List of commercially available antibodies against pathogens: the author’s experience.
\r\n\tWith this goal in mind, together with the US Prof. John M. Ballato and the InechOpen publishing house since 2011 we have published in 2011, 2013, 2015 and 2017 4 books of our serial “Optoelectronics” and the book “Excitons”, edited in 2018 by Prof. Sergei L. Pyshkin. Publishing the new book “Luminescence” we are pleased to note the growing number of countries participating in this undertaking as well as for a long time fruitfully cooperating scientists from the United States and the Republic of Moldova.
\r\n\tSpecialists from all over the world have published in edited by us books their works in the field of research of the luminescent properties of various materials suitable for use in optoelectronic devices, the development of new structures and the results of their application in practice.
Infectious diseases kill a significant number of people in the world. Of the top 10 leading causes of death in low-income countries in 2016, pneumonia, diarrheal diseases, acquired immune deficiency syndrome (AIDS), malaria, and tuberculosis are listed up. More than half of deaths in low-income countries were due to communicable diseases, maternal causes, conditions arising during pregnancy and childbirth, and nutritional deficiencies, while such causes shared less than 7% of deaths in high-income countries [1]. It is no double to say that the detection of infectious agents in the lesion is essential for the histopathological diagnosis of infectious diseases [2, 3]. For the correct diagnosis and appropriate treatment of the patient, immunohistochemical demonstration of pathogens within the lesion must be suitable and desirable [4, 5, 6, 7, 8, 9, 10].
Needless to say, the most important factor, the “life,” in the immunohistochemical analysis should be a high-specificity antibody for exactly demonstrating the corresponding antigen. A variety of immunohistochemical techniques for increasing the sensitivity of detection have been developed, in order to localize the antigens under highly specific and highly sensitive conditions in routinely processed (formalin-fixed, paraffin-embedded) sections [11, 12, 13]. Immunohistochemical approach is quite fitted to the histopathological diagnosis of infectious diseases, since the antigens of the pathogen are absent from the human tissue specimens [4, 7, 8, 9, 10].
However, pathogens express multiple antigens, and the antigens are often cross-reactive among different pathogens [14]. The pathogen in a single category further reveals a variety of serum types [15]. It is more difficult for us pathologists than expected to detect a certain pathogen using a single antibody [4, 7]. It is next to impossible to prepare and keep specific antibodies in hand for immunohistochemical diagnosis in a single institution simply because there are too many species of microbes pathogenic to humans. We have a limited number of commercially available antibodies against pathogens. Useful commercial antibodies may soon disappear from the market because of a simple reason: the dead stock [16].
In the routine practice of histopathological services using hematoxylin and eosin (H&E) staining, it is often the situation that the pathologists are requested to judge if the lesion is infective or not. Namely, the presence of some sort of pathogenic organisms within the lesion should be shown with the maximal priority in making the diagnosis, and the detailed identification of the species name should be analyzed using different technologies afterward. For example, if a lesion showing massive necrosis is experienced, we must comment that the necrosis is infective in origin or tumor-related. In such a situation, an antibody widely cross-reactive to bacteria but unreactive to human tissue is valuable. A monoclonal antibody H9 (a gift of Prof. Shigeru Kamiya, Department of Microbiology, Kyorin University School of Medicine, Mitaka, Tokyo) against bacteria-specific heat shock protein (HSP)-60, not cross-reactive animal mitochondrial HSP-60, is quite valuable [7, 17], but it is not commercially available. Lipopolysaccharide (LPS) or endotoxin, located in the outer layer of the bacterial wall, should be the good marker of Gram-negative bacteria (refer to Figure 11) [18], but it is practically difficult for us to get a monoclonal or polyclonal antibody detecting widely cross-reactive LPS.
In order to visualize pathogens in formalin-fixed, paraffin-embedded sections, we do not necessarily need to prepare antibodies with high specificity [4, 7, 19]. The author routinely uses four kinds of commercially available rabbit antisera raised against
The second approach for detecting unknown pathogens in the histopathological sections is the use of patient’s serum [4, 7, 8, 20, 21, 22, 23]. Patients’ sera diluted at 1:500 or 1:1000 become convenient probes for indirect immunoperoxidase localization of pathogens in formalin-fixed, paraffin-embedded sections, particularly when cellular tissue reactions have been confirmed under the microscope. Serum antibody titer should be high in the recovery or chronic stage of illness. The existence of inflammatory tissue reaction, such as an abscess or granuloma, indicates that immune cells in the patient have been activated against the causative pathogen. The second approach is of high value for protozoan and helminthic disorders.
In Table 1, commercially available antibodies against pathogens are listed up, simply for the convenience of the readers. The catalog is solely based on the author’s experience, so that the antibodies may not be most suitable for detecting pathogens in routinely prepared sections [8, 19]. Some antibodies may be no longer available, simply because of limited market. The specificity of the antibodies is categorized into three grades: high, moderate, and low. Even when we use the high-specificity antibody for immunostaining, careful judgment is requested for the final identification of the causative microbe.
Pathogen | Type (clone) | Company | Dilution | Pretreatment | Specificity |
---|---|---|---|---|---|
Mo (396AN1) | DSHB | 1:5 | CB6 | High | |
Rabbit | Abcam | 1:500 | CB6 | Low | |
Mo (H2A10) | Biocare | 1:100 | EDTA | High | |
BCG | Rabbit | Dako | 1:5000 | None | Low |
Mo (4080) | Novocastra | 1:50 | CB6 | Moderate | |
Mo (B104.1) | Biomeda | 1:5 | CB6 | High | |
Rabbit | Dako | 1:20,000 | PK | Low | |
Mo (MAB706) | Millipore | 1:50 | CB6 | High | |
Mo (2D7/1) | Abcam | 1:5000 | CB6 | Moderate | |
Rabbit | Abcam | 1:2000 | None | Moderate | |
Rabbit | Dako | 1:50 | PK | Moderate | |
Mo (UCL3R) | Novocastra | 1:100 | EDTA | High | |
Mo (70–2) | Monosan | 1:300 | None | High | |
Rabbit | Denka Seiken | 1:500 | EDTA | High | |
Mo (MAB738) | Chemicon | 1:3000 | EDTA | High | |
Rabbit | Abcam | 1:800 | CB6 | High | |
Mo (128/390) | Chemicon | 1:1000 | None | Moderate | |
Pneumolysin | Mo (9.1/2/3/6) | Novocastra | 1:50 | EDTA | High |
Protein A | Mo (SPA-27) | Sigma | 1:100 | PK | Moderate |
Protein G | Rabbit | Abcam | 1:500 | PK | Moderate |
Mo (B11) | Biogenesis | 1:800 | EDTA | High | |
Mo (STAPH11–248.2) | Chemicon | 1:500 | PK | Moderate | |
Goat | BioReagents | 1:500 | PK | Moderate | |
Rabbit | Biocare | 1:1000 | EDTA | Low | |
Mo (J010J) | Thermo | 1:50 | CB6 | High | |
Rabbit | Biocare | 1:200 | EDTA | Moderate | |
Mo (WF-AF-1) | Thermo | 1:50 | EDTA | High | |
Rabbit | Unitika | 1:8000 | PK | Moderate | |
Mo (MaB806) | Chemicon | 1:400 | Pepsin | High | |
Rabbit | Dako | 1:500 | None | Moderate | |
Mo (3F6) | Dako | 1:100 | CB6 | High | |
Mo (WSSA-RA-1) | Thermo | 1:50 | CB6 | High | |
Adenovirus | Mo (M58 + M73) | Abcam | 1:400 | PK | High |
BK virus | Mo (5E6) | Abnova | 1:500 | CB6 | High |
Cytomegalovirus | Mo (CCH2 + DDG9) | Dako | 1:200 | EDTA | High |
EB virus (LMP1) | Mo (CS1–CS4) | Dako | 1:50 | PK | High |
EB virus (EBNA2) | Mo (PE2) | Dako | 1:100 | EDTA | High |
Influenza virus A | Mo (1331) | AbD | 1:100 | PK | High |
Influenza virus A | Mo (1A52.9) | Acris | 1:100 | PK | High |
Influenza virus B | Guinea pig | Denka Seiken | 1:100 | EDTA | High |
HBs antigen | Goat | Bioss | 1:2000 | PK | High |
HBs antigen | Mo (HB-024) | Japan Biotest | 1:500 | None | High |
HBc antigen | Rabbit | Dako | 1:15,000 | EDTA | High |
HBe antigen | Mo (BE-05) | Institute of Immunology | 1:50 | PK | High |
HCV (NS3–NS4) | Mo (Tordji-22) | Signet | 1:200 | EDTA | High |
HCV (NS3) | Mo (MMM33) | Novocastra | 1:100 | CB7 | High |
HCV (NS4) | Mo (5D4-10E7) | Abcam | 1:300 | EDTA | High |
HCV (NS5a) | Mo (7-D4) | Fitzgerald | 1:100 | EDTA | High |
HCV (core) | Mo (Aa70–Aa90) | Chemicon | 1:100 | EDTA | High |
Herpes simplex virus-1 | Rabbit | Dako | 1:500 | None | Moderate |
Herpes simplex virus-2 | Rabbit | Dako | 1:1500 | None | Moderate |
HIV (p24) | Mo (kal-1) | Dako | 1:1000 | EDTA | High |
HPV | Mo (K1H8) | Dako | 1:500 | CB6 | High |
HPV16 | Mo (CamVir-1) | BioGenex | 1:5000 | EDTA | High |
JC virus | Rabbit | Dako | 1:300 | CB7 | High |
Merkel cell polyomavirus | Mo (CM2B4) | Santa Cruz | 1:100 | EDTA | High |
Measles virus | Rabbit | Novus | 1:1000 | EDTA | High |
Mumps virus | Mo (MAB846) | Chemicon | 1:400 | EDTA | High |
Norovirus (GII/4) | Rabbit | Denka Seiken | 1:500 | None | High |
Parvovirus B19 | Mo (R92.2.8) | Novocastra | 1:1000 | EDTA | High |
RS virus | Mo (603705) | Novocastra | 1:200 | EDTA | High |
SV40 (T-antigen) | Mo (PAb416) | Millipore | 1:100 | EDTA | High |
VZV | Mo (C90.2.8) | Novocastra | 1:100 | None | High |
Rabbit | Abcam | 1:200 | CB6 | High |
List of commercially available antibodies against pathogens: the author’s experience.
Antimicrobial antibodies the author is using are listed up for the readers’ convenience.
Immunoperoxidase application using four kinds of commercially available rabbit antisera raised against BCG,
Indirect immunoperoxidase staining using BCG rabbit antiserum (Dako/Agilent Technologies) diluted at a 1:5000 was highly sensitive for detecting mycobacteria in histopathological sections [4, 7, 8, 24, 25]. No pretreatment for antigen retrieval was given. Mycobacterial antigens were clearly demonstrable not only in caseous necrosis in active tuberculosis but also in a fibrous nodule of old calcified tuberculosis (Figure 1). BCG antigens were scarcely detectable in epithelioid granulomas. The BCG immunostaining was much more sensitive to detect mycobacteria than conventional acid-fast (Ziehl-Neelsen) staining, as indicated in Table 2 [4, 24]. In BCG immunostaining, the judgment of positivity can be done easily and quickly, while it takes minutes or longer in case of conventional acid-fast staining. It is evident that the antiserum is reactive with mycobacterial antigenic substances on destroyed bacterial fragments. The BCG immunostaining was also applicable to demonstrating non-tuberculous mycobacteria and
BCG immunostaining I (upper panels, cerebral tuberculoma; lower panels, old calcified nodule in the lung; left, H&E; right, BCG immunostaining). Mycobacterial antigens were clearly demonstrable not only in caseous necrosis but also in a fibrous nodule of old tuberculosis. Mycobacterial antigenic substances on destroyed bacterial fragments are detectable by the antiserum.
Disease | Acid-fast staining | BCG immunostaining |
---|---|---|
Exudative lesion | 5/6 (83%) | 6/6 (100%) |
Caseous granuloma | 3/11 (27%) | 5/11 (45%) |
Non-caseous granuloma | 0/6 (0%) | 1/6 (17%) |
Encapsulated caseous focus, non-calcified | 0/9 (0%) | 5/9 (56%) |
Encapsulated caseous focus, calcified | 0/11 (0%) | 8/11 (73%) |
Fibrous focus, calcified | 0/1 (0%) | 1/1 (100%) |
Lepromatous leprosy (multibacillary form) | 2/2 (100%)* | 2/2 (100%) |
Tuberculoid leprosy (paucibacillary form) | 0/3 (0%) | 0/3 (0%) |
Sarcoidosis | 0/7 (0%) | 0/7 (0%) |
Sarcoid-like reaction in lymph node | 0/3 (0%) | 0/3 (0%) |
Comparative detectability of mycobacteria with acid-fast staining and immunostaining for BCG antigens.
Fite modification employing oil-xylene for deparaffinization required.
Acid-fast staining and BCG immunostaining were compared using three types of granulomatous lesions embedded in paraffin.
BCG immunostaining II (upper panels, non-tuberculous mycobacterial lymphadenitis in AIDS; lower panels, lepromatous leprosy; left, H&E; right, BCG immunostaining; inset, acid-fast staining). Striated histiocytes in
The BCG antigens were extremely stable after prolonged fixation in formalin for a long period of time [19, 26]. Figure 3 displays dense-positive signals in an exudative pulmonary tuberculosis lesion fixed in formalin for nearly 70 years.
BCG immunostaining III (left, HE; right, BCG immunostaining). BCG antigens are very stable against fixation. Dense-positive signals are seen in a pulmonary exudative tuberculosis lesion fixed in formalin for 70 years. Of note is that the nuclei are poorly stained with hematoxylin due to prolonged fixation.
Lethal
Warthin-Starry’s silver method is technically difficult, frequently with a false-negative result in case of treponemal infection. In contrast, immunostaining (Simple Stain-Max, Nichirei) using
In Figure 6, a biopsied penile lesion with painless ulceration (chancre) in stage I and excised syphilitic granulomatous lymphadenitis in stage III are presented. In the penis, numerous spiral microbes were clustered mainly in the basal part of the squamous mucosa and around the dermal capillary vessels. In the stage III lesion with granulomatous reaction, coiled spirochetes were infrequently observed. Immunostaining was considerably supportive and useful in the clinical practice, when treponemal microbes were visualized in the tonsillar, gastric, and aortic valvular biopsy specimens (Figure 7).
Immunostaining (Simple Stain-Max, Nichirei) using
We diagnostic pathologists encounter lesions strongly suggestive of infection but with poor clinical information or with difficulty in microscopically supposing a causative pathogen. In such situations, immunostaining employing the abovementioned four kinds of rabbit antisera is worthy of application [8, 19]. We can prove the existence of pathogens in a certain part of the lesion. Background staining is negligible, whereas
Regrettably enough, the availability of antisera against microbes from commercial sources has become limited. In fact, antisera against BCG and
Table 3 summarizes reactivities of various microbes to the four kinds of rabbit antibacterial antisera.
Bacterium | Anti- | Anti-BCG | Anti- | Anti- |
---|---|---|---|---|
ND | − | − | + | |
ND | − | + | + | |
+ | + | + | + | |
Non-tuberculous | ND | + | + | − |
+ | + | + | + | |
+ | + | + | − | |
+ | + | + | − | |
+ | + | + | − | |
+ | + | + | − | |
ND | + | + | − | |
+ | + | + | (+) | |
+ | (+) | − | − | |
+ | − | − | − | |
+ | − | − | − | |
Brain abscess | + | − | − | − |
Chorioamnionitis | + | − | − | − |
Reactivities of various microbes to the four kinds of rabbit antibacterial antisera.
ND, not done, (+), focally positive.
Reactivities of various pathogens to commercial rabbit antisera against
Hamster liver experimentally infected with
Hamster liver in experimental leptospirosis (left, H&E; center,
Intestinal spirochetosis is caused by localized infection of
Intestinal spirochetosis (left upper, H&E; center upper, reactivity with
Non-tuberculous mycobacteria (
Non-tuberculous mycobacteriosis of the lung caused by
Gangrenous lesions in the extremity caused by lethal
Gangrene of the extremity caused by
Autopsied lung in pertussis (left upper, H&E; right upper, BCG antigens; left lower,
Secondary dense infection of
Nocardiosis is caused by filamentous Gram-positive saprophytic bacteria,
Pulmonary nocardiosis caused by
Cervical lymphadenopathy in cat-scratch disease, infection of
Splenic bartonellosis (left upper, H&E; right upper, reactivity with
Granulomatous mastitis is seen in childbearing women 2–4 years after breastfeeding [43]. The causative agent is lipophilic Gram-positive bacillus,
Granulomatous mastitis caused by
Rhinoscleroma is localized and indolent infective nodule in the nasal cavity, endemic in Egypt, South America and eastern Europe. The main causative microbe has been reported to be
Rhinoscleroma caused by Klebsiella rhinoscleromatis (left upper: H&E, right upper: reactivity with monoclonal antibody 70-2 to Klebsiella spp., left lower: B. cereus antigens, right lower:
In certain lesions,
The widest cross-reactivity shown by Bacillus cereus antiserum (left upper, brain abscess; right upper, ascending chorioamnionitis of placenta; lower panels, Propionibacterium acnes-induced folliculitis of the chest, combination of H&E, and
Lethal
Sera of patients suffering from infectious diseases expectedly contain high-titer IgG-type antibodies against the causative microbe, particularly when inflammatory reactions such as abscess and granuloma are histopathologically confirmed in immunocompetent individuals. It is well known that 2 weeks is needed to have specific antibodies to be raised in the serum. The diluted patients’ serum can be used as a probe for indirect immunoperoxidase staining on histopathologic specimens routinely embedded in paraffin [4, 7, 8, 20, 21, 22, 23]. A variety of infectious microbes were demonstrable with reliable sensitivity but limited specificity, as indicated below. Endogenous human immunoglobulins (IgG) in formalin-fixed, paraffin-embedded sections were scarcely detected by the peroxidase-labeled secondary antihuman immunoglobulins. High-sensitivity detection sequence such as the labeled polymer method naturally leads to high-background staining, because of the detection of endogenous immunoglobulins in sections. The method is simple, economic, useful, and beautiful for the histopathologic diagnosis of infectious diseases, and it is particularly suitable for the developing countries, since the patient’s serum is free in charge. This approach is especially effective for detecting protozoa and helminth [22], because the specific antibodies are often commercially unavailable.
There are two situations. In some cases, the causative pathogen has been identified by clinical, laboratory, and/or histopathological analysis, and thus the specificity of the patient’s serum can be expected before immunostaining. In other cases, the causative pathogen is unsettled yet or unknown. In the latter situation, the patient’s serum functions as a low-specificity and high-sensitivity probe in immunostaining.
Table 4 summarizes patients’ sera applicable to immunostaining in paraffin sections.
Infectious disease | Serum dilution | Comments |
---|---|---|
Tsutsugamushi disease (scrub typhus) | 1:100 | Immunoelectron microscopy performed |
Staphylococcal pyoderma | 1: 500 | |
1:500 | ||
Cutaneous sporotrichosis | 1:500 | Sporotrichin reaction positive |
1:500 | Multiple skin papules on the chest | |
Cutaneous alternariosis | 1:500 | Long-lasting skin lesion on the knee |
Cutaneous cryptococcosis in leukemia | 1:10 | Chemotherapy with steroid administration |
Hemorrhagic varicella | 1:500* | Bone marrow transplanted acute leukemia |
Cutaneous leishmaniasis (African type) | 1:1000 | High immunofluorescence titer |
Cutaneous leishmaniasis (Indian type) | 1:1000 | High immunofluorescence titer |
Visceral leishmaniasis (liver biopsy) | 1:500 | High immunofluorescence titer |
Acanthamebic encephalitis | 1:500 | Opportunistic infection in liver cirrhosis |
Amebic dysentery | 1:500* | High immunofluorescent titer |
Balamuthia encephalitis | 1:500 | |
Cerebral toxoplasmosis | 1:1000* | High immunofluorescence titer |
Cryptosporidiosis in AIDS | 1:1000* | High immunofluorescence titer |
Duodenal cystoisosporiasis | 1:500 | Chronic intractable diarrhea |
Blastocystosis (cell block of cultured microbes) | 1:500* | High immunofluorescence titer |
Cutaneous gnathostomiasis | 1:500 | Creeping disease on the abdominal skin |
Extra-gastrointestinal (omental) anisakiasis | 1:500 | Positive with monoclonal antibody |
Liver ascariasis (surgical material) | 1:500 | Ouchterlony’s diffusion-in-gel test positive |
Japanese schistosomiasis (colon) | 1:200 | Calcified ova seen (healed remote case) |
Bilharziasis (colon biopsy) | 1:500 | Spine-forming ova seen in urine |
Multilocular echinococcosis | 1:200 | Hepatectomy specimen in Hokkaido Island |
Neurocysticercosis | 1:20 | Multiple brain nodules |
Patients’ sera applicable to immunostaining in paraffin sections.
High-titer sera were obtained from other immunocompetent patients.
Human tissues and organs, obtained either by biopsy, during surgery or at autopsy, were routinely fixed in 10% unbuffered or buffered formalin for 1 day to 4 weeks. The indirect immunoperoxidase technique was applied to deparaffinized sections [4, 7, 8, 20, 21, 22, 23]. The serum of patient, principally not in an immunocompromised state, was diluted at 1:500 or 1:1000 and was incubated for 30 min or overnight. In case of protozoan infection, the presence of high-titer IgG antibodies in the patients’ serum was commonly confirmed by immunofluorescence titration, as shown in Table 4. The serum from patients positive for human immunodeficiency virus (HIV) or hepatitis virus markers must not be utilized, in order to avoid biohazard. The serum of immunocompromised, non-HIV patients may be utilized after dilution at 1:5 or 1:10. The second layer reagent was horseradish peroxidase-labeled goat IgG to human immunoglobulins (Dako/Agilent) at a 1:50 dilution. Endogenous peroxidase activity was quenched in methanol containing 0.3% hydrogen peroxide for 20 min. No other pretreatment procedures such as proteinase digestion or heat-induced antigen retrieval were needed, but heating pretreatment was infrequently necessary for certain instances (e.g., the detection of free-living amoeba,
It is of notice that IgG in the patients’ serum may show cross-reactivity to related pathogens to certain or considerable degrees [4, 20, 21]. In bacterial and fungal infections, the sera often serve as pan-bacterial or pan-fungal probes. The cross-reactivity may result from the naturally acquired antibodies in healthy individuals [20]. In viral, protozoan, and helminthic infections, in contrast, high-grade specificity with limited cross-reactivity can be expected [22]. When the specificity of the sera of patients with parasitic infestation is known, it is sufficiently satisfactory to enable them to be employed as specific antibody reagents for the following new cases.
Here, the immunohistochemical application of sera of patients with established or fixed diagnosis is shown, including bacterial, fungal, viral, protozoan, and helminthic infections.
Mite-borne Tsutsugamushi disease or scrub typhus endemic in Japan is caused by
Mite-bite eschar in Tsutsugamushi disease or scrub typhus (left, H&E; center, reactivity with patient’s own serum; right, pre-embedding immunoelectron microscopy using paraffin section). Hemophagocytic macrophages are clustered at the base of eschar. The patient’s serum gave positive granulated signals in the cytoplasm of the macrophages (arrows), and pre-embedding immunoelectron microscopy disclosed densely labeled granular material measuring 2 μm.
Skin biopsy specimen from
Sporotrichosis, skin infection of a dimorphic fungus
Sporotrichosis (left, periodic acid-Schiff reaction; right, reactivity with patient’s own serum). Suppurative granulomas are formed in the dermis. Periodic acid-Schiff-reactive small yeast-like fungal cells are phagocytized by macrophages or multinucleated giant cells and are reactive with the patient’s own serum.
Cutaneous alternariosis (left upper, gross appearance of the elbow; right upper, H&E; left lower, Grocott stain; right lower, reactivity with patient’s own serum). Biopsy specimen from the brown-colored skin infiltrate contains a few Grocott-reactive fungi,
Cutaneous lesions occur in 10-20% of life-threatening disseminated cryptococcosis seen in immunocompromised patients [51]. Opportunistic skin infection of
Cutaneous cryptococcosis (left, H&E; right, reactivity with patient’s own serum). Opportunistic skin infection of
Biopsy was taken from the vesicular skin lesion of lethal hemorrhagic varicella (small pox). The patient was a young boy suffering from intractable acute lymphoblastic leukemia treated with chemotherapy and bone marrow transplantation [52]. The 1:500 diluted serum of another adult patient with a recent history of varicella clearly reacted to the plasma membrane of acantholytic keratinocytes with intranuclear viral inclusion bodies, and the localization pattern was comparable with that of GP-1 antigen revealed by immunostaining using monoclonal antibody C90.2.8 (Figure 30) [21, 23]. The viral intranuclear inclusions remained unreactive. It is evident that antibodies raised in the infected patient were specific to GP-1 antigen of varicella-zoster virus, an immunodominant viral substance [53].
Hemorrhagic varicella (left, H&E; center, reactivity with the serum of another patient; right, reactivity with monoclonal antibody C90.2.8 to GP-1 antigen of varicella-zoster virus). Biopsy was taken from a hemorrhagic vesicle, as lethal manifestation of opportunistic varicella-zoster virus infection in a leukemic boy after bone marrow transplantation. The diluted serum of another adult patient with a recent history of varicella clearly reacts to the plasma membrane of acantholytic keratinocytes with unreactive intranuclear viral inclusion bodies. The localization pattern is comparable with that of GP-1 antigen.
Figure 31 demonstrates microscopic biopsy features of African-type cutaneous leishmaniasis (
African-type cutaneous leishmaniasis (left, gross appearance of the forearm; upper panels, the patient of gross photograph; lower panels, an older lesion of his friend; center, H&E; right, reactivity with patient’s serum). The Japanese men volunteered afforestation on the Saharan dessert in the Republic of Mali. Biopsy was taken from ulcerated skin lesions. The patient’s own serum demonstrates round pathogens (
Another form of cutaneous leishmaniasis, Indian type, is caused by
Indian-type cutaneous leishmaniasis (left, gross appearance of the neck; center, H&E; right, reactivity with patient’s own serum; inset, Giemsa stain on a stamp cytology preparation). Solitary skin ulcer is characteristic of this clinical form endemic in India. Biopsy specimen from a Japanese patient shows numerous round pathogens (
Acanthamebic keratitis is sight-threatening infection of the cornea by the genus
Acanthamebic keratitis (left, H&E; center, reactivity with the serum of patient of acanthamebic meningoencephalitis; right, reactivity with monoclonal antibody ACA5 to
Amebic dysentery, colonic infection of
Amebic dysentery (left, H&E; center, reactivity with patient’s own serum; right, reactivity with monoclonal antibody EHK153 to
Cryptogenic and asymptomatic infection of
Toxoplasmosis (upper panels, toxoplasma encephalitis in AIDS; lower panels, toxoplasma meningitis in a non-AIDS patient; left, H&E; right, reactivity with the serum from a healthy individual serologically with high-titer IgG). Ruptured protozoan cysts in AIDS-associated cerebral toxoplasmosis are reactive with the serum. The same serum decorates trophozoites of
Cryptosporidiosis is zoonotic and waterborne infection of
Cryptosporidiosis (upper panels, ileal mucosal biopsy from a young suffering from severe diarrhea after close contact with cows in a Hokkaido farm; lower panels, autopsied jejunum of an AIDS patient complaining of lethal diarrhea; left, H&E; right, reactivity with the serum of a cryptosporidiosis patient with high-titer IgG). The tiny microbes grow in the brush border of enterocytes (arrows). Immunostaining using the high-titer serum demonstrates dot-like positive signals on the apex of the columnar cells of both patients.
Cystoisosporiasis (left, H&E; right, reactivity with patient’s own serum). Duodenal biopsy specimen was taken from a Japanese male patient with adult T-cell leukemia in Kyushu Island, complaining of severe diarrhea. Large-sized schizonts of
Blastocystosis (cultured
Infestation of
Gnathostomiasis (left, H&E; right, reactivity with patient’s own serum). A Japanese male manifested creeping disease on the abdomen. Targeted biopsy reveals cut surfaces of
Ectopic anisakiasis (left, H&E; center, reactivity with patient’s own serum; right, reactivity with monoclonal antibody An2 to
Schistosomiasis is caused by digenetic blood trematodes (fluke). Water snail-mediated three main species infest humans:
Schistosomiasis japonicum (left, acid-fast staining; right, reactivity with patient’s own serum). In biopsied colonic mucosa of an asymptomatic individual living in a historical endemic area, acid-fast ova of
Bilharziasis (upper panels, egg tubercle in the sigmoid colon; lower panels, surgical material of brain lesion; left, H&E; right, reactivity with patient’s own serum). Two young Japanese male patients with a history of staying in African continent complained of hematuria and presented ectopic egg tubercles in the sigmoid colon and in the brain, respectively. The multinucleated (miracidial) content of the egg of
Multilocular (alveolar) echinococcosis, infestation of
Multilocular echinococcosis (left, H&E; right, reactivity with patient’s own serum). The liver infested by
Neurocysticercosis is infestation of
Neurocysticercosis (left, H&E; right, reactivity with patient’s own serum). The brain lesion of larva migrans in a Japanese female was surgically removed. A cysticercus body with scolex formation is microscopically lined by eosinophilic tegument and underlying subcuticular cells. The patient’s serum is weakly reactive with the tegument.
When the diagnosis is unsettled, the specificity of the patient’s serum remains unknown. If the positive signals reactive with the patient’s serum are seen within the inflammatory lesion, it is reasonable for us to regard that the target microbes are visualized. The size and shape of the stained targets suggested certain causative pathogens within the lesion [20, 21, 22, 23]. The final diagnosis can be made by combining clinical information and histopathological appearance with the morphology of the pathogen. Of no doubt, this gives us the most powerful and useful situation in applying immunostaining using the patient serum.
Invasive opportunistic infection of
Ectopic infestation of
Hepatic ascariasis (left upper, cut surface of the resected liver; right upper, Ouchterlony’s diffusion-in-gel test using the extract of varied helminths; left lower, H&E; right lower, reactivity with patient’s own serum). Yellow-colored xanthogranulomatous nodules are seen at the liver hilus. Microscopically, a small number of dead and calcified ova are distributed in necrotic substance. The content of the ova is immunoreactive with the patient’s serum. In Ouchterlony’s test, a precipitation line against
Figure 47 demonstrates a splenic lesion with ectopic migration of
Splenic ascariasis (left, cut surface of the formalin-fixed spleen; center, H&E; right, reactivity with the serum of patient with hepatic ascariasis). Ectopic migration of
Visceral leishmaniasis, sandfly-mediated systemic infection of
Visceral leishmaniasis (left, H&E; right, reactivity with patient’s own serum; inset, high-powered view). During the stay in India, a Japanese businessman manifested headache, high fever, thrombocytopenia, and liver dysfunction. Liver biopsy shows small epithelioid granulomas. A panel of immunohistochemical analysis has failed to identify the causal agent. The patient’s own serum demonstrates red cell-sized positive signals in the cytoplasm of epithelioid cells, strongly suggesting visceral leishmaniasis (kala azar) endemic in India. The final diagnosis was made by the serological study and successful treatment.
Free-living amoeba widely seen in soil and water may cause lethal meningoencephalitis as an opportunistic or non-opportunistic infection [78]. A Japanese male aged 60’s suffering from alcoholic liver cirrhosis manifested left hemiparesis [79]. Computed tomography disclosed multifocal low densities in his right hemisphere. Herpetic encephalitis was clinically suspected. HIV antibody was negative. Progressive intracranial edema necessitated decompressive craniotomy with brain biopsy. The brain tissue microscopically showed perivascular chronic active inflammation, with ameba-like cells somewhat resembling macrophages being scattered. The 1:500 diluted patient’s serum clearly reacted with the protozoan bodies, and mouse antiserum to
Acanthamebic meningoencephalitis (left upper, low-powered H&E; right upper, high-powered H&E; inset, an amebic cyst; left lower, reactivity with patient’s own serum; right lower, reactivity with mouse antiserum to
Of note is an exception that
Undoubtedly, the detection of causative pathogens in the inflammatory lesion is the key step directing to the correct histopathological diagnosis of infectious diseases. Even if the specificity of the serum is unknown, the final diagnosis can be reached, based on the morphology and distribution of the positive signals, when combined with tissue reactions, laboratory data and clinical features. In the present article, the author introduced two different approaches using low-specificity antisera. The targets were formalin-fixed and paraffin-embedded sections. One approach is the use of commercially available rabbit antisera showing wide cross-reactivity to a variety of bacteria, and another is the use of diluted patients’ sera.
Immunostaining using plural antimicrobial antisera commonly yielded clear positivity with low background, because of poor cross-reactivity of bacterial antigens to human cells and tissues. The approach described here was aimed at visualizing the causative bacteria within infectious lesions in routinely prepared paraffin sections through a wide cross-reactivity shown by low-specificity rabbit antisera against four kinds of bacteria.
Immunostaining using patients’ sera is also quite useful in making the histopathological diagnosis. Occasionally, IgG in the patients’ sera showed cross-reactivity to related pathogens wider than expected. In bacterial and fungal infection, the sera served as pan-bacterial and pan-fungal probes, respectively. Despite such broad/low specificity, this convenient procedure is excellent in selectively identifying the pathogen within the lesion in question. In viral, protozoal, and helminthic infection, the specificity was much narrower with limited cross-reactivities, and once the specificity is known, the patients’ sera turn to become specific primary antibodies for identifying pathogens in the following new cases.
In the latter approach, what one should do is, instead of ordering an expensive antibody of unknown quality, to make a brief phone call to clinicians or laboratory technicians to ask to save a small aliquot of patients’ sera, soon after microscopic confirmation of the host response in histopathology specimens. This is particularly true when specific antibodies are not listed in the commercial catalog. Of note is that informed consent is unnecessary when the patient’s serum is utilized primarily for making a diagnosis of the patient’s own. When the serum is applied to immunostaining for another case as the primary antibody, the author strongly recommends linking the preserved serum non-anonymously.
The author sincerely hopes that the approaches shown here will be applied to the histopathological diagnosis of infectious diseases in the readers’ laboratories.
The author deeply thanks many colleagues of technicians who supported the authors’ idea and kindly immunostained specimens. The author has no granting for the present study.
The author has no conflict of interest in the present study.
Edited by Jan Oxholm Gordeladze, ISBN 978-953-51-3020-8, Print ISBN 978-953-51-3019-2, 336 pages,
\nPublisher: IntechOpen
\nChapters published March 22, 2017 under CC BY 3.0 license
\nDOI: 10.5772/61430
\nEdited Volume
This book serves as a comprehensive survey of the impact of vitamin K2 on cellular functions and organ systems, indicating that vitamin K2 plays an important role in the differentiation/preservation of various cell phenotypes and as a stimulator and/or mediator of interorgan cross talk. Vitamin K2 binds to the transcription factor SXR/PXR, thus acting like a hormone (very much in the same manner as vitamin A and vitamin D). Therefore, vitamin K2 affects a multitude of organ systems, and it is reckoned to be one positive factor in bringing about "longevity" to the human body, e.g., supporting the functions/health of different organ systems, as well as correcting the functioning or even "curing" ailments striking several organs in our body.
\\n\\nChapter 1 Introductory Chapter: Vitamin K2 by Jan Oxholm Gordeladze
\\n\\nChapter 2 Vitamin K, SXR, and GGCX by Kotaro Azuma and Satoshi Inoue
\\n\\nChapter 3 Vitamin K2 Rich Food Products by Muhammad Yasin, Masood Sadiq Butt and Aurang Zeb
\\n\\nChapter 4 Menaquinones, Bacteria, and Foods: Vitamin K2 in the Diet by Barbara Walther and Magali Chollet
\\n\\nChapter 5 The Impact of Vitamin K2 on Energy Metabolism by Mona Møller, Serena Tonstad, Tone Bathen and Jan Oxholm Gordeladze
\\n\\nChapter 6 Vitamin K2 and Bone Health by Niels Erik Frandsen and Jan Oxholm Gordeladze
\\n\\nChapter 7 Vitamin K2 and its Impact on Tooth Epigenetics by Jan Oxholm Gordeladze, Maria A. Landin, Gaute Floer Johnsen, Håvard Jostein Haugen and Harald Osmundsen
\\n\\nChapter 8 Anti-Inflammatory Actions of Vitamin K by Stephen J. Hodges, Andrew A. Pitsillides, Lars M. Ytrebø and Robin Soper
\\n\\nChapter 9 Vitamin K2: Implications for Cardiovascular Health in the Context of Plant-Based Diets, with Applications for Prostate Health by Michael S. Donaldson
\\n\\nChapter 11 Vitamin K2 Facilitating Inter-Organ Cross-Talk by Jan O. Gordeladze, Håvard J. Haugen, Gaute Floer Johnsen and Mona Møller
\\n\\nChapter 13 Medicinal Chemistry of Vitamin K Derivatives and Metabolites by Shinya Fujii and Hiroyuki Kagechika
\\n"}]'},components:[{type:"htmlEditorComponent",content:'This book serves as a comprehensive survey of the impact of vitamin K2 on cellular functions and organ systems, indicating that vitamin K2 plays an important role in the differentiation/preservation of various cell phenotypes and as a stimulator and/or mediator of interorgan cross talk. Vitamin K2 binds to the transcription factor SXR/PXR, thus acting like a hormone (very much in the same manner as vitamin A and vitamin D). Therefore, vitamin K2 affects a multitude of organ systems, and it is reckoned to be one positive factor in bringing about "longevity" to the human body, e.g., supporting the functions/health of different organ systems, as well as correcting the functioning or even "curing" ailments striking several organs in our body.
\n\nChapter 1 Introductory Chapter: Vitamin K2 by Jan Oxholm Gordeladze
\n\nChapter 2 Vitamin K, SXR, and GGCX by Kotaro Azuma and Satoshi Inoue
\n\nChapter 3 Vitamin K2 Rich Food Products by Muhammad Yasin, Masood Sadiq Butt and Aurang Zeb
\n\nChapter 4 Menaquinones, Bacteria, and Foods: Vitamin K2 in the Diet by Barbara Walther and Magali Chollet
\n\nChapter 5 The Impact of Vitamin K2 on Energy Metabolism by Mona Møller, Serena Tonstad, Tone Bathen and Jan Oxholm Gordeladze
\n\nChapter 6 Vitamin K2 and Bone Health by Niels Erik Frandsen and Jan Oxholm Gordeladze
\n\nChapter 7 Vitamin K2 and its Impact on Tooth Epigenetics by Jan Oxholm Gordeladze, Maria A. Landin, Gaute Floer Johnsen, Håvard Jostein Haugen and Harald Osmundsen
\n\nChapter 8 Anti-Inflammatory Actions of Vitamin K by Stephen J. Hodges, Andrew A. Pitsillides, Lars M. Ytrebø and Robin Soper
\n\nChapter 9 Vitamin K2: Implications for Cardiovascular Health in the Context of Plant-Based Diets, with Applications for Prostate Health by Michael S. Donaldson
\n\nChapter 11 Vitamin K2 Facilitating Inter-Organ Cross-Talk by Jan O. Gordeladze, Håvard J. Haugen, Gaute Floer Johnsen and Mona Møller
\n\nChapter 13 Medicinal Chemistry of Vitamin K Derivatives and Metabolites by Shinya Fujii and Hiroyuki Kagechika
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He is currently a rated researcher by the National Research Foundation of South Africa at category C2. He has published widely in the field of infectious diseases and has overseen several MSc’s and PhDs. His research activities mostly cover topics on infectious diseases from epidemiology to control. His particular interest lies in the study of intestinal protozoan parasites and opportunistic infections among HIV patients as well as the potential impact of childhood diarrhoea on growth and child development. He also conducts research on water-borne diseases and water quality and is involved in the evaluation of point-of-use water treatment technologies using silver and copper nanoparticles in collaboration with the University of Virginia, USA. 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His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. 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. 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Saxena",hash:"105e347b2d5dbbe6b593aceffa051efa",volumeInSeries:1,fullTitle:"Influenza - Therapeutics and Challenges",editors:[{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",biography:"Professor Dr. Shailendra K. Saxena is a vice dean and professor at King George's Medical University, Lucknow, India. His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. 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"}}}]},{type:"book",id:"7064",title:"Current Perspectives in Human Papillomavirus",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7064.jpg",slug:"current-perspectives-in-human-papillomavirus",publishedDate:"May 2nd 2019",editedByType:"Edited by",bookSignature:"Shailendra K. Saxena",hash:"d92a4085627bab25ddc7942fbf44cf05",volumeInSeries:2,fullTitle:"Current Perspectives in Human Papillomavirus",editors:[{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",biography:"Professor Dr. Shailendra K. Saxena is a vice dean and professor at King George's Medical University, Lucknow, India. His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. 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"}}}]},{type:"book",id:"7123",title:"Current Topics in Neglected Tropical Diseases",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7123.jpg",slug:"current-topics-in-neglected-tropical-diseases",publishedDate:"December 4th 2019",editedByType:"Edited by",bookSignature:"Alfonso J. Rodriguez-Morales",hash:"61c627da05b2ace83056d11357bdf361",volumeInSeries:3,fullTitle:"Current Topics in Neglected Tropical Diseases",editors:[{id:"131400",title:"Prof.",name:"Alfonso J.",middleName:null,surname:"Rodriguez-Morales",slug:"alfonso-j.-rodriguez-morales",fullName:"Alfonso J. Rodriguez-Morales",profilePictureURL:"https://mts.intechopen.com/storage/users/131400/images/system/131400.png",biography:"Dr. Rodriguez-Morales is an expert in tropical and emerging diseases, particularly zoonotic and vector-borne diseases (especially arboviral diseases). He is the president of the Travel Medicine Committee of the Pan-American Infectious Diseases Association (API), as well as the president of the Colombian Association of Infectious Diseases (ACIN). He is a member of the Committee on Tropical Medicine, Zoonoses, and Travel Medicine of ACIN. He is a vice-president of the Latin American Society for Travel Medicine (SLAMVI) and a Member of the Council of the International Society for Infectious Diseases (ISID). Since 2014, he has been recognized as a Senior Researcher, at the Ministry of Science of Colombia. He is a professor at the Faculty of Medicine of the Fundacion Universitaria Autonoma de las Americas, in Pereira, Risaralda, Colombia. He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. He is currently the Editor in Chief of the journal Travel Medicine and Infectious Diseases. His Scopus H index is 47 (Google Scholar H index, 68).",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null}]},{type:"book",id:"7839",title:"Malaria",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7839.jpg",slug:"malaria",publishedDate:"December 11th 2019",editedByType:"Edited by",bookSignature:"Fyson H. Kasenga",hash:"91cde4582ead884cb0f355a19b67cd56",volumeInSeries:4,fullTitle:"Malaria",editors:[{id:"86725",title:"Dr.",name:"Fyson",middleName:"Hanania",surname:"Kasenga",slug:"fyson-kasenga",fullName:"Fyson Kasenga",profilePictureURL:"https://mts.intechopen.com/storage/users/86725/images/system/86725.jpg",biography:"Dr. Kasenga is a graduate of Tumaini University, Kilimanjaro Christian Medical College, Moshi, Tanzania and Umeå University, Sweden. He obtained a Master’s degree in Public Health and PhD in Public Health and Epidemiology. He has a background in Clinical Medicine and has taken courses at higher diploma levels in public health from University of Transkei, Republic of South Africa, and African Medical and Research Foundation (AMREF) in Nairobi, Kenya. Dr. Kasenga worked in different places in and outside Malawi, and has held various positions, such as Licensed Medical Officer, HIV/AIDS Programme Officer, HIV/AIDS resource person in the International Department of Diakonhjemet College, Oslo, Norway. He also managed an Integrated HIV/AIDS Prevention programme for over 5 years. He is currently working as a Director for the Health Ministries Department of Malawi Union of the Seventh Day Adventist Church. Dr. Kasenga has published over 5 articles on HIV/AIDS issues focusing on Prevention of Mother to Child Transmission of HIV (PMTCT), including a book chapter on HIV testing counseling (currently in press). Dr. Kasenga is married to Grace and blessed with three children, a son and two daughters: Happy, Lettice and Sungani.",institutionString:"Malawi Adventist University",institution:{name:"Malawi Adventist University",institutionURL:null,country:{name:"Malawi"}}}]}]},openForSubmissionBooks:{paginationCount:7,paginationItems:[{id:"11476",title:"Globalization and Sustainability - Recent Advances, New Perspectives and Emerging Issues",coverURL:"https://cdn.intechopen.com/books/images_new/11476.jpg",hash:"8d41fa5f3a5da07469bbc121594bfd3e",secondStepPassed:!0,currentStepOfPublishingProcess:4,submissionDeadline:"March 24th 2022",isOpenForSubmission:!0,editors:[{id:"335401",title:"Prof.",name:"Margherita",surname:"Mori",slug:"margherita-mori",fullName:"Margherita Mori"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{id:"11460",title:"Pluralistic Approaches for Conservation and Sustainability in Biodiversity",coverURL:"https://cdn.intechopen.com/books/images_new/11460.jpg",hash:"ab014f8ed1669757335225786833e9a9",secondStepPassed:!0,currentStepOfPublishingProcess:3,submissionDeadline:"April 22nd 2022",isOpenForSubmission:!0,editors:[{id:"101105",title:"Dr.",name:"Gopal",surname:"Shukla",slug:"gopal-shukla",fullName:"Gopal Shukla"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{id:"11475",title:"Food Security Challenges and Approaches",coverURL:"https://cdn.intechopen.com/books/images_new/11475.jpg",hash:"090302a30e461cee643ec49675c811ec",secondStepPassed:!0,currentStepOfPublishingProcess:3,submissionDeadline:"May 5th 2022",isOpenForSubmission:!0,editors:[{id:"292145",title:"Dr.",name:"Muhammad",surname:"Haseeb Ahmad",slug:"muhammad-haseeb-ahmad",fullName:"Muhammad Haseeb Ahmad"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{id:"11450",title:"Environmental Impacts of COVID-19 Pandemic on the World",coverURL:"https://cdn.intechopen.com/books/images_new/11450.jpg",hash:"a58c7b02d07903004be70f744f2e1835",secondStepPassed:!0,currentStepOfPublishingProcess:3,submissionDeadline:"May 10th 2022",isOpenForSubmission:!0,editors:[{id:"63465",title:"Prof.",name:"Mohamed Nageeb",surname:"Rashed",slug:"mohamed-nageeb-rashed",fullName:"Mohamed Nageeb Rashed"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{id:"11477",title:"Public Economics - 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Two Years After",coverURL:"https://cdn.intechopen.com/books/images_new/11573.jpg",subseries:{id:"6",title:"Viral Infectious Diseases"}}},{id:"80546",title:"Streptococcal Skin and Skin-Structure Infections",doi:"10.5772/intechopen.102894",signatures:"Alwyn Rapose",slug:"streptococcal-skin-and-skin-structure-infections",totalDownloads:48,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Streptococcal Infections",coverURL:"https://cdn.intechopen.com/books/images_new/10828.jpg",subseries:{id:"3",title:"Bacterial Infectious Diseases"}}}]},subseriesFiltersForOFChapters:[{caption:"Parasitic Infectious Diseases",value:5,count:1,group:"subseries"},{caption:"Viral Infectious Diseases",value:6,count:1,group:"subseries"},{caption:"Bacterial Infectious Diseases",value:3,count:2,group:"subseries"}],publishedBooks:{paginationCount:0,paginationItems:[]},subseriesFiltersForPublishedBooks:[],publicationYearFilters:[],authors:{paginationCount:249,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, Kuwait. His research interests include optimization, computer graphics, computer vision, image processing, machine learning, pattern recognition, soft computing, data science, and intelligent systems. Prof. Sarfraz has been a keynote/invited speaker at various platforms around the globe. He has advised/supervised more than 110 students for their MSc and Ph.D. theses. He has published more than 400 publications as books, journal articles, and conference papers. He has authored and/or edited around seventy books. Prof. Sarfraz is a member of various professional societies. He is a chair and member of international advisory committees and organizing committees of numerous international conferences. He is also an editor and editor in chief for various international journals.",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"32650",title:"Prof.",name:"Lukas",middleName:"Willem",surname:"Snyman",slug:"lukas-snyman",fullName:"Lukas Snyman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/32650/images/4136_n.jpg",biography:"Lukas Willem Snyman received his basic education at primary and high schools in South Africa, Eastern Cape. He enrolled at today's Nelson Metropolitan University and graduated from this university with a BSc in Physics and Mathematics, B.Sc Honors in Physics, MSc in Semiconductor Physics, and a Ph.D. in Semiconductor Physics in 1987. After his studies, he chose an academic career and devoted his energy to the teaching of physics to first, second, and third-year students. After positions as a lecturer at the University of Port Elizabeth, he accepted a position as Associate Professor at the University of Pretoria, South Africa.\r\n\r\nIn 1992, he motivates the concept of 'television and computer-based education” as means to reach large student numbers with only the best of teaching expertise and publishes an article on the concept in the SA Journal of Higher Education of 1993 (and later in 2003). The University of Pretoria subsequently approved a series of test projects on the concept with outreach to Mamelodi and Eerste Rust in 1993. In 1994, the University established a 'Unit for Telematic Education ' as a support section for multiple faculties at the University of Pretoria. In subsequent years, the concept of 'telematic education” subsequently becomes well established in academic circles in South Africa, grew in popularity, and is adopted by many universities and colleges throughout South Africa as a medium of enhancing education and training, as a method to reaching out to far out communities, and as a means to enhance study from the home environment.\r\n\r\nProfessor Snyman in subsequent years pursued research in semiconductor physics, semiconductor devices, microelectronics, and optoelectronics.\r\n\r\nIn 2000 he joined the TUT as a full professor. Here served for a period as head of the Department of Electronic Engineering. Here he makes contributions to solar energy development, microwave and optoelectronic device development, silicon photonics, as well as contributions to new mobile telecommunication systems and network planning in SA.\r\n\r\nCurrently, he teaches electronics and telecommunications at the TUT to audiences ranging from first-year students to Ph.D. level.\r\n\r\nFor his research in the field of 'Silicon Photonics” since 1990, he has published (as author and co-author) about thirty internationally reviewed articles in scientific journals, contributed to more than forty international conferences, about 25 South African provisional patents (as inventor and co-inventor), 8 PCT international patent applications until now. Of these, two USA patents applications, two European Patents, two Korean patents, and ten SA patents have been granted. A further 4 USA patents, 5 European patents, 3 Korean patents, 3 Chinese patents, and 3 Japanese patents are currently under consideration.\r\n\r\nRecently he has also published an extensive scholarly chapter in an internet open access book on 'Integrating Microphotonic Systems and MOEMS into standard Silicon CMOS Integrated circuitry”.\r\n\r\nFurthermore, Professor Snyman recently steered a new initiative at the TUT by introducing a 'Laboratory for Innovative Electronic Systems ' at the Department of Electrical Engineering. The model of this laboratory or center is to primarily combine outputs as achieved by high-level research with lower-level system development and entrepreneurship in a technical university environment. Students are allocated to projects at different levels with PhDs and Master students allocated to the generation of new knowledge and new technologies, while students at the diploma and Baccalaureus level are allocated to electronic systems development with a direct and a near application for application in industry or the commercial and public sectors in South Africa.\r\n\r\nProfessor Snyman received the WIRSAM Award of 1983 and the WIRSAM Award in 1985 in South Africa for best research papers by a young scientist at two international conferences on electron microscopy in South Africa. He subsequently received the SA Microelectronics Award for the best dissertation emanating from studies executed at a South African university in the field of Physics and Microelectronics in South Africa in 1987. In October of 2011, Professor Snyman received the prestigious Institutional Award for 'Innovator of the Year” for 2010 at the Tshwane University of Technology, South Africa. This award was based on the number of patents recognized and granted by local and international institutions as well as for his contributions concerning innovation at the TUT.",institutionString:null,institution:{name:"University of South Africa",country:{name:"South Africa"}}},{id:"317279",title:"Mr.",name:"Ali",middleName:"Usama",surname:"Syed",slug:"ali-syed",fullName:"Ali Syed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/317279/images/16024_n.png",biography:"A creative, talented, and innovative young professional who is dedicated, well organized, and capable research fellow with two years of experience in graduate-level research, published in engineering journals and book, with related expertise in Bio-robotics, equally passionate about the aesthetics of the mechanical and electronic system, obtained expertise in the use of MS Office, MATLAB, SolidWorks, LabVIEW, Proteus, Fusion 360, having a grasp on python, C++ and assembly language, possess proven ability in acquiring research grants, previous appointments with social and educational societies with experience in administration, current affiliations with IEEE and Web of Science, a confident presenter at conferences and teacher in classrooms, able to explain complex information to audiences of all levels.",institutionString:null,institution:{name:"Air University",country:{name:"Pakistan"}}},{id:"75526",title:"Ph.D.",name:"Zihni Onur",middleName:null,surname:"Uygun",slug:"zihni-onur-uygun",fullName:"Zihni Onur Uygun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/75526/images/12_n.jpg",biography:"My undergraduate education and my Master of Science educations at Ege University and at Çanakkale Onsekiz Mart University have given me a firm foundation in Biochemistry, Analytical Chemistry, Biosensors, Bioelectronics, Physical Chemistry and Medicine. After obtaining my degree as a MSc in analytical chemistry, I started working as a research assistant in Ege University Medical Faculty in 2014. In parallel, I enrolled to the MSc program at the Department of Medical Biochemistry at Ege University to gain deeper knowledge on medical and biochemical sciences as well as clinical chemistry in 2014. In my PhD I deeply researched on biosensors and bioelectronics and finished in 2020. Now I have eleven SCI-Expanded Index published papers, 6 international book chapters, referee assignments for different SCIE journals, one international patent pending, several international awards, projects and bursaries. In parallel to my research assistant position at Ege University Medical Faculty, Department of Medical Biochemistry, in April 2016, I also founded a Start-Up Company (Denosens Biotechnology LTD) by the support of The Scientific and Technological Research Council of Turkey. Currently, I am also working as a CEO in Denosens Biotechnology. The main purposes of the company, which carries out R&D as a research center, are to develop new generation biosensors and sensors for both point-of-care diagnostics; such as glucose, lactate, cholesterol and cancer biomarker detections. My specific experimental and instrumental skills are Biochemistry, Biosensor, Analytical Chemistry, Electrochemistry, Mobile phone based point-of-care diagnostic device, POCTs and Patient interface designs, HPLC, Tandem Mass Spectrometry, Spectrophotometry, ELISA.",institutionString:null,institution:{name:"Ege University",country:{name:"Turkey"}}},{id:"246502",title:"Dr.",name:"Jaya T.",middleName:"T",surname:"Varkey",slug:"jaya-t.-varkey",fullName:"Jaya T. Varkey",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/246502/images/11160_n.jpg",biography:"Jaya T. Varkey, PhD, graduated with a degree in Chemistry from Cochin University of Science and Technology, Kerala, India. She obtained a PhD in Chemistry from the School of Chemical Sciences, Mahatma Gandhi University, Kerala, India, and completed a post-doctoral fellowship at the University of Minnesota, USA. She is a research guide at Mahatma Gandhi University and Associate Professor in Chemistry, St. Teresa’s College, Kochi, Kerala, India.\nDr. Varkey received a National Young Scientist award from the Indian Science Congress (1995), a UGC Research award (2016–2018), an Indian National Science Academy (INSA) Visiting Scientist award (2018–2019), and a Best Innovative Faculty award from the All India Association for Christian Higher Education (AIACHE) (2019). She Hashas received the Sr. Mary Cecil prize for best research paper three times. She was also awarded a start-up to develop a tea bag water filter. \nDr. Varkey has published two international books and twenty-seven international journal publications. She is an editorial board member for five international journals.",institutionString:"St. Teresa’s College",institution:null},{id:"250668",title:"Dr.",name:"Ali",middleName:null,surname:"Nabipour Chakoli",slug:"ali-nabipour-chakoli",fullName:"Ali Nabipour Chakoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/250668/images/system/250668.jpg",biography:"Academic Qualification:\r\n•\tPhD in Materials Physics and Chemistry, From: Sep. 2006, to: Sep. 2010, School of Materials Science and Engineering, Harbin Institute of Technology, Thesis: Structure and Shape Memory Effect of Functionalized MWCNTs/poly (L-lactide-co-ε-caprolactone) Nanocomposites. Supervisor: Prof. Wei Cai,\r\n•\tM.Sc in Applied Physics, From: 1996, to: 1998, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Determination of Boron in Micro alloy Steels with solid state nuclear track detectors by neutron induced auto radiography, Supervisors: Dr. M. Hosseini Ashrafi and Dr. A. Hosseini.\r\n•\tB.Sc. in Applied Physics, From: 1991, to: 1996, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Design of shielding for Am-Be neutron sources for In Vivo neutron activation analysis, Supervisor: Dr. M. Hosseini Ashrafi.\r\n\r\nResearch Experiences:\r\n1.\tNanomaterials, Carbon Nanotubes, Graphene: Synthesis, Functionalization and Characterization,\r\n2.\tMWCNTs/Polymer Composites: Fabrication and Characterization, \r\n3.\tShape Memory Polymers, Biodegradable Polymers, ORC, Collagen,\r\n4.\tMaterials Analysis and Characterizations: TEM, SEM, XPS, FT-IR, Raman, DSC, DMA, TGA, XRD, GPC, Fluoroscopy, \r\n5.\tInteraction of Radiation with Mater, Nuclear Safety and Security, NDT(RT),\r\n6.\tRadiation Detectors, Calibration (SSDL),\r\n7.\tCompleted IAEA e-learning Courses:\r\nNuclear Security (15 Modules),\r\nNuclear Safety:\r\nTSA 2: Regulatory Protection in Occupational Exposure,\r\nTips & Tricks: Radiation Protection in Radiography,\r\nSafety and Quality in Radiotherapy,\r\nCourse on Sealed Radioactive Sources,\r\nCourse on Fundamentals of Environmental Remediation,\r\nCourse on Planning for Environmental Remediation,\r\nKnowledge Management Orientation Course,\r\nFood Irradiation - Technology, Applications and Good Practices,\r\nEmployment:\r\nFrom 2010 to now: Academic staff, Nuclear Science and Technology Research Institute, Kargar Shomali, Tehran, Iran, P.O. Box: 14395-836.\r\nFrom 1997 to 2006: Expert of Materials Analysis and Characterization. Research Center of Agriculture and Medicine. Rajaeeshahr, Karaj, Iran, P. O. Box: 31585-498.",institutionString:"Atomic Energy Organization of Iran",institution:{name:"Atomic Energy Organization of Iran",country:{name:"Iran"}}},{id:"248279",title:"Dr.",name:"Monika",middleName:"Elzbieta",surname:"Machoy",slug:"monika-machoy",fullName:"Monika Machoy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248279/images/system/248279.jpeg",biography:"Monika Elżbieta Machoy, MD, graduated with distinction from the Faculty of Medicine and Dentistry at the Pomeranian Medical University in 2009, defended her PhD thesis with summa cum laude in 2016 and is currently employed as a researcher at the Department of Orthodontics of the Pomeranian Medical University. She expanded her professional knowledge during a one-year scholarship program at the Ernst Moritz Arndt University in Greifswald, Germany and during a three-year internship at the Technical University in Dresden, Germany. She has been a speaker at numerous orthodontic conferences, among others, American Association of Orthodontics, European Orthodontic Symposium and numerous conferences of the Polish Orthodontic Society. She conducts research focusing on the effect of orthodontic treatment on dental and periodontal tissues and the causes of pain in orthodontic patients.",institutionString:"Pomeranian Medical University",institution:{name:"Pomeranian Medical University",country:{name:"Poland"}}},{id:"252743",title:"Prof.",name:"Aswini",middleName:"Kumar",surname:"Kar",slug:"aswini-kar",fullName:"Aswini Kar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252743/images/10381_n.jpg",biography:"uploaded in cv",institutionString:null,institution:{name:"KIIT University",country:{name:"India"}}},{id:"204256",title:"Dr.",name:"Anil",middleName:"Kumar",surname:"Kumar Sahu",slug:"anil-kumar-sahu",fullName:"Anil Kumar Sahu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204256/images/14201_n.jpg",biography:"I have nearly 11 years of research and teaching experience. I have done my master degree from University Institute of Pharmacy, Pt. Ravi Shankar Shukla University, Raipur, Chhattisgarh India. I have published 16 review and research articles in international and national journals and published 4 chapters in IntechOpen, the world’s leading publisher of Open access books. I have presented many papers at national and international conferences. I have received research award from Indian Drug Manufacturers Association in year 2015. My research interest extends from novel lymphatic drug delivery systems, oral delivery system for herbal bioactive to formulation optimization.",institutionString:null,institution:{name:"Chhattisgarh Swami Vivekanand Technical University",country:{name:"India"}}},{id:"253468",title:"Dr.",name:"Mariusz",middleName:null,surname:"Marzec",slug:"mariusz-marzec",fullName:"Mariusz Marzec",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/253468/images/system/253468.png",biography:"An assistant professor at Department of Biomedical Computer Systems, at Institute of Computer Science, Silesian University in Katowice. Scientific interests: computer analysis and processing of images, biomedical images, databases and programming languages. He is an author and co-author of scientific publications covering analysis and processing of biomedical images and development of database systems.",institutionString:"University of Silesia",institution:null},{id:"212432",title:"Prof.",name:"Hadi",middleName:null,surname:"Mohammadi",slug:"hadi-mohammadi",fullName:"Hadi Mohammadi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/212432/images/system/212432.jpeg",biography:"Dr. Hadi Mohammadi is a biomedical engineer with hands-on experience in the design and development of many engineering structures and medical devices through various projects that he has been involved in over the past twenty years. Dr. Mohammadi received his BSc. and MSc. degrees in Mechanical Engineering from Sharif University of Technology, Tehran, Iran, and his PhD. degree in Biomedical Engineering (biomaterials) from the University of Western Ontario. He was a postdoctoral trainee for almost four years at University of Calgary and Harvard Medical School. He is an industry innovator having created the technology to produce lifelike synthetic platforms that can be used for the simulation of almost all cardiovascular reconstructive surgeries. He’s been heavily involved in the design and development of cardiovascular devices and technology for the past 10 years. He is currently an Assistant Professor with the University of British Colombia, Canada.",institutionString:"University of British Columbia",institution:{name:"University of British Columbia",country:{name:"Canada"}}},{id:"254463",title:"Prof.",name:"Haisheng",middleName:null,surname:"Yang",slug:"haisheng-yang",fullName:"Haisheng Yang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/254463/images/system/254463.jpeg",biography:"Haisheng Yang, Ph.D., Professor and Director of the Department of Biomedical Engineering, College of Life Science and Bioengineering, Beijing University of Technology. He received his Ph.D. degree in Mechanics/Biomechanics from Harbin Institute of Technology (jointly with University of California, Berkeley). Afterwards, he worked as a Postdoctoral Research Associate in the Purdue Musculoskeletal Biology and Mechanics Lab at the Department of Basic Medical Sciences, Purdue University, USA. He also conducted research in the Research Centre of Shriners Hospitals for Children-Canada at McGill University, Canada. Dr. Yang has over 10 years research experience in orthopaedic biomechanics and mechanobiology of bone adaptation and regeneration. He earned an award from Beijing Overseas Talents Aggregation program in 2017 and serves as Beijing Distinguished Professor.",institutionString:"Beijing University of Technology",institution:null},{id:"255757",title:"Dr.",name:"Igor",middleName:"Victorovich",surname:"Lakhno",slug:"igor-lakhno",fullName:"Igor Lakhno",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255757/images/system/255757.jpg",biography:"Lakhno Igor Victorovich was born in 1971 in Kharkiv (Ukraine). \nMD – 1994, Kharkiv National Medical Univesity.\nOb&Gyn; – 1997, master courses in Kharkiv Medical Academy of Postgraduate Education.\nPhD – 1999, Kharkiv National Medical Univesity.\nDSc – 2019, PL Shupik National Academy of Postgraduate Education \nLakhno Igor has been graduated from an international training courses on reproductive medicine and family planning held in Debrecen University (Hungary) in 1997. Since 1998 Lakhno Igor has worked as an associate professor of the department of obstetrics and gynecology of VN Karazin National University and an associate professor of the perinatology, obstetrics and gynecology department of Kharkiv Medical Academy of Postgraduate Education. Since June 2019 he’s a professor of the department of obstetrics and gynecology of VN Karazin National University and a professor of the perinatology, obstetrics and gynecology department of Kharkiv Medical Academy of Postgraduate Education . He’s an author of about 200 printed works and there are 17 of them in Scopus or Web of Science databases. Lakhno Igor is a rewiever of Journal of Obstetrics and Gynaecology (Taylor and Francis), Informatics in Medicine Unlocked (Elsevier), The Journal of Obstetrics and Gynecology Research (Wiley), Endocrine, Metabolic & Immune Disorders-Drug Targets (Bentham Open), The Open Biomedical Engineering Journal (Bentham Open), etc. He’s defended a dissertation for DSc degree \\'Pre-eclampsia: prediction, prevention and treatment”. Lakhno Igor has participated as a speaker in several international conferences and congresses (International Conference on Biological Oscillations April 10th-14th 2016, Lancaster, UK, The 9th conference of the European Study Group on Cardiovascular Oscillations). His main scientific interests: obstetrics, women’s health, fetal medicine, cardiovascular medicine.",institutionString:"V.N. Karazin Kharkiv National University",institution:{name:"Kharkiv Medical Academy of Postgraduate Education",country:{name:"Ukraine"}}},{id:"89721",title:"Dr.",name:"Mehmet",middleName:"Cuneyt",surname:"Ozmen",slug:"mehmet-ozmen",fullName:"Mehmet Ozmen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/89721/images/7289_n.jpg",biography:null,institutionString:null,institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"243698",title:"M.D.",name:"Xiaogang",middleName:null,surname:"Wang",slug:"xiaogang-wang",fullName:"Xiaogang Wang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243698/images/system/243698.png",biography:"Dr. Xiaogang Wang, a faculty member of Shanxi Eye Hospital specializing in the treatment of cataract and retinal disease and a tutor for postgraduate students of Shanxi Medical University, worked in the COOL Lab as an international visiting scholar under the supervision of Dr. David Huang and Yali Jia from October 2012 through November 2013. Dr. Wang earned an MD from Shanxi Medical University and a Ph.D. from Shanghai Jiao Tong University. Dr. Wang was awarded two research project grants focused on multimodal optical coherence tomography imaging and deep learning in cataract and retinal disease, from the National Natural Science Foundation of China. He has published around 30 peer-reviewed journal papers and four book chapters and co-edited one book.",institutionString:"Shanxi Eye Hospital",institution:{name:"Shanxi Eye Hospital",country:{name:"China"}}},{id:"242893",title:"Ph.D. Student",name:"Joaquim",middleName:null,surname:"De Moura",slug:"joaquim-de-moura",fullName:"Joaquim De Moura",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/242893/images/7133_n.jpg",biography:"Joaquim de Moura received his degree in Computer Engineering in 2014 from the University of A Coruña (Spain). In 2016, he received his M.Sc degree in Computer Engineering from the same university. He is currently pursuing his Ph.D degree in Computer Science in a collaborative project between ophthalmology centers in Galicia and the University of A Coruña. His research interests include computer vision, machine learning algorithms and analysis and medical imaging processing of various kinds.",institutionString:null,institution:{name:"University of A Coruña",country:{name:"Spain"}}},{id:"267434",title:"Dr.",name:"Rohit",middleName:null,surname:"Raja",slug:"rohit-raja",fullName:"Rohit Raja",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRZkkQAG/Profile_Picture_2022-05-09T12:55:18.jpg",biography:null,institutionString:null,institution:null},{id:"294334",title:"B.Sc.",name:"Marc",middleName:null,surname:"Bruggeman",slug:"marc-bruggeman",fullName:"Marc Bruggeman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/294334/images/8242_n.jpg",biography:"Chemical engineer graduate, with a passion for material science and specific interest in polymers - their near infinite applications intrigue me. \n\nI plan to continue my scientific career in the field of polymeric biomaterials as I am fascinated by intelligent, bioactive and biomimetic materials for use in both consumer and medical applications.",institutionString:null,institution:null},{id:"244950",title:"Dr.",name:"Salvatore",middleName:null,surname:"Di Lauro",slug:"salvatore-di-lauro",fullName:"Salvatore Di Lauro",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0030O00002bSF1HQAW/ProfilePicture%202021-12-20%2014%3A54%3A14.482",biography:"Name:\n\tSALVATORE DI LAURO\nAddress:\n\tHospital Clínico Universitario Valladolid\nAvda Ramón y Cajal 3\n47005, Valladolid\nSpain\nPhone number: \nFax\nE-mail:\n\t+34 983420000 ext 292\n+34 983420084\nsadilauro@live.it\nDate and place of Birth:\nID Number\nMedical Licence \nLanguages\t09-05-1985. Villaricca (Italy)\n\nY1281863H\n474707061\nItalian (native language)\nSpanish (read, written, spoken)\nEnglish (read, written, spoken)\nPortuguese (read, spoken)\nFrench (read)\n\t\t\nCurrent position (title and company)\tDate (Year)\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. Private practise.\t2017-today\n\n2019-today\n\t\n\t\nEducation (High school, university and postgraduate training > 3 months)\tDate (Year)\nDegree in Medicine and Surgery. University of Neaples 'Federico II”\nResident in Opthalmology. Hospital Clinico Universitario Valladolid\nMaster in Vitreo-Retina. IOBA. University of Valladolid\nFellow of the European Board of Ophthalmology. Paris\nMaster in Research in Ophthalmology. University of Valladolid\t2003-2009\n2012-2016\n2016-2017\n2016\n2012-2013\n\t\nEmployments (company and positions)\tDate (Year)\nResident in Ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl.\nFellow in Vitreo-Retina. IOBA. University of Valladolid\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. \n\t2012-2016\n2016-2017\n2017-today\n\n2019-Today\n\n\n\t\nClinical Research Experience (tasks and role)\tDate (Year)\nAssociated investigator\n\n' FIS PI20/00740: DESARROLLO DE UNA CALCULADORA DE RIESGO DE\nAPARICION DE RETINOPATIA DIABETICA BASADA EN TECNICAS DE IMAGEN MULTIMODAL EN PACIENTES DIABETICOS TIPO 1. Grant by: Ministerio de Ciencia e Innovacion \n\n' (BIO/VA23/14) Estudio clínico multicéntrico y prospectivo para validar dos\nbiomarcadores ubicados en los genes p53 y MDM2 en la predicción de los resultados funcionales de la cirugía del desprendimiento de retina regmatógeno. Grant by: Gerencia Regional de Salud de la Junta de Castilla y León.\n' Estudio multicéntrico, aleatorizado, con enmascaramiento doble, en 2 grupos\nparalelos y de 52 semanas de duración para comparar la eficacia, seguridad e inmunogenicidad de SOK583A1 respecto a Eylea® en pacientes con degeneración macular neovascular asociada a la edad' (CSOK583A12301; N.EUDRA: 2019-004838-41; FASE III). Grant by Hexal AG\n\n' Estudio de fase III, aleatorizado, doble ciego, con grupos paralelos, multicéntrico para comparar la eficacia y la seguridad de QL1205 frente a Lucentis® en pacientes con degeneración macular neovascular asociada a la edad. (EUDRACT: 2018-004486-13). Grant by Qilu Pharmaceutical Co\n\n' Estudio NEUTON: Ensayo clinico en fase IV para evaluar la eficacia de aflibercept en pacientes Naive con Edema MacUlar secundario a Oclusion de Vena CenTral de la Retina (OVCR) en regimen de tratamientO iNdividualizado Treat and Extend (TAE)”, (2014-000975-21). Grant by Fundacion Retinaplus\n\n' Evaluación de la seguridad y bioactividad de anillos de tensión capsular en conejo. Proyecto Procusens. Grant by AJL, S.A.\n\n'Estudio epidemiológico, prospectivo, multicéntrico y abierto\\npara valorar la frecuencia de la conjuntivitis adenovírica diagnosticada mediante el test AdenoPlus®\\nTest en pacientes enfermos de conjuntivitis aguda”\\n. National, multicenter study. Grant by: NICOX.\n\nEuropean multicentric trial: 'Evaluation of clinical outcomes following the use of Systane Hydration in patients with dry eye”. Study Phase 4. Grant by: Alcon Labs'\n\nVLPs Injection and Activation in a Rabbit Model of Uveal Melanoma. Grant by Aura Bioscience\n\nUpdating and characterization of a rabbit model of uveal melanoma. Grant by Aura Bioscience\n\nEnsayo clínico en fase IV para evaluar las variantes genéticas de la vía del VEGF como biomarcadores de eficacia del tratamiento con aflibercept en pacientes con degeneración macular asociada a la edad (DMAE) neovascular. Estudio BIOIMAGE. IMO-AFLI-2013-01\n\nEstudio In-Eye:Ensayo clínico en fase IV, abierto, aleatorizado, de 2 brazos,\nmulticçentrico y de 12 meses de duración, para evaluar la eficacia y seguridad de un régimen de PRN flexible individualizado de 'esperar y extender' versus un régimen PRN según criterios de estabilización mediante evaluaciones mensuales de inyecciones intravítreas de ranibizumab 0,5 mg en pacientes naive con neovascularización coriodea secunaria a la degeneración macular relacionada con la edad. CP: CRFB002AES03T\n\nTREND: Estudio Fase IIIb multicéntrico, randomizado, de 12 meses de\nseguimiento con evaluador de la agudeza visual enmascarado, para evaluar la eficacia y la seguridad de ranibizumab 0.5mg en un régimen de tratar y extender comparado con un régimen mensual, en pacientes con degeneración macular neovascular asociada a la edad. CP: CRFB002A2411 Código Eudra CT:\n2013-002626-23\n\n\n\nPublications\t\n\n2021\n\n\n\n\n2015\n\n\n\n\n2021\n\n\n\n\n\n2021\n\n\n\n\n2015\n\n\n\n\n2015\n\n\n2014\n\n\n\n\n2015-16\n\n\n\n2015\n\n\n2014\n\n\n2014\n\n\n\n\n2014\n\n\n\n\n\n\n\n2014\n\nJose Carlos Pastor; Jimena Rojas; Salvador Pastor-Idoate; Salvatore Di Lauro; Lucia Gonzalez-Buendia; Santiago Delgado-Tirado. Proliferative vitreoretinopathy: A new concept of disease pathogenesis and practical\nconsequences. Progress in Retinal and Eye Research. 51, pp. 125 - 155. 03/2016. DOI: 10.1016/j.preteyeres.2015.07.005\n\n\nLabrador-Velandia S; Alonso-Alonso ML; Di Lauro S; García-Gutierrez MT; Srivastava GK; Pastor JC; Fernandez-Bueno I. Mesenchymal stem cells provide paracrine neuroprotective resources that delay degeneration of co-cultured organotypic neuroretinal cultures.Experimental Eye Research. 185, 17/05/2019. DOI: 10.1016/j.exer.2019.05.011\n\nSalvatore Di Lauro; Maria Teresa Garcia Gutierrez; Ivan Fernandez Bueno. Quantification of pigment epithelium-derived factor (PEDF) in an ex vivo coculture of retinal pigment epithelium cells and neuroretina.\nJournal of Allbiosolution. 2019. ISSN 2605-3535\n\nSonia Labrador Velandia; Salvatore Di Lauro; Alonso-Alonso ML; Tabera Bartolomé S; Srivastava GK; Pastor JC; Fernandez-Bueno I. Biocompatibility of intravitreal injection of human mesenchymal stem cells in immunocompetent rabbits. Graefe's archive for clinical and experimental ophthalmology. 256 - 1, pp. 125 - 134. 01/2018. DOI: 10.1007/s00417-017-3842-3\n\n\nSalvatore Di Lauro, David Rodriguez-Crespo, Manuel J Gayoso, Maria T Garcia-Gutierrez, J Carlos Pastor, Girish K Srivastava, Ivan Fernandez-Bueno. A novel coculture model of porcine central neuroretina explants and retinal pigment epithelium cells. Molecular Vision. 2016 - 22, pp. 243 - 253. 01/2016.\n\nSalvatore Di Lauro. Classifications for Proliferative Vitreoretinopathy ({PVR}): An Analysis of Their Use in Publications over the Last 15 Years. Journal of Ophthalmology. 2016, pp. 1 - 6. 01/2016. DOI: 10.1155/2016/7807596\n\nSalvatore Di Lauro; Rosa Maria Coco; Rosa Maria Sanabria; Enrique Rodriguez de la Rua; Jose Carlos Pastor. Loss of Visual Acuity after Successful Surgery for Macula-On Rhegmatogenous Retinal Detachment in a Prospective Multicentre Study. Journal of Ophthalmology. 2015:821864, 2015. DOI: 10.1155/2015/821864\n\nIvan Fernandez-Bueno; Salvatore Di Lauro; Ivan Alvarez; Jose Carlos Lopez; Maria Teresa Garcia-Gutierrez; Itziar Fernandez; Eva Larra; Jose Carlos Pastor. Safety and Biocompatibility of a New High-Density Polyethylene-Based\nSpherical Integrated Porous Orbital Implant: An Experimental Study in Rabbits. Journal of Ophthalmology. 2015:904096, 2015. DOI: 10.1155/2015/904096\n\nPastor JC; Pastor-Idoate S; Rodríguez-Hernandez I; Rojas J; Fernandez I; Gonzalez-Buendia L; Di Lauro S; Gonzalez-Sarmiento R. Genetics of PVR and RD. Ophthalmologica. 232 - Suppl 1, pp. 28 - 29. 2014\n\nRodriguez-Crespo D; Di Lauro S; Singh AK; Garcia-Gutierrez MT; Garrosa M; Pastor JC; Fernandez-Bueno I; Srivastava GK. Triple-layered mixed co-culture model of RPE cells with neuroretina for evaluating the neuroprotective effects of adipose-MSCs. Cell Tissue Res. 358 - 3, pp. 705 - 716. 2014.\nDOI: 10.1007/s00441-014-1987-5\n\nCarlo De Werra; Salvatore Condurro; Salvatore Tramontano; Mario Perone; Ivana Donzelli; Salvatore Di Lauro; Massimo Di Giuseppe; Rosa Di Micco; Annalisa Pascariello; Antonio Pastore; Giorgio Diamantis; Giuseppe Galloro. Hydatid disease of the liver: thirty years of surgical experience.Chirurgia italiana. 59 - 5, pp. 611 - 636.\n(Italia): 2007. ISSN 0009-4773\n\nChapters in books\n\t\n' Salvador Pastor Idoate; Salvatore Di Lauro; Jose Carlos Pastor Jimeno. PVR: Pathogenesis, Histopathology and Classification. Proliferative Vitreoretinopathy with Small Gauge Vitrectomy. Springer, 2018. ISBN 978-3-319-78445-8\nDOI: 10.1007/978-3-319-78446-5_2. \n\n' Salvatore Di Lauro; Maria Isabel Lopez Galvez. Quistes vítreos en una mujer joven. Problemas diagnósticos en patología retinocoroidea. Sociedad Española de Retina-Vitreo. 2018.\n\n' Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor Jimeno. iOCT in PVR management. OCT Applications in Opthalmology. pp. 1 - 8. INTECH, 2018. DOI: 10.5772/intechopen.78774.\n\n' Rosa Coco Martin; Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor. amponadores, manipuladores y tinciones en la cirugía del traumatismo ocular.Trauma Ocular. Ponencia de la SEO 2018..\n\n' LOPEZ GALVEZ; DI LAURO; CRESPO. OCT angiografia y complicaciones retinianas de la diabetes. PONENCIA SEO 2021, CAPITULO 20. (España): 2021.\n\n' Múltiples desprendimientos neurosensoriales bilaterales en paciente joven. Enfermedades Degenerativas De Retina Y Coroides. SERV 04/2016. \n' González-Buendía L; Di Lauro S; Pastor-Idoate S; Pastor Jimeno JC. Vitreorretinopatía proliferante (VRP) e inflamación: LA INFLAMACIÓN in «INMUNOMODULADORES Y ANTIINFLAMATORIOS: MÁS ALLÁ DE LOS CORTICOIDES. 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