Mean amount of minerals dissolved from first or second molars during each time interval (μg/four first or second molars; mean ± SEM).
\\n\\n
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
\n'}],latestNews:[{slug:"intechopen-supports-asapbio-s-new-initiative-publish-your-reviews-20220729",title:"IntechOpen Supports ASAPbio’s New Initiative Publish Your Reviews"},{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"}]},book:{item:{type:"book",id:"1285",leadTitle:null,fullTitle:"HIV-infection - Impact, Awareness and Social Implications of living with HIV/AIDS",title:"HIV-infection",subtitle:"Impact, Awareness and Social Implications of living with HIV/AIDS",reviewType:"peer-reviewed",abstract:"The past few decades have seen the escalation of HIV-infections and the 'frantic' search for new drugs to treat the millions of people that live with HIV-AIDS. However because HIV-AIDS cannot be cured, but only controlled with drugs, and the Antiretroviral (ARV) treatment itself results in some undesirable conditions, it is important to generate wider awareness of the plight of people living with this condition. This book attempts to provide information of the initiatives that have been used, successfully or unsuccessfully, to both prevent and combat this 'pandemic' taking into consideration the social, economic, cultural and educational aspects that involve individuals, communities and the countries affected.",isbn:null,printIsbn:"978-953-307-343-9",pdfIsbn:"978-953-51-6538-5",doi:"10.5772/1754",price:139,priceEur:155,priceUsd:179,slug:"hiv-infection-impact-awareness-and-social-implications-of-living-with-hiv-aids",numberOfPages:348,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"580311440677bce4d1bdfefb3a13726a",bookSignature:"Eugenia Barros",publishedDate:"October 26th 2011",coverURL:"https://cdn.intechopen.com/books/images_new/1285.jpg",numberOfDownloads:49651,numberOfWosCitations:5,numberOfCrossrefCitations:4,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:14,numberOfDimensionsCitationsByBook:0,hasAltmetrics:0,numberOfTotalCitations:23,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"November 3rd 2010",dateEndSecondStepPublish:"December 1st 2010",dateEndThirdStepPublish:"April 7th 2011",dateEndFourthStepPublish:"May 7th 2011",dateEndFifthStepPublish:"July 6th 2011",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"35597",title:"Dr.",name:"Eugenia",middleName:null,surname:"Barros",slug:"eugenia-barros",fullName:"Eugenia Barros",profilePictureURL:"https://mts.intechopen.com/storage/users/35597/images/1844_n.jpg",biography:"Eugenia Barros has a PhD in Microbiology from the University of Cape Town, South Africa and she is a Principal Researcher in the Biosciences Unit of CSIR (Council for Scientific and Industrial Research) in Pretoria, South Africa. She has led many scientific projects in the areas of Molecular Biology and has been instrumental in applying some of her research outcomes in the agricultural and food sectors. She has also been in the forefront of plant-made therapeutic antibodies through a collaborative project with European laboratories and has scaled-up the production of an HIV-AIDS monoclonal antibody. Living in South Africa she is very aware of the impact of HIV-AIDS in society and in the most vulnerable communities in rural Africa",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Council for Scientific and Industrial Research",institutionURL:null,country:{name:"South Africa"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1046",title:"Infectious Diseases",slug:"infectious-diseases"}],chapters:[{id:"22445",title:"HIV Epidemiology and Prevention",doi:"10.5772/19532",slug:"hiv-epidemiology-and-prevention",totalDownloads:1591,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:null,signatures:"Ayesha B.M. 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Caffeine (1,3,7-trimethylxanthine) is the substance most frequently consumed in our daily life. For example, coffee, most of the soft drinks and over-the-counter medications contain caffeine [1]. On the other hand, cocoa contains theobromine (3,7-dimethylxanthine). The main source of theobromine which is daily consumed by humans from childhood to adult is chocolate. Cocoa produces no adverse effect, in normal dosage [2]. These two similar families of xanthine, but the opposite properties on the crystal formation of the hydroxylapatite (HAP) of the teeth were discovered accidentally. Fluoride is the only known chemical that affected the HAP of the enamel by converting it to fluorohydroxylapatite.
In the dental community, fluoride has been used not only as the main ingredient of dentifrice but is also used in many others. However, recently fluoride was designated as one of the developmental neurotoxicants as more adverse effects of fluoride are revealed [3]. Although besides the developmental neurotoxicants, fluoride is also known to affect the pineal gland [4] and thyroid gland [5] and there is even some evidence between bone disease and fluoride exposure [6].
In addition, there are many reports [7, 8, 9, 10, 11, 12] that infants, newborns and young children were exposed to fluoride and fluorosis among them is common. Unfortunately, in dentistry, fluorosis was mainly considered as an esthetic problem to which no more serious consideration is paid attention. Recently, it was proposed that fluoride exposure in early life may become a root cause of the disease in later life [13].
Pups’ teeth were affected by the sucking milk of lactating dams which were given a caffeine-containing diet [14]. (In each animal experiment described, we obtained the permission to use the animals from the animal care committee at the LSU Health Sciences Center.) Then, eventually, non-fluoride dentifrices were developed.
Further studies were conducted to determine whether the effects of caffeine come from either enamel or dentin, or both. If certain effects come from enamel, it would be an extremely interesting phenomenon, because the only chemical known to affect the HAP of the enamel is fluoride. In addition, any changes in the HAP on the enamel by caffeine might be linked to possible incidences of future dental caries.
Using the method described [15] on how to study the enamel surface of the teeth which were affected by the nutritional deficiency, the condition of the enamel was studied. The samples from the first or second molars were obtained at postnatal day 22 which is the end of lactation. The teeth were exposed to weak acid for 80 minutes and four fractions were collected at 20 minutes intervals. The experimental procedures were described in detail [16, 17]. The enamel surface of secondary electron photomicrographs are shown in the control (Figure 1) and caffeine group (Figure 2).
Left: Before acid exposure in the control. Right: 80 minutes after the acid exposure.
Left: Before acid exposure of the caffeine group. Right: 80 minutes after the acid exposure.
The apparent effects of crystallization by caffeine on the enamel of first molars where calcium, phosphorus and magnesium were released more of the teeth in the caffeine exposed offspring (Table 1). The first molars showed a statistically significant amount of dissolution in the caffeine group of the respective ions measured for 80 minutes compared to the non-caffeine control group [16].
First molar | Second molar | ||||
---|---|---|---|---|---|
Control | Caffeine | Control | Caffeine | ||
20 min | |||||
Ca | 5.23 ± 0.33 | 8.63 ± 1.07* | 7.45 ± 1.29 | 7.36 ± 0.86 | |
P | 2.67 ± 0.36 | 5.66 ± 1.07* | 4.09 ± 0.98 | 4.41 ± 0.89 | |
Mg | 0.20 ± 0.02 | 0.44 ± 0.07* | 0.28 ± 0.04 | 0.31 ± 0.04 | |
40 min | |||||
Ca | 10.74 ± 1.17 | 16.83 ± 1.10* | 13.59 ± 1.15 | 13.63 ± 0.92 | |
P | 7.34 ± 0.77 | 12.49 ± 1.40* | 10.03 ± 1.45 | 8.68 ± 0.95 | |
Mg | 0.39 ± 0.06 | 0.72 ± 0.06* | 0.45 ± 0.04 | 0.55 ± 0.05 | |
60 min | |||||
Ca | 12.36 ± 1.22 | 18.19 ± 1.12* | 14.68 ± 1.15 | 14.85 ± 1.19 | |
P | 8.03 ± 0.78 | 14.72 ± 1.98* | 10.47 ± 1.15 | 10.42 ± 0.97 | |
Mg | 0.43 ± 0.04 | 0.74 ± 0.06* | 0.49 ± 0.03 | 0.55 ± 0.05 | |
80 min | |||||
Ca | 13.68 ± 1.30 | 19.64 ± 1.19* | 15.21 ± 1.22 | 15.94 ± 0.91 | |
P | 9.39 ± 0.91 | 18.12 ± 2.62* | 11.05 ± 1.10 | 12.88 ± 1.80 | |
Mg | 0.42 ± 0.04 | 0.71 ± 0.05* | 043 ± 0.05 | 052 ± 005 |
Mean amount of minerals dissolved from first or second molars during each time interval (μg/four first or second molars; mean ± SEM).
Significantly different from the control at
Each value is an average of seven determinations.
FWHM/M of apatite grown in vitro | ||
---|---|---|
Additive | mg/L | FWHM/M |
Control | 0 | 0.75 |
Caffeine | 200 | 1.00 |
Caffeine | 50 | 0.90 |
Theobromine | 200 | 0.15 |
Theobromine | 50 | 0.19 |
1-methylxanthine | 200 | 0.60 |
1-methylxanthine | 50 | 0.68 |
Hydroxylapatite which was grown in vitro of three xanthine families, caffeine, theobromine and 1-methylxanthine are shown.
Lower values of the ratio indicate better crystal size.
On the other hand, there is no significant difference between caffeine and the control group in each mineral dissolved in the second molars.
This difference in the caffeine’s effects between first and second molars can be explained as follows. The first stage of development is called the hyperplastic growth period which is primarily an increase of DNA of the organ. Synthesis of DNA and cell division at first take place rapidly [18], but thereafter, slow down. Further tissue growth can occur by cytoplasmic enlargement.
The measured DNA content as an index of cell number distinguishes growth by an increase of cell number (hyperplasia). Cell division eventually ceases will be seen to determine when the organ is no longer vulnerable to nutritional stress. If nutritional stress, such as caffeine exposure in the early part of life were applied hyperplastic growth period, the organ or body would never recover to the original condition. Therefore, this period is called a critical growth period.
The second stage is a gradual decrease in cell number and a slow increase of cell size in the organ. The third stage is primarily an increase in cell size, which is called the hypertrophic growth period. If the nutritional stress were applied in this period, organ or animal grows back normally, provided that enough nutrition is given [19, 20].
During the period of growth and development, the critical period of growth is the most important concept. For example, the huge increase of DNA in the brain occurs primarily during gestation and early lactation period whereas an increase of the DNA of the heart continues until adulthood [21]. This indicates that the critical period of growth is different among the organs, therefore, the effects of the nutritional stress on each organ is different, depending upon when the stress is applied.
Likewise, caffeine exposures for the growing period were different between the first and second molars, indicating that the critical period of growth during caffeine exposure was different between the first and second molars. First molars are affected by caffeine intake by the offspring during this period. Therefore, the experiments were conducted only using the first molars.
To find out what is happening to the enamel of the first molars, samples that were not used in the studies were powered and enamel was separated from dentin [22]. Then a pure enamel sample was run for 4 hours on a Gandolfi X-ray powder camera. Also, various other aspects of the samples were studied in detail [17].
The filmstrip run on the Gandolfi camera recorded more diffuse lines for the samples of the caffeine group compared to the control (Figure 3).
Top: control. Bottom: caffeine group.
X-ray diffraction analysis on enamel samples by the Gandolfi X-ray camera showed the caffeine supplementation in the maternal diet affected mineralization of enamel, as broader lines indicated smaller crystallites of enamel. Smaller crystallites increase susceptibility to dissolution.
This explains why the caffeine group of the teeth showed the higher dissolution of each ion from the surface of enamel throughout the experimental period [16].
Because the teeth were affected by caffeine it is natural to make a simple assumption, that is, is it possible to produce in vivo dental caries in the caffeine group [16].
Thus, the experiment was conducted by raising the offspring the same way as above. At weanling on postnatal day 22, offspring were fed the cariogenic diet until day 50 (a total of 28 days) to see whether the caffeine group show a response in dental caries using the methods described [23]. The caffeine group showed significantly higher caries scores than that of the non-caffeine control (
Therefore, the hypothesis turned to be true as is shown in Figures 4 and 5. The amount of caffeine that was added to the maternal diet was 2 mg/100 g bodyweight of the dam. The equivalent comparison between the caffeine in the rat and human is based on metabolic body weight (kg0.75) [25]. (Metabolic rates are expressed in terms of metabolic body size—i.e., kg0.75, the point at which the dependence on different body sizes disappears.) The human caffeine intake is comparable with slightly more than two cups of coffee daily.
Molar of the control at day 50 stained with 0.06% murexide in 70% ethanol for 16 hours (top), the caffeine group (bottom).
Secondary electron image of control at day 50 (left) and the caffeine group (right).
This is the normal amount of caffeine consumed by humans. Although extrapolation from rat data to human dental caries incidence requires extreme caution, nevertheless present data indicate that caffeine exposure during the early growth period impairs the structure of the enamel crystal formation of the developing teeth. Particularly, it may require attention where the offspring born from a pregnant woman who habitually consumes caffeine-containing soft drinks and/or coffee drinkers may develop teeth that are prone to dental caries of the offspring in the future. It seems clear that caffeine exposure during the critical growth period affects the amelogenesis of the enamel, affecting the crystal size of the HAP during mineralization.
A series of caffeine studies on crystallization research required more than several years. Thus, a simple in vitro study was conducted to see whether other xanthine family members could reveal if any, other different crystallization value(s) from caffeine.
All the solutions contained 0.01 molar CaCl2 and Na3PO4. Several sets of experiments were conducted with the addition of each of methylxanthine at low concentrations, 50 mg, and 200 mg/L. The effect of the xanthine compounds was compared with a control solution containing CaCl2 and Na3PO4 only. Solutions were mixed at 25°C, and pH adjusted to 9–9.5 with 0.1 molar NaOH and left to crystallize for 20 days. The crystalline was washed five times with distilled water and prepared for X-ray diffraction (Figure 6).
All the data from the various members of the xanthine family on the effects of crystallization were already reported [26, 27].
The (300) reflection was scanned to investigate crystallinity. FWHM (full width-half maximum peak height) divided by maximum peak height (FWHM/M) and for the (300) reflection is given in
To our surprise, the value of theobromine was much lower than caffeine. Specifically, 1-methylxanthine values were lower than the caffeine group but not as low as the theobromine group.
Caffeine (small crystal size) and theobromine (large crystal size) with the lack of one position of the methyl group, crystal size was opposite. Therefore, it should be further investigated how the methyl position 1 alone can influence the crystallization. The crystal size of position 1 alone did not have much effect on the crystal size. See the chemical formulae (Figure 7).
The chemical formula of three xanthines.
The crystal size of the theobromine group taken by an electron microscope was shown below and the size was four times bigger than that of the control group (Figure 8).
(Left) Theobromine group: 200 mg/L, Crystal size: 2 μm. (Right) Control group: Crystal size: 0.5 μm.
Theobromine and caffeine contents of the average commercial sweet chocolates are approximately 8:1 ratio [28]. The half-life of theobromine and caffeine is different and that of theobromine is longer than caffeine.
The inhibitory effect of cocoa which contains theobromine on plaque accumulation and cariostatic activity has been suggested [29]. However, its anticaries activity is not strong enough to suppress significantly cariogenic activity [30]. On the other hand, the addition of a water-soluble extract of cacao powder significantly reduced caries scores in specific pathogen-free rats infected with
The amount of theobromine added to the maternal diet in the study was 1 mg/100 g body weight. If this amount is converted by the metabolic body weight (kg0.75) [25], this corresponds approximately to slightly more than one to three bars of 1 oz milk chocolate for a 65 kg human. After raising the offspring fed with a maternal diet containing theobromine, molars were extracted and studied the following aspects.
A consistent relationship of higher crystallinity, i.e., larger crystallites, in the whole molars from the rats exposed to theobromine, compared to the control and/or caffeine group was observed in the X-ray diffractometry [27].
Calcium and phosphorus concentrations were determined in the enamel of molars extracted from theobromine exposed rats or control rats by an “ARL-SEMQ”™ electron microprobe analysis. The instrument was operated at an acceleration potential of 15 kV and a beam current of 1.0 × 10−7 A. Fluorapatite from Cerro de Mercado, Mexico, was used as a standard. The results obtained are shown in our previous report [26, 27].
This study was conducted to see whether the composition of crystallites of the enamel formed by theobromine is different from the control group. The overall content of CaO and P2O5 appears to be comparable within the expected margin of error. This suggests that the composition of crystallites of the enamel between control and experimental groups are the same.
The same experimental procedures, as was in the caffeine study [16], were conducted. The molars from the offspring whose dams were fed with the diet supplemented with theobromine were extracted. The dissolution studies were done. The result showed decreased dissolution (Ca, P, and Mg) of the ions from this group due to the larger crystal size (Figure 9) [27].
Calcium (upper left), phosphorus (upper right) and magnesium (bottom) theobromine group were significantly ∗ (
The unique roles of theobromine were accidentally discovered during the caffeine study. Because previously only fluoride has been known to affect the enamel, the next steps were to investigate the comparative studies between theobromine and fluoride on the effects of the enamel in a similar environment using the in vitro system.
If remineralization occurs, then the increased enamel is associated with increased microhardness [33]. The microhardness test was conducted using theobromine [34]. An in vitro study confirmed that theobromine increased the microhardness of the enamel [35, 36, 37].
The enamel of human teeth with varying concentrations of theobromine vs. sodium fluoride vs. control groups (distilled water) was performed. Scanning electron microscopy (SEM) and Knoop Microhardness Testing (NMT) were conducted. A Knoop microhardness instrument was used. Knoop Microhardness tests were performed every day for a period of 8 days on each sample and the data were recorded. Day 1 represents the baseline hardness.
On day 8, it was not tested to avoid interfering with the surface of the tooth before taking the scanning electron photomicrographs. The hardness data are shown at the end of the 8th day and the results were published [26]. Figure 10 shows SEM photomicrographs of the enamel of control, fluoride and theobromine.
Upper left: control group. Upper right: 0.15% w/v fluoride ion. Bottom: theobromine group: 500 mg/L.
In general, the teeth that were coated with theobromine appeared to be cleaner, smooth and excellent mineralization was observed under the electron microscope especially when compared with control group teeth.
Samples were covered with small uniformly cut circles of double-stick tape.
The tooth was covered in nail polish and the tape was removed to expose a fairly uniform enamel surface on each tooth.
Each tooth was immersed in either 0.15% w/v fluoride ion solution or theobromine 100 mg/L solution for 30 minutes. Then, each tooth was exposed to a 0.001 N HCl acid solution for 10 minutes to determine how much calcium is released from the enamel. The amount calcium (ppm) released from the surface of the enamel in the F-0.15% was an average of 0.930 whereas theobromine-100 mg was 0.848. The fluoride group of teeth released 9.66% more calcium compared to the theobromine group, suggesting that the pre-exposures by theobromine solution is more effective to make the enamel surface of teeth more resistant than fluoride solution. Theobromine is reported as an effective remineralizing agent [38].
Hypersensitivity is a short and sharp pain arising from exposed dentin by an external stimulus [39]. The prevalence of hypersensitivity varies [40]. The therapeutic approach is to occlude dentin tubules [41].
Clinical studies were conducted in four different samples. The detail of the experimental design has been already described [26, 42]. Importantly theobromine-based toothpaste has shown that the hypersensitivity disappeared within a week [42]. On the other hand, fluoride-based toothpastes indicated practically no effects to alleviate sensitivity without much occlusion on the dentinal tubes during this experimental period of 1 week.
A study using an established in vitro caries pH cycling model [43] was conducted [44]. Treatment with theobromine results in resistance to acid attack. A recent study has shown that theobromine gel had more effective remineralizing potential than fluoride gel [45].
In the oral environment, remineralization and demineralization are happening constantly. The hardness test conducted on the enamel surface [26] clearly showed that theobromine was much more effective than fluoride. However, in another study using pH cycling method, theobromine does not appear to offer any anti-caries benefits [46]. Applied theobromine to the demineralized enamel surface caused recrystallization and increased surface microhardness.
Crystallite size is the main factor that controls the dissolution of HAP. Small crystallites have a much higher surface area/volume ratio compared to larger crystallites. Dissolution is more rapid on smaller crystallites than on larger ones. Thus, larger crystallites of HAP in the enamel resist dissolution under cariogenic conditions better than smaller ones.
From the comparative studies between theobromine and fluoride each parameter measured indicated that theobromine is superior to fluoride. Recently, a clinical study on the evaluation of the anticaries activity of either theobromine or fluoride-based toothpaste against
In addition, a recent in vitro study indicated that theobromine is an effective cariostatic agent and a safe alternative to fluoride in preventive dental care [36, 49]. The theobromine group is superior compared to the fluoride group in each parameter studied.
In ancient times in the Mayan culture, cocoa was used only among the wealthy and even until recently, in certain countries, cocoa was used to exchange wealth. What is surprising about the skull is that jade was embedded as an inlay into each tooth (Figure 11), which required drilling the enamel surface of the tooth.
Mayan skull was reported to be 1100 years old. Note that Jades were embedded.
However, drilling the precise hole to embed the jade would have been difficult if not impossible. It seems that somehow after placing the jade into each tooth, they must have had the knowledge to fix the jade within the hole.
A simple experiment was conducted by us [26] to determine how ancient Mayan knew the unique role of cocoa 1100 years ago. We have experimented with the knowledge obtained in the past years with theobromine. One can see the study presented in the previous report [26]. Thus, the mystery of how ancient Mayan placed jade in the front teeth was solved. We know now that theobromine which was extracted from cocoa was used to fill the marginal space around the jade and initiate mineralization to fix the jade insert on the teeth. These results are strong evidence that ancient Mayans knew the role of theobromine in cocoa on the mineralization of hard tissue over 1100 years ago.
It is also interesting to note that the strong and unusually heavy-looking mandible of this skull supports the finding that theobromine also plays a role in the growth and development of bones [27]:
In the past, fluoride is the one that was solely used in the dental profession to prevent dental caries and added to most of the toothpaste. In addition, fluoride has been used a high amount of varnish solution [50] and glass-ionomer cement [51].
Fluoride has been described as the same category of alcohol, nicotine, and lead and advised to avoid them during pregnancy [52]. Fluorosis [53, 54] is very common.
Maternal exposure to fluoride during pregnancy was associated with lower IQ scores in children aged from 3 to 4 years [55]. This is the first report describing the possible effects of lower IQ scores of offspring as a result of maternal fluoride intake. Previously, numerous studies associated with fluoride exposures and lower IQ scores of children were already reported. This phenomenon was observed despite the parents’ education and family income in China [56], India [57] and Taiwan [58]. Cognitive alterations in children born from exposed mothers to fluoride could start in early prenatal stages of life and appear later at school age; and likely continue into adulthood [59].
One of the neurodevelopmental disabilities is autism [60] and the decreased secretion of melatonin from the pineal gland alters circadian rhythms and sleep patterns [61].
Another interesting aspect is the relationship between caffeine-containing drinks and fluoride. The higher fluorosis severity was associated with soft drinks and coffee consumption, as most soft drinks contain caffeine [62]. This was explained that the presence of fluoride would remain longer due to the ingestion of caffeine-containing beverages [63].
A 6 oz. container of 1500 ppm fluoride toothpastes contains 254.7 mg of fluoride. A one-year-old (8.14 kg) child ingesting less than one-fifth of the contents of the container would possibly exceed a toxic dose [9]. It has been well known that coronary heart disease and related disorders such as stokes, diabetes and hypertension may originate during fetal development [64]. As further examples, overfeeding of newborns tend to lead to obesity in later adult life. Caffeine exposures during the gestation and lactation periods appeared reduced locomotive activity in the later ages of animals [65]. By the undernourishment in utero, intrauterine programming during this period could contribute to the risk of osteoporotic fractures in later life [66]. “Programming phenomena” in the body of early life [67] is explained as nutritional stress during the critical period of growth that causes permanent or long-term changes in the structure or function of the organ.
Unfortunately, certain areas of the U.S. have an incidence of fluorosis of about 70% [54] to 80% [53] in children. These examples stipulate very high incidences of possible fluoride’s effects on growing children.
Consider each step. Fluorosis of teeth is a result of the effect of fluoride on ameloblasts cells. The other parts of the organs as well could have been affected by this chemical. Excess fluoride exposures have already been known to cause various diseases described above.
The exposure of fluoride must be not only the excess dose of fluoride but also the duration of exposure and timing [52] such as the critical growth period as explained. Fluorosis has been reported to be associated with the lower performance of neuropsychological tests [68]. Developmental enamel defect is twice as frequently with mental retardation [52]. However, there are not many studies that investigated the relationship between fluorosis in teeth and systemic diseases at the same time. For example, is the incidence of fluorosis related to specific diseases? To answer this question, there is a need for close clinical cooperation between dentistry and medicine in future studies of fluoride.
Patients with fluorosis may develop certain diseases in later life. The growth and development of organs or bodies on the surface could have been minor. However, genetic influences could have already occurred, possibly resulting in a slight alteration of structure or function at the cellular levels [67].
Despite little difference in average levels of tooth decay between fluoridated and unfluoridated water of the same country [69], there are still areas in the US where water is fluoridated and water fluoridation may add a small amount of fluoride into the bodies.
In the body, continuous formation and breakdown have been happening throughout the life cycle. If the periods of the formation far exceed breakdown such as the rapid growth period, minor changes of cellular levels might not appear readily. When the period of breakdown is exceeded in the later stages of life, diseases associated with fluoride exposures in early life could become a root cause of disease in later life [13].
We do not know at this time what kind of diseases, if any, might appear in later life by fluoride exposures in early life. However, early nutritional stresses on the developing fetus cause various diseases [64, 65, 66]. The current concept on the number of fluoride exposures in early life and root causes of disease in the future is not an unrealistic hypothesis. If this were proven to be true by future epidemiological studies and/or even one could argue “do we need to wait until such time”. The time might have come now to reexamine the routine use of fluoride in dental practice from a fundamental aspect.
During the study of caffeine on the effects of developing teeth, we have accidentally discovered that one of the xanthine family, theobromine, showed the opposite effects from caffeine on the crystallization of hydroxylapatite (HAP). Theobromine combined with calcium and phosphorus which is called “rennou” was added to accelerate the crystal formation of non-fluoride dentifrice.
Cacao contains theobromine. Chocolate which comes from cacao has been consumed without any ill effects by humans in the past. Cacao has an interesting history. In 1753, Swedish taxonomer Carl Linnaeus named the cacao plant “theo-broma” which translates to “food of gods”. He was a believer in the power of cacao. Ancient Mayans at least 1100 years ago already knew the unique roles of cacao on crystallization and possibly used it to fix jade inside of the enamel. The specific characteristics of theobromine led to the formation of fluoride-free toothpastes.
Theobromine-based dentifrice is revolutionary. This is because space travel in our future, military or even camping where the water supply is most often limited, it is not needed to rinse the mouth with water or just spit after brushing teeth. However, most importantly, even if one swallows it, there are no adverse effects. Theobromine changes the crystallization dynamics of apatite group species, resulting in fewer and larger crystallites. It likely interacts with ions being deposited at the growing HAP crystal surface. Thus, the ratio of surface area versus volume of the crystals is lowered and dissolution is not as rapid or pronounced as in smaller crystals.
In conclusion, non-fluoride-based dentifrice was introduced for the replacement of fluoride-based toothpastes. Further studies of theobromine-based dentifrice have to be examined as a reliable alternative of the safe replacement of fluoride-based dentifrice. This requires vigorous basic and clinical studies by scientists and clinicians.
So far, all the evidence presented shows that the theobromine is superior to that of fluoride and most importantly, the use of theobromine is safe. The current development of non-fluoride dentifrice is most timely. The flow chart in Figure 12 was added to summarize the development of this non-fluoride dentifrice.
The flow chart shows how non-fluoride dentifrice was developed.
Some of the comparative studies between theobromine and fluoride was conducted by Mr. Arman Sadeghpour as part of his Ph.D. dissertation under the strict guidance of Drs Tetsuo Nakamoto, and William B. Simmons Jr. and Mr. Alexander U. Falster. The authors met Mr. Joseph Fuselier who was organizing a biotechnology group interested in the New Orleans area after Hurricane Katrina, August, 2005. He has much-needed experience in the industrial aspects of biotechnology. Mr. R. Jantzen Hubbard and a little later, Ms. Natalie Borchers and Mr. Andrew Lisle Fuselier joined the group to develop and operate the non-fluoride toothpaste, now known to be chocolate toothpastes. The authors appreciate Ms. Julie Schiavo, librarian at LSU Health Sciences Center, for her help with various references.
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Firstly, it is a very effective way of communication between the technical idea and the final solution of the problem in engineering. The process engineering design (design) begins with visualization, i.e., reviewing the problem and possible solutions. Then, sketching leads to the preparation of the initial idea. Next step is preparation of geometric models, which are used for a variety of engineering analysis and, finally, creating detailed drawings and/or 3D models, which are used for the production process. Visualization, sketching, modelling and preparation of technical documentation are ways in which engineers and technologists communicate in creating new products and structures in the modern technical world. Essentially, graphic communication, which is done via engineering drawings and models, is the clean, practical language with defined rules that need to be overcome if one wants to be successful in engineering design (any kind of design). When that language can overcome any approach to solving engineering problems. Ninety‐two percent of the engineering design process is based on the graphic display. The remaining 8% is divided between the mathematical calculations and written and oral communication. Fifty percent of the projecting time a designer spends on are purely visual and graphic activities. We like precision in communication. Engineers use graphical tools, some of which are centuries old and are used day‐to‐day, while others are very new and conditioned by the rapid development of computer technology, such as Computer Aided Design (CAD) systems. 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His later study in cooperation with experts in nephrology and immunology resulted in the designation of the new diagnostic method of UTI, patented in 2017. He is currently working at the Department of Microbiology, Medical University of Gdańsk (GUMed), Poland. Since many years, he is a member of steering committee of Gdańsk branch of Polish Society of Microbiologists, a member of ESCMID. He is also a reviewer and a member of editorial boards of a number of international journals.",institutionString:"Medical University of Gdańsk, Poland",institution:null},editorTwo:{id:"484980",title:"Dr.",name:"Katarzyna",middleName:null,surname:"Garbacz",slug:"katarzyna-garbacz",fullName:"Katarzyna Garbacz",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003St8TAQAZ/Profile_Picture_2022-07-07T09:45:16.jpg",biography:"Katarzyna Maria Garbacz, MD, is an Associate Professor at the Medical University of Gdańsk, Poland and she is head of the Department of Oral Microbiology of the Medical University of Gdańsk. She has published more than 50 scientific publications in peer-reviewed journals. She has been a project leader funded by the National Science Centre of Poland. Prof. Garbacz is a microbiologist working on applied and fundamental questions in microbial epidemiology and pathogenesis. Her research interest is in antibiotic resistance, host-pathogen interaction, and therapeutics development for staphylococcal pathogens, mainly Staphylococcus aureus, which causes hospital-acquired infections. 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Completed the Course Medical Mycology, the Centraalbureau voor Schimmelcultures (CBS), Fungal Biodiversity Centre, Netherlands (2006). International Union of Microbiological Societies (IUMS) Fellow, and International Emerging Infectious Diseases (IEID) Fellow, Centers for Diseases Control and Prevention (CDC), Atlanta, USA. Diploma of Dermatological Scientist, Japanese Society for Investigative Dermatology. Ph.D. of Juntendo University, Japan. Bachelor’s and Master’s degree, Medicine, West China University of Medical Sciences. Chair of Sichuan Medical Association Dermatology Committee. General Secretary of The 19th Annual Meeting of Chinese Society of Dermatology and the Asia Pacific Society for Medical Mycology (2013). In charge of the Annual Medical Mycology Course over 20-years authorized by National Continue Medical Education Committee of China. Member of the board of directors of the Asia-Pacific Society for Medical Mycology (APSMM). Associate editor of Mycopathologia. 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He is an IEEE Senior Member and a member of several other research organizations worldwide. His main research interests are computer vision, intelligent systems, robotics, and image and video processing. He has participated in or coordinated several research projects and received more than thirty-five awards. He has 161 publications to his credit, including books, book chapters, journal articles, and conference papers. He has vast experience as a reviewer of several journals and conferences. As a professor, Dr. Neves has supervised several Ph.D. and master’s students and was involved in more than twenty-five different courses.",institutionString:null,institution:{name:"University of Aveiro",country:{name:"Portugal"}}},{id:"11317",title:"Dr.",name:"Francisco",middleName:null,surname:"Javier Gallegos-Funes",slug:"francisco-javier-gallegos-funes",fullName:"Francisco Javier Gallegos-Funes",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/11317/images/system/11317.png",biography:"Francisco J. Gallegos-Funes received his Ph.D. in Communications and Electronics from the Instituto Politécnico Nacional de México (National Polytechnic Institute of Mexico) in 2003. He is currently an associate professor in the Escuela Superior de Ingeniería Mecánica y Eléctrica (Mechanical and Electrical Engineering Higher School) at the same institute. His areas of scientific interest are signal and image processing, filtering, steganography, segmentation, pattern recognition, biomedical signal processing, sensors, and real-time applications.",institutionString:"Instituto Politécnico Nacional",institution:{name:"Instituto Politécnico Nacional",country:{name:"Mexico"}}},{id:"428449",title:"Dr.",name:"Ronaldo",middleName:null,surname:"Ferreira",slug:"ronaldo-ferreira",fullName:"Ronaldo Ferreira",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/428449/images/21449_n.png",biography:null,institutionString:null,institution:{name:"University of Aveiro",country:{name:"Portugal"}}},{id:"165328",title:"Dr.",name:"Vahid",middleName:null,surname:"Asadpour",slug:"vahid-asadpour",fullName:"Vahid Asadpour",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/165328/images/system/165328.jpg",biography:"Vahid Asadpour, MS, Ph.D., is currently with the Department of Research and Evaluation, Kaiser Permanente Southern California. 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:{name:"Association for Computing Machinery",country:{name:"United States of America"}}},{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:'"Politechnica" University Timişoara',institution:null},{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:{name:"Tecnalia",country:{name:"Spain"}}},{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:"310576",title:"Prof.",name:"Erick Giovani",middleName:null,surname:"Sperandio Nascimento",slug:"erick-giovani-sperandio-nascimento",fullName:"Erick Giovani Sperandio Nascimento",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y00002pDKxDQAW/ProfilePicture%202022-06-20%2019%3A57%3A24.788",biography:"Prof. Erick Sperandio is the Lead Researcher and professor of Artificial Intelligence (AI) at SENAI CIMATEC, Bahia, Brazil, also working with Computational Modeling (CM) and HPC. He holds a PhD in Environmental Engineering in the area of Atmospheric Computational Modeling, a Master in Informatics in the field of Computational Intelligence and Graduated in Computer Science from UFES. He currently coordinates, leads and participates in R&D projects in the areas of AI, computational modeling and supercomputing applied to different areas such as Oil and Gas, Health, Advanced Manufacturing, Renewable Energies and Atmospheric Sciences, advising undergraduate, master's and doctoral students. He is the Lead Researcher at SENAI CIMATEC's Reference Center on Artificial Intelligence. In addition, he is a Certified Instructor and University Ambassador of the NVIDIA Deep Learning Institute (DLI) in the areas of Deep Learning, Computer Vision, Natural Language Processing and Recommender Systems, and Principal Investigator of the NVIDIA/CIMATEC AI Joint Lab, the first in Latin America within the NVIDIA AI Technology Center (NVAITC) worldwide program. He also works as a researcher at the Supercomputing Center for Industrial Innovation (CS2i) and at the SENAI Institute of Innovation for Automation (ISI Automação), both from SENAI CIMATEC. He is a member and vice-coordinator of the Basic Board of Scientific-Technological Advice and Evaluation, in the area of Innovation, of the Foundation for Research Support of the State of Bahia (FAPESB). He serves as Technology Transfer Coordinator and one of the Principal Investigators at the National Applied Research Center in Artificial Intelligence (CPA-IA) of SENAI CIMATEC, focusing on Industry, being one of the six CPA-IA in Brazil approved by MCTI / FAPESP / CGI.br. He also participates as one of the representatives of Brazil in the BRICS Innovation Collaboration Working Group on HPC, ICT and AI. He is the coordinator of the Work Group of the Axis 5 - Workforce and Training - of the Brazilian Strategy for Artificial Intelligence (EBIA), and member of the MCTI/EMBRAPII AI Innovation Network Training Committee. He is the coordinator, by SENAI CIMATEC, of the Artificial Intelligence Reference Network of the State of Bahia (REDE BAH.IA). He leads the working group of experts representing Brazil in the Global Partnership on Artificial Intelligence (GPAI), on the theme \"AI and the Pandemic Response\".",institutionString:null,institution:null},{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. 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