].
The immune response against helminths is characterized by the induction of an early immune response of type Th1, with subsequent predominance of a Th2 type immune response, resulting in a mixture of both Th1/Th2 responses [85, 86], which are dependent on the immune responses mediated by CD4+ T cells [87]. These CD4+ T cells can function as APCs and play a key role in establishment the cytokine environment, thus directing their differentiation either by suppressing or favoring the inflammatory response at the intestinal level, which is crucial for the expulsion and elimination of the parasite (see Figure 4) [88].
Role of DCs in helminth infections. The immune response against helminths is characterized by the induction of an early immune response of type Th1, with subsequent predominance of a Th2 type immune response, resulting in a mixture of both Th1/Th2 responses. The polarization of the cellular immune response to a Th1/Th2 type immune response depends on the type of signal derived from DCs. Description in the text. (figure created by Muñoz-Carrillo
This implies that the helminths have developed strategies, such as the evasion or suppression of the host immune response, which prevent their expulsion and allow their long-term survival. It is believed that the modulating effects of the immune system arise from the ability of the helminth to regulate the host immune response, developing mechanisms for the modulation of DCs as key players in the initiation and polarization of adaptive immune responses [89, 90, 91].
During the intestinal infection by helminths, the polarization of the cellular immune response to a Th1 type immune response depends on the type of signal derived from DCs. For example,
Intestinal DCs are classified according to their unique or combined expression of CD11b and CD103, as well as the dependence on either interferon regulatory factor 4 or 8 (IRF4 or IRF8) for their development and/or survival. The intestinal DCs are capable of process antigens, migrating to mesenteric lymph nodes upon activation, and priming naive T cells. However, IRF8-dependent CD103+ DCs are important for the generation of type 1 responses of both helper and cytotoxic T cells, thus promoting
On the other hand, the PRRs from helminths can also activate the DCs for the induction of the Th2 response by interacting with the TLR and CLR. This interaction may promote Th2 responses by suppressing antigen presentation, co-stimulation and/or expression of Th1-promoting cytokines by directly interfering with these pathways. DCs that drive Th2 responses typically exhibit specialized markers, such as CD301b, PDL2, and CD11b, and several receptors for the Th2-related cytokines IL-4R, IL-13R, IL-25R, TSLP-R, and IL-33R. Additionally, the extracellular signal-regulated kinase (ERK) and signal transducer and activator of transcription 4 (STAT4) pathway upregulates the costimulatory molecules, CD40, OX40L, and Jagged. Activation of the major transcription factors interferon regulatory factor 4 (IRF4) and KLF4 inhibits IL-12 production and increased IL-10 secretion. These factors typically act individually or in concert to orchestrate Th2 responses in helminth infections [106, 107, 108].
In
Activated DCs are involved in the response to infections, which induces an increase in MHC expression, adhesion, and costimulatory molecules. The recognition of intracellular pathogens derived from mycobacterial cell wall components (lipids/glycolipids) such as phosphatidyl-myo-inositol mannoside, lipo-mannan, lipoarabinomannan, mycolic acids, lipopeptides, and phosphoinositol-containing lipids is given through the TLR-2, TLR-4, TLR-9, TLR-8 and the TLR1/TLR6 that heterodimerize with the TLR-2 [114, 115]. The signaling pathway that occurs in almost all TLRs is through MYD88, while for TLR4 the signaling pathway can be through MYD88 and TRIF [116, 117]. The activation of these receptors induces the activation of mitogen-activated protein kinase (MAPK) and NF-κB producing proinflammatory cytokines in DCs (see Figure 5). Other antigens derived from
Role of DCs in bacterial infections. The TLRs are involved in the recognition of mycobacterial antigens. The activation of TLR-4 and TLR-2 by these antigens leads to an intracellular signaling pathway, leading to a Th1 and Th2 response, respectively. NOD-like receptors (NOD 1 and NOD 2) recognize bacterial peptidoglycans (DAP and MDP), the downstream signaling activates NF-κB and MAPK generating a Th1 response. Description in the text (figure created by Muñoz-Carrillo
On the other hand, DCs infection with other bacteria of the type
Other receptors involved in the response to pathogens are NOD1 and NOD2 receptors make up the family of NOD-like receptors containing a CARD domain (NLRC) [137]. These receptors are highly expressed in DCs and act as intracellular PRRs that recognize bacterial peptidoglycans [138, 139, 140]. NOD1 mainly recognizes γ-D-Glu-meso-diaminopimelic acid (DAP) while NOD2 recognizes muramyl dipeptide (MDP) [141]. Once the activation of these receptors occur, the downstream signaling activates NFκB through the union of its CARD domain to the protein kinase RIP2, which in turn recruits IRAK2, TRAF6, TAK1 binding protein (TAB1) and transforming growth factor-β-activated kinase 1 (TAK1) to activate the IKK complex, these events result in the degradation of IκBα inhibitor which leads to the translocation of NFκB to the nucleus and induce the expression of proinflammatory mediators [142]. In addition to the NFκB pathway, the stimulation of NOD1 and NOD2 leads to the activation of MAP kinases p38, ERK, and JNK pathway
Role of DCs in fungal infection. Antigens derived from fungi such as b-glucan which are recognized by Dectin-1, this leads to a downstream signaling pathway activating NF-kB producing IL-6 and IL-23 leading to a Th17 phenotype. The union of Dectin-1 whit b-glucan also leads to the activation of ROS, which can NLRP3 inflammasome assembly activating caspase-1 which cuts the pro-IL-1 and pro-IL-18 generating its active forms, which together with IL-23 activates the Th17 phenotype. Description in the text (figure created by Muñoz-Carrillo
Infections caused by opportunistic fungal pathogens include
DCs are the only ones capable of decoding information related to fungi [146]. The activation of the various immunity mechanisms is carried out efficiently by the DC that decode the signals sent by the fungi and translate them into an immune response of T helper (Th)
Inflammatory DCs generate the responses of Th17 and Th2 antifungal cells
It has also been reported that NLRP3 linked with ASC and caspase 1, is triggering inflammation activated by pathogenic fungi such as
Many types of cells, including macrophages and DCs, produce IL-1β induces the differentiation of Th17 cells, which are necessary for effective defense of the host against
DCs are considered key cells as the first line of defense against viruses and to induce adaptive defense. In the innate immune response, they can exert virus phagocytosis and produce cytokines to activate NK cells to eliminate virus infected cells. In adaptive immune response, DCs induce differentiation of Th1-cells that in turn induce activation of antigen specific cytotoxic cells, macrophages, and antibody production to participate in viral clearance.
For the elimination of bacteria, a specific immune response is required, for intracellular bacteria a Th1 response is required as well as cytotoxic T lymphocytes, the latter to produce IFN-γ and can kill the cells that have been infected, in this response the Il −12 is important and its production by DCs requires stimuli derived from pathogens as well as from CD4+ T-cells; on the other hand, for extracellular bacteria a Th17 response is required, in this response DCs play an important role in producing pro-inflammatory cytokines so that a Th17 response can be given, thus these cells coordinate the recruitment of neutrophils that phagocytize extracellular bacteria and thus eliminate the bacterial infection.
DCs participate in the immune response against different opportunistic fungi, the latter are capable of producing different diseases including vulvovaginal candidiasis, oral candidiasis or disseminated candidiasis (
During parasitic infections, DCs play an important role, since, through them, the body can mount a specific immune response, mainly mediated by T lymphocytes. The DCs recognize the antigens of the parasites, and in the first instance, they induce a Th1-type immune response, characterized mainly by the production of pro-inflammatory cytokines and mediators. Nevertheless, parasites have the ability to polarize, through the activation of DCs, towards a Th2-type immune response, characterized mainly by the production of anti-inflammatory cytokines, eosinophilia and mastocytosis. However, due to the great diversity of parasites that exist, as well as their phenotypic variability, which involves different stages of antigenicity, conditioned by the life cycle of the parasite itself, these microorganisms have the ability to develop strategies that allow them to evade the immune system and facilitate their survival and spread in the host. Despite the different immune responses that the host assembles in contact with the different diseases caused by these microorganisms, DCs are very important, since they represent the junction point between the innate and adaptive immune responses, allowing the host to differentiate the type of microorganism by which it has been invaded and thus be able to mount a specific immune response.
Dendritic cells are a key cell type in the recognition of intracellular and extracellular pathogens through the different receptors that they express. The maturation of the DCs is an important event since through this mechanism these cells acquire the ability to express MHC as well as costimulatory molecules, thus conditioning the presentation of the antigen, producing cytokines and mounting immune in order to kill the invading pathogen. The response can be mediated by the PRRs as they will recognize different structures of the invading microorganism and execute a defensive response with the purpose of eliminating the invading microorganism through the production of antimicrobial cytokines and intermediaries, as well as activating transcription factors to produce cytokines that have an important role in the polarization of the T helper cell during priming by DCs.
Thanks to the authors who collaborated in the writing of this chapter: Dr. en C. José Luis Muñoz-Carrillo; Dr. en C. Oscar Gutiérrez-Coronado; Dr. en C. Juan Francisco Contreras-Cordero; Dra. en C. Paola Trinidad Villalobos-Gutiérrez; Dr. Luis Guillermo Ramos-Gracia, and Dra. Jazmín Monserrat Vargas-Barboza; as well as the Universities involved: Cuauhtémoc University Aguascalientes, University of Guadalajara, and Autonomous University of Nuevo Leon for financial support for chapter publication.
We have no conflict of interest related to this work.
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Abdel Rahman and Hosam El-Din Mostafa Saleh",coverURL:"https://cdn.intechopen.com/books/images_new/5154.jpg",editedByType:"Edited by",editors:[{id:"92718",title:"Prof.",name:"Rehab O.",middleName:"O.",surname:"Abdel Rahman",slug:"rehab-o.-abdel-rahman",fullName:"Rehab O. Abdel Rahman"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],booksByTopicTotal:1,seriesByTopicCollection:[],seriesByTopicTotal:0,mostCitedChapters:[{id:"50376",doi:"10.5772/62434",title:"Tungsten-Based Composites for Nuclear Fusion Applications",slug:"tungsten-based-composites-for-nuclear-fusion-applications",totalDownloads:2365,totalCrossrefCites:7,totalDimensionsCites:10,abstract:"This chapter provides a comprehensive knowledge about the potential role of tungsten-based composites in fusion reactors and the research work which has been done in this very important area of nuclear materials. The characteristics of tungsten, which make it the most potential candidate for plasma-facing applications, have been presented along with the shortcomings in pure tungsten. The research work that has been done so far in the field of tungsten-based composites to overcome the problems with pure tungsten has been included. The fabrication, characterization, types of reinforcements and the classes of composites have been reviewed. The behavior of tungsten-based composites under various kinds of loads (i.e. mechanical and thermal) and environments (radiations and oxidizing etc.) has been summarized.",book:{id:"5154",slug:"nuclear-material-performance",title:"Nuclear Material Performance",fullTitle:"Nuclear Material Performance"},signatures:"Owais A. Waseem and Ho Jin Ryu",authors:[{id:"178474",title:"Prof.",name:"Ho Jin",middleName:null,surname:"Ryu",slug:"ho-jin-ryu",fullName:"Ho Jin Ryu"},{id:"184864",title:"Mr.",name:"Owais Ahmed",middleName:null,surname:"Waseem",slug:"owais-ahmed-waseem",fullName:"Owais Ahmed Waseem"}]},{id:"50182",doi:"10.5772/62594",title:"Developing Tailor-Made Microbial Consortium for Effluent Remediation",slug:"developing-tailor-made-microbial-consortium-for-effluent-remediation",totalDownloads:1576,totalCrossrefCites:4,totalDimensionsCites:8,abstract:"The work describes a biofilm-based soluble sulphate reduction system, which can treat up to 1600 ppm of soluble sulphate within 3.5 hours of incubation to discharge level under ambient condition using a well-characterized sulphate-reducing bacterial (SRB) consortium. This system ensures the treatment of 1509 litres of sulphate solution in 24 hours using a 220-litre bioreactor. Performance of the system during series operation was compromised, indicating the presence of inhibitor in solution at a toxic level. A single unit bioreactor would be the ideal configuration for this consortium. Modified designs of bioreactors were tested for optimization of the process using response surface methodology (RSM), where the system could function optimally at an initial sulphate concentration of 1250 ppm with a flow rate of 1.8 litre/hour. The time course of sulphate reduction yielded a parabolic profile (with coefficient of determination r\n2 = 0.99 and p value < 0.05). The rate of sulphate reduction was found to be independent of seasonal variation as well as the specific design characteristic.",book:{id:"5154",slug:"nuclear-material-performance",title:"Nuclear Material Performance",fullTitle:"Nuclear Material Performance"},signatures:"Shaon Ray Chaudhuri, Indranil Mukherjee, Debabrata Datta,\nChaitali Chanda, Ganesh Prasath Krishnan, Swati Bhatt, Paulami\nDatta, Shashi Bhushan, Sourav Ghosh, Pinaki Bhattacharya, Ashoke\nRanjan Thakur, Debanik Roy and Parthasarathi Barat",authors:[{id:"179765",title:"Dr.",name:"Shaon",middleName:null,surname:"Ray Chaudhuri",slug:"shaon-ray-chaudhuri",fullName:"Shaon Ray Chaudhuri"}]},{id:"51035",doi:"10.5772/62856",title:"Introductory Chapter: Introduction to Current Trends in Nuclear material Research and Technology",slug:"introductory-chapter-introduction-to-current-trends-in-nuclear-material-research-and-technology",totalDownloads:2153,totalCrossrefCites:1,totalDimensionsCites:5,abstract:null,book:{id:"5154",slug:"nuclear-material-performance",title:"Nuclear Material Performance",fullTitle:"Nuclear Material Performance"},signatures:"Rehab O. Abdel Rahman",authors:[{id:"92718",title:"Prof.",name:"Rehab O.",middleName:"O.",surname:"Abdel Rahman",slug:"rehab-o.-abdel-rahman",fullName:"Rehab O. Abdel Rahman"}]},{id:"51107",doi:"10.5772/63652",title:"Gamma Uranium Molybdenum Alloy: Its Hydride and Performance",slug:"gamma-uranium-molybdenum-alloy-its-hydride-and-performance",totalDownloads:2257,totalCrossrefCites:0,totalDimensionsCites:1,abstract:"The high density metastable gamma uranium molybdenum alloy (γ‐UMo) is being qualified as a nuclear fuel for the conversion of high enriched uranium (HEU) to low enriched uranium (LEU) fuels in research nuclear reactors. γ‐UMo, with compositions between 7 and 10 wt.% molybdenum, has excellent properties to allocate fission gases but unacceptable behavior in contact with aluminum in the matrix of dispersed fuels. Development and processing alternatives are welcome to decide final working paths and new nuclear fuels design. A historical introduction on the development of materials testing reactors (MTR) nuclear fuels is presented to illustrate comings and goings to reach desired qualification objectives. Several studies performed on UMo probes, miniplates and full size plates are mentioned to contribute to the knowledge of fuel properties and to incorporate new process technologies. Focus is directed to the discovery of the gamma uranium molybdenum hydride and the hot rolling colamination of monolithic UMo with nonaluminum claddings. A scalable process of hydriding, milling and dehydriding (HMD) to comminute the ductile UMo was developed. Monolithic UMo miniplates with Zircaloy‐4 (Zry4) cladding was colaminated for the first time and under irradiation conditions showed excellent performance after high burn‐up.",book:{id:"5154",slug:"nuclear-material-performance",title:"Nuclear Material Performance",fullTitle:"Nuclear Material Performance"},signatures:"Enrique E. Pasqualini",authors:[{id:"178951",title:"Dr.",name:"Enrique E.",middleName:null,surname:"Pasqualini",slug:"enrique-e.-pasqualini",fullName:"Enrique E. Pasqualini"}]},{id:"50261",doi:"10.5772/62572",title:"Monte Carlo Simulations of Nuclear Fuel Burnup",slug:"monte-carlo-simulations-of-nuclear-fuel-burnup",totalDownloads:2740,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"In the operation of a nuclear power plant, it is very important to determine the time evolution of material composition and radionuclide inventory during the entire operation of the plant. In the experiments, the Monte Carlo N-Particle eXtended (MCNPX) code was found to be accurate in predicting the uranium fuel depletion, the plutonium production and the buildup of most of the fission products in a nuclear reactor. The goal in this chapter is to analyze the effect of different nuclear fuel grades on the total radioactivity of the reactor core by employing nuclear burnup calculations for the three different fuels: mixed oxide fuel (MOX), uranium oxide fuel (UOX) and commercially enriched uranium (CEU), utilizing simulations with MCNPX code. The calculated results indicate that there is a buildup of plutonium isotopes for UOX and CEU, whereas there is a decline in the plutonium radioisotopes for MOX fuel with burnup time. The study of reactor neutronic parameters showed UOX fuel performs better relative to MOX and CEU. Zircaloy, with low thermal neutron absorption cross-section and high thermal conductivity, produced better results for the effective multiplication factor Keff and hence proved to be a much more effective clad material.",book:{id:"5154",slug:"nuclear-material-performance",title:"Nuclear Material Performance",fullTitle:"Nuclear Material Performance"},signatures:"Raghava R. Kommalapati, Fiifi Asah-Opoku, Hongbo Du and Ziaul\nHuque",authors:[{id:"179935",title:"Dr.",name:"Raghava",middleName:"R",surname:"Kommalapati",slug:"raghava-kommalapati",fullName:"Raghava Kommalapati"},{id:"180165",title:"Dr.",name:"Hongbo",middleName:null,surname:"Du",slug:"hongbo-du",fullName:"Hongbo Du"},{id:"180166",title:"Prof.",name:"Ziaul",middleName:null,surname:"Huque",slug:"ziaul-huque",fullName:"Ziaul Huque"},{id:"180167",title:"Mr.",name:"Fiifi",middleName:null,surname:"Asah-Opoku",slug:"fiifi-asah-opoku",fullName:"Fiifi Asah-Opoku"}]}],mostDownloadedChaptersLast30Days:[{id:"50261",title:"Monte Carlo Simulations of Nuclear Fuel Burnup",slug:"monte-carlo-simulations-of-nuclear-fuel-burnup",totalDownloads:2740,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"In the operation of a nuclear power plant, it is very important to determine the time evolution of material composition and radionuclide inventory during the entire operation of the plant. In the experiments, the Monte Carlo N-Particle eXtended (MCNPX) code was found to be accurate in predicting the uranium fuel depletion, the plutonium production and the buildup of most of the fission products in a nuclear reactor. The goal in this chapter is to analyze the effect of different nuclear fuel grades on the total radioactivity of the reactor core by employing nuclear burnup calculations for the three different fuels: mixed oxide fuel (MOX), uranium oxide fuel (UOX) and commercially enriched uranium (CEU), utilizing simulations with MCNPX code. The calculated results indicate that there is a buildup of plutonium isotopes for UOX and CEU, whereas there is a decline in the plutonium radioisotopes for MOX fuel with burnup time. The study of reactor neutronic parameters showed UOX fuel performs better relative to MOX and CEU. Zircaloy, with low thermal neutron absorption cross-section and high thermal conductivity, produced better results for the effective multiplication factor Keff and hence proved to be a much more effective clad material.",book:{id:"5154",slug:"nuclear-material-performance",title:"Nuclear Material Performance",fullTitle:"Nuclear Material Performance"},signatures:"Raghava R. Kommalapati, Fiifi Asah-Opoku, Hongbo Du and Ziaul\nHuque",authors:[{id:"179935",title:"Dr.",name:"Raghava",middleName:"R",surname:"Kommalapati",slug:"raghava-kommalapati",fullName:"Raghava Kommalapati"},{id:"180165",title:"Dr.",name:"Hongbo",middleName:null,surname:"Du",slug:"hongbo-du",fullName:"Hongbo Du"},{id:"180166",title:"Prof.",name:"Ziaul",middleName:null,surname:"Huque",slug:"ziaul-huque",fullName:"Ziaul Huque"},{id:"180167",title:"Mr.",name:"Fiifi",middleName:null,surname:"Asah-Opoku",slug:"fiifi-asah-opoku",fullName:"Fiifi Asah-Opoku"}]},{id:"51107",title:"Gamma Uranium Molybdenum Alloy: Its Hydride and Performance",slug:"gamma-uranium-molybdenum-alloy-its-hydride-and-performance",totalDownloads:2257,totalCrossrefCites:0,totalDimensionsCites:1,abstract:"The high density metastable gamma uranium molybdenum alloy (γ‐UMo) is being qualified as a nuclear fuel for the conversion of high enriched uranium (HEU) to low enriched uranium (LEU) fuels in research nuclear reactors. γ‐UMo, with compositions between 7 and 10 wt.% molybdenum, has excellent properties to allocate fission gases but unacceptable behavior in contact with aluminum in the matrix of dispersed fuels. Development and processing alternatives are welcome to decide final working paths and new nuclear fuels design. A historical introduction on the development of materials testing reactors (MTR) nuclear fuels is presented to illustrate comings and goings to reach desired qualification objectives. Several studies performed on UMo probes, miniplates and full size plates are mentioned to contribute to the knowledge of fuel properties and to incorporate new process technologies. Focus is directed to the discovery of the gamma uranium molybdenum hydride and the hot rolling colamination of monolithic UMo with nonaluminum claddings. A scalable process of hydriding, milling and dehydriding (HMD) to comminute the ductile UMo was developed. Monolithic UMo miniplates with Zircaloy‐4 (Zry4) cladding was colaminated for the first time and under irradiation conditions showed excellent performance after high burn‐up.",book:{id:"5154",slug:"nuclear-material-performance",title:"Nuclear Material Performance",fullTitle:"Nuclear Material Performance"},signatures:"Enrique E. Pasqualini",authors:[{id:"178951",title:"Dr.",name:"Enrique E.",middleName:null,surname:"Pasqualini",slug:"enrique-e.-pasqualini",fullName:"Enrique E. Pasqualini"}]},{id:"50376",title:"Tungsten-Based Composites for Nuclear Fusion Applications",slug:"tungsten-based-composites-for-nuclear-fusion-applications",totalDownloads:2365,totalCrossrefCites:7,totalDimensionsCites:10,abstract:"This chapter provides a comprehensive knowledge about the potential role of tungsten-based composites in fusion reactors and the research work which has been done in this very important area of nuclear materials. The characteristics of tungsten, which make it the most potential candidate for plasma-facing applications, have been presented along with the shortcomings in pure tungsten. The research work that has been done so far in the field of tungsten-based composites to overcome the problems with pure tungsten has been included. The fabrication, characterization, types of reinforcements and the classes of composites have been reviewed. The behavior of tungsten-based composites under various kinds of loads (i.e. mechanical and thermal) and environments (radiations and oxidizing etc.) has been summarized.",book:{id:"5154",slug:"nuclear-material-performance",title:"Nuclear Material Performance",fullTitle:"Nuclear Material Performance"},signatures:"Owais A. Waseem and Ho Jin Ryu",authors:[{id:"178474",title:"Prof.",name:"Ho Jin",middleName:null,surname:"Ryu",slug:"ho-jin-ryu",fullName:"Ho Jin Ryu"},{id:"184864",title:"Mr.",name:"Owais Ahmed",middleName:null,surname:"Waseem",slug:"owais-ahmed-waseem",fullName:"Owais Ahmed Waseem"}]},{id:"50829",title:"Dedicated Monte Carlo Procedures Applied in Gamma-ray Spectrometry Used in Decommissioning of Nuclear Facilities",slug:"dedicated-monte-carlo-procedures-applied-in-gamma-ray-spectrometry-used-in-decommissioning-of-nuclea",totalDownloads:1884,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Because the experimental efficiency calibration is limited to several measurement geometries and cannot be applied directly to all measurement configurations, the efficiency transfer method for the efficiency computation was applied using ETNA software. An approach using efficiencies measured with point sources combined with theoretical procedures was applied for obtaining the peak efficiency ε(E) for disk sources measured with a NaI(Tl) detector. The transfer method was applied for the computation of the efficiency of an HPGe detector using as a reference a point source placed at 10 cm height from the face of the detector. The method was applied both for point sources and volume sources with varied compositions and densities. To correct the experimental values of the efficiencies, coincidence summing effects were evaluated using GESPECOR Monte Carlo code. The study of the response function characterization of the ISOCART and Segmented Gamma Scanner WS1100 gamma-ray spectrometry systems was related. GEANT 3.21 Monte Carlo code was used to simulate the spectra expected to be obtained for the photon energy range from 50 to 2000 keV. A big volume represented by a 220l cylindrical source was considered to be measured with the two systems. The full energy peak efficiency and the total efficiency were evaluated.",book:{id:"5154",slug:"nuclear-material-performance",title:"Nuclear Material Performance",fullTitle:"Nuclear Material Performance"},signatures:"Daniela Gurau",authors:[{id:"178770",title:"Dr.",name:"Daniela",middleName:null,surname:"Gurau",slug:"daniela-gurau",fullName:"Daniela Gurau"}]},{id:"51079",title:"Oxidation, Embrittlement, and Growth of TREAT Zircaloy-3 Cladding",slug:"oxidation-embrittlement-and-growth-of-treat-zircaloy-3-cladding",totalDownloads:1678,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"This chapter analyzes the effects of oxidation, embrittlement, and cladding growth on the Zircaloy-3 alloy used for 25 mil thick TREAT fuel assembly cladding. The fuel cladding is a protective shell which is used to prevent damage to the enclosed fuel. Therefore, its integrity is important to guarantee this protection. The above three factors which can affect the Zircaloy-3 cladding are considered in this chapter and investigated. Limits to operation are determined. The oxidation of Zircaloy-3 in air is of interest to air-cooled reactors and Zircaloy-2 and 4 for accidents in fuel storage pools. The temperature range of interest is from room temperature where the fuel is stored for long periods of time, through the temperature range encountered in normal operation (400 to 600°C) to the highest temperatures which are possible in extreme accident situations. This temperature range is considered in this chapter to be from room temperature to 1200°C.",book:{id:"5154",slug:"nuclear-material-performance",title:"Nuclear Material Performance",fullTitle:"Nuclear Material Performance"},signatures:"Charles W. Solbrig, Anthony LaPorta, Katelyn M. Wachs and James\nR. 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Radiotherapy and Nuclear Medicine Technology has always been my aspiration and my life. As years passed I accumulated a tremendous amount of skills and knowledge in Radiotherapy and Nuclear Medicine, Conventional Radiology, Radiation Protection, Bioinformatics Technology, PACS, Image processing, clinically and lecturing that will enable me to provide a valuable service to the community as a Researcher and Consultant in this field. 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He is the author or co-author of more than seventy papers in peer-reviewed journals and conferences as well as the co-author of several books. He serves as a reviewer for many scientific journals, international conferences, and research foundations. Since 2010, Dr. Placzek has been a reviewer of grants and projects (including EU projects) in the field of information technologies.",institutionString:"University of Silesia",institution:{name:"University of Silesia",country:{name:"Poland"}}},{id:"35000",title:"Prof.",name:"Ulrich H.P",middleName:"H.P.",surname:"Fischer",slug:"ulrich-h.p-fischer",fullName:"Ulrich H.P Fischer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/35000/images/3052_n.jpg",biography:"Academic and Professional Background\nUlrich H. P. has Diploma and PhD degrees in Physics from the Free University Berlin, Germany. He has been working on research positions in the Heinrich-Hertz-Institute in Germany. Several international research projects has been performed with European partners from France, Netherlands, Norway and the UK. He is currently Professor of Communications Systems at the Harz University of Applied Sciences, Germany.\n\nPublications and Publishing\nHe has edited one book, a special interest book about ‘Optoelectronic Packaging’ (VDE, Berlin, Germany), and has published over 100 papers and is owner of several international patents for WDM over POF key elements.\n\nKey Research and Consulting Interests\nUlrich’s research activity has always been related to Spectroscopy and Optical Communications Technology. Specific current interests include the validation of complex instruments, and the application of VR technology to the development and testing of measurement systems. He has been reviewer for several publications of the Optical Society of America\\'s including Photonics Technology Letters and Applied Optics.\n\nPersonal Interests\nThese include motor cycling in a very relaxed manner and performing martial arts.",institutionString:null,institution:{name:"Charité",country:{name:"Germany"}}},{id:"341622",title:"Ph.D.",name:"Eduardo",middleName:null,surname:"Rojas Alvarez",slug:"eduardo-rojas-alvarez",fullName:"Eduardo Rojas Alvarez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/341622/images/15892_n.jpg",biography:null,institutionString:null,institution:{name:"University of Cuenca",country:{name:"Ecuador"}}},{id:"215610",title:"Prof.",name:"Muhammad",middleName:null,surname:"Sarfraz",slug:"muhammad-sarfraz",fullName:"Muhammad Sarfraz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/215610/images/system/215610.jpeg",biography:"Muhammad Sarfraz is a professor in the Department of Information Science, Kuwait University, Kuwait. His research interests include optimization, computer graphics, computer vision, image processing, machine learning, pattern recognition, soft computing, data science, and intelligent systems. Prof. Sarfraz has been a keynote/invited speaker at various platforms around the globe. He has advised/supervised more than 110 students for their MSc and Ph.D. theses. He has published more than 400 publications as books, journal articles, and conference papers. He has authored and/or edited around seventy books. Prof. Sarfraz is a member of various professional societies. He is a chair and member of international advisory committees and organizing committees of numerous international conferences. He is also an editor and editor in chief for various international journals.",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"32650",title:"Prof.",name:"Lukas",middleName:"Willem",surname:"Snyman",slug:"lukas-snyman",fullName:"Lukas Snyman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/32650/images/4136_n.jpg",biography:"Lukas Willem Snyman received his basic education at primary and high schools in South Africa, Eastern Cape. He enrolled at today's Nelson Metropolitan University and graduated from this university with a BSc in Physics and Mathematics, B.Sc Honors in Physics, MSc in Semiconductor Physics, and a Ph.D. in Semiconductor Physics in 1987. After his studies, he chose an academic career and devoted his energy to the teaching of physics to first, second, and third-year students. After positions as a lecturer at the University of Port Elizabeth, he accepted a position as Associate Professor at the University of Pretoria, South Africa.\r\n\r\nIn 1992, he motivates the concept of 'television and computer-based education” as means to reach large student numbers with only the best of teaching expertise and publishes an article on the concept in the SA Journal of Higher Education of 1993 (and later in 2003). The University of Pretoria subsequently approved a series of test projects on the concept with outreach to Mamelodi and Eerste Rust in 1993. In 1994, the University established a 'Unit for Telematic Education ' as a support section for multiple faculties at the University of Pretoria. In subsequent years, the concept of 'telematic education” subsequently becomes well established in academic circles in South Africa, grew in popularity, and is adopted by many universities and colleges throughout South Africa as a medium of enhancing education and training, as a method to reaching out to far out communities, and as a means to enhance study from the home environment.\r\n\r\nProfessor Snyman in subsequent years pursued research in semiconductor physics, semiconductor devices, microelectronics, and optoelectronics.\r\n\r\nIn 2000 he joined the TUT as a full professor. Here served for a period as head of the Department of Electronic Engineering. Here he makes contributions to solar energy development, microwave and optoelectronic device development, silicon photonics, as well as contributions to new mobile telecommunication systems and network planning in SA.\r\n\r\nCurrently, he teaches electronics and telecommunications at the TUT to audiences ranging from first-year students to Ph.D. level.\r\n\r\nFor his research in the field of 'Silicon Photonics” since 1990, he has published (as author and co-author) about thirty internationally reviewed articles in scientific journals, contributed to more than forty international conferences, about 25 South African provisional patents (as inventor and co-inventor), 8 PCT international patent applications until now. Of these, two USA patents applications, two European Patents, two Korean patents, and ten SA patents have been granted. A further 4 USA patents, 5 European patents, 3 Korean patents, 3 Chinese patents, and 3 Japanese patents are currently under consideration.\r\n\r\nRecently he has also published an extensive scholarly chapter in an internet open access book on 'Integrating Microphotonic Systems and MOEMS into standard Silicon CMOS Integrated circuitry”.\r\n\r\nFurthermore, Professor Snyman recently steered a new initiative at the TUT by introducing a 'Laboratory for Innovative Electronic Systems ' at the Department of Electrical Engineering. The model of this laboratory or center is to primarily combine outputs as achieved by high-level research with lower-level system development and entrepreneurship in a technical university environment. Students are allocated to projects at different levels with PhDs and Master students allocated to the generation of new knowledge and new technologies, while students at the diploma and Baccalaureus level are allocated to electronic systems development with a direct and a near application for application in industry or the commercial and public sectors in South Africa.\r\n\r\nProfessor Snyman received the WIRSAM Award of 1983 and the WIRSAM Award in 1985 in South Africa for best research papers by a young scientist at two international conferences on electron microscopy in South Africa. He subsequently received the SA Microelectronics Award for the best dissertation emanating from studies executed at a South African university in the field of Physics and Microelectronics in South Africa in 1987. In October of 2011, Professor Snyman received the prestigious Institutional Award for 'Innovator of the Year” for 2010 at the Tshwane University of Technology, South Africa. This award was based on the number of patents recognized and granted by local and international institutions as well as for his contributions concerning innovation at the TUT.",institutionString:null,institution:{name:"University of South Africa",country:{name:"South Africa"}}},{id:"317279",title:"Mr.",name:"Ali",middleName:"Usama",surname:"Syed",slug:"ali-syed",fullName:"Ali Syed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/317279/images/16024_n.png",biography:"A creative, talented, and innovative young professional who is dedicated, well organized, and capable research fellow with two years of experience in graduate-level research, published in engineering journals and book, with related expertise in Bio-robotics, equally passionate about the aesthetics of the mechanical and electronic system, obtained expertise in the use of MS Office, MATLAB, SolidWorks, LabVIEW, Proteus, Fusion 360, having a grasp on python, C++ and assembly language, possess proven ability in acquiring research grants, previous appointments with social and educational societies with experience in administration, current affiliations with IEEE and Web of Science, a confident presenter at conferences and teacher in classrooms, able to explain complex information to audiences of all levels.",institutionString:null,institution:{name:"Air University",country:{name:"Pakistan"}}},{id:"75526",title:"Ph.D.",name:"Zihni Onur",middleName:null,surname:"Uygun",slug:"zihni-onur-uygun",fullName:"Zihni Onur Uygun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/75526/images/12_n.jpg",biography:"My undergraduate education and my Master of Science educations at Ege University and at Çanakkale Onsekiz Mart University have given me a firm foundation in Biochemistry, Analytical Chemistry, Biosensors, Bioelectronics, Physical Chemistry and Medicine. After obtaining my degree as a MSc in analytical chemistry, I started working as a research assistant in Ege University Medical Faculty in 2014. In parallel, I enrolled to the MSc program at the Department of Medical Biochemistry at Ege University to gain deeper knowledge on medical and biochemical sciences as well as clinical chemistry in 2014. In my PhD I deeply researched on biosensors and bioelectronics and finished in 2020. Now I have eleven SCI-Expanded Index published papers, 6 international book chapters, referee assignments for different SCIE journals, one international patent pending, several international awards, projects and bursaries. In parallel to my research assistant position at Ege University Medical Faculty, Department of Medical Biochemistry, in April 2016, I also founded a Start-Up Company (Denosens Biotechnology LTD) by the support of The Scientific and Technological Research Council of Turkey. Currently, I am also working as a CEO in Denosens Biotechnology. The main purposes of the company, which carries out R&D as a research center, are to develop new generation biosensors and sensors for both point-of-care diagnostics; such as glucose, lactate, cholesterol and cancer biomarker detections. My specific experimental and instrumental skills are Biochemistry, Biosensor, Analytical Chemistry, Electrochemistry, Mobile phone based point-of-care diagnostic device, POCTs and Patient interface designs, HPLC, Tandem Mass Spectrometry, Spectrophotometry, ELISA.",institutionString:null,institution:{name:"Ege University",country:{name:"Turkey"}}},{id:"246502",title:"Dr.",name:"Jaya T.",middleName:"T",surname:"Varkey",slug:"jaya-t.-varkey",fullName:"Jaya T. Varkey",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/246502/images/11160_n.jpg",biography:"Jaya T. Varkey, PhD, graduated with a degree in Chemistry from Cochin University of Science and Technology, Kerala, India. She obtained a PhD in Chemistry from the School of Chemical Sciences, Mahatma Gandhi University, Kerala, India, and completed a post-doctoral fellowship at the University of Minnesota, USA. She is a research guide at Mahatma Gandhi University and Associate Professor in Chemistry, St. Teresa’s College, Kochi, Kerala, India.\nDr. Varkey received a National Young Scientist award from the Indian Science Congress (1995), a UGC Research award (2016–2018), an Indian National Science Academy (INSA) Visiting Scientist award (2018–2019), and a Best Innovative Faculty award from the All India Association for Christian Higher Education (AIACHE) (2019). She Hashas received the Sr. Mary Cecil prize for best research paper three times. She was also awarded a start-up to develop a tea bag water filter. \nDr. Varkey has published two international books and twenty-seven international journal publications. She is an editorial board member for five international journals.",institutionString:"St. Teresa’s College",institution:null},{id:"250668",title:"Dr.",name:"Ali",middleName:null,surname:"Nabipour Chakoli",slug:"ali-nabipour-chakoli",fullName:"Ali Nabipour Chakoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/250668/images/system/250668.jpg",biography:"Academic Qualification:\r\n•\tPhD in Materials Physics and Chemistry, From: Sep. 2006, to: Sep. 2010, School of Materials Science and Engineering, Harbin Institute of Technology, Thesis: Structure and Shape Memory Effect of Functionalized MWCNTs/poly (L-lactide-co-ε-caprolactone) Nanocomposites. Supervisor: Prof. Wei Cai,\r\n•\tM.Sc in Applied Physics, From: 1996, to: 1998, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Determination of Boron in Micro alloy Steels with solid state nuclear track detectors by neutron induced auto radiography, Supervisors: Dr. M. Hosseini Ashrafi and Dr. A. Hosseini.\r\n•\tB.Sc. in Applied Physics, From: 1991, to: 1996, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Design of shielding for Am-Be neutron sources for In Vivo neutron activation analysis, Supervisor: Dr. M. Hosseini Ashrafi.\r\n\r\nResearch Experiences:\r\n1.\tNanomaterials, Carbon Nanotubes, Graphene: Synthesis, Functionalization and Characterization,\r\n2.\tMWCNTs/Polymer Composites: Fabrication and Characterization, \r\n3.\tShape Memory Polymers, Biodegradable Polymers, ORC, Collagen,\r\n4.\tMaterials Analysis and Characterizations: TEM, SEM, XPS, FT-IR, Raman, DSC, DMA, TGA, XRD, GPC, Fluoroscopy, \r\n5.\tInteraction of Radiation with Mater, Nuclear Safety and Security, NDT(RT),\r\n6.\tRadiation Detectors, Calibration (SSDL),\r\n7.\tCompleted IAEA e-learning Courses:\r\nNuclear Security (15 Modules),\r\nNuclear Safety:\r\nTSA 2: Regulatory Protection in Occupational Exposure,\r\nTips & Tricks: Radiation Protection in Radiography,\r\nSafety and Quality in Radiotherapy,\r\nCourse on Sealed Radioactive Sources,\r\nCourse on Fundamentals of Environmental Remediation,\r\nCourse on Planning for Environmental Remediation,\r\nKnowledge Management Orientation Course,\r\nFood Irradiation - Technology, Applications and Good Practices,\r\nEmployment:\r\nFrom 2010 to now: Academic staff, Nuclear Science and Technology Research Institute, Kargar Shomali, Tehran, Iran, P.O. Box: 14395-836.\r\nFrom 1997 to 2006: Expert of Materials Analysis and Characterization. Research Center of Agriculture and Medicine. Rajaeeshahr, Karaj, Iran, P. O. Box: 31585-498.",institutionString:"Atomic Energy Organization of Iran",institution:{name:"Atomic Energy Organization of Iran",country:{name:"Iran"}}},{id:"248279",title:"Dr.",name:"Monika",middleName:"Elzbieta",surname:"Machoy",slug:"monika-machoy",fullName:"Monika Machoy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248279/images/system/248279.jpeg",biography:"Monika Elżbieta Machoy, MD, graduated with distinction from the Faculty of Medicine and Dentistry at the Pomeranian Medical University in 2009, defended her PhD thesis with summa cum laude in 2016 and is currently employed as a researcher at the Department of Orthodontics of the Pomeranian Medical University. She expanded her professional knowledge during a one-year scholarship program at the Ernst Moritz Arndt University in Greifswald, Germany and during a three-year internship at the Technical University in Dresden, Germany. She has been a speaker at numerous orthodontic conferences, among others, American Association of Orthodontics, European Orthodontic Symposium and numerous conferences of the Polish Orthodontic Society. She conducts research focusing on the effect of orthodontic treatment on dental and periodontal tissues and the causes of pain in orthodontic patients.",institutionString:"Pomeranian Medical University",institution:{name:"Pomeranian Medical University",country:{name:"Poland"}}},{id:"252743",title:"Prof.",name:"Aswini",middleName:"Kumar",surname:"Kar",slug:"aswini-kar",fullName:"Aswini Kar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252743/images/10381_n.jpg",biography:"uploaded in cv",institutionString:null,institution:{name:"KIIT University",country:{name:"India"}}},{id:"204256",title:"Dr.",name:"Anil",middleName:"Kumar",surname:"Kumar Sahu",slug:"anil-kumar-sahu",fullName:"Anil Kumar Sahu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204256/images/14201_n.jpg",biography:"I have nearly 11 years of research and teaching experience. I have done my master degree from University Institute of Pharmacy, Pt. Ravi Shankar Shukla University, Raipur, Chhattisgarh India. I have published 16 review and research articles in international and national journals and published 4 chapters in IntechOpen, the world’s leading publisher of Open access books. I have presented many papers at national and international conferences. I have received research award from Indian Drug Manufacturers Association in year 2015. My research interest extends from novel lymphatic drug delivery systems, oral delivery system for herbal bioactive to formulation optimization.",institutionString:null,institution:{name:"Chhattisgarh Swami Vivekanand Technical University",country:{name:"India"}}},{id:"253468",title:"Dr.",name:"Mariusz",middleName:null,surname:"Marzec",slug:"mariusz-marzec",fullName:"Mariusz Marzec",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/253468/images/system/253468.png",biography:"An assistant professor at Department of Biomedical Computer Systems, at Institute of Computer Science, Silesian University in Katowice. Scientific interests: computer analysis and processing of images, biomedical images, databases and programming languages. He is an author and co-author of scientific publications covering analysis and processing of biomedical images and development of database systems.",institutionString:"University of Silesia",institution:null},{id:"212432",title:"Prof.",name:"Hadi",middleName:null,surname:"Mohammadi",slug:"hadi-mohammadi",fullName:"Hadi Mohammadi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/212432/images/system/212432.jpeg",biography:"Dr. Hadi Mohammadi is a biomedical engineer with hands-on experience in the design and development of many engineering structures and medical devices through various projects that he has been involved in over the past twenty years. Dr. Mohammadi received his BSc. and MSc. degrees in Mechanical Engineering from Sharif University of Technology, Tehran, Iran, and his PhD. degree in Biomedical Engineering (biomaterials) from the University of Western Ontario. He was a postdoctoral trainee for almost four years at University of Calgary and Harvard Medical School. He is an industry innovator having created the technology to produce lifelike synthetic platforms that can be used for the simulation of almost all cardiovascular reconstructive surgeries. He’s been heavily involved in the design and development of cardiovascular devices and technology for the past 10 years. He is currently an Assistant Professor with the University of British Colombia, Canada.",institutionString:"University of British Columbia",institution:{name:"University of British Columbia",country:{name:"Canada"}}},{id:"254463",title:"Prof.",name:"Haisheng",middleName:null,surname:"Yang",slug:"haisheng-yang",fullName:"Haisheng Yang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/254463/images/system/254463.jpeg",biography:"Haisheng Yang, Ph.D., Professor and Director of the Department of Biomedical Engineering, College of Life Science and Bioengineering, Beijing University of Technology. He received his Ph.D. degree in Mechanics/Biomechanics from Harbin Institute of Technology (jointly with University of California, Berkeley). Afterwards, he worked as a Postdoctoral Research Associate in the Purdue Musculoskeletal Biology and Mechanics Lab at the Department of Basic Medical Sciences, Purdue University, USA. He also conducted research in the Research Centre of Shriners Hospitals for Children-Canada at McGill University, Canada. Dr. Yang has over 10 years research experience in orthopaedic biomechanics and mechanobiology of bone adaptation and regeneration. He earned an award from Beijing Overseas Talents Aggregation program in 2017 and serves as Beijing Distinguished Professor.",institutionString:"Beijing University of Technology",institution:null},{id:"255757",title:"Dr.",name:"Igor",middleName:"Victorovich",surname:"Lakhno",slug:"igor-lakhno",fullName:"Igor Lakhno",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255757/images/system/255757.jpg",biography:"Lakhno Igor Victorovich was born in 1971 in Kharkiv (Ukraine). \nMD – 1994, Kharkiv National Medical Univesity.\nOb&Gyn; – 1997, master courses in Kharkiv Medical Academy of Postgraduate Education.\nPhD – 1999, Kharkiv National Medical Univesity.\nDSc – 2019, PL Shupik National Academy of Postgraduate Education \nLakhno Igor has been graduated from an international training courses on reproductive medicine and family planning held in Debrecen University (Hungary) in 1997. Since 1998 Lakhno Igor has worked as an associate professor of the department of obstetrics and gynecology of VN Karazin National University and an associate professor of the perinatology, obstetrics and gynecology department of Kharkiv Medical Academy of Postgraduate Education. Since June 2019 he’s a professor of the department of obstetrics and gynecology of VN Karazin National University and a professor of the perinatology, obstetrics and gynecology department of Kharkiv Medical Academy of Postgraduate Education . He’s an author of about 200 printed works and there are 17 of them in Scopus or Web of Science databases. Lakhno Igor is a rewiever of Journal of Obstetrics and Gynaecology (Taylor and Francis), Informatics in Medicine Unlocked (Elsevier), The Journal of Obstetrics and Gynecology Research (Wiley), Endocrine, Metabolic & Immune Disorders-Drug Targets (Bentham Open), The Open Biomedical Engineering Journal (Bentham Open), etc. He’s defended a dissertation for DSc degree \\'Pre-eclampsia: prediction, prevention and treatment”. Lakhno Igor has participated as a speaker in several international conferences and congresses (International Conference on Biological Oscillations April 10th-14th 2016, Lancaster, UK, The 9th conference of the European Study Group on Cardiovascular Oscillations). His main scientific interests: obstetrics, women’s health, fetal medicine, cardiovascular medicine.",institutionString:"V.N. Karazin Kharkiv National University",institution:{name:"Kharkiv Medical Academy of Postgraduate Education",country:{name:"Ukraine"}}},{id:"89721",title:"Dr.",name:"Mehmet",middleName:"Cuneyt",surname:"Ozmen",slug:"mehmet-ozmen",fullName:"Mehmet Ozmen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/89721/images/7289_n.jpg",biography:null,institutionString:null,institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"243698",title:"M.D.",name:"Xiaogang",middleName:null,surname:"Wang",slug:"xiaogang-wang",fullName:"Xiaogang Wang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243698/images/system/243698.png",biography:"Dr. Xiaogang Wang, a faculty member of Shanxi Eye Hospital specializing in the treatment of cataract and retinal disease and a tutor for postgraduate students of Shanxi Medical University, worked in the COOL Lab as an international visiting scholar under the supervision of Dr. David Huang and Yali Jia from October 2012 through November 2013. Dr. Wang earned an MD from Shanxi Medical University and a Ph.D. from Shanghai Jiao Tong University. Dr. Wang was awarded two research project grants focused on multimodal optical coherence tomography imaging and deep learning in cataract and retinal disease, from the National Natural Science Foundation of China. He has published around 30 peer-reviewed journal papers and four book chapters and co-edited one book.",institutionString:"Shanxi Eye Hospital",institution:{name:"Shanxi Eye Hospital",country:{name:"China"}}},{id:"242893",title:"Ph.D. Student",name:"Joaquim",middleName:null,surname:"De Moura",slug:"joaquim-de-moura",fullName:"Joaquim De Moura",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/242893/images/7133_n.jpg",biography:"Joaquim de Moura received his degree in Computer Engineering in 2014 from the University of A Coruña (Spain). In 2016, he received his M.Sc degree in Computer Engineering from the same university. He is currently pursuing his Ph.D degree in Computer Science in a collaborative project between ophthalmology centers in Galicia and the University of A Coruña. His research interests include computer vision, machine learning algorithms and analysis and medical imaging processing of various kinds.",institutionString:null,institution:{name:"University of A Coruña",country:{name:"Spain"}}},{id:"267434",title:"Dr.",name:"Rohit",middleName:null,surname:"Raja",slug:"rohit-raja",fullName:"Rohit Raja",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRZkkQAG/Profile_Picture_2022-05-09T12:55:18.jpg",biography:null,institutionString:null,institution:null},{id:"294334",title:"B.Sc.",name:"Marc",middleName:null,surname:"Bruggeman",slug:"marc-bruggeman",fullName:"Marc Bruggeman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/294334/images/8242_n.jpg",biography:"Chemical engineer graduate, with a passion for material science and specific interest in polymers - their near infinite applications intrigue me. \n\nI plan to continue my scientific career in the field of polymeric biomaterials as I am fascinated by intelligent, bioactive and biomimetic materials for use in both consumer and medical applications.",institutionString:null,institution:null},{id:"244950",title:"Dr.",name:"Salvatore",middleName:null,surname:"Di Lauro",slug:"salvatore-di-lauro",fullName:"Salvatore Di Lauro",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0030O00002bSF1HQAW/ProfilePicture%202021-12-20%2014%3A54%3A14.482",biography:"Name:\n\tSALVATORE DI LAURO\nAddress:\n\tHospital Clínico Universitario Valladolid\nAvda Ramón y Cajal 3\n47005, Valladolid\nSpain\nPhone number: \nFax\nE-mail:\n\t+34 983420000 ext 292\n+34 983420084\nsadilauro@live.it\nDate and place of Birth:\nID Number\nMedical Licence \nLanguages\t09-05-1985. Villaricca (Italy)\n\nY1281863H\n474707061\nItalian (native language)\nSpanish (read, written, spoken)\nEnglish (read, written, spoken)\nPortuguese (read, spoken)\nFrench (read)\n\t\t\nCurrent position (title and company)\tDate (Year)\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. Private practise.\t2017-today\n\n2019-today\n\t\n\t\nEducation (High school, university and postgraduate training > 3 months)\tDate (Year)\nDegree in Medicine and Surgery. University of Neaples 'Federico II”\nResident in Opthalmology. Hospital Clinico Universitario Valladolid\nMaster in Vitreo-Retina. IOBA. University of Valladolid\nFellow of the European Board of Ophthalmology. Paris\nMaster in Research in Ophthalmology. University of Valladolid\t2003-2009\n2012-2016\n2016-2017\n2016\n2012-2013\n\t\nEmployments (company and positions)\tDate (Year)\nResident in Ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl.\nFellow in Vitreo-Retina. IOBA. University of Valladolid\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. \n\t2012-2016\n2016-2017\n2017-today\n\n2019-Today\n\n\n\t\nClinical Research Experience (tasks and role)\tDate (Year)\nAssociated investigator\n\n' FIS PI20/00740: DESARROLLO DE UNA CALCULADORA DE RIESGO DE\nAPARICION DE RETINOPATIA DIABETICA BASADA EN TECNICAS DE IMAGEN MULTIMODAL EN PACIENTES DIABETICOS TIPO 1. Grant by: Ministerio de Ciencia e Innovacion \n\n' (BIO/VA23/14) Estudio clínico multicéntrico y prospectivo para validar dos\nbiomarcadores ubicados en los genes p53 y MDM2 en la predicción de los resultados funcionales de la cirugía del desprendimiento de retina regmatógeno. Grant by: Gerencia Regional de Salud de la Junta de Castilla y León.\n' Estudio multicéntrico, aleatorizado, con enmascaramiento doble, en 2 grupos\nparalelos y de 52 semanas de duración para comparar la eficacia, seguridad e inmunogenicidad de SOK583A1 respecto a Eylea® en pacientes con degeneración macular neovascular asociada a la edad' (CSOK583A12301; N.EUDRA: 2019-004838-41; FASE III). Grant by Hexal AG\n\n' Estudio de fase III, aleatorizado, doble ciego, con grupos paralelos, multicéntrico para comparar la eficacia y la seguridad de QL1205 frente a Lucentis® en pacientes con degeneración macular neovascular asociada a la edad. (EUDRACT: 2018-004486-13). Grant by Qilu Pharmaceutical Co\n\n' Estudio NEUTON: Ensayo clinico en fase IV para evaluar la eficacia de aflibercept en pacientes Naive con Edema MacUlar secundario a Oclusion de Vena CenTral de la Retina (OVCR) en regimen de tratamientO iNdividualizado Treat and Extend (TAE)”, (2014-000975-21). Grant by Fundacion Retinaplus\n\n' Evaluación de la seguridad y bioactividad de anillos de tensión capsular en conejo. Proyecto Procusens. Grant by AJL, S.A.\n\n'Estudio epidemiológico, prospectivo, multicéntrico y abierto\\npara valorar la frecuencia de la conjuntivitis adenovírica diagnosticada mediante el test AdenoPlus®\\nTest en pacientes enfermos de conjuntivitis aguda”\\n. National, multicenter study. Grant by: NICOX.\n\nEuropean multicentric trial: 'Evaluation of clinical outcomes following the use of Systane Hydration in patients with dry eye”. Study Phase 4. Grant by: Alcon Labs'\n\nVLPs Injection and Activation in a Rabbit Model of Uveal Melanoma. Grant by Aura Bioscience\n\nUpdating and characterization of a rabbit model of uveal melanoma. Grant by Aura Bioscience\n\nEnsayo clínico en fase IV para evaluar las variantes genéticas de la vía del VEGF como biomarcadores de eficacia del tratamiento con aflibercept en pacientes con degeneración macular asociada a la edad (DMAE) neovascular. Estudio BIOIMAGE. IMO-AFLI-2013-01\n\nEstudio In-Eye:Ensayo clínico en fase IV, abierto, aleatorizado, de 2 brazos,\nmulticçentrico y de 12 meses de duración, para evaluar la eficacia y seguridad de un régimen de PRN flexible individualizado de 'esperar y extender' versus un régimen PRN según criterios de estabilización mediante evaluaciones mensuales de inyecciones intravítreas de ranibizumab 0,5 mg en pacientes naive con neovascularización coriodea secunaria a la degeneración macular relacionada con la edad. CP: CRFB002AES03T\n\nTREND: Estudio Fase IIIb multicéntrico, randomizado, de 12 meses de\nseguimiento con evaluador de la agudeza visual enmascarado, para evaluar la eficacia y la seguridad de ranibizumab 0.5mg en un régimen de tratar y extender comparado con un régimen mensual, en pacientes con degeneración macular neovascular asociada a la edad. CP: CRFB002A2411 Código Eudra CT:\n2013-002626-23\n\n\n\nPublications\t\n\n2021\n\n\n\n\n2015\n\n\n\n\n2021\n\n\n\n\n\n2021\n\n\n\n\n2015\n\n\n\n\n2015\n\n\n2014\n\n\n\n\n2015-16\n\n\n\n2015\n\n\n2014\n\n\n2014\n\n\n\n\n2014\n\n\n\n\n\n\n\n2014\n\nJose Carlos Pastor; Jimena Rojas; Salvador Pastor-Idoate; Salvatore Di Lauro; Lucia Gonzalez-Buendia; Santiago Delgado-Tirado. Proliferative vitreoretinopathy: A new concept of disease pathogenesis and practical\nconsequences. Progress in Retinal and Eye Research. 51, pp. 125 - 155. 03/2016. DOI: 10.1016/j.preteyeres.2015.07.005\n\n\nLabrador-Velandia S; Alonso-Alonso ML; Di Lauro S; García-Gutierrez MT; Srivastava GK; Pastor JC; Fernandez-Bueno I. Mesenchymal stem cells provide paracrine neuroprotective resources that delay degeneration of co-cultured organotypic neuroretinal cultures.Experimental Eye Research. 185, 17/05/2019. DOI: 10.1016/j.exer.2019.05.011\n\nSalvatore Di Lauro; Maria Teresa Garcia Gutierrez; Ivan Fernandez Bueno. Quantification of pigment epithelium-derived factor (PEDF) in an ex vivo coculture of retinal pigment epithelium cells and neuroretina.\nJournal of Allbiosolution. 2019. ISSN 2605-3535\n\nSonia Labrador Velandia; Salvatore Di Lauro; Alonso-Alonso ML; Tabera Bartolomé S; Srivastava GK; Pastor JC; Fernandez-Bueno I. Biocompatibility of intravitreal injection of human mesenchymal stem cells in immunocompetent rabbits. Graefe's archive for clinical and experimental ophthalmology. 256 - 1, pp. 125 - 134. 01/2018. DOI: 10.1007/s00417-017-3842-3\n\n\nSalvatore Di Lauro, David Rodriguez-Crespo, Manuel J Gayoso, Maria T Garcia-Gutierrez, J Carlos Pastor, Girish K Srivastava, Ivan Fernandez-Bueno. A novel coculture model of porcine central neuroretina explants and retinal pigment epithelium cells. Molecular Vision. 2016 - 22, pp. 243 - 253. 01/2016.\n\nSalvatore Di Lauro. Classifications for Proliferative Vitreoretinopathy ({PVR}): An Analysis of Their Use in Publications over the Last 15 Years. Journal of Ophthalmology. 2016, pp. 1 - 6. 01/2016. DOI: 10.1155/2016/7807596\n\nSalvatore Di Lauro; Rosa Maria Coco; Rosa Maria Sanabria; Enrique Rodriguez de la Rua; Jose Carlos Pastor. Loss of Visual Acuity after Successful Surgery for Macula-On Rhegmatogenous Retinal Detachment in a Prospective Multicentre Study. Journal of Ophthalmology. 2015:821864, 2015. DOI: 10.1155/2015/821864\n\nIvan Fernandez-Bueno; Salvatore Di Lauro; Ivan Alvarez; Jose Carlos Lopez; Maria Teresa Garcia-Gutierrez; Itziar Fernandez; Eva Larra; Jose Carlos Pastor. Safety and Biocompatibility of a New High-Density Polyethylene-Based\nSpherical Integrated Porous Orbital Implant: An Experimental Study in Rabbits. Journal of Ophthalmology. 2015:904096, 2015. DOI: 10.1155/2015/904096\n\nPastor JC; Pastor-Idoate S; Rodríguez-Hernandez I; Rojas J; Fernandez I; Gonzalez-Buendia L; Di Lauro S; Gonzalez-Sarmiento R. Genetics of PVR and RD. Ophthalmologica. 232 - Suppl 1, pp. 28 - 29. 2014\n\nRodriguez-Crespo D; Di Lauro S; Singh AK; Garcia-Gutierrez MT; Garrosa M; Pastor JC; Fernandez-Bueno I; Srivastava GK. Triple-layered mixed co-culture model of RPE cells with neuroretina for evaluating the neuroprotective effects of adipose-MSCs. Cell Tissue Res. 358 - 3, pp. 705 - 716. 2014.\nDOI: 10.1007/s00441-014-1987-5\n\nCarlo De Werra; Salvatore Condurro; Salvatore Tramontano; Mario Perone; Ivana Donzelli; Salvatore Di Lauro; Massimo Di Giuseppe; Rosa Di Micco; Annalisa Pascariello; Antonio Pastore; Giorgio Diamantis; Giuseppe Galloro. Hydatid disease of the liver: thirty years of surgical experience.Chirurgia italiana. 59 - 5, pp. 611 - 636.\n(Italia): 2007. ISSN 0009-4773\n\nChapters in books\n\t\n' Salvador Pastor Idoate; Salvatore Di Lauro; Jose Carlos Pastor Jimeno. PVR: Pathogenesis, Histopathology and Classification. Proliferative Vitreoretinopathy with Small Gauge Vitrectomy. Springer, 2018. ISBN 978-3-319-78445-8\nDOI: 10.1007/978-3-319-78446-5_2. \n\n' Salvatore Di Lauro; Maria Isabel Lopez Galvez. Quistes vítreos en una mujer joven. Problemas diagnósticos en patología retinocoroidea. Sociedad Española de Retina-Vitreo. 2018.\n\n' Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor Jimeno. iOCT in PVR management. OCT Applications in Opthalmology. pp. 1 - 8. INTECH, 2018. DOI: 10.5772/intechopen.78774.\n\n' Rosa Coco Martin; Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor. amponadores, manipuladores y tinciones en la cirugía del traumatismo ocular.Trauma Ocular. Ponencia de la SEO 2018..\n\n' LOPEZ GALVEZ; DI LAURO; CRESPO. OCT angiografia y complicaciones retinianas de la diabetes. PONENCIA SEO 2021, CAPITULO 20. (España): 2021.\n\n' Múltiples desprendimientos neurosensoriales bilaterales en paciente joven. Enfermedades Degenerativas De Retina Y Coroides. SERV 04/2016. \n' González-Buendía L; Di Lauro S; Pastor-Idoate S; Pastor Jimeno JC. Vitreorretinopatía proliferante (VRP) e inflamación: LA INFLAMACIÓN in «INMUNOMODULADORES Y ANTIINFLAMATORIOS: MÁS ALLÁ DE LOS CORTICOIDES. 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Behind these definitions are hidden all the aspects of normal and pathological functioning of all processes that the topic ‘Metabolism’ will cover within the Biochemistry Series. 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Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. 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