Administration regimens proposed for Aglepristone (Alizine®, Virbac, France) treatments in feline mammary fibroepithelial hyperplasia.
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More than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
\\n\\nOur breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
\\n\\n“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
\\n\\nAdditionally, each book published by IntechOpen contains original content and research findings.
\\n\\nWe are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
\\n\\n\\n\\n
\\n"}]',published:!0,mainMedia:{caption:"IntechOpen Maintains",originalUrl:"/media/original/113"}},components:[{type:"htmlEditorComponent",content:'
Simba Information has released its Open Access Book Publishing 2020 - 2024 report and has again identified IntechOpen as the world’s largest Open Access book publisher by title count.
\n\nSimba Information is a leading provider for market intelligence and forecasts in the media and publishing industry. The report, published every year, provides an overview and financial outlook for the global professional e-book publishing market.
\n\nIntechOpen, De Gruyter, and Frontiers are the largest OA book publishers by title count, with IntechOpen coming in at first place with 5,101 OA books published, a good 1,782 titles ahead of the nearest competitor.
\n\nSince the first Open Access Book Publishing report published in 2016, IntechOpen has held the top stop each year.
\n\n\n\nMore than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
\n\nOur breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
\n\n“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
\n\nAdditionally, each book published by IntechOpen contains original content and research findings.
\n\nWe are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
\n\n\n\n
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Feline mammary masses are frequently suspected of being mammary tumours. Immediate attention is required as over 80% of mammary tumours in cats are malignant [1,2], albeit mammary masses in cats are less common than in dogs. However, prevalence of mammary tumours is highly variable with the geographic region, as it tends to be lower in areas where most cats are neutered at a young age. Due to the negative prognosis generally attributed to feline mammary tumours, little attention has been paid to benign mammary growths and mastectomy is still often performed to deal with feline mammary fibroepithelial hyperplasia.
Feline mammary fibroepithelial hyperplasia represents a benign, progesterone-associated fibroglandular proliferation of one or more mammary glands that may occur in both the female and male cat [3,4]. It is also named feline hypertrophy, fibroadenomatous changes, mammary hyperplasia or fibroadenoma complex [3-5].
Feline mammary fibroepithelial hyperplasia (FEH) is characterized by the sudden onset of mammary swollen within a short period of 2 to 5 weeks, frequently concerning several mammary glands. When exuberant it is often at the origin of the consultation [6-9]. Ulceration and abscessation of the mammary gland may occur due to gland enlargement and trauma, in chronic situations [9,10].
Feline mammary fibroepithelial hyperplasia is considered to be a benign condition, yet its behaviour and gross appearance is similar to mammary neoplasic lesions, in particular when solitary ulcerated or violaceous lesions are present. Although it rapid growth may cause concern, fibroepithelial mammary lesions are reversible, and the volume of the mammary masses tend to decrease after luteolysis or at the end of exogenous progestagen activity [4,5,11].
Tentative diagnosis of mammary fibroepithelial hyperplasia should be based on the gross appearance of the lesions and on the history despite that most frequently, historic information is limited or incomplete, as a previous occurring estrus is seldom detected. Thus, diagnosis of feline mammary fibroepithelial hyperplasia is a clinical issue, and is not difficult to be established when all the mammary glands show a rapid enlargement, independently of the size of the swollen mammary gland [4,9]. This diagnosis may be further supported by the raised blood progesterone levels or by reported recent progestin treatment. However, when fibroepithelial lesions develop in only one mammary gland, distinguish between hyperplasia and mammary tumour may become more challenging. Biopsies or excision of the mammary lesions are frequently performed. Nevertheless, differential diagnosis with mammary carcinomas has to be carefully established, as around 85% of all mammary neoplasias are malignant [9].
As FEH is a non-neoplastic progesterone-associated disorder, it is possible for most situations to apply medical treatment. Administration of antiprogestins remains the elective medical treatment, and its schedule and duration is usually related to the severity of the problem at presentation. Complete excision of the mammary chain, under the supposition of a mammary tumour, may become a really aggressive surgery. Nowadays, with the available medical options mastectomy should be avoided in case of FEH.
Recurrence of the situation, although possible, remains controversial [6,11-13]. Nevertheless it is an important issue when discussing the therapeutic approach with owners. Ovariohysterectomy remains an option in animals not intent to reproduction and in animals submitted to progesterone-based contraception, even if postponed until mammary glands regress into the normal size.
The objective of this work was to present and discuss the clinical approaches available to establish the diagnosis and the therapeutic options for feline mammary fibroepithelial hyperplasia. The final purpose in the diagnosis and treatment of such disease is not only to confirm that the clinical situation was correctly identified, but also to select the most suitable therapeutic approach to each patient, and also avoiding precipitate mastectomy and other complications of the surgical act, with the minimum repercussions on patients\' welfare.
Feline mammary fibroepithelial hyperplasia occurs in intact queens of any age, in pregnant females and in female or male cats under progestin treatment [6-8,14]. It predominantly affects younger intact female cats, a segment of the population that also presents an increased ratio of spontaneous ovulation [15,16]. The reported age range for FEH is 6 months to 13 years [17-20]. Not so frequently, the condition may also be seen in aged females, associated or not with a contraceptive treatment, and sporadically in hormonally treated male tomcats. In a local study, the age range for FEH was 10 months to 10 years (the median for the age was 3 years), and the condition was exclusively diagnosed in queens [21]. This contrast with the usual age at presentation in case of mammary neoplasia, which is middle-aged queens, since the risk for mammary tumour increase with the cat age, particularly at 10-12 years [1,22].
Moreover, few reports exist on the occurrence of FEH in males under treatment with antiandrogenic drugs, such as delmadinon acetate (Meisl et al., cited in [8]) and cyproterone acetate [12], frequently used by cat fanciers for eliminating the urine spraying in intact adult tomcats. Infrequently, descriptions of FEH in spayed queens or male cats supposedly not submitted to steroid treatment have been published [11,23], but the doubt remained on the absence of an involuntary hormonal treatment.
It is generally accepted that the incidence of this disturbance may reach up to 20% of the mammary masses detected in cats, its prevalence varying with the country or the region, which reflect cultural differences in the reproductive management of domestic and free-roaming felids. In a study developed in the north of Portugal, based on the excisional material sent for histopathology analysis, the mammary fibroepithelial hyperplasia reach 13% of the feline mammary masses [21]. Nevertheless, according to our experience, incidence of FEH seems to be in regression among the group of animals submitted to progesterone-based contraception, may be due to the fact that most contraceptive treatments are now based in oral, veterinary drugs (such as Megescat®) instead of human design depot products (like Depo-Provera®). Nevertheless, the medroxyprogesterone acetate and the megestrol acetate are the most frequently reported progestin associated to FEH, in particular when the drug is injected [13,14,18,24].
Mammary enlargement is usually observed within 1-2 weeks after estrus or within 2-6 weeks after hormone treatment.
Apparently, no breed predisposition has been suggested for FEH. Even so, the majority of the cases were described in domestic shorthaired cats, which could simply be due to the fact that it may constitute the majority of the population worldwide.
The exact pathogenesis of FEH remains unclear, although sex steroid involvement has been acknowledged for long. Progesterone or its synthetic analogues have being recognized as being at the origin of most of the FEH situations described.
The interaction between the activity of the mammary gland and the sex steroids is recognised for long. In brief, development and growth of the mammary gland is under the control of progesterone, which effects are mainly mediated through the progesterone receptor (PR) on stromal and epithelial cells [25]. Local activation of PR triggers a cascade of specific and sequential series of molecules, specific for each glandular element, which stimulates mammary gland proliferation. In physiological conditions, the cyclic changes between estrogens and progesterone stimulate or repress the cyclic activation of such PR-mediated pathways [25]. A decrease in PR levels is associated to a reduction of progesterone activity. Progesterone has been reported as having a major role in mammary ductal branching [26,27], while estrogens acting via the ER have been associated to ductal elongation and bifurcation [27].
An aberrant regulation or those pathways may be at the origin of the disturbed response to the progesterone stimulation and contribute to the development of mammary gland hyperplastic or neoplastic growth. It is possible that such response may be associated to two factors: the extreme sensitivity of the feline mammary gland to sex steroids action, as referred in older studies (Bässler, cited in [17]); and the fact that the mammary gland is usually very thin when non-pregnant or non-lactating [28].
In a recent study, the two progesterone receptors (PR) isoforms (A and B) have been evidenced in tissue samples from fibroepithelial hyperplasia lesions, with predominant expression in the ductal epithelium. It was also reported a higher expression of PR in the stroma of FEH lesions in comparison to those found in stroma from mammary carcinomas [29]. The presence of estrogen receptors (ER) in FEH lesions remains a subject of controversy, as the number of cases where ER has been detected varies along the reports [20,30,31]. Nevertheless, a slight reduction in ER expression seems to accompany the process. Expression of PR in a progesterone-target tissue is dependant of the previous stimulation by estrogens via ER, while progesterone effects also include the down-regulation of estrogen receptors. So it is also possible that the length of progesterone dominance or the circulating levels of progesterone may influence the amount of ER found in mammary tissue in the available studies.
The potential role of estrogens in the development of fibroepithelial hyperplasia needs clarification, as it may influence the relationship between the progesterone and estrogen receptors in mammary gland tissue. Further, in one recent study the concentrations of estradiol in animals suffering from FEH were higher than values typical for the luteal phase, both in case of the first appearance of fibroepithelial hyperplasia and in recurrences [13].
Progestagens (progesterone and synthetic progestins) influences on feline mammary glands result in the stimulation of the cellular proliferation through PR stimulation. It was proposed that binding of progestagens to PR would enhancement the local GH expression [29,32]. The GH presents a mitogenic action, which is mediated by insulin-like growth factor-1 (IGF-1) [32,33], a molecule shown to possess a strong mitogenic and anti-apoptotic effect on the mammary epithelial cells. The increased expression of GH, GH receptor and IGF-I was demonstrated in FEH lesions [29].
For fibroadenomatous hyperplasia associated to the cyproterone acetate administration it was found that this drug may present a “gestagenic” effect, which it was suggested to contribute to the development of fibroepithelial hyperplasia of mammary glands [12].
Comparative studies of the proliferative index (measured by Ki67/MIB1 expression) in feline fibroepithelial hyperplasia and other mammary tumours showed that, in spite of being a benign disturbance, it shows a very high proliferative index similar to the one observed in invasive mammary carcinomas [34,35]. Fibroepithelial hyperplasia, which exhibits unique morphological and biological features, is characterised by rapid proliferation of epithelium and stroma [35]. Regardless its classification as a hyperplastic lesion, with a favourable biological behaviour, all cases of fibroepithelial hyperplasia exhibited high rates of cell proliferation, with mean values similar to those of carcinomas in accordance with the results of a previous investigation [35].
Despite that increase expression of PR has been found in the FEH lesions in comparison to normal diestrous mammary tissue samples, the blood levels for progesterone are usually within the normal levels for the species [6], although cats may present considerable variation in their progesterone blood levels [36]. This is suggestive that the disease would correspond to a disturbed, exaggerated response of the tissue to the circulating hormones.
Macroscopically, FEH lesions appear as firm, well-circumscribed but unencapsulated masses, that may present two types of macroscopic patterns: the solid type, of smooth-surfaced tissue with scant fluid; and the parenchymal, intraductal pattern, with fluid-filled spaces [18]. The two patterns can be combined in the same lesion, or one of them can predominate over the other. The cut surface is solid, diffusely white or grey-white and homogeneous [9,37,38]. Areas containing gelatinous material may be found, disposed as cleft-like spaces created by the enlarged ducts [21,37] (Figure 1). Although necrosis or ulceration are rare [17], they can be found in long lasting situations or whenever the reduction of the mammary gland swelling was attempted by progestin administration.
Gross appearance of feline mammary fibroepithelial hyperplasia lesions. On the left, the cut surface of a formalin-fixed lesion showing a solid pattern. On the right, the cut surface of a fresh lesion showing several cleft-like areas (arrow), typical of the intraductal pattern.
Microscopically, the two patterns are similar [18]: the diseased mammary gland is characterized by the proliferation of glandular fibroepithelial elements. The lesions correspond to well-demarcated, non-encapsulated growths within the mammary gland [17,31], with the ducts forming pseudo-acinar or cystic structures, encircled by a loose, myxoid stroma [21]. Although the proportions of epithelial and connective tissue are variable with the lesion and distinct from the one found in the normal gland, the branched ducts and stroma retains its organization in lobular-like units. The branching ductal structures are lined by several layers of epithelial cells and surrounded by markedly proliferating and oedematous connective tissue. Loose periductal connective tissue, that gives higher prominence to the mammary stroma, is loose-textured and merged in the periphery to the more dense collagenous tissue that separates the mammary lobules [9,17,31,37,38]. Mitotic figures are commonly found both in the epithelium and the stroma [17,31], and apocrine differentiation is frequently found within the epithelial component. Further, it is often observed that the cells in the intralobular stroma lack polarity and show indistinct borders [17], and also some degree of cytological atypia, which is reactive [21]. Thereby, a falsely malignant appearance is created, which could be patent in the results for a fine needle aspiration biopsy. An inflammatory infiltrate is seldom found, and when present it is mostly of the lymphoplasmocitary type [21].
Usually, the main complaint for FEH is the existence of excessive mammary enlargement that evolved rapidly. This in fact characterises the disease.
Feline mammary glands thickness is minimal in cycling females, and also it does not change much until close to parturition [28]. Consequently, for most cases an increase of the volume of the mammary glands, either isolated or multiple, in otherwise clinically healthy animals, draws the attention of the cat owner. Time since the beginning of the mammary enlargement till the animal presentation seems to vary with the form of the FEH. It tends to be shorter in cases of more notorious swelling of multiple glands and may be longer in cases of solitary and smaller lesions.
The major clinical sign is the swollen, firm mammary gland tissue, that can be detected in as multiple, bilateral enlargement of the mammary chains, or develop as a solitary, unique lesion that may develop from any of the mammary glands (Figure 2). The size of the enlarged glands is quite variable, ranging from 1.5 to 18 cm [21]. In our experience, when multiple lesions develop, asymmetrical lesions are more frequently found in non-pregnant females, while females being pregnant tend to develop more homogeneous swellings of the mammary glands (Figure 2).
At the visual inspection, the skin covering the diseased mammary glands may be tense and erythematous, in particular in larger lesions. The nipples can be difficult to find due to the size of the gland. At palpation, the lesions are presented as diffuse, firm and consistent masses, or in some cases they present a soft and more gelatinous, floating consistency. If notorious swelling develops, the diseased mammary glands may become pendulous. In uncomplicated situations and unless the masses are too swollen, the lesions are not painful, although some distress may be elicit during mammary manipulation during the clinical examination. Further, when severe swelling of the mammary glands developed, locomotory problems may arise that may induce some distress with movement or reluctance to walk and a reduction of appetite. Less severe lesions usually evolve in the absence of an inflammatory reaction.
Whatever the dimensions of the mammary glands, when FEH develops in pregnant females, no milk is produced in the diseased glands [23]. Consequently, after parturition, kittens are unable to nurse satisfactorily and usually the owners refer to litter vocalisation, restless and fading, with offspring death over a short-time period in postpartum.
In some severe or prolonged situations, the primary FEH may co-exist with mastitis or ulceration (Figure 2). In our clinic, mastitis is more frequently found in lactating females suffering from FEH. However, ulceration may develop secondary to perfusion problems derived from skin overstretching, with local ischemia, leading to abscessation, or also due to excessive grooming. Ulceration predisposes the diseased gland to mastitis or abscessation and subsequently to systemic illness [10-12]. In such situations, depending on the severity of the process, the skin may be wet, exudative, haemorrhagic and abnormal glandular discharge, with necrotic debris or purulent. Involvement of the regional lymph nodes is possible [10]. Then, the animal may be presented to consultation with fever, lethargy, anorexia, pale mucous membranes and dehydration.
Diverse aspects of feline mammary fibroepithelial hyperplasia. A – A solitary lesion in a female cat submitted to megestrol acetate treatment. B - Multiple lesions showing asymmetric distribution of the diseased mammary glands, which also presented different dimensions, in a young spontaneous-ovulatory queen. C – In larger lesions, the skin around the nipple may be stretched, moist and violet, due to excessive grooming. D – FEH complicated with mastitis and ulceration in a female at post-partum day 6. E – FEH in a peri-partum young female that also showed skin erosion around the nipples of the caudal mammae.
Little information is available on the haematological and blood biochemistry changes in animals suffering from FEH. Nevertheless, in animals suffering from non-complicated mammary fibroepithelial hyperplasia, most parameters analysed (blood haematology and biochemistry) were within the normal range values for the species [11,14]. In animals with FEH co-existing with mastitis and ulceration, it can be found anaemia [10,39], normal to increase packed-cell volume [12,13,39] and the leukocyte count near the maximum normal limit or increased [10,12,39]. All these changes have been associated to inflammation and/or sequestration of fluid within the distended mammary tissue or to patient dehydration.
On what concerns the blood biochemistry, for most cases the values for blood urea and creatinine, or for the hepatic enzymes (such as the alkaline phosphatase, the alanine aminotransferase and the aspartate aminotransferase) were within the normal limits for cats [11-13], or slightly decreased [10].
Diagnosis of feline mammary fibroepithelial hyperplasia is always a clinical issue, and should be based on the symptoms, the patient signalment and on history [39,40]. Differential diagnoses should include the mammary tumours (adenocarcinoma or carcinoma, mammary adenoma, or mammary sarcoma) and the mammary fibroepithelial hyperplasia.
Usually it is not difficult to establish a diagnosis when multiple glands are enlarged. An important criterion is the rapid onset of the mammary swelling, independently of the size of the swollen mammary gland. Also the age of the female may be suggestive of FEH, as it is more frequently found in young females. The sex of the animal should not be an exclusion criterion, as FEH also develop in males submitted to hormonal treatment for urine spraying or skin conditions. Neither it should be the reproductive status of the cat, as FEH can develop in neutered cats with pyoderma or miliary dermatitis following hormonal treatment with progestins. Moreover, a rapid enlargement of the mammary chains in a early or mid-pregnant females should lead to the suspicion of FEH, as the mammary glands shows little development until near parturition in cats. Unless an excessive swelling of the mammary exits, FEH is painless.
Yet, when fibroepithelial lesions develop in a single mammary gland, distinguishing between hyperplasia and mammary tumour may become more challenging, particularly in mature or older animals. As in other FEH conditions, the lesion develops at a very rapid rate, is frequently painless and although firm it is also turgid with a regular oedematous texture at palpation. Although it should not be considered as a rule, frequently FEH solitary lesions reach larger volumes than those referred to feline mammary tumours [22], and are softener.
Discoloration of the skin underlying FEH lesions was once reported [41], but I was not able to confirm that association in my practice.
Occurrence of FEH indicates that the animal ovulated and endogenous progesterone is raised or that it was treated with progestins. Hence, the mammary fibroepithelial hyperplasia diagnosis may be further supported by determination of blood progesterone levels. However, one should be aware that progesterone levels may be low when the underlying cause are exogenous progestins, because nowadays progesterone analysis are quite specific and may not cross-label with the used progestin molecule. Thus, it is also of utmost importance to determine the existence of a recent progestin treatment.
Biopsies are often referred as being the most acceptable form to confirm the diagnosis of mammary fibroepithelial hyperplasia. However, cytological differentiation between benign and malignant mammary lesions is difficult. The accuracy of cytological differentiation is low, and its specificity has not yet been attributable. Further, the cytological analysis should be interpreted together with the symptoms and the sudden onset of the clinical signs [11].
It should be remembered that mammary fibroepithelial hyperplasia lesions are highly proliferative [34,35] and that some degree of cytological atypia [21] are often described, which along with the described loss of cell polarity [17] and the occurrence of mitosis [17,31], can create a falsely malignant appearance that could biased the diagnosis. Consequently, if a histopathological diagnosis is wanted, an excisional biopsy is preferable to a fine needle aspiration, despite being more expensive.
Diagnosis of FEH in cytological specimens should meet the following criteria: Two different cells (one of uniform epithelial cells and one of spindle-shaped mesenchymal cells) should co-exist, and may display a moderate anisocytosis and anisokaryosis, with only minimal nuclear criteria of malignancy. A large amount of eosinophilic extracellular matrix is expectably found in close proximity to the cells (Mesher, cited in [11]).
Mammary ultrasonography may also be helpful on the diagnosis of feline mammary fibroepithelial hyperplasia. Furthermore it is a rapid and easily performed method for assessment of the mammary gland structure. Generally, the ultrasonographic mammary echogenicity is higher in FEH lesions when compared to normal and lactational feline mammary glands (Figure 3). On ultrasound images, FEH lesions present mainly as a well-circumscribed solid mass of granular, slightly hyperechoic texture, with regularly delimited margins. It is also common to found small cleft-like structures, appearing as irregular anechoic areas, without acoustic enhancement, and small hyperechoic foci scattered within the glands image, which are independent of the form of FEH (multiple or solitary form). The presence of clefts in mammary fibroepithelial lesions provided a more heterogeneous appearance to the ultrasound images. In our practice clefts are more frequently found in animals under progestin treatment. The ultrasound pattern is more homogeneous in solid lesions, whilst when the intraductal pattern dominates, anechoic areas corresponding to clefts of different shapes are found within the mammary gland parenchyma (Figure 4).
Radiology is of little interest in cases of FEH, as for most situations lateral abdominal surveys only shows the enlargement of the mammary glands, an intact body wall and sporadically homogeneous fluid opacity in the diseased mammary glands [10]. In comparison, ultrasonography can bring you more information through the assessment of the lesion echogenicity and pattern. However, when attempting to establish a differential diagnosis with mammary carcinoma, thoracic and abdominal radiographs are advised to screen for possible metastases and calcification.
Ultrasound images of normal feline mammary gland in non-pregnant, late pregnant and lactating females (from left to right).
Ultrasound images of feline mammary fibroepithelial hyperplasia lesions. On the left, images from a solid pattern lesion. On the right, images from lesions presenting cleft-like anechoic areas, characteristics of the intraductal pattern.
Finally, confirmation of the tentative diagnosis can also be achieved through the response to Aglepristone treatment. Aglepristone as an antiprogesterone drug can elicit a positive response with a reduction of the mammary swelling and improvement of the clinical condition, which can be obtained around day 3 post-administration (for the doses and schedule, please see next section).
In most animals diagnosed with FEH, the extent of the swelling of the mammary glands and the possibility of necrosis and infection warrant treatment, though this is generally considered as a benign disturbance [23]. Even so, seldom sporadic recovery is observed [6], and when described it usually take several weeks to months.
The feline mammary fibroepithelial hyperplasia being a progesterone-associated disturbance, the therapeutic approach should focus on the removal of the progesterone influences in order to revert the symptoms. Thus, discontinuing of any ongoing hormone therapy is mandatory.
Available approaches should be discussed with the cat owner, including a prevision of the costs for the treatment, the time to full recovery and the possibility for the occurrence of a relapse. For most FEH situations 21-24 days may be needed to fully reversion of the mammary gland enlargement, but it may vary with the selected therapeutic approach.
In addition to the treatment directed to feline mammary fibroepithelial hyperplasia, situations complicated with mastitis and skin ulceration or abscessation or systemic illness, additional treatment targeting the recovery of the inflammatory condition and the stabilization of the patient may be needed. Adequate broad-spectrum antimicrobial treatment (with Amoxicillin-Clavulanic acid or Cephradine for example), or fluid replacement may be needed. Also, when pain or discomfort exists, short-time treatment with nonsteroidal anti-inflammatory drugs (such as Meloxicam, Ketoprofen or Carprofen) may be used to alleviate the symptoms.
Until the late 90´s decade, ovariectomy or ovariohysterectomy were considered the most suitable treatments [19]. The lateral surgical approach was preferable to the ventral to avoid the trauma of the mammary tissue. Excision of the ovaries usually leads to regression of the mammary tissue within three to four weeks, but in some situations regression was not achieved [11,23].
Mastectomy is discouraged as a first approach to the feline mammary fibroepithelial hyperplasia. Only in animals not responding to spaying or to the medical treatment, partial or total mastectomy may be considered, but the surgery is difficult to perform because of the extensiveness of the mammary glands. A radical mastectomy often leads to complications and is only to be recommended when other options have failed.
Nowadays, medical therapeutic approaches are available in most countries. Economic constraints may influence the drug of choice, and this may influence the recovery time. Also, when predicting the recovery time, one should be aware that FEH secondary to exogenous progestin would take longer to regress if antiprogesterone drugs are not selected.
Several studies demonstrated that the progesterone receptor blocker Aglepristone (Alizine®, Virbac, France) can successfully revert FEH [8,11,13,19,23]. Aglepristone is a molecule that competitively binds to the progesterone receptor without activating the hormone response cascade in target tissues. This drug binds to with a 9-fold affinity to progesterone receptor, and according to the manufacturer its residence time in the organism is of 6 days, if administered once in the dose of 20mg/kg or twice at 10mg/kg [23]. Although not licenced to be used in cats, this drug is commonly used to induce abortion or to treat pyometra in this species. By consequence, its application in cats is under the veterinarian responsibility.
Before starting the treatment with Aglepristone it is important to exclude pregnancy, as this drug may elicit abortion of a premature birth. When FEH develops in pregnant females it is mandatory that the therapeutic approaches are discussed with the cat owner in detail, and is important to mention that despite the mammary enlargement, the diseased glands will not produce milk and also that the kittens attempts to nurse may predispose to complications such as mastitis and ulceration, which will worsen the evolution of the primary condition.
Several therapeutic schedules have been described in the literature for Aglepristone in FEH (Table 1). Personally, I prefer to inject 10mg/kg of Aglepristone (Alizine®) on days 1 and 3, subcutaneously (SC), and to re-evaluate the situation a week later. If necessary, a second administration is performed following the same schedule. Rarely (only one situation in 25 cases treated with Alisine®) I needed to perform a third administration (again two doses 48h apart), in a female that was submitted to oral progestin treatment that started during estrus. Reduction of the mammary volume, in particular the mammary thickness, is the major parameter for assessment of the response to treatment. Mammary thickness can be assessed by ultrasonography. By using this schedule, it can be observed a slight reduction in the thickness of the disease mammary glands between days 1 and 3, which is predictive of the expected length of the treatment. For most cases, FEH recovery was obtained in 3 to 4 weeks, with only one situation (the one above mentioned) taking 6 weeks to obtain full regression of the mammary condition.
Varying with the reports, the a mean of 4 to 5 treatments (Table 1) are needed to recover from FEH [23,42], and full recovery was obtained in varying periods that last for 3 to 11 weeks [23].
Occasionally, short-term skin irritation at the site of injection has been reported [23], but it seldom originates a problem.
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t
0,33ml/kg/d corresponding to 10mg/kg/d | \n\t\t\t2 doses, 24h apart; Repeat at week intervals to full recovery | \n\t\t\t[13] | \n\t\t
4 to 5 consecutive days | \n\t\t\t[19] | \n\t\t|
4 to 5 consecutive days and again on day 7 | \n\t\t\t[8] | \n\t\t|
On days 1, 2, 7, 14 and 21 | \n\t\t\t[42] | \n\t\t|
2 doses, 24h apart, for 4 consecutive weeks | \n\t\t\t[23] | \n\t\t|
0,66ml/kg/d corresponding to 20mg/kg/d | \n\t\t\tOnce a week, for 4 consecutive weeks | \n\t\t|
0,33ml/kg/d corresponding to 10mg/kg/d | \n\t\t\tOn days 1, 2 and 7 | \n\t\t\t[40] | \n\t\t
0,5ml/kg/d corresponding to 15mg/kg/day | \n\t\t
Administration regimens proposed for Aglepristone (Alizine®, Virbac, France) treatments in feline mammary fibroepithelial hyperplasia.
In some case descriptions, dopamine agonists such as Cabergoline and Bromocriptine were also used for FEH treatment [40]. Though these products were not licenced for cats in some countries, they are commonly used in the feline practice. Vomiting or anorexia are described as side effects in a small proportion of cases, as well as a slight depression of the blood pressure, although these symptoms tend to disappear with continued treatment. Nonetheless, its usefulness in the treatment of feline mammary fibroepithelial hyperplasia remain uncertain, as prolactin has not been described as one of the players in FEH pathogenesis and FEH lesions are negative to prolactin [43]. Nevertheless, such drugs may be helpful when it is need to discontinue the queen lactation, in cases where FEH develops in lactating females.
Cabergoline (Galastop®, Ceva Santé Animale, France) is a dopaminergic agonist that produces a selective and long-lasting inhibitory effect on prolactin secretion, which in turn may be helpful to supress lactation. In dogs and cats it also induces luteolysis, and consequently it may induces abortion. Cabergoline is used for interrupt lactation at a dose of 5μg/kg body weight,
Bromocriptine (Parlodel® is the most frequently used pharmacological presentation) is used in the veterinary practice less often than Cabergoline, as it was found to induce abnormal behavioural effects, such as limb flicks, head/body shakes, and hallucinatory-like behaviour as well as excessive grooming [45]. This drug can be used at the dose of 0.25mg/cat/day, PO, for 5 to 7 days. Its use on FEH situations enrols the same concerns as for Cabergoline.
Generally, the prognosis for uncomplicated feline mammary fibroepithelial hyperplasia is good. The co-existence of mastitis or ulceration may induce some concern, particularly when the situation was left untreated for a long period. In rare situations, abscess formation and systemic illness worsen the prognosis.
Spontaneous regression of the enlarged mammary glands after removal of the progesterone influences may occur, but it may take up to 11 months. Nevertheless, ovariohysterectomy or withdrawal of the progestin treatment does not always result in regression of the masses. With the available progesterone antagonist, medical treatment of the condition has improved, and regression of the mammary swelling is usually obtained within a 4-8 weeks interval. It is possible that the co-existing mammary abscesses may require the surgical drainage of the abscess content, in a way to hasten the FEH regression [10].
Recurrence of the disease is controversial. Some studies refer that it is rarely observed [11]. However, in the absence of neutering, several reports of FEH in females describe the recurrence of the condition at a variable timing after the initial treatment [6,23,31]. Consequently, recurrence of the mammary lesions is important concern particularly in females that can maintain their full reproductive activity.
Thus, when debating the prognosis with the cat owner, it is important to discuss also the measures need for avoiding the recurrence of FEH. If a progestin administration for contraception was the causative agent it should be advised the cat spaying. This should also be advised whenever the female is not intended for breeding. In cases where the surgery for neutering is decided it can be performed later, when mammary enlargement regressed, making the procedure easier for the surgeon and less traumatic for the cat, avoiding undesirable trauma of the enlarged mammary glands during surgery. If progestin was used as treatment for skin disorders, alternative therapeutics should be found.
FEH is a progesterone-associated disease that is characterized by a very rapid swelling of mammary gland, which onset is usually within 2 to 4 weeks from the occurrence of an estrus or the administration of a progestin treatment. Occasionally, this primary lesion can be complicated with mastitis, ulceration or abscessation of the diseased mammary glands. Diagnosis of feline mammary fibroepithelial hyperplasia is exclusively a clinical issue, though some complementary methods of diagnosis may be helpful aids to confirm the diagnosis.
Treatment of feline mammary fibroepithelial hyperplasia has undergone major changes in the past three decades, and considerable improvement of cat welfare was achieved with the introduction of successful medical treatment. Nowadays, antiprogesterone drugs are available that ease the therapeutics and hastens a favourable outcome. With these drugs, the treatment targets the major causal mechanism, interrupting the progesterone-mediated pathways of mammary development and growth. Antiprogesterone molecules are now in the first line treatments for FEH, allowing to avoid massive mastectomy, a very aggressive approach to the cat. However, relapses are possible, and most frequently ovariectomy or ovariohysterectomy are advised to avoid recurrence of the problem.
Nevertheless, new studies on molecular pathways involved in the disease might strengthen additional interplaying factors of interest to design additional therapeutic approaches, as well as to highlight the factors underlying the relapses described in the literature in order to improve the medical treatment and the animal welfare.
Cardiovascular disease (CVD) (includes heart disease and stroke) is the leading cause of death in the United States [1] and worldwide [2]. In the United States, heart disease is the number one contributor to death, causing 647,457 deaths (23% of total deaths), while stroke is the fifth leading cause of death, contributing to 146,383 deaths (5.2% of total deaths) in 2017 [1]. Worldwide, heart disease is the leading cause of death, leading to 8.9 million deaths, or 16% of the total deaths globally in 2019. Stroke is the second leading contributor to deaths worldwide, causing more than 6 million deaths, or 11% of the deaths, worldwide [2].
A suggested dietary strategy to decrease the risk factors for CVD is to replace a portion of saturated fatty acids (SFAs) with monounsaturated fatty acids (MUFAs) and polyunsaturated fatty acids (PUFAs) [3, 4, 5, 6, 7, 8, 9, 10]. For example, the Nurses’ Health Study [11] demonstrated that replacing 5% of energy from SFAs with equivalent energy from MUFAs, PUFAs, or carbohydrates from whole grains, decreased the risk for coronary heart disease (CHD). A meta-analysis of randomized controlled trials reported that replacing saturated fat with polyunsaturated fat reduced CHD events [12].
However, certain authors and publications are not in agreement with these recommendations to decrease the risk factors for CVD, cardiovascular events, and/or mortality [13, 14, 15, 16, 17, 18, 19, 20, 21, 22]. The PURE prospective cohort study concluded that intakes of total, saturated, and unsaturated fats were not significantly associated with the risk of myocardial infarction or CVD mortality [23]. Meta-analyses of prospective cohort studies demonstrated that consumption of saturated fat was not associated with an increased risk of CVD [24]. Interestingly, there was an inverse association between saturated fat intake and the risk of stroke [25]. Additionally, a meta-analysis of randomized controlled trials reported that replacing saturated fat with primarily polyunsaturated fat is “unlikely” to reduce CVD events or mortality [26]. Hooper et al. [27], in a review of randomized controlled trials, stated that there is “little or no effect of reducing saturated fat on all-cause mortality or cardiovascular mortality.”
As noted, there is controversy regarding the effects of the consumption of fatty acids on CVD risk. One such controversy is the recommendation of linoleic acid, which is the essential omega-6 (or n-6) PUFA [28, 29, 30]. For example, it has been found that replacing saturated fat with linoleic acid lowers serum cholesterol, but does not lower the risk of death from CHD [21, 22]. Furthermore, there is concern regarding whether linoleic acid increases the risk for inflammation [31].
An analysis of prospective observational studies demonstrated that higher tissue and serum concentrations of linoleic acid decreased the risk for cardiovascular events [32]. The Cardiovascular Health Study, a prospective cohort study, discovered that higher circulating linoleic acid concentrations reduced total and CHD mortality [33]. A meta-analysis of prospective cohort studies found that decreased consumption of omega-6 PUFAs and increased intakes of saturated and trans-fatty acids increased CHD mortality [34]. Linoleic acid consumption reduced the risk of CHD events and death, according to another meta-analysis of prospective cohort studies [35]. A systematic review of randomized controlled trials, in which there was a replacement of dietary saturated and monounsaturated fatty acids with omega-6 fatty acids, concluded that omega-6 fatty acids lowered the risk of myocardial infarction. Additionally, the intake of omega-6 fatty acids reduced total serum cholesterol, but not “other blood fat fractions”. It was also highlighted that “the benefits of omega-6 fats remain to be proven” [36].
According to the diet-heart hypothesis, a high consumption of saturated fat and cholesterol – and a low intake of polyunsaturated fat – increase the build-up of cholesterol and plaques in artery walls; these developments, therefore, increase the risks for atherosclerosis, cardiovascular disease, and myocardial infarction [18, 21, 37]. However, the diet-heart hypothesis has been evolving, and thus, some individuals recommend focusing more on overall dietary patterns, rather than individual fatty acids [37]. Moreover, there are a variety of factors that contribute to increasing the risk for CVD, such as high blood pressure, arrhythmia, inflammation, thrombosis, insulin resistance, endothelial dysfunction, obesity, cigarette smoke, genetics, the microbiome, a lack of exercise, a high alcohol consumption, and overall dietary patterns [14, 18, 37, 38, 39, 40, 41, 42].
Lipid levels have also been proposed to be “strong” risk factors for CVD and mortality. These lipid risk factors include the following: high serum concentrations of total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C), lipoprotein(a), and very-low-density lipoprotein cholesterol (VLDL-C), as well as low serum concentrations of high-density lipoprotein cholesterol (HDL-C). In addition, apolipoprotein A1 (associated with HDL) and apolipoprotein B (associated with LDL) have been used as CVD risk markers [18, 43]. Interestingly, LDL particle size has also been utilized as a risk marker for CVD. The small, dense LDL subclass, compared to large, buoyant LDL particles, has been reported to be more atherogenic [44, 45, 46, 47, 48, 49, 50].
Therefore, this chapter will focus on the consumption of linoleic acid on lipid risk markers for CVD in healthy individuals, such as total cholesterol, triglycerides, LDL-C, LDL particle size, lipoprotein(a), VLDL-C, HDL-C, apolipoprotein A1, and apolipoprotein B. The associated mechanisms of action will also be covered. The chapter will conclude with recommendations to decrease the risk factors for CVD. Significant dietary sources of linoleic acid are presented in Tables 1 and 2. The chemical structure of linoleic acid is illustrated in Figure 1.
Oils | Linoleic acid (grams) |
---|---|
Corn oil | 53.5 |
Cottonseed oil | 51.9 |
Grapeseed oil | 69.6 |
Peanut oil | 32.0 |
Safflower oil | 12.7 |
Sesame oil | 41.3 |
Soybean oil | 51.0 |
Sunflower oil | 65.7 |
Walnut oil | 52.9 |
Nuts and seeds | Linoleic acid (grams) |
---|---|
Almonds | 3.49 |
Brazil nuts | 6.82 |
Pecans | 5.85 |
Pine nuts | 9.4 |
Pistachios | 4.0 |
Pumpkin seeds | 5.55 |
Sesame seeds | 5.78 |
Sunflower seeds | 9.29 |
Walnuts | 10.8 |
The chemical structure of linoleic acid [
The consumption of linoleic acid has been demonstrated to affect lipid risk markers for cardiovascular disease. The discussed studies include intervention trials that investigated the effects of linoleic acid consumption, in grams or percentage of energy, on CVD lipid risk markers in healthy individuals. Therefore, epidemiological, postprandial, and animal studies are not covered. The results are organized by the respective CVD lipid risk marker.
The consumption of linoleic acid decreased total cholesterol compared to a usual U.S. diet (high in saturated fat and cholesterol) [54], and diets high in SFAs [55] (including stearic acid [56] and palmitic acid [57]), MUFAs [58], or medium-chain fatty acids [59]. A high intake of alpha-linolenic acid, the essential omega-3 fatty acid, decreased cholesterol concentrations compared to the control diet with the same percentage of linoleic acid [60]. In contrast, no significant differences in total cholesterol were observed after linoleic acid consumption compared to diets containing eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (omega-3 fatty acids) [61, 62], alpha-linolenic acid [63], high and low amounts of linoleic acid [64], oleic acid (a MUFA) [65, 66], or stearic acid [66]. Interestingly, intakes of SFA- or linoleic acid-rich diets – both supplemented with EPA and DHA – produced no significant differences in cholesterol concentrations [67].
The consumption of linoleic acid decreased triglycerides compared to diets with significant amounts of oleic acid [58], stearic acid [56], or medium-chain fatty acids [59]. Intakes of linoleic acid, supplemented with EPA and DHA, reduced triglyceride concentrations versus a linoleic acid diet rich in oleic acid [62]. A SFA-rich diet and a diet high in linoleic acid, both with added EPA and DHA, lowered triglyceride concentrations, with no significant differences between diets [67]. In contrast, diets supplemented with EPA and DHA decreased triglycerides compared to linoleic acid intakes [55, 61]. No significant differences were observed regarding triglyceride concentrations between lower and higher linoleic acid intakes [54, 60, 64], and diets rich in linoleic acid versus diets high in alpha-linolenic acid [63], oleic acid [65], or stearic acid [66].
Intakes of linoleic acid decreased LDL-C versus diets rich in oleic acid [58], SFAs [55], palmitic acid [57], stearic acid [56, 68], trans-fatty acids [68], or medium-chain fatty acids [59]. Furthermore, higher amounts of linoleic acid more significantly lowered LDL-C concentrations [54, 57]. There were mixed results or no significant differences in comparison to oleic acid [62, 65, 66, 68]. Additionally, there were no significant differences when comparing linoleic acid consumption to alpha-linolenic acid [63] or stearic acid [66]. Consuming low and high amounts of linoleic acid – along with significant amounts of alpha-linolenic acid [64] or EPA and DHA [62] – also did not differ. Moreover, no significant differences were observed with respect to LDL-C after following a SFA-rich diet or a diet high in linoleic acid – both supplemented with EPA and DHA [67].
There were no significant differences in LDL particle size after consumption of low and high amounts of linoleic acid [60, 69], and intakes of linoleic acid compared to oleic acid or stearic acid [66]. Interestingly, there were decreases in large and small LDL particle concentrations after 10 days of a linoleic acid-rich diet compared to a diet high in SFAs, with both diets supplemented with EPA and DHA [70]. In contrast, no significant differences were observed in LDL particle size after 6 weeks of a linoleic acid-rich diet comparted to a SFA-rich diet (both supplemented with EPA and DHA) [67].
Following consumption of diets rich in linoleic acid, there were decreases in VLDL-C concentrations compared to diets containing significant amounts of oleic acid [58] or medium-chain fatty acids [59]. In contrast, intakes of a SFA- or linoleic acid-rich diet (both containing significant amounts of EPA and DHA) resulted in no significant differences between diets; however, both diets decreased VLDL-C concentrations [67].
HDL-C increased following consumption of linoleic acid compared to stearic acid [56]. In contrast, intakes of linoleic acid decreased HDL-C compared to EPA and DHA [61] or palmitic acid [57]. However, most studies noticed no significant differences regarding HDL-C concentrations after consuming low and high amounts of linoleic acid [54, 60, 62, 64], and linoleic acid compared to oleic acid [58, 65, 66], alpha-linolenic acid [60, 63], or stearic acid [66]. Interestingly, intakes of SFAs or linoleic acid (both diets supplemented with EPA and DHA) displayed no significant differences in HDL-C concentrations [67].
Linoleic acid consumption reduced lipoprotein(a) concentrations compared with a diet high in trans-fatty acids [68]. However, linoleic acid intake increased lipoprotein(a) compared to a diet rich in SFAs [55]. In contrast, no significant differences were found after consuming linoleic acid compared to SFAs, oleic acid, or stearic acid [68].
The consumption of linoleic acid increased apolipoprotein A1 compared to a typical U.S. diet [54]. Additionally, linoleic acid increased apolipoprotein A2 compared to EPA and DHA [55]. In contrast, apolipoproteins A1 and A2 decreased after following a diet rich in linoleic acid compared to a diet high in oleic acid [65]. Apolipoprotein A1 concentrations did not differ when comparing low and high linoleic acid intakes [60], and consumption of linoleic acid compared to diets containing high amounts of stearic acid or oleic acid [66]. There were decreases in apolipoprotein B concentrations after linoleic consumption compared to a typical U.S. diet [54], stearic acid, elaidic acid (a trans-fatty acid) [56], or SFAs [55]. There were no significant differences with respect to apolipoprotein B after intakes of linoleic acid compared with oleic acid [65, 66] or stearic acid [66].
Linoleic acid (or PUFAs) has been demonstrated to affect CVD lipid risk markers. The mechanisms involved in altering these risk markers will be discussed in this section.
PUFAs have been shown to increase liver X receptor alpha (LXRα) gene expression [71, 72] via peroxisome proliferator activated receptors (PPARs) [71]. LXRα stimulates the expression of cholesterol 7 α-hydroxylase (CYP7), thereby converting cholesterol to bile acids. Therefore, by increasing CYP7 activity, PUFAs participate in cholesterol catabolism [73].
PUFAs interact more strongly with PPARα compared to SFAs [74]. PPARα binds to peroxisome proliferator response elements (PPREs) located in the promotor regions of genes, such as apoC-III and lipoprotein lipase (LPL) [75]. It has been proposed that LPL may demonstrate increased activity towards VLDL triglycerides containing polyunsaturated fatty acids, thereby leading to increased breakdown of triglyceride-rich lipoproteins (chylomicrons and VLDL particles) [73, 76, 77]. LPL activity is inhibited by apoC-III, and thus, increases triglyceride concentrations [78]. It has been reported that PUFAs decrease apoC-III, thereby increasing LPL activity and, indeed, VLDL catabolism [73]. Moreover, omega-3 PUFAs have been shown to reduce triglycerides by lowering diacylglycerol acyltransferase, fatty acid synthase, and acetyl coenzyme A (CoA) carboxylase [79, 80, 81, 82, 83, 84].
Intakes of linoleic acid [85] or PUFAs [73] have been demonstrated to increase LDL receptor activity, protein, and mRNA compared to SFAs. Furthermore, PUFAs increase membrane fluidity [73, 85, 86], which increases LDL receptor activity, and thus, increases LDL catabolism [87, 88, 89].
It has been reported that consumption of SFAs increases large, buoyant LDL particles compared to lower SFA-containing diets [69, 90], whereas consumption of diets rich in PUFAs decreases large, buoyant LDL particles versus diets high in SFAs [70, 91]. It has been suggested that SFAs increase LPL and hepatic lipase activities [92, 93]. As such, LPL increases large, buoyant LDL particles, whereas hepatic lipase may stimulate the catabolism of triglyceride-rich lipoprotein remnants [92]. However, additional research is needed in this area regarding the mechanisms by which individual fatty acids affect LDL particle size.
The sterol regulatory element-binding protein-1 (SREBP-1) is associated with lipogenesis and cholesterol synthesis in the liver [94, 95]. PUFAs have been shown to inhibit SREBP-1 gene transcription and/or protein [96], thereby lowering VLDL secretion from the liver [73, 96]. In addition, intakes of PUFAs increase VLDL catabolism and uptake [59, 81].
Replacing SFAs with MUFAs and/or PUFAs generates lower total cholesterol and LDL-C concentrations, with modest HDL-C reductions; however, a lower total cholesterol: HDL-C ratio results [4, 97]. It is thought that dietary fat increases the “transport rate” and decreases the “fractional catabolic rate” of HDL cholesterol ester and apolipoprotein A1 [98]. However, more research is needed to describe the mechanisms by which individual fatty acids impact HDL-C.
Lipoprotein(a) is synthesized in the liver and contains apolipoprotein A, which is bound to apolipoprotein B-100 [99, 100, 101]. The biological activity of lipoprotein(a) is unknown [102]; however, high concentrations have been associated with CVD [101, 103, 104]. Genetics seem to be the primary determinant of lipoprotein(a) [105]. Hence, diet and exercise do not appear to be significant contributors to lipoprotein(a) concentrations. There have also been inconsistent findings of fatty acid consumption (including PUFAs) on lipoprotein(a) concentrations [106]. However, it has been suggested that fatty acids may affect liver apolipoprotein(a) synthesis, thereby impacting lipoprotein(a) [106, 107, 108]. As such, more research is needed to determine the effects of dietary composition on lipoprotein(a) concentrations.
HDL particles contain apolipoprotein A1, which interacts with the ATP-binding cassette transporter on the surface of cells. Furthermore, apolipoprotein A1 is a cofactor for lecithin cholesterol acyl transferase, which generates mature HDL particles [43, 109]. Plasma apolipoprotein A1 concentration typically coincide with HDL-C concentrations [43]. The significance of apolipoprotein A2 is less clear [110]. Interestingly, PPARα also interacts with PPREs in the promoter region of the apolipoprotein A1 gene in the liver [75]. Hence, PUFAs may exert their effects on apolipoprotein A1 via PPARα [73].
Apolipoprotein B also occurs in two forms: apolipoprotein B-48 and apolipoprotein B-100. The intestine synthesizes apolipoprotein B-48, which is a component of chylomicrons. The liver produces apolipoprotein B-100, which is associated with VLDL and LDL particles. Apolipoprotein B is necessary for the binding of lipoproteins to the LDL receptor. Apolipoprotein B plasma concentrations are significantly associated with LDL-C concentrations [43, 111]. It has been reported that high apolipoprotein B concentrations increase the risk for CVD, whereas apolipoprotein A1 concentrations decrease CVD risk [43, 112]. As mentioned previously, PUFAs increase LDL catabolism, thereby reducing apolipoprotein B [87].
The adequate intake (AI) values for linoleic acid for males and females (19-50 years) are 17 grams/day and 12 grams/day, respectively. Regarding males and females ages 51-70 years, the AI values for linoleic acid are 14 grams/day and 11 grams/day, respectively. The American Heart Association recommends consuming 5 to 10% of energy as linoleic acid to decrease CVD risk [29, 31]. Additionally, the World Health Organization recommends consuming 2.5 to 9% of energy from linoleic acid to decrease LDL and total cholesterol concentrations, and thus, lower the risk for CVD [113]. It is not recommended to consume more than 10% of energy as linoleic acid due to limited research.
In addition to linoleic acid recommendations, there are fat recommendations to reduce CVD risk, cardiovascular events, and/or mortality. For example, it has been suggested to replace approximately 5% of energy from SFAs with MUFAs and/or PUFAs [4, 8, 9, 10, 11, 12, 38, 113], and to consume less than 10% of energy as SFAs [113, 114]. On the other hand, certain studies do not coincide with these recommendations [14, 15, 16, 17, 21, 22, 23, 24, 25, 26, 27, 115]. In addition, low-fat, and in-turn, high-carbohydrate diets, decrease LDL-C; however, there is also a reduction in HDL-C and increased concentrations of VLDLs or triglycerides [37, 97, 116, 117, 118], which may produce higher amounts of small, dense LDL particles [41, 119, 120]. It has been reported that higher-fat versus lower-fat diets increase large, buoyant LDL and/or decrease small, dense LDL particles [69, 92, 121, 122, 123]. Interestingly, higher SFA intakes also increase large LDL and/or decrease small LDL particles [69, 90, 124, 125, 126]. These small, dense LDL particles may increase the risk for CVD in the following ways: 1) increased transport into arterial walls [127]; 2) increased attachment to proteoglycans [128]; 3) increased oxidation [129, 130]; and 4) reduced binding to the LDL receptor [127, 131, 132].
Various organizations have published dietary recommendations to decrease the risk factors for CVD. The American College of Cardiology/American Heart Association Task Force suggests consuming a diet rich in fruits, vegetables, whole grains, nuts, legumes, lean animal or plant protein sources, and fish. Additionally, it is recommended to decrease the consumption of red and processed meats, refined carbohydrates, trans-fatty acids, sodium, cholesterol, and sugar-sweetened drinks [38]. The Dietary Guidelines for Americans suggest consuming vegetable oils to replace sources rich in SFAs, such as butter, shortening, lard, palm oil, palm kernel oil, coconut oil, full-fat dairy products, and high-fat meats [114]. The World Health Organization also recommends replacing SFAs with unsaturated fatty acids, such as sunflower, safflower, corn, soybean, canola, and olive oils, as well as nuts, avocado, and fish [113].
It has been recently proposed, however, that guidelines to lower the risk for CVD should focus on overall dietary patterns, rather than individual fatty acids [14, 133]. The consumption of low-fat diets, for example, did not reduce CVD risk [134, 135]. Furthermore, certain individuals with higher intakes of saturated fat and cholesterol do not possess high CVD mortality rates, as they have an increased consumption of plant foods – in addition to MUFAs and PUFAs [15]. Furthermore, some foods that are higher in SFAs have not been demonstrated to increase the risk for CVD. A proposed explanation for these outcomes is the food matrix of these items, such as macro- and micronutrients, phytochemicals, and probiotics [14, 37].
This chapter focused on the effects of linoleic acid consumption on lipid risk markers for CVD in healthy individuals. Interestingly, linoleic acid reduced total cholesterol and LDL-C compared to diets that were lower in PUFAs and/or higher in SFAs. In contrast, linoleic acid generated inconsistent outcomes regarding triglycerides, whereas EPA and DHA more significantly reduced triglyceride concentrations. In limited studies, linoleic acid decreased VLDL-C compared to diets containing oleic acid or medium-chain fatty acids, and decreased HDL-C compared to palmitic acid or EPA and DHA; however, linoleic acid increased HDL-C compared with stearic acid. Additionally, linoleic acid reduced apolipoprotein B in comparison to a typical U.S. diet, SFAs, or trans-fatty acids. Interestingly, there were inconsistent results or no significant differences for selected CVD lipid risk markers – particularly when comparing linoleic acid to oleic acid. Therefore, additional research is needed regarding the effects of fatty acids on markers that increase the risk for CVD – in addition to the associated mechanisms.
The development of CVD is a complex process which involves many factors that influence the discussed lipid risk markers, such as exercise patterns, overweight/obesity, cigarette smoke, hypertension, high alcohol consumption, and genetics. To add to this complexity is our dietary patterns. As discussed, there are mixed results regarding the consumption of linoleic acid on CVD lipid risk markers. One such dietary explanation is the complex food matrices of these items, which may, therefore, influence CVD risk markers. In other words, we do not consume individual fatty acids; we consume food. For example, individual saturated and unsaturated fatty acids have differing effects on CVD risk markers; however, these individual effects may be diminished when these fatty acids are components of whole food items. This attribute may explain, in part, for the differing outcomes of saturated and unsaturated fat on CVD risk, events, and/or mortality. Perhaps, therefore, we should focus on whole foods and overall dietary patterns when providing guidelines to reduce the risk for CVD.
It is recommended that future studies investigate the effects of various dietary patterns on CVD risk markers, such as lower-carbohydrate versus higher-carbohydrate diets, lower-fat versus higher-fat diets, and plant-based versus meat-based diets. Based on the heterogeneity of the reviewed studies on the effects of linoleic acid consumption on lipid risk markers for CVD, future studies should be longer in duration – with more participants. Moreover, it should be clarified, in future publications, whether the discussed CVD lipid risk markers exist as strong and independent risk factors for CVD.
It is clear that the consumption of fat is a critical component to a healthy diet; consuming too much or too little can have detrimental effects on one’s health. Therefore, moderation is an important factor to keep in mind regarding fat consumption. It seems, however, that certain dietary recommendations focus on decreasing the intakes of saturated fatty acids, and increasing the consumption of monounsaturated and polyunsaturated fatty acids. These recommendations may not be optimal in the following ways: 1) foods consist of individual fatty acids, which have different effects on CVD lipid risk markers; 2) overall dietary patterns and food components may offset the effects of specific fatty acids; and 3) individuals may not be familiar with significant food sources of saturated, monounsaturated, and polyunsaturated fatty acids. Therefore, it seems that dietary guidelines to lower the risk for CVD should focus on overall dietary patterns, rather than individual fatty acids (Figure 2).
The progression from individual fatty acids to whole foods and overall dietary patterns on lipid risk markers for cardiovascular disease.
No funding was used for this project.
The author declares no conflict of interest.
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\\n\\nTERMS
\\n\\nAll Works published on the IntechOpen platform and in print are licensed under a Creative Commons Attribution 3.0 Unported and Creative Commons 4.0 International License, a license which allows for the broadest possible reuse of published material.
\\n\\nCopyright on the individual Works belongs to the specific Author, subject to an agreement with IntechOpen. The Creative Common license is granted to all others to:
\\n\\nAnd for any purpose, provided the following conditions are met:
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The CC BY 3.0 and CC BY 4.0 license permits Works to be freely shared in any medium or format, as well as the reuse and adaptation of the original contents of Works (e.g. figures and tables created by the Authors), as long as the source Work is cited and its Authors are acknowledged in the following manner:
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\\n\\nDISCLAIMER: Neither the CC BY 3.0 license, CC BY 4.0, nor any other license IntechOpen currently uses or has used before, applies to figures and tables reproduced from other works, as they may be subject to different terms of reuse. In such cases, if the copyright holder is not noted in the source of a figure or table, it is the responsibility of the User to investigate and determine the exact copyright status of any information utilised. Users requiring assistance in that regard are welcome to send an inquiry to permissions@intechopen.com.
\\n\\nAll rights to Books and Journals and all other compilations published on the IntechOpen platform and in print are reserved by IntechOpen.
\\n\\nThe copyright to Books, Journals and other compilations is subject to separate copyright from those that exist in the included Works.
\\n\\nAll Long Form Monographs/Compacts are licensed under the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) license granted to all others.
\\n\\nCopyright to the individual Works (Chapters) belongs to their specific Authors, subject to an agreement with IntechOpen and the Creative Common license granted to all others to:
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\\n\\nThere must be an Attribution, giving appropriate credit, provision of a link to the license, and indication if any changes were made.
\\n\\nNonCommercial - The use of the material for commercial purposes is prohibited. Commercial rights are reserved to IntechOpen or its licensees.
\\n\\nNo additional restrictions that apply legal terms or technological measures that restrict others from doing anything the license permits are allowed.
\\n\\nThe CC BY-NC 4.0 license permits Works to be freely shared in any medium or format, as well as reuse and adaptation of the original contents of Works (e.g. figures and tables created by the Authors), as long as it is not used for commercial purposes. The source Work must be cited and its Authors acknowledged in the following manner:
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\\n\\nAll Book cover design elements, as well as Video image graphics are subject to copyright by IntechOpen.
\\n\\nEvery reproduction of a front cover image must be accompanied by an appropriate Copyright Notice displayed adjacent to the image. The exact Copyright Notice depends on who the Author of a particular cover image is. Users wishing to reproduce cover images should contact permissions@intechopen.com.
\\n\\nAll Video Lectures under IntechOpen's production are subject to copyright and are property of IntechOpen, unless defined otherwise, and are licensed under the Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) license. This grants all others the right to:
\\n\\nShare — copy and redistribute the material in any medium or format
\\n\\nUnder the following terms:
\\n\\nUsers wishing to repost and share the Video Lectures are welcome to do so as long as they acknowledge the source in the following manner:
\\n\\n© {year} IntechOpen. Published under CC BY-NC-ND 4.0 license. Available from: {DOI}
\\n\\nUsers wishing to reuse, modify, or adapt the Video Lectures in a way not permitted by the license are welcome to contact us at permissions@intechopen.com to discuss waiving particular license terms.
\\n\\nAll software used on the IntechOpen platform, any used during the publishing process, and the copyright in the code constituting such software, is the property of IntechOpen or its software suppliers. As such, it may not be downloaded or copied without permission.
\\n\\nUnless otherwise indicated, all IntechOpen websites are the property of IntechOpen.
\\n\\nAll content included on IntechOpen Websites not forming part of contributed materials (such as text, images, logos, graphics, design elements, videos, sounds, pictures, trademarks, etc.), are subject to copyright and are property of, or licensed to, IntechOpen. Any other use, including the reproduction, modification, distribution, transmission, republication, display, or performance of the content on this site is strictly prohibited.
\\n\\nPolicy last updated: 2016-06-08
\\n"}]'},components:[{type:"htmlEditorComponent",content:'Copyright is the term used to describe the rights related to the publication and distribution of original Works. Most importantly from a publisher's perspective, copyright governs how Authors, publishers and the general public can use, publish, and distribute publications.
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\n\nHOW COPYRIGHT WORKS WITH OPEN ACCESS LICENSES?
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\n\nDEFINITIONS
\n\nThe following definitions apply in this Copyright Policy:
\n\nAuthor - in order to be identified as an Author, three criteria must be met: (i) Substantial contribution to the conception or design of the Work, or the acquisition, analysis, or interpretation of data for the Work; (ii) Participation in drafting or revising the Work; (iii) Approval of the final version of the Work to be published.
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\n\nTERMS
\n\nAll Works published on the IntechOpen platform and in print are licensed under a Creative Commons Attribution 3.0 Unported and Creative Commons 4.0 International License, a license which allows for the broadest possible reuse of published material.
\n\nCopyright on the individual Works belongs to the specific Author, subject to an agreement with IntechOpen. The Creative Common license is granted to all others to:
\n\nAnd for any purpose, provided the following conditions are met:
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\n\nDISCLAIMER: Neither the CC BY 3.0 license, CC BY 4.0, nor any other license IntechOpen currently uses or has used before, applies to figures and tables reproduced from other works, as they may be subject to different terms of reuse. In such cases, if the copyright holder is not noted in the source of a figure or table, it is the responsibility of the User to investigate and determine the exact copyright status of any information utilised. Users requiring assistance in that regard are welcome to send an inquiry to permissions@intechopen.com.
\n\nAll rights to Books and Journals and all other compilations published on the IntechOpen platform and in print are reserved by IntechOpen.
\n\nThe copyright to Books, Journals and other compilations is subject to separate copyright from those that exist in the included Works.
\n\nAll Long Form Monographs/Compacts are licensed under the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) license granted to all others.
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\n\nNo additional restrictions that apply legal terms or technological measures that restrict others from doing anything the license permits are allowed.
\n\nThe CC BY-NC 4.0 license permits Works to be freely shared in any medium or format, as well as reuse and adaptation of the original contents of Works (e.g. figures and tables created by the Authors), as long as it is not used for commercial purposes. The source Work must be cited and its Authors acknowledged in the following manner:
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\n\nAll software used on the IntechOpen platform, any used during the publishing process, and the copyright in the code constituting such software, is the property of IntechOpen or its software suppliers. As such, it may not be downloaded or copied without permission.
\n\nUnless otherwise indicated, all IntechOpen websites are the property of IntechOpen.
\n\nAll content included on IntechOpen Websites not forming part of contributed materials (such as text, images, logos, graphics, design elements, videos, sounds, pictures, trademarks, etc.), are subject to copyright and are property of, or licensed to, IntechOpen. Any other use, including the reproduction, modification, distribution, transmission, republication, display, or performance of the content on this site is strictly prohibited.
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We describe the marker-less technologies in the area of AR, indoor marker-less AR, outdoor marker-less AR, real-time solutions to the tracking problem, real-time registration, cultural heritage in AR, 3D remonstration techniques, as well as presenting the problems in each research.",book:{id:"7699",slug:"advanced-methods-and-new-materials-for-cultural-heritage-preservation",title:"Advanced Methods and New Materials for Cultural Heritage Preservation",fullTitle:"Advanced Methods and New Materials for Cultural Heritage Preservation"},signatures:"Hoshang Kolivand, Abdennour El Rhalibi, Mostafa Tajdini, Sarmad Abdulazeez\nand Pisit Praiwattana",authors:[{id:"151219",title:"Prof.",name:"Abdennour",middleName:null,surname:"El Rhalibi",slug:"abdennour-el-rhalibi",fullName:"Abdennour El Rhalibi"},{id:"225824",title:"Dr.",name:"Hoshang",middleName:null,surname:"Kolivand",slug:"hoshang-kolivand",fullName:"Hoshang Kolivand"},{id:"256916",title:"Dr.",name:"Sarmad",middleName:null,surname:"Abdulazeez",slug:"sarmad-abdulazeez",fullName:"Sarmad Abdulazeez"},{id:"256917",title:"Dr.",name:"Pisit",middleName:null,surname:"Praiwattana",slug:"pisit-praiwattana",fullName:"Pisit Praiwattana"},{id:"289071",title:"Dr.",name:"Mostafa",middleName:null,surname:"Tajdini",slug:"mostafa-tajdini",fullName:"Mostafa Tajdini"}]},{id:"36570",doi:"10.5772/45619",title:"Archaeological Geophysics - From Basics to New Perspectives",slug:"archaeological-geophysics-from-basics-to-new-perspectives",totalDownloads:6563,totalCrossrefCites:4,totalDimensionsCites:8,abstract:null,book:{id:"1999",slug:"archaeology-new-approaches-in-theory-and-techniques",title:"Archaeology",fullTitle:"Archaeology, New Approaches in Theory and Techniques"},signatures:"Roger Sala, Ekhine Garcia and Robert Tamba",authors:[{id:"131865",title:"Dr.",name:"Roger",middleName:null,surname:"Sala",slug:"roger-sala",fullName:"Roger Sala"}]},{id:"36574",doi:"10.5772/37679",title:"The Study of Shell Object Manufacturing Techniques from the Perspective of Experimental Archaeology and Work Traces",slug:"the-study-of-shell-object-manufacturing-techniques-from-the-perspective-of-experimental-archaeology-",totalDownloads:3119,totalCrossrefCites:1,totalDimensionsCites:5,abstract:null,book:{id:"1999",slug:"archaeology-new-approaches-in-theory-and-techniques",title:"Archaeology",fullTitle:"Archaeology, New Approaches in Theory and Techniques"},signatures:"Adrián Velázquez-Castro",authors:[{id:"113840",title:"Dr.",name:"Adrian",middleName:null,surname:"Velazquez",slug:"adrian-velazquez",fullName:"Adrian Velazquez"}]},{id:"70612",doi:"10.5772/intechopen.89154",title:"The Technological Diversity of Lithic Industries in Eastern South America during the Late Pleistocene-Holocene Transition",slug:"the-technological-diversity-of-lithic-industries-in-eastern-south-america-during-the-late-pleistocen",totalDownloads:684,totalCrossrefCites:1,totalDimensionsCites:4,abstract:"Brazilian archaeological literature has insisted for decades upon associating hunter-gatherer sites dated to the Pleistocene–Holocene transition either to the Itaparica tradition, if located in central or northeastern Brazil, or to the Umbu tradition and Humaitá tradition, if located in southern Brazil, Uruguay, or any other adjacent part of Paraguay and Argentina. These associations have been based almost entirely on the presence or absence of lesmas and “projectile points,” regardless of their morphological and technological features. In the Uruguayan archaeological literature, three other cultures are recognised: Fell industry, Catalanense industry, and Tigre tradition, all in the Uruguayan region. However, the last 10 years of systematic studies on the lithic assemblages from these sites have shown that Paleoindian societies from Eastern South America are more culturally diverse than expected and that previously defined archaeological cultures present several issues in their definition, suggesting that many of these “traditions” are not valid and should no longer be used. Instead, new lithic industries and archaeological cultures should be defined only when cultural patterns are observable through systematic analyses.",book:{id:"9251",slug:"pleistocene-archaeology-migration-technology-and-adaptation",title:"Pleistocene Archaeology",fullTitle:"Pleistocene Archaeology - Migration, Technology, and Adaptation"},signatures:"João Carlos Moreno De Sousa",authors:[{id:"303361",title:"Dr.",name:"João Carlos",middleName:null,surname:"Moreno De Sousa",slug:"joao-carlos-moreno-de-sousa",fullName:"João Carlos Moreno De Sousa"}]}],mostDownloadedChaptersLast30Days:[{id:"36570",title:"Archaeological Geophysics - From Basics to New Perspectives",slug:"archaeological-geophysics-from-basics-to-new-perspectives",totalDownloads:6552,totalCrossrefCites:4,totalDimensionsCites:8,abstract:null,book:{id:"1999",slug:"archaeology-new-approaches-in-theory-and-techniques",title:"Archaeology",fullTitle:"Archaeology, New Approaches in Theory and Techniques"},signatures:"Roger Sala, Ekhine Garcia and Robert Tamba",authors:[{id:"131865",title:"Dr.",name:"Roger",middleName:null,surname:"Sala",slug:"roger-sala",fullName:"Roger Sala"}]},{id:"36576",title:"Homage to Marcel Proust - Aspects of Dissemination and Didactic in a Museum and a Science Centre: Science Communication Visions for the Third Generation Museums",slug:"generations-of-ancient-history-dissemination-towards-the-public-at-the-university-museum-in-trondhei",totalDownloads:2644,totalCrossrefCites:1,totalDimensionsCites:1,abstract:null,book:{id:"1999",slug:"archaeology-new-approaches-in-theory-and-techniques",title:"Archaeology",fullTitle:"Archaeology, New Approaches in Theory and Techniques"},signatures:"Kistian Overskaug",authors:[{id:"117119",title:"Dr.",name:"Kristian",middleName:null,surname:"Overskaug",slug:"kristian-overskaug",fullName:"Kristian Overskaug"}]},{id:"63772",title:"Cultural Heritage in Marker-Less Augmented Reality: A Survey",slug:"cultural-heritage-in-marker-less-augmented-reality-a-survey",totalDownloads:1628,totalCrossrefCites:6,totalDimensionsCites:9,abstract:"Augmented reality (AR) is considered as one of the most significant technologies in the field of computer graphics and is utilised in many applications. In this chapter, we have presented a brief comprehensive survey of cultural heritage using augmented reality systems. This survey describes the main objectives and characteristics of marker-less augmented reality systems through presenting up-to-date research results in this area. We describe the marker-less technologies in the area of AR, indoor marker-less AR, outdoor marker-less AR, real-time solutions to the tracking problem, real-time registration, cultural heritage in AR, 3D remonstration techniques, as well as presenting the problems in each research.",book:{id:"7699",slug:"advanced-methods-and-new-materials-for-cultural-heritage-preservation",title:"Advanced Methods and New Materials for Cultural Heritage Preservation",fullTitle:"Advanced Methods and New Materials for Cultural Heritage Preservation"},signatures:"Hoshang Kolivand, Abdennour El Rhalibi, Mostafa Tajdini, Sarmad Abdulazeez\nand Pisit Praiwattana",authors:[{id:"151219",title:"Prof.",name:"Abdennour",middleName:null,surname:"El Rhalibi",slug:"abdennour-el-rhalibi",fullName:"Abdennour El Rhalibi"},{id:"225824",title:"Dr.",name:"Hoshang",middleName:null,surname:"Kolivand",slug:"hoshang-kolivand",fullName:"Hoshang Kolivand"},{id:"256916",title:"Dr.",name:"Sarmad",middleName:null,surname:"Abdulazeez",slug:"sarmad-abdulazeez",fullName:"Sarmad Abdulazeez"},{id:"256917",title:"Dr.",name:"Pisit",middleName:null,surname:"Praiwattana",slug:"pisit-praiwattana",fullName:"Pisit Praiwattana"},{id:"289071",title:"Dr.",name:"Mostafa",middleName:null,surname:"Tajdini",slug:"mostafa-tajdini",fullName:"Mostafa Tajdini"}]},{id:"73769",title:"Human Evolution in the Center of the Old World: An Updated Review of the South Asian Paleolithic",slug:"human-evolution-in-the-center-of-the-old-world-an-updated-review-of-the-south-asian-paleolithic",totalDownloads:847,totalCrossrefCites:0,totalDimensionsCites:1,abstract:"The Indian Subcontinent was an important geographic region for faunal and hominin evolution in Asia. While the Oldowan as the earliest technocomplex continues to be elusive, the oldest Acheulean is dated to ~1.5 Ma and the early Middle Paleolithic is ~385 ka (from the same site). New Late Pleistocene dates have been reported for the Middle Paleolithic which continues up to 38 Ka in southern India. The Upper Paleolithic remains ambiguous and requires critically multidisciplinary investigations. The microlithic evidence appears to spread rapidly across the subcontinent soon after its emergence at ~48 Ka (though its origin is debated) and continues into the Iron Age. The timeline of the initial arrival of Homo sapiens continues to be debated based on the archaeology (advanced Middle Paleolithic vs. microlithic) and genetic studies on indigenous groups. Other issues that need consideration are: interactions between archaics and arriving moderns, the marginal occurrence of symbolic behavior, the absolute dating of rock art and the potential role of hominins in specific animal extinctions and ecological marginalization. The region does not appear to have been a corridor for dispersals towards Southeast Asia (although gene flow may have occurred). Instead, once various prehistoric technologies appeared in the Subcontinent, they possibly followed complex trajectories within relative isolation.",book:{id:"9251",slug:"pleistocene-archaeology-migration-technology-and-adaptation",title:"Pleistocene Archaeology",fullTitle:"Pleistocene Archaeology - Migration, Technology, and Adaptation"},signatures:"Parth R. Chauhan",authors:[{id:"307040",title:"Dr.",name:"Parth",middleName:null,surname:"Chauhan",slug:"parth-chauhan",fullName:"Parth Chauhan"}]},{id:"73386",title:"Island Migration, Resource Use, and Lithic Technology by Anatomically Modern Humans in Wallacea",slug:"island-migration-resource-use-and-lithic-technology-by-anatomically-modern-humans-in-wallacea",totalDownloads:725,totalCrossrefCites:1,totalDimensionsCites:3,abstract:"Island migration and adaptation including both marine and terrestrial resource use and technological development by anatomically modern humans (AMH) are among the most significant issues for Pleistocene archaeology in Southeast Asia and Oceania, and directly related to the behavioral and technological advancements by AMH. This paper discusses such cases in the Wallacean islands, located between the past Sundaland and the Sahul continent during the Pleistocene. The Pleistocene open sea gaps between the Wallacean islands and both landmasses are very likely the major factor for the relative scarcity of animal species originating from Asia and Oceania and the high diversity of endemic species in Wallacea. They were also a barrier for hominin migration into the Wallacean islands and Sahul continent. We summarize three recent excavation results on the Talaud Islands, Sulawesi Island and Mindoro Island in Wallacea region and discuss the evidence and timeline for migrations of early modern humans into the Wallacean islands and their adaptation to island environments during the Pleistocene.",book:{id:"9251",slug:"pleistocene-archaeology-migration-technology-and-adaptation",title:"Pleistocene Archaeology",fullTitle:"Pleistocene Archaeology - Migration, Technology, and Adaptation"},signatures:"Rintaro Ono, Alfred Pawlik and Riczar Fuentes",authors:[{id:"177123",title:"Dr.",name:"Rintaro",middleName:null,surname:"Ono",slug:"rintaro-ono",fullName:"Rintaro Ono"},{id:"300616",title:"Dr.",name:"Alfred",middleName:null,surname:"Pawlik",slug:"alfred-pawlik",fullName:"Alfred Pawlik"},{id:"330591",title:"Dr.",name:"Riczar",middleName:null,surname:"Fuentes",slug:"riczar-fuentes",fullName:"Riczar Fuentes"}]}],onlineFirstChaptersFilter:{topicId:"263",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},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:287,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:null,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:10,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:"13",title:"Veterinary Medicine and Science",doi:"10.5772/intechopen.73681",issn:"2632-0517",scope:"Paralleling similar advances in the medical field, astounding advances occurred in Veterinary Medicine and Science in recent decades. These advances have helped foster better support for animal health, more humane animal production, and a better understanding of the physiology of endangered species to improve the assisted reproductive technologies or the pathogenesis of certain diseases, where animals can be used as models for human diseases (like cancer, degenerative diseases or fertility), and even as a guarantee of public health. Bridging Human, Animal, and Environmental health, the holistic and integrative “One Health” concept intimately associates the developments within those fields, projecting its advancements into practice. This book series aims to tackle various animal-related medicine and sciences fields, providing thematic volumes consisting of high-quality significant research directed to researchers and postgraduates. It aims to give us a glimpse into the new accomplishments in the Veterinary Medicine and Science field. By addressing hot topics in veterinary sciences, we aim to gather authoritative texts within each issue of this series, providing in-depth overviews and analysis for graduates, academics, and practitioners and foreseeing a deeper understanding of the subject. Forthcoming texts, written and edited by experienced researchers from both industry and academia, will also discuss scientific challenges faced today in Veterinary Medicine and Science. In brief, we hope that books in this series will provide accessible references for those interested or working in this field and encourage learning in a range of different topics.",coverUrl:"https://cdn.intechopen.com/series/covers/13.jpg",latestPublicationDate:"May 18th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:10,editor:{id:"38652",title:"Dr.",name:"Rita",middleName:null,surname:"Payan-Carreira",slug:"rita-payan-carreira",fullName:"Rita Payan-Carreira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRiFPQA0/Profile_Picture_1614601496313",biography:"Rita Payan Carreira earned her Veterinary Degree from the Faculty of Veterinary Medicine in Lisbon, Portugal, in 1985. She obtained her Ph.D. in Veterinary Sciences from the University of Trás-os-Montes e Alto Douro, Portugal. After almost 32 years of teaching at the University of Trás-os-Montes and Alto Douro, she recently moved to the University of Évora, Department of Veterinary Medicine, where she teaches in the field of Animal Reproduction and Clinics. Her primary research areas include the molecular markers of the endometrial cycle and the embryo–maternal interaction, including oxidative stress and the reproductive physiology and disorders of sexual development, besides the molecular determinants of male and female fertility. She often supervises students preparing their master's or doctoral theses. She is also a frequent referee for various journals.",institutionString:null,institution:{name:"University of Évora",institutionURL:null,country:{name:"Portugal"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:3,paginationItems:[{id:"19",title:"Animal Science",coverUrl:"https://cdn.intechopen.com/series_topics/covers/19.jpg",isOpenForSubmission:!0,editor:{id:"259298",title:"Dr.",name:"Edward",middleName:null,surname:"Narayan",slug:"edward-narayan",fullName:"Edward Narayan",profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",biography:"Dr. Edward Narayan graduated with Ph.D. degree in Biology from the University of the South Pacific and pioneered non-invasive reproductive and stress endocrinology tools for amphibians - the novel development and validation of non-invasive enzyme immunoassays for the evaluation of reproductive hormonal cycle and stress hormone responses to environmental stressors. \nDr. Narayan leads the Stress Lab (Comparative Physiology and Endocrinology) at the University of Queensland. A dynamic career research platform which is based on the thematic areas of comparative vertebrate physiology, stress endocrinology, reproductive endocrinology, animal health and welfare, and conservation biology. \nEdward has supervised 40 research students and published over 60 peer reviewed research.",institutionString:null,institution:{name:"University of Queensland",institutionURL:null,country:{name:"Australia"}}},editorTwo:null,editorThree:null},{id:"20",title:"Animal Nutrition",coverUrl:"https://cdn.intechopen.com/series_topics/covers/20.jpg",isOpenForSubmission:!0,editor:{id:"175967",title:"Dr.",name:"Manuel",middleName:null,surname:"Gonzalez Ronquillo",slug:"manuel-gonzalez-ronquillo",fullName:"Manuel Gonzalez Ronquillo",profilePictureURL:"https://mts.intechopen.com/storage/users/175967/images/system/175967.png",biography:"Dr. Manuel González Ronquillo obtained his doctorate degree from the University of Zaragoza, Spain, in 2001. He is a research professor at the Faculty of Veterinary Medicine and Animal Husbandry, Autonomous University of the State of Mexico. He is also a level-2 researcher. He received a Fulbright-Garcia Robles fellowship for a postdoctoral stay at the US Dairy Forage Research Center, Madison, Wisconsin, USA in 2008–2009. He received grants from Alianza del Pacifico for a stay at the University of Magallanes, Chile, in 2014, and from Consejo Nacional de Ciencia y Tecnología (CONACyT) to work in the Food and Agriculture Organization’s Animal Production and Health Division (AGA), Rome, Italy, in 2014–2015. He has collaborated with researchers from different countries and published ninety-eight journal articles. He teaches various degree courses in zootechnics, sheep production, and agricultural sciences and natural resources.\n\nDr. Ronquillo’s research focuses on the evaluation of sustainable animal diets (StAnD), using native resources of the region, decreasing carbon footprint, and applying meta-analysis and mathematical models for a better understanding of animal production.",institutionString:null,institution:{name:"Universidad Autónoma del Estado de México",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null},{id:"28",title:"Animal Reproductive Biology and Technology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/28.jpg",isOpenForSubmission:!0,editor:{id:"177225",title:"Prof.",name:"Rosa Maria Lino Neto",middleName:null,surname:"Pereira",slug:"rosa-maria-lino-neto-pereira",fullName:"Rosa Maria Lino Neto Pereira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bS9wkQAC/Profile_Picture_1624519982291",biography:"Rosa Maria Lino Neto Pereira (DVM, MsC, PhD and) is currently a researcher at the Genetic Resources and Biotechnology Unit of the National Institute of Agrarian and Veterinarian Research (INIAV, Portugal). She is the head of the Reproduction and Embryology Laboratories and was lecturer of Reproduction and Reproductive Biotechnologies at Veterinary Medicine Faculty. She has over 25 years of experience working in reproductive biology and biotechnology areas with a special emphasis on embryo and gamete cryopreservation, for research and animal genetic resources conservation, leading research projects with several peer-reviewed papers. Rosa Pereira is member of the ERFP-FAO Ex situ Working Group and of the Management Commission of the Portuguese Animal Germplasm Bank.",institutionString:"The National Institute for Agricultural and Veterinary Research. Portugal",institution:null},editorTwo:null,editorThree:null}]},overviewPageOFChapters:{paginationCount:19,paginationItems:[{id:"81793",title:"Canine parvovirus-2: An Emerging Threat to Young Pets",doi:"10.5772/intechopen.104846",signatures:"Mithilesh Singh, Rajendran Manikandan, Ujjwal Kumar De, Vishal Chander, Babul Rudra Paul, Saravanan Ramakrishnan and Darshini Maramreddy",slug:"canine-parvovirus-2-an-emerging-threat-to-young-pets",totalDownloads:6,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Recent Advances in Canine Medicine",coverURL:"https://cdn.intechopen.com/books/images_new/11580.jpg",subseries:{id:"19",title:"Animal Science"}}},{id:"81271",title:"The Diversity of Parvovirus Telomeres",doi:"10.5772/intechopen.102684",signatures:"Marianne Laugel, Emilie Lecomte, Eduard Ayuso, Oumeya Adjali, Mathieu Mével and Magalie Penaud-Budloo",slug:"the-diversity-of-parvovirus-telomeres",totalDownloads:23,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Recent Advances in Canine Medicine",coverURL:"https://cdn.intechopen.com/books/images_new/11580.jpg",subseries:{id:"19",title:"Animal Science"}}},{id:"79909",title:"Cryopreservation Methods and Frontiers in the Art of Freezing Life in Animal Models",doi:"10.5772/intechopen.101750",signatures:"Feda S. 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She obtained her Ph.D. in Veterinary Sciences from the University of Trás-os-Montes e Alto Douro, Portugal. After almost 32 years of teaching at the University of Trás-os-Montes and Alto Douro, she recently moved to the University of Évora, Department of Veterinary Medicine, where she teaches in the field of Animal Reproduction and Clinics. Her primary research areas include the molecular markers of the endometrial cycle and the embryo–maternal interaction, including oxidative stress and the reproductive physiology and disorders of sexual development, besides the molecular determinants of male and female fertility. She often supervises students preparing their master's or doctoral theses. 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Also he received Masters Degree and PhD from Córdoba University, Spain. He is currently a Professor at the Catholic University of Valencia San Vicente Mártir, at the Department of Medicine and Animal Surgery. He teaches diverse courses in the field of Animal Reproduction and he is the Director of the Veterinary Farm. He also participates in academic postgraduate activities at the Veterinary Faculty of Murcia University, Spain. His research areas include animal physiology, physiology and biotechnology of reproduction either in males or females, the study of gametes under in vitro conditions and the use of ultrasound as a complement to physiological studies and development of applied biotechnologies. 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He has both an MS and Ph.D. in Biomedical Engineering. He was previously a research scientist at the University of California Los Angeles (UCLA) and visiting professor and researcher at the University of North Dakota. He is currently working in artificial intelligence and its applications in medical signal processing. In addition, he is using digital signal processing in medical imaging and speech processing. Dr. Asadpour has developed brain-computer interfacing algorithms and has published books, book chapters, and several journal and conference papers in this field and other areas of intelligent signal processing. He has also designed medical devices, including a laser Doppler monitoring system.",institutionString:"Kaiser Permanente Southern California",institution:null},{id:"169608",title:"Prof.",name:"Marian",middleName:null,surname:"Găiceanu",slug:"marian-gaiceanu",fullName:"Marian Găiceanu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/169608/images/system/169608.png",biography:"Prof. Dr. Marian Gaiceanu graduated from the Naval and Electrical Engineering Faculty, Dunarea de Jos University of Galati, Romania, in 1997. He received a Ph.D. (Magna Cum Laude) in Electrical Engineering in 2002. Since 2017, Dr. Gaiceanu has been a Ph.D. supervisor for students in Electrical Engineering. He has been employed at Dunarea de Jos University of Galati since 1996, where he is currently a professor. Dr. Gaiceanu is a member of the National Council for Attesting Titles, Diplomas and Certificates, an expert of the Executive Agency for Higher Education, Research Funding, and a member of the Senate of the Dunarea de Jos University of Galati. He has been the head of the Integrated Energy Conversion Systems and Advanced Control of Complex Processes Research Center, Romania, since 2016. He has conducted several projects in power converter systems for electrical drives, power quality, PEM and SOFC fuel cell power converters for utilities, electric vehicles, and marine applications with the Department of Regulation and Control, SIEI S.pA. (2002–2004) and the Polytechnic University of Turin, Italy (2002–2004, 2006–2007). He is a member of the Institute of Electrical and Electronics Engineers (IEEE) and cofounder-member of the IEEE Power Electronics Romanian Chapter. He is a guest editor at Energies and an academic book editor for IntechOpen. He is also a member of the editorial boards of the Journal of Electrical Engineering, Electronics, Control and Computer Science and Sustainability. Dr. Gaiceanu has been General Chairman of the IEEE International Symposium on Electrical and Electronics Engineering in the last six editions.",institutionString:'"Dunarea de Jos" University of Galati',institution:{name:'"Dunarea de Jos" University of Galati',country:{name:"Romania"}}},{id:"4519",title:"Prof.",name:"Jaydip",middleName:null,surname:"Sen",slug:"jaydip-sen",fullName:"Jaydip Sen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/4519/images/system/4519.jpeg",biography:"Jaydip Sen is associated with Praxis Business School, Kolkata, India, as a professor in the Department of Data Science. His research areas include security and privacy issues in computing and communication, intrusion detection systems, machine learning, deep learning, and artificial intelligence in the financial domain. He has more than 200 publications in reputed international journals, refereed conference proceedings, and 20 book chapters in books published by internationally renowned publishing houses, such as Springer, CRC press, IGI Global, etc. Currently, he is serving on the editorial board of the prestigious journal Frontiers in Communications and Networks and in the technical program committees of a number of high-ranked international conferences organized by the IEEE, USA, and the ACM, USA. He has been listed among the top 2% of scientists in the world for the last three consecutive years, 2019 to 2021 as per studies conducted by the Stanford University, USA.",institutionString:"Praxis Business School",institution:null},{id:"320071",title:"Dr.",name:"Sidra",middleName:null,surname:"Mehtab",slug:"sidra-mehtab",fullName:"Sidra Mehtab",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00002v6KHoQAM/Profile_Picture_1584512086360",biography:"Sidra Mehtab has completed her BS with honors in Physics from Calcutta University, India in 2018. She has done MS in Data Science and Analytics from Maulana Abul Kalam Azad University of Technology (MAKAUT), Kolkata, India in 2020. Her research areas include Econometrics, Time Series Analysis, Machine Learning, Deep Learning, Artificial Intelligence, and Computer and Network Security with a particular focus on Cyber Security Analytics. Ms. Mehtab has published seven papers in international conferences and one of her papers has been accepted for publication in a reputable international journal. She has won the best paper awards in two prestigious international conferences – BAICONF 2019, and ICADCML 2021, organized in the Indian Institute of Management, Bangalore, India in December 2019, and SOA University, Bhubaneswar, India in January 2021. Besides, Ms. Mehtab has also published two book chapters in two books. Seven of her book chapters will be published in a volume shortly in 2021 by Cambridge Scholars’ Press, UK. Currently, she is working as the joint editor of two edited volumes on Time Series Analysis and Forecasting to be published in the first half of 2021 by an international house. Currently, she is working as a Data Scientist with an MNC in Delhi, India.",institutionString:"NSHM College of Management and Technology",institution:null},{id:"226240",title:"Dr.",name:"Andri Irfan",middleName:null,surname:"Rifai",slug:"andri-irfan-rifai",fullName:"Andri Irfan Rifai",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/226240/images/7412_n.jpg",biography:"Andri IRFAN is a Senior Lecturer of Civil Engineering and Planning. He completed the PhD at the Universitas Indonesia & Universidade do Minho with Sandwich Program Scholarship from the Directorate General of Higher Education and LPDP scholarship. He has been teaching for more than 19 years and much active to applied his knowledge in the project construction in Indonesia. His research interest ranges from pavement management system to advanced data mining techniques for transportation engineering. He has published more than 50 papers in journals and 2 books.",institutionString:null,institution:{name:"Universitas Internasional Batam",country:{name:"Indonesia"}}},{id:"314576",title:"Dr.",name:"Ibai",middleName:null,surname:"Laña",slug:"ibai-lana",fullName:"Ibai Laña",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314576/images/system/314576.jpg",biography:"Dr. Ibai Laña works at TECNALIA as a data analyst. He received his Ph.D. in Artificial Intelligence from the University of the Basque Country (UPV/EHU), Spain, in 2018. He is currently a senior researcher at TECNALIA. His research interests fall within the intersection of intelligent transportation systems, machine learning, traffic data analysis, and data science. He has dealt with urban traffic forecasting problems, applying machine learning models and evolutionary algorithms. He has experience in origin-destination matrix estimation or point of interest and trajectory detection. Working with large volumes of data has given him a good command of big data processing tools and NoSQL databases. He has also been a visiting scholar at the Knowledge Engineering and Discovery Research Institute, Auckland University of Technology.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"314575",title:"Dr.",name:"Jesus",middleName:null,surname:"L. Lobo",slug:"jesus-l.-lobo",fullName:"Jesus L. Lobo",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314575/images/system/314575.png",biography:"Dr. Jesús López is currently based in Bilbao (Spain) working at TECNALIA as Artificial Intelligence Research Scientist. In most cases, a project idea or a new research line needs to be investigated to see if it is good enough to take into production or to focus on it. That is exactly what he does, diving into Machine Learning algorithms and technologies to help TECNALIA to decide whether something is great in theory or will actually impact on the product or processes of its projects. So, he is expert at framing experiments, developing hypotheses, and proving whether they’re true or not, in order to investigate fundamental problems with a longer time horizon. He is also able to design and develop PoCs and system prototypes in simulation. He has participated in several national and internacional R&D projects.\n\nAs another relevant part of his everyday research work, he usually publishes his findings in reputed scientific refereed journals and international conferences, occasionally acting as reviewer and Programme Commitee member. Concretely, since 2018 he has published 9 JCR (8 Q1) journal papers, 9 conference papers (e.g. ECML PKDD 2021), and he has co-edited a book. He is also active in popular science writing data science stories for reputed blogs (KDNuggets, TowardsDataScience, Naukas). Besides, he has recently embarked on mentoring programmes as mentor, and has also worked as data science trainer.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"103779",title:"Prof.",name:"Yalcin",middleName:null,surname:"Isler",slug:"yalcin-isler",fullName:"Yalcin Isler",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRyQ8QAK/Profile_Picture_1628834958734",biography:"Yalcin Isler (1971 - Burdur / Turkey) received the B.Sc. degree in the Department of Electrical and Electronics Engineering from Anadolu University, Eskisehir, Turkey, in 1993, the M.Sc. degree from the Department of Electronics and Communication Engineering, Suleyman Demirel University, Isparta, Turkey, in 1996, the Ph.D. degree from the Department of Electrical and Electronics Engineering, Dokuz Eylul University, Izmir, Turkey, in 2009, and the Competence of Associate Professorship from the Turkish Interuniversity Council in 2019.\n\nHe was Lecturer at Burdur Vocational School in Suleyman Demirel University (1993-2000, Burdur / Turkey), Software Engineer (2000-2002, Izmir / Turkey), Research Assistant in Bulent Ecevit University (2002-2003, Zonguldak / Turkey), Research Assistant in Dokuz Eylul University (2003-2010, Izmir / Turkey), Assistant Professor at the Department of Electrical and Electronics Engineering in Bulent Ecevit University (2010-2012, Zonguldak / Turkey), Assistant Professor at the Department of Biomedical Engineering in Izmir Katip Celebi University (2012-2019, Izmir / Turkey). He is an Associate Professor at the Department of Biomedical Engineering at Izmir Katip Celebi University, Izmir / Turkey, since 2019. In addition to academics, he has also founded Islerya Medical and Information Technologies Company, Izmir / Turkey, since 2017.\n\nHis main research interests cover biomedical signal processing, pattern recognition, medical device design, programming, and embedded systems. He has many scientific papers and participated in several projects in these study fields. He was an IEEE Student Member (2009-2011) and IEEE Member (2011-2014) and has been IEEE Senior Member since 2014.",institutionString:null,institution:{name:"Izmir Kâtip Çelebi University",country:{name:"Turkey"}}},{id:"339677",title:"Dr.",name:"Mrinmoy",middleName:null,surname:"Roy",slug:"mrinmoy-roy",fullName:"Mrinmoy Roy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/339677/images/16768_n.jpg",biography:"An accomplished Sales & Marketing professional with 12 years of cross-functional experience in well-known organisations such as CIPLA, LUPIN, GLENMARK, ASTRAZENECA across different segment of Sales & Marketing, International Business, Institutional Business, Product Management, Strategic Marketing of HIV, Oncology, Derma, Respiratory, Anti-Diabetic, Nutraceutical & Stomatological Product Portfolio and Generic as well as Chronic Critical Care Portfolio. A First Class MBA in International Business & Strategic Marketing, B.Pharm, D.Pharm, Google Certified Digital Marketing Professional. Qualified PhD Candidate in Operations and Management with special focus on Artificial Intelligence and Machine Learning adoption, analysis and use in Healthcare, Hospital & Pharma Domain. Seasoned with diverse therapy area of Pharmaceutical Sales & Marketing ranging from generating revenue through generating prescriptions, launching new products, and making them big brands with continuous strategy execution at the Physician and Patients level. Moved from Sales to Marketing and Business Development for 3.5 years in South East Asian Market operating from Manila, Philippines. Came back to India and handled and developed Brands such as Gluconorm, Lupisulin, Supracal, Absolut Woman, Hemozink, Fabiflu (For COVID 19), and many more. In my previous assignment I used to develop and execute strategies on Sales & Marketing, Commercialization & Business Development for Institution and Corporate Hospital Business portfolio of Oncology Therapy Area for AstraZeneca Pharma India Ltd. Being a Research Scholar and Student of ‘Operations Research & Management: Artificial Intelligence’ I published several pioneer research papers and book chapters on the same in Internationally reputed journals and Books indexed in Scopus, Springer and Ei Compendex, Google Scholar etc. Currently, I am launching PGDM Pharmaceutical Management Program in IIHMR Bangalore and spearheading the course curriculum and structure of the same. I am interested in Collaboration for Healthcare Innovation, Pharma AI Innovation, Future trend in Marketing and Management with incubation on Healthcare, Healthcare IT startups, AI-ML Modelling and Healthcare Algorithm based training module development. I am also an affiliated member of the Institute of Management Consultant of India, looking forward to Healthcare, Healthcare IT and Innovation, Pharma and Hospital Management Consulting works.",institutionString:null,institution:{name:"Lovely Professional University",country:{name:"India"}}},{id:"1063",title:"Prof.",name:"Constantin",middleName:null,surname:"Volosencu",slug:"constantin-volosencu",fullName:"Constantin Volosencu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/1063/images/system/1063.png",biography:"Prof. Dr. Constantin Voloşencu graduated as an engineer from\nPolitehnica University of Timișoara, Romania, where he also\nobtained a doctorate degree. 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. He has developed automation equipment for machine tools, spooling\nmachines, high-power ultrasound processes, and more.",institutionString:"Polytechnic University of Timişoara",institution:{name:"Polytechnic University of Timişoara",country:{name:"Romania"}}},{id:"221364",title:"Dr.",name:"Eneko",middleName:null,surname:"Osaba",slug:"eneko-osaba",fullName:"Eneko Osaba",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/221364/images/system/221364.jpg",biography:"Dr. Eneko Osaba works at TECNALIA as a senior researcher. He obtained his Ph.D. in Artificial Intelligence in 2015. He has participated in more than twenty-five local and European research projects, and in the publication of more than 130 papers. He has performed several stays at universities in the United Kingdom, Italy, and Malta. Dr. Osaba has served as a program committee member in more than forty international conferences and participated in organizing activities in more than ten international conferences. He is a member of the editorial board of the International Journal of Artificial Intelligence, Data in Brief, and Journal of Advanced Transportation. He is also a guest editor for the Journal of Computational Science, Neurocomputing, Swarm, and Evolutionary Computation and IEEE ITS Magazine.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"275829",title:"Dr.",name:"Esther",middleName:null,surname:"Villar-Rodriguez",slug:"esther-villar-rodriguez",fullName:"Esther Villar-Rodriguez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/275829/images/system/275829.jpg",biography:"Dr. Esther Villar obtained a Ph.D. in Information and Communication Technologies from the University of Alcalá, Spain, in 2015. She obtained a degree in Computer Science from the University of Deusto, Spain, in 2010, and an MSc in Computer Languages and Systems from the National University of Distance Education, Spain, in 2012. Her areas of interest and knowledge include natural language processing (NLP), detection of impersonation in social networks, semantic web, and machine learning. Dr. Esther Villar made several contributions at conferences and publishing in various journals in those fields. Currently, she is working within the OPTIMA (Optimization Modeling & Analytics) business of TECNALIA’s ICT Division as a data scientist in projects related to the prediction and optimization of management and industrial processes (resource planning, energy efficiency, etc).",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"49813",title:"Dr.",name:"Javier",middleName:null,surname:"Del Ser",slug:"javier-del-ser",fullName:"Javier Del Ser",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49813/images/system/49813.png",biography:"Prof. Dr. Javier Del Ser received his first PhD in Telecommunication Engineering (Cum Laude) from the University of Navarra, Spain, in 2006, and a second PhD in Computational Intelligence (Summa Cum Laude) from the University of Alcala, Spain, in 2013. He is currently a principal researcher in data analytics and optimisation at TECNALIA (Spain), a visiting fellow at the Basque Center for Applied Mathematics (BCAM) and a part-time lecturer at the University of the Basque Country (UPV/EHU). His research interests gravitate on the use of descriptive, prescriptive and predictive algorithms for data mining and optimization in a diverse range of application fields such as Energy, Transport, Telecommunications, Health and Industry, among others. In these fields he has published more than 240 articles, co-supervised 8 Ph.D. theses, edited 6 books, coauthored 7 patents and participated/led more than 40 research projects. He is a Senior Member of the IEEE, and a recipient of the Biscay Talent prize for his academic career.",institutionString:"Tecnalia Research & Innovation",institution:null},{id:"278948",title:"Dr.",name:"Carlos Pedro",middleName:null,surname:"Gonçalves",slug:"carlos-pedro-goncalves",fullName:"Carlos Pedro Gonçalves",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRcmyQAC/Profile_Picture_1564224512145",biography:'Carlos Pedro Gonçalves (PhD) is an Associate Professor at Lusophone University of Humanities and Technologies and a researcher on Complexity Sciences, Quantum Technologies, Artificial Intelligence, Strategic Studies, Studies in Intelligence and Security, FinTech and Financial Risk Modeling. He is also a progammer with programming experience in:\n\nA) Quantum Computing using Qiskit Python module and IBM Quantum Experience Platform, with software developed on the simulation of Quantum Artificial Neural Networks and Quantum Cybersecurity;\n\nB) Artificial Intelligence and Machine learning programming in Python;\n\nC) Artificial Intelligence, Multiagent Systems Modeling and System Dynamics Modeling in Netlogo, with models developed in the areas of Chaos Theory, Econophysics, Artificial Intelligence, Classical and Quantum Complex Systems Science, with the Econophysics models having been cited worldwide and incorporated in PhD programs by different Universities.\n\nReceived an Arctic Code Vault Contributor status by GitHub, due to having developed open source software preserved in the \\"Arctic Code Vault\\" for future generations (https://archiveprogram.github.com/arctic-vault/), with the Strategy Analyzer A.I. module for decision making support (based on his PhD thesis, used in his Classes on Decision Making and in Strategic Intelligence Consulting Activities) and QNeural Python Quantum Neural Network simulator also preserved in the \\"Arctic Code Vault\\", for access to these software modules see: https://github.com/cpgoncalves. He is also a peer reviewer with outsanding review status from Elsevier journals, including Physica A, Neurocomputing and Engineering Applications of Artificial Intelligence. Science CV available at: https://www.cienciavitae.pt//pt/8E1C-A8B3-78C5 and ORCID: https://orcid.org/0000-0002-0298-3974',institutionString:"University of Lisbon",institution:{name:"Universidade Lusófona",country:{name:"Portugal"}}},{id:"241400",title:"Prof.",name:"Mohammed",middleName:null,surname:"Bsiss",slug:"mohammed-bsiss",fullName:"Mohammed Bsiss",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/241400/images/8062_n.jpg",biography:null,institutionString:null,institution:null},{id:"276128",title:"Dr.",name:"Hira",middleName:null,surname:"Fatima",slug:"hira-fatima",fullName:"Hira Fatima",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/276128/images/14420_n.jpg",biography:"Dr. Hira Fatima\nAssistant Professor\nDepartment of Mathematics\nInstitute of Applied Science\nMangalayatan University, Aligarh\nMobile: no : 8532041179\nhirafatima2014@gmal.com\n\nDr. Hira Fatima has received his Ph.D. degree in pure Mathematics from Aligarh Muslim University, Aligarh India. Currently working as an Assistant Professor in the Department of Mathematics, Institute of Applied Science, Mangalayatan University, Aligarh. She taught so many courses of Mathematics of UG and PG level. Her research Area of Expertise is Functional Analysis & Sequence Spaces. She has been working on Ideal Convergence of double sequence. She has published 17 research papers in National and International Journals including Cogent Mathematics, Filomat, Journal of Intelligent and Fuzzy Systems, Advances in Difference Equations, Journal of Mathematical Analysis, Journal of Mathematical & Computer Science etc. She has also reviewed few research papers for the and international journals. She is a member of Indian Mathematical Society.",institutionString:null,institution:null},{id:"414880",title:"Dr.",name:"Maryam",middleName:null,surname:"Vatankhah",slug:"maryam-vatankhah",fullName:"Maryam Vatankhah",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Borough of Manhattan Community College",country:{name:"United States of America"}}},{id:"414879",title:"Prof.",name:"Mohammad-Reza",middleName:null,surname:"Akbarzadeh-Totonchi",slug:"mohammad-reza-akbarzadeh-totonchi",fullName:"Mohammad-Reza Akbarzadeh-Totonchi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Ferdowsi University of Mashhad",country:{name:"Iran"}}},{id:"414878",title:"Prof.",name:"Reza",middleName:null,surname:"Fazel-Rezai",slug:"reza-fazel-rezai",fullName:"Reza Fazel-Rezai",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"American Public University System",country:{name:"United States of America"}}},{id:"302698",title:"Dr.",name:"Yao",middleName:null,surname:"Shan",slug:"yao-shan",fullName:"Yao Shan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Dalian University of Technology",country:{name:"China"}}},{id:"125911",title:"Prof.",name:"Jia-Ching",middleName:null,surname:"Wang",slug:"jia-ching-wang",fullName:"Jia-Ching Wang",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"National Central University",country:{name:"Taiwan"}}},{id:"357085",title:"Mr.",name:"P. 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Shukla",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}},{id:"356823",title:"MSc.",name:"Seonghee",middleName:null,surname:"Min",slug:"seonghee-min",fullName:"Seonghee Min",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Daegu University",country:{name:"Korea, South"}}},{id:"353307",title:"Prof.",name:"Yoosoo",middleName:null,surname:"Oh",slug:"yoosoo-oh",fullName:"Yoosoo Oh",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:"Yoosoo Oh received his Bachelor's degree in the Department of Electronics and Engineering from Kyungpook National University in 2002. He obtained his Master’s degree in the Department of Information and Communications from Gwangju Institute of Science and Technology (GIST) in 2003. In 2010, he received his Ph.D. degree in the School of Information and Mechatronics from GIST. In the meantime, he was an executed team leader at Culture Technology Institute, GIST, 2010-2012. In 2011, he worked at Lancaster University, the UK as a visiting scholar. In September 2012, he joined Daegu University, where he is currently an associate professor in the School of ICT Conver, Daegu University. Also, he served as the Board of Directors of KSIIS since 2019, and HCI Korea since 2016. From 2017~2019, he worked as a center director of the Mixed Reality Convergence Research Center at Daegu University. From 2015-2017, He worked as a director in the Enterprise Supporting Office of LINC Project Group, Daegu University. His research interests include Activity Fusion & Reasoning, Machine Learning, Context-aware Middleware, Human-Computer Interaction, etc.",institutionString:null,institution:{name:"Daegu Gyeongbuk Institute of Science and Technology",country:{name:"Korea, South"}}},{id:"262719",title:"Dr.",name:"Esma",middleName:null,surname:"Ergüner Özkoç",slug:"esma-erguner-ozkoc",fullName:"Esma Ergüner Özkoç",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Başkent University",country:{name:"Turkey"}}},{id:"346530",title:"Dr.",name:"Ibrahim",middleName:null,surname:"Kaya",slug:"ibrahim-kaya",fullName:"Ibrahim Kaya",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Izmir Kâtip Çelebi University",country:{name:"Turkey"}}},{id:"419199",title:"Dr.",name:"Qun",middleName:null,surname:"Yang",slug:"qun-yang",fullName:"Qun Yang",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Auckland",country:{name:"New Zealand"}}},{id:"351158",title:"Prof.",name:"David W.",middleName:null,surname:"Anderson",slug:"david-w.-anderson",fullName:"David W. Anderson",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Calgary",country:{name:"Canada"}}}]}},subseries:{item:{id:"92",type:"subseries",title:"Health and Wellbeing",keywords:"Ecology, Ecological, Nature, Health, Wellbeing, Health production",scope:"\r\n\tSustainable approaches to health and wellbeing in our COVID 19 recovery needs to focus on ecological approaches that prioritize our relationships with each other, and include engagement with nature, the arts and our heritage. This will ensure that we discover ways to live in our world that allows us and other beings to flourish. We can no longer rely on medicalized approaches to health that wait for people to become ill before attempting to treat them. We need to live in harmony with nature and rediscover the beauty and balance in our everyday lives and surroundings, which contribute to our well-being and that of all other creatures on the planet. This topic will provide insights and knowledge into how to achieve this change in health care that is based on ecologically sustainable practices.
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