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<xml><ArticleSet><Article><Journal><PublisherName>Radiance Research Academy</PublisherName><JournalTitle>International Journal of Current Research and Review</JournalTitle><PISSN>2231-2196</PISSN><EISSN>0975-5241</EISSN><Volume>8</Volume><Issue>19</Issue><IssueLanguage>English</IssueLanguage><SpecialIssue>N</SpecialIssue><PubDate><Year>-0001</Year><Month>November</Month><Day>30</Day></PubDate></Journal><ArticleType>Healthcare</ArticleType><ArticleTitle>UTILIZATION OF AGRICULTURAL WASTE FOR BIOETHANOL PRODUCTION- A REVIEW&#xD;
</ArticleTitle><ArticleLanguage>English</ArticleLanguage><FirstPage>01</FirstPage><LastPage>05</LastPage><AuthorList><Author>Nwosu-Obieogu K.</Author><AuthorLanguage>English</AuthorLanguage><Author> Chiemenem L.I.</Author><AuthorLanguage>English</AuthorLanguage><Author> Adekunle K.F.</Author><AuthorLanguage>English</AuthorLanguage></AuthorList><Abstract>The utilization of agricultural waste to produce bioethanol proves to be an alternative energy source for the limited non renewable energy and a dependable substitute for food crops. Though the process has several challenges and limitations such as biomass transport and handling, efficient pre-treatment methods, high cost based on current technologies which results in low yield and high cost of the hydrolysis process. This review highlights different classes of agricultural waste, their sources and the processes undergone to produce bioethanol economically.&#xD;
</Abstract><AbstractLanguage>English</AbstractLanguage><Keywords>Agricultural waste, Bioethanol, Pre-treatment, Lignocelluloses materials, Energy crop</Keywords><Fulltext>Introduction&#xD;
&#xD;
Energy is one of the most important factors to global prosperity, in view of continuously rising petroleum costs and dependence upon fossil fuel resources, considerable attention has been focused on alternative energy resources, hence the production of liquid biofuels which has been advocated as a sustainable option to tackle the problems associated with rising crude oil prices, global warming and diminishing petroleum reserves. &#xD;
&#xD;
Bioethanol produced from renewable biomass has received considerable attention in current years; it is one means to reduce fossil fuel use and emissions of greenhouse gases.Using ethanol as a gasoline fuel additive as well as transportation fuel helps to alleviate global warming and environmental pollution. It is a high octane number biofuel which is produced from fermentation of corn, potatoes, grain (wheat, barley and rye), sugar beet, sugar cane and vegetable residues. [1-3]&#xD;
&#xD;
In the last decade, most researchers tend to focus on developing an economical and ecofriendly ethanol production process. Much emphasis is being given to the production of ethanol from agricultural and forestry residues and other forms of biomass since they are most abundant and renewable resources on earth, which makes them attractive for production of ethanol.&#xD;
&#xD;
Fermentation of sugar-based raw materials is referred to as &#x201C;first generation&#x201D; bioethanol, whereas the use of lignocelluloses raw materials is commonly called &#x201C;second generation&#x201D; bioethanol. The &#x201C;third generation&#x201D; of algal bioethanol is at an early stage of investigation. &#xA0;Further the cellulosic plant material represents an as&#x2013;of&#x2013;yet untapped source of fermentable sugars for signi?cant use, especially non-food agricultural waste products like wheat straw, rice straw, baggasse, rice husk etc. Hence, second generation ethanol is derived from lignocellulosic materials. In these waste products, the polysaccharides, cellulose and hemicellulose are intimately associated with lignin in the plant cell wall. The lignin component acts as a physical barrier and must be removed to make the carbohydrates available for further transformation processes. Bioconversion of cellulosic biomass into fermentable sugar, for production of ethanol using microorganisms, especially cellulose degrading fungi, makes bioethanol production economic, environmental friendly and also renewable. [1, 4, 5]&#xD;
&#xD;
Hence, the main objective of this work is to harness the potentials of agricultural waste for the production of bioethanol rather than energy crops. [1]&#xD;
&#xD;
Agricultural Waste&#xD;
&#xD;
Agricultural waste consists of plant biomass wastes (cellulose, hemicelluloses and lignin) grouped into different categories such as wood residues, grasses, waste paper, agricultural residues and food industries [6-8]&#xD;
&#xD;
Taherzadeh J. M. et al [9] opined that in addition to inorganic wastes, different types of polymers such as polyesters and polypropylene are available in various waste materials. &#xD;
&#xD;
Researchers are more concerned in the production of bioethanol from wastes rather than energy crops because the latter competes for land and water with food crops to produce biofuel. Due to rise in food prices, energy crops are been discouraged from its use to produce biofuels due to current world wide rise in food prices, to resolve this conflict, it is necessary to integrate all kinds of biowaste into a biomass economy [10], though, it is mostly wasted in the form of pre-harvest and post-harvest agricultural handling in the food processing industries, due to its abundance and renewability, there has been a great deal of interest in utilizing lignocellulosic waste for the production and recovery of many value-added products [11-13]&#xD;
&#xD;
Classification of Agricultural Wastes&#xD;
&#xD;
Nibedita et al [14] pointed out some major agro wastes as the most favourable feed stocks for bioethanol production due to their availability throughout the year especially wheat straw and corn stover which is produced mainly at Asia and North America respectively. Lignocellulosic materials are renewable, low cost and are abundantly available. It includes Agricultural residues (wheat straw, corn Stover), municipal solid waste and forestry woody feedstock etc. &#xD;
&#xD;
Wheat Straw&#xD;
&#xD;
Among the agricultural residues, wheat straw is the largest biomass feedstock in Europe. About 21% of the world&#x2019;s food depends on the wheat crop. Hence, wheat straw would serve as a great potential feedstock for production of ethanol in 21st century. &#xA0;Like other biomass that has lignocellulosic constituents, it is composed of lignin, hemicellulose and cellulose. [15, 16]&#xD;
&#xD;
Corn Stover&#xD;
&#xD;
This is what remains on the ground after maize has been harvested. This raw material is abundantly available and demands no further investment in biomass, although not all of the corn Stover can be removed - 30% of it must be left on the ground to prevent erosion (by facilitating water infiltration and reducing evaporation), and as the main source of soil organic carbon (SOC) in order to preserve the soil&#x2019;s productivity. Corn Stover contains polymeric hemicellulose and cellulose, but their biodegradability by glycosidase is strongly inhibited by a small quantity (12-15%) of lignin. [15, 16]&#xD;
&#xD;
Municipal Solid Waste (MSW)&#xD;
&#xD;
Bioethanol production from food and vegetable industries is regarded more than other waste, for instance, fruit peels like orange, mango, banana, pineapple etc. Depending on a particular area determines the kind of waste generated, hence major waste in municipal areas consists of fruit waste, gardening waste, synthetic polymers, metals etc. [17, 18]&#xD;
&#xD;
Forestry Woody Feed Stock&#xD;
&#xD;
Fast growing short rotation forest trees can play an important role as feedstock for bioenergy production. However, forest is unevenly distributed.&#xA0; Forest play important environmental role in preservation of marginal land and reducing CO2 levels in the atmosphere. Forest woody feedstock account for approximately 370 million tons per year of lignocellulosic biomass in the US [20], other countries rich in forest are for example, Canada, the Russian Federation, Brazil, and China. Together, these countries account for more than half of the total forest area worldwide. Sources of woody materials include residues left in natural forest, forestry wastes, such as sawdust from sawmills, wood chips and branches from dead trees, and cultivated short rotation energy forest plantations utilizing several fast growing tree species. There are two types of woody materials, softwoods, or hardwoods. Softwoods originate from conifers and gymnosperm trees.&#xD;
&#xD;
Unlike hardwoods, softwoods possess lower densities and grow faster. These trees comprise of evergreen species such as pine, cedar, spruce, cypress, fire, hemlock, and redwood. Hardwoods are mainly found in the Northern hemisphere and include trees such as poplar, willow, oak, cottonwood, and aspen. In the US, hardwood species account for over 40 % of the trees. An advantage of woody biomass over agricultural plants is the flexibility in harvesting times as they do not depend on seasonality. Trees also contain less ash compared to crops and are of higher density, due to the thick secondary wall, which makes their transportation more economical [19-21].&#xD;
&#xD;
Conversion of Agricultural Waste to Ethanol&#xD;
&#xD;
In the last two decades, many researchers have worked on the conversion of lignocellulosic materials to ethanol extensively and came up with the conversion processes which include [22-24]. &#xA0;&#xD;
&#xD;
Hydrolysis of Cellulose in the Lignocellulosic Materials &#xD;
&#xD;
&#xA0;Cellulose can be hydrolysed using acid hydrolysis which is a traditional method and enzymatic hydrolysis (the current state of art method). Enzymatic hydrolysis is preferred to acid hydrolysis because it runs at a lower temperature, higher conversion and environmentally friendly, hence most recent research has focused on it. &#xD;
&#xD;
The hydrolysis is usually catalyzed by cellulase enzymes, cellulase enzyme depolymerize cellulose into fermentable sugars, cellulase synthesized by fungi and bacteria work together to degrade cellulose. [25]. Fermentation of Suger to Ethanol&#xD;
&#xD;
The best known microorganisms for ethanol production from hexoses are the yeast Sacchamyces cerevisiae and the bacterium Zymomonas mobilis offering high ethanol yields (90&#x2013;97% of the theoretical) and high ethanol tolerance up to ca. 10% (w/v) in fermentation medium. &#xD;
&#xD;
.[26,27]&#xD;
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Pretreatment Technologies for Agricultural Waste&#xD;
&#xD;
Within the context of production of fuels from biomass, pretreatment has come to interpret processes by which cellulosic biomass is made subsidiary to the action of hydrolytic enzymes. All naturally occurring, and most refined, cellulosic materials require pretreatment to become accessible to the enzymes that mediate hydrolysis. Typically, hydrolysis yields in the absence of pretreatment are less than 20% of theoretical yields, whereas yields after pretreatment often exceed 90% of theoretical. The limited effectiveness of current enzymatic processes on softwoods is thought to be due to the relative difficulty of pretreating these materials. [28]&#xD;
&#xD;
Pretreatment must meet the following requirements:&#xD;
&#xD;
&#xD;
	Destroy lignin shell protecting cellulose and hemicellulose&#xD;
	Decrease crystallinity of cellulose&#xD;
	Increase porosity&#xD;
	Must break this shell for enzyme to access substrate (sugar) [28].&#xD;
&#xD;
&#xD;
Pretreatments are roughly classi?ed into physical, chemical and biological processes.&#xD;
&#xD;
&#xA0;Physical Pretreatment&#xD;
&#xD;
The ?rst step in using wheat straw for ethanol production is size reduction through milling, grinding or chipping which can improve the efficiency of downstream processing. However, use of very small particles may not be desirable due to higher energy consumption in milling stage as well as imposing negative effect on the subsequent pretreatment method. Initial and ultimate particle size, moisture content and material properties are among variables that in?uence both energy consumption and the effectiveness of subsequent processing [29]. &#xD;
&#xD;
Physico-Chemical Pretreatment&#xD;
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Liquid hot water (LHW), steam explosion (SE) and ammonia ?ber explosion (AFEX) are among physico-chemical methods investigated for pretreatment of wheat straw further illustrated below&#xD;
&#xD;
Type-&#xA0; Steam-explosion&#xD;
&#xD;
Conditions-&#xA0;&#xA0;&#xA0; Pressure= 2.5-7 MPa.&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0; Temperature=&#xA0; 180-280oC&#xD;
&#xD;
Advantages&#xD;
&#xD;
&#xD;
	Well known and already used&#xD;
	high yields&#xD;
	no corrosion problems&#xD;
	undesired side products possible&#xD;
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&#xD;
Disadvantages&#xD;
&#xD;
&#xD;
	High energy demand&#xD;
&#xD;
&#xD;
&#xA0;&#xD;
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Type-&#xA0; Liquid Hot Water&#xD;
&#xD;
Condition-&#xA0;&#xA0;&#xA0;&#xA0;&#xA0; Temperature=&#xA0; 170-230oC&#xD;
&#xD;
Advantages&#xD;
&#xD;
&#xD;
	High yields&#xD;
	Less side products than in steam explosion&#xD;
	No corrosion problems&#xD;
&#xD;
&#xD;
Type-&#xA0; CO2 Explosion&#xD;
&#xD;
Condition-&#xA0;&#xA0;&#xA0;&#xA0;&#xA0; Pressure is greater than 7.3 MPa. Temperature is greater than 31.1oC. &#xD;
&#xD;
Advantages&#xD;
&#xD;
&#xD;
	Low environmental impact&#xD;
	Disadvantages&#xD;
	High cost expected&#xD;
&#xD;
&#xD;
Type- Ammonia Fibre Explosion&#xD;
&#xD;
Conditions-&#xA0;&#xA0;&#xA0;&#xA0; Temperature- 90-100oC&#xD;
&#xD;
Advantages&#xD;
&#xD;
&#xD;
	Media recoverable&#xD;
	Low inhibitor formation&#xD;
&#xD;
&#xD;
Disadvantages&#xD;
&#xD;
&#xD;
	Environmental issues due to ammonia&#xA0;&#xA0; [29,30]&#xD;
&#xD;
&#xD;
Chemical Pretreatment&#xD;
&#xD;
Chemical pretreatment for agricultural waste employ different chemicals such as acids, alkalis, and oxidizing agents e.g. peroxide and ozone. Among these methods, dilute acid pretreatment using H2SO4 is the most-widely used method. Depending on the type of chemical used, pretreatment could have different effects on lignocellulose structural components. Alkaline pretreatment, ozonolysis, &#xA0;peroxide and wet oxidation pretreatments are more effective in lignin removal whereas dilute acid pretreatment is more efficient in hemicellulose solubilization. Acid hydrolysis using inorganic acids such as H2SO4 have been used for pretreatment of agriculture waste to improve downstream enzymatic hydrolysis. Alkaline process is based on utilization of dilute bases in pretreatment of lignocellulosic feedstock. Using ooxidizing agents in Alkaline/oxidative pretreatment an oxidizing compound such as hydrogen peroxide (H2O2) or peracetic acid (C2H4O3) is used in combination with an alkaline (e.g. NaOH) and it is usually carried out under mild temperature. This treatment is more effective in improving of crop residue digestibility compared with NaOH treatment alone. In Ozonolysis, ozone is used to solubilise lignin and a small fraction of hemi- Cellulose from wheat straw. [31]&#xD;
&#xD;
Biological Pretreatment&#xD;
&#xD;
Biological pretreatment comprises of using microorganisms such as brown-, white-, and soft-rot fungi for selective degradation of lignin and hemicellulose among which white-rot fungi seems to be the most effective microorganism.&#xD;
&#xD;
The pretreatment types are illustrated further-&#xD;
&#xD;
Pretreatment Type- fungi treatment wit fungi&#xD;
&#xD;
Organisms Involved- white rot fungi, brown rot fungi, soft rot fungi&#xD;
&#xD;
Advantages&#xD;
&#xD;
&#xD;
	No chemicals required&#xD;
	Mild environment conditions&#xD;
	Low energy requirements&#xD;
&#xD;
&#xD;
Disadvantages&#xD;
&#xD;
Slow conversion&#xD;
&#xD;
Pretreatment Type- bacteria&#xD;
&#xD;
Organism Involved-&#xA0; Sphingomonas paucimobilis, Baillus circulans&#xD;
&#xD;
Advantages&#xD;
&#xD;
&#xD;
	No Chemicals Required&#xD;
	Mild Environment Conditions&#xD;
	Low Energy Requirements&#xD;
&#xD;
&#xD;
&#xA0;&#xD;
&#xD;
Disadvantages&#xD;
&#xD;
&#xD;
	Slow conversion [30]&#xD;
&#xD;
&#xD;
Challenges &#xD;
&#xD;
Currently researchers are looking for possible alternative fuels from cheap sources like agricultural wastes, this is faced with serious challenge, it is easier to produce bioethanol from energy crops, but it is not economically viable since the energy crops are consumed as food, during pre-treatment process, some inhibitory compounds like weak acids from derivatives and phenolic compounds inhibits the subsequent process of saccharification and fermentation. These compounds are yield limiting which ultimately affects the cost of whole process and now become a big challenge.&#xD;
&#xD;
This high price is because of some technological impediments encountered in all different steps of the process. Pretreatment is estimated to account for 33% of the total cost. The current leading pretreatment methods for lignocellulosic materials are capital intensive, also maintaining a stable performance of the genetically engineered yeasts in commercial scale fermentation operations, developing more efficient pretreatment technologies for lignocellulosic biomass, and integrating the optimal components into economic ethanol production systems.&#xD;
&#xD;
Also on report, that global demand for food and for transportation fuels is expected to increase more than 50 times, so there is a great need for renewable energy supplies that do not compete with food supply. Biofuels produced from agricultural residues such as underutilized cellulosic materials are likely to be more useful and economical feasible [19].&#xD;
&#xD;
Hence&#xA0;&#xA0; it is very important to control the production of these compounds, review the cost of the pretreatment process and encourage the use of agricultural waste. [32]&#xD;
&#xD;
Conclusion&#xD;
&#xD;
It has been proven that conversion of agricultural wastes to bioethanol has paved way for underutilised resources and encouraged environmental sustainability, hence ethanol-from-cellulose (EFC) holds great potential due to the widespread availability, abundance, and relatively low cost of cellulosic materials biomass resources, nevertheless biological pretreatments should be encouraged because it is &#xA0;safe, environmentally friendly and less energy intensive compared to other pretreatment methods. &#xD;
&#xD;
Acknowledgement&#xD;
&#xD;
Authors acknowledge the immense help received from the scholars whose articles are cited and included in references of this manuscript. The authors are also grateful to authors/editors/publishers of all those articles, journals and books from where the literature for this article has been reviewed and discussed.&#xD;
</Fulltext><FulltextLanguage>English</FulltextLanguage><URLs><Abstract>http://ijcrr.com/abstract.php?article_id=259</Abstract><Fulltext>http://ijcrr.com/article_html.php?did=259</Fulltext></URLs><References>1 Koshy, J., Nambisan, P. (2012) Pretreatment of Agricultural waste with pleurotus sp for&#xA0;&#xA0; ethanol&#xA0; production.&#xA0; International journal of plant, animal, and enviromental sciences. 2&#xA0;:2&#xD;
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25 McMillan, J.D., (1994). Pretreatment of lignocellulosic biomass. In: Himmel, M.E., Baker, J.O., Overend, R.P. (Eds.), Enzymatic Conversion of Biomass for Fuels Production. American Chemical Society, Washington, DC, pp. 292&#x2013;324.&#xD;
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28 Shahabaldin, R., Mohd Fadhil, M. D., Shaza E. M., Hesam, K.,and Farzaneh S. M., (2012). A bioethanol from cellulosic materials. International conference on environment .&#xD;
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29 Saini, J.K, Saini, R., Tewari, L (2015) Lignocellulosic agriculture wastes and biomass feedstocks for second generation bioethanol production&#xA0;: concepts and recent development. 3 Biotech. 5&#xA0;: 337-353.&#xD;
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31 Talebnia, F., Karakashev, D., Angelidaki, L (2009) Prodcution of bioethanol from wheat straw&#xA0;: and overview on pretreatment, hydrolysis and fermentation. Bioresources technology 101:4744-4753&#xD;
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</References></Article></ArticleSet><ArticleSet><Article><Journal><PublisherName>Radiance Research Academy</PublisherName><JournalTitle>International Journal of Current Research and Review</JournalTitle><PISSN>2231-2196</PISSN><EISSN>0975-5241</EISSN><Volume>8</Volume><Issue>19</Issue><IssueLanguage>English</IssueLanguage><SpecialIssue>N</SpecialIssue><PubDate><Year>-0001</Year><Month>November</Month><Day>30</Day></PubDate></Journal><ArticleType>Healthcare</ArticleType><ArticleTitle>ASSESSMENT OF SALIVARY ENZYMES-ALANINE AMINOPEPTIDASE(ALAP) AND DIPEPTIDYL PEPTIDASE IV (DPP IV) IN PATIENTS WITH CHRONIC PERIODONTITIS&#xD;
</ArticleTitle><ArticleLanguage>English</ArticleLanguage><FirstPage>06</FirstPage><LastPage>11</LastPage><AuthorList><Author>S. Rajasekar</Author><AuthorLanguage>English</AuthorLanguage><Author> V. Ramasubramanian</Author><AuthorLanguage>English</AuthorLanguage><Author> Sethupathi</Author><AuthorLanguage>English</AuthorLanguage></AuthorList><Abstract>Introduction: Alanine Aminopeptidase (ALAP) and dipeptidylpeptidase (DPP IV) are proteolytic enzymes released in the periodontal tissues from leukocytes, host cells and microorganisms. Both enzymes play an important role in collagen degradation and destruction of periodontal tissues. Therefore, detection of these enzymes might be useful in the diagnosis of periodontal disease.&#xD;
Aim: To assess the salivary levels of ALAP and DPP IV in periodontally healthy and those with chronic Periodontitis and to correlate the enzyme levels with the severity of disease. A prospective comparative case control study was done on 60 systemically healthy patients in the age group of 25-55 and was divided into four groups with 15 patients in each as Periodontally healthy, Mild, Moderate and Severe Periodontitis. Methodology: Parameters like Plaque index, Gingival bleeding index, Probing pocket depth and clinical attachment loss were recorded at baseline and unstimulated whole saliva was collected from each patient and quantified for levels of ALAP and DPP IV using spectroscopic quantification method. Statistical analysis used ANOVA, Students t test and Pearson&#x2019;s correlation coefficient analysis was used.&#xD;
Results: The salivary levels of ALAP and DPP IV were found to be higher in patients with Periodontitis than p healthy controls and were higher in severe (42.34&#xB1;8.96) (8.41&#xB1;1.44) and moderate group) (25.46&#xB1;6.79) (5.17&#xB1;1.31) than mild Periodontitis group) (15.83&#xB1;4.54) (3.69&#xB1;1.00) which was statistically significant.&#xD;
Discussion and Conclusion: ALAP and DPP IV were higher in saliva of patients with chronic Periodontitis and positive correlation existed between the levels of these enzymes with the severity of Periodontitis.&#xD;
</Abstract><AbstractLanguage>English</AbstractLanguage><Keywords>Alanine aminopeptidase (ALAP), Dipeptidylpeptidase IV (DPP IV), Saliva, Periodontitis</Keywords><Fulltext>INTRODUCTION&#xD;
&#xD;
Periodontitis is a poly microbial infectious disease affecting the supporting tissues of the teeth and is a major cause of tooth loss in adults. Periodontal destruction probably results from the action of various toxic products released from specific pathogenic sub gingival plaque bacteria as well as from the host responses elicited against bacteria and their products.1&#xD;
&#xD;
&#xA0;Bacterial virulence factors either result in direct degradation of host tissues or cause the release of biologic mediators from the host tissue cells that lead to host tissue destruction. Mediators produced as a part of the host response that contribute to tissue destruction include proteinases, cytokines and prostaglandins. Another important class of molecules in tissue destruction is the variety of enzymes produced by Periodontal microorganisms such as collagen degrading enzymes, elastase like enzymes, trypsin like proteases, amino peptidases and dipeptidylpeptidases.2&#xD;
&#xD;
&#xA0;Saliva is an important physiologic fluid that contains a highly complex mixture of substances. Over the last few years salivary diagnostics have received increasing attention. Saliva contains a variety of enzymes including esterases, proteinases, amino peptidases etc, synthesized and secreted by host cells and bacteria.3&#xD;
&#xD;
Amino peptidase is a zinc dependent enzyme produced and secreted by glands of small intestine. It helps the enzymatic digestion of proteins.&#xA0; Dipeptidyl peptidase IV (DPP IV) also known as adenine deaminase complexing protein 2 or CD 26 is a protein that, in humans, is encoded by the DPP IV gene. This enzyme is associated with immune regulation, signal transduction and apoptosis.4&#xD;
&#xD;
&#xA0;Alanine amino peptidase (ALAP) and Dipeptidyl peptidase IV (DPP IV) activity in whole saliva of patients with Periodontitis were found to be increased when compared with healthy individuals. Both these enzymes were found to be involved in degradation of collagen.5&#xD;
&#xD;
Thus the present study was aimed to assess the levels of Alanine amino peptidase (ALAP) and Dipeptidyl peptidase IV (DPP IV) enzymes in saliva of Periodontally healthy subjects and in patients with chronic Periodontitis and also to correlate the level of these enzymes with the severity of Periodontal disease.&#xD;
&#xD;
MATERIALS AND METHODS&#xD;
&#xD;
This study was conducted in the Department of Periodontics, Rajah Muthiah Dental College &amp; Hospital, Annamalai University. Tamil Nadu, India from July 2011 to March 2012. The study was approved by Institutional human ethical committee on 19-07-2011 and a written informed consent was obtained from all subjects participated in the study.&#xD;
&#xD;
Sample size determination &#xD;
&#xD;
Sample size was determined by power analysis procedure for ANOVA test based on pilot study done 3 months before in which mean and SD for all clinical and biochemical parameters were calculated and accordingly the required sample size for each group was 15&#xD;
&#xD;
&#xA0;A total of 60 systemically healthy subjects aged 25-55 were selected from the outpatient Department&#xA0; and divided in to four groups as ; Group 1 (Periodontally healthy) , Group 2 (Generalized chronic mild Periodontitis) , Group 3 (Generalized chronic moderate Periodontitis) and Group 4 (Generalized chronic severe Periodontitis) with 15 patients in each group. The following were the inclusion criteria for enrolment of study subjects.6&#xD;
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Group 1 ; Healthy Periodontium, absence of bleeding on probing, pockets and attachment loss.&#xD;
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Group 2;&#xA0; More than 30 % of sites with BoP , pockets &#x2265;4 mm / CAL 1-2 mm.&#xD;
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Group 3 ; More than 30% of sites with BoP , pockets &#x2265; 4mm / CAL 3-4 mm.&#xD;
&#xD;
Group 4 ; More than 30% of sites with BoP , pockets &#x2265; 5mm / CAL &#x2265; 5 mm.&#xD;
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Patients with known systemic diseases, smokers, pregnant and lactating women, those who were administered any systemic antibiotics, anti-inflammatory drugs or steroids in the preceding 3 months, and any form of periodontal therapy within the preceding 6 months were excluded from the study.&#xD;
&#xD;
A special proforma was prepared for each subject and clinical parameters like plaque index7 , Gingival bleeding index8, Probing pocket depth and Clinical attachment loss were recorded by a single examiner (SR). On the subsequent day un stimulated whole saliva was collected between 9 and 10 am by the second examiner (RS).The subject selection bias was avoided by intra examiner calibration prior to study and the investigator who collected and analysed the saliva was masked about the Group of patients as a dummy code number was given to the samples. &#xD;
&#xD;
The subjects were first asked to rinse their mouth with distilled water to remove the food debris and saliva was collected every 60 seconds to yield a total of 5 ml of each sample in a sterile plastic container. The samples were immediately transferred to the laboratory and were centrifuged at 3000 rpm for 15 minutes.&#xD;
&#xD;
The supernatant was collected and stored at -70&#xB0;c until enzymatic assay.&#xD;
&#xD;
Chemical reagents used for detection of ALAP&#xD;
&#xD;
&#xD;
	L-alanyl-b-napthylamide (1mmol)&#xD;
	Phosphate buffer (10 mmol)&#xD;
	Trichloro acetic acid (40% weight/volume)&#xD;
	Sodium nitrate (0.1 % weight/volume)&#xD;
	Ammonium sulfamate (0.5% weight/volume)&#xD;
	N-(1-naphthyl)-ethylenediamine dihydrochloride &#xA0;(0.05% weight/volume)&#xD;
&#xD;
&#xD;
Calculation formula; standard absorbent value= {optical density value&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0; optical density value} x 12.5x protein value&#xD;
&#xD;
&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0; With sample&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0; -&#xA0;&#xA0;&#xA0;&#xA0; without sample&#xA0;&#xA0;&#xA0; &#xD;
&#xD;
Chemical reagents used for detection of DPP IV&#xD;
&#xD;
&#xD;
	Glycyl-prolyl-p-nitroanilide (3Mm)&#xD;
	Sodium hydroxide (71 Mm)&#xD;
	Acetate buffer&#xD;
&#xD;
&#xD;
Calculation formula; optical density value (OD) &#x2022;1.058&#x2022;protein value &#xD;
&#xD;
Chemical reagents were prepared manually for the detection of ALAP and DPP IV. ALAP was assessed by spectroscopic assay measuring the extent of hydrolysis of L-alanyl b-naphthylamide.9&#xD;
&#xD;
DPP IV was assessed by spectroscopic quantification of glycyl-prolyl-p-nitroanilide hydrolysis.10&#xA0; &#xD;
&#xD;
Statistical analysis&#xD;
&#xD;
The data obtained were subjected to statistical analysis with systat 12 software programme using ANOVA, Student t test and Pearson correlation co efficient analysis and the results were plotted in the form of tables.&#xD;
&#xD;
RESULTS&#xD;
&#xD;
The Result was as following&#xD;
&#xD;
ANOVA test comparing age range of patients revealed no significant difference within the test groups (P-0.08)&#xD;
&#xD;
(Table 1 A &amp; 1B).&#xD;
&#xD;
ANOVA test comparing the ALAP enzyme levels (table 2) revealed significant difference in the groups studied (P= 0.01). Student t test process was applied to compare the levels of ALAP enzymes within the groups and it was observed that the enzyme level in saliva was significantly higher in test group than the controls and within the test group the severe Periodontitis group (Group 4) exhibited highest values (42.34&#xB1;8.96) followed by the moderate Periodontitis (Group 3) (25.46&#xB1;6.79) and mild Periodontitis (Group 2 ) (15.83&#xB1;4.54) and this was statistically significant (P- 0.01).&#xD;
&#xD;
ANOVA test comparing the DPP IV enzyme levels (table 3) revealed significant difference in the groups studied (P=0.01). Student t test process was applied to compare the levels of DPP IV enzymes within the groups and it was observed that the enzyme level in saliva was significantly higher in test group than the controls and within the test group the severe Periodontitis group (Group 4) exhibited highest values (8.41&#xB1;1.44) followed by moderate Periodontitis group (Group 3) (5.17&#xB1;1.31) and mild Periodontitis group (Group 2) (3.69&#xB1;1.00) and this was statistically significant (P- 0.01).&#xD;
&#xD;
DISCUSSION&#xD;
&#xD;
Chronic Periodontitis is an inflammatory condition affecting the tissues surrounding and supporting the teeth. As a result of inflammatory process, Proteolytic enzymes are released in the periodontal tissues from inflammatory cells. In addition, collagen degrading enzymes, trypsin like proteases, aminopeptidases and dipeptidylpeptidases may be produced by microorganisms. These proteolytic enzymes have an important role in periodontal destruction. Therefore, detection of these enzymes in saliva and GCF may help in periodontal diagnosis as well as to assess the progression of disease.&#xD;
&#xD;
Our study consisted of 60 subjects with age ranging from 25-55 years and the patients were divided into four group&#x2019;s namely Periodontally healthy controls (Group 1), Mild Periodontitis (Group 2), Moderate Periodontitis (Group 3) and Severe Periodontitis (Group 4) with 15 subjects in each group.&#xD;
&#xD;
To the best of our knowledge this is the first study attempting to assess and compare ALAP and DPP IV enzyme levels in saliva of patients with mild, moderate and severe Periodontitis with respect to healthy controls.&#xD;
&#xD;
&#xA0;The subjects enrolled in this study were in the age group between 25-55 years and the mean age of patients in the test group were 36.53, 40.47, and 43.13 for mild, moderate and severe Periodontitis respectively. In the present study we categorized the test group patients as mild, moderate and severe based on the stage of their disease and to the best of our knowledge this was the first such design and this helps to assess the progression of the disease with respect to the level of enzymes. Also saliva was chosen as a medium to study the enzyme activity as it has a good potential as diagnostic marker and the collection involves non invasive procedure. &#xD;
&#xD;
&#xA0;ALAP is a proteolytic enzyme that plays a role in peptide hydrolysis and collagen degradation. Periodontitis is known to be a chronic inflammatory process that is characterized by an immune response that results in the release of cytokines which trigger PMNs and macrophages. Macrophages have been found to produce ALAP, while cytokines to stimulate ALAP activity. Thus several factors might be responsible for the high salivary expression of ALAP in Periodontitis.&#xD;
&#xD;
The results of our study revealed significantly higher levels of ALAP enzyme in saliva of Periodontitis subjects when compared with healthy controls. This observation of our study was in accordance with Serenay Elgum et.al 20002.&#xD;
&#xD;
&#xA0;DPP IV is a peptidyl peptidase which seems to be involved in collagen degradation. Protease activity was found to be partly associated with inflammatory cells while DPP IV was localized in T lymphocytes and macrophages5.&#xD;
&#xD;
In our study we observed significantly higher levels of DPP IV in saliva of Periodontitis subjects than healthy controls (p=0.01) and this was similar to the findings of Serenay Elugum et.al 20002. Who in their study found elevated levels of DPP IV enzyme in saliva of chronic Periodontitis patients as compared to periodontally healthy controls.&#xD;
&#xD;
In studies done by Eley BM et al 11 and Abiko et al 12 the percentage of sites positive for P.gingivalis was positively correlated with DPP IV activity. However, we in our study did not correlate the enzyme activities with sites for P.gingivalis. &#xD;
&#xD;
In the present study we observed that the ALAP and DPP IV enzyme levels were greater as the severity of the disease increased. The enzyme levels were significantly higher in severe Periodontitis followed by moderate Periodontitis when compared to the mild Periodontitis group (p =0.01).&#xD;
&#xD;
Limitations&#xD;
&#xD;
The limitation of our study was not correlating the enzyme level with the microbial load and this along with long term interventional study can be a future direction of Research.&#xD;
&#xD;
CONCLUSION&#xD;
&#xD;
The following conclusions were drawn from the present study;&#xD;
&#xD;
&#xD;
	The salivary levels of enzymes Alanine amino peptidase (ALAP) and Dipeptidyl peptidase IV (DPP IV) were significantly higher in Periodontitis group as compared to healthy controls.&#xD;
	In Periodontitis patients, there was a positive correlation between the salivary levels of enzymes ALAP and DPP IV and the severity of the disease.&#xD;
&#xD;
&#xD;
The results of our study suggest that the ALAP and DPP IV enzyme levels in saliva could reflect the extent of disease progression and hence these enzymes can be very useful biomarkers in diagnosis and treatment planning. However, further longitudinal and interventional studies are needed to validate our findings.&#xD;
&#xD;
KEY POINTS &#xD;
&#xD;
Periodontitis is a chronic microbial and inflammatory disease. Various enzymes and cytokines are elevated in the tissues during the progression of the disease and these molecules are useful biomarkers of the disease. Saliva is a useful diagnostic tool for estimation of these biomarkers. In chronic inflammatory conditions like Periodontitis, proteolytic enzymes like ALAP and DPP IV are released from leukocytes and bacteria into the tissues and are responsible for collagen degradation. Estimation of these enzymes in saliva helps to assess the progression of the disease.&#xD;
&#xD;
Acknowledgement&#xD;
&#xD;
Authors acknowledge the immense help received from the scholars whose articles are cited and included in references of this manuscript. The authors are also grateful to authors/ editors/ publishers of all those articles, journals and books from where the literature for this article has been reviewed and discussed.&#xD;
&#xD;
The authors also thank the Professors Dr. R. Mythili and Dr. S. Senthil Kumar for their guidance and moral support.&#xD;
&#xD;
Source of funding- Nil&#xD;
&#xD;
Conflicts of interest- Nil&#xD;
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&#xA0;&#xD;
</Fulltext><FulltextLanguage>English</FulltextLanguage><URLs><Abstract>http://ijcrr.com/abstract.php?article_id=260</Abstract><Fulltext>http://ijcrr.com/article_html.php?did=260</Fulltext></URLs><References>1 Nurdan ozmeric. Advances in periodontal disease markers. Clinica chimica Acta 2004; 343:1-16.&#xD;
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2 Serenay Elgum, Nurdan ozmeric, Selda Demirtas. Alanine aminopeptidase and Dipeptidyl peptidase IV in saliva ; a possible role in periodontal disease. Clinica Chimica Acta 2000;298:187 &#xD;
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3 Edgar WM. Saliva, its secretion, composition and functions. British dental journal 1992;172:305&#xD;
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4 Wikipedia.com. Alanine aminopeptidases and Dipeptidyl peptidase IV.&#xD;
&#xD;
5 Piyamas Aemaimanan, Nison sattayasai, Nawarat waracaswapati, Waranuch pitiphet, Saengsome prajaneh.&#xA0; Alanine aminopeptidase and Dipeptidylpeptidase IV in saliva of chronic Periodontitis patients. J Periodontol 2009; 80:1809-1814.&#xD;
&#xD;
6 Michael G Newman, Henry H Takei, Fermin A Carranza. Clinical Periodontology 9th edition; &#xA0;WB Saunders company, The Curtis centre independence square west Philadelphia, PA 19106 2003&#xA0; ISBN 0-7216-8331-2, An imprint of Elsevier Science.p121-149 ,p190-192.&#xD;
&#xD;
7 Silness P, Loe H . Periodontal disease in pregnancy; correlation between oral hygiene and periodontal condition. Acta odontol scand 1964; 2: 121-135.&#xD;
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Ainamo J, Bay I. Problems and proposals for recording gingivitis and plaque. Int Dent J 1975; 25:229-235.&#xD;
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&#xA0;Sidorowiez, Wen Cheng Hsia, Olgomaslej zownir, Behal FJ. Multiple molecular forms of human alanine aminopeptidase ; Immunohistochemical properties. Clinica Chimica Acta 1980; 107: 245-256.&#xD;
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Toshikaru Nagatsu, Masami Hino, Hiroshi Fuyamada, Taro Hayakawa, Yasuo Nakagawa. New chromogenic substrates for X-prolyl dipeptidyl aminopeptidase. Analytical Biochemistry 1976; 74:466-477&#xD;
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Eley BM, Cox SW. Cathepsin, elastase, trypsin and dipeptidylpeptidase in GCF ; Correlations with clinical parameters in untreated chronic Periodontitis patients. J Periodont Research 1992; 27: 62-69&#xD;
&#xD;
Abiko Y, Hayakawa M, Murai S, Takiguchi H. Glycyl prolyl dipeptidyl aminopeptidase from Bacteroides gingivalis. J Dent Research 1985;64 :106-111&#xD;
</References></Article></ArticleSet><ArticleSet><Article><Journal><PublisherName>Radiance Research Academy</PublisherName><JournalTitle>International Journal of Current Research and Review</JournalTitle><PISSN>2231-2196</PISSN><EISSN>0975-5241</EISSN><Volume>8</Volume><Issue>19</Issue><IssueLanguage>English</IssueLanguage><SpecialIssue>N</SpecialIssue><PubDate><Year>-0001</Year><Month>November</Month><Day>30</Day></PubDate></Journal><ArticleType>Healthcare</ArticleType><ArticleTitle>IN-VITRO SUSCEPTIBILITY TO TIGECYCLINE IN MULTIDRUG RESISTANT BACTERIAL ISOLATES FROM A TERTIARY CARE HOSPITAL&#xD;
</ArticleTitle><ArticleLanguage>English</ArticleLanguage><FirstPage>12</FirstPage><LastPage>16</LastPage><AuthorList><Author>Kusuma G.R.</Author><AuthorLanguage>English</AuthorLanguage><Author> Tejashree A.</Author><AuthorLanguage>English</AuthorLanguage><Author> Vijay Kumar G.S.</Author><AuthorLanguage>English</AuthorLanguage></AuthorList><Abstract>Objective: The present study was conducted to evaluate the in vitro activity of tigecycline against a contemporary collection of multidrug resistant (MDR) bacterial isolates by disc diffusion and MIC by E-Test method.&#xD;
Methods: A total of 100 non repetitive clinically significant MDR bacterial isolates from urine, pus, sputum endotracheal aspirates, Skin and soft tissue and surgical site infection of patients in a tertiary care teaching hospital in Karnataka, south India from March 2013 to December 2013 were included in the study. MDR bacteria tested for Tigecycline susceptibility were: Methicillin resistant S.aureus (MRSA) (15), ESBL producing Escherichia coli (E.col) (15), Klebsiella pneumoniae (35) and MDR Acinetobacter species (35).&#xD;
Result: Tigecycline was found to be effective against all MRSA, MDR E.coli and Acinetobacter isolates by disc diffusion and E-test method. Among the selected K. pneumoniae isolates all were sensitive by disc diffusion and 34 (97.1%) were found sensitive with the MIC range 0.25- 1.5&#x3BC;g/ml, One (2.9%) isolate was found intermediate resistant with the MIC of 3&#x3BC;g/ml by E-test.&#xD;
Conclusion: To conclude, the present study showed that, tigecycline is a potent antimicrobial agent against MRSA, ESBL producing Enterobacteriaceae Acinetobacter species and disc diffusion is simple to perform, highly reproducible and inexpensive method to predict tigecycline resistance. It is also prudent to reserve tigecycline for life threatening infections.&#xD;
</Abstract><AbstractLanguage>English</AbstractLanguage><Keywords>Tigecycline, MDR, E-Test, India</Keywords><Fulltext>INTRODUCTION&#xD;
&#xD;
Antimicrobial resistance has been identified as one of the major challenges facing public health, as it has increased rates of morbidity, mortality and socioeconomic costs1.&#xD;
&#xD;
The rates of multiple drug resistance are increasing among Enterobacteriaceae, metallo beta lactamase [MBL] producing non fermenting&#xA0; gram negative bacilli and Gram-positive pathogens such as methicillin resistant Staphylococcus aureus [MRSA] vancomycin resistant enterococci [VRE] &#xA0;that commonly cause serious life-threatening diseases and present a &#xA0;challenge for clinicians by limiting the &#xA0;potentially active antimicrobial agents to treat. Thus, the development and evaluation of new antimicrobial agents that overcome existing mechanisms of resistance is urgently needed.2&#xA0; &#xD;
&#xD;
In this scenario, research has led to development of a new group of drugs called glycylcyclines, a broad spectrum tetracycline analogues that overcome the resistance mechanisms and the most promising compound being the tigecycline, a glycyclamido derivative of minocycline3&#xD;
&#xD;
Tigecycline [TGC] is the first of a new class of modified tetracycline antimicrobials known as glycylcyclines. It exerts its bacterostatic effect by binding to the bacterial 30S ribosome and inhibits protein biosynthesis, but its unique feature is its ability to evade the major determinants of tetracycline resistance, that provide ribosomal protection. Its structural modification is the addition of a 9-t-butyl-glycylamido side chain to the central skeleton of minocycline . This provides the drug with an expanded spectrum of activities, including those against susceptible and multidrug-resistant Gram-positive and Gram-negative organisms, anaerobes, and atypical Mycobacteria but tigecycline has poor activities against certain organisms, most importantly Pseudomonas spp. and Proteus spp. as they carry inherently encoded resistance-nodulation-division (RND) efflux pumps that confer decreased sensitivity.4&amp;5&#xD;
&#xD;
Tigecycline was approved in 2005 by the U.S. Food and Drug Administration (FDA) and in 2006 by the European Medicines Agency for the treatment of complicated skin and skin structure infections and complicated intra abdominal infections 6&#xD;
&#xD;
Thus the present study was conducted to evaluate the in vitro activity of tigecycline against a contemporary collection of multidrug resistant bacteria isolated from clinical specimens, by disc diffusion and MIC by E-Test method.&#xD;
&#xD;
Materials and Methods:&#xD;
&#xD;
This prospective study was conducted in the microbiology department, at JSS Hospital, Mysore a Tertiary Care Teaching Hospital in Karnataka, South India from March 2013 to December 2013.&#xA0; &#xD;
&#xD;
A total of 100 non repetitive clinically significant MDR bacterial isolates were included in the study. Susceptible bacteria, Pseudomonas spp. and Proteae were excluded from the study as tigecycline has decreased activity against Pseudomonas and Proteae.&#xD;
&#xD;
The specimens such as&#xA0; urine, pus, sputum and endotracheal aspirates ,swabs from skin and soft tissue and surgical site infection&#xA0; &#xA0;received for culture and sensitivity testing from various departments in our hospital were immediately processed and initial isolation , identification and antibiotic susceptibility testing &#xA0;was done according to standard recommended procedure &#xA0;in the clinical laboratory.7&#xD;
&#xD;
All Gram negative pathogens were tested for extended spectrum beta lactamase [ESB production by CLSI phenotypic confirmatory method using ceftazidime (CAZ) and ceftazidime +clavulinic acid (CAZ+clav) disc according to CLSI guidelines Acinetobacter species were tested for MBL production by imipenem-EDTA combined disk test11. Screening of MRSA was done by using cefoxitin (30&#x3BC;g) disc. Interpretation was done according to clinical laboratory standards institute [CLSI] guidelines8.&#xD;
&#xD;
MDR&#xA0; Gram negative bacterial isolates&#xA0; and MRSA randomly selected for tigecycline susceptibility testing&#xA0; by disc diffusion &amp; E &#x2013;test were&#xA0; MRSA (15), ESBL producing Escherichia coli [E.coli] (15), Klebsiella pneumonia (35) and MDR Acinetobacter species (35), both MBL and non MBL producers were included.&#xA0; &#xD;
&#xD;
Selected isolates were tested for tigecycline susceptibility by Kirby Bauer disc diffusion method using commercially available tigecycline (15&#x3BC;g) disc. [Hi media]. S.aureus strain 25923 and ATCC E.coli strain 25922 were used as control.7&amp;8.&#xD;
&#xD;
The minimum inhibitory concentration of tigecycline for all the selected MDR bacteria was done by E- Test method .The E-test strips were procured from Biomeriux SA, France, and the test was performed according to manufacturer&#x2019;s instructions. Since there were no CLSI recommended interpretative criteria for MIC of tigecycline, the US FDA breakpoints were used.For Enterobacteriaceae sensitive isolates were those with MIC &#x2264; 2&#x3BC;g/ml, and &#x2265; 19 mm zone size and resistance was defined as MIC &#x2265; 8 &#x3BC;g/ml and zone size &#x2264; 14 mm. For S. aureus MIC &#x2264; 0.5&#x3BC;g/ml and &#x2265; 19mm zone size was considered sensitive 9&#xD;
&#xD;
RESULTS&#xD;
&#xD;
&#xA0;All randomly selected MRSA [15] isolates for tigecycline susceptibility testing by disc diffusion &amp; E &#x2013;test were found susceptible to tigecycline by both methods. The MIC range by E-test was 0.125 &#x2013; 0.032&#x3BC;g/ml .The range of diameter of the zone of inhibition around tigecycline disc was 19mm -25mm.There was a gradual reduction of &#xA0;tigecycline zone diameter as the MICs for the isolates increased.&#xD;
&#xD;
All selected E.coli [15] and K.pneumoniae [35] isolates were ESBL producers and resistant to Amikacin , Gentamycin, Cephalosporins, Ciprofloxacin, Cotrimoxozole.&#xA0;&#xA0; Among K.pneumoniae isolates 30 were resistant to Piperacillin/tazobactam&#xA0; and&#xA0; 06 isolates&#xA0; were resistant to Imipenem.&#xD;
&#xD;
Susceptibility to tigecycline among E.coli isolates was found 100% by both methods. MIC range by E-test was 0.064 &#x2013; 0.25&#x3BC;g/ml. The diameter of the zone of inhibition around tigecycline disc was in the range of 21mm &#x2013; 25mm and there was correlation between MIC and disc diffusion.&#xD;
&#xD;
Among the selected K.pneumoniae isolates, 34(97.1%) were found sensitive by E-test with the MIC range 0.25- 1.5&#x3BC;g/ml. One isolate was found intermediate resistant with the MIC of 3&#x3BC;g/ml. &#xA0;All isolates were in the sensitive &#xA0;range 19mm &#x2013; 21mm by disc diffusion . &#xD;
&#xD;
Acinetobacter species [35] were resistant to Amikacin, Gentamycin, Tobramycin, Cefipime, Piperacillin/ tazobactam and Ciprofloxacin .11 isolates were resistant to Imipenem.&#xD;
&#xD;
By disc diffusion method all Acinetobacter species were in the sensitive range. The zone of inhibition remains between 19mm-24mm. All isolates were found to be sensitive with the MIC range between 1.5 &#x2013; 0.032 &#x3BC;g/ml by E-test.&#xD;
&#xD;
Discussion&#xD;
&#xD;
Tigecycline shows high potency against Gram-negative bacilli belonging to family Enterobacteriaceae in whom multi-drug resistant strains have emerged as important nosocomial pathogens. Tigecycline is also very active against non-fermentative GNB, such as&#xA0; Acinetobacter species. and tigecycline has promising microbiological, &#xA0;pharmacodynamics &amp; pharmacokinetic profile .Therefore it is considered as a good alternative to treat infections due to multidrug resistant organisms.10&#xD;
&#xD;
In our study tigecycline showed 100% activity against all, MRSA by a concentration of&#xA0; &#x2264;0.25 &#x3BC;g/ml of tigecycline&#xA0; with a zone of inhibition of&#xA0; &#x2265; 19mm. The results of our study were in concordance with study conducted by Bijayani Behra et al11, Rouchelle Tellis et al6, Manisha Mane et al13, Maria Souli et al12&#xD;
&#xD;
ESBLs are one of the most evolving mechanism of antibiotic resistance among the family Enterobacteriaceae &#xA0;&#xA0;and therapeutic options &#xA0;are limited.&#xA0; Although Carbapenems are the drug of choice in the treatment of infections due to ESBL producing strains of Enterobacteriaceae, the emergence and proliferation of bacteria resistant to this important group of drug is jeopardizing the use of carbapenems and &#xA0;&#xA0;options are limited to tigecycline, colistin and polymyxin 13&amp;14 . &#xD;
&#xD;
In our study tigecycline remains an important option against the management of &#xA0;E.coli infections by retaining 100% in vitro activity against &#xA0;E.coli isolates with the MIC90&#x2264;0.25. &#xB5;g/ml by &#xA0;E-test. All isolates showed zone of inhibition &#x2265; 19mm. the zone diameter remains within a range of 21mm- 25mm.and shows the correlation between E-test and disc diffusion. Similar results were found in studies conducted by Soham Gupta et al, Shanti. M et al15 , Anand Manoharan et al16,&#xA0; Rouchelle Tellis et al, Te-Din Huang et al17 ,Goran Kronvall et al18 .&#xD;
&#xD;
Among our selected&#xA0;&#xA0; K. pneumoniae isolates 34/35 (97.1%) were found sensitive with the MIC range 0.25- 1.5&#x3BC;g/ml. One isolate was found intermediate with the MIC of 3&#x3BC;g/ml&#xA0; by E-test. None were found resistant /intermediate by disc diffusion. All the isolates showed zone of inhibition &#x2265; 19mm. the zone diameter remains within a narrow range of 19mm- 21mm.Other studies by Shanthi.M et al 100%, Anand Manoharan et al,100% Simit Kumar et al19 100% Bijayini Behera et al 97% Soham Gupta&#xA0; et al20 85.7%&#xA0; also showed&#xA0; high in vitro activity of tigecycline against K.pneumoniae. In the study conducted by Subhash C. Arya2166% were found sensitive. It was also noted that in our study, increased MIC of 1-3&#xB5;g/ml in K.pneumoniae compared&#xA0; to E.coli with MIC90&#x2264; 0.25&#xB5;g/ml. Similar results with increased MIC were found by Soham Gupta et al, and Maria Souli et al.&#xD;
&#xD;
Break points for Tigecycline &#xA0;MIC and disc diffusion for Acinetobacter were not included &#xA0;in the CLSI guidelines. Therefore cut off values given for Enterobacteriaceae were used and all selected Acinetobacter species isolates were in the sensitive range. The zone of inhibition between 19 mm-24 mm. &#xA0;The MIC remains between 0.75 &#x2013; 0.032 &#x3BC;g/ml with MIC90 &#x2264;0.75 by&#xA0; E-test. It was observed that there was gradual reduction in the size of zone of inhibition as MIC increases .This was also observed by Bijayini Behera et al&#xA0; &#xA0;In our study, the E test correlated 100 percent with the inhibition zone diameters, which was in contrast to the findings of a study which was done by Behera et al.&#xA0; But, it was similar to the findings of a study which was done by Venezia et al22,Surapee Tiengrim A et al23.&#xD;
&#xD;
&#xA0;In our study Tigecycline remains as a good option for the management of MRSA, multidrug resistant &#xA0;E.coli , Klebsiella species and Acinetobacter infections &#xA0;by retaining 100% activity against these pathogens&#xA0;&#xD;
&#xD;
We carried out the in-vitro activity of tigecycline by disc diffusion and E test. By both methods all isolates were found to be sensitive except one Klebsiella isolate which was found to be intermediate by E-test and sensitive by disc diffusion. Thus we found no significant difference between these two methods. Disc diffusion method is simple to perform, highly reproducible and inexpensive while E test is though costly for routine use, it can be used to determine MIC.&#xD;
&#xD;
Tigecycline does not require dose adjustment in patients with impaired renal function and is conveniently administered every 12 h. It has a long terminal half-life and a large volume of distribution and has low potential for organ toxicity and drug-drug interactions. These properties make the use of this antibiotic relatively uncomplicated, but patients may develop moderate-to-severe nausea and vomiting during tigecycline therapy. It can be used as a life saving antimicrobial in polymicrobial infections due to Gram-positive and enteric Gram-negative bacteria.&#xD;
&#xD;
Conclusion &#xD;
&#xD;
&#xA0;The present study shows that, tigecycline is a potent antimicrobial agent against MRSA, ESBL producing Enterobacteriaceae &#xA0;and multi-drug resistant Acinetobacter baumannii and &#xA0;disc diffusion &#xA0;is simple to perform, highly reproducible and inexpensive method to predict tigecycline resistance. However, use of tigecycline needs to be strictly monitored to prevent development and dissemination of resistance against this one of the last available antimicrobial molecule and it is prudent to reserve tigecycline for life threatening infections. &#xD;
&#xD;
Acknowledgement&#xD;
&#xD;
Authors acknowledge the immense help received from the scholars whose articles are cited and included in references of this manuscript. The authors are also grateful to authors / editors / publishers of all those articles, &#xA0;journals and books from where the literature for this article has been reviewed and discussed. &#xD;
&#xD;
&#xD;
</Fulltext><FulltextLanguage>English</FulltextLanguage><URLs><Abstract>http://ijcrr.com/abstract.php?article_id=261</Abstract><Fulltext>http://ijcrr.com/article_html.php?did=261</Fulltext></URLs><References>&#xD;
	Cai Y, Wang R, Liang B, Nan B, and Liu Y.&#xA0; Systematic Review and Meta-Analysis of the Effectiveness and Safety of Tigecycline for Treatment of Infectious Disease. Antimicrobial agents and chemotherapy 2011: 1162&#x2013;1172. &#xD;
	&#xA0;Kelesidis T, Drosos E. poulos K, Kelesidis. &#xA0;I and Matthew E. &#xA0;Tigecycline for the treatment of multidrug-resistant Enterobacteriaceae: a systematic review of the evidence from microbilogical and clinical studies. Journal of Antimicrobial Chemotherapy (2008); &#xA0;62 :895&#x2013;904.&#xD;
	Gupta K, Kaushal S, Chopra S. C. Tigecycline: A novel glycil cycline antibiotic. Indian J Pharmacol &#xA0;2006 June , 38 ; Issue 3 : 218-19&#xA0;&#xA0; &#xD;
	Rossi F, Andreazzi D .Overview of Tigecycline and Its Role in the Era of Antibiotic Resistance The Brazilian Journal of Infectious Diseases 2006; 10(3):203-216.&#xD;
	Anton YP, Adams J,. Paterson DL. Tigecycline Efflux as a Mechanism for Non susceptibility in Acinetobacter baumannii._Antimicrobial Agents And Chemotherapy, June 2007: 2065&#x2013;2069&#xD;
	Tellis R, Rao S, Lobo A Dept. of Microbiology, An in-vitro study of tigecycline&#xA0; susceptibility among multidrug resistant bacteria in a tertiary care hospital . International Journal of Biomedical Research&#xA0; IJBR 2012 March; 3 [04]: 192?195&#xD;
	Winn C, Allen D, Janda M, Koneman WE, Procap W. Schreckenberger C, Woods L Koneman&#x2019;s color atlas and text book of diagnostic Microbiology. The role of the Microbiology Laboratory in the diagnosis of infectious diseases: Guidelines to practice and management.6th edition New York :Lippncott Williams and Wilkins:2006.p 2-61&#xD;
	Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing: CLSI document M100-S22. Wayne, PA: Clinical and Laboratory Standards Institute, 2012&#xD;
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	Wyeth Pharmaceuticals. Tygacil (tigecycline) for injection [Package insert]. 2005. Wyeth Pharmaceuticals Inc., Philadelphia, PA. NDA 21-821/S-016 &#xD;
	Daryl J, HobanaT, &#xA0;Bouchillona SK, Brian M, &#xA0;Jack J, Johnsona L, Michael JD .In vitro activity of tigecycline against 6792 Gram-negative and Gram-positive clinical isolates from the global Tigecycline Evaluation and Surveillance Trial (TEST Program, 2004) Diagnostic Microbiology and Infectious Disease ;52 (2005): 215&#x2013;227&#xD;
	&#xA0;Behera B, &#xA0;Das A, Mathur P, &#xA0;Kapil A, &#xA0;Gadepalli R , Dhawan D. Tigecycline susceptibility report from an Indian tertiary care hospital. Indian J Med Res 129, April 2009: 446-450&#xD;
	Souli M ,Flora V, Koratzanis K E, Antoniadou A, GiannitsiotiE, &#xA0;Evangelopoulou P, &#xA0;Kannavaki S and Giamarellou&#xA0; H. In Vitro Activity of Tigecycline against Multiple-Drug-Resistant, Including Pan-Resistant, Gram-Negative and Gram-Positive Clinical Isolates from Greek Hospitals. Antimicrobial Agents And Chemotherapy, Sept. 2006: 3166&#x2013;3169&#xD;
	Manisha M, Nita G. In Vitro Activity of Tigecycline against Methicillin Resistant Staphylococcus aureus (MRSA) and Vancomycin resistant Enterococci (VRE) As Evaluated by Disc diffusion method and E-test .International Journal of Collaborative Research on Internal Medicine &amp; Public Health (2013);Vol. 5 No. 8: 567&#xD;
	Priya D, Varsha G, Shivani G, Jagdish C, Phenotypic method for differentiation of carbapenemases in Enterobacteriaceae: Study from north India ,Indian&#xA0; jornal of&#xA0; Pathology&#xA0; and&#xA0; Microbiology&#xA0; july - september 2012; 55(3 ) ;357-60&#xD;
	Shanthi M, Uma S.&#xA0; Invitro&#xA0; Activity of&#xA0; Tigecycline&#xA0; Against GramPositive and Gram Negative Isolates in a Tertiary Care&#xA0; Hospital . Journal of Clinical and Diagnostic Research.2011 December ;5(8):1559-1563&#xD;
	Anand M, Saradiya C, S.Madan, Dilip M. Evaluation of the tigecycline activity in clinical isolates among Indian medical centre. Indian journal of Pathology and Microbiology. 53(4),Oct-Dec-2010&#xD;
	Yen-Hsu C, Po-Liang L Cheng H H. Trends in the Susceptibility of Clinically Important Resistant Bacteria to Tigecycline: Results from the Tigecycline In Vitro Surveillance in Taiwan Study, 2006 to 2010Antimicrobial Agents and Chemotherapy : 1452&#x2013;1457.&#xD;
	Goran K, Inga K, Mats W, Mikael S. Epidemiological MIC cut-off values for tigecycline calculated from Etest MIC values using normalized resistance interpretation. &#xA0;Journal of Antimicrobial Chemotherapy (2006) 57, 498&#x2013;505&#xD;
	Simit K, Maitreyi B, Soma M, Nupur P, Tapashi G, Manas B, Parthajit B. Tigecycline activity against metallo?beta?lactamase producing bacteria. Avicenna Journal of Medicine / Oct-Dec 2013; 3 Issue 4&#xD;
	Soham G, &#xA0;Aruna C, Savitha N, Mary D and Muralidharan S. In vitro activity of tigecycline against multidrug-resistant Gram-negative blood culture isolates from critically ill patients. J Antimicrob Chemother 2012&#xD;
	Subhash C.A, Nirmala A .Tigecycline in-vitro susceptibility and antibiotics fitness for gram negative pathogens. &#xA0;MED J.2008;vol.29(11);1558-1560&#xD;
	&#xA0;Navon-Venezia S, Azita L, and Yehuda C. High tigecycline resistance in multidrug-resistantAcinetobacter baumannii . Journal of Antimicrobial Chemotherapy 2007 ;59: 772&#x2013;774&#xD;
	Surapee T,&#xA0; Chanwit T, Visanu T.In Vitro Activity of Tigecycline against Clinical Isolates of Multidrug-Resistant Acinetobacter baumannii in Siriraj Hospital, Thailand.J Med Assoc Thai 2006; 89 (Suppl 5): S102-5 &#xD;
&#xD;
</References></Article></ArticleSet><ArticleSet><Article><Journal><PublisherName>Radiance Research Academy</PublisherName><JournalTitle>International Journal of Current Research and Review</JournalTitle><PISSN>2231-2196</PISSN><EISSN>0975-5241</EISSN><Volume>8</Volume><Issue>19</Issue><IssueLanguage>English</IssueLanguage><SpecialIssue>N</SpecialIssue><PubDate><Year>-0001</Year><Month>November</Month><Day>30</Day></PubDate></Journal><ArticleType>Healthcare</ArticleType><ArticleTitle>SEROPOSITIVITY OF HEPATITIS B VIRUS AND HEPATITIS C VIRUS AMONG BLOOD DONORS AT A TERTIARY CARE HOSPITAL IN KASHMIR: A TEN-YEAR STUDY&#xD;
</ArticleTitle><ArticleLanguage>English</ArticleLanguage><FirstPage>17</FirstPage><LastPage>20</LastPage><AuthorList><Author>Mohammad Zubair Qureshi</Author><AuthorLanguage>English</AuthorLanguage><Author> Humaira Bashir</Author><AuthorLanguage>English</AuthorLanguage><Author> Peer Maroof</Author><AuthorLanguage>English</AuthorLanguage><Author> Samoon Jeelani</Author><AuthorLanguage>English</AuthorLanguage><Author> Nazia Bhat</Author><AuthorLanguage>English</AuthorLanguage><Author> Fehmeeda Akhter</Author><AuthorLanguage>English</AuthorLanguage></AuthorList><Abstract>Objectives: Hepatitis B virus (HBV) and Hepatitis C virus (HCV) are important transfusion-transmissible infections. This study was performed to assess the Seropositivity of HBV and HCV Seropositivity among blood donors at a Tertiary Care Hospital based blood bank at SKIMS, Kashmir.&#xD;
Materials and Methods: The blood donation records over 10 years from Jan- 2003 to Dec-2012 were reviewed, retrospectively, for the seropositivity and yearly trends of HBV and HCV.&#xD;
Results: A total of 97427 donations were received. The overall number of HBV seropositive donations was 469 and that for HCV was 194, with the seroprevalence rates of 0.48% for hepatitis B surface antigen (HBsAg) and 0.20% for HCV. The seropositivity rate was higher in the replacement donors compared to the voluntary donors and 0% in repeat voluntary donors. The annual rates showed decreasing trends for both HBsAg and HCV.&#xD;
Conclusion: The seropositivity of viral markers was lower in our study as compared with studies from other parts of the country. It was significantly lower in voluntary donors compared to replacement donors and repeat voluntary donors were found to be much safer.&#xD;
</Abstract><AbstractLanguage>English</AbstractLanguage><Keywords>Hepatitis B virus, Hepatitis C virus, Seropositivity, Hepatitis B Surface Antigen</Keywords><Fulltext>INTRODUCTION&#xD;
&#xD;
Hepatitis B virus (HBV) and Hepatitis C virus (HCV) are worldwide healthcare problems, especially in developing countries. It is estimated that approximately one third and 3% of the global population has been infected with HBV and HCV, respectively.1, 2 Viral hepatitis, caused by HBV and HCV is one of the common transmissible cause of chronic liver morbidity and mortality. The main modes of transmission include blood transfusion, unsafe sex, use of parental drugs, and the vertical transmission from mother to child. Blood transfusion contribute to the ever widening pool of these infection, wherein even an asymptomatic person (carrier) can transmit the infection.3 &#xD;
&#xD;
Initially, progression of blood-borne infections led the scientists to design method of prevention. Characterization &#xA0;of &#xA0;transfusion-transmitted pathogens, development of strategies to measure infection &#xA0;rates in blood donors as well as in recipient populations, characterization of the early viremia, and &#xA0;implementation of more restrictive donor eligibility criteria and increasingly sensitive laboratory techniques for donor screening have made blood supplies be safe in developed countries.4,5 In developing countries, the prevention and determination of blood borne infections have not been well improved yet. So, transfusion as a main way for blood-borne infections continues to cause serious problems in developing countries and less serious in developed countries.6&#xD;
&#xD;
Screening and assessment of blood donors not only alleviates the risk of transmission through infected blood products, but also gives an idea about the prevalence rates of the infections in the community. This cross sectional observational study was carried out in the department of Transfusion Medicine, SKIMS (Srinagar, Jammu and Kashmir, India) a Tertiary Care Hospital. This study was aimed to assess the seropositivity of the markers of HBV and HCV in the blood donors at the blood bank over the period of 10 years. &#xD;
&#xD;
MATERIALS AND METHODS&#xD;
&#xD;
The blood donation records over 10 years (2003-2012) were reviewed retrospectively, for a total of 97427 donors, ranging from 18-60 years age. The hospital has a policy of using a standard blood donor screening questionnaire and excluding the high-risk donors. Replacement donations (from family, relatives and friends of the patient) accounted for the majority of the donations while the voluntary donors formed the rest.&#xD;
&#xD;
Third generation ELISA kits were used for detection of HBV and HCV. HBsAg ELISA Test kit, manufactured by In Tec Products, INC. The advanced HBsAg test kit is an enzyme-linked immunosorbent assay (ELISA) for the qualitative determination of Hepatitis B Surface Antigen (HBsAg) in human serum or plasma. HCV detection was done Using Zhongshan HCV ELISA kit, manufactured by Zhongshan Bio-tech Co, Ltd. This test is enzyme-linked immunosorbent assay (ELISA) for the qualitative determination of antibody to Hepatitis C virus in human plasma. All the donors who turned out to be reactive for HBsAg and HCV initially were subjected to reconfirmation by testing them again twice on consecutive days. The blood that was still seropositive was discarded. All the donors who turned out to be positive for viral markers were notified and counselled about this via telephone/mobile calls or letters and were requested to come to our hospital for further medical evaluation and possible treatment.&#xD;
&#xD;
Data was collected, coded, entered and analysed using Statistical Package for Social Sciences (SPSS), Version 17 and Minitab Packages. Data was expressed as percentage and the respective comparisons were made by Chi-square test. Seropositivity rates were calculated and a p value of less than 0.05 was taken to be significant.&#xD;
&#xD;
RESULTS&#xD;
&#xD;
&#xA0;Total of 97427 donations were received over a period of 10 years (Jan 2003- Dec 2012). Of total donations 95258 (97.8%) were males and 2169 (2.2%) were females. Maximum donors 46181 (47.4%) were in the age group of 18-30 years, 25234 (25.9%) were between 31-40 years, 16757 (17.2%) were between 41-50 years and 9255 (9.5%) were between 51-60 years. The replacement donations comprised 94406 (96.9%) while voluntary donations were 3021 (3.1%) of total donations. First time voluntary donors, which had no history of previous voluntary blood donation were 2018 (66.8%) and repeat voluntary donors which had history of one or more previous voluntary blood donations were 1003 (33.2%).&#xD;
&#xD;
The number of HBsAg seropositive donations was 469 and that for HCV was 194, with the Seropositivity rates of 0.48% for HBsAg and 0.20% for HCV. The annual Seropositivity and their trends over 10 years are shown in Figure 1.&#xD;
&#xD;
&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0; The Seropositivity of HBsAg and HCV on the basis of Gender, Age, and Type of donation and H/O previous voluntary donation is depicted in Table1.&#xD;
&#xD;
DISCUSSION:&#xD;
&#xD;
Every blood transfusion carries a potential risk for transmissible disease.7 This reflects the need and importance of the mandatory screening of the above infectious markers in blood donations. The prevalence of infection among blood donors has been used as a surrogate marker for the prevalence of infection in the population at large. Although certain pitfalls, like the exclusion of people below 18 years and over 60 years and low number of female donors have been cited, it is still an important indicator of the disease burden. &#xD;
&#xD;
HBV and HCV are important transfusion transmissible diseases. The HBsAg testing on the donated blood has been done for several years now, but in our country, compulsory testing for HCV came into full effect only after 2002.8 HBV is one of the major global public health problems. HBV infection is the 10th leading cause of death and HBV-related hepatocellular carcinoma is the fifth most frequent cancer worldwide. Approximately 30% of the world&#x2019;s population has serologic evidence of current or past infection with HBV. India lies in an intermediate HBV endemicity zone and the number of HBV carriers is estimated to be 50 million, forming the second largest global pool of chronic HBV infections.9&#xD;
&#xD;
HBV prevalence in general population in India is 2% to 8% and 1% to 2% in the blood donors, according to various studies.9-11 &#xA0;Panda and Kar11 did a study in Orissa, a state in the eastern part of the country, and reported the prevalence of HBsAg in blood donors to be 1.13%. Pahuja and colleagues12 reported the prevalence to be 2.23% in Delhi. Garg and co-workers13 reported that the prevalence was as high as 3.44% in the western part of the country. &#xD;
&#xD;
&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0; In our study, the overall seropositivity for HBV over 10 years was 0.48%. The seropositivity ranged from 0.53% in 2003 to 0.36% in 2012, showing decreasing trends. The overall seropositivity rate in males was 0.48% while in females it was 0.41%. The seropositivity rates of hepatitis B were lower among young donors between 18-30 years of age (0.45%), as compared to older donors between 51-60 years of age (0.66%). This may be explained on the basis of increased exposure with age and on the fact that a high awareness of blood-borne viral infections has developed and a comprehensive vaccination program against hepatitis B has been implemented. The seropositivity in voluntary donors was significantly lower compared to replacement donors (0.16% vs. 0.49%) and 0% in repeat voluntary donors emphasizing the fact that donor recruitment is vital and repeat voluntary donations should be encouraged to ensure more safe blood supply. &#xD;
&#xD;
&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0; HCV infection is an evolving public health problem globally. This virus infects approximately 3% of the world population; placing approximately 170 million people at risk for developing HCV related chronic liver disease.14 The global seroprevalence of HCV among blood donors varies from 0.4% to 19.2%. However, overall HCV prevalence in India has been reported to be less than 2%. The seroprevalence of HCV in voluntary blood donors in India is between 0.12 and 2.5%. 10-13 &#xA0;In two studies performed in different parts of Delhi, the prevalence of HCV in blood donors has been reported to range from 0.66% to 2.5%.12,15 Garg and co-workers13 reported the HCV prevalence in blood donors in western India to be 0.28%. In Orissa, the HCV prevalence was reported to be 1.98% by Panda and coworkers.11 &#xD;
&#xD;
&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0; In our study, the overall 10 year HCV seropositivity was 0.20%. The seropositivity of HCV infection among blood donors in the past 10 years showed a decreasing trend, from 0.28 in 2003 to 0.12 in 2012. Seropositivity of HCV was seen more in males (0.20%) as compared to females (0.14%). Seropositivity of HCV was found higher in the age group of 51-60 years (0.26%), with the lowest seropositivity in age group of 18-30 years (0.18%). Beenu et al16 in their study found that the HCV seropositivity increased with age in voluntary donors, with the lowest prevalence in the age group of 18-30 years, and highest in the age group of 51-60 years. This was comparable with one study.&#xA0; The prevalence seems to increase with age either because of a continuing risk of exposure or a cohort effect with declining risk in more recent time. In our study, seropositivity of HCV in voluntary donors was significantly lower compared to the replacement donors (0.09% vs. 0.20%) and 0% in repeat voluntary donors again emphasizing that repeat voluntary donations should be encouraged.&#xD;
&#xD;
CONCLUSION&#xD;
&#xD;
The seropositivity of viral markers was lower in our study as compared with studies from other parts of the country. It was lower among younger age groups and significantly lower in voluntary donors compared to replacement donors and repeat voluntary donors were found to be much safer. Stringent measures need to be taken including, dissemination of information, better donor recruitment and retention strategies, promoting repeat voluntary blood donations and strict screening of blood and blood products to increase the blood safety.&#xD;
&#xD;
ACKNOWLEDGEMENTS: &#xD;
&#xD;
Authors acknowledge the immense help received from the scholars whose articles are cited and included in references of this manuscript. The authors are also grateful to authors / editors / publishers of all those articles, journals and books from where the literature for this article has been reviewed and discussed. &#xD;
&#xD;
FINANCIAL SUPPORT: None&#xD;
&#xD;
CONFLICT OF INTEREST: None&#xD;
&#xD;
&#xD;
</Fulltext><FulltextLanguage>English</FulltextLanguage><URLs><Abstract>http://ijcrr.com/abstract.php?article_id=262</Abstract><Fulltext>http://ijcrr.com/article_html.php?did=262</Fulltext></URLs><References>1. Rezvan H, Abolghassemi H, Kafiabad SA. Transfusion transmitted infections among multitransfused patients in Iran: a review. Transfuse Med 2007; 17(6):425&#x2013;33.&#xD;
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2. Livramento A, Cordova CM, Spada C, Treitinger A. Seroprevalence of hepatitis&#xD;
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B and C infection markers among children and adolescentsin the southern Brazilian region. Rev Inst Med Trop Sao Paulo 2011; 53(1) :13-7.&#xD;
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3. Simmonds P.The origin and evolution of hepatitis viruses in humans. J Gen Virol 2001;82:693-712.&#xD;
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4. YeeTT, Lee CA. Transfusion transmitted infection in hemophilia in developing countries. Semin Thromb Hemost. 2005; 31(5):527-37.&#xD;
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&#xA0;5. Samimi-Rad K , Shahbaz B. Hepatitis C virus genotypes among patients with thalassemia and inherited bleeding disorders in Markazi province, Iran. Haemophilia 2007;13(2):156-63.&#xD;
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6. Burki MF, Hassan M, Hussain H, Nisar Y, Krishan J. Prevalence of anti-hepatitis C antibodies in multiply transfused beta thalassemia major patients. Ann Pak Inst Med Sci 2005;1:150-3.&#xD;
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7. Kleinman SH, Lelie N, Busch MP. Infectivity of human immunodeficiency virus-1, hepatitis C virus, and hepatitis B virus and risk of transmission by transfusion. Transfusion 2009;49:2454-89.&#xD;
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8. Mukhopadhyaya A. Hepatitis C in India. J Biosci 2008;33:465-73. &#xD;
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9. Datta S. An overview of molecular epidemiology of hepatitis B virus (HBV) in India. Virol J 2008;5:156.&#xD;
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10. Gupta N, Kumar V, Kaur A. Seroprevalence of HIV, HBV,HCV and syphilis in voluntary blood donors. Indian J Med Sci 2004;58:255-7.&#xD;
&#xD;
11. Panda M, Kar K. HIV, hepatitis B and C infection status of the blood donors in a blood bank of a tertiary health care centre of Orissa. Indian J Public Health 2008;52:43-4.&#xD;
&#xD;
12. Pahuja S, Sharma M, Baitha B, Jain M. Prevalence and trends of markers of hepatitis C virus, hepatitis B virus and human immunodeficiency virus in Delhi blood donors: a hospital based study. Jpn J Infect Dis 2007;60:389-91.&#xD;
&#xD;
13. Garg S, Mathur DR, Garg DK. Comparison of seropositivity of HIV, HBV, HCV and syphilis in replacement and voluntary blood donors in western India. Indian J Pathol Microbiol 2001;44:409-12.&#xD;
&#xD;
14. WHO. Global surveillance and control of hepatitis C. Report of a WHO consultation organized in collaboration with the viral hepatitis prevention Board, Antwerp, Belgium. J Viral Hepat 1999;6:35-47.&#xD;
&#xD;
15. Sood G, Chauhan A, Sehgal S, Agnihotri S, Dilawari JB. Antibodies to hepatitis C virus in blood donors. Indian JGastroenterol 1992;11:44.&#xD;
&#xD;
16. Beenu T, Nelam M, Chawla YK et al.&#xA0; Prevalence and significance of hepatitis C virus (HCV) seropositivity in blood donors.&#xA0; Indian J Med Res. 2006 (Oct.); 124:431-438. &#xD;
</References></Article></ArticleSet><ArticleSet><Article><Journal><PublisherName>Radiance Research Academy</PublisherName><JournalTitle>International Journal of Current Research and Review</JournalTitle><PISSN>2231-2196</PISSN><EISSN>0975-5241</EISSN><Volume>8</Volume><Issue>19</Issue><IssueLanguage>English</IssueLanguage><SpecialIssue>N</SpecialIssue><PubDate><Year>-0001</Year><Month>November</Month><Day>30</Day></PubDate></Journal><ArticleType>Healthcare</ArticleType><ArticleTitle>TREATMENT OF SPECIAL CHILDREN: AN ORTHODONTIC PERSPECTIVE&#xD;
</ArticleTitle><ArticleLanguage>English</ArticleLanguage><FirstPage>21</FirstPage><LastPage>24</LastPage><AuthorList><Author>Shyama Dash1</Author><AuthorLanguage>English</AuthorLanguage><Author> Uday N. Soni</Author><AuthorLanguage>English</AuthorLanguage><Author> Rahul S. Baldawa</Author><AuthorLanguage>English</AuthorLanguage><Author> N. G. Toshniwal</Author><AuthorLanguage>English</AuthorLanguage><Author> Shubhangi A. Mani</Author><AuthorLanguage>English</AuthorLanguage></AuthorList><Abstract>Orthodontic care may seem out of reach for many children with special needs due to physical and developmental disabilities. Orthodontists who lack education and experience to work with such patients with disabilities end up denying treatment of these patients, as a result, patients and parents become frustrated.Orthodontic treatment is an elective procedure for essentially all patients, including those with medical problems. Correction of disfiguring dental and facial problems contributes in an important way to an individual&#x2019;s self-esteem. The positive benefits of orthodontic treatment influence social integration and interaction, and can lead to significant improvement in overall well-being.&#xD;
</Abstract><AbstractLanguage>English</AbstractLanguage><Keywords>Special children, Special needs, Orthodontics</Keywords><Fulltext>INTRODUCTION&#xD;
&#xD;
As a result of tremendous progress made in the fields of medicine and dentistry in the 20th century, a remarkable improvement in the survival rates, longevity and quality of life of children affected by congenital, developmental or pathologic conditions is continually occurring. Coupled with elevations in public awareness, changing social policies and opinion, and favorable legislation, higher standards of non-institutionalized medical and dental care are becoming routinely available to these individuals. In the present scenario, the practicing clinician in the community responsible for addressing the needs of these special patients has to be accessible to them, and competent and willing to provide them the required optimal level of care. Orthodontic treatment is an elective procedure for essentially all patients, including those with medical problems. Correction of disfiguring dental and facial problems contributes in an important way to an individual&#x2019;s self-esteem. The positive benefits of orthodontic treatment influence social integration and interaction, and can lead to significant improvement in overall well-being (1, 2). However, there are important considerations while planning and rendering orthodontic care to children with special needs. The goal of this review is to discuss the indications and implications of orthodontic therapy for children in some of these special situations.&#xD;
&#xD;
MENTAL RETARDATION&#xD;
&#xD;
Mental retardation is defined as a significant decrease in the intellectual ability with consequent limited ability to adapt to the environment. The degree of retardation varies among individuals, ranging from mild to severe, and often occurs along with other systemic problems. Mental retardation is frequently associated with a greater occurrence of malocclusion. &#xD;
&#xD;
Orthodontic Care&#xD;
&#xD;
&#xD;
	Orthodontic treatment can provide significant esthetic and functional benefits to affected individuals. The orthodontic treatment plan for a mentally challenged patient should be individualized and developed keeping the child&#x2019;s strengths and weaknesses in sight. &#xD;
	Short appointments should be planned&#xD;
	The clinician should ensure that a good level of communication is established with the child, and that all explanations and instructions are simple and well understood by the patient. &#xD;
&#xD;
&#xD;
DOWN&#x2019;S SYNDROME&#xD;
&#xD;
Down&amp;#39;s syndrome (3-8), is a genetic disorder caused by trisomy of chromosome 21, which is an autosomal chromosome. This syndrome is associated with physical growth delays, typical facial features, and mild to moderate intellectual disability. In some conditions, such as Down syndrome, a generalized retardation of growth and development is often found. &#xD;
&#xD;
Clinical Manifestation&#xD;
&#xD;
&#xD;
	Eruption of both deciduous and permanent teeth is frequently delayed, and there is also a delay in the exfoliation of the deciduous teeth. &#xD;
	Pseudoprognathism decreased lower facial height, small midface, perioral hypotonia, a large and protruded tongue, crossbite, anterior open bite, and crowding are common associated craniofacial features. &#xD;
	Additionally, children with Down syndrome have an increased susceptibility to rapid, destructive periodontal disease due to both local and systemic factors. &#xD;
	These children are also more prone to suffer from cardiac defects, leukemia&#x2019;s and respiratory infections. &#xD;
&#xD;
&#xD;
&#xD;
	Children with Down syndrome are frequently the victims of a stereotype image that has come to be associated with their mental condition even though their mental retardation is usually of a mild or moderate nature, and these children often have a wide range of comprehensive and performance capabilities. &#xD;
&#xD;
&#xD;
Orthodontic Care&#xD;
&#xD;
&#xD;
	The orthodontist should be careful to assess the potential of each child individually and structure treatment strategies accordingly. &#xD;
	The extent to which orthodontic appliance therapy can be successfully instituted varies with the cooperative abilities of the patient, but a good orthodontic treatment result is certainly achievable for many patients.&#xD;
	In the more severely mentally retarded patients, the initial placement of limited fixed appliances or bonded/cemented bite planes can be accomplished under general anesthesia. Surgical orthodontic treatment is an important consideration in this in group of patients.&#xD;
&#xD;
&#xD;
CEREBRAL PALSY&#xD;
&#xD;
Cerebral palsy (9-10) is a collection of disabling conditions due to permanent brain damage in the prenatal and perinatal period. One newborn in approximately 200 live births is afflicted with this condition.&#xD;
&#xD;
Clinical Manifestations&#xD;
&#xD;
&#xD;
	Cerebral palsy is characterized by variable severities of muscle weakness, stiffness or paralysis, poor balance, irregular gait, and uncoordinated, involuntary movements. &#xD;
	Mental retardation, seizures, strabismus and speech problems may accompany the neurological problems. &#xD;
	A wide range of neuromuscular dysfunction is seen, which presents as spasticity, dyskinesia, ataxia or a mixture of these. &#xD;
	These children also may suffer from abnormalities of the cervical spine. &#xD;
&#xD;
&#xD;
Oral Manifestations&#xD;
&#xD;
&#xD;
	They lack intraoral, perioral and masticatory muscle coordination and have limited control of the neck muscles, which contributes to the risk of head roll in the supine position. &#xD;
	Children with cerebral palsy often have severe attrition due to bruxism, and a higher frequency of periodontal disease and gingival hyperplasia that is related to both local factors and anticonvulsant therapy. &#xD;
	They frequently have a marked overjet, open bite, posterior cross bite, and are more susceptible to trauma to the anterior maxilla, thus implicating the need for orthodontic treatment. &#xD;
&#xD;
&#xD;
Orthodontic Care&#xD;
&#xD;
&#xD;
	Depending on the severity of neuromuscular dysfunction, specific goal-oriented orthodontic treatment, often in conjunction with orthognathic surgery to correct the large overjet and open bite can be undertaken for them. &#xD;
	Care should be taken to stabilize the patient&#x2019;s head and to avoid a completely supine position in the dental chair during treatment.&#xD;
	In general, for patients with a known history of seizures, orthodontic treatment can be carried out safely when the disease is under good medical control and there is no active seizure activity in the recent history of the disease.&#xD;
	Gingival surgery for reducing the hyperplasia may be required to facilitate orthodontic treatment.&#xD;
&#xD;
&#xD;
Cystic Fibrosis&#xD;
&#xD;
Cystic fibrosis(11-14) has an occurrence of one in 2,000 births, is the most common lethal genetic disorder in Caucasians. Children with cystic fibrosis have progressive obstructive lung disease and are at a high risk of infection. Antibiotic administration is the mainstay of therapy for the treatment of cystic fibrosis. New and potent antibiotics, more aggressive antibiotic treatment and multiple routes of administration have contributed to improved survival among cystic fibrosis patients.&#xD;
&#xD;
Oral Manifestations&#xD;
&#xD;
&#xD;
	Oral implications associated with cystic fibrosis include enamel hypoplasia and tooth discoloration&#xD;
	Salivary gland dysfunction&#xD;
	Reduced levels of dental plaque, caries and oral disease. &#xD;
&#xD;
&#xD;
These are also related to the effects of antibiotics in these patients. Cystic fibrosis patients are always at a high risk of developing lethal lung infection(15), and the mouth may act as a reservoir for potentially pathogenic respiratory bacteria. They have deficient salivary secretion, and are at a greater risk of decalcification around fixed orthodontic appliance attachments. When undertaking orthodontic treatment, precautions should be taken to avoid the possibility of the patient aspirating infective material. (16)&#xD;
&#xD;
Orthodontic Care&#xD;
&#xD;
&#xD;
	For this reason, and also to avoid restricting their already diminished lung volume, these children should be treated in a more upright rather than fully reclined position. &#xD;
	However, since longevity in affected children varies widely among individual patients, an evaluation by the patient&#x2019;s physician of the severity of the problem and life expectancy should be included while planning possible orthodontic treatment.&#xD;
&#xD;
&#xD;
Juvenile Rheumatoid Arthritis (17)&#xD;
&#xD;
It is an inflammatory condition of the joints, probably of autoimmune origin, in which the inflamed and hyperplastic synovial membrane encroaches on the articulating joint surfaces and leads to the destruction of the articular cartilage and underlying bone if left untreated.&#xD;
&#xD;
It is the major arthritic problem in children and young adults, and is extremely variable in onset, severity and clinical course. The proliferative arthritis involving multiple joints may frequently affect the temporomandibular joint in children, either unilaterally or bilaterally. It may be self-limiting with satisfactory recovery in many cases, or may, in severely affected patients, progress to irreversible damage to the joint spaces, leading to significant functional disability. &#xD;
&#xD;
Clinical Manifestations&#xD;
&#xD;
&#xD;
	The patient may have varying degrees of mandibular retrognathia(24,25) with a steep mandibular plane, anterior open bite(18), mandibular asymmetry in patients with unilateral involvement, and signs and symptoms of temporomandibular joint dysfunction. &#xD;
	These may include difficulty in wide mouth opening, pain on mandibular movements and joint sounds.&#xD;
	Erosion of the cortical outline in the TMJ is the most common radiographic finding, followed by flattening with or without erosion, and the complete loss of the condylar head in the very severely affected patients.&#xD;
	A multidisciplinary approach is usually required for the management of various componentsof juvenile rheumatoid arthritis.(19-21)&#xD;
	Medical treatment involves steroidal and non-steroidal anti-inflammatory agents, while gold salts, d penicillamine and cytotoxic drugs may be required for select patients. Temporomandibular therapy is aimed at reducing pain and dysfunction in the masticatory system, restoring and maintaining mandibular mobility to correct and prevent occlusion problems and deformities, and at stimulating mandibular growth.(22,23)&#xD;
	Therapeutic exercises against resistance and chewing training are beneficial to increase muscle strength andmandibular mobility. Occlusal splints or passive activators may be helpful to decrease the load on the TMJ and reduce masticatory muscle tension.&#xD;
&#xD;
&#xD;
Orthodontic Care&#xD;
&#xD;
&#xD;
	Children with juvenile rheumatoid arthritis should have annual orthodontic examinations, which should include a functional evaluation of the masticatory system, and radiographic studies of the face and the temporomandibular joints. &#xD;
	Orthodontic treatment in patients with juvenile rheumatoid arthritis should be attempted only when the disease is under control. It must be remembered that stress on the joint during orthodontic treatment may result in further degeneration of the condyle. &#xD;
	Functional appliances with large mandibular propulsions, heavy intermaxillary elastics and orthognathic surgery involving large mandibular advancements can lead to increased joint stress. &#xD;
&#xD;
&#xD;
&#xD;
	Therefore, in the more severely retrognathic patients, surgical orthodontic treatment options involving maxillary surgery and genioplasty should be considered when possible.&#xD;
&#xD;
&#xD;
Discussion&#xD;
&#xD;
Children with special needs are refrained from having normal activities because of any physical or mental disability. They require special orthodontic attention due to increased prevalence and severity of malocclusion.In order to deal with such patients the most important quality an orthodontist must have is &#x201C;communication skill&#x201D;. Good soft skills can help convincing the parents as well as patients to undergo treatment. Before starting such cases it is always advisable to take advice from the patients&#x2019; physician. This will help us for being more cautious while framing the treatment plan. The orthodontist should be careful to assess the potential of each child individually and structure treatment strategies accordingly. The extent to which orthodontic appliance therapy can be successfully instituted varies with the cooperative abilities of the patient, but a good orthodontic treatment result is certainly achievable for many patients .most of these patients present with poor oral hygiene and they should be educated for the same.&#xD;
&#xD;
Conclusion&#xD;
&#xD;
These patients had these disabilities by chance not by choice, so we as clinicians must not differentiate them from our normal patients. Rather we should make efforts to help them to establish their self &#x2013;esteem and giving them a better quality of life.&#xD;
&#xD;
Conflict of interest: None&#xD;
&#xD;
Source of funding: None&#xD;
</Fulltext><FulltextLanguage>English</FulltextLanguage><URLs><Abstract>http://ijcrr.com/abstract.php?article_id=263</Abstract><Fulltext>http://ijcrr.com/article_html.php?did=263</Fulltext></URLs><References>&#xD;
	Uday N. Soni et al. &#x201C;Patient&#x2019;s expectations of orthodontic treatment at first visit&#x201D;. Indian Journal of Orthodontics and Dentofacial Research, April&#x2013;June 2016; 2(2):39-42.&#xD;
	UN Soni et al. &#x201C;Knowledge and awareness of malocclusion among rural population in India&#x201D; Asian Pac. J. Health Sci., 2014; 1(4): 329-334&#xD;
	Patterson, D (Jul 2009). "Molecular genetic analysis of Down syndrome." Human Genetics 126 (1): 195&#x2013;214. &#xD;
	Weijerman, ME; de Winter, JP (Dec 2010). "Clinical practice. The care of children with Down syndrome.". European journal of pediatrics 169 (12): 1445&#x2013;52. &#xD;
	Cohen MM, Winner RA. Dental and facial characteristics in Down syndrome. J Dent Res. 1965; 44:197&#x2013;208. &#xD;
	Townsend GC. Tooth size in children and young adults with trisomy 21 (Down syndrome). Arch Oral Biol. 1983; 28:159&#x2013; 166. &#xD;
	Peretz B et al. Modification of tooth size and shape in Down&#x2019;s syndrome. J Anat. 1996; 188: 167&#x2013;172. &#xD;
	Peretz B et al, Modified cuspal relationship of mandibular molar teeth in children with Down&#x2019;s syndrome. J Anat. 1998; 193:529&#x2013;533.&#xD;
	Oskoui, M et al, "An update on the prevalence of cerebral palsy: a systematic review and meta-analysis."Developmental medicine and child neurology&#xA0;(June 2013). 55&#xA0;(6): 509&#x2013;19.&#xD;
	Nieuwenhuijsen et al.; Transition Research Group South West Netherlands "Experienced problems of young adults with cerebral palsy: targets for rehabilitation care".&#xA0;Archives of Physical Medicine and Rehabilitation (2009);90&#xA0;(11): 1891&#x2013;1897.&#xD;
	Anderson DH: Cystic fibrosis of the pancreas and its relation to celiac disease clinical and pathological study. Am J Dis Child 56:344-99, 1938. &#xD;
	Blacharsh C: Dental aspects of patients with cystic fibrosis: a preliminary clinical study. J Am Dent Assoc 95:106-110, 1977.&#xD;
	Boat TF et al: Cystic fibrosis, in The Metabolic Basis of Inherited Disease, 6th ed. Scriver CR et al., eds. McGraw Hill: New York, 1989, pp 2649-80. &#xD;
	Cystic fibrosis: a current review: The American Academy of Pediatric Dentistry April/May, 1990 - Volume 12, 71-78. &#xD;
	Cheng PW et al: Increased sulfation of glycoconjugates by cultured nasal epithelial cells from patients with cystic fibrosis. J Clin Invest 84:68-72, 1989.&#xD;
	DiSant&#x2019;Agnese PA, Davis PB: Research in cystic fibrosis. N Engl J Med 295:481-85; 534-41; 597-602, 1976. &#xD;
	David L. Turpin ;Juvenile rheumatoid arthritis: a 14-year posttreatment evaluation&#xA0;The Angle Orthodontist Sep 1989, Vol. 59, No. 3 pp. 233-238.&#xD;
	Bertha Barriga et al : An Investigation of the Dental Occlusion in Children with Juvenile Rheumatoid Arthritis;The Angle Orthodontist Oct 1974, Vol. 44, No. 4&#xA0; pp. 329-335&#xD;
	Grokoest AW et al. Some aspects of juvenile rheumatoid arthritis. Bull Rheum Dis. 1957; 8: 147&#x2013;148. 13. &#xD;
	Schaller J, Wedgwood RJ. Juvenile rheumatoid arthritis: a review. Pediatrics. 1972; 50:940&#x2013;953.&#xD;
	Cassidy JT, Martel W. Juvenile rheumatoid arthritis: clinicoradiologic correlations. Arthritis Rheum. 1977; 20(2 suppl):207&#x2013;211.&#xD;
	Twilt M et al. Facioskeletal changes in children with juvenile idiopathic arthritis. Ann Rheum Dis. 2006; 65:823&#x2013;825. &#xD;
	Kjellberg H et al. Craniofacial structure in children with juvenile chronic arthritis (JCA) compared with healthy children with ideal or postnormal occlusion. Am J OrthodentofacialOrthop. 1995; 107:67&#x2013;78. &#xD;
	Stabrun AE et al. Reduced mandibular dimensions and asymmetry in juvenile rheumatoid arthritis. Pathogenetic factors. Arthritis Rheum. 1988; 31:602&#x2013;611. &#xD;
	Stabrun AE. Impaired mandibular growth and micrognathic development in children with juvenile rheumatoid arthritis. A longitudinal study of lateral cephalographs. Eur J Orthod. 1991; 13:423&#x2013;434. &#xD;
&#xD;
</References></Article></ArticleSet><ArticleSet><Article><Journal><PublisherName>Radiance Research Academy</PublisherName><JournalTitle>International Journal of Current Research and Review</JournalTitle><PISSN>2231-2196</PISSN><EISSN>0975-5241</EISSN><Volume>8</Volume><Issue>19</Issue><IssueLanguage>English</IssueLanguage><SpecialIssue>N</SpecialIssue><PubDate><Year>-0001</Year><Month>November</Month><Day>30</Day></PubDate></Journal><ArticleType>Healthcare</ArticleType><ArticleTitle>PREVALENCE OF CHRONIC DAILY HEADACHE (CDH) IN PEOPLE OF AGE GROUP 18-80 YEARS IN MAX SUPERSPECIALTY HOSPITAL, SAKET, NEW DELHI " INDIA - A PROSPECTIVE STUDY&#xD;
</ArticleTitle><ArticleLanguage>English</ArticleLanguage><FirstPage>25</FirstPage><LastPage>35</LastPage><AuthorList><Author>Maqsood Ahmad Dar</Author><AuthorLanguage>English</AuthorLanguage><Author> Baseerat Ali</Author><AuthorLanguage>English</AuthorLanguage><Author> Rajasheikar Redid</Author><AuthorLanguage>English</AuthorLanguage><Author> Rommel Roshan Tickoo</Author><AuthorLanguage>English</AuthorLanguage><Author> Owais Hamid Dar</Author><AuthorLanguage>English</AuthorLanguage></AuthorList><Abstract>Introduction: Chronic daily headache defined as headache occurring on 15 or more days in a month for at least three months affects around 4% of the general population causes significant distress with substantial impact on the quality of life of an individual and huge economic cost to the society through occupational disability and healthcare consultations.&#xD;
Objectives of the Study: To study the prevalence of chronic daily headaches in people of age group 18-80 years in Max Super Specialty Hospital and to identify risk factors associated with CDH (stressful life events, obesity, and medicine overuse.)&#xD;
Material and Methods: It was a prospective study conducted in Max Super Specialty Hospital, Saket, and New Delhi between Aug 2014 to May 2015. Patients coming with complaints of headache in age group of 18-80 yrs and fulfilling the inclusion criteria and exclusion criteria were enrolled in the study. Sample size was calculated by using n-Master (2.0) software and 176 subjects were enrolled. History of the patient including the precipitating factors and drug history was taken. MIDAS and HIT score was used to know the severity of headache; medical conditions were noted by taking brief interviews. Data was analyzed by using chi square test, Pearson&#x2019;s correlation coefficient.&#xD;
Result: Of the 4500 subjects presented to our hospital with complaints of headache, 176 fulfilled the criteria of chronic daily headache (CDH) with a prevalence of about 4.5%.In our study we observed that 103 (58.5%) had migraine without aura, 30.6(20.5%) migraine with aura, 33(18.8%) tension type headache (TTH), 2 (1.1%) hemicranias continua and 2(1.1%) mixed-migraine and TTH.We observed that out of 176 patients in age group of 18-80 years ,maximum number of patients were in age group of 30-39 yrs- 67 patients(38.1%) and the least common age group was &gt;70yrs where only 1 patient had chronic daily headache(CDH). It was observed that out of 176 patients 123 (69.9%) were females and 53 (30.1%) were males and type of headache was statistically significantly (p=0.00) associated with gender.&#xD;
Conclusion: We conclude that Migraine without aura was the most common type (58.5%) and least common type being mixed chronic migraine and tension type headache and Hemicrania continua 1.1%. We found chronic daily headache was more prevalent in females as compared to males, 123 (69.9%) were females and 53 (30.1%) were males. The most common age group affected was 30-39 years and was more common in married. We observed that most of the patients (61.9%) had BMI between 18.5 and 25.After analyzing risk factors it was observed that history of drug intake was present in 154 subjects, most common being Acetaminophen, Naproxen, Triptans, Ergotamine the rest were using preventive. In our study prevalence of medication overuse headache (MOH) among 176 patients of chronic daily headache is (108/176) 61.36% whereas prevalence of MOH in subjects coming to our hospital with headache is 2.4% (108/4500). Stress was the most common precipitating factor of chronic daily headache (CDH), stress was present in 146 patients (85.9%) others being lack of sleep, hunger, working on computer, noise, menstruation, sunlight, travel.&#xD;
&#xD;
Recommendations: Chronic daily headache is under estimated due to lack of awareness; screening of patients should be done on primary and secondary care centers to estimate the actual burden of disease. Stress, anxiety should be handled as early as possible to prevent transformation of episodic headache to chronic daily headache.&#xD;
</Abstract><AbstractLanguage>English</AbstractLanguage><Keywords>Hemicranias continua, Chronic daily headache, Tension type headache, Medication overuse headache</Keywords><Fulltext>Introduction&#xD;
&#xD;
Chronic Daily Headache (CDH) is a descriptive term and not a diagnosis per se. It is commonly defined as headache occurring on 15 or more days in a month for at least three months and affects around 4% of the general population [1]. &#xA0;It causes significant distress with substantial impact on the quality of life of an individual and huge economic cost to the society through occupational disability and healthcare consultations. In comparison to episodic headache disorders, CDH is less responsive to acute and preventive treatments. The term CDH is mainly referred to the primary headache disorder, although secondary CDH must be excluded. It includes chronic migraine, chronic tension type headaches, and new daily persistent headache and hemicrania continue. Common ones being chronic migrane and chronic tension type headache [2]. CDH may evolve from episodic headache through gradual transformation over months to years. An estimated 3-6% of patients move from episodic to chronic and vice versa each year [3]&#xA0;&#xD;
&#xD;
Definitions:&#xD;
&#xD;
Chronic migraine: Headache occurring on 15 or more days per month for more than 3 months, which has the features of migraine headache on at least 8 days per month. [4]&#xD;
&#xD;
Migraine without aura: Headache attack lasting for 4- 72hrs (untreated or successfully treated) .Two of following characteristics should be present:&#xD;
&#xD;
Unilateral location, pulsating quality, moderate or severe pain intensity, aggravated by or causes avoidance of routine physical activity.&#xD;
&#xD;
During headache at least one of the following:&#xD;
&#xD;
Nausea/or vomiting and photophobia / phonophobia&#xD;
&#xD;
Migraine with Aura: At least two attacks as follows:&#xD;
&#xD;
One or more of the following fully reversible aura symptoms:&#xD;
&#xD;
Visual, sensory, speech and/or language, motor, brainstem, retinal&#xD;
&#xD;
At least two of the following four characteristics:&#xD;
&#xD;
1. At least one aura symptom spreads gradually over 5 minutes, and/or two or more symptoms occur in succession&#xD;
&#xD;
2. Each individual aura symptom lasts 5-60 minutes&#xD;
&#xD;
3. At least one aura symptom is unilateral&#xD;
&#xD;
4. The aura is accompanied, or followed within 60 minutes, by headache&#xD;
&#xD;
Not better explained by another diagnosis&#xD;
&#xD;
New Daily Persistent Headache (NDPH)] [4]&#xD;
&#xD;
Previously used terms:&#xA0; Chronic headache with acute onset, de novo chronic headache.&#xD;
&#xD;
New daily persistent headache (NDPH) is a persistent headache is daily from onset, which is clearly remembered, with pain becoming continuous and unremitting within 24 hours and very soon unremitting, it is present for more than 3 months.&#xD;
&#xD;
It&#xA0;&#xA0; typically occurs in individuals without a prior headache history. &#xD;
&#xD;
Patients with prior headache (Migraine or Tension-type headache) are not excluded from this diagnosis, but they should not describe increasing headache frequency prior to its onset. &#xD;
&#xD;
Similarly, patients with prior headache should not describe exacerbation followed by medication overuse.&#xD;
&#xD;
Chronic Tension Type Headache (CTTH) [4] &#xD;
&#xD;
Chronic tension type headache (CTTH) is a featureless bilateral headache occurring on 15 days or more in a month for more than three months lasts hours to days, or unremitting.&#xD;
&#xD;
It has following features:&#xD;
&#xD;
&#xA0; At least two of the following four characteristics:&#xD;
&#xD;
1. Bilateral location&#xD;
&#xD;
2. Pressing or tightening (non-pulsating) quality&#xD;
&#xD;
3. Mild or moderate intensity&#xD;
&#xD;
4. Not aggravated by routine physical activity such as walking or climbing stairs&#xD;
&#xD;
&#xA0;&#xD;
&#xD;
And both of the following:&#xD;
&#xD;
1. No more than one of photophobia, phonophobia or mild nausea&#xD;
&#xD;
2. Neither moderate nor severe nausea not vomiting&#xD;
&#xD;
&#xA0;&#xA0; Not better accounted for by another disorder.&#xD;
&#xD;
&#xA0;&#xD;
&#xD;
Chronic tension-type headache is of two types:&#xD;
&#xD;
1. Chronic tension-type headache associated with pericranial tenderness&#xD;
&#xD;
2. Chronic tension-type headache not associated with pericranial tenderness&#xD;
&#xD;
Hemicrania Continua [4] &#xD;
&#xD;
&#xA0;&#xD;
&#xD;
Persistent, strictly unilateral headache &gt;3 months, with exacerbations of moderate or greater intensity associated with either or both of the following:&#xD;
&#xD;
1. Atleast one of following signs or symptoms ipsilateral to headache:&#xD;
&#xD;
conjunctival injection and /or lacrimation, nasal congestion and/or rhinorrhoea, eyelid edema, forehead and &#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;facial sweating, forehead and facial flushing, sensation of fullness in the ear, miosis and /or ptosis,&#xD;
&#xD;
2. Sense of restlessness or agitation or aggravation of pain by movement. &#xD;
&#xD;
&#xA0;&#xA0; It is not better accounted by other disorder.&#xD;
&#xD;
&#xA0;&#xD;
&#xD;
&#xA0;&#xD;
&#xD;
Aims and Objectives:&#xD;
&#xD;
To study the prevalence of chronic daily headaches in people of age group 18-80 years in Max Super Specialty Hospital, Saket New Delhi. To identify risk factors associated with CDH (stressful life events, snoring, obesity and medicine overuse)&#xD;
&#xD;
Material and Methods:&#xD;
&#xD;
Study Design:&#xD;
&#xD;
This study was carried out in the department of internal medicine and department of neurology in Max Superspeciality Hospital Saket New Delhi. All patients who were fulfilling inclusion and exclusion criteria &amp; coming to internal medicine and neurology department of Max Hospital, Saket, New Delhi, as outpatient &amp; indoor patients were enrolled in the study. The study was a prospective study of 176 patients who fulfilled the criteria of chronic daily headache in age group of 18 to 80 years. The study was conducted over a period of one year from august 2014 to July 2015. &#xD;
&#xD;
Method of Measurement of Outcome of Interest: &#xD;
&#xD;
&#xA0;Patients fulfilling the inclusion and exclusion criteria were recruited in the study after informed consent. Data was collected for basic demographics, alcohol/tobacco/any drug intake history, past medical history, history of any head or cervical trauma, their socioeconomic status.&#xD;
&#xD;
Data was also collected regarding medication intake for acute attacks of headache and adherence of patients to any preventive medication (if present).&#xD;
&#xD;
We also collected data regarding the relevant lab investigations, radiological imaging and certified headache scoring systems -Migraine Disability Assessment Score (MIDAS), Headache Intensity (HIT) Score. Subjects were enrolled in this study after informed consent.&#xD;
&#xD;
Inclusion Criteria:&#xD;
&#xD;
Patients coming to hospital with headaches &gt; 15 episodes /month for &gt;3 months in age group 18-80 years either Male or Female. &#xD;
&#xD;
Exclusion criteria:&#xD;
&#xD;
Patients having secondary headaches&#xD;
&#xD;
Patients having abnormal LFT, TFT, RFT, vitamin B12 (2 times the upper limit)&#xD;
&#xD;
Any organic pathology&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0;&#xA0; &#xD;
&#xD;
Investigations:&#xD;
&#xD;
Blood/urine tests (chemistry, hematology, drug screen, endocrine workup)&#xD;
&#xD;
CT/MRI scans (Head, cervical spine, sinuses) if required&#xD;
&#xD;
Statistical Analysis:&#xD;
&#xD;
Descriptive statistical methods were used to calculate the number of subjects (n), mean, median, standard deviation (SD) for continuous data and frequencies and percentages for categorical data. Pearson correlation was used to calculate the correlation between continuous variables or Spearman correlation for categorical variables. Chi- square test or Fisher exact test was used to find the association between the categorical variables. STATA 9.0 software was used for statistical analysis&#xD;
&#xD;
Institutional Ethics Committee (IEC) Review:&#xD;
&#xD;
&#xA0;The study was carried out only after getting approved by institutional ethics committee.&#xD;
&#xD;
There was not any conflict of interest with the study and not much funding was involved in the study as this was a prevalence study.&#xA0; &#xD;
&#xD;
Observations:&#xD;
&#xD;
A total of 4500 patients presented with headache to our hospital during the study period, out of these 176 fulfilled criteria for chronic daily headache (CDH), prevalence of CDH was found to be 4.5%. We observed that out of 176 patients in age group of 18-80 years maximum patients were in the age group of 30-39 years (67 patients 38.1%) and minimum patients were in age group of more than 70 years (1 patient 0.6%). Figure 1 is showing the age distribution of the subjects with respect to the percentage of the CHD. Among 176 patients with CDH, 123(69.9%) were females and 53 (30.1%) were males (Table 1) &#xD;
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