\r\n\tThe development of sustainable waste management strategies has become a major concern throughout the world. Therefore, the new book focuses on “recycling” and “recovery” of waste material while paving the way towards a circular economy including land reclamation, and water and wastewater treatments.
\r\n\r\n\tThe book aims to provide a platform to present research in regards to:
\r\n\t(1) Sustainable Waste Management;
\r\n\t(2) Micro(nano)plastics in the Environments;
\r\n\t(3) Electronic Waste and Circular Economy;
\r\n\t(4) Reducing, Recycling and Recovery of Agricultural and Food Waste;
\r\n\t(5) Biomass Valorization: Waste to Resources;
\r\n\t(6) Governmental Policy on Waste Management and Valorization.
\r\n\tThis book will offer a timely opportunity for knowledge exchange of sustainable management agenda for biological waste and remediation of soil, water and air in the local context, which satisfies the environmental compatibility, financial feasibility and social needs. It will deliberate on state-of-the-art treatment technologies, advanced management strategies, and political issues pertaining to recycling and recovery of organic waste.
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Over time, the interest of clinicians on spasticity has increased more and more, topics ranging from pathophysiology to clinical relevance and treatment options [2, 3, 4, 5, 6, 7, 8].
However, in everyday management of patients’ spasticity symptoms, much more complex situation would be there, full of clinical problems. In fact, other positive and/or negative signs may be observed together with increased muscle tone and deep tendon reflexes. Abnormal cutaneous reflexes, spasms, co-contraction, Babinski reflex, and also dystonia, are described as positive phenomena, and weakness, fatigability, and reduced dexterity are considered negative ones. In clinical practice each problem that we have to treat may have different pathophysiological explanations [9]. A central nervous system lesion determines the upper motor neuron syndrome, induced by an interruption of descending pathways, which connect the highest centres to the spinal cord. Alternatively, reactivity of spinal cord circuits may be modified by a direct damage, through a different way to elaborate the input from peripheral afferents. It is important to differentiate immediate to delayed consequences of damage to the highest centres in the CNS. The delayed consequences lead to a rearrangement of reactivity in spinal cord circuits, in which it is considered a basis of spasticity. Moreover, spasticity may itself be modified by the consequences of paresis and immobilisation, i.e. development of contractures. Several pathophysiological mechanisms may explain the development of spasticity due to CNS lesions. These mainly include defective inhibition, such as postsynaptic inhibition of alpha motor neurons or presynaptic inhibition of 1a afferents. There is also a defective excitation of inhibitory interneurons underlying reciprocal inhibition, autogenetic inhibition, or recurrent inhibition [10].
Dystonia is defined as a neurological disorder characterised by sustained or intermittent muscle contractions, determining unusual movements and postures or both. Typically dystonic movements are patterned and twisting and may be tremulous. Often, dystonic movements may be started by voluntary action, worsening with typically an overflow muscle activation (Consensus 2013) [11]. Dystonia classification is based on clinical characteristics and aetiology. Indeed, except for hereditary forms, dystonic syndromes may be caused by birth-related or other physical trauma, infection, and poisoning or due to pharmacological treatments, particularly neuroleptics. The clinical characteristics include age at onset, temporal pattern, body distribution, and coexistence of other movement disorders. The etiologic characteristics are the presence or absence of nervous system pathology and the pattern of inheritance [11].
Focal dystonia is a neurologic movement disorder, due to an incorrect sensorimotor modulation, determining involuntary, excessive muscle contractions. Writer’s cramp is a specific type of focal dystonia that affects the fingers, hand, or forearm. Writer’s cramp is a task-specific dystonia, characterised by hands twisting into odd postures. A specific task induces this sign. Other skilled task-specific movements may induce focal hand dystonia, such as playing a musical instrument, typing, or sewing. Writer’s cramp is known also as musician’s cramp, focal hand dystonia, arm dystonia, finger dystonia, task-specific dystonia, and occupational cramp or dystonia.
Task-specific dystonia like writer’s cramp may appear in anyone. It usually appears between 30 and 50 years of age. Task-specific dystonia, particularly musician’s cramp, is more common in men.
Two types of writer’s cramp could be described:
Simple writer’s cramp, which appears only during writing. The abnormal postures spring up soon after you pick up a pen. So, it only affects the ability to write.
Dystonic writer’s cramp appears not only during writing but also during other activities with your hands, like shaving, dressing, or applying makeup.
Probably, repetitive movements determine a remapping of the brain’s sensorimotor areas. Bad posture of the hands while holding a pen or pencil associated with overuse seems to cause simple writer’s cramp. Dystonic writer’s cramp is less common than simple ones and may represent a symptom of generalised dystonia. In this case, the involuntary movements can appear also during other non-writing tasks, such as using a fork or handwashing. Rarely, writer’s cramp could be the early onset of a generalised dystonia, which is associated with the DYT1 gene [12].
Typically, spasticity is considered as a specific “pyramidal” sign; nevertheless, selective lesions of the primary motor cortex or corticospinal tract often induce hypotonia, deficit, or weakness in distal movements, without inducing spasticity [4]. Only the involvement of non-primary motor areas (premotor and supplementary areas) and the corticoreticulospinal fibres together with cortical lesions may induce spasticity. Corticoreticulospinal fibres sends through the dorsolateral reticulospinal tract descending just anteriorly to the corticospinal tract, a massive bilateral inhibitory projection to spinal motor neurons, which are located in the lateral funiculus of the spinal cord. So the fact that a selective lesion of the anterior limb or the genu of the internal capsula predominantly induces spasticity without an evident motor deficit and vice versa can be explained by the different courses of corticoreticular and corticospinal fibres in the internal capsula. Hence, a lesion involving the corticoreticulospinal fibres will lead to a decreased inhibition (or to an increased facilitation) of the spinal cord and ultimately to spasticity [13, 14]. Three fundamental phenomena occur after a lesion to the central motor pathways assigned to motor command execution:
Among these changes, which gradually develop, spasticity represents the principal sign detectable. A simple definition of spasticity is an
Principal key points:
A tonic stretch reflex.
Mediated by type 1a fibre nerve, predominantly in the muscle spindle. Passive muscle stretch induces exciting of muscle spindle, which sends sensory input back to the spinal cord through monosynaptic way principally but also oligo- and polysynaptic reflexes, which at the end induce an efferent impulse to the muscle, causing contraction.
Velocity-dependent.
Length-dependent.
The term “spastic dystonia” was coined by Denny-Brown in 1966 to define tonic-chronic muscle activity that is present in a spasticity pattern, during rest [15]. Thus, spastic dystonia could be described as a spontaneous overactivity at rest, not induced by a primary triggering factor [14, 15, 16]. It is easy to recognise it in patients with spastic paresis, as spastic dystonia causes specific bad postures in joints and body. For example, in the upper limb, the shoulder can stay internally rotated and adducted with a flexed and pronated elbow and flexed wrist and fingers. Equinovarus deformity represents a specific spastic dystonia in the lower limb, and it is characterised by plantar flexors and/or toe flexors, which may be painful and disabling during walking.
Spastic co-contraction is defined as an “unwanted, excessive, level of antagonistic muscle activity during voluntary command on an agonist muscle, which is aggravated by tonic stretch in the co-contracting muscle” [13]. Spastic co-contraction in spasticity pattern is a descending phenomenon, most probably due to misdirection of the supraspinal drive. It may be caused by loss of reciprocal inhibition during voluntary command [9, 10]. So, voluntary command of an agonist muscle is the first step, which induces spastic co-contraction. In patients with good or fairly good motor control, spastic co-contraction is certainly the most disabling form of muscle overactivity, because it obstacles muscle physiological muscle voluntary recruitment.
For each movement evaluated, the corresponding muscles and joints are stretched at a very slow speed, in order to keep below the threshold for eliciting a stretch reflex. The angle at which soft tissue offers a maximum resistance is defined as the passive range of motion for that joint [17].
For each movement evaluated, the clinician should stretch the corresponding muscles and joints as fast as possible for the examiner. The spasticity grade is determined by the joint angle at which catch or clonus appears, according to Tardieu scale [18].
For each passive movement evaluated at first, the clinician asks the patient to carry out an active movement at maximal range, until the active movement produced by the agonist muscles is contrasted by the passive resistance together with the spastic co-contraction of antagonist ones. This angle measure is the effective active range of motion [18].
Tardieu score is a scale realised to measure spasticity that evaluates resistance to passive movement at both slow and fast speed. Individuals are evaluated both in in sit and supine position. There are two types of measures:
Quality of muscle reaction.
Angle of muscle reaction.
The quality of muscle reaction is scored as follows (range 0–4):
0. No resistance throughout the course of the passive movement.
1. Slight resistance throughout the course of the passive movement, followed by release.
2. Clear catch at precise angle, interrupting the passive movement, followed by release.
3. Fatigable clonus (<10 seconds when maintaining pressure) occurring at precise angle.
4. Infatigable clonus (>10 seconds when maintaining pressure) occurring at precise angle.
In order to consider joint angle, speed movement has to be defined:
V1 is slow as possible.
V2 speed of limb falling under gravity.
V3 moving as fast as possible.
Regarding the joint angle, modified Tardieu describes:
R1 as the angle of muscle reaction.
R2 as the full PROM.
The angle of full ROM (R2) is defined at a very slow speed (V1). The angle of muscle reaction (R1) is detected when a catch or clonus appears during a quick stretch (V3) [19].
Ashworth scale, original version (1964), is a test which quantifies resistance to passive movement, with respect to a joint and with varying degrees of velocity. Scores range from 0 to 4:
0. No increase in tone.
1. Slight increase in tone giving a catch when the limb was moved in flexion or extension.
2. More marked increase in tone but limb easily flexed.
3. Considerable increase in tone, passive movement difficult.
4. Limb rigid, sometimes fixed in flexion or extension.
The modified Ashworth scale (Bohannon & Smith, 1987) is similar to the original one, except for a 1+ scoring category to indicate resistance through less than half of the movement [20].
It’s demonstrated that burden of care is higher in neurological patients who developed spasticity than that of those without it, in particular regarding treatment costs, quality of life, caregiver burden, and the effects of comorbidities [21]. The treatment of muscle overactivity may be considered when the condition is disabling. Muscle overactivity usually impairs motor command, so this itself justifies the treatment. Moreover, independently from the aetiological context, it contributes to impair patient’s function [22]. Nevertheless, not all patients with muscle overactivity need a specific treatment. Treatment in spasticity should be carried out only after rigorous clinical analysis, in order to determine the severity of functional impairment. A multidisciplinary approach is necessary in order to obtain this specific assessment, being different according to patient’s clinical condition; it may include variably physician, physical therapist, occupational therapist, nurse, and/or caregiver [22]. In order to obtain an individual, task-oriented therapeutic strategy, it is necessary to analyse a list of personal measurable objectives, which may be different for each patient. The clinical follow-up is required in order to show the benefits as well as adverse events. Muscle spasticity, which usually is responsive to drug treatment, is not the only motor impairment in spastic paresis. It is necessary also that physiotherapy is associated to drug treatment, in order to obtain maximum gain in paresis. For example, stretch programmes can be used to treat soft tissue shortening. Therefore, before treatment, the following three questions must be answered:
Is muscle overactivity handicap an activity of daily living? Only after a detailed analysis of the functional impairment induced by spasticity, it is possible to carry out an appropriate treatment, which could be really effective to improve patient’s quality of life.
Is disability caused by muscle spasticity, or is it only a comorbidity? In the latter case, which components are involved? It is important to specify the quality of motor control and weakness. If motor impairment is induced or worsened by muscle overactivity, its treatment is to be considered mandatory, in order to be helpful to the patient [23].
Does muscle overactivity involve one specific muscle group, or does it spread to other? The correct therapeutic approach depends on the answer.
Pharmacological interventions for spasticity can be divided into two groups: those that act systemically and those that act locally [24] with the locally acting treatments tending to be more invasive, systemically acting drugs used as a first step [24]. If a systematic approach, which includes baclofen, tizanidine, or dantrolene, is not successful, local treatment is allowed [25], such as muscle botulinum toxin (BTX) injection or peripheral neurolytic blockade with alcohol or phenol [26]. Surgery is to be considered as the final treatment option; however, it is rarely used. If the principal aim is to inhibit neurotransmitter activity at one or more sites within the central nervous system, a systemic approach with specific drugs is to be evaluated. Targeted therapy could regard pre- or postsynaptic sites in spinal interneurons (at varying levels of the upper motor neuron pathway), alpha motor neurons, as well as primary sensory afferent neurons. So, the central nervous system is influenced by inhibitory effects of the neurotransmitters [27]. Oral administration needs high drug dose in order to cross the blood–brain barrier; therefore, side effects like dizziness could occur. In order to reduce the probability for these negative effects, it is possible to introduce some drugs directly into the cerebrospinal fluid, for example, by an intrathecal pump. For drugs used peripherally via injection directly to the nerve or muscle, systemic side effects are fewer.
Physiotherapy is the basic treatment for all patients with spasticity [28, 29]. It may help limit muscle contractures and reduce overactivity for a short period. Physiotherapy together with drug treatment is fundamental to obtain the best functional gain, in order to help patients adapt to changes. In all cases, physiotherapy must be considered as complementary to drugs and surgery. In fact, stretching is considered an import goal in a physiotherapy session, as largely demonstrated [30]. Functional electrical stimulation allows spasticity reduction in antagonists of the stimulated muscles. An interesting use of electrical stimulation is the stimulation of hand and finger extensors during prehension training and mixing of overactive flexor inhibition with extensor activation [31]. Finally, it is important to educate patient in self-rehabilitation sessions comprehensive of stretching postures and active exercises, eventually assisted by caregivers and/or orthoses.
Pharmacologic approaches emphasise oral drugs, neuromuscular blocks, and intrathecal agents. Usually, antispastic therapy is initiated with oral drugs, even though adverse side effects are frequently reported as a systematic effect [32]. Treatment decisions on specific pharmacologic approach are influenced by chronicity, severity, and localisation of spasticity. It was demonstrated that pharmacologic treatments are most effective if used early, in order to avoid muscle shortening and contracture development [33]. However, the time to treat is the first problem to resolve, in particular for drugs. Correctly, spasticity treatment is recommended when it induces a significant functional impairment, in particular regarding daily living activities, or clinical disability such as bad posture, motor capacity, or nursing. When spasticity is diffusely distributed above all in lower limbs, often observed as a consequence of spinal lesions, its treatment is firstly indicated, than in cerebral lesions.
The general goal of medical treatment is to decrease spinal reflex excitability by reducing the release of excitatory neurotransmitters or by potentiating the activity of inhibitory circuits. In clinical practice it is important to differentiate objectives in giving spasticity drugs. The technical objectives are focused to induce tone reduction, in order to increase range of motion or ameliorating joint position and promote rehabilitative procedures. Nevertheless, we also have functional therapeutic objectives regarding gait improvement, daily living activity, self-care, and spasm and pain reduction. When we evaluate the real effectiveness of different drug approaches, it is important to differentiate these therapeutic objectives. In order to achieve these therapeutic goals, most of the drugs currently used in spasticity influence the activity of the CNS neurotransmitters. Inhibitory neurotransmitters (GABA or glycine), as well as excitatory neurotransmitters (glutamate or the monoamines), are the main target. Diazepam, baclofen, tizanidine, and dantrolene represent the principal drugs more frequently used.
Diazepam, probably the first and oldest drug used in treating spasticity [34, 35], is a GABA-A receptor agonist. Its binding, to GABA-A receptors diffused in the brainstem and spinal cord, acts in increasing presynaptic inhibition. Consequently, reduction in the resistance to stretch is the principal clinical effect, showing an objectively increasing range of motion. Other clinical effects are also a reduction of deep tendon stretch reflexes and painful spasms [36]. Nevertheless, significant side effects are to be considered. The depressant effect of the drug on the CNS is the principal side effect, causing an influence on cognitive-level, consciousness status, leading to sedation, drowsiness, and attention or memory impairment. The same physiological mechanism explains weakness and motor discoordination caused by diazepam. Tolerance or dependency phenomena are often observed [37, 38]. Spasticity caused by spinal cord lesion, above all incomplete ones like in patients with multiple sclerosis (MS), is the principal indication to use diazepam, since the drug binding is mainly in the brainstem. Less literature are available for the use of diazepam in spasticity caused by cerebral accident, such as traumatic brain injuries, cerebral palsy, and stroke. In literature, a double-blind protocol is available showing the antispastic efficacy of diazepam, only in spinal cord lesions [39]. However, a possible strength and gait deterioration was also shown consistently in placebo-controlled studies.
Gabapentin is approved as an antiepileptic drug. It is indicated also for postherpetic neuralgia treatment and as add-on therapy in partial seizures. GABA-B receptors are its target. Moreover, it is quietly safe. In a prospective, double-blind, placebo-controlled, crossover study, conducted on multiple sclerosis patients, a statistically significant reduction of spasticity was shown in gabapentin-treated patients compared to placebo [40]. The most efficient and safe dose range is still an open question. A dose range between 2700 and 3600 mg/day, as therapy for spasticity due to upper motor neuron syndrome, was found as efficient and safe. However, doses of 400 mg orally three times a day, in another double-blind, placebo-controlled crossover study, were shown to be effective in the treatment of spasticity and muscle painful cramps in patients with MS [41]. Nevertheless, considering the magnitude of the effect and the good tolerability of the drug, the evidence is on a weak recommendation for using gabapentin to reduce spasticity in MS [42].
Baclofen is another common drug diffusely used in spasticity. This drug is a GABA-B receptor agonist. Its physiological effect is a suppression of excitatory neurotransmitter release and, as a consequence, a potentiation of presynaptic inhibition. The main clinical effects are related mainly to the reduction in flexor-extensor spasms and mono- and polysynaptic reflexes. Obviously, related to its mechanism of action, this drug may induce dose-dependent side effects, quite similar to those seen with diazepam [43], although less frequent and less severe. However, sedation, confusion, dizziness, drowsiness, fatigue, and ataxia have been described as the common side effects observed in baclofen studies. Spasticity due to spinal cord lesions is the main indication to treat with baclofen. Unfortunately, in literature, there are very little studies focused on functional changes, so as a consequence, there is no evidence for effectiveness on functional activities such as gait, ambulation, or daily living activities. Moreover, also for oral baclofen, a weak recommendation for treatment of spasticity in MS has been shown [42]. It’s notable that there is no evidence of significant differences between diazepam, tizanidine, and oral baclofen, regarding therapeutic effects on spasticity [43, 44].
Tizanidine, an imidazole derivative approved for the treatment of patients with spasticity [45], acts as an alpha-2 agonist, both in the spinal and supraspinal level. Presynaptic activity reduction of the excitatory interneurons represents the main physiological effect of this treatment. The coeruleo-spinal pathway, because of its involvement in the control of spinal cord activities, was shown as the main target in order to induce clinical effect during tizanidine treatment [46]. Consequently, reduction in tonic and stretch polysynaptic reflexes can be observed. Because of co-contraction reduction, which is observed, a possible effect on reciprocal inhibition is questionable. Possible side effects include sedation, dizziness, and dry mouth. Nevertheless, with respect to diazepam or baclofen, weakness is not reported as a great problem [47]. From the literature, the indications for its use are mainly in spasticity due to spinal cord lesions [48]. It has been particularly used in multiple sclerosis patients [49]. In spasticity caused by cerebral lesions, its efficacy is less well documented in literature. However, there are a certain number of reports regarding its antispastic efficacy, also in controlled studies vs. placebo. In the treatment of spasticity due to cerebral lesions, there are some evidences of its greater efficacy than diazepam [47]. However, there is very little information about the possible functional changes resulting from this treatment, i.e. quality of life and self-care. In fact, although it has been shown to have an antispastic effect, we do not know whether this will translate into long-term functional benefit for the patients. In clinical practice, tizanidine is usually well-tolerated. Drowsiness and dry mouth are the most common although are rare side effects. A range of 24–36 mg is normally the therapeutic dose (20% mean reduction in muscle tone), usually divided in three daily doses [50]. Like oral baclofen and diazepam, there is a consensus for a weak recommendation for the use of tizanidine [42].
Among the oral dugs, dantrolene is the only one which acts outside the central nervous system [51]. It acts on the inhibition of calcium release from the sarcoplasmic reticulum, so, as a final effect, it reduces in muscle the excitation-coupling reaction between actin and myosin fibres. The documented clinical effects are a reduction of muscle tone and phasic reflexes, reduction of spasm, and an increased range of passive motion. Unfortunately, a frequent occurrence of side effects is described with this drug, such as gastrointestinal symptoms, weakness, and sedation although this is less than that seen with other treatments. Over all, a serious side effect with the use of dantrolene is hepatotoxicity, which occurs frequently [51]. In patients with spasticity due to cerebral lesions, dantrolene is the only drug with evidence of efficacy, so from a pure clinical point of view, this is very disappointing. In fact, dantrolene in approved in patients with stroke, cerebral palsy, traumatic brain injuries, and spinal cord lesions. As shown for baclofen, also for dantrolene, there are many evidences of efficacy and safety of its antispastic effect proven vs. placebo, but no studies focused on functional changes in activities of daily living. It’s notable that dantrolene is also used to prevent muscle stiffness and spasms caused by malignant hyperthermia (a rapid rise in body temperature and severe muscle contractions) that can occur during surgery with certain types of anaesthesia [52].
It is known, from many evidences, that the psychoactive ingredient in cannabis, delta-9-tetrahydrocannabinol (delta-9-THC), is able to treat muscle spasticity and pain. Two types of cannabinoid receptors can be described: CB1 and CB2. CB1s are located both in the central and peripheral neurons. CB1 and CB2 receptors are equally activated by delta-9-THC, a cannabinoid receptor agonist [53, 54]. On the contrary, cannabidiol, a natural cannabinoid, is inactive on the CB1 receptor. Some studies reported that cannabis extracts, containing approximately equal concentrations of delta-9-THC and cannabidiol administered through sublingual way, can significantly reduce spasticity. During the last years, several studies investigated and argued on the efficacy and safety of oral cannabinoid administration in MS patients as an add-on treatment for spasticity. A multicentre, double-blind, placebo-controlled trial showed that in MS spasticity treatment, cannabinoid may help to treat MS-related spasticity and pain [53]. However, according to the results from clinical trials, it is not allowed to use cannabinoids in MS as a general use. In a recent study, 630 MS patients affected by muscle spasticity were randomised to be treated with oral delta-9-THC, cannabis extract, or placebo for up to 12 months. The results showed a controversial effect; in fact, there was a small treatment effect on muscle spasticity and disability as functional independence measure, but patients’ sensation was that these drugs were helpful in treating their disease [54]. Adverse side effects are generally mild, in particular dry mouth, somnolence, dizziness, nausea, and rarely intoxication. However, there is a need of longer-term studies to evaluate other, well-known, adverse side effects of cannabinoid such as risks of lung cancer and other respiratory dysfunctions. A recent multicentre observational study confirmed the efficacy and safety of delta-9-THC in clinical practice, as an effective and safe option for patients with MS with moderate to severe spasticity resistant to common antispastic drugs [55]. In a recent consensus, a significant recommendation for the use of cannabinoids in spasticity emerged, particularly for oromucosal spray nabiximols, as treatment of spasticity in MS; the strength of the recommendation is strong [42].
BTX type A is considered as the first-line treatment of multifocal muscle overactivity, thanks to its better efficacy and safety profile with respect to systemic approach with drugs. Different from baclofen or tizanidine, the efficacy of BTX type A has been demonstrated in self-care improvement (in particular for washing and dressing) and in active movements for the leg, with gait improvement if possible. Except for using kinematic analysis, no improvement was possibly shown in active movement or function in the upper limb. Pain was also reduced by BTX treatment as demonstrated in literature. Four forms of BTX are currently available in Europe: three type As (BOTOX®, Allergan; Dysport®, Ipsen-Pharma; Xeomin®, Merz) and one type B (Neurobloc®, Elan-Pharma). It is absolutely recommended to keep in mind that the units of these four toxins are different, being specific for each one. Injection sites are better detected, using electrical stimulation, as anatomical markers alone may induce to an inaccurate target. The use of ultrasound guidance, particularly in children, in identifying muscle site injection, is an interesting study object; however, this technique has not been evaluated with respect to electrical stimulation guidance for its efficiency. Generally, there are no immediate postinjection complications (except for a little pain as a side effect related to injection itself). Above all, during the first 3 weeks after each injection treatment, there would be a low risk of adverse events (swallowing disorders and botulism-like syndrome), so patients and caregivers must be warned as well as encouraged to eventually consult if necessary. The effects of treatment could be assessed 1–6 weeks after the injection, based on personalised goals decided before treatment. The effect of the toxin is not permanent, so repeated injections are often needed; nevertheless, a long-lasting effect is also observed. No repeated treatment is recommended without a specific assessment. When and if needed according to functional evaluation, a minimum delay of 2–3 months between injections must be respected, in order to reduce the risk of an immunologic reaction that may induce a permanent inefficacy of subsequent treatments. Each subsequent treatment should be planned after an accurate functional evaluation according to the pre-therapeutic identified goals and task, as well as tolerance. So, a review of the dose and treated muscles could be scheduled. If therapeutic effects continue to be evident, repeated injections can be planned [33, 56, 57, 58, 59, 60]. Physical therapy has to be considered after BOTOX injections. Regarding maximum doses, according to European Consensus, it should be considered:
Per session: 1500 MU Dysport® 600 U BOTOX®.
Per site: 125 MU Dysport® 50 U BOTOX®.
It is notable that these dosages are identified relatively to acceptable side effects, in order to be safe. Moreover, each product could be effective with different doses for each patient, in terms of both efficacy and safety [61]. As well as the cannabinoid, there is a strong recommendation of the use of BTX to reduce muscle tone in spasticity do to multiple sclerosis [42].
Localised and loco-regional spasticity may effectively be treated by selective neurolysis. Coagulation and denaturing of proteins induced by phenol perineurally injected lead to cellular and axonal damage. Unfortunately, this chemical denervation is irreversible; moreover, the effects of phenol are not selective because also vascular and sensory structures can be destroyed [62]. In fact, the main recommendation choosing this approach is to identify preferably the nerves to be treated with a low sensory activity and a high motor predominance (i.e. obturator or musculocutaneous nerves, etc.). However, this focal treatment is usually not used as a first-line therapy, except in the case of particularly problematic overactivity affecting a big area under a single motor nerve control, for example, musculocutaneous nerve for biceps brachii muscle or obturator nerve for thigh adductor muscles. This may allow to use in the same patient BTX to treat other muscles, without the risk of an overdose. Electrical stimulation is used to identify a nerve, in order to perform injection on it. Firstly, a transient motor block may be a plan, in order to evaluate if chemical neurolysis might be significantly effective and safe. In fact, the efficacy and/or advantages eventually deriving from alcohol or phenol treatment could be evaluated before, in particular with respect to surgery (above all, tissue fibrosis induced by alcohol or phenol, which may hamper surgery approach). Advantages are the low cost and the long duration of effect. In clinical practice, 5–7% concentrations of phenol in aqueous solution are administered.
Intrathecal baclofen (ITB) is a long-term treatment with continuous, intra-spinal administration via an implanted pump that reduces spasticity, especially in spinal injury patients and in multiple sclerosis [63, 64]. For this reason, ITB has become the first choice in intractable generalised spasticity, especially when oral administration fails to be effective. ITB efficacy in reducing spasticity was demonstrated by several studies [65]. Through direct infusion into the cerebrospinal fluid, the baclofen can be concentrated regionally, avoiding liver metabolism, so it is totally available for its therapeutic effects. In fact, with respect to oral baclofen administration, the ITB, bypassing the blood–brain barrier entirely, needs much lower dose in order to obtain the same CSF concentrations; it has been determined that the ITB dose is 100–1000 times smaller than the oral daily dose. Depending on the pump model, it is possible to modify infusion rate, according to the patient’s needs. In several studies ITB was shown as safe and effective in reducing spasticity. The complication rate was found to be low, and the efficacy was maintained over time [64]. A reduction in the Ashworth scale from 3 to 4 to 1 after ITB implantation was reported in several studies. Also spasm frequency significantly decreased. Some activities of daily living, in particular the ability to sit in a wheelchair and nursing care, improved after ITB implant. In some cases, authors showed that patients with less severe disability experienced an improvement in the ability to transfer, thanks to ITB effect [66]. Side effects, such as vertigo, nausea, nystagmus, dysmetria, mouth dryness, headache, amnesia, bladder, and sexual dysfunction, have been described in about 4% of patients and mainly are not life-threatening. As a red flag, it is notable that concerning gastrointestinal function, ITB could affect peristalsis, which could be severely slowed down to paralytic ileus. Nevertheless, constipation has previously been reported as an infrequent ITB-induced adverse effect, ranging from 3 to 10% of treated patients [67], rarely leading to death [68]. Therefore, recognition of constipation in patients treated with ITB is very important, not only because constipation is a possible side effect, being reported in some study, but also because it may be also a life-threatening complication. ITB has been used in patients with leg diffuse muscle overactivity. This type of treatment should be used above all in patients, in which muscle overactivity impaired posture, nursing, and personal independence or causes pain [63]. Several assessments are required before planning a definite pump implantation, performing drug test injection via lumbar puncture or via a temporary access device. Efficacy may be evaluated during the following 3–4 h. The first test dose is usually recommended up to 50 μg in adults, picking up gradually to a maximum dose of 150 μg, eventually reached after 3 days. A risk of overdose should be always evaluated, in particular regarding the effects on consciousness level and respiratory disorders. So, a specialised medical team is needed in order to monitor patient after and during the 4 h following the test. Only after the end of this test, if the treatment has been well-tolerated and effective, the team may make the decision to implant the pump. It is important to monitor the patient during the entire follow-up period, in order to prevent and/or detect collateral effects related to the procedure (displacement and/or obstruction of the catheter, infection, etc.), which may induce a serious withdrawal syndrome. ITB is often recommended for the treatment of spasticity, with a strong evidence of efficacy [42].
Surgery may play an important role in the treatment of chronic muscle overactivity or for the after-effects induced by spasticity that become functional impairments (e.g. irreducible equinovarus foot), but it is not the first-line treatment. Because of its potential adverse events and its definite effects, surgical techniques should be reserved only in selected patients in order to reach different goals: hygiene, standing, transferring, walking, and the use of assistive devices. It involves neurosurgery and orthopaedic surgery. Surgical procedures may include one or more of the techniques described below. Peripheral neurotomy may include partial or segmental resection of a motor nerve, involving spastic muscles. In order to balance agonists and antagonists overlapping the muscle activity, a selective peripheral neurotomy is recommended to maintain a “functional” muscle tone. Collateral branches of the posterior tibial nerves and obturator nerves are commonly the main targets for the legs (e.g. ankle clonus, equinus, inversion of the foot). For the arms, neurotomy of the musculocutaneous, median, and ulnar nerves showed good results regarding efficacy and safety [69]. Other surgery techniques, such as rhizotomies, although used, have potential collateral effects and complications [70]. Musculoskeletal surgery, performed on the muscle or the tendon itself, aims to treat spasticity consequences, such as contracture and joint deformities. Tendon transfers (e.g.
Treatment options of the management of dystonia include pharmacological therapies, injections, and surgical interventions. The main pharmacological therapies are anticholinergics (particularly trihexyphenidyl), baclofen, benzodiazepines (particularly clonazepam), and dopamine-related medications. However, medical therapy in dystonia is largely empiric and at times may seem anecdotal. Three main neurotransmitter systems are involved: cholinergic generally acting as antagonist at postsynaptic M1 receptor, GABAergic-like baclofen, and dopaminergic systems. Dopaminergic treatments can be divided into two: levodopa and dopamine reducing medications like presynaptic dopamine depleters such as tetrabenazine and postsynaptic dopamine-blocking agents, such as clozapine or neuroleptics. The therapeutic strategy, carried out by Fahn [71], is to “start low and go slow”: medications should be started at a low dose and upped slowly to the lowest effective dose, in order to reduce symptoms without side effects. The rate of titration may depend on age: every 3–4 days in children, compared to every 1 week in adults. A combination approach is used when monotherapy achieves a “good” dose, but symptom control is incomplete. The question is which medications should be started first?
In 1952, beneficial effects of trihexyphenidyl in writer’s cramp and “dystonia musculorum deformans” were first reported [72, 73]. The first open-label study of high-dose anticholinergics in dystonia using trihexyphenidyl and ethopropazine was conducted by Fahn [71]. Various forms of dystonia, both “primary and secondary,” can be treated with anticholinergics, except for tardive dystonia and Meige syndrome. Studies showed a good effect in 61% of the children and 38% of the adults, with mean trihexyphenidyl doses of 41 and 24 mg, respectively. More benefit was demonstrated in children, possibly due to better tolerability, and in patients who received treatment earlier, within 5 years of disease onset [74]. Several studies have demonstrated that anticholinergic drugs may be useful to treat various forms of dystonia including focal [75], cranial [76], and secondary dystonia including dystonia in cerebral palsy [74], after ischemic stroke [77], and in tardive dystonia [78]. Side effects can be divided into central ones, which include sedation, cognitive slowing, confusion, memory impairment, psychosis and chorea, and autonomic side effects, which include blurred vision, due to mydriasis, dry mouth, urinary retention, and constipation.
Baclofen was reported to be useful in tardive dystonia [79]. Just in 1988, Greene published a retrospective open-label study, showing that 20% of 108 patients had benefits from baclofen at a mean daily dose of 82 mg [80]. Later, Greene and Fahn also reported beneficial effects of baclofen in 7 of 16 patients with idiopathic childhood dystonia [81]. ITB was tried initially for spasticity and later in dystonia [82]. In 1991 Narayan and colleagues showed the efficacy of ITB in axial dystonia not responding to other drugs [83] and subsequently in dystonic cerebral palsy with lower extremity involvement [84]. Albright reported the use of intraventricular baclofen in two patients with dystonic cerebral palsy, one of whom previously failed ITB therapy and the other has a complex spinal anatomy precluding the intrathecal procedure [85]. Nevertheless, baclofen is generally considered as a second-line agent, due to its significant side effects like drowsiness, dizziness, fatigue, and nausea. Regarding benzodiazepines, diazepam therapy was described in “dystonia musculorum deformans progressiva” and spasmodic torticollis [86]. In 1988, the benefit of clonazepam was shown by Greene in 16% of 115 patients with dystonia, also including secondary dystonia [80]. Also in acquired hemidystonia, as shown in a report of 33 patients, clonazepam and diazepam were found to be the most effective drugs. Clonazepam and diazepam are the two most commonly used drugs, partly due to their relatively long half-lives. The side effects of benzodiazepines include sedation, depression, nocturnal drooling, and behavioural disinhibition. Benzodiazepines are considered a second- or third-line agent.
In 1976 Segawa firstly used levodopa as a treatment in dystonia, showing a dramatic response to low-dose levodopa in two patients affected by “hereditary progressive dystonia with marked diurnal fluctuations” [87], later named Segawa syndrome. In dystonia therapy, levodopa is used (1) as an aetiology-specific treatment in dopa responder dystonia and (2) as a symptomatic therapy in other forms of dystonia where the dramatic response to levodopa is unfortunately not replicated. Levodopa may also be used to treat dystonia symptoms which may complicate a parkinsonian syndrome [88]. In clinical practice, levodopa or dopamine agonists are rarely used to treat dystonia symptomatically. The side effects of levodopa include nausea, orthostatic hypotension, and psychosis. In 1972, Swash reported only a slight benefit of tetrabenazine in spasmodic torticollis [89]. In 1982, a double-blind crossover trial by Jankovic demonstrated an improvement in 11 of 12 patients [90]. Tetrabenazine has been used in various forms of dystonia; however, benefits are greater in tardive dystonia than that of the other forms [91]. Tetrabenazine is rarely used as a first-line agent, except in tardive dystonia [92].
Spasticity and dystonia syndromes and their consequences negatively impact the quality of life of patients, so management of symptoms represents an important care issue. The best choice of antispastic treatments depends not only on the level of spasticity but also on the outcome achievable, according to a task-oriented rehabilitation programme. In this respect, it is important to underline the importance of the individualised rehabilitative project, which can be carried out only through a multidisciplinary approach, in which all available options must be targeted to the real needs of the patients, keeping into account that the final goal is the reduction of disability and improvement of the quality of life. With advances in diagnosis and treatment, therapeutic strategies for the management of spasticity and dystonia symptoms, including pharmacological treatments, have evolved. Progresses in other areas such as BTX, neuromodulation, and disease-specific treatment have changed the way patients are treated. Nevertheless, dystonia remains a challenging field in both diagnostic and therapeutic aspects. Further understanding of its pathophysiology may shed light on more specific therapies. In conclusion, the management of spasticity and dystonia may include a proper diagnosis and classification with an evaluation of the aetiology underlying the pathological features and a clinical assessment of the functional impairment. For both conditions, therapeutic approaches, usually limited to symptomatic therapy, must then be tailored to the individual needs of the patient.
Vincenzo Cimino has received grants for congress participation from Biogen Idec, Merck Serono, Novartis, Roche, Sanofi Genzyme, and TEVA.
Clara Grazia Chisari has received grants for congress participation from Almirall, Biogen Idec, Merck Serono, Novartis, Roche, Sanofi Genzyme, and TEVA.
Francesco Patti has received honoraria for speaking activities by Almirall, Bayer Schering, Biogen Idec, Merck Serono, Novartis, Roche, Sanofi Genzyme, and TEVA; he also served as an advisory board member of the following companies: Bayer Schering, Biogen Idec, Merck Serono, Novartis, Roche, Sanofi Genzyme, and TEVA; he was also funded by Pfizer and FISM for epidemiological studies; he received grants for congress participation from Almirall, Bayer Schering, Biogen Idec, Merck Serono, Novartis, Roche, Sanofi Genzyme, and TEVA.
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Singh",profilePictureURL:"https://mts.intechopen.com/storage/users/329385/images/system/329385.png",institutionString:"Punjab Technical University",institution:{name:"Punjab Technical University",institutionURL:null,country:{name:"India"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"8018",title:"Extracellular Matrix",subtitle:"Developments and Therapeutics",coverURL:"https://cdn.intechopen.com/books/images_new/8018.jpg",slug:"extracellular-matrix-developments-and-therapeutics",publishedDate:"October 27th 2021",editedByType:"Edited by",bookSignature:"Rama Sashank Madhurapantula, Joseph Orgel P.R.O. and Zvi Loewy",hash:"c85e82851e80b40282ff9be99ddf2046",volumeInSeries:23,fullTitle:"Extracellular Matrix - Developments and Therapeutics",editors:[{id:"212416",title:"Dr.",name:"Rama Sashank",middleName:null,surname:"Madhurapantula",slug:"rama-sashank-madhurapantula",fullName:"Rama Sashank Madhurapantula",profilePictureURL:"https://mts.intechopen.com/storage/users/212416/images/system/212416.jpg",institutionString:"Illinois Institute of Technology",institution:{name:"Illinois Institute of Technology",institutionURL:null,country:{name:"United States of America"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"9759",title:"Vitamin E in Health and Disease",subtitle:"Interactions, Diseases and Health Aspects",coverURL:"https://cdn.intechopen.com/books/images_new/9759.jpg",slug:"vitamin-e-in-health-and-disease-interactions-diseases-and-health-aspects",publishedDate:"October 6th 2021",editedByType:"Edited by",bookSignature:"Pınar Erkekoglu and Júlia Scherer Santos",hash:"6c3ddcc13626110de289b57f2516ac8f",volumeInSeries:22,fullTitle:"Vitamin E in Health and Disease - Interactions, Diseases and Health Aspects",editors:[{id:"109978",title:"Prof.",name:"Pınar",middleName:null,surname:"Erkekoğlu",slug:"pinar-erkekoglu",fullName:"Pınar Erkekoğlu",profilePictureURL:"https://mts.intechopen.com/storage/users/109978/images/system/109978.jpg",institutionString:"Hacettepe University",institution:{name:"Hacettepe University",institutionURL:null,country:{name:"Turkey"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null}]},subseriesFiltersForPublishedBooks:[{group:"subseries",caption:"Proteomics",value:18,count:4},{group:"subseries",caption:"Metabolism",value:17,count:6},{group:"subseries",caption:"Cell and Molecular Biology",value:14,count:9},{group:"subseries",caption:"Chemical Biology",value:15,count:13}],publicationYearFilters:[{group:"publicationYear",caption:"2022",value:2022,count:8},{group:"publicationYear",caption:"2021",value:2021,count:7},{group:"publicationYear",caption:"2020",value:2020,count:12},{group:"publicationYear",caption:"2019",value:2019,count:3},{group:"publicationYear",caption:"2018",value:2018,count:2}],authors:{paginationCount:250,paginationItems:[{id:"274452",title:"Dr.",name:"Yousif",middleName:"Mohamed",surname:"Abdallah",slug:"yousif-abdallah",fullName:"Yousif Abdallah",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/274452/images/8324_n.jpg",biography:"I certainly enjoyed my experience in Radiotherapy and Nuclear Medicine, particularly it has been in different institutions and hospitals with different Medical Cultures and allocated resources. 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. My method of translating this into day to day in clinical practice is non-exhaustible and my habit of exchanging knowledge and expertise with others in those fields is the code and secret of success.",institutionString:null,institution:{name:"Majmaah University",country:{name:"Saudi Arabia"}}},{id:"313277",title:"Dr.",name:"Bartłomiej",middleName:null,surname:"Płaczek",slug:"bartlomiej-placzek",fullName:"Bartłomiej Płaczek",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/313277/images/system/313277.jpg",biography:"Bartłomiej Płaczek, MSc (2002), Ph.D. (2005), Habilitation (2016), is a professor at the University of Silesia, Institute of Computer Science, Poland, and an expert from the National Centre for Research and Development. His research interests include sensor networks, smart sensors, intelligent systems, and image processing with applications in healthcare and medicine. 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. His research interests include computer graphics, computer vision, image processing, machine learning, pattern recognition, soft computing, data science, intelligent systems, information technology, and information systems. Prof. Sarfraz has been a keynote/invited speaker on various platforms around the globe. He has advised various students for their MSc and Ph.D. theses. He has published more than 400 publications as books, journal articles, and conference papers. He is a member of various professional societies and a chair and member of the International Advisory Committees and Organizing Committees of various international conferences. Prof. Sarfraz is also an editor-in-chief and editor of 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:"267434",title:"Dr.",name:"Rohit",middleName:null,surname:"Raja",slug:"rohit-raja",fullName:"Rohit Raja",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/267434/images/system/267434.jpg",biography:"Dr. Rohit Raja received Ph.D. in Computer Science and Engineering from Dr. CVRAMAN University in 2016. His main research interest includes Face recognition and Identification, Digital Image Processing, Signal Processing, and Networking. Presently he is working as Associate Professor in IT Department, Guru Ghasidas Vishwavidyalaya (A Central University), Bilaspur (CG), India. He has authored several Journal and Conference Papers. He has good Academics & Research experience in various areas of CSE and IT. He has filed and successfully published 27 Patents. He has received many time invitations to be a Guest at IEEE Conferences. He has published 100 research papers in various International/National Journals (including IEEE, Springer, etc.) and Proceedings of the reputed International/ National Conferences (including Springer and IEEE). He has been nominated to the board of editors/reviewers of many peer-reviewed and refereed Journals (including IEEE, Springer).",institutionString:"Guru Ghasidas Vishwavidyalaya",institution:{name:"Guru Ghasidas Vishwavidyalaya",country:{name:"India"}}},{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:null,institution:{name:"Beijing University of Technology",country:{name:"China"}}},{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:"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:"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:"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:"Igor Victorovich Lakhno 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.\nPh.D. – 1999, Kharkiv National Medical Univesity.\nDSC – 2019, PL Shupik National Academy of Postgraduate Education \nProfessor – 2021, Department of Obstetrics and Gynecology of VN Karazin Kharkiv National University\nHead of Department – 2021, Department of Perinatology, Obstetrics and gynecology of Kharkiv Medical Academy of Postgraduate Education\nIgor Lakhno has been graduated from international training courses on reproductive medicine and family planning held at Debrecen University (Hungary) in 1997. Since 1998 Lakhno Igor has worked as an associate professor in 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 been a professor in the department of obstetrics and gynecology of VN Karazin National University and a professor of the perinatology, obstetrics, and gynecology department. He’s affiliated with Kharkiv Medical Academy of Postgraduate Education as a Head of Department from November 2021. Igor Lakhno has participated in several international projects on fetal non-invasive electrocardiography (with Dr. J. A. Behar (Technion), Prof. D. Hoyer (Jena University), and José Alejandro Díaz Méndez (National Institute of Astrophysics, Optics, and Electronics, Mexico). He’s an author of about 200 printed works and there are 31 of them in Scopus or Web of Science databases. Igor Lakhno is a member of the Editorial Board of Reproductive Health of Woman, Emergency Medicine, and Technology Transfer Innovative Solutions in Medicine (Estonia). He is a medical Editor of “Z turbotoyu pro zhinku”. Igor Lakhno is a reviewer of the Journal of Obstetrics and Gynaecology (Taylor and Francis), British Journal of Obstetrics and Gynecology (Wiley), 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 a DSc degree “Pre-eclampsia: prediction, prevention, and treatment”. Three years ago Igor Lakhno has participated in a training course on innovative technologies in medical education at Lublin Medical University (Poland). 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: are obstetrics, women’s health, fetal medicine, and cardiovascular medicine. \nIgor Lakhno is a consultant at Kharkiv municipal perinatal center. He’s graduated from training courses on endoscopy in gynecology. He has 28 years of practical experience in the field.",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. RELACION DE PONENCIAS DE LA SOCIEDAD ESPAÑOLA DE OFTALMOLOGIA. 10/2014.",institutionString:null,institution:null},{id:"265335",title:"Mr.",name:"Stefan",middleName:"Radnev",surname:"Stefanov",slug:"stefan-stefanov",fullName:"Stefan Stefanov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/265335/images/7562_n.jpg",biography:null,institutionString:null,institution:null},{id:"243698",title:"Dr.",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:null,institution:null},{id:"7227",title:"Dr.",name:"Hiroaki",middleName:null,surname:"Matsui",slug:"hiroaki-matsui",fullName:"Hiroaki Matsui",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Tokyo",country:{name:"Japan"}}},{id:"318905",title:"Prof.",name:"Elvis",middleName:"Kwason",surname:"Tiburu",slug:"elvis-tiburu",fullName:"Elvis Tiburu",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Ghana",country:{name:"Ghana"}}},{id:"336193",title:"Dr.",name:"Abdullah",middleName:null,surname:"Alamoudi",slug:"abdullah-alamoudi",fullName:"Abdullah Alamoudi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Majmaah University",country:{name:"Saudi Arabia"}}},{id:"318657",title:"MSc.",name:"Isabell",middleName:null,surname:"Steuding",slug:"isabell-steuding",fullName:"Isabell Steuding",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Harz University of Applied Sciences",country:{name:"Germany"}}},{id:"318656",title:"BSc.",name:"Peter",middleName:null,surname:"Kußmann",slug:"peter-kussmann",fullName:"Peter Kußmann",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Harz University of Applied Sciences",country:{name:"Germany"}}},{id:"338222",title:"Mrs.",name:"María José",middleName:null,surname:"Lucía Mudas",slug:"maria-jose-lucia-mudas",fullName:"María José Lucía Mudas",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Carlos III University of Madrid",country:{name:"Spain"}}}]}},subseries:{item:{id:"2",type:"subseries",title:"Prosthodontics and Implant Dentistry",keywords:"Osseointegration, Hard tissue, Peri-implant soft tissue, Restorative materials, Prosthesis design, Prosthesis, Patient satisfaction, Rehabilitation",scope:"