\\n\\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\\n\\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
\\n"}]',published:!0,mainMedia:null},components:[{type:"htmlEditorComponent",content:'IntechOpen is proud to announce that 179 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\nThroughout the years, the list has named a total of 252 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\nReleased this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
\n'}],latestNews:[{slug:"stanford-university-identifies-top-2-scientists-over-1-000-are-intechopen-authors-and-editors-20210122",title:"Stanford University Identifies Top 2% Scientists, Over 1,000 are IntechOpen Authors and Editors"},{slug:"intechopen-authors-included-in-the-highly-cited-researchers-list-for-2020-20210121",title:"IntechOpen Authors Included in the Highly Cited Researchers List for 2020"},{slug:"intechopen-maintains-position-as-the-world-s-largest-oa-book-publisher-20201218",title:"IntechOpen Maintains Position as the World’s Largest OA Book Publisher"},{slug:"all-intechopen-books-available-on-perlego-20201215",title:"All IntechOpen Books Available on Perlego"},{slug:"oiv-awards-recognizes-intechopen-s-editors-20201127",title:"OIV Awards Recognizes IntechOpen's Editors"},{slug:"intechopen-joins-crossref-s-initiative-for-open-abstracts-i4oa-to-boost-the-discovery-of-research-20201005",title:"IntechOpen joins Crossref's Initiative for Open Abstracts (I4OA) to Boost the Discovery of Research"},{slug:"intechopen-hits-milestone-5-000-open-access-books-published-20200908",title:"IntechOpen hits milestone: 5,000 Open Access books published!"},{slug:"intechopen-books-hosted-on-the-mathworks-book-program-20200819",title:"IntechOpen Books Hosted on the MathWorks Book Program"}]},book:{item:{type:"book",id:"7038",leadTitle:null,fullTitle:"Vitamin D Deficiency",title:"Vitamin D Deficiency",subtitle:null,reviewType:"peer-reviewed",abstract:'Vitamin D is the topic for many discussions in the scientific community. Nowadays, a different interpretation of this secosteroid hormone is needed. Today the term "vitamin" may be considered outdated. This compound may be correctly be called a vitamin only when it is administered to humans or animals that suffer from its deficiency. This book attempts to clarify the role of Vitamin D deficiency in many pathological processes in the whole organism. Chapters in this book cover such issues as the earliest clinical and preclinical investigations of the consequences of Vitamin D deficiency for cognitive, cardiovascular, metabolic, immune, and renal disorders.',isbn:"978-1-83880-776-4",printIsbn:"978-1-83880-775-7",pdfIsbn:"978-1-83880-777-1",doi:"10.5772/intechopen.73799",price:119,priceEur:129,priceUsd:155,slug:"vitamin-d-deficiency",numberOfPages:282,isOpenForSubmission:!1,isInWos:1,hash:"ba24f0913341357b0779ff9529c4bbfc",bookSignature:"Julia Fedotova",publishedDate:"February 26th 2020",coverURL:"https://cdn.intechopen.com/books/images_new/7038.jpg",numberOfDownloads:5077,numberOfWosCitations:1,numberOfCrossrefCitations:3,numberOfDimensionsCitations:3,hasAltmetrics:1,numberOfTotalCitations:7,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"May 16th 2019",dateEndSecondStepPublish:"August 26th 2019",dateEndThirdStepPublish:"October 25th 2019",dateEndFourthStepPublish:"November 18th 2019",dateEndFifthStepPublish:"January 17th 2020",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,editors:[{id:"269070",title:"Prof.",name:"Julia",middleName:null,surname:"Fedotova",slug:"julia-fedotova",fullName:"Julia Fedotova",profilePictureURL:"https://mts.intechopen.com/storage/users/269070/images/system/269070.jfif",biography:"Julia O. Fedotova, MD, PhD habil., Doc. Biol. Sci, was born in\nSt. Petersburg (Russia), in 1973. She graduated with her Diploma of Pharmacist, Pharmaceutical Faculty, St. Petersburg State\nChemical-Pharmaceutical Academy in 1996. She received her\nPhD in specialties – experimental and clinical pharmacology and\nphysiology of human and animals in 1999. She attended Medical\nSchool, Department of Pharmacology, University of Catania in\n2002, and the Institute of Physiology, Medical School, University of Pecs. She graduated from the special doctoral course in neuropharmacology at the Department\nof Neuropharmacology in the Institute for Experimental Medicine of the Russian\nAcademy of Medical Sciences and she received her doctor of Biological Sciences\n(Ph.D. habil.) in 2008. She is currently a professor at the ITMO University and the\nleading researcher at the I.P. Pavlov Institute of Physiology. She has more 200 publications (mostly in Russian), 2 patents, and 4 journal articles in collaboration, as\nwell as 6 chapters in journals.\nShe is a head of the project “The studying of Vitamin D3 role in development of\naffective-related disorders in women with climacteric period, the search of ways for\npharmacorrection”, from the highly prestige Russian Scientific Foundation.",institutionString:"ITMO University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"ITMO University",institutionURL:null,country:{name:"Russia"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"379",title:"Vitaminology",slug:"alimentology-vitaminology"}],chapters:[{id:"68649",title:"Vitamin D and Its Deficiency in Saudi Arabia",doi:"10.5772/intechopen.88745",slug:"vitamin-d-and-its-deficiency-in-saudi-arabia",totalDownloads:531,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Fawzi F. 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The use of ultrasound in regional anesthesia has shown the reduction of complications, which makes it mandatory to knowledge and acquire skills in all ultrasound-guided techniques.
\r\n\r\n\tUltrasound-guided regional blocks will be reviewed extensively, as well as intravenous regional anesthesia, thoracic spinal anesthesia. The role of regional anesthesia and analgesia in critically ill patients is of paramount importance. In addition, we will review the current role of regional techniques during the Covid-19 pandemic. Complications and malpractice is another topic that should be reviewed. Regional anesthesia procedures in some specialties such as pediatrics, orthopedics, cancer surgery, neurosurgery, acute and chronic pain will be discussed.
",isbn:"978-1-83969-570-4",printIsbn:"978-1-83969-569-8",pdfIsbn:"978-1-83969-571-1",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,hash:"264f7f37033b4867cace7912287fccaa",bookSignature:"Prof. Víctor M. Whizar-Lugo and Dr. José Ramón Saucillo-Osuna",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/10708.jpg",keywords:"Regional Anesthesia, Ultrasound-Guided Regional Anesthesia, Local Anesthetics, Preventive Analgesia, Peripheral Blocks, Pediatric Regional Anesthesia, Intravenous Regional Anesthesia, Techniques, Complications, Adjuvants in Regional Anesthesia, Opioids, Alfa2 Agonists",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"February 23rd 2021",dateEndSecondStepPublish:"March 23rd 2021",dateEndThirdStepPublish:"May 22nd 2021",dateEndFourthStepPublish:"August 10th 2021",dateEndFifthStepPublish:"October 9th 2021",remainingDaysToSecondStep:"18 days",secondStepPassed:!1,currentStepOfPublishingProcess:2,editedByType:null,kuFlag:!1,biosketch:"Dr. Whizar-Lugo has published more than 100 publications on Anesthesia, Pain, Critical Care, and Internal Medicine. He works as an anesthesiologist at Lotus Med Group and belongs to the Institutos Nacionales de Salud as an associated researcher.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"169249",title:"Prof.",name:"Víctor M.",middleName:null,surname:"Whizar-Lugo",slug:"victor-m.-whizar-lugo",fullName:"Víctor M. Whizar-Lugo",profilePictureURL:"https://mts.intechopen.com/storage/users/169249/images/system/169249.jpg",biography:"Víctor M. Whizar-Lugo graduated from Universidad Nacional Autónoma de México and completed residencies in Internal Medicine at Hospital General de México and Anaesthesiology and Critical Care Medicine at Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán in México City. He also completed a fellowship at the Anesthesia Department, Pain Clinic at University of California, Los Angeles, USA. Currently, Dr. Whizar-Lugo works as anesthesiologist at Lotus Med Group, and belongs to the Institutos Nacionales de Salud as associated researcher. He has published many works on anesthesia, pain, internal medicine, and critical care, edited four books, and given countless conferences in congresses and meetings around the world. He has been a member of various editorial committees for anesthesiology journals, is past chief editor of the journal Anestesia en México, and is currently editor-in-chief of the Journal of Anesthesia and Critical Care. Dr. Whizar-Lugo is the founding director and current president of Anestesiología y Medicina del Dolor (www.anestesiologia-dolor.org), a free online medical education program.",institutionString:"Institutos Nacionales de Salud",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"5",totalChapterViews:"0",totalEditedBooks:"3",institution:null}],coeditorOne:{id:"345887",title:"Dr.",name:"José Ramón",middleName:null,surname:"Saucillo-Osuna",slug:"jose-ramon-saucillo-osuna",fullName:"José Ramón Saucillo-Osuna",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000033rFXmQAM/Profile_Picture_1611740683590",biography:"Graduated from the Facultad de Medicina de la Universidad Autónoma de Guadalajara, he specialized in anesthesiology at the Centro Médico Nacional de Occidente in Guadalajara, México. He is one of the most important pioneers in Mexico in ultrasound-guided regional anesthesia. Dr. Saucillo-Osuna has lectured at multiple national and international congresses and is an adjunct professor at the Federación Mexicana de Colegios de Anestesiología, AC, former president of the Asociación Mexicana de Anestesia Regional, and active member of the Asociación Latinoamericana de Anestesia Regional.",institutionString:"Centro Médico Nacional de Occidente",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:null},coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"16",title:"Medicine",slug:"medicine"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"347258",firstName:"Marica",lastName:"Novakovic",middleName:null,title:"Dr.",imageUrl:"//cdnintech.com/web/frontend/www/assets/author.svg",email:"marica@intechopen.com",biography:null}},relatedBooks:[{type:"book",id:"6550",title:"Cohort Studies in Health Sciences",subtitle:null,isOpenForSubmission:!1,hash:"01df5aba4fff1a84b37a2fdafa809660",slug:"cohort-studies-in-health-sciences",bookSignature:"R. 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Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"878",title:"Phytochemicals",subtitle:"A Global Perspective of Their Role in Nutrition and Health",isOpenForSubmission:!1,hash:"ec77671f63975ef2d16192897deb6835",slug:"phytochemicals-a-global-perspective-of-their-role-in-nutrition-and-health",bookSignature:"Venketeshwer Rao",coverURL:"https://cdn.intechopen.com/books/images_new/878.jpg",editedByType:"Edited by",editors:[{id:"82663",title:"Dr.",name:"Venketeshwer",surname:"Rao",slug:"venketeshwer-rao",fullName:"Venketeshwer Rao"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"4816",title:"Face Recognition",subtitle:null,isOpenForSubmission:!1,hash:"146063b5359146b7718ea86bad47c8eb",slug:"face_recognition",bookSignature:"Kresimir Delac and Mislav Grgic",coverURL:"https://cdn.intechopen.com/books/images_new/4816.jpg",editedByType:"Edited by",editors:[{id:"528",title:"Dr.",name:"Kresimir",surname:"Delac",slug:"kresimir-delac",fullName:"Kresimir Delac"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"49542",title:"Cancer Stem Cells — Perspectives and How to Target Them",doi:"10.5772/61861",slug:"cancer-stem-cells-perspectives-and-how-to-target-them",body:'Cancer remains one of the leading causes of human death, and even though extraordinary efforts and budget have been spent, clinical trials in the eradication or control of cancer progression have generally created disappointing outcomes [1, 2]. Cancer develops originally from normal cells through the accumulation of multiple genetic alterations that ultimately convert to malignant phenotypes [3, 4]. Despite a better understanding of cancer biology and evolutionary genomic characteristics, translating these achievements into feasible and successful clinical outcomes continues to be a problem [5]. One attractive theory, the concept of cancer stem cells (CSCs), being explored recently in cancer research may hold the answer [6]. This chapter summarizes the major characteristics of CSCs and highlights several key approaches used for CSC study, where they could be of help for efficient CSC-targeted therapy.
Cancer biology and genomics have increasingly validated cancer as a complex adaptive system. This landmark perspective was introduced by Peter Nowell in 1976, who viewed cancer development as an evolutionary process driven by stepwise mutations with sequential, subclonal selection at the nuclei acid level, a theory that is similar to Darwinian natural selection [7]. This theory includes several key aspects. (1) Genetic instability: cells possess a battery of mechanisms to preserve their DNA structural integrity. Cellular genetic structural varies (deletions, duplications, and rearrangements) or DNA point mutations can initiate cell biological changes that may lead to tumor formation. Thus, the perturbation of mechanisms controlling genomic stability is responsible for the oncogenic processes [8]. (2) Error-prone repair processes and a genotoxic exposure could result in particular mutational spectra of cancer cells, including cigarette carcinogens, ultraviolet light, and chemotherapeutics. (3) Recurrent, mutation specific traits in cancer can potentially affect clonal selection [9] (Figure 1).
Genetic diversification and clonal dynamics of cancer development.
The microenvironment surrounding a tumor complexes with multiple cellular components that provide an adaptive landscape and necessary elements for natural selection of cancer growth [10]. The interaction between cancer cells and their surroundings is mutually beneficial [11]. Cancer cells can reset the extracellular environment to be specialized niches for further cancer growth and migration. The cancer niche in turn provides external signals for cancer-clone expansion and tumor cell survival and proliferation. The spatial heterogeneity is critical for evolving cancer cell to be a malignant phenotype and beneficial for cell migration and distant invasion [12]. During the process of cancer-clone expansion, migrating cells invade new habitats where they face new selective pressures, thereby increasing the rate of further cancer mutation [13].
The cancer niche is an unclosed system. In addition to the tissue positions and associated etiological environmental exposure of patients, the tissue microecosystem is manipulated by multiple systemic or external factors [14]. Genotoxic exposures, such as ultraviolet light, pathogenic infection, and long-term dietary habits, are able to modulate energy metabolism. They are speculated to be the primary etiological causes of tumor initiation and further evolution of cancer clones [14]. Cancer cell ecosystems can be altered following clinical treatment, in which most cancer cells together with healthy tissues are killed under intensive therapies. However, some specialized niches protect cells from cancer treatment, where variant or therapy-resistant cancer cells emerge [15]. On the way of cancer progression and tumor recurrence after therapy, the primary unit of selection is a specialized cell, known as CSC, which possesses extensive self-renewal potential (Figure 2).
The cancer ecosystem.
Cancer research was previously dominated by the clonal evolution model, also known as a conventional stochastic model, a concept whereby all cells within a tumor have equal potential to propagate and maintain a tumor following stepwise genetic and/or epigenetic changes, but they are hard to identify the tumorigenic subset [7, 16–19]. Recently, accumulated studies suggest cancers as hierarchical organizations, which is the basis of the hierarchical or CSC model [20]. In the CSC model, only a small subset of cancer cells possesses the ability to self-renew, differentiates, and reforms a tumor. CSCs, as “roots of cancer” operating in a hierarchical fashion, are defined by their abilities [20–24] (1) to form new tumors with high efficiency that histologically resembles the original tumors when xenotransplanted into immunodeficient mice, (2) to generate descendant cells possessing unlimited self-renewal (regeneration) potential but uncommitted differentiation options, and (3) to generate large populations of differentiated offspring and progenitor cells that exit the stem cell state and lose the ability to self-renew, thus no longer possessing tumorigenic potential. Such differentiated daughter cells can undergo limited rounds of cell division because they lack the intrinsic clonogenic characteristics that are essential for tumor initiation and long-term progression of the malignancy. The increasingly widespread attraction of the CSC model is due to the fact that it can provide a plausible account for poorly understood clinical phenomena, such as therapy resistance, as CSCs can resume growth and contribute to a new relapse after therapy suspension. It is critical to appreciate that both the stochastic and CSC models share the same conviction that only a small population of cancer cells are capable of maintaining cancer. The main difference is that CSCs within the CSC model are characterized with the help of distinct cellular phenotypes [20].
Critically, the CSC model stands on the basis that CSCs are reliable and stable over time, and their unique traits could not be obtained by differentiated descendants. It is worth to note that the persuading of CSC model has been accompanying with intense debates amongst cancer researchers. As evident from a new concept, the dynamic CSC model suggests that the CSC phenotype is much more fluid than previously predicted and can be regulated by external signals [25, 26]. Thus, not only can CSCs self-renew to create new progeny and differentiate to non-CSCs but the de-differentiation of non-CSCs to CSCs can also occur and thus return to the malignancy growth cycle [26–28]. This latest finding has significant implications for oncology in that future effective anticancer therapeutic strategies should aim at targeting both CSCs and non-CSCs (Figure 3).
Stochastic cancer model versus hierarchical and dynamic CSC models of tumor heterogeneity.
Several challenges the CSC theory is now facing should be addressed before this concept can fetch benefits for the clinically relevant entity [29].
One challenge that is intensely debated is how many CSCs exist within a tumor. Some studies suggested that the frequency of CSCs is less than 1 in every 1000 cells in a tumor, which supports the hierarchical status between CSCs and non-CSCs [30, 31]. However, recent evidences reported that the number of cells that possess intrinsic tumorigenic potential is relatively higher [32, 33]. Hepatocytes possess the potential of self-renewal and unlimited proliferation under certain conditions [34, 35]. It is shown that various colorectal cancers do not follow the same hierarchy as their CSC frequencies vary [36]. More importantly, the prediction of the number of CSCs in a particular tumor type depends on multiple manual factors, including the experimental procedure designed, the choice of cell surface markers, and the types of immunodeficient mice into which the CSCs were injected. Chiba et al. used the technique of side population (SP) analysis to detect the subpopulations that act CSC functions and revealed that SP cells possess abilities of high proliferation and antiapoptosis in both Huh7 and PLC/PRF/5 cells with a percentage of 0.25% and 0.8%, respectively [37]. Kimura et al. determined the frequency of CSCs by analyzing cell surface markers and the percentage of CD133+ cells in Huh7 and PLC/PRF/5 were 2.7% and 23.5%, which is totally different with the number obtained on the base of EpCAM-positive cells, with a proportion of 89.1% and 40.7%, respectively [38]. However, Cao et al. found the CSC frequency of PLC/PRF/5 cells was 8.8% by using the sphere-forming assay [39]. Thus, considering a tumor as a hierarchical malignancy has intrinsic limitations, as a large population of cancer cells cooperate and contribute to tumor growth, which is consistent with the conventional nonhierarchical model of malignancies [40].
The failure of cancer initial treatment is normally explained due to the presence of a subset of resistant cancer cells. CSCs are supposed to be one of such cells; they are logically resistant to traditional chemotherapies owing to their “stem-like” features, including enhanced abilities of DNA damage repair and cellular detoxification capacity via elevated aldehyde dehydrogenase (ALDH) activity, increased expression of enhancement of ATP-binding cassette (ABC) surface transporters, and their nature quiescence [41–43]. CSCs with an up-regulation of antiapoptotic molecules or a high expression of drug efflux pumps respond quite differently when exposed to drugs; they can both survive after cancer treatment [44]. The rapid relapse of the malignancy suggests that the clonogenic core of the cancer was not effectively targeted, and this might be due to the de-differentiation of non-CSCs to CSCs [45]. Even though CSCs are believed to be the most promising candidates for overcoming chemoresistance and tumor recurrence, both CSCs and non-CSCs should be targeted eventually.
The isolation and subsequent assessment of CSCs are clearly a rapidly developing area in which diverse strategies were incorporated for obtaining higher CSC purities. One continual concern after isolation assays is that whether the proposed CSCs separated from the bulk of the tumor can still possess the intrinsic cellular properties. The selected CSCs require the distinct phenotypes that can generate a similar malignancy to the parental tumor when transplanted into immunodeficient mice [46]. The subsequent challenge is to optimize experimental procedures to allow xenotransplantation of viable single suspension cells into animals.
Due to the relevance of cancer development, CSCs are ideal targets for molecular-directed therapies. The limitation is that CSCs are typically present at very low levels. In addition, CSC markers overlap with normal stem cells or between CSCs [47]. These drawbacks indicate that the identification of CSC markers for guiding molecular therapeutics is still in its infancy. Many CSC markers are not strictly CSC antigens since they present on normal cancer cells as well, but they are molecules that support CSCs in their niche.
The characterization of CSCs has led to some experimentally “confirmed” markers or markers involved in the process of targeting or interaction with CSCs. Epithelial cell adhesion molecule (EpCAM) is one of the most highly expressed tumor-associated markers, being found in a broad range of epithelial cancers. EpCAM has been “rediscovered” as a CSC antigen in breast, colon, prostate, and pancreatic cancers [48–50]. In studies on colon cancer tumorigenicity, EpCAMhighCD44+ was considered as a robust marker of more “stem-like” subpopulations. Also, recruiting effector cells to tumors using an anti-EpCAM/anti-CD3 bispecific antibody has been shown to be a promising strategy in the treatment of cancer [51].
In addition to cell-surface markers that are frequently utilized to identify CSCs, the high activity of signal transduction routes can also contribute to CSCs features [52]. The self-renewal capacity of CSCs leads to a long-term clonogenicity mutation, which might be effectively therapeutically targeted. The activation of intracellular signaling pathways associated with the self-renew of CSCs, including Wnt pathway, Hedgehog (Hh) pathway, and Notch pathway, can stimulate a more immature tumor phenotype, facilitate tumor invasion, and promote therapy resistance [53]. The interference of such pathways that promote CSC function might provide an effective therapeutic window for drugs in the war against cancer. These stem cell-associated surface marker proteins and pathways are promising targets for anticancer drug development
The primary challenge to study CSCs is the ability to identify and investigate CSCs in laboratories using both in vitro and in vivo assays. This section addresses the methodologies that have been widely used for isolation and characterization of CSCs.
Limiting dilution assays (LDAs) have been used in a broad variety of biological fields. LDA is an experimental technique that attempts to quantify the frequency of biological particles that perform a particular function within a larger mixed population [54]. The aim of LDA is to obtain highly precise data at the macro level. To achieve this goal, several conditions must be considered [55, 56]. First, the cells should be Poisson distributed. Second, the assay should be designed with maximum information containing both negative and positive cultures. Moreover, the conditions must be performed at the state that the response of a single limiting particle can be detected. Thus, the culture conditions should be uniform in all paralleled groups and wells [56].
The ability to determine the number of CSCs is a critical step for the success of in vivo transplantation. However, there has been little or no attempt to standardize this approach [57]. In all conditions tested, the statistical behavior of the system (Es) and changes in condition over time and statistical noise were the two major contributors to overall uncertainty [57]. However, as expected from statistical principles, Es declines with increasing number of replicates analyzed. Also, increasing the number of replicates beyond 96 is unlikely to provide substantial decreases in error, and fewer wells can be used to obtain results with similar precision. Another requirement that arises in stem cell research is the need to accommodate small numbers of replicates in a statistically consistent and defensible manner. Operator error, mouse-to-mouse error, and other errors appear to play minor roles. These findings establish parameters that contribute to the variability of LDA and provide strategies for the optimization and interpretation of the LDA-based CSC estimates. To this end, extreme limiting dilution analysis (ELDA) has emerged as the preferred method that is based on sound statistical principle and methodologies [58]. ELDA works well when the number of replicates is small.
The CSC concept brings essential predictions of cancer research including susceptibility to chemotherapy, aggressiveness of the disease, and the pace of recurrence that may largely be influenced by the functional properties of CSCs [48, 49, 59–61]. To functionally measure CSC potential, the operational assay of evaluating CSCs has been developed. The creation of an array of genetically modified immunodeficient mice enabling analogous xenograft experiments can be used to determine and quantify cells that obtain tumor-initiating activity in human tumors [48, 49, 59–61]. These xenograft models are considered the “gold standard” in CSC research; they are able to guide the biology and therapeutic responses of human CSCs.
The enumeration of CSCs has been performed using phenotypic markers in in vitro limiting dilution transplantation assays. Some key aspects should be considered [32]: (1) inefficient engraftment in mice may result in underestimation of the actual CSC frequency; (2) phenotypic characterization of CSCs may lead to different rates depending on the antibody combinations used, and the use of specific antibodies may induce immune-mediated clearance of CSCs [48]; (3) the approach of tumor implantation (e.g., intravenously, intrafemorally) critically defines engraftment and affects the export of stem cell frequency [62]; and (4) the kind of mouse strain used as tumor recipient and the degree of mouse immunodeficiency are other factors need to be considered [32]. It is reported that the use of adjuvants/culture supplementary (e.g., Matrigel or growth factors) influences not only the measured frequency of CSCs but their phenotypes as well [30, 32].
In addition to the isolation and identification of CSCs through a set of cell surface markers (such as CD44+/CD24low/lin-/ALDH+, CD44+/CD24low, EpCAM+/CD44+/CD24–, or CD34+/CD38–). The SP discrimination assay is another flow cytometry method used to detect stem cells based on the properties of the Hoechst dye efflux via the ABC transporters [63]. The SP assay has been used to identify stem cell and progenitor populations in various tissues [64, 65]. However, several reports have stated that dye efflux is not a universal property of all stem cells although SPs are much abundant within stem cells [66]. SPs are not just restricted to the stem cell phenotypes as ABC transporters are also expressed by specialized cells in certain organs [67]. The ABC transporters are believed to play a key role in those tissues, protecting the cytotoxic effects of toxins [68]. However, the identification of CSCs has raised interests in the SP assay, and SP subpopulations isolated from some cancers possess capabilities of drug-resistant, self-renewal, and tumorigenicity when transplanted into immunocompromised mice [63]. The SP assay can play an extremely valuable role in the primary isolation and identification of potential stem/progenitor cells, when specific cell surface markers were absent.
The clonal sphere formation assay is another functional method used for the identification of CSCs and their purification from the rest of neighboring cells [69, 70]. This assay begins with reliable single cell suspensions originating from primary tumors or established cancer cell lines. Serial dilutions of the single cancer cell suspensions are seeded on ultra-low attachment substrata in the presence of serum-free media with growth factors [71]. CSCs can grow into 3D nonadherent structures called spheres, while non-CSCs cannot survive in such culture conditions. The results of the assay may become more reliable if the spheres are serially passaged. The self-renewal capacity of sphere-generating cells can be estimated by evaluating the sphere formation frequency through LDA and measuring sphere size [72]. The sphere formation assay has been used to identify adult stem cells or CSCs from a number of tissues, including mammary gland, brain, skin, and human melanoma [73–76].
CSCs can be isolated by the enzymatic activities (ALDH activity) [77, 78]. The measurement of ALDH activity by ALDEFLUOR staining is useful to screen tumor cells for resistance to alkylating agents and to identify heterogeneity within tumor cells [79]. The ALDH+ population is consistent with CSC characteristics, generating tumors that recapitulate the phenotypic heterogeneity of the initial tumor. The measurement of ALDH populations revealed that the ALDH+ cells were capable of self-renewing into both ALDH+ and ALDH− cells [80]. A recent study in melanoma described both ALDH+ and ALDH− cells derived from patient biopsies (100 or 2000 cells, respectively) were able to efficiently form tumors. It is also reported that ALDH cells alone may not be sufficient for CSC selection [32]. Despite this, studies in breast cancer combining other CSC surface markers with Aldefluor have improved tumorigenic enrichment and this combination may prove to be a better strategy for enrichment of CSCs [32].
The slow-cycling population assay can be used to distinguish CSCs from progenitor cells, which determines the incorporation of labeled precursor of nucleotides for cellular DNA synthesis [81]. The slow-cycling cells, such as CSCs, maintaining sufficient labels allow their detection by the anti-BrdU antibody staining or radioactive label [82]. Some technical issues impede the accuracy of BrdU detection: (1) it is hard to demonstrate that cells have a similar cycling in vitro and in vivo because of the destructive nature of the BrdU detection procedure, (2) it is not expected that all the stem cells can be equally labeled because the BrdU incorporation occurs only during the S phase of cell cycle, and (3) the label retention depends on the length of the cell cycle, while the later status appears to alter as the organ matures [83]. Thus, quantification of stem cells through this assay requires further confirmation through other methods.
The lineage labeling assay was initially developed for understanding and tracing the biological developments of a cell, including the identification of cell origin, measuring lineage relationships, and determination of division patterns [84]. In this assay, cells are labeled (usually with a fluorescent dye or tag), followed by tracing in vitro and in vivo. There are several inherent limitations with this technique: (1) the experimental procedure can damage cells or some cells may have weak and/or transient expression of markers and unrestricted clonality [84] and (2) with whole-mount labeling, it is not possible to identify spatial relationships between stem cells and its transit amplifying progeny [85]. In this case, targeted cells are noninvasively labeled in their native environment, and the development of a progenitor cell and a composition of their lineages can be followed. It remains unclear whether the combination of these techniques can be extended to identify CSCs and metastatic initiating stem/progenitor cells.
While there has been a hot debate in recent years as to whether the CSC theory is correct, very recent lineage tracing studies have provided proof that a relatively small number of cells are capable of generating and maintaining a tumor. These studies used fluorescently labeled tumor cells and showed that the quiescent cells remained after further in vivo passages [86]. Furthermore, following treatment, these quiescent cells started to proliferate and generate proliferative progenitor cells that were capable of maintaining a tumor [87–89]. By eliminating these quiescent cells, tumor growth was impaired. These results link back to the theory that leaving a small population of CSCs after the conventional treatment lead to a recurrence of the tumor. Therefore, it is necessary to eliminate both populations of cells within a tumor to produce effective anticancer therapeutic strategies [90].
Whole genome sequencing has made tremendous contributions to cancer research, which enables researchers to discover and understand the rules of cancer development at the nucleic acid level [91, 92]. However, the genome instability and genetic variants limit to demonstrate cancer progression. It was speculated that there exist a senior layer of information, besides genome sequence for regulating differential gene expressions and thus determining cancer evolving. This concept was early prospected by Conrad Hal Waddington in 1942 and subsequently described as “epigenetic control system” by Nanney in 1958 [93, 94]. Epigenetics primarily refers to the study of chromosome variations that modulate gene transcription without alterations in the DNA sequences [95, 96]. Epigenome contains genetic information, not as stable as genome, representing the cellular epigenetic state varying with influence from external factors. Mechanisms produce such changes mainly include DNA methylation, histone modifications, nucleosome positioning, and chromatin remodeling [96]. These epigenetic regulation mechanisms are reported to be closely related with the gaining of stem cell-specific properties, whereby contributing to tumor inheterogeneous [97, 98]. Epigenetic alterations would offer survival benefits in CSC subpopulation which promotes the genetic expression to the self-renewal state, resulting in tumor initiation and further progression [99, 100]. The relevance of the DNA methylation and histone modifications in CSC regulation, subsequently with advancing tumor growth, were recently illustrated in various cancer models [97, 99, 101].
Next-generation sequencing (NGS), also known as high-throughput sequencing, has revolutionized the study of genomics and opened a new chapter of the epigenome research of cancer and stem cell [102, 103]. Four mainly NGS-based approaches have been developed to identify epigenome research, including methylated DNA immunoprecipitation sequencing (MeDIP-Seq), whole genome bisulfite sequencing (WGBS), reduced representation bisulfite sequencing (RRBS), and chromatin immunoprecipitation sequencing (ChIP-Seq). Compared with the previous approach, the innovative advantages of NGS have significantly accelerated the sequence of DNA and RNA and promoted the scientific sightings in CSC epigenome research.
Current failure of cancer treatment is normally due to the existence and functionalities of CSCs, which possess more chemoresistance than their non-CSC counterparts, to conventional treatments. Recently, multiple strategies have been developed for targeting and eradicating CSCs while sparing healthy tissues, thereby minimizing the patients to face therapy risks.
Since CSCs are attractive targets for anticancer treatment, the CSC-correlated cell surface proteins have been monitored extensively for identification, probable isolation and monitoring the variation of leukemic and solid CSCs in preclinical and clinical settings [104]. Studies using certain ligands or antibodies against CSC surface maker proteins, including EpCAM, CD47, CD44, CD90, CD133, IL-3R, immunoglobulin mucin TIM-3, ALDH+, and others, have advanced the therapeutic efficacy [105–108]. Limitations, such as the expression of such cell surface makers, may vary in different stages of cancer development; only a small subpopulation of CSCs standing in the summit among bunk of cancer cells, as well as overlapping of CSC-associated marker proteins with normal stem cells, impede the effectively targeting of CSCs [47]. For bench assays, it is recommended to employ functional studies such as in vivo LDA upon xenotransplantation to ascertain CSCs, rather than solely be dependent on the incidence of a single or a combination of multiple CSC markers. However, in case of in vivo CSC-based therapy, the CSC surface marker proteins present one of the very few feasible options for targeting CSCs in animals and patients, given the practical and ethical restrictions related with lineage tracing and xenotransplantation.
Accumulated attractions have been grasped in the development of aptamers (also known as chemical antibodies) and monoclonal antibodies for targeting CSCs via targeting surface marker proteins. Shigdar et al. have isolated two RNA aptamers using SELEX for targeting CSC surface markers, EpCAM, and CD133 [109, 110]. These CSC-targeting aptamers internalize into target cells through receptor-mediated endocytosis, which is capable of circumventing ATP-binding cassette transporters that function multiple drug resistance in CSCs [26]. In addition, this newly developed EpCAM RNA aptamer is more sensitive than counterpart antibodies for detecting the surface EpCAM proteins in formalin-fixed paraffin-embedded primary breast cancers, with no nonspecific staining or cross-reactivity with non-EpCAM-expression tissues [111]. This shows the potential of aptamers for specific targeting of cancers but with minimized side effects observation. To optimize promising approaches by targeting cell surface markers might be one of the answers for tracing CSCs and eventually eradiating CSCs, thereby preventing patients from suffering from cancer attacking.
The failure of cancer chemotherapy mainly results from increased efflux of anticancer drugs from cancer cells, resulting in the impairment of drug cellular entrance and consequent reduction of chemotherapeutic sensitivity [112]. A considerable root of multidrug resistance (MDR) involves the augmented expression of the ABC transporter superfamily, many of these transmembrane proteins are responsible for effluxion of various xenobiotics (including anticancer agents) from cancer intracellular membranes [112, 113]. The well-characterized MDR transporters consist with ABCB1 (MDR1 or P-glycoprotein), ABCC1 (MRP1), and ABCG2 (BCRP or MXR) [112, 114–116]. Although projects focusing on understanding the mechanisms of these ABC transporters behind chemotherapy failure have been broadly developed, clinical outcomes in these fields have been generally unsatisfactory [113, 117]. The recurrence of primary and metastatic cites can occur following the escaped chemotherapy, in which CSCs, possessing enhanced efflux of therapeutic agents through ABC transporters, have been proven to provide major contributions [114, 118, 119].
Due to the correlation of ABC transporters with CSC phenotypes, one approach circumventing CSC-based chemoresistance involves the use of specific molecular inhibitors against certain functions of individual MDR transporters [114]. Verapamil, an agent targeting general ABC transporters, has been moved to the clinical trials, but the further study was suspended due to the dose-limiting toxicity [120]. Thus, the more specific molecules targeting individual MDR transporters are required [121]. A considerable body of evidence has shown positive outcomes of overcoming CSC drug resistance by developing physical conjugation or chemical nanoparticle-functionalized drug delivery of anticancer agents. Chou et al. indicated that the conjugation of doxorubicin (DOX) into nanodiamonds reduced efflux of DOX in MDR1 overexpressing cancer cells and facilitated the anticancer efficacy in DOX-resistant cancer models [122]. While CSC-related chemoresistance and tumor relapse arise mainly due to the increased expression of ABC transporters, the therapeutic strategies developed for specifically disturbing actions of ABC transporter proteins would be an attractive potential for targeting and eradicating CSCs.
The CSC concept is still an evolving model moving forward. Recent lineage tracing strategy has proven the existence and functions of CSCs in progression of solid tumors. CSCs with intrinsic activities of chemoresistance are the culprit in tumor recurrence and the root of treatment failures. Challenges remain on how to efficiently identify and target CSCs in vivo and monitor CSCs posttreatment. Cancer biology has proofed that traditional clonal evolution, and CSC models are not exclusive but co-exist with each other in tumorigenesis. Therefore, future elucidation of molecular mechanisms underlying CSC biology should open a new window of efficacious novel therapy strategies that eliminate both CSCs and non-CSCs.
According to Tannahill [1], health promotion is an umbrella term covering overlapping fields of health education, prevention and attempts to protect public health through social engineering, legislations, fiscal measures and institutional policies which entail the combination of the best in terms of both theory and practice from a wide range of expert groups (educationists, behavioral scientists, medical practitioners) and non-professionals including the communities involved. For him, health promotion stems largely from a new focus for health services that recognize some basic facts: many contemporary health problems are preventable or avoidable through lifestyle change; modern technology is a bundle of mixed blessings bringing both benefits and risks to health; medical technology is at the phase of diminishing returns (losing efficacy and connection to ordinary people); such non-medical factors as better nutrition, improved living conditions and public health measures have contributed to both health and longevity even more than medical measures; that doctors can cause as well as cure disease; and increasing public desire to attain better or improved quality of life and at the same time demystifying and demedicalising the attainment (achievement) of good health [1].
For the World Health Organization (WHO), health promotion is essentially about engendering a context in which the health and well-being of whole populations or groups are owned mainly by the people concerned, i.e., enabling citizens of local communities to achieve political control and determination of their health [2, 3]. Therefore, health promotion goes beyond mere healthcare but puts health on the policymaking agenda in all sectors and at all levels, directing policymakers to be cognisant or conscious of the health consequences of their decisions and accept responsibilities for health.
Health promotion can be seen as the whole process of enabling or empowering people to increase control over and improve their overall health. It focuses on creating awareness of health issues, engendering behaviour modification consistent with prevention and attitudes to ill health and motivating increased usage of available health facilities. In the pursuit of good health (physical, mental and social well-being), individuals and groups through health promotion are enabled to identify and realize aspirations, satisfy needs and change or cope with the environment in manners consistent with complete good health.
Health promotion is expected to contribute to programme impact by enabling prevention of disease, reduction of the risk factors or behaviors associated with given diseases, promoting and fostering lifestyles and conditions that are conducive to good health and enabling increasing use of available health facilities. Therefore, health promotion creates both the awareness and conscientisation that leads to disease prevention, control of health situations and usage of health services and facilities. It implies individual and collective control and participation in health focusing on behavioral change, socio-economic lifestyles and the physical environment.
Without doubt the WHO’s Ottawa Charter definition of health promotion is very comprehensive and encompasses the core values and guiding objectives of health promotions [3]. It summarily sees health promotion as the process of enabling people to increase control over and improve their health. In line with the above definition, Macdonald and Davies [4] contend that it calls attention to the critical role of the concepts of process and control as the real essence of health promotion. For them, “the key concepts in this definition are ‘process’ and ‘control’, and therefore effectiveness and quality assurance in health promotion must focus on enablement and empowerment. If the activity under consideration is not enabling and empowering it is not health promotion” [4], p. 6.
As the burgeoning literature on health promotion over the years indicate it is a community-driven (inspired), multifaceted and multidisciplinary area of concern that also involves critical sociopolitical, economic and environmental elements and dynamics (see [4, 5, 6, 7, 8, 9, 10]).
It is important to also understand that even though one can make a distinction between public health and health promotion, in reality both are interconnected and hardly practically separable. In other words, public health is built on health promotion and health promotion is imperative for public health delivery. As has been argued, public health “is synonymous with health promotion in that it aims to implement co-ordinated community action to produce a healthier society” [11], p. 315.
There is no gainsaying the fact that health promotion nowadays has an overwhelming sociopolitical component that is really definitive. In fact, as has been posited, “health promotion activities are by their nature inherently politically based and driven, thus making it impossible to divorce them from the political arena” [11], p. 314. Health promotion becomes a dynamic area of interface between public policy institutions (the state and its agencies), the public (community/people) and the professionals (ranging from the media professionals, public health advocates, social workers to medical practitioners).
The chapter depended on the desk review of extant literature and documents for its information. The main exclusionary criteria in this regard were materials not related to health promotion and materials published before 1984, which were considered extreme-dated. The inclusive criteria were determined by such concepts as public health, public health in Africa, health promotion, health education and awareness and theories and models in health promotion. Such prominent Internet information sites like the WHO, American Public Health Association (APHA), Health Resources and Services Administration (HRSA) and the Universitats Bibliothek Leipzig (UBL) Online Resources were utilized in gathering materials for the chapter.
There is no gainsaying the fact that effective and result-oriented health promotion practice depends on sound theory [12]. In other words, theory becomes very informative of health promotion practice and activities. In recognition of the above, one would examine briefly the main theories that have implicated health promotion globally. It is important, however, to state here that the choice of a theory or model to guide health promotion should be determined largely by the specific nature of the health issue being addressed, the community or population in view and the sociopolitical context in question. This is because theories and models are simply used in practice in order to plan health programmes, explain and understand health behaviour as well as underpin the identification of appropriate intervention and implement such intervention in ways that are both effective and sustainable.
Despite a plethora of theories and models utilized in health promotion, I will only focus on five of the most popular and commonly used. These are ecological models of health promotion, the Health Belief Model (HBM), Stages of Change Model or the Trans-theoretical Model, Theory of Reasoned Action or Planned Behaviour and the Social Cognitive Theory.
As the name implies, these models focus on the interaction of people with their physical and sociocultural environments. The approach thus recognizes that there are multiple levels of influence on health and health behaviour especially the health seeking behaviour and choices that people make. The ecological models are anchored on five overriding influences which determine and guide health behaviour and response to health issues [13, 14, 15, 16]. These influences are intrapersonal or individual factors (these impact on individual behaviour, e.g., beliefs, knowledge, attitude, etc.); interpersonal factors (these are produced through living with and interacting with other people, e.g., family, friends and social groups/networks; these other people can function as both the source of solidarity and support as well as sources of barriers and constraints to health-promoting behaviour of the individual, e.g., dwelling among chronic smokers or having intense interaction with them may expose one to the dangers of either smoking or the influence of second-hand smoke); community factors (these make reference to social norms that are shared by groups or communities, and such norms whether formal or informal can influence health behaviour and health seeking behaviour of the individual and group members, e.g., relationship between institutions, groups and organizations); institutional factors (policies, rules, regulations and institutional structures that may constrain or even promote healthy behaviour in a given society, e.g., the workplace and voluntary organizations to which the individual belongs are prime examples); public policy factors (policies at different level of governance that regulate, structure or support actions and practices targeted at health outcomes like disease prevention policies and structures enabling early detection, control or response and management of health crisis in the society; these stem from the position of the government and are critical in achieving the goals of public health delivery) (Figure 1).
Ecological models of health promotion (simplified).
As the above pyramid, suggests the individual, interpersonal and community factors are at the base. These factors therefore exert more influence and pressure over the individual’s health behaviour than the institutional and public policy factors as these are more important. In other words, the institutional and public policy factors are literally far from the individual and do not exert as much pressure on his behaviour as those factors that are very close to him both spatially and otherwise. In an age of increasing pessimism in government, people are much driven by interpersonal and community factors than what comes from a typical further off entity.
Given the above, it is obvious that the ecological approach is very pertinent in the understanding of the range of factors that influence people’s health. Its main strength is that it can provide what is called a complete perspective on factors that affect health behaviour and response to health issues especially the role of social and cultural factors or normative patterns on health in the society. It is perhaps very well suited to health intervention and practice in developing societies with an overbearing influence of sociocultural factors on behaviour, attitudes and practice of the people.
This is a theoretical model that has been found useful in guiding both health promotion and strategies for disease prevention. As the name suggests, it focuses on individual beliefs about specific health conditions which predict or direct individual health behaviour [17, 18]. The specific components of this belief that influence health behaviour include perceived susceptibility to the disease; perceived severity of the disease in question; perceived benefits of action (positive benefits of such action) as well as cues to action (awareness of factors that engender action); self-efficacy (belief that action would lead to success); and perceived barriers or obstacles to action (especially if such obstacles are seen as daunting or insurmountable or otherwise).
In the utilization of the HBM in health promotion, there are five main action-related segments that would help in identifying key decision-making points and thus facilitate the utilization of knowledge in guiding health intervention. These are: collection of information (through needs assessments; rapid rural appraisal, etc. in order to determine those at risk of the disease or affliction and specify which population or component of the population to be targeted in the intervention); conveying in unambiguous and clear terms the likely consequences of the health issue in question and its associated risk behaviors in order to facilitate a clear apprehension of its severity; communication (getting information to the target population on the recommended steps to take and the perceived or likely benefits of the recommended action); provision of needed assistance (help the people in both the identification of and reduction of barriers or constraints to action); and demonstration (actions and activities that enable skill development and support aimed at enhancing self-efficacy and increased chances of successful behaviour modification targeted at the health issue in question) (Figure 2).
Health belief model (HBM).
In Africa, the HBM has been very useful in understanding people’s response and behaviour to HIV/AIDS and other chronic diseases. Being a society very flushed with beliefs, the degree of responsiveness to a health situation is often the direct product of a set of beliefs held by the individual and/or by his immediate community.
This model is focused on examining and explaining the individual’s readiness to change his behaviour and sees such change as occurring or happening in successive stages. It therefore adopts a quasi-evolutionary framing of behaviour change in which behaviour change, sustenance and termination are encompassed in six stages. These stages are pre-contemplation (existence of no intention to take any action by the individual); contemplation (thinking about taking action and ruminating on plans to do this soon); preparation (signifies intention to take action and includes the possibility that some steps or preliminary steps to action have been taken already); action (discernible change in behaviour for a brief period of time); maintenance (sustenance of the action taken; behaviour change that is maintained in the long run or long-term behaviour change); and termination (the expressed and discernible desire never to return to prior negative behaviour by the individual concerned).
The above stages are very important in planning behaviour change or modification and recognize that behaviour change is both gradual and takes time. What is needed from the health promoter is that at each of these stages specific interventions or programmes are devised to help the individual progress to the next stage. Also, the recognition that the model may in reality be cyclical rather than lineal, i.e., individuals may progress to the next stage or even regress to previous or lower stages, is important in planning health promotion interventions utilizing this model. It also calls attention to understanding that there are individual differences in the adoption of change, i.e., some people may be swift in behaviour modification, while others may take longer time; but each needs support in order to pull through.
The main contention of this theory is that an individual’s health behaviour is usually determined by his intention to exhibit or display a given behaviour. Therefore, the intention to exhibit a given behaviour (or behaviour intention) is predicated upon or predicted by two main factors, viz. personal attitude to the behaviour in question and subjective or personal norms (an individual’s social and environmental context and the perception the individual has over that behaviour) related to that behaviour.
The basic assumption here is that both positive attitudes and positive subjective norms will generate greater perceived control of behaviour and increase the chances of intentions towards changes in behaviour. The theory generally provides information that can be used in predicting people’s health behaviour and thus in planning and driving through health interventions. It anchors in recognizing the predictors of behaviour-oriented action and the need for supportive social and environmental contexts that facilitate and sustain desirable health behaviour.
This theory combines both the cognition of the individual and the social context of the individual in offering explanation and understanding of health behaviour and response. It seeks to describe the influence of the experience of the individual, his perception of the actions of other people near him and the factors in the person’s immediate environment on health behaviour of the individual. It moves from this general perspective to provide opportunities for social support (defined as conducive to healthy behaviour) and reinforcements that generate behaviour change or modification. In this sense, the SCT depends on the idea of reciprocal determinism which denotes the continuing or uninterrupted interaction among the person’s characteristics, his behaviour and the social context or environment in which the behaviour takes place.
However, the best way to appreciate the SCT is to examine the main components the theory isolates as related to behaviour change at the individual level. These are self-efficacy (belief in one’s ability to control and execute behaviour within a given context); behaviour capability (thorough comprehension of behaviour and the ability to exhibit or perform it); expectations (outcomes or outputs of the behaviour change in question); expectancies (the assignation of value to the above outcome of behaviour and which is important in sustaining the behaviour); self- control (the regulation and monitoring of behaviour of the individual); observational learning (the act of watching others performing the desired behaviour and the outcomes therein as well as modeling that behaviour in question); and reinforcements (incentives and rewards seen as eliciting, encouraging and sustaining behaviour change in the individual) [19].
The three components as the above diagram shows reinforce each other and in the process condition and determine behaviour of the individual even in the context of health as well as choices made therein (Figure 3). The SCT is very pertinent in contexts where desirable health outcomes can be achieved by behaviour modification or change. For instance, certain chronic diseases or health conditions can be tackled through healthy lifestyles and dieting that reduce risk factors and chances of individuals succumbing to such conditions. Therefore, the theory can help frame intervention programmes in this area that focus on changing people’s behaviour and in the process achieve desirable health outcomes.
Illustration of the social cognitive theory (SCT).
Theories and perspectives or models as already indicated are critical in providing explanations of a problem or issue (broadening our understanding and perspective as it were) and also very important in the effort to tackle a given problem or issue in the society especially by way of developing and implementing programmes and interventions. Perhaps, the above underscores why some scholars [20, 21, 22] would highlight the difference between the so-called theories of the problem and theories of action, meaning that while the former aids our apprehension of a given issue or social reality, the latter is important in terms of taking actions or evolving activities to tackle the issue in question.
Health promotion generally implicates a huge element of politics and power dynamics in the sense that only political will and cognition can build discernible changes in health. Lobbying and advocacy are critical tools of health promotion and function within the political arena. The sociopolitical contexts and influences are especially recognizable in the public health sector in the developing world where political will and doggedness are often necessary to drive through even the most salutary change or innovation in the health sector. Also, political forces are equally dominant in the provision of crucial health infrastructure and facilities as well as the reasonable funding demanded by any effective public health system. As Harrison opines health promotion “requires concerted, sophisticated and integrated political action to bring about change and requires professionals concerned with public health to engage with the politics of systems and organizations” [5], 165.
Therefore, health promotion seeks to empower and transform communities by getting them involved in activities that influence public health especially through agenda setting, lobbying and advocacy, consciousness raising and social education [11, 22]. All these are accomplished on terms that are either defined or strictly affected by the socio-economic realities of the people themselves. By its emphasis on the community, health promotion has a heavy sociological frame that prioritizes the values of society as well as mobilization and solidarity in the quest for good and sustainable health. It thus makes assumption that individual members of the society would give equal weight to their own health and the health of their neighbors. In other words, it is often anchored on the uncanny assumption that the health of the individual member of a given society is intertwined with the health of the community as a collective. This means the reference point of health promotion is that one’s health is as good as the health of the members of the community or society as a whole, i.e., common health destiny. Therefore, such things as community empowerment, community competence and overwhelming sense of community are all apprehended as contributing to the health of the communities [23].
Traditionally there are five approaches utilized in health promotion. These are medical (the focus here is to make people free from medically defined diseases and afflictions; it is mainly anchored on prevention strategies and the role of the medical practitioner or expert in ensuring that the patients comply with recommendations); behavioural change (behaviour modification approach that recognizes that people’s behaviour and lifestyles can be changed in order to enable them attain good health, i.e., facilitate adoption of healthy lifestyle); educational (provision of information and knowledge that enable understanding of health issues and build awareness for informed decision-making and choice among people); client-centred (in this situation health practitioners work with clients in order to identify what they know about a given disease and take appropriate action; emphasis on perceiving the client as equal and building the clients self-empowerment that enable them make good choices and control their health outcomes); and societal change (the focus here is on the society or community rather than the individual and seeks to change or modify both the physical and social environments in order to make them consistent with or conducive to good health).
The conventional health promotion methods (modes of operationalizing health promotion and achieving its goals) include health education (the conscious and systematic effort at providing education or knowledge to people on particular and general aspects of health; it is about enabling people through proper and right knowledge on what to do and how to do it; it is empowering and improving people’s capacity to act with regard to their health issues and conditions), information, communication (the above three are often captured in the popular acronym IEC), social mobilization, mediation, community theater and advocacy and lobbying. However, while these methods are okay in differing contexts, a decision on the specific medium to use should be guided by both environment (community conditions) and the nature of the health issue involved. The use of more than one method in any given case is highly recommended especially in Africa where there are broad inequalities in access to social goods and the media. The increasing use of social media especially among young Africans calls attention to their deployment equally in core health promotion. Social media platforms like WhatsApp and blogs can be very potent in this regard.
There is an undeniable need to give high priority to health promotion research in Africa. Such research should aim at enabling a realistic and focused achievement of the goals of health promotion. Broadly, health promotion aims inter alia at:
The prevention of communicable and non-communicable diseases
The reduction of risk factors associated with diseases
The fostering of lifestyles and conditions in the general population that are consistent with overall well-being or good health
The effective/maximal utilization of existing health services and stimulating demand for others where/when necessary
According to the WHO [24] Health Promotion Strategy for the African Region, the contributions of health promotion to the achievement of health objectives include increasing individual knowledge and skills especially through IEC; strengthening community action through the use of social mobilization; enabling the emergence of environments supportive and protective of health by making optimal use of mediation and negotiation; enabling the development of public policies, legislation and fiscal controls which enhance and support health and overall development using advocacy and lobbying; and making prevention and consumer needs the core focus of health services delivery. All these can be positively influenced by research and studies which evaluate the effectiveness of what has been done as well as explore new strategies suitable to the socio-environmental context in question.
However, while research is very critical to achieving the goals of health promotion, it should be concise and focus essentially on the priority health programmes which have been identified by the WHO for the continent. Some of such programmes include the Global Fund for Malaria, HIV/AIDS and Tuberculosis, Immunization, Mental Health, the Tobacco Free Initiative and Reproductive Health as well as the fight against recurrent scourge of Ebola, etc. Such research should focus on identifying effective health promotion approaches and communication media to embody and convey the outcomes to communities through community participation; the extent or effectiveness of these means and seeking to still improve overall programme effectiveness and sustainability. Therefore, health promotion research should focus on ascertaining goals/outcomes of health promotion (to guide policy), provide reliable conditions associated with these outcomes or goals, precisely define the changes intended and delineate reliable mechanisms and indicators of M and E of health promotion strategies in specific country/community contexts.
The importance of research is essentially derived from the fact that it calls attention to the need for verification and evidence-based activities in health promotion. These are without doubt the ways of knowing if real empowerment and enabling has been achieved in the process. Thus,
Health promotion is about enabling people to improve their health; and secondly, evidence relevant to health promotion should bear directly on factors that support or prevent enablement and empowerment (determinants of health) activities that support enablement and empowerment (health promotion) and assessing whether these activities have been successful (evaluation of health promotion). [25], p. 357
The above clearly suggest that health promotion should be anchored on evidence or should rest on experience and reality regarding what works or what is possible and effective in any context. In this manner, “evidence-based health promotion involves explicit application of quality research evidence when making decisions” [26], p. 126. Research is even more foundational in health promotion since health promotion efforts need to be anchored on agreed definitions and values of health promotion. As Seedhouse contends the failure to be explicit about definitions and values generates conceptual confusion in research as well as sloppy practice [27].
The evaluation of health promotion which should be a core research activity may be based on the three main forms of evidence/knowledge associated with health promotion [28]: instrumental (controlling social and physical environments), interactive (understanding of diseases/health issues; lived experiences; solidarity) and critical (reflection and action; raising consciousness regarding causes and means of overcoming them). These three evidences are anchored on the given scientific/philosophical traditions, viz. instrumental (positivism, quantitative, experimental, scientific knowledge), interactive (constructivist, naturalistic, ethnographic/qualitative knowledge) and critical (materialist, structural and feminist theory).
There is also an overwhelming need for health promotion research to be aware of the difference between health promotion outcomes and health outcomes. Health outcomes crudely imply the consequences or benefits of healthcare delivery (e.g., reduction of mortality rate) related to a disease (which may be the case in spite of an increment in number of those affected by the disease). But health promotion outcomes signify the form of control and attitudinal re-orientation groups and individuals adopt in facing a given disease which may impact on the number of people affected by the disease and improve attitudes and behaviour towards those affected by the disease. Health promotion outcomes can be seen directly through community members’ perception and interpretations of a given health issue which makes the achievement of control possible.
Health promotion research should utilize both quantitative and qualitative methods. In addition to complementing quantitative methods in health promotion research, qualitative research enables the researcher reach the heart of issues in engagement with community members. In Africa, where a good percentage of the population are still domiciled in the rural areas, qualitative approach offers the possibility of profound insights into the why and how of health behaviors which may not be possible or easily achieved with the quantitative or traditional biomedical approaches. As a result, “the increasing popularity of qualitative methods is as a result of perceived failure of traditional methods to provide insights into the determinants – both structural and personal – of whether people pursue or do not pursue health-promoting actions” [25], p. 359.
It is important to recognize that in spite of apparent good intentions, health promotion can actually generate negative or counterproductive effects when not well managed. Thus, “negative outcomes occur where professionally paternalistic and disempowering health policy decisions force health-related outcomes that are irrelevant to sustained community development and are not based on or resourced according to the social reality of the community” [11], p. 315. The above sentiments caution one against embarking on health promotion activities and initiatives that are not anchored on the health realities of the community concerned. Often, overzealous health professionals unintentionally betray the health priorities of communities by assuming knowledge of all there is to know about the health situations and needs of the people.
Perhaps a critical shortfall of some health promotion activities and processes is the adoption of what can be termed the pathogenic paradigm which over-relies on risk instead of emphasizing protective mechanisms. This essentially entails a focus on the failure of communities and individuals to avoid disease or their apparent susceptibility to diseases instead of seeking to unleash their potential and capacity to engender and sustain good health and development. It is an approach that relies too much on health practitioners and experts and hardly gives voice to the people and their own knowledge cum realities.
Generally health promotion in Africa suffers from some of the debilitating challenges which confront the practice of health promotion broadly in many countries in the continent. These challenges, among others, include:
Poor definition and rudimentary elaboration of expected health outcomes
Ambiguous elaboration of factors and conditions to be targeted in health promotions
Ambiguity of health promotion policies and guidelines
Lack of capacity (or inadequate capacity) to develop, implement and evaluate health promotion programmes
A general context of inadequate investment in health promotion
Underdeveloped sectoral collaboration
Low political will and commitment to health promotion programmes as well as institutional corruption and resource mismanagement
The above challenges have implications for research in health promotions in the continent. There is no gainsaying the need for health promotion to be evidence based because essentially it is the only way to make it responsive to the health needs and interests of the people.
Health promotion combines varied but complementary indicators like legislation, health finance including fiscal measures and taxation, gender inclusiveness, mapping of priorities and organizational change. In spite of their differences, these issues are in reality intertwined or systematically connected in the sense that, for the public health system to function well and optimally, there should be a synergy between these indicators. Briefly:
This revolves around having the political will to make and drive through policies and laws that improve and sustain healthcare delivery. It also involves public health sector governance and leadership which aim at ensuring that only competent and qualified people lead the sector and that activities are governed by a democratic and free process which place emphasis on human rights, dignity and self-worth of all stakeholders.
Without doubt efficient health promotion and by implication the entire health delivery system cannot function without finance. In fact, the extent and impact of health promotion depend to a significant extent on the availability of funds. The problem of finance is especially critical in developing nations in Africa where political corruption and competing needs whittle down whatever gets to health from the yearly appropriation of government. However, there is a need to understand that a lot needs to be done in terms of the fiscal policies in these nations in order to achieve the desire for good health and improved life expectancy. In other words, the process of fiscal policymaking and budgetary allocation should prioritize health promotion and health delivery in these countries.
There is no gainsaying the fact that the health system as a whole is dynamic especially so in Africa where apart from battling known ailments new ones (or novel presentation of the old ailments) spring up now and then. The above entails that the health system calls for dynamic organizational setting that is robust enough to deal with changes while making improvements in the system. There is apparently no denying the fact that health promotion as a critical component of health delivery would benefit from organizational change. This is particularly so in the face of the reality that health promotion in most of the continent is still below the expectation. This is not to deny that health promotion has worked well in specific instances like the HIV/AID scourge and maternal health. However, such grab and slash system which focuses on only one of such delimited issues in the system cannot be seen as either robust or effective in the long run.
There is an obvious need to ‘en-gender’ health promotion as a very critical issue in Africa. This would entail ensuring that those involved in health promotion ensure that in all key phases of health promotion (planning, implementation and evaluation) women and men should be equal partners and collaborators. Gender, in this case, while calling attention to the needs of women, should also ensure that the men are not left behind even in approaching health issues traditionally seen as the concerns of women. Typical example here is in the area of family planning or reproductive health which demands the active collaboration or participation of both men and women to achieve desired results.
For the WHO [24], the priority interventions in Africa in respect of health promotions include capacity building, development of plans, incorporation of health promotion components in non-health sectors and strengthening of priority programmes using health promotion interventions. These essentially mean pursuing health promotion through capacity building, action planning, advocacy and multisectoral orientation. They are also in tune with relating to the determinants of health promotion in the continent. These include socio-economic conditions and physical (environment), biological, and behavioral lifestyles which impact on health in Africa. Countries can be encouraged to map out their priorities taking into consideration such factors as disease and financial burdens, threats, intervention tools and agencies, acuity, management capabilities, persistent challenges, etc.
Generally, there is a need for stepping up health promotion research in Africa in the areas of family and reproductive health targeting such issues as VVF, antenatal care, diabetes, cardiovascular issues, new disease forms/resurgence of old diseases (including Ebola), etc. especially in terms of communicating with those who are marginal to the formal sector of the society or who are less privileged by virtue of education, economic opportunities or physical/mental challenges, etc. in both urban and rural contexts. Health promotion can profit from an acute awareness of the fact that what works in one socio-geographical setting may not work in another since no two societies are exactly the same. This would entail designing programmes that even where the general principles or goals remain the same embody recognition of the socio-geographical peculiarities of the society/community concerned.
Given the usual paucity of funds in the continent, it makes sense that to minimize cost and save time, there should be incorporation of both needs assessment and evaluation into ongoing health promotion activities. This approach offers a smart way of pursuing health promotion goals without elaborate budget.
In spite of country differences and specific structural challenges, there is a need to build a culture of sharing and documenting outcomes and evidences of health promotion between different countries and organizations. This is a step towards achieving the desirable goal of multinational coordination especially for infectious diseases and epidemics. Equally, African nations need to invest more in capacity building for media and theater practitioners in both private and public sectors on health promotion. There is no gainsaying the media’s crucial role in health information dissemination. Actually, health promotion is largely media driven and should be programmed as such.
In addition to media practitioners, there should be health programme or intervention specific to health promotion capacity building for different cadres of public sector workers. Such capacity building or training should be anchored on acute awareness of current research trends and best practices globally. There should also be increased attention to the need for specific health promotion for under-represented health issues and priority to non-communicable diseases should be targeted. It should also improve capacity on how to incorporate methods of targeting members of the society marginal or vulnerable within each country context.
The Edited Volume, also known as the IntechOpen Book, is an IntechOpen pioneered publishing product. Edited Volumes make up the core of our business - and as pioneers and developers of this Open Access book publishing format, we have helped change the way scholars and scientists publish their scientific papers - as scientific chapters.
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