Diagnostic criteria proposed by Eichenfield et al. in 2003.
\r\n\tNot all mixtures of particles and liquids can be considered slurries. A slurry has its character quite different from the carrying liquid (sometimes referred to as the vehicle). A Newtonian liquid has its shear stress directly proportional to its rate of deformation, but this is seldom the case for a slurry. In general, slurries are referred to as non-Newtonian liquids and ways of dealing with them are important threads in this text.
\r\n\r\n\tPipe blockages and pipe wear cause high costs to industry, in both maintenance and loss of production. This waste, and environmental damage which comes with it, can be shown to be reduced by careful application of slurry technology. This book will welcome recent research efforts to understand slurries related to the above-mentioned topics.
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Patients frequently have high levels of total immunoglobin E (IgE) and a personal or family history of atopic-related diseases.
AD is one of the most common inflammatory cutaneous diseases with an incidence that has tripled in the last 3 decades in industrialized countries. Prevalence in children population is approximately 15–20%, while it is much lower in adults, between 1 and 3%.
Several studies demonstrate that AD has a high impact on patients’ quality of life (QoL). For some of them, the impairment in QoL is more significant than in some other chronic diseases such as hypertension, diabetes, or even psoriasis [1].
In this chapter, we will make a dual approach to AD. First, we will concentrate on the immunological mechanisms of AD and then will discuss the clinical and therapeutic aspects of the disease.
The immune system is a very complex and interactive network of cells and molecules to protect the host against potentially dangerous pathogens while keeping at the same time a state of tolerance against self and innocuous non-self-antigens [2, 3]. The immune system employs a large number of molecular and cellular mechanisms that must be tightly regulated to perform this vital function. Alterations on these mechanisms lead to the appearance of immune-related diseases such as recurrent infections, autoimmunity, tumor tolerance, organ rejection, as well as allergic and skin diseases such as AD [2, 4, 5, 6].
AD is one of the most prevalent chronic inflammatory diseases of the skin affecting both children and adults [7, 8]. The clinical features that characterize the disease are dry and scaly skin, eczema lesions, and chronic itching. AD is a very complex and debilitating disease that should be considered as a systemic disease associated with different comorbidities. The development of AD depends on the integration of multiple factors such as genetic background, environmental exposure, skin barrier, and immune alterations [9, 10, 11]. All these factors cooperate and synergize leading to the clinical manifestations of AD. Over the last years, our understanding on the immunological mechanisms underlying AD has significantly improved [12]. Today, it is well accepted that the inflammatory component of AD is mainly driven by aberrant type 2 immune responses, which significantly contribute also to barrier defects and itching [5, 13]. Other immune responses including Th17, Th22, and, to a lesser extent, Th1 cells can also contribute to AD at different stages of the disease as well as in different subsets of patients and phenotypes [11, 14, 15].
The immune system employs type 2 immune responses to combat parasites and helminths, as well as toxins and venoms [16, 17]. Parasites are pathogens very large in size that cannot be engulfed and eliminated by innate immune cells, and dangerous venoms/toxins might rapidly spread throughout the body. Therefore, the main aim of type 2 immune responses is to expulse away the pathogen from the body or destroy the toxins, thus avoiding their systemic dissemination and the lethal consequences for the host. Aberrant type 2 immune responses, due to different and sometimes unknown etiologies, might lead to the development of allergic diseases such as asthma or food allergy as well as to skin diseases such as AD [2, 4, 18]. Initially, AD was regarded as a Th2-mediated disease; however, recent findings showed that type 2 innate lymphoid cells (ILC2s) and other innate immune and effector cells also contribute to the orchestration of these responses. Therefore, the term type 2-mediate disease is more adequate according to our current knowledge [19, 20].
Different cell subsets from both arms of the immune system, as well as tissues and non-hematopoietic cells, directly contribute to the orchestration of type 2 immune responses, both locally and systemically [19]. Under normal conditions, the presence of helminths or toxic substances triggers the production of large amounts of alarmins such as TSLP, IL-33, or IL-25 by epithelial cells (ECs). Alarmins directly activate and expand ILC2s by mechanisms depending on IL-7 and condition the capacity of dendritic cells (DCs) to induce T helper (Th)2 and type 2 CD8+ cytotoxic T-cell (Tc2) responses by mechanisms depending on IL-4 [21]. Activated ILC2s, Th2, and Tc2 cells produce type 2 cytokines such as IL-4, IL-13, or IL-5, which contribute to the recruitment and activation of different effector cells such as eosinophils, basophils, and mast cells to the inflamed tissue. Type 2 cytokines also participate in the activation of non-hematopoietic cells and tissues, which in cooperation with the activated immune effectors’ cells aim at eliminating the potentially dangerous invading pathogen/toxin, avoiding systemic dissemination.
DCs are antigen professional presenting cells (APCs) that link innate and adaptive immune responses [2, 22]. They are localized in all peripheral tissues, circulating in the blood and lymphoid organs. Their primary function is to scan and collect antigens in the periphery (skin, airways, or gut), process these antigens into peptide fragments, and present them in the context of MHC molecules to naïve T cells. DCs express costimulatory molecules and produce polarizing cytokines, which, together with their migratory capacity, empower them as the essential APCs in the priming of T cell responses [15, 23].
Depending on the type of encountered antigen and the signals that DCs receive in the periphery and during the travel to the lymph node, they can generate different types of effector CD4+ T cells [24, 25]. When DCs encounter intracellular pathogens (viruses or bacteria), they produce large amounts of IL-12 and induce IFN-γ-producing Th1 cells that in turn activate NK cells and CD8+ T cells to combat these infections. Aberrant Th1 responses also associate other autoimmune diseases [25]. In contrast, extracellular pathogens (bacteria or fungi) condition DCs to produce large quantities of IL-23, IL-1β, TGF-β, and IL-6, thus promoting the generation of IL-17A-producing Th17 cells that contribute to neutrophilic infiltration to eliminate these pathogens. Alterations of Th17 responses have been associated with different autoimmune diseases and psoriasis [26]. Under certain circumstances, mucosal DCs can also generate IL-9-producing Th9 or IL-22-producing Th22 cells, which contribute to activate mast cells and to promote epidermal hyperplasia, respectively [24, 26]. As above discussed, the presence of parasites or venoms activates ECs and instructs DCs to polarize Th2 cells producing large amounts of type 2 cytokines such as IL-4, IL-13, IL-5, or IL-9. Aberrant Th2 responses are the main drivers of allergic diseases and AD [12, 25]. In addition to these effectors CD4+ T-cell responses, DCs can also generate regulatory T cells with potent suppressive capacity, which play a crucial role in keeping homeostasis avoiding excessive immune activation and tolerance induction [2, 3, 18, 27].
In humans, blood DCs are classified into two main groups: (i) myeloid dendritic cells (mDCs) and (ii) plasmacytoid dendritic cells (pDCs) [28]. According to the expression of specific markers, mDCs can be further divided into type 1 mDCs and type 2 mDCs [28, 29, 30].
pDCs are the primary producers of type I IFNs and are essential in antiviral responses, whereas different subsets of mDCs contribute to the orchestration of different types of immune responses. Both mDCs and pDCs are different phenotypic and functional DC subsets that cooperate to integrate and mount immune responses.
In the healthy skin, under non-inflammatory conditions, the number of DCs is relatively low with a clear predominance of epidermal and dermal Langerhans cells (LCs) [12, 31]. In contrast, the number and composition of DC subsets in the lesional skin of AD patients are altered with significant infiltration of inflammatory dendritic epidermal and dermal cells (IDECs and IDDCs, respectively) [12, 31]. DCs in the skin of AD patients express high levels of the high-affinity receptor for IgE (FcεRI), which might play a critical role in the priming and expansion of memory T cells. Besides, after IgE-FcεRI cross-linking, DCs produce a plethora of chemokines that add to the recruitment of Th2 cells and other inflammatory cells into the skin, thus enhancing inflammation. IDECs can also migrate to lymph node and polarize and increase the frequency of Th2 cells but also Th1, Th17, and Th22 as observed during the most chronic phases of AD [12, 31]. Overall, DCs play an essential role in the initiation and maintenance of type 2 immune responses in the context of AD as well as in the generation of other Th cell subsets detected during the chronic phases and in different phenotypes of AD patients.
The knowledge of the immunological mechanisms involved in the pathogenesis of AD has significantly improved over the last years. There are three phases in AD development involving different cytokines and cellular signatures that account for the clinical manifestations of the disease: (i) initial non-lesional stage, (ii) acute stage, and (iii) chronic stage.
The structural integrity and permeability to environmental insults are severely compromised in susceptible patients displaying skin barrier defects [5, 10]. These skin alterations might be originated due to different factors including genetic susceptibility (mutations in filaggrin and/or other key genes for stratum corneum and skin integrity), alterations in tight junction proteins (TJ), dysregulation of skin lipid composition, changes in pH, altered microbiome, high transepithelial water loss (TWEL), or high susceptibility to infections and irritants. These skin barrier defects allow the penetration of large amounts of allergens, pathogen-derived antigens, and/or other environmental insults into the lower epidermal layers, leading to the activation of keratinocytes [7]. Skin DCs uptake the encountered allergens and migrate to the closer lymph nodes conditioned by keratinocyte-derived alarmins such as TSLP, IL-33, or IL-25. These alarmins also activate tissue-resident ILC2s, which produce large amounts of type 2 cytokines facilitating DC migration and recruitment of inflammatory cells into the skin [7, 10]. Under these circumstances, DCs polarize naïve CD4+ T cells into allergen-specific Th2 cells by mechanisms depending on IL-4. The clonal expansion and activation of Th2 cells significantly contribute to IgE class-switching at the B level. The generated IgE+ B cells differentiate into plasma cells that produce large amounts of allergen-specific IgE antibodies that bind to the surface of mast cells and basophils, leading to the allergic sensitization [2, 4]. The induced Th2 cells home back and infiltrate the skin through lymph and circulation, leading to the classical skin inflammation observed of this initial stage even in the absence of skin lesions.
During the acute stage of AD, activated Th2 cells and ILC2s produce large amounts of IL-4, IL-13, IL-31, and IL-5 [12, 24]. IL-5 favors eosinophil recruitment into the skin and IL-31 in cooperation with IL-4 and IL-13 play a critical role in itching, thus initiating the vicious circle of itching-scratching that contributes to increase the damage of the already altered skin barrier and to enhance inflammation [12]. IL-31 directly act on sensory neurons, but it also promotes the growth of sensory nerves and skin hyperinnervation [32, 33]. IL-4 not only contributes to increasing the expression of IL-31 [34] but also together with IL-13 to sensitize neurons to a large variety of pruritogens such IL-33 and TSLP that increase after scratching, thus potentially contributing to chronic itch [32]. IL-4 and IL-13 also directly act on keratinocytes by inhibiting their differentiation, the production of antimicrobial peptides (AMPs), and altering lipid metabolism, thus enhancing barrier disruption. Six IL-13-activated keratinocytes produce an extensive battery of chemokines such as CCL17 (TARC), CCL26 (eotaxin), CCL18, and CCL22. In cooperation with the increment of vascular permeability induced by IL-4 through the increased of vascular cell adhesion molecule-1 (VCAM-1) on vascular endothelial cells, a massive infiltration of different types of inflammatory cells and vascular leakage takes place [5, 7]. Collectively, all these mechanisms account for the typical clinical symptoms of the AD acute stage, including itching and eczema lesions characterized by edema and spongiosis.
The perpetuation of this predominant type 2 inflammation might lead to the chronicity of the disease [5]. In this phase, inflammation increases and persists due to constant activation of keratinocytes, vascular endothelium, inflammatory cells, and chronic itching. Remarkably, in the chronic stage, other Th cell subsets including IFN-γ-producing Th1, IL-17-producing Th17, and IL-22-producing Th22 are also infiltrating the skin lesions [11, 15]. Depending on the AD subtypes, the relative frequency and contribution of these inflammatory Th cell subsets might vary significantly [11, 35, 36]. For example, in Asian AD patients as well as in some AD children subtypes, IL-17-producing Th17 cells might contribute to parakeratosis resembling typical features of psoriasis. In European-American, African American, and children AD patients, IL-22 produced by Th22 cells in cooperation with high levels of type 2 cytokines IL-4/IL-13 reinforce defective barrier function. It also enhances keratinocyte proliferation and promotes epidermal hyperplasia, leading to the lichenification and chronic itching typical of chronic stage [5, 10, 11, 35, 36].
Although AD frequently appears during childhood and tends to subside as the patient grows, there is a considerable number of patients who persist in adulthood.
Recently, adult-onset and elderly onset phenotypes have been described [37, 38].
The essential features of AD are eczematous lesions and pruritus. Former can be acute, subacute, or chronic
The clinical presentations, the lesion type and its distribution, are age specific, and this is a crucial aspect to consider when examining patients so as not to miss diagnose them.
AD phenotypes can be stratified according to multiple characteristics. One of the most used is the age-related clinical stratification, which classifies patients into four groups [39].
Lichenified lesions on the posterior part of the legs.
Chronic eczema in an adult patient with lichenified brown lesions on the lateral aspects of the neck that resemble dirt.
Widespread eczema in an elderly patient.
Patients can also be classified according to the age of onset [39]. Bieber et al. proposed six phenotypes, which included very early-onset (3 months–2 years), early-onset (2–6 yeas), childhood-onset (6–14 years), adolescent-onset (14–20 years), adult-onset (20–60 years), and very late-onset (>60 years). The majority of patients fall into the first group; however, adult-onset is a recently identified group, which represents about 20% of all the cases. The latter group includes two subsets, those with AD in the past and a long period of remission and those with a very late-onset.
It is important to consider that patients can present not only with widespread lesions but also with localized or morphologically distinct phenotypes.
Localized variants include selective eczema of the nipples, hands, eyelids, periauricular area, cheilitis, subnasal region, and genital area. The head and neck type are typical of the adult group and show involvement of the upper trunk and scalp.
Morphological variants comprise the follicular type, which presents as aggregated follicular papules, the papulo-lichenoid variant, the prurigo variant that resembles a prurigo nodularis, the nummular variant, and erythroderma [5, 37, 40] (Figure 4).
Erythrodermic variant of AD.
Silvestre Salvador et al. [37] recently described and classified the clinical forms of presentation of AD in adult patients. They identified 11 groups: lichenified/exudative flexural dermatitis, head-and-neck eczema, seborrheic dermatitis-like dermatitis, portrait dermatitis, hand eczema, generalized eczema, prurigo nodularis, nummular eczema, erythroderma, psoriasiform dermatitis, and multiple lesions of lichen simplex.
The diagnostic of AD is based on clinical features since no specific biomarkers or histological hallmarks exist. It relies on the morphology and distribution of the lesions, clinical history, and other clinical signs.
Multiple sets of diagnostic criteria have been developed since 1980 when Hanifin-Rajka proposed the first, which included major and minor features. It requires 3 out of the four major and 3 out of the 23 minor criteria to establish a diagnosis. Later, the “United Kingdom Working Party” settled a set, which followed the essence of the Hanifin-Rajka’s, but adapted it for epidemiological and clinical studies [5].
In 2003, Eichenfield et al. [41] revised the original criteria and elaborated a set dividing features into essential, important, and associated (Table 1). It also includes exclusionary criteria to help with the differential diagnostic. Probably, these criteria are the most used in a clinical setting.
Diagnostic criteria for SD | |||
---|---|---|---|
Essential features (must be present) | Pruritus | ||
Eczema (acute, subacute or chronic) | Typical morphology and age-specific patterns | Facial, neck, and extensor involvement in infants and children | |
Current or prior flexural lesions in any age group | |||
Sparing of groin and axillary regions | |||
Chronic or relapsing | |||
Important features (seen in most of the cases, adding support to the diagnosis) | Early onset | ||
Atopy | Personal and/or family history | ||
IgE reactivity | |||
Xerosis | |||
Associated features (help to suggest the diagnosis of AD but are too non-specific to be used for defining or detecting AD) | Atypical vascular response | ||
Keratosis pilaris/pityriasis alba/hyperlinear palms/ichthyosis | |||
Ocular or periorbital changes | |||
Other regional findings | |||
Perifollicular accentuation/lichenification/prurigo lesions | |||
Exclusionary conditions | Scabies | ||
Seborrheic dermatitis | |||
Contact dermatitis | |||
Ichthyosis | |||
Cutaneous T-cell lymphoma | |||
Psoriasis | |||
Photosensitivity dermatoses | |||
Immune deficiency diseases | |||
Erythroderma of other causes |
Diagnostic criteria proposed by Eichenfield et al. in 2003.
Adapted from Eichenfield et al. [41].
In 2016, Liu P et al. [42] proposed an easy-to-use set for adolescents and adults. They based the diagnostic on the presence of symmetric eczema for more than 6 months associated to one or more of the following: family or personal history of atopic-related diseases, eosinophilia, and elevated total or specific IgE.
When considering the diagnostic of AD, it is crucial making a thorough clinical history, which includes information regarding the chronicity of eczema, the presence of itch, and the personal and family history of atopy. In children, AD is one of the first diagnostics to consider, while in the adult population, probably due to a lack of familiarity with adult-onset disease and even when dealing with patients with a compatible clinical picture, the first diagnostic suspicion tends to be contact dermatitis. Physical examination is also mandatory to determine the morphology and distribution of the lesions, which can help to consider or even establish the diagnostic [37].
There are controversies regarding complementary tests, which are useful at ruling out differential diagnostics. According to the AAD guidelines, AD is a diagnostic of exclusion and should only be established after excluding other diseases [43].
Patch testing should be considered in patients with adult-onset disease, those with a chronic disease who fail to respond to adequate treatment, patients with atypical or changing distribution, as well as patients with patterns suggestive of allergic contact dermatitis. Patch test should always be assessed according to clinical history to determine the relevance of the results [37].
The utility of the prick test is somewhat controversial. A prick for airborne allergens could be useful in adults with an airborne pattern eczema involving the face, particularly eyelid area, neck, and exposed regions of upper limbs. Testing for food allergies might be of help in pediatric patients with generalized eczema that worsen when exposed to certain foods, but also in adult patients who are sensitized to pollen, as pollen-related foods can cause cross-reaction with airborne allergens and trigger flares. Ruling out a protein contact dermatitis could be indicated in patients with chronic hand eczema that flares when handling food [37, 44].
A blood test is not mandatory but can be useful at supporting the diagnostic of AD. High IgE levels and eosinophilia are frequent in these patients. Other parameters such as lactate dehydrogenase (LDH), serum thymic activation regulator chemokine (sTARC)/CCL17, CCL27, cationic eosinophilic protein (CEP), and antitransglutaminase antibodies may provide with information regarding the severity or helping in the differential diagnostic (see biomarkers).
Although the histopathologic picture of atopic dermatitis does not differ from other types of eczema, a skin biopsy may help rule out other diagnostics such as cutaneous T-cell lymphoma (CTCL), psoriasis, or drug reactions [37].
Including a simple blood test with hemogram, liver function, renal function, LDH, total IgE (and specific if the clinical history suggests it), IgA, and antitransglutaminase antibodies would be reasonable during the initial diagnostic workup. Indications for a patch test and prick test are those specified before.
After setting up the diagnostic of AD, it is essential to assess the severity of the disease and its impact on patient’s quality of life.
Several scales evaluate the severity; some of them include just objective signs, while others also include subjective patient’s symptoms.
Most of the scales are composite score systems, which assess different aspects of the disease (Table 2).
Severity | Quality of life | ||||||
---|---|---|---|---|---|---|---|
Scale | Score | Description | Msc | Scale | Score | Description | Msc |
SCORAD | 0–103 | <25 mild 25–50 moderate >50 severe | 8.7 | HADS | 0–42 (A/D) | 0–7 normal 8–10 borderline abnormal 11–21 abnormal | N/A |
EASI | 0–72 | ≤7 mild >7–21 moderate >21 severe | 6.6 | DLQI | 0–30 | 0–1 no effect at all on patient’s life 2–5 small effect 6–10 moderate effect 11–20 very large effect 21–30 extremely large effect | 4 |
IGA | 0–4 | 0 clear 1 almost clear 2 mild 3 moderate 4 severe | N/A | ||||
POEM | 0–28 | 0–2 clear or almost clear 3–7 mild 8–16 moderate 17–24 severe 25–28 very severe | 3.4 | ||||
VAS pruritus | 0–10 | The higher the score, the more severe the pruritus | 2–3 | ||||
VAS sleep | 0–10 | The higher the score, the more sleeplessness | 2–3 |
Scales of severity and quality of life.
SCORAD, scoring of atopic dermatitis; EASI, eczema area and severity index; HADS, hospital anxiety and depression scale; DLQI, dermatology life quality index; POEM, patient-oriented eczema measures for eczema; VAS, visual analogue scale; MSC, minimal significant change.
The most used in European countries is the Scoring of Atopic Dermatitis (SCORAD). It first evaluates the body surface area (BSA) affected and then gives a score from 0 to 3 for each of the following clinical features: erythema, edema, excoriation, swelling/crusts, lichenification, and xerosis. Finally, the patient is asked to rank pruritus and sleeplessness from 0 (best situation) to 10 (worst situation), giving a total score that ranges from 0 to 103, being the latter the most severe. It is considered a score from 0 to 25 as a mild disease, 25–50 as moderate, and 50 and above as severe.
Eczema area and severity index (EASI) is a scale based on PASI score.
EASI is a more objective tool, which does not include the patient’s symptoms, which is widely used in the US and also in the setting of most of the clinical trials. It divides the body into four parts, head and neck, trunk, upper limbs, and lower limbs. The first step is to assess the affected surface in each of the zones and then score erythema, edema, excoriation, and lichenification from 0 to 3. Each score is multiplied by a specific quotient, obtaining a final number that ranges from 0 to 72.
The patient-oriented eczema measures for eczema (POEM) is a symptom score that measures the subjective symptoms of the patient. The final result ranges from 0 to 28, being the latter the worst.
Investigator global assessment (IGA) is an easy-to-use scale that describes the overall appearance of the lesions and scores the severity from 0 to 3, 0 means a clear, 1 almost clear, 2 mild, 3 moderate, and 4 severe disease. Unlike the other three scales, it is not a validated score, but a global assessment of the disease.
Assessing disease impact on patient’s quality of life is as important as evaluating the severity.
There are over ten disease-specific tests available for AD and more than 25 generic instruments that can be used in AD [45]. Each of these tools focuses on different aspects of the disease, not only regarding the patient but also their family or close relatives. Table 2 shows two of the most used scales in assessing QoL.
There are also non-disease-specific questionnaires that study the school or work productivity, focusing not only on work absenteeism but also on presenteeism. One of the most known is WPAI (Work Productivity and Activity Impairment), which is composed of 6 questions regarding the effect of the disease on the ability to work and perform regular activities.
Biomarkers are an interesting matter of debate nowadays. Although there is plenty of literature on the topic, the utility and applicability of them still present some concerns.
A biomarker is a common term used across the atopic dermatitis literature. There are two definitions proposed by the World Health Organization (WHO) and by the National Institutes of Health (NIH) biomarkers definition group, which largely overlap. The WHO defines it as “any substance, structure or process that can be measured in the body or its products and influence or predict the incidence of outcome or disease. Biomarkers can be classified into markers of exposure, effect and susceptibility” [46], while the NIH definition is “a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention.” [47].
There are two types of biomarkers, those used for selection or stratification of the patients and those used for monitoring the clinical response.
The former includes screening, diagnostic, prognostic, and predictive biomarkers, while the latter comprises severity and pharmacodynamic markers [48].
Other parameters, such as high levels of cord IgE, infantile a-lymphotoxin and FcεRI-β during pregnancy, as well as high TEWL and SPINK5/LEKTI, could also be useful as screening biomarkers [48].
Filaggrin and leukotriene B4 serum levels could be two valuable biomarkers, as they have been shown to differ from healthy controls significantly. AD patients tend to present higher levels of the former and lower of the latter [51].
Recently, Wollenberg et al. described that higher levels of serum periostin and dipeptidyl-dipeptidase 4 (DDP4) conditioned a better response to anti-IL-13 therapies. On the other hand, the presence of single-nucleotide polymorphism (SNP) in the gene promoter region of UGT1A9 is related to low mycophenolate blood levels, and thus a worse response to the drug. Increasing the dose could solve this lack of response [48, 52].
Tacrolimus is metabolized by CYP3A4 and CYP3A5. CYP3A4*22 and CYP3A5*3 are seen in slow metabolizers, leading to high blood levels. CYP3A5*3 is associated with a fast metabolism, and it entails low blood levels.
Increased activity of UGT1A9 caused by SNPs can lead to a lack of response to mycophenolate due to low blood levels [48].
Azathioprine (AZA) adverse events can be predicted by genotyping thiopurine methyltransferase. The risk of myelotoxicity and liver toxicity can be assessed by monitoring AZA metabolites 6-thioguanine nucleotides and 6-methylmercaptopurine ribonucleotides [53].
Table 3 summarizes these biomarkers.
Biomarker | Cross-sectional studies | Longitudinal studies | Conclusion |
---|---|---|---|
sTARC/CCL17 | Yes | Yes | Potential biomarker for severity and evolution of the disease. Best characterized biomarker [54] |
Total IgE | Yes | Yes | Could be a good biomarker for the severity but not for the disease evolution [54] |
cTACK/CCL27 | Yes | No | Potential biomarker for severity [54] |
ECP | Yes | Yes | Questionable value as a severity and evolution biomarker [54] |
EDN | Yes | No | Potential biomarker for the severity. Could be a predictor of relapse in severe AD [57] |
LDH | Yes | No | Potential biomarker for severity [54] |
Periostin | Yes | No | Good correlation with disease severity and chronicity [58] |
IL-18 | Yes | No | Potential biomarker for severity [54] |
E-selectin | Yes | No | Potential biomarker for severity [54] |
CD30 | Yes | No | Potential biomarker for severity [54] |
IL-2R, IL-4R, IL-31, and tryptase | Yes | No | May correlate with severity. More studies needed [54, 59] |
Severity biomarkers.
ECP, eosinophil cationic protein; EDN, eosinophil derived neurotoxin; LDH, lactate dehydrogenase.
Several factors have been associated with the development of AD. Some are regarded as risk factors, while others have a protective role.
Atopy family history and loss-of-function mutations in the gene of filaggrin are two clear risk factors for AD. About 70% of the patients have a positive family history of atopic diseases. The OR for children with one parent affected, compared to those without any, is 2–3, while those with the two parents affected it is 3–5.
FLG-null mutations condition a more severe, persistent and early-onset disease with a higher tendency to eczema herpeticum [43, 60].
Kelleher et al., have recently described that skin barrier dysfunction at 2 days and 2 months of life, as well as neonatal adiposity, increases the risk of AT during the first year of life.
An increase in the transepidermal water loss (TWEL) at 2 days and 2 months of life conditions to a higher incidence of AD at 6 and 12 months, regardless of the FLG mutations, family history, or presence of itchy flexural rash at 2 months [61].
Besides, a fat mass of the 80th percentile or higher at day two might also be a predictor for AD at 6 and 12 months of age [62].
Risk and protective factors are summarized in Table 4.
Risk factors |
|
Not risk factors |
|
Protective factors |
|
Compared to non-AD patients, patients with AD have a higher incidence of comorbidities that include not only the atopic march associated diseases but also other disorders. The sequential appearance, since early ages, of atopic dermatitis, allergic rhinitis, asthma, and rhinitis is known as the atopic march and is frequently seen together in patients with AD. Other diseases as chronic pulmonary disease, chronic rhinosinusitis, urticaria, autoimmune disorders, conjunctivitis, eosinophilic esophagitis, nasal polyposis, obesity, bacterial, fungal, and viral infections are also seen more frequently in these patients. Neuropsychiatric disorders including anxiety, depression, attention deficit hyperactivity disorder (ADHD), and sleep disturbances are also more prevalent in AD patients than controls.
In a study from the US, authors showed that not only these diseases are more frequent among AD patients but also that are more likely to occur in those with severe disease compared to less severe patients [64].
Finally, an increase in cardiovascular events has been reported in these patients. Andersen et al. showed that this higher incidence was due to an increased burden of comorbidities and detrimental lifestyle behavior [65]. Brunner et al., later suggested that inflammatory mediators involved in the atherosclerosis development such as CCL7, IL16, PI3, and E-selectin would be responsible for this increase in the incidence and that they were strongly related to the severity of cutaneous inflammation rather than obesity or lifestyle behavior [66].
There is not a single approach to the treatment of patients with AD. It is a patient-tailored treatment, which depends on the patients’ predominant symptoms and past medical history.
The therapy aims to control the skin barrier disruption, the altered immune response, and microbial infections, as well as pruritus [67].
Baseline treatment for AD is moisturizers to help to prevent water loss and maintaining skin hydration. Emollients, humectants, or occlusive agents should be used as a maintenance treatment for all patients with AD. The recommended weekly amount is 250-500 g in adult patients and about 100 g in children.
The use of emollients in inflamed skin is poorly tolerated, it is advised to treat the inflammation first with topical treatments and then apply the moisturizer, at least twice a day [68].
According to the European guidelines for the treatment of AD, an “emollient” is a “topical formulation with vehicle-type substances lacking active ingredients,” whereas “emollients plus” refers to “topical formulations with vehicle-type substances and additional active, non-medicated substances” and are meant to target specific lesions [68].
Simpson et al. showed that strict emollient therapy from birth in children at a high risk of developing AD (a parent or full sibling with AD, asthma, or allergic rhinitis) was a practical preventive approach [69].
It is also essential to keep optimal skin hygiene. There are some controversies regarding daily bath; however, a short bath of up to 5 minutes with bath oils or non-irritant and low-allergen formulas, to eliminate crusts and bacterial contaminants, is advised.
Adding antiseptics to the bathwater may be useful in cases that show bacterial superinfection [68].
Topical corticosteroids and calcineurin inhibitors are the treatments of choice for flares in patients with mild disease (SCORAD <25/EASI <7). Moderate or recurrent cases (SCORAD 25–50/EASI 7–21) require proactive therapy with more potent corticosteroids, calcineurin inhibitors, or phototherapy. The proactive scheme consists of daily application of emollients to unaffected skin combined with intermittent use (twice weekly) of the anti-inflammatory drug in usually affected sites. Studies have proven long-term security and efficacy in reducing relapses [68].
The amount of topical anti-inflammatory drugs should follow the fingertip unit rule (0.5 g), which is the adequate amount for application to two adult palm area (approx. 2% of adult body surface area).
Phototherapy, UVA1 and narrow-band UVB, has shown its long-term efficacy in AD in multiple studies. Except for high doses of UVA1, it is not indicated during flares, but in pruritic and lichenified chronic forms. Most of the times, concomitant use of emollients and/or anti-inflammatory therapy is advised.
Severe patients (SCORAD > 50/EASI > 20) require a more aggressive approach with immunosuppressive agents or biologicals.
Crisaborole is a topical phosphodiesterase 4 (PDE4) blocker approved in the US for the treatment of mild-to-moderate AD in patients 2 years old and older, which has shown to be more effective than the vehicle alone. There are no comparative studies with topical corticosteroids or calcineurin inhibitors [67, 68, 70].
Topical Janus kinase inhibitors are still not licensed for the treatment of AD, but they are in the pipeline of multiple laboratories that are currently conducting phase II studies.
Although there is not enough evidence to support the use of both first and second-generation anti-H1, the former should be used with caution in patients with AD and sleep disturbances.
Other immunosuppressants such as methotrexate (15–25 mg/week), azathioprine (1–3 mg/kg/day), and mycophenolate mofetil (up to 3 g/day) are used off-label. These tend to have a slower onset of the effect, around 8–12 weeks, but with a more prolonged residual effect once the treatment is stopped [71].
No studies are comparing the efficacy of the three agents; however, Eckert et al. have recently shown that patients receiving mycophenolate mofetil required more oral corticosteroid than the other treatments, whereas those receiving CsA were the patients who needed the least [72].
Two studies compared the overall efficacy of methotrexate and azathioprine and concluded to be equivalent [73, 74].
It is essential to regularly monitor these patients for possible side effects, mainly liver toxicity.
Dupilumab is the first biological licensed for AD. It is a fully human monoclonal antibody that blocks a chain of the IL-4 receptor, which is common in the receptor for IL-4 and IL-13. It is approved as first-line therapy for adult moderate-to-severe AD who are candidates to systemic therapy. Clinical trials showed its efficacy and favorable safety profile on AD patients. Taking all the clinical trials together, about 70% of the patients achieved an EASI 75 or higher with a time-to-full-clinical-response of about 4 weeks. Pruritus showed a rapid response with an initial improvement at 2 weeks [71, 75].
Recent case series have observed a similar response [76].
It has been shown that dupilumab improves the AD inflammatory signature [77].
The main reported side effects were conjunctivitis and local reaction at the site of injection.
The recommended dose of dupilumab in adults is an initial dose of 600 mg followed by 300 mg every 15 days. There is no need for complementary studies before starting the treatment.
Only patients with previous helminthic infections should receive specific treatment before dupilumab.
Due to a lack of data, live and live attenuated vaccines should not be given currently with dupilumab. It is recommended to be up to date with immunization prior to the treatment. Contraindications include hypersensitivity to dupilumab or any of its excipients [78].
Currently, dupilumab is also licensed for asthma.
Several other molecules are under investigation [70].
Tralokinumab and lebrikizumab are fully human monoclonal antibodies that target IL-13. They have shown sustained clinical improvement in moderate-to-severe AD patients in phase II studies with an acceptable safety and tolerability profile. Wollenberg et al. showed that patients with higher serum levels of periostin and DDP4 had a better response to tralokinumab compared to those with lower levels [52].
Tralokinumab has already begun phase III trials, whereas lebrikizumab has yet to start.
Nemolizumab, a humanized monoclonal antibody against the receptor A of IL-31, has also shown efficacy in phase II trials in patients with moderate-to-severe AD. IL-31 plays a role in the pathogenesis of AD and pruritus. The two phase 2 clinical trial showed not only a rapid and maintained effect on pruritus but also AD scores (EASI and BSA) [79, 80].
Fezakinumab is a fully human monoclonal antibody against IL-22. The phase 2a clinical trial showed a sustained clinical improvement in severe AD patients [81].
Tezepelumab is a fully human monoclonal antibody that targets TSLP. In the phase 2a trial, a non-statistically significant improvement over placebo at week 12 was observed [82].
There are contradictory papers regarding the efficacy of ustekinumab, a fully human monoclonal antibody against the p40 subunit shared by IL-12 and IL-23 [83, 84, 85, 86, 87, 88].
There are several small molecules in development for AD.
Apremilast is an oral PDE4 inhibitor approved for the treatment of obstructive pulmonary disease, plaque psoriasis, and psoriatic arthritis [89]. Small series of cases have shown its potential as a treatment for AD [90, 91].
Baricitinib, a JAK 1 and 2 inhibitors, abrocitinib and upadacitinib, selective JAK 1 inhibitors, are currently running phase 3 trials. Phase 2 showed positive results regarding efficacy and safety for the three molecules [92].
Finally, delgocitinib, a small molecule that targets JAK 1, 2, 3 and TYK 2 demonstrated rapid improvement in clinical signs and symptoms with a favorable safety profile, in a phase 2 trial [93].
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Recently, silver nanoparticles have been harnessed as delivery vehicles for therapeutic agents, including antisense oligonucleotides, and other small molecules. Silver is the most profit-oriented precious metal used in the preparation of nanoparticles and nanomaterials because of its antibacterial, antiviral, antifungal, antioxidant and unusually enhanced physicochemical properties compared to the bulk material such as optical, thermal, electrical, and catalytic properties. Small silver nanoparticles offer many advantages as drug carriers, including adjustable size and shape, enhanced stability of surface-bound nucleic acids, high-density surface ligand attachment, transmembrane delivery without harsh transfection agents, protection of the attached therapeutics from degradation, and potential for improved timed/controlled intracellular drug-delivery. Plant-mediated synthesis of silver nanoparticles is gaining interest due to its inexpensiveness, providing a healthier work environment, and protecting human health leading to lessening waste and safer products. The chapter presents the essential physicochemical characteristics, antibacterial, and anticancer properties which silver nanoparticles obtained by plant-mediated methods possess, and their application as drug-delivery systems with a critical view on the possible toxicity on the human body.",book:{id:"7437",slug:"nanomedicines",title:"Nanomedicines",fullTitle:"Nanomedicines"},signatures:"Nadezhda Ivanova, Viliana Gugleva, Mirena Dobreva, Ivaylo\nPehlivanov, Stefan Stefanov and Velichka Andonova",authors:[{id:"202958",title:"Dr.",name:"Velichka",middleName:null,surname:"Andonova",slug:"velichka-andonova",fullName:"Velichka Andonova"},{id:"265332",title:"MSc.",name:"Nadezhda",middleName:null,surname:"Ivanova",slug:"nadezhda-ivanova",fullName:"Nadezhda Ivanova"},{id:"265333",title:"MSc.",name:"Viliana",middleName:null,surname:"Gugleva",slug:"viliana-gugleva",fullName:"Viliana Gugleva"},{id:"265334",title:"MSc.",name:"Mirena",middleName:null,surname:"Dobreva",slug:"mirena-dobreva",fullName:"Mirena Dobreva"},{id:"265335",title:"Mr.",name:"Stefan",middleName:"Radnev",surname:"Stefanov",slug:"stefan-stefanov",fullName:"Stefan Stefanov"},{id:"265336",title:"MSc.",name:"Ivaylo",middleName:null,surname:"Pehlivanov",slug:"ivaylo-pehlivanov",fullName:"Ivaylo Pehlivanov"}]},{id:"63035",doi:"10.5772/intechopen.80225",title:"Biological Function of Exosomes as Diagnostic Markers and Therapeutic Delivery Vehicles in Carcinogenesis and Infectious Diseases",slug:"biological-function-of-exosomes-as-diagnostic-markers-and-therapeutic-delivery-vehicles-in-carcinoge",totalDownloads:2190,totalCrossrefCites:12,totalDimensionsCites:23,abstract:"Exosomes are nano-sized vesicles that are formed during inward budding of multivesicular bodies and the maturation of endosomes. They are secreted by almost all cell types under normal, pathological, and physiological conditions. They are found in mostly all biological fluids, such as breast milk, blood, urine, and semen. Exosomes are involved in cell-to-cell communication through the biological transfer of lipids, proteins, DNAs, RNAs, mRNAs, and miRNAs. Exosomes are enriched in tetraspanins, enzymes, heat shock proteins, and membrane trafficking proteins. There are numerous techniques that are used to isolate, purify, and characterize exosomes from biofluids. Isolation/purification techniques include ultracentrifugation, filtration, sucrose density gradient centrifugation, etc. Characterization techniques include flow cytometry, electron microscopy, NanoSight tracking analysis, Western blot, etc. These techniques are often used to help principal investigators understand the properties and biological functions of exosomes. However, some of these techniques can be very complicated and challenging, resulting in various drawbacks. Exosomes can be used as potential carriers for therapeutics. Thus, they can serve as biomarkers to diagnosis various diseases that are associated with cancer, genetics, viruses, bacteria, parasites, etc. Therefore, with advances in science and technology, many innovative techniques have been established to exploit the biological properties of exosomes.",book:{id:"7437",slug:"nanomedicines",title:"Nanomedicines",fullTitle:"Nanomedicines"},signatures:"Brennetta J. Crenshaw, Brian Sims and Qiana L. Matthews",authors:[{id:"254038",title:"Ph.D.",name:"Qiana",middleName:null,surname:"Matthews",slug:"qiana-matthews",fullName:"Qiana Matthews"},{id:"254039",title:"Ms.",name:"Brennetta",middleName:null,surname:"Crenshaw",slug:"brennetta-crenshaw",fullName:"Brennetta Crenshaw"},{id:"266042",title:"Dr.",name:"Brian",middleName:null,surname:"Sims",slug:"brian-sims",fullName:"Brian Sims"}]},{id:"56634",doi:"10.5772/intechopen.70122",title:"Biomaterials and Stem Cells: Promising Tools in Tissue Engineering and Biomedical Applications",slug:"biomaterials-and-stem-cells-promising-tools-in-tissue-engineering-and-biomedical-applications",totalDownloads:1568,totalCrossrefCites:7,totalDimensionsCites:15,abstract:"Biomaterial sciences and tissue engineering approaches are currently fundamental strategies for the development of regenerative medicine. Stem cells (SCs) are a unique cell type capable of self‐renewal and reconstructing damaged tissues. At the present time, adult SCs isolated from postnatal tissues are widely used in clinical applications. Their characteristics such as a multipotent differentiation capacity and immunomodulatory activity make them a promising tool to use in patients. Modern material technologies allow for the development of innovative biomaterials that closely correspond to requirements of the current biomedical application. Biomaterials, such as ceramics and metals, are already used as implants to replace or improve the functionality of the damaged tissue or organ. However, the continuous development of modern technology opens new insights of polymeric and smart material applications. Moreover, biomaterials may enhance the SCs biological activity and their implementation by establishing a specific microenvironment mimicking natural cell niche. Thus, the synergistic advancement in the fields of biomaterial and medical sciences constitutes a challenge for the development of effective therapies in humans including combined applications of novel biomaterials and SCs populations.",book:{id:"5951",slug:"biomaterials-in-regenerative-medicine",title:"Biomaterials in Regenerative Medicine",fullTitle:"Biomaterials in Regenerative Medicine"},signatures:"Małgorzata Sekuła and Ewa K. Zuba‐Surma",authors:[{id:"202773",title:"Prof.",name:"Ewa",middleName:null,surname:"Zuba-Surma",slug:"ewa-zuba-surma",fullName:"Ewa Zuba-Surma"},{id:"202775",title:"Dr.",name:"Malgorzata",middleName:null,surname:"Sekula",slug:"malgorzata-sekula",fullName:"Malgorzata Sekula"}]},{id:"56100",doi:"10.5772/intechopen.69718",title:"Properties of Co-Cr Dental Alloys Fabricated Using Additive Technologies",slug:"properties-of-co-cr-dental-alloys-fabricated-using-additive-technologies",totalDownloads:1592,totalCrossrefCites:5,totalDimensionsCites:14,abstract:"The aim of the present paper is to make a review of the properties of dental alloys, fabricated using Additive Technologies (AT). The microstructure and mechanical properties of Co-Cr alloys as well as the accuracy and surface roughness of dental constructions are discussed. In dentistry two different approaches can be applied for production of metal frameworks using AT. According to the first one the wax/polymeric cast patterns are fabricated by 3D printing, than the constructions are cast from dental alloy with as-printed patterns. Through the second one the metal framework is manufactured form powder alloy directly from 3D virtual model by Selective Electron Beam Melting (SEBM) or Selective Laser Melting (SLM). The microstructure and mechanical properties of Co-Cr dental alloys, cast using 3D printed patterns, are typical for cast alloys. Their dimensional and adjustment accuracy is higher comparing to constructions, produced by traditional lost-wax casting or by SLM. The surface roughness is higher than that of the samples, cast by conventional technology, but lower comparing to the SLM objects. The microstructure of SLM Co-Cr dental alloys is fine grained and more homogeneous comparing that of the cast alloys, which defines higher hardness and mechanical properties, higher wear and corrosion resistance.",book:{id:"5951",slug:"biomaterials-in-regenerative-medicine",title:"Biomaterials in Regenerative Medicine",fullTitle:"Biomaterials in Regenerative Medicine"},signatures:"Tsanka Dikova",authors:[{id:"205539",title:"Dr.",name:"Tsanka",middleName:null,surname:"Dikova",slug:"tsanka-dikova",fullName:"Tsanka Dikova"}]},{id:"31995",doi:"10.5772/35937",title:"Air-Solids Flow Measurement Using Electrostatic Techniques",slug:"air-solids-flow-measurement-using-electrostatic-techniques",totalDownloads:5001,totalCrossrefCites:6,totalDimensionsCites:11,abstract:null,book:{id:"1649",slug:"electrostatics",title:"Electrostatics",fullTitle:"Electrostatics"},signatures:"Jianyong Zhang",authors:[{id:"106435",title:"Dr.",name:"Jianyong",middleName:null,surname:"Zhang",slug:"jianyong-zhang",fullName:"Jianyong Zhang"}]}],mostDownloadedChaptersLast30Days:[{id:"69398",title:"New Generation Peptide-Based Vaccine Prototype",slug:"new-generation-peptide-based-vaccine-prototype",totalDownloads:1129,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"Synthetic peptide-based vaccine prototypes are the future potential vaccination. Antigens, which belong to minimal microbial component and produce antibodies such as peptides and polysaccharides, can promote long-term protection against pathogens that can cause infectious diseases. Production of peptides becomes simple with solid phase peptide synthesis and microwave-assisted solid phase peptide synthesis using automatic synthesizers. The use of synthetic peptides was approved by the health authorities for vaccine design. Peptides are themselves very weak immunogens and need adjuvants to provide an effective autoimmune response. For this reason, peptide antigens are conjugated with biopolymers and loaded with nanoparticles. The toxicity of vaccine prototypes is evaluated in cell culture, and non-toxic prototypes are selected for vaccinating experimental animals. The most effective peptide-based vaccine prototype is determined as the one with the highest antibody level. The goal of this book chapter is to illustrate the use of peptides vaccine systems and present their opportunities with their future development.",book:{id:"9048",slug:"current-and-future-aspects-of-nanomedicine",title:"Current and Future Aspects of Nanomedicine",fullTitle:"Current and Future Aspects of Nanomedicine"},signatures:"Öznur Özge Özcan, Mesut Karahan, Palanirajan Vijayaraj Kumar, Shen Leng Tan and Yi Na Tee",authors:[{id:"305705",title:"Dr.",name:"Mesut",middleName:null,surname:"Karahan",slug:"mesut-karahan",fullName:"Mesut Karahan"},{id:"310005",title:"MSc.",name:"Öznur Özge",middleName:null,surname:"Özcan",slug:"oznur-ozge-ozcan",fullName:"Öznur Özge Özcan"},{id:"310006",title:"Prof.",name:"Palanirajan Vijayaraj",middleName:null,surname:"Kumar",slug:"palanirajan-vijayaraj-kumar",fullName:"Palanirajan Vijayaraj Kumar"},{id:"310008",title:"MSc.",name:"Shen Leng",middleName:null,surname:"Tan",slug:"shen-leng-tan",fullName:"Shen Leng Tan"},{id:"310009",title:"MSc.",name:"Yi Na",middleName:null,surname:"Tee",slug:"yi-na-tee",fullName:"Yi Na Tee"}]},{id:"56614",title:"Systematic Study of Ethylene-Vinyl Acetate (EVA) in the Manufacturing of Protector Devices for the Orofacial System",slug:"systematic-study-of-ethylene-vinyl-acetate-eva-in-the-manufacturing-of-protector-devices-for-the-oro",totalDownloads:1674,totalCrossrefCites:3,totalDimensionsCites:4,abstract:"Fracture of facial bones and dental elements, and laceration of soft tissue, have increased in sports over recent years. Dentist is the only professional responsible for the mouth protection design, the knowledge about suitable materials is essential. EVA is a thermoplastic material, available in the market, easy of handling and processing, and low-cost. However, it is important to understand the mechanical properties and ability to absorb and to dissipate the impact energy, when this material is submitted to different environments, such as oral cavity with saliva and different temperatures. This chapter show provides a systematic evaluation of the EVA application in orofacial protectors while focusing on sports. The research comprises two aspects: experimental tests and numerical analyses. During experimental tests, EVA was analyzed in special buccal conditions, concerning temperature and presence of saliva. Regarding the presence of saliva, more specific studies about its influence on the mechanical behavior of EVA were performed. In the numerical analyses of the EVA orofacial protector, the studies focused on its effect on the nasal bone integrity, and in the zygomatic bone protection. However, life cycle should be analyzed, since its performance deteriorates over time. Mainly due to the saliva-originated changes to the EVA mechanical characteristics, it can behave as a rigid material. For facial protection, a better performance is obtained with a combination of rigid and soft EVA material. According to the experimental and numerical results from a systematic study of EVA, its application to orofacial protection can be considered satisfactory.",book:{id:"5951",slug:"biomaterials-in-regenerative-medicine",title:"Biomaterials in Regenerative Medicine",fullTitle:"Biomaterials in Regenerative Medicine"},signatures:"Reinaldo Brito e Dias, Neide Pena Coto, Gilmar Ferreira Batalha and\nLarissa Driemeier",authors:[{id:"204968",title:"Dr.",name:"Neide",middleName:null,surname:"Pena Coto",slug:"neide-pena-coto",fullName:"Neide Pena Coto"}]},{id:"63035",title:"Biological Function of Exosomes as Diagnostic Markers and Therapeutic Delivery Vehicles in Carcinogenesis and Infectious Diseases",slug:"biological-function-of-exosomes-as-diagnostic-markers-and-therapeutic-delivery-vehicles-in-carcinoge",totalDownloads:2190,totalCrossrefCites:12,totalDimensionsCites:23,abstract:"Exosomes are nano-sized vesicles that are formed during inward budding of multivesicular bodies and the maturation of endosomes. They are secreted by almost all cell types under normal, pathological, and physiological conditions. They are found in mostly all biological fluids, such as breast milk, blood, urine, and semen. Exosomes are involved in cell-to-cell communication through the biological transfer of lipids, proteins, DNAs, RNAs, mRNAs, and miRNAs. Exosomes are enriched in tetraspanins, enzymes, heat shock proteins, and membrane trafficking proteins. There are numerous techniques that are used to isolate, purify, and characterize exosomes from biofluids. Isolation/purification techniques include ultracentrifugation, filtration, sucrose density gradient centrifugation, etc. Characterization techniques include flow cytometry, electron microscopy, NanoSight tracking analysis, Western blot, etc. These techniques are often used to help principal investigators understand the properties and biological functions of exosomes. However, some of these techniques can be very complicated and challenging, resulting in various drawbacks. Exosomes can be used as potential carriers for therapeutics. Thus, they can serve as biomarkers to diagnosis various diseases that are associated with cancer, genetics, viruses, bacteria, parasites, etc. Therefore, with advances in science and technology, many innovative techniques have been established to exploit the biological properties of exosomes.",book:{id:"7437",slug:"nanomedicines",title:"Nanomedicines",fullTitle:"Nanomedicines"},signatures:"Brennetta J. Crenshaw, Brian Sims and Qiana L. Matthews",authors:[{id:"254038",title:"Ph.D.",name:"Qiana",middleName:null,surname:"Matthews",slug:"qiana-matthews",fullName:"Qiana Matthews"},{id:"254039",title:"Ms.",name:"Brennetta",middleName:null,surname:"Crenshaw",slug:"brennetta-crenshaw",fullName:"Brennetta Crenshaw"},{id:"266042",title:"Dr.",name:"Brian",middleName:null,surname:"Sims",slug:"brian-sims",fullName:"Brian Sims"}]},{id:"64869",title:"Transethosomes and Nanoethosomes: Recent Approach on Transdermal Drug Delivery System",slug:"transethosomes-and-nanoethosomes-recent-approach-on-transdermal-drug-delivery-system",totalDownloads:1621,totalCrossrefCites:3,totalDimensionsCites:9,abstract:"In the past few decades, an emerging drug delivery system that came into light is transdermal drug delivery system. It has become the talk of the town in the field of drug delivery because of its better and easy accessibility. Though it is one of the attractive routes, transport of drug through the skin has remained a challenge. To overcome the challenge, vesicular system has been adopted so as to have better skin permeation of bioactive agents. Vesicular system like liposome has shown inefficiency to cross the layers of skin. Then transethosomes and nanoethosomes are employed for delivering drug into the deeper layer of skin. Nanoethosomes and transethosomes have same composition that is water, ethanol and phospholipid. Transethosome contains edge activator additionally. Due to the presence of ethanol and edge activator, it displayed enhanced skin permeation. Vesicular system gives a better patient compliance, being a non-invasive method of drug administration. In this chapter, we attempted to provide brief information about methods of preparation, characterization and pharmaceutical uses of nanoethosomes and transethosomes.",book:{id:"7437",slug:"nanomedicines",title:"Nanomedicines",fullTitle:"Nanomedicines"},signatures:"Koushlesh Kumar Mishra, Chanchal Deep Kaur, Shekhar Verma, Anil\nKumar Sahu, Deepak Kumar Dash, Pankaj Kashyap and Saraswati\nPrasad Mishra",authors:[{id:"204256",title:"Dr.",name:"Anil",middleName:"Kumar",surname:"Kumar Sahu",slug:"anil-kumar-sahu",fullName:"Anil Kumar Sahu"},{id:"211230",title:"Mr.",name:"Pankaj",middleName:null,surname:"Kashyap",slug:"pankaj-kashyap",fullName:"Pankaj Kashyap"},{id:"221419",title:"Mr.",name:"Koushlesh",middleName:null,surname:"Mishra",slug:"koushlesh-mishra",fullName:"Koushlesh Mishra"},{id:"221420",title:"Mr.",name:"Sarawati Prasad",middleName:null,surname:"Mishra",slug:"sarawati-prasad-mishra",fullName:"Sarawati Prasad Mishra"},{id:"250558",title:"Dr.",name:"Deepak Kumar",middleName:null,surname:"Dash",slug:"deepak-kumar-dash",fullName:"Deepak Kumar Dash"},{id:"270359",title:"Dr.",name:"Chanchal Deep",middleName:null,surname:"Kaur",slug:"chanchal-deep-kaur",fullName:"Chanchal Deep Kaur"},{id:"270998",title:"Prof.",name:"Shekhar",middleName:null,surname:"Verma",slug:"shekhar-verma",fullName:"Shekhar Verma"}]},{id:"68412",title:"Self-Emulsifying Drug Delivery Systems: Easy to Prepare Multifunctional Vectors for Efficient Oral Delivery",slug:"self-emulsifying-drug-delivery-systems-easy-to-prepare-multifunctional-vectors-for-efficient-oral-de",totalDownloads:1111,totalCrossrefCites:2,totalDimensionsCites:3,abstract:"Self-emulsifying drug delivery systems (SEDDS) have been mainly investigated to enhance the oral bioavailability of drugs belonging to class II of the Biopharmaceutics Classification System. However, in the past few years, they have shown promising outcomes in the oral delivery of various types of therapeutic agents. In this chapter, we discuss the recent progress in the application of SEDDS for oral delivery of protein therapeutics and genetic materials. The role of SEDDS in enhancing the oral bioavailability of P-glycoprotein and cytochrome P450 3A4 substrate drugs is also highlighted. Also, we discuss the most critical evaluation criteria of SEDDS. Additionally, we summarize various solidification techniques employed to transform liquid SEDDS to the more stable solid self-emulsifying drug delivery systems (s-SEDDS) that are associated with high patient compliance. This chapter provides a comprehensive approach to develop high utility SEDDS and their further transformation into s-SEDDS.",book:{id:"9048",slug:"current-and-future-aspects-of-nanomedicine",title:"Current and Future Aspects of Nanomedicine",fullTitle:"Current and Future Aspects of Nanomedicine"},signatures:"Khaled AboulFotouh, Ayat A. Allam and Mahmoud El-Badry",authors:[{id:"299910",title:"Prof.",name:"Mahmoud",middleName:null,surname:"El-Badry",slug:"mahmoud-el-badry",fullName:"Mahmoud El-Badry"},{id:"299914",title:"MSc.",name:"Khaled",middleName:null,surname:"Abulftooh",slug:"khaled-abulftooh",fullName:"Khaled Abulftooh"},{id:"299916",title:"Dr.",name:"Ayat",middleName:null,surname:"Allam",slug:"ayat-allam",fullName:"Ayat Allam"}]}],onlineFirstChaptersFilter:{topicId:"282",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:0,limit:8,total:null},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:87,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:98,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:27,numberOfPublishedChapters:288,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:139,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:0,numberOfUpcomingTopics:2,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!1},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:10,numberOfPublishedChapters:103,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:0,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!1},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:11,numberOfOpenTopics:4,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}}]},series:{item:{id:"14",title:"Artificial Intelligence",doi:"10.5772/intechopen.79920",issn:"2633-1403",scope:"Artificial Intelligence (AI) is a rapidly developing multidisciplinary research area that aims to solve increasingly complex problems. In today's highly integrated world, AI promises to become a robust and powerful means for obtaining solutions to previously unsolvable problems. This Series is intended for researchers and students alike interested in this fascinating field and its many applications.",coverUrl:"https://cdn.intechopen.com/series/covers/14.jpg",latestPublicationDate:"May 18th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:9,editor:{id:"218714",title:"Prof.",name:"Andries",middleName:null,surname:"Engelbrecht",slug:"andries-engelbrecht",fullName:"Andries Engelbrecht",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRNR8QAO/Profile_Picture_1622640468300",biography:"Andries Engelbrecht received the Masters and PhD degrees in Computer Science from the University of Stellenbosch, South Africa, in 1994 and 1999 respectively. He is currently appointed as the Voigt Chair in Data Science in the Department of Industrial Engineering, with a joint appointment as Professor in the Computer Science Division, Stellenbosch University. Prior to his appointment at Stellenbosch University, he has been at the University of Pretoria, Department of Computer Science (1998-2018), where he was appointed as South Africa Research Chair in Artifical Intelligence (2007-2018), the head of the Department of Computer Science (2008-2017), and Director of the Institute for Big Data and Data Science (2017-2018). In addition to a number of research articles, he has written two books, Computational Intelligence: An Introduction and Fundamentals of Computational Swarm Intelligence.",institutionString:null,institution:{name:"Stellenbosch University",institutionURL:null,country:{name:"South Africa"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:6,paginationItems:[{id:"22",title:"Applied Intelligence",coverUrl:"https://cdn.intechopen.com/series_topics/covers/22.jpg",isOpenForSubmission:!0,editor:{id:"27170",title:"Prof.",name:"Carlos",middleName:"M.",surname:"Travieso-Gonzalez",slug:"carlos-travieso-gonzalez",fullName:"Carlos Travieso-Gonzalez",profilePictureURL:"https://mts.intechopen.com/storage/users/27170/images/system/27170.jpeg",biography:"Carlos M. Travieso-González received his MSc degree in Telecommunication Engineering at Polytechnic University of Catalonia (UPC), Spain in 1997, and his Ph.D. degree in 2002 at the University of Las Palmas de Gran Canaria (ULPGC-Spain). He is a full professor of signal processing and pattern recognition and is head of the Signals and Communications Department at ULPGC, teaching from 2001 on subjects on signal processing and learning theory. His research lines are biometrics, biomedical signals and images, data mining, classification system, signal and image processing, machine learning, and environmental intelligence. He has researched in 52 international and Spanish research projects, some of them as head researcher. He is co-author of 4 books, co-editor of 27 proceedings books, guest editor for 8 JCR-ISI international journals, and up to 24 book chapters. He has over 450 papers published in international journals and conferences (81 of them indexed on JCR – ISI - Web of Science). He has published seven patents in the Spanish Patent and Trademark Office. He has been a supervisor on 8 Ph.D. theses (11 more are under supervision), and 130 master theses. He is the founder of The IEEE IWOBI conference series and the president of its Steering Committee, as well as the founder of both the InnoEducaTIC and APPIS conference series. He is an evaluator of project proposals for the European Union (H2020), Medical Research Council (MRC, UK), Spanish Government (ANECA, Spain), Research National Agency (ANR, France), DAAD (Germany), Argentinian Government, and the Colombian Institutions. He has been a reviewer in different indexed international journals (<70) and conferences (<250) since 2001. He has been a member of the IASTED Technical Committee on Image Processing from 2007 and a member of the IASTED Technical Committee on Artificial Intelligence and Expert Systems from 2011. \n\nHe has held the general chair position for the following: ACM-APPIS (2020, 2021), IEEE-IWOBI (2019, 2020 and 2020), A PPIS (2018, 2019), IEEE-IWOBI (2014, 2015, 2017, 2018), InnoEducaTIC (2014, 2017), IEEE-INES (2013), NoLISP (2011), JRBP (2012), and IEEE-ICCST (2005)\n\nHe is an associate editor of the Computational Intelligence and Neuroscience Journal (Hindawi – Q2 JCR-ISI). He was vice dean from 2004 to 2010 in the Higher Technical School of Telecommunication Engineers at ULPGC and the vice dean of Graduate and Postgraduate Studies from March 2013 to November 2017. He won the “Catedra Telefonica” Awards in Modality of Knowledge Transfer, 2017, 2018, and 2019 editions, and awards in Modality of COVID Research in 2020.\n\nPublic References:\nResearcher ID http://www.researcherid.com/rid/N-5967-2014\nORCID https://orcid.org/0000-0002-4621-2768 \nScopus Author ID https://www.scopus.com/authid/detail.uri?authorId=6602376272\nScholar Google https://scholar.google.es/citations?user=G1ks9nIAAAAJ&hl=en \nResearchGate https://www.researchgate.net/profile/Carlos_Travieso",institutionString:null,institution:{name:"University of Las Palmas de Gran Canaria",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"23",title:"Computational Neuroscience",coverUrl:"https://cdn.intechopen.com/series_topics/covers/23.jpg",isOpenForSubmission:!0,editor:{id:"14004",title:"Dr.",name:"Magnus",middleName:null,surname:"Johnsson",slug:"magnus-johnsson",fullName:"Magnus Johnsson",profilePictureURL:"https://mts.intechopen.com/storage/users/14004/images/system/14004.png",biography:"Dr Magnus Johnsson is a cross-disciplinary scientist, lecturer, scientific editor and AI/machine learning consultant from Sweden. \n\nHe is currently at Malmö University in Sweden, but also held positions at Lund University in Sweden and at Moscow Engineering Physics Institute. \nHe holds editorial positions at several international scientific journals and has served as a scientific editor for books and special journal issues. \nHis research interests are wide and include, but are not limited to, autonomous systems, computer modeling, artificial neural networks, artificial intelligence, cognitive neuroscience, cognitive robotics, cognitive architectures, cognitive aids and the philosophy of mind. \n\nDr. Johnsson has experience from working in the industry and he has a keen interest in the application of neural networks and artificial intelligence to fields like industry, finance, and medicine. \n\nWeb page: www.magnusjohnsson.se",institutionString:null,institution:{name:"Malmö University",institutionURL:null,country:{name:"Sweden"}}},editorTwo:null,editorThree:null},{id:"24",title:"Computer Vision",coverUrl:"https://cdn.intechopen.com/series_topics/covers/24.jpg",isOpenForSubmission:!0,editor:{id:"294154",title:"Prof.",name:"George",middleName:null,surname:"Papakostas",slug:"george-papakostas",fullName:"George Papakostas",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002hYaGbQAK/Profile_Picture_1624519712088",biography:"George A. 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He has (co)authored more than 150 publications in indexed journals, international conferences and book chapters, 1 book (in Greek), 3 edited books, and 5 journal special issues. His publications have more than 2100 citations with h-index 27 (GoogleScholar). His research interests include computer/machine vision, machine learning, pattern recognition, computational intelligence. \nDr. Papakostas served as a reviewer in numerous journals, as a program\ncommittee member in international conferences and he is a member of the IAENG, MIR Labs, EUCogIII, INSTICC and the Technical Chamber of Greece (TEE).",institutionString:null,institution:{name:"International Hellenic University",institutionURL:null,country:{name:"Greece"}}},editorTwo:null,editorThree:null},{id:"25",title:"Evolutionary Computation",coverUrl:"https://cdn.intechopen.com/series_topics/covers/25.jpg",isOpenForSubmission:!0,editor:{id:"136112",title:"Dr.",name:"Sebastian",middleName:null,surname:"Ventura Soto",slug:"sebastian-ventura-soto",fullName:"Sebastian Ventura Soto",profilePictureURL:"https://mts.intechopen.com/storage/users/136112/images/system/136112.png",biography:"Sebastian Ventura is a Spanish researcher, a full professor with the Department of Computer Science and Numerical Analysis, University of Córdoba. Dr Ventura also holds the positions of Affiliated Professor at Virginia Commonwealth University (Richmond, USA) and Distinguished Adjunct Professor at King Abdulaziz University (Jeddah, Saudi Arabia). Additionally, he is deputy director of the Andalusian Research Institute in Data Science and Computational Intelligence (DaSCI) and heads the Knowledge Discovery and Intelligent Systems Research Laboratory. He has published more than ten books and over 300 articles in journals and scientific conferences. Currently, his work has received over 18,000 citations according to Google Scholar, including more than 2200 citations in 2020. In the last five years, he has published more than 60 papers in international journals indexed in the JCR (around 70% of them belonging to first quartile journals) and he has edited some Springer books “Supervised Descriptive Pattern Mining” (2018), “Multiple Instance Learning - Foundations and Algorithms” (2016), and “Pattern Mining with Evolutionary Algorithms” (2016). He has also been involved in more than 20 research projects supported by the Spanish and Andalusian governments and the European Union. He currently belongs to the editorial board of PeerJ Computer Science, Information Fusion and Engineering Applications of Artificial Intelligence journals, being also associate editor of Applied Computational Intelligence and Soft Computing and IEEE Transactions on Cybernetics. Finally, he is editor-in-chief of Progress in Artificial Intelligence. He is a Senior Member of the IEEE Computer, the IEEE Computational Intelligence, and the IEEE Systems, Man, and Cybernetics Societies, and the Association of Computing Machinery (ACM). Finally, his main research interests include data science, computational intelligence, and their applications.",institutionString:null,institution:{name:"University of Córdoba",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"26",title:"Machine Learning and Data Mining",coverUrl:"https://cdn.intechopen.com/series_topics/covers/26.jpg",isOpenForSubmission:!0,editor:{id:"24555",title:"Dr.",name:"Marco Antonio",middleName:null,surname:"Aceves Fernandez",slug:"marco-antonio-aceves-fernandez",fullName:"Marco Antonio Aceves Fernandez",profilePictureURL:"https://mts.intechopen.com/storage/users/24555/images/system/24555.jpg",biography:"Dr. Marco Antonio Aceves Fernandez obtained his B.Sc. (Eng.) in Telematics from the Universidad de Colima, Mexico. 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He is currently a principal researcher in data analytics and optimisation at TECNALIA (Spain), a visiting fellow at the Basque Center for Applied Mathematics (BCAM) and a part-time lecturer at the University of the Basque Country (UPV/EHU). His research interests gravitate on the use of descriptive, prescriptive and predictive algorithms for data mining and optimization in a diverse range of application fields such as Energy, Transport, Telecommunications, Health and Industry, among others. In these fields he has published more than 240 articles, co-supervised 8 Ph.D. theses, edited 6 books, coauthored 7 patents and participated/led more than 40 research projects. 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He is currently a full professor in\nthe Department of Automation and Applied Informatics at the\nsame university. Dr. Voloşencu is the author of ten books, seven\nbook chapters, and more than 160 papers published in journals\nand conference proceedings. He has also edited twelve books and\nhas twenty-seven patents to his name. He is a manager of research grants, editor in\nchief and member of international journal editorial boards, a former plenary speaker, a member of scientific committees, and chair at international conferences. His\nresearch is in the fields of control systems, control of electric drives, fuzzy control\nsystems, neural network applications, fault detection and diagnosis, sensor network\napplications, monitoring of distributed parameter systems, and power ultrasound\napplications. 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conducts his research at the Hamidiye Faculty of Pharmacy, Department of Basic Pharmaceutical Sciences, Division of Biochemistry, University of Health Sciences, Turkey. He is also a faculty member in the Molecular Oncology Program. He obtained his MSc and Ph.D. at Oregon State University and Texas Tech University, respectively. He pursued his postdoctoral studies at Rutgers University Medical School and the National Institutes of Health (NIH/NIDDK), USA. His research focuses on biochemistry, biophysics, genetics, molecular biology, and molecular medicine with specialization in the fields of drug design, protein structure-function, protein folding, prions, microRNA, pseudogenes, molecular cancer, epigenetics, metabolites, proteomics, genomics, protein expression, and characterization by spectroscopic and calorimetric methods.",institutionString:"University of Health Sciences",institution:null},{id:"180528",title:"Dr.",name:"Hiroyuki",middleName:null,surname:"Kagechika",slug:"hiroyuki-kagechika",fullName:"Hiroyuki Kagechika",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180528/images/system/180528.jpg",biography:"Hiroyuki Kagechika received his bachelor’s degree and Ph.D. in Pharmaceutical Sciences from the University of Tokyo, Japan, where he served as an associate professor until 2004. He is currently a professor at the Institute of Biomaterials and Bioengineering (IBB), Tokyo Medical and Dental University (TMDU). From 2010 to 2012, he was the dean of the Graduate School of Biomedical Science. Since 2012, he has served as the vice dean of the Graduate School of Medical and Dental Sciences. He has been the director of the IBB since 2020. Dr. Kagechika’s major research interests are the medicinal chemistry of retinoids, vitamins D/K, and nuclear receptors. He has developed various compounds including a drug for acute promyelocytic leukemia.",institutionString:"Tokyo Medical and Dental University",institution:{name:"Tokyo Medical and Dental University",country:{name:"Japan"}}},{id:"40482",title:null,name:"Rizwan",middleName:null,surname:"Ahmad",slug:"rizwan-ahmad",fullName:"Rizwan Ahmad",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/40482/images/system/40482.jpeg",biography:"Dr. Rizwan Ahmad is a University Professor and Coordinator, Quality and Development, College of Medicine, Imam Abdulrahman bin Faisal University, Saudi Arabia. Previously, he was Associate Professor of Human Function, Oman Medical College, Oman, and SBS University, Dehradun. Dr. Ahmad completed his education at Aligarh Muslim University, Aligarh. He has published several articles in peer-reviewed journals, chapters, and edited books. His area of specialization is free radical biochemistry and autoimmune diseases.",institutionString:"Imam Abdulrahman Bin Faisal University",institution:{name:"Imam Abdulrahman Bin Faisal University",country:{name:"Saudi Arabia"}}},{id:"41865",title:"Prof.",name:"Farid A.",middleName:null,surname:"Badria",slug:"farid-a.-badria",fullName:"Farid A. Badria",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/41865/images/system/41865.jpg",biography:"Farid A. Badria, Ph.D., is the recipient of several awards, including The World Academy of Sciences (TWAS) Prize for Public Understanding of Science; the World Intellectual Property Organization (WIPO) Gold Medal for best invention; Outstanding Arab Scholar, Kuwait; and the Khwarizmi International Award, Iran. He has 250 publications, 12 books, 20 patents, and several marketed pharmaceutical products to his credit. He continues to lead research projects on developing new therapies for liver, skin disorders, and cancer. Dr. Badria was listed among the world’s top 2% of scientists in medicinal and biomolecular chemistry in 2019 and 2020. He is a member of the Arab Development Fund, Kuwait; International Cell Research Organization–United Nations Educational, Scientific and Cultural Organization (ICRO–UNESCO), Chile; and UNESCO Biotechnology France",institutionString:"Mansoura University",institution:{name:"Mansoura University",country:{name:"Egypt"}}},{id:"329385",title:"Dr.",name:"Rajesh K.",middleName:"Kumar",surname:"Singh",slug:"rajesh-k.-singh",fullName:"Rajesh K. Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329385/images/system/329385.png",biography:"Dr. Singh received a BPharm (2003) and MPharm (2005) from Panjab University, Chandigarh, India, and a Ph.D. (2013) from Punjab Technical University (PTU), Jalandhar, India. He has more than sixteen years of teaching experience and has supervised numerous postgraduate and Ph.D. students. He has to his credit more than seventy papers in SCI- and SCOPUS-indexed journals, fifty-five conference proceedings, four books, six Best Paper Awards, and five projects from different government agencies. He is currently an editorial board member of eight international journals and a reviewer for more than fifty scientific journals. He received Top Reviewer and Excellent Peer Reviewer Awards from Publons in 2016 and 2017, respectively. He is also on the panel of The International Reviewer for reviewing research proposals for grants from the Royal Society. He also serves as a Publons Academy mentor and Bentham brand ambassador.",institutionString:"Punjab Technical University",institution:{name:"Punjab Technical University",country:{name:"India"}}},{id:"142388",title:"Dr.",name:"Thiago",middleName:"Gomes",surname:"Gomes Heck",slug:"thiago-gomes-heck",fullName:"Thiago Gomes Heck",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/142388/images/7259_n.jpg",biography:null,institutionString:null,institution:{name:"Universidade Regional do Noroeste do Estado do Rio Grande do Sul",country:{name:"Brazil"}}},{id:"336273",title:"Assistant Prof.",name:"Janja",middleName:null,surname:"Zupan",slug:"janja-zupan",fullName:"Janja Zupan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/336273/images/14853_n.jpeg",biography:"Janja Zupan graduated in 2005 at the Department of Clinical Biochemistry (superviser prof. dr. Janja Marc) in the field of genetics of osteoporosis. Since November 2009 she is working as a Teaching Assistant at the Faculty of Pharmacy, Department of Clinical Biochemistry. In 2011 she completed part of her research and PhD work at Institute of Genetics and Molecular Medicine, University of Edinburgh. She finished her PhD entitled The influence of the proinflammatory cytokines on the RANK/RANKL/OPG in bone tissue of osteoporotic and osteoarthritic patients in 2012. From 2014-2016 she worked at the Institute of Biomedical Sciences, University of Aberdeen as a postdoctoral research fellow on UK Arthritis research project where she gained knowledge in mesenchymal stem cells and regenerative medicine. She returned back to University of Ljubljana, Faculty of Pharmacy in 2016. She is currently leading project entitled Mesenchymal stem cells-the keepers of tissue endogenous regenerative capacity facing up to aging of the musculoskeletal system funded by Slovenian Research Agency.",institutionString:null,institution:{name:"University of Ljubljana",country:{name:"Slovenia"}}},{id:"357453",title:"Dr.",name:"Radheshyam",middleName:null,surname:"Maurya",slug:"radheshyam-maurya",fullName:"Radheshyam Maurya",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/357453/images/16535_n.jpg",biography:null,institutionString:null,institution:{name:"University of Hyderabad",country:{name:"India"}}},{id:"311457",title:"Dr.",name:"Júlia",middleName:null,surname:"Scherer Santos",slug:"julia-scherer-santos",fullName:"Júlia Scherer Santos",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/311457/images/system/311457.jpg",biography:"Dr. Júlia Scherer Santos works in the areas of cosmetology, nanotechnology, pharmaceutical technology, beauty, and aesthetics. Dr. Santos also has experience as a professor of graduate courses. Graduated in Pharmacy, specialization in Cosmetology and Cosmeceuticals applied to aesthetics, specialization in Aesthetic and Cosmetic Health, and a doctorate in Pharmaceutical Nanotechnology. Teaching experience in Pharmacy and Aesthetics and Cosmetics courses. She works mainly on the following subjects: nanotechnology, cosmetology, pharmaceutical technology, aesthetics.",institutionString:"Universidade Federal de Juiz de Fora",institution:{name:"Universidade Federal de Juiz de Fora",country:{name:"Brazil"}}},{id:"219081",title:"Dr.",name:"Abdulsamed",middleName:null,surname:"Kükürt",slug:"abdulsamed-kukurt",fullName:"Abdulsamed Kükürt",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRNVJQA4/Profile_Picture_2022-03-07T13:23:04.png",biography:"Dr. Kükürt graduated from Uludağ University in Turkey. He started his academic career as a Research Assistant in the Department of Biochemistry at Kafkas University. In 2019, he completed his Ph.D. program in the Department of Biochemistry at the Institute of Health Sciences. He is currently working at the Department of Biochemistry, Kafkas University. He has 27 published research articles in academic journals, 11 book chapters, and 37 papers. He took part in 10 academic projects. He served as a reviewer for many articles. He still serves as a member of the review board in many academic journals.",institutionString:null,institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"178366",title:"Associate Prof.",name:"Volkan",middleName:null,surname:"Gelen",slug:"volkan-gelen",fullName:"Volkan Gelen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178366/images/system/178366.jpg",biography:"Volkan Gelen is a Physiology specialist who received his veterinary degree from Kafkas University in 2011. Between 2011-2015, he worked as an assistant at Atatürk University, Faculty of Veterinary Medicine, Department of Physiology. In 2016, he joined Kafkas University, Faculty of Veterinary Medicine, Department of Physiology as an assistant professor. Dr. Gelen has been engaged in various academic activities at Kafkas University since 2016. There he completed 5 projects and has 3 ongoing projects. He has 60 articles published in scientific journals and 20 poster presentations in scientific congresses. His research interests include physiology, endocrine system, cancer, diabetes, cardiovascular system diseases, and isolated organ bath system studies.",institutionString:"Kafkas University",institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"418963",title:"Dr.",name:"Augustine Ododo",middleName:"Augustine",surname:"Osagie",slug:"augustine-ododo-osagie",fullName:"Augustine Ododo Osagie",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/418963/images/16900_n.jpg",biography:"Born into the family of Osagie, a prince of the Benin Kingdom. I am currently an academic in the Department of Medical Biochemistry, University of Benin. Part of the duties are to teach undergraduate students and conduct academic research.",institutionString:null,institution:{name:"University of Benin",country:{name:"Nigeria"}}},{id:"192992",title:"Prof.",name:"Shagufta",middleName:null,surname:"Perveen",slug:"shagufta-perveen",fullName:"Shagufta Perveen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/192992/images/system/192992.png",biography:"Prof. Shagufta Perveen is a Distinguish Professor in the Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. Dr. Perveen has acted as the principal investigator of major research projects funded by the research unit of King Saud University. She has more than ninety original research papers in peer-reviewed journals of international repute to her credit. She is a fellow member of the Royal Society of Chemistry UK and the American Chemical Society of the United States.",institutionString:"King Saud University",institution:{name:"King Saud University",country:{name:"Saudi Arabia"}}},{id:"49848",title:"Dr.",name:"Wen-Long",middleName:null,surname:"Hu",slug:"wen-long-hu",fullName:"Wen-Long Hu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49848/images/system/49848.jpg",biography:"Wen-Long Hu is Chief of the Division of Acupuncture, Department of Chinese Medicine at Kaohsiung Chang Gung Memorial Hospital, as well as an adjunct associate professor at Fooyin University and Kaohsiung Medical University. Wen-Long is President of Taiwan Traditional Chinese Medicine Medical Association. He has 28 years of experience in clinical practice in laser acupuncture therapy and 34 years in acupuncture. He is an invited speaker for lectures and workshops in laser acupuncture at many symposiums held by medical associations. He owns the patent for herbal preparation and producing, and for the supercritical fluid-treated needle. Dr. Hu has published three books, 12 book chapters, and more than 30 papers in reputed journals, besides serving as an editorial board member of repute.",institutionString:"Kaohsiung Chang Gung Memorial Hospital",institution:{name:"Kaohsiung Chang Gung Memorial Hospital",country:{name:"Taiwan"}}},{id:"298472",title:"Prof.",name:"Andrey V.",middleName:null,surname:"Grechko",slug:"andrey-v.-grechko",fullName:"Andrey V. Grechko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/298472/images/system/298472.png",biography:"Andrey Vyacheslavovich Grechko, Ph.D., Professor, is a Corresponding Member of the Russian Academy of Sciences. He graduated from the Semashko Moscow Medical Institute (Semashko National Research Institute of Public Health) with a degree in Medicine (1998), the Clinical Department of Dermatovenerology (2000), and received a second higher education in Psychology (2009). Professor A.V. Grechko held the position of Сhief Physician of the Central Clinical Hospital in Moscow. He worked as a professor at the faculty and was engaged in scientific research at the Medical University. Starting in 2013, he has been the initiator of the creation of the Federal Scientific and Clinical Center for Intensive Care and Rehabilitology, Moscow, Russian Federation, where he also serves as Director since 2015. He has many years of experience in research and teaching in various fields of medicine, is an author/co-author of more than 200 scientific publications, 13 patents, 15 medical books/chapters, including Chapter in Book «Metabolomics», IntechOpen, 2020 «Metabolomic Discovery of Microbiota Dysfunction as the Cause of Pathology».",institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"199461",title:"Prof.",name:"Natalia V.",middleName:null,surname:"Beloborodova",slug:"natalia-v.-beloborodova",fullName:"Natalia V. Beloborodova",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/199461/images/system/199461.jpg",biography:'Natalia Vladimirovna Beloborodova was educated at the Pirogov Russian National Research Medical University, with a degree in pediatrics in 1980, a Ph.D. in 1987, and a specialization in Clinical Microbiology from First Moscow State Medical University in 2004. She has been a Professor since 1996. Currently, she is the Head of the Laboratory of Metabolism, a division of the Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Moscow, Russian Federation. N.V. Beloborodova has many years of clinical experience in the field of intensive care and surgery. She studies infectious complications and sepsis. She initiated a series of interdisciplinary clinical and experimental studies based on the concept of integrating human metabolism and its microbiota. Her scientific achievements are widely known: she is the recipient of the Marie E. Coates Award \\"Best lecturer-scientist\\" Gustafsson Fund, Karolinska Institutes, Stockholm, Sweden, and the International Sepsis Forum Award, Pasteur Institute, Paris, France (2014), etc. Professor N.V. Beloborodova wrote 210 papers, five books, 10 chapters and has edited four books.',institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"354260",title:"Ph.D.",name:"Tércio Elyan",middleName:"Azevedo",surname:"Azevedo Martins",slug:"tercio-elyan-azevedo-martins",fullName:"Tércio Elyan Azevedo Martins",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/354260/images/16241_n.jpg",biography:"Graduated in Pharmacy from the Federal University of Ceará with the modality in Industrial Pharmacy, Specialist in Production and Control of Medicines from the University of São Paulo (USP), Master in Pharmaceuticals and Medicines from the University of São Paulo (USP) and Doctor of Science in the program of Pharmaceuticals and Medicines by the University of São Paulo. Professor at Universidade Paulista (UNIP) in the areas of chemistry, cosmetology and trichology. Assistant Coordinator of the Higher Course in Aesthetic and Cosmetic Technology at Universidade Paulista Campus Chácara Santo Antônio. Experience in the Pharmacy area, with emphasis on Pharmacotechnics, Pharmaceutical Technology, Research and Development of Cosmetics, acting mainly on topics such as cosmetology, antioxidant activity, aesthetics, photoprotection, cyclodextrin and thermal analysis.",institutionString:null,institution:{name:"University of Sao Paulo",country:{name:"Brazil"}}},{id:"334285",title:"Ph.D. Student",name:"Sameer",middleName:"Kumar",surname:"Jagirdar",slug:"sameer-jagirdar",fullName:"Sameer Jagirdar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334285/images/14691_n.jpg",biography:"I\\'m a graduate student at the center for biosystems science and engineering at the Indian Institute of Science, Bangalore, India. I am interested in studying host-pathogen interactions at the biomaterial interface.",institutionString:null,institution:{name:"Indian Institute of Science Bangalore",country:{name:"India"}}},{id:"329795",title:"Dr.",name:"Mohd Aftab",middleName:"Aftab",surname:"Siddiqui",slug:"mohd-aftab-siddiqui",fullName:"Mohd Aftab Siddiqui",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329795/images/15648_n.jpg",biography:"Dr. Mohd Aftab Siddiqui is currently working as Assistant Professor in the Faculty of Pharmacy, Integral University, Lucknow for the last 6 years. He has completed his Doctor in Philosophy (Pharmacology) in 2020 from Integral University, Lucknow. He completed his Bachelor in Pharmacy in 2013 and Master in Pharmacy (Pharmacology) in 2015 from Integral University, Lucknow. He is the gold medalist in Bachelor and Master degree. He qualified GPAT -2013, GPAT -2014, and GPAT 2015. His area of research is Pharmacological screening of herbal drugs/ natural products in liver and cardiac diseases. He has guided many M. Pharm. research projects. He has many national and international publications.",institutionString:"Integral University",institution:null},{id:"255360",title:"Dr.",name:"Usama",middleName:null,surname:"Ahmad",slug:"usama-ahmad",fullName:"Usama Ahmad",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255360/images/system/255360.png",biography:"Dr. Usama Ahmad holds a specialization in Pharmaceutics from Amity University, Lucknow, India. He received his Ph.D. degree from Integral University. Currently, he’s working as an Assistant Professor of Pharmaceutics in the Faculty of Pharmacy, Integral University. From 2013 to 2014 he worked on a research project funded by SERB-DST, Government of India. He has a rich publication record with more than 32 original articles published in reputed journals, 3 edited books, 5 book chapters, and a number of scientific articles published in ‘Ingredients South Asia Magazine’ and ‘QualPharma Magazine’. He is a member of the American Association for Cancer Research, International Association for the Study of Lung Cancer, and the British Society for Nanomedicine. Dr. Ahmad’s research focus is on the development of nanoformulations to facilitate the delivery of drugs that aim to provide practical solutions to current healthcare problems.",institutionString:"Integral University",institution:{name:"Integral University",country:{name:"India"}}},{id:"30568",title:"Prof.",name:"Madhu",middleName:null,surname:"Khullar",slug:"madhu-khullar",fullName:"Madhu Khullar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/30568/images/system/30568.jpg",biography:"Dr. Madhu Khullar is a Professor of Experimental Medicine and Biotechnology at the Post Graduate Institute of Medical Education and Research, Chandigarh, India. She completed her Post Doctorate in hypertension research at the Henry Ford Hospital, Detroit, USA in 1985. She is an editor and reviewer of several international journals, and a fellow and member of several cardiovascular research societies. Dr. Khullar has a keen research interest in genetics of hypertension, and is currently studying pharmacogenetics of hypertension.",institutionString:"Post Graduate Institute of Medical Education and Research",institution:{name:"Post Graduate Institute of Medical Education and Research",country:{name:"India"}}},{id:"223233",title:"Prof.",name:"Xianquan",middleName:null,surname:"Zhan",slug:"xianquan-zhan",fullName:"Xianquan Zhan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/223233/images/system/223233.png",biography:"Xianquan Zhan received his MD and Ph.D. in Preventive Medicine at West China University of Medical Sciences. He received his post-doctoral training in oncology and cancer proteomics at the Central South University, China, and the University of Tennessee Health Science Center (UTHSC), USA. He worked at UTHSC and the Cleveland Clinic in 2001–2012 and achieved the rank of associate professor at UTHSC. Currently, he is a full professor at Central South University and Shandong First Medical University, and an advisor to MS/PhD students and postdoctoral fellows. He is also a fellow of the Royal Society of Medicine and European Association for Predictive Preventive Personalized Medicine (EPMA), a national representative of EPMA, and a member of the American Society of Clinical Oncology (ASCO) and the American Association for the Advancement of Sciences (AAAS). He is also the editor in chief of International Journal of Chronic Diseases & Therapy, an associate editor of EPMA Journal, Frontiers in Endocrinology, and BMC Medical Genomics, and a guest editor of Mass Spectrometry Reviews, Frontiers in Endocrinology, EPMA Journal, and Oxidative Medicine and Cellular Longevity. He has published more than 148 articles, 28 book chapters, 6 books, and 2 US patents in the field of clinical proteomics and biomarkers.",institutionString:"Shandong First Medical University",institution:{name:"Affiliated Hospital of Shandong Academy of Medical Sciences",country:{name:"China"}}},{id:"297507",title:"Dr.",name:"Charles",middleName:"Elias",surname:"Assmann",slug:"charles-assmann",fullName:"Charles Assmann",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/297507/images/system/297507.jpg",biography:"Charles Elias Assmann is a biologist from Federal University of Santa Maria (UFSM, Brazil), who spent some time abroad at the Ludwig-Maximilians-Universität München (LMU, Germany). He has Masters Degree in Biochemistry (UFSM), and is currently a PhD student at Biochemistry at the Department of Biochemistry and Molecular Biology of the UFSM. His areas of expertise include: Biochemistry, Molecular Biology, Enzymology, Genetics and Toxicology. He is currently working on the following subjects: Aluminium toxicity, Neuroinflammation, Oxidative stress and Purinergic system. Since 2011 he has presented more than 80 abstracts in scientific proceedings of national and international meetings. Since 2014, he has published more than 20 peer reviewed papers (including 4 reviews, 3 in Portuguese) and 2 book chapters. He has also been a reviewer of international journals and ad hoc reviewer of scientific committees from Brazilian Universities.",institutionString:"Universidade Federal de Santa Maria",institution:{name:"Universidade Federal de Santa Maria",country:{name:"Brazil"}}},{id:"217850",title:"Dr.",name:"Margarete Dulce",middleName:null,surname:"Bagatini",slug:"margarete-dulce-bagatini",fullName:"Margarete Dulce Bagatini",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/217850/images/system/217850.jpeg",biography:"Dr. Margarete Dulce Bagatini is an associate professor at the Federal University of Fronteira Sul/Brazil. She has a degree in Pharmacy and a PhD in Biological Sciences: Toxicological Biochemistry. She is a member of the UFFS Research Advisory Committee\nand a member of the Biovitta Research Institute. She is currently:\nthe leader of the research group: Biological and Clinical Studies\nin Human Pathologies, professor of postgraduate program in\nBiochemistry at UFSC and postgraduate program in Science and Food Technology at\nUFFS. She has experience in the area of pharmacy and clinical analysis, acting mainly\non the following topics: oxidative stress, the purinergic system and human pathologies, being a reviewer of several international journals and books.",institutionString:"Universidade Federal da Fronteira Sul",institution:{name:"Universidade Federal da Fronteira Sul",country:{name:"Brazil"}}},{id:"226275",title:"Ph.D.",name:"Metin",middleName:null,surname:"Budak",slug:"metin-budak",fullName:"Metin Budak",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/226275/images/system/226275.jfif",biography:"Metin Budak, MSc, PhD is an Assistant Professor at Trakya University, Faculty of Medicine. He has been Head of the Molecular Research Lab at Prof. Mirko Tos Ear and Hearing Research Center since 2018. His specializations are biophysics, epigenetics, genetics, and methylation mechanisms. He has published around 25 peer-reviewed papers, 2 book chapters, and 28 abstracts. He is a member of the Clinical Research Ethics Committee and Quantification and Consideration Committee of Medicine Faculty. His research area is the role of methylation during gene transcription, chromatin packages DNA within the cell and DNA repair, replication, recombination, and gene transcription. His research focuses on how the cell overcomes chromatin structure and methylation to allow access to the underlying DNA and enable normal cellular function.",institutionString:"Trakya University",institution:{name:"Trakya University",country:{name:"Turkey"}}},{id:"243049",title:"Dr.",name:"Anca",middleName:null,surname:"Pantea Stoian",slug:"anca-pantea-stoian",fullName:"Anca Pantea Stoian",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243049/images/system/243049.jpg",biography:"Anca Pantea Stoian is a specialist in diabetes, nutrition, and metabolic diseases as well as health food hygiene. She also has competency in general ultrasonography.\n\nShe is an associate professor in the Diabetes, Nutrition and Metabolic Diseases Department, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania. She has been chief of the Hygiene Department, Faculty of Dentistry, at the same university since 2019. Her interests include micro and macrovascular complications in diabetes and new therapies. Her research activities focus on nutritional intervention in chronic pathology, as well as cardio-renal-metabolic risk assessment, and diabetes in cancer. She is currently engaged in developing new therapies and technological tools for screening, prevention, and patient education in diabetes. \n\nShe is a member of the European Association for the Study of Diabetes, Cardiometabolic Academy, CEDA, Romanian Society of Diabetes, Nutrition and Metabolic Diseases, Romanian Diabetes Federation, and Association for Renal Metabolic and Nutrition studies. She has authored or co-authored 160 papers in national and international peer-reviewed journals.",institutionString:null,institution:{name:"Carol Davila University of Medicine and Pharmacy",country:{name:"Romania"}}},{id:"279792",title:"Dr.",name:"João",middleName:null,surname:"Cotas",slug:"joao-cotas",fullName:"João Cotas",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/279792/images/system/279792.jpg",biography:"Graduate and master in Biology from the University of Coimbra.\n\nI am a research fellow at the Macroalgae Laboratory Unit, in the MARE-UC – Marine and Environmental Sciences Centre of the University of Coimbra. My principal function is the collection, extraction and purification of macroalgae compounds, chemical and bioactive characterization of the compounds and algae extracts and development of new methodologies in marine biotechnology area. \nI am associated in two projects: one consists on discovery of natural compounds for oncobiology. The other project is the about the natural compounds/products for agricultural area.\n\nPublications:\nCotas, J.; Figueirinha, A.; Pereira, L.; Batista, T. 2018. An analysis of the effects of salinity on Fucus ceranoides (Ochrophyta, Phaeophyceae), in the Mondego River (Portugal). Journal of Oceanology and Limnology. in press. DOI: 10.1007/s00343-019-8111-3",institutionString:"Faculty of Sciences and Technology of University of Coimbra",institution:null},{id:"279788",title:"Dr.",name:"Leonel",middleName:null,surname:"Pereira",slug:"leonel-pereira",fullName:"Leonel Pereira",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/279788/images/system/279788.jpg",biography:"Leonel Pereira has an undergraduate degree in Biology, a Ph.D. in Biology (specialty in Cell Biology), and a Habilitation degree in Biosciences (specialization in Biotechnology) from the Faculty of Science and Technology, University of Coimbra, Portugal, where he is currently a professor. In addition to teaching at this university, he is an integrated researcher at the Marine and Environmental Sciences Center (MARE), Portugal. His interests include marine biodiversity (algae), marine biotechnology (algae bioactive compounds), and marine ecology (environmental assessment). Since 2008, he has been the author and editor of the electronic publication MACOI – Portuguese Seaweeds Website (www.seaweeds.uc.pt). He is also a member of the editorial boards of several scientific journals. Dr. Pereira has edited or authored more than 20 books, 100 journal articles, and 45 book chapters. He has given more than 100 lectures and oral communications at various national and international scientific events. He is the coordinator of several national and international research projects. In 1998, he received the Francisco de Holanda Award (Honorable Mention) and, more recently, the Mar Rei D. Carlos award (18th edition). He is also a winner of the 2016 CHOICE Award for an outstanding academic title for his book Edible Seaweeds of the World. In 2020, Dr. Pereira received an Honorable Mention for the Impact of International Publications from the Web of Science",institutionString:"University of Coimbra",institution:{name:"University of Coimbra",country:{name:"Portugal"}}},{id:"61946",title:"Dr.",name:"Carol",middleName:null,surname:"Bernstein",slug:"carol-bernstein",fullName:"Carol Bernstein",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/61946/images/system/61946.jpg",biography:"Carol Bernstein received her PhD in Genetics from the University of California (Davis). She was a faculty member at the University of Arizona College of Medicine for 43 years, retiring in 2011. Her research interests focus on DNA damage and its underlying role in sex, aging and in the early steps of initiation and progression to cancer. In her research, she had used organisms including bacteriophage T4, Neurospora crassa, Schizosaccharomyces pombe and mice, as well as human cells and tissues. She authored or co-authored more than 140 scientific publications, including articles in major peer reviewed journals, book chapters, invited reviews and one book.",institutionString:"University of Arizona",institution:{name:"University of Arizona",country:{name:"United States of America"}}},{id:"182258",title:"Dr.",name:"Ademar",middleName:"Pereira",surname:"Serra",slug:"ademar-serra",fullName:"Ademar Serra",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/182258/images/system/182258.jpeg",biography:"Dr. Serra studied Agronomy on Universidade Federal de Mato Grosso do Sul (UFMS) (2005). He received master degree in Agronomy, Crop Science (Soil fertility and plant nutrition) (2007) by Universidade Federal da Grande Dourados (UFGD), and PhD in agronomy (Soil fertility and plant nutrition) (2011) from Universidade Federal da Grande Dourados / Escola Superior de Agricultura Luiz de Queiroz (UFGD/ESALQ-USP). Dr. Serra is currently working at Brazilian Agricultural Research Corporation (EMBRAPA). His research focus is on mineral nutrition of plants, crop science and soil science. Dr. Serra\\'s current projects are soil organic matter, soil phosphorus fractions, compositional nutrient diagnosis (CND) and isometric log ratio (ilr) transformation in compositional data analysis.",institutionString:"Brazilian Agricultural Research Corporation",institution:{name:"Brazilian Agricultural Research Corporation",country:{name:"Brazil"}}}]}},subseries:{item:{id:"26",type:"subseries",title:"Machine Learning and Data Mining",keywords:"Intelligent Systems, Machine Learning, Data Science, Data Mining, Artificial Intelligence",scope:"The scope of machine learning and data mining is immense and is growing every day. It has become a massive part of our daily lives, making predictions based on experience, making this a fascinating area that solves problems that otherwise would not be possible or easy to solve. This topic aims to encompass algorithms that learn from experience (supervised and unsupervised), improve their performance over time and enable machines to make data-driven decisions. It is not limited to any particular applications, but contributions are encouraged from all disciplines.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/26.jpg",hasOnlineFirst:!0,hasPublishedBooks:!0,annualVolume:11422,editor:{id:"24555",title:"Dr.",name:"Marco Antonio",middleName:null,surname:"Aceves Fernandez",slug:"marco-antonio-aceves-fernandez",fullName:"Marco Antonio Aceves Fernandez",profilePictureURL:"https://mts.intechopen.com/storage/users/24555/images/system/24555.jpg",biography:"Dr. Marco Antonio Aceves Fernandez obtained his B.Sc. (Eng.) in Telematics from the Universidad de Colima, Mexico. He obtained both his M.Sc. and Ph.D. from the University of Liverpool, England, in the field of Intelligent Systems. He is a full professor at the Universidad Autonoma de Queretaro, Mexico, and a member of the National System of Researchers (SNI) since 2009. Dr. Aceves Fernandez has published more than 80 research papers as well as a number of book chapters and congress papers. He has contributed in more than 20 funded research projects, both academic and industrial, in the area of artificial intelligence, ranging from environmental, biomedical, automotive, aviation, consumer, and robotics to other applications. He is also a honorary president at the National Association of Embedded Systems (AMESE), a senior member of the IEEE, and a board member of many institutions. 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