Indications for initiation of oral or IV bisphosphonates in the adult or pediatric cystic fibrosis population.
\\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:"927",leadTitle:null,fullTitle:"Thermodynamics - Physical Chemistry of Aqueous Systems",title:"Thermodynamics",subtitle:"Physical Chemistry of Aqueous Systems",reviewType:"peer-reviewed",abstract:"Thermodynamics is one of the most exciting branches of physical chemistry which has greatly contributed to the modern science. 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Medicine: From Bench to Commercial Scale",slug:"electrospinning-of-functional-nanofibers-for-regenerative-medicine-from-bench-to-commercial-scale",signatures:"Chris J. Mortimer, Jonathan P. Widdowson and Chris J. Wright",authors:[{id:"180027",title:"Dr.",name:"Chris",middleName:null,surname:"Wright",fullName:"Chris Wright",slug:"chris-wright"},{id:"225425",title:"Mr.",name:"Chris",middleName:null,surname:"Mortimer",fullName:"Chris Mortimer",slug:"chris-mortimer"},{id:"225426",title:"Mr.",name:"Jonathan",middleName:null,surname:"Widdowson",fullName:"Jonathan Widdowson",slug:"jonathan-widdowson"}]},{id:"59584",title:"Effect of Barium Titanate Reinforcement on Tensile Strength and Dielectric Response of Electrospun Polyvinylidene Fluoride Fibers",slug:"effect-of-barium-titanate-reinforcement-on-tensile-strength-and-dielectric-response-of-electrospun-p",signatures:"Avinash Baji and Yiu-Wing Mai",authors:[{id:"219294",title:"Ph.D.",name:"Avinash",middleName:null,surname:"Baji",fullName:"Avinash Baji",slug:"avinash-baji"},{id:"230729",title:"Prof.",name:"Yiu-Wing",middleName:null,surname:"Mai",fullName:"Yiu-Wing Mai",slug:"yiu-wing-mai"}]}]}],publishedBooks:[{type:"book",id:"1504",title:"Fingerprints 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Petaccia",coverURL:"https://cdn.intechopen.com/books/images_new/5402.jpg",editedByType:"Edited by",editors:[{id:"19478",title:"Dr.",name:"Mehdi",surname:"Khodaei",slug:"mehdi-khodaei",fullName:"Mehdi Khodaei"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8823",title:"On the Properties of Novel Superconductors",subtitle:null,isOpenForSubmission:!1,hash:"7ac9708760da3a91f84d9183feb90be2",slug:"on-the-properties-of-novel-superconductors",bookSignature:"Heshmatollah Yavari",coverURL:"https://cdn.intechopen.com/books/images_new/8823.jpg",editedByType:"Edited by",editors:[{id:"24773",title:"Dr.",name:"Heshmatollah",surname:"Yavari",slug:"heshmatollah-yavari",fullName:"Heshmatollah Yavari"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"2257",title:"Quantum 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The most common gene alteration present in CF patients is a deletion of phenylalanine at position 508 (ΔF508). Fortunately, researchers and pharmaceutical companies have produced allele-specific drugs targeting CF genetic mutations. These work through multiple potential mechanisms, but allele potentiation (ivacaftor) and allele correction (tezacaftor) are some of the more promising therapeutics to date [1, 2].
Historically, patients with any combination of CFTR gene mutations could invariably expect a progressive course of worsening respiratory and endocrine function, resulting in irreversible and severe lung and pancreas damage. However, the introduction of allele-specific drugs has had a profound impact on improving both the length and quality of life in CF patients [3]. Given the improved life expectancy, orthopedic providers can expect to see a resultant increase in the proportion of patients with CF.
Throughout this chapter, we will discuss the three most likely scenarios for orthopedic consultation in the CF population: bone health/fracture, muscle and soft tissue dysfunction, and joint pain and arthralgia. In order to understand each of these topics appropriately, each subtopic will be prefaced by an in-depth introduction to the basic science causing the musculoskeletal pathology with subsequent detailed management of the disease.
Healthy bone undergoes continuous remodeling – bone resorption is mediated by osteoclasts through the RANK-RANKL (receptor activator of nuclear factor kappa-β ligand) pathway. Meanwhile, bone deposition occurs through activation of osteoblasts, which signal through the WNT-β-catenin pathway [4]. Osteoblasts also secrete osteoprotegrin, which binds to RANKL thus limiting activation of osteoclasts. In this manner, osteoblasts and osteoclasts are in delicate balance, and their goal is to optimize bone mineral density (BMD) while minimizing unnecessary storage of essential nutrients via reorganization of the boney trabecular microarchitecture. Bones under continual heavy loads (stress) or tension (strain) will adapt to the increase in forces imparted to the bone, while bones undergoing less frequent loading, will have a resultant leach of essential nutrients, thus allowing each bone to maximize its function (Wolff’s Law) [5].
Mounting research is focused on improving our understanding of osteoblast and osteoclast function in CF patients. Emerging evidence indicates CF patients with pulmonary exacerbations caused by underlying indolent lung infections, have elevated cytokine levels [6]. The systemic increase in pro-inflammatory cytokines during these CF “flare-ups” leads to formation and activation of osteoclasts, resulting in bone resorption [7]. Additionally, the ΔF508 phenotype is known to promote RANKL production, which is normalized with the allele specific drug ivacaftor [8, 9, 10] and the drug miglustat [11].
Cystic Fibrosis not only increases osteoclast activity, but it also detrimentally affects osteoblast function and uncouples osteoblast–osteoclast homeostatsis leading to severe trabecular and cortical bone osteopenia through net bone mineral resorption [12]. Diminished ΔF508 osteoblast activity is thought to contribute to poor COX-2, PGE2, and osteoprotegrin expression [13]. One potential therapeutic to mitigate poor bone quality and inhibited fracture healing is ivacaftor, which works through allele potentiation of the ΔF508-CFTR channel and channel optimization returns osteoblast function to 85% of normal [14]. This effectively increases systemic levels of cyclooxygenase-2 (COX-2) and PGE2, which are integral for effective bone maturation and fracture healing [13].
Translational research performed in mouse models indicates that Cftr−/− mice have 50% less cortical bone width, thinner and less plentiful trabeculae and greater trabecular separation compared to normal mice [15]. Trabecular bone formation was also decreased by 92% in Cftr−/− mice likely due to the density of osteoclasts near the cortical surface [15]. Skeletal growth also appears to be hindered by 40% in Cftr−/− mice, due to a reduction in the hypertrophic zone of the growth plate [15]. The combination of these findings results in smaller bones that have decreased thickness and strength compared to normal bones [16]. This results in CF bones being able to tolerate less load to failure, which increases fracture risk [17]. It is believed that issues with poor BMD and increased fracture risk manifest prior to age six with no further significant worsening of BMD until after adolescence [18]. However, exercise programs in pre-adolescent children may increase BMD by 7% and these programs should be routinely implemented in all children with CF [19].
Aside from the poor bone quality imparted from phenotypic alterations by the CFTR gene, additional causes of lower BMD in CF patients include female sex, cystic fibrosis related diabetes (CFRD), vitamin D malabsorption, malnutrition, pancreatic insufficiency, exogenous corticosteroid use, chronic inflammation/chronic pulmonary infections, and decreased activity levels (Figure 1). It should be noted that there is a paucity of well-designed studies demonstrating female sex [15, 20, 21], pancreatic [21, 22], CFRD [22, 23], and chronic inflammation/pulmonary infections [18, 24] have a significant effect on BMD. However, sufficient evidence does appear to suggest decreased activity levels, malnutrition, exogenous corticosteroid use, and vitamin D deficiency or malabsorption are potentially controllable risk factors that lead to a significant reduction in BMD [18, 21, 22, 25].
Risk factors for decreased bone mineral density (BMD) in patients with cystic fibrosis. * bold ovals indicate high quality evidence for risk factor contribution to decreased BMD in cystic fibrosis patients, while non-bolded ovals indicate poor quality evidence of contribution to diminished BMD.
The net bone resorption in CF patients can be evaluated through serum or urinary analysis of type I collagen N-telopeptides, free deoxypyridinoline, and alkaline phosphatase. Increased levels of each of these molecular markers is common in CF patients, which may be further elevated by increased serum parathyroid hormone (PTH) levels and diminished serum 25-hydoxyvitamin D levels in these patients [26]. PTH and 25-hydoxyvitamin D create a positive feedback loop signaling the body to continue to resorb bone and increase serum calcium levels [27]. The combination of elevated osteoclast function and diminished osteoblast function results in early osteopenia or osteoporosis, which are diagnosed in 23.5% and 38% of the adult CF population, respectively [28].
Vitamin D deficiency affects up to 90% of patients with CF [29]. This is predominantly caused by poor systemic vitamin D absorption since CF patients absorb less than 50% of the dietary vitamin D absorbed by normal patients and 20% of CF patients have no measurable vitamin D absorption [30]. For this reason, the Cystic Fibrosis Foundation recommends each CF patient be given a daily prescription of vitamin D3 to maintain baseline 25-hyroxyvitamin D levels at a minimum of 30 ng/ml [31]. However, even with sufficient vitamin D levels, patients with CF should undergo a dual energy X-ray absorptiometry (DEXA) scan at the age of 18 [26]. Repeat DEXA scans should occur every five years if the BMD is normal but repeat testing should occur every 2–4 years if the DEXA scan is between the ranges of <−1 and > −2 (osteopenia range) [26].
Current recommendations for initiation of bisphosphonate administration can be seen in Table 1 [32]. In patients who are started on an oral or intravenous (IV) course of bisphosphonates, an approximate 3–6% increase in BMD can be expected at 1-year in the lumbar spine and femoral neck [33, 34, 35]. However, IV bisphosphonates are associated with severe bone pain and flu-like symptoms that should be discussed with patients prior to initiation [33, 36]. Additionally, atypical femur fractures and jaw osteonecrosis are risk factors for long-term treatment with bisphosphonates [37]. Clinicians should also keep in mind that BMD increases after bisphosphonate administration, but there is currently no evidence to support bisphosphonates ability to reduce the likelihood of sustaining a lower extremity or spine fracture [36].
Adults | Children/Adolescents |
---|---|
Scheduled for or have previously had an organ transplant AND have a BMD Z or T score of ≤ −1.5 | Scheduled for or have previously had an organ transplant AND have a BMD Z or T score of ≤ −2 |
Utilization of systemic glucocorticoids for longer than 3 months AND have a BMD Z or T score of ≤ −1.5 | Utilization of systemic glucocorticoids for longer than 3 months AND have a BMD Z or T score of ≤ −2 OR have a low energy mechanism fracture |
Sustain a low-energy mechanism fracture while on a course of systemic glucocorticoids | Sustain or have a history of fracture AND have a BMD Z or T score of ≤ −2 |
Sustain a low-energy mechanism fracture OR have a femoral neck BMD Z or T score of ≤ −2 AND have more than 4% BMD loss per year | About to start a prolonged course of systemic glucocorticoids AND have a BMD Z or T score of ≤ −2 |
Indications for initiation of oral or IV bisphosphonates in the adult or pediatric cystic fibrosis population.
Historically, there has been concern about fracture healing during bisphosphonate use. While there does appear to be a delay in fracture callus reorganization (immature woven bone is not replaced as quickly with mature lamellar bone), bisphosphonates do not inhibit fracture callus formation [38]. This type of fracture healing is referred to as secondary bone healing or endochondral ossification (examples of this type of healing include patients placed in a cast, surgery which involves an intramedullary nail/rod, or a bridge plate where the bone is not compressed together). While this type of fracture healing appears to be less affected by bisphosphonates, animal models suggest primary fracture healing (e.g. compression plating) is affected by bisphosphonates and causes lower BMD at the fracture site, decreases load to failure, and increases the presence of cartilaginous tissue at the fracture site [38]. However, clinical studies have not found any evidence to support a significant difference in fracture healing based on the administration of bisphosphonates, so at this time CF patients should be allowed to continue taking bisphosphonates even in the presence of a fracture [39, 40].
Cystic Fibrosis predisposes patients to fracture even with minimal or no traumatic etiology due to their low BMD. Appendicular skeleton fractures occur at a rate of approximately 20% [28]. Notably, one case report described a femur fracture in an adolescent male baseball player who was running and had no associated trauma. In this instance, the femur fracture healed after treatment with an intramedullary nail; however, the patient then had an atraumatic contralateral femur fracture months later that was treated in the same manner [41]. There have also been reports of a unilateral femoral neck fracture in a 25-year-old male without associated trauma and bilateral femoral neck fractures in a 34-year-old male after a grand mal seizure [42, 43]. The 25-year-old patient had severe osteoporosis and was treated with internal fixation, while the 34-year-old was treated with bilateral bipolar hemiarthroplasties [42, 43]. It should be noted that in non-CF patients, the femoral neck fractures would have been treated with fracture fixation instead of hip replacement. Since CF patients are now frequently treated with allele-specific drugs, there is no evidence to indicate CF patients should have fractures managed any different from patients without a diagnosis of Cystic Fibrosis. In instances of delayed fracture healing, subcutaneous teriparatide may be another effective tool to promote fracture healing, although there is poor quality evidence to support this management [44].
Up to 94% of CF patients have back pain with potential etiologies often multifactorial, but they include muscle weakness, rib fracture, scoliosis, spinous process bursitis, and vertebral fracture [45, 46, 47]. A significantly higher rate of vertebral fractures are identified in CF patients with an incidence of approximately 14%, but interestingly BMD and the risk of vertebral fracture is not correlated [28, 48]. Vertebral fractures often result in vertebral wedging, which progresses to structural kyphosis if wedging is greater than 15% [45]. Since vertebral wedging is typically minimal, only 8% of pediatric patients develop structural kyphosis, with the rate nearly doubling in adult patients [45, 49]. This may be due to the increased rates of muscle weakness and osteopenia/osteoporosis as patients age [50].
Additional considerations for spinal pain include spinal process bursitis, which may be caused by improperly fitting high frequency chest wall oscillation devices (vest) [46]. In these instances, the bursitis should be managed expectantly as it will resolve without surgical intervention after appropriate vest adjustment [46]. Another consideration of spinal pain is idiopathic scoliosis, which is more prevalent in the CF population and typically manifests as a short mid thoracic curve [51]. Idiopathic scoliosis in CF patients is often treated non-surgically with bracing [47]. However, in skeletally immature patients with curve progression to 50 degrees the scoliosis should be managed with surgical correction [52].
Diminished muscle mass and force is a common affliction of CF patients and lower extremity muscles are frequently affected to a greater degree than the upper extremity [53]. Theories abound as to the potential causes of muscle weakness and include elevated cytokine (IL-6) levels, low vitamin D levels, corticosteroids, presence of the ΔF508 phenotype, altered CFTR function in the sarcoplasmic reticulum, muscle disuse, and poor pulmonary function (Figure 2) [54, 55, 56, 57]. The reality is the cumulative effect of each of these mechanisms contributes to decreased muscle mass since each theory is intertwined.
Potential contributors to muscle dysfunction and muscle weakness in cystic fibrosis patients. * CFTR = cystic fibrosis transmembrane conductance regulator; SR = sarcoplasmic reticulum.
One of the more prominent theories for muscle dysfunction in CF patients includes abnormal function of the CFTR chloride channels in the sarcoplasmic reticulum, which results in inappropriate regulation of calcium homeostasis [57]. Since calcium is essential for muscle depolarization, dysregulation of these channels may lead to muscle mass loss, early fatigue, and generalized weakness. This mechanism was further evaluated in human and mice diaphragms, where intracellular calcium was significantly elevated after muscle depolarization in the presence of an inflammatory environment [54]. In the presence of
The net loss of peripheral muscle strength has continuously been associated with poor pulmonary function [50, 58]. When decreased muscle strength is coupled with poor anaerobic capacity – evidenced by the decreased oxygenation of muscles due to the suboptimal VO2 max – [59, 60] early lactic acid accumulation may occur [58]. This can result in muscle disuse through early muscle fatigue. Additional contributing factors include low vitamin D levels, which have been linked to poor peripheral muscle strength although the exact mechanistic role linking vitamin D and muscle weakness is incompletely understood [61]. Luckily, muscle atrophy may not be permanent. Ivacaftor appears to independently increase fat free mass by one kilogram and significantly increases lung function, which may lead to significant long-term improvements in CF patients’ health, endurance, and muscle function [62, 63].
Muscle dysfunction may also be linked to low-energy muscle injuries. A single case report identified an adolescent CF patient with an atraumatic mid-substance muscle rupture caused by running during a basketball game. Management of these injuries are typically non-surgical with gradual return to sport [46]. Similar to bony injuries, muscle injuries in the CF population should be treated comparably to muscle injuries in the general population. Future research is necessary to improve our understanding of muscle dysfunction in CF patients and to identify if allele specific drugs are effective at reducing CF patient’s predisposition to muscle atrophy and subsequent muscle rupture.
Baseline muscle weakness is present in CF patients, which is linked to decreased quality of life [64]. Therefore, multiple studies have explored the effect of exercise on improvements in strength, endurance, and quality of life [65, 66, 67]. An eight-week resistance and aerobic training program demonstrated improved strength, pulmonary function, and % fat free mass [68]. Similar results were found comparing CF patients who participated versus those who did not in a six-month weight training program, which demonstrated effectiveness of the program at increasing muscle size, strength, and overall weight gain [66]. Further, a combined home exercise program including aerobic exercise and resistance training resulted in improved weight gain and quality of life [65]. Respiratory muscle endurance training has also been found to improve both respiratory endurance and exercise endurance [67]. Based on the overwhelming positive effects of exercise on lung and peripheral muscle endurance, consensus guidelines on aerobic activity and resistance training has been established [69]. These guidelines recommend that children and adolescents with CF should engage in at least moderate intensity exercise for 60 minutes per day, while adults should ideally participate in at least moderate intensity exercise for 300 minutes per week [69]. Adults should also participate in upper body, lower body, and trunk resistance training 3–5 times per week with 1–3 sets of 8–15 repetitions. The weight should be based on 70% of maximum weight. In fact, patients with severe CF may maximally benefit from resistance training since they may struggle to have the aerobic capacity for prolonged endurance training [69].
Arthropathy is commonly identified in CF patients at a rate of ranging from 8.5 to 29% [70, 71, 72]. Two main forms of CF-related arthropathy exist: cystic fibrosis related arthropathy (CFA) and hypertrophic osteoarthropathy (HOA), although lesser forms of arthropathy have also been described including fluoroquinolone associated arthropathy and an elevated incidence of rheumatoid arthritis [72]. Although no definitive pathway has established the causality of arthropathy in the CF population, risk factors appear to include pulmonary exacerbations with
Potential risk factors contributing to arthropathy episodes in cystic fibrosis patients.
Patients with CF commonly have elevated levels of inflammatory markers including CRP and ESR [76, 77]. The combination of elevated inflammatory markers and a propensity to develop joint pain makes consults for potential septic arthritis more likely for orthopedists. Therefore, physicians need to carefully evaluate the patient’s cause of joint pain. Although arthrocentesis may be necessary to rule out septic arthritis for disabling joint pain, inflammatory markers are typically significantly elevated with septic arthritis while they may only be marginally elevated in cases of CFA or HOA [78]. A meticulous physical exam aimed at identifying limited passive range of motion and an inability to ambulate on the affected joint may further distinguish septic arthritis from either CFA or HOA.
CFA is the more common form of joint related pain with typical age of onset of approximately 13 years [79]. Although the incidence of CFA ranges from 8.5 to 29%, as the CF population continues to have a longer life span, the expected number of patients with CFA is expected to grow tremendously [71]. As such, practitioners should be cognizant of the symptoms of CFA and should systematically differentiate it from HOA and a septic joint.
CFA has distinct symptoms including, but not limited to, short bursts of recurring episodes of joint pain, fevers, joint swelling, and a rash that resembles erythema nodosum. However, pain and swelling are the most commonly identified forms of CFA and they typically present in the small joints of the hands, although knees and shoulders are also commonly affected [72, 80]. The combination of joint pain, joint swelling, overlying joint reddening, and severe pain causing loss of function is only present in around 13% of patients, allowing CFA to typically be easily differentiated from septic arthritis [72]. Further, CFA is often seen in the setting of oligo- or polyarthritis, which is uncommonly seen in patients with septic arthritis [72]. The onset of CFA symptoms occurs in less than 24 hours but the pain is often limited to four days after initiation of NSAIDs. After symptom resolution, the patient typically has no pain, but the arthropathy typically returns at variable, seemingly random time points. Further, there is often no evidence of radiographic abnormalities if x-rays are taken of the involved joint [79]. Although less commonly associated with pulmonary exacerbations, elevated systemic cytokines may exacerbate CFA [80].
HOA is characterized by a combination of medical conditions including periostitis of long bones, digital clubbing, and severe joint arthropathy with or without synovial effusions. Radiographs can help differentiate HOA from CFA due to characteristic periosteal elevation on the distal aspect of the tubular bones [81]. HPOA is also more commonly seen after initiation of a pulmonary exacerbation [82]. CF patients presenting with HOA also typically present with polyarthralgia, which may allow physicians to differentiate it from septic arthritis.
Two main pathways have been proposed for the underlying cause of HOA: humoral and vagal. The humoral pathway has two subtypes: (1) elevated cytokine levels and hypoxemia, which produces hypoxia-inducing factors including VEGF and PDGF or (2) lung arteriovenous [83]. VEGF and PDGF induce proliferation of the endothelial smooth muscle and vascular permeability resulting in angiogenesis. VEGF also stimulates osteoblast and osteoclast induction and the combination of these effects ultimately results in subperiosteal collagen deposition leading to periosteal elevation of the distal portion of the tubular bones [83]. The periosteal reaction seen in this condition results in the variable pain responses seen in these patients. From a mechanistic standpoint, this pathway has the most traction, especially amongst the CF population. The vagal pathway is not as well supported but includes stimulation of organs innervated by the vagal nerve resulting in peripheral vasodilation of the extremities [84]. However, to date, neither mechanism has been unequivocally supported with evidence.
Musculoskeletal manifestations are common in Cystic Fibrosis patients with most patients having arthropathy, muscular dysfunction or decreased bone quality at some point during their lifetime. The decrease in BMD in CF patients leads to an elevated risk of both appendicular and axial skeletal fractures, which can be mitigated with allele specific drugs due to their ability to return osteoblast function to near normal levels, while also significantly improving BMD. Vitamin D supplementation is also an important adjunct to maximize both bone health and muscular function. Although a combination of factors ultimately leads to skeletal and muscular dysfunction, targeted exercise and resistance programs have been shown to be effective at improving both BMD and muscular function (Figure 4).
Treatment algorithm for the varying presentations of the musculoskeletal manifestations of Cystic Fibrosis.
As CF patients have improved life expectancies due to rapid improvements in pharmaceuticals and CF treatment protocols, the prevalence of arthropathy will continue to increase. Differentiating CFA and HOA from septic arthritis via non-invasive measures can help minimize unnecessary procedures including arthrocentesis, while optimizing outcomes. Additionally, both CFA and HOA can be treated with NSAIDs with abrupt minimization of symptoms. Future research is necessary to document the role of allele specific drugs in improving the musculoskeletal manifestations of Cystic Fibrosis.
The author declares no conflict of interest.
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On September, 29th 2006 he has won a post PhD fellowship from the university of Bologna (from October 2006 to October 2008), at the competitive examination he was ranked first in the industrial engineering area. He extensively served as referee for several international journals. He is author/coauthor of more than 100 research papers. He has been involved in some projects supported by MURST and European Community. 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Delac received his B.Sc.E.E. degree in 2003 and is currentlypursuing a Ph.D. degree at the University of Zagreb, Faculty of Electrical Engineering andComputing. His current research interests are digital image analysis, pattern recognition andbiometrics.",institutionString:null,institution:{name:"University of Zagreb",country:{name:"Croatia"}}},{id:"557",title:"Dr.",name:"Andon",middleName:"Venelinov",surname:"Topalov",slug:"andon-topalov",fullName:"Andon Topalov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/557/images/1927_n.jpg",biography:"Dr. Andon V. Topalov received the MSc degree in Control Engineering from the Faculty of Information Systems, Technologies, and Automation at Moscow State University of Civil Engineering (MGGU) in 1979. He then received his PhD degree in Control Engineering from the Department of Automation and Remote Control at Moscow State Mining University (MGSU), Moscow, in 1984. From 1985 to 1986, he was a Research Fellow in the Research Institute for Electronic Equipment, ZZU AD, Plovdiv, Bulgaria. In 1986, he joined the Department of Control Systems, Technical University of Sofia at the Plovdiv campus, where he is presently a Full Professor. He has held long-term visiting Professor/Scholar positions at various institutions in South Korea, Turkey, Mexico, Greece, Belgium, UK, and Germany. And he has coauthored one book and authored or coauthored more than 80 research papers in conference proceedings and journals. His current research interests are in the fields of intelligent control and robotics.",institutionString:null,institution:{name:"Technical University of Sofia",country:{name:"Bulgaria"}}},{id:"585",title:"Prof.",name:"Munir",middleName:null,surname:"Merdan",slug:"munir-merdan",fullName:"Munir Merdan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/585/images/system/585.jpg",biography:"Munir Merdan received the M.Sc. degree in mechanical engineering from the Technical University of Sarajevo, Bosnia and Herzegovina, in 2001, and the Ph.D. degree in electrical engineering from the Vienna University of Technology, Vienna, Austria, in 2009.Since 2005, he has been at the Automation and Control Institute, Vienna University of Technology, where he is currently a Senior Researcher. 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Aalborg University has Two Satellite Campuses, one in Copenhagen (Aalborg University Copenhagen) and the other in Esbjerg (Aalborg University Esbjerg).\n· He is a member of prestigious IEEE (Institute of Electrical and Electronics Engineers), and IAENG (International Association of Engineers) organizations. \n· He is the chief Editor of the Journal of Software Engineering.\n· He is the member of the Editorial Board of International Journal of Computer Science and Software Technology (IJCSST) and International Journal of Computer Engineering and Information Technology. \n· He is also the Editor of Communication in Computer and Information Science CCIS-20 by Springer.\n· Reviewer For Many Conferences\nHe is the lead person in making collaboration agreements between Aalborg University and many universities of Pakistan, for which the MOU’s (Memorandum of Understanding) have been signed.\nProfessor Akbar is working in Academia since 1990, he started his career as a Lab demonstrator/TA at the University of Sussex. After finishing his P. hD degree in 1992, he served in the Industry as a Scientific Officer and continued his academic career as a visiting scholar for a number of educational institutions. In 1996 he joined National University of Science & Technology Pakistan (NUST) as an Associate Professor; NUST is one of the top few universities in Pakistan. In 1999 he joined an International Company Lineo Inc, Canada as Manager Compiler Group, where he headed the group for developing Compiler Tool Chain and Porting of Operating Systems for the BLACKfin processor. The processor development was a joint venture by Intel and Analog Devices. In 2002 Lineo Inc., was taken over by another company, so he joined Aalborg University Denmark as an Assistant Professor.\nProfessor Akbar has truly a multi-disciplined career and he continued his legacy and making progress in many areas of his interests both in teaching and research. 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These fibrillary deposits ultimately cause tissue destruction and progressive disease. Amyloidosis can be either systemic affecting multiple organs or localized. Renal involvement by amyloidosis (amyloid nephropathy) is a frequent manifestation of systemic amyloidosis. Immunofluorescence, immunohistochemistry (IHC), and more recently laser microdissection and mass spectrometry (LMD/MS) are important techniques in typing of amyloid nephropathy. This in-depth review discusses practical diagnostic approach and pathogenesis of amyloid nephropathy and includes discussion of treatment and prognosis.",book:{id:"5194",slug:"exploring-new-findings-on-amyloidosis",title:"Exploring New Findings on Amyloidosis",fullTitle:"Exploring New Findings on Amyloidosis"},signatures:"Paisit Paueksakon",authors:[{id:"180754",title:"Associate Prof.",name:"Paisit",middleName:null,surname:"Paueksakon",slug:"paisit-paueksakon",fullName:"Paisit Paueksakon"}]},{id:"51051",title:"A Nanobody‐Based Approach to Amyloid Diseases, the Gelsolin Case Study",slug:"a-nanobody-based-approach-to-amyloid-diseases-the-gelsolin-case-study",totalDownloads:1636,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Gelsolin amyloidosis (AGel) is an autosomal‐dominant inherited disease caused by point mutations in the gelsolin gene. At the protein level, these mutations result in the loss of a Ca2+‐binding site, crucial for the correct folding and function. In the trans‐Golgi network, this mutant plasma gelsolin is cleaved by furin, giving rise to a 68 kDa C-terminal fragment. When secreted in the extracellular matrix, this fragment undergoes proteolysis by MT1‐MMP–like proteases, resulting in the production of 8 and 5 kDa amyloidogenic peptides. Nanobodies, the variable part of the heavy chain of heavy‐chain antibodies, have been used as molecular chaperones for mutant plasma gelsolin and the 68 kDa C‐terminal fragment in an attempt to inhibit their pathogenic proteolysis. Furthermore, these nanobodies have also been tested and applied as a 99mTc‐based imaging agent in the gelsolin amyloidosis mouse model.",book:{id:"5194",slug:"exploring-new-findings-on-amyloidosis",title:"Exploring New Findings on Amyloidosis",fullTitle:"Exploring New Findings on Amyloidosis"},signatures:"Adriaan Verhelle and Jan Gettemans",authors:[{id:"181057",title:"Prof.",name:"Jan",middleName:null,surname:"Gettemans",slug:"jan-gettemans",fullName:"Jan Gettemans"},{id:"186102",title:"MSc.",name:"Adriaan",middleName:null,surname:"Verhelle",slug:"adriaan-verhelle",fullName:"Adriaan Verhelle"}]},{id:"35947",title:"Oxidative Stress and Mitochondrial Dysfunction in Cardiovascular Diseases",slug:"oxidative-stress-and-mitochondrial-dysfunction-in-cardiovascular-diseases",totalDownloads:3027,totalCrossrefCites:1,totalDimensionsCites:3,abstract:null,book:{id:"2134",slug:"oxidative-stress-and-diseases",title:"Oxidative Stress and Diseases",fullTitle:"Oxidative Stress and Diseases"},signatures:"Sauri Hernández-Reséndiz, Mabel Buelna-Chontal, Francisco Correa and Cecilia Zazueta",authors:[{id:"102566",title:"Dr.",name:"Cecilia",middleName:null,surname:"Zazueta",slug:"cecilia-zazueta",fullName:"Cecilia Zazueta"},{id:"102568",title:"BSc.",name:"Sauri",middleName:null,surname:"Hernández-Reséndiz",slug:"sauri-hernandez-resendiz",fullName:"Sauri Hernández-Reséndiz"},{id:"102569",title:"BSc.",name:"Mabel",middleName:null,surname:"Buelna-Chontal",slug:"mabel-buelna-chontal",fullName:"Mabel Buelna-Chontal"},{id:"102570",title:"Dr.",name:"Francisco",middleName:null,surname:"Correa",slug:"francisco-correa",fullName:"Francisco Correa"}]},{id:"50968",title:"Advances in AFM Imaging Applications for Characterizing the Biophysical Properties of Amyloid Fibrils",slug:"advances-in-afm-imaging-applications-for-characterizing-the-biophysical-properties-of-amyloid-fibril",totalDownloads:2157,totalCrossrefCites:1,totalDimensionsCites:5,abstract:"Although the formation mechanism of amyloid fibrils in bodies is still debated, it has recently been reported how amyloid fibrils can be formed in vitro. Accordingly, we have gained a better understanding of the self-assembly mechanism and intrinsic properties of amyloid fibrils. Because the structure of amyloid fibrils consists of nanoscaled insoluble strands (a few nanometers in diameter and micrometers long), a special tool is needed to study amyloid fibrils at length. Atomic force microscopy (AFM) is supposed to be a versatile toolkit to probe such a tiny biomolecule. The physical/chemical properties of amyloid fibrils have been explored by AFM. In particular, AFM enables the visualization of amyloid fibrillation with different incubation times as well as the concentrations of the formed amyloid fibrils as affected by fibril diameters and lengths. Very recently, the minute structural changes and/or electrical properties of amyloid fibrils have been made by using advanced AFM techniques including dynamic liquid AFM, PeakForce QNM (quantitative nanomechanical mapping), and Kelvin probe force microscopy (KPFM). Herein, we summarize the biophysical properties of amyloid fibrils that are newly discovered with the help of those advanced AFM techniques and suggest our perspectives and future directions for the study of amyloid fibrils.",book:{id:"5194",slug:"exploring-new-findings-on-amyloidosis",title:"Exploring New Findings on Amyloidosis",fullTitle:"Exploring New Findings on Amyloidosis"},signatures:"Wonseok Lee, Hyungbeen Lee, Gyudo Lee and Dae Sung Yoon",authors:[{id:"180553",title:"Prof.",name:"Dae Sung",middleName:null,surname:"Yoon",slug:"dae-sung-yoon",fullName:"Dae Sung Yoon"},{id:"185225",title:"Mr.",name:"Wonseok",middleName:null,surname:"Lee",slug:"wonseok-lee",fullName:"Wonseok Lee"},{id:"185226",title:"Mr.",name:"Hyungbeen",middleName:null,surname:"Lee",slug:"hyungbeen-lee",fullName:"Hyungbeen Lee"},{id:"185227",title:"Dr.",name:"Gyudo",middleName:null,surname:"Lee",slug:"gyudo-lee",fullName:"Gyudo Lee"}]}],onlineFirstChaptersFilter:{topicId:"412",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:0,limit:8,total:null},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:89,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:104,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:32,numberOfPublishedChapters:317,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:141,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:113,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:105,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:5,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:15,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}}]},series:{item:{id:"11",title:"Biochemistry",doi:"10.5772/intechopen.72877",issn:"2632-0983",scope:"Biochemistry, the study of chemical transformations occurring within living organisms, impacts all areas of life sciences, from molecular crystallography and genetics to ecology, medicine, and population biology. Biochemistry examines macromolecules - proteins, nucleic acids, carbohydrates, and lipids – and their building blocks, structures, functions, and interactions. 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. This Biochemistry Series will address the current research on biomolecules and the emerging trends with great promise.",coverUrl:"https://cdn.intechopen.com/series/covers/11.jpg",latestPublicationDate:"June 28th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:32,editor:{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"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:4,paginationItems:[{id:"38",title:"Pollution",coverUrl:"https://cdn.intechopen.com/series_topics/covers/38.jpg",isOpenForSubmission:!0,annualVolume:11966,editor:{id:"110740",title:"Dr.",name:"Ismail M.M.",middleName:null,surname:"Rahman",slug:"ismail-m.m.-rahman",fullName:"Ismail M.M. Rahman",profilePictureURL:"https://mts.intechopen.com/storage/users/110740/images/2319_n.jpg",biography:"Ismail Md. Mofizur Rahman (Ismail M. M. Rahman) assumed his current responsibilities as an Associate Professor at the Institute of Environmental Radioactivity, Fukushima University, Japan, in Oct 2015. He also has an honorary appointment to serve as a Collaborative Professor at Kanazawa University, Japan, from Mar 2015 to the present. \nFormerly, Dr. Rahman was a faculty member of the University of Chittagong, Bangladesh, affiliated with the Department of Chemistry (Oct 2002 to Mar 2012) and the Department of Applied Chemistry and Chemical Engineering (Mar 2012 to Sep 2015). Dr. Rahman was also adjunctly attached with Kanazawa University, Japan (Visiting Research Professor, Dec 2014 to Mar 2015; JSPS Postdoctoral Research Fellow, Apr 2012 to Mar 2014), and Tokyo Institute of Technology, Japan (TokyoTech-UNESCO Research Fellow, Oct 2004–Sep 2005). \nHe received his Ph.D. degree in Environmental Analytical Chemistry from Kanazawa University, Japan (2011). He also achieved a Diploma in Environment from the Tokyo Institute of Technology, Japan (2005). Besides, he has an M.Sc. degree in Applied Chemistry and a B.Sc. degree in Chemistry, all from the University of Chittagong, Bangladesh. \nDr. Rahman’s research interest includes the study of the fate and behavior of environmental pollutants in the biosphere; design of low energy and low burden environmental improvement (remediation) technology; implementation of sustainable waste management practices for treatment, handling, reuse, and ultimate residual disposition of solid wastes; nature and type of interactions in organic liquid mixtures for process engineering design applications.",institutionString:null,institution:{name:"Fukushima University",institutionURL:null,country:{name:"Japan"}}},editorTwo:{id:"201020",title:"Dr.",name:"Zinnat Ara",middleName:null,surname:"Begum",slug:"zinnat-ara-begum",fullName:"Zinnat Ara Begum",profilePictureURL:"https://mts.intechopen.com/storage/users/201020/images/system/201020.jpeg",biography:"Zinnat A. Begum received her Ph.D. in Environmental Analytical Chemistry from Kanazawa University in 2012. She achieved her Master of Science (M.Sc.) degree with a major in Applied Chemistry and a Bachelor of Science (B.Sc.) in Chemistry, all from the University of Chittagong, Bangladesh. Her work affiliations include Fukushima University, Japan (Visiting Research Fellow, Institute of Environmental Radioactivity: Mar 2016 to present), Southern University Bangladesh (Assistant Professor, Department of Civil Engineering: Jan 2015 to present), and Kanazawa University, Japan (Postdoctoral Fellow, Institute of Science and Engineering: Oct 2012 to Mar 2014; Research fellow, Venture Business Laboratory, Advanced Science and Social Co-Creation Promotion Organization: Apr 2018 to Mar 2021). The research focus of Dr. Zinnat includes the effect of the relative stability of metal-chelator complexes in the environmental remediation process designs and the development of eco-friendly soil washing techniques using biodegradable chelators.",institutionString:null,institution:{name:"Fukushima University",institutionURL:null,country:{name:"Japan"}}},editorThree:null},{id:"39",title:"Environmental Resilience and Management",coverUrl:"https://cdn.intechopen.com/series_topics/covers/39.jpg",isOpenForSubmission:!0,annualVolume:11967,editor:{id:"137040",title:"Prof.",name:"Jose",middleName:null,surname:"Navarro-Pedreño",slug:"jose-navarro-pedreno",fullName:"Jose Navarro-Pedreño",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRAXrQAO/Profile_Picture_2022-03-09T15:50:19.jpg",biography:"Full professor at University Miguel Hernández of Elche, Spain, previously working at the University of Alicante, Autonomous University of Madrid and Polytechnic University of Valencia. Graduate in Sciences (Chemist), graduate in Geography and History (Geography), master in Water Management, Treatment, master in Fertilizers and Environment and master in Environmental Management; Ph.D. in Environmental Sciences. His research is focused on soil-water and waste-environment relations, mainly on soil-water and soil-waste interactions under different management and waste reuse. His work is reflected in more than 230 communications presented in national and international conferences and congresses, 29 invited lectures from universities, associations and government agencies. Prof. Navarro-Pedreño is also a director of the Ph.D. Program Environment and Sustainability (2012-present) and a member of several societies among which are the Spanish Society of Soil Science, International Union of Soil Sciences, European Society for Soil Conservation, DessertNet and the Spanish Royal Society of Chemistry.",institutionString:"Miguel Hernández University of Elche, Spain",institution:null},editorTwo:null,editorThree:null},{id:"40",title:"Ecosystems and Biodiversity",coverUrl:"https://cdn.intechopen.com/series_topics/covers/40.jpg",isOpenForSubmission:!0,annualVolume:11968,editor:{id:"209149",title:"Prof.",name:"Salustiano",middleName:null,surname:"Mato",slug:"salustiano-mato",fullName:"Salustiano Mato",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRLREQA4/Profile_Picture_2022-03-31T10:23:50.png",biography:"Salustiano Mato de la Iglesia (Santiago de Compostela, 1960) is a doctor in biology from the University of Santiago and a Professor of zoology at the Department of Ecology and Animal Biology at the University of Vigo. He has developed his research activity in the fields of fauna and soil ecology, and in the treatment of organic waste, having been the founder and principal investigator of the Environmental Biotechnology Group of the University of Vigo.\r\nHis research activity in the field of Environmental Biotechnology has been focused on the development of novel organic waste treatment systems through composting. The result of this line of work are three invention patents and various scientific and technical publications in prestigious international journals.",institutionString:null,institution:{name:"University of Vigo",institutionURL:null,country:{name:"Spain"}}},editorTwo:{id:"60498",title:"Prof.",name:"Josefina",middleName:null,surname:"Garrido",slug:"josefina-garrido",fullName:"Josefina Garrido",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRj1VQAS/Profile_Picture_2022-03-31T10:06:51.jpg",biography:"Josefina Garrido González (Paradela de Abeleda, Ourense 1959), is a doctor in biology from the University of León and a Professor of Zoology at the Department of Ecology and Animal Biology at the University of Vigo. She has focused her research activity on the taxonomy, fauna and ecology of aquatic beetles, in addition to other lines of research such as the conservation of biodiversity in freshwater ecosystems; conservation of protected areas (Red Natura 2000) and assessment of the effectiveness of wetlands as priority areas for the conservation of aquatic invertebrates; studies of water quality in freshwater ecosystems through biological indicators and physicochemical parameters; surveillance and research of vector arthropods and invasive alien species.",institutionString:null,institution:{name:"University of Vigo",institutionURL:null,country:{name:"Spain"}}},editorThree:{id:"464288",title:"Dr.",name:"Francisco",middleName:null,surname:"Ramil",slug:"francisco-ramil",fullName:"Francisco Ramil",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003RI7lHQAT/Profile_Picture_2022-03-31T10:15:35.png",biography:"Fran Ramil Blanco (Porto de Espasante, A Coruña, 1960), is a doctor in biology from the University of Santiago de Compostela and a Professor of Zoology at the Department of Ecology and Animal Biology at the University of Vigo. His research activity is linked to the taxonomy, fauna and ecology of marine benthic invertebrates and especially the Cnidarian group. Since 2004, he has been part of the EcoAfrik project, aimed at the study, protection and conservation of biodiversity and benthic habitats in West Africa. He also participated in the study of vulnerable marine ecosystems associated with seamounts in the South Atlantic and is involved in training young African researchers in the field of marine research.",institutionString:null,institution:{name:"University of Vigo",institutionURL:null,country:{name:"Spain"}}}},{id:"41",title:"Water Science",coverUrl:"https://cdn.intechopen.com/series_topics/covers/41.jpg",isOpenForSubmission:!0,annualVolume:11969,editor:{id:"349630",title:"Dr.",name:"Yizi",middleName:null,surname:"Shang",slug:"yizi-shang",fullName:"Yizi Shang",profilePictureURL:"https://mts.intechopen.com/storage/users/349630/images/system/349630.jpg",biography:"Prof. Dr. Yizi Shang is a pioneering researcher in hydrology and water resources who has devoted his research career to promoting the conservation and protection of water resources for sustainable development. He is presently associate editor of Water International (official journal of the International Water Resources Association). He was also invited to serve as an associate editor for special issues of the Journal of the American Water Resources Association. He has served as an editorial member for international journals such as Hydrology, Journal of Ecology & Natural Resources, and Hydro Science & Marine Engineering, among others. He has chaired or acted as a technical committee member for twenty-five international forums (conferences). Dr. Shang graduated from Tsinghua University, China, in 2010 with a Ph.D. in Engineering. Prior to that, he worked as a research fellow at Harvard University from 2008 to 2009. Dr. Shang serves as a senior research engineer at the China Institute of Water Resources and Hydropower Research (IWHR) and was awarded as a distinguished researcher at National Taiwan University in 2017.",institutionString:"China Institute of Water Resources and Hydropower Research",institution:{name:"China Institute of Water Resources and Hydropower Research",institutionURL:null,country:{name:"China"}}},editorTwo:null,editorThree:null}]},overviewPageOFChapters:{paginationCount:19,paginationItems:[{id:"82196",title:"Multi-Features Assisted Age Invariant Face Recognition and Retrieval Using CNN with Scale Invariant Heat Kernel Signature",doi:"10.5772/intechopen.104944",signatures:"Kamarajugadda Kishore Kumar and Movva Pavani",slug:"multi-features-assisted-age-invariant-face-recognition-and-retrieval-using-cnn-with-scale-invariant-",totalDownloads:6,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Pattern Recognition - New Insights",coverURL:"https://cdn.intechopen.com/books/images_new/11442.jpg",subseries:{id:"26",title:"Machine Learning and Data Mining"}}},{id:"82063",title:"Evaluating Similarities and Differences between Machine Learning and Traditional Statistical Modeling in Healthcare Analytics",doi:"10.5772/intechopen.105116",signatures:"Michele Bennett, Ewa J. Kleczyk, Karin Hayes and Rajesh Mehta",slug:"evaluating-similarities-and-differences-between-machine-learning-and-traditional-statistical-modelin",totalDownloads:6,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Machine Learning and Data Mining - Annual Volume 2022",coverURL:"https://cdn.intechopen.com/books/images_new/11422.jpg",subseries:{id:"26",title:"Machine Learning and Data Mining"}}},{id:"81791",title:"Self-Supervised Contrastive Representation Learning in Computer Vision",doi:"10.5772/intechopen.104785",signatures:"Yalin Bastanlar and Semih Orhan",slug:"self-supervised-contrastive-representation-learning-in-computer-vision",totalDownloads:28,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Pattern Recognition - New Insights",coverURL:"https://cdn.intechopen.com/books/images_new/11442.jpg",subseries:{id:"26",title:"Machine Learning and Data Mining"}}},{id:"79345",title:"Application of Jump Diffusion Models in Insurance Claim Estimation",doi:"10.5772/intechopen.99853",signatures:"Leonard Mushunje, Chiedza Elvina Mashiri, Edina Chandiwana and Maxwell Mashasha",slug:"application-of-jump-diffusion-models-in-insurance-claim-estimation-1",totalDownloads:8,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Data Clustering",coverURL:"https://cdn.intechopen.com/books/images_new/10820.jpg",subseries:{id:"26",title:"Machine Learning and Data Mining"}}}]},overviewPagePublishedBooks:{paginationCount:9,paginationItems:[{type:"book",id:"7723",title:"Artificial Intelligence",subtitle:"Applications in Medicine and Biology",coverURL:"https://cdn.intechopen.com/books/images_new/7723.jpg",slug:"artificial-intelligence-applications-in-medicine-and-biology",publishedDate:"July 31st 2019",editedByType:"Edited by",bookSignature:"Marco Antonio Aceves-Fernandez",hash:"a3852659e727f95c98c740ed98146011",volumeInSeries:1,fullTitle:"Artificial Intelligence - Applications in Medicine and Biology",editors:[{id:"24555",title:"Dr.",name:"Marco Antonio",middleName:null,surname:"Aceves Fernandez",slug:"marco-antonio-aceves-fernandez",fullName:"Marco Antonio Aceves Fernandez",profilePictureURL:"https://mts.intechopen.com/storage/users/24555/images/system/24555.jpg",biography:"Dr. Marco Antonio Aceves Fernandez obtained his B.Sc. (Eng.) in Telematics from the Universidad de Colima, Mexico. He obtained both his M.Sc. and Ph.D. from the University of Liverpool, England, in the field of Intelligent Systems. He is a full professor at the Universidad Autonoma de Queretaro, Mexico, and a member of the National System of Researchers (SNI) since 2009. Dr. Aceves Fernandez has published more than 80 research papers as well as a number of book chapters and congress papers. He has contributed in more than 20 funded research projects, both academic and industrial, in the area of artificial intelligence, ranging from environmental, biomedical, automotive, aviation, consumer, and robotics to other applications. He is also a honorary president at the National Association of Embedded Systems (AMESE), a senior member of the IEEE, and a board member of many institutions. His research interests include intelligent and embedded systems.",institutionString:"Universidad Autonoma de Queretaro",institution:{name:"Autonomous University of Queretaro",institutionURL:null,country:{name:"Mexico"}}}]},{type:"book",id:"7726",title:"Swarm Intelligence",subtitle:"Recent Advances, New Perspectives and Applications",coverURL:"https://cdn.intechopen.com/books/images_new/7726.jpg",slug:"swarm-intelligence-recent-advances-new-perspectives-and-applications",publishedDate:"December 4th 2019",editedByType:"Edited by",bookSignature:"Javier Del Ser, Esther Villar and Eneko Osaba",hash:"e7ea7e74ce7a7a8e5359629e07c68d31",volumeInSeries:2,fullTitle:"Swarm Intelligence - Recent Advances, New Perspectives and Applications",editors:[{id:"49813",title:"Dr.",name:"Javier",middleName:null,surname:"Del Ser",slug:"javier-del-ser",fullName:"Javier Del Ser",profilePictureURL:"https://mts.intechopen.com/storage/users/49813/images/system/49813.png",biography:"Prof. Dr. Javier Del Ser received his first PhD in Telecommunication Engineering (Cum Laude) from the University of Navarra, Spain, in 2006, and a second PhD in Computational Intelligence (Summa Cum Laude) from the University of Alcala, Spain, in 2013. He is currently a principal researcher in data analytics and optimisation at TECNALIA (Spain), a visiting fellow at the Basque Center for Applied Mathematics (BCAM) and a part-time lecturer at the University of the Basque Country (UPV/EHU). His research interests gravitate on the use of descriptive, prescriptive and predictive algorithms for data mining and optimization in a diverse range of application fields such as Energy, Transport, Telecommunications, Health and Industry, among others. In these fields he has published more than 240 articles, co-supervised 8 Ph.D. theses, edited 6 books, coauthored 7 patents and participated/led more than 40 research projects. 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He is currently a full professor in\nthe Department of Automation and Applied Informatics at the\nsame university. Dr. Voloşencu is the author of ten books, seven\nbook chapters, and more than 160 papers published in journals\nand conference proceedings. He has also edited twelve books and\nhas twenty-seven patents to his name. He is a manager of research grants, editor in\nchief and member of international journal editorial boards, a former plenary speaker, a member of scientific committees, and chair at international conferences. His\nresearch is in the fields of control systems, control of electric drives, fuzzy control\nsystems, neural network applications, fault detection and diagnosis, sensor network\napplications, monitoring of distributed parameter systems, and power ultrasound\napplications. 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Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. 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