Digital solutions developed to prevent and manage COVID-19 around the world.
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More than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
\\n\\nOur breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
\\n\\n“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
\\n\\nAdditionally, each book published by IntechOpen contains original content and research findings.
\\n\\nWe are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
\\n\\n\\n\\n
\\n"}]',published:!0,mainMedia:null},components:[{type:"htmlEditorComponent",content:'
Simba Information has released its Open Access Book Publishing 2020 - 2024 report and has again identified IntechOpen as the world’s largest Open Access book publisher by title count.
\n\nSimba Information is a leading provider for market intelligence and forecasts in the media and publishing industry. The report, published every year, provides an overview and financial outlook for the global professional e-book publishing market.
\n\nIntechOpen, De Gruyter, and Frontiers are the largest OA book publishers by title count, with IntechOpen coming in at first place with 5,101 OA books published, a good 1,782 titles ahead of the nearest competitor.
\n\nSince the first Open Access Book Publishing report published in 2016, IntechOpen has held the top stop each year.
\n\n\n\nMore than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
\n\nOur breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
\n\n“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
\n\nAdditionally, each book published by IntechOpen contains original content and research findings.
\n\nWe are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
\n\n\n\n
\n'}],latestNews:[{slug:"intechopen-signs-new-contract-with-cepiec-china-for-distribution-of-open-access-books-20210319",title:"IntechOpen Signs New Contract with CEPIEC, China for Distribution of Open Access Books"},{slug:"150-million-downloads-and-counting-20210316",title:"150 Million Downloads and Counting"},{slug:"intechopen-secures-indefinite-content-preservation-with-clockss-20210309",title:"IntechOpen Secures Indefinite Content Preservation with CLOCKSS"},{slug:"intechopen-expands-to-all-global-amazon-channels-with-full-catalog-of-books-20210308",title:"IntechOpen Expands to All Global Amazon Channels with Full Catalog of Books"},{slug:"stanford-university-identifies-top-2-scientists-over-1-000-are-intechopen-authors-and-editors-20210122",title:"Stanford University Identifies Top 2% Scientists, Over 1,000 are IntechOpen Authors and Editors"},{slug:"intechopen-authors-included-in-the-highly-cited-researchers-list-for-2020-20210121",title:"IntechOpen Authors Included in the Highly Cited Researchers List for 2020"},{slug:"intechopen-maintains-position-as-the-world-s-largest-oa-book-publisher-20201218",title:"IntechOpen Maintains Position as the World’s Largest OA Book Publisher"},{slug:"all-intechopen-books-available-on-perlego-20201215",title:"All IntechOpen Books Available on Perlego"}]},book:{item:{type:"book",id:"7612",leadTitle:null,fullTitle:"Electrospinning and Electrospraying - Techniques and Applications",title:"Electrospinning and Electrospraying",subtitle:"Techniques and Applications",reviewType:"peer-reviewed",abstract:"This book focuses on the recent advancements in the process parameters, research, and applications of electrospinning and electrospraying. 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\r\n\tNonlinear optics is a separate field of physics in general and optics in particular which studies the nonlinear phenomena that occur during the light and matter interaction. The typical nonlinear optical effects are the light self-focusing and self-trapping, second harmonic generation (SHG), third-harmonic generation (THG), four-wave mixing (FWM), parametric processes including the sum and difference frequency harmonic generation, different types of stimulated light scattering (SLS), soliton generation, and propagation. The observation of nonlinear optical effects started with the creation of lasers as the sources of the high intensity coherent light radiation. The nonlinear optical phenomena are widely used in modern communication systems for different applications such as the generation of ultra-short pulses, all-optical signal processing, wavelength conversion, and ultrafast switching. Novel fields of nonlinear optics such as strong-field
\r\n\tnano-optics, nonlinear plasmonics, and nonlinear metamaterials emerged in the last decades due to the progress in nanotechnology.
\r\n\tThe essential subject of this book is the publication of novel theoretical and experimental results concerning the nonlinear optical phenomena in photonic and plasmonic nanostructures, nonlinear metamaterials including liquid crystals, and devices based on nonlinear optical waveguides. In particular, the following topics will be considered: the interaction of solid-state nanostructures with the intense electromagnetic fields, the surface plasmon polariton propagation and interaction near the metal-dielectric interface, active nano-photonic devices for lasing and optical sources, nonlinear metamaterials, the nonlinear optics of liquid crystals and the possible combination of liquid crystals with plasmonic and metamaterials. We do not limit the book to these topics.
\r\n\r\n\tThe novel results in other fields of nonlinear optics would be also welcome. We hope that the proposed book will be interesting for researchers and engineers occupied in optical fiber telecommunications, optical signal processing, novel active materials, and devices.
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He was an invited researcher at the Max Planck Institute High Magnetic Field Laboratory at Grenoble, France.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"2359",title:"Dr.",name:"Boris",middleName:"I.",surname:"Lembrikov",slug:"boris-lembrikov",fullName:"Boris Lembrikov",profilePictureURL:"https://mts.intechopen.com/storage/users/2359/images/system/2359.jpg",biography:"Boris I. Lembrikov is a senior lecturer at the Faculty of Electronics, Electrical and Communication Engineering of the Holon Institute of Technology (HIT), Holon, Israel. B. I. Lembrikov received his Ph.D. in Nonlinear Optics at the Technion – Israel Institute of Technology in 1996. Since then he was an invited researcher at the Haifa University, at the Max Planck Institute High Magnetic Field Laboratory at Grenoble, France, at the Technion, Haifa, Israel. Dr. B. I. Lembrikov is an author of the book \\Electrodynamics of Magnetoactive Media\\, a number of chapters in scientific books, a large number of papers in international peer reviewed journals and reports delivered at the international scientific conferences. He actively participated in a number of research projects concerning optics of nanoparticles, optical communications, UWB communications. The main research fields of interest of Dr. B. I. Lembrikov are nonlinear optics, optical and UWB communications, nanostructures, quantum dot lasers.",institutionString:"Holon Institute of Technology (HIT)",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"11",totalChapterViews:"0",totalEditedBooks:"3",institution:{name:"Holon Institute of Technology",institutionURL:null,country:{name:"Israel"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"20",title:"Physics",slug:"physics"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"345821",firstName:"Darko",lastName:"Hrvojic",middleName:null,title:"Mr.",imageUrl:"https://mts.intechopen.com/storage/users/345821/images/16410_n.",email:"darko@intechopen.com",biography:null}},relatedBooks:[{type:"book",id:"3674",title:"Ultra Wideband",subtitle:null,isOpenForSubmission:!1,hash:null,slug:"ultra-wideband",bookSignature:"Boris Lembrikov",coverURL:"https://cdn.intechopen.com/books/images_new/3674.jpg",editedByType:"Edited by",editors:[{id:"2359",title:"Dr.",name:"Boris",surname:"Lembrikov",slug:"boris-lembrikov",fullName:"Boris Lembrikov"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"189",title:"Novel Applications of the UWB Technologies",subtitle:null,isOpenForSubmission:!1,hash:"ed2f8e92a107244ca4c22888843e374f",slug:"novel-applications-of-the-uwb-technologies",bookSignature:"Boris Lembrikov",coverURL:"https://cdn.intechopen.com/books/images_new/189.jpg",editedByType:"Edited by",editors:[{id:"2359",title:"Dr.",name:"Boris",surname:"Lembrikov",slug:"boris-lembrikov",fullName:"Boris Lembrikov"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7582",title:"Nonlinear Optics",subtitle:"Novel Results in Theory and Applications",isOpenForSubmission:!1,hash:"a3ad4a3553a3ec59f7992d4f6495ac07",slug:"nonlinear-optics-novel-results-in-theory-and-applications",bookSignature:"Boris I. 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Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"72",title:"Ionic Liquids",subtitle:"Theory, Properties, New Approaches",isOpenForSubmission:!1,hash:"d94ffa3cfa10505e3b1d676d46fcd3f5",slug:"ionic-liquids-theory-properties-new-approaches",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/72.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"314",title:"Regenerative Medicine and Tissue Engineering",subtitle:"Cells and Biomaterials",isOpenForSubmission:!1,hash:"bb67e80e480c86bb8315458012d65686",slug:"regenerative-medicine-and-tissue-engineering-cells-and-biomaterials",bookSignature:"Daniel Eberli",coverURL:"https://cdn.intechopen.com/books/images_new/314.jpg",editedByType:"Edited by",editors:[{id:"6495",title:"Dr.",name:"Daniel",surname:"Eberli",slug:"daniel-eberli",fullName:"Daniel Eberli"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"18946",title:"Cryopreservation of Skin Tissues for Skin Grafts",doi:"10.5772/23268",slug:"cryopreservation-of-skin-tissues-for-skin-grafts",body:'Preservation of living tissue and organs are very important to ensure successful transplantation. The storage of living tissue, from the time of removal of the donor tissue until transplantation, is one of the most important factors for successful tissue transplantation. The purpose of living tissue storage is to maintain the viability of the mammalian cells, and various methods have been developed to lengthen the time donor tissue can be stored without loss of cell integrity.
At present, low temperature is used as the major organ preservation method. Generally, cells are preserved in a frozen state at -196°C(1-3). The survival rate after such storage has been enhanced by controlled temperature freezing. However, cell survival after freezing can be low (namely, 20~40%), as with ES cells (embryonic stem cells),EG cells (embryonic genital cells) and induced pluripotent stem (iPS) cells. It would be of great advantage to researchers in the field of stem cell researchto be able to preserve these cells more successfully. It would also be of benefit to be able to preserve other cells, such as platelets, over the long term without freezing. Likewise, research continues in our attempts to prolong the time for transplantation of solid organs, and in the development of optimal perfusion fluids that protect against ischemia remains an active subject of investigation. Various storage solutions for organ preservation, such as the UW solution developed at the University of Wisconsin (USA) are also in current clinical use.However, it is necessary to develop storage solutions that can maintain the viability of tissues and organs for longer periods because of the limitations of storage in UW solution.
After transplantation, many organs suffer from the generation of free radicals following reperfusion. The restoration of blood flow becomes a trigger for injury, with subsequent lipid peroxidation of the biomembrane leading to membrane failure and as a result, the transplanted organ fails. A logical goal would then be the development of a preservation fluid that would limit cell damage by preventing peroxylipid generation. Such a preservation fluid should limit cell division and multiplication. A room temperature storage state could also potentially prevent the injury to the small vessel endothelium seen with freezing and to delicate tissues, such as the cornea, which do not survive freezing well. Although these tissues can be held from 4 to 24 hours at 4oC, large organs impose a severe time limitation on the medical team(4-6). In addition, through advances in tissue engineering, cultured skin and cultured cartilage have reached the level of clinical application and demanded long term storage techniques for optimum utilization. Transplantation of xenogeneic organs from genetically prepared animal donors would likewise benefit from the possibility of longer periods of organ storage.
It has now been found that the polyphenols in green tea promote the preservation of tissues, such as blood vessels, cornea, nerves, islet tissues, articular cartilage and myocardium, at room temperature.(24) Furthermroe, in the case of hematopoetic stem cells, the polyphenols suppress the differentiation of the cells into erythrocytes, T cells and B cells. These findings suggest the possibility of a new method for tissue banking that does not require freezing.
We have been conducting the research on the applications of green tea polyphenol (epigallocatechin-3-
Polyphenols have recently attracted attention as components of functional foods, and have been shown to have various bioactivities such as anticancer activity, antimicrobal and anti-virus activity since the 1980’s.(7-11)Therefore, there are many papers and patents on theuse of polyphenols for various applications. However, there has been no research which applies to the use of polyphenolsfor the preservation of various tissues and organs. We believe that such applications are possible, and we recentlyfound aninteresting phenomena related to the effects of polyphenols on mammalian cells and living tissues. Weherein describe the effects of polyphenols on living cells and tissues, and present possible applications of polyphenols for their preservation.
Polyphenols have a hydroxyl group attached to the 2nd carbon, and have propertiescompletely different from other phenolic chemicals such as hydroxybenzene. The chemical structure of green tea polyphenol is shown in Figure 1. It is possible to classify these polyphenols into flavonoid hydrolysis type tannins and other polyphenols. Various chemical compounds are known within the polyphenol group. Representative members include catechin, which is mainly found in green tea and oolong tea, and anthocyanin, which is the red pigment in red wine The antioxidative effects of green tea polyphenol and catechin, as well as proanthocyanidin, are especially potent, and these agents are known to be associated with a lower morbidity from heart disease (35-37). It has also recently been reported in
The success rate of organ transplantation has increased due to the improvements in surgical techniques and the development of new immunosuppressive agents in recent ten years. For instance, in the USA where transplantation is frequently practiced with organs or tissues from brain-dead donors, therewere 4 million transplants performed in 2002.
The chemical structure of green tea polyphenol.
The donor organs or tissues are routinely transported in various preservation solutions. The UW (University of Wisconsin) solution and Euro-Collins solution are the first and the second most frequently used preservation solutions. These preservation solutions are mainly used for the transport of kidneys, liver, or pancreas. However, they cannot preserve the organs for longer than 24 hours at 4℃ (40-44). In light of the increasing demand for donor organs and tissues, preservation solutions with better preserving abilities and the research and development of such solutions are urgently needed.
When organs or tissues are isolated from a donor, their blood circulation stops, and physiological activities rapidly decrease. Varying degrees of ischemia are commonly observed for these organs, and free radicals are generated upon the restart of blood flow, which leads to lipid peroxidation of the cell membrane, causing membrane damage and various dysfunctions of the transplanted organs. Thedevelopment of a preservation solution that can minimize the oxidation and cell damage can solve this problem.
One of the traditional methods used to solve this problem has been freeze preservation (45-47). Although living tissues and cells are routinely preserved at -196℃, freezing and subsequent thawing cause some structural damage. For example, frozen blood vessels have damage that often make their transplantation difficult, and corneas cannot be preserved at 4℃for longer than one week without a significant degree of damage. Studies indicate that the cell damage is primarily caused by activated oxygen molecules emerging from the freezing and thawing processes, but also occurs even after exposing the living tissues and cells to ordinary temperatures after removal from the donor.
Recent advances in tissue engineering are now on the cusp of providing clinically useful cultured skin, cartilage and corneaspecimens. However, these cultured tissues also require preservation, and better methods for long term preservation would be beneficial for ensuring that they can be successfully applied in the clinic field.To this end, we introduce the anti-oxidant polyphenol, EGCG, as a means to prevent the cell damage associated with organ and tissue preservation. Using EGCG, we can preserve living tissues and organs allowing for longer storage and more successful transplantation (13-34).
To study the effects of EGCG on cell proliferation, the rat fibroblast cell line, L-929, was cultivated in EMEM (with kanamycin 60mg/1) supplemented with 10% fetal bovine serum. A cell proliferation test was carried out at a cell density of 1.76×105 cells/ml. The polyphenol (250 μg/ml concentration) was added to another culture system as a control. The effects of the polyphenol in the rat fibroblast culture are shown in Figure 2.In the polyphenol system, the cells became round, although cell proliferation was still active, and the cell population was increased to 1×106cells/ml onthe fourth day after cultivation, but the proliferation decreased after 1 week of treatment, and resumed when the polyphenol was removed from the culture media.
The effect of polyphenols on the multiplication of the fibroblast. (→) The polyphenol free.(- - -) The polyphenol addition.
We also assessed the effects of the polyphenol on the cell cycle. The results of treatment of the fibroblasts with the polyphenol as determined by flow cytometry are shown in Table 1. For the polyphenol-treated cells, the number of cells in the G0, G1 and G2/M-phases increased, although after 9 hours in culture, the number of cells in the S phase reached 0. A similar phenomenon was observed in porcine hepatocytes. In addition, the viable cell population did not decrease. Good results were also obtained for the protective effects of the green tea polyphenol against reactive oxygen species that induce oxidative stress in cultured rat calvarial osteoblasts.
Time changes in cell cycle of untreated and polyphenol treated (250 mcg/ml) fibroblasts.
Although skin allografts are used in the treatment of serious burn injuries, skin disorders, and skin defects their use is limited because of the limited amount of normal skin that can be removed for such grafts (48). The best graft for the functional closure of wounds is the autograft. At the end of an autograft procedure, the remaining donor skin is routinely stored in a saline solution and applied to the open wound when graft loss or superficial wound breakdown occurs postoperatively. (49) However, long-time storage in saline leads to poor engraftment, and we were prompted to study other preservation media which would extend the storage time of skingrafts. Recently, it has been found that the polyphenols in green tea promote the preservation of tissues, such as the blood vessel, cornea, nerve, islet cells, articular cartilage and myocardium, at room temperature (12-34). These findings suggest the possibility of a new method for tissue banking without freezing.
As previously stated thedysfunction of transplants occurs as a result of free radicals due to ischemia, which triggers lipid peroxidation of the cell membrane when blood flow is restarted. It is reported that EGCG prevents peroxylipid generation. (50)
To determine whether the addition of EGCG to conventional cell culture medium could enhance the viability of stored skin grafts and also extend storage time, we performed a study using the skin from rats. The storage solution chosen for this study was Dulbecco\'s Modified Eagle Medium (Sigma, St. Louis, MO, USA) supplemented with 10% Fetal Calf Serum (FCS; Sigma),add and 1% antibiotic solution (including 10000U penicillin and 10mg streptomycin, Sigma). EGCG was dissolved in the storage solution at a final concentration of 1mg/ml. Transgenic Sprague-Dawley rats (8 weeks old, male) expressing the green fluorescent protein (GFP) (green 2 Kim et al., produced with the constructs used for the green mouse (51)), were a kind gift from Dr. Masaru Okabe (Genomic Information Research Center, Osaka, Japan).
For anesthesia, pentobarbital (50 mg/Kg) was administered intraperitoneally to the GFP transgenic rats. After shaving and depilating the backs of the rats, the back skins were biopsied.The muscular layers were immediately stripped from the skin biopsies. Skin samples measuring 1×1cm were kept in sterile containers with 50ml preservation solution at 4℃ and 37℃for up to 8 weeks. Periodically, some of preserved skin (30min, 1, 2, 4, 6, 7, 8weeks) were used for grafts in nude mice or were directly examined histologically.
From histological examinations of the 4℃ preservation skin, it was noted that there was a decrease in the GFP value in the non-EGCG skinnoted during the second week (Figure 3), as was a slight degeneration of the epidermal layer. The degeneration of the epidermal and dermal layers were noted beginning at 5 weeks in all 4℃ groups (Figure 4).
Photographs showing cryosection of the preserved GFP rat skins. GFP value was slightly decreased according to preservation time.
In the 37℃ preserved groups, degeneration and flakiness of the epidermal layer were notedbeginning after one week of preservation, both with or without EGCG, and a decrease in the GFP value was observed, regardless of the presence of EGCG,at 2 weeks. Moreover, the epidermis was damaged in the tissue samples preserved without EGCG, although not in the EGCG group.
Photographs showing H.E. stain of preservation GFP rat’s skins. Degeneration of the epidermis and dermis was observed, according to preservation time. The degeneration is improved in EGCG groups compared to EGCG(-) groups.
Appearances 4 weeks after grafting the preserved skins to the nude mice. Thirty minutes preserved skin with EGCG, holds hair (a). On the other hand, skin without EGCG (b) has no hair and the graft size is smaller than that with EGCG groups (a). After 2 weeks preservation with EGCG at 4℃, grafts color were dark like necrosis, but it only remain EGCG. Grafts size were smaller or only scar were observed at all groups, except preservation under 4℃ with EGCG, after 2weeks preservation.
The rat skin grafted onto the nude mice after 30 minute preservation with EGCG showed a better condition than those implanted without EGCG, which showed loss of hair and shrinkage. In the EGCG-preserved groups, the skin color was dark and looked like there was necrosis superficially, however, the color was found to be due to the presence of the EGCG (Figure 5). After 2 to 7 weeks of preservationin EGCG at 4℃, there was good graft survival. In the other groups, the grafts shrunk or were only scar-like because of contracture or rejection.
In the histological analysis, grafts preserved at 4℃ with EGCG werefound to have been completely accepted, with both epidermal and dermal layers remaining. On the other hand, grafts preserved at 4℃ without EGCG had no GFP positive keratinocytesor fibroblasts observed, and only phagocytes were observed in the dermal layer (likely targeting the GFP). In the 37℃ preserved groups, no GFP positive rat cells were observed, with or without EGCG (Figure 6).No grafts were successful from the 37℃ preserved groups (with or without EGCG). However, the 4℃preserved grafts were accepted, and the success rate for the EGCG-treated grafts was 100% even after 4 weeks of preservation (Figure 7).
Wide skin defects caused by burnsor trauma should be covered with skin grafts, but sometimes skin grafts fail due to various causes such as hematoma. When skin grafts are partially unsuccessful, small skin defects can be repaired, using the skin leftover from the primary grafting, if it is preserved. Moreover, injuries leading to complicated tears or small flap-like. In such cases, if the skin can be temporarily preserved, it can later be used as part of the graft after the wound condition is improved. Freeze-drying porcine skin, xenografts,
Photographs showing cryosection of the GFP rat skins 28 days after grafting to nude mice (n=4-6). EGCG positive keratinocytes were observed only in the grafts preserved in 30 minutes preservation groups and 4℃ preservation groups with EGCG, 2weeks to 6 weeks (a, c, g, k). EGCG positive fibroblasts were seen only in grafts preserved at 4℃ with EGCG, 30 minutes to 7 weeks (a, c, g, k, m). In other groups, only phagocytes which ate the GFP were observed.
and frozen allografts are also used for wound coverage, but they are not usually permanently incorporated. Therefore, it is very useful to develop better technologies for the preservation of autografts.
The take rate of preserved skin grafts to nude mice, judged 28 days after surgery. No grafts took in 37℃ preserved groups with or without EGCG. Take rates were improved by addition of EGCG, at 4℃ preservation.
There have been a few reports on the preservation of the cornea, blood vessels, nerves, pancreatic islet cells, saphenous veins and peripheral nervesusing EGCG. In the first reported experiment, histological examination revealed that EGCG improved the length of preservation time a skin sample. With time, skinsamples start to degenerate from the epidermal layer to the dermal layer. Skins samples preserved at 4℃ seem to undergo less degeneration than the ones at 37℃. However, it was difficult to judge the cell viabilities based on only histological examinations, because GFP was still present in all of the skinsamples. Therefore, we investigated the viability of the skin specimens by examining whether the samples could lead to successful grafts. It has been reported that the dead tissue or skin is rejected by around two weeks after implantation. (52, 53)
We used immunodeficient mice as recipient animals and judged the success of skin grafts from GFP-Tg rats. The results indicated that the preservation of the skin with 37℃ is not possible even if EGCG is added. Similarly, AE CRAM etal. reported that only 1/3 of their grafts were successful at ten days after transplanting skin samples preserved at 4℃ for two weeks. In our study, at 4 weeks after transplantation of skins preserved for 4 weeks at 4℃ with EGCG were successful, and one-third were still successful even after preservation for 7weeks at 4℃ with EGCG. We therefore concluded that EGCG was beneficial for the preservation of skin samples by decreasing the degeneration of the epidermal layer and suppressing the postoperative graft contraction.
There might be several reasons why EGCG improved the preservation of the skin. EGCG has strong anti-oxidative activities. The strong anti-oxidative activity of EGCG might inhibit the lipid peroxidation of cell membrane of the preserved skin. M. Kapoor et al. reported that EGCG had anti-inflammatory and free radical scavenging effects
Ourresults suggest the possibility of the future clinical use of EGCG for skin preservation without freezing, although the mechanism underlying how EGCG exerts its beneficial effects on skin preservation still remains unclear.
EGCG enhances the viability of stored skin grafts and also extends the storage time for up to 7 week at 4°C. The addition of EGCG to conventional freezing medium, “Cell Banker” (CB), could enhance the viability of skin grafts stored at −196°C and also extend their storage time. Metabolic assays have been used as a surrogate measure of overall viability in the grafts. Skin tissue was transplanted from GFP transgenic ratsinto immunodeficient mice, and cell migration in graft tolerance of GFP positive cells was investigated after transplantation (55).
For anesthesia, pentobarbital (50 mg/kg) was administered intraperitoneally. After shaving and depilating the back of the rats, the back skin was elevated. After procurement, the muscular layer was immediately stripped from the skin biopsies. Skin samples from GFP rats measuring 1 × 1 cm were kept under sterile containers and refrigerated with PBS solution with or without EGCG for 1 night. Skin samples were then transferred to CB solution with or without EGCG and were stored in liquid nitrogen (-196°C) for up to about 24 weeks. Periodically, the preserved skin grafts of GFT rats were transplanted into nude mice (2, 8, and 24 weeks). Circular skin biopsies (8 mm in diameter) were also made using a sterile dermal biopsy punch (Kai Industries Co., Ltd. Gifu, Japan) and preserved in the same way for in vitro analysis.
A full-thickness excisional square wound (1 × 1 cm) was created on the dorsum of each nude mouse, and the GFP rat skin specimens were sutured to the adjacent normal skin with 6-0 ProleneTM thread. After surgery, the mice were housed in separate cages. Skin grafts were excised with 2–3 mm of the surrounding tissue, bisected, and processed for histology 14 days after transplantation (
The
The optimum concentration of EGCG for rat skinpreservation was determined by measuring the metabolic activity.Skin biopsy samples were preserved in cell culture mediumwith various concentrations of EGCG and preserved at−196ºC for 2 weeks. Glucose consumption was measured after6 days of 37ºC incubation after thawin.
Glucose consumption of the preserved skin biopsies after thawing. Skin biopsy samples were preserved in freezingmedium (CB) with or without EGCG at −196ºC for 4 and 8 weeks. There was no significant difference; however, the amount ofglucose consumption in the EGCG groups showed faster metabolic recovery in comparison to the CB groups.
consumption by the 2-week-preserved skin samples treated with only EGCG after 6 days was about 220 mg/dl while the 4-week skin samples preserved with EGCG and DMSO was almost 300 mg/dl. After day 7 the possibility of bacterial contamination increased and false-positive data were obtained. All skin samples were washed with PBS containing antibiotics every 2 days. The GFP fluorescence appeared to be similar between the 2- and 8-week-preserved groups (Figure 10). The degradation of the epidermal layer to the dermal layer was observed in all groups, regardless of preservation. However, while the Skin grafts of GFP rats preserved in CB showed only green florescence around the dermis of the transplanted area in the 24-week-preserved group, the fluorescence of the epidermal layer and some viable cells were confirmed in the EGCG- preserved skin grafts. The degradation was therefore improved by EGCG in comparison to the CB group. An evaluation of the viability of the transplanted skin grafts was difficult with GFP confirmation only. The histology of the transplanted skin grafts of the GFP rats and nude mice was also therefore evaluated using H&E-stained sections (Figure 11). The grafts preserved with EGCG showed a dense dermal matrix and an intact epidermal layer, as shown in the GFP pictures. Micrographs of CB preserved skin grafts were not fully rejected; however, separation between the transplanted skin of the GFP rat and immunodeficient mouse was observed near the location of the original epidermal layer. The histological score was marked with micrographs of H&E-stained specimens based on the attached area of the transplanted skin graft and the condition of the surviving skin grafts (Figure 12). Dead and completely rejected skin grafts scored 0. The surviving skin grafts with a widely attached area, intact epidermis, and dermis with hair follicles and a dense matrix scored 5. Neither the survival rate of the skin grafts nor the histological scores indicated a clear difference between the 2-, 8-,and 24-week-preserved groups. However, both the survival rate of the skin grafts and the histological scores were increased by EGCG in all groups.
Cryosections of GFP rat skin graft to a nude mouse (left: 2-week-preserved group, middle: 8-week-preserved group,fight: 24-week-preserved group). These micrographs are representative of four to six independent experiments, and showed similarresults.
EGCG therefore enhances the viability of stored skin grafts and extends the storage time up to 7 weeks at 4℃. In this study, the storage time of the skin grafts was extended to 24 weeks by cryopreservation with both DMSO and EGCG. The survival rate of the transplanted skin grafts reached almost 100% in the 24-week-preserved group, indicating that long term storage is possible.(62)
Cryopreserved cells and tissues are increasingly being used for stem cell transplantation and tissue engineering. However, they are highly sensitive to freezing, storage, and thawing, which suggests the need for improved cryopreservation methods. When storing any living tissue, the destructive effects of hypoxic metabolism must be controlled. A tissue removed from its blood supply will die unless cellular metabolic activity is decreased or nutrients are provided. By reducing metabolism and providing nutrients, viability can be improved (56). EGCG was reported to control cell division, which causes the energy metabolism to decrease
Histological observation in skin grafts with H&E-stained micrographs (top: original magnification 5 , bottom: originalmagnification 20 ). Degradation of the epidermal layer to the dermal layer was observed in the CB groups. The degradation wasimproved by EGCG in comparison to the CB groups. These photographs are representative of four to six independent experiments,and showed similar results.
A) The survival rate of grafted GFP rat skin after 2 weeks. (B) Considering the epidermal morphology and dermalintegrity of the transplanted grafts, a score was given from 0 to 5. A higher score indicates better condition of the skin grafts. Theresults are reported as the mean ± SE (
by inhibiting the cell cycle. Therefore, the combination of such effects improves the condition of the preserved skin. In addition, EGCG reduces ischemia/reperfusion injury by attenuating nitric oxide synthase expression and activity, and improving hypoxic metabolism in preserved skin (57). Furthermore, other activities of EGCG, such as strengthening of the scaffold structure, immunomodulatory effects, and antibacterial activity, may also contribute to its preservative effects.
In the present study, the protection afforded by EGCG was similar for all three groups. EGCG and DMSO in the freezing medium were more effective for maintaining glucose consumption. These results suggest that oxygen radicals scavenged by EGCG may be responsible for damage at the membrane level, and thus, exogenous EGCG can protect cell membranes. These phenomena may be related to the intrinsic characteristics of polyphenol compounds, which readily penetrate cell membranes due to their amphipathic properties. These compounds are easily absorbed by lipid bilayers, extracellular matrices (e.g., collagen, fibronectin), and various cell membrane receptors. The absorption of polyphenolic compounds by such proteins is rapid,while the adsorption rates are slow. Consequently, the skin graft could be protected from freeze–thaw injuries due to absorption of EGCG by various membrane proteins and lipids (28). The glucose consumption of thawed tissues was assessed after 2, 4, and 6 days of incubation under tissue culture conditions. This post-thaw incubation period was selected to allow for recovery of the metabolic activity in damaged cells. These delayed measurements may be more characteristic of the actual viability of the skin allografts than measurements taken immediately after thawing and dilution. The cells may sustain lethal damage during the thawing and dilution process but have not yet completely disintegrated; thus, there may be residual metabolic activity in the lethally damaged cells immediately after thawing.
The viability of the preserved skin biopsy samples was investigated by examining whether skin specimens could be successfully grafted after preservation. It is reported that dead tissue or skin is rejected in around 2 weeks (58,59). Therefore, immunodeficient mice were used as recipient animals to judge the success of skin grafts from GFP rats (61). GFP fluorescent protein does not need any chemical substrate for visualization. By using a GFP transgenic animal, transplanted cells or tissues having GFP can be detected by direct visualization. Therefore, the GFP transgenic rat is thought to be a suitable skin donor for skin storage and transplantation studies.
A histological analysis demonstrated that the preserved skin began to degenerate from the epidermis to the dermis. The epidermis is easily degenerated during the preservation processes. Considering the histological data presented in previous studies, the results obtained after 2 weeks of preservation seem to be better for samples stored at 4℃ than those with cryopreservation. However, the success of the 4℃ preserved skin grafts was limited to a 7-week or shorter period, as the samples at 8 weeks no longer led to successful grafts.
EGCG therefore enhances the viability of stored skin grafts and extends the storage time up to 7 weeks at 4℃ (61). In this study, the storage time of skin grafts was extended to 24 weeks by cryopreservation using EGCG, and the survival rate was almost 100% in the samples preserved for 24weeks. These findings suggest that theremay be future clinical applications for EGCG as an agent for skin preservation without freezing, although the mechanism by which EGCG promotes skin preservation remains to be elucidated(62).
The control of cellular proliferation may be important for the prolonged storage of tissues in polyphenol solutions without freezing. Polyphenol is a kind of antioxidant that has similar antioxidant potential as vitamins C and E and superoxide dismutase (SOD). Because of its amphiphilic properties, it also dissolves well in both water and oil. It also has a very high affinity for protein,which allows it to combine with the protein, and yet dissociate with the progression of time, which is characteristic of a reversible adsorption. For the control of cell proliferation and tissue preservation, the latter characteristic is very important. Due to the high affinity between the polyphenol and proteins, the polyphenol can adsorb to a receptor on the cell surface that is integral to the process of cell division when cells are cultured, as shown in Figure 13. The signaling between cells is then blocked when the polyphenol bonds to this receptor, and the cell cycle is inhibited, resulting in no cells entering the S phase, inducing a type of hybernation. As the polyphenol reversibly leaves the cell membrane with the progression of time, the S phase of the cell cycle, and cell proliferation, can resume. The successful long-term storage in the unfrozen state is probably also due to the adsorption of the polyphenol to the collagen and proteoglycan of the extracellular matrix, where it may easily generate temporary cross-linking reactions. Basic research on the interaction between polyphenols and proteins have demonstrated interesting reversible absorption phenomena.(63)
The cell hibernation mechanism induced by the polyphenol.
All of these studies were started based on the author’s observation that polyphenols appeared to be useful for the physiological preservation of tissues or organs, particularly rat pancreatic islet cells [13]. Since then, evidence has been accumulating showing the beneficial effects of polyphenols on cell preservation. The extension of that observation to the preservation of tissues or even organs for transplantation will make it possible to store them for longer periods by regulating the concentration of polyphenols present in the storage solutions. Recently, it was reported that polyphenols can reduce the ischemia/reperfusion injury in rat lungs and preserve various types of tissues or organs including canine lungs, rat aorta, rat peripheral nerves and mammalian pancreatic islet cells (12-34), supporting the author’s hypothesis.
As shown in Figure 13, this non-frozen preservation of mammalian cells, tissues or organs might be mediated by hibernation, a reversible regulation of cell proliferation and survival through modulation of cell cycle-related genes by the polyphenols at the cellular level. With regard to this hypothesis, it has already been reported that the hibernation phenomenon triggered by polyphenols might be related to their intrinsic characteristics, including their bind with and penetration into the cell membrane or tissue matrix due to their amphipathic properties. The absorption of polyphenolic compounds to the proteins is generated early, but the desorption rate is very slow. Consequently, mammalian cells, tissues or organs could be physiologically preserved through adsorption of the compounds to membranous proteins and extracellular matrices, leading to both the reduction in structural deterioration and the prevention of oxidative damage (12-34).
As described above, the polyphenol was able to control the proliferation of various cell types, and was demonstrated to be very useful for the long term storage of various tissues, including islet cells, blood vessels, cartilage, corneas, nerves, and skin. Currently in the U.S.A., approximately 850,000 tissue allografts are transplanted into patients annually. Much of this tissue is stored frozen. The method of cryopreservation at -196℃ was adopted at the University of Tokyo Hospital and the Osaka National Cardiovascular Center in April 1999. Cryopreservation methods are being used for the long term storage of blood vessel, cartilage and skin. However, current research is still being directed at improving the effectiveness of cryopreservation and of preservation fluids, such as the University of Wisconsin solution, for tissue transplantation. We have herein demonstrated that the preservation of various tissues for up to three months without freezing is now possible, with excellent maintenance of the histological and biomechanical characteristics of the tissue. The authors have also succeeded in preserving the rat sciatic nerve, guinea pig periodontal ligament and rat myocardium in a non-frozen condition for long term storage prior to preservation. This has been made possible by the development of a new preservation fluid with polyphenol as an additive antioxidant. Therefore, the cryopreservation of many tissues may eventually be superseded by their storage in the newly developed polyphenol tissue banking fluid. This method of cell and tissue preservation would be of great benefit, not only in Japan, but throughout the world, especially in developing countries where cryopreservation is often not possible.
A cluster of cases of pneumonia with unknown etiology was first reported in Wuhan, Hubei Province, China in December 2019. Subsequent analysis identified a novel coronavirus, later named severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The disease caused by the virus was eventually called coronavirus disease 2019 (COVID-19) [1, 2]. On January 30, 2020, the World Health Organization (WHO) declared the outbreak a Public Health Emergency of International Concern; on March 11, a pandemic was declared [3].
Coronaviruses are widely distributed globally [2]. Most human coronavirus infections are mild; however, two previous outbreaks led to many illnesses and deaths. The epidemics of severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002–2003 and Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012 resulted in many people developing severe pneumonia, with mortality rates of 10% and 36%, respectively [4].
According to the WHO, a patient with suspected COVID-19 infection is anyone meeting the clinical criteria with respect to signs and symptoms associated with the disease, including fever, dry cough, and fatigue. Other less common symptoms include myalgia, nasal congestion, headache, conjunctivitis, sore throat, diarrhea, and smell or taste disorders (anosmia and dysgeusia). Epidemiologic criteria include exposure to an area with a high risk of viral transmission or community transmission owing to work, residence, or travel [5].
COVID-19 infection exhibits different effects in different groups and individuals. Most infected people have mild- or moderate-intensity symptoms and approximately 80% recover without the need for hospitalization. One in five people develop severe illness and experience breathing difficulties, among other serious symptoms. Importantly, it is possible that transmission can occur from someone who either has mild symptoms, remains asymptomatic, or is in the incubation period [6].
According to the United States Centers for Disease Control and Prevention (CDC), the incubation period (time from infection to illness onset) is from 2 to 14 days after exposure, and symptoms develop in 97.5% of infected individuals within 12 days [7]. Adopting a 14-day period of quarantine has become the standard procedure for individuals who have been in contact with someone with a confirmed COVID-19 diagnosis or who have traveled to high-risk areas [8].
SARS-CoV-2 is transmitted through droplets produced when an infected person coughs, sneezes or talks, which are ingested or inhaled by an individual nearby (within a distance of approximately 2 meters). A person can also become infected by touching a contaminated surface or object that has been contaminated with the virus and subsequently touching the mouth, nose, or eyes [9]. The diagnosis of COVID-19 is confirmed via a positive nucleic acid test result using sputum, a throat swab, or lower respiratory tract secretion sample [10].
The Lancet COVID-19 Commission has offered a list of practical solutions to the challenges during the current pandemic. One set of solutions is focused on nonpharmaceutical interventions in which governments, non-governmental organizations (NGOs), and the private sector collaborate to mitigate negative consequences of the pandemic [11]. In line with this, the WHO has recommended the use of face masks, proper hand hygiene, physical distancing and mobility restrictions, among other measures [12, 13, 14]. In Mexico, the federal government announced the National Social Distancing Period Intervention, which included closure of non-essential public and private activities with the objective of reducing population mobility to limit community transmission, especially among those with a high risk of developing complications (age 60 years and older; people with hypertension, type 2 diabetes, obesity, respiratory diseases, or immunosuppression [15, 16, 17]; and pregnant women) [18].
The Carso Group (CG) is a Mexico-based conglomerate of companies spanning five sectors: commercial, infrastructure and construction, industrial, energy, and banking [19]. CG comprises more than 50 companies, with operations in over 5000 locations throughout Mexico and approximately 180,000 employees. CG companies are located in 1333 municipalities (54.2% of the total municipalities) within the 32 Mexican states, and 83% of these are located in 20 metropolitan areas: 45.6% in the Mexico City Metropolitan Area, 4.1% in Puebla-Tlaxcala, 4.1% in Guadalajara, 3.9% in Tijuana, and 3.8% in Monterrey.
The COVID-19 pandemic has affected all economic activities globally, forcing governments and entities to implement actions to contain its transmission [20, 21, 22]. Among the most important of these, most economic activity has shifted to telework, with the exception of activities that are deemed essential [12, 15, 23]. Importantly, some CG companies are engaged in essential economic activities in areas such as telecommunications, banking, mining, and energy. In addition, CG employees have varying levels of risk, either owing to older age or underlying non communicable diseases (NCDs). Some employees are more vulnerable because the nature of their work requires constant interaction with others, such as those working in retail stores, or because their household or workplace is located in a municipality with a high risk of contagion.
In response to the COVID-19 pandemic, the CG Board of Directors commissioned the Carlos Slim Foundation (CSF), a non-profit independent organization linked with the Group, to design and implement a comprehensive response protocol to contain the spread of COVID-19 in the workplace, with the goal of protecting the health of employees and their families, as well as suppliers and clients.
The CSF was founded in 1986. Its aim is to address social inequalities by improving quality of life for the most vulnerable populations by training human resources and promoting greater opportunities. The scope of work of the CSF spans education, employment, health, nutrition, social justice, culture, human development, natural disaster support, economic development, and environmental protection [24].
The Carso COVID Protocol is the result of the abovementioned efforts. The protocol is divided into two components, launched at different times during the COVID-19 pandemic in Mexico; Annex 1 provides greater detail regarding the policies and recommendations outlined in the Protocol:
Prevention and containment of COVID-19, launched on March 13, 2020
Safe return to work, launched on May 22, 2020.
The CSF has extensive expertise in the design, development, implementation, and scale-up of digital health (DH)-based solutions aimed at improving health care service delivery to strengthen primary care, with a strong focus on prevention [25]. Hence, the CSF convened a team of experts in different disciplines to design a COVID-19 digital health ecosystem to facilitate implementation of the Carso COVID Protocol.
One of the basic epidemiological principles in mitigating infectious disease outbreaks is to stop transmission through timely detection and isolation of cases [26]. Hence, leveraging DH contributes to an effective public health strategy to prevent and mitigate the spread of an infectious disease [27].
DH is the new paradigm in health care, defined as “the convergence of four disruptive technologies: 1) the use of digital platforms, connected through micro-services, 2) cloud-based services with robust infrastructure to support big data transactions, 3) use of inter-connected wearables, devices and tracers, and 4) connecting communities through mobile phone apps and social media. These technologies are enhanced by Artificial Intelligence.” [28]. The potential of DH has been demonstrated in detecting and mitigating infectious disease outbreaks and epidemics in countries worldwide [29]. Some examples of successful DH-based strategies include the 2014–2016 Ebola outbreak across West Africa [27] and the 2003 global outbreak of SARS-CoV [29]. In Mexico, there is evidence of the benefits of a mobile phone-based intervention to support surveillance during the H1N1 influenza pandemic in 2009 [30].
The current COVID-19 pandemic highlights the need for innovation in continuous surveillance, rapid diagnosis, and real-time contact-tracing of emerging infectious diseases. Health systems are structured around face-to-face medical visits, which involve direct interaction between patients and their health care providers [31]. This operating model can contribute to faster spread of infection among uninfected individuals, quickly overwhelming available critical care services [31, 32]. Additionally, health care providers are at high risk of exposure to COVID-19 infection, which leads to reduced availability of skilled clinicians over time. When health care resources are strained to a breaking point, patient care may be compromised, which is associated with negative outcomes and increased mortality rates [33].
Given the aforementioned scenario, there is a window of opportunity to implement, expand, and integrate DH technologies across the health care system [34]. The use of digital platforms has become the primary means of communication whereby people, governments, organizations, and health institutions can communicate, work, interact, share and exchange knowledge and information, and generate data [35].
DH has become increasingly instrumental in the response of governments and organizations to COVID-19 [36]. DH solutions include, but are not limited to, telemedicine/telehealth, electronic medical records, public health surveillance leveraging on big data and AI algorithms, wireless health sensors, georreference-based tracing technologies, mobile health applications (apps), and health analytics platforms for public health and clinical decision-making [33]. In the case of COVID-19, DH can offer real-time access to comprehensive individualized reliable data, to enable personalized monitoring and provide AI-based assistance. DH can also be implemented to access reliable data and information, participate in social media, use risk-based algorithms to support self-diagnosis, seek health professionals to receive clinical support, and maintain work activities, among other applications [35, 37]. Table 1 shows some DH solutions that have been developed and are being used by institutions, governments, and NGOs around the world to prevent, manage, and mitigate COVID-19.
Type of solution | Type of tool | Country and developer |
---|---|---|
Coronavirus symptoms | Government websites, apps, chatbots, forums, SMS text messaging, call centers | WHO: Chatbot [38], website [39] PAHO: Website [40] Uruguay: Call center [41] Paraguay: Ministry of Health free call center [42] Mexico: COVID-19MX App [43], chatbot [44], websites [44, 45, 46] Trinidad and Tobago: Website [47] Argentina: Chatbot [48] Jamaica: Website [49] USA: CDC website [8] Spain: Ministry of Health website [50] and AsistenciaCOVID19 App [51] Canada: COVID-19 Virtual Assistant and website [52] Colombia: Government website, telephone lines, and virtual assistant [53] Bolivia: Government COVID-19 call center and BoliviaSegura App [54] |
Real-time information regarding the status of the epidemic in each country | Dashboards, websites, apps | WHO: Interactive dashboard [55] PAHO: Big data tool [56] Google: COVID-19 Situation Dashboard [57] Humanitarian response: Interactive map [58] HealthMap: Interactive map [59] Johns Hopkins: Interactive dashboard [60, 61] Spain: Ministry of Health website [62] Brazil: Ministry of Health Interactive map [63] Mexico: COVID-19 Situation Dashboard UNAM [64] and COVID-19 Traffic Light Monitoring System SSA [65] Jamaica: Interactive dashboard [66] Colombia: Interactive map [67] |
General questions regarding COVID-19 | Government websites | PAHO: COVID-19 website [68] WHO: COVID-19 website [39] Mexico: COVID-19 web page [44] Spain: Ministry of Health website [62] USA: CDC website [69] and Department of Health and Human Services [70] Canada: COVID-19 website [71] Colombia: Government website [53] Bolivia: Government COVID-19 website [54] |
Self-diagnosis support to seek medical care | Apps, chatbots, websites, call centers, self-assessment tools | WHO: Chatbot [38] Google: COVID-19 self-assessment [72] Johns Hopkins: Coronavirus self-checker tool [73] Peru: COVID-19 coronavirus evaluation CDC: Coronavirus self-checker tool [74] Jamaica: Call centers [75] MAYO Clinic: Coronavirus self-assessment tool [76] Canada: COVID-19 self-assessment tool [77] Colombia: COVID-19 self-diagnosis tool [78] and virtual assistant [53] USA: Veterans Crisis Line Veterans Health Administration - COVID-19 Response Plan [79] |
General guidance from health care professionals | Apps, call centers | Argentina: National call center [80] Uruguay: Chatbot and call center [81] Mexico: National Call Center [82], UNAM call center [83] |
Patient monitoring and follow-up, contact tracing | Apps, call centers, teleconsultations | Brazil: Monitora COVID-19 App [84] Uruguay: Coronavirus UY App [85] France: StopCovid App [86] China: Beijing Cares App [87] Australia: COVIDSafe App [88] South Korea: Self-quarantine Safety Protection App [89] India: AarogyaSetu App [90] USA: Veterans Health Administration - COVID-19 Response Plan [79] Indonesia: PeduliLindungi App [86] Germany: Corona-Datenspende [91] and Corona-Warn-App [86] Hong-Kong: StayHomeSafe App [92] Colombia: CoronApp [93] |
Clinical support from health professionals | Apps, call centers, teleconsultations | Guatemala: Online doctor app [94] Peru: Telephone line [95] USA: Veterans Health Administration - COVID-19 Response Plan [79] USA: Department of Health and Human Services [70] |
Follow-up of suspected cases in quarantine | Apps, call centers, teleconsultations | Brazil: Monitora COVID-19 App [84] Colombia: CoronApp [93] Costa Rica: EDUS COVID-19 app [96] Poland: Kwarantanna domowa App [86] |
Remote clinical management | Call centers, teleconsultations | Mexico: phone line, WhatsApp for emotional, nutritional, and medical attention for TecSalud workers [97] |
Evidence-based public health information regarding COVID-19 | Web-based information, specialized interactive websites for researchers | WHO: Virtual Health Library COVID-19 [98] Cochrane Library on COVID-19 [99] PubMed: LitCovid literature hub [100] OAS: Organization of American States COVID-19 Repository [101] Elsevier: National Library of Medicine Elsevier Information Center [102] |
Evidence-based materials for ongoing training | Virtual campuses, webinars, interactive platforms | WHO: Virtual Campus [103] PAHO: Virtual Campus [104] Mexico: Mexican Government website COVID-19 courses [105] Coursera: Virtual Campus [106] CDC: Virtual Campus [107] |
Digital solutions developed to prevent and manage COVID-19 around the world.
The first case of COVID-19 in Mexico was reported on February 27, 2020 [108, 109]. Fully aware of the benefits of DH, the CSF had begun to work on the design of a robust response plan in January 2020. On March 13, 2020, the Carso COVID Protocol was launched, including a comprehensive set of actions and recommendations to prevent and contain COVID-19 in the workplace. As part of implementation of the Protocol, the CSF launched the MONITOR digital health ecosystem (MDHE), aimed at monitoring the wellbeing of CG employees and their families.1
MONITOR was initially designed based on WHO and CDC guidelines, and its recommendations are in compliance with current regulations of Mexico’s Ministry of Health. Furthermore, MONITOR has been continuously updated with the latest available scientific evidence.
The MDHE comprises three interconnected platforms operating concurrently: a mobile phone application and a web portal for employees and their families to register and report symptoms on a daily basis, the Integrated Measurement for Early Detection (MIDO)-COVID Platform to assess NCDs and COVID-19 serological status among employees at worksites, and the Health Intelligence Platform with robust analytics to support decision making. Importantly, the MDHE is compliant with Mexico’s regulatory standards in terms of confidentiality, security and privacy.
MONITOR enables the implementation of a COVID-19 prevention and containment strategy according to the following stepwise process:
An employee registers in MONITOR using either the mobile phone app or a secure web portal. During registration, the employee is asked to provide information on any existing NCDs.
On a daily basis, individuals report whether they have any symptoms and if so, describe those symptoms. Using a point-based risk algorithm, MONITOR automatically assesses and classifies each person’s risk and provides immediate recommendations, as follows:
No risk (no symptoms): the employee is encouraged to continue notifying on a daily basis.
Mild risk: the employee is encouraged to increase the number of notifications to twice a day and to continue monitoring.
Moderate risk: the employee is encouraged to increase notifications to twice a day and if necessary, to call a dedicated call medical center operating 24/7/365.
Severe risk: the employee is encouraged to increase notifications to twice a day and to call a medical call center. In addition, an alert is triggered to the human resources (HR) department of the employee’s company, to signal a potential complication.
At the medical call center, a general physician provides remote counseling, and assesses whether the employee requires a reverse transcription polymerase chain reaction (RT-PCR) test to confirm a diagnosis of COVID-19 infection, or whether they need to be referred for immediate medical assessment.
If a person is referred for an RT-PCR test, the general physician schedules an appointment at any of the CG-dedicated lab facilities in Mexico City and 27 cities throughout the country. Once the employee has been tested, they are instructed to remain in isolation until their test results are obtained, within 24–48 hours.
Upon confirmation of COVID-19 infection:
The employee receives a pulse oximeter for self-monitoring during the 14-day isolation period. The employee is required to notify symptoms via MONITOR.
The CSF epidemiology team, in coordination with company HR departments, conducts an outbreak investigation for each employee with confirmed COVID-19 infection, including tracing of all work and family contacts. A contact is defined as someone who has remained in close proximity (less than 2-meter distance) with the employee for at least 15 minutes while not wearing personal protective equipment; this definition is in line with WHO recommendations [9, 10].
All identified contacts are sent for confirmatory laboratory testing and are closely monitored throughout the period in which they are ill.
All collected data are available through the Health Intelligence Platform for real-time analytics, follow-up, and clinical support, for both HR departments and the CSF epidemiology team.
With ongoing transmission of SARS-CoV-2 during the phased reopening of non-essential activities in Mexico, a series of measures were implemented in CG’s workplaces to ensure the safe return of employees. These measures are described in Annex 1.
There is ample scientific evidence demonstrating that the presence of comorbidities increase the risk of severity and complications of COVID-19, particularly cardiovascular disease, diabetes, hypertension, chronic lung or renal disease, and obesity [17]. In light of this evidence and building on previous experience [110, 111, 112], the CSF designed and developed the MIDO-COVID Digital Platform, aimed at assessing NCDs and COVID-19 serological status among employees resuming operations in the workplace.
Like MONITOR, MIDO-COVID is implemented following a stepwise process, performed by a MIDO expert2:
Registration of employees in MIDO-COVID, retrieving their data from the MDHE.
Measurement of weight/waist circumference and height, blood pressure, and capillary blood glucose, either fasting or random.
Performance of rapid antibody tests.
Recording of measurements and serologic test results.
Analytical algorithm with integrated risk profiling:
NCDs profile with interpretation and recommendations.
Serology test results with interpretation and recommendations.
The MIDO-COVID Digital Platform automatically delivers certified serologic test results. Importantly, this assessment confirms the presence of NCDs and validates the self-reports provided by employees using the mobile phone app. Finally, in the case of active COVID-19 infection, the employee is quarantined and the contact tracing protocol is begun, as described above.
In sum, joint coordination of the HR department at each company with the epidemiology team at the CSF has enabled effective deployment of the Carso COVID Protocol through the use of MONITOR. Table 2 shows the main results of the MDHE as of October 31, 2020.
Registrants in MONITOR | N = 254,043 |
---|---|
Employees | 184,117 |
Family relatives | 69,926 |
Medical call center calls | 257,803 |
Laboratory tests performed | 29,693 |
Positive cases (positivity rate) | 5124 (17.2%) |
Outbreak studies in workplaces | 1840 |
Total assessments | 46,740 |
Main results of serology tests | |
IgM − / IgG – (not exposed) | 39,505 (84.5%) |
IgM + / IgG – (early-stage infection) | 322 (0.7%) |
IgM + / IgG + (acute infection) | 2013 (4.3%) |
IgM − / IgG + (past infection) | 4812 (10.3%) |
Main results of the MONITOR digital health ecosystem (13 march to 31 October, 2020).
Given that the COVID-19 pandemic has changed the way that companies function, the CG intends to retain certain strategies to protect employees’ health. The COVID-19 pandemic has provided an excellent opportunity to improve the workplace environment in terms of health and safety at every worksite. The CG is fully committed to providing every employee with all the preventive tools, measures, and strategies needed to maintain a physically and mentally healthy community. In this sense, the CSF encourages joining MONITOR together with MIDO, with the recognition that poor control of NCDs increases the risk for COVID-19 complications [113]. MIDO screening can facilitate early detection of type 2 diabetes, hypertension, and dyslipidemia, focusing specifically on pre-disease stages and early treatment. MIDO offers a systematic risk assessment of screened individuals, identifying those with a healthy, at-risk (pre-disease), or disease status [112].
Inter-connecting MONITOR and MIDO-COVID in a digital ecosystem allows HR personnel to identify COVID-19 positive employees or those with high-risk of complications. Daily information can be used to better monitor, diagnose, track and control employees’ infection risk and overall health. Moreover, data are stored in a secure cloud, where it can be retrieved to generate predictive models for each company and type of workplace, as a strategy to better understand and control risk factors in each sector.
Flexible schedules, in which employees alternate teleworking and working at a CG location when necessary, are very important. If an employee feels unwell, they must notify their direct manager and should not present to their work location. In worksite dining rooms, menus should be based on nutritional recommendations following the EAT-LANCET Commission on healthy diets and sustainable food production. Every meal is to be prepared according to the planetary health plate, characterized by at least 50% vegetables (fruits and vegetables) and the remainder comprising whole grains, plant-source protein, animal-source protein, dairy foods, and unsaturated plant oils [114].
Workplaces are implementing programs to promote wellbeing and healthy lifestyles among employees and their household members. In this way, the CG seeks to empower its employees through health promotion initiatives conducted by trained multidisciplinary health professionals in topics including nutrition, NCDs prevention, physical activity, vaccination, mental health awareness, and wellbeing.
As part of its response to COVID-19 as well as other novel pathogens, the CG plans to create emergency response teams and permanent communication via DH among HR departments across all CG businesses. Frequent intervention assessments will be carried out to gauge adherence to protocols and determine where improvements are needed.
This chapter describes the CG COVID-19 mitigation strategy within a corporate group in Mexico. Priorities for the CG during this outbreak have been to protect employees’ health and wellbeing by implementing protocols and strategies based on scientific evidence. Consequently, occupational safety and health have taken on greater relevance in all kinds of workplaces.
First, our experience shows that Digital Health can be used to quickly identify people with any infection risk, during early stages. CG employees are empowered through advice and counseling using IT tools such as a mobile phone app or website. The MONITOR strategy has proven to be an effective intervention. The use of DH has been instrumental in outbreak control and maintaining workplace activities. Second, we have learned that the use of a Digital Health ecosystem is effective in detecting and controlling COVID-19 outbreaks in work settings.
This experience can be useful for other organizations in the process of implementing and operating digital health based strategies to cope with outbreaks of viral disease.
We wish to acknowledge the work of the different HR departments of CG in the implementation and follow-up of the Carso COVID Protocol. The strategy and results included in this chapter were only possible because of their dedication, and their hard work.
On the other hand, we acknowledge the help provided by Alejandra Cantoral, ScD., Larissa Betanzos, ScM, and Adriana Granich, MD, for the data compilation of digital health solutions around the world. We also acknowledge Analisa Avila, of Edanz Evidence Generation, for editorial support.
All authors declare no conflicts of interest.
To support the Carso Group (CG) COVID-19 response plan, the Carlos Slim Foundation prepared and designed the Carso COVID Protocol, called the “Recommendations and guidelines for the prevention and management of COVID-19 in an organization”. The Protocol has two components, launched at two time points during the course of the pandemic:
Prevention and containment of COVID-19, launched on March 13, 2020 (Supplementary Table 1)
Safe return to work, launched on May 22, 2020 (Supplementary Table 2).
This Protocol is based on scientific evidence regarding infectious diseases and the most important available evidence regarding COVID-19 to date. Most recommendations are based on WHO and CDC guidelines and are continuously updated as new evidence becomes available.
The Protocol was designed with consideration for the needs of the different CG workplaces. Nonetheless, each company within the CG has adapted the recommendations to the operational needs of each workplace. For example, most employees in workplace settings that were not considered essential switched to teleworking whereas employees performing activities classified as essential implemented different schemes, such as staggered working schedules. It is noteworthy that the Protocol was implemented at all CG worksites.
Section | Description | Main actions/recommendations |
---|---|---|
Continuity of Operations Group | In each company, this refers to a team comprising employees with decision-making capacity. This group designs, coordinates, and establishes the organization’s continuous operations policies and guidelines. |
|
Communication strategies | Identifying the point of contact in each workplace and department to communicate new policies and guidelines. |
|
General containment measures | This refers to general containment measures for employees. | Measures are classified according to risk:
|
General preventive measures | This describes hygiene and physical distancing measures that must be implemented in each workplace. The supplies needed to implement these policies are also listed. Recommendations for working from home are given. |
|
Employee dining rooms | Describes sanitary measures that dining room staff must implement during the preparation of meals and cleaning of the dining room. |
|
Cleaning company staff | Describes policies and guidelines that all cleaning staff must comply with. |
|
Travel, business meetings and events | Describes general policies for travel, meetings, and events. This section emphasizes the importance of transitioning to tele- or video conferences. |
|
Customer service workplaces | This section describes the general policies for workplaces that provide customer service, such as retail and post-sales services and banking. |
|
Call centers |
|
Supplementary Table 1. Prevention and containment of COVID-19 (summary).
Section | Main actions/recommendations |
---|---|
Preparation and adaptation of workspaces |
|
Measures to reduce physical interaction |
|
Measures to reduce risk of infection |
|
Employee training and awareness campaigns |
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Supplementary Table 2. Safe return to work (summary).
None
artificial intelligence Centers for Disease Control and Prevention Carso Group Carlos Slim Foundation digital health human resources MONITOR digital health ecosystem Middle East respiratory syndrome coronavirus Integrated Measurement for Early Detection non-communicable diseases non-governmental organization Pan American Health Organization reverse transcription polymerase chain reaction severe acute respiratory syndrome coronavirus severe acute respiratory syndrome coronavirus-2 Ministry of Health World Health Organization
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