Summary of antifungal agents used in Fungal Keratitis.
\\n\\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\\n\\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\\n"}]',published:!0,mainMedia:{caption:"Highly Cited",originalUrl:"/media/original/117"}},components:[{type:"htmlEditorComponent",content:'IntechOpen is proud to announce that 191 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\nThroughout the years, the list has named a total of 261 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\nReleased this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\n'}],latestNews:[{slug:"intechopen-supports-asapbio-s-new-initiative-publish-your-reviews-20220729",title:"IntechOpen Supports ASAPbio’s New Initiative Publish Your Reviews"},{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"}]},book:{item:{type:"book",id:"1374",leadTitle:null,fullTitle:"Aspects of Today's Cosmology",title:"Aspects of Today's Cosmology",subtitle:null,reviewType:"peer-reviewed",abstract:"This book presents some aspects of the cosmological scientific odyssey that started last century. The chapters vary with different particular works, giving a versatile picture. It is the result of the work of many scientists in the field of cosmology, in accordance with their expertise and particular interests. Is a collection of different research papers produced by important scientists in the field of cosmology. A sample of the great deal of efforts made by the scientific community, trying to understand our universe. And it has many challenging subjects, like the possible doomsday to be confirmed by the next decade of experimentation. May be we are now half way in the life of the universe. Many more challenging subjects are not present here: they will be the result of further future work. Among them, we have the possibility of cyclic universes, and the evidence for the existence of a previous universe.",isbn:null,printIsbn:"978-953-307-626-3",pdfIsbn:"978-953-51-4924-8",doi:"10.5772/1838",price:139,priceEur:155,priceUsd:179,slug:"aspects-of-today-s-cosmology",numberOfPages:410,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"6f152698fbe6139a2fe31a70ec8668d0",bookSignature:"Antonio Alfonso-Faus",publishedDate:"September 9th 2011",coverURL:"https://cdn.intechopen.com/books/images_new/1374.jpg",numberOfDownloads:39266,numberOfWosCitations:22,numberOfCrossrefCitations:5,numberOfCrossrefCitationsByBook:2,numberOfDimensionsCitations:16,numberOfDimensionsCitationsByBook:2,hasAltmetrics:0,numberOfTotalCitations:43,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"November 23rd 2010",dateEndSecondStepPublish:"December 21st 2010",dateEndThirdStepPublish:"April 27th 2011",dateEndFourthStepPublish:"May 27th 2011",dateEndFifthStepPublish:"July 26th 2011",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"62140",title:"Prof.",name:"Antonio",middleName:null,surname:"Alfonso-Faus",slug:"antonio-alfonso-faus",fullName:"Antonio Alfonso-Faus",profilePictureURL:"https://mts.intechopen.com/storage/users/62140/images/1128_n.png",biography:"Professor Antonio Alfonso-Faus holds a Diploma Space Science (Physics and Dynamics) from the University College, London (U.K. 1965), a M. Sci. and a Ph.D. degree in Physics and Mathematics from the University of Minnesota (U.S.A., 1968), and a Ph.D. degree in Aeronautical Engineering from the Technical University of Madrid (T.U.M., Spain, 1969). He was a Research Student, and a Research Fellow, in the field of Space Research (ESRO in Europe and NASA in the U.S.A.). He held the chair of mechanics, as Full Professor (E.U.I.T. Aeronáutica, Madrid, Spain, 1986). At present he is Emeritus Professor at the Technical University of Madrid (Spain, 2010). \nHis research work includes: the interplanetary magnetic field, the interaction of the solar wind with the Moon, the Moon´s wake observed by the satellite Explorer 35. The angular momentum of the sun, the rotation of the planets, the structure and evolution of the universe and quantum gravity as related to entropy-information theory.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Technical University of Madrid",institutionURL:null,country:{name:"Spain"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"633",title:"Physical Cosmology",slug:"cosmology-physical-cosmology"}],chapters:[{id:"18674",title:"Warm Inflationary Universe Models",doi:"10.5772/23035",slug:"warm-inflationary-universe-models",totalDownloads:2515,totalCrossrefCites:0,totalDimensionsCites:7,hasAltmetrics:0,abstract:null,signatures:"Sergio del Campo",downloadPdfUrl:"/chapter/pdf-download/18674",previewPdfUrl:"/chapter/pdf-preview/18674",authors:[{id:"50288",title:"Prof.",name:"Sergio",surname:"Del Campo",slug:"sergio-del-campo",fullName:"Sergio Del Campo"}],corrections:null},{id:"18675",title:"The Strained State Cosmology",doi:"10.5772/23164",slug:"the-strained-state-cosmology",totalDownloads:1760,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:null,signatures:"Angelo Tartaglia",downloadPdfUrl:"/chapter/pdf-download/18675",previewPdfUrl:"/chapter/pdf-preview/18675",authors:[{id:"50875",title:"Prof.",name:"Angelo",surname:"Tartaglia",slug:"angelo-tartaglia",fullName:"Angelo Tartaglia"}],corrections:null},{id:"18676",title:"Introduction to Modified Gravity: From the Cosmic Speedup Problem to Quantum Gravity Phenomenology",doi:"10.5772/25094",slug:"introduction-to-modified-gravity-from-the-cosmic-speedup-problem-to-quantum-gravity-phenomenology",totalDownloads:2182,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:null,signatures:"Gonzalo J. 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The operators may be presented abstractly by their characteristics, such as bounded linear operators or closed operators and consideration may be given to nonlinear operators. The study, which depends heavily on the topology of function spaces, is a branch of functional analysis. If a collection of operators forms an algebra over a field, then it is an operator algebra. The description of operator algebras is part of operator theory. Single operator theory deals with the properties and classification of operators, considered one at a time. For example, the classification of normal operators in terms of their spectra falls into this category.
\r\n\r\n\tThe theory of operator algebras brings algebras of operators such as C*-algebras to the fore. Many operators that are studied are operators on Hilbert spaces of holomorphic functions, and the study of the operator is intimately linked to questions in function theory. For example, Beurling's theorem describes the invariant subspaces of the unilateral shift in terms of inner functions, which are bounded holomorphic functions on the unit disk with unimodular boundary values almost everywhere on the circle. Beurling interpreted the unilateral shift as multiplication by the independent variable on the Hardy space. The success in studying multiplication operators, and more generally Toeplitz operators (which are multiplication, followed by projection onto the Hardy space) has inspired the study of similar questions in other spaces, such as the Bergman space. Hence, operator theory has a connection with complex analysis. Additionally, this book will be intended to be an illustration of the use of operator theory when applied to solve specific problems in pure and applied mathematics, engineering, physics, or science in general.
\r\n\t
Infectious keratitis is an inflammation of the cornea caused by microorganism. It is most commonly associated with bacterial, fungal or viral microorganisms that invade into the corneal stroma, resulting in inflammation and destruction of these structures; ultimately leading to visual impairment and blindness. Fungal keratitis (FK) or keratomycosis is one of the most challenging to diagnose and difficult to treat. The prevalence of fungal keratitis is variable depending upon the geographic location. It is more common in tropical and subtropical areas and relatively rare in temperate countries. It is reported about 1–60% of all cases of microbial keratitis in various studies [1, 2, 3]. A recent review including 37 countries reported highest proportion in Vietnam (59.58%) followed by Paraguay (58%) [2, 3, 4]. The fungi that commonly cause infection of the cornea include Fusarium, Aspergillus, Curvularia, Bipolaris, and Candida [1, 2, 5].
Most of the currently available antifungal medications have limitations, such as poor bioavailability and limited ocular penetration, especially in cases with deep keratitis [6, 7, 8]. This results in slow resolution of fungal infections. In addition, fungi can penetrate deeper into corneal stroma and Descemet membrane, therefore more difficult to eradicate. Surgical excision of the infected cornea is required to control the infection in nonresponsive cases [9, 10, 11, 12]. In recent years, considerable research is being continue in the field of management of fungal keratitis and several newer antifungal agents and drug delivery techniques are being evolved to overcome these limitations and improve outcome. In this chapter, we discuss the recent advances in diagnosis and treatment of fungal keratitis with a brief discussion on pathogenesis and future considerations.
Pathogenesis of FK has not been fully elucidated. Recent studies and advances have contributed in better understanding of the complicated process and host immune response.
The common risk factors for fungal keratitis are trauma with vegetative matter or objects contaminated with soil, contact lenses, ocular surface disease, lacrimal duct occlusion, fungal skin infections, long-term use of antibiotics or steroids locally or systemically [2, 13, 14, 15, 16, 17]. Other relatively rare risk factors include history of eye surgery, herpes simplex virus keratitis, eyelid abnormalities, etc. [18, 19].
Still in developing countries, the most common risk factor for fungal keratitis is ocular trauma but in developed countries, contact lens emerged as more common risk factor. This change has been occurred due to industrialization of farming and increase use of contact lens in developed world. In a large case series of 695 cases with fungal keratitis reported from 10 tertiary eye care centres across the United States over a 7-year period, 283 (40.71%) cases involved the use of contact lens [1]. Similarly Keay et al. in a multicentre case series of 733 cases from 11 tertiary care centres across the United States reported that 37% cases were associated with refractive contact lens wear, 25% were associated with ocular trauma, and 29% were associated with ocular surface disease [20].
In a study, the storage of the anti-microbial agent alexidine in its plastic containers at higher than room temperatures was found as the reason for decreased effectiveness [21]. This temperature difference in the plastic containers led to decreased concentration of the agent in solution (2.8 times less) and a corresponding higher concentration in the walls of its plastic containers (3.1 times higher) [22]. The lens type and its soaking time significantly influences the fungicidal activity of cleaning and storage solutions and poor compliance significantly increase the risk of contamination [23, 24].
A review article found about 144 species of fungi from 92 genera as causative agents in keratitis, showing largest diversity; whereas 77 species from 42 genera of bacteria, 12 species from 4 genera of protozoa and only 4 types of viruses were implicated in infectious keratitis. However, in the majority of cases of FK the causative organism belong to a few genera: Fusarium, Aspergillus, and Candida [25]. Other fungi implicated in mycotic keratitis are Curvularia, Alternaria, and Penicillium [2, 13, 14]. The rarely reported fungal pathogens include Lasiodiplodia theobromae, Cylindrocarpon species, Metarhizium anisopliae, Paecilomyces species, and Pythium insidiosum [15, 26, 27, 28, 29].
Fungal infections initiates with adhesion of fungal cells with epithelial surfaces. Fungi produce various surface proteins to contribute to the adhesion to the corneal epithelium, which has potential fungal binding sites such as laminins, fibronectins, and collagens [30, 31]. Alterations of the corneal surface due to trauma or other predisposing condition result in easy invasion of organisms deeper into underlying layers, which leads to an innate and adaptive immune-mediated inflammation, resulting in subsequent tissue necrosis of the surrounding area, consequently leads to further tissue damage, scarring, and opacification of the cornea.
The contact between fungi and host, result in expression of pattern recognition receptors (PRRs) on host epithelial and immune cells, which recognize the fungi. PPRs are Toll-like receptors (TLRs, including TLR2 and TLR4), C-type Lectin receptors (CLRs, including Dectin-1, Dectin-2 and Mincle). Dectin-1 recognizes β-glucan in fungal cell wall, while Dectin-2 and Mincle recognize mannan of cell wall [32].
Leal et al. found that neutrophils produced NADPH oxidase to control the growth of fungi. The antifungal activity of neutrophils depended on CD18, and inhibiting thioredoxin, an antioxidant increased the sensitivity of fungal hyphae to neutrophil-mediated killing in vitro [41]. The expression of PPRs, promote the production of pro-inflammatory cytokines, as well as the recruitment of neutrophils that can also cause serious inflammatory damages to cornea leading to opacification [32, 40, 42]. In fungal keratitis, the levels of pro-inflammatory IL-1β, IL-6, IL-8, IL-17, IL-23 and IFN-γ in aqueous humor were significantly higher in comparison to the non-keratitis control group [38]. A study among a Han Chinese population of patients with FK compared controls found a particular TLR4 allele that was associated with an increased risk of developing FK [43].
Fungi can produce enzymes that degrade physical barriers and facilitate tissue invasion. The mycotoxins produced from Fusarium species can inhibit immunity, break down tissues, and promote the fungal survival in host. Corneal epithelial cells can be destroyed by some cytosolic proteins and peptide toxins produced by fungi [44]. The protease and phospholipase activities detected in
Autophagy is a lysosome-mediated degradation process, which regulates intracellular homeostasis of eukaryotes by mediating the degradation of proteins and organelles [47]. It can be activated in response to starvation, stress, hypoxia, tumor, and infection [48]. Autophagy is proved to be involved in immune responses, a previous study found that autophagy maintains the cellular and immune homeostasis during the
A study by Li C et al. reported that the progression of FK caused by
Biofilm formation is one of the primary mechanisms through which fungi evade the immune response and establish infection. Clinical isolates of Fusarium, Candida and Aspergillus have been shown to form biofilms. A study reported that
Fungal keratitis can be diagnosed based on characteristic clinical features. Patients with keratitis usually present with sudden onset of pain, photophobia, watering and discharge and reduced vision. In fungal keratitis, symptoms are much milder than the signs [53].
A fungal keratitis classically presents as a dry, raised lesion with crenate or feathery borders, presence of satellite lesions and a hypopyon. An immune ring of Wesseley may be visible due to deposition of immune complexes and inflammatory cells around the ulcer (Figures 1–5). However, a study reported that Clinicians could correctly distinguished the microbial kingdom for 54 (73%) of 74 culture-positive infections, including 41 (79%) of 52 bacterial keratitis, 5 (38%) of 13 fungal keratitis, and 8 (89%) of 9 amoebic keratitis correctly [54]. In a photographic survey, clinician were able to distinguish between bacterial and fungal aetiologies 66% of the time. In 39 cases of fungal keratitis, the clinicians predicted genus in 27% of cases and species in 7.9% of cases [55].
Plaque-like ulcer with slightly defined margins, marked conjunctival injection and chemosis; fungal isolate- candida albicans.
A dry looking lesion with greyish white raised exudate appearing as plaque with hypopyon in a 56-year-old male with fugal keratitis from Aspergillus.
A greyish white infiltrate with feathery borders and a satellite lesion in a case fungal keratitis caused by Fusarium.
Severe fungal keratitis with feathery edges in case Fusarium Keratitis.
Corneal thinning and necrosis in severe fungal keratitis caused by Fusarium in a 48-year-old male with history of topical steroid instillation.
In vivo confocal microscopy (IVCM) of the cornea has been emerged as clinically useful non-invasive technique for early diagnosis of FK. It produces images from the cornea with a resolution of one micrometer (μm), which is enough for imaging of microorganisms larger than one μm, such as Acanthamoeba cysts and fungal hyphae [56]. This provides rapid and reliable diagnosis however, a clinical consensus in the interpretation of IVCM images is still lacking.
IVCM can directly visualize filamentous fungi within the whole cornea of patients. Confocal microscopy in vivo uses serial images to create optical sections through the full-thickness of the living cornea. It allows rapid identification of fungi and can be used to differentiate between fungal species.
Brasnu et al. diagnosed all the cases of suspected fungal keratitis (five out of five) caused by different fungal species using IVCM with sensitivity equal to the direct microscopy and culture [56]. They analyzed IVCM images of keratitis obtained using the Heidelberg Retina Tomograph (HRT) II confocal microscope (Heidelberg Engineering, Heidelberg, Germany) in five patients (four patients with
The hyper-reflective elements seen on IVCM must be differentiated from the basal corneal epithelial nerves, which have a more regular branching pattern. Stromal nerves, on the other hand, are much larger in diameter (25–50 μm). There are now several studies reported the use of IVCM in diagnosis and monitoring of treatment of fungal keratitis with reported sensitivity of 80–94% [57, 58, 59, 60].
IVCM is a noninvasive in vivo technique useful for early identification of fungal elements, monitoring and guidance of treatment, and determination of the depth of infection. The limitation of IVCM are that technique is extremely user-dependent, need a skilled operator and experienced viewer. The dense corneal infiltrates or scarring could preclude proper tissue penetration and visualization.
Conventional methods for the diagnosis of fungal keratitis include staining of tissue scrapings with Gram-stain, 10% potassium hydroxide (KOH) wet mount, lactophenol cotton blue, Giemsa, or calcofluor white. Reported sensitivity of Gram staining is in the range of 36–50% [61]. KOH is a rapid and an inexpensive and one of the most commonly performed procedures for detection of fungi with a sensitivity of 61–94% and specificity of 91–97% for detecting fungus (Figure 6). Lactophenol cotton blue mounts had reported sensitivity of 85% and specificity of 90–91% [62]. Sabouraud dextrose agar medium is considered as a culture medium of choice for isolating fungi however it cause delay in diagnosis. Initial growth occurs within 72 hours in 83% of cultures and within 1 week in 97% of cultures [63]. Sometimes it may be necessary to wait for two weeks to confirm no growth in culture. Over the last decade, a number of newer methods have been devised for detection of fungi.
Fungal hyphae in KOH wet mount counterstained with methylene blue.
Polymerase chain reaction (PCR) involves repeated cycles of denaturation, amplification, and replication, in which segments of deoxyribonucleic acid (DNA) are continuously multiplied. Specific DNA primers are employed to indicate the presence of the microorganism in question [64]. PCR has emerged as a sensitive and specific test for the diagnosis of fungal keratitis. Several techniques of PCR have been evolved and currently used for identification of fungi.
Traditional PCR by using single pair of primer to amplify the target genomic sequence is simple and efficient technique, but generation of nonspecific products can affect the results. In Nested PCR, two pairs of primers are used; one set of primer is an amplified sequence, and the other is complementary to the sequence amplified by the first one. It is more specific than traditional PCR; amplifies only the specific sequences looked for; but identify a set of fungal pathogens, not a single specific species.
In multiplex PCR Multiple primer, pairs are used. Advantage is Rapid amplification of multiple sequences, conserves template DNA, and minimizes expense; recognizes many pathogens at once. In real time PCR, one set of primers is used; amplified sequence is linked with a fluorescent probe, which emits light when bound to the amplified product. It is more specific, sensitive, and reproducible but not ideal for multiplexing [65, 66, 67].
PCR reported higher sensitivity in comparison to culture and stains for both bacteria and fungi [68, 69]. Zhao et al. reported significantly higher positive detection rate of PCR for fungal keratitis (84.5%) as compare to the positivity rate for culture (35.3%) and stain (64.7%) [69]. A higher sensitivity of PCR for infectious keratitis compared to culture (98% versus 47%), but a slightly lower specificity (83% versus 100%) is reported in this study [69].
The PCR is rapid test, it takes 4–8 h, and only a small clinical sample is needed for diagnosis
Metagenomic deep sequencing (MDS) is a new technique for the diagnosis of FK; with next generation sequencing rapid and accurate diagnosis is possible. Next generation sequencing is high-throughput sequencing methods where billions of nucleic acid fragments can be sequenced simultaneously and independently. MDS is an unbiased approach that interrogates all genomes in a clinical sample and identify any organism whereas PCR is a targeted test the clinician must know the suspected causative organism.
It has been shown to enhance detection of common and unusual pathogens from the intraocular fluid of patients with infectious uveitis and other systemic infections [70, 71, 72]. A study by Seitzman et al. in a case series of nine patients of infectious keratitis diagnosed by conventional methods reported that MDS detected all the microorganisms identified by culture or PCR. MDS was able to identify parasitic, fungal, bacterial, and viral infections as a single assay. The pathogenic organisms ranged in size from smaller genomes (
Polyenes (Amphotericin B and Natamycin) and azoles (fluconazole, itraconazole, ketoconazole, miconazole, voriconazole, and posaconazole) constitute two major classes of antifungal drugs used to treat ocular fungal infections including fungal keratitis. In Comparison to antibacterial agents, antifungals have a lower efficacy due to their mechanism of action (usually fungistatic, with dose dependent fungicidal action), lower tissue penetration, and the indolent nature of the fungal infection [74]. Still for the management of fungal keratitis, the traditional anti-fungal drugs like natamycin and fluconazole in topical and oral form are used most commonly. In recent years, other new drugs and drug delivery system to increase bioavailability of drugs have been evaluated. Anti-fungal agents are summarized in Table 1.
Agent | Route of administration/ Dose | Indication | Limitations |
---|---|---|---|
Amphotericin B | Topical 1.5-5 mg/ml *IS 5-10 μg *IC 5-10 μg/0.1 ml | First line therapy for Candida species. Good to moderate activity against filamentous fungi. Deep keratitis with partial response to topical therapy | Not commercially available. Side effects: cataract, transient iritis and corneal oedema |
Natamycin | Topical 5% (50 mg/ml) suspension | First choice for Fusarium, Good activity against Aspergillus, less effective against Candida species | Low corneal penetration |
Econazole | Topical 2% | Effective against Fusarium, Aspergillus, and Candida species | Not commercially available for ophthalmic use |
Miconazole | Topical 10 mg/ml *SC 1.2 to 10 mg | Effective against candida Adjuvant with topical therapy in patients with low compliance | Less effective than polyenes |
Ketoconazole | Topical 1-2% Oral 200-400 mg/day | Broad spectrum As an adjuvant in deep keratitis | Less effective systemic toxicity (gastric intolerance, hepatotxicity) |
Fluconazole | Topical 0.2 % SC 2 mg/1 ml Oral 100-400 mg/day oral | Effective against yeast, less effective against filamentous fungi Good intraocular penetration used as adjuvant with topical agents | Filamentous fungi exhibit resistance liver enzyme monitoring |
Itraconazole | Topical 1% Oral 200-400 mg/day | Effective against Aspergillus, Candida, less effective against Fusarium As adjuvant with topical therapy in deep keratitis/ intraocular involvement by yeasts | Less effective than natamycin Lower bioavailability, and penetration into ocular tissues than other azoles |
Voriconazole | Topical 1-2% IS 50 μg/0,1 m IC 50μg/0,1 m Oral 200 mg **BID | Broad spectrum, FK resistant to polyenes/ first-line triazoles. Deep keratitis and Intraocular involvement | Less effective than natamycin Side effects- blurred vision change in colour perception; liver enzyme monitoring during oral use |
Posaconazole | Topical 100 mg/ml; 40 mg/ml Oral 200 mg **QID/ 400 mg BID | Broad spectrum, FK resistant to polyenes/first-line triazoles. | Limited information |
Flucytosine | Topical 10 mg/ml | Synergistic effect with topical Amphotericin B in FK due to yeasts | Narrow spectrum/ low penetration into ocular tissues |
Capsofungin | Topical 0.5% | Yeasts resistant to polyenes and first-line triazoles | Limited information |
Micafungin | Topical 0.1% | Yeasts resistant to polyenes and first-line triazoles | Limited information |
Terbinafine | Topical 0.5 % Oral 250 mg/day | Active against Aspergillus, Fusarium, Scedosporium and Candida. | Limited information |
Summary of antifungal agents used in Fungal Keratitis.
IC: Intracameral, IS: Intrastromal, SC: Subconjunctival.
BID: Twice a day, QID: for times a day.
Natamycin is first antifungal agent approved for FK by Food and Drug Administration in the 1960s. After that, many antifungal agents have been evaluated, no single agent has emerged as the best and most cost effective agent [7]. Cochrane systematic review in 2008 and 2012, found no evidence that any single drug, or combination of drugs, is more effective in the management of fungal keratitis. The trials included in this review were of variable quality and were generally underpowered [75, 76].
Natamycin is a polyene antifungal drug, it binds preferentially to ergosterol on the fungal plasma membrane and causes localized membrane disruptions by altering membrane permeability. Natamycin is currently considered the most effective medication against Fusarium and Aspergillus [7]. Cochrane systematic review in 2015 found that there is evidence that natamycin is more effective than voriconazole in the treatment of fungal ulcers. However, the trials included in this review were of variable quality and were generally underpowered. Future research should evaluate treatment effects according to fungus species [77].
Several studies reported that fungal keratitis due to fusarium responded better to Natamycin as compare to itraconazole and voriconazole [77]. NTM is the treatment of choice for filamentous keratitis, especially that due to Fusarium species. However its poor penetration into corneal stroma, limits its use in deep stromal keratitis. In deep keratitis or with involvement of intraocular structures, natamycin should be associated with other antifungal agents using a different route of administration.
Amphotericin B is the first broad-spectrum antifungal agent, produced by the actinomycetes,
Amphotericin B has poor ocular penetration after intravenous administration and is toxic to human cells at a higher dose. Due to systemic (nephrotoxicity) and ocular toxicity (punctate epithelial erosions and greenish discoloration of the cornea), amphotericin B is not currently a first line agent in treating fungal keratitis. In a study, Morand K, et al. compared the commercial 0.15% Amphotericin B with a liposomal formulation and found that the liposomal form was more stable and less toxic. The liposomal formulation also increased the potential amount of loaded drug by 3-fold compared with the conventional form [78].
Fluconazole is a synthetic bistriazole available in oral, topical, and IV preparations. It has good intraocular penetration with low side effect. It shown to have excellent absorption from the gastrointestinal tract. Its plasma concentrations with oral use reach almost the same levels as with intravenous administration. Intraocular Penetration is effective, with aqueous concentrations similar to those in the plasma [74, 79]. Topical 0.2% fluconazole is effective against
Voriconazole, a newer-generation triazole, with excellent ocular penetration and broad spectrum. Most of fungal isolates commonly implicated in keratitis were found to be susceptible to voriconazole.
Voriconazole has been reported to be effective in the treatment of fungal keratitis caused by different species and in cases not responding to other antifungal like natamycin and amphotericin [79, 80, 81, 82, 83, 84, 85]. Voriconazole has good intraocular penetration following oral administration. Advantage of oral administration is that it may provide steadier drug levels at the site of infection. Theil et al. compared aqueous samples after topical and oral voriconazole found that topical administration of voriconazole resulted in highly variable aqueous concentrations with troughs well below the minimum inhibitory concentration at which 90% of fungal isolates are inhibited (MIC90). Whereas, oral voriconazole provided relatively constant therapeutic concentration [84]. Many case reports reported successful treatment with topical voriconazole in conjunction oral or intravenous voriconazole [85, 86].
Posaconazole is a new triazole, a synthetic structural analogue of itraconazole. It is available as an oral suspension (40 mg/ml), administered at a dose of 200 mg four times daily or 400 mg twice daily. Now also available as delayed release tablets (100 mg) and injection (18mg/ml). In vitro and in vivo studies showed that posaconazole has a broad spectrum against Candida spp.,
Evidence on its use in ocular infections is still limited, but initial results are encouraging. Sponsel et al. also describe a case of keratitis by
Echinocandins (caspofungin and micafungin) are semisynthetic lipopeptides act by inhibiting the synthesis of glucan in the fungal cell wall causing osmotic imbalance and cell lysis. Matsumoto et al. have reported successful use of topical 0.2% micafungin in cases of refractory fungal keratitis [92]. In another study by Matsumoto et al. usiing topical micafungin 1 mg/ml reported found an efficacy comparable or superior to fluconazole in the treatment of keratitis by
Surgical intervention may be an option for patients with refractory FK not responding to medical treatment and severe fungal infections. Penetrating keratoplasty is considered the most common surgical intervention for serious fungal keratitis and cases with perforation or impending perforation. Recent advances have added more options such as targeted drug delivery at the site of infection in the form of intrastromal injections, collagen cross-linking and rose Bengal aided photodynamic therapy.
The efficacy of topical, as well as systemic, voriconazole is well established. Intra stromal voriconazole has been found as an effective approach for targeted drug delivery in the management of deep FK not responding to standard topical therapy [95, 96, 97]. Targeted drug delivery overcomes the issue of poor bioavailability of drugs in cases of deep fungal keratitis. It provides a depot of drug, close to the infected area. However, risk of introducing a new infection, inadvertent anterior chamber entry while performing the procedure in a hazy cornea are associated.
Intracameral Amphotericin B is another approach for targeted drug delivery, indicated when medical treatment with topical and systemic antifungal has failed, especially in cases with deep mycosis, endothelial plaque and presence of hypopyon with inflammation of the anterior chamber. The concentration injected, ranges between 5 and 10 μg/0.1 ml [98, 99].
Penetrating Keratoplasty (PK) is indicated for treatment of refractory or severe fungal keratitis, corneal thinning and perforation in FK [100]. A retrospective study including 52 eyes which underwent PK for corneal perforations secondary to FK, reported improved visual acuity in 46 eyes (88.5%) and clear grafts in 44 eyes (84.6%) at final follow-up [101]. The common complications of PK are graft rejection, recurrence of infection, and secondary glaucoma. Following PK, oral and topical antifungal medications are usually continued for 2 weeks and if pathology reports presence of fungus on the margin of the cornea sample, treatment continues for 6–8 weeks.
Cyclosporine has been recommended after PK in cases of fungal keratitis as it has been suggested to have dual antifungal and anti-immune properties [102]. However; evidences at present are limited, further studies are required to evaluate the risk and benefit of cyclosporine patients undergoing corneal transplant for fungal keratitis.
Amniotic membrane transplantation (AMT) has emerged as an option to delay or prevent PK secondary to fungal keratitis. Amniotic membranes have been used to facilitate ocular surface reconstructions in other ocular surface conditions. AMT support re-epithelialization of tissue, and the active components present in the membrane like nerve growth factors are thought to reduce pain [103]. In a study, 23 culture-proven, acute fungal keratitis patients with non-healing corneal ulcers, or impending corneal perforation underwent AMT to prevent PK or to promote re-epithelialization. Following AMT, 25% of patients with persistent positive culture for fungus required PK. The final visual outcome was BCVA > 20/400. It improved in 17, did not changed in four and worsened in two patients [104].
In an inflamed eye, there is increased risk of infection to be introduced into the anterior chamber or vitreous after PK and the use of corticosteroids, to prevent corneal graft rejection, may increase the risk of recurrence of fungal infection. Delay in PK can avoid these complications.
Lamellar keratoplasty (LK) is emerged as an alternate surgical procedure for fungal keratitis in which only diseased layers of the corneal surface are excised and replaced by donor cornea. In a study from China, reported the leading indication for LK in 2008 was infectious keratitis, and fungal keratitis constituted 67% of the infectious keratitis cases [105]. In another study, 55 antifungal refractory patients underwent LK with intensive topical and oral antifungal medication. In 93% of the patients, the fungal infection was eradicated. The remaining four patients were treated by a secondary PK. Visual acuity ranged from 20/20 to 20/63 with a few complications after 6–18 months follow-up [106].
Corneal collagen cross-linking (CXL) has been found successful in halting the progression of keratoconus by using riboflavin and UV-A light. In recent years, role of CXL in infectious keratitis is investigated in several studies with conflicting results on the efficacy of CXL in infectious keratitis [107, 108, 109, 110, 111, 112, 113]. Specifically the term photoactivated chromophore cross-linking (PACK-CXL) is used for CXL to treat infectious keratitis [108].
CXL may act in cases of fungal keratitis by a direct antifungal effect and by halting the ongoing melting, thus helping to avoid emergency keratoplasty [109, 110, 111]. Said et al. found that although PACK-CXL did not shorten the time to corneal healing, it prevented corneal melting [107]. PACK-CXL is found to be useful in fungal keratitis [108, 109, 110]. Abbouda et al. reported halting of corneal melting with PACK-CXL in one case while the other developed perforation [112]. The safety of CXL is of concern because the ultraviolet (UV) -A could damage intraocular structures. Spoerl et al. analyzed the expected damage compared with acceptable damage thresholds. During standard CXL of a cornea with a 400-μm thickness, the irradiances of the UV light reaching the iris, lens, and retina are less than the damage thresholds, and only the microbes, the corneal endothelium, and the keratocytes are at risk [113]. Minor complications after CXL, like transient limbitis and a transient increase in the size of the hypopyon in the first 24 h after CXL reported to be regress subsequently [107].
Photodynamic therapy (PDT) has been used in treatment of choroidal neovascularization in age-related macular degeneration, corneal neovascularization and in infectious keratitis due to Acanthamoeba [114]. PDT involves the activation of photosensitizers using light of varying wavelengths. Rose Bengal photodynamic therapy (RB-PDT) involved a photochemical process using Rose Bengal, excited with green light (wavelength: 500–550 nm) to generate reactive oxygen species (ROS), which, react with various intracellular components to cause cell death. In an in vitro study, Arboleda et al. have demonstrated RB PDT to be successful in fungal keratitis [115].
In a pilot clinical study by Naranjo et al., RB-PDAT was performed in 18 patients with progressive infectious keratitis unresponsive to standard medical therapy. RB-PDAT was considered successful in 13 individuals, defined as control of infection without the need for a therapeutic PK [116]. Amescua G et al. in an vitro and in a case study evaluated the efficacy of rose bengal photodynamic antimicrobial therapy (PDAT). They found that Riboflavin CXL demonstrated no inhibition of fungal isolate growth, whereas rose bengal PDAT inhibited fungal isolate growth within the irradiation zone. In addition, a case with resistant fusarium keratitis was treated successfully [117].
In a study, the role of vitamin D receptor (VDR) in innate immunity being discovered, may be a new target of treatment that can be explored for FK [118].Liposomes-encapsulated mannan extracts from
Recently, many efforts have been made to improve topical ocular drug delivery by designing various novel drug delivery systems (NDDS), including liposomes, nanoparticles, nanoemulsions, nanosuspensions, micelles, nanofibers, etc.
Several in vitro and in vivo experimental studies have reported encouraging results with NDDS. In a study, the liposomal formulation of the antifungal drug voriconazole found to exhibit a sustained drug release profile, and an 8-fold increase in the amount of drug retained in the cornea after 1 hour of exposure compared with the conventional suspension formulation [121]. The nanoparticle formulation of amphotericin B showed a sustained and controlled drug release for up to 11 hours, while the conventional drug formulation (0.15%) released the entire drug in only 4 hours. Nanoparticle formulation has also shown better pharmacokinetic properties, including 1.5-fold increase in half-life compared to the conventional solution formulation [122]. The microemulsion formulations of fluconazole showed a controlled release profile, releasing 50–80% of the drug in 12 hours, compared to the conventional drug solution, which released almost the entire drug in the first 6 hours [123]. In future, these newer formulations can be very useful in management of fungal keratitis.
Antimicrobial peptides (AMPs) have significant potential for use as antimicrobial agents for ocular or other infections [124]. AMPs, also known as host defense peptides, are naturally produced, small, cationic, amphiphilic peptides ranging in length from 12 to 50 amino acids. They are present on the surfaces of the eyes and in tears. More than 500 AMPs have been reported, including large molecules (RNases and S100A proteins); small peptides α and β defensins in human cationic antibacterial protein (CAP) 18, and α 37 amino acids; proteins like lysozyme and peptidoglycan recognition protein with significant bactericidal activity. The cations carried by AMPs can bind to the anion surface of the bacterial plasma membrane, causing the perforation of cell membrane and subsequently microbial death. AMPs also prevent microbial adhesion to and access into host cells and cause digestion of fungal cell wall by lysozyme [124, 125].
In vitro studies have shown AMPs Pc-C and Pc-E reduced binding of
Early diagnosis and treatment of fungal keratitis remains a challenge. A better understanding of pathogenesis can broadened the approach to management. Recent advances in techniques such as in vivo confocal microscopy and the evolution of PCR and MDS can useful in rapid and accurate diagnosis. Newer antifungal agents and newer methods of targeted drug delivery system can be helpful in treating refractory cases and improving outcome. New evolving technique like PACK-CXL and RB-PDT can be useful as adjuvant therapy.
New researches are continue to investigate the new aspects of pathogenesis, to device the novel drug delivery system to overcome the poor ocular penetration of antifungal drugs and enhance their efficacy and evaluate newer antifungal drugs. In recent years focus on modifying the immune response to the infection, thereby reducing the corneal melting and scarring which lead to poor vision, may have the greatest potential to improve visual outcomes.
The authors declare no conflict of interest.
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Abdurakhmonov"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],booksByTopicTotal:14,seriesByTopicCollection:[],seriesByTopicTotal:0,mostCitedChapters:[{id:"56013",doi:"10.5772/intechopen.69660",title:"Vitamin C: An Antioxidant Agent",slug:"vitamin-c-an-antioxidant-agent",totalDownloads:7808,totalCrossrefCites:26,totalDimensionsCites:59,abstract:"Vitamin C or ascorbic acid (AsA) is a naturally occurring organic compound with antioxidant properties, found in both animals and plants. It functions as a redox buffer which can reduce, and thereby neutralize, reactive oxygen species. It is a cofactor for enzymes involved in regulating photosynthesis, hormone biosynthesis, and regenerating other antioxidants; which also regulates cell division and growth, is involved in signal transduction, and has roles in several physiological processes, such as immune stimulation, synthesis of collagen, hormones, neurotransmitters, and iron absorption, has also roles in detoxifying the body of heavy metals. Severe deficiency of vitamin C causes scurvy, whereas limited vitamin C intake causes symptoms, such as increased susceptibility to infections, loosening of teeth, dryness of the mouth and eyes, loss of hair, dry itchy skin, fatigue, and insomnia. In contrast, vitamin C can also act as a prooxidant, especially in the presence of transition metals, such as iron and copper, starting different hazardous radical reactions. Vitamin C can both act as a strong, efficient, and cheap antioxidant agent and, at the same time, behave as a radical promoter. Further investigations are needed to illuminate the dual roles of vitamin C",book:{id:"5940",slug:"vitamin-c",title:"Vitamin C",fullTitle:"Vitamin C"},signatures:"Fadime Eryılmaz Pehlivan",authors:[{id:"200567",title:"Dr.",name:"Fadime",middleName:null,surname:"Eryılmaz Pehlivan",slug:"fadime-eryilmaz-pehlivan",fullName:"Fadime Eryılmaz Pehlivan"}]},{id:"56440",doi:"10.5772/intechopen.70162",title:"Vitamin C: Sources, Functions, Sensing and Analysis",slug:"vitamin-c-sources-functions-sensing-and-analysis",totalDownloads:6423,totalCrossrefCites:15,totalDimensionsCites:28,abstract:"Vitamin C is a water-soluble compound found in living organisms. It is an essential nutrient for various metabolism in our body and also serves as a reagent for the preparation of many materials in the pharmaceutical and food industry. In this perspective, this chapter can develop interest and curiosity among all practicing scientists and technologists by expounding the details of its sources, chemistry, multifunctional properties and applications.",book:{id:"5940",slug:"vitamin-c",title:"Vitamin C",fullTitle:"Vitamin C"},signatures:"Sudha J. Devaki and Reshma Lali Raveendran",authors:[{id:"187911",title:"Associate Prof.",name:"Sudha",middleName:null,surname:"J Devaki",slug:"sudha-j-devaki",fullName:"Sudha J Devaki"},{id:"204937",title:"Mrs.",name:"Reshma",middleName:null,surname:"Laly Ravindran",slug:"reshma-laly-ravindran",fullName:"Reshma Laly Ravindran"}]},{id:"50921",doi:"10.5772/63712",title:"Menaquinones, Bacteria, and Foods: Vitamin K2 in the Diet",slug:"menaquinones-bacteria-and-foods-vitamin-k2-in-the-diet",totalDownloads:3315,totalCrossrefCites:10,totalDimensionsCites:21,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.",book:{id:"5169",slug:"vitamin-k2-vital-for-health-and-wellbeing",title:"Vitamin K2",fullTitle:"Vitamin K2 - Vital for Health and Wellbeing"},signatures:"Barbara Walther and Magali Chollet",authors:[{id:"184784",title:"Dr.",name:"Barbara",middleName:null,surname:"Walther",slug:"barbara-walther",fullName:"Barbara Walther"},{id:"188194",title:"Mrs.",name:"Magali",middleName:null,surname:"Chollet",slug:"magali-chollet",fullName:"Magali Chollet"}]},{id:"66098",doi:"10.5772/intechopen.84445",title:"Golden Rice: To Combat Vitamin A Deficiency for Public Health",slug:"golden-rice-to-combat-vitamin-a-deficiency-for-public-health",totalDownloads:3377,totalCrossrefCites:12,totalDimensionsCites:17,abstract:"Vitamin A deficiency (VAD) has been recognised as a significant public health problem continuously for more than 30 years, despite current interventions. The problem is particularly severe in populations where rice is the staple food and diversity of diet is limited, as white rice contains no micronutrients. Golden Rice is a public-sector product designed as an additional intervention for VAD. There will be no charge for the nutritional trait, which has been donated by its inventors for use in public-sector rice varieties to assist the resource poor, and no limitations on what small farmers can do with the crop—saving and replanting seed, selling seed and selling grain are all possible. Because Golden Rice had to be created by introducing two new genes—one from maize and the other from a very commonly ingested soil bacterium—it has taken a long time to get from the laboratory to the field. Now it has been formally registered as safe as food, feed, or in processed form by four industrialised counties, and applications are pending in developing countries. The data are summarised here, and criticisms addressed, for a public health professional audience: is it needed, will it work, is it safe and is it economic? Adoption of Golden Rice, the next step after in-country registration, requires strategic and tactical cooperation across professions, non-governmental organisations (NGOs) and government departments often not used to working together. Public health professionals need to play a prominent role.",book:{id:"7978",slug:"vitamin-a",title:"Vitamin A",fullTitle:"Vitamin A"},signatures:"Adrian Dubock",authors:[{id:"273220",title:"Ph.D.",name:"Adrian",middleName:null,surname:"Dubock",slug:"adrian-dubock",fullName:"Adrian Dubock"}]},{id:"62836",doi:"10.5772/intechopen.79350",title:"The Role of Thiamine in Plants and Current Perspectives in Crop Improvement",slug:"the-role-of-thiamine-in-plants-and-current-perspectives-in-crop-improvement",totalDownloads:1564,totalCrossrefCites:7,totalDimensionsCites:11,abstract:"Current research is focusing on selecting potential genes that can alleviate stress and produce disease-tolerant crop variety. The novel paradigm is to investigate the potential of thiamine as a crop protection molecule in plants. Thiamine or vitamin B1 is important for primary metabolism for all living organisms. The active form, thiamine pyrophosphate (TPP), is a cofactor for the enzymes involved in the synthesis of amino acids, tricarboxylic acid cycle and pentose phosphate pathway. Recently, thiamine is shown to have a role in the processes underlying protection of plants against biotic and abiotic stresses. The aim of this chapter is to review the role of thiamine in plant growth and disease protection and also to highlight that TPP and its intermediates are involved in management of stress. The perspectives on its potential for manipulating the biosynthesis pathway in crop improvement will also be discussed.",book:{id:"6709",slug:"b-group-vitamins-current-uses-and-perspectives",title:"B Group Vitamins",fullTitle:"B Group Vitamins - Current Uses and Perspectives"},signatures:"Atiqah Subki, Aisamuddin Ardi Zainal Abidin and Zetty Norhana\nBalia Yusof",authors:[{id:"240031",title:"Dr.",name:"Zetty-Norhana Balia",middleName:null,surname:"Yusof",slug:"zetty-norhana-balia-yusof",fullName:"Zetty-Norhana Balia Yusof"},{id:"261167",title:"Mr.",name:"Aisamuddin Ardi",middleName:null,surname:"Zainal Abidin",slug:"aisamuddin-ardi-zainal-abidin",fullName:"Aisamuddin Ardi Zainal Abidin"},{id:"261169",title:"Ms.",name:"Atiqah",middleName:null,surname:"Subki",slug:"atiqah-subki",fullName:"Atiqah Subki"}]}],mostDownloadedChaptersLast30Days:[{id:"56440",title:"Vitamin C: Sources, Functions, Sensing and Analysis",slug:"vitamin-c-sources-functions-sensing-and-analysis",totalDownloads:6429,totalCrossrefCites:15,totalDimensionsCites:28,abstract:"Vitamin C is a water-soluble compound found in living organisms. It is an essential nutrient for various metabolism in our body and also serves as a reagent for the preparation of many materials in the pharmaceutical and food industry. In this perspective, this chapter can develop interest and curiosity among all practicing scientists and technologists by expounding the details of its sources, chemistry, multifunctional properties and applications.",book:{id:"5940",slug:"vitamin-c",title:"Vitamin C",fullTitle:"Vitamin C"},signatures:"Sudha J. Devaki and Reshma Lali Raveendran",authors:[{id:"187911",title:"Associate Prof.",name:"Sudha",middleName:null,surname:"J Devaki",slug:"sudha-j-devaki",fullName:"Sudha J Devaki"},{id:"204937",title:"Mrs.",name:"Reshma",middleName:null,surname:"Laly Ravindran",slug:"reshma-laly-ravindran",fullName:"Reshma Laly Ravindran"}]},{id:"56013",title:"Vitamin C: An Antioxidant Agent",slug:"vitamin-c-an-antioxidant-agent",totalDownloads:7817,totalCrossrefCites:27,totalDimensionsCites:60,abstract:"Vitamin C or ascorbic acid (AsA) is a naturally occurring organic compound with antioxidant properties, found in both animals and plants. It functions as a redox buffer which can reduce, and thereby neutralize, reactive oxygen species. It is a cofactor for enzymes involved in regulating photosynthesis, hormone biosynthesis, and regenerating other antioxidants; which also regulates cell division and growth, is involved in signal transduction, and has roles in several physiological processes, such as immune stimulation, synthesis of collagen, hormones, neurotransmitters, and iron absorption, has also roles in detoxifying the body of heavy metals. Severe deficiency of vitamin C causes scurvy, whereas limited vitamin C intake causes symptoms, such as increased susceptibility to infections, loosening of teeth, dryness of the mouth and eyes, loss of hair, dry itchy skin, fatigue, and insomnia. In contrast, vitamin C can also act as a prooxidant, especially in the presence of transition metals, such as iron and copper, starting different hazardous radical reactions. Vitamin C can both act as a strong, efficient, and cheap antioxidant agent and, at the same time, behave as a radical promoter. Further investigations are needed to illuminate the dual roles of vitamin C",book:{id:"5940",slug:"vitamin-c",title:"Vitamin C",fullTitle:"Vitamin C"},signatures:"Fadime Eryılmaz Pehlivan",authors:[{id:"200567",title:"Dr.",name:"Fadime",middleName:null,surname:"Eryılmaz Pehlivan",slug:"fadime-eryilmaz-pehlivan",fullName:"Fadime Eryılmaz Pehlivan"}]},{id:"69402",title:"Vitamin D Deficiency and Diabetes Mellitus",slug:"vitamin-d-deficiency-and-diabetes-mellitus",totalDownloads:1604,totalCrossrefCites:2,totalDimensionsCites:3,abstract:"Vitamin D (VD) is a molecule that can be synthesized directly in the humans’ body or enter the organism with food in the form of inactive precursors. To exert its biological action, VD undergoes two-stage hydroxylation (at the 25th and 1st position) catalyzed by cytochromes P450, the presence of which has already been shown in almost all tissues of the human body. The product of hydroxylation is hormone-active form of vitamin D–1,25(OH)2D. 1,25(OH)2D binds to specific vitamin D receptor (VDR) and regulates the expression of genes involved in bone remodeling (classical function) and genes that control immune response, hormone secretion, cell proliferation, and differentiation (nonclassical functions). VD deficiency is prevalent around the globe and may be one of the key factors for diabetes development. The direct association between vitamin D deficiency and type 1 (T1D) and type 2 (T2D) diabetes has been proven. Detection of VDR in pancreas and adipose tissue, skeletal muscles, and immune cells allowed implying the antidiabetic role of vitamin D by enhancing insulin synthesis and exocytosis, increasing the expression of the insulin receptor, and modulating immune cells’ functions. This chapter summarizes data about relationship between VD insufficiency/deficiency and development of T1D and T2D, and their complications.",book:{id:"7038",slug:"vitamin-d-deficiency",title:"Vitamin D Deficiency",fullTitle:"Vitamin D Deficiency"},signatures:"Ihor Shymanskyi, Olha Lisakovska, Anna Mazanova and Mykola Veliky",authors:null},{id:"76108",title:"Vitamin D Metabolism",slug:"vitamin-d-metabolism",totalDownloads:498,totalCrossrefCites:2,totalDimensionsCites:3,abstract:"Vitamin D plays an important role in bone metabolism. Vitamin D is a group of biologically inactive, fat-soluble prohormones that exist in two major forms: ergocalciferol (vitamin D2) produced by plants in response to ultraviolet irradiation and cholecalciferol (vitamin D3) derived from animal tissues or 7-dehydrocholesterol in human skin by the action of ultraviolet rays present in sunlight. Vitamin D, which is biologically inactive, needs two-step hydroxylation for activation. All of these steps are of crucial for Vitamin D to show its effect properly. In this section, we will present vitamin D synthesis and its action steps in detail.",book:{id:"10631",slug:"vitamin-d",title:"Vitamin D",fullTitle:"Vitamin D"},signatures:"Sezer Acar and Behzat Özkan",authors:[{id:"29878",title:"Dr.",name:"Behzat",middleName:null,surname:"Özkan",slug:"behzat-ozkan",fullName:"Behzat Özkan"},{id:"348287",title:"Dr.",name:"Sezer",middleName:null,surname:"Acar",slug:"sezer-acar",fullName:"Sezer Acar"}]},{id:"50754",title:"Medicinal Chemistry of Vitamin K Derivatives and Metabolites",slug:"medicinal-chemistry-of-vitamin-k-derivatives-and-metabolites",totalDownloads:1917,totalCrossrefCites:2,totalDimensionsCites:2,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. 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Singh",profilePictureURL:"https://mts.intechopen.com/storage/users/329385/images/system/329385.png",institutionString:"Punjab Technical University",institution:{name:"Punjab Technical University",institutionURL:null,country:{name:"India"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"8018",title:"Extracellular Matrix",subtitle:"Developments and Therapeutics",coverURL:"https://cdn.intechopen.com/books/images_new/8018.jpg",slug:"extracellular-matrix-developments-and-therapeutics",publishedDate:"October 27th 2021",editedByType:"Edited by",bookSignature:"Rama Sashank Madhurapantula, Joseph Orgel P.R.O. and Zvi Loewy",hash:"c85e82851e80b40282ff9be99ddf2046",volumeInSeries:23,fullTitle:"Extracellular Matrix - Developments and Therapeutics",editors:[{id:"212416",title:"Dr.",name:"Rama Sashank",middleName:null,surname:"Madhurapantula",slug:"rama-sashank-madhurapantula",fullName:"Rama Sashank Madhurapantula",profilePictureURL:"https://mts.intechopen.com/storage/users/212416/images/system/212416.jpg",institutionString:"Illinois Institute of Technology",institution:{name:"Illinois Institute of Technology",institutionURL:null,country:{name:"United States of America"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null}]},subseriesFiltersForPublishedBooks:[{group:"subseries",caption:"Proteomics",value:18,count:4},{group:"subseries",caption:"Metabolism",value:17,count:6},{group:"subseries",caption:"Cell and Molecular Biology",value:14,count:9},{group:"subseries",caption:"Chemical Biology",value:15,count:14}],publicationYearFilters:[{group:"publicationYear",caption:"2022",value:2022,count:9},{group:"publicationYear",caption:"2021",value:2021,count:7},{group:"publicationYear",caption:"2020",value:2020,count:12},{group:"publicationYear",caption:"2019",value:2019,count:3},{group:"publicationYear",caption:"2018",value:2018,count:2}],authors:{paginationCount:250,paginationItems:[{id:"274452",title:"Dr.",name:"Yousif",middleName:"Mohamed",surname:"Abdallah",slug:"yousif-abdallah",fullName:"Yousif Abdallah",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/274452/images/8324_n.jpg",biography:"I certainly enjoyed my experience in Radiotherapy and Nuclear Medicine, particularly it has been in different institutions and hospitals with different Medical Cultures and allocated resources. 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. His research interests include computer graphics, computer vision, image processing, machine learning, pattern recognition, soft computing, data science, intelligent systems, information technology, and information systems. Prof. Sarfraz has been a keynote/invited speaker on various platforms around the globe. He has advised various students for their MSc and Ph.D. theses. He has published more than 400 publications as books, journal articles, and conference papers. He is a member of various professional societies and a chair and member of the International Advisory Committees and Organizing Committees of various international conferences. Prof. Sarfraz is also an editor-in-chief and editor of 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:"267434",title:"Dr.",name:"Rohit",middleName:null,surname:"Raja",slug:"rohit-raja",fullName:"Rohit Raja",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/267434/images/system/267434.jpg",biography:"Dr. Rohit Raja received Ph.D. in Computer Science and Engineering from Dr. CVRAMAN University in 2016. His main research interest includes Face recognition and Identification, Digital Image Processing, Signal Processing, and Networking. Presently he is working as Associate Professor in IT Department, Guru Ghasidas Vishwavidyalaya (A Central University), Bilaspur (CG), India. He has authored several Journal and Conference Papers. He has good Academics & Research experience in various areas of CSE and IT. He has filed and successfully published 27 Patents. He has received many time invitations to be a Guest at IEEE Conferences. He has published 100 research papers in various International/National Journals (including IEEE, Springer, etc.) and Proceedings of the reputed International/ National Conferences (including Springer and IEEE). He has been nominated to the board of editors/reviewers of many peer-reviewed and refereed Journals (including IEEE, Springer).",institutionString:"Guru Ghasidas Vishwavidyalaya",institution:{name:"Guru Ghasidas Vishwavidyalaya",country:{name:"India"}}},{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:{name:"University of Silesia",country:{name:"Poland"}}},{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:null,institution:{name:"Beijing University of Technology",country:{name:"China"}}},{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:"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:{name:"Medical University Plovdiv",country:{name:"Bulgaria"}}},{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:"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:"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:"Igor Victorovich Lakhno 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.\nPh.D. – 1999, Kharkiv National Medical Univesity.\nDSC – 2019, PL Shupik National Academy of Postgraduate Education \nProfessor – 2021, Department of Obstetrics and Gynecology of VN Karazin Kharkiv National University\nHead of Department – 2021, Department of Perinatology, Obstetrics and gynecology of Kharkiv Medical Academy of Postgraduate Education\nIgor Lakhno has been graduated from international training courses on reproductive medicine and family planning held at Debrecen University (Hungary) in 1997. Since 1998 Lakhno Igor has worked as an associate professor in 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 been a professor in the department of obstetrics and gynecology of VN Karazin National University and a professor of the perinatology, obstetrics, and gynecology department. He’s affiliated with Kharkiv Medical Academy of Postgraduate Education as a Head of Department from November 2021. Igor Lakhno has participated in several international projects on fetal non-invasive electrocardiography (with Dr. J. A. Behar (Technion), Prof. D. Hoyer (Jena University), and José Alejandro Díaz Méndez (National Institute of Astrophysics, Optics, and Electronics, Mexico). He’s an author of about 200 printed works and there are 31 of them in Scopus or Web of Science databases. Igor Lakhno is a member of the Editorial Board of Reproductive Health of Woman, Emergency Medicine, and Technology Transfer Innovative Solutions in Medicine (Estonia). He is a medical Editor of “Z turbotoyu pro zhinku”. Igor Lakhno is a reviewer of the Journal of Obstetrics and Gynaecology (Taylor and Francis), British Journal of Obstetrics and Gynecology (Wiley), 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 a DSc degree “Pre-eclampsia: prediction, prevention, and treatment”. Three years ago Igor Lakhno has participated in a training course on innovative technologies in medical education at Lublin Medical University (Poland). 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: are obstetrics, women’s health, fetal medicine, and cardiovascular medicine. \nIgor Lakhno is a consultant at Kharkiv municipal perinatal center. He’s graduated from training courses on endoscopy in gynecology. He has 28 years of practical experience in the field.",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:"243698",title:"Dr.",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:null,institution:null},{id:"7227",title:"Dr.",name:"Hiroaki",middleName:null,surname:"Matsui",slug:"hiroaki-matsui",fullName:"Hiroaki Matsui",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Tokyo",country:{name:"Japan"}}},{id:"312999",title:"Dr.",name:"Bernard O.",middleName:null,surname:"Asimeng",slug:"bernard-o.-asimeng",fullName:"Bernard O. 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Dr. Saxena is a fellow of various international societies/academies including the Royal College of Pathologists, United Kingdom; Royal Society of Medicine, London; Royal Society of Biology, United Kingdom; Royal Society of Chemistry, London; and Academy of Translational Medicine Professionals, Austria. He was named a Global Leader in Science by The Scientist. He is also an international opinion leader/expert in vaccination for Japanese encephalitis by IPIC (UK).",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",institutionURL:null,country:{name:"India"}}},editorTwo:null,editorThree:null,series:{id:"6",title:"Infectious Diseases",doi:"10.5772/intechopen.71852",issn:"2631-6188"},editorialBoard:[{id:"188773",title:"Prof.",name:"Emmanuel",middleName:null,surname:"Drouet",slug:"emmanuel-drouet",fullName:"Emmanuel Drouet",profilePictureURL:"https://mts.intechopen.com/storage/users/188773/images/system/188773.png",institutionString:null,institution:{name:"Grenoble Alpes University",institutionURL:null,country:{name:"France"}}},{id:"188219",title:"Prof.",name:"Imran",middleName:null,surname:"Shahid",slug:"imran-shahid",fullName:"Imran Shahid",profilePictureURL:"https://mts.intechopen.com/storage/users/188219/images/system/188219.jpeg",institutionString:null,institution:{name:"Umm al-Qura University",institutionURL:null,country:{name:"Saudi Arabia"}}},{id:"214235",title:"Dr.",name:"Lynn",middleName:"S.",surname:"Zijenah",slug:"lynn-zijenah",fullName:"Lynn Zijenah",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSEJGQA4/Profile_Picture_1636699126852",institutionString:null,institution:{name:"University of Zimbabwe",institutionURL:null,country:{name:"Zimbabwe"}}},{id:"178641",title:"Dr.",name:"Samuel Ikwaras",middleName:null,surname:"Okware",slug:"samuel-ikwaras-okware",fullName:"Samuel Ikwaras Okware",profilePictureURL:"https://mts.intechopen.com/storage/users/178641/images/system/178641.jpg",institutionString:null,institution:{name:"Uganda Christian University",institutionURL:null,country:{name:"Uganda"}}}]},onlineFirstChapters:{paginationCount:20,paginationItems:[{id:"82800",title:"Repurposing Drugs as Potential Therapeutics for the SARS-Cov-2 Viral Infection: Automatizing a Blind Molecular Docking High-throughput Pipeline",doi:"10.5772/intechopen.105792",signatures:"Aldo Herrera-Rodulfo, Mariana Andrade-Medina and Mauricio Carrillo-Tripp",slug:"repurposing-drugs-as-potential-therapeutics-for-the-sars-cov-2-viral-infection-automatizing-a-blind-",totalDownloads:5,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Molecular Docking - Recent Advances",coverURL:"https://cdn.intechopen.com/books/images_new/11451.jpg",subseries:{id:"7",title:"Bioinformatics and Medical Informatics"}}},{id:"82582",title:"Protecting Bioelectric Signals from Electromagnetic Interference in a Wireless World",doi:"10.5772/intechopen.105951",signatures:"David Marcarian",slug:"protecting-bioelectric-signals-from-electromagnetic-interference-in-a-wireless-world",totalDownloads:4,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Biosignal Processing",coverURL:"https://cdn.intechopen.com/books/images_new/11153.jpg",subseries:{id:"7",title:"Bioinformatics and Medical Informatics"}}},{id:"82586",title:"Fundamentals of Molecular Docking and Comparative Analysis of Protein–Small-Molecule Docking Approaches",doi:"10.5772/intechopen.105815",signatures:"Maden Sefika Feyza, Sezer Selin and Acuner Saliha Ece",slug:"fundamentals-of-molecular-docking-and-comparative-analysis-of-protein-small-molecule-docking-approac",totalDownloads:26,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Molecular Docking - Recent Advances",coverURL:"https://cdn.intechopen.com/books/images_new/11451.jpg",subseries:{id:"7",title:"Bioinformatics and Medical Informatics"}}},{id:"82184",title:"Biological Sensing Using Infrared SPR Devices Based on ZnO",doi:"10.5772/intechopen.104562",signatures:"Hiroaki Matsui",slug:"biological-sensing-using-infrared-spr-devices-based-on-zno",totalDownloads:10,totalCrossrefCites:0,totalDimensionsCites:0,authors:[{name:"Hiroaki",surname:"Matsui"}],book:{title:"Biosignal Processing",coverURL:"https://cdn.intechopen.com/books/images_new/11153.jpg",subseries:{id:"7",title:"Bioinformatics and Medical Informatics"}}},{id:"82122",title:"Recent Advances in Biosensing in Tissue Engineering and Regenerative Medicine",doi:"10.5772/intechopen.104922",signatures:"Alma T. 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