\r\n\r\n \r\n\r\nVitamin K2 - Vital for Health and Wellbeing has been produced and distributed through the support from Kappa Bioscience, Norway.\r\n',isbn:"978-953-51-3020-8",printIsbn:"978-953-51-3019-2",pdfIsbn:"978-953-51-4895-1",doi:"10.5772/61430",price:139,priceEur:155,priceUsd:179,slug:"vitamin-k2-vital-for-health-and-wellbeing",numberOfPages:338,isOpenForSubmission:!1,isInWos:1,isInBkci:!1,hash:"b2f9f024939ddc4f5da2a8afa3fcd9c9",bookSignature:"Jan Oxholm Gordeladze",publishedDate:"March 22nd 2017",coverURL:"https://cdn.intechopen.com/books/images_new/5169.jpg",numberOfDownloads:35089,numberOfWosCitations:31,numberOfCrossrefCitations:27,numberOfCrossrefCitationsByBook:4,numberOfDimensionsCitations:49,numberOfDimensionsCitationsByBook:4,hasAltmetrics:1,numberOfTotalCitations:107,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"October 6th 2015",dateEndSecondStepPublish:"January 31st 2016",dateEndThirdStepPublish:"March 25th 2016",dateEndFourthStepPublish:"May 30th 2016",dateEndFifthStepPublish:"August 31st 2016",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:'
\n \n\nVitamin K2 - Vital for Health and Wellbeing has been produced and distributed through the support from Kappa Bioscience, Norway.\n\n
',editors:[{id:"36345",title:"Prof.",name:"Jan",middleName:"Oxholm",surname:"Gordeladze",slug:"jan-gordeladze",fullName:"Jan Gordeladze",profilePictureURL:"https://mts.intechopen.com/storage/users/36345/images/3823_n.jpg",biography:"Dr. Jan O. Gordeladze, Ph.D. (born 25th of April, 1950), holds a triple professor competence (Medical Biochemistry, Physiology, and Pharmacology), and is presently working as a Professor Emeritus at the Department of Biochemistry, Institute of Basic Medical Science, University of Oslo, Norway. He has previously been employed as the Medical Director of MSD, Norway, serving two years as a Fulbright scholar at the NIH, Bethesda, Maryland, USA. From 2006-2009 he was employed as Associate Professor at the University of Montpellier, France. He is a member of the Norwegian Stem Cell Center, and his research has over the past 7-10 years been devoted to differentiation of osteochondral cells from stem cells focusing on the impact of transcription factors and microRNA species constituting regulatory loop interactions with functional target genes. He has published more than 120 scientific articles, reviews/book chapters and presented more than 250 abstracts/posters/talks at conferences worldwide. Dr. Gordeladze has served as a Fulbright Scholar at The National Institute of Health, Bethesda, Washington DC during the years 1990-91.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"9",totalChapterViews:"0",totalEditedBooks:"3",institution:null}],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:"53889",title:"Introductory Chapter: Vitamin K2",doi:"10.5772/66384",slug:"introductory-chapter-vitamin-k2",totalDownloads:1769,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:null,signatures:"Jan Oxholm Gordeladze",downloadPdfUrl:"/chapter/pdf-download/53889",previewPdfUrl:"/chapter/pdf-preview/53889",authors:[{id:"36345",title:"Prof.",name:"Jan",surname:"Gordeladze",slug:"jan-gordeladze",fullName:"Jan Gordeladze"}],corrections:null},{id:"51057",title:"Vitamin K, SXR, and GGCX",doi:"10.5772/63983",slug:"vitamin-k-sxr-and-ggcx",totalDownloads:1792,totalCrossrefCites:0,totalDimensionsCites:3,hasAltmetrics:0,abstract:"Vitamin K was discovered in 1929 as a substance essential for blood coagulation and had been clinically utilized before the precise mechanism of action became aware in 1970s. The function as a cofactor of γ-glutamyl carboxylase (GGCX) was the mechanism firstly discovered with the identification of several substrate proteins including blood coagulation factors and osteocalcin. Recently, we and others have shown that vitamin K has other modes of function, such as ligand of nuclear receptor SXR (steroid and xenobiotic receptor) and its murine ortholog PXR (pregnane X receptor) and modulator of protein kinase A (PKA) activity. Besides its importance in blood coagulation, involvement of vitamin K has been shown in two major aging-related diseases, osteoporosis and osteoarthritis. Based on clinical and epidemiological studies, vitamin K is shown to have protective roles for both of them. Interestingly, clinical studies concerning single nucleotide polymorphisms (SNPs) of GGCX and γ-carboxylated status of osteocalcin suggested relationship between GGCX activity and bone-protective effect, while recent findings from basic research indicated that vitamin K functions mediated by SXR/PXR as well as GGCX are important in the bone metabolism. We also suggested that cartilage-protective effect is mediated by SXR/PXR signaling by animal experiments using Pxr knockout mice.",signatures:"Kotaro Azuma and Satoshi Inoue",downloadPdfUrl:"/chapter/pdf-download/51057",previewPdfUrl:"/chapter/pdf-preview/51057",authors:[{id:"184194",title:"Dr.",name:"Satoshi",surname:"Inoue",slug:"satoshi-inoue",fullName:"Satoshi Inoue"},{id:"189851",title:"Dr.",name:"Kotaro",surname:"Azuma",slug:"kotaro-azuma",fullName:"Kotaro Azuma"}],corrections:null},{id:"51024",title:"Vitamin K2 Rich Food Products",doi:"10.5772/63902",slug:"vitamin-k2-rich-food-products",totalDownloads:2064,totalCrossrefCites:2,totalDimensionsCites:2,hasAltmetrics:1,abstract:"Naturally, vitamin K exists in two bioactive forms mainly phylloquinone (vitamin K1) and menaquinones (vitamin K2). Phylloquinone is mostly found in green leafy vegetables such as kale, spinach, broccoli, and vegetable oils. However, menaquinones abundantly occurs in fermented vegetable products as menaquinones‐7 (MK‐7) and in animal‐based products as menaquinone‐4 (MK‐4). Diverse concentrations of menaquinones are present in various dietary sources such as fermented pulses and milk‐based products, cheese, meat, and animal organs. Presently, MK‐7 and MK‐4 contribute about 24 and 7%, respectively, of the total vitamin K dietary intake in the population consuming fermented products regularly. However, about 10% of menaquinones are pooled in the liver out of total intake of vitamin K. Conclusively, fermented soybean products and fermented milk‐based products such as cheese and soured milk contain ample amount of MK‐7, whereas animal organs, meat, fish, and egg contain appreciable amount of MK‐4.",signatures:"Muhammad Yasin, Masood Sadiq Butt and Aurang Zeb",downloadPdfUrl:"/chapter/pdf-download/51024",previewPdfUrl:"/chapter/pdf-preview/51024",authors:[{id:"178785",title:"Dr.",name:"Muhammad",surname:"Yasin",slug:"muhammad-yasin",fullName:"Muhammad Yasin"},{id:"182656",title:"Prof.",name:"Masood Sadiq",surname:"Butt",slug:"masood-sadiq-butt",fullName:"Masood Sadiq Butt"},{id:"189674",title:"Dr.",name:"Aurang",surname:"Zeb",slug:"aurang-zeb",fullName:"Aurang Zeb"}],corrections:null},{id:"50921",title:"Menaquinones, Bacteria, and Foods: Vitamin K2 in the Diet",doi:"10.5772/63712",slug:"menaquinones-bacteria-and-foods-vitamin-k2-in-the-diet",totalDownloads:3272,totalCrossrefCites:10,totalDimensionsCites:21,hasAltmetrics:1,abstract:"Vitamin K2 is a collection of isoprenologues that mostly originate from bacterial synthesis, also called menaquinones (MKs). Multiple bacterial species used as starter cultures for food fermentation are known to synthesize MK. Therefore, fermented food is the best source of vitamin K2. In the Western diet, dairy products are one of the best known and most commonly consumed group of fermented products.",signatures:"Barbara Walther and Magali Chollet",downloadPdfUrl:"/chapter/pdf-download/50921",previewPdfUrl:"/chapter/pdf-preview/50921",authors:[{id:"184784",title:"Dr.",name:"Barbara",surname:"Walther",slug:"barbara-walther",fullName:"Barbara Walther"},{id:"188194",title:"Mrs.",name:"Magali",surname:"Chollet",slug:"magali-chollet",fullName:"Magali Chollet"}],corrections:null},{id:"54263",title:"The Impact of Vitamin K2 on Energy Metabolism",doi:"10.5772/67152",slug:"the-impact-of-vitamin-k2-on-energy-metabolism",totalDownloads:1880,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Environmental and behavioral adaptations introduced during the last decades have synergistically enhanced man’s lifespan, but also paved the ground for disease states involving impairment of multiple organs, which are both modulating and depending on homeostatic calorie “accounting.”",signatures:"Mona Møller, Serena Tonstad, Tone Bathen and Jan Oxholm\nGordeladze",downloadPdfUrl:"/chapter/pdf-download/54263",previewPdfUrl:"/chapter/pdf-preview/54263",authors:[{id:"184157",title:"M.Sc.",name:"Mona",surname:"Møller",slug:"mona-moller",fullName:"Mona Møller"}],corrections:null},{id:"52078",title:"Vitamin K2 and Bone Health",doi:"10.5772/64876",slug:"vitamin-k2-and-bone-health",totalDownloads:2083,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"During the last 20 years, the main clinical effects of vitamin K2 on bone homeostasis have been investigated in both indirect and direct vitamin K treatment regimens. This chapter is mainly based on randomized clinical trials (RCT) lasting for more than 1 year. As for vitamin K1 (phylloquinone, indirect treatment) and vitamin K2 (menaquinone MK‐4 and MK‐7 direct treatment), respectively, the clinical trials have consistently shown decreased fracture rate incidents, however, mainly in Asian populations. In 2013, a major breakthrough was observed by Knapen et al. in the Netherlands, where menaquinone MK‐7 supplementation of 180 μg/day for 3 years to healthy postmenopausal women significantly decreased the age‐related decline in BMC (bone mineral contents) and BMD (bone mineral density) at the lumbar spine and femoral neck, but not at the total hip, as compared to placebo. Thus, MK‐7 supplementation has shown a significant “double”‐positive action through (1) increased bone building and (2) decreased bone resorption. We look forward to seeing the clinical effects on low bone mass and osteoporosis as well as other bone diseases.",signatures:"Niels Erik Frandsen and Jan Oxholm Gordeladze",downloadPdfUrl:"/chapter/pdf-download/52078",previewPdfUrl:"/chapter/pdf-preview/52078",authors:[{id:"186115",title:"M.D.",name:"Niels Erik",surname:"Frandsen",slug:"niels-erik-frandsen",fullName:"Niels Erik Frandsen"}],corrections:null},{id:"54291",title:"Vitamin K2 and its Impact on Tooth Epigenetics",doi:"10.5772/66383",slug:"vitamin-k2-and-its-impact-on-tooth-epigenetics",totalDownloads:2152,totalCrossrefCites:2,totalDimensionsCites:2,hasAltmetrics:1,abstract:"The impact of nutritional signals plays an important role in systemic-based «models» of dental caries. Present hypotheses now focus both on the oral environment and other organs, like the nervous system and brain. The tooth is subjected to shear forces, nourishing and cleansing, and its present “support system” (the hypothalamus/parotid axis) relays endocrine signaling to the parotid gland. Sugar consumption enhances hypothalamic oxidative stress (ROS), reversing dentinal fluid flow, thus creating an enhanced vulnerability to the oral bacterial flora. The acid, produced by the oral bacterial flora, then leads to erosion of the dentine, and an irreversible loss of dental enamel layers. This attack brings about inflammatory responses, yielding metalloproteinase-based “dissolution”. However, vitamin K2 (i.e. MK-4/MK-7) may come to the rescue with its antioxidant property, locally (mouth cavity) or systemically (via the brain), thus sustaining/preserving hormone-induced dentinal fluid flow (encompassing oxidative stress) and boosting/magnifying bodily inflammatory responses. However, sugars may also reduce the tooth’s natural defences through endocrine signaling, thus enhancing acid-supported enamel dentine erosion. Vitamin K2 sustains and improves the salivary buffering capacity via its impact on the secretion/flow of calcium and inorganic phosphates. Interestingly, primitive cultures’ diets (low-sugar and high-K2 diets) preserve dental health.",signatures:"Jan Oxholm Gordeladze, Maria A. Landin, Gaute Floer Johnsen,\nHåvard Jostein Haugen and Harald Osmundsen",downloadPdfUrl:"/chapter/pdf-download/54291",previewPdfUrl:"/chapter/pdf-preview/54291",authors:[{id:"36345",title:"Prof.",name:"Jan",surname:"Gordeladze",slug:"jan-gordeladze",fullName:"Jan Gordeladze"}],corrections:null},{id:"51205",title:"Anti-Inflammatory Actions of Vitamin K",doi:"10.5772/63891",slug:"anti-inflammatory-actions-of-vitamin-k",totalDownloads:2249,totalCrossrefCites:4,totalDimensionsCites:8,hasAltmetrics:1,abstract:"Naphthoquinone compounds have received attention for their ability to regulate diseases from bacterial and parasite infections through to chronic human diseases. Inflammation is widely considered to be at the root of many chronic diseases. The reports of anti-inflammatory activity of naphthoquinones, including vitamin K1 (phylloquinone) and vitamin K2s (menaquinones), are of interest due to their very low toxicity. Most of the evidence for the anti-inflammatory mechanisms of vitamin K suggests a role in the inhibition of the cell signalling complex nuclear factor kappa-B (NF-κB).",signatures:"Stephen J. Hodges, Andrew A. Pitsillides, Lars M. Ytrebø and Robin\nSoper",downloadPdfUrl:"/chapter/pdf-download/51205",previewPdfUrl:"/chapter/pdf-preview/51205",authors:[{id:"184368",title:"Dr.",name:"Stephen",surname:"Hodges",slug:"stephen-hodges",fullName:"Stephen Hodges"},{id:"184370",title:"Dr.",name:"Robin",surname:"Soper",slug:"robin-soper",fullName:"Robin Soper"},{id:"184371",title:"Prof.",name:"Andrew",surname:"Pitsillides",slug:"andrew-pitsillides",fullName:"Andrew Pitsillides"}],corrections:null},{id:"50916",title:"Vitamin K2: Implications for Cardiovascular Health in the Context of Plant-Based Diets, with Applications for Prostate Health",doi:"10.5772/63413",slug:"vitamin-k2-implications-for-cardiovascular-health-in-the-context-of-plant-based-diets-with-applicati",totalDownloads:3664,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Vitamin K was originally discovered as a blood coagulation factor. But observations regarding intakes in populations and health outcomes lead to a deeper understanding of the differences between vitamins K1 and K2. Studies of warfarin-treated rats and MGP -deficient mice led to understanding the central role of MGP in controlling calcification of arteries. A sensitive biomarker assay was then developed, based on a particular species of matrix γ–carboxylation protein OR matrix GLA protein (MGP). Warfarin therapy in people, especially those suffering from chronic kidney disease, was found to cause the highest level of this biomarker desphospho-uncarboxylated MGP (dp-ucMGP). Intervention studies with vitamin K2 brought down levels of dp-ucMGP and also led to relief of some disease endpoints. The process of varicose vein formation includes a role for vitamin K, implicating a lack of vitamin K in the development of varicoceles, which leads to benign prostate hyperplasia. It is likely that much good will be accomplished using vitamin K2 in interventions. Complex, multifaceted diseases will not be treated by single-nutrient solutions. The best interventions will be those which combine vitamin K2 treatment with a healthy diet rich in fruits and vegetables, combined with a healthy lifestyle.",signatures:"Michael S. Donaldson",downloadPdfUrl:"/chapter/pdf-download/50916",previewPdfUrl:"/chapter/pdf-preview/50916",authors:[{id:"180516",title:"Dr.",name:"Michael",surname:"Donaldson",slug:"michael-donaldson",fullName:"Michael Donaldson"}],corrections:null},{id:"50958",title:"Menaquinone‐4 Enhances Steroidogenesis in Testis Derived Tumor Cells Via the Elevation of cAMP Level",doi:"10.5772/63982",slug:"menaquinone-4-enhances-steroidogenesis-in-testis-derived-tumor-cells-via-the-elevation-of-camp-level",totalDownloads:1571,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Naturally existing vitamin K consists of vitamins K1 and K2. Menaquinone‐4 (MK‐4), an analog of vitamin K2 and a product of vitamin K1 metabolism, can be detected in several organs, including the testis; however, the function of MK‐4 in these tissues has not been well characterized. Recent studies have suggested that vitamin K is involved in enhancing protein kinase A (PKA) activity in several cell types, thus regulating numerous PKA‐dependent biological processes. To highlight the effect of vitamin K, we focused on its role in the steroidogenic pathway. Experiments on vitamin K–deficient rats revealed a reduced expression of genes involved in the biosynthesis of cholesterol and steroid hormones in the testis. Moreover, compared with control animals, rats fed on MK‐4 diet presented significantly higher testosterone levels in the plasma and testis. These results suggest that vitamin K is involved in the steroidogenic pathway in the testis. Testosterone levels were found to increase in a dose‐dependent manner also in cell‐based experiments upon addition of MK‐4, but such an effect was not observed in vitamin K1 levels. Furthermore, the effect of MK‐4 on testosterone production was abolished by the specific PKA inhibitor H89, thus confirming the regulatory role of MK‐4 on PKA activation. Here, we describe how MK‐4 modulates PKA activation by enhancing intracellular 3′,5′‐cyclic adenosine monophosphate (cAMP) levels in testis‐derived I‐10 cells. The presented evidence supports the role of MK‐4 in cAMP/PKA signaling and steroidogenesis.",signatures:"Hsin‐Jung Ho, Hitoshi Shirakawa and Michio Komai",downloadPdfUrl:"/chapter/pdf-download/50958",previewPdfUrl:"/chapter/pdf-preview/50958",authors:[{id:"180389",title:"Dr.",name:"Hitoshi",surname:"Shirakawa",slug:"hitoshi-shirakawa",fullName:"Hitoshi Shirakawa"},{id:"180489",title:"MSc.",name:"Hsin-Jung",surname:"Ho",slug:"hsin-jung-ho",fullName:"Hsin-Jung Ho"},{id:"180490",title:"Prof.",name:"Michio",surname:"Komai",slug:"michio-komai",fullName:"Michio Komai"}],corrections:null},{id:"54241",title:"Vitamin K2 Facilitating Inter-Organ Cross-Talk",doi:"10.5772/67153",slug:"vitamin-k2-facilitating-inter-organ-cross-talk",totalDownloads:1743,totalCrossrefCites:3,totalDimensionsCites:3,hasAltmetrics:0,abstract:"This chapter features how vitamin K2 is instrumental in bringing about inter-organ communication, thus facilitating (a) a synthesis/secretion of the endocrine, humoral factors from various organs and (b) physiological responses to the said factors by a multitude of organ systems of the body, thus creating a ‘lattice’ of reciprocal regulatory loops in order to ensure endocrine homeostasis.",signatures:"Jan O. Gordeladze, Håvard J. Haugen, Gaute Floer Johnsen and\nMona Møller",downloadPdfUrl:"/chapter/pdf-download/54241",previewPdfUrl:"/chapter/pdf-preview/54241",authors:[{id:"36345",title:"Prof.",name:"Jan",surname:"Gordeladze",slug:"jan-gordeladze",fullName:"Jan Gordeladze"}],corrections:null},{id:"51126",title:"Vitamin K2 in Animal Health: An Overview",doi:"10.5772/63901",slug:"vitamin-k2-in-animal-health-an-overview",totalDownloads:1747,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:1,abstract:"The role of vitamin K in animal health has not received much attention. Vitamin K studies have, for the most part, addressed the use of animals in the investigation of vitamin K physiology and pathophysiology, often using the rodent as a model system. However, vitamin K performs the same role in animals as it does in man and there are areas, such as animal nutrition, where a better understanding of animal requirements in general, and with ageing, could benefit animal health and continued well‐being.",signatures:"Jayde O’Neil, Bethany Scarrott, Ragnhild Aven Svalheim, Jonathan\nElliott and Stephen J. Hodges",downloadPdfUrl:"/chapter/pdf-download/51126",previewPdfUrl:"/chapter/pdf-preview/51126",authors:[{id:"184368",title:"Dr.",name:"Stephen",surname:"Hodges",slug:"stephen-hodges",fullName:"Stephen Hodges"},{id:"184369",title:"Ms.",name:"Jayde",surname:"O'Neil",slug:"jayde-o'neil",fullName:"Jayde O'Neil"},{id:"184748",title:"Ms.",name:"Bethany",surname:"Scarrott",slug:"bethany-scarrott",fullName:"Bethany Scarrott"},{id:"184749",title:"Prof.",name:"Jonathan",surname:"Elliott",slug:"jonathan-elliott",fullName:"Jonathan Elliott"},{id:"184750",title:"Ms.",name:"Ragnhild",surname:"Svalheim",slug:"ragnhild-svalheim",fullName:"Ragnhild Svalheim"}],corrections:null},{id:"50754",title:"Medicinal Chemistry of Vitamin K Derivatives and Metabolites",doi:"10.5772/63511",slug:"medicinal-chemistry-of-vitamin-k-derivatives-and-metabolites",totalDownloads:1872,totalCrossrefCites:2,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Vitamin K acts as a cofactor for γ‐glutamyl carboxylase. Recently, various biological activities of vitamin K have been reported. Anti‐proliferative activities of vitamin K, especially in vitamin K3, are well known. In addition, various physiological and pharmacological functions of vitamin K2, such as transcription modulators as nuclear steroid and xenobiotic receptor (SXR) ligands and anti‐inflammatory effects, have been revealed in the past decade. Characterization of vitamin K metabolites is also important for clinical application of vitamin K and its derivatives. In this chapter, recent progress on the medicinal chemistry of vitamin K derivatives and metabolites is discussed.",signatures:"Shinya Fujii and Hiroyuki Kagechika",downloadPdfUrl:"/chapter/pdf-download/50754",previewPdfUrl:"/chapter/pdf-preview/50754",authors:[{id:"180528",title:"Dr.",name:"Hiroyuki",surname:"Kagechika",slug:"hiroyuki-kagechika",fullName:"Hiroyuki Kagechika"},{id:"180529",title:"Dr.",name:"Shinya",surname:"Fujii",slug:"shinya-fujii",fullName:"Shinya Fujii"}],corrections:null},{id:"50681",title:"From Protein Folding to Blood Coagulation: Menaquinone as a Metabolic Link between Bacteria and Mammals",doi:"10.5772/63342",slug:"from-protein-folding-to-blood-coagulation-menaquinone-as-a-metabolic-link-between-bacteria-and-mamma",totalDownloads:1892,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Menaquinones have long played a central role in bacterial metabolism due to their solubility in membranes and their ability to mediate electron transfer reactions between a large variety of enzymes. In addition to acting as important nodes in fermentation and respiration, menaquinones are critical to the formation of disulphide bonds in the periplasm. Their utility as molecular wires has also led to their incorporation into redox reactions in higher‐order organisms, where they participate in numerous physiological processes, including blood coagulation. Through studying the menaquinone‐dependent pathways in organisms across the phylogenetic spectrum, researchers have begun to uncover intriguing metabolic links and have identified novel compounds for modulating these vital pathways.",signatures:"Brian M. Meehan and Jonathan Beckwith",downloadPdfUrl:"/chapter/pdf-download/50681",previewPdfUrl:"/chapter/pdf-preview/50681",authors:[{id:"180269",title:"Dr.",name:"Brian",surname:"Meehan",slug:"brian-meehan",fullName:"Brian Meehan"},{id:"185054",title:"Prof.",name:"Jon",surname:"Beckwith",slug:"jon-beckwith",fullName:"Jon Beckwith"}],corrections:null},{id:"52618",title:"Vitamin K2 Biosynthesis: Drug Targets for New Antibacterials",doi:"10.5772/65487",slug:"vitamin-k2-biosynthesis-drug-targets-for-new-antibacterials",totalDownloads:2122,totalCrossrefCites:1,totalDimensionsCites:3,hasAltmetrics:0,abstract:"In prokaryotes, vitamin K2 (menaquinone) transfers two electrons in a process of aerobic or anaerobic respiration. Respiration occurs in the cell membrane of prokaryotic cells. Electron donors transfer two electrons to menaquinone (MK). Menaquinone in turn transfers these electrons to an electron acceptor. Menaquinones are vital for the electron transport chain. In the spectrum of Gram‐positive bacteria and Mycobacterium spp., vitamin K2 serves as the only quinone molecule in their electron shuffling systems. Hence, the bacterial enzymes associated with biosynthesis of the menaquinone(s) serve as potential target molecules for the development of new antibacterial drugs. This chapter summarizes the effects of vitamin K2 in bacteria and describes in more detail the aspects of menaquinone in bacterial electron transport in general, while also featuring the discoveries of menaquinone biosynthesis inhibitors.",signatures:"Michio Kurosu",downloadPdfUrl:"/chapter/pdf-download/52618",previewPdfUrl:"/chapter/pdf-preview/52618",authors:[{id:"33087",title:"Prof.",name:"Michio",surname:"Kurosu",slug:"michio-kurosu",fullName:"Michio Kurosu"}],corrections:null},{id:"50717",title:"Toxicological and Pharmacological Effects of VKOR Inhibitors",doi:"10.5772/63512",slug:"toxicological-and-pharmacological-effects-of-vkor-inhibitors",totalDownloads:1709,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Vitamin K1 2,3-epoxide reductase (VKOR) inhibition is the main pharmacological effect of warfarin, an anticoagulant that is typically used in the prevention of thrombosis and thromboembolism. The repeated oral administration of sodium dehydroacetate (DHA-S), which has been used as a food additive, preservative, and antimicrobial agent, induced severe hemorrhage in multiple organs and prolonged blood coagulation factors with VKOR inhibition in rats. On the other hand, VKOR and the vitamin K–dependent growth arrest–specific gene 6 (Gas6)/Axl pathway play a key role in mesangial cell proliferation in glomerulonephritis (GN). We herein indicated the potential of the VKOR inhibitor, 3-acetyl-5-methyltetronic acid (AMT), to prevent the proliferation of glomerular mesangial cells and suppress the progression of GN. DHA-S-induced hemorrhage was caused by the depletion of blood VK, associated with any factors including VKOR inhibition. The novel VKOR inhibitor, AMT, reduced renal mesangial cell proliferation and may be a supportive treatment for GN.",signatures:"Yohei Miyamoto",downloadPdfUrl:"/chapter/pdf-download/50717",previewPdfUrl:"/chapter/pdf-preview/50717",authors:[{id:"172105",title:"Ph.D.",name:"Yohei",surname:"Miyamoto",slug:"yohei-miyamoto",fullName:"Yohei Miyamoto"}],corrections:null},{id:"50994",title:"Enhanced Intracellular Delivery and Improved Antitumor Efficacy of Menaquinone-4",doi:"10.5772/63343",slug:"enhanced-intracellular-delivery-and-improved-antitumor-efficacy-of-menaquinone-4",totalDownloads:1513,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Hepatocellular carcinoma (HCC) is a major malignant tumor type that occurs globally. HCC incidence is increasing, especially in Asian countries. Despite many therapeutic approaches, the long-term prognosis of HCC remains poor because of frequent recurrence due to intrahepatic metastasis or multicentric carcinogenesis. Therefore, it is necessary to develop effective and safe chemopreventive agents to improve the prognosis of HCC. Menaquinone-4 (MK-4) has a suppressive effect on HCC, but cellular delivery is poor. We hypothesized that effective cellular delivery of menahydroquinone-4 (MKH), a fully reduced form of MK-4, would regulate HCC growth and metastasis. We developed a bioreductive activation-independent delivery system with the N,N-dimethylglycine ester of MKH (MKH-bis-DMG) to deliver MKH to HCC cells without any bioreductive processing of MK-4. MKH-bis-DMG inhibited the proliferation of both DCP-positive and DCP-negative HCC cell lines in a time- and dose-dependent manner via G1/S cell-cycle arrest. We assessed the effect of MKH-derivatives on HCC metastasis using a mouse model of spleen-liver metastasis. The mean tumor hepatic replacement area of MKH-bis-DMG treated mice was significantly less than that of untreated mice. 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\r\n\tThe pipeline system is an integral part of our current civilization. All across the globe, it ensures the economical transmission of essential fluids to different industries, including oil and gas production, food processing, residential and industrial buildings, water supply, pulp and paper mills, pharmaceutical/medical manufacturing, and chemical manufacturing. Pipeline transportation plays a significant role in running the world economy, similar to the contribution of blood vessels in ensuring life. In this background, it is imperative to disseminate a comprehensive understanding of the fundamental and advanced knowledge in various disciplines of pipeline engineering. The successful design, construction, and operation of a pipeline require establishing a balance of production, cost, safety, and integrity. This book intends to provide the reader with a comprehensive overview of the current state-of-the-art in technology, networks, modeling, and management with a specific focus on the most important evidence-based developments in this important area. The exploration of the technological details would competently support the decision-making process.
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1. Introduction
The dawn of the new millennium has seen many possibilities for growth and development in Africa. Africa is positioned as the centre of trade and growth of the economy by 2050. Growth in the areas of the economy, agriculture, technology, transportation, and education will drive the current and prospects of economic prosperity in Africa. As economic growth in Africa is inevitable, the aspects of sustainable development are of particular concern. As the desire for economic growth improved standards comes into the picture in Africa, there is a need to carefully consider stabilising the natural resources as they are exploited to support growth. Access and use of Information and knowledge in Africa are important to support future economic growth and consequently sustainable development. This chapter will attempt to create a convincing association between access and use of information and knowledge and sustainable development in Africa. The discussion will revolve around sustainable environmental management, sustainable agriculture development, economy, technology, transportation, business and education for sustainable development. The concepts of information and knowledge and sustainable development have been discussed to offer a context for information for sustainable development in Africa.
The sources of literature for the chapter were journal articles, published and unpublished dissertations, technical and research reports, and archival documents and collections. The sources of literature were accessed from databases such as World Bank, United Nations Development Programme, United Nations Conference on Trade and Development, United Nations Office of the Special Advisor on Africa, Food and Agriculture Organisation, New Partnership for Africa’s Development, World Health Organisation, Government Ministers and Departments in Africa. Other sources were from journals such as Information Development, Developing Countries Studies, Journal of the American Planning Association, Chelsea Green, and Development. Other sources for the chapter were accessed from digital repositories such as Mzuzu University and University of Malawi repositories in Malawi, University of South Africa repository and Makerere University repository in South Africa and Uganda respectively. The search terms for the review were Information, Knowledge, rural development, sustainable development, and Africa. The inclusion criteria for information sources was that the information sources have to be peer-reviewed, less than 14 years old, except where the information source(s) was or were important and cannot be replaced with current source(s). The work has to be related to information and sustainable development in Africa and as such the sources reviewed were limited to African countries with a bias to a rural setting. Similar methodologies adopted for the chapter were used in literature review studies on agriculture information in developing countries in Africa by Phiri, Chipeta and Chawinga in 2019, Duta in 2009 [1, 2].
1.1 Concept of information and knowledge
Information and knowledge are highly regarded as the new ‘factor of production’, with equal contribution to human development as the traditional factors of production – land, labour and capital. It is an open secret and common knowledge in the twenty-first century that information and knowledge is the solution to any society’s economic and social problems. Furthermore, information is considered as the most basic human need and a right. Despite the major contribution of information in social and economic development for the developing world, little attention is placed on managing and using such information. It is now a cliche´ to pronounce that Africa is the most underdeveloped continent in the world, where the majority lacks access to development-oriented information [3]. Trevor Haywood has called this marginalised group that has no access to the world’s surplus knowledge, ‘the information poor’ and another with access to the essential information resources “the information-rich” [4]. There are numerous contributing factors to this sad situation in African and the situation is dire in a rural set-up with limited access to infrastructure and other basic facilities such as information centres, roads, schools, and hospitals. Partly, the cause of the problem is the lack of exposure to the importance of evidence/information which is key to development. This writing will demonstrate the practical contribution of information to sustainable rural socio-economic development in Africa.
Access and use of information resources largely depend on physical and technical connectivity. Rural setup in Africa is largely marginalised in terms of the availability of the physical infrastructures and let alone technical connectivity [5]. Most of the rural areas of the continent have no access to these information resources due to the lack of relevant infrastructures. Therefore, there is an urgent need to construct roads, schools, information centres and internet cafes to enable the rural population to access all types of information that concerns their everyday lives [5]. Further still, ICT skills (or lack thereof) represent yet another defining characteristic of access to and use of information and technology. Equipping the rural people with skills on means of navigating the web can greatly influence their ability to access and use the information and consequently help others in accessing the information on the internet and other information centres. Therefore, understanding the social dimensions of the society such as poverty, race, age, caste can greatly influence access and use of information for the sustainable social-economic development of Africa. According to the International Federation of Library Associations and Institutions, studying the social context that enables meaningful use of information also reveals the intersectional nature of information use – where the personal dimensions of identity overlap, reinforce, and multiply the resources and barriers of people and communities [6].
1.2 Concept of sustainable development
Sustainable development is the principle for meeting development goals while simultaneously sustaining the ability of natural systems to provide the natural resources and ecosystems on which the economy and society depend. The implication is that system of continuously using the resources to meet the needs of the society without undermining the stability of natural resources. Sustainable development can be defined as development that meets the needs of the present without compromising the ability of future generations to meet their own needs. The current framework of the United Nations Sustainable Development Goals addresses the issues such as poverty, inequality, climate change, environmental degradation, peace, and justice. Under the framework, United Nations Charter on Millennium Declaration identified principles to achieving global sustainable development such as economic development, social development and environmental protection. The term sustainable development as used by the United Nations incorporates both issues associated with land development and broader issues of human development such as education, public health, and standard of living [7].
Over the years, the concept of sustainable development has developed and the focus has been towards the issues of economic development, social development and environmental protection. Developed economies are striving to streamline their economic development agenda with obligations of protecting natural resources and ecosystems. This also shifts the focus from mere conducting round table commitments towards sustainable development to leveraging the same for economic development. The result is the economic development that recognises the existence and needs for sustaining the environment and ecosystem called Managed Sustainable Development (MSD). In the context of this chapter, the concepts of information and sustainable development will be discussed in the dimensions of four domains: ecology, economics, politics and culture. An attempt for discussion on the close relation of the concept of information and sustainable development in the light of the domains will be exemplified across the chapter.
2. Sustainable development themes and information
2.1 Environmental (or ecological) management
Sustainable development in the realm of the environment (ecology) is the act of creating a co-existence between human settlements and the environment. Therefore, human ecology broadens the focus of sustainable development to include the concept of human health. Human health includes the availability and quality of air, water, food and shelter are also the ecological foundations for sustainable development [8]. Environmental sustainability concerns the natural environment and how it endures and remains productive. Since natural resources are derived from the environment, the state of air, water, and the climate is of particular concern. The issue of environmental protection is of importance in Africa. According to the Data from Institute for Security Studies summarised in Figure 1, Africa’s population is the fastest-growing in the world and it is expected to increase by roughly 50 per cent over the next 18 years, growing from 1.2 billion people today to over 1.8 billion in 2035 [9]. It is further predicted that Africa will account for nearly half of global population growth over the next two decades [9]. These statistics are very worrisome and they eventually threaten the environment as the scramble for natural resources such as air, water and minerals will exponentially increase in the next decade. Therefore, environmental sustainability will require society to design activities or processes that address the demanding needs of the population while preserving the planet. This entails using water, renewable energy, and material supplies sustainably [10].
Figure 1.
Population increase forecast in millions, 2017–2035. Source: IFs v 7.26, historical data from US Census Bureau via CIA and United Nations population division (UNPD) 2015.
Integral elements for sustainable use of the environment in Africa are research and innovation activities. This eventually generates information and knowledge that inform present and future decision making on environmental protection. Access to information and knowledge at all levels of decision making and systems in the African society can truly create a lasting behavioural change on the human perspective of the environment and the responsibilities therein. Universities and research institutions can lead these activities of generating knowledge for environmental protection. Issues of funding are equally critical in this equation and more resources need to be allocated towards activities that lead to the generation of research data for environment protection. Public libraries and other information centres can support the dissemination and access of environmental information by the public. Many public libraries in African can provide information services beyond their physical location. Many public libraries have mobile libraries services that serve people in rural communities, offering books, services, and internet access. In Namibia, a country with one of the world’s lowest rates of population density, mobile libraries travel hundreds of kilometres from the country’s regional libraries to loan out books, provide Wi-Fi access, and allow visitors to use a computer and printer [6]. Equally, several initiatives are being done on access to information that could benefit Africa as far as environmental protection is concerned. The most famous are the projects of Research 4 Life such as AGORA (Access to Global Online Research in Agriculture) and OARE (Online Access to Research in the Environment) with a focus on access to information on sustainable agriculture and environment in developing countries and Africa inclusive [11]. AGORA programme enables least-developed countries to gain access to a digital library collection of 3,500 journals and 3,300 books in the fields of food, agriculture, environmental science and related social sciences [11]. In addition, OARE provides access to information resources in a wide range of disciplines contributing to our understanding of the natural environment, including environmental toxicology and pollution, ecology, geography, environmental economics, environmental law, conservation policy, environmental engineering. The prospects of gaining potential from such huge literature can help support environmental protection initiatives in Africa through the provision of relevant information resources.
2.2 Sustainable agriculture development
Agriculture is the main economic activity for the majority of the rural population in Africa and a major contributor to the Gross Domestic Product index of the continent. According to the statistics in Table 1 prepared by World Bank, African economies rely heavily on agriculture; for Sub-Saharan Africa, the agriculture sector’s share in GDP was 12.7 per cent in 2009 and employed more than 60 per cent of the labour force [12]. Statistics on trade in Africa are indicated in Table 1. Therefore, venturing into sustainable agriculture would greatly support the African population and economy. Elements of sustainable agriculture include permaculture, agroforestry, mixed farming, multiple cropping and crop rotation [13]. It involves agricultural methods that ensure the stability and quality environment for humans for survival.
Sector
2005
2006
2007
2008
2009
Agriculture
16.9
16.4
15.4
12.4
12.7
Industry (inc. mining and manufacturing)
31.4
31.9
32.4
32.5
30.6
Manufacturing
13.1
12.6
14.0
13.6
12.9
Services
51.7
51.8
52.3
55.1
56.6
Table 1.
Trade indicators in Africa.
Source: Based on World Bank World Development Indicators 2010 Database.
Access and openness of agriculture information and knowledge can positively contribute to creating lasting awareness among smallholder farmers in Africa on sustainable farming methods that stabilise the natural environment without depleting its natural ingredients. Individuals and communities engaged in the agricultural sector need accurate, timely and reliable information to increase production and improve their living standards [14]. Phiri, Chipeta and Chawinga further argue that a positive relationship exists between agricultural productivity and information access and use of rural smallholder farmers in Africa. Therefore, extension agents have a role to play in disseminating such information to smallholder farmers [14]. Generation and dissemination of such information would help tackle the emerging challenges such as improving efficiency in market supply chains, climate change and shrinking natural resources [3]. A sample of the projects on generating agricultural information for the developing world are Agricultural Learning Repositories Task Force – AgLR-TF, AgriLORE, and e-Agriculture community. Agricultural Learning Repositories Task Force – AgLR-TF is run by the Food and Agriculture (FAO) of the United Nations to create a network of organisations that promotes the development of an open and interoperable global infrastructure to facilitate sharing and reuse of learning resources on topics related to agricultural and rural development worldwide. AgriLORE is part of the National Agricultural Innovation Project (NAIP) being implemented by ICAR in India. One of the objectives of the project is to generate, review, manage and publish approved learning materials for wider use and re-use by distance learning institutions and interested rural and community organisations and extension agencies. The e-Agriculture Community is a global community of practice in which people worldwide exchange information, ideas and resources related to the use of ICT for sustainable agriculture and rural development. The essence of the projects is to enhance the generation and use of data and information through ICT for sustainable agricultural development in developing countries such as Africa.
2.3 Economy for sustainable development
Rural poverty strains the environmental resources as the majority of the population scramble for resources for their daily living. Therefore, environmental resources are important economic assets. In the 21st Century, the quality of life largely depends on sustainable use of the environment. According to United Nations Development Programme 2017 Poverty Statistics in Africa, indicated in Figure 2, poverty rates range from a high of 74.8 per cent in Niger to a low of 45.3 per cent in Burundi (See Figure 2) [15]. Therefore, access to knowledge and information resources would help to mitigate poverty levels in Africa and enhance the economic activities of millions of people on the continent. Poverty and economic standing significantly affect people’s ability to use information meaningfully. At the same time, access does offer an avenue for reducing poverty and creating economic opportunity. Access to information, in its fullest sense, includes the production and sharing of information and multimedia, as well as the creation of physical objects. The use of wireless technology can help access information on the internet through mobile phones and computers. This approach can also help the youth to acquire skills and reduce illiteracy, inequality, ill-health and spur agricultural development in Africa. This can also be seen in outreach programs that target groups such as workers in the agricultural or small-business sectors to help them improve their yields, find new markets, or increase sales through more effective business practices [6]. In this way, libraries support individuals’ growth from passive consumers of agricultural products to active producers.
Figure 2.
Poverty levels in selected African countries. Source: United Nations development Programme, 2019.
2.4 Technology for sustainable development
The last decade has witnessed the growth of the ICT sector in Africa and the information economy is becoming one of the main drivers for economic growth in general. For example, according to data in Figure 3 by the South African Government, South Africa’s ICT sector contributed more than 2.9 per cent to the country’s gross domestic product (GDP) in 2012. The ICT sector in Tanzania contributed about 20 per cent to the country’s GDP in the same while. It is projected that the ICT sector in the continent is growing rapidly with annual revenues estimated at around USD50 billion. One of the core concepts in sustainable development is that technology can be used to assist people to meet their developmental needs. Technology that endeavours to meet these human needs is referred to as appropriate technology. For example, In Burkina Faso, the Girls’ Mobile Health Clubs found in four village libraries expand access to quality health information while also providing support to the participants to increase their information literacy and technology skills. In Ghana, the Volta Regional Library mobile library in 2012 to improve educational opportunities for students attending schools with limited resources through the provision of hands-on computer classes [6]. This intervention contributed to an increase of pass rate in ICT among the students to 50 per cent and additional funding for the expansion of the programme to other schools. These initiatives in these countries and other countries not discussed here demonstrate the tremendous contribution of ICT to sustainability in various sectors of the economy such as health and education. Therefore, investment and consequential growth of ICT in Africa can improve the lives of the people through lifelong learning and access to various information through the infrastructure. Another landmark project with equal significance to the growth of ICT is ARDI (Access to Research for Development and Innovation) launched in 2009 by World Intellectual Property Organisation (WIPO) and partners in the publishing industry [11]. ARDI offers access to scholarly literature from diverse fields of science and technology and also promotes the integration of developing and least developed countries into the global knowledge economy, reinforcing the knowledge infrastructure and supporting researchers in creating and developing new solutions to technical challenges on a local and global level [11]. African countries can exploit these outstanding ICT initiatives and enhance the growth of the sector for sustainable socio-economic development.
Figure 3.
South Africa’s ICT sector contribution to GDP. Source: Information and communication technology satellite account for South Africa, 2012.
2.5 Transportation for sustainable development
Sustainable economic growth and poverty reduction call for the development of all sectors of the economy to meet the needs of the current and future generations. Transport is one of the key sectors that play crucial roles in achieving the goals of poverty eradication and sustainable development. The transport sector in Africa is linked and stimulate developments in other sectors of the economy. Consequently, transportation contributes to the attainment of Millennium Development Goals (MDGs). Sustainable transport has many social and economic benefits that can accelerate local sustainable development. According to a series of reports by the Low Emission Development Strategies Global Partnership (LEDS GP), sustainable transport can help create jobs [16], improve commuter safety through investment in bicycle lanes and pedestrian pathways [17], make access to employment and social opportunities more affordable and efficient. It also offers a practical opportunity to save people’s time and household income as well as government budgets [18], investing in sustainable transport a ‘win-win’ opportunity. World trade, in our increasingly globalised and networked economy, depends on the rapid and timely transportation of goods from manufacturing places to market areas [19]. Despite the positive contribution of the transport services to the sustainable development of Africa, the sector faces numerous challenges such as huge costs of transport systems and accidents and contribution to greenhouse gas emissions.
According to Working Paper no. 72 of March 2018 of Export–Import Bank of India, Africa’s transport and insurance costs represent 30 per cent of the total value of exports, which compares unfavourably with 8.6 per cent for all developing countries [20]. The working paper further argues that some African countries incur high transport costs due to their landlocked nature. Accidents associated with the transport sector is huge in Africa. For example, over 225,000, or 19 per cent of 1.2 million people killed in the word were accounted for by deaths on African roads alone. Moreover, Africa has the highest number of road traffic accidents per capita. It is estimated that one-third of all gases produced are due to transportation [21]. Motorised transport also releases exhaust fumes that contain particulate matter which is hazardous to human health and a contributor to climate change [22]. Information can help to facilitate the logistical challenges in Africa as far as transport is concerned. Access and use of information can ensure the efficiency and effectiveness of an organisations operations. Information can help to quickly make decisions about issues of transport in the organisation. Efficiency and effectiveness in decision making can help to reduce delay costs of transporting goods and services by opting for efficient logistical organisations to handle the goods thereby reducing delays in transportation. Information forms an important ingredient for improving the transport systems in Africa. Having access to the right information by institutions involved in the transport sector can help to reduce the risks of travelling through accidents and others by electing appropriate traffic signs and symbols. Information is equally important in reducing greenhouse gases emissions in Africa. Statistics on the amount of greenhouse may help policy formulation on instituting measures for reducing such emissions through various legislations on car manufacturing and certification.
2.6 Business for sustainable development
Currently, some African countries such as South Africa, Ghana, Mauritius and Tunisia are experiencing exponential growth in their economies [23]. In addition, the World Investment Report data of 2021 in Figure 4 indicate that Foreign Domestic Investment (FDI) inflows to Africa are equally increasing year-to-year from 19.3 per cent and 3.5 per cent for the Democratic Republic of Congo and Nigeria respectively [24]. Economies in the African region are registering a steady growth attracting foreign investors. Several factors have positively contributed to this trajectory such as democratic and accountable government systems, economic policies, innovative information and communication technologies and the emerging spirit of entrepreneurship. Despite these opportunities, several challenges exist in the continent that impeded the further growth of business ventures. One such challenge is corruption which has serious consequences on the growth of businesses and economic stability. Others include civil unrest, poverty, high-interest rates of borrowing money and underinvestment in information and communication technologies. These challenges, among the others, pose a serious threat to the present and future growth of business and the economy in Africa. Of particular importance in the growth of the business in Africa is the power of data and information. Data and information are the facts and statistics needed for decision making in business and sustainable competitive advantage. It is believed that businesses with the right information on customers, products and others can influence the market potential of the products and grow their business. Therefore, to grow and manage business sustainably in the 21st century, high-quality data and information have to be available at all times at the disposal of the decision-makers. The value of data and information is equally important to the decisions made. This implies data and information on their own are meaningless without action/decision making. The value of data and information in business is equally dependent on actions being taken which may stimulate sustainable business development in Africa.
Figure 4.
Africa: FDI flows, top 5 host economies, 2021. Source: UNCTAD, world investment report, 2021.
2.7 Education for sustainable development
According to United Nations Development Programme Report, Africa is the most youthful continent in the world with more than 200 million youth aged 15 to 24 [15]. A robust education system and employment opportunities for the majority of youth is key for economic development and growth in nations across the continent. The education system in African continues to grow with more students being enrolled in various schools. This calls for the huge infrastructure, teaching and learning materials and recruitment of several well-trained and qualified teachers. Students and teachers need access to relevant information resources to support their curricula. Access to relevant information is restricted in Africa due to several factors such as low budget allocation to purchasing teaching and learning information resources such as books and subscriptions to journals. In the 21st century, the internet is the major source of educational information globally but access to the facility is privileged. The Internet provides access to e-books, electronic journals and other important teaching and learning resources. Internet access by students and teachers in most educational institutions in Africa is compromised either due to lack of ICT infrastructure or the exorbitant cost of internet subscription fees. A positive development is that most African countries are devoting substantial portions of their government budgets to their education sectors, despite often relatively modest GDP’s and many other developmental issues. It is a fact that the increase in government spending on education is by far not enough to reach essential education levels and to provide decent education opportunities for their young people. Despite all these problems, positive development and momentum are arising as the African countries are allocating the largest portion of their governments’ expenditure to their education systems reaching as far as 18.5 per cent. It is envisaged that this expenditure will positively impact internet access by students and teachers, thereby, providing avenues for access to relevant information resources for sustainable education development.
3. Conclusion
The discussion has offered arguments that information and knowledge contribute to sustainable development in Africa. Information has the potential to support different sectors of the African economy from environmental management to business growth. Access to information and knowledge in decision making can create a lasting behavioural change in our perspective of the environment. Dissemination of information would help tackle the emerging challenges such as improving efficiency in market supply chains, climate change and shrinking natural resources. In addition, access does offer an avenue for reducing poverty and creating economic opportunity. Investment and consequential growth of ICT can support lifelong learning and access to various information. Access and use of information can support the efficiency and effectiveness of an organisation’s transport operations. Information can also help businesses to make informed decisions by presenting data in a way that can be interpreted by management. Access to relevant information resources can support teaching and learning and improve quality sustainable education development in Africa. Designing and improving information infrastructures such as the internet and information centres would facilitate access to information at a low cost in Africa. Improving the skills of information providers through short-term and long-term training would also help users access information easily. Legislations such as Access to Information and others would compel African governments and institutions to reconsider the role of information for sustainable development and consequently use it for decision making and competitive advantage.
\n',keywords:"information, knowledge, rural development, sustainable development, Africa",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/78053.pdf",chapterXML:"https://mts.intechopen.com/source/xml/78053.xml",downloadPdfUrl:"/chapter/pdf-download/78053",previewPdfUrl:"/chapter/pdf-preview/78053",totalDownloads:58,totalViews:0,totalCrossrefCites:0,totalDimensionsCites:0,totalAltmetricsMentions:0,impactScore:0,impactScorePercentile:0,impactScoreQuartile:0,hasAltmetrics:0,dateSubmitted:"June 4th 2021",dateReviewed:"July 30th 2021",datePrePublished:null,datePublished:"February 2nd 2022",dateFinished:"August 12th 2021",readingETA:"0",abstract:"Information is one of the major contributors to sustainable development in Africa. Access to relevant information would offset the emerging challenges in market supply chains, climate change and shrinking natural resources. At the same time, information can help to reduce poverty and creating economic opportunity for the majority of the rural populace in Africa. Further growth of ICT can enhance lifelong learning and impart skills and knowledge for individual and societal growth. This growth in skills and knowledge would also impact access and use of information in agriculture, health, transportation and economy. Information is very important in business by presenting data in a way that can be interpreted by management and support growth in the industry. Relevant information can support teaching and learning and improve quality sustainable education development in Africa. The chapter proposes that access and use of information in Africa can be enhanced by designing and improving the existing information infrastructures such as the internet and information centres. Legislations such as Access to Information and others would compel African governments and institutions to reconsider the role of information for sustainable development and consequently use it for decision making and competitive advantage.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/78053",risUrl:"/chapter/ris/78053",book:{id:"10227",slug:"rural-development-education-sustainability-multifunctionality"},signatures:"Austine Phiri",authors:[{id:"331001",title:"M.A.",name:"Austine",middleName:null,surname:"Phiri",fullName:"Austine Phiri",slug:"austine-phiri",email:"austine_phiri@yahoo.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_1_2",title:"1.1 Concept of information and knowledge",level:"2"},{id:"sec_2_2",title:"1.2 Concept of sustainable development",level:"2"},{id:"sec_4",title:"2. Sustainable development themes and information",level:"1"},{id:"sec_4_2",title:"2.1 Environmental (or ecological) management",level:"2"},{id:"sec_5_2",title:"2.2 Sustainable agriculture development",level:"2"},{id:"sec_6_2",title:"2.3 Economy for sustainable development",level:"2"},{id:"sec_7_2",title:"2.4 Technology for sustainable development",level:"2"},{id:"sec_8_2",title:"2.5 Transportation for sustainable development",level:"2"},{id:"sec_9_2",title:"2.6 Business for sustainable development",level:"2"},{id:"sec_10_2",title:"2.7 Education for sustainable development",level:"2"},{id:"sec_12",title:"3. Conclusion",level:"1"}],chapterReferences:[{id:"B1",body:'Phiri A, Chipeta GT, Chawinga WD. Information behaviour of rural smallholder farmers in some selected developing countries: A literature review. Information Development. 2019 Nov;35(5):831-838'},{id:"B2",body:'Dutta R (2009) Information needs and information-seeking behaviour in developing countries: a review of the research. 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Oxford University Press. ISBN 978-0-19-975190-7. (2013)'},{id:"B9",body:'Bello-Schünemann, J. Africa’s population boom: burden or opportunity? ISS Today 15 May 2017'},{id:"B10",body:'Othman MH, Razali R, Faidzul M. Key Factors for E-Government towards Sustainable Development Goals. Development. 2020;29(6s):2864-2876'},{id:"B11",body:'World Health Organization. 2021. Research4Life Programme. Available at: https://www.research4life.org/ [Accessed: 2021-06-22]'},{id:"B12",body:'United Nations Office of the Special Advisor on Africa. 2005. Africa Fact Sheet. United Nations Office of the Special Advisor on Africa (OSAA) and NEPAD-OECD Africa Investment Initiative. Available at: www.un.org/africa/osaa and www.oecd.org/daf/investment/africa [Accessed: 2021-07-26]'},{id:"B13",body:'Ben Falk, The resilient farm and homestead: An innovative permaculture and whole systems design approach. Chelsea Green, 2013. pp. 61-78'},{id:"B14",body:'Phiri A, Chipeta GT, Chawinga WD. Information needs and barriers of rural smallholder farmers in developing countries: A case study of rural smallholder farmers in Malawi. Information Development. 2019 Jun;35(3):421-434'},{id:"B15",body:'United Nations Development Programme. Africa’s Defining Challenge (2017). Available at: https://www.africa.undp.org/content/rba/en/home/blog/2017/8/7/africa_defining_challenge.html [Accessed: 2021-06-22]'},{id:"B16",body:'Grayson D, Hodges A. Corporate social opportunity!: Seven steps to make corporate social responsibility work for your business. Routledge; 2017 Dec 4'},{id:"B17",body:'LEDS in Practice: Save Money and Time. The Low Emission Development Strategies Global Partnership'},{id:"B18",body:'Barbour E, Deakin EA. Smart growth planning for climate protection: Evaluating California\'s Senate Bill 375. Journal of the American Planning Association. 2012 Jan 1;78(1):70-86'},{id:"B19",body:'Gidado U. Consequences of port congestion on logistics and supply chain in African ports. Developing Country Studies. 2015;5(6):160-167'},{id:"B20",body:'Export-Import Bank of India. 2018. Connecting Africa: Role of Transport Infrastructure. Working paper no. 72. Available at: https://www.tralac.org/images/docs/12896/connecting-africa-role-of-transport-infrastructure-exim-bank-working-paper-march-2018.pdf [Accessed: 2021-06-22]'},{id:"B21",body:'LEDS in Practice: Breathe Clean. The Low Emission Development Strategies Global Partnership'},{id:"B22",body:'LEDS in Practice: Create Jobs. The Low Emission Development Strategies Global Partnership'},{id:"B23",body:'Growth Africa. (2021). Available at: https://growthafrica.com/ [Accessed: 22 July 2021]'},{id:"B24",body:'United Nations Conference on Trade and Development. 2020. World Investment Report. Available at: https://unctad.org/webflyer/world-investment-report-2021 [Accessed: 2021-06-22]'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Austine Phiri",address:"austine_phiri@yahoo.com",affiliation:'
Mzuzu University, Mzuzu, Malawi
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1. Incidence and etiology of plantar fasciitis
About 7% of the population >65 years suffer from a painful heel, even though younger people are often affected, too [1]. The most common cause of this symptom is the so‐called “plantar fasciitis” [2]. This term is widely used, although “plantar fasciopathy” or “plantar fasciosis” would be a better description to point out the degenerative nature of the disease. However, as more than 1100 citations in Pubmed quote “plantar fasciitis” (in comparison with only 50), we will use the traditional term in the following.
Plantar fasciitis has been associated with obesity, with acute or chronic work overload, or with work on hard surfaces [2, 3]. It seems that physiological degeneration of the fascia at the calcaneal insertion exacerbates due to repetitive microtraumas caused by vertical compression [4]. This causes inflammatory tissue reactions. As a result, the fascia is thickened with an associated fluid collection to 4.0 mm and more in ultrasonography [5]. Furthermore, this inflammation may trigger bone formation, the so‐called “plantar heel spur.” This process has been studied intensively by Kumai and Benjamin [6]. They proposed three stages of spur growth: “(a) an initial formation of cartilage cell clusters and fissures at the plantar fascia enthesis; (b) thickening of the subchondral bone plate at the enthesis as small spurs form; and (c) development of vertically oriented trabeculae buttressing the proximal end of larger spurs” [6]. The first description of this spur formation and correlation with the clinical symptoms was carried out by Plettner in 1900 [7]. However, not every heel spur is associated with heel pain, as these spurs are found in 11–16% of the normal asymptomatic population [4]. On the other hand, some patients with painful plantar fasciitis do not have a radiographic confirmation of a spur formation.
A similar mechanism (although caused by longitudinal traction and not by vertical compression) of bone formation has been described at the insertion of the Achilles tendon [8].
According to the American clinical practice guidelines from 2010, diagnosis is established by the typical anamnesis and the characteristic localizations of tenderness. Still, weight‐bearing radiographs are also recommended [9].
2. Treatment with LD‐EBRT
2.1. Biological effects of LD‐EBRT on lymphocytes and inflammatory processes
Single doses of external beam radiotherapy (EBRT) in the range of 0.3–1 Gy are called “low dose EBRT” (LD‐EBRT). These single fractions are applied two or three times a week until a total dose of about 3–6 Gy is reached. Such radiotherapeutic concepts are used for diverse nonmalignant conditions, e.g., osteoarthrosis, tendinopathy, epicondylitis, or bursitis. A comprehensive review of the historical developments in LD‐EBRT for benign diseases is given by Trott [10].
In contrast, EBRT in oncology is characterized by much higher single and total doses. “Normofractionation” describes single doses of 1.8–2 Gy, applied about five times a week. To treat breast cancer, the total doses of about 62 Gy are necessary, in prostate cancer even more than 72 Gy. From a radiobiological point of view, these high cumulative doses are used to induce DNA double strand breaks. Due to errors in a repair mechanism (nonhomologous end joining), dicentric chromosomes can occur. These can result in unfinished mitoses, the so‐called “mitotic catastrophe,” the main mechanism to reduce clonogenic survival in tumor cells [11]. High doses of EBRT induce local inflammation and tissue reactions.
The much lower doses of LD‐EBRT act via different mechanisms. In the last two decades, several anti‐inflammatory effects have been discovered, contrary to the effects of the above‐mentioned high EBRT doses.
In vitro LD‐EBRT has been shown to induce apoptosis in peripheral blood mononuclear cells (PBMC) [12]. Interestingly, there was not a linear correlation between dose and the amount of apoptotic cells. Instead, the maximal induction of apoptosis was observed after a single dose between 0.3 and 0.7 Gy, higher doses (up to 3 Gy) not being more effective [12].
Furthermore, doses between 0.1 and 0.5 Gy reduced the adhesion of PBMC significantly to endothelial cells (ECs) in vitro, probably by suppressing the expression of L‐selectin on the surface of PBMC [13]. This is a very important finding, as the adhesion of leukocytes to the cells of the vessel wall is the first event of tissue invasion in inflammatory processes [13]. An-other reason for the reduced adhesion between PBMC and EC was identified by Rödel et al. [14]: In irradiated EC mRNA expression and protein secretion of transforming growth factor β1 (TGF‐β1) were highest after 0.5 Gy, higher doses resulted in a decline to basal levels [14]. Neutralization TGF‐β1 with specific antibodies restored the adhesion between PBMC and EC. These in vitro results were confirmed in vivo in a mouse model for 0.3 Gy [15]. TGF‐β expression is dependent on activation of the nuclear factor‐kappa B (NF‐κB) [16]. Also, NF‐kB DNA‐binding activity showed a biphasic response to LD‐EBRT with a first maximum at 0.5 Gy, a relative minimum between 0.6 and 0.8 Gy, and a second increase at 1 and 3 Gy [16]. The above‐mentioned findings show a biphasic time course with reduced adhesion of PBMC 4 and 24 h after LD‐EBRT, with a relative maximum of adhesion after 12h [17].
A third mechanism was the suppression of nitric oxide (NO) production in activated macrophages by LD‐EBRT between 0.3 and 1.25 Gy [18]. As the expression of inducible nitric oxide synthases (iNOS) proteins was not altered, the LD‐EBRT seemed to act at the translational or posttranslational level. Furthermore, a dose of 0.5 Gy significantly reduced oxidative burst and superoxide production of stimulated macrophages [19]. A diminished release of reactive oxygen species (ROS) can also contribute to the anti‐inflammatory effects of LD‐EBRT.
Taken together, all of these pathways and mechanisms showed a similar dose dependence with a maximum effect between 0.3 and 0.7 Gy regarding a discontinuous dose‐effect relation [20].
There are several in vivo studies in different animal models about the effects of LD‐EBRT, especially on osteoarthritis. A comprehensive overview is given in Ref. [20], however, as they are not directly related to calcaneodynia, we will not further comment on them.
2.2. Results of randomized trials on radiotherapy for painful heel spur
Since 1937 [21] for decades, large retrospective studies on the efficacy of LD‐EBRT in calcaneodynia have been published (overview in 22). In 1970, one negative randomized trial was reported and heavily criticized but had not been repeated [23]. Starting in the 1980s, patients were systematically clinically examined and interrogated in a structured manner to try to control for diverse risk factors and to compare the efficacy of different fractionation schemes and total doses [24].
It took until the past decade to perform and report prospectively randomized trials to proof the efficacy of LD‐EBRT and to identify the optimal dose fractionation schedule. In the following, we report the design and the results of these trials. Table 1 gives a short overview of the studied dose concepts and the results. Due to methodological reasons, we will describe the studies not following their publications dates, but according to a systematic order.
2.2.1. Clinical proof of the efficacy of LD-EBRT
Since the publication of the first randomized trial on LD-EBRT in 1970, the efficacy of LD‐EBRT was questioned [23]. Goldie et al. randomized 399 patients, however, only nine patients suffered from calcaneodynia. This is why these results cannot be extrapolated to LD‐EBRT of a painful heel spur. Furthermore, endpoints were not clearly defined, and therapy was started in an acute stage of the disease [25].
The landmark study to prove the efficacy of LD‐EBRT was performed by the German cooperative group on the radiotherapy for benign diseases (GCGBD) under the responsibility of Niewald et al. [26]. A very low dose EBRT (6 × 0.1 Gy applied twice a week up to a total dose of 0.6 Gy) was randomized to a standard dose LD‐EBRT (6 × 1 Gy twice a week up to a total dose of 6 Gy). In the case of an unfavorable response after 3 months, the patient was offered a second treatment series (“reirradiation”) applying a standard dose. The dosage of the experimental arm was chosen to examine if very low doses are effective at all. Second, it acted as a placebo irradiation, as a sham irradiation was regarded unethical. LD‐EBRT was applied using a linear accelerator (4‐ to 6‐MV photons) using lateral parallel opposing fields.
Inclusion criteria were tenderness of the calcaneus with a limitation of the painless walking distance and duration of the symptoms for more than 6 months. Furthermore, a radiological proof of a heel spur was required, and the patients had to be least 40 years of age. Patients with previous traumata to the foot, rheumatic or vascular diseases, lymphatic edema, pregnancy, or breastfeeding were excluded. Concomitant therapy with oral analgesics was not limited. However, local injections with steroids during the study period were not permitted.
Initially, 200 patients were planned [27] to detect a difference of 10% in the quality of life (QOL) sum score (SF‐12) [28] and calcaneodynia sum score (CS) [29] (Table 2) with a power of 80% and an error probability of 5%. Furthermore, the visual analogue scale (VAS) to evaluate pain intensity was used. However, after randomization of 66 patients and interim analysis of 62 patients (4 had to be excluded due to a withdrawal of informed consent or violation of the inclusion criteria), the differences in efficacy between the two treatment arms were so pronounced, that the trial was closed early.
Author
Year
N
Standard arm
Experimental arm
Results
Conclusions
Niewald et al. [26]
2012
66
6 × 1 Gy twice a week
6 × 0.1 Gy
3 months: VAS/CS/SF12 sig. better with standard
1. Dose‐response relationship
1 year: less second treatment series with standard
2. Proof of therapeutic effect of LD‐EBRT
Heyd et al. [30]
2007
130
6 × 1 Gy twice a week
6 × 0.5 Gy
6 months: CS no sig. differences
6 × 0.5 Gy as standard fractionation
Ott et al. [32]
2014
457
6 × 1 Gy twice a week
6 × 0.5 Gy
6 weeks, 2.5 years: VAS/CS no sig. differences
6 × 0.5 Gy as standard confirmed
Niewald et al. [25]
2015
127
6 × 1 Gy twice a week
12 × 0.5 Gy thrice a week
3 months: VAS/CS/SF12 no sig. differences
Efficacy not increased with 12 × 0.5 Gy standard still 6 × 0.5 Gy
Table 1.
Summary of contemporary randomized trials on LD‐EBRT of painful heel spurs: tested schedules, results, and conclusions.
Criteria
Extent of symptoms/alteration
Points
1. Pain symptoms
S = Pain at strain
6 / 4 / 2 / 0
(total: 30%)
N = Pain during night time D = Pain during day time (continuously) R = Pain at rest (following any kind of strain) I = Pain at initiation of movement/morning stiffness none = 6 ; slight = 4 ; moderate = 2 ; severe = 0 points ⇨
None Orthopedic shoe, insoles, heel cushion One cane or crutch Two canes or crutches ⇨
15 10 5 0
3. Professional activities (total: 20%)
No limitation, maximum professional strain possible Slight limitation, normal professional work possible Moderate limitation, reduced professional activity Severe limitation, daily professional work impossible ⇨
20 10 5 0
4. Daily/leisure activities (total: 15%)
No limitation of daily and leisure activities and sports Slightly limitation/reduced leisure activities and sports Moderate limitation/no leisure activities and sports Complete limitation of any daily and leisure activities ⇨
15 10 5 0
5. Gait/limp (total: 20%)
No limp, normal walking is possible without a limitation Slightly altered, limp after walking > 1 km (2 blocks) Moderately altered, limp after walking < 1 km (2 blocks) Severely altered, normal walking is impossible ⇨
20 10 5 0
Total score
Sum of the single scores 1 + 2 + 3 + 4 + 5 ⇨
Table 2.
Calcaneodynia score of the GCG‐BD [29], based on [31].
The mean age of patients was 54 years in the standard dose group and 58 years in the 6 × 0.1 Gy group. Sixty‐one patients had a plantar, one patient a dorsal heel spur. In mean, patients in the standard dose group suffered for 15.3 months before the start of LD‐EBRT, in the 6 × 0.1 Gy group for 18.8 months. Twenty‐one patients had symptoms on both sides. In 28 patients the pain irradiated into the calf, only in 18 patients it was localized to the sole of the foot. Two patients had received surgery for LD‐EBRT.
Three months after therapy VAS values, CS‐ and QOL‐scores were significantly better after the standard dose in comparison with the very low dose treatment arm. The higher pain relief resulted in a better QOL. Twelve months after therapy about 64% of the patients after 6 × 0.1 Gy had to receive a second treatment series due to insufficient treatment results, in comparison with only 17% of the patients in the standard dose treatment group. As the second series was applied with a standard dose (6 × 1 Gy), patients in the 6 × 0.1 Gy group who were reirradiated showed equally favorable results compared with those in the standard‐dose group who did not receive a second course [26]. This is why the second treatment series in this clinical setting acted as a “salvage therapy.” Another interesting finding was that patients with a good response already at 3 months remained stable or even improved at 12 months. Furthermore, this underlines the long‐lasting efficacy of LD‐EBRT.
Acute side effects or long‐term toxicity did not occur.
In conclusion, this randomized trial established a dose‐response‐relationship of the analgesic effect of LD‐EBRT, thus providing a clinical and methodological proof of the efficacy of 6 × 1 Gy LD‐EBRT on the clinical course of painful heel spurs. The early termination of the study was justified due the interim analysis showing significant differences in the clinical outcome between both treatment arms. Still, the trial was not blinded, so both the patients and the staff were aware of the received dose. With modern linear accelerators, a complete blinding of the staff is nearly impossible. The only option would be a shame irradiation with closed collimator jaws, reducing the dose to the unavoidable “leakage” radiation. A much easier and straight forward way was used in the above‐mentioned study by application of a minimal physical dose with 0.1 Gy. Another critical point might be that only half of the patients were examined 12 months after therapy (n = 36). This reduces the reliability of the study results at this time point. However, this does not affect the results concerning treatment efficacy 3 months after LD‐EBRT.
Another potential confounder not only in this study but also in all other published prospective and retrospective case series might be that a lot of the patients had received diverse and other conservative therapies before being referred to LD‐EBRT. An interaction between one of these other treatments and LD‐EBRT cannot be ruled out due to methodological reasons. This reflects clinical reality. Still, an interaction between one of these therapies and LD‐EBRT is rather unlikely and counter‐intuitive, as patients were referred to LD‐EBRT after the clinical failure of all the other conservative treatments.
2.2.2. Looking for the minimum effective dose: optimization of fractionation and total dose of LD-EBRT
2.2.2.1. Single dose 0.5 vs. 1 Gy
Two randomized studies investigated the efficacy of 0.5 Gy single dose in comparison to 1 Gy.
The first trial was conducted by Heyd et al. [30]. They randomized 130 patients between 6 × 0.5 Gy twice weekly (low dose) and 6 × 1 Gy (standard dose). A linear accelerator was used, applying a single field technique.
Inclusion criteria were clinical signs of a painful heel spur, radiological evidence of spur formation, patient age ≥30 years and a relapse after previous conservative treatments, in patients >45 years LD‐EBRT could be used as the primary treatment. Endpoints of the study were changes in the “original” calcaneodynia score [31], that was documented before LD‐EBRT, at the end of the course, and 6 weeks and 6 months afterward.
One hundred and thirty patients were randomized. Mean age was 58.4 years. A 102 patients suffered from a plantar, one patient from a dorsal, and 27 patients from combined spurs. In mean, patients had been suffering from symptoms for 9.8 months. The symptoms had been present in 58 patients for less than 6 months, in 72 patients for a longer time. In 7 heels LD‐EBRT was the first therapeutic approach.
At the end of LD‐EBRT, 66% in the low dose group vs. 59% in the standard dose experienced an improvement in symptoms, 6 weeks later 80 vs. 85%. At this time point, 1.5% in each group reported an increase in symptoms, 19 vs. 14% no change. No statistically significant differences were noted. In case of insufficient treatment results patients were offered a second EBRT series. Thus 26 vs. 37% were treated a second time. Six weeks after that, 71 vs. 79% of these patients reported a further improvement. Six months after LD‐EBRT 88% of the patients in both groups had an amelioration of their symptoms, the remaining patients reported no change. During the EBRT series a slight increase in pain was reported by 26 vs. 29% of the patients. No other acute or late toxicity occurred.
In conclusion, 6 × 0.5 Gy twice weekly was as effective as 6 × 1 Gy.
These results were confirmed by a second randomized trial [32, 33]. Ott et al. randomized 457 patients between 6 × 0.5 Gy (low dose) and 6 × 1 Gy (standard dose). In contrast to the above‐cited “Heyd‐study” [30] an X‐ray unit (orthovoltage) and not linear accelerators was used. Patients received a single field (6 × 8 cm on the plantar calcaneus) with 150 kV, 15 mA, 1 mm Cu‐filter, with source‐to‐skin distance (SSD) of 40 cm. Six weeks after the LD‐EBRT a second series was offered to patients with an insufficient response. The endpoint was pain reduction. CS score and VAS values were measured before and at the end of LD‐EBRT (early response), 6 weeks (delayed), and 2.5 years (long‐term) afterward.
With a median follow‐up of 32 months the mean VAS values before treatment, for early, delayed, and long‐term response for the 0.5 and 1.0 Gy groups were 65.5 ± 22.1 and 64.0 ± 20.5 (p = 0.19), 34.8 ± 24.7 and 39.0 ± 26.3 (p =0.12), 25.1 ± 26.8 and 28.9 ± 26.8 (p =0.16), and 16.3 ± 24.3 and 14.1 ± 19.7 ( p =0.68) [31]. Similar results were obtained for the CS score without any significant differences between both dose groups.
Taken together, the above‐mentioned studies proofed an equivalent clinical efficacy of 6 × 0.5 Gy in comparison to 6 × 1 Gy, thus defining a new clinical treatment standard with six times 0.5 Gy twice weekly as the minimum effective dose.
Before proofing 0.5 Gy as the new standard single dose, another randomized study tried to increase efficacy in reaching the “old” cumulative dose of 6 Gy with a single dose of 0.5 Gy. Niewald et al. randomized between 6 × 1 Gy twice a week (old “standard dose”) and 12 × 0.5 Gy three times a week (“experimental dose”) [25]. The aim was not just to get comparable results, but to further improve the analgesic effects. Linear accelerators (6 MV photons) applying a lateral opposing field technique were used.
Inclusion and exclusion criteria were quite similar to the ones used in the landmark study [26]: Clinical evidence of a painful heel spur, and duration of the symptoms for more than 6 months; radiological proof of a spur formation; age at least 40 years; Karnofsky‐Index at least 70%. Patients with previous radiotherapy or previous trauma to the foot, rheumatic or vascular diseases, lymphatic edema, pregnancy, breastfeeding, or severe psychiatric disorders were excluded. Concomitant therapy with analgesics was allowed. However, patients receiving surgery or shock wave therapy after randomization were excluded.
Endpoints were the SF‐12 sum score, the CS sum score (Table 2), and VAS. Follow‐up was scheduled every 6 weeks for 1 year.
Two‐hundred and forty patients were calculated to detect a difference of 15% in the VAS and CS score, with a power of 80%, and an error probability of 5%. After randomization of 127 patients and an interim analysis of 107 patients, the study was closed early, as the intended increase in analgesic efficacy by the experimental treatment was very unlikely to be achieved.
The mean age of the patients in the standard group was 56.1 Gy in comparison with 58.1 Gy in the experimental group. The mean duration of symptoms before initiation of LD‐EBRT was 17 vs. 16 months. In 98% of the standard group and 93% of the experimental group a plantar spur was treated, in 2 and 7% a combined (plantar and dorsal) spur.
Results after 3 months have been issued so far [25], longer follow‐up has yet to be published. After 3 months, there were no significant differences neither in the VAS (standard 42.3 vs. experimental 44.4) nor the CS sum score (28 vs. 28.4) nor in the QOL (SF‐12) scores. Although longer follow‐up has to be awaited, a further increase in the analgesic effect by applying 12 × 0.5 Gy three times a week is unlikely. This is why this fractionation schedule is currently not recommended, as it does not follow the “as low as reasonable achievable” principle of radiation protection.
2.2.2.2. Single dose 0.3 vs. 1 Gy
Further reduced single doses in LD‐EBRT (with the exception of 0.1 Gy [26]) have never been tested in a prospectively randomized clinical trial. In radiotherapy of degenerative joint disorders, single doses of about 0.3–0.4 Gy were established by von Pannewitz in the late 1920s and published in 1933 and 1970 [34, 35]. However, two studies on calcaneodynia have raised serious concerns on single doses as low as 0.3 Gy.
Seegenschmiedt et al. analyzed treatment efficacy in 141 patients (170 irradiated heels), who were treated from 1984–1994 with X‐ray units (250 kV/200 kV, 20 mA, 40 cm SSD), applying a single field of 6 × 8 cm [24]. Seventy‐two heels received 12 Gy with 6 × 1 Gy (three times a week) –6 weeks break – 6 × 1 Gy (group A), 50 heels were treated with 10 × 0.3 Gy every day (group B1), and 38 heels 10 × 0.5 Gy every day (group B2). The endpoint was the value of a semiquantitative pain score 3 months and in mean 4 years after LD‐EBRT.
The median age of patients was 55 years in group A and 59 years in group B1/B2. The mean duration of symptoms before LD‐EBRT was 8 months, in one‐third, the symptoms persisted for more than 6 months.
Complete pain remission was achieved in 68–71% of the patients without significant differences between the treatment groups. However, there were differences in the clinical course of patients with partial remission of the symptoms: The best results in these patients were achieved during longer follow‐up in group B1 (10 × 0.5 Gy), followed by group A (6 × 1–6 × 1 Gy), followed by group B2 (10 × 0.3 Gy). The latter group showed a significantly worse amelioration of symptoms than the other groups.
A reduced efficacy was also reported in another retrospective case series, comprising 673 heels treated with a single dose of 0.3 Gy three times weekly up to 1.5 Gy (X‐ray) [36]. In case of insufficient treatment results the patients were offered a second course. After the first treatment, only 13% reported CR, nearly all patients had undergone a second LD‐EBRT.
Taken together, to the best of our current knowledge a single dose of 0.5 Gy is standard of care and should only be modified in controlled clinical trials.
2.3. Risk factors potentially associated with treatment failure
In Table 3 selected contemporary randomized trials and patient series are shown broken down into several factors that might be correlated with treatment efficacy. For a better overview, we did not differentiate between univariate and multivariate analyses. We did not try to collect all ever published data.
2.3.1. History of symptoms
Duration of symptoms before start of LD‐EBRT has been shown to be correlated with treatment efficacy in numerous studies.
Muecke et al. analyzed in a retrospective multicenter study 502 patients [22]. Duration of symptoms ≤6 months was associated with 76% treatment success vs. 44% after a history >6 months. Also Seegenschmiedt et al. found in their large collectives a correlation between the duration of heel pain and treatment outcome [24]. A significant influence of duration of symptoms before LD‐EBRT was also reported in 73 heels by Schneider et al. [37]. With a history of 3–6 months, the VAS value was reduced by 85%, 28 months after LD‐EBRT in comparison with a reduction of 58% with a history > 6 months. Similar results were obtained by Hermann et al. in 285 heels comparing <12 month history of pain vs. >12 months [38].
In contrary, another study could not confirm these results [30].
2.3.2. Gender
To the best of our knowledge, in no study, an influence of gender on treatment outcome has been confirmed [22, 24, 30, 38, 39]. In contrast to radiotherapy for oncological indications with high doses, efficacy and tolerability of LD‐EBRT seems to be the same concerning gender.
2.3.3. Patients’ age
Several studies described a correlation between older age and better treatment results, at least 6 weeks after LD‐EBRT [37]. Age somewhat over 50 years seems to be important: >50 years [40], > 53 [38], or > 58 [22]. For a possible explanation see Section 2.3.7.
However, other studies found no influence of this patient characteristic on treatment outcome [24, 30, 39].
2.3.4. Initial increase in pain during LD-EBRT
A very precise registration of changes in pain intensity (VAS) was done by Schneider at al. [37]. Sixty‐two patients (73 treated heels) were prospectively scored every week during LD‐EBRT, at the end of therapy, 6 weeks, 28 months, and 40 months later. Additionally, subjective mechanical heel stress during LD‐EBRT was estimated. A linear accelerator (10 MV) was used, applying one single field with a size of 12 × 17 cm. Patients were treated twice a week to a total dose of 5 Gy, with increasing single fraction doses (0.25 – 0.25 – 0.5 – 1 – 1 – 1 – 1 Gy). Mean patient age was 54 years, and all had a radiologically proven plantar spurn, mean symptom duration before LD‐EBRT was 6.5 months. Nearly all patients had received other conservative therapies before LD‐EBRT with insufficient results.
Interestingly, VAS scores decreased continuously during LD‐EBRT: before treatment the mean value was 6.3 ± 1.5, after the first week of LD‐EBRT 6.2 ± 1.8, after the second week 5.5 ± 2 (p < 0.05), after the third 4.7 ± 2.4, and 3.8 ± 2.1 at the end of therapy (p < 0.001). Six weeks later the value further decreased to 3 ± 2.5 (p < 0.004), 28 months after LD‐EBRT to 1.6 ± 2.2 (p < 0.01). One year later no further decrease was noticed (1.8 ± 2.3). Only two patients reported intensification of pain during the LD‐EBRT series. However, these data are not to be extrapolated, as increasing single doses (see above) were used to avoid this phenomenon.
In standard schedules with fixed single doses a slight increase in pain during the treatment series was reported by 26% (during 6 × 0.5 Gy) vs. 29% (6 × 1 Gy) of the patients [30]. Unfortunately, a possible correlation of this phenomenon with definite treatment results was not investigated.
Without further quantification, another study (6 × 1 vs. 6 × 0.1 Gy) stated, that this initial increase in symptoms “had no influence on the final pain relief 3 and 12 months after treatment” [26]. Older studies postulated a temporary reduction of the pH value in the irradiated tissues at the beginning of the treatment series, without consequences for the long‐term efficacy of LD‐EBRT [41].
This is contrasted by observations of LD‐EBRT in peritendinitis humeroscapularis [42]. In 73 patients (86 shoulders) initial increase of pain during the treatment course was significantly associated with a good response.
2.3.5. Use of megavoltage techniques/linear accelerators
Muecke et al. analyzed in a retrospective multicenter study the influence of different treatment techniques in 502 patients [22]. Treatment failure was defined as pain persistence after LD‐EBRT and recurrence of pain during follow‐up. Treatment with MV (6–10 MV) was a significant prognostic factor for pain relief in multivariate analysis, as MV was associated with an eight‐year event‐free probability of 68 vs. 61% after X‐ray beams (175 kV). There are two possible explanations for this finding: besides the possibility of a random result, the authors postulate a more homogenous dose distribution with MV treatment in comparison with KV [22].
2.3.6. Number of therapy courses required
Schneider et al. reported an efficacy of just one‐third after a second LD‐EBRT course (so‐called “re‐irradiation”) in comparison with the effects of the first course [37]. Out of 73 heels treated with 5 Gy LD‐EBRT 18 heels received reirradiation due to insufficient treatment response. However, pain reduction measured by means of changes in VAS shortly after the second course and during long‐term follow‐up was significantly diminished in comparison with the efficacy of the first course (about 30% reduction in pain at the last evaluation vs. 86%).
Similar results were obtained in the large retrospective series (502 patients) by Muecke et al. [22]. Treatment failure was significantly associated with the number of treatment series: eight‐year event‐free probability was about 70% after the first course in comparison with just about 30% after reirradiation.
A systematic study on the efficacy of a reirradiation has been published by Hautmann et al. [43]. Eighty‐three patients (101 heels) with insufficient response to the first course or recurrent pain afterward due to plantar fasciitis (83 heels), or achillodynia (28 heels) received a second LD‐EBRT course in median 10 weeks (range 4 weeks to 63 months) after the first LD‐EBRT. About 75% of the patients were treated with 6 × 1 Gy, the others 6 × 0.5 Gy. The pain was assessed using the numeric rating scale (NRS) before and at the end of LD‐EBRT, 6, and 12 weeks, and 6, 12, and 24 months thereafter.
Before reirradiation NRS values were 6 (interquartile range 5–8), at the end of LD‐EBRT 5 (2–6), 6 weeks later 2 (1–4), at 12 weeks 1 (0–3), at 6 months 0 (0–2), at 12 and 24 months 0 (0–1). Interestingly, not only the patients with recurrent pain after the first course but also patients with insufficient responses to the first course experienced a profound and long‐lasting amelioration of their symptoms after the second course.
This is why a second treatment course should be recommended in case of insufficient efficacy of the first course.
2.3.7. Heel stress during LD-EBRT
A significant correlation between avoidance of heel stress during LD‐EBRT and efficacy of LD‐EBRT 6 weeks after therapy was reported by Schneider et al. in 73 heels [37]. With a Pearson\'s correlation coefficient of -0.467 (p < 0.01) there was an impressing influence of this variable on pain reduction measured by VAS values. However, this correlation was not seen 28 and 40 months after LD‐EBRT.
An intuitive explanation is given by the authors [37]: As patient age was associated with positive treatment results, too, they proposed that older patients are often retired, thus being able to take more care of their heels.
2.3.8. Spur size
Interestingly, all randomized trials required the radiological proof of a heel spur before including patients into the studies. Furthermore, most of the prospective and retrospective series warranted such an objective sign. However, as a substantial part of the patients suffers from plantar heel pain without having developed a heel spur, LD‐EBRT should be effective in these patients, too.
Hermann et al. analyzed treatment efficacy in 250 patients (285 heels), who received LD‐EBRT predominantly with 6 × 1 Gy [38]. In this series, 33% of the treated heels were without radiological evidence of a spur. In 185 patients a spur was confirmed with a mean length of 6.5 mm (range 0.6–25 mm). Patients without evidence of a plantar heel spur had a significantly higher chance of CR after LD‐EBRT (43 vs. 35%). Furthermore, the length of the spurs correlated directly with treatment outcome. Spurs >6.5 mm had just a 30% chance of experiencing CR in comparison with shorter ones. No statistical differences were found between treatment results of heels without spurs and those with spurs ≤6.5 mm.
Miszczyk et al. reported on 327 patients (623 LD‐EBRT series) mostly treated with X‐ray (180 kV, usually 1mm Cu filters) with single doses of 1.5 Gy (range 1–3 Gy) up to a total dose between 9 and 12 Gy (range 1–45 Gy) [39]. Mean spur size was 9 mm (range 1–30 mm). With a mean follow‐up of 74 months, no correlation between spur size and duration of pain relief was found. Analysis concerning spur length and treatment outcome in itself were unfortunately not reported.
2.3.9. The combination of different factors
Multivariate logistic regression enables the identification of factors independently predicting treatment outcome. By combining these factors, models can be calculated, that predict treatment outcome with a high probability. An example from the study of Hermann et al. is given in Table 4: in 285 heels treated with 6 × 1 Gy/6 × 0.5 Gy the influences of the patient characteristics age, spur length, and duration of symptoms before LD-EBRT alone and in combination were calculated [38]. The best results were obtained for patients > 53 years, spur length <6 mm, and a duration of symptoms <12 months with a probability for CR of 55% (CI 36–73%) and PR of 38% (CI 22–58%). Without these characteristics, the chance for CR was just 18% (CI 9–33%), for PR 31% (17–48%).
entire dorsal foot vs. calcaneus vs. insertion of plantar fascia
Dose
6 × 1 vs. 6 × 0.5 Gy
6 × 1 Gy vs. 6 × 0.1 Gy
12, 3, 5 Gy
5 Gy (increasing single dose)
1.5 (1–3) up to 9–12 Gy (1–45)
5–10 × 0.5–1 Gy
6 × 1 Gy6 × 0.5 Gy
6 × 1 Gy
0.3–1.5 Gy; 2–3x weekly 2.5–18.76 Gy
Potential factors
History of symptoms
0
n.i.
+
+
0
+
+
+
+
Gender
0
n.i.
0
n.i.
0
0
0
n.i.
n.i.
Patient\'s age
0
n.i.
0
+
0
+
+
+
n.i.
Initial worsening of pain during LD‐EBRT
n.i.
n.i.
n.i.
n.i.
n.i.
n.i.
n.i.
n.i.
n.i.
MV vs. KV
n.i.
n.i.
n.i.
n.i.
n.i.
+
n.i.
n.i.
0
Number of therapy series
n.i.
n.i.
n.i.
+
n.i.
+
n.i.
n.i.
+
Heel stress during LD‐EBRT
n.i.
0
n.i.
+
n.i.
n.i.
n.i.
n.i.
n.i.
Table 3.
Factors associated with treatment efficacy in contemporary studies.
Note: 0: no correlation with treatment outcome; +: correlation with treatment outcome; n.i.: not investigated; prospect: prospective case series; rand: randomized clinical trial; retrospect: retrospective case series; KV: kilovoltage; MV: megavoltage.
Patient\'s age >53
No spur or spur ≤6.5 mm
Duration of symptoms <12 months
Probability of
No change
Partial remission
Complete remission
1
1
1
0.07 (0.03–0.14)
0.38 (0.22–0.58)
0.55 (0.36–0.73)
1
1
0
0.13 (0.07–0.28)
0.37 (0.21–0.57)
0.50 (0.30–0.70)
1
0
1
0.15 (0.06–0.24)
0.53 (0.33–0.72)
0.32 (0.17–0.53)
1
0
0
0.25 (0.13–0.45)
0.48 (0.27–0.69)
0.27 (0.13–0.48)
0
1
1
0.17 (0.10–0.31)
0.33 (0.19–0.50)
0.50 (0.33–0.66)
0
1
0
0.34 (0.20–0.53)
0.40 (0.24–0.59)
0.26 (0.13–0.45)
0
0
1
0.30 (0.20–0.46)
0.29 (0.18–0.43)
0.41 (0.27–0.56)
0
0
0
0.51 (0.35–0.69)
0.31 (0.17–0.48)
0.18 (0.09–0.33)
Table 4.
Probabilities (95%‐CI) for NC, PR and CR calculated by polytomous logistic regression in dependence of the risk factors age, spur length, and duration of symptoms before LD‐EBRT according to Hermann et al. in a collective of 285 heels treated with 6 × 1/6 × 0.5 Gy (taken from [38]).
2.4. Technique
In modern radiotherapeutic departments, X‐ray sources are less and less available. This is why nowadays most patients are treated with linear accelerators, which were initially developed for the treatment of oncological diseases. However, these machines can be used in the treatment of benign diseases without any modifications or problems. Due to the high efforts in physical, technical, and organizational quality assurances for the operation of an accelerator or an X-ray source, the concentration on accelerators and their use for all indications is recommended.
For irradiation of the heel, the patient has to be placed on the treatment couch with the feet toward the gantry of the accelerator (so‐called “feet first”). Two different patient positions are widely used. He can be placed in supine position, with the irradiated leg is stretched out, while the other leg is angled. Another option is to place the patient in a lateral decubitus position on the side of the involved heel. Again, the symptomatic leg is stretched, while the contralateral leg is bent, with a cushion placed beneath the knee. Using X‐rays, the ipsilateral knee is bent by 90% and the foot is positioned on the treatment table. One anterior‐posterior (AP) beam is usually applied in this technique.
For the treatment itself, there are also two different options. Irradiation may be given as a single stationary field (SSD 100cm by convention). Alternatively, parallel opposing fields from 0° and 180° gantry position (in decubitus position) or lateral opposing fields (90° and 270° in supine position) are also applicable but take a little bit longer in daily clinical practice. The hypothetical advantage of using two opposing fields is a uniform dose distribution in the entire beam path in the calcaneus (Figure 1). However, there has never been a clinical proof, whether this theoretical assumption translates into any clinical advantage for the patient. When applying opposing fields, the dose is specified according to the ICRU 50 report, normally in the center of the calcaneus.
Figure 1.
Dose distribution of two different treatment techniques generated in a treatment planning system (XIO®). In A and B just one single 6 MV photon field (8 × 8 cm) is applied, while C and D shows the dose distribution with two opposing fields from 0 and 180°. In the upper row, the so‐called “beams eye views” are given, while in the lower row the respective dose distributions on an axial CT scan directly at the calcaneal insertion are shown. Note the more uniform dose distribution with opposing fields. The 95% isodose is given as a green line (2.85 Gy). This dose encompasses larger parts of the calcaneal bone in D (opposing fields) than in B (single field). More information is given in Section 2.4.
A third option is the so‐called “plantar field” with the patient lying in prone position. A single field is positioned directly over the plantar insertion/calcaneus, potentially with rotations of the patient table and the gantry to compensate for inclinations of the patients surface in the irradiated field. However, this technique is regarded problematic when using linear accelerators due to the dose build‐up effect in the critical tissue depth. This problem is illustrated in Figure 2: photons with 6 MV reach just the half of the prescribed dose at the skin level, 100% is reached at 1.5 cm tissue depth. This would result in an insufficient dose in the critical structures (plantar fascia and heel spur). To overcome this problem, a silicone flap of about 1 cm diameter must be positioned on the skin before radiation.
Figure 2.
Depth curves of different megavoltage energies. Blue 6 MV photons, red 15 MV photons. At the surface of the body/skin (depth 0 mm), only half (or even less with 15 MV) of the prescribed dose is applied. By physical interactions between photons and the tissue/water, there is a steep increase in dose. A 100% is reached at 1.5 cm depth with 6 MV and at about 3 cm depth with 15 MV. KV‐radiation reaches the maximum dose directly under the surface/skin (not shown). More information is given in Section 2.4.
3. Toxicity and potential risks of LD‐EBRT
Patients are often sent to the radiotherapist after a long unsuccessful history of diverse conservative treatments. The reason for this is a widespread fear among general practitioners that LD‐EBRT might be associated with severe side effects and risks. These fears are not substantiated, as reactions of the nerves or vessels require much higher doses than used for LD‐EBRT. For example, a dose of 45 Gy in normofractionated oncological therapy is considered to be safe for the spinal cord and therefore daily clinical practice [44]. Peripheral nerves are even more radioresistant. Acute or chronic side‐effects have never been reported in all contemporary studies on LD‐EBRT.
3.1. Acute reactions of the skin
Acute side effects are negligible, as very low doses of ionizing radiation (in comparison with oncological treatments) are applied to a distal extremity. The total dose of LD‐EBRT with 3 or 6 Gy is far too low to cause any acute or late reactions on the skin overlaying the calcaneus. During normofractionated EBRT (single doses of 1.8–2 Gy, treatment on 5 days a week) erythema and mild edema develop at about 30 Gy [45]. Hyperpigmentation occurs at about 45 Gy, moist epitheliolyses at about 50 Gy. A 50–60 Gy might cause telangiectasias years after the therapy. This is why there is no report on acute treatment side effects in LD‐EBRT until now to the best of our knowledge.
3.2. Initial increase in pain during LD‐EBRT
About one‐third of the patients might experience a slight increase in pain during LD‐EBRT. In the randomized trial by Heydt et al. this phenomenon was seen in 26% (during 6 × 0.5 Gy) vs. 29% (6 × 1 Gy) [30]. It does not seem to be correlated with treatment outcome; further detailed information is given in Section 2.3.4.
3.3. Impairment of gonad function
The dose scattered to the male gonads is somewhat higher than to the ovaries. Jansen et al. calculated for 6 × 0.5 Gy about 1.5 mSv received by the testes and 0.75 mSv to the ovaries [46]. Comparable results have repeatedly been measured in the past [47, 48].
Taken together, the dose received by the gonads is insignificant. As the distal extremity is irradiated, scattered dose to the gonads is comparable to normal diagnostic radiological imaging [49]. The hereditary effects of these doses are very small and very likely negligible [46].
Although spermatogonial cells are very radiosensitive, a single dose of at least 100 mSv is needed to induce a temporary failure of spermatogenesis [50]. A single dose of 1000 mSv (equivalent to 1 Gy photon irradiation) results in an azoospermia for 9–18 months [51]. Interestingly, fractionated doses harm these cells even more. A temporary oligospermia is reported after receiving several fractions up to a cumulative dose of 160 mSv [52]. An azoospermia lasting for 14–22 months has been reported for fractionated doses of 620–860 mSv [53]. The actually during LD‐EBRT received testicular dose is about 100 times smaller than the lowest dose causing temporary changes in testicular tissues.
The dose to the testicles can be further reduced by utilizing a special testicular shielding. However, clinically meaningful dose reductions have been only measured in MV treatment of subdiaphragmatic/pelvine lymphatic regions or tumors [54, 55].
The mean lethal dose for human oocytes has been estimated at 2 Gy (2000 mSv) [56]. Permanent ovarian failure after radiotherapy is age dependent: in perimenopausal women, a dose of 6 Gy is sufficient [57], while in younger women up to 20 Gy are tolerated. The dose scattered to the ovaries during LD‐EBRT for calcaneodynia cannot cause such sequelae (0.75 mSv).
Naturally, pregnancy has to be excluded in all premenopausal women before beginning with LD‐EBRT, to avoid any risk to the fetus.
3.4. Induction of malignancies
So far, no studies with long‐term observation periods have been published, describing a case of malignancy induced by LD‐EBRT for calcaneodynia. However, induction of malignancies is a stochastic effect of ionizing radiation. This means that there is no threshold dose—in contrast for example to the above‐mentioned reactions of the skin. A photon can accidentally trigger a mutation, which in turn leads to tumor formation many years later. The higher the radiation dose, the higher the probability of such an event occurring.
The best available data on tumor induction of full dose EBRT in oncology has been collected in patients treated with breast cancer. Almost 11,000 patients have been followed for over 20 years. The risk of a radiation‐induced tumor was approx. 1% per decade after radiotherapy [58].
To estimate the risk associated with much lower doses of LD‐EBRT, mathematical models on the basis of epidemiological long‐term observations of atomic bomb victims have been developed by the ICRP [59].
Jansen et al. applied the ICRP model on LD‐EBRT of a painful heel spur [46]. Assumed was a single field entering at the foot sole with a size of 8 × 10 cm, 200 kV photons, SSD 40 cm. For an LD‐EBRT series with 6 × 1 Gy the average attributable lifetime risk for induction of a fatal tumor was calculated to be about 0.5 in a thousand patients. An important risk factor for radiogenic‐induced cancer is the patient\'s age by the time the radiation exposure occurs. The risk is already reduced in the 3rd decade of the patient\'s life, it starts to decrease steadily from the age of 40 [60]. Applying these calculations, the estimated lifetime risk per one thousand patients for a fatal tumor accounts for the age of 25 0.6 (male)/0.8 (female), for the age of 50 0.2/0.3, for the age of 75 0.07/0.1 [46].
However, it must be critically noted that this mathematical model was developed for radiation protection and relates to the exposure of complete organ systems with approx. 1 Gy. Therefore, other groups argue that a significantly lower risk of radiogenic cancer induction— approx. ten times less—should be adopted [49, 61]. Furthermore, taken the new standard scheme with 6 × 0.5 Gy into account, these risks are additionally halved.
This risk (max. 1/1000, very likely much lower) must be seen in relation to the tumor risk of the not additionally radiotherapeutical‐treated population. In 2008, the lifetime risk of a man in Germany to suffer from cancer was 50.7% (25.9% to die from malignancy), in women 42.8% and 20.2% respectively [62].
By limiting the application of LD‐EBRT treatment to patients > 30 years of age, an exposure of the juvenile “relatively higher risk” patient population is avoided.
4. Future perspectives: Definition of questions in further randomized trials and future research
4.1. Target volume definition in LD‐EBRT
Traditionally target volume definition has been quite large. Field sizes of 12 × 17cm were treated, including the entire dorsal and middle foot, and not just the calcaneus [37, 82] (Figure 3A).
Figure 3.
Field definitions in LD‐EBRT of a painful plantar heel spur/fasciitis. (A) traditional field definition including the entire dorsal and middle foot. (B) In randomized trials and large prospective series commonly used field definition encompassing the entire calcaneus, including insertion of the plantar fascia and the Achilles tendon. (C) Proposed small field definition for localized painful plantar fasciitis/plantar spur, encompassing only the painful area with 2 cm margins extending into the neighboring areas (calcaneus, fascia, fat pad).
In the recent randomized trials and prospective observational studies target volume definition was more restricted and confined to the calcaneus (Figure 3B). “The target volume consisted of the calcaneus and the region of the plantar aponeurosis” [26]. “The ventral margin is corresponding to the ventral surface of the calcaneus, the plantar and dorsal margins are surrounding the soft‐tissue border, and the cranial margin is below the ankle” [30]. “Target volume is the calcaneus, normally with a field size of 6 cm × 8 cm” [32]. “The calcaneus and the plantar aponeurosis were included in the target volume” [25].
In a German national survey 2001 on LD‐EBRT of painful heel spurs the target volume definition “large” (dorsal and middle foot) vs. “small” (entire calcaneus) was not correlated with treatment outcome [83]. Consequently, very large field definitions should be regarded as obsolete.
However, as the pathophysiological cause of calcaneodynia is thought to be a localized inflammatory process (see Section 1), it is questionable, whether the entire calcaneus has to be irradiated (as long as there are not a plantar as well as a painful dorsal spurs). There are some clinical data that support a further restriction of target volume definition.
Field sizes have been given in the study by Miszczyk et al. on 327 patients treated with X‐ray beams [39]. Target volume was “… the insertion of the plantar fascia with a calcaneal spur and a reasonable margin. The field size varied from 27 to 150 cm2 (mean 47 cm2).” However, although not explicitly stated, no correlation was found between field size and duration of pain relief after LD‐EBRT. Treatment efficacy in itself was apparently not investigated.
In the above‐mentioned series of 285 heels Hermann et al. analyzed treatment efficacy in dependence of field sizes, too [38]. The mean field size was 74 cm2. No correlation between field size (smaller vs. larger than 74 cm2) with treatment efficacy was found. Further analyses of small fields (< 6 × 6 cm), medium‐sized fields (36–64 cm2) and larger fields revealed no significant differences.
This is why it seems to suffice to encompass the painful region with 2 cm margins extending into the neighboring areas (calcaneus, fascia, fat pad; Figure 3C). However, this recommendation is deducted from pathophysiological considerations and the above‐mentioned case series. A randomized trial is necessary to proof clinical equivalence of a field definition “entire calcaneus” (Figure 3B) vs. “insertion of the plantar fascia” (Figure 3C).
4.2. Fractionation of LD‐EBRT
The optimal fractionation schedule has not been elucidated yet. All randomized trial used twice weekly treatments. Only one experimental arm was scheduled three times a week [25]. In a National Survey in Germany with 146 answering institutions, about 45% applied two fractions and 37.5% three fractions weekly [83].
Interestingly, in the landmark study by von Pannewitz a fractionation schedule of only once per week was established [34]. Until now, there is no proof of a higher efficacy applying LD‐EBRT twice or three times per week.
In radiotherapy of another benign disease (endocrine orbitopathy) a 1 Gy per week over 20 weeks schedule was more effective than the standard schedules (10 × 2 Gy or 10 × 1 Gy every working day) [84]. Although other immunological mechanisms cause endocrine orbitopathy in comparison with plantar fasciitis, there is sufficient clinical evidence to test in a randomized trial different fractionation schedules (twice a week vs. once a week, possibly thrice a week).
4.3. Comparison of LD‐EBRT with other therapies
Other therapies than LD‐EBRT have been applied in painful heel spur. In the following, just a rough overview can be given.
Different kinds of insoles and foot orthoses have been developed. The goal was to reduce plantar contact pressure and to distribute the pressure uniformly over the whole rearfoot [63]. Magnetic insoles do not seem to provide additional benefit [64]. As a short‐term treatment, low‐Dye taping techniques are often used. However, in a randomized trial only a modest improvement in ‘first‐step’ pain was seen in comparison with sham‐intervention [65].
Manual stretching is often recommended. A systematic review of six studies found only statistically significant differences in comparison with the control in one study combining calf muscle and plantar fascia stretches [66].
Several trials have investigated acupuncture. A systematic review from 2010 showed (limited) evidence for the effectiveness [67]. A randomized trial published in 2014 recruited 84 patients [68]. The authors concluded, that “dry needling provided statistically significant reductions in plantar heel pain, but the magnitude of this effect should be considered against the frequency of minor transitory adverse events.”
Ultrasound therapy has led to questionable results [69], but a randomized trial on cryo‐ultrasound with about 100 patients published in 2014 showed good effectiveness [70].
Low‐level laser light (635 nm), given twice a week for a total of six applications, reduced in a randomized trial VAS scores significantly after 8 weeks in comparison with placebo [71]. However, the study comprised of just 69 patients; other similar studies have not been reported so far.
Extracorporeal shock waves are widely applied. Three metaanalyses comprising at least five randomized trials found significant short‐term pain relief and improved functional outcomes for this therapeutic option [72–74]. Another study compared the analgesic efficacy of ultrasound and shock wave therapy in 47 patients [75]. The results suggested that the shock wave therapy had greater analgesic efficacy.
Another basic approach is the oral administration of nonsteroidal anti‐inflammatory drugs (NSAID) to achieve a symptomatic relief. Injections into the painful area are also recommended. A recent review summarized ten randomized trials on corticosteroid injections into the plantar fascia [76]. A significant effect of the steroids on the pain has been shown. However, it was usually short‐term, lasting 4–12 weeks in duration. No advantage of ultrasound‐guided injection techniques in comparison with palpation guidance was found, and no superiority of one type of corticosteroid over another was seen. A longer lasting pain relief has been suggested by a small randomized trial of botulinum toxin injections [77]. Another option is the injection of autologous platelet‐rich plasma. A recent review identified three randomized trials, all showing promising results [78]. However, a very small trial challenged this method of plasma preparation, as the same clinical effectivity was observed after the injection of whole blood [79].
Different surgical approaches have been developed. Releases of the plantar fascia are done, in some studies combined with a spur resection [80]. Due to a probably faster recovery after surgery with comparable functional results endoscopic procedures are recommended nowadays [81]. Surgery is usually indicated after failure of conservative therapies as the ultimate “salvage‐therapy.”
There is only a limited amount of studies randomizing patients between LD‐EBRT and the above‐mentioned alternative therapies.
Canyilmaz et al. randomized 123 patients between LD‐EBRT (6 × 1 Gy, three times a week) and 1 ml injection of 40 mg methylprednisolone and 0.5 ml 60 mg 1% lidocaine under the guidance of palpation [85]. After 3 and 6 months, VAS values and CS‐scores were compared between both groups. After 3 months, the results in the radiotherapy arm were significantly superior compared with those after injections.
To corroborate these findings, similar studies should be conducted. Furthermore, more studies randomizing LD‐EBRT against other therapies (e.g. extracorporeal shock waves) are needed. A minimum size of 50 patients per treatment arm should be assured to gain more statistically relevant results. Recruiting patients without prior excessive other therapies for these studies would be optimal.
The goal must be an evidence‐based algorithm defining the therapeutic sequence of the different conservative treatment modalities for plantar fasciitis.
5. Conclusions
LD‐EBRT for painful plantar fasciitis/heel spur is an effective and safe treatment option for patients over 30 years of age and after exclusion of pregnancy. A fractionation of 6 × 0.5 Gy twice weekly up to a total dose of 3 Gy is currently recommended. In the case of an insufficient response a second course can be offered to the patient.
Randomized trials on target volume definition and further optimization of LD‐EBRT fractionation are currently in the process of planning. Further trials to compare the different conservative therapies for plantar fasciitis with each other are necessary to allow the development of an evidence‐based treatment algorithm.
Acknowledgments
This chapter is dedicated to Professor Gisela Hermann‐Brennecke on the occasion of her 70th birthday.
Abbreviations
AP
anterior‐posterior
CI
confidence interval
CR
complete remission
CS
Calcaneodynia score
Cu
chemical element symbol for copper
EC
endothelial cells
GCG‐BD
German Cooperative Group on Radiotherapy for Benign Diseases
Gy
Gray
ICRP
International Commission on Radiological Protection
IL
interleukin
iNOS
inducible nitric oxide synthases
KV
kilovoltage
LD‐EBRT
low dose external beam radiotherapy
mA
milliampere
mRNA
messenger ribonuclein acid
mSv
milliSievert
MV
megavoltage
NC
no change
NF‐κB
nuclear factor kappa B
NO
nitric oxide
NSAID
non‐steroidal anti‐inflammatory drug
PBMC
peripheral blood mononuclear cells
PR
partial remission
QOL
quality of life
ROS
reactive oxygen species
SSD
skin‐to‐source distance
TGF‐β1
transforming growth factor β1
VAS
visual analogue scale
\n',keywords:"low dose radiotherapy, heel spur, plantar fasciitis, reizbestrahlung, target volume definition",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/53798.pdf",chapterXML:"https://mts.intechopen.com/source/xml/53798.xml",downloadPdfUrl:"/chapter/pdf-download/53798",previewPdfUrl:"/chapter/pdf-preview/53798",totalDownloads:2492,totalViews:768,totalCrossrefCites:0,dateSubmitted:"June 1st 2016",dateReviewed:"November 24th 2016",datePrePublished:null,datePublished:"May 17th 2017",dateFinished:"January 8th 2017",readingETA:"0",abstract:"Degenerative changes in the plantar fascia may cause the so‐called “painful heel” with typical projections of tenderness. This condition is often associated with a plantar heel spur. Radiotherapy with low doses (LD‐EBRT) has been well known for its anti‐inflammatory potential. In the recent years, several microbiological mechanisms were elucidated to explain immunomodulation by LD‐EBRT. Furthermore, a randomized study proved the clinical efficacy of this therapy in plantar fasciitis. Two other trials defined a fractionation schedule of 6 × 0.5 Gy twice weekly as the new standard therapy. Taken together, LD‐EBRT is an effective and safe therapeutic option for patients over 30 years of age and after exclusion of pregnancy. In case of an insufficient response, a second course can be offered to the patient. There are still open questions concerning target volume definition and fractionation of LD‐EBRT. Furthermore, studies randomizing LD‐EBRT with other conservative therapeutic approaches are missing.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/53798",risUrl:"/chapter/ris/53798",signatures:"Robert Michael Hermann, Frank Bruns and Mirko Nitsche",book:{id:"5611",type:"book",title:"Radiotherapy",subtitle:null,fullTitle:"Radiotherapy",slug:"radiotherapy",publishedDate:"May 17th 2017",bookSignature:"Cem Onal",coverURL:"https://cdn.intechopen.com/books/images_new/5611.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",isbn:"978-953-51-3150-2",printIsbn:"978-953-51-3149-6",pdfIsbn:"978-953-51-4833-3",isAvailableForWebshopOrdering:!0,editors:[{id:"43940",title:"Dr.",name:"Cem",middleName:null,surname:"Onal",slug:"cem-onal",fullName:"Cem Onal"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"192941",title:"Prof.",name:"Robert",middleName:"Michael",surname:"Hermann",fullName:"Robert Hermann",slug:"robert-hermann",email:"hermann@strahlentherapie-westerstede.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Hannover Medical School",institutionURL:null,country:{name:"Germany"}}},{id:"194730",title:"Dr.",name:"Mirko",middleName:null,surname:"Nitsche",fullName:"Mirko Nitsche",slug:"mirko-nitsche",email:"Nitsche@strahlentherapie-bremen.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"194927",title:"Dr.",name:"Frank",middleName:null,surname:"Bruns",fullName:"Frank Bruns",slug:"frank-bruns",email:"bruns.frank@mh-hannover.de",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null}],sections:[{id:"sec_1",title:"1. Incidence and etiology of plantar fasciitis",level:"1"},{id:"sec_2",title:"2. Treatment with LD‐EBRT",level:"1"},{id:"sec_2_2",title:"2.1. Biological effects of LD‐EBRT on lymphocytes and inflammatory processes",level:"2"},{id:"sec_3_2",title:"2.2. Results of randomized trials on radiotherapy for painful heel spur",level:"2"},{id:"sec_3_3",title:"Table 1.",level:"3"},{id:"sec_4_3",title:"2.2.2. Looking for the minimum effective dose: optimization of fractionation and total dose of LD-EBRT",level:"3"},{id:"sec_4_4",title:"2.2.2.1. Single dose 0.5 vs. 1 Gy",level:"4"},{id:"sec_5_4",title:"2.2.2.2. Single dose 0.3 vs. 1 Gy",level:"4"},{id:"sec_8_2",title:"2.3. Risk factors potentially associated with treatment failure",level:"2"},{id:"sec_8_3",title:"2.3.1. History of symptoms",level:"3"},{id:"sec_9_3",title:"2.3.2. Gender",level:"3"},{id:"sec_10_3",title:"2.3.3. Patients’ age",level:"3"},{id:"sec_11_3",title:"2.3.4. Initial increase in pain during LD-EBRT",level:"3"},{id:"sec_12_3",title:"2.3.5. Use of megavoltage techniques/linear accelerators",level:"3"},{id:"sec_13_3",title:"2.3.6. Number of therapy courses required",level:"3"},{id:"sec_14_3",title:"2.3.7. Heel stress during LD-EBRT",level:"3"},{id:"sec_15_3",title:"2.3.8. Spur size",level:"3"},{id:"sec_16_3",title:"Table 3.",level:"3"},{id:"sec_18_2",title:"2.4. Technique",level:"2"},{id:"sec_20",title:"3. Toxicity and potential risks of LD‐EBRT",level:"1"},{id:"sec_20_2",title:"3.1. Acute reactions of the skin",level:"2"},{id:"sec_21_2",title:"3.2. Initial increase in pain during LD‐EBRT",level:"2"},{id:"sec_22_2",title:"3.3. Impairment of gonad function",level:"2"},{id:"sec_23_2",title:"3.4. Induction of malignancies",level:"2"},{id:"sec_25",title:"4. Future perspectives: Definition of questions in further randomized trials and future research",level:"1"},{id:"sec_25_2",title:"4.1. Target volume definition in LD‐EBRT",level:"2"},{id:"sec_26_2",title:"4.2. Fractionation of LD‐EBRT",level:"2"},{id:"sec_27_2",title:"4.3. Comparison of LD‐EBRT with other therapies",level:"2"},{id:"sec_29",title:"5. Conclusions",level:"1"},{id:"sec_30",title:"Acknowledgments",level:"1"},{id:"sec_32",title:"Abbreviations",level:"1"}],chapterReferences:[{id:"B1",body:'Yi TI, Lee GE, Seo IS, Huh WS, Yoon TH, Kim BR. Clinical characteristics of the causes of plantar heel pain. Ann Rehabil Med. 2011;35:507–513. DOI: 10.5535/arm.2011.35.4.507'},{id:"B2",body:'Irving DB, Cook JL, Young MA, Menz HB. Obesity and pronated foot type may increase the risk of chronic plantar heel pain: a matched case‐control study. BMC Musculoskelet Disord. 2007;8:41. DOI: 10.1186/1471‐2474‐8‐41'},{id:"B3",body:'Sahin N, Oztürk A, Atıcı T. Foot mobility and plantar fascia elasticity in patients with plantar fasciitis. Acta Orthop Traumatol Turc. 2010;44:385–91. 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DOI: 10.17886/rkipubl‐2015‐004'},{id:"B63",body:'Chia KK, Suresh S, Kuah A, Ong JL, Phua JM, Seah AL. Comparative trial of the foot pressure patterns between corrective orthotics, formthotics, bone spur pads and flat insoles in patients with chronic plantar fasciitis. Ann Acad Med Singapore. 2009;38:869–875. PMID: 19890578'},{id:"B64",body:'Winemiller MH, Billow RG, Laskowski ER, Harmsen WS. Effect of magnetic vs sham‐magnetic insoles on plantar heel pain: a randomized controlled trial. JAMA. 2003;290:1474–1478. DOI: 10.1001/jama.290.11.1474'},{id:"B65",body:'Radford JA, Landorf KB, Buchbinder R, Cook C. Effectiveness of low‐Dye taping for the short‐term treatment of plantar heel pain: a randomised trial. BMC Musculoskelet Disord. 2006;7:64. DOI: 10.1186/1471‐2474‐7‐64'},{id:"B66",body:'Sweeting D, Parish B, Hooper L, Chester R. The effectiveness of manual stretching in the treatment of plantar heel pain: a systematic review. J Foot Ankle Res. 2011;4:19. DOI: 10.1186/1757‐1146‐4‐19'},{id:"B67",body:'Cotchett MP, Landorf KB, Munteanu SE. Effectiveness of dry needling and injections of myofascial trigger points associated with plantar heel pain: a systematic review. J Foot Ankle Res. 2010;3:18. DOI: 10.1186/1757‐1146‐3‐18'},{id:"B68",body:'Cotchett MP, Munteanu SE, Landorf KB. Effectiveness of trigger point dry needling for plantar heel pain: a randomized controlled trial. Phys Ther. 2014;94:1083–1094. DOI: 10.2522/ptj.20130255'},{id:"B69",body:'Crawford F, Snaith M. How effective is therapeutic ultrasound in the treatment of heel pain? Ann Rheum Dis. 1996;55:265–267. DOI: 10.1136/ard.55.4.265'},{id:"B70",body:'Costantino C, Vulpiani MC, Romiti D, Vetrano M, Saraceni VM. Cryoultrasound therapy in the treatment of chronic plantar fasciitis with heel spurs. A randomized controlled clinical study. Eur J Phys Rehabil Med. 2014;50:39–47. PMID: 24172641'},{id:"B71",body:'Macias DM, Coughlin MJ, Zang K, Stevens FR, Jastifer JR, Doty JF. Low‐Level laser therapy at 635 nm for treatment of chronic plantar fasciitis: a placebo‐controlled, randomized study. J Foot Ankle Surg. 2015;54:768–72. DOI: 10.1053/j.jfas.2014.12.014'},{id:"B72",body:'Yin MC, Ye J, Yao M, Cui XJ, Xia Y, Shen QX, Tong ZY, Wu XQ, Ma JM, Mo W. Is extracorporeal shock wave therapy clinical efficacy for relief of chronic, recalcitrant plantar fasciitis? A systematic review and meta‐analysis of randomized placebo or active‐treatment controlled trials. Arch Phys Med Rehabil. 2014;95:1585–1593. DOI: 10.1016/j.apmr.2014.01.033'},{id:"B73",body:'Aqil A, Siddiqui MR, Solan M, Redfern DJ, Gulati V, Cobb JP. Extracorporeal shock wave therapy is effective in treating chronic plantar fasciitis: a meta‐analysis of RCTs. Clin Orthop Relat Res. 2013;471:3645–3652. DOI: 10.1007/s11999‐013‐3132‐2'},{id:"B74",body:'Zhiyun L, Tao J, Zengwu S. Meta‐analysis of high‐energy extracorporeal shock wave therapy in recalcitrant plantar fasciitis. Swiss Med Wkly. 2013;143:w13825. DOI: 10.4414/smw.2013.13825'},{id:"B75",body:'Krukowska J, Wrona J, Sienkiewicz M, Czernicki J. A comparative analysis of analgesic efficacy of ultrasound and shock wave therapy in the treatment of patients with inflammation of the attachment of the plantar fascia in the course of calcaneal spurs. Arch Orthop Trauma Surg. 2016. [Epub ahead of print] DOI: 10.1007/s00402‐016‐2503‐z'},{id:"B76",body:'Ang TW. The effectiveness of corticosteroid injection in the treatment of plantar fasciitis. Singapore Med J. 2015;56:423–432. DOI: 10.11622/smedj.2015118'},{id:"B77",body:'Díaz‐Llopis IV, Gómez‐Gallego D, Mondéjar‐Gómez FJ, López‐García A, Climent‐Barberá JM, Rodríguez‐Ruiz CM. Botulinum toxin type A in chronic plantar fasciitis: clinical effects one year after injection. Clin Rehabil. 2013;27:681–685. DOI: 10.1177/0269215512469217'},{id:"B78",body:'Franceschi F, Papalia R, Franceschetti E, Paciotti M, Maffulli N, Denaro V. Platelet‐rich plasma injections for chronic plantar fasciopathy: a systematic review. Br Med Bull. 2014;112:83–95. DOI: 10.1093/bmb/ldu025'},{id:"B79",body:'Vahdatpour B, Kianimehr L, Ahrar MH. Autologous platelet‐rich plasma compared with whole blood for the treatment of chronic plantar fasciitis; a comparative clinical trial. Adv Biomed Res. 2016;5:84. DOI: 10.4103/2277‐9175.182215'},{id:"B80",body:'Tomczak RL, Haverstock BD. A retrospective comparison of endoscopic plantar fasciotomy to open plantar fasciotomy with heel spur resection for chronic plantar fasciitis/heel spur syndrome. J Foot Ankle Surg. 1995;34:305–311. DOI: 10.1016/S1067‐2516(09)80065‐3'},{id:"B81",body:'Chou AC, Ng SY, Koo KO. Endoscopic plantar fasciotomy improves early postoperative results: a retrospective comparison of outcomes after endoscopic versus open plantar fasciotomy. J Foot Ankle Surg. 2016;55:9–15. DOI: 10.1053/j.jfas.2015.02.005'},{id:"B82",body:'Mantell BS. Radiotherapy for painful heel syndrome. Br Med J. 1978;2:90–91. PMID: 667574'},{id:"B83",body:'Micke O, Seegenschmiedt MH. Radiotherapy in painful heel spurs (plantar fasciitis): results of a national patterns of care study. Int J Radiat Oncol Biol Phys 2004;58:828–843. DOI: 10.1016/S0360‐3016(03)01620‐1'},{id:"B84",body:'Kahaly GJ, Rösler HP, Pitz S, Hommel G. Low‐ versus high‐dose radiotherapy for Graves’ ophthalmopathy: a randomized, single blind trial. J Clin Endocrinol Metab. 2000;85:102–108. DOI: 10.1210/jcem.85.1.6257'},{id:"B85",body:'Canyilmaz E, Canyilmaz F, Aynaci O, Colak F, Serdar L, Uslu GH, Aynaci O, Yoney A. Prospective randomized comparison of the effectiveness of radiation therapy and local steroid injection for the treatment of plantar fasciitis. Int J Radiat Oncol Biol Phys. 2015;92:659–666. DOI: 10.1016/j.ijrobp.2015.02.009'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Robert Michael Hermann",address:"hermann@strahlentherapie-westerstede.com",affiliation:'
Center for Radiotherapy and Radiooncology, Bremen and Westerstede, Westerstede, Germany
Department of Radiotherapy and Special Oncology, Hannover Medical School, Hannover, Germany
Center for Radiotherapy and Radiooncology, Bremen and Westerstede, Westerstede, Germany
Department of Radiotherapy, Karl‐Lennert Cancer Center, University of Schleswig‐Holstein, Kiel, Germany
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In the present chapter, we have evaluated whether CP-154,526, a selective CRF1 receptor (CRF1R) antagonist, or genetic deletion of CRF1R (KO mice) have comparable effects on conditioned place preference (CPP) and conditioned place aversion (CPA) learning. We also investigated CP-154,526 effects on morphine-induced CPP activation of CRF, CREB phosphorylation, and thioredoxin (Trx1) expression in dentate gyrus (DG), a brain region involved in memory consolidation, and the role of hypothalamic-pituitary-adrenocortical (HPA) axis in CPA expression and extinction. The CRF1R antagonist abolished the acquisition of morphine CPP, Trx-1 and BDNF increased expression, and pCREB/Trx-1 co-localization in the DG. The increase in adrenocorticotropic hormone (ACTH) plasma levels observed after CPA expression was attenuated in CRF1R KO mice, suggesting a role of HPA axis in aversive memories. 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These water quality parameters are reviewed in terms of definition, sources, impacts, effects, and measuring methods.",book:{id:"7718",slug:"water-quality-science-assessments-and-policy",title:"Water Quality",fullTitle:"Water Quality - Science, Assessments and Policy"},signatures:"Nayla Hassan Omer",authors:null},{id:"40180",title:"Plant Tissue Culture: Current Status and Opportunities",slug:"plant-tissue-culture-current-status-and-opportunities",totalDownloads:66252,totalCrossrefCites:42,totalDimensionsCites:87,abstract:null,book:{id:"3568",slug:"recent-advances-in-plant-in-vitro-culture",title:"Recent Advances in Plant in vitro Culture",fullTitle:"Recent Advances in Plant in vitro Culture"},signatures:"Altaf Hussain, Iqbal Ahmed Qarshi, Hummera Nazir and Ikram Ullah",authors:[{id:"147617",title:"Dr.",name:"Altaf",middleName:null,surname:"Hussain",slug:"altaf-hussain",fullName:"Altaf Hussain"}]},{id:"66996",title:"Ethiopian Common Medicinal Plants: Their Parts and Uses in Traditional Medicine - Ecology and Quality Control",slug:"ethiopian-common-medicinal-plants-their-parts-and-uses-in-traditional-medicine-ecology-and-quality-c",totalDownloads:3905,totalCrossrefCites:3,totalDimensionsCites:7,abstract:"The main purpose of this review is to document medicinal plants used for traditional treatments with their parts, use, ecology, and quality control. Accordingly, 80 medicinal plant species were reviewed; leaves and roots are the main parts of the plants used for preparation of traditional medicines. The local practitioners provided various traditional medications to their patients’ diseases such as stomachaches, asthma, dysentery, malaria, evil eyes, cancer, skin diseases, and headaches. The uses of medicinal plants for human and animal treatments are practiced from time immemorial. Stream/riverbanks, cultivated lands, disturbed sites, bushlands, forested areas and their margins, woodlands, grasslands, and home gardens are major habitats of medicinal plants. Generally, medicinal plants used for traditional medicine play a significant role in the healthcare of the majority of the people in Ethiopia. The major threats to medicinal plants are habitat destruction, urbanization, agricultural expansion, investment, road construction, and deforestation. Because of these, medicinal plants are being declined and lost with their habitats. Community- and research-based conservation mechanisms could be an appropriate approach for mitigating the problems pertinent to the loss of medicinal plants and their habitats and for documenting medicinal plants. Chromatography; electrophoretic, macroscopic, and microscopic techniques; and pharmaceutical practice are mainly used for quality control of herbal medicines.",book:{id:"8502",slug:"plant-science-structure-anatomy-and-physiology-in-plants-cultured-in-vivo-and-in-vitro",title:"Plant Science",fullTitle:"Plant Science - Structure, Anatomy and Physiology in Plants Cultured in Vivo and in Vitro"},signatures:"Admasu Moges and Yohannes Moges",authors:[{id:"249746",title:"Ph.D.",name:"Admasu",middleName:null,surname:"Moges",slug:"admasu-moges",fullName:"Admasu Moges"},{id:"297761",title:"MSc.",name:"Yohannes",middleName:null,surname:"Moges",slug:"yohannes-moges",fullName:"Yohannes Moges"}]},{id:"29764",title:"Underlying Causes of Paresthesia",slug:"underlying-causes-of-paresthesia",totalDownloads:192588,totalCrossrefCites:3,totalDimensionsCites:7,abstract:null,book:{id:"1069",slug:"paresthesia",title:"Paresthesia",fullTitle:"Paresthesia"},signatures:"Mahdi Sharif-Alhoseini, Vafa Rahimi-Movaghar and Alexander R. Vaccaro",authors:[{id:"91165",title:"Prof.",name:"Vafa",middleName:null,surname:"Rahimi-Movaghar",slug:"vafa-rahimi-movaghar",fullName:"Vafa Rahimi-Movaghar"}]}],onlineFirstChaptersFilter:{topicId:"2",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"81904",title:"Bioactive Ingredients in Functional Foods: Current Status and Future Trends",slug:"bioactive-ingredients-in-functional-foods-current-status-and-future-trends",totalDownloads:0,totalDimensionsCites:null,doi:"10.5772/intechopen.104416",abstract:"Bioactive ingredients (BI) bestow various health-promoting outcomes on consumers, including treating or preventing diabetes, obesity, cancer, coronary heart diseases, and so on. Several BI have been found in nature, such as flavonoids, carotenoids, polyphenols, curcumin, phytosterols, probiotics, bioactive peptide, minerals, and nano-bio minerals, which can be incorporated into foodstuffs to improve their nutritional values. The foods containing BI are considered functional food. This review shed light on the health benefits of various BI for consumers. Due to the growing rate of population and surging demands for healthy foods in the future, it is pivotal to use affordable natural sources of BI to provide functional foods for a vast majority of people. Thus, in this review article, some potent by-products are addressed as alternative sources of BI.",book:{id:"11363",title:"Functional Food",coverURL:"https://cdn.intechopen.com/books/images_new/11363.jpg"},signatures:"Fatemeh Hosseini, Mohammad Reza Sanjabi, Mehran Kazemi and Nasim Ghaemian"},{id:"81903",title:"Development of Antibiofilm Substances by Endophytic Microorganisms with an Emphasis on Medicine",slug:"development-of-antibiofilm-substances-by-endophytic-microorganisms-with-an-emphasis-on-medicine",totalDownloads:0,totalDimensionsCites:null,doi:"10.5772/intechopen.104522",abstract:"The growing antimicrobial resistance and persistence of pathogenic microorganisms in infections–particularly in nosocomial infections–have become a major problem for public health worldwide. One of the main causes of these issues is the formation of biofilms, which are microbial communities associated with extracellular polymeric substances (EPS) that form a slimy extracellular matrix, causing the bacteria to become more tolerant to usual drugs in these structures. Thus, the search for new antibiofilm compounds is part of a strategy to deal with this problem. Endophytic microorganisms such as bacteria and fungi, mutualistically associated with plants, are sources of compounds with biological properties, including antimicrobials, and can be important allies in the synthesis of antibiofilm. These secondary metabolites can interfere with cell-to-cell communication and cell adhesion ability, promoting the dispersal of bacterial colonies and affecting biofilm. Since endophytes are cultivable in laboratory conditions, these microorganisms are environmentally friendly, as they do not contribute to pollution, are easy to handle and are produced on a large scale. Furthermore, metabolites from endophytes are of natural origin and may contribute to the reduced use of synthetic drugs. Considering these aspects, this chapter will focus on the characterization of endophytic microorganisms as potential active sources of antibiofilm and antimicrobial compounds with applications in medicine.",book:{id:"11092",title:"Bacterial Biofilms",coverURL:"https://cdn.intechopen.com/books/images_new/11092.jpg"},signatures:"Saulo Henrique Rodrigues, Marcelo Assis, Camila Cristina de Foggi, Andréa Cristina Bogas, Mariana Ottaiano Gonçalves, Lavinia Cipriano, Elson Longo, Evandro Leite de Souza and Cristina Paiva de Sousa"},{id:"81803",title:"Malnutrition and Sarcopenia",slug:"malnutrition-and-sarcopenia",totalDownloads:1,totalDimensionsCites:0,doi:"10.5772/intechopen.104967",abstract:"Malnutrition caused by aging or disease can be defined as a state resulting from the lack of intake or uptake of nutrition, which leads to a change in body composition and the consequent impairment of physical and mental functions. Sarcopenia is a geriatric syndrome characterized by a progressive loss of skeletal muscle mass, strength, and performance. In this chapter, we (a) summarize the relationship between malnutrition and sarcopenia in various subjects, (b) review nutritional epidemiological evidence related to the prevention of sarcopenia, and (c) show evidence for the efficacy of nutrient supplementation in attenuating muscle atrophy in several patients. Malnutrition is closely related to severe sarcopenia, especially in older hospitalized adults, patients with chronic kidney disease (CKD), those undergoing hemodialysis, and those with cancer. Healthy diets (i.e., those ensuring a sufficient intake of beneficial foods, such as vegetables, fish, nuts, fruits, low-fat foods, and whole-grain products) are useful in preventing sarcopenia. The Mediterranean diet is a particularly healthy diet, but other diets, such as the healthy Nordic diet and traditional Asian diet, also help attenuate sarcopenia in older adults. Proteins, vitamins, minerals, and n-3 polyunsaturated fatty acids are important nutrients for patients with CKD, those on hemodialysis, and those with cancer.",book:{id:"11090",title:"Malnutrition",coverURL:"https://cdn.intechopen.com/books/images_new/11090.jpg"},signatures:"Muneshige Shimizu and Kunihiro Sakuma"},{id:"81891",title:"Alternatives to Antibiotics in Semen Extenders Used in Artificial Insemination",slug:"alternatives-to-antibiotics-in-semen-extenders-used-in-artificial-insemination",totalDownloads:2,totalDimensionsCites:0,doi:"10.5772/intechopen.104226",abstract:"Antimicrobial resistance is a serious global threat requiring a widespread response. Both veterinarians and medical doctors should restrict antibiotic usage to therapeutic use only, after determining the sensitivity of the causal organism. However, the addition of antibiotics to semen extenders for animal artificial insemination represents a hidden, non-therapeutic use of antimicrobial substances. Artificial insemination for livestock breeding is a huge global enterprise with hundreds of million sperm doses prepared annually. However, reporting of antimicrobial resistance in semen is increasing. This review discusses the consequences of bacteria in semen samples, as well as the effect of antimicrobial substances in semen extenders on bacteria in the environment and even on personnel. Alternatives to antibiotics have been reported in the scientific literature and are reviewed here. The most promising of these, removal of the majority of bacteria by colloid centrifugation, is considered in detail, especially results from an artificial insemination study in pigs. In conclusion, colloid centrifugation is a practical method of physically removing bacteria from semen, which does not induce antibiotic resistance. Sperm quality in stored semen samples may be improved at the same time.",book:{id:"11373",title:"The Global Antimicrobial Resistance Epidemic – Innovative Approaches and Cutting-Edge Solutions",coverURL:"https://cdn.intechopen.com/books/images_new/11373.jpg"},signatures:"Jane M. Morrell, Pongpreecha Malaluang, Aleksandar Cojkic and Ingrid Hansson"},{id:"81295",title:"Inflammation-Based Markers of Nutrition in Cancer Patients",slug:"inflammation-based-markers-of-nutrition-in-cancer-patients",totalDownloads:5,totalDimensionsCites:0,doi:"10.5772/intechopen.104428",abstract:"Malnutrition and cachexia are common findings in cancer patients, and they predict poorer clinical outcomes. Close to half of cancer patients regardless of cancer type have malnutrition and will require one form of nutritional support either before or during treatment. The early identification of malnutrition is thus important to physicians and caregivers. The role of inflammation in the development and progression of malnutrition and cachexia is being unravelled. Increasing evidence shows that systemic inflammatory response and nutritional status are involved in tumour development and influence the clinical prognosis. Serum proteins such as albumin and prealbumin have traditionally been used by physicians to determine patient nutritional status. More recently, inflammation-based prognostic scores including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), C reactive protein-to-albumin ratio (CAR), prognostic nutritional index (PNI), Glasgow Prognostic Score (GPS) have shown promise and have begun to be used in clinical practice to predict prognosis of cancer patients. This chapter highlights the role and pathophysiology of inflammation-based markers in assessing malnutrition and cachexia and their relationship to clinical screening tools.",book:{id:"11090",title:"Malnutrition",coverURL:"https://cdn.intechopen.com/books/images_new/11090.jpg"},signatures:"Ogochukwu Izuegbuna"},{id:"81883",title:"Winter Strawberries Production in Greenhouse Soilless Culture under an Arid Climate—Cultivars, Phenology, Physiology, and Consequent Practices",slug:"winter-strawberries-production-in-greenhouse-soilless-culture-under-an-arid-climate-cultivars-phenol",totalDownloads:2,totalDimensionsCites:0,doi:"10.5772/intechopen.104390",abstract:"Fifteen years of research and development aimed at the production of high-quality early-winter strawberries in the Negev desert, are concluded. This goal required synchronization of seasonal yields with the peaks of the markets\\' demand, November−February. For this purpose, selected infra short-day (ISD) cultivars were used. Rooted plug plants with enhanced capacity of simultaneous fast vegetative growth and fruiting were produced. Production was carried out in greenhouses and various protocols aimed at yield enhancement were tested. Currently, drip-fertigated, eye-level hanging soilless system, with plant density at about 200,000 plants ha−1, combined with biological pest management program, are employed. This system brought about a two-fold increase in yield compared to soil culture (80–100 t ha−1), significantly reduced risks of soil- and air-borne diseases, reduced the use of fungicides, and eased extensive labor demands. However, beyond substantial refinements of practices, a significant proportion, 15–25% of the seasonal high-quality yield, was harvested during the earlier two months with no reduction in the total yield or fruit quality. In this chapter, the state of art in early-winter strawberry production is portrayed, including principles, approaches, and methods that have been used and improved during the project. Additionally, ideas for further possible enhancement are discussed.",book:{id:"11338",title:"Strawberries",coverURL:"https://cdn.intechopen.com/books/images_new/11338.jpg"},signatures:"Ofer Guy, Nir Dai, Shabtai Cohen and Amnon Bustan"}],onlineFirstChaptersTotal:589},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:87,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:98,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:27,numberOfPublishedChapters:287,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:139,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:0,numberOfUpcomingTopics:2,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!1},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:10,numberOfPublishedChapters:103,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:0,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!1},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:10,numberOfOpenTopics:4,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}},{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}}]},series:{item:{id:"25",title:"Environmental Sciences",doi:"10.5772/intechopen.100362",issn:"2754-6713",scope:"
\r\n\tScientists have long researched to understand the environment and man’s place in it. The search for this knowledge grows in importance as rapid increases in population and economic development intensify humans’ stresses on ecosystems. Fortunately, rapid increases in multiple scientific areas are advancing our understanding of environmental sciences. Breakthroughs in computing, molecular biology, ecology, and sustainability science are enhancing our ability to utilize environmental sciences to address real-world problems. \r\n\tThe four topics of this book series - Pollution; Environmental Resilience and Management; Ecosystems and Biodiversity; and Water Science - will address important areas of advancement in the environmental sciences. They will represent an excellent initial grouping of published works on these critical topics.
",coverUrl:"https://cdn.intechopen.com/series/covers/25.jpg",latestPublicationDate:"April 13th, 2022",hasOnlineFirst:!1,numberOfPublishedBooks:1,editor:{id:"197485",title:"Dr.",name:"J. Kevin",middleName:null,surname:"Summers",slug:"j.-kevin-summers",fullName:"J. Kevin Summers",profilePictureURL:"https://mts.intechopen.com/storage/users/197485/images/system/197485.jpg",biography:"J. Kevin Summers is a Senior Research Ecologist at the Environmental Protection Agency’s (EPA) Gulf Ecosystem Measurement and Modeling Division. He is currently working with colleagues in the Sustainable and Healthy Communities Program to develop an index of community resilience to natural hazards, an index of human well-being that can be linked to changes in the ecosystem, social and economic services, and a community sustainability tool for communities with populations under 40,000. He leads research efforts for indicator and indices development. Dr. Summers is a systems ecologist and began his career at the EPA in 1989 and has worked in various programs and capacities. This includes leading the National Coastal Assessment in collaboration with the Office of Water which culminated in the award-winning National Coastal Condition Report series (four volumes between 2001 and 2012), and which integrates water quality, sediment quality, habitat, and biological data to assess the ecosystem condition of the United States estuaries. He was acting National Program Director for Ecology for the EPA between 2004 and 2006. He has authored approximately 150 peer-reviewed journal articles, book chapters, and reports and has received many awards for technical accomplishments from the EPA and from outside of the agency. Dr. Summers holds a BA in Zoology and Psychology, an MA in Ecology, and Ph.D. in Systems Ecology/Biology.",institutionString:null,institution:{name:"Environmental Protection Agency",institutionURL:null,country:{name:"United States of America"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:11,paginationItems:[{id:"38",title:"Pollution",coverUrl:"https://cdn.intechopen.com/series_topics/covers/38.jpg",editor:{id:"110740",title:"Dr.",name:"Ismail M.M.",middleName:null,surname:"Rahman",slug:"ismail-m.m.-rahman",fullName:"Ismail M.M. Rahman",profilePictureURL:"https://mts.intechopen.com/storage/users/110740/images/2319_n.jpg",biography:"Ismail Md. Mofizur Rahman (Ismail M. M. Rahman) assumed his current responsibilities as an Associate Professor at the Institute of Environmental Radioactivity, Fukushima University, Japan, in Oct 2015. He also has an honorary appointment to serve as a Collaborative Professor at Kanazawa University, Japan, from Mar 2015 to the present. \nFormerly, Dr. Rahman was a faculty member of the University of Chittagong, Bangladesh, affiliated with the Department of Chemistry (Oct 2002 to Mar 2012) and the Department of Applied Chemistry and Chemical Engineering (Mar 2012 to Sep 2015). Dr. Rahman was also adjunctly attached with Kanazawa University, Japan (Visiting Research Professor, Dec 2014 to Mar 2015; JSPS Postdoctoral Research Fellow, Apr 2012 to Mar 2014), and Tokyo Institute of Technology, Japan (TokyoTech-UNESCO Research Fellow, Oct 2004–Sep 2005). \nHe received his Ph.D. degree in Environmental Analytical Chemistry from Kanazawa University, Japan (2011). He also achieved a Diploma in Environment from the Tokyo Institute of Technology, Japan (2005). Besides, he has an M.Sc. degree in Applied Chemistry and a B.Sc. degree in Chemistry, all from the University of Chittagong, Bangladesh. \nDr. Rahman’s research interest includes the study of the fate and behavior of environmental pollutants in the biosphere; design of low energy and low burden environmental improvement (remediation) technology; implementation of sustainable waste management practices for treatment, handling, reuse, and ultimate residual disposition of solid wastes; nature and type of interactions in organic liquid mixtures for process engineering design applications.",institutionString:null,institution:{name:"Fukushima University",institutionURL:null,country:{name:"Japan"}}},editorTwo:{id:"201020",title:"Dr.",name:"Zinnat Ara",middleName:null,surname:"Begum",slug:"zinnat-ara-begum",fullName:"Zinnat Ara Begum",profilePictureURL:"https://mts.intechopen.com/storage/users/201020/images/system/201020.jpeg",biography:"Zinnat A. Begum received her Ph.D. in Environmental Analytical Chemistry from Kanazawa University in 2012. She achieved her Master of Science (M.Sc.) degree with a major in Applied Chemistry and a Bachelor of Science (B.Sc.) in Chemistry, all from the University of Chittagong, Bangladesh. Her work affiliations include Fukushima University, Japan (Visiting Research Fellow, Institute of Environmental Radioactivity: Mar 2016 to present), Southern University Bangladesh (Assistant Professor, Department of Civil Engineering: Jan 2015 to present), and Kanazawa University, Japan (Postdoctoral Fellow, Institute of Science and Engineering: Oct 2012 to Mar 2014; Research fellow, Venture Business Laboratory, Advanced Science and Social Co-Creation Promotion Organization: Apr 2018 to Mar 2021). The research focus of Dr. Zinnat includes the effect of the relative stability of metal-chelator complexes in the environmental remediation process designs and the development of eco-friendly soil washing techniques using biodegradable chelators.",institutionString:null,institution:{name:"Fukushima University",institutionURL:null,country:{name:"Japan"}}},editorThree:null,editorialBoard:[{id:"252368",title:"Dr.",name:"Meng-Chuan",middleName:null,surname:"Ong",slug:"meng-chuan-ong",fullName:"Meng-Chuan Ong",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRVotQAG/Profile_Picture_2022-05-20T12:04:28.jpg",institutionString:null,institution:{name:"Universiti Malaysia Terengganu",institutionURL:null,country:{name:"Malaysia"}}},{id:"63465",title:"Prof.",name:"Mohamed Nageeb",middleName:null,surname:"Rashed",slug:"mohamed-nageeb-rashed",fullName:"Mohamed Nageeb Rashed",profilePictureURL:"https://mts.intechopen.com/storage/users/63465/images/system/63465.gif",institutionString:null,institution:{name:"Aswan University",institutionURL:null,country:{name:"Egypt"}}},{id:"187907",title:"Dr.",name:"Olga",middleName:null,surname:"Anne",slug:"olga-anne",fullName:"Olga Anne",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSBE5QAO/Profile_Picture_2022-04-07T09:42:13.png",institutionString:null,institution:{name:"Klaipeda State University of Applied Sciences",institutionURL:null,country:{name:"Lithuania"}}}]},{id:"39",title:"Environmental Resilience and Management",coverUrl:"https://cdn.intechopen.com/series_topics/covers/39.jpg",editor:{id:"137040",title:"Prof.",name:"Jose",middleName:null,surname:"Navarro-Pedreño",slug:"jose-navarro-pedreno",fullName:"Jose Navarro-Pedreño",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRAXrQAO/Profile_Picture_2022-03-09T15:50:19.jpg",biography:"Full professor at University Miguel Hernández of Elche, Spain, previously working at the University of Alicante, Autonomous University of Madrid and Polytechnic University of Valencia. Graduate in Sciences (Chemist), graduate in Geography and History (Geography), master in Water Management, Treatment, master in Fertilizers and Environment and master in Environmental Management; Ph.D. in Environmental Sciences. His research is focused on soil-water and waste-environment relations, mainly on soil-water and soil-waste interactions under different management and waste reuse. His work is reflected in more than 230 communications presented in national and international conferences and congresses, 29 invited lectures from universities, associations and government agencies. Prof. Navarro-Pedreño is also a director of the Ph.D. Program Environment and Sustainability (2012-present) and a member of several societies among which are the Spanish Society of Soil Science, International Union of Soil Sciences, European Society for Soil Conservation, DessertNet and the Spanish Royal Society of Chemistry.",institutionString:"Miguel Hernández University of Elche, Spain",institution:null},editorTwo:null,editorThree:null,editorialBoard:[{id:"177015",title:"Prof.",name:"Elke Jurandy",middleName:null,surname:"Bran Nogueira Cardoso",slug:"elke-jurandy-bran-nogueira-cardoso",fullName:"Elke Jurandy Bran Nogueira Cardoso",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRGxzQAG/Profile_Picture_2022-03-25T08:32:33.jpg",institutionString:"Universidade de São Paulo, Brazil",institution:null},{id:"211260",title:"Dr.",name:"Sandra",middleName:null,surname:"Ricart",slug:"sandra-ricart",fullName:"Sandra Ricart",profilePictureURL:"https://mts.intechopen.com/storage/users/211260/images/system/211260.jpeg",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}}]},{id:"40",title:"Ecosystems and Biodiversity",coverUrl:"https://cdn.intechopen.com/series_topics/covers/40.jpg",editor:{id:"209149",title:"Prof.",name:"Salustiano",middleName:null,surname:"Mato",slug:"salustiano-mato",fullName:"Salustiano Mato",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRLREQA4/Profile_Picture_2022-03-31T10:23:50.png",biography:"Salustiano Mato de la Iglesia (Santiago de Compostela, 1960) is a doctor in biology from the University of Santiago and a Professor of zoology at the Department of Ecology and Animal Biology at the University of Vigo. He has developed his research activity in the fields of fauna and soil ecology, and in the treatment of organic waste, having been the founder and principal investigator of the Environmental Biotechnology Group of the University of Vigo.\r\nHis research activity in the field of Environmental Biotechnology has been focused on the development of novel organic waste treatment systems through composting. The result of this line of work are three invention patents and various scientific and technical publications in prestigious international journals.",institutionString:null,institution:{name:"University of Vigo",institutionURL:null,country:{name:"Spain"}}},editorTwo:{id:"60498",title:"Prof.",name:"Josefina",middleName:null,surname:"Garrido",slug:"josefina-garrido",fullName:"Josefina Garrido",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRj1VQAS/Profile_Picture_2022-03-31T10:06:51.jpg",biography:"Josefina Garrido González (Paradela de Abeleda, Ourense 1959), is a doctor in biology from the University of León and a Professor of Zoology at the Department of Ecology and Animal Biology at the University of Vigo. 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Radiotherapy and Nuclear Medicine Technology has always been my aspiration and my life. As years passed I accumulated a tremendous amount of skills and knowledge in Radiotherapy and Nuclear Medicine, Conventional Radiology, Radiation Protection, Bioinformatics Technology, PACS, Image processing, clinically and lecturing that will enable me to provide a valuable service to the community as a Researcher and Consultant in this field. My method of translating this into day to day in clinical practice is non-exhaustible and my habit of exchanging knowledge and expertise with others in those fields is the code and secret of success.",institutionString:null,institution:{name:"Majmaah University",country:{name:"Saudi Arabia"}}},{id:"313277",title:"Dr.",name:"Bartłomiej",middleName:null,surname:"Płaczek",slug:"bartlomiej-placzek",fullName:"Bartłomiej Płaczek",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/313277/images/system/313277.jpg",biography:"Bartłomiej Płaczek, MSc (2002), Ph.D. (2005), Habilitation (2016), is a professor at the University of Silesia, Institute of Computer Science, Poland, and an expert from the National Centre for Research and Development. His research interests include sensor networks, smart sensors, intelligent systems, and image processing with applications in healthcare and medicine. He is the author or co-author of more than seventy papers in peer-reviewed journals and conferences as well as the co-author of several books. He serves as a reviewer for many scientific journals, international conferences, and research foundations. Since 2010, Dr. Placzek has been a reviewer of grants and projects (including EU projects) in the field of information technologies.",institutionString:"University of Silesia",institution:{name:"University of Silesia",country:{name:"Poland"}}},{id:"35000",title:"Prof.",name:"Ulrich H.P",middleName:"H.P.",surname:"Fischer",slug:"ulrich-h.p-fischer",fullName:"Ulrich H.P Fischer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/35000/images/3052_n.jpg",biography:"Academic and Professional Background\nUlrich H. P. has Diploma and PhD degrees in Physics from the Free University Berlin, Germany. He has been working on research positions in the Heinrich-Hertz-Institute in Germany. Several international research projects has been performed with European partners from France, Netherlands, Norway and the UK. He is currently Professor of Communications Systems at the Harz University of Applied Sciences, Germany.\n\nPublications and Publishing\nHe has edited one book, a special interest book about ‘Optoelectronic Packaging’ (VDE, Berlin, Germany), and has published over 100 papers and is owner of several international patents for WDM over POF key elements.\n\nKey Research and Consulting Interests\nUlrich’s research activity has always been related to Spectroscopy and Optical Communications Technology. Specific current interests include the validation of complex instruments, and the application of VR technology to the development and testing of measurement systems. He has been reviewer for several publications of the Optical Society of America\\'s including Photonics Technology Letters and Applied Optics.\n\nPersonal Interests\nThese include motor cycling in a very relaxed manner and performing martial arts.",institutionString:null,institution:{name:"Charité",country:{name:"Germany"}}},{id:"341622",title:"Ph.D.",name:"Eduardo",middleName:null,surname:"Rojas Alvarez",slug:"eduardo-rojas-alvarez",fullName:"Eduardo Rojas Alvarez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/341622/images/15892_n.jpg",biography:null,institutionString:null,institution:{name:"University of Cuenca",country:{name:"Ecuador"}}},{id:"215610",title:"Prof.",name:"Muhammad",middleName:null,surname:"Sarfraz",slug:"muhammad-sarfraz",fullName:"Muhammad Sarfraz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/215610/images/system/215610.jpeg",biography:"Muhammad Sarfraz is a professor in the Department of Information Science, Kuwait University, Kuwait. His research interests include optimization, computer graphics, computer vision, image processing, machine learning, pattern recognition, soft computing, data science, and intelligent systems. Prof. Sarfraz has been a keynote/invited speaker at various platforms around the globe. He has advised/supervised more than 110 students for their MSc and Ph.D. theses. He has published more than 400 publications as books, journal articles, and conference papers. He has authored and/or edited around seventy books. Prof. Sarfraz is a member of various professional societies. He is a chair and member of international advisory committees and organizing committees of numerous international conferences. He is also an editor and editor in chief for various international journals.",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"32650",title:"Prof.",name:"Lukas",middleName:"Willem",surname:"Snyman",slug:"lukas-snyman",fullName:"Lukas Snyman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/32650/images/4136_n.jpg",biography:"Lukas Willem Snyman received his basic education at primary and high schools in South Africa, Eastern Cape. He enrolled at today's Nelson Metropolitan University and graduated from this university with a BSc in Physics and Mathematics, B.Sc Honors in Physics, MSc in Semiconductor Physics, and a Ph.D. in Semiconductor Physics in 1987. After his studies, he chose an academic career and devoted his energy to the teaching of physics to first, second, and third-year students. After positions as a lecturer at the University of Port Elizabeth, he accepted a position as Associate Professor at the University of Pretoria, South Africa.\r\n\r\nIn 1992, he motivates the concept of 'television and computer-based education” as means to reach large student numbers with only the best of teaching expertise and publishes an article on the concept in the SA Journal of Higher Education of 1993 (and later in 2003). The University of Pretoria subsequently approved a series of test projects on the concept with outreach to Mamelodi and Eerste Rust in 1993. In 1994, the University established a 'Unit for Telematic Education ' as a support section for multiple faculties at the University of Pretoria. In subsequent years, the concept of 'telematic education” subsequently becomes well established in academic circles in South Africa, grew in popularity, and is adopted by many universities and colleges throughout South Africa as a medium of enhancing education and training, as a method to reaching out to far out communities, and as a means to enhance study from the home environment.\r\n\r\nProfessor Snyman in subsequent years pursued research in semiconductor physics, semiconductor devices, microelectronics, and optoelectronics.\r\n\r\nIn 2000 he joined the TUT as a full professor. Here served for a period as head of the Department of Electronic Engineering. Here he makes contributions to solar energy development, microwave and optoelectronic device development, silicon photonics, as well as contributions to new mobile telecommunication systems and network planning in SA.\r\n\r\nCurrently, he teaches electronics and telecommunications at the TUT to audiences ranging from first-year students to Ph.D. level.\r\n\r\nFor his research in the field of 'Silicon Photonics” since 1990, he has published (as author and co-author) about thirty internationally reviewed articles in scientific journals, contributed to more than forty international conferences, about 25 South African provisional patents (as inventor and co-inventor), 8 PCT international patent applications until now. Of these, two USA patents applications, two European Patents, two Korean patents, and ten SA patents have been granted. A further 4 USA patents, 5 European patents, 3 Korean patents, 3 Chinese patents, and 3 Japanese patents are currently under consideration.\r\n\r\nRecently he has also published an extensive scholarly chapter in an internet open access book on 'Integrating Microphotonic Systems and MOEMS into standard Silicon CMOS Integrated circuitry”.\r\n\r\nFurthermore, Professor Snyman recently steered a new initiative at the TUT by introducing a 'Laboratory for Innovative Electronic Systems ' at the Department of Electrical Engineering. The model of this laboratory or center is to primarily combine outputs as achieved by high-level research with lower-level system development and entrepreneurship in a technical university environment. Students are allocated to projects at different levels with PhDs and Master students allocated to the generation of new knowledge and new technologies, while students at the diploma and Baccalaureus level are allocated to electronic systems development with a direct and a near application for application in industry or the commercial and public sectors in South Africa.\r\n\r\nProfessor Snyman received the WIRSAM Award of 1983 and the WIRSAM Award in 1985 in South Africa for best research papers by a young scientist at two international conferences on electron microscopy in South Africa. He subsequently received the SA Microelectronics Award for the best dissertation emanating from studies executed at a South African university in the field of Physics and Microelectronics in South Africa in 1987. In October of 2011, Professor Snyman received the prestigious Institutional Award for 'Innovator of the Year” for 2010 at the Tshwane University of Technology, South Africa. This award was based on the number of patents recognized and granted by local and international institutions as well as for his contributions concerning innovation at the TUT.",institutionString:null,institution:{name:"University of South Africa",country:{name:"South Africa"}}},{id:"317279",title:"Mr.",name:"Ali",middleName:"Usama",surname:"Syed",slug:"ali-syed",fullName:"Ali Syed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/317279/images/16024_n.png",biography:"A creative, talented, and innovative young professional who is dedicated, well organized, and capable research fellow with two years of experience in graduate-level research, published in engineering journals and book, with related expertise in Bio-robotics, equally passionate about the aesthetics of the mechanical and electronic system, obtained expertise in the use of MS Office, MATLAB, SolidWorks, LabVIEW, Proteus, Fusion 360, having a grasp on python, C++ and assembly language, possess proven ability in acquiring research grants, previous appointments with social and educational societies with experience in administration, current affiliations with IEEE and Web of Science, a confident presenter at conferences and teacher in classrooms, able to explain complex information to audiences of all levels.",institutionString:null,institution:{name:"Air University",country:{name:"Pakistan"}}},{id:"75526",title:"Ph.D.",name:"Zihni Onur",middleName:null,surname:"Uygun",slug:"zihni-onur-uygun",fullName:"Zihni Onur Uygun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/75526/images/12_n.jpg",biography:"My undergraduate education and my Master of Science educations at Ege University and at Çanakkale Onsekiz Mart University have given me a firm foundation in Biochemistry, Analytical Chemistry, Biosensors, Bioelectronics, Physical Chemistry and Medicine. After obtaining my degree as a MSc in analytical chemistry, I started working as a research assistant in Ege University Medical Faculty in 2014. In parallel, I enrolled to the MSc program at the Department of Medical Biochemistry at Ege University to gain deeper knowledge on medical and biochemical sciences as well as clinical chemistry in 2014. In my PhD I deeply researched on biosensors and bioelectronics and finished in 2020. Now I have eleven SCI-Expanded Index published papers, 6 international book chapters, referee assignments for different SCIE journals, one international patent pending, several international awards, projects and bursaries. In parallel to my research assistant position at Ege University Medical Faculty, Department of Medical Biochemistry, in April 2016, I also founded a Start-Up Company (Denosens Biotechnology LTD) by the support of The Scientific and Technological Research Council of Turkey. Currently, I am also working as a CEO in Denosens Biotechnology. The main purposes of the company, which carries out R&D as a research center, are to develop new generation biosensors and sensors for both point-of-care diagnostics; such as glucose, lactate, cholesterol and cancer biomarker detections. My specific experimental and instrumental skills are Biochemistry, Biosensor, Analytical Chemistry, Electrochemistry, Mobile phone based point-of-care diagnostic device, POCTs and Patient interface designs, HPLC, Tandem Mass Spectrometry, Spectrophotometry, ELISA.",institutionString:null,institution:{name:"Ege University",country:{name:"Turkey"}}},{id:"246502",title:"Dr.",name:"Jaya T.",middleName:"T",surname:"Varkey",slug:"jaya-t.-varkey",fullName:"Jaya T. Varkey",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/246502/images/11160_n.jpg",biography:"Jaya T. Varkey, PhD, graduated with a degree in Chemistry from Cochin University of Science and Technology, Kerala, India. She obtained a PhD in Chemistry from the School of Chemical Sciences, Mahatma Gandhi University, Kerala, India, and completed a post-doctoral fellowship at the University of Minnesota, USA. She is a research guide at Mahatma Gandhi University and Associate Professor in Chemistry, St. Teresa’s College, Kochi, Kerala, India.\nDr. Varkey received a National Young Scientist award from the Indian Science Congress (1995), a UGC Research award (2016–2018), an Indian National Science Academy (INSA) Visiting Scientist award (2018–2019), and a Best Innovative Faculty award from the All India Association for Christian Higher Education (AIACHE) (2019). She Hashas received the Sr. Mary Cecil prize for best research paper three times. She was also awarded a start-up to develop a tea bag water filter. \nDr. Varkey has published two international books and twenty-seven international journal publications. She is an editorial board member for five international journals.",institutionString:"St. Teresa’s College",institution:null},{id:"250668",title:"Dr.",name:"Ali",middleName:null,surname:"Nabipour Chakoli",slug:"ali-nabipour-chakoli",fullName:"Ali Nabipour Chakoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/250668/images/system/250668.jpg",biography:"Academic Qualification:\r\n•\tPhD in Materials Physics and Chemistry, From: Sep. 2006, to: Sep. 2010, School of Materials Science and Engineering, Harbin Institute of Technology, Thesis: Structure and Shape Memory Effect of Functionalized MWCNTs/poly (L-lactide-co-ε-caprolactone) Nanocomposites. Supervisor: Prof. Wei Cai,\r\n•\tM.Sc in Applied Physics, From: 1996, to: 1998, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Determination of Boron in Micro alloy Steels with solid state nuclear track detectors by neutron induced auto radiography, Supervisors: Dr. M. Hosseini Ashrafi and Dr. A. Hosseini.\r\n•\tB.Sc. in Applied Physics, From: 1991, to: 1996, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Design of shielding for Am-Be neutron sources for In Vivo neutron activation analysis, Supervisor: Dr. M. Hosseini Ashrafi.\r\n\r\nResearch Experiences:\r\n1.\tNanomaterials, Carbon Nanotubes, Graphene: Synthesis, Functionalization and Characterization,\r\n2.\tMWCNTs/Polymer Composites: Fabrication and Characterization, \r\n3.\tShape Memory Polymers, Biodegradable Polymers, ORC, Collagen,\r\n4.\tMaterials Analysis and Characterizations: TEM, SEM, XPS, FT-IR, Raman, DSC, DMA, TGA, XRD, GPC, Fluoroscopy, \r\n5.\tInteraction of Radiation with Mater, Nuclear Safety and Security, NDT(RT),\r\n6.\tRadiation Detectors, Calibration (SSDL),\r\n7.\tCompleted IAEA e-learning Courses:\r\nNuclear Security (15 Modules),\r\nNuclear Safety:\r\nTSA 2: Regulatory Protection in Occupational Exposure,\r\nTips & Tricks: Radiation Protection in Radiography,\r\nSafety and Quality in Radiotherapy,\r\nCourse on Sealed Radioactive Sources,\r\nCourse on Fundamentals of Environmental Remediation,\r\nCourse on Planning for Environmental Remediation,\r\nKnowledge Management Orientation Course,\r\nFood Irradiation - Technology, Applications and Good Practices,\r\nEmployment:\r\nFrom 2010 to now: Academic staff, Nuclear Science and Technology Research Institute, Kargar Shomali, Tehran, Iran, P.O. Box: 14395-836.\r\nFrom 1997 to 2006: Expert of Materials Analysis and Characterization. Research Center of Agriculture and Medicine. Rajaeeshahr, Karaj, Iran, P. O. Box: 31585-498.",institutionString:"Atomic Energy Organization of Iran",institution:{name:"Atomic Energy Organization of Iran",country:{name:"Iran"}}},{id:"248279",title:"Dr.",name:"Monika",middleName:"Elzbieta",surname:"Machoy",slug:"monika-machoy",fullName:"Monika Machoy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248279/images/system/248279.jpeg",biography:"Monika Elżbieta Machoy, MD, graduated with distinction from the Faculty of Medicine and Dentistry at the Pomeranian Medical University in 2009, defended her PhD thesis with summa cum laude in 2016 and is currently employed as a researcher at the Department of Orthodontics of the Pomeranian Medical University. She expanded her professional knowledge during a one-year scholarship program at the Ernst Moritz Arndt University in Greifswald, Germany and during a three-year internship at the Technical University in Dresden, Germany. She has been a speaker at numerous orthodontic conferences, among others, American Association of Orthodontics, European Orthodontic Symposium and numerous conferences of the Polish Orthodontic Society. She conducts research focusing on the effect of orthodontic treatment on dental and periodontal tissues and the causes of pain in orthodontic patients.",institutionString:"Pomeranian Medical University",institution:{name:"Pomeranian Medical University",country:{name:"Poland"}}},{id:"252743",title:"Prof.",name:"Aswini",middleName:"Kumar",surname:"Kar",slug:"aswini-kar",fullName:"Aswini Kar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252743/images/10381_n.jpg",biography:"uploaded in cv",institutionString:null,institution:{name:"KIIT University",country:{name:"India"}}},{id:"204256",title:"Dr.",name:"Anil",middleName:"Kumar",surname:"Kumar Sahu",slug:"anil-kumar-sahu",fullName:"Anil Kumar Sahu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204256/images/14201_n.jpg",biography:"I have nearly 11 years of research and teaching experience. I have done my master degree from University Institute of Pharmacy, Pt. Ravi Shankar Shukla University, Raipur, Chhattisgarh India. I have published 16 review and research articles in international and national journals and published 4 chapters in IntechOpen, the world’s leading publisher of Open access books. I have presented many papers at national and international conferences. I have received research award from Indian Drug Manufacturers Association in year 2015. My research interest extends from novel lymphatic drug delivery systems, oral delivery system for herbal bioactive to formulation optimization.",institutionString:null,institution:{name:"Chhattisgarh Swami Vivekanand Technical University",country:{name:"India"}}},{id:"253468",title:"Dr.",name:"Mariusz",middleName:null,surname:"Marzec",slug:"mariusz-marzec",fullName:"Mariusz Marzec",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/253468/images/system/253468.png",biography:"An assistant professor at Department of Biomedical Computer Systems, at Institute of Computer Science, Silesian University in Katowice. Scientific interests: computer analysis and processing of images, biomedical images, databases and programming languages. He is an author and co-author of scientific publications covering analysis and processing of biomedical images and development of database systems.",institutionString:"University of Silesia",institution:null},{id:"212432",title:"Prof.",name:"Hadi",middleName:null,surname:"Mohammadi",slug:"hadi-mohammadi",fullName:"Hadi Mohammadi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/212432/images/system/212432.jpeg",biography:"Dr. Hadi Mohammadi is a biomedical engineer with hands-on experience in the design and development of many engineering structures and medical devices through various projects that he has been involved in over the past twenty years. Dr. Mohammadi received his BSc. and MSc. degrees in Mechanical Engineering from Sharif University of Technology, Tehran, Iran, and his PhD. degree in Biomedical Engineering (biomaterials) from the University of Western Ontario. He was a postdoctoral trainee for almost four years at University of Calgary and Harvard Medical School. He is an industry innovator having created the technology to produce lifelike synthetic platforms that can be used for the simulation of almost all cardiovascular reconstructive surgeries. He’s been heavily involved in the design and development of cardiovascular devices and technology for the past 10 years. He is currently an Assistant Professor with the University of British Colombia, Canada.",institutionString:"University of British Columbia",institution:{name:"University of British Columbia",country:{name:"Canada"}}},{id:"254463",title:"Prof.",name:"Haisheng",middleName:null,surname:"Yang",slug:"haisheng-yang",fullName:"Haisheng Yang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/254463/images/system/254463.jpeg",biography:"Haisheng Yang, Ph.D., Professor and Director of the Department of Biomedical Engineering, College of Life Science and Bioengineering, Beijing University of Technology. He received his Ph.D. degree in Mechanics/Biomechanics from Harbin Institute of Technology (jointly with University of California, Berkeley). Afterwards, he worked as a Postdoctoral Research Associate in the Purdue Musculoskeletal Biology and Mechanics Lab at the Department of Basic Medical Sciences, Purdue University, USA. He also conducted research in the Research Centre of Shriners Hospitals for Children-Canada at McGill University, Canada. Dr. Yang has over 10 years research experience in orthopaedic biomechanics and mechanobiology of bone adaptation and regeneration. He earned an award from Beijing Overseas Talents Aggregation program in 2017 and serves as Beijing Distinguished Professor.",institutionString:"Beijing University of Technology",institution:null},{id:"255757",title:"Dr.",name:"Igor",middleName:"Victorovich",surname:"Lakhno",slug:"igor-lakhno",fullName:"Igor Lakhno",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255757/images/system/255757.jpg",biography:"Lakhno Igor Victorovich was born in 1971 in Kharkiv (Ukraine). \nMD – 1994, Kharkiv National Medical Univesity.\nOb&Gyn; – 1997, master courses in Kharkiv Medical Academy of Postgraduate Education.\nPhD – 1999, Kharkiv National Medical Univesity.\nDSc – 2019, PL Shupik National Academy of Postgraduate Education \nLakhno Igor has been graduated from an international training courses on reproductive medicine and family planning held in Debrecen University (Hungary) in 1997. Since 1998 Lakhno Igor has worked as an associate professor of the department of obstetrics and gynecology of VN Karazin National University and an associate professor of the perinatology, obstetrics and gynecology department of Kharkiv Medical Academy of Postgraduate Education. Since June 2019 he’s a professor of the department of obstetrics and gynecology of VN Karazin National University and a professor of the perinatology, obstetrics and gynecology department of Kharkiv Medical Academy of Postgraduate Education . He’s an author of about 200 printed works and there are 17 of them in Scopus or Web of Science databases. Lakhno Igor is a rewiever of Journal of Obstetrics and Gynaecology (Taylor and Francis), Informatics in Medicine Unlocked (Elsevier), The Journal of Obstetrics and Gynecology Research (Wiley), Endocrine, Metabolic & Immune Disorders-Drug Targets (Bentham Open), The Open Biomedical Engineering Journal (Bentham Open), etc. He’s defended a dissertation for DSc degree \\'Pre-eclampsia: prediction, prevention and treatment”. Lakhno Igor has participated as a speaker in several international conferences and congresses (International Conference on Biological Oscillations April 10th-14th 2016, Lancaster, UK, The 9th conference of the European Study Group on Cardiovascular Oscillations). His main scientific interests: obstetrics, women’s health, fetal medicine, cardiovascular medicine.",institutionString:"V.N. Karazin Kharkiv National University",institution:{name:"Kharkiv Medical Academy of Postgraduate Education",country:{name:"Ukraine"}}},{id:"89721",title:"Dr.",name:"Mehmet",middleName:"Cuneyt",surname:"Ozmen",slug:"mehmet-ozmen",fullName:"Mehmet Ozmen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/89721/images/7289_n.jpg",biography:null,institutionString:null,institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"243698",title:"M.D.",name:"Xiaogang",middleName:null,surname:"Wang",slug:"xiaogang-wang",fullName:"Xiaogang Wang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243698/images/system/243698.png",biography:"Dr. Xiaogang Wang, a faculty member of Shanxi Eye Hospital specializing in the treatment of cataract and retinal disease and a tutor for postgraduate students of Shanxi Medical University, worked in the COOL Lab as an international visiting scholar under the supervision of Dr. David Huang and Yali Jia from October 2012 through November 2013. Dr. Wang earned an MD from Shanxi Medical University and a Ph.D. from Shanghai Jiao Tong University. Dr. Wang was awarded two research project grants focused on multimodal optical coherence tomography imaging and deep learning in cataract and retinal disease, from the National Natural Science Foundation of China. He has published around 30 peer-reviewed journal papers and four book chapters and co-edited one book.",institutionString:"Shanxi Eye Hospital",institution:{name:"Shanxi Eye Hospital",country:{name:"China"}}},{id:"242893",title:"Ph.D. Student",name:"Joaquim",middleName:null,surname:"De Moura",slug:"joaquim-de-moura",fullName:"Joaquim De Moura",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/242893/images/7133_n.jpg",biography:"Joaquim de Moura received his degree in Computer Engineering in 2014 from the University of A Coruña (Spain). In 2016, he received his M.Sc degree in Computer Engineering from the same university. He is currently pursuing his Ph.D degree in Computer Science in a collaborative project between ophthalmology centers in Galicia and the University of A Coruña. His research interests include computer vision, machine learning algorithms and analysis and medical imaging processing of various kinds.",institutionString:null,institution:{name:"University of A Coruña",country:{name:"Spain"}}},{id:"267434",title:"Dr.",name:"Rohit",middleName:null,surname:"Raja",slug:"rohit-raja",fullName:"Rohit Raja",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRZkkQAG/Profile_Picture_2022-05-09T12:55:18.jpg",biography:null,institutionString:null,institution:null},{id:"294334",title:"B.Sc.",name:"Marc",middleName:null,surname:"Bruggeman",slug:"marc-bruggeman",fullName:"Marc Bruggeman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/294334/images/8242_n.jpg",biography:"Chemical engineer graduate, with a passion for material science and specific interest in polymers - their near infinite applications intrigue me. \n\nI plan to continue my scientific career in the field of polymeric biomaterials as I am fascinated by intelligent, bioactive and biomimetic materials for use in both consumer and medical applications.",institutionString:null,institution:null},{id:"244950",title:"Dr.",name:"Salvatore",middleName:null,surname:"Di Lauro",slug:"salvatore-di-lauro",fullName:"Salvatore Di Lauro",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0030O00002bSF1HQAW/ProfilePicture%202021-12-20%2014%3A54%3A14.482",biography:"Name:\n\tSALVATORE DI LAURO\nAddress:\n\tHospital Clínico Universitario Valladolid\nAvda Ramón y Cajal 3\n47005, Valladolid\nSpain\nPhone number: \nFax\nE-mail:\n\t+34 983420000 ext 292\n+34 983420084\nsadilauro@live.it\nDate and place of Birth:\nID Number\nMedical Licence \nLanguages\t09-05-1985. Villaricca (Italy)\n\nY1281863H\n474707061\nItalian (native language)\nSpanish (read, written, spoken)\nEnglish (read, written, spoken)\nPortuguese (read, spoken)\nFrench (read)\n\t\t\nCurrent position (title and company)\tDate (Year)\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. Private practise.\t2017-today\n\n2019-today\n\t\n\t\nEducation (High school, university and postgraduate training > 3 months)\tDate (Year)\nDegree in Medicine and Surgery. University of Neaples 'Federico II”\nResident in Opthalmology. Hospital Clinico Universitario Valladolid\nMaster in Vitreo-Retina. IOBA. University of Valladolid\nFellow of the European Board of Ophthalmology. Paris\nMaster in Research in Ophthalmology. University of Valladolid\t2003-2009\n2012-2016\n2016-2017\n2016\n2012-2013\n\t\nEmployments (company and positions)\tDate (Year)\nResident in Ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl.\nFellow in Vitreo-Retina. IOBA. University of Valladolid\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. \n\t2012-2016\n2016-2017\n2017-today\n\n2019-Today\n\n\n\t\nClinical Research Experience (tasks and role)\tDate (Year)\nAssociated investigator\n\n' FIS PI20/00740: DESARROLLO DE UNA CALCULADORA DE RIESGO DE\nAPARICION DE RETINOPATIA DIABETICA BASADA EN TECNICAS DE IMAGEN MULTIMODAL EN PACIENTES DIABETICOS TIPO 1. Grant by: Ministerio de Ciencia e Innovacion \n\n' (BIO/VA23/14) Estudio clínico multicéntrico y prospectivo para validar dos\nbiomarcadores ubicados en los genes p53 y MDM2 en la predicción de los resultados funcionales de la cirugía del desprendimiento de retina regmatógeno. Grant by: Gerencia Regional de Salud de la Junta de Castilla y León.\n' Estudio multicéntrico, aleatorizado, con enmascaramiento doble, en 2 grupos\nparalelos y de 52 semanas de duración para comparar la eficacia, seguridad e inmunogenicidad de SOK583A1 respecto a Eylea® en pacientes con degeneración macular neovascular asociada a la edad' (CSOK583A12301; N.EUDRA: 2019-004838-41; FASE III). Grant by Hexal AG\n\n' Estudio de fase III, aleatorizado, doble ciego, con grupos paralelos, multicéntrico para comparar la eficacia y la seguridad de QL1205 frente a Lucentis® en pacientes con degeneración macular neovascular asociada a la edad. (EUDRACT: 2018-004486-13). Grant by Qilu Pharmaceutical Co\n\n' Estudio NEUTON: Ensayo clinico en fase IV para evaluar la eficacia de aflibercept en pacientes Naive con Edema MacUlar secundario a Oclusion de Vena CenTral de la Retina (OVCR) en regimen de tratamientO iNdividualizado Treat and Extend (TAE)”, (2014-000975-21). Grant by Fundacion Retinaplus\n\n' Evaluación de la seguridad y bioactividad de anillos de tensión capsular en conejo. Proyecto Procusens. Grant by AJL, S.A.\n\n'Estudio epidemiológico, prospectivo, multicéntrico y abierto\\npara valorar la frecuencia de la conjuntivitis adenovírica diagnosticada mediante el test AdenoPlus®\\nTest en pacientes enfermos de conjuntivitis aguda”\\n. National, multicenter study. Grant by: NICOX.\n\nEuropean multicentric trial: 'Evaluation of clinical outcomes following the use of Systane Hydration in patients with dry eye”. Study Phase 4. Grant by: Alcon Labs'\n\nVLPs Injection and Activation in a Rabbit Model of Uveal Melanoma. Grant by Aura Bioscience\n\nUpdating and characterization of a rabbit model of uveal melanoma. Grant by Aura Bioscience\n\nEnsayo clínico en fase IV para evaluar las variantes genéticas de la vía del VEGF como biomarcadores de eficacia del tratamiento con aflibercept en pacientes con degeneración macular asociada a la edad (DMAE) neovascular. Estudio BIOIMAGE. IMO-AFLI-2013-01\n\nEstudio In-Eye:Ensayo clínico en fase IV, abierto, aleatorizado, de 2 brazos,\nmulticçentrico y de 12 meses de duración, para evaluar la eficacia y seguridad de un régimen de PRN flexible individualizado de 'esperar y extender' versus un régimen PRN según criterios de estabilización mediante evaluaciones mensuales de inyecciones intravítreas de ranibizumab 0,5 mg en pacientes naive con neovascularización coriodea secunaria a la degeneración macular relacionada con la edad. CP: CRFB002AES03T\n\nTREND: Estudio Fase IIIb multicéntrico, randomizado, de 12 meses de\nseguimiento con evaluador de la agudeza visual enmascarado, para evaluar la eficacia y la seguridad de ranibizumab 0.5mg en un régimen de tratar y extender comparado con un régimen mensual, en pacientes con degeneración macular neovascular asociada a la edad. CP: CRFB002A2411 Código Eudra CT:\n2013-002626-23\n\n\n\nPublications\t\n\n2021\n\n\n\n\n2015\n\n\n\n\n2021\n\n\n\n\n\n2021\n\n\n\n\n2015\n\n\n\n\n2015\n\n\n2014\n\n\n\n\n2015-16\n\n\n\n2015\n\n\n2014\n\n\n2014\n\n\n\n\n2014\n\n\n\n\n\n\n\n2014\n\nJose Carlos Pastor; Jimena Rojas; Salvador Pastor-Idoate; Salvatore Di Lauro; Lucia Gonzalez-Buendia; Santiago Delgado-Tirado. Proliferative vitreoretinopathy: A new concept of disease pathogenesis and practical\nconsequences. Progress in Retinal and Eye Research. 51, pp. 125 - 155. 03/2016. DOI: 10.1016/j.preteyeres.2015.07.005\n\n\nLabrador-Velandia S; Alonso-Alonso ML; Di Lauro S; García-Gutierrez MT; Srivastava GK; Pastor JC; Fernandez-Bueno I. Mesenchymal stem cells provide paracrine neuroprotective resources that delay degeneration of co-cultured organotypic neuroretinal cultures.Experimental Eye Research. 185, 17/05/2019. DOI: 10.1016/j.exer.2019.05.011\n\nSalvatore Di Lauro; Maria Teresa Garcia Gutierrez; Ivan Fernandez Bueno. Quantification of pigment epithelium-derived factor (PEDF) in an ex vivo coculture of retinal pigment epithelium cells and neuroretina.\nJournal of Allbiosolution. 2019. ISSN 2605-3535\n\nSonia Labrador Velandia; Salvatore Di Lauro; Alonso-Alonso ML; Tabera Bartolomé S; Srivastava GK; Pastor JC; Fernandez-Bueno I. Biocompatibility of intravitreal injection of human mesenchymal stem cells in immunocompetent rabbits. Graefe's archive for clinical and experimental ophthalmology. 256 - 1, pp. 125 - 134. 01/2018. DOI: 10.1007/s00417-017-3842-3\n\n\nSalvatore Di Lauro, David Rodriguez-Crespo, Manuel J Gayoso, Maria T Garcia-Gutierrez, J Carlos Pastor, Girish K Srivastava, Ivan Fernandez-Bueno. A novel coculture model of porcine central neuroretina explants and retinal pigment epithelium cells. Molecular Vision. 2016 - 22, pp. 243 - 253. 01/2016.\n\nSalvatore Di Lauro. Classifications for Proliferative Vitreoretinopathy ({PVR}): An Analysis of Their Use in Publications over the Last 15 Years. Journal of Ophthalmology. 2016, pp. 1 - 6. 01/2016. DOI: 10.1155/2016/7807596\n\nSalvatore Di Lauro; Rosa Maria Coco; Rosa Maria Sanabria; Enrique Rodriguez de la Rua; Jose Carlos Pastor. Loss of Visual Acuity after Successful Surgery for Macula-On Rhegmatogenous Retinal Detachment in a Prospective Multicentre Study. Journal of Ophthalmology. 2015:821864, 2015. DOI: 10.1155/2015/821864\n\nIvan Fernandez-Bueno; Salvatore Di Lauro; Ivan Alvarez; Jose Carlos Lopez; Maria Teresa Garcia-Gutierrez; Itziar Fernandez; Eva Larra; Jose Carlos Pastor. Safety and Biocompatibility of a New High-Density Polyethylene-Based\nSpherical Integrated Porous Orbital Implant: An Experimental Study in Rabbits. Journal of Ophthalmology. 2015:904096, 2015. DOI: 10.1155/2015/904096\n\nPastor JC; Pastor-Idoate S; Rodríguez-Hernandez I; Rojas J; Fernandez I; Gonzalez-Buendia L; Di Lauro S; Gonzalez-Sarmiento R. Genetics of PVR and RD. Ophthalmologica. 232 - Suppl 1, pp. 28 - 29. 2014\n\nRodriguez-Crespo D; Di Lauro S; Singh AK; Garcia-Gutierrez MT; Garrosa M; Pastor JC; Fernandez-Bueno I; Srivastava GK. Triple-layered mixed co-culture model of RPE cells with neuroretina for evaluating the neuroprotective effects of adipose-MSCs. Cell Tissue Res. 358 - 3, pp. 705 - 716. 2014.\nDOI: 10.1007/s00441-014-1987-5\n\nCarlo De Werra; Salvatore Condurro; Salvatore Tramontano; Mario Perone; Ivana Donzelli; Salvatore Di Lauro; Massimo Di Giuseppe; Rosa Di Micco; Annalisa Pascariello; Antonio Pastore; Giorgio Diamantis; Giuseppe Galloro. Hydatid disease of the liver: thirty years of surgical experience.Chirurgia italiana. 59 - 5, pp. 611 - 636.\n(Italia): 2007. ISSN 0009-4773\n\nChapters in books\n\t\n' Salvador Pastor Idoate; Salvatore Di Lauro; Jose Carlos Pastor Jimeno. PVR: Pathogenesis, Histopathology and Classification. Proliferative Vitreoretinopathy with Small Gauge Vitrectomy. Springer, 2018. ISBN 978-3-319-78445-8\nDOI: 10.1007/978-3-319-78446-5_2. \n\n' Salvatore Di Lauro; Maria Isabel Lopez Galvez. Quistes vítreos en una mujer joven. Problemas diagnósticos en patología retinocoroidea. Sociedad Española de Retina-Vitreo. 2018.\n\n' Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor Jimeno. iOCT in PVR management. OCT Applications in Opthalmology. pp. 1 - 8. INTECH, 2018. DOI: 10.5772/intechopen.78774.\n\n' Rosa Coco Martin; Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor. amponadores, manipuladores y tinciones en la cirugía del traumatismo ocular.Trauma Ocular. Ponencia de la SEO 2018..\n\n' LOPEZ GALVEZ; DI LAURO; CRESPO. OCT angiografia y complicaciones retinianas de la diabetes. PONENCIA SEO 2021, CAPITULO 20. (España): 2021.\n\n' Múltiples desprendimientos neurosensoriales bilaterales en paciente joven. Enfermedades Degenerativas De Retina Y Coroides. SERV 04/2016. \n' González-Buendía L; Di Lauro S; Pastor-Idoate S; Pastor Jimeno JC. Vitreorretinopatía proliferante (VRP) e inflamación: LA INFLAMACIÓN in «INMUNOMODULADORES Y ANTIINFLAMATORIOS: MÁS ALLÁ DE LOS CORTICOIDES. RELACION DE PONENCIAS DE LA SOCIEDAD ESPAÑOLA DE OFTALMOLOGIA. 10/2014.",institutionString:null,institution:null},{id:"265335",title:"Mr.",name:"Stefan",middleName:"Radnev",surname:"Stefanov",slug:"stefan-stefanov",fullName:"Stefan Stefanov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/265335/images/7562_n.jpg",biography:null,institutionString:null,institution:null},{id:"318905",title:"Prof.",name:"Elvis",middleName:"Kwason",surname:"Tiburu",slug:"elvis-tiburu",fullName:"Elvis Tiburu",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Ghana",country:{name:"Ghana"}}},{id:"336193",title:"Dr.",name:"Abdullah",middleName:null,surname:"Alamoudi",slug:"abdullah-alamoudi",fullName:"Abdullah Alamoudi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Majmaah University",country:{name:"Saudi Arabia"}}},{id:"318657",title:"MSc.",name:"Isabell",middleName:null,surname:"Steuding",slug:"isabell-steuding",fullName:"Isabell Steuding",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Harz University of Applied Sciences",country:{name:"Germany"}}},{id:"318656",title:"BSc.",name:"Peter",middleName:null,surname:"Kußmann",slug:"peter-kussmann",fullName:"Peter Kußmann",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Harz University of Applied Sciences",country:{name:"Germany"}}},{id:"338222",title:"Mrs.",name:"María José",middleName:null,surname:"Lucía Mudas",slug:"maria-jose-lucia-mudas",fullName:"María José Lucía Mudas",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Carlos III University of Madrid",country:{name:"Spain"}}},{id:"147824",title:"Mr.",name:"Pablo",middleName:null,surname:"Revuelta Sanz",slug:"pablo-revuelta-sanz",fullName:"Pablo Revuelta Sanz",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Carlos III University of Madrid",country:{name:"Spain"}}}]}},subseries:{item:{id:"86",type:"subseries",title:"Business and Management",keywords:"Demographic shifts, Innovation, Technology, Next-gen leaders, Worldwide environmental issues and clean technology, Uncertainty and political risks, Radical adjacency, Emergence of new business ecosystem type, Emergence of different leader and leader values types, Universal connector, Elastic enterprise, Business platform, Supply chain complexity",scope:"
\r\n\tThe Business and Management series topic focuses on the most pressing issues confronting organizations today and in the future. Businesses are trying to figure out how to lead in a time of global uncertainty. In emerging markets, issues such as ill-defined or unstable policies, as well as corrupt practices, can be hugely problematic. Changes in governments can result in new policy, regulations, and interest rates, all of which can be detrimental to foreign businesses and investments. A growing trend towards economic nationalism also makes the current global political landscape potentially hostile towards international businesses.
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\r\n\tThe demographic shifts are creating interesting challenges. People are living longer, resulting to an aging demographic. We have a large population of older workers and retirees who are living longer lives, combined with a declining birthrate in most parts of the world. Businesses of all types are looking at how technology is affecting their operations. Several questions arise, such as: How is technology changing what we do? How is it transforming us internally, how is it influencing our clients and our business strategy? It is about leveraging technology to improve efficiency, connect with customers more effectively, and drive innovation. The majority of innovative companies are technology-driven businesses. Realizing digital transformation is today’s top issue and will remain so for the next five years. Improving organizational agility, expanding portfolios of products and services, creating, and maintaining a culture of innovation, and developing next -generation leaders were also identified as top challenges in terms of both current and future issues.
\r\n
\r\n\tThe most sustained profitable growth occurs when a company expands its core business into an adjacent space. This has significant implications for management because innovation in business ecosystems differs from traditional, vertically integrated firms. Every organization in the ecosystem must be aware of the bigger picture. Innovation in ecosystems necessitates collaborative action to invent and appraise, efficient, cross-organizational knowledge flows, modular architectures, and good stewardship of legacy systems. It is built on multiple, interconnected platforms. Environmental factors have already had a significant impact in the West and will continue to have an impact globally. Businesses must take into account the environmental impact of their daily operations. The advantage of this market is that it is expected to grow more rapidly than the overall economy. Another significant challenge is preparing the next generation of leaders to elevate this to the number one priority within the next five years. There can be no culture of innovation unless there is diverse leadership or development of the next generation of leaders; and these diverse, next-generation leaders are the ones who will truly understand the digital strategies that will drive digital transformation.
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