Histologic grading of follicular lymphoma.
\\n\\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\\n\\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\\n"}]',published:!0,mainMedia:{caption:"Highly Cited",originalUrl:"/media/original/117"}},components:[{type:"htmlEditorComponent",content:'IntechOpen is proud to announce that 191 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\nThroughout the years, the list has named a total of 261 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\nReleased this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"3310",leadTitle:null,fullTitle:"Encephalitis",title:"Encephalitis",subtitle:null,reviewType:"peer-reviewed",abstract:"Encephalitises are a group of inflammatory human and animal diseases of brain caused essentially by different pathogens. 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Nomophobia is described as an experience of anxiety due to fear of not having access to mobile phones. Smartphone addiction leads to restless night, anxiety, social isolation, nervous breakdown, weight changes, insomnia & anger [1]. Nomophobia is described as” the discomfort or tension because of the non-availability of a cell cellphone, non-public computer (laptop) or any other digital device” [2].
Nomophobia is described as “the soreness or tension as a result of the non-availability of a cellular telephone, personal laptop (pc) or any some other digital verbal exchange device” [2]. Clayton et al. references Belk (2013) of their explanation of smart-phone loss as the “unintentional lack of a ownership need to be regarded as a loss or lessening of self” [3].
Long time usage of smartphones by the kids lead to musculoskeletal problems due to the faulty posture maintained like forward neck posture problems, rounded shoulder or slouched posture for a prolonged period of time [4]. The structural problems caused by faulty posture may lead to decrease in proprioception there by resulting in decreased balance ability. The maintenance of proprioception is extremely important in order to prevent injuries & this is mainly subjected to proprioceptive input from mechanoreceptors in the capsule, ligament & tendon added to vestibular & visual input to central nervous system.
The proprioceptive system is part of the central nervous system. Proprioception is one’s personal sensation of the body. Proprioception is the feel arising from joints, muscle groups, tendons and related deep tissues that offer statistics to the central nervous system (CNS) about static and dynamic motion of limbs and the body. Proprioception information is processed at exclusive levels of the central nervous system in order to meet physical needs positioned at the body and aides a mover to arrive at motor choices. Proprioception strongly contributes to the fitness of joint balance; sensing passive or energetic joint articulation; joint load absorption and rebound; and muscle duration, force and velocity. Abnormality and tissue trauma excluded, the proprioception is a basic part of all people’s neuro-anatomy [5].
The proprioception experience end result of a collection of fact derived from sensory receptors found within, muscular tissues, tendons, ligaments and fascia. The sensory receptors answerable for proprioception are referred to as mechanoreceptors and are the subgroup of somatosensory system. All mechanoreceptor facts is grouped collectively in the central nervous system (CNS) and are processed at distinct ranges of the consistent with unique movement and environmental demands.
The proprioception information is blended with body senses on a moment by using secondary basis for the duration of real time events. The simultaneous interaction of many sensory procedures create a collective internet notion of the body in area and contributes to motion choices.
Nonpublic, bodily and perceptual sources are mixed with genetic, cultural and societal sources as contributing factors to motion or action selections. Throughout the body & nervous system proprioception plays the role of a loop which continuously feedback & forward input. The vital importance of optimal orientation and postural control is relied on the complex reflex & central interaction between cervical proprioception, vestibular & visual information [6]. When there is an increased use of smartphone by the kids the proprioception lies at the boundary between neurophysiology & neuropsychology. The nomophobia children will soon develop poor balance, poor co-ordination and increased postural sway.
From an engineering perspective the human neuro musculoskeletal machine can be appeared as a robot, consisting of a linkage system (the skeleton) with motors (muscles), sensors (proprioceptors), and a control gadget (the CNS) [7]. The nerves and neurons are the wires and connectors, which shipping the data from the proprioceptors to the CNS and from the CNS to the muscular tissues.
The CNS integrates intentions with facts from the proprioceptor to coordinate motion ofthe skeleton through selectively (de-)activating muscle groups. Manage engineers will directly recognize a feedback loop: the movement outcomes from commands from the CNS, which on their flip (in part) rely upon the movement sensed via the proprioceptors there is a mutual interaction among CNS and limb movement. Postural manipulate is a specific case inside human movement control [8].
The human has to maintain a posture, i.e. an equilibrium position. At some point of postural manipulate unbiased strategies contribute to stability and performance: (1) intrinsic residences of the muscles and (2) proprioceptive reflexes. Balance is controlled and maintained by a complex set of sensory-motor control system which include the sensory input, receptors, input from vestibular system, integration of sensory input and the motor output [9].
All children receive information from their internal and outside environments through the following senses: imaginative, motion (vestibular), prescient (ocular), hearing (auditory), taste (gustatory), odor (olfactory), contact (tactile), Joint and muscle cognizance (Proprioceptive).
The term sensory integration refers back to the manner of receiving and responding to the incoming facts. It starts off evolved while your toddler gets information from their senses, then the vital nervous device directs the records to the correct parts of the mind, and the records is integrated so the child can reply in the perfect manner.
The term proprioceptor comes from the Latin ‘proprius’, one’s own, and ‘recipio’, to get. It was characterized by Sherrington (1906): ‘In muscular receptivity we see the body itself going about as an upgrade to its own receptors – the proprioceptors’. Types of proprioceptors include muscle spindle, golgi tendon organs and the mechanoreceptors in the joint capsule.
When muscles lengthen, the spindles gets stretched. This stretch activates the muscle spindle that successively sends an impulse to the neural structure. This impulse leads to the activation of a lot of motor neurons at spinal level that send an impulse back to the muscle [10]. The Golgi connective tissue Organ could be a propioception receptor that’s situated at intervals the tendons found on every finish of a muscle. It responds to inflated muscle tension or contraction as exerted on the connective tissue, by inhibiting any muscular contraction. Mechanoreceptors meant as primary neurons or nerve endings that reply to mechanical stimuli by firing action potentials. When mechanoreceptor receives a input, it begins to fire action potentials at raised frequency [11].
Proprioceptive system has three overlapping major functions:
Regulation of tone
Posture and body movement is mediate by proprioception through the afferent information it receives from all sensory receptors, and by the efferent data it sends to the extrapyramidal motor tracts.
Egocentric abstraction localization
By integration and modulating the knowledge that comes from sensory receptors, the proprioceptive system informs the brain about the relative position of the sensory organs, the relation between every body segment, and also the relative position of the body within the close setting.
Modulation of multisensory data
Proprioceptive data well-known to be transmitted within the multisensorial deep layers of the nerve center within the midbrain is believed to possess a task in modulating multisensory integration. This modulation has consequences in motor behavior and better psychological feature functions [12].
The receptors of proprioception as major role in movement of eye control and construction of extra personal space. It was Thomas Reid in 1785 who clearly explained the mechanism of the function of eye proprioception. The visual gaze direction as direct concern with the neck muscles control during vestibular stimulation. The extra ocular muscle afferent signals are determined in patterned inhabitation of forelimb and neck muscles & there by influence the head position on the body [13].
Its miles possible to steer body proprioception by using stimulating no longer simplest direct mechanoreceptors like neuromuscular spindles, or joint or tendon neurologic terminations, however additionally through modulating the information from different sensory input as well. These range from visible receptors linked to the retinocolicular pathway in the uppermost location of the body to the only plantar receivers underfoot.
Brain will tend to combine various available source of extra-retinal signals to foster visual clarity during eye and head movements with proprioception as major contribution visual fatigue caused by usage of smartphones for a prolonged period of time as highly impact with visual ability to control posture thereby reducing the ability to balance. Thus it is very clear that continuous usage of smartphones by the kid for the sake of games & YouTube may lead to posture and balance disturbances through visual gaze [14].
Proprioception is a chain of feedback between the sensory receptors which are located in the skin, joints and muscles when the duration of smartphones usage increases it will surely have an negative impact of cervical proprioception & dynamic balance ability.
Prolonged flexed neck, posture in turn will increases the muscle activity which will cause the musculoskeletal pain in neck and shoulder on comparison fast muscles, muscle fibers cause more fatigue than slow muscle fiber when static posture is maintained for a prolonged duration as the cervical flexion angle is decreased. When the head is inforward headed posture the muscular tissue perform cervical extension in the back of the neck are contracted isometrically creating a force which is against gravity, which will lead to prevention of cervical flexion or forward head movement, & long term isometric contraction of the muscles in the back of neck involved in the extension of cervical & can also cause pain by stimulating trigger points. The combination of extension within the higher cervical region and flexion within the lower cervical region seems in patients with forward head posture attribute to head posture. Changes in the cervical region by sustained poor head posture, cause excessive joint and muscle loading, and later on influencing weakness of the deep cervical muscles. Among several body structures set within the cervical region, the muscle is thought to be a main part for position sense through its receptors, like muscle spindles. The cervical vertebrae contribute proprioception sense input [15].
The proprioceptive sensing of the cervical vertebrae transmits data to correct arrangement and plays a crucial role in bodily property management. Additionally, it reacts sensitively to the fine movement of the top by acting in coordination with sensing from the vestibular apparatus. Asymmetrical alignment of the top and neck ends up in errors within the data received as visual and proprioception sensing this eventually reduces the balance and will increase the chance of falling and contractile organ injuries whereas acting activities.
The central and peripheral vestibular organs, in conjunction with the visual and somatosensory systems, are responsible for balance, equilibrium, and orientation in space. Vestibular system as major role in subjective awareness of body position and movements in space, postural tone and equilibrium and stabilization of the eyes in space during head movement along with visual system and proprioception continuous use of smart phones may lead the child hyper expressive and also lead to gravitational insecurity, which is an sensory integration issue which may cause to react to movements in an extreme way. This is due to the impact of vestibular system by which the child’s gravity receptors become extra sensitive.
Proprioception is caused out to all the levels of central nervous system where it gives out unique sensory component to effectively use motor control neuromuscular control of dynamic restraints very necessarily needs proprioceptive information. The motor control is disturbed in nomophobia kids through stress imposed on other bodily system. Perception is extraordinarily necessary in control as a result of it carries the relevant info concerning objects, environments and bodies that is employed in organizing and initiating actions and movements.
proprioceptive data plays an integral role within the ability to change internal models used with feed forward management that has been incontestible to be solely part paid for by visual information. The planning of movements additionally needs attention to environmental constraints. Children using smartphone for a prolonged period of time lack attention thereby their planning and control of movements is not proper.
Balance Issues
uncoordinated Movement
Clumsiness
Poor Postural Control
Trouble Recognizing Your Own Strength
Avoiding Certain Movements Or Activities
There are a few test Physiotherapists can use to assess proprioception, depending at the body element being assessed. That includes:
The patient is asked to the touch the heel of 1 foot to the opposite knee after which to drag their heel in a instantly line all of the way down the front in their shin and lower back up once more. With a view to get rid of the impact of gravity in moving the heel down the shin, this test have to continually be done in the supine position [16].
The subject is asked to alternately touch their nose and the examiner’s finger as fast as possible [3].
The tester will be made to circulate the joints of the hip, knee ankle and big toe up and down as it is watched. Then ask the subject to repeat the equal movement together with eyes closed.
Asking the affected person to match a verified joint angle, and measuring the distinction among the real joint angle, and the reproduced joint perspective.
The affected person is requested to remove his/her footwear and stand with two feet together. The clinician asks the patient to first stand quietly with eyes open, and ultimately with eyes closed. The Romberg test is scored by counting the seconds the person is able to stand with eyes closed [3].
This procedure developed by Pankhurst and writer for assessing the proprioception of lower back. It is composed of a motor operated device that produces passive motion of lumberspine in three planes whereas the trunk stayed fastened. The apparatus detects motion and identifies the neutral position and the direction of movement. It assesses movement in 3 planes as advantage, but the employment during a clinical population might not be possible because it utilizes the advanced equipment [17].
Developed by Hobbs to assess lumbar proprioception. It depends on discriminating the position differences in 11–19° of lumbar flexion. It consists of free standing with stopper at five preset distances. The subject had to discriminate preset trained flexion positions while standing. The test’s disadvantage is that the subject’s head is also moving through the test so the vestibular system might be adding to the proprioception sense [18, 19].
Kristjansson et al. described the test. It has fast track sensors. Various uses of the test described such as relocation of the head to the natural position after active turn to left and right or active relocation to 30° turn from the natural head position. Passive trunk rotation of 30° or figure of eight motion can also be used before subjects repositioning head to a natural position [8].
Described by Kaplan [7]. This test can be used for assessing the proprioception of various joints such as knee or elbow. The test requires active reproduction of ipsi- and contralateral positions of the limb. Goniometer measures the error between reproduction and the target.
Delete all the social media apps on mobile phones.
Set specific boundaries for usage of smartphones.
Lock the smartphones with long password.
Parents spend time with kids playing with them.
Parents avoid smartphones before kids.
Hand pushes
Hand pulls
Head compressions
Chair push ups
Theraband on chair
Squeezing a stress ball
Wall pushes
Push ups
Lifting weights e.g. tins, books, dumbells
Jogging on the spot
Star jumps
Bouncing on therapy/exercise ball
Climbing wall bars/ropes
Throwing/catching weighted ball
Crawling obstacle course
Wheelbarrow walks
Gymnastics- handstands, cartwheels, using gym equipment
Jumping e.g. hop scotch
Tug of war
Bouncing on space hopper
Lying on stomach over exercise ball and weight-bearing through arms
Wiping benches and tables
Brushing/mopping floors
Holding doors open
Carrying piles of books
Carrying a backpack with a heavy item in it
Stacking chairs
Moving furniture
Roll it up on a wall.
Dribble it. Pushing the ball into the ground is great for the proprioceptive sense as well as when it bounces back.
Bounce on it alone.
Kick it against a wall.
In line with King et al. [2], this study purports that nomophobia, or no mobile phone phobia, is thought of a contemporary age phobia introduced to our lives with the speedy proliferation and adoption of smartphone.
The proprioceptive system has an extensive influence at the protection of human fitness. When the proprioception is dysfunctional, the vital anxious device does no longer recognize the ideal fame of tonicity ofthe muscular tissues at rest or in motion, does no longer combine effectively the records that comes from sensory receptors, and has issue in modulating multi-sensory integration, with outcomes in motor behavior and cognitive function. This outcomes in a wide variety of proprioceptive abnormalities which are clinically related and are handled collectively termed as Postural Deficiency Syndrome (PDS). Kids using smart phones for a prolonged period of time lack attention, lack posture and motor control. Smart phone usage for extended period may change the brain activity, and postural disturbance.
I would like to thank the authorities of Dr. MGR Educational and Research Institute, University, Honorable chairman Dr. AC. SHANMUGAM, Honorable president ACS. ARUNKUMAR, Honorable secretary Thiru A. RAVIKUMAR and our Principal, Faculty of Physiotherapy Dr. CV. SENTHIL NATHAN for providing facilities required to complete the chapter with their support and guidance. With great privilege I thank my husband Er. S Elangovan and my mother for their support and motivation.
Follicular lymphoma (FL) is one of the most common forms of indolent lymphoma constituting 20–25% of all non-Hodgkin’s lymphoma (NHL) in the United States and Europe. However, it is less common in the African and Asian population accounting for 10% of all NHL [1, 2, 3, 4]. There is no known risk factor for follicular lymphoma [5]. It is a disease of the elderly with a median age of 65 years, and the young are only rarely affected [6]. It is an indolent disease that typically manifests as asymptomatic adenopathy. Involvement of the bone marrow is frequent, occurring in up to 80% of cases. B symptoms and high serum lactate dehydrogenase (LDH) levels are observed in approximately 20% of patients. Extranodal involvement is less prevalent, occurring in about 10% of cases [7, 8].
On histopathologic examination, Follicular lymphoma shows densely packed follicles with attenuated mantle zones that obscure nodal architecture. The follicles consist of two major cell types, centrocytes, and centroblasts. Centrocytes are small to medium-sized with scarce cytoplasm, elongated or cleft nuclei, and small nucleoli. Centroblasts are large cells (about three times the size of a lymphocyte) with a basophilic cytoplasm ring, round to oval non-cleaved nuclei, and prominent nucleoli. Histological grading (Table 1) is based on the proportion of centrocytes and centroblasts present in the germinal centers. FL grades 1 to 3a is considered a low-grade indolent disease, whereas FL grade 3b is considered an aggressive form of lymphoma [9]. Follicular lymphoma has a paratrabecular pattern of involvement in the bone marrow, and the appearance of tumor cells is similar to that found in lymph nodes.
Histologic grade | Microscopic features |
---|---|
Grade 1 (follicular small cleaved) | Up to 5 centroblasts per HPF |
Grade 2 (follicular mixed) | 6–15 centroblasts per HPF |
Grade 3a (follicular large cell) | More than 15 centroblasts per HPF |
Grade 3b | Solid sheets of centroblasts |
Histologic grading of follicular lymphoma.
HPF high power field.
On immunohistochemistry (IHC) Follicular lymphoma cells express B-cell antigens (CD19, CD20, CD22, and CD79a), BCL2, BCL6, and CD10. Surface expression of immunoglobulin is observed in about one-half of cases. BCL2 overexpression is present in the majority of grade 1 FL–2 FL, however, it is less common in grade 3 FL [10]. CD 10 negative FL are commonly high grade, express IRF4/MUMI and BCL 6 but lacks BCL2 expression.
The germinal center B cell expressing CD20 and B-cell leukemia/lymphoma 2 (BCL2) is the cell of origin for follicular lymphoma [11]. The characteristic translocation [t(14,18)] involving the BCL2 gene on chromosome 18q21.3 and immunoglobulin heavy chain gene on chromosome 14q32; q21 is observed in up to 90% of patients. It provides a survival advantage to malignant B cells by upregulation of anti-apoptotic signals [11]. However, BCL2 overexpression alone is insufficient for malignant transformation to FL, and additional hits are required [12]. KMT2D, CREBBP, EZH2, EP300, KMT2C, and ARID1A mutations are commonly identified, although their significance in FL remains unknown [13, 14].
The initial evaluation should entail recording a detailed history and completing a comprehensive physical examination. A biopsy of the afflicted lymph node, either excisional or incisional, is required [9, 15]. Biopsy samples should be evaluated by an expert haemato-pathologist. For baseline staging, either contrast-enhanced computed tomography (CECT) of the neck, chest, and abdomen or whole-body positron emission tomography (PET) with computed tomography, should be performed [16, 17]. PET is preferable in early-stage patients and for assessing response at the end of treatment (EOT) [10, 18]. All individuals with early-stage FL should have a unilateral bone marrow biopsy (stages I and II). However, it can be omitted in patients with advanced disease (stage III and IV) as it provides no extra information in such a scenario [19, 20]. For assessment of organ functions and prognostic information, baseline complete blood count, renal and hepatic functions, serology for hepatitis B and C, β2-microglobulin, and LDH are necessary. Patients planned for anthracycline-based therapy should have their cardiac function evaluated by 2D-ECHO or a MUGA scan. Fertility preservation should be discussed with all patients of reproductive age [21].
Histological transformation of FL to high-grade lymphoma during the natural history of disease is a well-known entity. 15–20% patients demonstrating transformation at 5 years of follow up [22, 23]. Risk of transformation is about 1–3 percent per year. Histological examination reveals loss of follicular architecture and replacement by large-sized cells with a high proliferation index. FL most commonly transforms to diffuse large B cell lymphoma (DLBCL), but other histology like Burkitt’s lymphoma, lymphoblastic lymphoma, and Hodgkin’s disease have also been reported [24]. Rapidly progressing lymphadenopathy, unusual extra-nodal involvement, constitutional symptoms, elevated lactate dehydrogenase (LDH) and hypercalcemia are clinical pointers of histological transformation. Diagnosis is confirmed by guided biopsy of the highest metabolically active lesion in case of high clinical suspicion [25, 26].
Age, stage, nodal burden, LDH, hemoglobin, and β2-microglobulin have been recognized as important prognostic factors. Various prognostic models have been developed based on these factors (Table 2), including FLIPI (follicular lymphoma international prognostic index), FLIPI 2, and PRIMA-PI (Primary Rituximab and Maintenance study prognostic index). FLIPI is a widely used tool developed in the pre-rituximab era, but it has been validated in several prospective trials in patients receiving rituximab [27, 28, 29]. PRIMA-PI incorporates only two parameters, serum 2-microglobulin levels, and bone marrow involvement, however it has not been prospectively validated [30]. POD24 (progression within 24 months of therapy) has recently been found as a key prognostic and predictive marker [31, 32]. It may be used method for predicting relapse and aid in therapy selection.
Prognostic model and risk factors | Risk stratification |
---|---|
| Low: 0–1 risk factors5-year OS: 92%; Intermediate: 2 risk factors5-year OS: 78% High: 3–5 risk factors5-year OS: 52% |
| Low: 0–1 risk factors 3-year OS: 99% Intermediate: 2 risk factors 3-year OS: 96% High: 3–5 risk factors 3-year OS: 84% |
| Low: 0 risk factors5-year PFS: 69% Intermediate: 1 risk factor5-year PFS: 55% High: 2 risk factors5-year PFS: 37% |
(Progression of disease within 24 months of chemoimmunotherapy) | POD >24 months 5-year OS 90% POD <24 months 5-year OS 50% |
Prognostics tools in follicular lymphoma.
ECOG, Eastern Cooperative Oncology Group; FLIPI, follicular lymphoma international prognostic index; Hb, hemoglobin; LDH, lactate dehydrogenase; OS, overall survival; PFS, progression-free survival; POD, Progression of disease; PRIMA-PI, Primary Rituximab and Maintenance study prognostic index; PS, performance status; ULN, upper limit of normal.
Management of FL is based on the stage at presentation, tumor grade, and burden of disease. Early-stage local diseases are treated with curative intent, while in advanced diseases aim is to reduce symptom burden, increase survival, and enhance the quality of life.
Early-stage (stage I and II) patients have an excellent prognosis with median survival approaching 20 years [33, 34, 35]. There are several management options available, including radiation, single-agent rituximab, chemo-immunotherapy, and observation. The recommended radiation dosage is involved site radiotherapy (ISRT) with 24 Gy (Gray) administered in 12 fractions [36]. Higher dose does not provide any survival advantage and is associated with greater toxicity [37]. When compared to observation alone, patients who receive RT have better disease-specific survival as well as overall survival [38, 39]. PFS benefit was observed by adding rituximab or chemotherapy to the radiotherapy, however, there was no difference in overall survival [40, 41]. Patients unwilling for treatment may also be considered for observation [42]. High grade (grade 3B) FL patients are managed on the lines of other high-grade NHL like DLBCL (diffuse large B cell lymphoma). Combination chemo-immunotherapy R-CHOP (rituximab, cyclophosphamide, vincristine, doxorubicin, prednisone) is preferred in such cases. If involved sites cannot be encompassed in a single radiation field, patients should be treated as advanced FL.
Advanced stage FL is a very diverse group, with some patients having an indolent course and long-term survival and others having a more aggressive course, with frequent relapses. Although the majority of patients respond to currently available therapies, relapses are common. The treatment of advanced FL is determined by the histologic grade and disease load [43]. For assessing disease load in advanced FL, Groupe d’Etude des Lymphomes Folliculaires (GELF) criteria are widely employed (Table 3). Patient with any of the GELF feature is categorized as high tumor load disease [44].
GELF criteria |
---|
1. Nodal or extra nodal tumor size: any site >7 cm or ≥ 3 sites >3 cm |
2. Presence of B symptoms* |
3. Presence of compressive symptoms |
4. Palpable spleen below umbilicus |
5. Presence of ascites or pleural effusions |
6. Presence of leukemic phase (circulating malignant cells >5 × 109/L) |
7. Presence of cytopenia due to disease: neutropenia (<1 × 109/L) or thrombocytopenia (<100 × 109/L) |
B symptoms are defined as recurrent unexplained fever >38°C, or recurrent night sweats or unexplained ≥10% loss of bodyweight in last 6 months. GELF Groupe d-Etude des Lymphomes Folliculaires.
High tumor load is defined if any one or more risk factors are present.
Patients who do not fulfill any of the GELF features are considered to have a low disease load and can be initially observed. This is based on the results of a randomized trial, which showed no difference in cause-specific survival and overall survival between observation and active treatment with chlorambucil [44]. Another approach is to use single-agent rituximab followed by maintenance. In a randomized trial comparing observation, single-agent rituximab and rituximab followed by maintenance rituximab for 2 years, PFS and time to start of new treatment was better with rituximab treatment. However, there is no survival benefit with rituximab [45]. Similarly, no survival benefit was observed with rituximab maintenance in the RESORT study. In this study, patients received four cycles of weekly rituximab followed by randomization to maintenance rituximab or retreatment on progression [46]. Due to lack of any overall survival advantage with upfront treatment over observation, low burden FL may be kept on close follow-up.
FL with a high disease load warrants immediate treatment with chemo-immunotherapy. Various chemo-immunotherapy induction regimens available for patients with FL are R-CVP (rituximab, cyclophosphamide, vincristine, and prednisone), R-CHOP (rituximab, cyclophosphamide, adriamycin, vincristine, and prednisone), and BR (bendamustine and rituximab). Patients who have a partial or complete remission with the above therapies are further treated with rituximab maintenance. Choice of chemo-immunotherapy regimen is based on patients performance status, pre-existing comorbidities, and side effect profile of drugs as no overall survival advantage has been shown for any regimen above other in a randomized trial. R-CVP has lower response rates and progression-free survival compared to R-CHOP. BR is associated with better progression-free survival and lower rates of neutropenia, infections, neuropathy, and alopecia. However, there was no difference concerning overall survival over R-CHOP and R-CVP [47, 48, 49]. Use of newer anti-CD20 agent obinutuzumab has shown improvement in progression-free survival but no overall survival benefit and is associated with higher infusion reactions, neutropenia, and infections [50]. Use of chemotherapy-free regimens using lenalidomide and rituximab (R2) has similar survival with a different toxicity profile compared to chemo-immunotherapy regimens [51].
The role of maintenance rituximab in patients with either complete or partial remission after initial chemo-immunotherapy has not been proven beyond doubt. In the PRIMA (Primary Rituximab And Maintenance) trial, patients were randomized to rituximab maintenance (every 8 weeks for 2 years) or a placebo after initial chemo-immunotherapy. Rituximab arm had higher progression-free survival but at the cost of higher adverse effects (infusion reaction, neutropenia, and infections). However, initial chemo-immunotherapy regimens did not include a bendamustine-based regimen, which is most commonly used in the current era [52]. So these results could not be extrapolated after initial bendamustine-based therapy in absence of prospective evidence. Similarly, there was no survival benefit with rituximab maintenance in patients aged 60–75 years [53].
FL has a protracted course with multiple remissions and relapses. About 20% of patients do not respond to initial therapy and another 20% of patients relapse within 24 months of initial therapy [54]. Interval between initial treatment and relapse is the most important prognostic and predictive factor for relapsed FL. Those who relapse after 24 months of initial therapy have good long-term outcomes, while those relapsing within 24 months have a dismal prognosis. There is no set consensus on the management of relapsed patients. Multiple options are available including chemo-immunotherapy, novel agents, and stem cell transplant. Choice of therapy depends upon the disease burden, prior therapy, response to prior therapies, duration of previous remission, performance status, comorbidities, and adverse effect profile of the drugs. The goal of therapy is improvement in symptoms, increase survival, and a better quality of life.
Patients who relapse more than 24 months after initial chemoimmunotherapy are considered late relapses. These late relapses have an indolent course and survivals rates can approximate that of the general population [55]. Patients who do not meet GELF criteria have no immediate requirement to initiate treatment and may be observed. An alternate approach is to use single-agent rituximab. Symptomatic FL patients with high disease load may be managed with single-agent rituximab, chemoimmunotherapy, lenalidomide plus rituximab (R2), or novel agents. Single-agent rituximab is preferred in patients with comorbidities and poor performance status [56]. Relapsed FL with good performance status can be treated with anti CD20 monoclonal antibody in combination with chemotherapy or lenalidomide. If the patient has previously received BR-based therapy, R-CHOP, R-CVP, or R2 may be used at the time of relapse. Similarly, if the patient has received R-CHOP-based therapy, he may be considered for BR or R2. If the patient has relapsed during anti-CD20 monoclonal antibody maintenance, it is preferable to use an alternate anti-CD20 agent like obinutuzumab [57, 58]. Radio-immunoconjugates have been used for management of FL in patients with good bone marrow reserve but because of the associated high risk of secondary malignancies and difficult administration have not gained much acceptance [59].
Patients who have progression of disease within 24 months (POD 24) of initial chemo-immunotherapy are considered early relapses and have poor outcomes. 5-year overall survival in this group is 50% compared to 90% for patients who do not progress in 2 years [54]. Histological transformation should be ruled out in these patients with a repeat biopsy. The patient’s further therapy is determined by whether he or she is transplant eligible or not. Transplant eligible patients are managed by chemo-immunotherapy followed by autologous hematopoietic stem cell transplant (HSCT). Autologous HSCT in early relapse has shown 20% improvement in 5-year overall survival. There is no survival benefit of allogenic over autologous HSCT [60, 61]. For patients with late relapse autologous HSCT may be deferred for later relapses. Allogenic stem cell transplant may be reserved for fit patients who have persistent marrow involvement, poor mobilizers stem cells for autologous HSCT and failure of autologous HSCT.
Newer drugs in the arena of follicular lymphoma management are PI3K inhibitors (idelalisib, copanlisib, duvelisib, umbralisib). EZH2 (enhancer of zeste homolog 2) mutations are observed in up to 20% of cases of relapsed FL and predict a favorable outcome. EZH2 inhibitor tazemetostat is an oral drug approved in relapsed FL patients in the first relapse in presence of EZH2 mutations and post two lines irrespective of EZH2 mutation status. Responses are observed in approximately 70% of patients with EZH2 mutations and 35% without EZH2 mutations. Adverse effects are mild and include hematotoxicity, hepatotoxicity, and elevation in serum creatinine [51]. Phosphatidylinositol-3- kinase (PI3K) inhibitors are approved in relapsed FL post multiple lines of therapy. Overall response rates range from 40 to 60%, most of which are partial responses. Common toxicities include fatigue, gastrointestinal toxicity (diarrhea, colitis), hepatotoxicity, pneumonitis, opportunistic infections, and metabolic derangements (hypertriglyceridemia, hyperglycemia). Idelalisib is an oral inhibitor of PI3K delta isoform. Copanlisib is an intravenous drug inhibiting PI3K alpha and delta isoforms. Duvelisib is an oral drug, is a dual inhibitor of delta and gamma isoforms of PI3K. Umbralisib is an oral multikinase inhibitor, acting on PI3K delta and casein kinase [62, 63, 64, 65].
Two chimeric antigen receptor T (CART) therapy products have been approved for relapsed/refractory FL post two or more lines of therapy are tisagenlecleucel and axicabtagene ciloleucelis [66, 67]. Response are seen in about 90% of patients with the majority achieving complete remission. Characteristic adverse effects include cytokine release syndrome (CRS), neurotoxicity, cytopenia, infections, and hypogammaglobulinemia.
Multiple newer therapies are currently under trial in patients with relapsed follicular lymphoma including checkpoint inhibitors, monoclonal antibodies, immunomodulatory drugs, vaccines, and chimeric antigen receptor T cell therapy. Future research should focus on identifying the predictive and prognostic biomarkers to identify patients at risk of early relapse and the role of therapy intensification in such cases.
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Raygoza and Susana Ortega",authors:[{id:"18069",title:"Dr.",name:"Jorge",middleName:null,surname:"Rivera",slug:"jorge-rivera",fullName:"Jorge Rivera"},{id:"22689",title:"Prof.",name:"Luis",middleName:null,surname:"Garcia",slug:"luis-garcia",fullName:"Luis Garcia"},{id:"22690",title:"Prof.",name:"Christian",middleName:null,surname:"Mora",slug:"christian-mora",fullName:"Christian Mora"},{id:"23671",title:"Dr.",name:"Juan José",middleName:null,surname:"Raygoza",slug:"juan-jose-raygoza",fullName:"Juan José Raygoza"},{id:"23672",title:"Dr.",name:"Susana",middleName:null,surname:"Ortega",slug:"susana-ortega",fullName:"Susana Ortega"}]}],mostDownloadedChaptersLast30Days:[{id:"53024",title:"Key Aspects for Implementing ISO/IEC 17025 Quality Management Systems at Materials Science Laboratories",slug:"key-aspects-for-implementing-iso-iec-17025-quality-management-systems-at-materials-science-laborator",totalDownloads:2823,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"Implementing a quality management system based on the requirements specified in ISO/IEC 17025 standard at materials science laboratories is challenging, mainly due to two main factors: (i) the high technical complexity degree of some tests used for materials characterization and (ii) the fact that most materials science laboratories provide materials characterization tests and also carry out research and development activities. In this context, this chapter presents key subjects while implementing a quality management system at materials science laboratories and some considerations on strategies for effectively implementing such systems.",book:{id:"5486",slug:"quality-control-and-assurance-an-ancient-greek-term-re-mastered",title:"Quality Control and Assurance",fullTitle:"Quality Control and Assurance - An Ancient Greek Term Re-Mastered"},signatures:"Rodrigo S. Neves, Daniel P. Da Silva, Carlos E. C. Galhardo, Erlon H.\nM. Ferreira, Rafael M. Trommer and Jailton C. Damasceno",authors:[{id:"20571",title:"Prof.",name:"Erlon H.",middleName:null,surname:"Martins Ferreira",slug:"erlon-h.-martins-ferreira",fullName:"Erlon H. 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The quality practices or quality management systems adopted by industries will further evolve due to the changes of quality concepts as time goes by. This chapter discusses the change of quality concepts and the related revolution of quality management systems in the past century. The quality concepts were gradually changed from the achievement of quality standards, satisfaction of customer needs, and expectations to customer delight. Since merely satisfying customers is not enough to ensure customer loyalty, the enterprises gradually focus on customers’ emotional responses and their delight in order to pursue their loyalty. The emotion of “delight” is composed of “joy” and “surprise,” which can be achieved as the customers’ latent requirements are satisfied. Thus, the concept of “customer delight” and the means to provide the innovative quality so as to meet the unsatisfied customers’ latent needs are elaborated on. Finally, a framework of innovation creation is developed that is based on the mining of customer's latent requirements. This outline will manifest the essential elements of the related operation steps.",book:{id:"5486",slug:"quality-control-and-assurance-an-ancient-greek-term-re-mastered",title:"Quality Control and Assurance",fullTitle:"Quality Control and Assurance - An Ancient Greek Term Re-Mastered"},signatures:"Ching-Chow Yang",authors:[{id:"11862",title:"Prof.",name:"Ching-Chow",middleName:null,surname:"Yang",slug:"ching-chow-yang",fullName:"Ching-Chow Yang"}]},{id:"62915",title:"Advanced Methods of PID Controller Tuning for Specified Performance",slug:"advanced-methods-of-pid-controller-tuning-for-specified-performance",totalDownloads:3476,totalCrossrefCites:10,totalDimensionsCites:16,abstract:"This chapter provides a concise survey, classification and historical perspective of practice-oriented methods for designing proportional-integral-derivative (PID) controllers and autotuners showing the persistent demand for PID tuning algorithms that integrate performance requirements into the tuning algorithm. The proposed frequency-domain PID controller design method guarantees closed-loop performance in terms of commonly used time-domain specifications. One of its major benefits is universal applicability for both slow and fast-controlled plants with unknown mathematical model. Special charts called B-parabolas were developed as a practical design tool that enables consistent and systematic shaping of the closed-loop step response with regard to specified performance and dynamics of the uncertain controlled plant.",book:{id:"6323",slug:"pid-control-for-industrial-processes",title:"PID Control for Industrial Processes",fullTitle:"PID Control for Industrial Processes"},signatures:"Štefan Bucz and Alena Kozáková",authors:[{id:"21933",title:"Ms.",name:"Alena",middleName:null,surname:"Kozakova",slug:"alena-kozakova",fullName:"Alena Kozakova"},{id:"213658",title:"Dr.",name:"Štefan",middleName:null,surname:"Bucz",slug:"stefan-bucz",fullName:"Štefan Bucz"}]},{id:"75699",title:"Data Clustering for Fuzzyfier Value Derivation",slug:"data-clustering-for-fuzzyfier-value-derivation",totalDownloads:292,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"The fuzzifier value m is improving significant factor for achieving the accuracy of data. Therefore, in this chapter, various clustering method is introduced with the definition of important values for clustering. To adaptively calculate the appropriate purge value of the gap type −2 fuzzy c-means, two fuzzy values m1 and m2 are provided by extracting information from individual data points using a histogram scheme. Most of the clustering in this chapter automatically obtains determination of m1 and m2 values that depended on existent repeated experiments. Also, in order to increase efficiency on deriving valid fuzzifier value, we introduce the Interval type-2 possibilistic fuzzy C-means (IT2PFCM), as one of advanced fuzzy clustering method to classify a fixed pattern. In Efficient IT2PFCM method, proper fuzzifier values for each data is obtained from an algorithm including histogram analysis and Gaussian Curve Fitting method. Using the extracted information form fuzzifier values, two modified fuzzifier value m1 and m2 are determined. These updated fuzzifier values are used to calculated the new membership values. Determining these updated values improve not only the clustering accuracy rate of the measured sensor data, but also can be used without additional procedure such as data labeling. It is also efficient at monitoring numerous sensors, managing and verifying sensor data obtained in real time such as smart cities.",book:{id:"9976",slug:"fuzzy-systems-theory-and-applications",title:"Fuzzy Systems",fullTitle:"Fuzzy Systems - Theory and Applications"},signatures:"JaeHyuk Cho",authors:[{id:"329648",title:"Prof.",name:"JaeHyuk",middleName:null,surname:"Cho",slug:"jaehyuk-cho",fullName:"JaeHyuk Cho"}]},{id:"39778",title:"GPS and the One-Way Speed of Light",slug:"gps-and-the-one-way-speed-of-light",totalDownloads:3478,totalCrossrefCites:0,totalDimensionsCites:0,abstract:null,book:{id:"2387",slug:"new-approach-of-indoor-and-outdoor-localization-systems",title:"New Approach of Indoor and Outdoor Localization Systems",fullTitle:"New Approach of Indoor and Outdoor Localization Systems"},signatures:"Stephan J.G. Gift",authors:[{id:"141106",title:"Prof.",name:"Stephan",middleName:null,surname:"Gift",slug:"stephan-gift",fullName:"Stephan Gift"}]}],onlineFirstChaptersFilter:{topicId:"115",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"77466",title:"Optimization of Model Predictive Control Weights for Control of Permanent Magnet Synchronous Motor by Using the Multi Objective Bees Algorithm",slug:"optimization-of-model-predictive-control-weights-for-control-of-permanent-magnet-synchronous-motor-b",totalDownloads:141,totalDimensionsCites:0,doi:"10.5772/intechopen.98810",abstract:"In this study, the model predictive control (MPC) method was used within the scope of the control of the permanent magnet synchronous motor (PMSM). The strongest aspect of the MPC, the ability to control multiple components with a single function, is also one of the most difficult parts of its design. The fact that each component of the function has different effects requires assigning different weight coefficients to these components. In this study, the Bees Algorithm (BA) is used to determine the weights. Using the multi-objective function in BA, it has been tried to determine the weights that reduce the current values together with the speed error. Three different PI controllers have been designed to compare the MPC method. The coefficients of one of these are tuned with BA. Good Gain Method and Tyreus-Luyben Method were used in the other two. As a result of experimental studies, it has been observed that MPC can control PMSM more smoothly and accurately than PI controllers, with weights optimized with BA. With MPC, PMSM has been controlled with 15% settling time than other controllers and also with no overshoot.",book:{id:"10778",title:"Model-Based Control Engineering - Recent Design and Implementations for Varied Applications",coverURL:"https://cdn.intechopen.com/books/images_new/10778.jpg"},signatures:"Murat Sahin"},{id:"78164",title:"Use of Discrete-Time Forecast Modeling to Enhance Feedback Control and Physically Unrealizable Feedforward Control with Applications",slug:"use-of-discrete-time-forecast-modeling-to-enhance-feedback-control-and-physically-unrealizable-feedf",totalDownloads:65,totalDimensionsCites:0,doi:"10.5772/intechopen.99340",abstract:"When the manipulated variable (MV) has significantly large time delay in changing the control variable (CV), use of the currently measured CV in the feedback error can result in very deficient feedback control (FBC). However, control strategies that use forecast modeling to estimate future CV values and use them in the feedback error have the potential to control as well as a feedback controller with no MV deadtime using the measured value of CV. This work evaluates and compares FBC algorithms using discrete-time forecast modeling when MV has a large deadtime. When a feedforward control (FFC) law results in a physically unrealizable (PU) controller, the common approach is to use approximations to obtain a physically realizable feedforward controller. Using a discrete-time forecast modeling method, this work demonstrates an effective approach for PU FFC. The Smith Predictor is a popular control strategy when CV has measurement deadtime but not MV deadtime. The work demonstrates equivalency of this discrete-time forecast modeling approach to the Smith Predictor FBC approach. Thus, this work demonstrates effectiveness of the discrete-time forecast modeling approach for FBC with MV or DV deadtime and PU FFC.",book:{id:"10778",title:"Model-Based Control Engineering - Recent Design and Implementations for Varied Applications",coverURL:"https://cdn.intechopen.com/books/images_new/10778.jpg"},signatures:"Derrick K. 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Much of biochemistry is devoted to enzymes, proteins that catalyze chemical reactions, enzyme structures, mechanisms of action and their roles within cells. Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. 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Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. 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Other positions she has held at the university include Vice-Dean of Master Programs, Vice-Dean of the Degree in Biology and Vice-Dean for Mobility and Enterprise and Engagement at the Faculty of Science (University of Alicante). She received her Bachelor in Biology in 1998 (University of Alicante) and her PhD in 2003 (Biochemistry, University of Alicante). She undertook post-doctoral research at the University of East Anglia (Norwich, U.K. 2004-2005; 2007-2008).\nHer multidisciplinary research focuses on investigating archaea and their potential applications in biotechnology. She has an H-index of 21. She has authored one patent and has published more than 70 indexed papers and around 60 book chapters.\nShe has contributed to more than 150 national and international meetings during the last 15 years. Her research interests include archaea metabolism, enzymes purification and characterization, gene regulation, carotenoids and bioplastics production, antioxidant\ncompounds, waste water treatments, and brines bioremediation.\nRosa María’s other roles include editorial board member for several journals related\nto biochemistry, reviewer for more than 60 journals (biochemistry, molecular biology, biotechnology, chemistry and microbiology) and president of several organizing committees in international meetings related to the N-cycle or respiratory processes.",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"15",title:"Chemical Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",isOpenForSubmission:!0,editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",slug:"sukru-beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",biography:"Dr. Şükrü Beydemir obtained a BSc in Chemistry in 1995 from Yüzüncü Yıl University, MSc in Biochemistry in 1998, and PhD in Biochemistry in 2002 from Atatürk University, Turkey. He performed post-doctoral studies at Max-Planck Institute, Germany, and University of Florence, Italy in addition to making several scientific visits abroad. He currently works as a Full Professor of Biochemistry in the Faculty of Pharmacy, Anadolu University, Turkey. Dr. Beydemir has published over a hundred scientific papers spanning protein biochemistry, enzymology and medicinal chemistry, reviews, book chapters and presented several conferences to scientists worldwide. He has received numerous publication awards from various international scientific councils. He serves in the Editorial Board of several international journals. 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He is a member of the Turkish Biochemical Society, American Chemical Society, and German Genetics society. Dr. Ekinci published around ninety scientific papers, reviews and book chapters, and presented several conferences to scientists. He has received numerous publication awards from several scientific councils. 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He worked on the structure-function relationships of glycoconjugates and his main project was the investigations on the biological roles of the de-N-glycosylation enzymes (Endo-N-acetyl-β-D-glucosaminidase and peptide-N4-(N-acetyl-β-glucosaminyl) asparagine amidase). From 2002 he contributes to the understanding of the Blood-brain barrier functioning using proteomics approaches. He has published more than 70 papers. 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Since then, he has been working as an Adjunct Professor in the same Department at the University of Pavia. His research activity during the first years was primarily focused on the purification and structural characterization of enzymes from animal and plant sources. During this period, Prof. Iadarola familiarized himself with the conventional techniques used in column chromatography, spectrophotometry, manual Edman degradation, and electrophoresis). Since 1995, he has been working on: i) the determination in biological fluids (serum, urine, bronchoalveolar lavage, sputum) of proteolytic activities involved in the degradation processes of connective tissue matrix, and ii) on the identification of biological markers of lung diseases. 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She gained considerable experience in developing and validating new methodologies whose applications allowed her to determine both the amount of biomarkers (Desmosine and Isodesmosine) in the urine of patients affected by COPD, and the activity of proteolytic enzymes (HNE, Cathepsin G, Pseudomonas aeruginosa elastase) in the sputa of these patients. Simona Viglio was also involved in research dealing with the supplementation of amino acids in patients with brain injury and chronic heart failure. She is presently engaged in the development of 2-DE and LC-MS techniques for the study of proteomics in biological fluids. The aim of this research is the identification of potential biomarkers of lung diseases. 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Waisundara",profilePictureURL:"https://mts.intechopen.com/storage/users/194281/images/system/194281.jpg",biography:"Dr. Viduranga Waisundara obtained her Ph.D. in Food Science\nand Technology from the Department of Chemistry, National\nUniversity of Singapore, in 2010. She was a lecturer at Temasek Polytechnic, Singapore from July 2009 to March 2013.\nShe relocated to her motherland of Sri Lanka and spearheaded the Functional Food Product Development Project at the\nNational Institute of Fundamental Studies from April 2013 to\nOctober 2016. She was a senior lecturer on a temporary basis at the Department of\nFood Technology, Faculty of Technology, Rajarata University of Sri Lanka. She is\ncurrently Deputy Principal of the Australian College of Business and Technology –\nKandy Campus, Sri Lanka. She is also the Global Harmonization Initiative (GHI)",institutionString:"Australian College of Business & Technology",institution:null}]},{type:"book",id:"6820",title:"Keratin",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/6820.jpg",slug:"keratin",publishedDate:"December 19th 2018",editedByType:"Edited by",bookSignature:"Miroslav Blumenberg",hash:"6def75cd4b6b5324a02b6dc0359896d0",volumeInSeries:2,fullTitle:"Keratin",editors:[{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"Blumenberg",slug:"miroslav-blumenberg",fullName:"Miroslav Blumenberg",profilePictureURL:"https://mts.intechopen.com/storage/users/31610/images/system/31610.jpg",biography:"Miroslav Blumenberg, Ph.D., was born in Subotica and received his BSc in Belgrade, Yugoslavia. He completed his Ph.D. at MIT in Organic Chemistry; he followed up his Ph.D. with two postdoctoral study periods at Stanford University. Since 1983, he has been a faculty member of the RO Perelman Department of Dermatology, NYU School of Medicine, where he is codirector of a training grant in cutaneous biology. Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}}]},{type:"book",id:"7978",title:"Vitamin A",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7978.jpg",slug:"vitamin-a",publishedDate:"May 15th 2019",editedByType:"Edited by",bookSignature:"Leila Queiroz Zepka, Veridiana Vera de Rosso and Eduardo Jacob-Lopes",hash:"dad04a658ab9e3d851d23705980a688b",volumeInSeries:3,fullTitle:"Vitamin A",editors:[{id:"261969",title:"Dr.",name:"Leila",middleName:null,surname:"Queiroz Zepka",slug:"leila-queiroz-zepka",fullName:"Leila Queiroz Zepka",profilePictureURL:"https://mts.intechopen.com/storage/users/261969/images/system/261969.png",biography:"Prof. Dr. Leila Queiroz Zepka is currently an associate professor in the Department of Food Technology and Science, Federal University of Santa Maria, Brazil. She has more than fifteen years of teaching and research experience. She has published more than 550 scientific publications/communications, including 15 books, 50 book chapters, 100 original research papers, 380 research communications in national and international conferences, and 12 patents. She is a member of the editorial board of five journals and acts as a reviewer for several national and international journals. 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