Average duration of presence (± standard deviation) in one roost by a number of forest-dwelling bat species demonstrating a fission-fusion society, in New Zealand (1), North America (2) and in Europe (3).
\r\n\tEqually important are the consequences deriving from the extraordinary nature of the present times. The COVID-19 pandemic and the restrictive measures to contain the infection (lockdown and "physical distancing" in primis) have revolutionized the lives, and a distortion/modification of habits, rhythms, arrangements will continue to be necessary.
\r\n\tGovernments have implemented a series of actions to mitigate the spread of infections and alleviate the consequent pressure on the hospital system. On the other hand, the Covid-19 pandemic has caused a series of other cascading effects that will probably be much more difficult to mitigate and which expose to complex consequences. The past two years have brought many challenges, particularly for healthcare professionals, students, family members of COVID-19 patients, people with mental disorders, the frail, the elderly, and more generally those in disadvantaged socio-economic conditions, and workers whose livelihoods have been threatened. Indeed, the substantial economic impact of the pandemic may hinder progress towards economic growth as well as progress towards social inclusion and mental well-being.
\r\n\t
\r\n\tAlthough in all countries the knowledge on the impact of the pandemic on mental health is still limited and mostly derived from experiences only partially comparable to the current epidemic, such as those referring to the SARS or Ebola epidemics, it is likely that the demand for intervention it will increase significantly in the coming months and years. The extraordinary growth of scientific research in the field of neuroscience now offers the possibility of a new perspective on the relationship between mind and brain and generates new scenarios in understanding the long wave of the pandemic and in the prospects for treatment. Moreover, the pandemic also has led to opportunities to implement remote monitoring and management interventions.
\r\n\t
\r\n\tOverall this volume will address the complex relationship existing between COVID-19, mental health, acquired knowledge, and possible interventions taking a highly multidisciplinary approach; from physiological and psychobiological mechanisms, and neuromodulation through medical treatment, psychosocial interventions, and self-management.
In Europe, forests cover an area of approximately 4.5 million km2, from the boreal forests of Scandinavia and Russia to the forests of the Mediterranean, including natural forests, plantations and intensive production forest systems [1]. They constitute a habitat particularly attractive to bats by providing the potential for roosting and foraging. Since the 1990s, conservation biologists have considered the forest as one of the most important refuges for biodiversity, in particular for a number of terrestrial mammals and bats [1, 2, 3]. Moreover, forests probably represent one of the least altered habitats across the continental landscape. Thus, forest managers must engage in implementing favourable management strategies for these species [2, 4]. Our knowledge about bats was still largely considered fragmentary at the beginning of the twenty-first century, outlined in a review on the relationships between bats and forests in North America [5]. In Europe, studies have multiplied in recent years promoting a greater understanding of the impacts of forest management on bats. This path to knowledge has revealed the relationships between bats, roosting sites, and foraging habitats across a number of settings, from natural forests, to intensive production forests, and to plantations with exotic species [6]. Unsurprisingly, bat species abundance and richness is considerably higher in forests that resemble a natural state [2, 7], which is probably in response to a greater presence of certain habitats related to the abandonment of logging practices, such as deadwood and tree cavities [8, 9, 10]. However, provided society’s demand for wood products persists, the sometimes intensive exploitation of forests will continue to have a strong impact on biodiversity. In Europe, some sites already have high-quality favourable habitats at the landscape scale, principally in forests, and contribute markedly to the concentration of bats, especially the most specialised species [8]. These sites have consequently been included in the Natura 2000 network and are subject to contractual or regulatory management measures favouring biodiversity at the landscape scale. However, recent studies on certain forest habitats within the Natura 2000 network, notably beech (
In forests exploited for timber production, the number of available trees with cavities that can be used by bats are generally low, as young vigorous trees are favoured for wood production [12, 13]. The formation of cavities is very slow. Less than 1% of
Bat colonies use tree cavities. As a result, their reproduction is all the more favoured if the forest area they occupy has a high density of potential roosting sites [27]. However, the majority of European forests are subject to the effects of timber harvest, presenting a considerable constraint to the biodiversity associated with tree microhabitats. This therefore constitutes the first major pressure facing bats in forests [2, 12, 13]. Any conservation strategy at the regional scale must therefore take into account the bat species present and the available cavities. Furthermore, the type of cavity selected indeed varies according to the species,
With increasing pressure for timber products in European forests, tree-dwelling bats must demonstrate sufficient plasticity in their behaviour in order to adapt to the challenge of a fluctuating availability of suitable roosts.
Bat colonies select cavities of which the size and the type govern the structure and the numbers of the group occupying them. Consequently, pregnant females of
Fission-fusion may limit the risk of parasitism [38, 40, 41], as tree cavities being confined spaces are conducive to the development of micro-organisms linked to wood degradation [19] and maintain an increase in humidity and heat favouring the development of bat parasites. In mammals, parasite density decreases with the frequent changing of rest sites [42]. For bats, this phenomenon outlines the importance of using a large number and diversity of cavities. The changing of roosts also allows bats to limit the risk of predation, as predators would no longer know which cavity exit to prowl [41]. Though, the frequency in which bats switch roosts is more dependent on meteorological conditions and the individuals’ reproductive status [31, 43]. A disadvantage is that over time, these repeated fissions can lead to a loss of familiarity among individuals as life in a fission-fusion society imposes constant regroupings of different individuals [17, 22, 44, 45].
The turnover of roosts in relation to fission-fusion dynamics occurs, on average, every 2 or 3 days (Table 1). As a result, a substantial quantity of available cavities within the home range of a given bat colony is essential. The frequency in which bats change roost is largely influenced by the individuals’ reproductive status, as outlined above. Females often change roosts when pregnant and tend to stay longer in the same cavity when lactating because maintaining higher temperatures, which is crucial, is energy-intensive for animals [22]. Accordingly,
Species | Duration in number of days | Reference |
---|---|---|
1.7 ± 2.0 | [51] | |
5.6 ± 6.9 | [52] | |
1.7 ± 0.7 | [53] | |
1.6 ± 0.5 | [54] | |
1.26 ± 0.40 to 1.20 ± 0.49 | [55] | |
2.1 ± 1.1 | [56] | |
1.3 ± 0.8 | [31] | |
1.2 ± 0.6 | [31] | |
2.6 ± 1.6 | [27] | |
2.0 ± 1.8 | [28] | |
2.68 ± 0.82 | [50] | |
1.4 ± 0.8 | [31] |
Average duration of presence (± standard deviation) in one roost by a number of forest-dwelling bat species demonstrating a fission-fusion society, in New Zealand (1), North America (2) and in Europe (3).
The literature is rich in identifying the main forest characteristics utilised by most European bat species [2, 6], as forests undoubtedly remain complex environments offering foraging habitats for these species, even when insect populations fluctuate. Studying forest habitats rather than prey abundance can thus contribute to a greater understanding of foraging behaviours [52, 53]. Regardless of the species, certain forest habitats are more attractive than others, broadleaved forests above all [50, 54, 55, 56, 57, 58, 59]. It is therefore difficult for a forest manager to apply bat-friendly practices without a precise description of the factors determining habitat selection. According to the numerous studies, forest management causes changes (in terms of the composition and the structure of a forest stand) that are either acceptable or not for bats, as foraging behaviour may be jeopardised [60]. Logging forests for timber production may therefore reduce a colony’s ability to sustain itself due to a lack of feeding resources [60, 61].
At the bat community level, the silvicultural parameters that best explain the selection of certain forest habitats are that of structure, composition, and the quantity of foliage among other elements beyond the stand itself.
The maximal diameter of trees, different from stand age (but related) generally translates to a forest stand of overmature trees with the presence of microhabitats [10]. Microhabitats can even serve occasionally as refuge for bats that forage several kilometres from their roosting site, when weather conditions dramatically change [31]. Indeed, old forest stands are the most important habitats for bats as they offer a great potential for roosting [31, 60]. In a diverse forest landscape, bats will predominantly select broadleaved tree stands dominated by oaks and tend to avoid conifers [31]. This is in direct response to the entomological richness associated with these tree species [62]. Native
In Europe few bat species roost in dead trees.
Deadwood constitutes an important support for the development of wood decaying insects with nearly a third of all forest insects directly depending on it [19, 26, 75]. Foraging bats can indeed take advantage of the presence of fresh deadwood by targeting any emerging
The spatial distribution of foraging bats in a forest stand. Gleaners (
Bats respond differently to roosts as well as foraging habitats (or home ranges) according to their reproductive state. The energy needs of reproductive females are such that they become a lot more demanding than the other individuals [82].
Regardless of the type of silvicultural practice undertaken in forests around the world, biodiversity will be affected. Harvest exclusion areas or setting aside reserves within production forests constitute sites that are richer in terms of species present, whereas timber plantations with more economically profitable methods employed, notably short rotation forestry, are the most impacting of approaches [1, 26, 71]. For bats, silvicultural logging reduces food resources, destroys breeding sites, and can kill individuals or colonies when trees are felled [2, 5, 6, 71]. Females of
Given the major differences in the ecological functioning of forest habitats, i.e. different compositions and structures, combined with a diverse range of silvicultural techniques employed to manipulate growth conditions, it becomes difficult for the conservation biologists to propose bat-friendly management measures [2, 81]. The growing literature comparing managed and non-managed forests demonstrates that bats do have the ability to occupy exploited forest systems, which gives hope for improving the conservation status of many species throughout European forests [1]. However, so as to implement effective conservation measures for bats, it is vital to know what habitat parameters to conserve and balance this with appropriate silvicultural treatments that ensure the continuing exploitation of wood while assuring the safety of the loggers themselves and the public who use the forests for recreational purposes. Although it is necessary to further improve knowledge on the relationship between bats and forest management [2], some recommendations can already be put forward. In order to conserve both roosts and foraging habitats, it is imperative that the manager ensures the temporal and spatial continuity of mature broadleaved stands composed of native species by maintaining at least 35% of the surface area of each forest (about 1000 ha). One way of maintaining suitable habitats for bats in forests would be by setting aside a number of small sites of no more than a few hectares in size, leaving the forest within each site to complete its natural cycle. By doing so, this would assure the presence of tree cavities, deadwood, and certain heterogeneity to naturally occur across an entire forest mosaic. In addition, within production forest plots, maintaining a small number of live or dead trees possessing cavities even after felling treatments have been carried out can ensure a minimum continuation of usable roosts. This can be of particular ecological interest: live trees possessing cavities surrounding a dead tree form a group of trees representing a particularly attractive habitat for bats. Also, a tree possessing a large voluminous cavity at a high position can accommodate certain species for an extended period of time such as
In Europe, the accumulation of knowledge over the last decade on the relationships between bats and forests has orientated programmes geared towards a greater consideration for bats. In addition, the Natura 2000 network has been adopted in the European Community making it possible to designate numerous sites considered as fundamental for these animals [2, 13]. Forests being a key issue for the conservation of bats need to be taken into account as part of regional planning and forest management policies [2]. However, even though the number of appropriate management recommendations has increased in recent years the implementation of concrete conservation strategies is challenging, and unfortunately slow. Furthermore, forest managers must meet society’s growing demand for wood products among other objectives such as reducing fossil fuel consumption, curtailing the impacts of climate change.
Of the 15 million hectares of forests in France (including overseas territories), 4.5 million hectares are managed by the French Forest Office who are mainly financed by timber production. This management body has integrated key conservation issues for biodiversity at various spatial scales within production forest systems. First, a number of harvest exclusion areas, whereby no silvicultural intervention occurs, have been created, each area ranging in size from ten to hundreds of hectares, totalling nearly 50,000 ha. Second, 3% of managed forests are “habitat islands” (generally ranging from 1 to 10 ha in size) where a true naturalness approach allows the natural cycle of forests to ensue ageing and decomposition of trees. Third, three microhabitat-bearing trees or dead trees are systematically protected per hectare. Fourth, at least one-third of a mature broadleaved forest’s area is maintained in each forest canton as often as possible. The exploitation by clearcutting cannot exceed a few dozen hectares for any single block and the natural regeneration of the ecosystem is favoured, which is thus less degrading to biodiversity than plantations. Lastly, a team of 45 conscientious forest engineers, technicians and ecologists set up in 2004 carry out forest inventories and studies to improve knowledge on the relations between bats and forests and to evaluate the impact of forestry in this Office. They convert the collected information into management guidelines that favour bat conservation. These people are trained in forestry and have years of experience in managing forest plots, and can use the technical terminology required when communicating appropriate strategies to silviculture. The internalisation of these issues by teams dedicated to the preservation of bats within forest management organisations is the best assurance of successful bat conservation within exploited forest systems worldwide.
We would like to reserve a special thanks to the entire Mammal Network Team at the French Forest Office, who have greatly contributed to considering the conservation of bats within the context of forest management in France.
Systemic lupus erythematosus is a well-recognized multi-system disease [1].
\nHallmarks of the disorder include the prevalence of antinuclear antibodies (ANA) and double stranded antibodies (DNA). The disease often presents with rashes and/or arthritis or arthralgias. Lupus is “the great imitator,” as no organ system is excluded, when diagnosing and treating a lupus patient.
\nWhile lupus remains evasive in novel therapies with true benefit; one issue has been consistent, in that the preponderance of the evidence thus far, leads to B cell dysfunction. More recently Belimumab was indicated for use in lupus patients, which is an immunomodulator B-Lymphocyte Stimulator (BLyS)-Specific Inhibitor. This drug was approved by the Food and Drug Administration (FDA) for use in lupus patients in 2011 [2]. The majority of patients afflicted with lupus, autoreactive B-cells remain in the body longer than necessary. Belimumab binds to BLyS, causing it to no longer bind to and stimulate the autoreactive B cell.
\nInformation recently discussed at the ACR2020, provides evidence of Belimumab standard therapy ameliorating the outcome for patients with active renal lupus. A combination of Belimumab, with either mycophenolate mofetil or Azathioprine, was shown to be more effective than either of these therapies alone. While studies are not yet conclusive, a combination of Belimumab with cyclophosphamide, posed no higher risk than cyclophosphamide alone. This combination in a class IV nephritis group exceeded those who received cyclophosphamide alone [3].
\nAnifrolumab, an interleukin-1 inhibitor, was not shown to be effective in systemic lupus, it did show promise in TULIP-1 and 2 and skin lesions related to lupus. Anifrolumab’s effect on non-skin lupus disease activity however, was nominal [4].
\nIn this section, lupus will be discussed pragmatically. Most practitioners are unaccustomed to viewing disease features from a rheumatologic standpoint. Typically, the practitioner that approaches a patient with a plethora of symptoms, would order blood tests, and conclude a diagnosis of lupus; however, in this part of the chapter, we will discuss the need to focus “outside the box” and perhaps consider lupus as simply one of various other scenarios.
\nFeatures of lupus considered in the differential diagnoses of other conditions include rashes, arthritis, renal disease (glomerular or tubular), Raynaud’s phenomenon, sicca syndrome and muscle weakness. The differential diagnoses for these features often include lymphoma, sarcoidosis, phospholipid antibody syndrome, rheumatoid arthritis, inflammatory myopathy, Sjogren’s syndrome, IgG4-related disease and scleroderma.
\nA lupus rash, seen with or without vasculitis, typically small vessel-showing leukocytoclastic vasculitis, is seen at the dermal/epidermal junction with immunofluorescence positive for IgG and complements [5]. Small vessel vasculitis is responsible for much of the severe abdominal pain seen in lupus patients.
\nArthritis of lupus is inflammatory but not erosive. Differential diagnoses would include rheumatoid arthritis, gout, or psoriatic arthritis. Rheumatoid arthritis, psoriatic arthritis, scleroderma, sarcoid and gout are all destructive arthritic diseases [6].
\nRenal pathology is often noted due to blood or protein in the urine. It may be diagnosed by a decrease in renal function, which is differentiated on biopsy. Lupus tends to involve glomerulus with a “full house” pattern on immunofluorescent staining (i.e., presence of glomerular deposits that stain for IgG, IgM, IgA, C3 and C1q). This is the only organ finding to satisfy the SLICC criteria on its own in patients with systemic lupus. IgG and complements would be suggestive of lupus nephritis in a patient with proliferative glomerulonephritis. This may be focal, diffuse or pure membranous nephropathy [7]. A patient with pure membranous disease, high double stranded DNA and low complements often do not apply. Proliferative lesions are often seen in the face of rising double stranded DNA and consumption of complement levels. These levels are not subject to change in Sjogren’s, scleroderma, sarcoid, or IgG4-related disease. (IgG4-related disease is unique, as both tubulointerstitial diseases occur simultaneously with glomerular disease). ANCA vasculitis shows pauci-immune deposits [8], while sarcoidosis would show granulomas without positive stain for immunofluorescence. Goodpasture syndrome will show anti-GBM antibodies [9]. Sjogren’s syndrome will show renal tubular acidosis, and only rarely, glomerular disease [10]. Most cases of tubulointerstitial nephritis are drug-induced, and may be caused by medications, such as antibiotics medications, NSAIDs, proton pump inhibitors, and immune-checkpoint inhibitors [11]. Uncommonly, NSAIDs may cause a combination of interstitial nephritis and nephrotic syndrome. Infections (i.e., legionella or
Pulmonary renal syndromes can be seen in a very similar fashion, adding that lupus may present with acute glomerulonephritis, proliferative in nature, in addition to concurrent alveolar hemorrhage or diffuse interstitial infiltrates [17]. This pattern of disease seen in ANCA vasculitis is predominantly granulomatous polyangiitis, microscopic polyangiitis, and cryoglobulinemia, which is associated with hepatitis C infection [18].
\nOral and ocular dryness, with or without uveitis, are features of lupus [19]. Uveitis is frequently seen in sarcoidosis and described in IgG4-related disease and HLA-B27-related conditions, while corneal-related disease has a differential diagnosis in rheumatoid arthritis, myopathy, and phospholipid antibody syndrome.
\nPrimary muscle weakness while in lupus, [20] is part of a differential diagnoses that includes polymyositis, dermatomyositis, immune mediated necrotizing myopathy, lupus with myopathy, sarcoidosis with myopathy and Crohn’s with myopathy. The latter two, show non-caseating granuloma disease on biopsy, while lupus shows diffuse immunofluorescence, mainly immunoglobulins and complements. This could be referred to as a “recurring theme” in lupus deposits of immunoglobulin and complements. Cocaine-laced with levamisole is in the differential diagnosis systemic lupus, myopathy and vasculitis [21].
\nA rheumatologist should recognize a lupus patient by the malar rash sparing the nasolabial folds, “classic kidney biopsy” and other constellations, such as “non-scarring alopecia” and “discoid lupus”. These cases are often straightforward, and do not require biopsy. The classic malar rash sparing the nasolabial folds, is a known hallmark of lupus; although it may be confused with rosacea or polymorphous light eruption. The malar rash with autoantibodies, particularly ANA (almost 100% sensitive), and anti-double stranded DNA (95% specific), will lend themselves to a conclusive diagnosis [22]. Nonetheless, it should be noted that research criteria is not necessary for a diagnosis of lupus. The research criterion is merely a tool, used to randomize patients into homogeneous groups, while in fact physicians are treating a heterogeneous disease. So, in the quest to stratify patients by nonskilled physicians, or those not comfortable diagnosing or treating lupus properly, diagnostic criteria is often helpful, but certainly cannot be the quintessential element of a lupus diagnosis. In reality, actually “labeling” a patient with a lupus diagnosis may require a protracted course. Theoretically, a patient may carry a label of unspecified connective tissue disease (UCTD) for some time, before a conclusive diagnosis can be given. In time, this patient may develop lupus, Sjogren’s syndrome, rheumatoid arthritis, scleroderma, myositis, an overlap syndrome, anti-synthetase syndrome, Sjogren’s syndrome, IgG4-related disease, or sarcoid.
\nPhysicians should consider lupus as every disease they see, and work backward from that point. Note the following:
When a patient presents with hair loss (i.e., a bald spot - non-scarring alopecia); the differential diagnoses are broad and lupus should be investigated, the patient will need to be followed and skin biopsies performed [23].
Lesions, such as discoid lupus, which are characteristic scaly lesions, discolored, typically hyper-pigmented, and located within the ears, are common in lupus [24]. Although these lesions may be seen in other conditions, lupus should be considered.
Uveitis, typically anterior, is common in lupus [25]. It may occur one time, and may be infectious. Diagnostic possibilities included syphilis, tuberculosis or Lyme disease. If these infections are excluded, then undoubtedly, even if the patient’s uveitis is a first-time occurrence, a lupus workup should be initiated.
As with all patients presenting any of the above features, clinicians should initiate confirmatory laboratory workup, including phospholipids, ANA, DNA, ENA, SSA, and SSB, in order to establish a baseline, when a patient exhibits a potential lupus feature at any point. Hypothetically a young patient, between 15 and 20 years of age, may present to a clinic with anterior uveitis. Rather than labeling this as viral, the practitioner should immediately consider a differential diagnosis that includes lupus. Other differential possibilities would include syphilis, tuberculosis, HLA-B27 diseases (including but not limited to psoriatic arthritis), HLA-B27 uveitis, ankylosing spondylitis, reactive arthritis, Crohn’s colitis and ulcerative colitis. Regardless of the ultimate diagnosis, the treatment does not change; however, if the patient requires treatment with hydroxychloroquine, early diagnosis may lead to a more favorable outcome. Hydroxychloroquine is paramount. Many clinical trials over decades support its efficacy in prevention of lupus flares, thrombosis in lupus patients, and lipid-lowering potential [26].
\nIn addition to the three presentations listed above, mouth sores also occur in lupus, Crohn’s disease, Behcet’s disease, phospholipid antibody syndrome, tuberculosis, syphilis, sarcoidosis, Sjogren’s syndrome, IgG4-related disease, and viral infections [27]. Viral ulcers tend to be painful. Behcet’s ulcers generally reveal large, circumscribed, beefy-red borders. Ulcers associated with Crohn’s disease are usually shallow painful ulcers, similar to those seen in sarcoidosis. Lupus ulcers are frequently painless and often noticed surreptitiously [28].
\nAdditionally, isolated lymphadenopathy does not necessarily have to be hilar or mediastinal; it could be epitrochlear, glandular swelling, lacrimal, parotid, or submandibular. However, the finding, incidental or not, with or without dry eyes and dry mouth, may be an indication of lupus (\nTable 1\n).
\nPositive antinuclear antibody (ANA) | \n97% | \n
Malaise and fatigue | \n90% | \n
Arthralgia, myalgia | \n90% | \n
Sun sensitivity, skin changes | \n70% | \n
Cognitive dysfunction | \n70% | \n
Low C3 or C4 complement | \n61% | \n
Fever due to lupus | \n57% | \n
Antibodies to ds DNA | \n50% | \n
Arthritis | \n50% | \n
Leukopenia | \n46% | \n
Pleuritis | \n44% | \n
Anemia | \n42% | \n
Alopecia | \n40% | \n
Nephritis, proteinuria | \n40% | \n
Anticardiolipin antibody | \n35% | \n
Malar rash | \n35% | \n
Central nervous system | \n32% | \n
Increased gamma globulin | \n32% | \n
Weight loss due to lupus | \n27% | \n
Raynaud’s | \n25% | \n
Hypertension | \n25% | \n
Sjogren’s | \n25% | \n
Oral ulcerations (mouth, nose) | \n20% | \n
Discoid lesions | \n20% | \n
Central nervous system vasculitis | \n15% | \n
Adenopathy | \n15% | \n
Pleural effusion | \n12% | \n
Subacute cutaneous lupus | \n10% | \n
Myositis | \n10% | \n
Avascular necrosis | \n10% | \n
Approximate prevalence (%) of selected symptoms, signs, and laboratory abnormalities of systemic lupus erythematosus during the course of the disease in the United States [29].
The following represents selected symptoms and abnormalities in patients diagnosed with lupus within in the United States.
\nApproximately 50% of lupus patients suffer from arthritis [29]. Joint disease, quite often a small joint polyarthritis, typically symmetric, is noted with typical involvement of PIPs, MCPs and wrists, inflammatory in nature; however, this is not erosive, which differentiates it from rheumatoid arthritis [30]. However, the practitioner should keep in mind that the differential diagnosis of IgG4-related disease, lymphomas, Sjogren’s, sarcoidosis, or spondyloarthropathies, can also present with a phenotypic appearance of lupus arthritis. The definitive finding of arthritis only seen in lupus would be lupus arthropathy or acute rheumatic fever, which is followed by Jaccoud’s arthropathy. Jaccoud’s arthropathy is a chronic, non-erosive, reversible (with proper splinting) joint disorder that may occur after repeated bouts of arthritis. This arthropathy is caused by inflammation of the joint capsule and subsequent fibrotic retraction, causing ulnar deviation of the fingers, through metacarpophalangeal joint subluxation, primarily of the fourth and fifth fingers [31].
\nThe greatest emphasis should be placed on the fact that all joints could be involved in lupus. Arthritis of lupus may be the presenting feature, and therefore, all cases of inflammatory arthritis must be evaluated with x-rays and a thorough history and physical, to exclude other diseases. Treatment would begin with the use of hydroxychloroquine and the addition of methotrexate. If necessary, abatacept (a CTLA4 inhibitor drug), could be added, as well as the newer medication discussed earlier, belimumab. Additionally, low dose steroids are often effective. While some practitioners may view steroids as poison, others feel the patient’s quality of life, on Prednisone (5 mg or less), even permanently could be appropriate, if this is necessary for disease control and improvement in the patient’s quality of life. The patient should be informed of necessity for vigilance with regard to sleep, lipid and blood pressure monitoring, and the risk of osteoporosis. In the final analysis, the ratio of logic needs to be brought into consideration. As a practicing rheumatologist, with a personal experience of 32 years, experience dictates that 5 mg of Prednisone or less in virtually all the inflammatory patients that cannot be weaned, failed to cause significant steroid side effects. In the minority of patients who do suffer steroid side effects from a 5 mg daily equivalent or less as they begin to age, skin fragility or perhaps early cataracts can be seen; however, this may be difficult to ascertain, unless their ophthalmologist is convinced that any posterior subscapular cataract is the definite consequence of steroid use. Otherwise, this would be difficult to ascertain [32].
\nApproximately 42–46% of patients develop a cytopenia, including leukopenia and anemia [29]. Cytopenias in lupus are typically recognized with anemia, often hemolytic or of chronic disease, thrombocytopenia, or thrombocytosis [33]. Thrombocytosis indicates inflammation, while thrombocytopenia is often autoimmune and antiplatelet antibodies lower platelet counts; however, this should not be taken for granted. As in Sjogren’s, the mechanism would be hypersplenism; however, the finding of thrombocytopenia must prompt a probe for lupus. This protocol also stands in the case of a low white blood cell count. A WBC less than 4000 units for all, or lymphocyte of less than 1000, should both prompt an evaluation and workup for lupus. These findings while not specific are quite typical. Please note that one isolated sample needs repeating.
\nApproximately 40% of lupus patients are diagnosed with nephritis [29]. The patient presents with blood or protein in the urine [34]. A renal biopsy is performed. A diagnosis is established - Mesangial proliferative, diffuse or focal proliferation, or pure membranous. The treatments for this vary. The current main stay treatment is mycophenolate mofetil. A new medication, which will be available in the near future, is calcineurin inhibitor, Voclasporin [35]. The data regarding this is promising. Rituximab, anecdotally, and in Pureview Data, indicates that it may also be helpful, although it is not the standard of care. Emphasis should be placed on the actuality that “the standard of care” should supersede the Food and Drug Administration’s indications for any drug. Approval for a drug by the Food and Drug Administration is solely based on the drug company’s actual “indication application” for that particular drug. While it may be used exclusively for its indication, in some cases it should be noted that the drug may prove more effective for off label use. This unfortunately seems to be a matter of “dollars and cents” where the pharmaceutical companies are concerned when determining the indication, they seek from the FDA.
\nRoughly 32% of lupus patients develop lupus that attacks the central nervous system [29]. Lupus involving the central nervous system is both a confusing and interesting aspect of the disease [36, 37]. Virtually any central nervous system or peripheral nervous system problem including, but not limited to, neuropathy, mononeuritis multiplex, seizures, blindness, loss of hearing, cranial nerve palsy, encephalopathy, psychosis and movement disorders, are not uncommon in the lupus population, and may frequently present as an initial feature of the disease.
\nTo reemphasize, all symptomatology that has been mentioned in this chapter may be an initial feature of lupus; however, the lack of swift rheumatology involvement often ultimately leads to a delay in diagnosis, which is always detrimental to the patient. Therefore, it is important to perform a comprehensive evaluation, including biopsy, angiogram, or other internal organ imaging, as well as complete serologic testing. Additionally, most patients are not willing to take medication for extended periods of time, unless it can be proven to them by their physician that the medication will indeed benefit them by alleviating the symptoms they are experiencing. This will assist in a more accurate diagnosis of lupus versus another disease process. As in every case involving a possible autoimmune process, emphasis should be placed on the importance of swift initiation of workup, as this will facilitate the timely establishment of proper treatment.
\nIf a patient is acutely ill with psychosis, they will typically be treated in a hospital setting, being initially seen by neurology and psychiatry, as other specialists. Unfortunately, this occurs before a rheumatologist is consulted [38]. An immediate MRI of the brain and lumbar puncture should be ordered, along with autoantibodies and cerebrospinal fluid, to assess the ribosomal P antibody, GAD65 antibody and NMO. With these proper evaluations, the likelihood of a CNS lupus diagnosis may be determined.
\nIt is quite typical in that lupus patients, including those with renal and central nervous system involvement, in general, do quite well with medical compliance. Published death rates, transplant rates, and dialysis rates for lupus nephritis are decidedly dependent upon the population type that is investigated. A well-educated compliant group of patients has a very low incidence of end stage renal disease while the noncompliant group almost certainly ultimately develop end stage renal disease [39].
\nAnother presentation would be abdominal pain, rather than splenomegaly. This would account for approximately 27% of lupus symptomatology [29]. A patient with severe abdominal pain, who is known to have lupus, after a proper workup for exclusion of perforated viscus or ischemic disease, the treatment would be steroids for what is mesenteric arteritis or serositis. The prognosis would not change, as they are both treated with moderate high dose steroids, oral or IV. Again, this can be a presenting feature of lupus. To the detriment of the patient, they are often are seen by gastroenterologists, who run a plethora of tests, including CTAs and MRIs of various organs, only to ultimately discover a case of hepatosplenomegaly with pain. At that point, to the misfortune of the patient, unnecessary surgery is generally performed for the hepatosplenomegaly, and sadly, the patient passes away as a result. If the patient had been treated properly, their life could have been saved, as they would have been successfully treated with 1 to 2 mg/kg of prednisolone or similar [40].
\nPancreatitis is an excellent example of a disease, which is not part of the listed diagnostic criteria for lupus. Raynaud’s phenomenon also not listed in the diagnostic criteria, although approximately 25% of lupus patients suffer from this condition [29, 41]. While either of those may be the presenting feature of systemic lupus, neither are listed as diagnostic criteria which is fine; however, the practitioner should perform a thorough workup to determine if a patient who has pancreatitis, as they may well have lupus. It should be noted however, that alcoholism, gallstone disease and pancreatic divisum, without the atypical sausage pancreas of IgG4-related disease, must be ruled out.
\nWith regard to Raynaud’s, the reversible spasm of vessels, usually induced by cold or emotional provocation, typically with triple phase color response from 5 to 60 minutes, is a frequent feature in lupus patients and may well be the initial finding of the disease. The practitioner must look past scleroderma, which has a more ominous prognosis than Raynaud’s related to lupus. This is often differentiated with a simple in-office nailfold capillaroscopy, which by in large, is a tremendously underutilized tool [42]. For the well-seasoned rheumatologist, this technique is used more often, but it should be used with regularity. In fact, nailfold capillaroscopy should be used as a baseline in all potential cases of autoimmune patients.
\nAttention to the heart and lungs is essential [43]. A patient with recurrent pneumonias is more likely to have lupus pneumonitis or an autoinflammatory disease, rather than the occurrence of infectious pneumonia every three months. After the onset of a second case of pneumonia, a rheumatologist should be consulted, but commonly, this does not occur. Regrettably, the patient who is suffering from an autoimmune disease has now suffered without a proper diagnosis for an unspecified amount of time. At this point, it would be advantageous to the patient to be seen by a rheumatologist without further delay.
\nOther common heart and lung manifestations of lupus include pleurisy and/or pericardial effusion [44]. Approximately 12% of lupus patients will develop a pericardial effusion [29]. Alarmingly, in several medical institutions, the treatment of choice for pericardial effusion is a pericardial window. Unfortunately, as in the case of inappropriate splenectomy with abdominal pain in a case of lupus, as mentioned earlier, a pericardial window is carries equal efficacy in a lupus patient presenting with pericardial effusion. As there is no indication for abdominal surgery for a patient with lupus abdominal pain, there is also virtually no indication for pericardial window in a lupus pericarditis patient. The incidence of tamponade is extraordinarily low. Myxomatosis valvular heart disease or so-called Libman-Sacks endocarditis, with or without phospholipid antibodies, is another finding that should be noted, although this is often woefully overlooked.
\nMany lupus patients suffer from autoimmunity that is frequently overlooked and therefore; the percentage of sufferers remains uncalculated [45]. The most common is likely Hashimoto’s thyroid disease; however, other conditions include Graves’ disease, myasthenia gravis, Addison’s disease, primary biliary cirrhosis, and autoimmune hepatitis. Each of these has autoimmune associations that should not be overlooked. Many of the features potentially seen in Sjogren’s syndrome, or many lupus-like features such as interstitial lung disease, should never be taken for granted based on the positive ANA or research criteria, as those patients may well have myositis or scleroderma. As mentioned in Part 2 of this chapter, “A Rheum with a Different View”, lupus should be considered in every disease.
\nThere are deep gaps between the thought process and treatment plans of a rheumatologist versus that of a general internist, family practitioner, ophthalmologist, or orthopedic surgeon or any other practitioner involved in a patient’s care.
\nRheumatology remains greatly underutilized. This regrettably adds substantial delay to the diagnosis and treatment of a patient. It bears mentioning again that all organ systems may be involved in lupus. Based on this, the all-purpose criteria is preferable to the new SLICC criteria for diagnosis of lupus, as it was far more practical [46]. It also bears mentioning again that no practitioner may diagnose lupus, or any other disease process, based solely on research criteria. Criteria are to be used merely as a guideline. For example, a patient presents to their physician, stating they are “not feeling well”. Subsequently, blood studies are ordered that reveal an ANA with a very high titer and upon further perusal, a very high DNA is also discovered, yet the physician fails to recognize that this patient has a forme-fruste of lupus. A rheumatologist would have started the patient on Plaquenil and educated them with regard to their diagnosis, and the physical ramifications to expect in the future.
\nTwo of the most interesting, but also difficult to treat diseases, a physician may encounter include pulmonary renal syndrome, presenting with alveolar hemorrhage, and glomerular nephritis with ANA, DNA, successfully treated with cyclophosphamide [47]. Another rare, but not uncommon complication of lupus, would be TTP with or without the ADAMTS13 gene and ocular inflammation and orbital pseudotumor. Consider the case of a patient who presented with true renal failure, visual hallucinations and movement disorder. At that point the patient was treated with IV Cytoxan and pulse steroids. Therefore, the patient did not have fever; however the patient was anemic and had schistocytes with an elevated reticulocyte count. Thus, the patient did not fulfill all of the criteria for TTP; therefore, a clinical diagnosis was made of the same. The patient responded almost immediately to with all features of the disease disappearing with plasma exchange. This is a wonderful case to recall, when a hematologist says to a patient, “It cannot be TTP because there is no fever”, apparently, this hematologist has lost sight of the fact that the high dose steroids likely blunted the fever. They may argue that there are not enough schistocytes [48] to fulfill the bacteria, however when schistocytes should not exist, and anemia cannot be explained, it can only be rationalized that the use of cyclophosphamides and high dose steroids lowered the schistocytes [49, 50]. This is a fantastic example of why research criteria alone, should never be used for diagnostic purposes.
\nIt is very important to understand the mechanism of action for each disease feature, as it will impact a patient’s treatment. For the purpose of example, thrombocytopenia will be seen in Sjogren’s syndrome and hypersplenism, while in lupus platelet antibodies, both conditions can be present with dry eyes and dry mouth. A salivary gland biopsy may not differentiate, as a positive lymphocyte score of 50 lymphocytes 4mm2, may presumably be seen in either condition. This may lead to an overlap diagnosis, or based on the mechanism of thrombocytopenia, it may also sway the diagnosis. Pneumonitis, while common in lupus, is seen in other autoimmune diseases, including sarcoidosis. All conditions mentioned may have a positive rheumatoid factor or positive ANA. Even CCP antibodies can be seen in autoimmune diseases with low values [51].
\nLupus is a great mimicker. This is due in part to a woeful lack of knowledge by most practitioners, as well as the absence of specific treatments. However, based on our available knowledge, with earlier institution of proper rheumatologic assistance, patients would be diagnosed with greater accuracy and proper treatments begun in a timely manner. Also, with patient compliance, education and understanding outcome is better reference. Consulting a rheumatologist promptly, would not only benefit the patient, but also profit the medical system by eradicating useless tests and treatment options that are often unmerited. Unfortunately, in a world of protocol, many are afraid to take an unconventional approach. It is because of this; other physicians often fail to consider a rheumatologic consultation [52].
\nIntechOpen aims to ensure that original material is published while at the same time giving significant freedom to our Authors. To that end we maintain a flexible Copyright Policy guaranteeing that there is no transfer of copyright to the publisher and Authors retain exclusive copyright to their Work.
',metaTitle:"Publication Agreement - Journals",metaDescription:"IntechOpen aims to ensure that original material is published while at the same time giving significant freedom to our Authors",metaKeywords:null,canonicalURL:"/page/publication-agreement-journals",contentRaw:'[{"type":"htmlEditorComponent","content":"The Corresponding Author (acting on behalf of all Authors) and INTECHOPEN LIMITED, incorporated and registered in England and Wales with company number 11086078 and a registered office at 5 Princes Gate Court, London, United Kingdom, SW7 2QJ conclude the following Agreement regarding the publication of a Journal Article:
\\n\\n1. DEFINITIONS
\\n\\nCorresponding Author: The Author of the Article who serves as a Signatory to this Agreement. The Corresponding Author acts on behalf of any other Co-Author. Co-Author: All other Authors of the Article besides the Corresponding Author. IntechOpen: IntechOpen Ltd., the Publisher of the Journal.
\\n\\nJournal: The publication as a collection of Articles compiled by IntechOpen .
\\n\\nArticle: The original literary work created by Corresponding Author and any Co Author that is the subject of this Agreement.
\\n\\n2. CORRESPONDING AUTHOR'S GRANT OF RIGHTS
\\n\\n2.1 Subject to the following Article, the Corresponding Author grants and shall ensure that each Co-Author grants, to IntechOpen, during the full term of copyright and any extensions or renewals of that term the following:
\\n\\n• An irrevocable, worldwide, royalty-free, perpetual, transferable, sublicensable, non-exclusive right to publish, communicate to the public, reproduce, republish, transmit, sell, distribute and otherwise use and make available the Article in whole, partial or adapted from and/or incorporated in or in conjunction with other works, in electronic and print editions of the Publication and in derivative works and on any platform owned and/or operated by IntechOpen, throughout the world, in all languages, and in all media and formats now known or later developed.
\\n\\n• An irrevocable, worldwide, royalty-free, perpetual, transferable, sublicensable, non-exclusive right to create and store electronic archival copies of the Article, including the right to deposit the Article in open access digital repositories.
\\n\\n• An irrevocable, worldwide, royalty-free, perpetual, transferable, sublicensable, non-exclusive right to license others to reproduce, translate, republish, transmit and distribute the Article in whole, partial or adapted from and/or incorporated in or in conjunction with other works under the condition that the Corresponding Author and each Co-Author is attributed (currently this is carried out by publishing the Article under a Creative Commons 4.0 International Licence).
\\n\\nThe aforementioned licenses shall survive the expiry or termination of this Agreement for any reason.
\\n\\n2.2 The Corresponding Author (on their own behalf and on behalf of any Co-Author) reserves the following rights to the Article but agrees not to exercise them in such a way as to adversely affect IntechOpen's ability to utilize the full benefit of this Publication Agreement: (i) reprographic rights worldwide, other than those which subsist in the typographical arrangement of the Article as published by IntechOpen; and (ii) public lending rights arising under the Public Lending Right Act 1979, as amended from time to time, and any similar rights arising in any part of the world. The Corresponding Author confirms that they (and any Co-Author) are and will remain a member of any applicable licensing and collecting society and any successor to that body responsible for administering royalties for the reprographic reproduction of copyright works.
\\n\\nSubject to the license granted above, copyright in the Article and all versions of it created during IntechOpen's editing process (including the published version) is retained by the Corresponding Author and any Co-Author.
\\n\\nSubject to the license granted above, the Corresponding Author and any Co-Author retains patent, trademark and other intellectual property rights to the Article.
\\n\\n2.3 All rights granted to IntechOpen in this Article are assignable, sublicensable or otherwise transferrable to third parties without the Corresponding Author's or any Co-Author’s specific approval.
\\n\\n2.4 The Corresponding Author (on their own behalf and on behalf of each Co Author) will not assert any rights under the Copyright, Designs and Patents Act 1988 to object to derogatory treatment of the Article as a consequence of IntechOpen's changes to the Article arising from translation of it, corrections and edits for house style, removal of problematic material and other reasonable edits.
\\n\\n3. CORRESPONDING AUTHOR'S DUTIES
\\n\\n3.1 When distributing or re-publishing the Article, the Corresponding Author agrees to credit the Journal in which the Article has been published as the source of first publication, as well as IntechOpen. The Corresponding Author warrants that each Co-Author will also credit the Journal in which the Article has been published as the source of first publication, as well as IntechOpen, when they are distributing or re publishing the Article.
\\n\\n3.2 When submitting the Article, the Corresponding Author agrees to:
\\n\\n• Comply with all instructions and guidelines provided by IntechOpen;
\\n\\n• Produce the Article with all due skill, care and diligence, and in accordance with good scientific practice;
\\n\\n• Submit all the corrections in due time as defined during the publishing process schedule.
\\n\\nThe Corresponding Author will be held responsible for the payment of the Article Processing Charge.
\\n\\nAll payments shall be due 30 days from the date of the issued invoice. The Corresponding Author or the payer on the Corresponding Author's and Co-Authors' behalf will bear all banking and similar charges incurred.
\\n\\n3.3 The Corresponding Author shall obtain in writing all consents necessary for the reproduction of any material in which a third-party right exists, including quotations, photographs and illustrations, in all editions of the Article worldwide for the full term of the above licenses, and shall provide to IntechOpen upon request the original copies of such consents for inspection (at IntechOpen's option) or photocopies of such consents.
\\n\\nThe Corresponding Author shall obtain written informed consent for publication from people who might recognize themselves or be identified by others (e.g. from case reports or photographs).
\\n\\n3.4 The Corresponding Author and any Co-Author shall respect confidentiality rights during and after the termination of this Agreement. The information contained in all correspondence and documents as part of the publishing activity between IntechOpen and the Corresponding Author and any Co-Author are confidential and are intended only for the recipient. The contents may not be disclosed publicly and are not intended for unauthorized use or distribution. Any use, disclosure, copying, or distribution is prohibited and may be unlawful.
\\n\\n4. CORRESPONDING AUTHOR'S WARRANTY
\\n\\n4.1 The Corresponding Author represents and warrants that the Article does not and will not breach any applicable law or the rights of any third party and, specifically, that the Article contains no matter that is defamatory or that infringes any literary or proprietary rights, intellectual property rights, or any rights of privacy. The Corresponding Author warrants and represents that: (i) the Article is the original work of themselves and any Co-Author and is not copied wholly or substantially from any other work or material or any other source; (ii) the Article has not been formally published in any other peer-reviewed journal or in a Journal or edited collection, and is not under consideration for any such publication; (iii) they themselves and any Co-Author are qualifying persons under section 154 of the Copyright, Designs and Patents Act 1988; (iv) they themselves and any Co-Author have not assigned and will not during the term of this Publication Agreement purport to assign any of the rights granted to IntechOpen under this Publication
\\n\\nAgreement; and (v) the rights granted by this Publication Agreement are free from any security interest, option, mortgage, charge or lien.
\\n\\nThe Corresponding Author also warrants and represents that: (i) they have the full power to enter into this Publication Agreement on their own behalf and on behalf of each Co-Author; and (ii) they have the necessary rights and/or title in and to the Article to grant IntechOpen, on behalf of themselves and any Co-Author, the rights and licenses expressed to be granted in this Publication Agreement. If the Article was prepared jointly by the Corresponding Author and any Co-Author, the Corresponding Author warrants and represents that: (i) each Co-Author agrees to the submission, license and publication of the Article on the terms of this Publication Agreement; and (ii) they have the authority to enter into this Publication Agreement on behalf of and bind each Co-Author. The Corresponding Author shall: (i) ensure each Co-Author complies with all relevant provisions of this Publication Agreement, including those relating to confidentiality, performance and standards, as if a party to this Publication Agreement; and (ii) remain primarily liable for all acts and/or omissions of each such Co-Author.
\\n\\nThe Corresponding Author agrees to indemnify and hold IntechOpen harmless against all liabilities, costs, expenses, damages and losses and all reasonable legal costs and expenses suffered or incurred by IntechOpen arising out of or in connection with any breach of the aforementioned representations and warranties. This indemnity shall not cover IntechOpen to the extent that a claim under it results from IntechOpen's negligence or willful misconduct.
\\n\\n4.2 Nothing in this Publication Agreement shall have the effect of excluding or limiting any liability for death or personal injury caused by negligence or any other liability that cannot be excluded or limited by applicable law.
\\n\\n5. TERMINATION
\\n\\n5.1 IntechOpen has a right to terminate this Publication Agreement for quality, program, technical or other reasons with immediate effect, including without limitation (i) if the Corresponding Author or any Co-Author commits a material breach of this Publication Agreement; (ii) if the Corresponding Author or any Co Author (being an individual) is the subject of a bankruptcy petition, application or order; or (iii) if the Corresponding Author or any Co-Author (being a company) commences negotiations with all or any class of its creditors with a view to rescheduling any of its debts, or makes a proposal for or enters into any compromise or arrangement with any of its creditors.
\\n\\nIn case of termination, IntechOpen will notify the Corresponding Author, in writing, of the decision.
\\n\\n6. INTECHOPEN’S DUTIES AND RIGHTS
\\n\\n6.1 Unless prevented from doing so by events outside its reasonable control, IntechOpen, in its discretion, agrees to publish the Article attributing it to the Corresponding Author and any Co-Author.
\\n\\n6.2 IntechOpen has the right to use the Corresponding Author’s and any Co-Author’s names and likeness in connection with scientific dissemination, retrieval, archiving, web hosting and promotion and marketing of the Article and has the right to contact the Corresponding Author and any Co-Author until the Article is publicly available on any platform owned and/or operated by IntechOpen.
\\n\\n6.3 IntechOpen is granted the authority to enforce the rights from this Publication Agreement, on behalf of the Corresponding Author and any Co-Author, against third parties (for example in cases of plagiarism or copyright infringements). In respect of any such infringement or suspected infringement of the copyright in the Article,
\\n\\nIntechOpen shall have absolute discretion in addressing any such infringement which is likely to affect IntechOpen's rights under this Publication Agreement, including issuing and conducting proceedings against the suspected infringer.
\\n\\n7. MISCELLANEOUS
\\n\\n7.1 Further Assurance: The Corresponding Author shall and will ensure that any relevant third party (including any Co-Author) shall, execute and deliver whatever further documents or deeds and perform such acts as IntechOpen reasonably requires from time to time for the purpose of giving IntechOpen the full benefit of the provisions of this Publication Agreement.
\\n\\n7.2 Third Party Rights: A person who is not a party to this Publication Agreement may not enforce any of its provisions under the Contracts (Rights of Third Parties) Act 1999.
\\n\\n7.3 Entire Agreement: This Publication Agreement constitutes the entire agreement between the parties in relation to its subject matter. It replaces and extinguishes all prior agreements, draft agreements, arrangements, collateral warranties, collateral contracts, statements, assurances, representations and undertakings of any nature made by or on behalf of the parties, whether oral or written, in relation to that subject matter. Each party acknowledges that in entering into this Publication Agreement it has not relied upon any oral or written statements, collateral or other warranties, assurances, representations or undertakings which were made by or on behalf of the other party in relation to the subject matter of this Publication Agreement at any time before its signature (together "Pre-Contractual Statements"), other than those which are set out in this Publication Agreement. Each party hereby waives all rights and remedies which might otherwise be available to it in relation to such Pre-Contractual Statements. Nothing in this clause shall exclude or restrict the liability of either party arising out of its pre-contract fraudulent misrepresentation or fraudulent concealment.
\\n\\n7.4 Waiver: No failure or delay by a party to exercise any right or remedy provided under this Publication Agreement or by law shall constitute a waiver of that or any other right or remedy, nor shall it preclude or restrict the further exercise of that or any other right or remedy. No single or partial exercise of such right or remedy shall preclude or restrict the further exercise of that or any other right or remedy.
\\n\\n7.5 Variation: No variation of this Publication Agreement shall be effective unless it is in writing and signed by the parties (or their duly authorized representatives).
\\n\\n7.6 Severance: If any provision or part-provision of this Publication Agreement is or becomes invalid, illegal or unenforceable, it shall be deemed modified to the minimum extent necessary to make it valid, legal and enforceable. If such modification is not possible, the relevant provision or part-provision shall be deemed deleted.
\\n\\nAny modification to or deletion of a provision or part-provision under this clause shall not affect the validity and enforceability of the rest of this Publication Agreement.
\\n\\n7.7 No partnership: Nothing in this Publication Agreement is intended to, or shall be deemed to, establish or create any partnership or joint venture or the relationship of principal and agent or employer and employee between IntechOpen and the Corresponding Author or any Co-Author, nor authorize any party to make or enter into any commitments for or on behalf of any other party.
\\n\\n7.8 Governing law: This Publication Agreement and any dispute or claim (including non-contractual disputes or claims) arising out of or in connection with it or its subject matter or formation shall be governed by and construed in accordance with the law of England and Wales. The parties submit to the exclusive jurisdiction of the English courts to settle any dispute or claim arising out of or in connection with this Publication Agreement (including any non-contractual disputes or claims).
\\n"}]'},components:[{type:"htmlEditorComponent",content:"The Corresponding Author (acting on behalf of all Authors) and INTECHOPEN LIMITED, incorporated and registered in England and Wales with company number 11086078 and a registered office at 5 Princes Gate Court, London, United Kingdom, SW7 2QJ conclude the following Agreement regarding the publication of a Journal Article:
\n\n1. DEFINITIONS
\n\nCorresponding Author: The Author of the Article who serves as a Signatory to this Agreement. The Corresponding Author acts on behalf of any other Co-Author. Co-Author: All other Authors of the Article besides the Corresponding Author. IntechOpen: IntechOpen Ltd., the Publisher of the Journal.
\n\nJournal: The publication as a collection of Articles compiled by IntechOpen .
\n\nArticle: The original literary work created by Corresponding Author and any Co Author that is the subject of this Agreement.
\n\n2. CORRESPONDING AUTHOR'S GRANT OF RIGHTS
\n\n2.1 Subject to the following Article, the Corresponding Author grants and shall ensure that each Co-Author grants, to IntechOpen, during the full term of copyright and any extensions or renewals of that term the following:
\n\n• An irrevocable, worldwide, royalty-free, perpetual, transferable, sublicensable, non-exclusive right to publish, communicate to the public, reproduce, republish, transmit, sell, distribute and otherwise use and make available the Article in whole, partial or adapted from and/or incorporated in or in conjunction with other works, in electronic and print editions of the Publication and in derivative works and on any platform owned and/or operated by IntechOpen, throughout the world, in all languages, and in all media and formats now known or later developed.
\n\n• An irrevocable, worldwide, royalty-free, perpetual, transferable, sublicensable, non-exclusive right to create and store electronic archival copies of the Article, including the right to deposit the Article in open access digital repositories.
\n\n• An irrevocable, worldwide, royalty-free, perpetual, transferable, sublicensable, non-exclusive right to license others to reproduce, translate, republish, transmit and distribute the Article in whole, partial or adapted from and/or incorporated in or in conjunction with other works under the condition that the Corresponding Author and each Co-Author is attributed (currently this is carried out by publishing the Article under a Creative Commons 4.0 International Licence).
\n\nThe aforementioned licenses shall survive the expiry or termination of this Agreement for any reason.
\n\n2.2 The Corresponding Author (on their own behalf and on behalf of any Co-Author) reserves the following rights to the Article but agrees not to exercise them in such a way as to adversely affect IntechOpen's ability to utilize the full benefit of this Publication Agreement: (i) reprographic rights worldwide, other than those which subsist in the typographical arrangement of the Article as published by IntechOpen; and (ii) public lending rights arising under the Public Lending Right Act 1979, as amended from time to time, and any similar rights arising in any part of the world. The Corresponding Author confirms that they (and any Co-Author) are and will remain a member of any applicable licensing and collecting society and any successor to that body responsible for administering royalties for the reprographic reproduction of copyright works.
\n\nSubject to the license granted above, copyright in the Article and all versions of it created during IntechOpen's editing process (including the published version) is retained by the Corresponding Author and any Co-Author.
\n\nSubject to the license granted above, the Corresponding Author and any Co-Author retains patent, trademark and other intellectual property rights to the Article.
\n\n2.3 All rights granted to IntechOpen in this Article are assignable, sublicensable or otherwise transferrable to third parties without the Corresponding Author's or any Co-Author’s specific approval.
\n\n2.4 The Corresponding Author (on their own behalf and on behalf of each Co Author) will not assert any rights under the Copyright, Designs and Patents Act 1988 to object to derogatory treatment of the Article as a consequence of IntechOpen's changes to the Article arising from translation of it, corrections and edits for house style, removal of problematic material and other reasonable edits.
\n\n3. CORRESPONDING AUTHOR'S DUTIES
\n\n3.1 When distributing or re-publishing the Article, the Corresponding Author agrees to credit the Journal in which the Article has been published as the source of first publication, as well as IntechOpen. The Corresponding Author warrants that each Co-Author will also credit the Journal in which the Article has been published as the source of first publication, as well as IntechOpen, when they are distributing or re publishing the Article.
\n\n3.2 When submitting the Article, the Corresponding Author agrees to:
\n\n• Comply with all instructions and guidelines provided by IntechOpen;
\n\n• Produce the Article with all due skill, care and diligence, and in accordance with good scientific practice;
\n\n• Submit all the corrections in due time as defined during the publishing process schedule.
\n\nThe Corresponding Author will be held responsible for the payment of the Article Processing Charge.
\n\nAll payments shall be due 30 days from the date of the issued invoice. The Corresponding Author or the payer on the Corresponding Author's and Co-Authors' behalf will bear all banking and similar charges incurred.
\n\n3.3 The Corresponding Author shall obtain in writing all consents necessary for the reproduction of any material in which a third-party right exists, including quotations, photographs and illustrations, in all editions of the Article worldwide for the full term of the above licenses, and shall provide to IntechOpen upon request the original copies of such consents for inspection (at IntechOpen's option) or photocopies of such consents.
\n\nThe Corresponding Author shall obtain written informed consent for publication from people who might recognize themselves or be identified by others (e.g. from case reports or photographs).
\n\n3.4 The Corresponding Author and any Co-Author shall respect confidentiality rights during and after the termination of this Agreement. The information contained in all correspondence and documents as part of the publishing activity between IntechOpen and the Corresponding Author and any Co-Author are confidential and are intended only for the recipient. The contents may not be disclosed publicly and are not intended for unauthorized use or distribution. Any use, disclosure, copying, or distribution is prohibited and may be unlawful.
\n\n4. CORRESPONDING AUTHOR'S WARRANTY
\n\n4.1 The Corresponding Author represents and warrants that the Article does not and will not breach any applicable law or the rights of any third party and, specifically, that the Article contains no matter that is defamatory or that infringes any literary or proprietary rights, intellectual property rights, or any rights of privacy. The Corresponding Author warrants and represents that: (i) the Article is the original work of themselves and any Co-Author and is not copied wholly or substantially from any other work or material or any other source; (ii) the Article has not been formally published in any other peer-reviewed journal or in a Journal or edited collection, and is not under consideration for any such publication; (iii) they themselves and any Co-Author are qualifying persons under section 154 of the Copyright, Designs and Patents Act 1988; (iv) they themselves and any Co-Author have not assigned and will not during the term of this Publication Agreement purport to assign any of the rights granted to IntechOpen under this Publication
\n\nAgreement; and (v) the rights granted by this Publication Agreement are free from any security interest, option, mortgage, charge or lien.
\n\nThe Corresponding Author also warrants and represents that: (i) they have the full power to enter into this Publication Agreement on their own behalf and on behalf of each Co-Author; and (ii) they have the necessary rights and/or title in and to the Article to grant IntechOpen, on behalf of themselves and any Co-Author, the rights and licenses expressed to be granted in this Publication Agreement. If the Article was prepared jointly by the Corresponding Author and any Co-Author, the Corresponding Author warrants and represents that: (i) each Co-Author agrees to the submission, license and publication of the Article on the terms of this Publication Agreement; and (ii) they have the authority to enter into this Publication Agreement on behalf of and bind each Co-Author. The Corresponding Author shall: (i) ensure each Co-Author complies with all relevant provisions of this Publication Agreement, including those relating to confidentiality, performance and standards, as if a party to this Publication Agreement; and (ii) remain primarily liable for all acts and/or omissions of each such Co-Author.
\n\nThe Corresponding Author agrees to indemnify and hold IntechOpen harmless against all liabilities, costs, expenses, damages and losses and all reasonable legal costs and expenses suffered or incurred by IntechOpen arising out of or in connection with any breach of the aforementioned representations and warranties. This indemnity shall not cover IntechOpen to the extent that a claim under it results from IntechOpen's negligence or willful misconduct.
\n\n4.2 Nothing in this Publication Agreement shall have the effect of excluding or limiting any liability for death or personal injury caused by negligence or any other liability that cannot be excluded or limited by applicable law.
\n\n5. TERMINATION
\n\n5.1 IntechOpen has a right to terminate this Publication Agreement for quality, program, technical or other reasons with immediate effect, including without limitation (i) if the Corresponding Author or any Co-Author commits a material breach of this Publication Agreement; (ii) if the Corresponding Author or any Co Author (being an individual) is the subject of a bankruptcy petition, application or order; or (iii) if the Corresponding Author or any Co-Author (being a company) commences negotiations with all or any class of its creditors with a view to rescheduling any of its debts, or makes a proposal for or enters into any compromise or arrangement with any of its creditors.
\n\nIn case of termination, IntechOpen will notify the Corresponding Author, in writing, of the decision.
\n\n6. INTECHOPEN’S DUTIES AND RIGHTS
\n\n6.1 Unless prevented from doing so by events outside its reasonable control, IntechOpen, in its discretion, agrees to publish the Article attributing it to the Corresponding Author and any Co-Author.
\n\n6.2 IntechOpen has the right to use the Corresponding Author’s and any Co-Author’s names and likeness in connection with scientific dissemination, retrieval, archiving, web hosting and promotion and marketing of the Article and has the right to contact the Corresponding Author and any Co-Author until the Article is publicly available on any platform owned and/or operated by IntechOpen.
\n\n6.3 IntechOpen is granted the authority to enforce the rights from this Publication Agreement, on behalf of the Corresponding Author and any Co-Author, against third parties (for example in cases of plagiarism or copyright infringements). In respect of any such infringement or suspected infringement of the copyright in the Article,
\n\nIntechOpen shall have absolute discretion in addressing any such infringement which is likely to affect IntechOpen's rights under this Publication Agreement, including issuing and conducting proceedings against the suspected infringer.
\n\n7. MISCELLANEOUS
\n\n7.1 Further Assurance: The Corresponding Author shall and will ensure that any relevant third party (including any Co-Author) shall, execute and deliver whatever further documents or deeds and perform such acts as IntechOpen reasonably requires from time to time for the purpose of giving IntechOpen the full benefit of the provisions of this Publication Agreement.
\n\n7.2 Third Party Rights: A person who is not a party to this Publication Agreement may not enforce any of its provisions under the Contracts (Rights of Third Parties) Act 1999.
\n\n7.3 Entire Agreement: This Publication Agreement constitutes the entire agreement between the parties in relation to its subject matter. It replaces and extinguishes all prior agreements, draft agreements, arrangements, collateral warranties, collateral contracts, statements, assurances, representations and undertakings of any nature made by or on behalf of the parties, whether oral or written, in relation to that subject matter. Each party acknowledges that in entering into this Publication Agreement it has not relied upon any oral or written statements, collateral or other warranties, assurances, representations or undertakings which were made by or on behalf of the other party in relation to the subject matter of this Publication Agreement at any time before its signature (together "Pre-Contractual Statements"), other than those which are set out in this Publication Agreement. Each party hereby waives all rights and remedies which might otherwise be available to it in relation to such Pre-Contractual Statements. Nothing in this clause shall exclude or restrict the liability of either party arising out of its pre-contract fraudulent misrepresentation or fraudulent concealment.
\n\n7.4 Waiver: No failure or delay by a party to exercise any right or remedy provided under this Publication Agreement or by law shall constitute a waiver of that or any other right or remedy, nor shall it preclude or restrict the further exercise of that or any other right or remedy. No single or partial exercise of such right or remedy shall preclude or restrict the further exercise of that or any other right or remedy.
\n\n7.5 Variation: No variation of this Publication Agreement shall be effective unless it is in writing and signed by the parties (or their duly authorized representatives).
\n\n7.6 Severance: If any provision or part-provision of this Publication Agreement is or becomes invalid, illegal or unenforceable, it shall be deemed modified to the minimum extent necessary to make it valid, legal and enforceable. If such modification is not possible, the relevant provision or part-provision shall be deemed deleted.
\n\nAny modification to or deletion of a provision or part-provision under this clause shall not affect the validity and enforceability of the rest of this Publication Agreement.
\n\n7.7 No partnership: Nothing in this Publication Agreement is intended to, or shall be deemed to, establish or create any partnership or joint venture or the relationship of principal and agent or employer and employee between IntechOpen and the Corresponding Author or any Co-Author, nor authorize any party to make or enter into any commitments for or on behalf of any other party.
\n\n7.8 Governing law: This Publication Agreement and any dispute or claim (including non-contractual disputes or claims) arising out of or in connection with it or its subject matter or formation shall be governed by and construed in accordance with the law of England and Wales. The parties submit to the exclusive jurisdiction of the English courts to settle any dispute or claim arising out of or in connection with this Publication Agreement (including any non-contractual disputes or claims).
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He serves as a reviewer for more than eighty international journals, books, and research proposals as well as an editor for special issues of renowned scientific journals.",institutionString:"Centro de Investigación en Materiales Avanzados",institution:{name:"Centro de Investigación en Materiales Avanzados",country:{name:"Mexico"}}},{id:"76477",title:"Prof.",name:"Mirza",middleName:null,surname:"Hasanuzzaman",slug:"mirza-hasanuzzaman",fullName:"Mirza Hasanuzzaman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/76477/images/system/76477.png",biography:"Dr. Mirza Hasanuzzaman is a Professor of Agronomy at Sher-e-Bangla Agricultural University, Bangladesh. He received his Ph.D. in Plant Stress Physiology and Antioxidant Metabolism from Ehime University, Japan, with a scholarship from the Japanese Government (MEXT). Later, he completed his postdoctoral research at the Center of Molecular Biosciences, University of the Ryukyus, Japan, as a recipient of the Japan Society for the Promotion of Science (JSPS) postdoctoral fellowship. He was also the recipient of the Australian Government Endeavour Research Fellowship for postdoctoral research as an adjunct senior researcher at the University of Tasmania, Australia. Dr. Hasanuzzaman’s current work is focused on the physiological and molecular mechanisms of environmental stress tolerance. Dr. Hasanuzzaman has published more than 150 articles in peer-reviewed journals. He has edited ten books and written more than forty book chapters on important aspects of plant physiology, plant stress tolerance, and crop production. According to Scopus, Dr. Hasanuzzaman’s publications have received more than 10,500 citations with an h-index of 53. He has been named a Highly Cited Researcher by Clarivate. He is an editor and reviewer for more than fifty peer-reviewed international journals and was a recipient of the “Publons Peer Review Award” in 2017, 2018, and 2019. He has been honored by different authorities for his outstanding performance in various fields like research and education, and he has received the World Academy of Science Young Scientist Award (2014) and the University Grants Commission (UGC) Award 2018. He is a fellow of the Bangladesh Academy of Sciences (BAS) and the Royal Society of Biology.",institutionString:"Sher-e-Bangla Agricultural University",institution:{name:"Sher-e-Bangla Agricultural University",country:{name:"Bangladesh"}}},{id:"187859",title:"Prof.",name:"Kusal",middleName:"K.",surname:"Das",slug:"kusal-das",fullName:"Kusal Das",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSBDeQAO/Profile_Picture_1623411145568",biography:"Kusal K. Das is a Distinguished Chair Professor of Physiology, Shri B. M. Patil Medical College and Director, Centre for Advanced Medical Research (CAMR), BLDE (Deemed to be University), Vijayapur, Karnataka, India. Dr. Das did his M.S. and Ph.D. in Human Physiology from the University of Calcutta, Kolkata. His area of research is focused on understanding of molecular mechanisms of heavy metal activated low oxygen sensing pathways in vascular pathophysiology. He has invented a new method of estimation of serum vitamin E. His expertise in critical experimental protocols on vascular functions in experimental animals was well documented by his quality of publications. He was a Visiting Professor of Medicine at University of Leeds, United Kingdom (2014-2016) and Tulane University, New Orleans, USA (2017). For his immense contribution in medical research Ministry of Science and Technology, Government of India conferred him 'G.P. Chatterjee Memorial Research Prize-2019” and he is also the recipient of 'Dr.Raja Ramanna State Scientist Award 2015” by Government of Karnataka. He is a Fellow of the Royal Society of Biology (FRSB), London and Honorary Fellow of Karnataka Science and Technology Academy, Department of Science and Technology, Government of Karnataka.",institutionString:"BLDE (Deemed to be University), India",institution:null},{id:"243660",title:"Dr.",name:"Mallanagouda Shivanagouda",middleName:null,surname:"Biradar",slug:"mallanagouda-shivanagouda-biradar",fullName:"Mallanagouda Shivanagouda Biradar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243660/images/system/243660.jpeg",biography:"M. S. Biradar is Vice Chancellor and Professor of Medicine of\nBLDE (Deemed to be University), Vijayapura, Karnataka, India.\nHe obtained his MD with a gold medal in General Medicine and\nhas devoted himself to medical teaching, research, and administrations. He has also immensely contributed to medical research\non vascular medicine, which is reflected by his numerous publications including books and book chapters. Professor Biradar was\nalso Visiting Professor at Tulane University School of Medicine, New Orleans, USA.",institutionString:"BLDE (Deemed to be University)",institution:{name:"BLDE University",country:{name:"India"}}},{id:"289796",title:"Dr.",name:"Swastika",middleName:null,surname:"Das",slug:"swastika-das",fullName:"Swastika Das",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/289796/images/system/289796.jpeg",biography:"Swastika N. Das is Professor of Chemistry at the V. P. Dr. P. G.\nHalakatti College of Engineering and Technology, BLDE (Deemed\nto be University), Vijayapura, Karnataka, India. She obtained an\nMSc, MPhil, and PhD in Chemistry from Sambalpur University,\nOdisha, India. Her areas of research interest are medicinal chemistry, chemical kinetics, and free radical chemistry. She is a member\nof the investigators who invented a new modified method of estimation of serum vitamin E. She has authored numerous publications including book\nchapters and is a mentor of doctoral curriculum at her university.",institutionString:"BLDEA’s V.P.Dr.P.G.Halakatti College of Engineering & Technology",institution:{name:"BLDE University",country:{name:"India"}}},{id:"248459",title:"Dr.",name:"Akikazu",middleName:null,surname:"Takada",slug:"akikazu-takada",fullName:"Akikazu Takada",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248459/images/system/248459.png",biography:"Akikazu Takada was born in Japan, 1935. After graduation from\nKeio University School of Medicine and finishing his post-graduate studies, he worked at Roswell Park Memorial Institute NY,\nUSA. He then took a professorship at Hamamatsu University\nSchool of Medicine. In thrombosis studies, he found the SK\npotentiator that enhances plasminogen activation by streptokinase. He is very much interested in simultaneous measurements\nof fatty acids, amino acids, and tryptophan degradation products. By using fatty\nacid analyses, he indicated that plasma levels of trans-fatty acids of old men were\nfar higher in the US than Japanese men. . He also showed that eicosapentaenoic acid\n(EPA) and docosahexaenoic acid (DHA) levels are higher, and arachidonic acid\nlevels are lower in Japanese than US people. By using simultaneous LC/MS analyses\nof plasma levels of tryptophan metabolites, he recently found that plasma levels of\nserotonin, kynurenine, or 5-HIAA were higher in patients of mono- and bipolar\ndepression, which are significantly different from observations reported before. In\nview of recent reports that plasma tryptophan metabolites are mainly produced by\nmicrobiota. He is now working on the relationships between microbiota and depression or autism.",institutionString:"Hamamatsu University School of Medicine",institution:{name:"Hamamatsu University School of Medicine",country:{name:"Japan"}}},{id:"137240",title:"Prof.",name:"Mohammed",middleName:null,surname:"Khalid",slug:"mohammed-khalid",fullName:"Mohammed Khalid",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/137240/images/system/137240.png",biography:"Mohammed Khalid received his B.S. degree in chemistry in 2000 and Ph.D. degree in physical chemistry in 2007 from the University of Khartoum, Sudan. He moved to School of Chemistry, Faculty of Science, University of Sydney, Australia in 2009 and joined Dr. Ron Clarke as a postdoctoral fellow where he worked on the interaction of ATP with the phosphoenzyme of the Na+/K+-ATPase and dual mechanisms of allosteric acceleration of the Na+/K+-ATPase by ATP; then he went back to Department of Chemistry, University of Khartoum as an assistant professor, and in 2014 he was promoted as an associate professor. In 2011, he joined the staff of Department of Chemistry at Taif University, Saudi Arabia, where he is currently an assistant professor. His research interests include the following: P-Type ATPase enzyme kinetics and mechanisms, kinetics and mechanisms of redox reactions, autocatalytic reactions, computational enzyme kinetics, allosteric acceleration of P-type ATPases by ATP, exploring of allosteric sites of ATPases, and interaction of ATP with ATPases located in cell membranes.",institutionString:"Taif University",institution:{name:"Taif University",country:{name:"Saudi Arabia"}}},{id:"63810",title:"Prof.",name:"Jorge",middleName:null,surname:"Morales-Montor",slug:"jorge-morales-montor",fullName:"Jorge Morales-Montor",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/63810/images/system/63810.png",biography:"Dr. Jorge Morales-Montor was recognized with the Lola and Igo Flisser PUIS Award for best graduate thesis at the national level in the field of parasitology. He received a fellowship from the Fogarty Foundation to perform postdoctoral research stay at the University of Georgia. He has 153 journal articles to his credit. He has also edited several books and published more than fifty-five book chapters. He is a member of the Mexican Academy of Sciences, Latin American Academy of Sciences, and the National Academy of Medicine. He has received more than thirty-five awards and has supervised numerous bachelor’s, master’s, and Ph.D. students. Dr. Morales-Montor is the past president of the Mexican Society of Parasitology.",institutionString:"National Autonomous University of Mexico",institution:{name:"National Autonomous University of Mexico",country:{name:"Mexico"}}},{id:"217215",title:"Dr.",name:"Palash",middleName:null,surname:"Mandal",slug:"palash-mandal",fullName:"Palash Mandal",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/217215/images/system/217215.jpeg",biography:null,institutionString:"Charusat University",institution:null},{id:"49739",title:"Dr.",name:"Leszek",middleName:null,surname:"Szablewski",slug:"leszek-szablewski",fullName:"Leszek Szablewski",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49739/images/system/49739.jpg",biography:"Leszek Szablewski is a professor of medical sciences. He received his M.S. in the Faculty of Biology from the University of Warsaw and his PhD degree from the Institute of Experimental Biology Polish Academy of Sciences. He habilitated in the Medical University of Warsaw, and he obtained his degree of Professor from the President of Poland. Professor Szablewski is the Head of Chair and Department of General Biology and Parasitology, Medical University of Warsaw. Professor Szablewski has published over 80 peer-reviewed papers in journals such as Journal of Alzheimer’s Disease, Biochim. Biophys. Acta Reviews of Cancer, Biol. Chem., J. Biomed. Sci., and Diabetes/Metabol. Res. Rev, Endocrine. He is the author of two books and four book chapters. He has edited four books, written 15 scripts for students, is the ad hoc reviewer of over 30 peer-reviewed journals, and editorial member of peer-reviewed journals. Prof. Szablewski’s research focuses on cell physiology, genetics, and pathophysiology. He works on the damage caused by lack of glucose homeostasis and changes in the expression and/or function of glucose transporters due to various diseases. He has given lectures, seminars, and exercises for students at the Medical University.",institutionString:"Medical University of Warsaw",institution:{name:"Medical University of Warsaw",country:{name:"Poland"}}},{id:"173123",title:"Dr.",name:"Maitham",middleName:null,surname:"Khajah",slug:"maitham-khajah",fullName:"Maitham Khajah",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/173123/images/system/173123.jpeg",biography:"Dr. Maitham A. Khajah received his degree in Pharmacy from Faculty of Pharmacy, Kuwait University, in 2003 and obtained his PhD degree in December 2009 from the University of Calgary, Canada (Gastrointestinal Science and Immunology). Since January 2010 he has been assistant professor in Kuwait University, Faculty of Pharmacy, Department of Pharmacology and Therapeutics. His research interest are molecular targets for the treatment of inflammatory bowel disease (IBD) and the mechanisms responsible for immune cell chemotaxis. He cosupervised many students for the MSc Molecular Biology Program, College of Graduate Studies, Kuwait University. Ever since joining Kuwait University in 2010, he got various grants as PI and Co-I. He was awarded the Best Young Researcher Award by Kuwait University, Research Sector, for the Year 2013–2014. He was a member in the organizing committee for three conferences organized by Kuwait University, Faculty of Pharmacy, as cochair and a member in the scientific committee (the 3rd, 4th, and 5th Kuwait International Pharmacy Conference).",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"195136",title:"Dr.",name:"Aya",middleName:null,surname:"Adel",slug:"aya-adel",fullName:"Aya Adel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/195136/images/system/195136.jpg",biography:"Dr. Adel works as an Assistant Lecturer in the unit of Phoniatrics, Department of Otolaryngology, Ain Shams University in Cairo, Egypt. Dr. Adel is especially interested in joint attention and its impairment in autism spectrum disorder",institutionString:"Ain Shams University",institution:{name:"Ain Shams University",country:{name:"Egypt"}}},{id:"94911",title:"Dr.",name:"Boulenouar",middleName:null,surname:"Mesraoua",slug:"boulenouar-mesraoua",fullName:"Boulenouar Mesraoua",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94911/images/system/94911.png",biography:"Dr Boulenouar Mesraoua is the Associate Professor of Clinical Neurology at Weill Cornell Medical College-Qatar and a Consultant Neurologist at Hamad Medical Corporation at the Neuroscience Department; He graduated as a Medical Doctor from the University of Oran, Algeria; he then moved to Belgium, the City of Liege, for a Residency in Internal Medicine and Neurology at Liege University; after getting the Belgian Board of Neurology (with high marks), he went to the National Hospital for Nervous Diseases, Queen Square, London, United Kingdom for a fellowship in Clinical Neurophysiology, under Pr Willison ; Dr Mesraoua had also further training in Epilepsy and Continuous EEG Monitoring for two years (from 2001-2003) in the Neurophysiology department of Zurich University, Switzerland, under late Pr Hans Gregor Wieser ,an internationally known epileptologist expert. \n\nDr B. Mesraoua is the Director of the Neurology Fellowship Program at the Neurology Section and an active member of the newly created Comprehensive Epilepsy Program at Hamad General Hospital, Doha, Qatar; he is also Assistant Director of the Residency Program at the Qatar Medical School. \nDr B. Mesraoua's main interests are Epilepsy, Multiple Sclerosis, and Clinical Neurology; He is the Chairman and the Organizer of the well known Qatar Epilepsy Symposium, he is running yearly for the past 14 years and which is considered a landmark in the Gulf region; He has also started last year , together with other epileptologists from Qatar, the region and elsewhere, a yearly International Epilepsy School Course, which was attended by many neurologists from the Area.\n\nInternationally, Dr Mesraoua is an active and elected member of the Commission on Eastern Mediterranean Region (EMR ) , a regional branch of the International League Against Epilepsy (ILAE), where he represents the Middle East and North Africa(MENA ) and where he holds the position of chief of the Epilepsy Epidemiology Section; Dr Mesraoua is a member of the American Academy of Neurology, the Europeen Academy of Neurology and the American Epilepsy Society.\n\nDr Mesraoua's main objectives are to encourage frequent gathering of the epileptologists/neurologists from the MENA region and the rest of the world, promote Epilepsy Teaching in the MENA Region, and encourage multicenter studies involving neurologists and epileptologists in the MENA region, particularly epilepsy epidemiological studies. \n\nDr. Mesraoua is the recipient of two research Grants, as the Lead Principal Investigator (750.000 USD and 250.000 USD) from the Qatar National Research Fund (QNRF) and the Hamad Hospital Internal Research Grant (IRGC), on the following topics : “Continuous EEG Monitoring in the ICU “ and on “Alpha-lactoalbumin , proof of concept in the treatment of epilepsy” .Dr Mesraoua is a reviewer for the journal \"seizures\" (Europeen Epilepsy Journal ) as well as dove journals ; Dr Mesraoua is the author and co-author of many peer reviewed publications and four book chapters in the field of Epilepsy and Clinical Neurology",institutionString:"Weill Cornell Medical College in Qatar",institution:{name:"Weill Cornell Medical College in Qatar",country:{name:"Qatar"}}},{id:"282429",title:"Prof.",name:"Covanis",middleName:null,surname:"Athanasios",slug:"covanis-athanasios",fullName:"Covanis Athanasios",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/282429/images/system/282429.jpg",biography:null,institutionString:"Neurology-Neurophysiology Department of the Children Hospital Agia Sophia",institution:null},{id:"190980",title:"Prof.",name:"Marwa",middleName:null,surname:"Mahmoud Saleh",slug:"marwa-mahmoud-saleh",fullName:"Marwa Mahmoud Saleh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/190980/images/system/190980.jpg",biography:"Professor Marwa Mahmoud Saleh is a doctor of medicine and currently works in the unit of Phoniatrics, Department of Otolaryngology, Ain Shams University in Cairo, Egypt. She got her doctoral degree in 1991 and her doctoral thesis was accomplished in the University of Iowa, United States. Her publications covered a multitude of topics as videokymography, cochlear implants, stuttering, and dysphagia. She has lectured Egyptian phonology for many years. Her recent research interest is joint attention in autism.",institutionString:"Ain Shams University",institution:{name:"Ain Shams University",country:{name:"Egypt"}}},{id:"259190",title:"Dr.",name:"Syed Ali Raza",middleName:null,surname:"Naqvi",slug:"syed-ali-raza-naqvi",fullName:"Syed Ali Raza Naqvi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259190/images/system/259190.png",biography:"Dr. Naqvi is a radioanalytical chemist and is working as an associate professor of analytical chemistry in the Department of Chemistry, Government College University, Faisalabad, Pakistan. Advance separation techniques, nuclear analytical techniques and radiopharmaceutical analysis are the main courses that he is teaching to graduate and post-graduate students. In the research area, he is focusing on the development of organic- and biomolecule-based radiopharmaceuticals for diagnosis and therapy of infectious and cancerous diseases. Under the supervision of Dr. Naqvi, three students have completed their Ph.D. degrees and 41 students have completed their MS degrees. He has completed three research projects and is currently working on 2 projects entitled “Radiolabeling of fluoroquinolone derivatives for the diagnosis of deep-seated bacterial infections” and “Radiolabeled minigastrin peptides for diagnosis and therapy of NETs”. He has published about 100 research articles in international reputed journals and 7 book chapters. Pakistan Institute of Nuclear Science & Technology (PINSTECH) Islamabad, Punjab Institute of Nuclear Medicine (PINM), Faisalabad and Institute of Nuclear Medicine and Radiology (INOR) Abbottabad are the main collaborating institutes.",institutionString:"Government College University",institution:{name:"Government College University, Faisalabad",country:{name:"Pakistan"}}},{id:"58390",title:"Dr.",name:"Gyula",middleName:null,surname:"Mozsik",slug:"gyula-mozsik",fullName:"Gyula Mozsik",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/58390/images/system/58390.png",biography:"Gyula Mózsik MD, Ph.D., ScD (med), is an emeritus professor of Medicine at the First Department of Medicine, Univesity of Pécs, Hungary. He was head of this department from 1993 to 2003. His specializations are medicine, gastroenterology, clinical pharmacology, clinical nutrition, and dietetics. His research fields are biochemical pharmacological examinations in the human gastrointestinal (GI) mucosa, mechanisms of retinoids, drugs, capsaicin-sensitive afferent nerves, and innovative pharmacological, pharmaceutical, and nutritional (dietary) research in humans. He has published about 360 peer-reviewed papers, 197 book chapters, 692 abstracts, 19 monographs, and has edited 37 books. He has given about 1120 regular and review lectures. He has organized thirty-eight national and international congresses and symposia. He is the founder of the International Conference on Ulcer Research (ICUR); International Union of Pharmacology, Gastrointestinal Section (IUPHAR-GI); Brain-Gut Society symposiums, and gastrointestinal cytoprotective symposiums. He received the Andre Robert Award from IUPHAR-GI in 2014. Fifteen of his students have been appointed as full professors in Egypt, Cuba, and Hungary.",institutionString:"University of Pécs",institution:{name:"University of Pecs",country:{name:"Hungary"}}},{id:"277367",title:"M.Sc.",name:"Daniel",middleName:"Martin",surname:"Márquez López",slug:"daniel-marquez-lopez",fullName:"Daniel Márquez López",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/277367/images/7909_n.jpg",biography:"Msc Daniel Martin Márquez López has a bachelor degree in Industrial Chemical Engineering, a Master of science degree in the same área and he is a PhD candidate for the Instituto Politécnico Nacional. His Works are realted to the Green chemistry field, biolubricants, biodiesel, transesterification reactions for biodiesel production and the manipulation of oils for therapeutic purposes.",institutionString:null,institution:{name:"Instituto Politécnico Nacional",country:{name:"Mexico"}}},{id:"196544",title:"Prof.",name:"Angel",middleName:null,surname:"Catala",slug:"angel-catala",fullName:"Angel Catala",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/196544/images/system/196544.jpg",biography:"Angel Catalá studied chemistry at Universidad Nacional de La Plata, Argentina, where he received a Ph.D. in Chemistry (Biological Branch) in 1965. From 1964 to 1974, he worked as an Assistant in Biochemistry at the School of Medicine at the same university. From 1974 to 1976, he was a fellow of the National Institutes of Health (NIH) at the University of Connecticut, Health Center, USA. From 1985 to 2004, he served as a Full Professor of Biochemistry at the Universidad Nacional de La Plata. He is a member of the National Research Council (CONICET), Argentina, and the Argentine Society for Biochemistry and Molecular Biology (SAIB). His laboratory has been interested for many years in the lipid peroxidation of biological membranes from various tissues and different species. Dr. Catalá has directed twelve doctoral theses, published more than 100 papers in peer-reviewed journals, several chapters in books, and edited twelve books. He received awards at the 40th International Conference Biochemistry of Lipids 1999 in Dijon, France. He is the winner of the Bimbo Pan-American Nutrition, Food Science and Technology Award 2006 and 2012, South America, Human Nutrition, Professional Category. In 2006, he won the Bernardo Houssay award in pharmacology, in recognition of his meritorious works of research. Dr. Catalá belongs to the editorial board of several journals including Journal of Lipids; International Review of Biophysical Chemistry; Frontiers in Membrane Physiology and Biophysics; World Journal of Experimental Medicine and Biochemistry Research International; World Journal of Biological Chemistry, Diabetes, and the Pancreas; International Journal of Chronic Diseases & Therapy; and International Journal of Nutrition. He is the co-editor of The Open Biology Journal and associate editor for Oxidative Medicine and Cellular Longevity.",institutionString:"Universidad Nacional de La Plata",institution:{name:"National University of La Plata",country:{name:"Argentina"}}},{id:"186585",title:"Dr.",name:"Francisco Javier",middleName:null,surname:"Martin-Romero",slug:"francisco-javier-martin-romero",fullName:"Francisco Javier Martin-Romero",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSB3HQAW/Profile_Picture_1631258137641",biography:"Francisco Javier Martín-Romero (Javier) is a Professor of Biochemistry and Molecular Biology at the University of Extremadura, Spain. He is also a group leader at the Biomarkers Institute of Molecular Pathology. Javier received his Ph.D. in 1998 in Biochemistry and Biophysics. At the National Cancer Institute (National Institute of Health, Bethesda, MD) he worked as a research associate on the molecular biology of selenium and its role in health and disease. After postdoctoral collaborations with Carlos Gutierrez-Merino (University of Extremadura, Spain) and Dario Alessi (University of Dundee, UK), he established his own laboratory in 2008. The interest of Javier's lab is the study of cell signaling with a special focus on Ca2+ signaling, and how Ca2+ transport modulates the cytoskeleton, migration, differentiation, cell death, etc. He is especially interested in the study of Ca2+ channels, and the role of STIM1 in the initiation of pathological events.",institutionString:null,institution:{name:"University of Extremadura",country:{name:"Spain"}}},{id:"217323",title:"Prof.",name:"Guang-Jer",middleName:null,surname:"Wu",slug:"guang-jer-wu",fullName:"Guang-Jer Wu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/217323/images/8027_n.jpg",biography:null,institutionString:null,institution:null},{id:"148546",title:"Dr.",name:"Norma Francenia",middleName:null,surname:"Santos-Sánchez",slug:"norma-francenia-santos-sanchez",fullName:"Norma Francenia Santos-Sánchez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/148546/images/4640_n.jpg",biography:null,institutionString:null,institution:null},{id:"272889",title:"Dr.",name:"Narendra",middleName:null,surname:"Maddu",slug:"narendra-maddu",fullName:"Narendra Maddu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/272889/images/10758_n.jpg",biography:null,institutionString:null,institution:null},{id:"242491",title:"Prof.",name:"Angelica",middleName:null,surname:"Rueda",slug:"angelica-rueda",fullName:"Angelica Rueda",position:"Investigador Cinvestav 3B",profilePictureURL:"https://mts.intechopen.com/storage/users/242491/images/6765_n.jpg",biography:null,institutionString:null,institution:null},{id:"88631",title:"Dr.",name:"Ivan",middleName:null,surname:"Petyaev",slug:"ivan-petyaev",fullName:"Ivan Petyaev",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Lycotec (United Kingdom)",country:{name:"United Kingdom"}}},{id:"423869",title:"Ms.",name:"Smita",middleName:null,surname:"Rai",slug:"smita-rai",fullName:"Smita Rai",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Integral University",country:{name:"India"}}},{id:"424024",title:"Prof.",name:"Swati",middleName:null,surname:"Sharma",slug:"swati-sharma",fullName:"Swati Sharma",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Integral University",country:{name:"India"}}},{id:"439112",title:"MSc.",name:"Touseef",middleName:null,surname:"Fatima",slug:"touseef-fatima",fullName:"Touseef Fatima",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Integral University",country:{name:"India"}}},{id:"424836",title:"Dr.",name:"Orsolya",middleName:null,surname:"Borsai",slug:"orsolya-borsai",fullName:"Orsolya Borsai",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Agricultural Sciences and Veterinary Medicine of Cluj-Napoca",country:{name:"Romania"}}},{id:"422262",title:"Ph.D.",name:"Paola Andrea",middleName:null,surname:"Palmeros-Suárez",slug:"paola-andrea-palmeros-suarez",fullName:"Paola Andrea Palmeros-Suárez",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Guadalajara",country:{name:"Mexico"}}}]}},subseries:{item:{id:"41",type:"subseries",title:"Water Science",keywords:"Water, Water resources, Freshwater, Hydrological processes, Utilization, Protection",scope:"