Polycyclic aromatic hydrocarbons (PAH4) and structures.
\\n\\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\\n\\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\\n"}]',published:!0,mainMedia:{caption:"Highly Cited",originalUrl:"/media/original/117"}},components:[{type:"htmlEditorComponent",content:'IntechOpen is proud to announce that 191 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\nThroughout the years, the list has named a total of 261 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\nReleased this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"1363",leadTitle:null,fullTitle:"Numerical Analysis - Theory and Application",title:"Numerical Analysis",subtitle:"Theory and Application",reviewType:"peer-reviewed",abstract:"Numerical Analysis - Theory and Application is an edited book divided into two parts: Part I devoted to Theory, and Part II dealing with Application. The presented book is focused on introducing theoretical approaches of numerical analysis as well as applications of various numerical methods to either study or solving numerous theoretical and engineering problems. Since a large number of pure theoretical research is proposed as well as a large amount of applications oriented numerical simulation results are given, the book can be useful for both theoretical and applied research aimed on numerical simulations. 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From the consumer’s point of view, quality is intrinsically linked to health, well-being, and sensory aspect of the products, which makes this concept quite diffuse and subjective [1, 2].
The measurability of the food quality parameter can allow its conversion to be more objective. For producers, the precision in the parameterization of this concept is very important, because the consumer’s perception of quality greatly affects the purchase decision, which in Europe is directly correlated with information subjective [2].
According to Tothill and Stephen [3], a large investment is needed in terms of providing relevant information and industrial marketing practices. This gap has been reduced with the regulation on labeling, requiring the definition of consistent norms and standards, a rigorous food quality control process in order to keep the consumer safe [4], and confident in their decision to purchase the product. This point is in line with Organization for Economic Co-operation and Development (OECD) indications, as there are data indicating that the content of food labels influences consumer behavior more than energy efficiency labeling [5].
Food quality control involves the specification of ingredients and the consequent physical, chemical, and microbiological characterization of food and food products [6].
All food quality control is carried out, using acceptable and well-established methodologies, in order to maintain product characteristics, but is increasingly associated with food safety, for the prevention of chemical and biological hazards that may result in contamination [6, 7].
Since food quality and safety are two increasingly interconnected domains, it is of great value to identify which constituents in food make it unfeasible to consume. These components, called contaminants, are increasingly regulated and controlled, because their improper consumption can interfere with consumer health.
In 1963, a harmonized international collection of food standards, guidelines, and codes of practice was created by the Codex Alimentarius Commission, a joint intergovernmental body of the Food Agriculture Organization (FAO) and the World Health Organization (WHO), to protect consumer health and ensure fair food trade practices.
Since contaminants are defined as substances that are not intentionally added to food and may result from various stages such as production, packaging, transport or storage, or environmental factors, the Codex Committee on Contaminants in Food (CCCF) establishes and endorses maximum allowable levels or guideline levels for naturally occurring contaminants and toxins in food and feed. Codex has established 17 maximum levels for these types of substances, including some hazardous metals, mycotoxins produced by certain fungi, and radionuclides [8].
EU legislation, through its Regulations 315/93/EEC [9], 1881/2006 [10], and amendments, imposes procedures for the determination of contaminants and their maximum levels. Thus, in this issue we will cover three main topics related to the intrinsic quality of food, namely heavy metals, polycyclic aromatic hydrocarbons (PAHs), mycotoxins.
There is a wide variety of synthetic and natural organic pollutants found in the environment, contaminating air, water, soils, and therefore, animals and plants, many of them are used for human food. However, within this vast array are the PAHs that present a great structural diversity, possessing two or more benzene rings. These hydrocarbons can be produced by pyrolysis or incomplete combustion of carbon compounds, such as oil and coal [11, 12].
Highly important and problematic is the fact that this group of aromatic organic compounds can be teratogenic, carcinogenic, and mutagenic, can cause serious problems in human health, and can therefore be used as a marker for the occurrence of polycyclic aromatic hydrocarbons in food [13]. Processing of food, such as smoking, heating, and drying processes, and cooking at high temperatures are the major sources of contamination by PAHs because those processes allow combustion products to come into contact with food. High levels of PAH are found in dried fruits, olive pomace oil, teas, smoked fish, grape seed oil, smoked meat products, fresh mollusks, and condiments [12, 14].
Existence of PAH and its relationship with human health and nutrition is an issue that goes back more than half a century. To protect public health, maximum levels are also necessary for foods where environmental pollution may cause high levels of contamination especially in fish and fishery products that contact contaminated water [15]. The detection, identification, monitoring, and regulation that exist today rely on identities such as the Joint FAO/WHO Expert Committee on Food Additives (JECFA), the European Food Safety Authority (EFSA), the Scientific Committee on Food (SCF), the United States Environmental Protection Agency (U.S. EPA), the International Agency for Research on Cancer (IACR), and the International Programme on Chemical Safety (IPCS), that have joined forces to raise alert to this issue [16].
Based on the evaluation of PAHs, in 2002, the European Union through SCF concluded that 15 PAHs, namely benz[a]anthracene, benzo[b]fluoranthene, benzo[j]fluoranthene, benzo[k]fluoranthene, benzo[ghi]perylene, benzo[a]pyrene, chrysene, cyclopenta[cd]pyrene, dibenzo[a,h]anthracene, dibenzo[a,e]pyrene, dibenzo[a,h]pyrene, dibenzo[a,i]pyrene, dibenzo[a,l]pyrene, indeno[1,2,3-cd]pyrene, and 5-methylchrysene showed evidence of mutagenicity, genotoxicity [14]. In 2005, EFSA concluded that benzo[a]pyrene could be used as marker to exposure to, and effect of, genotoxic and carcinogenic PAHs. Later, in 2008, the evaluations showed that 50% of the thousands of samples analyzed contained benzo[a]pyrene, but that 30% of the samples that showed carcinogenic properties contained no benzo[a]pyrene. Based on these and other findings, the CONTAM Panel concluded that the risk characterization should be based upon oral carcinogenicity data of eight PAHs, explicitly benzo[a]pyrene, benz[a]anthracene, benzo[b]fluoranthene, benzo[k]fluoranthene, benzo[ghi]perylene, chrysene, dibenz[a,h]anthracene, and indeno[1,2,3-cd]pyrene (PAH8). These polycyclic aromatic hydrocarbons either individually or in a combination were considered possible indicators of the carcinogenic potency in food. In addition to the effects of the sum of PAH8, the sum of benzo[a]pyrene, chrysene, benz[a]anthracene, and benzo[b]fluoranthene (PAH4), as well as the sum of benzo[a]pyrene and chrysene (PAH2), and the correlation between PAH2, PAH4, and PAH8 were calculated. The CONTAM Panel later concluded that benzo[a]pyrene is not an appropriate indicator for PAH in food and that PAH4 and PAH8 are the most appropriate indicators of PAH in food, with PAH8 not providing much added value compared with PAH4, which are presented in Table 1 [16, 17].
Polycyclic aromatic hydrocarbons (PAH4) and structures.
The foods with maximum levels of PAH4, benzo(a)pyrene, benzo(a)anthracene, benzo(b)fluoranthene and chrysene, above those laid down in EU Regulations 315/93/EEC [9], and 1881/2006 [10] may not be consumed nor used for the edible part of the food. However, recently new data have been collected in order to obtain more useful information on PAHs. An example of this is the new regulated values for powders of food of plant origin used for the preparation of beverages, contained in Regulation 2020/1255 [18], where the maximum thresholds of 10 μg/kg for benzo(a)pyrene and 50 μg/kg for the sum of benzo(a)pyrene, benz(a)anthracene, benzo(b)fluoranthene, and chrysene are established. The same regulation warns of the need to look for new alternative smoking practices to reduce PAH contaminants. This last point is illustrative of the regulators’ concern for maintaining food safety, but also shows the concern for food quality, which has great weight at consumer level and also directly in the production and marketing of smoked products and their derivatives.
European Union also establishment, in Commission Regulation (EC) No 1881/2006 [10], the maximum levels for cadmium (Cd), lead, mercury (Hg), inorganic tin (Sn), and arsenic (As), knowing that the exposure of these heavy metals may lead to oxidation stress, which may induce DNA damage, protein modification, lipid peroxidation, and consequently, toxicity in plants and humans [19, 20]. It is important to mention, from a chemical point of view, that arsenic, although being classified as a nonmetal, is included in the group of heavy metals when it comes to environmental parameters. Consequently, from this point on we will roughly call arsenic a heavy metal [21].
For these metallic elements, the European Commission, through Regulation EC No 1881/2006 [10], sets the maximum levels for certain contaminants in foodstuffs, has fixed the tolerable weekly intake (PTWI) of mercury and lead at 1.6 and 25 μg/kg body weight (bw), respectively, Regulation EC No 488/2014 [22] sets the tolerable weekly intake (TWI) at 2.5 μg/kg bw/week for cadmium, and EC Regulation 2015/1006 [23] annexed to the Regulation EC No 1881/2006 [10], estimated maximum dietary exposures BMDL01 between 0.3 and 8 μg/kg bw/day for arsenic.
Chemical contamination is a consumer concern, but microbiological is the greatest one [24]. The presence of mycotoxins in food and feed is an important concern of the authorities concerning food safety and quality, as their presence may have an important impact on the health of consumers both in the short term and in the long term [25]. Due to its toxicity, the Rapid Alert System for Food and Feed (RASFF) in 2017 considered mycotoxins among the top 10 risk categories in terms of contaminants for food and products [26].
Mycotoxins are products resulting from the secondary metabolic by certain filamentous fungi, they are not essential for their growth and reproduction but can cause biochemical, physiological, and pathological changes in many species [27]. Fungi frequently occur in several crops, such as wheat, corn, soybeans, sorghum, and dried fruits, as well as in derived products used in human food and feed; they can accumulate in maturing products already in the field, or during harvesting, in transportation or also in storage [28, 29, 30].
Depending on microclimatic conditions, such as moisture content, temperature, pH value, and food matrix composition, fungi can produce more than one mycotoxin, and some mycotoxins are produced by more than one fungal species [31, 32]; once produced they can be modified as a result of interactions between fungi and host or during processing, so when humans or animals are exposed to several mycotoxins simultaneously synergistic effects can be observed [25]. Most mycotoxins are low-molecular-weight compounds (less than 1000 Daltons) [33], highly liposoluble, very stable, and can accumulate over time both during crop growth and post-harvest. The European Union authorities produce documentation regarding a comprehensive strategy to be implemented by the food production chain in terms of correct pre-harvest management and post-harvest strategies and also on sanitary conditions as well on the technology and operating conditions in live cycle products [25] to prevent and minimize the contents of mycotoxins as a food contaminant [34].
The main fungi producing mycotoxin belonging to the genera
We can also distinguish between the field toxins, present in the crops, represented mainly by Fusarium deoxynivalelol mycotoxins (DON), zearalenone, fumonisins, and T-2/HT-2 toxins and the storage toxins of which the main ones are aflatoxins (Aflatoxin B1) and ochratoxins (Ochratoxin A).
Human and animals can be exposed to mycotoxins through oral (i.e., dietary consumption) inhalation (dust), and dermal routes, due to their chemical characteristics they are easily absorbed and undergo systemic distribution. In systemic circulation they reach several organs, such as the liver, kidneys, nervous system, and immunological system [33], causing alterations in the immunological response carcinogenicity, teratogenicity, hepatotoxicity, neurotoxicity, nephrotoxicity, reproductive and developmental toxicity, gastrointestinal disorders, among others [32, 35].
Considering that carcinogenic and mutagenic mycotoxin actions are the main health risk in prolonged exposure, Claeys et al. in their systematic review in 2020 [36] classify the main mycotoxins according to International Agency for Research on Cancer (IRCA) criteria into three groups: group 1—The agent is carcinogenic to humans; group 2A—The agent is probably carcinogenic to humans; group 2B—The agent is possibly carcinogenic to humans; group 3—The agent is not classifiable as to its carcinogenic to humans [37]. In Table 2, we gather the IARC toxic effects by Claeys et al. with disease-related problem, fungal species, their occurrence, and the limited daily intake, when studied.
Mycotoxins | Toxic effect | Disease-related problem/targeting system | Fungal species | Frequently contaminated products | Maximum tolerable daily intake |
---|---|---|---|---|---|
Aflatoxins B1, B2, G1, G2 (AFB1, AFB2, AFG1, AFG2) e Aflatoxin M1(AFM1) | IARC Group 1 | Liver cancer, immune system | Cereals (e.g., sorghum, rice, corn, wheat, barely), oil seed (e.g., cotton, rape, sunflower) nuts (e.g., peanuts, groundnut, pistachio), spices (e.g., turmeric, black and red pepper, ginger), meat, fruit juices, eggs, feed, and foods derived from these products. | <1 ng/g [38] | |
Ochratoxin A (OTA) | IARC Group 2B | Renal cancer, liver, cardiovascular and immune systems | Soya bean, nuts, red pepper, cereals, green coffee beans, coffee beans Grapes, red pepper, peanuts, cereals dry ham, salami | 4 ng/kg bw/day [39] | |
Fumonisins B1, B2 (FB1, FB2) | Hepatocarcinoma, stimulation and suppression of the immune system, defects in the neural-tube, nephrotoxicity | Peanut, maize, and grape, feed, and foods derived from these products | 2 μg/kg bw/day [40] | ||
Sterigmatocystin (STC) | Hepatocellular carcinomas, hemangiosarcomas of the liver and pulmonary adenomas | Cheese, spices (e.g., turmeric, black, white, red and chilli, pepper, cumin, and marjoram, caraway), cereals (barely, oat, wheat, corn, rice, buckwheat, soybean, sorghum) and derived from cereals (pastas, breakfast cereals) | 1.5 μg/kg [41] | ||
Fusarin C | Mutagen and immunosuppressive activities (comparable to aflatoxins B1 and sterigmatocystin) Human esophageal cancer [42] | Cereals (wheat, oats, barley, and maize), and fruit (banana and pineapple), lentils, tomato, and pea | No available data | ||
Deoxynivalenol (DON)1 | IARC Group 3 | Vomiting, digestive disorders and oxidative damage. Cytotoxicity and genotoxicity. | Wheat, barley, oats, rye, maize, rice, sorghum and triticale | PMTDI2, PDI3 1 μg/kg bw/day4 [43] | |
Zearalenone (ZEN) | Endocrine disruptor (interaction with estrogen-receptors) | Wheat, barley, oats, rye, and maize | PMTDI 0.5 μg/kg bw/day TDI5 0.25 μg/kg bw/day (20) [44] | ||
Citrinin (CIT) | Nephrotoxic6. Involved in induction of apoptosis though oxidative stress [45] | Mainly in stored grain. Benas, fruit, vegetables herbs and spices | |||
Patulin (PAT) | Gastrointestinal ulceration, immunotoxicity and neurotoxicity | Fruits especially apples silage | PMTDI 0.4 μg/kg bw/day [44] |
Main mycotoxins, toxic effect according to IARC, fungal species, frequently contaminated products, and maximum tolerable daily intake.
A recent study with 3000 Swedish students [47] evaluated the concentrations in urine of various mycotoxins, the data showed a worrying concentration of DON levels.
PMTDI, provisional maximum tolerable daily intake.
PDI, probable daily intake.
bw, body weight per day.
TDI, tolerable daily intake.
The co-occurrence with other mycotoxins, special ochratoxin A, is usually associated with endemic nephropathy.
EU MLs, European maximum levels (EFSA).
The action of mycotoxins as carcinogenic agents is explained by their chemical characteristics, which allow them to easily penetrate both in human and animal cells, reaching the genome, where they can cause mutations in the nucleotide sequence, which can lead to important and permanent alterations in the natural cellular processes of transcription and translation, giving rise to mutations that can exacerbate and deregulate cell growth [32].
According to the above, the study of mycotoxin toxicity goes beyond its carcinogenic and teratogenic effects; its local action in the various systems is of particular importance, aerial topical action at the level of the skin and respiratory system [48, 49, 50, 51, 52]. In the digestive system beyond its acute action at the level of vomiting and diarrhea, the effects on microbiota cause changes in the phylum, genus, and microbiota species level of the various animals exposed. The alterations of microbiota have an important consequence on health, as it causes alterations in the composition of short-chain volatile fatty acids and the sphingolipids normally present in the digestive tract; these alterations have been related to the appearance of several chronic diseases in human [35].
It is necessary to process food under standardized and well-controlled conditions and control each food production cycle and storage chain. Preventive measures capable of reducing contamination to a minimum must be implemented. If contamination occurs, methods to reduce or eliminate mycotoxins should be implemented independently of several parameters such as food or feed properties.
The prevalence of mycotoxin in food and feeds calls for the attention of food safety organizations to create awareness on their control and the need to put in place strict regulations to avoid high levels of exposure. Recent studies show that children may be exposed to mycotoxins from the time of breastfeeding resulting from the prevalence of mycotoxins in the mother’s diet [32].
In fact, food quality is a very broad concept, which, according to Jeantet et al. [53], covers five different components: safety, health, sensory, service, and society, which converge in numerous aspects and criteria. This categorization is much broader than the definition of food quality from the consumer’s point of view, which is much narrower, focusing mainly on sensory and health aspects [2]. Thus, when focusing on food quality, it is inevitable to mention food safety, which, in our view, is one of the fundamental bases for consuming quality food. The implementation and application of regulations and standards of good practice in production and processing, the application of sanitary controls, the design of production and processing facilities, and the continuous monitoring of all processes are elements that help reduce the risk of contamination and hygiene that can seriously compromise public health.
This research was funded by Fundação para a Ciência e a Tecnologia (FCT, Portugal), through projects UIDP/04567/2020 and UIDB/04567/2020. P.P. gratefully acknowledges the support of the CERENA strategic project FCT-UID/ECI/04028/2019.
The authors declare no conflict of interest.
Giant cell arteritis (GCA), also known as temporal arteritis or Horton disease, is a systemic inflammatory large-vessel vasculitis that usually affects the aorta and its major branches [1].
The pathophysiology of GCA is complex and not fully understood. Histopathology studies reveal inflammation of the artery wall with predominance of CD4+ T lymphocytes and macrophages, which frequently undergo granulomatous organization with formation of giant cells. Immunopathology and molecular studies performed with temporal artery biopsies have led to the current pathogenic model [2],
GCA is primarily an immune-mediated disease due to a maladaptive response to endothelial injury, occurring in susceptible individuals and triggered by factors that have not been identified with certainty. Several microbe and viral sequences, including varicella-zoster virus, have been detected in temporal artery lesions, but no convincing causal relationship has been demonstrated [3].
The initial inflammatory response involves the activation of dendritic cells, present in the adventitia of normal arteries, through pathogen- or damage-sensing receptors, such as toll-like receptors, producing chemokines able to attract and retain dendritic cells as well as lymphocytes and macrophages. Once activated, dendritic cells are enabled to process and present antigens and strongly express major histocompatability complex (MHC) class II and costimulatory molecules (CD83 and CD86) required for T-cell recruitment [4].
Once activated, both T helper (Th)1 and Th17 differentiation pathways contribute to the development of vascular inflammation. Interleukin (IL)-12 and IL-18 produced by dendritic cells stimulate Th1 differentiation and production of interferon (IFN)-gamma which is noticeably expressed in GCA-involved arteries. IFN-gamma causes endothelial cells and vascular smooth muscle to recruit more Th1 cells, CD8+ T cells, and monocytes which differentiate into macrophages and the characteristic giant cells that produce growth factors, interleukins and proteolytic enzymes playing a distinctive role granuloma formation that progressively narrow and obstruct the vessel wall [5].
Moreover, IL-1-beta, IL-6, and IL-21 promote Th17 differentiation, which is maintained by IL-23 and results in IL-17A expression. IL-17A, profusely expressed in GCA lesions, is a proinflammatory cytokine having pleiotropic effects on a variety of cells, namely macrophages, fibroblasts, endothelial cells and vascular smooth muscle cells [6].
Systemic manifestations are related the inflammatory process and cytokine amplification. Inflammation-induced vascular remodeling leads to concentric intimal hyperplasia occurring as a repair mechanism in response to injury of the blood vessel wall. End-organ involvement results from mural hyperplasia which can narrow the arterial lumen, resulting in distal ischemia and ischemic complications of the disease [7].
Clinical presentation of GCA tends to be subacute, but may occur over the course of a few days. Although symptoms of GCA are nonspecific, some key findings may strongly suggest this diagnosis. Systemic symptoms are common in GCA and vascular involvement can be widespread, causing stenosis and aneurysm of affected vessels. It is the targeting of the tiny muscular arteries from cranial branches of the aortic arch, however, that gives rise to many of the most characteristic symptoms of GCA. External carotid branch involvement accounts for the high frequency of cranial symptoms [8].
Systemic symptoms associated with GCA are frequent and include fever, fatigue, anorexia and weight loss. These symptoms may occur for a few days and may prolong to several weeks. Fever is usually low grade and occurs in up to one-half of patients. It has been stated as well that 1 out of 6 fevers of unknown origin in older adults was due to GCA [9]. About 10% of patients with GCA present with constitutional symptoms and laboratory evidence of inflammation as the only clues to the diagnosis [10]. Thus, in an older adult with fever or constitutional symptoms not explained by an initial evaluation for infection or malignancy, a diagnosis of GCA warrants consideration [11].
Headache is a common presentation of GCA, being the initial symptom in 33% of cases and present in about 80% of patients [12]. Importantly, the headache is either new, in a patient without previous history of headaches, or of a new type in a patient with chronic headache.
While the headache has no pathognomonic features, headaches due to GCA are typically throbbing and continuous, located over the temples, but can also be frontal, occipital, unilateral or generalized. Descriptions of the pain range from a dull or burning sensation to focal tenderness on direct palpation. Patients may note scalp tenderness with hair combing or when wearing a hat. The headache can progressively worsen, wax and wane, or sometimes recede before treatment is started [13].
Jaw claudication results from ischemia of the maxillary artery supplying the masseter muscles and is highly predictive of temporal arteritis. Nearly 50% of patients experience jaw claudication, a symptom consisting of mandibular pain, discomfort or fatigue triggered by mastication or prolonged speaking and relieved by stopping [14]. An analysis of the diagnostic value of temporal artery biopsies, which correlated positive biopsies with clinical symptoms, revealed jaw claudication as the symptom most highly associated with a positive biopsy [15].
In some cases, patients note a trismus-like symptom, with either perceived or actual limitation of temporomandibular joint excursion. Claudication symptoms occasionally affect the tongue, with repeated swallowing and tongue infarction being almost pathognomonic for GCA [16, 17].
The reported incidence of visual symptoms in GCA ranges widely [18]. These include permanent visual loss, transient monocular (and, rarely, binocular) vision impairment, consisting of unilateral visual blurring, vision loss or diplopia. Patients refer an abrupt partial field defect or temporary curtain effect in the field of vision of one eye [19]. It can be useful in the course of evaluating the possible significance of a reported visual disturbance to inquire if the patient tried to cover each eye since explicit monocular visual loss would heighten concern for GCA. Transient visual loss can be a harbinger of permanent visual loss, especially if treatment is not started promptly and thus mandates urgent attention in a patient with suspected GCA.
The most feared complication of GCA is permanent loss of vision, frequently sudden and painless, may be partial or complete, and may be unilateral or bilateral. Permanent loss of vision in GCA results from arteritic anterior ischemic optic neuropathy, central or branch retinal artery occlusion, posterior ischemic optic neuropathy, or, rarely, cerebral ischemia [20]. Even in the current era effective therapy, the incidence of permanent loss of vision ranged from 15 to 20% of patients [20]. Though permanent visual loss may be preceded by single or multiple episodes of transient visual loss, it can also occur with devastating swiftness. When untreated, contralateral eye involvement commonly occurs between the first two weeks after initial onset [21]. With adequate glucocorticoid treatment, if there is no further visual deterioration within the first week, existing vision in affected eye and the vision in the unaffected eye will remain intact, virtually stopping the subsequent risk of sight loss [22].
Extraocular motility disorders occur in approximately 5% of atients and include diplopia which has a high specificity when accompanied by other symptoms suggestive of GCA [23]. Diplopia, which is usually transient, can result from ischemia of any portion of the oculomotor system, including the brainstem, oculomotor nerves, and the extraocular muscles themselves [24].
Although rare, GCA can manifest with Charles Bonnet syndrome, a phenomenon of visual hallucinations in psychologically normal individuals who have visual loss due to lesions in either peripheral or central visual pathways [25].
GCA is closely linked to polymyalgia rheumatica (PMR) and this well-known association has therapeutic and prognostic consequences. About 40 to 60% of GCA patients have manifestations of PMR, an inflammatory rheumatic condition clinically characterized by symmetrical proximal polyarthralgia and myalgia, with aching and stiffness on shoulders, hip girdle, neck, torso and an unfamiliar sense of fatigue [26].
Less commonly, distal findings can occur, involving synovitis of peripheral joints, especially at the wrists and metacarpophalangeal joints, with distal extremity swelling and pitting edema, known as remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome, puffy edematous hand syndrome or distal extremity swelling with pitting edema [27]. In this syndrome symptoms can appear abruptly, with significant swelling, usually pitting, extending over the dorsal side of the wrists and metacarpophalangeal joints producing a “boxing glove” appearance, and with limited range of motion of the hands and wrists. The term seronegative refers to the absence of antibodies namely rheumatoid factor (RF) and cyclic citrullinated peptide (anti-CCP) for differential diagnosis with rheumatoid arthritis. Imaging with ultrasonography and MRI reveal tenosynovitis of the extensor tendon of the forearms and hands, with less flexor tenosynovitis and synovitis of the metacarpophalangeal and proximal interphalangeal joints [28]. A paraneoplastic association with solid tumors and hematologic disorders has been reported, but in clinical practice such an occurrence is rare [29].
Involvement of the extracranial branches of the carotid artery is the source of the classic cranial symptoms of GCA. However, besides the carotid arteries, GCA often involves the aorta and its major branches which is designated large vessel (LV) -GCA. The clinical consequences of LV-GCA include aneurysms and dissections of the aorta, particularly the thoracic aorta, as well as stenosis, occlusion, and ectasia of large arteries. This subset of patients with predominantly upper extremity arterial vasculitis, may have variable clinical presentations and diagnostic delay [30].
While symptomatic LV involvement is uncommon, a key point is that subclinical LV-GCA involvement is present in a significant number of patients and can underlie a systemic presentation of GCA without having necessarily cranial symptomatology. Different publications using imaging modalities such as fluorodeoxyglucose positron emission tomography (FDG-PET), computed tomographic (CT) angiography and color-coded duplex ultrasonography have consistently highlighted the involvement of subclavian, axillary, brachial arteries or the thoracic aorta in more than 30% of patients with confirmed GCA diagnosis [31, 32].
Although the disease pattern of LV-GCA differs from cranial GCA, clinical features overlap. Systematic screening of patients with the cranial phenotype can demonstrate large artery involvement. On the other hand, temporal artery biopsies are positive in only approximately one-half of patients with LV GCA, underlining the essential role of imaging for the diagnosis of this phenotype.
In contrast with the cranial phenotype, LV-GCA patients were younger at disease onset (66 vs. 72 years), had longer duration of symptoms prior to the diagnosis (median 3.5 months vs. 2.2 months), fewer cranial symptoms (41% vs. 83%) and were more likely to have arm claudication at presentation (51% vs. 0%) [33].
Aortic aneurysms have been recognized in 10% of cases [34]. The thoracic aorta is more frequently affected than the abdominal aorta, and within the thoracic aorta the descending segment is the main site. It is important to note that in these cases, there is often little or no clinical or laboratory evidence of systemic activity of GCA. When compared with the general population, patients with GCA have a twofold increased risk of aortic aneurysm and this should be considered within the range of other risk factors such as male gender, age or smoking [35]. Histopathologic examination of specimens from surgery or autopsy show fibrosis and different degrees of active aortitis, including giant cells. These findings suggest two mechanisms of disease: chronic recrudescent aortitis causing elastin and collagen disruption, or mechanical stress on an aortic wall weakened in the early active phase of the disease. Aortic dissection or rupture is a rare major complication of aortitis and was identified in 5% of patients with LV-GCA with aortic aneurysm [36]. Involvement of the ascending aorta can lead to aortic rupture, and coronary arteritis may result in myocardial infarction.
GCA can also affect the subclavian arteries distal to the take-off of the vertebral arteries and extend through the axillary arteries to the proximal brachial arteries. On physical examination, arterial bruits, diminished or absent blood pressures and arm claudication can be identified. Cold intolerance of the involved extremity is common, but explicit digital ulcerations and gangrene are rare because of adequate collateral arterial supply. The vessel wall is circumferentially affected, in contrast to the eccentric appearance of atherosclerosis. The descending aorta and mesenteric, renal, iliac, and femoral arteries can less commonly be affected, with attendant complications of intestinal infarction, renal infarction, crural infarction and ischemic mononeuropathies [37]. Clinically evident lower-extremity arterial involvement can occur but is also uncommon [38].
Stroke is a rare but important complication of GCA and is typically due to stenosis of carotid and the vertebral or basilar arteries. Even with aggressive steroid and immunosuppressive therapy it is associated with high morbidity and mortality. In descriptive cohorts, the frequency of stroke within the first four weeks of the diagnosis of GCA, and thus construed as potentially disease-related, has ranged from 1.5 to 7.5% [39].
Though strokes due to GCA can occur in the distribution of both the internal carotid and vertebrobasilar arteries, they are noticeably more frequent in the latter location. More than one-half of strokes attributable to GCA occur in the vertebrobasilar system This figure contrasts with population-based studies of transient ischemic attacks and stroke overall, which occur five times more often in the territory of the internal carotid arteries compared with the vertebrobasilar arteries [40]. Arteritic involvement of the vertebral arteries can result in vertigo, ataxia, dysarthria, homonymous hemianopsia, or bilateral cortical blindness. Bilateral vertebral artery involvement, which causes rapidly progressive brainstem or cerebellar neurologic deficits with high mortality, is highly suggestive of GCA.
Peripheral neuropathy, myelopathy, higher cortical dysfunction or dementia, and pachymeningitis are uncommon complications of GCA.
Patients with GCA can present upper respiratory tract symptoms, in particular a non-productive cough. The cause of cough is unknown, but may result from vasculitis in the area of cough receptors, which are located throughout the respiratory tree, or vasculitis of the ascending pharyngeal artery, a branch of the external carotid artery. Vasculitis of the bronchial arteries has been observed in the post-mortem examination of a patient with disseminated GCA. Furthermore, involvement of the lungs in GCA has also been reported as cases of interstitial lung disease (ILD) as an uncommon clinical manifestation of GCA [41].
Patients with GCA are at increased risk for cardiovascular events, but cardiac involvement is rare. Myocardial infarction is an example of serious complication that may arise. Cases of GCA patients developing myocarditis and myopericarditis are uncommon but have been reported [42].
Branches of the external carotid artery may often be affected in GCA, namely the superficial temporal artery. Jaw claudication results from arteritic involvement of the muscles of mastication (masseter, temporalis, and medial and lateral pterygoid muscles), all of which are supplied by the branches of the external carotid artery. Involvement of other branches of the external carotid artery accounts for many of the other extracranial symptoms that can accompany the presentation of GCA, including: maxillary and dental pain, facial swelling, throat pain, tongue pain and macroglossia [43].
GCA of the female genital tract was first reported by Ritawa in 1951 [44]. Female genital tract involvement (ovary, fallopian tubes, or uterus) was identified by chance on histopathologic inspection of surgical specimens surgically removed for gynecological reasons unrelated to GCA.
Vasculitis of the breast does occur and should require exclusion of systemic involvement. When constitutional symptoms, especially arthralgia and myalgia, are present and acute phase reactants are elevated, a work-up for systemic disease is especially warranted. Histologic characteristics included vessel size and type of inflammatory infiltrates including foamy macrophages and giant cells [45]. These features did not correlate with disease extent, plus constitutional and musculoskeletal manifestations were usually absent. Patients generally did not require systemic therapy and may be cured by resection alone.
GCA should always be considered in the differential diagnosis of a new-onset headache in patients 50 years of age or older with an elevated erythrocyte sedimentation rate. Temporal artery biopsy remains the criterion standard for diagnosis of this granulomatous vasculitis but increasing evidence supports the use of imaging studies such as ultrasonography as a less invasive from of diagnosis.
The onset of symptoms in GCA tends to be subacute, but abrupt presentations occur in some patients. Although systemic manifestations are characteristic of GCA and although vascular involvement can be widespread, clinical manifestations of the disease most frequently result from involvement of the cranial branches of arteries originating from the aortic arch. When taking the patient’s history, the clinician must ask about the following types of symptoms: systemic symptoms, such as fever, fatigue, and weight loss; headache; jaw claudication, which is the symptom most highly predictive of a positive temporal artery for the diagnosis of GCA; visual symptoms, particularly transient monocular visual loss and diplopia. The most threatening complication of GCA, visual loss, is a potential result of the cranial phenotype arteritis.
A close relationship exists between GCA and PMR but the precise nature of this association is poorly understood. Several authors have suggested that these two entities are actually different stages of the same disease process. Symptoms of polymyalgia rheumatica occurring in a patient with GCA include characteristic proximal polyarthralgias and myalgias, sometimes accompanied by remitting seronegative symmetrical synovitis with pitting edema (RS3PE).
Most GCA patients present with clinical manifestations that are the result of vascular involvement but a variable proportion of patients may present without obvious vascular manifestations. Imaging may be particularly helpful in the diagnosis of GCA of large arteries in patients with atypical or occult GCA disease. Subclinical involvement of the aorta and large arteries is frequent, a clinical consequence of which can be aortic aneurysm which rarely can be complicated with dissection or rupture. Measurement of the blood pressures in both arms and careful assessment of the arterial tree by palpation and auscultation should be performed in all patients with suspected GCA. When compared with cranial disease, LV-GCA patients have higher relapse rate, greater corticosteroid requirements and increased prevalence of aortic aneurysm. It should be noted that both the 1990 and the revised 2016 American College of Rheumatology criteria may fail to recognize the LV-GCA phenotype, since a portion of LV-GCA do not have cranial symptoms.
The major risk factor for developing giant cell arteritis is aging. The disease almost never occurs before age 50 years, and its incidence rises steadily thereafter. Giant cell arteritis is a more heterogeneous condition than previously thought. Clear knowledge of all the potential clinical manifestations is essential to avoid a delayed diagnosis and associated complications. Although most of these manifestations occur prior to steroid therapy, they may also develop during the early phase of therapy or relapse with tapering of the dose of steroids. Earlier diagnosis, close monitoring and improving the treatment protocols may prevent mortality and improve morbidity in these cases.
The authors declare no conflict of interest.
No funding was received for the development of this paper.
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After finishing his P. hD degree in 1992, he served in the Industry as a Scientific Officer and continued his academic career as a visiting scholar for a number of educational institutions. In 1996 he joined National University of Science & Technology Pakistan (NUST) as an Associate Professor; NUST is one of the top few universities in Pakistan. In 1999 he joined an International Company Lineo Inc, Canada as Manager Compiler Group, where he headed the group for developing Compiler Tool Chain and Porting of Operating Systems for the BLACKfin processor. The processor development was a joint venture by Intel and Analog Devices. In 2002 Lineo Inc., was taken over by another company, so he joined Aalborg University Denmark as an Assistant Professor.\nProfessor Akbar has truly a multi-disciplined career and he continued his legacy and making progress in many areas of his interests both in teaching and research. 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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:"268659",title:"Ms.",name:"Xianquan",middleName:null,surname:"Zhan",slug:"xianquan-zhan",fullName:"Xianquan Zhan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/268659/images/8143_n.jpg",biography:"Dr. Zhan received his undergraduate and graduate training in the fields of preventive medicine and epidemiology and statistics at the West China University of Medical Sciences in China during 1989 to 1999. He received his post-doctoral training in oncology and cancer proteomics for two years at the Cancer Research Institute of Human Medical University in China. In 2001, he went to the University of Tennessee Health Science Center (UTHSC) in USA, where he was a post-doctoral researcher and focused on mass spectrometry and cancer proteomics. Then, he was appointed as an Assistant Professor of Neurology, UTHSC in 2005. He moved to the Cleveland Clinic in USA as a Project Scientist/Staff in 2006 where he focused on the studies of eye disease proteomics and biomarkers. He returned to UTHSC as an Assistant Professor of Neurology in the end of 2007, engaging in proteomics and biomarker studies of lung diseases and brain tumors, and initiating the studies of predictive, preventive, and personalized medicine (PPPM) in cancer. In 2010, he was promoted to Associate Professor of Neurology, UTHSC. Currently, he is a Professor at Xiangya Hospital of Central South University in China, Fellow of Royal Society of Medicine (FRSM), the European EPMA National Representative in China, Regular Member of American Association for the Advancement of Science (AAAS), European Cooperation of Science and Technology (e-COST) grant evaluator, Associate Editors of BMC Genomics, BMC Medical Genomics, EPMA Journal, and Frontiers in Endocrinology, Executive Editor-in-Chief of Med One. He has\npublished 116 peer-reviewed research articles, 16 book chapters, 2 books, and 2 US patents. His current main research interest focuses on the studies of cancer proteomics and biomarkers, and the use of modern omics techniques and systems biology for PPPM in cancer, and on the development and use of 2DE-LC/MS for the large-scale study of human proteoforms.",institutionString:null,institution:{name:"Xiangya Hospital Central South University",country:{name:"China"}}},{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:"418340",title:"Dr.",name:"Jyotirmoi",middleName:null,surname:"Aich",slug:"jyotirmoi-aich",fullName:"Jyotirmoi Aich",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000038Ugi5QAC/Profile_Picture_2022-04-15T07:48:28.png",biography:"Biotechnologist with 15 years of research including 6 years of teaching experience. Demonstrated record of scientific achievements through consistent publication record (H index = 13, with 874 citations) in high impact journals such as Nature Communications, Oncotarget, Annals of Oncology, PNAS, and AJRCCM, etc. Strong research professional with a post-doctorate from ACTREC where I gained experimental oncology experience in clinical settings and a doctorate from IGIB where I gained expertise in asthma pathophysiology. A well-trained biotechnologist with diverse experience on the bench across different research themes ranging from asthma to cancer and other infectious diseases. An individual with a strong commitment and innovative mindset. Have the ability to work on diverse projects such as regenerative and molecular medicine with an overall mindset of improving healthcare.",institutionString:"DY Patil Deemed to Be University",institution:null},{id:"349288",title:"Prof.",name:"Soumya",middleName:null,surname:"Basu",slug:"soumya-basu",fullName:"Soumya Basu",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035QxIDQA0/Profile_Picture_2022-04-15T07:47:01.jpg",biography:"Soumya Basu, Ph.D., is currently working as an Associate Professor at Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune, Maharashtra, India. With 16+ years of trans-disciplinary research experience in Drug Design, development, and pre-clinical validation; 20+ research article publications in journals of repute, 9+ years of teaching experience, trained with cross-disciplinary education, Dr. Basu is a life-long learner and always thrives for new challenges.\r\nHer research area is the design and synthesis of small molecule partial agonists of PPAR-γ in lung cancer. She is also using artificial intelligence and deep learning methods to understand the exosomal miRNA’s role in cancer metastasis. Dr. Basu is the recipient of many awards including the Early Career Research Award from the Department of Science and Technology, Govt. of India. She is a reviewer of many journals like Molecular Biology Reports, Frontiers in Oncology, RSC Advances, PLOS ONE, Journal of Biomolecular Structure & Dynamics, Journal of Molecular Graphics and Modelling, etc. She has edited and authored/co-authored 21 journal papers, 3 book chapters, and 15 abstracts. She is a Board of Studies member at her university. She is a life member of 'The Cytometry Society”-in India and 'All India Cell Biology Society”- in India.",institutionString:"Dr. D.Y. Patil Vidyapeeth, Pune",institution:{name:"Dr. D.Y. Patil Vidyapeeth, Pune",country:{name:"India"}}},{id:"354817",title:"Dr.",name:"Anubhab",middleName:null,surname:"Mukherjee",slug:"anubhab-mukherjee",fullName:"Anubhab Mukherjee",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y0000365PbRQAU/ProfilePicture%202022-04-15%2005%3A11%3A18.480",biography:"A former member of Laboratory of Nanomedicine, Brigham and Women’s Hospital, Harvard University, Boston, USA, Dr. Anubhab Mukherjee is an ardent votary of science who strives to make an impact in the lives of those afflicted with cancer and other chronic/acute ailments. He completed his Ph.D. from CSIR-Indian Institute of Chemical Technology, Hyderabad, India, having been skilled with RNAi, liposomal drug delivery, preclinical cell and animal studies. He pursued post-doctoral research at College of Pharmacy, Health Science Center, Texas A & M University and was involved in another postdoctoral research at Department of Translational Neurosciences and Neurotherapeutics, John Wayne Cancer Institute, Santa Monica, California. In 2015, he worked in Harvard-MIT Health Sciences & Technology as a visiting scientist. He has substantial experience in nanotechnology-based formulation development and successfully served various Indian organizations to develop pharmaceuticals and nutraceutical products. He is an inventor in many US patents and an author in many peer-reviewed articles, book chapters and books published in various media of international repute. Dr. Mukherjee is currently serving as Principal Scientist, R&D at Esperer Onco Nutrition (EON) Pvt. Ltd. and heads the Hyderabad R&D center of the organization.",institutionString:"Esperer Onco Nutrition Pvt Ltd.",institution:null},{id:"319365",title:"Assistant Prof.",name:"Manash K.",middleName:null,surname:"Paul",slug:"manash-k.-paul",fullName:"Manash K. Paul",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/319365/images/system/319365.png",biography:"Manash K. Paul is a Principal Investigator and Scientist at the University of California Los Angeles. He has contributed significantly to the fields of stem cell biology, regenerative medicine, and lung cancer. His research focuses on various signaling processes involved in maintaining stem cell homeostasis during the injury-repair process, deciphering lung stem cell niche, pulmonary disease modeling, immuno-oncology, and drug discovery. He is currently investigating the role of extracellular vesicles in premalignant lung cell migration and detecting the metastatic phenotype of lung cancer via machine-learning-based analyses of exosomal signatures. Dr. Paul has published in more than fifty peer-reviewed international journals and is highly cited. He is the recipient of many awards, including the UCLA Vice Chancellor’s award, a senior member of the Institute of Electrical and Electronics Engineers (IEEE), and an editorial board member for several international journals.",institutionString:"University of California Los Angeles",institution:{name:"University of California Los Angeles",country:{name:"United States of America"}}},{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://mts.intechopen.com/storage/users/219081/images/system/219081.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:"Kafkas University",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:"329248",title:"Dr.",name:"Md. Faheem",middleName:null,surname:"Haider",slug:"md.-faheem-haider",fullName:"Md. Faheem Haider",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329248/images/system/329248.jpg",biography:"Dr. Md. Faheem Haider completed his BPharm in 2012 at Integral University, Lucknow, India. In 2014, he completed his MPharm with specialization in Pharmaceutics at Babasaheb Bhimrao Ambedkar University, Lucknow, India. He received his Ph.D. degree from Jamia Hamdard University, New Delhi, India, in 2018. He was selected for the GPAT six times and his best All India Rank was 34. Currently, he is an assistant professor at Integral University. Previously he was an assistant professor at IIMT University, Meerut, India. He has experience teaching DPharm, Pharm.D, BPharm, and MPharm students. He has more than five publications in reputed journals to his credit. Dr. Faheem’s research area is the development and characterization of nanoformulation for the delivery of drugs to various organs.",institutionString:"Integral University",institution:{name:"Integral University",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:"333824",title:"Dr.",name:"Ahmad Farouk",middleName:null,surname:"Musa",slug:"ahmad-farouk-musa",fullName:"Ahmad Farouk Musa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/333824/images/22684_n.jpg",biography:"Dato’ Dr Ahmad Farouk Musa\nMD, MMED (Surgery) (Mal), Fellowship in Cardiothoracic Surgery (Monash Health, Aust), Graduate Certificate in Higher Education (Aust), Academy of Medicine (Mal)\n\n\n\nDato’ Dr Ahmad Farouk Musa obtained his Doctor of Medicine from USM in 1992. He then obtained his Master of Medicine in Surgery from the same university in the year 2000 before subspecialising in Cardiothoracic Surgery at Institut Jantung Negara (IJN), Kuala Lumpur from 2002 until 2005. He then completed his Fellowship in Cardiothoracic Surgery at Monash Health, Melbourne, Australia in 2008. He has served in the Malaysian army as a Medical Officer with the rank of Captain upon completing his Internship before joining USM as a trainee lecturer. He is now serving as an academic and researcher at Monash University Malaysia. He is a life-member of the Malaysian Association of Thoracic & Cardiovascular Surgery (MATCVS) and a committee member of the MATCVS Database. He is also a life-member of the College of Surgeons, Academy of Medicine of Malaysia; a life-member of Malaysian Medical Association (MMA), and a life-member of Islamic Medical Association of Malaysia (IMAM). Recently he was appointed as an Interim Chairperson of Examination & Assessment Subcommittee of the UiTM-IJN Cardiothoracic Surgery Postgraduate Program. As an academic, he has published numerous research papers and book chapters. He has also been appointed to review many scientific manuscripts by established journals such as the British Medical Journal (BMJ). He has presented his research works at numerous local and international conferences such as the European Association for Cardiothoracic Surgery (EACTS) and the European Society of Cardiovascular Surgery (ESCVS), to name a few. He has also won many awards for his research presentations at meetings and conferences like the prestigious International Invention, Innovation & Technology Exhibition (ITEX); Design, Research and Innovation Exhibition, the National Conference on Medical Sciences and the Annual Scientific Meetings of the Malaysian Association for Thoracic and Cardiovascular Surgery. He was awarded the Darjah Setia Pangkuan Negeri (DSPN) by the Governor of Penang in July, 2015.",institutionString:null,institution:{name:"Monash University Malaysia",country:{name:"Malaysia"}}},{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. 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