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A model to predict low birth weight infants and affecting factors using data mining techniques 2 2 Introduction: Birth weight is a reliable indication of intrauterine growth and determines the child's future physical and intellectual development. The purpose of this study was to use data mining technique in identifying accurate predictors of (low birth weight) LBW. Materials and methods: This study used secondary data from 450 medical records of newborns in the educational Hospitals affiliated to Ilam University of Medical Sciences. The birth records were reviewed from April 2015 to April 2016.  The checklist used to collect data comprised of two parts: demographic and effective factors (13 factors of medical and neonatal, 4 factors of mother's lifestyle and 8 about mother factors). Data were analyzed by SPSS version 21 and WEKA software. Results: Our findings showed that mean weight of infants was 2289 ± 864 gr. The mean gestational age was 35.2 ± 4.63 weeks. 14.9% of mothers suffer from placenta previa and 14.4% suffer from preeclampsia. The results of ANOVA showed that neonatal weight was significantly higher among mothers with weight range of 84-110 Kg. The random forest algorithm showed that gestational age less than 36 weeks is main predictor and number of fetuses, preeclampsia, and premature rupture of membrane, placenta previa, the number of pregnancies and the degree of mother education were other predictors of low birth weight. Conclusion: This study confirmed that low birth weight is a multifactorial condition requiring a systematic and accurate program to reduce LBW. Individual and group education through mass media, repeated monitoring of pregnant mothers, activation of the referral system and pursuit of a family health care technician may reduce prevalence of LBW. 1 8 2018/01/14 1396/10/24 2018/03/17 1396/12/26 Shiva Ghaderighahfarokhi Shiva Ghaderighahfarokhi Department of Information Technology Management, Islamic Azad University, E-Campus, Tehran, Iran Iran Shivaghaderi92@gmail.com Jamil Sadeghifar Jamil Sadeghifar Department of Health Management, Faculty of Health, Ilam University of Medical Science, Ilam, Iran Iran Jamil.Sadeghifar@gmail.com Mossayeb Mozafari Mossayeb Mozafari Department of Nursing, Faculty of Nursing and Midwifery, Ilam University of Medical Science, Ilam, Iran Iran Mozafaric@yahoo.com Low birth weight Data mining Gestational age Shadzi SH MZ, Mostafavi F, Hassan Zadeh A. [Prevalence of low birth weight and their relation with some of maternal risk factors in Isfahan]. J Gilan Uni Medical Sci. 2000;9(33-34):55-61. (Persian) ##Behrman RE KR, Jenson HB Obesity. In: Patrica AD. Nelson Textbook of Pediatrics. 17th ed: Philadelphia, PA Saunders; 2004. ##Darling RD, Atav AS. Risk factors for low birth weight in New York state counties. Policy Polit Nurs Pract. 2012;13(1):17-26. doi: 10.1177/1527154412442391.##Hashemian Nejad N, Pejhan A, Rakhshani MH, Hoseini BL. The incidence of low birth weight (LBW) and small-for-gestational age (SGA) and its related factors in neonates, Sabzevar, Iran. Int J Pediatr. 2014;2(4.2):73-78. doi: 10.22038/ijp.2014.3502.##Noursalehi E. [Relationship between prenatal care and low-birth-weight newborns in Guilan/Iran]. Iran J Pediatr. 2003; 13(1): 66-8. (Persian)##Demelash H, Motbainor A, Nigatu D, Gashaw K, Melese A. Risk factors for low birth weight in Bale zone hospitals, South-East Ethiopia : a case-control study. BMC Pregnancy Childbirth. 2015;15:264. doi: 10.1186/s12884-015-0677-y.##Fanaroff AAM, Fanaroff RJAA, Martin RJ. Neonatal-perinatal medicine: diseases of the fetus and infant: Mosby; 2002.##Mohammadian S, Vakili M, Tabandeh A. Survey of related factors in prematurity Birth. 2000.##Nelson E. Textbook of pediatrics/Nelson E., Richard E. Behrman MD–WB Saunders company. Philadelphia, London, Toronto. 2000:262-266.##Podja J, Kelley L. Administrative Committee on Coordination/Sub–Committee on Nutrition. The UN Systems Forum for Nutrition. Nutrition Policy Paper. 2000;8.##Stoll BJ CI. The High-Risk Infant. In: Kliegman B, Jenson, Stanton editors, editor. Nelson Text book of Pediatrics. 18th ed. Saunders Elsevier, Philadelphia USA.2007.##Alexander G, Wingate M, Mor J, Boulet S. Birth outcomes of Asian-Indian-Americans. Int J Gynaecol Obstet. 2007; 97(3):215-20.##Eghbalian F. Low birth weight causes survey in neonates. Iran J Pediatr. 2007;17(Suppl 1):27-33.##Eshraghian M, Abou AJ, Ghafari Z, Rajaei S. [The effects of risk factor of pregnancy period on infant’s weight]. J Qazvin Uni Med Sci. 2008;11(4):60-65. (Persian)##Adleshoar M. [Factors predictive of underweight neonates in mothers that Referred to hospital in Rasht]. J Uni Shahid Beheshti Nurs Midwifery. 2006. 2005; 6:12-5. (Persian)##Firouzi Jahantigh F, Nazarnejad R, Firouzi Jahantigh M. [Investigating the Risk Factors for Low Birth Weight Using Data Mining: A Case Study of Imam Ali Hospital, Zahedan, Iran]. J Mazandaran Univ Med Sci. 2016; 25 (133):171-88. (Persian)##Mosayebi Z, Fakhraee SH, Movahedian AH. [Prevalence and risk factors of low birth weight infants in Mahdieh hospital, Tehran. Mosayebi Z, Fakhraee S H, Movahedian A H. Prevalence and risk factors of low birth weight infants in Mahdieh hospital, Tehran]. Feyz. 2004; 8 (2):58-67. (Persian)##Chen Y, Li G, Ruan Y, Zou L, Wang X, Zhang W. An epidemiological survey on low birth weight infants in China and analysis of outcomes of full-term low birth weight infants. BMC Pregnancy Childbirth. 2013; 13:242. doi: 10.1186/1471-2393-13-242.##Nayak RK, Metgud CS, Mallapur MD, Naik VA. Prevalence of low birth weight at Primary health centre of north Karnataka. Int J Pharm Med Bio Sci. 2013; 1:1-4.##Namakin K, Sharifzadeh G. [The evaluation of infants mortality causes and its related factors in Birjand]. J Isfahan Med Sch. 2009;27(95):275-82. (Persian)##Feresu SA, Harlow SD, Welch K, Gillespie BW. Incidence of and socio‐demographic risk factors for stillbirth, preterm birth and low birthweight among Zimbabwean women. Paediatr Perinat Epidemiol. 2004;18(2):154-63.##Coutinho PR, Cecatti JG, Surita FG, Costa ML, Morais SS. Perinatal outcomes associated with low birth weight in a historical cohort. Reprod Health. 2011;8:18. doi: 10.1186/1742-4755-8-18.##Lin RX. [Maternal, medical and obstetric complications are major risk factors for low birth weight infant]. Zhonghua Fu Chan Ke Za Zhi. 1993; 28(1):24-6. (Chinese) ##Ruiz RJ, Fullerton J, Dudley DJ. The interrelationship of maternal stress, endocrine factors and inflammation on gestational length. Obstet Gynecol Surv. 2003; 58(6):415-28.##Esmaeili MR, Haji AM, Asgardoon GH, Ghadimi R, Balegh M, Bizhani A, et al. [Effect of risk factors on low birth weight neonates]. J Babol Uni Med Sci. 2004;22(6):18-24. (Persian)##Delaram M, Akbari N. [Weight gain in pregnancy and its correlation with birth weight of infants]. Knowledge Health. 2008;3(2):39-43. (Persian)##Hajian K. [A study on mother'srisk factors for low birth weight in Babol in1999]. J Mazandaran Uni Med Si. 2001;10(26):50-4. (Persian)##Murphy CC, Schei B, Myhr TL, Du Mont J. Abuse: a risk factor for low birth weight? A systematic review and meta-analysis. CMAJ. 2001;164(11):1567-72.##Rahimi S, Moghimi R, Shadafza B, Shafaie S. The frequency of lbw and factors related to it at hospitals of tehran uniiversity of medical sciences. J Med Councile Islamic Republic of Iran (MJIRI). 2002; 20(2):83-8.##Ershadi A Ea, Sharif M. [Status of low birth weight infants in Kashan]. J Zanjan Uni Med Sci. 2000;8(30):54-60. (Persian)##Takimoto H, Yokoyama T, Yoshiike N, Fukuoka H. Increase in low‐birth‐weight infants in Japan and associated risk factors, 1980–2000. J Obstet Gynaecol Res. 2005;31(4):314-22.##Tough SC, Svenson LW, Johnston DW, Schopflocher D. Characteristic of preterm delivery and low birthweight among 113,994 infants in Alberta: 1994-1996. Can J Public Health. 2001;92(4):276-80.##Rafiei M. [Prevalence of low birth weight and obesity and some concomitant factors in live offspring’s in 2006 and compare with 2002 result’s in Arak Talleghani Hospital]. Iran J Pediatr. 2007;17(Suppl 1):47-53. (Persian)## ##

Designing of potential vaccine candidates of fused cathepsin L and tropomyosin genes of Rhipicephalus (Boophilus) annulatus tick larva 2 2 Introduction: Regarding emerging tick resistance against acaricides, researches have been shifted toward alternative approaches such as immunologic methods. Vaccine preparation is an alternative way in which choosing appropriate protein with high immune induction potency is a prerequisite. In addition according to studies, using more than one protein could better enhance the immune induction and antibody production. Choosing immunogenic epitopes from selected proteins and adjoining them with a suitable linker is one of the novel approaches in vaccine design. Materials and methods: Based on the fact that both cathepsin and tropomyosin proteins of Rhipicephalus tick were previously recognized as potent immunogenic antigens, we predicted the immunogenic epitopes of these proteins by immunoinformatic methods. Among studied epitopes, those that were met by multiple bioinformatics tools were used. Results: Finally, the polytopic construction was designed by assembling the selected epitopes and connecting them with linkers. Conclusion: Using immunoinformatic tools, we predicted the characteristics of two genes of Rhipicephalus annulatus tick larva as fused potent vaccine candidates namely, cathepsin and tropomyosin.   9 16 2018/01/142017/12/1 1396/9/10 2018/03/172018/04/21 1397/2/1 Zahra Asadollahi Zahra Asadollahi Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran Iran asadollahi.z@ut.ac.ir Sedigheh Nabian Sedigheh Nabian Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran Iran nabian@ut.ac.ir Mohammad Taheri Mohammad Taheri Rastegar Reference Laboratory, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran Iran Taherim@ut.ac.ir Elahe Ebrahimzadeh Elahe Ebrahimzadeh Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran Iran eebrahimzade@ut.ac.ir Mohammad Mehdi Ranjbar Mohammad Mehdi Ranjbar Razi Vaccine and Serum Research Institute, Agricultural Research, Education and Extension Organization (AREEO), Karaj, Iran Iran mm.ranjbar.phd@gmail.com Tropomyosin Cathepsin Rhipicephalus annulatus vaccine design Iran Guglielmone AA, Robbins RG, Apanaskevich DA, Petney TN, Estrada-Peña A, Horak I. The hard ticks of the world. Springer. 2014. P. 978-994. doi: 10.1007/978-94-007-7497-1##Nabian S, Rahbari S, Shayan P, Haddadzadeh H. Current status of tick fauna in north of Iran. Iran J Parasitol. 2007; 2(1):12-7.##Walker JB, Keirans JE, Horak IG. The genus Rhipicephalus (Acari, Ixodidae): a guide to the brown ticks of the world. Cambridge University Press. 2005. P. 2-4. ##Cakabay T, Gokdogan O, Kocyigit M. Human otoacariasis: Demographic and clinical outcomes in patients with ear-canal ticks and a review of literature. J Otol. 2016; 11(3):111-17.##Roush RT, McKenzie JA. Ecological genetics of insecticide and acaricide resistance. Annu Rev Entomol. 1987; 32:361-80. doi: 10.1146/annurev.en.32.010187.002045##Rodríguez MA. Developing Anti-tick Vaccines. Vaccine Design: Methods and Protocols. Vaccines for Veterinary Diseases. 2016. (2)243-259. doi: 10.1007/978-1-4939-3389-1##Ranjbar MM, Nabian S, Ahmadi NA, Ghorban K, Sazmand A, Dadmanesh M, et al. Immunoinformatics and similarity analysis of house dust mite tropomyosin. Novelty Biomed. 2015; 3(4):161-70. doi: http://dx.doi.org/10.22037/nbm.v3i4.6964##Gunning PW, Schevzov G, Kee AJ, Hardeman EC. Tropomyosin isoforms: divining rods for actin cytoskeleton function. Trends Cell Biol. 2005;15(6):333-41. doi: 10.1016/j.tcb.2005.04.007##Nabian S, Taheri M, Fard RM, Aramoon M. Identification of tropomyosin and its immunological properties from larvae of cattle tick, Boophilus annulatus. Iran J Parasitol. 2013;8(2):242-8.##Turk V, Stoka V, Vasiljeva O, Renko M, Sun T, Turk B, et al. Cysteine cathepsins: from structure, function and regulation to new frontiers. Biochim Biophys Acta. 2012;1824(1):68-88. doi: 10.1016/j.bbapap.2011.10.002##Franta Z, Frantová H, Konvičková J, Horn M, Sojka D, Mareš M, et al. Dynamics of digestive proteolytic system during blood feeding of the hard tick Ixodes ricinus. Parasit Vectors. 2010;3:119. doi: 10.1186/1756-3305-3-119.##Nisbet A, Huntley J, Mackellar A, Sparks N, McDevitt R. A house dust mite allergen homologue from poultry red mite Dermanyssus gallinae (De Geer). Parasite Immunol. 2006; 28(8):401-5. doi: 10.1111/j.1365-3024.2006.00862.x.##Sabhnani L, Manocha M, Sridevi K, Shashikiran D, Rayanade R, Rao DN. Developing subunit immunogens using B and T cell epitopes and their constructs derived from the F1 antigen of Yersinia pestis using novel delivery vehicles. FEMS Immunol Med Microbiol. 2003; 38(3):215-29.##Seib KL, Dougan G, Rappuoli R. The key role of genomics in modern vaccine and drug design for emerging infectious diseases. PLoS Genet. 2009; 5(10):e1000612. doi: 10.1371/journal.pgen.1000612##Kyte J, Doolittle RF. A simple method for displaying the hydropathic character of a protein. J Mol Biol. 1982; 157(1): 105-32.##Razmi GR, Glinsharifodini M, Sarvi S. Prevalence of ixodid ticks on cattle in Mazandaran province, Iran. Korean J Parasitol. 2007; 45(4): 307-10.##Nabian S, Taheri M, Ranjbar MM, Sazmand A, Youssefy P, Nazaralipour GR. Assessment and partial purification of serine protease inhibitors from Rhipicephalus (Boophilus) annulatus larvae. Rev Bras Parasitol Vet. 2014; 23( 2): 187-93.##Taheri M, Nabian S, Ranjbar M, Mazaheri NFR, Gerami SA, Sazmand A. Study of vitellogenin in Boophilus annulatus tick larvae and its immunological aspects; Trop Biomed. 2014; 31(3): 398-405.##McGowan MJ, Homer JT, O Dell GV, Mcnew RW, Barker RW. Performance of ticks fed on rabbits inoculated with extracts derived from homogenized ticks, Anaplasma maculatum Koch (Acarina: Ixodidae). J Parasitol. 1980; 66: 42-48.##Parizi LF, Pohl PC, Masuda A, Vaz Ida S Jr. New approaches toward anti-Rhipicephalus (Boophilus) microplus tick vaccine. Rev Bras Parasitol Vet. 2009;18(1):1-7.##Guerrero FD, Andreotti R, Bendele KG, Cunha RC, Miller RJ, Yeater K, et al. Rhipicephalus (Boophilus) microplus aquaporin as an effective vaccine antigen to protect against cattle tick infestations. Parasit Vectors. 2014;7:475. doi: 10.1186/s13071-014-0475-9. doi: 10.1186/s13071-014-0475-9##Rodrıguez M, Penichet ML, Mouris AE, Labarta V, Lorenzo LL, Rubiera R, et al. Control of B. microplus populations in grazing cattle vaccinated with a recombinant Bm86 antigen preparation. Vet Parasitol. 1995;57(4):339-49.##Willadsen P, Bird P, Cobon GS, Hungerford J. Commercialization of a recombinant vaccine against Boophilus microplus. Parasitology. 1995;110 Suppl:S43-50.##De la Fuente J, Rodriguez M, Garcia-Garcia JC. Immunological control of ticks through vaccination with Boophilus microplus gut antigens. Ann N Y Acad Sci. 2000;916:617-21.##De Vos S, Zeinstra L, Taoufik O, Willadsen P, Jongejan F. Evidence for the utility of the Bm86 antigen from Boophilus microplus in vaccination against other tick species. Exp Appl Acarol. 2001;25(3):245-61.##Zimic M, Gutiérrez AH, Gilman RH, López C, Quiliano M, Evangelista W, et al. Immunoinformatics prediction of linear epitopes from Taenia solium TSOL18. Bioinformation. 2011; 6(7):271-4. doi.10.6026/97320630006271##Bueno LL, Lobo FP, Morais CG, Mourão LC, de Ávila RAM, Soares IS, et al. Identification of a highly antigenic linear B cell epitope within Plasmodium vivax apical membrane antigen 1 (AMA-1). PLoS One. 2011;6(6):e21289. doi: 10.1371/journal.pone.0021289.##Fuaad AAH, Roubille R, Pearson MS, Pickering DA, Loukas AC, Skwarczynski M, et al. The use of a conformational cathepsin D-derived epitope for vaccine development against Schistosoma mansoni. Bioorg Med Chem. 2015 Mar 15;23(6):1307-12. doi: 10.1016/j.bmc.2015.01.033##Woollard DJ, Gauci CG, Heath DD, Lightowlers MW. Protection against hydatid disease induced with the EG95 vaccine is associated with conformational epitopes. Vaccine. 2000; 19(4):498-507.##Gomase VS, Chitlange NR. 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Evaluation of thinking style among medical and dental students of Ilam University of Medical Sciences in academic year of 2016-2017 2 2 Introduction: Education and research are two thinking based processes. Nowadays, the main function of educational institutions is evaluated by thinking. This study aimed to determine the dominant thinking styles among medical and dental students of Ilam University of Medical Sciences (IUMS). Materials and methods: This cross-sectional study was conducted on all medical and dental students of IUMS in the academic year of 2016-2017. Data was collected by Sternberg’s standard thinking style inventory and a demographic data questionnaire. Data analysis was carried out with the software SPSS 20 using descriptive statistical analysis methods and t-test. Results: In total, 497 students of IUMS participated in the study. Among whom 395 (79.5%) were medicals students and 102 (20.5%) were dental students. The findings showed significant differences between the legislative and executive thinking styles of medical and dental students (P=0.042 and P=0.024 respectively), more specifically, the mean score of legislative thinking style was found to be higher among dental students than that of medical students, and the opposite relation was found in the mean scores  of executive thinking style. Comparison of mean scores of thinking style dimensions between medical and dental students showed significant differences in some but not all dimensions. Conclusion: Considering the differences found in thinking styles of medical and dental students and their effects in emergence of unique behavioral and decision-making characteristics in medical and dental students, educational planners and professors should attempt to adjust their teaching methods and professional approach according to students individual features in terms of thinking style and preferences so as to foster the growth and flourish of their thinking, academic, and clinical capabilities. The results of the study showed significant differences between the legislative and executive thinking styles of medical and dental students, also regarding the different dimensions of thinking styles of medical and dental students, some significant differences in some but not all dimensions were reported. 17 22 2018/01/142017/12/12017/10/25 1396/8/3 2018/03/172018/04/212017/12/27 1396/10/6 Sareh Shakerian Rostami Sareh Shakerian Rostami School of Medical Education, Shahid Behesti University of Medical Sciences, Tehran, Iran Iran sarehshakerian@gmail.com Ali Sohrabnejad Ali Sohrabnejad School of Medical Education, Shahid Behesti University of Medical Sciences, Tehran, Iran Iran asnsohrabi@gmail.com Alireza Mirzaei Alireza Mirzaei The Center for Research and Development in Medical Education, Ilam University of Medical Sciences, Ilam, Iran Iran Thinking Thinking style Medical and dental students Simin S, Azizollah A, Nasrin M. Progression trend of critical thinking among nursing students in Iran. Int J Med Res Health Sci. 2017;6(1): 98-102. ##Keshtkaran A, Sadeghifar J. [A study on the relationship between thinking styles and preference learning methods among students of Shiraz University of Medical Sciences]. J Med Educ Dev 2013, 6(10): 50-5. (Persian) ##Seif A. [Educational psychology]. Tehran. Agah Publications. 2006. (Persian) ##Ko S. Do thinking styles of entrepreneurs matter in innovation? J Glob Busin Technol. 2008; 4(2): 24-33.##Shokri O, Kadivar P, Farzad V E, Daneshvarpour Z. Thinking styles and learning approaches in relation to students’ academic achievement. Advance Cognit Sci. 2006; 8 (2) :44-52.##Goodbrand A. The art of thinking: the classic guide to increasing brain Power Berkley; Reprint edition (February 5, 2002).##Zhang LF. Revisiting the predictive power of thinking styles for academic performance. J Psychol. 2004; 138(4):351-70. doi: 10.3200/JRLP.138.4.351-370##Mahboubeh H, Leila Z, Akram M. Relationship between types of thinking styles and academic adjustment with academic achievement among high school students. Social Sci. 2016;11(9): 2241-9. doi: 10.3923/sscience.2016.2241.2249##Ahanchian M, Hassanian Z. Relationship between thinking and problem solving styles in nursing students. J Nurs Educ. 2013; 2(3): 38-48.##Sarvghad S, Rezaei A, Masoomi F. Relationship of thinking styles with self-efficacy among male and female senior high school students in Shiraz. Sociol Women. 2011; 1(4): 135-56. ##Ghazivakili Z, Norouzi Nia R, Panahi F, Karimi M, Gholsorkhi H, Ahmadi Z. The role of critical thinking skills and learning styles of university students in their academic performance. J Adv Med Educ Prof. 2014;2(3):95-102.##Hendel T, Fish M, Galon V. Leadership style and choice of strategy in conflict management among Israeli nurse managers in general hospitals. J Nurs Manag. 2005;13(2):137-46.##Yahya S, Nasrin Y, Raoshan A. [Assessing dimensions of students' thinking style and its relationship with academic performance in Kermanshah University of medical sciences]. J Med Educ Dev. 2015, 8(17): 38-46. (Persian)## ##

Oral administration of triethylenetetramine (TETA) reduces some inflammatory markers in streptozotocin-induced diabetes mellitus in rat 2 2 Introduction: Owing to harmful effects of inflammatory markers on occurrence and progression of diabetic complications, hence, studying the possible effect of chemical components on these markers seems to be effective in diabetes mellitus. This study aimed to assess whether the triethylenetetramine (TETA), as a copper chelator, affects the plasma level of inflammatory markers such as visfatin (Vis), cholinesterase (CholE), total sialic acid (TSA) and hepcidin (Hep) in streptozotocin- induced diabetes mellitus rat. Materials and methods: Thirty male Wistar rats were assigned for this study. After induction of diabetes mellitus, TETA with different doses (10, 20 and 40 mg/kg/day) was orally administrated for 6 months. Thereupon, the above inflammatory factors were measured in all treatment groups. Results: Plasma concentrations of Vis, CholE, TSA, Hep and glucose decreased significantly (P<0.01) in the highest dose group (40 mg/kg/day) compared with control group. Interestingly, by enhancement of TETA dose, these levels were lowered. Conclusion: The results suggested that TETA administration in the dose of 40 mg/kg/day leads to profound reduction of the inflammatory markers Vis, CholE, TSA and Hep, therefore may have beneficial effect on diabetes mellitus. 23 31 2018/01/142017/12/12017/10/252017/11/1 1396/8/10 2018/03/172018/04/212017/12/272018/05/15 1397/2/25 Kaveh Azimzadeh Kaveh Azimzadeh Young Researcher and Elite Club, Urmia Branch, Islamic Azad University, Urmia, Iran Iran kaclinpath@gmail.com Hossein Jafarpour Hossein Jafarpour Department of Veterinary Medicine, Veterinary faculty, Urmia Branch, Islamic Azad University, Urmia, Iran Iran jafarpour_h@yahoo.com Farid Digeleh Farid Digeleh Department of Veterinary Medicine, Veterinary faculty, Urmia Branch, Islamic Azad University, Urmia, Iran Iran digale_f@yahoo.com Armin Gargarechi Armin Gargarechi Department of Veterinary Medicine, Veterinary faculty, Urmia Branch, Islamic Azad University, Urmia, Iran Iran gargarehchi_a@yahoo.com Triethylenetetramine Diabetes mellitus Novel inflammatory markers Ekin S, Mert N, Gunduz H, Meral I. Serum sialic acid levels and selected mineral status in patients with type 2 diabetes mellitus. Biol Trace Elem Res. 2003; 94(3):193-201. doi: 10.1385/BTER:94:3:193##Ugarte M, Brown M, Hollywood KA, Cooper GJ, Bishop PN, Dunn WD. Metabolomic analysis of rat serum in streptozotocin-induced diabetes and after treatment with oral triethylenetetramine (TETA). Genome Med. 2012;4(4):35. doi: 10.1186/gm334##Gong D, Lu J, Chen X, Reddy S, Crossman DJ, Glyn-Jones S, et al. A copper (II)-selective chelator ameliorates diabetes-evoked renal fibrosis and albuminuria, and suppresses pathogenic TGF-beta activation in the kidneys of rats used as a model of diabetes. Diabetologia. 2008;51(9):1741-51. doi: 10.1007/s00125-008-1088-7.##Walter JY, Uriu-Hare KL, Olin KL, Oster MH, Anawalt BD, Critchfield JW, et al. Zinc, manganese and magnesium status and complications of diabetes mellitus. Diabetes Care. 1991;14(11):1050-6.##Lu J, Gong D, Choong SY, Xu H, Chan YK, Chen X, et al. Copper(II)-selective chelation improves function and antioxidant defenses in cardiovascular tissues of rats as a model of diabetes: comparisons between triethylenetetramine and three less copper-selective transition-metal-targeted treatments. Diabetologia. 2010; 53(6):1217–26. doi: 10.1007/s00125-010-1698-8##Fukuhara A, Matsuda M, Nishizawa M, Segawa K, Tanaka M, Kishimoto K, et al. Visfatin: a protein secreted by visceral fat that mimics the effects of insulin. Science. 2005;307(5708):426-30. 010.1126/science.1097243##Fantuzzi G, Mazzone T. Adipose tissue and atherosclerosis: exploring the connection. Arterioscler Thromb Vasc Biol. 2007;27(5):996-1003. doi:10.1161/ATVBAHA.106.131755##Brentano F, Schorr O, Ospelt C, Stanczyk J, Gay RE, Gay S, et al. Pre-B cell colony-enhancing factor/visfatin, a new marker of inflammation in rheumatoid arthritis with pro-inflammatory and matrix-degrading activities. Arthritis Rheum. 2007; 56(9):2829-39. doi:10.1002/art.22833##Chen MP, Chung FM, Chang DM, Tsai JC, Huang HF, Shin SJ, et al. Elevated plasma level of visfatin/pre-B cell colony enhancing factor in patients with type 2 diabetes mellitus. J Clin Endocrinol Metab. 2006;91(1):295-9. doi:10.1210/jc.2005-1475##Kimura R, Ushiyama N, Fuji T, Kawashima K. Nicotine induced Ca2+ signaling and down-regulation of nicotinic acetylcholine receptor subunit expression in the CEM human leukemic T-cell line. Life Sci. 2003; 72(18-19):2155-8. doi.org/10.1016/S0024-3205(03)00077-8##Da Silva CB, Wolkmer P, Da Silva AS, Paim FC, Tonin AA, Castro VSP, et al. Cholinesterases as markers of the inflammatory process in rats infected with Leptospira interrogans serovar Icterohaemorrhagiae. J Med Microbiol. 2012; 61(Pt 2):278-84. doi: 10.1099/jmm.0.035501-0.##Park CH, Valore EV, Waring AJ, Ganz T. Hepcidin, a urinary antimicrobial peptide synthesized in the liver. 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An assessment of agility in selected hospitals of Mazandaran province, Iran 2 2 Introduction: Evaluating agility effectively and efficiently is necessary and challenging for organizations. Therefore, this article aimed to assess the performance of hospitals with organizational agility (OA) approach. Materials and methods: A descriptive-analytical study was done in which the statistical population consisted of managers and experts of hospital courses including medicine, nursing, midwifery, and paramedics. A total of 283 managers and experts were enrolled as the sample using the Krejcie and Morgan table with stratified random sampling. Data were analyzed using one-sample t test with SPSS20. Results: Among 13 elements of agility, the results showed that competence (P=0.032) had a significant difference with customer satisfaction (P=0.029). The results also showed that OA was not optimal in selected hospitals of Mazandaran province, Iran. Concerning the indicators, introduction of new product (8.56) and staff skill development indicator (5.32) were maximum and minimum, respectively. Conclusion: The results showed that OA was not optimal in selected hospitals. Introduction of new product scored the top, while staff skill development was the lowest. As a result, health policy makers are recommended to plan for customer satisfaction, timely utilization of facilities, elimination of weak points, lost cost reduction, encouragement and punishment system for staff, and staff empowerment. 32 41 2018/01/142017/12/12017/10/252017/11/12018/02/20 1396/12/1 2018/03/172018/04/212017/12/272018/05/152018/04/26 1397/2/6 Ghahraman Mahmoudi Ghahraman Mahmoudi Research Center of Hospital Administration, Faculty of Medicine, Sari Branch, Islamic Azad University, Sari, Iran Iran Ghahraman48@yahoo.com Masoomeh Abdi Talarposhti Masoomeh Abdi Talarposhti Department of Health Services Management, Sari Branch, Islamic Azad University, Sari, Iran Iran talarposhtiabdi@yahoo.com Organizational agility Accountability Competence Flexibility Speed Hospital Yang J. Supply chain agility: securing performance for Chinese Manufacturers. Int J Prod Econ. 2014; 150(C): 104–13. doi:10.1016/j.ijpe.2013.12.018.##Dahmardeh N, Banihashemi SA. Organizational agility and agile manufacturing. Euro Journals, Inc. 2010; 27: 178-84. ISSN 1450-2275 Issue 27 (2010).##Pan F, Nagi P. Multi-echelon supply chain network design in agile manufacturing. Omega. 2013; 41(6): 969-83. doi:10.1016/j.omega.2012.12.004. ##Zain M, Rose RC, Abdullah I, Masrom M. The relationship between information technology acceptance and organizational agility in Malaysia. Info Manag. 2005; 42(6):829-39. doi.org/10.1016/j.im.2004.09.001.##Agarwal A, Shankar R, Tiwari MK. Modeling agility of supply chain. Indus Market Manag.2007; 36(4):443-57. doi.org/10.1016/jindmarman.2005.12.004. ##Tsai Y. Relationship between organizational culture, leadership behavior and job satisfaction. BMC Health Serv Res. 2011; 11: 98. doi: 10.1186/1472-6963-11-98.##Chen H, Fuller SS, Friedman C, Hersh W. Medical informatics: knowledge management and data mining in biomedicine. New York: Springer Science and Business Media; 2006.##Popowich F. Using text mining and natural language processing for health care claims processing. ACM SIGKDD Explorations Newsletter. 2005; 7(1): 59-66. doi:10.1145/1089815.1089824.##Hamidieh A, Mirzazadeh A. Prioritizing the performance evaluation indicators of the academic e-learning system using fuzzy approach. Ind J Sci Technol . 2015; 8 (28):1-11. doi: 10.17485/ijst/2015/v8i28/71900.##Senkubuge F, Modisenyane M, Bishaw T. Strengthening health systems by health sector reforms. Glob Health Act. 2014; 7: 23568-69. doi: 10.3402/gha.v7.23568.##Lotfi F, Bastani P, Hadian M, Hamidi H, Nouraei Motlagh S, Delavari S. prowess. [Evaluating the performance of hospitals affiliated with Iran University of medical sciences: the use of economic techniques in the field of health]. Manag Slamt J. 2015; 18 (59): 43-54. (Persian)##Griffin D. Translation: Arab M, Ravangard R, Vali L, Kavosi Z. Hospitals: What They Are and How they Work? Tehran. 2012.##Yauch CA. Measuring agility as a performance outcome. J Manufactur Technol Manag. 2011; 22(3):384-404. doi.org/10.1108/17410381111112738.##Zariei Gavgani F, PourReza A, Hosseini M, Akbari F. [The views of senior managers of private hospitals in Tehran about the problems of private hospitals]. Payesh J. 2010; 10(1): 73-81. (Persian)##Wyatt JC, Sullivan F. What is health information? BMJ. 2005; 331 (7516): 566-68. doi: 10.1136/bmj.331.7516.566##Hotho A, Nürnberger A, Paaß G. A brief survey of text mining. LDV-Forum 20 (2005), No.1, pp.19-62. ##Karami M, Rahimi A, Shahmirzadi A H. Clinical data warehouse: an effective tool to create intelligence in disease management. Health Care Manag. 2017;36(4):380-84. doi: 10.1097/HCM.0000000000000113##Yusuf YY, Gunasekaran A, Musa A, Dauda M, El-Berishy NM, Cang S. A Relational study of supply chain agility, competitiveness and business performance in the oil and gas industry. Int J Prod Econ. 2014; 147:531-43.doi: 10.1016/j.ijpe.2012.10.009.##Belay H, Azim T, Kassahun H. Assessment of health management information system (HMIS) performance in SNNPR, Ethiopia.2014.##Yarmohammadian MH, Samooie R, Khodayari ZR, Ayoobian A, Bagherian MH. Agility in Isfahan hospitals, Iran. Health Info Manag. 2012; 8 (8):1122-8. (Persian)##Bagheri Kerachi A, Abbaspour A. Adaptation rate of universities with agile organization indices in the viewpoint of faculty members. Educ Strategy Med Sci. 2014; 7 (4):207-14. (Persian) ##Levitt DS, Hauer KE, Poncelet A, Mookherjee S. An innovative quality improvement curriculum for third-year medical students. Med Educ Online. 2012; 17. doi: 10.3402/meo.v17i0.18391. ##Treiger TM1, Fink-Samnick E. COLLABORATE©, Part IV: Ramping Up Competency-Based Performance Management. Prof Case Manag. 2017;22(3):101-115. doi: 10.1097/NCM.0000000000000217.##Bagherzadeh MR, Baloui JA, Moafi Madani SR. [Investigating the status of agility capabilities in government organizations (Case Study of Mazandaran Post Office)]. J Industr Strateg Manag. 2010; 7(18):37-49. (Persian)##Qasimi Sh. Identification and analysis of factors affecting the staff’s agility of the national bank of Sanandaj. Int J Human Cultur Stud. 2016; (Special Issue):1445-58.##Ribeiro L, Barata J, Colombo A. Supporting agile supply chain using a service-oriented shop floor. Eng Appl Artif Intell. 2009; 22(6):950-60. Doi:10.1016/j.engappai.2008.10.023 ##Lin CT, Chiu H, Tseng YH. Agility evaluation using fuzzy logic. Int J Produc Econom. 2006; 101:353-68. www.elsevier.com/locate/ijpe##Vaezi R, Sedaghatpour F. E-government and organization agility (Research in Civil Registration Organization of Tehran Province). J Med Sci. 2012; 22(67): 1-17. (Persian)##Zeng J, Jumbo A, Zhang J. embracing agile health analytics: a use case for stroke registry. Int J Health Res Innov. 2014; 2(2): 1-10.##Van Hoek R, Harrison A, Christopher M. Measuring agile capabilities in the supply chain. 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A delivery framework for health data mining and analytics. Austr Comput Soc. 2005; 38:381-87.##Abdi Talarposhti M, Mahmodi G, Jahani MA. [Factors affecting supply chain agility at hospitals in Iran. J Health Admin]. 2016; 19(64): 7-18. (Persian)##Laanti M, Salo O, Abrahamsoon P. Agile methods rapidly replacing traditional methods at Nokia: a survey of opinions on agile transformation. Inf Softw Technol. 2011; (53): 276-90. doi:10.1016/J.Infsof.2010.11.010.##Karami M. [Application of data-mining and text-mining analyzer tools in agility on healthcare organizations]. J Health Admin. 2007; 10(30):15-9. (Persian)##Prather JC, Lobach DF, Goodwin LK, Hales JW, Hage ML Hommond WE. Medical data mining: knowledge discovery in a clinical data warehouse. Proc AMIA Annu Fall Symp. 1997:101-5.##Ramadas K. Agile banking – managing the challenge of change. Finance from Infosys; 2014. P.54.##Kitzmiller R, Hunt E, Sproat SB. 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Comparison of high-intensity interval versus low-intensity continuous training for myelin synthesis related genes in C57BL/6 mice 2 2 Abstract  Introduction: By increasing the scientific focus on myelination, identifying factors that influence the myelination is an important goal for brain health. There are some studies that regular exercise improves myelin sheath and neuronal regeneration. However, the effects of exercise intensities on the myelination remain unclear. Therefore, the purpose of this study was to compare the effect of high-intensity interval (HIIT) versus low-intensity continuous training (LICT) on myelin synthesis-related genes in hippocampus of C57BL/6 mice. Materials and methods: Male C57BL/6 mice (n = 30) were randomly assigned to 3 groups: control (C), Interval training (IT), and Continuous training (CT). Training programs on the treadmill were performed for 8 weeks and then, the hippocampus of animals was analyzed for the expression of myelin basic protein (MBP) and proteolipid protein (PLP) genes. Data were analyzed using ANOVA. Results: The result showed that HIIT program significantly increased the mRNA levels of MBP and PLP in comparison with LICT and Control groups (P<0.05), while no significant differences were observed among the LICT and Control groups (P>0.05). Conclusion: Our results showed that HIIT had a more efficient by improving the expression of MBP and PLP genes compared to LICT in the hippocampus. 42 48 2018/01/142017/12/12017/10/252017/11/12018/02/202018/03/12 1396/12/21 2018/03/172018/04/212017/12/272018/05/152018/04/262018/07/19 1397/4/28 Maryam Naghibzadeh Maryam Naghibzadeh Department of Physical Education and Sports Science, Faculty of Literature and Humanities, Ilam University, Ilam, Iran Iran naghibzadehmaryam@yahoo.com Rouhollah Ranjbar Rouhollah Ranjbar Department of Exercise Physiology, Faculty of Sport Sciences, Shahid Chamran University of Ahvaz, Ahvaz, Iran Iran r.11ranjbar@gmail.com Mohammad Reza Tabandeh Mohammad Reza Tabandeh Department of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran Iran mtabandeh06@gmail.com Abdolhamid Habibi Abdolhamid Habibi Department of Exercise Physiology, Faculty of Sport Sciences, Shahid Chamran University of Ahvaz, Ahvaz, Iran Iran ma1.minaee@gmail.com Zohreh Ghotbeddin Zohreh Ghotbeddin Department of Physiology, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran Iran mnaghib4@gmail.com Interval training Continuous training Myelin basic protein Proteolipid protein Hippocampus Lindner M, Heine S, Haastert K, Garde N, Fokuhl J, Linsmeier F, et al. Sequential myelin protein expression during remyelination reveals fast and efficient repair after central nervous system demyelination. Neuropathol Appl Neurobiol. 2008; 34(1): 105-14. doi: 10.1111/j.1365-2990.2007.00879.x##Quarles RH, Macklin WB, Morell P. Myelin formation, structure and biochemistry. In Basic neurochemistry: molecular, cellular and medical aspects. 7th edn (Siegel G. J., Albers R. W., Brady S. T. and Price D., eds.), Academic Press Elsevier, New York; 2006. 51-71. ##Pagnini F, Bosma CM, Phillips D, Langer E. Symptom changes in multiple sclerosis following psychological interventions: a systematic review. BMC Neurol. 2014; 14(1): 222. doi.org/10.1186/s12883-014-0222-z##Motl RW, Sandroff BM, Kwakkel G, Dalgas U, Feinstein A, Heesen C, et al. Exercise in patients with multiple sclerosis. Lancet Neurol. 2017; 16(10): 848-56. doi: 10.1016/S1474-4422(17)30281-8.##Bernardes D, Brambilla R, Bracchi‐Ricard V, Karmally S, Dellarole A, Carvalho‐Tavares J, et al. Prior regular exercise improves clinical outcome and reduces demyelination and axonal injury in experimental autoimmune encephalomyelitis. J Neurochem. 2016; 136: 63-73. doi: 10.1111/jnc.13354.##Patel DI, White LJ. Effect of 10-day forced treadmill training on neurotrophic factors in experimental autoimmune encephalomyelitis. Appl Physiol Nutr Metab. 2013; 38(2): 194-9. doi: 10.1139/apnm-2012-0303.##Kim K, Shin MS, Cho HS, Kim YP. Effects of endurance exercise on expressions of glial fibrillary acidic protein and myelin basic protein in developing rats with maternal infection-induced cerebral palsy. J Exerc Rehabil. 2014;10(1):9-14. doi: 10.12965/jer.140084.##Naghibzadeh M, Ranjbar R, Tabandeh MR, Habibi A. Effects of two training programs on transcriptional levels of neurotrophins and glial cells population in hippocampus of experimental multiple sclerosis. Int J Sports Med. 2018; 39(8):604-12. doi: 10.1055/a-0608-4635.##Afzalpour ME, Chadorneshin HT, Foadoddini M, Eivari HA. Comparing interval and continuous exercise training regimens on neurotrophic factors in rat brain. Physiol Behav. 2015; 147: 78-83. doi: 10.1016/j.physbeh.2015.04.012.##Zimmer P, Bloch W, Schenk A, Oberste M, Riedel S, Kool J, et al. High-intensity interval exercise improves cognitive performance and reduces matrix metalloproteinases-2 serum levels in persons with multiple sclerosis: A randomized controlled trial. Mult Scler J. 2017: 1352458517728342. doi: 10.1177/1352458517728342.##Pin-Barre C, Constans A, Brisswalter J, Pellegrino C, Laurin J. Effects of high-versus moderate-intensity training on neuroplasticity and functional recovery after focal ischemia. Stroke. 2017; 48(10): 2855-64. doi: 10.1161/STROKEAHA.117.017962.##Baek S-S. Role of exercise on the brain. J Exerc Rehabil. 2016; 12(5): 380–5. doi: 10.12965/jer.1632808.404##Kim HN, Pak ME, Shin MJ, Kim SY, Shin YB, Yun YJ, et al. Comparative analysis of the beneficial effects of treadmill training and electroacupuncture in a rat model of neonatal hypoxia-ischemia. Int J Mol Med. 2017; 39(6): 1393-402. doi: 10.3892/ijmm.2017.2970##Lee JM, Park JM, Song MK, Oh YJ, Kim CJ, Kim YJ. The ameliorative effects of exercise on cognitive impairment and white matter injury from blood-brain barrier disruption induced by chronic cerebral hypoperfusion in adolescent rats. Neurosci Lett. 2017; 638: 83-9. doi: 10.1016/j.neulet.2016.12.018.##Yoon H, Kleven A, Paulsen A, Kleppe L, Wu J, Ying Z, et al. Interplay between exercise and dietary fat modulates myelinogenesis in the central nervous system. Biochim Biophys Acta. 2016; 1862(4): 545-55. doi: 10.1016/j.bbadis.2016.01.019.##White LJ, Castellano V. Exercise and Brain Health—Implications for Multiple Sclerosis. Sports Med. 2008; 38(2): 91-100. doi: 10.2165/00007256-200838020-00001##Kim TW, Sung YH. Regular exercise promotes memory function and enhances hippocampal neuroplasticity in experimental autoimmune encephalomyelitis mice. Neuroscience. 2017; 346: 173-81. doi: 10.1016/j.neuroscience.2017.01.016.##Cotman CW, Berchtold NC. Exercise: a behavioral intervention to enhance brain health and plasticity. Trends Neurosci. 2002; 25(6): 295-301. doi: 10.1016/S0166-2236(02)02143-4.##Gibbons TE, Pence BD, Petr G, Ossyra JM, Mach HC, Bhattacharya TK, et al. Voluntary wheel running, but not a diet containing (−)-Epigallocatechin-3-gallate and β-Alanine, improves learning, memory and hippocampal neurogenesis in aged mice. Behav Brain Res. 2014; 272: 131-40. doi: 10.1016/j.bbr.2014.05.049.##Feter N, Freitas M, Gonzales N, Umpierre D, Cardoso R, Rombaldi A. Effects of physical exercise on myelin sheath regeneration: A systematic review and meta-analysis. Sci Sports. 2017; 33(1):8-21. doi: 10.1016/j.scispo.2017.06.009.## Pedersen BK, Hoffman-Goetz L. Exercise and the immune system: regulation, integration, and adaptation. Physiol Rev. 2000; 80(3): 1055-81. doi: 10.1152/physrev.2000.80.3.1055.##Terra R, Silva SAGd, Pinto VS, Dutra PML. Effect of exercise on immune system: response, adaptation and cell signaling. Rev Bras Med Esport. 2012; 18(3): 208-14. doi: 10.1590/S1517-86922012000300015.## Houdebine L, Gallelli CA, Rastelli M, Sampathkumar NK, Grenier J. Effect of physical exercise on brain and lipid metabolism in mouse models of multiple sclerosis. Chem Phys Lipids. 2017. doi: 10.1016/j.chemphyslip.2017.06.002.##Tomlinson L, Leiton CV, Colognato H. Behavioral experiences as drivers of oligodendrocyte lineage dynamics and myelin plasticity. Neuropharmacology. 2016; 110: 548-62. doi: 10.1016/j.neuropharm.2015.09.016.## ##

Age related changes in clinicopathologic features of oral squamous cell carcinoma (OSCC) in Iranian patients: An epidemiologic study 2 2 Introduction: Clinicopathologic characteristics of oral Squamous cell carcinoma (OSCC) affected by age, although it is controversial. In this study the differences in clinicopathological features of OSCC were compared between patients younger and older than 40 years' old. Materials and methods: In this retrospective study the histopathologic records of OSCC patients who underwent surgery in Cancer Institute of Iran during 2005-2015 were retrieved. The demographic and histopathologic features of patients in two groups of younger than 40 and older than 40 years old were recorded and descriptive analysis was used for statistical interpretation between groups. Results: The most cases of OSCC in both groups was registered in males with 14.3% and 85.7% of cases in younger and older than 40, retrospectively. Tongue was the most prevalent anatomic location of OSCC in both groups (39%). Based on clinicopathologic features, most prevalent pathologic degree of OSCC in younger aged patients was moderately differentiated OSCC (14.5%). In patients older than 40, well differentiated OSCC (87.7%) was more prevalent. Conclusion: Based on histopathologic features, the moderately differentiated and well differentiated OSCC were more in younger and older patients than 40, respectively. The finding suggests that OSCC has more malignant feature in young patients. 49 51 2018/01/142017/12/12017/10/252017/11/12018/02/202018/03/122018/04/12 1397/1/23 2018/03/172018/04/212017/12/272018/05/152018/04/262018/07/192018/06/14 1397/3/24 Ramin Ghafari Ramin Ghafari Faculty of Dentistry, Shahed University, Tehran, Iran Iran ramin.ghaffari.s3@gmail.com Noushin Jalayer Naderi Noushin Jalayer Naderi Department of Oral and Maxillofacial Pathology, Faculty of Dentistry, Shahed University, Tehran, Iran Iran jalayer@shahed.ac.ir Amirnader Emami Razavi Amirnader Emami Razavi 3. Iran National Tumor Bank, Cancer Biology Research Center, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran, Iran Iran razavinader@gmail.com Squamous cell carcinoma Oral cavity Prognosis Neville BW, Dam DD, Allen CM, Bouquoct JE. Oral and maxillofacial pathology, 2nd ed. Philadelphia, Pensylvania: W.B. Saunders Company; 2016: 374-389.##Cuasumano RJ, Persky MS. 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Squamous cell carcinoma of the oral cavity and the oropharynx in patients less than 40 years of age: a 20-year analysis. Head Neck Oncol. 2012;4:28-34. doi: 10.1186/1758-3284-4-28.##Amsterdam JT, Strawitz JG.Squamous cell carcinoma of the oral cavity inyoung patients. J Surg Oncol. 1982; 19(2): 65-8.##Falaki F, Dalirsani Z, Pakfetrat A, FalakiA, Saghravanian N, Nosratzehi T, et al. Clinical and histopathological analysis of oral squamous cell carcinoma ofyoung patients in Mashhad, Iran: a retrospective study and review of literature. Med Oral Patol Oral Cir Bucal. 2011; 16(4): e473-e7.##Razavi SM, Khalesi S. Clinico-pathological differences of oral squamous cell carcinoma amongyounger and older patients. J Clin Exp Pathol. 2017; 7: 316.##Fan Y, Zheng L, Mao MH, Huang MW, Liu SM, Zhang J, et al. Survival analysis of oral squamous cell carcinoma in a subgroup of young patients. Asian Pac J Cancer Prev. 2014; 15(20): 8887-91.##Koo K, Barrowman R, McCullough M, Iseli T, Wiesenfeld D. Non-smoking non-drinking elderly females: a clinically distinct subgroup of oral squamous cell carcinoma patients. Int J Oral Maxillofac Surg. 2013; 42(8): 929-33.doi: 10.1016/j.ijom.2013.04.010.##Ur Rahaman SM, Ahmed Mujib B. Histopathological correlation oforal squamous cell carcinoma among younger and older patients. J Oral Maxillofac Pathol. 2014; 18(2): 183-8. doi: 10.4103/0973-029X.140734.##Siriwardena BS, Tilakaratne A, Amaratunga EA, Udagama MN, Ogawa I, Kudo Y, et al. Analysis of histopathological and immunohistochemicaldifferences of oral squamous cell carcinoma in young and old patients in Sri Lanka. J Oral Pathol Med. 2017; 36(6): 357-62.##Sun Q, Fang Q, Guo S. A comparison of oral squamous cellcarcinoma between young and old patients in a single medical center in China. Int J Clin Exp Med. 2015; 8(8): 12418-23.##Sasaki T, Moles DR, Imai Y, Speight PM.Clinico-pathological features of squamous cell carcinoma of the oral cavity in patients <40years of age. 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Expression of Toll-Like receptors in metabolic syndrome: A systematic review 2 2 Introduction: Toll-Like Receptors (TLRs) of innate immune system have documented roles in the pathogenesis of metabolic disorders. This study aims to systematically review the expression of TLRs on metabolic syndrome (MetS). Materials and methods: We systematically searched PubMed/Medline, ISI web of Science, Scopus, Google Scholar, EMBASE, and OVID databases until February 2017. The terms ‘‘Metabolic Syndrome’’ OR ‘‘Mets’’ AND ‘‘Toll like receptor’’ OR ‘‘Toll like’’ OR ‘‘TLRs’’ OR ‘‘TLR’’ were used. “Expression” advertently was not used in our search and was considered in the selection process. Three steps for selecting the articles and then their qualification were conducted. Results: First, 1373 articles were found in the international databases. After removing duplicates, 963 papers remained and after two steps of selection, this number reached 410 and then 27, respectively. After full text screening and qualifying processes, we finally included 13 articles consisting of five animal and eight human studies. All human studies reported overexpression of TLRs (types 2, 4, 5, 9) in MetS, and most animal studies documented an increased TLRs expression. Conclusion: This systematic review provides evidence for the relation of innate immune system with MetS. Its findings regarding overexpression of special TLRs (e.g. types 2, 4, 5, 9) in MetS and their basic mechanisms and clinical implications might be investigated in further studies. 52 56 2018/01/142017/12/12017/10/252017/11/12018/02/202018/03/122018/04/122017/12/31 1396/10/10 2018/03/172018/04/212017/12/272018/05/152018/04/262018/07/192018/06/142018/05/18 1397/2/28 Manijeh Mahdavi Manijeh Mahdavi Pediatric Inherited Diseases Research Center, Research Institute for Primordial Prevention of Non-Communicable disease, Isfahan University of Medical Sciences, Isfahan, Iran Iran manijeh.mahdavi@gmail.com Zahra Fallah Zahra Fallah Department of pediatrics, Child Growth and Development Research Center, Research Institute for Primordial Prevention of Non-Communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran Iran z_fallah@mail.mui.ac.ir Roya Kelishadi Roya Kelishadi Department of pediatrics, Child Growth and Development Research Center, Research Institute for Primordial Prevention of Non-Communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran Iran kelishadi@med.mui.ac.ir Metabolic Syndrome Toll-Like Receptors Chronic disease Inflammation Ramic E, Prasko S, Mujanovic OB, Gavran L. Metabolic syndrome-theory and practicE. Mater Sociomed. 2016; 28(1):71-3. doi: 10.5455/msm.2016.28.71-73.##Miranzadeh-Mahabadi H, Emadi-Baygi M, Nikpour P, Kelishadi R. Association study between metabolic syndrome and rs8066560 polymorphism in the promoter region of sterol regulatory element-binding transcription factor 1 gene in Iranian children and adolescents. Int J Prev Med. 2016; 7:41. doi: 10.4103/2008-7802.177314.##Fallah Z, Feizi A, Hashemipour M, Kelishadi R. Effect of fermented camel milk on glucose metabolism, insulin resistance and inflammatory biomarkers of adolescents with metabolic syndrome: A double-blind, randomized, cross-over trial. J Res Med Sci. 2018; 23:32. doi: 10.4103/jrms.JRMS_1191_17.##Fallah Z, Feizi A, Hashemipour M, Kelishadi R. Positive effect of fermented camel milk on liver enzymes of adolescents with metabolic syndrome: A double-blind, randomized, cross-over trial. Mater Sociomed. 2018 Mar; 30(1):20-25. doi: 10.5455/msm.2018.30.20-25.##Fessler MB, Rudel LL, Brown JM. Toll-like receptor signaling links dietary fatty acids to the metabolic syndrome. Curr Opin Lipidol. 2009; 20(5):379-85. doi: 10.1097/MOL.0b013e32832fa5c4.##Himes RW, Smith CW. Tlr2 is critical for diet-induced metabolic syndrome in a murine model. FASEB J. 2010; 24(3):731-9. doi: 10.1096/fj.09-141929.##Fresno M, Alvarez R, Cuesta N. Toll-like receptors, inflammation, metabolism and obesity. Arch Physiol Biochem. 2011;117(3):151-64. doi: 10.3109/13813455.2011.562514.##Eguchi K, Manabe I. Toll-like receptor, lipotoxicity and chronic inflammation: the pathological link between obesity and cardiometabolic disease. J Atheroscler Thromb. 2014;21(7):629-39.##Mogensen TH. Pathogen recognition and inflammatory signaling in innate immune defenses. Clin Microbiol Rev. 2009;22(2):240-73, Table of Contents. doi: 10.1128/CMR.00046-08.##Konner AC, Bruning JC. Toll-like receptors: linking inflammation to metabolism. Trends Endocrinol Metab. 2011;22(1):16-23. doi: 10.1016/j.tem.2010.08.007.##Fusaru AM, Stanciulescu CE, Surlin V, Taisescu C, Bold A, Pop OT, et al. Role of innate immune receptors TLR2 and TLR4 as mediators of the inflammatory reaction in human visceral adipose tissue. Rom J Morphol Embryol. 2012;53(3 Suppl):693-701.##Sunshine H, Iruela-Arispe ML. Membrane lipids and cell signaling. Curr Opin Lipidol. 2017;28(5):408-413. doi: 10.1097/MOL.0000000000000443.##Zhang W, Hartmann R, Tun HM, Elson CO, Khafipour E, Garvey WT. Deletion of the Toll-Like Receptor 5 Gene Per Se Does Not Determine the Gut Microbiome Profile That Induces Metabolic Syndrome: Environment Trumps Genotype. PLoS One. 2016;11(3):e0150943. doi: 10.1371/journal.pone.0150943.##Oosenbrug T, van de Graaff MJ, Ressing ME, van Kasteren SI. Chemical Tools for Studying TLR Signaling Dynamics. Cell Chem Biol. 2017;24(7):801-812. doi: 10.1016/j.chembiol.2017.05.022.##Lucas K, Maes M. Role of the Toll Like receptor (TLR) radical cycle in chronic inflammation: possible treatments targeting the TLR4 pathway. Mol Neurobiol. 2013;48(1):190-204. doi: 10.1007/s12035-013-8425-7.##Jialal I, Kaur H, Devaraj S. Toll-like receptor status in obesity and metabolic syndrome: a translational perspective. J Clin Endocrinol Metab. 2014;99(1):39-48. doi: 10.1210/jc.2013-3092.##Sharifnia T, Antoun J, Verriere TG, Suarez G, Wattacheril J, Wilson KT, et al. Hepatic TLR4 signaling in obese NAFLD. Am J Physiol Gastrointest Liver Physiol. 2015;309(4):G270-8. doi: 10.1152/ajpgi.00304.2014.##Cuevas AM, Lazo M, Zuniga I, Carrasco F, Potter JJ, Alvarez V, et al. Expression of MYD88 in Adipose Tissue of Obese People: Is There Some Role in the Development of Metabolic Syndrome? Metab Syndr Relat Disord. 2017;15(2):80-85. doi: 10.1089/met.2016.0104.##Zwolak A, Slabczynska O, Semeniuk J, Daniluk J, Szuster-Ciesielska A. Metformin Changes the Relationship between Blood Monocyte Toll-Like Receptor 4 Levels and Nonalcoholic Fatty Liver Disease-Ex Vivo Studies. PLoS One. 2016;11(3):e0150233. doi: 10.1371/journal.pone.0150233.##Devaraj S, Adams-Huet B, Jialal I. Endosomal Toll-Like Receptor Status in Patients with Metabolic Syndrome. Metab Syndr Relat Disord. 2015;13(10):477-80. doi: 10.1089/met.2015.0116.##Hong CP, Yun CH, Lee GW, Park A, Kim YM, Jang MH. TLR9 regulates adipose tissue inflammation and obesity-related metabolic disorders. Obesity (Silver Spring). 2015;23(11):2199-206. doi: 10.1002/oby.21215.##Jialal I, Devaraj S, Bettaieb A, Haj F, Adams-Huet B. Increased adipose tissue secretion of Fetuin-A, lipopolysaccharide-binding protein and high-mobility group box protein 1 in metabolic syndrome. Atherosclerosis. 2015;241(1):130-7. doi: 10.1016/j.atherosclerosis.2015.04.814.##Mishra J, Verma RK, Alpini G, Meng F, Kumar N. Role of Janus Kinase 3 in Predisposition to Obesity-associated Metabolic Syndrome. J Biol Chem. 2015;290(49):29301-12. doi: 10.1074/jbc.M115.670331.##Chassaing B, Ley RE, Gewirtz AT. Intestinal epithelial cell toll-like receptor 5 regulates the intestinal microbiota to prevent low-grade inflammation and metabolic syndrome in mice. Gastroenterology. 2014;147(6):1363-77.e17. doi: 10.1053/j.gastro.2014.08.033.##Jialal I, Rajamani U, Adams-Huet B, Kaur H. Circulating pathogen-associated molecular pattern - binding proteins and High Mobility Group Box protein 1 in nascent metabolic syndrome: implications for cellular Toll-like receptor activity. Atherosclerosis. 2014;236(1):182-7. doi: 10.1016/j.atherosclerosis.2014.06.022.##Orsatti CL, Petri Nahas EA, Nahas-Neto J, Orsatti FL, Giorgi VI, Witkin SS. Evaluation of Toll-Like receptor 2 and 4 RNA expression and the cytokine profile in postmenopausal women with metabolic syndrome. PLoS One. 2014;9(10):e109259. doi: 10.1371/journal.pone.0109259.##Hardy OT, Kim A, Ciccarelli C, Hayman LL, Wiecha J. Increased Toll-like receptor (TLR) mRNA expression in monocytes is a feature of metabolic syndrome in adolescents. Pediatr Obes. 2013;8(1):e19-23. doi: 10.1111/j.2047-6310.2012.00098.x.##Jialal I, Huet BA, Kaur H, Chien A, Devaraj S. Increased toll-like receptor activity in patients with metabolic syndrome. Diabetes Care. 2012;35(4):900-4. doi: 10.2337/dc11-2375.##Vijay-Kumar M, Aitken JD, Carvalho FA, Cullender TC, Mwangi S, Srinivasan S, et al. Metabolic syndrome and altered gut microbiota in mice lacking Toll-like receptor 5. Science. 2010;328(5975):228-31. doi: 10.1126/science.1179721.##Ahmad R, Al-Mass A, Atizado V, Al-Hubail A, Al-Ghimlas F, Al-Arouj M, et al. Elevated expression of the toll like receptors 2 and 4 in obese individuals: its significance for obesity-induced inflammation. J Inflamm (Lond). 2012;9(1):48. doi: 10.1186/1476-9255-9-48.##Catalan V, Gomez-Ambrosi J, Rodriguez A, Ramirez B, Rotellar F, Valenti V, et al. Increased tenascin C and Toll-like receptor 4 levels in visceral adipose tissue as a link between inflammation and extracellular matrix remodeling in obesity. J Clin Endocrinol Metab. 2012;97(10):E1880-9. doi: 10.1210/jc.2012-1670.##Jang HJ, Kim HS, Hwang DH, Quon MJ, Kim JA. Toll-like receptor 2 mediates high-fat diet-induced impairment of vasodilator actions of insulin. Am J Physiol Endocrinol Metab. 2013;304(10):E1077-88. doi: 10.1152/ajpendo.00578.2012.##Thompson JA, Webb RC. Potential role of Toll-like receptors in programming of vascular dysfunction. Clin Sci (Lond). 2013;125(1):19-25. doi: 10.1042/CS20120673.##McMillan RP, Wu Y, Voelker K, Fundaro G, Kavanaugh J, Stevens JR, et al. Selective overexpression of Toll-like receptor-4 in skeletal muscle impairs metabolic adaptation to high-fat feeding. Am J Physiol Regul Integr Comp Physiol. 2015;309(3):R304-13. doi: 10.1152/ajpregu.00139.2015.##Frisard MI, McMillan RP, Marchand J, Wahlberg KA, Wu Y, Voelker KA, et al. Toll-like receptor 4 modulates skeletal muscle substrate metabolism. Am J Physiol Endocrinol Metab. 2010;298(5):E988-98. doi: 10.1152/ajpendo.00307.2009.##Jialal I, Rajamani U. Endotoxemia of metabolic syndrome: a pivotal mediator of meta-inflammation. Metab Syndr Relat Disord. 2014;12(9):454-6. doi: 10.1089/met.2014.1504.##Vila IK, Badin PM, Marques MA, Monbrun L, Lefort C, Mir L, et al. Immune cell Toll-like receptor 4 mediates the development of obesity- and endotoxemia-associated adipose tissue fibrosis. Cell Rep. 2014;7(4):1116-29. doi: 10.1016/j.celrep.2014.03.062.##Goralska M, Majewska-Szczepanik M, Szczepanik M. [Immunological mechanisms involved in obesity and their role in metabolic syndrome]. Postepy Hig Med Dosw (Online). 2015;69:1384-404. (Polish)##Kanczkowski W, Ziegler CG, Zacharowski K, Bornstein SR. Toll-like receptors in endocrine disease and diabetes. Neuroimmunomodulation. 2008;15(1):54-60. doi: 10.1159/000135624.##Belforte FS, Coluccio Leskow F, Poskus E, Penas Steinhardt A. Toll-like receptor 4 D299G polymorphism in metabolic disorders: a meta-analysis. Mol Biol Rep. 2013;40(4):3015-20. doi: 10.1007/s11033-012-2374-5.##Cuda C, Badawi A, Karmali M, El-Sohemy A. Polymorphisms in Toll-like receptor 4 are associated with factors of the metabolic syndrome and modify the association between dietary saturated fat and fasting high-density lipoprotein cholesterol. Metabolism. 2011;60(8):1131-5. doi: 10.1016/j.metabol.2010.12.006.##Steinhardt AP, Aranguren F, Tellechea ML, Gomez Rosso LA, Brites FD, Martinez-Larrad MT, et al. A functional nonsynonymous toll-like receptor 4 gene polymorphism is associated with metabolic syndrome, surrogates of insulin resistance, and syndromes of lipid accumulation. Metabolism. 2010 y;59(5):711-7. doi: 10.1016/j.metabol.2009.09.015.##Ladefoged M, Buschard K, Hansen AM. Increased expression of toll-like receptor 4 and inflammatory cytokines, interleukin-6 in particular, in islets from a mouse model of obesity and type 2 diabetes. APMIS. 2013;121(6):531-8. doi: 10.1111/apm.12018.##Li J, Chen S, Qiang J, Wang X, Chen L, Zou D. Diet-induced obesity mediates a proinflammatory response in pancreatic beta cell via toll-like receptor 4. Cent Eur J Immunol. 2014;39(3):306-15. doi: 10.5114/ceji.2014.45940.##Prajapati B, Jena PK, Rajput P, Purandhar K, Seshadri S. Understanding and modulating the Toll like Receptors (TLRs) and NOD like Receptors (NLRs) cross talk in type 2 diabetes. Curr Diabetes Rev. 2014;10(3):190-200.##Strodthoff D, Ma Z, Wirstrom T, Strawbridge RJ, Ketelhuth DF, Engel D, et al. Toll-Like Receptor 3 Influences Glucose Homeostasis and beta-Cell Insulin Secretion. Diabetes. 2015;64(10):3425-38. doi: 10.2337/db14-0838.##Li D, Wang X, Lan X, Li Y, Liu L, Yi J, et al. Down-regulation of miR-144 elicits proinflammatory cytokine production by targeting toll-like receptor 2 in nonalcoholic steatohepatitis of high-fat-diet-induced metabolic syndrome E3 rats. Mol Cell Endocrinol. 2015;402:1-12. doi: 10.1016/j.mce.2014.12.007.##Miura K, Ohnishi H. Role of gut microbiota and Toll-like receptors in nonalcoholic fatty liver disease. World J Gastroenterol. 2014;20(23):7381-91. doi: 10.3748/wjg.v20.i23.7381.##Ye D, Li FY, Lam KS, Li H, Jia W, Wang Y, et al. Toll-like receptor-4 mediates obesity-induced non-alcoholic steatohepatitis through activation of X-box binding protein-1 in mice. Gut. 2012;61(7):1058-67. doi: 10.1136/gutjnl-2011-300269.##Zhang W, Hartmann R, Tun HM, Elson CO, Khafipour E, Garvey WT. Deletion of the Toll-Like Receptor 5 Gene Per Se Does Not Determine the Gut Microbiome Profile That Induces Metabolic Syndrome: Environment Trumps Genotype. PLoS One. 2016;11(3):e0150943. doi: 10.1371/journal.pone.0150943.##Ramic E, Prasko S, Mujanovic OB, Gavran L. Metabolic syndrome-theory and practicE. Mater Sociomed. 2016; 28(1):71-3. doi: 10.5455/msm.2016.28.71-73.##Miranzadeh-Mahabadi H, Emadi-Baygi M, Nikpour P, Kelishadi R. Association study between metabolic syndrome and rs8066560 polymorphism in the promoter region of sterol regulatory element-binding transcription factor 1 gene in Iranian children and adolescents. Int J Prev Med. 2016; 7:41. doi: 10.4103/2008-7802.177314.##Fallah Z, Feizi A, Hashemipour M, Kelishadi R. Effect of fermented camel milk on glucose metabolism, insulin resistance and inflammatory biomarkers of adolescents with metabolic syndrome: A double-blind, randomized, cross-over trial. J Res Med Sci. 2018; 23:32. doi: 10.4103/jrms.JRMS_1191_17.##Fallah Z, Feizi A, Hashemipour M, Kelishadi R. Positive effect of fermented camel milk on liver enzymes of adolescents with metabolic syndrome: A double-blind, randomized, cross-over trial. Mater Sociomed. 2018 Mar; 30(1):20-25. doi: 10.5455/msm.2018.30.20-25.##Fessler MB, Rudel LL, Brown JM. Toll-like receptor signaling links dietary fatty acids to the metabolic syndrome. Curr Opin Lipidol. 2009; 20(5):379-85. doi: 10.1097/MOL.0b013e32832fa5c4.##Himes RW, Smith CW. Tlr2 is critical for diet-induced metabolic syndrome in a murine model. FASEB J. 2010; 24(3):731-9. doi: 10.1096/fj.09-141929.##Fresno M, Alvarez R, Cuesta N. Toll-like receptors, inflammation, metabolism and obesity. Arch Physiol Biochem. 2011;117(3):151-64. doi: 10.3109/13813455.2011.562514.##Eguchi K, Manabe I. Toll-like receptor, lipotoxicity and chronic inflammation: the pathological link between obesity and cardiometabolic disease. J Atheroscler Thromb. 2014;21(7):629-39.##Mogensen TH. Pathogen recognition and inflammatory signaling in innate immune defenses. Clin Microbiol Rev. 2009;22(2):240-73, Table of Contents. doi: 10.1128/CMR.00046-08.##Konner AC, Bruning JC. Toll-like receptors: linking inflammation to metabolism. Trends Endocrinol Metab. 2011;22(1):16-23. doi: 10.1016/j.tem.2010.08.007.##Fusaru AM, Stanciulescu CE, Surlin V, Taisescu C, Bold A, Pop OT, et al. Role of innate immune receptors TLR2 and TLR4 as mediators of the inflammatory reaction in human visceral adipose tissue. Rom J Morphol Embryol. 2012;53(3 Suppl):693-701.##Sunshine H, Iruela-Arispe ML. Membrane lipids and cell signaling. Curr Opin Lipidol. 2017;28(5):408-413. doi: 10.1097/MOL.0000000000000443.##Zhang W, Hartmann R, Tun HM, Elson CO, Khafipour E, Garvey WT. Deletion of the Toll-Like Receptor 5 Gene Per Se Does Not Determine the Gut Microbiome Profile That Induces Metabolic Syndrome: Environment Trumps Genotype. PLoS One. 2016;11(3):e0150943. doi: 10.1371/journal.pone.0150943.##Oosenbrug T, van de Graaff MJ, Ressing ME, van Kasteren SI. Chemical Tools for Studying TLR Signaling Dynamics. Cell Chem Biol. 2017;24(7):801-812. doi: 10.1016/j.chembiol.2017.05.022.##Lucas K, Maes M. Role of the Toll Like receptor (TLR) radical cycle in chronic inflammation: possible treatments targeting the TLR4 pathway. Mol Neurobiol. 2013;48(1):190-204. doi: 10.1007/s12035-013-8425-7.##Jialal I, Kaur H, Devaraj S. Toll-like receptor status in obesity and metabolic syndrome: a translational perspective. J Clin Endocrinol Metab. 2014;99(1):39-48. doi: 10.1210/jc.2013-3092.##Sharifnia T, Antoun J, Verriere TG, Suarez G, Wattacheril J, Wilson KT, et al. Hepatic TLR4 signaling in obese NAFLD. Am J Physiol Gastrointest Liver Physiol. 2015;309(4):G270-8. doi: 10.1152/ajpgi.00304.2014.##Cuevas AM, Lazo M, Zuniga I, Carrasco F, Potter JJ, Alvarez V, et al. Expression of MYD88 in Adipose Tissue of Obese People: Is There Some Role in the Development of Metabolic Syndrome? Metab Syndr Relat Disord. 2017;15(2):80-85. doi: 10.1089/met.2016.0104.##Zwolak A, Slabczynska O, Semeniuk J, Daniluk J, Szuster-Ciesielska A. Metformin Changes the Relationship between Blood Monocyte Toll-Like Receptor 4 Levels and Nonalcoholic Fatty Liver Disease-Ex Vivo Studies. PLoS One. 2016;11(3):e0150233. doi: 10.1371/journal.pone.0150233.##Devaraj S, Adams-Huet B, Jialal I. Endosomal Toll-Like Receptor Status in Patients with Metabolic Syndrome. Metab Syndr Relat Disord. 2015;13(10):477-80. doi: 10.1089/met.2015.0116.##Hong CP, Yun CH, Lee GW, Park A, Kim YM, Jang MH. TLR9 regulates adipose tissue inflammation and obesity-related metabolic disorders. Obesity (Silver Spring). 2015;23(11):2199-206. doi: 10.1002/oby.21215.##Jialal I, Devaraj S, Bettaieb A, Haj F, Adams-Huet B. Increased adipose tissue secretion of Fetuin-A, lipopolysaccharide-binding protein and high-mobility group box protein 1 in metabolic syndrome. Atherosclerosis. 2015;241(1):130-7. doi: 10.1016/j.atherosclerosis.2015.04.814.##Mishra J, Verma RK, Alpini G, Meng F, Kumar N. Role of Janus Kinase 3 in Predisposition to Obesity-associated Metabolic Syndrome. J Biol Chem. 2015;290(49):29301-12. doi: 10.1074/jbc.M115.670331.##Chassaing B, Ley RE, Gewirtz AT. Intestinal epithelial cell toll-like receptor 5 regulates the intestinal microbiota to prevent low-grade inflammation and metabolic syndrome in mice. Gastroenterology. 2014;147(6):1363-77.e17. doi: 10.1053/j.gastro.2014.08.033.##Jialal I, Rajamani U, Adams-Huet B, Kaur H. Circulating pathogen-associated molecular pattern - binding proteins and High Mobility Group Box protein 1 in nascent metabolic syndrome: implications for cellular Toll-like receptor activity. Atherosclerosis. 2014;236(1):182-7. doi: 10.1016/j.atherosclerosis.2014.06.022.##Orsatti CL, Petri Nahas EA, Nahas-Neto J, Orsatti FL, Giorgi VI, Witkin SS. Evaluation of Toll-Like receptor 2 and 4 RNA expression and the cytokine profile in postmenopausal women with metabolic syndrome. PLoS One. 2014;9(10):e109259. doi: 10.1371/journal.pone.0109259.##Hardy OT, Kim A, Ciccarelli C, Hayman LL, Wiecha J. Increased Toll-like receptor (TLR) mRNA expression in monocytes is a feature of metabolic syndrome in adolescents. Pediatr Obes. 2013;8(1):e19-23. doi: 10.1111/j.2047-6310.2012.00098.x.##Jialal I, Huet BA, Kaur H, Chien A, Devaraj S. Increased toll-like receptor activity in patients with metabolic syndrome. Diabetes Care. 2012;35(4):900-4. doi: 10.2337/dc11-2375.##Vijay-Kumar M, Aitken JD, Carvalho FA, Cullender TC, Mwangi S, Srinivasan S, et al. Metabolic syndrome and altered gut microbiota in mice lacking Toll-like receptor 5. Science. 2010;328(5975):228-31. doi: 10.1126/science.1179721.##Ahmad R, Al-Mass A, Atizado V, Al-Hubail A, Al-Ghimlas F, Al-Arouj M, et al. Elevated expression of the toll like receptors 2 and 4 in obese individuals: its significance for obesity-induced inflammation. J Inflamm (Lond). 2012;9(1):48. doi: 10.1186/1476-9255-9-48.##Catalan V, Gomez-Ambrosi J, Rodriguez A, Ramirez B, Rotellar F, Valenti V, et al. Increased tenascin C and Toll-like receptor 4 levels in visceral adipose tissue as a link between inflammation and extracellular matrix remodeling in obesity. J Clin Endocrinol Metab. 2012;97(10):E1880-9. doi: 10.1210/jc.2012-1670.##Jang HJ, Kim HS, Hwang DH, Quon MJ, Kim JA. Toll-like receptor 2 mediates high-fat diet-induced impairment of vasodilator actions of insulin. Am J Physiol Endocrinol Metab. 2013;304(10):E1077-88. doi: 10.1152/ajpendo.00578.2012.##Thompson JA, Webb RC. Potential role of Toll-like receptors in programming of vascular dysfunction. Clin Sci (Lond). 2013;125(1):19-25. doi: 10.1042/CS20120673.##McMillan RP, Wu Y, Voelker K, Fundaro G, Kavanaugh J, Stevens JR, et al. Selective overexpression of Toll-like receptor-4 in skeletal muscle impairs metabolic adaptation to high-fat feeding. Am J Physiol Regul Integr Comp Physiol. 2015;309(3):R304-13. doi: 10.1152/ajpregu.00139.2015.##Frisard MI, McMillan RP, Marchand J, Wahlberg KA, Wu Y, Voelker KA, et al. Toll-like receptor 4 modulates skeletal muscle substrate metabolism. Am J Physiol Endocrinol Metab. 2010;298(5):E988-98. doi: 10.1152/ajpendo.00307.2009.##Jialal I, Rajamani U. Endotoxemia of metabolic syndrome: a pivotal mediator of meta-inflammation. Metab Syndr Relat Disord. 2014;12(9):454-6. doi: 10.1089/met.2014.1504.##Vila IK, Badin PM, Marques MA, Monbrun L, Lefort C, Mir L, et al. Immune cell Toll-like receptor 4 mediates the development of obesity- and endotoxemia-associated adipose tissue fibrosis. Cell Rep. 2014;7(4):1116-29. doi: 10.1016/j.celrep.2014.03.062.##Goralska M, Majewska-Szczepanik M, Szczepanik M. [Immunological mechanisms involved in obesity and their role in metabolic syndrome]. Postepy Hig Med Dosw (Online). 2015;69:1384-404. (Polish)##Kanczkowski W, Ziegler CG, Zacharowski K, Bornstein SR. Toll-like receptors in endocrine disease and diabetes. Neuroimmunomodulation. 2008;15(1):54-60. doi: 10.1159/000135624.##Belforte FS, Coluccio Leskow F, Poskus E, Penas Steinhardt A. Toll-like receptor 4 D299G polymorphism in metabolic disorders: a meta-analysis. Mol Biol Rep. 2013;40(4):3015-20. doi: 10.1007/s11033-012-2374-5.##Cuda C, Badawi A, Karmali M, El-Sohemy A. Polymorphisms in Toll-like receptor 4 are associated with factors of the metabolic syndrome and modify the association between dietary saturated fat and fasting high-density lipoprotein cholesterol. Metabolism. 2011;60(8):1131-5. doi: 10.1016/j.metabol.2010.12.006.##Steinhardt AP, Aranguren F, Tellechea ML, Gomez Rosso LA, Brites FD, Martinez-Larrad MT, et al. A functional nonsynonymous toll-like receptor 4 gene polymorphism is associated with metabolic syndrome, surrogates of insulin resistance, and syndromes of lipid accumulation. Metabolism. 2010 y;59(5):711-7. doi: 10.1016/j.metabol.2009.09.015.##Ladefoged M, Buschard K, Hansen AM. Increased expression of toll-like receptor 4 and inflammatory cytokines, interleukin-6 in particular, in islets from a mouse model of obesity and type 2 diabetes. APMIS. 2013;121(6):531-8. doi: 10.1111/apm.12018.##Li J, Chen S, Qiang J, Wang X, Chen L, Zou D. Diet-induced obesity mediates a proinflammatory response in pancreatic beta cell via toll-like receptor 4. Cent Eur J Immunol. 2014;39(3):306-15. doi: 10.5114/ceji.2014.45940.##Prajapati B, Jena PK, Rajput P, Purandhar K, Seshadri S. Understanding and modulating the Toll like Receptors (TLRs) and NOD like Receptors (NLRs) cross talk in type 2 diabetes. Curr Diabetes Rev. 2014;10(3):190-200.##Strodthoff D, Ma Z, Wirstrom T, Strawbridge RJ, Ketelhuth DF, Engel D, et al. Toll-Like Receptor 3 Influences Glucose Homeostasis and beta-Cell Insulin Secretion. Diabetes. 2015;64(10):3425-38. doi: 10.2337/db14-0838.##Li D, Wang X, Lan X, Li Y, Liu L, Yi J, et al. Down-regulation of miR-144 elicits proinflammatory cytokine production by targeting toll-like receptor 2 in nonalcoholic steatohepatitis of high-fat-diet-induced metabolic syndrome E3 rats. Mol Cell Endocrinol. 2015;402:1-12. doi: 10.1016/j.mce.2014.12.007.##Miura K, Ohnishi H. Role of gut microbiota and Toll-like receptors in nonalcoholic fatty liver disease. World J Gastroenterol. 2014;20(23):7381-91. doi: 10.3748/wjg.v20.i23.7381.##Ye D, Li FY, Lam KS, Li H, Jia W, Wang Y, et al. Toll-like receptor-4 mediates obesity-induced non-alcoholic steatohepatitis through activation of X-box binding protein-1 in mice. Gut. 2012;61(7):1058-67. doi: 10.1136/gutjnl-2011-300269.##Zhang W, Hartmann R, Tun HM, Elson CO, Khafipour E, Garvey WT. Deletion of the Toll-Like Receptor 5 Gene Per Se Does Not Determine the Gut Microbiome Profile That Induces Metabolic Syndrome: Environment Trumps Genotype. PLoS One. 2016;11(3):e0150943. doi: 10.1371/journal.pone.0150943.##Ramic E, Prasko S, Mujanovic OB, Gavran L. Metabolic syndrome-theory and practicE. Mater Sociomed. 2016; 28(1):71-3. doi: 10.5455/msm.2016.28.71-73.##Miranzadeh-Mahabadi H, Emadi-Baygi M, Nikpour P, Kelishadi R. 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Role of innate immune receptors TLR2 and TLR4 as mediators of the inflammatory reaction in human visceral adipose tissue. Rom J Morphol Embryol. 2012;53(3 Suppl):693-701.##Sunshine H, Iruela-Arispe ML. Membrane lipids and cell signaling. Curr Opin Lipidol. 2017;28(5):408-413. doi: 10.1097/MOL.0000000000000443.##Zhang W, Hartmann R, Tun HM, Elson CO, Khafipour E, Garvey WT. Deletion of the Toll-Like Receptor 5 Gene Per Se Does Not Determine the Gut Microbiome Profile That Induces Metabolic Syndrome: Environment Trumps Genotype. PLoS One. 2016;11(3):e0150943. doi: 10.1371/journal.pone.0150943.##Oosenbrug T, van de Graaff MJ, Ressing ME, van Kasteren SI. Chemical Tools for Studying TLR Signaling Dynamics. Cell Chem Biol. 2017;24(7):801-812. doi: 10.1016/j.chembiol.2017.05.022.##Lucas K, Maes M. Role of the Toll Like receptor (TLR) radical cycle in chronic inflammation: possible treatments targeting the TLR4 pathway. Mol Neurobiol. 2013;48(1):190-204. doi: 10.1007/s12035-013-8425-7.##Jialal I, Kaur H, Devaraj S. Toll-like receptor status in obesity and metabolic syndrome: a translational perspective. J Clin Endocrinol Metab. 2014;99(1):39-48. doi: 10.1210/jc.2013-3092.##Sharifnia T, Antoun J, Verriere TG, Suarez G, Wattacheril J, Wilson KT, et al. Hepatic TLR4 signaling in obese NAFLD. Am J Physiol Gastrointest Liver Physiol. 2015;309(4):G270-8. doi: 10.1152/ajpgi.00304.2014.##Cuevas AM, Lazo M, Zuniga I, Carrasco F, Potter JJ, Alvarez V, et al. Expression of MYD88 in Adipose Tissue of Obese People: Is There Some Role in the Development of Metabolic Syndrome? Metab Syndr Relat Disord. 2017;15(2):80-85. doi: 10.1089/met.2016.0104.##Zwolak A, Slabczynska O, Semeniuk J, Daniluk J, Szuster-Ciesielska A. Metformin Changes the Relationship between Blood Monocyte Toll-Like Receptor 4 Levels and Nonalcoholic Fatty Liver Disease-Ex Vivo Studies. PLoS One. 2016;11(3):e0150233. doi: 10.1371/journal.pone.0150233.##Devaraj S, Adams-Huet B, Jialal I. Endosomal Toll-Like Receptor Status in Patients with Metabolic Syndrome. Metab Syndr Relat Disord. 2015;13(10):477-80. doi: 10.1089/met.2015.0116.##Hong CP, Yun CH, Lee GW, Park A, Kim YM, Jang MH. TLR9 regulates adipose tissue inflammation and obesity-related metabolic disorders. Obesity (Silver Spring). 2015;23(11):2199-206. doi: 10.1002/oby.21215.##Jialal I, Devaraj S, Bettaieb A, Haj F, Adams-Huet B. Increased adipose tissue secretion of Fetuin-A, lipopolysaccharide-binding protein and high-mobility group box protein 1 in metabolic syndrome. Atherosclerosis. 2015;241(1):130-7. doi: 10.1016/j.atherosclerosis.2015.04.814.##Mishra J, Verma RK, Alpini G, Meng F, Kumar N. Role of Janus Kinase 3 in Predisposition to Obesity-associated Metabolic Syndrome. J Biol Chem. 2015;290(49):29301-12. doi: 10.1074/jbc.M115.670331.##Chassaing B, Ley RE, Gewirtz AT. Intestinal epithelial cell toll-like receptor 5 regulates the intestinal microbiota to prevent low-grade inflammation and metabolic syndrome in mice. Gastroenterology. 2014;147(6):1363-77.e17. doi: 10.1053/j.gastro.2014.08.033.##Jialal I, Rajamani U, Adams-Huet B, Kaur H. Circulating pathogen-associated molecular pattern - binding proteins and High Mobility Group Box protein 1 in nascent metabolic syndrome: implications for cellular Toll-like receptor activity. Atherosclerosis. 2014;236(1):182-7. doi: 10.1016/j.atherosclerosis.2014.06.022.##Orsatti CL, Petri Nahas EA, Nahas-Neto J, Orsatti FL, Giorgi VI, Witkin SS. Evaluation of Toll-Like receptor 2 and 4 RNA expression and the cytokine profile in postmenopausal women with metabolic syndrome. PLoS One. 2014;9(10):e109259. doi: 10.1371/journal.pone.0109259.##Hardy OT, Kim A, Ciccarelli C, Hayman LL, Wiecha J. Increased Toll-like receptor (TLR) mRNA expression in monocytes is a feature of metabolic syndrome in adolescents. Pediatr Obes. 2013;8(1):e19-23. doi: 10.1111/j.2047-6310.2012.00098.x.##Jialal I, Huet BA, Kaur H, Chien A, Devaraj S. Increased toll-like receptor activity in patients with metabolic syndrome. Diabetes Care. 2012;35(4):900-4. doi: 10.2337/dc11-2375.##Vijay-Kumar M, Aitken JD, Carvalho FA, Cullender TC, Mwangi S, Srinivasan S, et al. Metabolic syndrome and altered gut microbiota in mice lacking Toll-like receptor 5. Science. 2010;328(5975):228-31. doi: 10.1126/science.1179721.##Ahmad R, Al-Mass A, Atizado V, Al-Hubail A, Al-Ghimlas F, Al-Arouj M, et al. Elevated expression of the toll like receptors 2 and 4 in obese individuals: its significance for obesity-induced inflammation. J Inflamm (Lond). 2012;9(1):48. doi: 10.1186/1476-9255-9-48.##Catalan V, Gomez-Ambrosi J, Rodriguez A, Ramirez B, Rotellar F, Valenti V, et al. Increased tenascin C and Toll-like receptor 4 levels in visceral adipose tissue as a link between inflammation and extracellular matrix remodeling in obesity. J Clin Endocrinol Metab. 2012;97(10):E1880-9. doi: 10.1210/jc.2012-1670.##Jang HJ, Kim HS, Hwang DH, Quon MJ, Kim JA. Toll-like receptor 2 mediates high-fat diet-induced impairment of vasodilator actions of insulin. Am J Physiol Endocrinol Metab. 2013;304(10):E1077-88. doi: 10.1152/ajpendo.00578.2012.##Thompson JA, Webb RC. Potential role of Toll-like receptors in programming of vascular dysfunction. Clin Sci (Lond). 2013;125(1):19-25. doi: 10.1042/CS20120673.##McMillan RP, Wu Y, Voelker K, Fundaro G, Kavanaugh J, Stevens JR, et al. Selective overexpression of Toll-like receptor-4 in skeletal muscle impairs metabolic adaptation to high-fat feeding. Am J Physiol Regul Integr Comp Physiol. 2015;309(3):R304-13. doi: 10.1152/ajpregu.00139.2015.##Frisard MI, McMillan RP, Marchand J, Wahlberg KA, Wu Y, Voelker KA, et al. Toll-like receptor 4 modulates skeletal muscle substrate metabolism. Am J Physiol Endocrinol Metab. 2010;298(5):E988-98. doi: 10.1152/ajpendo.00307.2009.##Jialal I, Rajamani U. Endotoxemia of metabolic syndrome: a pivotal mediator of meta-inflammation. Metab Syndr Relat Disord. 2014;12(9):454-6. doi: 10.1089/met.2014.1504.##Vila IK, Badin PM, Marques MA, Monbrun L, Lefort C, Mir L, et al. Immune cell Toll-like receptor 4 mediates the development of obesity- and endotoxemia-associated adipose tissue fibrosis. Cell Rep. 2014;7(4):1116-29. doi: 10.1016/j.celrep.2014.03.062.##Goralska M, Majewska-Szczepanik M, Szczepanik M. [Immunological mechanisms involved in obesity and their role in metabolic syndrome]. Postepy Hig Med Dosw (Online). 2015;69:1384-404. (Polish)##Kanczkowski W, Ziegler CG, Zacharowski K, Bornstein SR. Toll-like receptors in endocrine disease and diabetes. Neuroimmunomodulation. 2008;15(1):54-60. doi: 10.1159/000135624.##Belforte FS, Coluccio Leskow F, Poskus E, Penas Steinhardt A. Toll-like receptor 4 D299G polymorphism in metabolic disorders: a meta-analysis. Mol Biol Rep. 2013;40(4):3015-20. doi: 10.1007/s11033-012-2374-5.##Cuda C, Badawi A, Karmali M, El-Sohemy A. Polymorphisms in Toll-like receptor 4 are associated with factors of the metabolic syndrome and modify the association between dietary saturated fat and fasting high-density lipoprotein cholesterol. Metabolism. 2011;60(8):1131-5. doi: 10.1016/j.metabol.2010.12.006.##Steinhardt AP, Aranguren F, Tellechea ML, Gomez Rosso LA, Brites FD, Martinez-Larrad MT, et al. A functional nonsynonymous toll-like receptor 4 gene polymorphism is associated with metabolic syndrome, surrogates of insulin resistance, and syndromes of lipid accumulation. Metabolism. 2010 y;59(5):711-7. doi: 10.1016/j.metabol.2009.09.015.##Ladefoged M, Buschard K, Hansen AM. Increased expression of toll-like receptor 4 and inflammatory cytokines, interleukin-6 in particular, in islets from a mouse model of obesity and type 2 diabetes. APMIS. 2013;121(6):531-8. doi: 10.1111/apm.12018.##Li J, Chen S, Qiang J, Wang X, Chen L, Zou D. Diet-induced obesity mediates a proinflammatory response in pancreatic beta cell via toll-like receptor 4. Cent Eur J Immunol. 2014;39(3):306-15. doi: 10.5114/ceji.2014.45940.##Prajapati B, Jena PK, Rajput P, Purandhar K, Seshadri S. Understanding and modulating the Toll like Receptors (TLRs) and NOD like Receptors (NLRs) cross talk in type 2 diabetes. Curr Diabetes Rev. 2014;10(3):190-200.##Strodthoff D, Ma Z, Wirstrom T, Strawbridge RJ, Ketelhuth DF, Engel D, et al. Toll-Like Receptor 3 Influences Glucose Homeostasis and beta-Cell Insulin Secretion. Diabetes. 2015;64(10):3425-38. doi: 10.2337/db14-0838.##Li D, Wang X, Lan X, Li Y, Liu L, Yi J, et al. Down-regulation of miR-144 elicits proinflammatory cytokine production by targeting toll-like receptor 2 in nonalcoholic steatohepatitis of high-fat-diet-induced metabolic syndrome E3 rats. Mol Cell Endocrinol. 2015;402:1-12. doi: 10.1016/j.mce.2014.12.007.##Miura K, Ohnishi H. Role of gut microbiota and Toll-like receptors in nonalcoholic fatty liver disease. World J Gastroenterol. 2014;20(23):7381-91. doi: 10.3748/wjg.v20.i23.7381.##Ye D, Li FY, Lam KS, Li H, Jia W, Wang Y, et al. Toll-like receptor-4 mediates obesity-induced non-alcoholic steatohepatitis through activation of X-box binding protein-1 in mice. Gut. 2012;61(7):1058-67. doi: 10.1136/gutjnl-2011-300269.##Zhang W, Hartmann R, Tun HM, Elson CO, Khafipour E, Garvey WT. Deletion of the Toll-Like Receptor 5 Gene Per Se Does Not Determine the Gut Microbiome Profile That Induces Metabolic Syndrome: Environment Trumps Genotype. PLoS One. 2016;11(3):e0150943. doi: 10.1371/journal.pone.0150943.## ##