Excerpts from interviews.
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Barely three months into the new year and we are happy to announce a monumental milestone reached - 150 million downloads.
\n\nThis achievement solidifies IntechOpen’s place as a pioneer in Open Access publishing and the home to some of the most relevant scientific research available through Open Access.
\n\nWe are so proud to have worked with so many bright minds throughout the years who have helped us spread knowledge through the power of Open Access and we look forward to continuing to support some of the greatest thinkers of our day.
\n\nThank you for making IntechOpen your place of learning, sharing, and discovery, and here’s to 150 million more!
\n\n\n\n\n'}],latestNews:[{slug:"intechopen-supports-asapbio-s-new-initiative-publish-your-reviews-20220729",title:"IntechOpen Supports ASAPbio’s New Initiative Publish Your Reviews"},{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"}]},book:{item:{type:"book",id:"9686",leadTitle:null,fullTitle:"Brassica Breeding and Biotechnology",title:"Brassica Breeding and Biotechnology",subtitle:null,reviewType:"peer-reviewed",abstract:"The family Brassicaceae constitutes one of the world’s most economically important plant groups. These plants are important sources of vegetable oil, vegetables, and condiments. Most of these crops belong to the genus Brassica, which includes common crops such as oilseeds (oilseed rape, mustard) and vegetables (broccoli, cauliflower, brussels sprouts, cabbage, turnip, Chinese cabbage, etc.). Brassica species play an essential role in horticulture and agriculture as well as contribute to the health of populations around the world. The current global climatic model predicts a significant decrease in growth, yield, and productivity of Brassica due to various biotic and abiotic stress factors. Thus, high-yielding, climate-resilient, and disease-resistant Brassica varieties are required to maintain as well as increase future agricultural production. The development of improved cultivars of these crops may become exhausted and improvement could become stagnant when plant breeding is merely based on a single breeding approach. Therefore, the goal of a breeding program should be to develop genetically superior Brassica cultivars suitable for a wide range of environments. This book examines the introgression of insect and disease resistance and other desirable traits into Brassica crops using inter-and/or intra-specific hybridization as well as biotechnological and molecular techniques, which could be useful for improving Brassica crops to ensure food security.",isbn:"978-1-83968-697-9",printIsbn:"978-1-83968-696-2",pdfIsbn:"978-1-83968-698-6",doi:"10.5772/intechopen.87490",price:119,priceEur:129,priceUsd:155,slug:"brassica-breeding-and-biotechnology",numberOfPages:174,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"1afe175ea39b01d4e6e0c9d6427486a6",bookSignature:"A. K. M. Aminul Islam, Mohammad Anwar Hossain and A. K. M. Mominul Islam",publishedDate:"July 7th 2021",coverURL:"https://cdn.intechopen.com/books/images_new/9686.jpg",numberOfDownloads:3476,numberOfWosCitations:3,numberOfCrossrefCitations:9,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:15,numberOfDimensionsCitationsByBook:0,hasAltmetrics:0,numberOfTotalCitations:27,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"September 4th 2020",dateEndSecondStepPublish:"October 2nd 2020",dateEndThirdStepPublish:"December 1st 2020",dateEndFourthStepPublish:"February 19th 2021",dateEndFifthStepPublish:"April 20th 2021",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"191072",title:"Prof.",name:"A. K. M. Aminul",middleName:null,surname:"Islam",slug:"a.-k.-m.-aminul-islam",fullName:"A. K. M. Aminul Islam",profilePictureURL:"https://mts.intechopen.com/storage/users/191072/images/system/191072.png",biography:"Prof. Dr. A. K. M. Aminul Islam is Professor of Genetics and Plant Breeding at Bangabandhu Sheikh Mujibur Rahman Agricultural University (BSMRAU), Gazipur, Bangladesh, where he is also a director of research. He received bachelor’s and master’s degrees from Bangladesh Agricultural University (BAU), Mymensingh, Bangladesh, and a Ph.D. in Chemical and Process Engineering from Universiti Kebangsaan Malaysia. Dr. Islam is the author of 120 articles published in nationally and internationally reputed journals, twenty book chapters, and four books. He is an editorial board member and referee for several national and international journals. He is also the general secretary of the Plant Breeding and Genetics Society of Bangladesh, the seminar and research secretary of JICA Alumni Association of Bangladesh, and a lifetime member of several professional societies. Dr. Islam developed and released nineteen varieties of different crops for commercial cultivation by farmers. He supervised twenty-two MS and two Ph.D. students as major professor and forty MS and two Ph.D. students as a committee member. His major areas of research are the development of hybrid vegetables, canola-grade Brassica napus using a CMS system, and salinity-tolerant rice, as well as renewable energy research with Jatropha curcas.",institutionString:"Bangabandhu Sheikh Mujibur Rahman Agricultural University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"4",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Bangabandhu Sheikh Mujibur Rahman Agricultural University",institutionURL:null,country:{name:"Bangladesh"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:{id:"321236",title:"Prof.",name:"Mohammad Anwar",middleName:null,surname:"Hossain",slug:"mohammad-anwar-hossain",fullName:"Mohammad Anwar Hossain",profilePictureURL:"https://mts.intechopen.com/storage/users/321236/images/system/321236.png",biography:"Dr. Mohammad Anwar Hossain is a professor in the Department of Genetics and Plant Breeding, Bangladesh Agricultural University (BAU), Mymensingh, Bangladesh. He received his BSc in Agriculture and MS in Genetics and Plant Breeding from BAU. He also received an MSc in Agriculture from Kagawa University, Japan, in 2008, and a Ph.D. in Abiotic Stress Physiology and Molecular Biology from Ehime University, Japan, in 2011 through a Monbukagakusho scholarship. As a JSPS postdoctoral researcher in 2015–2017, he worked on isolating low-phosphorus, stress-tolerant genes from rice at the University of Tokyo, Japan. His current research program focuses on understanding physiological, biochemical, and molecular mechanisms underlying abiotic stress tolerance in crop plants and the generation of stress-tolerant and nutrient-efficient plants through breeding and biotechnology. He has more than sixty peer-reviewed publications to his credit and has edited twelve books, including this one.",institutionString:null,position:null,outsideEditionCount:null,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:null},coeditorTwo:{id:"234696",title:"Prof.",name:"A. K. M. Mominul",middleName:null,surname:"Islam",slug:"a.-k.-m.-mominul-islam",fullName:"A. K. M. Mominul Islam",profilePictureURL:"https://mts.intechopen.com/storage/users/234696/images/system/234696.png",biography:"Dr. A. K. M. Mominul Islam is a professor in the Department of Agronomy, Bangladesh Agricultural University (BAU), Mymensingh, Bangladesh. He received both bachelor’s and master’s degrees from BAU. Dr. Islam obtained a second master’s degree in Physical Land Resources from Ghent University, Belgium, and a Ph.D. in Plant Allelopathy from United Graduate School of Agricultural Science, Ehime University, Japan, with his dissertation “Allelopathy of five Lamiaceae medicinal plant species.” Dr. Islam also completed his post-doctoral research at the Department of Horticulture and Landscape Architecture, Purdue University, Indiana, USA. Dr. Islam is the author of seventy-four articles published in nationally and internationally reputed journals, six book chapters, and three books. He is an editorial board and referee for several national and international journals. To date, he has supervised twenty-one MS students. Dr. Islam is currently supervising the research of two MS and six Ph.D. students in the areas of field crop production and management.",institutionString:"Bangladesh Agricultural University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Bangladesh Agricultural University",institutionURL:null,country:{name:"Bangladesh"}}},coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"341",title:"Olericulture",slug:"olericulture"}],chapters:[{id:"74816",title:"Advances in Breeding in Vegetable Brassica rapa Crops",doi:"10.5772/intechopen.95769",slug:"advances-in-breeding-in-vegetable-em-brassica-rapa-em-crops",totalDownloads:364,totalCrossrefCites:2,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Brassica rapa includes oil and vegetable crops having a variety of forms, such as oilseeds, leafy vegetables and turnips. Leafy types, which are called turnip greens and turnip tops, are popular crops in NW Spain, and they represent an important part of the diet. However, their cultivation is limited in southern areas or in the Mediterranean basin, probably due to a lack of adaptation. Still, they could occupy a prominent place in the Mediterranean diet, which is based on a high consumption of fruits and vegetables. In this review, we summarize the studies on the agronomical and nutritional value of these crops when grown under Mediterranean climate conditions. Data reported here might be useful for a deeper understanding of these crops for both nutritional quality and bioaccessibility, and for selecting varieties adapted to the two abovementioned Mediterranean conditions, as well as for organic farming systems, thus contributing to the diversification of traditional Brassica vegetable production systems.",signatures:"María Elena Cartea, Fernando Cámara-Martos, Sara Obregón, Francisco Rubén Badenes-Pérez and Antonio De Haro",downloadPdfUrl:"/chapter/pdf-download/74816",previewPdfUrl:"/chapter/pdf-preview/74816",authors:[{id:"142197",title:"Prof.",name:"Fernando",surname:"Cámara-Martos",slug:"fernando-camara-martos",fullName:"Fernando Cámara-Martos"},{id:"229534",title:"Dr.",name:"Antonio",surname:"De Haro-Bailón",slug:"antonio-de-haro-bailon",fullName:"Antonio De Haro-Bailón"},{id:"334691",title:"Dr.",name:"María Elena",surname:"Cartea",slug:"maria-elena-cartea",fullName:"María Elena Cartea"},{id:"335952",title:"Dr.",name:"Sara",surname:"Obregon-Cano",slug:"sara-obregon-cano",fullName:"Sara Obregon-Cano"},{id:"342339",title:"Dr.",name:"Francisco",surname:"Badenes-Pérez",slug:"francisco-badenes-perez",fullName:"Francisco Badenes-Pérez"}],corrections:null},{id:"75542",title:"Rapeseed-Mustard Breeding in India: Scenario, Achievements and Research Needs",doi:"10.5772/intechopen.96319",slug:"rapeseed-mustard-breeding-in-india-scenario-achievements-and-research-needs",totalDownloads:736,totalCrossrefCites:3,totalDimensionsCites:6,hasAltmetrics:0,abstract:"Brassica spp., commonly known as rapeseed-mustard, plays a significant role in the Indian economy by providing edible oils, vegetables, condiments and animal feed. Globally, India holds second and third position in rapeseed-mustard area under cultivation and production, respectively. However, anthropogenically accelerated climate change thwarts yield potential of rapeseed-mustard by employing abiotic (drought, flood, temperature variation and salinity) and biotic (disease and insects) stresses. Various approaches such as molecular breeding, pre-breeding, −omics and biotechnological interventions have been used to develop varieties for improved yield and oil quality, climate resilient and resistance or tolerance to abiotic and biotic stresses. In this context, this chapter highlighted the different cytoplasmic male sterility (CMS) sources and their potential use for hybrid development. At the end, this chapter also enlisted salient achievement by the government and non-government institutes and briefly described the future perspective for improvement of rapeseed-mustard in India.",signatures:"Subhash Chand, Om Prakash Patidar, Rajat Chaudhary, Ranjit Saroj, Kailash Chandra, Vijay Kamal Meena, Omkar M. Limbalkar, Manoj Kumar Patel, Priya P. Pardeshi and Prashant Vasisth",downloadPdfUrl:"/chapter/pdf-download/75542",previewPdfUrl:"/chapter/pdf-preview/75542",authors:[{id:"249796",title:"Dr.",name:"Kailash",surname:"Chandra",slug:"kailash-chandra",fullName:"Kailash Chandra"},{id:"326742",title:"Dr.",name:"Subhash",surname:"Chand",slug:"subhash-chand",fullName:"Subhash Chand"},{id:"348860",title:"Dr.",name:"Om Prakash",surname:"Patidar",slug:"om-prakash-patidar",fullName:"Om Prakash Patidar"},{id:"348861",title:"Dr.",name:"Rajat",surname:"Chaudhary",slug:"rajat-chaudhary",fullName:"Rajat Chaudhary"},{id:"348862",title:"Dr.",name:"Ranjit",surname:"Saroj",slug:"ranjit-saroj",fullName:"Ranjit Saroj"},{id:"348863",title:"Dr.",name:"Vijay Kamal",surname:"Meena",slug:"vijay-kamal-meena",fullName:"Vijay Kamal Meena"},{id:"348865",title:"Dr.",name:"Omkar M.",surname:"Limbalkar",slug:"omkar-m.-limbalkar",fullName:"Omkar M. Limbalkar"},{id:"348867",title:"Dr.",name:"Manoj Kumar",surname:"Patel",slug:"manoj-kumar-patel",fullName:"Manoj Kumar Patel"},{id:"348868",title:"Dr.",name:"Priya P.",surname:"Pardeshi",slug:"priya-p.-pardeshi",fullName:"Priya P. Pardeshi"},{id:"348869",title:"Dr.",name:"Prashant",surname:"Vasisth",slug:"prashant-vasisth",fullName:"Prashant Vasisth"}],corrections:null},{id:"75023",title:"Innovative Strategies to Develop Abiotic and Biotic Stress Tolerance in Mustard (Brassicaceae)",doi:"10.5772/intechopen.95973",slug:"innovative-strategies-to-develop-abiotic-and-biotic-stress-tolerance-in-mustard-brassicaceae-",totalDownloads:357,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Mustard crop is the third important source of vegetable oil randomly below soybean L. and palm, all over the world. Brassica crop is extremely susceptible to some biotic and abiotic stresses and they significantly influence the quality and quantity of the crop. In the past generally breeding techniques are used to develop resistance in mustard to avoid diseases though various pathogens are soon able to overcome that resistance by modifying their metabolic cycles. To bear the challenge there is an urgent need to develop abiotic as well as biotic stress tolerant plants using advanced techniques by understanding metabolic and biochemical pathways of plants and pathogens. Several techniques such selection of stress tolerance microbes, metabolite, enzymes, and genes are very important to avoid stresses. Whereas several techniques such as deployment of molecular markers for breeding, identification of Quantitative trait loci (QTL), in vitro tissue culture etc. can be more useful to improve biotic and abiotic stress tolerance in mustard. To develop healthy and high yield varieties, the mix of these techniques is needs to be implemented.",signatures:"Bahaderjeet Singh, Amanpreet Singh Sran and Gagandeep Singh Sohi",downloadPdfUrl:"/chapter/pdf-download/75023",previewPdfUrl:"/chapter/pdf-preview/75023",authors:[{id:"331114",title:"Assistant Prof.",name:"Bahaderjeet",surname:"Singh",slug:"bahaderjeet-singh",fullName:"Bahaderjeet Singh"}],corrections:null},{id:"75263",title:"Embryo Culture and Embryo Rescue in Brassica",doi:"10.5772/intechopen.96058",slug:"embryo-culture-and-embryo-rescue-in-em-brassica-em-",totalDownloads:362,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Somatic embryogenesis is the best demonstration of totipotency in higher plants in which somatic cell produce whole plant like zygotic embryo. It is also demonstrated that immature, weak, hybrid or sometimes inviable embryos can be saved through in vitro culture to prevents its degradation. It may help to cross the reproductive barriers when interspecific hybrids developed. Brasssica is an economically valuable oil yielding and vegetable crop and India is the largest producer of oil seed rape in the world. Various factors affect the embryo rescue in Brassica like growth stage of the embryos, types and composition of the rescue medium etc. The embryo regeneration potential can improve through the modification of culture conditions in both zygotic as well as somatic embryo. Except the embryo culture other parts like ovule, ovary culture can also be done to developed interspecific hybrids. This chapter is focused on the embryo rescue techniques in the genus Brassica and summarizes possible ways of improving the technique used.",signatures:"Mohammad Akmal",downloadPdfUrl:"/chapter/pdf-download/75263",previewPdfUrl:"/chapter/pdf-preview/75263",authors:[{id:"181036",title:"Dr.",name:"Mohammad",surname:"Akmal",slug:"mohammad-akmal",fullName:"Mohammad Akmal"}],corrections:null},{id:"74043",title:"Breeding Mustard (Brassica juncea) for Salt Tolerance: Problems and Prospects",doi:"10.5772/intechopen.94551",slug:"breeding-mustard-em-brassica-juncea-em-for-salt-tolerance-problems-and-prospects",totalDownloads:303,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Salt stress is currently one of the most critical factors, reducing agricultural production. Indian mustard (Brassica juncea) is a major oilseed crop in these areas. However, salt affects as much as 50–90% worldwide yield reduction. Salt tolerance is a very complex factor controlled by a number of independent and/or interdependent mechanisms and genetic modification that lead to many changes in physiology and biochemistry at the cellular level. The classical methods of plant breeding for salt tolerance involves the widespread use of inter and intraspecific variations in the available germplasm which is essential for any crop development program. This large germplasm is then tested under various salt levels in microplots, which is a quick, reliable, reproducible and inexpensive method of salt tolerance. Genotypes that have shown better indications of stress tolerance without significant yield reduction are considered to be tolerant and are also used as potential donor in the breeding programs. In this way, ICAR-Central Soil Salinity Research Institute (ICAR-CSSRI), Karnal developed and produced five varieties of Indian mustard that tolerate high salt namely, CS 52, CS 54, CS 56, CS 58 and CS 60 in the country, and many other high-quality pipeline lines exploration and development. These salt-tolerant species work better under conditions of salt stress due to various manipulations (physiology, genes and molecular level) to fight salt stress has led to detrimental effects. Recent molecular tools to add classical breeding systems to improve saline-tolerant mustard varieties in a short span of time, including the Marker Assisted Selection (MAS) and backcrossing, that have helped using simple sequence repeats (SSR) and single nucleotide polymorphisms (SNP) markers to identify quantitative trait loci (QTLs) that control the polygenic traits like tolerance of salt and seed yield.",signatures:"Jogendra Singh, Parbodh Chander Sharma and Vijayata Singh",downloadPdfUrl:"/chapter/pdf-download/74043",previewPdfUrl:"/chapter/pdf-preview/74043",authors:[{id:"245615",title:"Dr.",name:"Jogendra",surname:"Singh",slug:"jogendra-singh",fullName:"Jogendra Singh"}],corrections:null},{id:"75554",title:"Salinity Tolerance in Canola: Insights from Proteomic Studies",doi:"10.5772/intechopen.96649",slug:"salinity-tolerance-in-canola-insights-from-proteomic-studies",totalDownloads:350,totalCrossrefCites:2,totalDimensionsCites:4,hasAltmetrics:0,abstract:"Salinity considerably lowers crop yield worldwide. Production of salt stress-tolerant species will be essential to maintain the food supply in the coming decades. Brassicas, including various members of the family Brassicaceae, are very necessary sources of human food. Importantly, the key crop species that are members of the Brassicaceae family are genetically diverse and therefore their response reaction and adaptation to salinity varies greatly. Canola (Brassica napus L.) is commonly grown for edible oils and other uses such as biodiesel fuel production. Although most types of canola are identified as salt-resistant, plant yield and development are reduced significantly by rising salinity levels. In saline situations, the plant’s genome supports a range of physiological changes in some plant characteristics. Since the function of genes cannot indicate the exact condition of cells, proteomic approaches are emerged as methods to investigate the plant’s responses to stresses in the molecular levels. Exploring the proteome complements research at the genome and transcriptome level and helps elucidate the mechanism of salt tolerance in plants. Proteins are reliable indicators of salinity responses, as they are directly involved in forming the new phenotype providing adaptation to salinity. In this chapter, we review the response of the rapeseed proteome to salinity stress.",signatures:"Ali Bandehagh, Zahra Dehghanian, Robert Henry and Mohammad Anwar Hossain",downloadPdfUrl:"/chapter/pdf-download/75554",previewPdfUrl:"/chapter/pdf-preview/75554",authors:[{id:"321236",title:"Prof.",name:"Mohammad Anwar",surname:"Hossain",slug:"mohammad-anwar-hossain",fullName:"Mohammad Anwar Hossain"},{id:"333759",title:"Dr.",name:"Ali",surname:"Bandehagh",slug:"ali-bandehagh",fullName:"Ali Bandehagh"},{id:"333782",title:"BSc.",name:"Zahra",surname:"Dehghanian",slug:"zahra-dehghanian",fullName:"Zahra Dehghanian"},{id:"349347",title:"Dr.",name:"Robert",surname:"Henry",slug:"robert-henry",fullName:"Robert Henry"}],corrections:null},{id:"75610",title:"Epidemiology, Genetics and Resistance of Alternaria Blight in Oilseed Brassica",doi:"10.5772/intechopen.96454",slug:"epidemiology-genetics-and-resistance-of-em-alternaria-em-blight-in-oilseed-em-brassica-em-",totalDownloads:300,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Alternaria blight is one of the most deadly diseases of oilseed Brassica. This recalcitrant disease causes up to 50% yield loss across the globe. The disease is mainly caused by Alternaria brassicae and Alternaria brassicicola. These pathogens lack sexual stages and survive as conidia or condiospores on the debris of previous crops and susceptible weeds. Developing resistant oilseed Brassica cultivars to this disease has become a prime concern for researchers over the years. In absence of resistant oilseed Brassica cultivar, identification and introgression of resistance related genes can be a potential source for Alternaria blight resistance. As resistance toward Alternaria blight is governed by polygenes, intercrossing between the tolerant genotypes and subsequent selection will be the most appropriate way to transfer the quantitative resistance. For that reason, future breeding goal should focus on screening of germplasms for selecting genotypes containing resistance genes and structural features that favors resistance, like thick epicuticular wax, biochemical components such as phenols, phytoalexins and lower soluble sugars, reducing sugars and soluble nitrogen. Selected genotypes should be brought under appropriate breeding programs for attaining Alternaria blight resistance.",signatures:"Subroto Das Jyoti, Naima Sultana, Lutful Hassan and Arif Hasan Khan Robin",downloadPdfUrl:"/chapter/pdf-download/75610",previewPdfUrl:"/chapter/pdf-preview/75610",authors:[{id:"322667",title:"Prof.",name:"Arif Hasan Khan",surname:"Robin",slug:"arif-hasan-khan-robin",fullName:"Arif Hasan Khan Robin"},{id:"329291",title:"Prof.",name:"Lutful",surname:"Hassan",slug:"lutful-hassan",fullName:"Lutful Hassan"},{id:"330722",title:"Mr.",name:"Subroto Das",surname:"Jyoti",slug:"subroto-das-jyoti",fullName:"Subroto Das Jyoti"},{id:"342026",title:"Ms.",name:"Naima",surname:"Sultana",slug:"naima-sultana",fullName:"Naima Sultana"}],corrections:null},{id:"75379",title:"Breeding for Disease Resistance in Brassica Vegetables Using DNA Marker Selection",doi:"10.5772/intechopen.96263",slug:"breeding-for-disease-resistance-in-brassica-vegetables-using-dna-marker-selection",totalDownloads:380,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:"The Brassica genus comprises of agro-economically important vegetables. Disease causes great yield loss of Brassica vegetables worldwide. Different traditional methods such as crop rotation and chemical control have limited effect on different diseases of Brassica vegetables and cannot completely eradicate the pathogens by these methods. Development of disease resistant cultivars is one of the most effective, ecofriendly, and cheapest measure to control Brassica diseases. With the development of genomics, molecular biology techniques, and biological methods, it is possible to discover and introduce resistance (R) genes to efficiently control the plant diseases caused by pathogens. Some R genes of major diseases such as Fusarium wilt and clubroot in Brassica vegetables have been already identified. Therefore, we will focus to review the Fusarium wilt and clubroot resistance in Brassica vegetables and the methodologies for identification, mapping, and pyramiding of R genes/quantitative trait loci (QTLs) to develop disease resistant cultivars. These techniques will be helpful for sustainable crop production and to maintain global food security and contribute to ensure protection of food supply in the Asian country as well as throughout the world.",signatures:"Mst Arjina Akter, Hasan Mehraj, Takeru Itabashi, Tomoe Shindo, Masaaki Osaka, Ayasha Akter, Naomi Miyaji, Naoki Chiba, Junji Miyazaki and Ryo Fujimoto",downloadPdfUrl:"/chapter/pdf-download/75379",previewPdfUrl:"/chapter/pdf-preview/75379",authors:[{id:"233726",title:"Dr.",name:"Ryo",surname:"Fujimoto",slug:"ryo-fujimoto",fullName:"Ryo Fujimoto"},{id:"233727",title:"Ms.",name:"Ayasha",surname:"Akter",slug:"ayasha-akter",fullName:"Ayasha Akter"},{id:"345922",title:"Ms.",name:"Mst Arjina",surname:"Akter",slug:"mst-arjina-akter",fullName:"Mst Arjina Akter"},{id:"345923",title:"Dr.",name:"Hasan",surname:"Mehraj",slug:"hasan-mehraj",fullName:"Hasan Mehraj"},{id:"345924",title:"Mr.",name:"Takeru",surname:"Itabashi",slug:"takeru-itabashi",fullName:"Takeru Itabashi"},{id:"345925",title:"Ms.",name:"Tomoe",surname:"Shindo",slug:"tomoe-shindo",fullName:"Tomoe Shindo"},{id:"345926",title:"Mr.",name:"Naoki",surname:"Chiba",slug:"naoki-chiba",fullName:"Naoki Chiba"},{id:"345927",title:"Dr.",name:"Masaaki",surname:"Osaka",slug:"masaaki-osaka",fullName:"Masaaki Osaka"},{id:"345928",title:"Ms.",name:"Naomi",surname:"Miyaji",slug:"naomi-miyaji",fullName:"Naomi Miyaji"},{id:"345929",title:"Dr.",name:"Junji",surname:"Miyazaki",slug:"junji-miyazaki",fullName:"Junji Miyazaki"}],corrections:null},{id:"75968",title:"Brassica-Aphid Interaction: Modulated Challenges and Sustainable Approach for Management",doi:"10.5772/intechopen.96903",slug:"brassica-aphid-interaction-modulated-challenges-and-sustainable-approach-for-management",totalDownloads:324,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Insect pests act as main barrier in enhancing yield potential of Brassica crops. Lipaphis erysimi is considered as one of the most destructive insect species in mustard production due to its voracious type feeding and multiplication. Therefore application of insecticide is inevitable for cultivation of cruciferous crops, although systemic insecticides has been found to be suitable for management of aphid, despite of high cost, residual effect and ecological ramification have necessitated the application of bio and botanical insecticides as novel approach and are recorded significant in research. Aphids having exclusively viviparous parthenogenesis type reproduction from January to March month with the completion of eight generations are helpful in quick mass multiplication. Natural enemies Coccinella spp., Syrphid larvae and bio-pesticide found effective in suppress aphid numbers. Manipulation in sowing dates of mustard crop provides good yield and less incidence of aphid which is proved through research. Lack of environmental resistant varieties has dispensed toward non feasibility of conventional breeding approaches for developing aphid-resistant Brassica. Although application of genetic engineering plan has resulted in moderate success in development of aphid resistance, so far commercialization of such genetically modified crops has not conceivable, intimate the necessity of further insights in to host plant and aphid communication to form effective approach against aphid resistance. Therefore in this chapter the components involved in Brassica aphid communication are highlighted and present statuses and problem in aphid management are discussed.",signatures:"S.A. Dwivedi, Lelika Nameirakpam and Ajay Tomer",downloadPdfUrl:"/chapter/pdf-download/75968",previewPdfUrl:"/chapter/pdf-preview/75968",authors:[{id:"330948",title:"Dr.",name:"S.A.",surname:"Dwivedi",slug:"s.a.-dwivedi",fullName:"S.A. 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Imagine that in a ward or in an acute care unit, a patient develops a sudden and severe laryngeal edema and stops breathing for obstruction of the respiratory tract. Nurse and medical staff starts‐up advanced life support (ALS) maneuvers. The primary and emerging interventions are to permeabilize the airway accessing the trachea through an endotracheal tube. Not being possible to access it by the usual routes, the only solution is to perform a tracheotomy or cricothyrotomy, using a tracheotomy surgical tray (TST) or an emergency cricothyrotomy kit (ECK). However, the health team most of the times do not know its existence, location, or has difficulties in accessing it in due time, what could have as consequence the loss of a life.
\nPortuguese Directorate‐General of Health (DGS) points out on the Circular Normative no. 15/ DQS/DQCO of 22/06/2010 [1] that “patients who are admitted in hospitals believe that they are being admitted to a safe environment. They feel confident that if their clinical condition gets worse, they are in the best place for a prompt and effective intervention. However, there is some evidence that this does not always happen” (p. 1). This Circular also states, “ALL inpatient areas should have easy and immediate access to equipment, supplies and emergency drugs. They should be organized and stored in a standardized way… throughout the health unit” (p.6). However, compliance with these recommendations depends, above all, on political and management decisions of legislators, regulators, managers, and industry providers, and it is at the health institutions jurisdiction to “adequate resources and create the structures that leads to quality professional practice” [2]. For the Portuguese Republic Government (Governo da República Portuguesa—GRP) is “fundamental, that the available resources are better used, avoiding waste, that is, improving management, transparency, and accountability for the use of money from the citizens” [3]. Corvi [4] draws attention to the “waste epidemic in health care,” as acknowledge by the GRP, and so a great opportunity to improve, being fundamental a spirit of continuous learning as part of “implementing a lean management system” [4].
\nThe Intensive Care Society [5] recommends “all critical care areas should have their own, appropriately stocked and checked difficult airway trolley to deal with airway and tracheostomy emergencies” (p.11). The absence or inaccessibility to this kind of equipment can lead to adverse events with huge impact on the safety and lives of patients, mainly the critical ones. To the matter of the impact of layout configurations in hospital environment, Soriano‐Meier et al. [6] points out that “inadequate facility layout negatively affects the performance of the service staff, the quality of care provision and the service temporally over time” (p. 255).
\nAt a particular neurosurgery high dependency unit (NHDU) of a central hospital in Lisbon, problems related to design, layout, architectural barriers, accessibility to life support equipment (LSE) and wastes of time, handling, and transport were identified. Those that may infer greater impact on patients and on the provision of care taken by nurses are as follows: (a) accessibility to LSE, (b) difficulty/inexperience in the use of the resuscitation trolley (RT), and (c) lack of knowledge of ECK and TST existence and location. This chapter summarizes the action research study embarked with the purpose of testing the application of Lean methodologies at NHDU for a quality and safety provision of care to acute neuropatients and to reduce at least by half, time, steps, and distance travelled by nurses’ accessing LSE. Gemba walk, value stream mapping, spaghetti diagrams, 5S, and JIT (just‐in‐time) were the main Lean methodologies used.
\nGemba is the Japanese term used for Shop floor, where products are produced, or where the services are provided [7, 8]. To start an improvement project, it is critical to analyze the current and real situation of an organization or its workplace. Therefore, the gemba should analyze processes, time of setups, physical layout and surroundings with an open mind, to detect where, how, and why clients and staff experience problems [7–9].
\nThe value stream mapping (VSM) is one of the main lean methodologies that engages waste elimination in any organization [10]. VSM will help to identify and analyze, for example, problems experienced by stakeholders, errors in medicine, flow of processes and work, financial analysis, among others. VSM allows checking (visual and graphically) the current state of a particular procedure, its productive time (value‐added), and the non‐productive time (non‐value‐added) [11].
\nJackson [12] argues that 5S is the foundation of the Toyota production system (TPS). What this methodology tries to ensure is an orderly organized workspace for an efficient and safe work environment [10], increased productivity, fewer errors, and less waste [8]. 5S represents the five levels of this methodology starting with the letter “S”. In Japanese vocabulary: SEIRI (sort), SEITON (set in order), SEISO (shine), SEIKETSU (standardize), and SHITSUKE (sustain). Smart [13] summarizes this methodology with the expression “a place for everything and everything in its place” (p. 62).
\nJIT is a production process that targets the optimization of the process as a whole in a continuous flow improvement and tries to answer to the organization or service needs. Briefly, it means producing no sooner, no later, neither more or less, only and just the necessary [8, 10].
\nAnother Lean methodology is the spaghetti diagram. This diagram consists on a graphic reproduction of the architectural floor plan of a structure, where you draw lines from one space to another, representing the path taken by employees, customers, and objects along a particular process (round trip) [12, 14]. It allows documenting and visualizing the physical flow, in order to identify waste motion or transportation, architectural barriers, and improvement opportunities to expedite process flow [15].
\nThis chapter is organized as follows: Following the introduction, a literature review on Lean philosophy is performed, then the methodology used in the research, and the results of the action research are described. Finally, some discussion and conclusions are drawn.
\nIt was through Krafcik [16] that the Lean term was released thus referring to the TPS as a lean production system: A system that uses less resources compared to the mass production systems. Less effort, less capital investment, less space, and less time [17]. The Lean philosophy is essentially focused on waste reduction as a means to increase actual value‐added, in order to fulfill customer needs and maintain profitability [17]. The fundamental focuses of Lean are respect for people, teamwork, waste elimination, continuous improvement, value, quality, and safety [8, 16–18]. Several authors have highlighted this and other key principles of Lean philosophy, such as follows: (i) customer relationship [19]; (ii) total quality management (TQM) [20]; (iii) JIT [21, 22]; (iv) pull production/flow [19, 20]; (v) supplier relationships/long‐term business relationship [21]; (vi) mistake‐proofing [23]; (vii) total productive maintenance (TPM) [22]; and (viii) physical layout [6]. At the operational level, the Lean paradigm is implemented using a number of techniques such as kanban, 5S, visual control, takt‐time, poke‐yoke, and single minute exchange of die (SMED) [24].
\nTo Imai [8], the importance of applying a Lean philosophy in an organization has at least three components: (1) any activity or process that does not add value is waste, independently of being practiced by people or machines; (2) the reduction or elimination of waste may be the most cost‐effective way for improving productivity and reduce operating costs instead of increasing investment in the hope of adding value. Moreover, investing in new equipment is expensive while eliminating waste, in most cases, has no costs. (3) Standardization of processes ensures quality and error prevention. Womack et al. [17] documented the benefits of Lean philosophy compared to the mass production model, arguing that this philosophy would succeed, not only in the automotive industry or aviation, but also in all activities from distribution, retail, and healthcare. Not being the solution to all the problems that health services faces today, the Lean philosophy can bring significant benefits to this sector and in a range of hospital areas [25], contributing to develop the continuous improvement into the organizational culture and improving quality of care, efficiency and effectiveness, while reducing costs, errors, and waste.
\nIn the Portuguese healthcare sector, the implementation of Lean philosophy has been focused on some specific areas such as quality [26, 27] logistics, supply and storage [28–30], agility and continuous process improvement [31–33], workplace reorganization [34], and reducing waiting times [35, 36]. Particularly in services such as community health centers [37], operating room, imaging, ophthalmology, outpatient, ward, pharmacy, and warehouse. Other studies focused on conducting systematic reviews [38, 39]. There is thus a research gap in applying the Lean philosophy to inhospital medical emergency, especially in inpatient critical care services.
\nThe methodology used in this study was an action research, supported by a longitudinal mixed method approach with a one‐group within‐subjects pretest‐posttest experimental type design.
\nLewin [40] suggests the existence of a cycle in action research. It begins with the diagnosis and identification of the problem(s) with all participants in a democratic way and then follows the proposal, planning interventions, and actions of change. Subsequently, the impact of the changes is monitored, the data collected, analyzed, interpreted, and finally results are reported. This is a flexible research methodology that integrates an exploratory action in order to investigate and support the implementation of changes according to the diagnosis raised [41]. Action research claims that the researcher participates in the change process since the changes suggested are implemented by himself, that is, he “take action to improve the practice and study … the effects of the action taken” [42]. Yin [43] considers this methodology as a variant of qualitative research that emphasizes the researcher action role and his active collaboration with the research participants.
\nThe research was performed at a level 2 patient care four‐bedded NHDU. This unit shares human resources, equipment, and materials with the 44‐bedded standard care neurosurgery and neurotraumatology wards. NHDU is a healthcare facility specialized in the care of neuropatients undergoing neurological, hemodynamic, and respiratory instability with the eventual need of non‐invasive or invasive ventilatory support by tracheotomy. These patients require critical care nursing and permanent vigilance that, although not requiring intensive care, may potential and quickly evolve to a severe status and thus the need of an immediate intervention. Nurse:patient ratio is 1:4. Located in one of an 802‐bedded triple hospital centre at the metropolitan area of Lisbon (Portugal), this centre serves about a million people population. Data available from 2013 institutional performance reports show a surgical movement of 1423 neurosurgeries and a bed occupancy rate of 87.7% and 91.4% at the neurotrauma and neurosurgery wards, respectively.
\nThe research was authorized by the NHDU Medical Director, the NHDU Chief Nurse, and the Ethics for Health Committee of the hospital centre. The unit of analysis is the NHDU with the corresponding nurse team. A convenience sampling was used attending to nurses’ availability during the period that took place the visit of the researcher. The two nurses of the management team (chief and coordinator) were excluded from this sample since the purpose was to simulate the performance of the direct care nurses. Thus, from a population of 20 nurses, a sample of 12 nurses (60%) was selected. This is a longitudinal research in which data were collected from two points in time, which allowed studying the changes that have occurred during the period in which it was conducted (November 2014 to January 2015).
\nThe research design follows several phases. The main three phases were (1) pre‐intervention, (2) intervention, and (3) post‐intervention, in which a simultaneous mixed method approach (qualitative and quantitative) was applied. The pre‐intervention phase was further divided into three sub‐phases: (i) diagnostic assessment (qualitative approach), (ii) simulation (quantitative approach), and (iii) proposal of changes (qualitative approach). The intervention phase consisted on the application of 5S and JIT lean methodologies. The post‐intervention phase was divided into two qualitative approaches: (i) simulation and (ii) unstructured interview.
\nThe pre‐intervention diagnostic assessment sub‐phase involved the following activities: (a) direct observation of the physical space performed by the participant researcher (PR) which focused mainly on the layout of the NHDU and the location of existing materials and equipment. To support the gemba walk, pictures and paper record with graphical representation of the service plan were used to complement the visual management and spaghetti diagram. The transition to digital record was made using Microsoft® Office® 2013 software. (b) Personal unstructured interviews performed by the PR to the nurse team, and questionnaires to identify the difficulties and constraints of nurses in their professional daily routines, especially in emergency situations. The questionnaires were anonymous and blind in order to guarantee their confidentiality. The participants returned them in a sealed envelope deposited at a container left in the nursing room. The analysis of questionnaires and interviews was performed using qualitative content analysis, and it was organized according to the research variables, the types of wastes considered by the Lean philosophy and the suggestions of change by the participants.
\nThe pre‐intervention simulation sub‐phase was accomplished by measuring time, distance, and number of steps (dependent variables) undertaken by nurses in the access to LSE (RT, ECK, TST, and automated infusion systems (AIS)). The simulation context was used because during the research it was not possible to monitor the tasks developed by nurses in a real context. As measuring instruments, the Nokia® 6230 mobile phone chronometer was used to monitor timing performance in seconds, rounded to the unit. Sixty meters’ tape Stanley PowerWinder® was used to measure the distance travelled by nurses, with data rounded to the first decimal place. The PR counted the number of steps, and the data were triangulated with the participant itself. The monitoring was performed from the point of departure (nurses’ station), arrival to LSE and return to the starting point with the respective LSE.
\nThe third pre‐intervention sub‐phase was completed by the suggestion of changes presented, as a proposal like determined by Lewin [40], to the Medical Director and Chief Nurse of NHDU.
\nThe intervention phase consisted on the application of lean 5S and JIT methodologies for the reorganization of physical space, equipment location, and NHDU inventory. The tasks performed by the researcher in this phase consisted on the organization of the contents in the NHDU large cabinet, relocation, and availability of TST and AIS. The reorganization of RT, ECK, and NHDU small cabinets was performed with the help of the nurses’ management and direct care team. Other human resources such as nurses’ aides and the hospital carpentry services were involved to perform small changes and to construct small furniture. Stock boxes abandoned in the hospital storage were recycled and used for better storage and visual management of cabinet contents.
\nThe post‐intervention phase was divided into two sub‐phases: (i) simulations, using the same methodology and equipments applied in the pre‐intervention. (ii) Unstructured interviews, using the same methodology as in the pre‐intervention to collect the opinion of nurses regarding the interventions made to the unit, and how this influenced their daily routines and professional practice.
\nThe quantitative results are presented comparing the pre‐intervention with the post‐intervention phases, allowing a more direct comparison of the data. The IBM SPSS Statistics version 21 and Microsoft® Office® 2013 Excel version 15 software were used for the statistical analysis of data. For the statistical hypothesis tests, the parametric Student’s t‐test with a significance level of 0.025 (one‐sided) was used, such as the nonparametric Wilcoxon W‐test with the exact significance of 0.025 (one‐sided) for the poorly distributed data situations [44]. Standardized response mean, calculated through MedCalc Statistical Software version 15.2.2, was used to analyze the effect size (Cohen’s d) of the intervention made by the application of Lean methodologies, representing the independent variable. The qualitative results are summarized in tables with transcription of the nurses opinions collected from the interviews and the summary of the answers given by them in the questionnaires. Spaghetti diagrams and photographs are also used for better contextualization.
\nAttending to the literature review and the pre‐intervention phase the following hypotheses are formulated:\n
H01: The difference of TST time of access between pre‐ and post‐intervention equals zero.
H02: The difference of TST distance of access travelled between pre‐ and post‐intervention equals zero.
H03: The difference of TST number of steps of access between pre‐ and post‐intervention equals zero.
H04: The difference of AIS time of access between pre‐ and post‐intervention equals zero.
H05: The difference of AIS distance of access travelled between pre‐ and post‐intervention equals zero.
H06: The difference of AIS number of steps of access between pre‐ and post‐intervention equals zero.
Throughout Gemba Walk, twelve unstructured interviews were carried out to nurses in order to identify their difficulties in their professional daily routines and what kind of improvements they would like to implement in NHDU (Table 1). The collected data focused mainly on the inadequate layout and location of equipment, poor organization of clinical material in NHDU cabinets and units of patients, obstacles, restricted circulation and workspaces, frequent journeys out of NHDU to supply missing materials and equipment, and difficulty in implementing improvements because of a great resistance to change. According to these interviews only 50% of nurses knew the existence and location of TST, and only 33.3% of nurses knew the ECK existence or location. For AIS and RT, all participants were aware of them. After Lean methodologies’ intervention and education, 100% of the participants were aware of all life support equipment.
\nIn addition to the interviews, questionnaires were delivered to 12 nurses and eight were returned, representing a 67% response rate. The purpose of the questionnaire was to identify the set of difficulties felt by nurses in their daily professional life in NHDU, mainly in emergencies, monitoring and surveillance of the acute neurosurgical patient. The questionnaire made also possible to study the kind of wastes (according to Lean philosophy) the nurses identify. The collected data from questionnaires are summarized in Table 2 that includes suggestions provided by the respondents.
\nA | \n“My greatest difficulty in NHDU is to always have to go out of the unit to look for supplies …either because we do not have a specific location for them either it was not replaced… Medication and serums, forget it…” | \n
B | \n“We should have an adequate level of stocks according to our needs and not have to always go ‘out there’ seek for supplies.” | \n
C | \n“The NHDU should be independent from all resources of Neurosurgery… Nurses and nurses’ aides should be dedicated to NHDU… Stock, equipment and supplies should be replenished regularly and directly by the supply and pharmacy services.” | \n
D | \n“The vital signs monitors should be fixed to the wall for not taking up space in patients’ desk . . . and because sometimes they drop of the desk, usually when pulled by confused patients.” | \n
E | \n“It’s hard to work when there is not enough space to move around the patient bed without going against curtains, literally upon us, against wheelchairs and other patient’s beds.” | \n
F | \n“There is neither space nor conditions to lift patients to an armchair or wheelchair.” | \n
G | \n“Patients from one bed can touch and reach things of next patients because everything is so tight and so close to each other… Patients are potentially contaminating each other … and we ourselves have a hard time for this cross‐contamination doesn’t happen, I am sure it does eventually happen. “ | \n
H | \n“We have no space to put a RT next to the patient’s units … it is impossible to make secure ALS with the available space that we have.” | \n
I | \n“We usually are trained in basic life support every year, but we should also be trained in the use of RT and ALS… I have some difficulties in perceiving the location of clinical materials in the RT because there is a bad visual perception of it.” | \n
J | \n“I have little practice in the use of the RT, mainly the defibrillator… We should have training…” | \n
K | \n“Practices adopted in NHDU goes against scientific evidences … but it is difficult here to make whatever change we need … some people do not understand what good practices are.” | \n
L | \n“The NHDU has a lack of identity and autonomy.” | \n
M | \n“There is a lack of standards for admittance and clearance of patients… Even the doctors and some nurses do not understand that we only have capacity for 4 patients” | \n
N | \n“We cannot take any initiative to improve anything, because they fear us to take their place.” | \n
O | \n“They never listen to us. They do not realize, or understand, the staff who are working with them. We could make a great contribution to the better functioning of the unit.” | \n
P | \n“There is a huge resistance to change… There is a fear of loss or prestige transfer.” | \n
Excerpts from interviews.
Data Collected from Questionnaires.
According to the previous results and analysis of the interviews, questionnaires, spaghetti diagrams, value stream mapping (data not shown), and simulations, a set of suggestions were proposed by the PR to the Medical Director and Chief Nurse of NHDU (third pre‐intervention sub‐phase). This proposal was drawn up from the data collected attending to the Lean philosophy, the recommendations of best practices, and the standards of Portuguese regulatory institutions. The proposal considers several suggestions for amendments procedures, layout updates of the physical space, RT and NHDU cabinets content, and different locations of the clinical material and equipment. Briefly, these suggestions were the following:
\n\nPlace suction probes supports on the wall at each bed side (accepted);
Place water bottles supports to ensure suction tubes washing after manipulation (accepted);
Place mobile IV pole with AIS mounted at each bed side (accepted);
Remove vital signs monitors from patients’ desks and fixate them on the wall (accepted);
ALS and RT handling workshops for nurse training and education (accepted);
RT standardization (accepted);
Place TST at NHDU next to nurse station (accepted);
Reorganization of NHDU cabinets to improve contents access, variety, and identification (accepted);
Place drug vault at NHDU (rejected);
Place double air and oxygen pressure regulators at each patient unit (rejected);
Place manual ventilator at each unit in the presence of tracheotomized patient (rejected);
Organize trolley with clinical material for isolation room (rejected);
Eliminate one of the beds to increase circulation space (rejected).
After approval, or disapproval, of each suggestion, Lean methodologies (5S, JIT) were undertaken to ensure a better and safer work environment for patients and staff. The cabinets were reorganized into categories to cover the various patients’ needs like breathing, elimination, circulation, and administration, dressings and skin integrity, feeding, individual protection equipment. Sliding frosted glasses were removed from the cabinets, and it was possible to reduce and optimize the occupied space without decreasing the amount of material, but rather increasing its variety and availability, as seen in Figure 1 that also illustrates the post‐intervention TST location. The patients’ units were likewise reorganized with the inclusion of supports for suction probes, water bottles, and AIS (in mobile IV poles). Vital signs monitors were placed at a new shelve on each patient’s unit and ALS, and RT workshops has been schedule for nurse training and education.
\nSupplies in NHDU large cabinet before and after Lean intervention.
Spaghetti diagram for TST access before and after Lean intervention.
The presence of tracheotomized patients or at risk of being tracheotomized in NHDU is constant; therefore, the availability and accessibility to LSE, particularly ECK and TST, are of extreme importance. In the pre‐intervention phase, TST was in the treatment room of neurosurgery, about 63 m (round trip) far from NHDU nurse station. Changing its location into the large cabinet inside NHDU the distance decreased to 6 m (round trip) from the nurse station. Figure 2 represents the spaghetti diagram made before and after Lean intervention for the TST.
\nTable 3 shows the quantitative results obtained from the simulations of TST accessibility before and after Lean intervention. Data show the reduction of waste in time (−87.35%), distance (−90.47%), and steps (−87.12%) achieved with the application of Lean methodologies. According to Cohen’s d, the effect size is large. Shapiro‐Wilk normality test (data not shown) rejected the normality of the distance distribution (p < 0.001). So, for a one‐sided significance level of 0.025, were accepted the alternative hypothesis that time (p = 0.0017), number of steps (p = 0.000015) and distance (p = 0.016) were statistical and significantly lower after the application of Lean methodologies.
\n\n | \n | Time | \nDistance | \nSteps | \n|||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
\n | \n | A | \nB | \n∆ | \n∆% | \nA | \nB | \n∆ | \n∆% | \nA | \nB | \n∆ | \n∆% | \n
\n | \n | Collective | \n\n | Paired | \n\n | Collective | \n\n | Paired | \n\n | Collective | \n\n | Paired | \n\n |
Collective and paired data | \nM | \n45.5 | \n4.58 | \n−40.5 | \n−87.35 | \n64.03 | \n6 | \n−58.03 | \n−90.62 | \n60.17 | \n7.5 | \n−52.5 | \n−87.12 | \n
\n | Mdn | \n39.5 | \n5 | \n−34 | \n−86.1 | \n63 | \n6 | \n−57 | \n−90.47 | \n60.05 | \n8 | \n−52.5 | \n−87.32 | \n
\n | SD | \n18.87 | \n0.79 | \n19.07 | \n5.08 | \n2.43 | \n0 | \n2.43 | \n0.34 | \n9.75 | \n0.91 | \n9.05 | \n1.71 | \n
\n | Max | \n76 | \n6 | \n−71 | \n−93.42 | \n69 | \n6 | \n−63 | \n−91.3 | \n70 | \n9 | \n−62 | \n−89.09 | \n
\n | Min | \n26 | \n3 | \n−21 | \n−80.77 | \n63 | \n6 | \n−57 | \n−90.48 | \n45 | \n6 | \n−38 | \n−84.44 | \n
\n | Range | \n50 | \n3 | \n−50 | \n−12.65 | \n3 | \n0 | \n6 | \n−0.82 | \n25 | \n3 | \n−24 | \n−4.65 | \n
t-test | \n\n | 95% CI | \n\n | \n | [−60.52; −20.48] | \n\n | \n | \n | \n | \n | \n | \n | [−61.99; −43] | \n
\n | \n | \n | t (df) | \n\n | −5.2 (5) | \n\n | \n | \n | \n | \n | \n | \n | −14.21 (5) | \n
\n | \n | \n | pa | \n\n | 0.0017 | \n\n | \n | \n | \n | \n | \n | \n | 0.000015 | \n
Wb‐test | \nZ | \n\n | \n | \n | \n | \n | \n | −2.264 | \n\n | \n | \n | \n | \n |
\n | pa | \n\n | \n | \n | \n | \n | \n | 0.016 | \n\n | \n | \n | \n | \n |
Effect size | \nCohen’s d | \n\n | \n | \n | −2.12 | \n\n | \n | −23.84 | \n\n | \n | \n | \n | −5.8 | \n
Results from TST accessibility.
A: Pre‐intervention (n = 6). B: Post‐intervention (n = 12).
aOne‐sided 0.025 significance.
bW‐test with exact significance.
Although the ECK is correctly located in the RT, 66.7% (n = 8) of nurses were unaware of its existence or location. For ethical reasons, there was an imperative and urgent need to educate them, which was done by the PR to all nurses’ team. In order to identify the difficulties of nurses in using the RT, simulations were performed. These simulations consisted in locating and accessing all RT contents, especially ECK. Through direct observation, it was found that all 12 nurses had some difficulties such as follows: safety seal breakage; retraction of safety latch; removal of back board; opening drawers by poor perception of the handle; finding and identifying critical medications and supplies; swing arm handling; and use of equipment including heart defibrillator. After the simulations, nurses justified their difficulties as a result of little practice and/or experience. An ALS and RT handling workshop intervention were scheduled to nurse’s continuous education plan.
\nIn the pre‐intervention phase, the AIS were in a storeroom forcing nurses to a constant movement and transportation of about 84 m (round trip). Lean 5S and JIT methodologies determined changing AIS location into a mobile IV pole next to the patients’ unit, permanently connected to electricity in order to ensure its permanent availability (Figures 3 and 4).
\nAIS location before and after Lean intervention.
Spaghetti diagram for AIS access before and after Lean intervention.
\n | Time | \nDistance | \nSteps | \n||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
\n | A | \nB | \nA | \nB | \nA | \nB | \n|||||||
\n | Collective | \nPaired | \nCollective | \nPaired | \nCollective | \nPaired | \n|||||||
Collective and paired data | \nM | \n79.5 | \n3 | \n−76.5 | \n−96.27 | \n83.6 | \n3 | \n−80.6 | \n−96.41 | \n107 | \n4.5 | \n−102.5 | \n−95.83 | \n
Mdn | \n78.5 | \n3 | \n−76 | \n−96.29 | \n83.6 | \n3 | \n−80.6 | \n−96.41 | \n104 | \n4.5 | \n−99 | \n−95.84 | \n|
SD | \n8.13 | \n0.95 | \n7.44 | \n0.91 | \n0 | \n0 | \n0 | \n0 | \n9.72 | \n1.17 | \n8.85 | \n0.85 | \n|
Max | \n92 | \n5 | \n−87 | \n−97.40 | \n83.6 | \n3 | \n−80.6 | \n−96.41 | \n130 | \n6 | \n−124 | \n−97.00 | \n|
Min | \n65 | \n2 | \n−63 | \n−94.57 | \n83.6 | \n3 | \n−80.6 | \n−96.41 | \n97 | \n3 | \n−94 | \n−94.55 | \n|
Range | \n27 | \n3 | \n−24 | \n−2.83 | \n0 | \n0 | \n0 | \n−0 | \n33 | \n3 | \n−30 | \n−2.45 | \n|
95% CI | \n\n | \n | [−81.23, −71.77] | \n\n | \n | \n | \n | \n | \n | \n | \n | \n | |
\n | t (df) | \n\n | \n | −35.62 (11) | \n\n | \n | \n | \n | \n | \n | \n | \n | \n |
\n | pa | \n\n | \n | 5.64×10−13 | \n\n | \n | \n | \n | \n | \n | \n | \n | \n |
W b‐test | \nZ | \n\n | \n | \n | \n | \n | \n | −3.46 | \n\n | \n | \n | −3.06 | \n\n |
\n | pa | \n\n | \n | \n | \n | \n | \n | 0.00024 | \n\n | \n | \n | 0.00024 | \n\n |
Effect size | \nCohen’s d | \n\n | \n | −10.28 | \n\n | \n | \n | −5×1015 | \n\n | \n | \n | −11.58 | \n\n |
Results from AIS accessibility.
A: Pre‐intervention (
aOne‐sided 0.025 significance.
b
After the intervention and application of Lean methodologies, the AIS mean access was 96.27% in time, 95.83% in steps, and 96.41% in distance lower than in the pre‐intervention. The effect size is large (or very large) with d = −10.28 for time, d = −11.58 to number of steps, and d = −5×1015 to distance. For the hypothesis test, the Shapiro‐Wilk normality test rejected the normality of steps (p = 0.039) and distance (this one constant) distribution. So, for a one‐sided significance level of 0.025, were accepted the alternative hypothesis that time (p = 5.64×10−13), number of steps (p = 0.00024) and distance (p = 0.00024) were statistical and significantly lower after Lean methodologies application, as shown in Table 4.
\n\nThe results of quantitative data associated to the hypothesis test, the size effect, and the improvements in accessibility to TST and AIS are summarized in Table 5.
\n\nHypotheses | \nStatistical test | \nSize effect | \nPercentage variation (decrease) | \nPercentage variation (improvement) | \n|
---|---|---|---|---|---|
H01: The difference of TST time of access between pre and post‐ intervention equals zero. | \nPaired samples | \n0.0017 | \n−2.12 | \n−87.35% | \n837.22% | \n
H02: The difference of TST distance of access travelled between pre and post‐intervention equals zero. | \nPaired samples | \n0.016 | \n−23.84 | \n−90.47% | \n950% | \n
H03: The difference of TST number of steps of access between pre and post‐intervention equals zero. | \nPaired samples | \n0.0000151 | \n−5.8 | \n−87.12% | \n687.46% | \n
H04: The difference of AIS time of access between pre and post‐ intervention equals zero. | \nPaired samples | \n5.64×10−13 | \n−10.28 | \n−96.27% | \n2733.8% | \n
H05: The difference of AIS distance of access travelled between pre and post‐intervention equals zero. | \nPaired samples | \n0.00024 | \n−5×1015 | \n−96.41% | \n2686.7% | \n
H06: The difference of AIS number of steps of access between pre and post‐intervention equals zero. | \nPaired samples | \n0.00024 | \n−11.58 | \n−95.84% | \n2310% | \n
Summary results from quantitative data.
aα = 0.025 one‐sided.
After all the action research phases performed, it was demonstrated that the application of Lean methodologies contributes for improving the accessibility to equipment and material that are essential to nurses’ safe practice. With the application of the Lean methodologies, it is possible to provide optimized care to acute neurosurgical patients, in emergency and life support situations. Lean methodologies such as Gemba walk and spaghetti diagram made possible to identify wastes and difficulties in LSE accessibility, organization, and provision of other clinical equipment and supplies, and security issues such as potential cross‐contamination provoked by exiguous work areas and architectural barriers. 5S and JIT philosophies together with interviews and questionnaires led to the development of a grounded interventional proposal for a functional and organizational harmonization of NHDU. Each suggestion on the proposal was then analyzed by medical and nurse unit managers giving deferral or refusal to certain interventions. The implementation of 5S and JIT methodologies led to the reorganization of NHDU and the allocation of the equipment closer to patients and nurses as well as to the decrease of waste, non‐value‐added activities and to significant improvements. These same results are argued in Carvalho et al. [45] since they defend that the layout must “reflect the need to reduce the time spent traveling” (p. 291) since “time ‘lost’ in travel between the various services… represents a cost to the organization in question, and that, in most cases, is not noticed or accounted for” (p. 291). For example, a nurse who searches for drugs, supplies, and equipment are doing it to serve the needs of patients, but may not notice that it can result in a waste of time, transport, handling, and human potential. But according to the Institute for Healthcare Improvement [46], if these materials were readily available when, how, and where they are needed (JIT), the time that nurses wasted looking for them would be instantly devoted to other more appropriate and critical tasks.
\nThrough action research and the application of Lean methodologies, nurses of NHDU actually take only 10% of time, 9.37% of the distance travelled and 12.46% of the steps spent accessing TST compared to pre‐intervention. The results of the intervention in AIS showed an improvement even more significant since the post‐intervention access time is just 3.77% of pre‐intervention time, the distance just 3.59%, and the number of steps only 4.21% compared to pre‐intervention. To achieve this, nurses were educated about the location of LSE, and the need for training these nurses in ALS and RT handling was identified. Wastes and barriers that conditioned rapid access and action to acute patients were identified, reduced, or removed. Time, steps, and distance travelled accessing LSE were shortened and reduced more than half (−87.12 to −96.41%).
\nThe same results were reached in other researches. Virginia Mason Medical Center (VMMC), in Seattle (USA), is credited to be one of the pioneers in healthcare industry to implement Lean by applying their own Virginia Mason Production System (based on TPS) [47]. Since 2001 VMMC makes efforts with the reorganization of spaces and workflows, minimizing transportation, and handling wastes, where all clinical equipment and supplies essential to care are placed in the point‐of‐use in UK Hereford Hospital, Lean methodologies led also to reductions of delay in nurses’ response time between 40 and 93% [48]. In Scotland, from a sample of 19 critical care units, nurses available time increased from 35 to 64%, in which 32% of these units reached changes greater than 100%, supported by the program Releasing Time to Care: The Productive Ward, based on Lean and six sigma methodology [49].
\nIn this study, there is a significant and serious lack of nurses’ knowledge on the existence and location of LSE. Intervention trough education, awareness, and change of its location resulted in an improvement of 100% to TST and 200% to ECK leading to health benefits for patient’s safety and quality of care. Still on the ECK and the RT, the simulation demonstrated the difficulties experienced by nurses in the use of the RT, particularly in opening it, use of drawers, location, and rapid visualization of contents. It was retrieved from this analysis that the imperative and urgent need for nurse’s professional training and the need for a clearly defined intervention criteria in emergency situations. This is in line with Silich et al. [50] that also highlights that informed and trained professionals provide better care with potential reduction of adverse events, bad practices, and less waste of resources.
\nCatchpole [51] argues that the undesirable effects of an inadequate working environment can result in fatigue, frustration, reduced performance, and human capacity, increased risk, and adverse events. Hence, the importance that health facility managers have and the impact of their decisions on patients and staff, and “usually, it is the intermediate and elementary level manager, involved in everyday decisions, that affect the care that is actually provided to patients” [52].
\nThis research was intended to interfere in the reality studied by solving identified problems in an effective and participatory manner (through action), not only explain it or proposing a problem solution. The impact for practice and health services (quality indicators, safety, and satisfaction) of the Lean interventions carried out by the PR is well grounded by the results. In this research, it was verified that 66.7% of nurses were unaware of the existence or location of ECK and 50% of the TST. The education intervention resulted in an improvement of knowledge of 100% in the TST and 200% in the ECK, leading to potentially high health gains for the patient, because trained professionals provide better care with fewer mistakes. Furthermore, this research identified needs for periodic training and education on ALS and RT practice. Through Lean methodologies such as 5S, JIT, and spaghetti diagrams, it was possible to decrease time, steps, and distance travelled by nurses accessing TST and AIS between 87.12% and 96.41% and to improve this accessibility between 687.46% and 2733.8%.
\nThese results confirm the contribution of this research to address the need of this healthcare unit to improve the care of neurosurgical acute/critically ill patients. The implementation of Lean 5S and just‐in‐time methodologies led to the reorganization of NHDU environment by allocating LSE closer to patients and nurses station, contributing by this way for improving the security and responsiveness of nurses’ team for having more knowledge and quick access to LSE. In addition, it contributes to overcoming emergency, life support situations, and day‐to‐day professional life action to the needs of patients, freeing up time and availability of nurses for direct care by a work environment with less waste of time, distance, steps, handling, and setup procedures.
\nAlthough not focused in this research, for the unit and hospital management, there are potential economic and financial benefits attained from the application of Lean methodologies through the following factors: hand labor and human capital gains by reducing the time required to perform certain tasks (setup time); reduction of the “snowball” effect that leads to the accumulation of everyday work; reprocessing gains from potential reduction of costs in time of hospital internment and patient morbidity.
\nBesides the advantages reached with the application of the lean methodologies the research findings, however, are tempered by several shortcomings such as the unavailability of participants to collaborate with the research and resistance to change. Financial impact of the intervention was not recorded. Moreover, the results cannot be generalized; other realities can compare them and encounter similar situations that may benefit with the application of Lean methodologies in an attempt to overcome their problems.
\nIt is expected that health professionals, especially their leaders and managers, can take some lessons from the different approaches adopted in this research and may act as a catalyst for future positive changes in all health services.
\nAs a suggestion for future research it would be interesting to study the financial impact (time saved vs. value/hour) of the application of these lean methodologies, the impact on the quality of nurses daily professional life (satisfaction, fatigue, stress, burnout) and on emergency scenarios (LSE accessibility/availability vs. morbidity and mortality).
\nChronic myeloproliferative disorders are a group of clonal diseases of the stem cell. It is a group of several diseases with some common features. They derive from a multipotential hematopoietic stem cell. A clone of neoplastic cells in all these neoplams is characterized by a lower proliferative activity than that of acute myeloproliferative diseases. In each of these diseases, leukocytosis, thrombocythemia, and polyglobulia may appear at some stage, depending on the diagnosis [1, 2].
The research on interferon has been going on since the 1950s [3]. Then, the attention was paid to its influence on the immune system. It has been noted that it can exert an antiproliferative effect by stimulating cells of the immune system [4]. In 1987, a publication by Ludwig et al. was published, which reported the effectiveness of interferon alpha in the treatment of chronic myeloproliferative disorders [5].
More and more new studies have been showing the effectiveness of interferon alpha in reducing the number of platelets, reducing the need for phlebotomies in patients with polycythemia vera and also in reducing the number of leukocytes. Moreover, interferon reduced the symptoms of myeloproliferative disorders such as redness and itching of the skin. Additionally, it turned out to be effective in reducing the size of the spleen.
Further studies on the assessment of remission using molecular-level response assessments indicate that the interferon action in chronic myeloproliferation diseases targets cells from the mutant clone with no effect on normal bone marrow cells [6].
Over the years, interferon alpha-2a and interferon alpha-2b have been introduced into the treatment of chronic myeloproliferation, followed by their pegylated forms. The introduction of pegylated forms allowed for a reduction in the number of side effects and less frequent administration of the drug to patients. In recent years, monopegylated interferon alpha-2b has been used to further increase the interval between drug administrations while maintaining its antiproliferative efficacy.
The exact mechanism of action of interferon alpha in the treatment of chronic myeloproliferative disease is still not fully understood, but it has an impact on JAK2 (Janus Kinase) signal transducers and activates the STAT signal pathway (Janus Kinase/SignalTransducer and Activator of Transcription).
Interferon alpha binds to IFNAR1 and IFNAR2c, which are type I interferon receptors. Interferon alpha has an impact on JAK2(Janus Kinase) signal transducers and activates the STAT signal pathway. The disturbances in this signaling pathway are observed in chronic myeloproliferative disorders [7].
Interferon inhibits the JAK-STAT signaling pathway by directly inhibiting the action of thrombopoietin in this pathway [8].
So far, three driver mutations have been described in the course of chronic myeloproliferative diseases that affect the functioning of the JAK-STAT pathway.
JAK2 kinase and JAK1, JAK3, and TYK2 kinases belong to the family of non-receptor tyrosine kinases. They are involved in the intracellular signal transduction of the JAK-STAT pathway. It is a system of intracellular proteins used by growth factors and cytokines to express genes that regulate cell activation, proliferation, and differentiation. The mechanism of JAK activation is based on the autophosphorylation of tyrosine residues that occurs after ligand binds to the receptor. JAK2 kinase transmits signals from the hematopoietic cytokine receptors of the myeloid lineage (erythropoietin, granulocyte-colony stimulating factor thrombopoietin, and lymphoid lineage [9].
A somatic G/T point mutation in exon 14 of the JAK2 kinase gene converts valine to phenylalanine at position 617 (V617F) in the JAK2 pseudokinase domain, which allows constitutive, ligand-independent activation of the receptor to trigger a proliferative signal [10].
Mutation of the MPL gene, which encodes the receptor for thrombopoietin, increases the sensitivity of magekaryocytes to the action of thrombopoietin, which stimulates their proliferation [11].
Malfunction of calreticulin as a result of mutation of the CARL gene leads to the activation of the MPL-JAK/STAT signaling pathway, which is independent of the ligand, as calreticulin is responsible, for the proper formation of the MPL receptor. Consequently, there is a clonal proliferation of hematopoietic stem cells [12].
Below, we provide an overview of some clinical studies on the efficacy of interferon in chronic myeloproliferative disorders.
Polycythemia vera (PV) is characterized by an increase in the number of erythrocytes in the peripheral blood.
Polycythemia vera is caused by a clonal mutation in the multipotential hematopoietic stem cell of the bone marrow. The mutation leads to an uncontrolled proliferation of the mutated cell clone, independent of erythropoietin and other regulatory factors. As the mutation takes place at an early stage of hematopoiesis, an increase of the number of erythrocytes as well as of leukocytes and platelets is observed in the peripheral blood. The cause of proliferation in PV independent from external factors is a mutation in the Janus 2 (JAK2) tyrosine kinase gene. The V617F point mutation in the JAK2 gene is responsible for about 96% mutation, and in the remaining cases the mutation arises in exon 12. Both mutations lead to constitutive activation of the JAK-STAT signaling pathway [13].
As a result of the uncontrolled proliferation, blood viscosity increases, which generates symptoms such as headaches and dizziness, visual disturbances, or erythromelalgia. As the number of all hematopoietic cells, including the granulocytes ones, increases, the difficult to control symptoms of their hyperdegranulation may appear, among which gastric ulcer or skin itching is often observed. During the disease progression, the spleen and liver become enlarged.
The most common complication of the disease is episodes of thrombosis, especially arterial one. During the course of the disease, it can also evolve into myelofibrosis or acute myeloid leukemia.
The treatment of PV is aimed at preventing thromboembolic complications, relieving the general symptoms, the appearance of hepatosplenomegaly as well as preventing its progression.
Each patient should receive an antiplatelet drug chronically, and usually acetylsalicylic acid is the choice. Most often, the treatment is started with phlebotomy in order to rapidly lower the hematocrit level. If cytoreductive therapy is necessary, the drugs of first choice are hydroxycarbamide and interferon [2].
However, the research on the mechanism of the action of interferons is still ongoing. In vitro studies with CD34+ cells from peripheral blood of patients diagnosed with polycythemia vera showed that interferon inhibits clonal changed cells selectively. It was found that interferon alpha-2b and pegylated interferon alpha-2a reduce the percentage of cells with JAK2 V617F mutation by about 40%. Pegylated interferon alpha-2a works by activating mitogen-activated protein kinase P38. It affects CD34+ cells of patients with polycythemia vera by increasing the rate of their apoptosis [6].
A case of a patient with PV with a confirmed chromosomal translocation t(6;8) treated with interferon alpha-2b, which resulted in a reduction of the clone with translocation by 50% from the baseline value, was also described [14].
In 2019, the results of a phase II multicenter study were published, which aimed at assessing the effectiveness of recombinant pegylated interferon alpha-2a in cases of refractory to previously hydroxycarbamide therapy. The study included 65 patients with essential thrombocythemia (ET) and 50 patients with polycythemia vera. All patients had previously been treated with hydroxycarbamide and showed resistance to this drug or its intolerance.
The assessment of the response was performed after 12 months of treatment. Overall response rate to interferon was higher in patients diagnosed with ET than in patients with polycythemia vera. In essential thrombocythemia, the percentage of achieved complete remissions was 43 and 26% of partial remissions. The remission rate in ET patients was higher if calreticulin CALR gene mutation was present. Patients with polycythemia vera achieved complete remission in 22% of cases and partial remission in 38% of cases.
Treatment-related side effects that follow to discontinuation of treatment were reported in almost 14% of patients [15].
The duration of response to treatment with pegylated interferon alpha-2a and the assessment of its safety in long-term use in patients with chronic myeloproliferative disorders was the goal of a phase II of the single-center study. Forty-three adult patients with polycythemia vera and 40 patients with essential thrombocythemia were enrolled in the study. The complete hematological response was defined as a decrease in hemoglobin concentration below 15.0 g/l, without phlebotomies, a resolution of splenomegaly, and no thrombotic episodes in the case of PV, and for essential thrombocythemia—a decrease platelet count below 440,000/μl and two other conditions as above. The assessment of the hematological response was performed every 3–6 months. The median follow-up was 83 months.
The hematological response was obtained in 80% of cases for the entire group. In patients with polycythemia vera, 77% of patients achieved a complete response (CR) while 7% a partial response (PR). The duration of response averaged 65 months for CR and 35 months for PR. In the group of patients diagnosed with essential thrombocythemia, CR was achieved in 73% and PR in 3%. The durance of CR was 58 months and PR was 25 months.
The molecular response for the entire group was achieved in 63% of cases.
The overall analysis showed that the duration of hematological remission and its achievement with pegylated interferon alpha-2a treatment is not affected neither by baseline disease characteristics nor JAK2 allele burden and disease molecular status. There was also no effect on age, sex, or the presence of splenomegaly.
During the course of the study, 22% of patients discontinued the treatment, because of toxicity. Toxicity was the greatest at the beginning of treatment. The starting dose was 450 μg per week and was gradually tapered off.
Thus, on the basis of the above observations, the researchers established that pegylated interferon alpha-2a may give long-term hematological and molecular remissions [16].
The assessment of pegylated interferon alpha-2a in group of patients diagnosed with polycythemia vera only was performed. The evaluation was carried out on a group of 27 patients. Interferon decreased the JAK2 V617F allele burden in 89% of cases. In three patients who were JAK2 homozygous at baseline, after the interferon alpha-2a treatment wild-type of JAK2 reappeared. The reduction of the JAK2 allele burden was estimated from 49% to an average 27%, and additional in one patient the mutant JAK2 allele was not detectable after treatment. It can therefore be postulated that the action of pegylated interferon alpha-2a is directed to cells of the polycythemia vera clone [17].
In 2005, the results of treatment by pegylated interferon alpha-2b of 21 patients diagnosed with polycythemia vera and 21 patients diagnosed with essential thrombocythemia were published. In the case of polycythemia vera in 14 patients, PRV-1 gene mutation was initially detected. In 36% of cases, PRV-1 expression normalized after treatment with pegylated interferon alpha-2b. For the entire group of 42 patients, the remission assessment showed that complete remission was achieved in 69% cases after 6 months of treatment. However, only in 19 patients remission was still maintained 2 years after the start of the study. Pegylated interferon alpha-2b was equally effective in patients with PV and ET. The use and the type of prior therapy did not affect the achievement of remission [18].
Another study with enrolled only PV patients included 136 patients. They were divided into two arms. One group received interferon alpha-2b and the other group received hydroxycarbamide. Interferon dosage was administered in 3 million units three times a week for 2 years and then 5 million units two times a week. Hydroxycarbamide was administered at a dose between 15 and 20 mg/kg/day.
In the group of patients treated with interferon, a significantly lower percentage of patients developed erythromelalgia (9.4%) and distal parasthesia (14%) compared with the group treated with hydroxycarbamide, for whom these percentages were respectively: 29 and 37.5%. Interferon alpha-2b was found to be more effective in inducing a molecular response, which was achieved in 54.7% of cases, in comparison with hydroxycarbamide—19.4% of cases, despite the fact that the percentage of achieved general hematological responses did not differ between the groups and amounted about 70%. The 5-year progression free period in the interferon group was achieved in a higher percentage (66%) than in the hydroxycarbamide group (46.7%) [19].
The most recent form of interferon approved by the
Thanks to these changes to the structure of the molecule, it was possible to achieve a significant increase in its half-life. Ropeginterferon can be administered subcutaneously to patients every 14 days. The clinical trials conducted so far have assessed the ropeginterferon dose from 50 micrograms to a maximum dose of 500 microgams administered as standard every 2 weeks. The possible dose change in case of side effects includes not only the reduction of the drug dose itself, but also the extension of the interval between doses. The extension of the dosing interval up to 4 weeks was assessed.
Ropeginterforn was approved in 2019 by the EMA for the use in patients diagnosed with polycythemia vera without splenomegaly, as monotherapy.
Ropeginterferon, like the previous forms of interferons used in treatment, is contraindicated in patients with severe mental disorders, such as severe depression. It is also a contraindication in patients with noncompensatory standard treatment of disorders of the thyroid gland as well as severe forms of autoimmune diseases. The safety profile of ropeginterferon is similar to that of other forms of alpha interferons. The most common side effects are flu-like symptoms [20].
Ropeginterferon has been shown to exhibit in vitro activity against JAK2-mutant cells. The activity of ropeginterferon against JAK2-positive cells is similar to that of other forms of interferons used actually for standard therapy. Ropeginterferon has an inhibitory effect on erythroid progenitor cells with a mutant JAK2 gene. At the same time, it has almost no effect on progenitor cells without the mutated allele (JAK2-wile-type) and normal CD34+ cells. A gradual decrease of JAK2-positive cells was observed in patients with PV during ropeginterferon treatment. The examination was performed after 6 and 12 months of treatment. In comparison, the reduction in the percentage of JAK2 positive cells in patients treated with hydroxycarbamide was significantly lower.
These results may suggest that ropeginterferon may cause elimination of the mutant clone, but further prospective clinical trials are needed to confirm this theory. The evaluation was performed on a group of patients enrolled in the PROUD-PV study who were treated in France [21].
In 2017, a multicenter study was opened in Italy. The study was of the second phase. In total, 127 patients with polycythemia vera were included in the study. All patients enrolled on the study had low-risk PV. The clinical trial consisted of two arms. Patients received phlebotomies and low-dose aspirin in one arm and ropeginterferon in the other arm. The aim of the study was to achieve a hematocrit of 45% or lower without any evidence of disease progression. Ropeginterferon was administered every 2 weeks at a constant dose of 100 μg.
The response to the treatment was assessed after 12 months. The reduction of hematocrit to the assumed level was achieved in significantly higher percentage of patients in the ropeginterferon group than of patients who received only phlebotomies and aspirin. In addition, none of the patients treated with ropeginterferon experienced disease progression during the course of the study, while among those treated with phlebotomies, 8% of patients progressed.
Grade 4 or 5 adverse events were not observed in patients treated with ropeginterferon, and the incidence of remaining adverse event (AE) was small and comparable in both arms. The most common side effects in the ropeginterferon group were flu-like symptoms and neutropenia; however, the third-grade neutropenia was the most common (8% of cases) [22].
One of the most important clinical studies on the use of ropeginterferon was the PROUD-PV study and its continuation: the CONTINUATION-PV study. These were three-phase, multicenter studies. The aim of the study was to compare the effectiveness of ropeginterferon in relation to hydroxycarbamide. The study included adult patients diagnosed with polycythemia vera treated with hydroxycarbamide for less than 3 years and no cytoreductive treatment at all. In total, 257 patients received this treatment. The patients were divided into two groups: those receiving ropeginterferon or the other being given hydroxycarbamide.
During the PROUD-study, drug doses were increased until the hematocrit was achieved below 45% without the use of phlebotomies, and the normalization of the number of leukocytes and platelets was reached.
The PROUD-PV study lasted 12 months. After this time, the patients continued the treatment under the CONTINUATION-PV study for further 36 months. After the final analysis performed in the 12th month at the end of PROUD study, it was found that the hematological response rates did not differ between the ropeginterferon and hydroxycarbamide treatment groups. These were consecutively 43% in the ropeginterferon arm and 46% in the control arm.
However, after analyzing the CONTINUATION- PV study, it turned out that after 36 months of treatment, the rates of hematological responses begin to prevail in the group of patients receiving ropeginterferon, 53% versus 38% in the control group. Thus, from the above data, it can be seen that the response rate to ropeginterferon increases with the duration of treatment [23].
Another analysis of patients participating in the PROUD and CONTINUATION studies was based on the assessment of treatment results after 24 months, dividing patients into two groups according to age (under and over 60 years).
The initial comparison of both groups of patients showed that older patients had a more aggressive course of the disease. Patients over 60 years of age had a higher percentage of cells with a mutant JAK2 allele. They experienced both general symptoms and some complications, such as thrombosis, more frequently. Both patients under 60 years of age and over 60 years of age in the ropeginterferon arm had a higher rate of molecular response, namely 77.1 and 58.7% compared with the HU remission: 33.3 and 36.1%, respectively. Significantly higher reductions in the JAK2 allele were observed in both groups of patients after ropeginterferon treatment: it was 54.8% for younger patients and 35.1% for elderly patients. For comparison, this difference in the group of patients treated with HU was 4.5 and 18.4%, respectively.
What is more, the age did not affect the frequency of ropeginterferon side effects. In addition, the incidence of adverse ropeginterferon disorders was similar to that observed in the hydroxycarbamide group [24].
Essential thrombocythemia is a clonal growth of multipotential stem cells in the bone marrow. The consequence of this is increased proliferation of megakaryocytes in the bone marrow and an increase in the number of platelets in the peripheral blood. The level of platelets above 450,000/μl is considered a diagnostic criterion.
Essential thrombocythemia may progress over time to a more aggressive form of myeloproliferation, i.e., myelofibrosis. The disease can also evolve into acute myeloid leukemia or myelodysplastic syndrome, both with very poor prognosis. Thromboembolic complications are serious, and they concern over 20% of patients. Thrombosis occurs in the artery and venous area. Moreover, in patients with a very high platelet count, above 1,000,000/μl, bleeding may occur as a result of secondary von Willebrand syndrome [1, 2].
The treatment of ET is primarily aimed to prevent thrombotic complications.
In low-risk patients, only acetylsalicylic acid is used. In cases of high-risk patients, hydroxycarbamide is the first-line drug for most patients. Anagrelide and interferon are commonly used as second-line drugs.
Due to the possible effects of hydroxycarbamide of cytogenetic changes in the bone marrow cells after long-lasting usage, some experts recommend the use of interferon in younger patients in the first line. Interferon is also used as the drug of choice in patients planning a pregnancy [25].
The efficacy of pegylated interferon alpha-2a was assessed on the basis of the group of 39 patients with essential thrombocythemia and 40 patients with polycythemia vera.
Of the overall group, 81% of patients were previously treated prior to the study entry. The patients received pegylated interferon alpha-2a in a dose of 90 μg once a week. The dose of 450 μg was associated with a high percentage of intolerance.
In patients with essential thrombocythemia, the complete remission was achieved in 76%, while the overall hematological response rate brought 81%. Moreover, the molecular remission was achieved in 38%, in 14% of cases, JAK2 transcript became not detectable.
Patients diagnosed with polycythemia vera achieved 70% complete hematological remission and 80% general hematological response to treatment. JAK2 transcript was undetectable in 6% of patients. Molecular remission was achieved in 54% of cases.
Pegylated interferon alpha-2a at the dose of 90 μg per week was very well tolerated. In total, 20% of patients experienced a grade of 3 or 4 of adverse reaction, which was neutropenia. In addition, an increase in liver function tests was observed. Grade 4 of AE was not observed among patients who started the treatment with 90 μg/week while grade 3 neutropenia was an adverse event in only 7% of cases [26].
The effect of interferon alpha-2b treatment in patients with ET and PV was investigated. The study was prospective. Some of the results concerning the group of patients with polycythemia vera are presented in the subsection on polycythemia vera. In total, 123 patients with diagnosed essential thrombocythemia participated in the study. All of them received interferon alpha-2b. The patients were divided into two groups depending on the presence of the JAK2 V617F mutation. The enrolled patients were between 18 and 65 years of age. The treatment they received was, sequentially, interferon alpha-2b in the dose of 3 million units three times a week for the first 2 years, after which time the dose was changed into a maintenance dose, which amounted to 5 million units two times a week.
The analysis showed that the patients with the JAK2 V617F mutation present in a higher percentage achieved an overall hematological response as well as a complete hematological response. The overall hematological response was achieved in 83% of patients with JAK2 mutation, and the complete hematological remission was achieved in 23 cases. In the group of ET patients without the JAK2 V617F mutation, overall hematological response was achieved in 61.4%, while the complete hematological remission was achieved in 12 patients. The 5-year progression-free survival was obtained in 75.9% in the JAKV617F group and only in 47.6% without the mutation.
A significant proportion of patients experienced mild side effects. Grade 3 and 4 of adverse events were severe, most of them being a fever. The isolated cases of elevated liver tests and nausea have also been reported [19].
Pegylated interferon alpha-2b in patients with essential thrombocythemia who were previously treated with hydroxycarbamide, anagrelide, and other forms of interferon alpha, however, due to the lack of efficacy or toxicity, the patients required a change of treatment, was assessed. Pegylated interferon alpha-2b turned out to be effective in these cases. It led to the complete hematological remission in 91% of patients after 2 months of therapy, and in 100% of patients after 4 months. However, merely 11 patients participated in the study. Also only two patients required treatment discontinuation due to the side effects such as depression and general fatigue grade 3 [27].
In case of pregnant patients, interferon is currently considered the only safe cytoreductive drug. Over the years, several analyses of the results of interferon treatment during pregnancy have been carried out.
The assessment of 34 pregnancies in 23 women diagnosed with ET was performed retrospectively. All the pregnancies included in the analysis were of high risk. This high risk was associated with a high platelet count above 1,500,000/μl, a history of thrombotic episode, severe microcirculation disorders, or a history of major hemorrhage.
It turned out that the use of interferon allowed the birth of an alive child in 73.5% of cases. There was no difference in efficacy between the basic and pegylated forms of interferon alpha. In pregnancies without interferon treatment, the percentage of live births was only 60%. Moreover, it was not found if the presence of the JAK2 V617F mutation had any influence on the course of pregnancy [28].
An analysis of the course of pregnancy in patients with ET was assessed in Italy. Data from 17 centers were taken into account. Data from 122 pregnancies were collected from 92 women. In patients diagnosed with essential thrombocythemia, the risk of the spontaneous loss of pregnancy is about 2.5 times higher than among the general population. In the contrary to the study quoted above, it was found that the presence of the JAK2 mutation increases the risk of pregnancy loss. The proportion of live births in patients exposed to interferon during pregnancy was 95%, compared with 71.6% in the group of patients not treated with interferon.
The multivariate analysis also showed that the use of acetylsalicylic acid during pregnancy had no effect on the live birth rate of patients with ET [29].
Whatever its form, interferon is the drug of first choice in pregnancy. Hydroxycarbamide and anagrelide should be withdrawn for about 6 months, and at least for 3 months, before the planned conception. Experts recommend the use of interferon in high-risk pregnancies [30]. A Japanese analysis of 10 consecutive pregnancies in ET patients showed 100% live births in patients who received interferon [31].
In myelofibrosis (MF), monoclonal megakaryocytes produce cytokines that stimulate the proliferation of normal, non-neoplastic fibroblasts and stimulate angiogenesis. The consequence of this is the gradual fibrosis of the bone marrow, impaired hematopoiesis in the bone marrow, and the formation of extramedullary location mainly in the sites of fetal hematopoiesis, i.e., in the spleen and the liver.
The production of various cytokines by neoplastic megakaryocytes leads to the proliferation of normal, noncancerous fibroblasts as well as to increased angiogenesis.
Progressive bone marrow fibrosis leads to worsening anemia and thrombocytopenia. On the other hand, the production of proinflammatory cytokines by megakaryoblasts leads to the general symptoms such as weight loss, fever, joint pain, night sweats, and consequently, progressive worsening of general condition.
The prognosis for myelofibrosis is poor. In about 20% of patients, myelofibrosis evolves into acute myeloid leukemia with poor prognosis.
Currently, the only effective method of treatment that gives a chance to prolong the life is allogeneic bone marrow transplantation. However, this method is only available to younger patients.
The goal of treatment of patients who have not been qualified for allotranspalntation is to reduce the symptoms and to improve the patient’s quality of life. In case of leukocytosis cytoreducing drugs, such as hydroxycarbamide, melphalan, or cladribine can be used. They cause a reduction in the number of leukocytes and may, to some extent, inhibit splenomegaly. Interferon alpha has been used successfully for the treatment of myelofibrosis for many years. The results of its effectiveness will be presented below [2].
Currently, the JAK2 inhibitor ruxolitinib is approved for the treatment of myelofibrosis with enlarged spleen in intermediate and high-risk patients. Ruxolitinib reduces the size of the spleen, reduces general symptoms, and improves the quality of life; however, it does not prolong the overall survival of patients [32].
In 2015, the results of a retrospective study were published to compare the histological parameters of the bone marrow before and after interferon treatment. Twelve patients diagnosed with primary myelofibrosis as well as post-PV MF and post-ET MF were enrolled in the study. Patients were treated with pegylated recombinant interferon alpha-2a or recombinant interferon alpha-2b in standard doses. The time of treatment was from 1 to 10 years. Some patients had previously been treated with hydroxycarbamide or anagrelide. In all cases, karyotype was normal. The prognostic factor of Dynamic International Prognostic Scoring System (DIPSS) was assessed at the beginning as well as during the treatment.
Bone marrow cellularity decreased in cases with increased bone marrow cellularity before the treatment. After the interferon treatment, a reduction in the degree of bone marrow fibrosis was found. The parameters, such as the density of naked nuclei and the density of megakaryocytes in the bone marrow, also improved.
It proves that if the JAK2 V617F mutation had been present, DIPSS was decreased after interferon treatment. This relationship was not observed in patients without the JAK2 V617F mutation. The improvement in peripheral blood morphological parameters and the overall clinical improvement correlated with the improvement in the assessed histological parameters of the bone marrow.
Before the initiation of interferon, seven patients had splenomegaly. During the treatment with interferon, the complete resolution of splenomegaly was achieved in 17% of patients (two cases), and its size decreased in 25% (three cases). A good clinical response was achieved in 83% during interferon therapy. There was no significant difference in response between the two types of interferon used [33].
A prospective study was also conducted in patients with low and intermediate-1 risk group myelofibrosis. Seventeen patients were enrolled. Patients received interferon alpha-2b (0.5–3 milion units/three times a week) or pegylated interferon alpha-2a (45–90 μg/week). The duration of therapy was on average 3.3 years.
Most of the patients responded to the treatment. Partial remission was found in seven patients and complete remission in two patients. Moreover, in four cases, the disease was stabilized and in one case the clinical improvement was achieved. Three patients did not respond to treatment at all and progressed to myelofibrosis. Additionally, the assessment in reducing spleen size was performed. At baseline, 15 patients have splenomegaly, nine of them achieved the compete regression of spleen size [34].
However, the efficacy of interferon in the treatment of myelofibrosis appears to be limited only to a less advanced form, when the bone marrow still has an adequate percentage of normal hemopoiesis and the marrow stroma is not significantly fibrotic. In more advanced stages, interferon was not shown to have any significant effect on the regression of the fibrosis process [35].
In 2020, the results of the COMBI study were published. That was a two-phase, multicenter, single-arm study that investigated the efficacy and safety of the combination of ruxolitinib and pegylated interferon alpha. Thirty-two patients with PV and 18 patients with primary and secondary myelofibrosis participated in the study. The patients were at age 18 and older. Remission was achieved in 44% of myelofibrosis cases, including 28% (5 patients) of complete remission. In patients with PV, the results were slightly worse: 31% of remissions, including 9% of complete remissions. Patients received pegylated interferon alpha-2a (45 μg/week) or pegylated interferon alpha-2b (35 μg/week) in low doses and ruxolitinib in doses of 5–20 mg twice a day.
For the entire group of patients (with PV and MF), the initial JAK2 allele burden was 47% at baseline, and after 2 years of treatment with interferon and ruxolitinib, it decreased to 12%.
The treatment toxicity was low. The highest incidence of side effects occurred at initiation of therapy. It was mostly anemia and thrombocytopenia.
The observations from the COMBI study show that, for the combination of interferon in lower doses with ruxolitinib, it may be effective and well tolerated even in the group of patients who had intolerance to interferon used as the only drug in higher doses. The combined treatment improved the bone marrow in terms of fibrosis and its cellularity. It also allowed to improve the value of peripheral blood counts [36].
It is currently known that some of the additional mutations are associated with a worse prognosis in patients with myelorpoliferation, including patients with myelofibrosis. Some of these mutations have been identified as high-risk molecular mutations. These are ASXL1, EZH2, IDH1/2, or SRSF2. Earlier studies have shown their association with a more aggressive course of the disease, worse prognosis, and shorter survival of patients, as well as a poorer response to treatment. Due to their importance, they have been included in the diagnostic criteria of myelofibrosis [37].
It is also known that the presence of driver mutations, i.e., JAK2, CALR, and MPL or triple negativity, may affect the course of myeloproliferation, including the incidence of thromboembolic complications.
The assessment of the influence of driver mutations and a panel of selected additional mutations on the effectiveness of interferon treatment in patients with myelofibrosis was performed on a group of 30 patients. Only the patients with low- and intermediate-1-risk were enrolled in the study. The treatment with pegylated interferon alpha-2a or interferon alpha-2b resulted in a complete remission in two patients and partial remission in nine patients. The disease progressed in three cases. One patient relapsed and four died. The remaining patients achieved a clinical improvement or disease stabilization. In the studied group, it was not found if the effectiveness of interferon treatment was influenced by the lack of driver mutations. Among the group of four patients with additional mutations, two died and one had disease progression. It was a mutation of ASXL1 and SRSF2. The treatment with interferon in patients without additional molecular mutations in the early stages of the disease may prevent further progression of the disease [38].
The side effects of interferon in the group of patients with myelofibrosis are similar to those occurring after the treatment of other chronic myeloproliferative diseases. The most frequently described are hematological toxicity- anemia and thrombocytopenia, less often is the appearance of leukopenia. Hematological toxicity usually resolves with dose reduction or extension of the dose interval. The most frequently nonhematological toxicity was fatigue, muscle pain, weakness, and depression symptoms. All symptoms are usually mild and do not exceed grade 2 [38].
However, the use of interferon in the treatment of myelofibrosis has not been recommended as a standard therapy. Interferon is still being evaluated in clinical trials, or it is used in selected patients as a nonstandard therapy in this diagnosis.
Mastocytosis is characterized by an excessive proliferation of abnormal mast cells and their accumulation in various organs.
The basis for the development of mastocytosis is ligand-independent activation of the KIT receptor, resulting from mutations in the KIT proto-oncogene. The KIT receptor is a trans membrane receptor with tyrosine kinase’s activity. Its activation stimulates the proliferation of mast cells. That excessive numbers of mast cells infiltrate tissues and organs and release mediators such as histamine, interleukine-6, tryptase, heparin, and others, which are responsible for the appearance of symptoms typical of mastocytosis. In addition, the infiltration of tissues for mast cells itself causes damage to the affected organs.
The prognosis of mastocytosis depends on the type of the disease. In the case of cutaneous mastocytosis (CM), in the majority of cases prognosis is good and the disease does not shorten the patient’s life, but in aggressive systemic mastocytosis (ASM), the average follow-up is about 40 months. Mast cell leukemia has a poor prognosis with a median follow-up of approximately 1 year.
Systemic mastocytosis usually requires the implementation of cytoreductive therapy. The first line of therapy is interferon alone or its combination with corticosteroids. In aggressive systemic mastocytosis, the first line in addition to interferon 2-CdA can be used. An effective drug turned out to be midostaurin in the case of the present KIT mutation. In patients without the KIT D816V mutation, treatment with imatinib may be effective. In the case of mast cell leukemia, multidrug chemotherapy is most often required, as in acute leukemias, followed by bone marrow transplantation [39].
Systemic mastocytosis requiring treatment is a rare disease, this is why the studies available in the literature evaluating various therapies concern mostly small groups of patients.
In 2002, the French authors presented their experiences on the use of interferon in patients with systemic mastocytosis. They included 20 patients. The patients received interferon alpha-2b in gradually increased doses.
The patients were assessed after 6 months. In cases in which bone marrow was infiltrated for mast cells at baseline, it still remained infiltrated after 6 months of treatment.
However, the responses were obtained in terms of symptoms related to mast cell degranulation. Partial remission was achieved in 35% of patients and minor remission in 30%. It concerns mainly skin lesions and vascular congestion. Moreover, the assessment of the histamine level in the plasma revealed a decrease of it in patients who previously presented symptoms related to the degranulation of mast cells, such as gastrointestinal disorders and flushing.
A high percentage of side effects were found during treatment. They concerned 35% of patients. Depression and cytopenia were most frequent ones [40].
Another analysis was a report of five patients with systemic mastocytosis treated with interferon and prednisolone. All patients received interferon alpha-2b in a dose of 3 million units three times a week and four patients additionally received prednisolone. Four patients responded to interferon treatment at varying degrees. One patient, who at baseline had bone marrow involvement by mast cells in above 10%, progressed to mast cell leukemia. In two patients, the symptoms C resolved completely and in one of them they partially disappeared. In one case, stabilizing disease was achieved [41].
In 2009, a retrospective analysis of patients treated with cytoreductive therapy due to mastocytosis was published. The authors collected data from 108 patients treated at the Mayo Clinic. This analysis allowed for the comparison of the efficacy of four drugs used in systemic mastocytosis. There were interferon alpha alone or in the combination with prednisone—among 40 patients, hydroxycarbamide—among 26 ones, imatinib—among 22 persons, and 2-chlorodeoxyadenosine (2-CdA)—among 22 patients.
After dividing the patients into three additional groups on the basis of the type of mastocytosis—indolent systemic mastocytosis, aggressive systemic mastocytosis, and systemic mastocytosis associated with another clonal hematological nonmast cell lineage disease (SM-AHNMD)—the effectiveness of each of type of therapy was assessed.
The highest response rates in indolent and aggressive mastocytosis were achieved with interferon treatment. They were 60% of the responses in both groups, and in the SM-AHNMD group of patients, the percentage was also one of the highest and amounted to 45%. The second most effective drug was 2-CdA. The response rates were 56% for indolent MS, 50% for aggressive MS, and 55% for SM-AHNMD. The patients treated with imatinib achieved response in 14, 50, and 9% by following groups, respectively. In contrast, patients with indolent and aggressive systemic mastocytosis did not respond to hydroxycarbamide treatment at all. The response rate in both groups was 0%. However, patients with MS associated with another clonal hematological nonmast cell lineage disease achieved 21% response to hydroxycarbamide. Additionally, it was found that only interferon relieved symptoms caused by the release of inflammatory mediators by mast cells.
The additional analysis showed no influence of the TET 2 mutation on the response to treatment [42].
In the literature, there are also single cases of mastocytosis presenting trials of nonstandard treatment. That is description of a patient with systemic mastocytosis with mast cell bone marrow involvement. Mutation of c-kit Asp816Val was present. Patient progressed despite treatment with dasatinib and 2-chlorodeoxyadenosine. The patient developed symptoms related to the degranulation of mast cells and increased ascites.
The patient was treated with pranlukast, which is an anti-leukotriene receptor antagonist due to an asthma episode. The rate of ascites growth decreased significantly after one administration. The patient required paracentesis every 10 days and not every 3 days, as before starting to take the drug. After 15 days of treatment with pranlukast, the patient received interferon alpha, which resulted in complete regression of ascites, resolution of pancytopenia, and complete disappearance of the c-kit mutation clone. The infiltration of mast cells in the bone marrow significantly decreased [43].
Interferon alpha was also effective in a patient with systemic mastocytosis associated with myelodysplastic syndrome with the c-kit D816V mutation, which was refractory to imatinib treatment [44].
Interferon alpha also proved to be effective in the treatment of osteoporotic lesions appearing in the course of mastocytosis.
The series of 10 cases with resolved mastocytosis and osteoporosis-related fractures was presented in 2011. The patients received interferon alpha in a dose of 1.5 million units three times a week as well as pamindronic acid. The patients were treated for an average of 60 months. For the first 2 years, pamindronate was given at a dose of 1 mg/kg every month, and then every 3 months.
During the course of the study, no patient had a new-bone fracture. The level of alkaline phosphatase decreased by 25% in relation to the value before treatment and tryptase by 34%. Bone density increased during treated with interferon and pamindronate. The increase was on average 12% in the spine bones and 1.9% in the hip bones. At the same time, there was no increase in the density of the hip bone and a minimal increase in the density of the spine in patients treated with pamindronate alone.
The results of this observation suggest that it is beneficial to add low doses of interferon alpha to pamindronate treatment in terms of bone density increase [45].
That experiences show that interferon used in systemic mastocytosis significantly improves the quality of life of patients by inhibiting the symptoms caused by degranulation of mast cells. They prevent bone fractures and, in some patients, they cause remission of bone marrow infiltration by mast cells.
Chronic neutrophilic leukemia (CNL) is a very rare disease. It is characterized by the clonal proliferation of mature neutrophils.
The diagnostic criteria proposed by the World Health Organization (WHO) comprise leukocyte counts above 25,000/μl (including more than 80% of rod and segmented
Physical examination often shows enlargement of the liver and spleen, moreover, patients complain on weight loss and weakness [1].
The prognosis varies. The average survival time for patients with CNL is less than 2 years.
Only few descriptions of chronic neutrophilic leukemia are available in the literature, and these are mostly single case reports.
Because it is an extremely rare disease, there are no established and generally accepted treatment standards. In most cases, patients are given hydroxycarbamide or interferon. Patients who are eligible for a bone marrow transplant may benefit from this treatment. Bone marrow allotransplantation remains the only method that gives a chance for a significant extension of life.
The German authors presented a series of 14 cases of chronic neutrophilic leukemia. The group of patients consisted of eight women and six men. The average age was 64.7 years. From the entire group of patients, longer survival was achieved only in three cases. One of these patients was treated with interferon alpha and achieved hematological remission, the other underwent bone marrow allotransplantation from a family donor, and the third one was treated with hydroxycarbamide and transfusions as needed. The follow-up period of the patient after allogeneic matched related donor transplantation (allo-MRD) was 73 months, and for the patient after interferon treatment it was 41 months.
The remaining patients died within 2 years of diagnosis. Six patients, the largest group, died due to intracranial bleeding, three patients died because of leukemia cell tissue infiltration, one patient because of the disease transformation into leukemia, and one patient because of pneumonia [46].
It can be seen from these experiences that treatment with interferon alpha can significantly extend the survival time of patients.
The case of a 40-year-old woman diagnosed with chronic neutrophilic leukemia is presented by Yassin and coauthors. Initially, the patient had almost 41,000 leukocytes in the peripheral blood. In a physical examination, splenomegaly and hepatomegaly were not present. Patient received pegylated interferon alpha-2a. The initially dose was 50 μg once a week for the first 2 weeks, then the dose was increased to 135 μg weekly for 6 weeks, and then the dose interval was extended to another 2 weeks. As a result of the treatment, the general condition of the patient improved and the parameters of peripheral blood counts were normalized [47].
Another case report presented in the literature describes a 41-year-old woman diagnosed with CNL accompanied by focal segmental glomerulosclerosis (FSGS). The patient had increasing leukocytosis for several months. On the admission to the hospital, leukocytosis was 94,000/μl. Moreover, the number of platelets in the morphology exceeded 1,000,000/μl. More than a year earlier, the patient had splenectomy due to splenomegaly and spleen infraction.
Additionally, JAK2 V617F mutation was found. Some authors suggest that the presence of JAK2 mutation may be associated with longer survival in CNL.
The patient received hydroxycarbamide for 3 months and reduction in the number of leukocytes was achieved. After this time, interferon alpha-2b was added to hydroxycarbamide. As a result, focal segmental glomerulosclerosis disappeared and the renal tests improved [48].
Another case of chronic neutrophilic leukemia with a JAK2 gene mutation concerns a 53-year-old man. The patient’s baseline leukocytosis was 33,500/μl, including the neutrophil count of 29,700/μl. The patient also had splenomegaly.
The treatment with interferon alpha-2b at a dose of 3 million units every other day was started. After a month of treatment, the number of leukocytes was reduced to less than 10,000/μl. Then the patient was treated chronically with interferon alpha-2b in doses of 3 million units every 2 weeks. As a result of the therapy, the number of leukocytes remains between 8 and 10,000/μl. The patient remains in general good condition [49].
A series of two CNL cases are also shown. The first patient was a 70-year-old woman with stable leukocytosis of about 35,000/μl and the remaining morphology parameters in normal range. The patient was only observed for 5 years until hepasplenomegaly progressed rapidly. Then, interferon alpha-2b was included. Due to the treatment, the rapid regression of hepatosplenomegaly was achieved.
The second case is a 68-year-old woman with baseline leukocytosis of almost 14,000/μl. In this case, the treatment with hydroxycarbamide was started immediately. However, no improvement was achieved. After 6 weeks of HU treatment, interferon alpha-2b 3 million units 3 times a week was implemented and leukocytosis decreased. Due to the interferon treatment, the disease stabilized for a long time. Because the patient experienced an adverse reaction, a severe flu-like syndrome, interferon was discontinued. After interferon withdrawal, the disease progressed gradually and the treatment attempts by busulfan and 6-mercaptopurine were unsuccessful. Therefore, interferon was readministered and the disease went into remission. Interferon treatment was continued at a reduced dose. The disease regression was achieved again.
Additionally, the patient showed an improvement in the function of granulocytes in terms of phagocytosis and an improvement in neutral killer (NK) cell function after treatment with interferon [50].
The above examples show that interferon alpha is effective in the treatment of chronic neutrophilic leukemia. The side effects are rare and can be managed with dose reductions. Moreover, in these cases, interferon is also effective in a reduced dose. Disease remission or regression can be achieved without typical of CNL complications, such as intracranial bleeding.
Interferon has been used in the past to treat chronic myeloid leukemia. The treatment with tyrosine kinase inhibitors is now a standard practice. However, in a small number of patients, they are ineffective or exhibit unmanageable toxicity. Therefore, the attempts are underway to use interferon in combination with TKI in lower doses, which is to ensure the enhancement of the antiproliferative effect while reducing the toxicity.
There are ongoing attempts to use ropeginterferon in patients diagnosed with chronic myeloid leukemia, in whom treatment with imatinib alone has not led to deep molecular response (DMR). The first phase study was conducted in a small group of patients with chronic myeloid leukemia. The patients in first chronic phase treated with imatinib who did not achieve DMR, but in complete hematologic remission and complete cytogenetic remission, were included in the study. Patients have been treated with imatinib for at least 18 months. Twelve patients were enrolled in the study, and they completed the study according to the protocol. These patients received additional ropeginterferon to imatinib and four achieved DMR. Low toxicity was observed during the treatment. Among the hematological toxicities, neutropenia was the most common. There was no nonhematological toxicity with a degree higher than 1/2 during the treatment. Moreover, it has been found that better effects and fewer side effects are obtained when ropeginterferon is administered for a longer time, but in lower doses. The comparison of the effectiveness of interferon in chronic myeloproliferative disorders based on selected articles is presented in Table 1 [51].
Source | Type of trial | Interferon | Diagnosis | No. | Prior treatment status | Response rate |
---|---|---|---|---|---|---|
Yacoubet al. [15] | Phase II, multicenter | Pegylated IFN alfa-2a | PV | 50 | Resistance to HU or HU intolerance | CR:22% PR:38% |
ET | 65 | CR:43% PR:26% | ||||
Masarova et al. [16] | Phase II, single-center | Pegylated IFN alfa-2a | PV | 43 | Untreated or previously treated with cytoreductive therapy | CR:77% PR:7% |
ET | 40 | CR:73% PR:3% | ||||
Samuelsson et al. [18] | Phase II | Pegylated IFN alfa-2b | PV | 21 | Untreated or previously treated with cytoreductive therapy | CR: 69% for the entire group |
ET | 21 | |||||
Huang BT et al. [19] | Open label, multicenter | IFN alfa-2b | PV | 136 | Untreated or previously treated with cytoreductive therapy | OHR:70% Molecular response:54.7% |
ET | 123 | OHR (JAK2+ patients):83% CHR:23 cases OHR (JAK2-patients): 61.4% CHR:12 cases | ||||
Gisslinger et al. [23] | phase III, multicenter | Ropeginterferon | PV | 257 | Previously treated | OHR:53% |
Quintás-Cardama et al. [26] | phase II | Pegylated IFN alfa-2a | PV | 40 | Untreated or previously treated with cytoreductive therapy | OHR:80% CR:70% Molecular remission:54% |
ET | 39 | OHR:81% CR:76% Molecular remission:38% | ||||
Sørensen et al. [36] | Phase III, multicenter, COMBI | Pegylated IFN alfa-2a with ruxolitinib or Pegylated IFN alfa-2b with ruxolitinib | PV | 32 | Untreated or previously treated with cytoreductive therapy | OHR:44% CR:28% |
MF | 18 | OHR:31% CR:9% | ||||
Casassus et al. [40] | Open label, multicenter | IFN alpha-2b | Mastocytosis | 20 | Untreated and previously treated | PR:35% Minor remission: 30% |
Comparison of the effectiveness of interferon in chronic myeloproliferative disorders.
PV: polycythemia vera; ET: essential thrombocythemia; MF: myelofibrosis; HU: hydroxycarbamide/hydroxyurea; CR: complete remission; PR: partial remission; and OHR: overall hematological response.
Interferon alpha appears to be an effective and safe drug in the most type of chronic myeloproliferative disorders. Nowadays, all forms of its using have similar effectiveness. Interferon alpha can be effective even in cases of resistance for first-line treatment. Trial research is currently underway to combine it with some new drugs, such as ruxolitinib, and to add it to the already well-established therapy, it is a promising option for patients with refractory disease.
From time to time, new forms of interferon, such as ropeginterferon, are introduced, which gives hope for better effectiveness, better safety profile, and greater comfort in its use for patients who have to be treated for many years. In the case of the use of interferons alpha in the treatment of chronic myeloproliferative diseases, there are still opportunities to extend its use and to study its combination with newly introduced drugs.
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Achilias"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10681",title:"Biodegradation Technology of Organic and Inorganic Pollutants",subtitle:null,isOpenForSubmission:!1,hash:"9a6e10e02788092872fd249436898e97",slug:"biodegradation-technology-of-organic-and-inorganic-pollutants",bookSignature:"Kassio Ferreira Mendes, Rodrigo Nogueira de Sousa and Kamila Cabral Mielke",coverURL:"https://cdn.intechopen.com/books/images_new/10681.jpg",editedByType:"Edited by",editors:[{id:"197720",title:"Ph.D.",name:"Kassio",middleName:null,surname:"Ferreira Mendes",slug:"kassio-ferreira-mendes",fullName:"Kassio Ferreira Mendes"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10843",title:"Persistent Organic Pollutants (POPs)",subtitle:"Monitoring, Impact and Treatment",isOpenForSubmission:!1,hash:"f5b1589f0a990b6114fef2dadc735dd9",slug:"persistent-organic-pollutants-pops-monitoring-impact-and-treatment",bookSignature:"Mohamed Nageeb Rashed",coverURL:"https://cdn.intechopen.com/books/images_new/10843.jpg",editedByType:"Edited by",editors:[{id:"63465",title:"Prof.",name:"Mohamed Nageeb",middleName:null,surname:"Rashed",slug:"mohamed-nageeb-rashed",fullName:"Mohamed Nageeb Rashed"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],booksByTopicTotal:218,seriesByTopicCollection:[],seriesByTopicTotal:0,mostCitedChapters:[{id:"29369",doi:"10.5772/32373",title:"Textile Organic Dyes – Characteristics, Polluting Effects and Separation/Elimination Procedures from Industrial Effluents – A Critical Overview",slug:"textile-organic-dyes-characteristics-polluting-effects-and-separation-elimination-procedures-from-in",totalDownloads:29487,totalCrossrefCites:128,totalDimensionsCites:321,abstract:null,book:{id:"872",slug:"organic-pollutants-ten-years-after-the-stockholm-convention-environmental-and-analytical-update",title:"Organic Pollutants Ten Years After the Stockholm Convention",fullTitle:"Organic Pollutants Ten Years After the Stockholm Convention - Environmental and Analytical Update"},signatures:"Zaharia Carmen and Suteu Daniela",authors:[{id:"91196",title:"Prof.",name:"Carmen",middleName:null,surname:"Zaharia",slug:"carmen-zaharia",fullName:"Carmen Zaharia"},{id:"92084",title:"Dr.",name:"Daniela",middleName:null,surname:"Suteu",slug:"daniela-suteu",fullName:"Daniela Suteu"}]},{id:"42059",doi:"10.5772/54048",title:"Adsorption Technique for the Removal of Organic Pollutants from Water and Wastewater",slug:"adsorption-technique-for-the-removal-of-organic-pollutants-from-water-and-wastewater",totalDownloads:30043,totalCrossrefCites:51,totalDimensionsCites:221,abstract:null,book:{id:"3426",slug:"organic-pollutants-monitoring-risk-and-treatment",title:"Organic Pollutants",fullTitle:"Organic Pollutants - Monitoring, Risk and Treatment"},signatures:"Mohamed Nageeb Rashed",authors:[{id:"63465",title:"Prof.",name:"Mohamed Nageeb",middleName:null,surname:"Rashed",slug:"mohamed-nageeb-rashed",fullName:"Mohamed Nageeb Rashed"}]},{id:"27305",doi:"10.5772/39363",title:"Water Stress in Plants: Causes, Effects and Responses",slug:"water-stress-in-plants-causes-effects-and-responses",totalDownloads:28496,totalCrossrefCites:72,totalDimensionsCites:172,abstract:null,book:{id:"911",slug:"water-stress",title:"Water Stress",fullTitle:"Water Stress"},signatures:"Seyed Y. S. Lisar, Rouhollah Motafakkerazad, Mosharraf M. Hossain and Ismail M. M. Rahman",authors:[{id:"110740",title:"Dr.",name:"Ismail M.M.",middleName:null,surname:"Rahman",slug:"ismail-m.m.-rahman",fullName:"Ismail M.M. Rahman"}]},{id:"62247",doi:"10.5772/intechopen.77315",title:"Application of Biosorption for Removal of Heavy Metals from Wastewater",slug:"application-of-biosorption-for-removal-of-heavy-metals-from-wastewater",totalDownloads:7645,totalCrossrefCites:75,totalDimensionsCites:152,abstract:"Fresh water accounts for 3% of water resources on the Earth. Human and industrial activities produce and discharge wastes containing heavy metals into the water resources making them unavailable and threatening human health and the ecosystem. Conventional methods for the removal of metal ions such as chemical precipitation and membrane filtration are extremely expensive when treating large amounts of water, inefficient at low concentrations of metal (incomplete metal removal) and generate large quantities of sludge and other toxic products that require careful disposal. Biosorption and bioaccumulation are ecofriendly alternatives. These alternative methods have advantages over conventional methods. Abundant natural materials like microbial biomass, agro-wastes, and industrial byproducts have been suggested as potential biosorbents for heavy metal removal due to the presence of metal-binding functional groups. Biosorption is influenced by various process parameters such as pH, temperature, initial concentration of the metal ions, biosorbent dose, and speed of agitation. Also, the biomass can be modified by physical and chemical treatment before use. The process can be made economical by regenerating and reusing the biosorbent after removing the heavy metals. Various bioreactors can be used in biosorption for the removal of metal ions from large volumes of water or effluents. The recent developments and the future scope for biosorption as a wastewater treatment option are discussed.",book:{id:"6137",slug:"biosorption",title:"Biosorption",fullTitle:"Biosorption"},signatures:"Sri Lakshmi Ramya Krishna Kanamarlapudi, Vinay Kumar\nChintalpudi and Sudhamani Muddada",authors:[{id:"238433",title:"Associate Prof.",name:"Sudhamani",middleName:null,surname:"Muddada",slug:"sudhamani-muddada",fullName:"Sudhamani Muddada"},{id:"244937",title:"Mrs.",name:"S L Ramyakrishna",middleName:null,surname:"Kanamarlapudi",slug:"s-l-ramyakrishna-kanamarlapudi",fullName:"S L Ramyakrishna Kanamarlapudi"},{id:"244938",title:"Mr.",name:"Vinay Kumar",middleName:null,surname:"Chintalpudi",slug:"vinay-kumar-chintalpudi",fullName:"Vinay Kumar Chintalpudi"}]},{id:"53211",doi:"10.5772/66416",title:"Biofloc Technology (BFT): A Tool for Water Quality Management in Aquaculture",slug:"biofloc-technology-bft-a-tool-for-water-quality-management-in-aquaculture",totalDownloads:16966,totalCrossrefCites:65,totalDimensionsCites:148,abstract:"Biofloc technology (BFT) is considered the new “blue revolution” in aquaculture. Such technique is based on in situ microorganism production which plays three major roles: (i) maintenance of water quality, by the uptake of nitrogen compounds generating in situ microbial protein; (ii) nutrition, increasing culture feasibility by reducing feed conversion ratio (FCR) and a decrease of feed costs; and (iii) competition with pathogens. The aggregates (bioflocs) are a rich protein-lipid natural source of food available in situ 24 hours per day due to a complex interaction between organic matter, physical substrate, and large range of microorganisms. This natural productivity plays an important role recycling nutrients and maintaining the water quality. The present chapter will discuss some insights of the role of microorganisms in BFT, main water quality parameters, the importance of the correct carbon-to-nitrogen ratio in the culture media, its calculations, and different types, as well as metagenomics of microorganisms and future perspectives.",book:{id:"5355",slug:"water-quality",title:"Water Quality",fullTitle:"Water Quality"},signatures:"Maurício Gustavo Coelho Emerenciano, Luis Rafael Martínez-\nCórdova, Marcel Martínez-Porchas and Anselmo Miranda-Baeza",authors:[{id:"146126",title:"Dr.",name:"Maurício Gustavo Coelho",middleName:null,surname:"Emerenciano",slug:"mauricio-gustavo-coelho-emerenciano",fullName:"Maurício Gustavo Coelho Emerenciano"},{id:"186970",title:"Prof.",name:"Marcel",middleName:null,surname:"Martínez-Porchas",slug:"marcel-martinez-porchas",fullName:"Marcel Martínez-Porchas"},{id:"186971",title:"Prof.",name:"Anselmo",middleName:null,surname:"Miranda-Baeza",slug:"anselmo-miranda-baeza",fullName:"Anselmo Miranda-Baeza"},{id:"195101",title:"Dr.",name:"Luis Rafael",middleName:null,surname:"Martínez-Córdoba",slug:"luis-rafael-martinez-cordoba",fullName:"Luis Rafael Martínez-Córdoba"}]}],mostDownloadedChaptersLast30Days:[{id:"69568",title:"Water Quality Parameters",slug:"water-quality-parameters",totalDownloads:10165,totalCrossrefCites:14,totalDimensionsCites:36,abstract:"Since the industrial revolution in the late eighteenth century, the world has discovered new sources of pollution nearly every day. So, air and water can potentially become polluted everywhere. Little is known about changes in pollution rates. The increase in water-related diseases provides a real assessment of the degree of pollution in the environment. This chapter summarizes water quality parameters from an ecological perspective not only for humans but also for other living things. According to its quality, water can be classified into four types. Those four water quality types are discussed through an extensive review of their important common attributes including physical, chemical, and biological parameters. These water quality parameters are reviewed in terms of definition, sources, impacts, effects, and measuring methods.",book:{id:"7718",slug:"water-quality-science-assessments-and-policy",title:"Water Quality",fullTitle:"Water Quality - Science, Assessments and Policy"},signatures:"Nayla Hassan Omer",authors:null},{id:"58138",title:"Water Pollution: Effects, Prevention, and Climatic Impact",slug:"water-pollution-effects-prevention-and-climatic-impact",totalDownloads:21554,totalCrossrefCites:18,totalDimensionsCites:38,abstract:"The stress on our water environment as a result of increased industrialization, which aids urbanization, is becoming very high thus reducing the availability of clean water. Polluted water is of great concern to the aquatic organism, plants, humans, and climate and indeed alters the ecosystem. The preservation of our water environment, which is embedded in sustainable development, must be well driven by all sectors. While effective wastewater treatment has the tendency of salvaging the water environment, integration of environmental policies into the actor firms core objectives coupled with continuous periodical enlightenment on the present and future consequences of environmental/water pollution will greatly assist in conserving the water environment.",book:{id:"6157",slug:"water-challenges-of-an-urbanizing-world",title:"Water Challenges of an Urbanizing World",fullTitle:"Water Challenges of an Urbanizing World"},signatures:"Inyinbor Adejumoke A., Adebesin Babatunde O., Oluyori Abimbola\nP., Adelani-Akande Tabitha A., Dada Adewumi O. and Oreofe Toyin\nA.",authors:[{id:"101570",title:"MSc.",name:"Babatunde Olufemi",middleName:null,surname:"Adebesin",slug:"babatunde-olufemi-adebesin",fullName:"Babatunde Olufemi Adebesin"},{id:"187738",title:"Dr.",name:"Adejumoke",middleName:"Abosede",surname:"Inyinbor",slug:"adejumoke-inyinbor",fullName:"Adejumoke Inyinbor"},{id:"188818",title:"Dr.",name:"Abimbola",middleName:null,surname:"Oluyori",slug:"abimbola-oluyori",fullName:"Abimbola Oluyori"},{id:"188819",title:"Mrs.",name:"Tabitha",middleName:null,surname:"Adelani-Akande",slug:"tabitha-adelani-akande",fullName:"Tabitha Adelani-Akande"},{id:"208501",title:"Dr.",name:"Adewumi",middleName:null,surname:"Dada",slug:"adewumi-dada",fullName:"Adewumi Dada"},{id:"208502",title:"Ms.",name:"Toyin",middleName:null,surname:"Oreofe",slug:"toyin-oreofe",fullName:"Toyin Oreofe"}]},{id:"45422",title:"Urban Waterfront Regenerations",slug:"urban-waterfront-regenerations",totalDownloads:14203,totalCrossrefCites:4,totalDimensionsCites:12,abstract:null,book:{id:"3560",slug:"advances-in-landscape-architecture",title:"Advances in Landscape Architecture",fullTitle:"Advances in Landscape Architecture"},signatures:"Umut Pekin Timur",authors:[{id:"165480",title:"Dr.",name:"Umut",middleName:null,surname:"Pekin Timur",slug:"umut-pekin-timur",fullName:"Umut Pekin Timur"}]},{id:"24941",title:"Tsunami in Makran Region and Its Effect on the Persian Gulf",slug:"tsunami-in-makran-region-and-its-effect-on-the-persian-gulf",totalDownloads:7575,totalCrossrefCites:4,totalDimensionsCites:7,abstract:null,book:{id:"406",slug:"tsunami-a-growing-disaster",title:"Tsunami",fullTitle:"Tsunami - A Growing Disaster"},signatures:"Mohammad Mokhtari",authors:[{id:"52451",title:"Dr.",name:"Mohammad",middleName:null,surname:"Mokhtari",slug:"mohammad-mokhtari",fullName:"Mohammad Mokhtari"}]},{id:"66307",title:"Bio-hydrogen and Methane Production from Lignocellulosic Materials",slug:"bio-hydrogen-and-methane-production-from-lignocellulosic-materials",totalDownloads:2953,totalCrossrefCites:6,totalDimensionsCites:8,abstract:"This chapter covers the information on bio-hydrogen and methane production from lignocellulosic materials. Pretreatment methods of lignocellulosic materials and the factors affecting bio-hydrogen production, both dark- and photo-fermentation, and methane production are addressed. Last but not least, the processes for bio-hydrogen and methane production from lignocellulosic materials are discussed.",book:{id:"7608",slug:"biomass-for-bioenergy-recent-trends-and-future-challenges",title:"Biomass for Bioenergy",fullTitle:"Biomass for Bioenergy - Recent Trends and Future Challenges"},signatures:"Apilak Salakkam, Pensri Plangklang, Sureewan Sittijunda, Mallika Boonmee Kongkeitkajorn, Siriporn Lunprom and Alissara Reungsang",authors:null}],onlineFirstChaptersFilter:{topicId:"12",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"82624",title:"Protective Forests for Ecosystem-based Disaster Risk Reduction (Eco-DRR) in the Alpine Space",slug:"protective-forests-for-ecosystem-based-disaster-risk-reduction-eco-drr-in-the-alpine-space",totalDownloads:0,totalDimensionsCites:null,doi:"10.5772/intechopen.99505",abstract:"Mountain forests are an efficient Forest-based Solution (FbS) for Ecosystem-based Disaster Risk Reduction (Eco-DRR) by lowering the frequency, magnitude, and/or intensity of natural hazards. Technical protection measures are often poor solutions as stand-alone measures to reduce disaster risk limited by material wear and fatigue or financial resources and aesthetical values. Protective forests should therefore be considered as key elements in integrated risk management strategies. However, the definition of protective forests and the understanding and assessment of their protective functions and effects differ greatly among Alpine Space countries. In this chapter, we present a short introduction to the concept of Eco-DRR and companion terms and propose a definition of FbS as a specific case of Nature-based Solutions for an ecosystem-based and integrated risk management of natural hazards. That is, we guide the reader through the maze of existing definitions and concepts and try to disentangle their meanings. Furthermore, we present an introduction to forest regulations in the Alpine Space and European protective forest management guidelines. Our considerations and recommendations can help strengthen the role of protective forests as FbS in Eco-DRR and the acknowledgment of the key protective function they have and the crucial protective effects they provide in mountain areas.",book:{id:"10812",title:"Protective forests as Ecosystem-based solution for Disaster Risk Reduction (ECO-DRR)",coverURL:"//cdnintech.com/web/frontend/www/assets/cover.jpg"},signatures:"Michaela Teich, Cristian Accastello, Frank Perzl and Frédéric Berger"},{id:"82465",title:"Agroforestry: An Approach for Sustainability and Climate Mitigation",slug:"agroforestry-an-approach-for-sustainability-and-climate-mitigation",totalDownloads:10,totalDimensionsCites:0,doi:"10.5772/intechopen.105406",abstract:"Agroforestry Systems (AFS), or the association of trees with crops (or animals), is a strategy for land management and use that allows production within the sustainable development: (a) environmentally (production environmentally harmonic); (b) technically (integrating existing resources on the farm); (c) economically (increase in production), and (d) socially (equality of duties and opportunities, quality of life of the family group). As an intentional integration of trees or shrubs with crop and animal production, this practice makes environmental, economic, and social benefits to farmers. Given that there is a set of definitions, rather than a single definition of Agroforestry (AF) and AFS, it is justified to explore the historical evolution and the minimum coincidences of criteria to define them and apply them in the recovery of degraded areas. Knowing how to classify AFS allows us to indicate which type or group of AFS is suitable for a particular area with its characteristics. The greatest benefit that AFS can bring to degraded or sloping areas lies in their ability to combine soil conservation with productive functions. In other words, AF is arborizing agriculture and animal production to obtain more benefits including climate change adaptation and mitigation by ecosystem services.",book:{id:"11663",title:"Vegetation Dynamics, Changing Ecosystems and Human Responsibility",coverURL:"https://cdn.intechopen.com/books/images_new/11663.jpg"},signatures:"Ricardo O. Russo"},{id:"82754",title:"Impact of Revegetation on Ecological Restoration of a Constructed Soil in a Coal Mining in Southern Brazil",slug:"impact-of-revegetation-on-ecological-restoration-of-a-constructed-soil-in-a-coal-mining-in-southern-",totalDownloads:5,totalDimensionsCites:0,doi:"10.5772/intechopen.105895",abstract:"The main problems in the constructed soils are the generation of acid mine drainage promoted by the presence of coal debris in the overburden layer and the compaction of the topsoil promoted by the machine traffic when the material used in the overburden cover is more clayey. This book chapter aimed to show an overview of the impact of more than a decade of revegetation with different perennial grasses on the chemical, physical, and biological quality of constructed soil after coal mining. The study was carried out in a coal mining area, located in southern Brazil. The soil was constructed in early 2003 and the perennial grasses, Hemarthria altissima; Paspalum notatum cv. Pensacola; Cynodon dactylon cv Tifton; and Urochloa brizantha; were implanted in November/December 2003. In 11.5, 17.6 and 18 years of revegetation soil samples were collected and the chemical, physical, and biological attributes were determined. Our results show that liming is an important practice in the restoration of these strongly anthropized soils because this positively impacts the plants’ development, facilitating the roots system expansion. Biological attributes such as soil fauna and the microorganism’s population are the attributes that possibly takes longer to establish itself in these areas.",book:{id:"11663",title:"Vegetation Dynamics, Changing Ecosystems and Human Responsibility",coverURL:"https://cdn.intechopen.com/books/images_new/11663.jpg"},signatures:"Lizete Stumpf, Maria Bertaso De Garcia Fernandez, Pablo Miguel, Luiz Fernando Spinelli Pinto, Ryan Noremberg Schubert, Luís Carlos Iuñes de Oliveira Filho, Tania Hipolito Montiel, Lucas Da Silva Barbosa, Jeferson Diego Leidemer and Thábata Barbosa Duarte"},{id:"82936",title:"Soil Degradation Processes Linked to Long-Term Forest-Type Damage",slug:"soil-degradation-processes-linked-to-long-term-forest-type-damage",totalDownloads:4,totalDimensionsCites:0,doi:"10.5772/intechopen.106390",abstract:"Forest degradation impairs ability of the whole landscape adaptation to environmental change. The impacts of forest degradation on landscape are caused by a self-organization decline. At the present time, the self-organization decline was largely due to nitrogen deposition and deforestation which exacerbated impacts of climate change. Nevertheless, forest degradation processes are either reversible or irreversible. Irreversible forest degradation begins with soil damage. In this paper, we present processes of forest soil degradation in relation to vulnerability of regulation adaptability on global environmental change. The regulatory forest capabilities were indicated through soil organic matter sequestration dynamics. We devided the degradation processes into quantitative and qualitative damages of physical or chemical soil properties. Quantitative soil degradation includes irreversible loss of an earth’s body after claim, erosion or desertification, while qualitative degradation consists of predominantly reversible consequences after soil disintegration, leaching, acidification, salinization and intoxication. As a result of deforestation, the forest soil vulnerability is spreading through quantitative degradation replacing hitherto predominantly qualitative changes under continuous vegetation cover. Increasing needs to natural resources using and accompanying waste pollution destroy soil self-organization through biodiversity loss, simplification in functional links among living forms and substance losses from ecosystem. We concluded that subsequent irreversible changes in ecosystem self-organization cause a change of biome potential natural vegetation and the land usability decrease.",book:{id:"11457",title:"Forest Degradation Under Global Change",coverURL:"https://cdn.intechopen.com/books/images_new/11457.jpg"},signatures:"Pavel Samec, Aleš Kučera and Gabriela Tomášová"},{id:"82828",title:"Vegetation and Avifauna Distribution in the Serengeti National Park",slug:"vegetation-and-avifauna-distribution-in-the-serengeti-national-park",totalDownloads:6,totalDimensionsCites:0,doi:"10.5772/intechopen.106165",abstract:"In order to examine the bird species changes within different vegetation structures, the variations were compared between Commiphora-dominated vegetations with those of Vachellia tortilis and Vachellia robusta-dominated vegetations, and also compared the birds of grassland with those of Vachellia drepanolobium and Vachellia seyal-dominated vegetations. This study was conducted between February 2010 and April 2012. A total of 40 plots of 100 m × 100 m were established. Nonparametric Mann-Whitney U-test was used to examine differences in bird species between vegetations. Species richness estimates were obtained using the Species Diversity and Richness. A total of 171 bird species representing 103 genera, 12 orders, and 54 families were recorded. We found differences in bird species distribution whereby V. tortilis has higher bird species richness (102 species), abundance, and diversity when compared with Commiphora with 66 species and V. robusta with 59 species. These results suggest that variations in bird species abundance, diversity, and distribution could be attributed to differences in the structural diversity of vegetation. Therefore it is important to maintain different types of vegetation by keeping the frequency of fire to a minimum and prescribed fire should be employed and encouraged to control wildfire and so maintain a diversity of vegetation and birds community.",book:{id:"11663",title:"Vegetation Dynamics, Changing Ecosystems and Human Responsibility",coverURL:"https://cdn.intechopen.com/books/images_new/11663.jpg"},signatures:"Ally K. Nkwabi and Pius Y. 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He previously worked as a post-doctoral fellow at the Ben-Gurion University of Negev, Israel; University of the Free State, South Africa; and Central University of Technology Bloemfontein, South Africa. He obtained his Ph.D. in Organic Chemistry from Nagaoka University of Technology, Japan. He has published more than seventy-four journal articles and attended several national and international conferences as speaker and chair. Dr. Kendrekar has received many international awards. He has several funded projects, namely, anti-malaria drug development, MRSA, and SARS-CoV-2 activity of curcumin and its formulations. He has filed four patents in collaboration with the University of Central Lancashire and Mayo Clinic Infectious Diseases. His present research includes organic synthesis, drug discovery and development, biochemistry, nanoscience, and nanotechnology.",institutionString:"Visiting Scientist at Lipid Nanostructures Laboratory, Centre for Smart Materials, School of Natural Sciences, University of Central Lancashire",institution:null},{id:"428125",title:"Dr.",name:"Vinayak",middleName:null,surname:"Adimule",slug:"vinayak-adimule",fullName:"Vinayak Adimule",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/428125/images/system/428125.jpg",biography:"Dr. Vinayak Adimule, MSc, Ph.D., is a professor and dean of R&D, Angadi Institute of Technology and Management, India. He has 15 years of research experience as a senior research scientist and associate research scientist in R&D organizations. He has published more than fifty research articles as well as several book chapters. He has two Indian patents and two international patents to his credit. Dr. Adimule has attended, chaired, and presented papers at national and international conferences. He is a guest editor for Topics in Catalysis and other journals. He is also an editorial board member, life member, and associate member for many international societies and research institutions. His research interests include nanoelectronics, material chemistry, artificial intelligence, sensors and actuators, bio-nanomaterials, and medicinal chemistry.",institutionString:"Angadi Institute of Technology and Management",institution:null},{id:"284317",title:"Prof.",name:"Kantharaju",middleName:null,surname:"Kamanna",slug:"kantharaju-kamanna",fullName:"Kantharaju Kamanna",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/284317/images/21050_n.jpg",biography:"Prof. K. Kantharaju has received Bachelor of science (PCM), master of science (Organic Chemistry) and Doctor of Philosophy in Chemistry from Bangalore University. He worked as a Executive Research & Development @ Cadila Pharmaceuticals Ltd, Ahmedabad. He received DBT-postdoc fellow @ Molecular Biophysics Unit, Indian Institute of Science, Bangalore under the supervision of Prof. P. Balaram, later he moved to NIH-postdoc researcher at Drexel University College of Medicine, Philadelphia, USA, after his return from postdoc joined NITK-Surthakal as a Adhoc faculty at department of chemistry. Since from August 2013 working as a Associate Professor, and in 2016 promoted to Profeesor in the School of Basic Sciences: Department of Chemistry and having 20 years of teaching and research experiences.",institutionString:null,institution:{name:"Rani Channamma University, Belagavi",country:{name:"India"}}},{id:"158492",title:"Prof.",name:"Yusuf",middleName:null,surname:"Tutar",slug:"yusuf-tutar",fullName:"Yusuf Tutar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/158492/images/system/158492.jpeg",biography:"Prof. Dr. Yusuf Tutar conducts his research at the Hamidiye Faculty of Pharmacy, Department of Basic Pharmaceutical Sciences, Division of Biochemistry, University of Health Sciences, Turkey. He is also a faculty member in the Molecular Oncology Program. He obtained his MSc and Ph.D. at Oregon State University and Texas Tech University, respectively. He pursued his postdoctoral studies at Rutgers University Medical School and the National Institutes of Health (NIH/NIDDK), USA. His research focuses on biochemistry, biophysics, genetics, molecular biology, and molecular medicine with specialization in the fields of drug design, protein structure-function, protein folding, prions, microRNA, pseudogenes, molecular cancer, epigenetics, metabolites, proteomics, genomics, protein expression, and characterization by spectroscopic and calorimetric methods.",institutionString:"University of Health Sciences",institution:null},{id:"180528",title:"Dr.",name:"Hiroyuki",middleName:null,surname:"Kagechika",slug:"hiroyuki-kagechika",fullName:"Hiroyuki Kagechika",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180528/images/system/180528.jpg",biography:"Hiroyuki Kagechika received his bachelor’s degree and Ph.D. in Pharmaceutical Sciences from the University of Tokyo, Japan, where he served as an associate professor until 2004. He is currently a professor at the Institute of Biomaterials and Bioengineering (IBB), Tokyo Medical and Dental University (TMDU). From 2010 to 2012, he was the dean of the Graduate School of Biomedical Science. Since 2012, he has served as the vice dean of the Graduate School of Medical and Dental Sciences. He has been the director of the IBB since 2020. Dr. Kagechika’s major research interests are the medicinal chemistry of retinoids, vitamins D/K, and nuclear receptors. He has developed various compounds including a drug for acute promyelocytic leukemia.",institutionString:"Tokyo Medical and Dental University",institution:{name:"Tokyo Medical and Dental University",country:{name:"Japan"}}},{id:"94311",title:"Prof.",name:"Martins",middleName:"Ochubiojo",surname:"Ochubiojo Emeje",slug:"martins-ochubiojo-emeje",fullName:"Martins Ochubiojo Emeje",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94311/images/system/94311.jpeg",biography:"Martins Emeje obtained a BPharm with distinction from Ahmadu Bello University, Nigeria, and an MPharm and Ph.D. from the University of Nigeria (UNN), where he received the best Ph.D. award and was enlisted as UNN’s “Face of Research.” He established the first nanomedicine center in Nigeria and was the pioneer head of the intellectual property and technology transfer as well as the technology innovation and support center. Prof. Emeje’s several international fellowships include the prestigious Raman fellowship. He has published more than 150 articles and patents. He is also the head of R&D at NIPRD and holds a visiting professor position at Nnamdi Azikiwe University, Nigeria. He has a postgraduate certificate in Project Management from Walden University, Minnesota, as well as a professional teaching certificate and a World Bank certification in Public Procurement. Prof. Emeje was a national chairman of academic pharmacists in Nigeria and the 2021 winner of the May & Baker Nigeria Plc–sponsored prize for professional service in research and innovation.",institutionString:"National Institute for Pharmaceutical Research and Development",institution:{name:"National Institute for Pharmaceutical Research and Development",country:{name:"Nigeria"}}},{id:"436430",title:"Associate Prof.",name:"Mesut",middleName:null,surname:"Işık",slug:"mesut-isik",fullName:"Mesut Işık",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/436430/images/19686_n.jpg",biography:null,institutionString:null,institution:{name:"Bilecik University",country:{name:"Turkey"}}},{id:"268659",title:"Ms.",name:"Xianquan",middleName:null,surname:"Zhan",slug:"xianquan-zhan",fullName:"Xianquan Zhan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/268659/images/8143_n.jpg",biography:"Dr. Zhan received his undergraduate and graduate training in the fields of preventive medicine and epidemiology and statistics at the West China University of Medical Sciences in China during 1989 to 1999. He received his post-doctoral training in oncology and cancer proteomics for two years at the Cancer Research Institute of Human Medical University in China. In 2001, he went to the University of Tennessee Health Science Center (UTHSC) in USA, where he was a post-doctoral researcher and focused on mass spectrometry and cancer proteomics. Then, he was appointed as an Assistant Professor of Neurology, UTHSC in 2005. He moved to the Cleveland Clinic in USA as a Project Scientist/Staff in 2006 where he focused on the studies of eye disease proteomics and biomarkers. He returned to UTHSC as an Assistant Professor of Neurology in the end of 2007, engaging in proteomics and biomarker studies of lung diseases and brain tumors, and initiating the studies of predictive, preventive, and personalized medicine (PPPM) in cancer. In 2010, he was promoted to Associate Professor of Neurology, UTHSC. Currently, he is a Professor at Xiangya Hospital of Central South University in China, Fellow of Royal Society of Medicine (FRSM), the European EPMA National Representative in China, Regular Member of American Association for the Advancement of Science (AAAS), European Cooperation of Science and Technology (e-COST) grant evaluator, Associate Editors of BMC Genomics, BMC Medical Genomics, EPMA Journal, and Frontiers in Endocrinology, Executive Editor-in-Chief of Med One. He has\npublished 116 peer-reviewed research articles, 16 book chapters, 2 books, and 2 US patents. His current main research interest focuses on the studies of cancer proteomics and biomarkers, and the use of modern omics techniques and systems biology for PPPM in cancer, and on the development and use of 2DE-LC/MS for the large-scale study of human proteoforms.",institutionString:null,institution:{name:"Xiangya Hospital Central South University",country:{name:"China"}}},{id:"40482",title:null,name:"Rizwan",middleName:null,surname:"Ahmad",slug:"rizwan-ahmad",fullName:"Rizwan Ahmad",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/40482/images/system/40482.jpeg",biography:"Dr. Rizwan Ahmad is a University Professor and Coordinator, Quality and Development, College of Medicine, Imam Abdulrahman bin Faisal University, Saudi Arabia. Previously, he was Associate Professor of Human Function, Oman Medical College, Oman, and SBS University, Dehradun. Dr. Ahmad completed his education at Aligarh Muslim University, Aligarh. He has published several articles in peer-reviewed journals, chapters, and edited books. His area of specialization is free radical biochemistry and autoimmune diseases.",institutionString:"Imam Abdulrahman Bin Faisal University",institution:{name:"Imam Abdulrahman Bin Faisal University",country:{name:"Saudi Arabia"}}},{id:"41865",title:"Prof.",name:"Farid A.",middleName:null,surname:"Badria",slug:"farid-a.-badria",fullName:"Farid A. Badria",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/41865/images/system/41865.jpg",biography:"Farid A. Badria, Ph.D., is the recipient of several awards, including The World Academy of Sciences (TWAS) Prize for Public Understanding of Science; the World Intellectual Property Organization (WIPO) Gold Medal for best invention; Outstanding Arab Scholar, Kuwait; and the Khwarizmi International Award, Iran. He has 250 publications, 12 books, 20 patents, and several marketed pharmaceutical products to his credit. He continues to lead research projects on developing new therapies for liver, skin disorders, and cancer. Dr. Badria was listed among the world’s top 2% of scientists in medicinal and biomolecular chemistry in 2019 and 2020. He is a member of the Arab Development Fund, Kuwait; International Cell Research Organization–United Nations Educational, Scientific and Cultural Organization (ICRO–UNESCO), Chile; and UNESCO Biotechnology France",institutionString:"Mansoura University",institution:{name:"Mansoura University",country:{name:"Egypt"}}},{id:"329385",title:"Dr.",name:"Rajesh K.",middleName:"Kumar",surname:"Singh",slug:"rajesh-k.-singh",fullName:"Rajesh K. Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329385/images/system/329385.png",biography:"Dr. Singh received a BPharm (2003) and MPharm (2005) from Panjab University, Chandigarh, India, and a Ph.D. (2013) from Punjab Technical University (PTU), Jalandhar, India. He has more than sixteen years of teaching experience and has supervised numerous postgraduate and Ph.D. students. He has to his credit more than seventy papers in SCI- and SCOPUS-indexed journals, fifty-five conference proceedings, four books, six Best Paper Awards, and five projects from different government agencies. He is currently an editorial board member of eight international journals and a reviewer for more than fifty scientific journals. He received Top Reviewer and Excellent Peer Reviewer Awards from Publons in 2016 and 2017, respectively. He is also on the panel of The International Reviewer for reviewing research proposals for grants from the Royal Society. He also serves as a Publons Academy mentor and Bentham brand ambassador.",institutionString:"Punjab Technical University",institution:{name:"Punjab Technical University",country:{name:"India"}}},{id:"142388",title:"Dr.",name:"Thiago",middleName:"Gomes",surname:"Gomes Heck",slug:"thiago-gomes-heck",fullName:"Thiago Gomes Heck",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/142388/images/7259_n.jpg",biography:null,institutionString:null,institution:{name:"Universidade Regional do Noroeste do Estado do Rio Grande do Sul",country:{name:"Brazil"}}},{id:"336273",title:"Assistant Prof.",name:"Janja",middleName:null,surname:"Zupan",slug:"janja-zupan",fullName:"Janja Zupan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/336273/images/14853_n.jpeg",biography:"Janja Zupan graduated in 2005 at the Department of Clinical Biochemistry (superviser prof. dr. Janja Marc) in the field of genetics of osteoporosis. Since November 2009 she is working as a Teaching Assistant at the Faculty of Pharmacy, Department of Clinical Biochemistry. In 2011 she completed part of her research and PhD work at Institute of Genetics and Molecular Medicine, University of Edinburgh. She finished her PhD entitled The influence of the proinflammatory cytokines on the RANK/RANKL/OPG in bone tissue of osteoporotic and osteoarthritic patients in 2012. From 2014-2016 she worked at the Institute of Biomedical Sciences, University of Aberdeen as a postdoctoral research fellow on UK Arthritis research project where she gained knowledge in mesenchymal stem cells and regenerative medicine. She returned back to University of Ljubljana, Faculty of Pharmacy in 2016. She is currently leading project entitled Mesenchymal stem cells-the keepers of tissue endogenous regenerative capacity facing up to aging of the musculoskeletal system funded by Slovenian Research Agency.",institutionString:null,institution:{name:"University of Ljubljana",country:{name:"Slovenia"}}},{id:"357453",title:"Dr.",name:"Radheshyam",middleName:null,surname:"Maurya",slug:"radheshyam-maurya",fullName:"Radheshyam Maurya",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/357453/images/16535_n.jpg",biography:null,institutionString:null,institution:{name:"University of Hyderabad",country:{name:"India"}}},{id:"418340",title:"Dr.",name:"Jyotirmoi",middleName:null,surname:"Aich",slug:"jyotirmoi-aich",fullName:"Jyotirmoi Aich",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000038Ugi5QAC/Profile_Picture_2022-04-15T07:48:28.png",biography:"Biotechnologist with 15 years of research including 6 years of teaching experience. Demonstrated record of scientific achievements through consistent publication record (H index = 13, with 874 citations) in high impact journals such as Nature Communications, Oncotarget, Annals of Oncology, PNAS, and AJRCCM, etc. Strong research professional with a post-doctorate from ACTREC where I gained experimental oncology experience in clinical settings and a doctorate from IGIB where I gained expertise in asthma pathophysiology. A well-trained biotechnologist with diverse experience on the bench across different research themes ranging from asthma to cancer and other infectious diseases. An individual with a strong commitment and innovative mindset. Have the ability to work on diverse projects such as regenerative and molecular medicine with an overall mindset of improving healthcare.",institutionString:"DY Patil Deemed to Be University",institution:null},{id:"349288",title:"Prof.",name:"Soumya",middleName:null,surname:"Basu",slug:"soumya-basu",fullName:"Soumya Basu",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035QxIDQA0/Profile_Picture_2022-04-15T07:47:01.jpg",biography:"Soumya Basu, Ph.D., is currently working as an Associate Professor at Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune, Maharashtra, India. With 16+ years of trans-disciplinary research experience in Drug Design, development, and pre-clinical validation; 20+ research article publications in journals of repute, 9+ years of teaching experience, trained with cross-disciplinary education, Dr. Basu is a life-long learner and always thrives for new challenges.\r\nHer research area is the design and synthesis of small molecule partial agonists of PPAR-γ in lung cancer. She is also using artificial intelligence and deep learning methods to understand the exosomal miRNA’s role in cancer metastasis. Dr. Basu is the recipient of many awards including the Early Career Research Award from the Department of Science and Technology, Govt. of India. She is a reviewer of many journals like Molecular Biology Reports, Frontiers in Oncology, RSC Advances, PLOS ONE, Journal of Biomolecular Structure & Dynamics, Journal of Molecular Graphics and Modelling, etc. She has edited and authored/co-authored 21 journal papers, 3 book chapters, and 15 abstracts. She is a Board of Studies member at her university. She is a life member of 'The Cytometry Society”-in India and 'All India Cell Biology Society”- in India.",institutionString:"Dr. D.Y. Patil Vidyapeeth, Pune",institution:{name:"Dr. D.Y. 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He pursued post-doctoral research at College of Pharmacy, Health Science Center, Texas A & M University and was involved in another postdoctoral research at Department of Translational Neurosciences and Neurotherapeutics, John Wayne Cancer Institute, Santa Monica, California. In 2015, he worked in Harvard-MIT Health Sciences & Technology as a visiting scientist. He has substantial experience in nanotechnology-based formulation development and successfully served various Indian organizations to develop pharmaceuticals and nutraceutical products. He is an inventor in many US patents and an author in many peer-reviewed articles, book chapters and books published in various media of international repute. Dr. Mukherjee is currently serving as Principal Scientist, R&D at Esperer Onco Nutrition (EON) Pvt. 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