Comparing the chromium ion release rate from stainless steel orthodontic wires with and without surface abrasion in an artificial saliva solution: An in-vitro study

Comparing the chromium ion release rate from stainless steel orthodontic wires with and without surface abrasion in an artificial saliva solution: An in-vitro study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Comparing the chromium ion release rate from stainless steel orthodontic wires with and without surface abrasion in an artificial saliva solution: An in-vitro study Parisa Kazemi, Mohammad Reza Soltani, Mehrnaz Moradinezhad, Minou Najar Nobari, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6680924/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Introduction : Placing orthodontic wires in the oral cavity, exposing them to saliva, can cause corrosion and the release of metal ions, such as chromium. If this release of metal ions exceeds a certain amount, it could lead to cell toxicity and other complications. This study aimed to determine the chromium ion release rate from stainless steel orthodontic wires in an artificial saliva solution. Methods and Materials : In this laboratory study, we selected 24 sections of stainless-steel orthodontic wires from two brands: American Orthodontics and Ortho Organizer. The wires from each brand were then divided into two groups, one with scratches and one without. In each group, we placed three pairs of upper and lower jaw orthodontic wires into Falcon tubes filled with 50cc of artificial saliva solution. After ensuring complete sealing, we incubated the samples at 37 degrees Celsius. The concentration of chromium ions released in each sample was measured using an ICP-OES device at three intervals: 1, 14, and 28 days. We analyzed the obtained data using SPSS version 24 software. Results : The study results demonstrate a significant difference (P<0.001) in the amount of chromium ion released between wires without surface scratches and those with surface scratches for both brands. On average, the release of chromium ions was higher in wires with surface scratches. Additionally, a significant difference (P<0.001) in chromium ion release was observed between the two brands. In this case, the Ortho Organizer brand exhibited a higher average release of chromium ions, both in wires with surface scratches and those without. Conclusion: This study demonstrates that chromium ions are released at a faster rate from stainless steel (SS) orthodontic wires with surface scratches. Nevertheless, it's important to note that the maximum amount of chromium ion released remains below the toxic threshold for the human body. Chromium ion release orthodontic wire surface scratching artificial saliva Figures Figure 1 Figure 2 Introduction Fixed orthodontics is an effective method for treating facioskeletal abnormalities. In this approach, brackets are affixed to the tooth surfaces using specialized orthodontic composites, and they are then connected by strong wires. During the course of treatment, patients are required to keep these orthodontic appliances in their mouths without removal until treatment completion. [ 1 ] Orthodontic brackets and wires are crafted from various metal alloys, including stainless steel, chrome alloy, cobalt, and nickel. It is crucial that the metal wires used in the oral cavity are free from any potentially hazardous products resulting from corrosion. [ 2 , 3 ] Stainless steel alloys have been widely used in both fixed and mobile orthodontic treatments since 1932 [ 3 ]. Chromium, a key component of stainless steel, can effectively prevent rusting and enhance the strength of alloys. Stainless steel wires typically contain chromium in the range of 17–22% [ 4 , 5 ]. Direct exposure of metals and alloys to food in the oral cavity creates an environment that can lead to corrosion. Oral saliva serves as an electrolyte, influenced by factors such as temperature fluctuations, enzymatic and microbial activities, saliva pH, and various chemicals introduced through food and drink [ 6 – 9 ]. This corrosion process can result in the release of metal ions, including nickel, chromium, cobalt, and iron, into the human body. For example, in a study conducted by Dr. Brigitte Wendl in Australia in 2017 [ 10 ], it was observed that a significant amount of nickel and chromium ions were released from orthodontic brackets and wires when exposed to an artificial saliva solution. It's worth noting that although these metal ions were released, their levels remained below the threshold considered toxic to the human body. The release of corrosion ions can lead to pain, swelling, and the potential for secondary infections in the treatment area. Additionally, there have been reported cases of allergies, dermatitis [Dermatitis], and asthma triggered by the release of chromium ions from orthodontic appliances. In addition to allergic reactions, the release of chromium ions can cause local pain and have cytotoxic effects, potentially leading to mutagenesis and, in rare instances, cancer [ 2 , 4 , 6 – 11 ]. The normal levels of chromium ions in blood serum and urine are typically 0.1 mg and 0.2 mg, respectively. Chromium, nickel, and iron ions can induce the release of free radicals, which can result in cytotoxic effects [Cytotoxicity] [ 12 – 13 ]. Hence, the European Food Safety Authority (EFSA) has established a safe weekly limit for chromium ion exposure in patients using orthodontic appliances at 2.1 micrograms per kilogram of body weight. Research indicates that toxic effects tend to manifest when body tissues are subjected to high levels of metal ions over an extended duration [ 11 – 14 ]. Conversely, in order to minimize friction between the orthodontic wire and the bracket, particularly in the posterior region, and to facilitate sliding movements, control torque and the angle of the anterior teeth, and enhance patient comfort, companies have introduced a new type of orthodontic wire known as the Bidimensional [Bidimensional] wire. This wire is manufactured and supplied with ball ends [ 15 , 16 ]. At times, due to the high cost or limited availability of bidimensional wires, there may be no alternative but to use regular-sized stainless-steel wires. To minimize the contact surface between the brackets and the wire in such cases, practitioners often trim the edges in the posterior region and create scratches on both ends of the stainless-steel wires. This process results in a rounded cross-section at the ends of the wire, making it smaller than the anterior part. However, it's important to note that these scratched surfaces can increase the release of metal ions, particularly chromium, from the orthodontic wires [ 17 ]. Methods and Materials Based on the aforementioned theory, this study aimed to compare the chromium ion release from stainless steel orthodontic wires with and without surface scratches in an artificial saliva solution. Design and population This research represents an experimental laboratory study ([In vitro]) conducted in the central laboratory of Shahid Chamran University of Ahvaz in the year 2022. For this study, 24 pieces of stainless-steel orthodontic wire with dimensions of 0.025 x 0.019 inches and a rectangular cross-section were selected from American Orthodontics and Ortho Organizer (12 pieces from each brand). These wires were then divided into four groups as follows (table1) According to Mirhashmi et al.'s study (4) and based on the following formula, the sample size was estimated to be 6 in each group (24 in each group). Entry criteria in this study include; Stainless steel orthodontic wire owned by Ortho Organizer and American Orthodontics. Dimensions are 0.019 x 0.025 inches, with rectangular cross-section, no previous scratches and having maintenance conditions. It was standard. Procedure Initially, all orthodontic wire samples were sourced from reputable centers and transported to the central laboratory of Shahid Chamran University of Ahvaz while maintaining the original factory packaging conditions. To prepare the surfaces, the orthodontic wires were immersed in an acetone solution for 2 minutes, followed by rinsing with distilled water and thorough drying. Subsequently, 12 laboratory Falcon tubes were prepared and divided into 4 groups, each containing three tubes. Using sterile forceps, two orthodontic wires, comprising one upper jaw arch wire and one lower jaw arch wire, were placed inside each tube. In both groups A and C, orthodontic wires were scratched in the region of teeth 5–7 using a scratch operator, specifically the Saeshin micro-motor model Strong-207B from South Korea, with a speed of 10,000 rpm. This was performed using a Saeshin handpiece and a cylindrical diamond drill, number 837, made in Switzerland, with scratching taking place at both ends of the wires over a 20 mm length. Subsequently, each Falcon tube was filled with 50cc of artificial saliva solution, ensuring complete saturation of the orthodontic wire pieces. The artificial saliva solution used in this study was Fusayama's [Fusaya], which closely mimics natural saliva and was prepared under laboratory conditions by the Department of Clinical Biochemistry, Faculty of Chemistry, Shahid Chamran University (table2). The tubes were tightly sealed and completely closed before being placed in an incubator set at 37°C for a duration of 28 days. To ensure that the artificial saliva solution matched the concentration and physiological pH of human saliva (pH 6.5), it was mixed with a NaOH solution. Information collection method : We collected samples at specific intervals following the initiation of the intervention: the first 24 hours, two weeks, and four weeks. At the conclusion of each time period, we extracted 5cc of artificial saliva solution from each tube using sterile plastic syringes. The released chromium ions were then transferred to 5ml Falcon tubes and measured using an Inductively Coupled Plasma Optical Emission Spectrometer (ICP-OES), specifically the Optima 8300 model by Perkin Elmer Company of America. Spectroscopy, an instrumental method in analytical chemistry, is capable of detecting a wide range of ground-state elements known as analytes [components or chemical species present in a substance or chemical compound] (55). To ensure the accurate operation of the device, it was calibrated by a qualified operator. Prior to sample analysis, we calibrated the device using a known amount of chromium solution. Subsequently, artificial saliva samples were measured for released chromium ions in parts per billion (ppb) units. For precise monitoring, we placed an artificial saliva sample without wire into the ICP-OES device to confirm that the solution itself did not contain any chromium. The protocol of this study is approved by ethical board. Data analysis method In this research, we employed both descriptive and analytical statistical methods to investigate the release of chromium ions in the samples. After confirming the normality of data distribution and the equality of variances through the Kolmogorov-Smirnov test and Levin's test, we utilized the two-sample independent T-parametric statistical method to compare the means and frequencies of the variables under study. Throughout this study, we maintained a significance level of 5% in all our statistical tests. Statistical analyses were performed using SPSS version 24. This article has an ethical code IR.MEDILAM.REC.1400.169, issued by Ilam University of Medical Sciences. Results The results of the independent t-test revealed a significant difference (P-value < 0.001) in the release of chromium ions from wires with surface scratches compared to wires without surface scratches at all three measurement stages (24 hours, two weeks, and four weeks after the start of the intervention) for both the American Orthodontics and Ortho Organizer groups. In other words, wires with surface scratches had a higher average release of chromium ions, although this remained below the toxic limit. Further details can be found in table3. The results of the independent T-test indicate a significant difference (P < 0.001) in the average release of chromium ions from wires with surface scratches in both the American Orthodontics and Ortho Organizer groups. Notably, the average release was higher in the Ortho Organizer wires. For further details, please refer to Fig. 1 ." Furthermore, the independent T-test results revealed a significant difference (P < 0.001) in the average release of chromium ions from wires without surface scratches in both the American Orthodontics and Ortho Organizer groups. Notably, the average release was higher in the wires from the Ortho Organizer company. You can find more details in Fig. 2 . Discussion In this study, an inductively coupled plasma (ICP) device was employed to quantify the amount of chromium release. It's worth noting that Rabindra Nayak [Rabindra S Nayak] also utilized an ICP device in his study to measure ion release from fixed orthodontic appliances. His findings indicated that this device offers a high level of accuracy compared to some previous studies that employed a spectrophotometer for ion measurements via atomic absorption [ 18 ]. The results of our study consistently show that the average release of chromium ions in wires with surface scratches from both brands exceeds that of wires without surface scratches. Furthermore, it's noteworthy that the amount of chromium ion release was lower in American Orthodontics wires, whether with surface scratches or without, in comparison to the Ortho Organizer brand. Peak release in the intervals The release peak was observed during the two-week period, after which the amount of chromium ion release decreased. Nevertheless, the average concentration of chromium in the scratched samples remained at 0.05983 mg, which falls within the daily safe limit for chromium as determined by the World Health Organization. Over the four-week period, the saturation of chromium ions declined in all samples. It is plausible that the corrosion products on the surface of the arch wires may inhibit further release of metal ions. However, this hypothesis warrants more comprehensive investigation in future studies. In alignment with our findings, Sandeep Parashar and colleagues conducted a similar study, demonstrating that the maximum amount of chromium ions released from wires occurred after 14 days, followed by a decrease. In their study, the estimated average daily release of chromium in four quadrants over one month was 47,664 micrograms, which remains below the toxic limit for chromium in the human body and the average daily dietary intake of chromium [ 19 ]. Additionally, Brigitte Wendel and colleagues explored the release rates of chromium, manganese, and nickel ions from various parts of an orthodontic appliance. They selected a range of orthodontic bands, brackets, and wires from three different manufacturers and immersed them in artificial saliva solution. Over 44 days of incubation, the levels of released ions were monitored at regular intervals using an ICP device. Their observations revealed a daily release of 47 micrograms of chromium, once again falling within the normal range for chromium ions [ 10 ]. In a study conducted by Marcin Mikulovich [Marcin Mikulovich] and his colleagues [ 20 ], the release of chromium ions from orthodontic devices during a 4-week incubation period was measured at 5.47 micrograms, which is lower than the amount of chromium ion release observed in our study. This variance could potentially be attributed to differences in the methods of immersing the appliances, including wires, variations in the study protocols, and the fact that the wires used in our study were in segmented form rather than intact. Notably, in both Marcin's study and our own, the estimated chromium release during the treatment period remained well below toxic levels for the human body. Furthermore, in Abdolreza Jamilian's study, SS and NITI arch wires were immersed in artificial saliva solution and mouthwash produced by two different companies for durations of 1, 6, 24 hours, and 7 days. Their findings indicated an increase in the levels of nickel and chromium ions in the samples after up to 7 days, with chromium ion release from SS wires reaching 4.4 µg after one week [ 22 ]. The differences between the values reported in this study and our own could be attributed to variations in arch wire brands, shorter immersion times, differences in the compositions and pH of the artificial saliva solutions used in each study compared to those in our research. Conclusion The results consistently indicate that ion release from orthodontic wires with surface scratches at various time intervals is higher than that from wires without surface scratches. However, it's essential to note that in all cases, the concentration levels did not exceed toxic thresholds, and no serious health concerns are expected. Nonetheless, considering the differences between laboratory conditions and the physiological environment of the oral cavity, it is advisable to conduct further research in human mouths to obtain more precise and clinically relevant results. Declarations Data availability: I confirm that I understand BMC Oral Health is an open access journal that levies an article processing charge per articles accepted for publication. By submitting my article I agree to pay this charge in full if my article is accepted for publication. Conflict of interests: The authors declare no conflicts of interest regarding the publication of this article. No financial or personal relationships with other people or organizations have influenced the work reported in this paper. Ethical statement : This article has an ethical code IR.MEDILAM.REC.1400.169, issued by Ilam University of Medical Sciences. Funding Statement: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Patient Consent Statement: Written informed consent was obtained from all individual participants included in the study. Oure study adhered to the Declaration of Helsinki. Permission to Reproduce Material: All figures, tables, or textual materials reproduced from other sources have been appropriately cited, and necessary permissions were obtained from the original copyright holders. Consent to Publish All authors have read and approved the final version of the manuscript and consent to its submission for publication. The authors affirm that the work is original, has not been published previously, and is not currently under consideration for publication elsewhere. There are no legal, ethical, or financial conflicts that would prevent publication of this work. Acknowledgments: This research forms part of a thesis aimed at achieving a professional doctorate degree in dentistry. We are grateful to the Ethics Committee of the Research Vice-Chancellor at Ilam University of Medical Sciences and Shahid Beheshti University of Medical Sciences, under the number 123, for approving this study. We would like to extend our sincere thanks and appreciation to all those who collaborated with us in conducting this research. Authors contribution: All authors contributed to the writing of this article, and the details of each author's work are as follows: Parisa Kazemi: Conceptualization, Methodology, Supervision, Writing – Original Draft. Mohammad Reza Soltani: conceptualization,Data Curation, Writing – Review & Editing. Mehrnaz Moradinezhad: Methodology, Validation, Formal Analysis, Supervision, Laboratory Procedures. Minou Najar Nobari: Visualization. Writing, Review and editing Mina Ahmadianghalehsorkh: Conceptualization, Literature Review, Resources, Writing – Review & Editing. Seyed Reza Mousavianfard: preparing for submit, submitting, writing some parts of the article, Laboratory Procedures. Seyed Mehdi Hosseini: Project Administration, Laboratory Procedures, Data Collection, investigation Consent for publication: Not Applicable References Babaei Hatkehlouei M, Dadgar S, Shokrzadeh M, Mousavi J, Sobouti F. A review of the release of cytotoxic ions from fixed orthodontic wires in laboratory environments. Clin Excell. 2020;10(3):56–63. Tahmasbi S, Ghorbani M, Sheikh T, Yaghoubnejad Y. Galvanic corrosion and ion release from different orthodontic brackets and wires in acidic artificial saliva. J Dent SCH Shahid Beheshti Univ Med Sci. 2019;32(1):37–44. Chaturvedi T, Upadhayay S. An overview of orthodontic material degradation in oral Cavity. Indian J Dent Res. 2010;21(2):275. Mirhashemi SA, Jahangiri S, Moghaddam MM, Bahrami R. ASSeSSment of the rate of orthodontic appliances ion release in different mouthwashes: An overview. J Dent Med. 2020;4(32):255–64. Mikulewicz M, Wo\lowiec P, Janeczek M, Gedrange T, Chojnacka K. The release of metal ions from orthodontic appliances animal tests. Angle Orthos. 2014;84(4):673–9. Natarajan M, Padmanabhan S, Chitharanjan A, Narasimhan M. Evaluation of the genotoxic effects of fixed appliances on oral mucosal cells and the relationship to nickel and chromium concentrations: an in-vivo study. Am J Orthos Dentofac Orthop. 2011;140(3):383–8. Amini F, Borzabadi Farahani A, Jafari A, Rabbani M. In vivo study of metal content of oral mucosa cells in patients with and without fixed orthodontic appliances. Ortho CraniofacRes. 2008;11(1):51–6. Hafez HS, Selim EMN, Eid FHK, Tawfik WA, Al-Ashkar EA, Mostafa YA. Cytotoxicity, genotoxicity, and metal release in patients with fixed orthodontic appliances: A longitudinal in-vivo study. Am J Orthos Dentofac Orthos. 2011;140(3):298–308. Downarowicz P, Mikulewicz M. Trace metal ions release from fixed orthodontic appliances and DNA damage in oral mucosa cells by in-vivo studies: A literature review. Adv Clin Exp Med Off Organ Wroclaw Med Univ. 2017;26(7):1155–62. Wendl B, Wiltsche H, Lankmayr E, Winsauer H, Walter A, Muchitsch A, et al. Metal release profiles of orthodontic bands, brackets, and wires: An in-vitro study. J Orofac Orthos Kieferorthopädie. 2017;78(6):494–503. Cortizo MC, De Mele MFL, Cortizo AM. Metallic dental material biocompatibility inosteoblast like cells. Biol Trace Elem Res. 2004;100(2):151–68. Ortiz AJ, Fernández E, Vicente A, Calvo JL, Ortiz C. Metallic ions released from stainless steel, nickel-free, and titanium orthodontic alloys: Toxicity and DNA damage. Am J Orthod Dentofac Orthop. 2011;140(3):e115–22. Olszewska A, Hanć A, Bara\lkiewicz D, Rzymski P. Metals and metalloids release from orthodontic elastomeric and stainless-steel ligatures: In-vitro risk assessment of human exposure. Biol Trace Elem Res. 2020;196(2):646–53. Huang H-H. Variation in corrosion resistance of nickel-titanium wires from different manufacturers. Angle Orthod. 2005;75(4):661–5. Schumacher H-A, Bourauel C, Drescher D. Frictional forces when rectangular guiding arches with varying edge bevels are employed. J Orofac Orthop Kieferorthopädie. 1998;59(3):139–49. Cantarella D, Lombardo L, Siciliani G. The dynforce archwire. Ann Stomatol (Roma). 2013;4(2):204. Secchi AG, Puente JA. Contemporary straight wire biomechanics. Orthod-Inkling enhance E-Book Curr Princ Tech. 2016; 437. Nayak RS, Khanna B, Pasha A, Vinay K, Narayan A, Chaitra K. Evaluation of nickel and chromium ion release during fixed orthodontic treatment using inductively coupled plasma-mass spectrometer: An in-vivo study. J Int Oral Health JIOH. 2015;7(8):14. Parashar S, Maurya R, Gupta A, Hegde C, Anand N. Estimation of release of Nickel and Chromium by Indian Made Orthodontic Appliance in Saliva. J Clin Diagn Res JCDR. 2015;9(9):ZC75. Mikulewicz M, Chojnacka K, Wo\lowiec P. Release of metal ions from fixed orthodontic appliance: an in vitro study of continuous flow systems. Angle Orthod. 2014;84(1):140–8. Kuhta M, Pavlin D, Slaj M, Varga S, Lapter-Varga M, Slaj M. Type of archwire and level of acidity: effects on the release of metal ions from orthodontic appliances. Angle Orthod. 2009;79(1):102–10. Jamilian A, Moghaddas O, Toopchi S, Perillo L. Comparison of nickel and chromium ions released from stainleSS steel and Miti wires after immersion in Oral B®, Orthokin® and artificial saliva. J Contemp Dent Pract. 2014;15(4):403–6. Tables Table 1. Grouping test samples. 6 pieces of scratched American Orthodontics wire are A group 6 pieces of unscratched American Orthodontics wire B group 6 pieces of scratched ortho organizer wire C group 6 pieces of unscratched ortho organizer wire D group Table 2. Soluble compounds of artificial saliva. grams per liter Contents 0.4 NaCl 0.4 KCl 0. 795 CaCl 2 .2H 2 O 0. 005 Na 2 S.9H 2 O 0. 69 NaH 2 PO 4 .2H 2 O 1 Urea Table 3. Comparison of 4 groups in terms of the amount of chromium ion release (in ppm) in the first, second and third measurement. Measurement time Group Pipe number 1 st analysis 2 nd analysis 3 rd analysis Total average Total standard deviation Test statistics Degrees of freedom P-value 24 hours after the start of the intervention A 1 0.0 6 0 0.0 55 0.0 59 0.016 0.002 6.130 16 >0.001 2 0.0 49 0.0 56 0.0 49 3 0.0 52 0.0 53 0.0 58 B 1 0.0 30 0.0 27 0.0 35 0.010 0.012 2 0.0 40 0.0 41 0.0 36 3 0.0 29 0.0 33 0.0 39 C 1 0.0 62 0.0 65 0.0 60 0.021 0.003 8.141 16 >0.001 2 0.059 0.065 0.066 3 0.073 0.071 0.065 D 1 0.047 0.050 0.053 0.012 0.001 2 0.048 0.047 0.041 3 0.045 0.045 0.048 Two weeks after the start of the intervention A 1 0.060 0.055 0.059 0.054 0.004 9.276 16 >0.001 2 0.049 0.056 0.049 3 0.052 0.053 0.058 B 1 0.030 0.027 0.035 0.034 0.005 2 0.040 0.041 0.036 3 0.029 0.033 0.039 C 1 0.062 0.065 0.060 0.065 0.004 440.9 16 >0.001 2 0.059 0.065 0.066 3 0.073 0.071 0.045 D 1 0.047 0.050 0.053 0.047 0.003 2 0.048 0.047 0.041 3 0.045 0.045 0.048 Four weeks after the start of the intervention A 1 0.028 0.032 0.035 0.0333 0.00339 5.159 16 >0.001 2 0.038 0.036 0.031 3 0.033 0.030 0.037 B 1 0.023 0.025 0.026 0.02511 0.00337 2 0.025 0.031 0.029 3 0.020 0.022 0.025 C 1 0.054 0.046 0.049 0.046 0.036 8.366 16 >0.001 2 0.041 0.048 0.044 3 0.045 0.045 0.046 D 1 0.038 0.035 0.029 0.029 0.004 2 0.025 0.028 0.024 3 0.045 0.045 0.048 Additional Declarations No competing interests reported. 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12:53:15","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6680924/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6680924/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":84697031,"identity":"62e15eec-9067-4657-b786-33eccc8367fb","added_by":"auto","created_at":"2025-06-16 10:47:24","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":17608,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of chromium ion diffusion process from the surface of American Orthodontics wires compared to Ortho organizer wires in scratched mode.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-6680924/v1/8a253c16a6a8e87d12789028.png"},{"id":84696377,"identity":"4ee6ddcf-d844-410f-a8c4-badab419bf63","added_by":"auto","created_at":"2025-06-16 10:39:24","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":18727,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of chromium ion diffusion process from the surface of American Orthodontics wire compared to Ortho organizer in unscratched condition.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-6680924/v1/41ccddea3806be45ae6fdf4e.png"},{"id":84953397,"identity":"8c1067b6-99cc-4c7f-bd62-3f1b810dea85","added_by":"auto","created_at":"2025-06-19 07:39:32","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":813080,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6680924/v1/6f119407-81c0-42c3-b9ed-299f597b7b8f.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Comparing the chromium ion release rate from stainless steel orthodontic wires with and without surface abrasion in an artificial saliva solution: An in-vitro study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eFixed orthodontics is an effective method for treating facioskeletal abnormalities. In this approach, brackets are affixed to the tooth surfaces using specialized orthodontic composites, and they are then connected by strong wires. During the course of treatment, patients are required to keep these orthodontic appliances in their mouths without removal until treatment completion. [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eOrthodontic brackets and wires are crafted from various metal alloys, including stainless steel, chrome alloy, cobalt, and nickel. It is crucial that the metal wires used in the oral cavity are free from any potentially hazardous products resulting from corrosion. [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eStainless steel alloys have been widely used in both fixed and mobile orthodontic treatments since 1932 [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Chromium, a key component of stainless steel, can effectively prevent rusting and enhance the strength of alloys. Stainless steel wires typically contain chromium in the range of 17\u0026ndash;22% [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eDirect exposure of metals and alloys to food in the oral cavity creates an environment that can lead to corrosion. Oral saliva serves as an electrolyte, influenced by factors such as temperature fluctuations, enzymatic and microbial activities, saliva pH, and various chemicals introduced through food and drink [\u003cspan additionalcitationids=\"CR7 CR8\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. This corrosion process can result in the release of metal ions, including nickel, chromium, cobalt, and iron, into the human body.\u003c/p\u003e \u003cp\u003eFor example, in a study conducted by Dr. Brigitte Wendl in Australia in 2017 [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e], it was observed that a significant amount of nickel and chromium ions were released from orthodontic brackets and wires when exposed to an artificial saliva solution. It's worth noting that although these metal ions were released, their levels remained below the threshold considered toxic to the human body.\u003c/p\u003e \u003cp\u003eThe release of corrosion ions can lead to pain, swelling, and the potential for secondary infections in the treatment area. Additionally, there have been reported cases of allergies, dermatitis [Dermatitis], and asthma triggered by the release of chromium ions from orthodontic appliances. In addition to allergic reactions, the release of chromium ions can cause local pain and have cytotoxic effects, potentially leading to mutagenesis and, in rare instances, cancer [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan additionalcitationids=\"CR7 CR8 CR9 CR10\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe normal levels of chromium ions in blood serum and urine are typically 0.1 mg and 0.2 mg, respectively. Chromium, nickel, and iron ions can induce the release of free radicals, which can result in cytotoxic effects [Cytotoxicity] [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHence, the European Food Safety Authority (EFSA) has established a safe weekly limit for chromium ion exposure in patients using orthodontic appliances at 2.1 micrograms per kilogram of body weight. Research indicates that toxic effects tend to manifest when body tissues are subjected to high levels of metal ions over an extended duration [\u003cspan additionalcitationids=\"CR12 CR13\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eConversely, in order to minimize friction between the orthodontic wire and the bracket, particularly in the posterior region, and to facilitate sliding movements, control torque and the angle of the anterior teeth, and enhance patient comfort, companies have introduced a new type of orthodontic wire known as the Bidimensional [Bidimensional] wire. This wire is manufactured and supplied with ball ends [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAt times, due to the high cost or limited availability of bidimensional wires, there may be no alternative but to use regular-sized stainless-steel wires. To minimize the contact surface between the brackets and the wire in such cases, practitioners often trim the edges in the posterior region and create scratches on both ends of the stainless-steel wires. This process results in a rounded cross-section at the ends of the wire, making it smaller than the anterior part. However, it's important to note that these scratched surfaces can increase the release of metal ions, particularly chromium, from the orthodontic wires [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e"},{"header":"Methods and Materials","content":"\u003cp\u003eBased on the aforementioned theory, this study aimed to compare the chromium ion release from stainless steel orthodontic wires with and without surface scratches in an artificial saliva solution.\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eDesign and population\u003c/strong\u003e \u003cp\u003eThis research represents an experimental laboratory study ([In vitro]) conducted in the central laboratory of Shahid Chamran University of Ahvaz in the year 2022.\u003c/p\u003e \u003c/p\u003e \u003cp\u003eFor this study, 24 pieces of stainless-steel orthodontic wire with dimensions of 0.025 x 0.019 inches and a rectangular cross-section were selected from American Orthodontics and Ortho Organizer (12 pieces from each brand). These wires were then divided into four groups as follows (table1)\u003c/p\u003e \u003cp\u003eAccording to Mirhashmi et al.'s study (4) and based on the following formula, the sample size was estimated to be 6 in each group (24 in each group).\u003c/p\u003e \n\u003cp\u003e\u003cimg 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\" height=\"83\" width=\"460\"\u003e\u003c/p\u003e\n\u003cp\u003eEntry criteria in this study include; Stainless steel orthodontic wire owned by Ortho Organizer and American Orthodontics.\u003c/p\u003e \u003cp\u003eDimensions are 0.019 x 0.025 inches, with rectangular cross-section, no previous scratches and having maintenance conditions. It was standard.\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eProcedure\u003c/strong\u003e \u003cp\u003eInitially, all orthodontic wire samples were sourced from reputable centers and transported to the central laboratory of Shahid Chamran University of Ahvaz while maintaining the original factory packaging conditions. To prepare the surfaces, the orthodontic wires were immersed in an acetone solution for 2 minutes, followed by rinsing with distilled water and thorough drying.\u003c/p\u003e \u003c/p\u003e \u003cp\u003eSubsequently, 12 laboratory Falcon tubes were prepared and divided into 4 groups, each containing three tubes. Using sterile forceps, two orthodontic wires, comprising one upper jaw arch wire and one lower jaw arch wire, were placed inside each tube.\u003c/p\u003e \u003cp\u003eIn both groups A and C, orthodontic wires were scratched in the region of teeth 5\u0026ndash;7 using a scratch operator, specifically the Saeshin micro-motor model Strong-207B from South Korea, with a speed of 10,000 rpm. This was performed using a Saeshin handpiece and a cylindrical diamond drill, number 837, made in Switzerland, with scratching taking place at both ends of the wires over a 20 mm length.\u003c/p\u003e \u003cp\u003eSubsequently, each Falcon tube was filled with 50cc of artificial saliva solution, ensuring complete saturation of the orthodontic wire pieces. The artificial saliva solution used in this study was Fusayama's [Fusaya], which closely mimics natural saliva and was prepared under laboratory conditions by the Department of Clinical Biochemistry, Faculty of Chemistry, Shahid Chamran University (table2).\u003c/p\u003e \u003cp\u003eThe tubes were tightly sealed and completely closed before being placed in an incubator set at 37\u0026deg;C for a duration of 28 days. To ensure that the artificial saliva solution matched the concentration and physiological pH of human saliva (pH 6.5), it was mixed with a NaOH solution.\u003c/p\u003e \u003cp\u003e \u003cb\u003eInformation collection method\u003c/b\u003e: We collected samples at specific intervals following the initiation of the intervention: the first 24 hours, two weeks, and four weeks. At the conclusion of each time period, we extracted 5cc of artificial saliva solution from each tube using sterile plastic syringes. The released chromium ions were then transferred to 5ml Falcon tubes and measured using an Inductively Coupled Plasma Optical Emission Spectrometer (ICP-OES), specifically the Optima 8300 model by Perkin Elmer Company of America.\u003c/p\u003e \u003cp\u003eSpectroscopy, an instrumental method in analytical chemistry, is capable of detecting a wide range of ground-state elements known as analytes [components or chemical species present in a substance or chemical compound] (55). To ensure the accurate operation of the device, it was calibrated by a qualified operator. Prior to sample analysis, we calibrated the device using a known amount of chromium solution. Subsequently, artificial saliva samples were measured for released chromium ions in parts per billion (ppb) units.\u003c/p\u003e \u003cp\u003eFor precise monitoring, we placed an artificial saliva sample without wire into the ICP-OES device to confirm that the solution itself did not contain any chromium.\u003c/p\u003e \u003cp\u003eThe protocol of this study is approved by ethical board.\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eData analysis method\u003c/strong\u003e \u003cp\u003eIn this research, we employed both descriptive and analytical statistical methods to investigate the release of chromium ions in the samples. After confirming the normality of data distribution and the equality of variances through the Kolmogorov-Smirnov test and Levin's test, we utilized the two-sample independent T-parametric statistical method to compare the means and frequencies of the variables under study.\u003c/p\u003e \u003c/p\u003e \u003cp\u003eThroughout this study, we maintained a significance level of 5% in all our statistical tests. Statistical analyses were performed using SPSS version 24.\u003c/p\u003e \u003cp\u003e This article has an ethical code IR.MEDILAM.REC.1400.169, issued by Ilam University of Medical Sciences.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eThe results of the independent t-test revealed a significant difference (P-value\u0026thinsp;\u0026lt;\u0026thinsp;0.001) in the release of chromium ions from wires with surface scratches compared to wires without surface scratches at all three measurement stages (24 hours, two weeks, and four weeks after the start of the intervention) for both the American Orthodontics and Ortho Organizer groups. In other words, wires with surface scratches had a higher average release of chromium ions, although this remained below the toxic limit. Further details can be found in table3.\u003c/p\u003e \u003cp\u003eThe results of the independent T-test indicate a significant difference (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) in the average release of chromium ions from wires with surface scratches in both the American Orthodontics and Ortho Organizer groups. Notably, the average release was higher in the Ortho Organizer wires. For further details, please refer to Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\"\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFurthermore, the independent T-test results revealed a significant difference (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) in the average release of chromium ions from wires without surface scratches in both the American Orthodontics and Ortho Organizer groups. Notably, the average release was higher in the wires from the Ortho Organizer company. You can find more details in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study, an inductively coupled plasma (ICP) device was employed to quantify the amount of chromium release. It's worth noting that Rabindra Nayak [Rabindra S Nayak] also utilized an ICP device in his study to measure ion release from fixed orthodontic appliances. His findings indicated that this device offers a high level of accuracy compared to some previous studies that employed a spectrophotometer for ion measurements via atomic absorption [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe results of our study consistently show that the average release of chromium ions in wires with surface scratches from both brands exceeds that of wires without surface scratches. Furthermore, it's noteworthy that the amount of chromium ion release was lower in American Orthodontics wires, whether with surface scratches or without, in comparison to the Ortho Organizer brand.\u003c/p\u003e \u003cp\u003e \u003cstrong\u003ePeak release in the intervals\u003c/strong\u003e \u003cp\u003eThe release peak was observed during the two-week period, after which the amount of chromium ion release decreased. Nevertheless, the average concentration of chromium in the scratched samples remained at 0.05983 mg, which falls within the daily safe limit for chromium as determined by the World Health Organization.\u003c/p\u003e \u003c/p\u003e \u003cp\u003eOver the four-week period, the saturation of chromium ions declined in all samples. It is plausible that the corrosion products on the surface of the arch wires may inhibit further release of metal ions. However, this hypothesis warrants more comprehensive investigation in future studies.\u003c/p\u003e \u003cp\u003eIn alignment with our findings, Sandeep Parashar and colleagues conducted a similar study, demonstrating that the maximum amount of chromium ions released from wires occurred after 14 days, followed by a decrease. In their study, the estimated average daily release of chromium in four quadrants over one month was 47,664 micrograms, which remains below the toxic limit for chromium in the human body and the average daily dietary intake of chromium [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAdditionally, Brigitte Wendel and colleagues explored the release rates of chromium, manganese, and nickel ions from various parts of an orthodontic appliance. They selected a range of orthodontic bands, brackets, and wires from three different manufacturers and immersed them in artificial saliva solution. Over 44 days of incubation, the levels of released ions were monitored at regular intervals using an ICP device. Their observations revealed a daily release of 47 micrograms of chromium, once again falling within the normal range for chromium ions [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn a study conducted by Marcin Mikulovich [Marcin Mikulovich] and his colleagues [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e], the release of chromium ions from orthodontic devices during a 4-week incubation period was measured at 5.47 micrograms, which is lower than the amount of chromium ion release observed in our study. This variance could potentially be attributed to differences in the methods of immersing the appliances, including wires, variations in the study protocols, and the fact that the wires used in our study were in segmented form rather than intact. Notably, in both Marcin's study and our own, the estimated chromium release during the treatment period remained well below toxic levels for the human body.\u003c/p\u003e \u003cp\u003eFurthermore, in Abdolreza Jamilian's study, SS and NITI arch wires were immersed in artificial saliva solution and mouthwash produced by two different companies for durations of 1, 6, 24 hours, and 7 days. Their findings indicated an increase in the levels of nickel and chromium ions in the samples after up to 7 days, with chromium ion release from SS wires reaching 4.4 \u0026micro;g after one week [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. The differences between the values reported in this study and our own could be attributed to variations in arch wire brands, shorter immersion times, differences in the compositions and pH of the artificial saliva solutions used in each study compared to those in our research.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe results consistently indicate that ion release from orthodontic wires with surface scratches at various time intervals is higher than that from wires without surface scratches. However, it's essential to note that in all cases, the concentration levels did not exceed toxic thresholds, and no serious health concerns are expected. Nonetheless, considering the differences between laboratory conditions and the physiological environment of the oral cavity, it is advisable to conduct further research in human mouths to obtain more precise and clinically relevant results.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eData availability:\u0026nbsp;\u003c/strong\u003eI confirm that I understand BMC Oral Health is an open access journal that levies an article processing charge per articles accepted for publication. By submitting my article I agree to pay this charge in full if my article is accepted for publication.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interests:\u0026nbsp;\u003c/strong\u003eThe authors declare no conflicts of interest regarding the publication of this article. No financial or personal relationships with other people or organizations have influenced the work reported in this paper.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical statement\u003c/strong\u003e: This article has an ethical code IR.MEDILAM.REC.1400.169, issued by Ilam University of Medical Sciences.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding Statement:\u003c/strong\u003e This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePatient Consent Statement:\u003c/strong\u003e Written informed consent was obtained from all individual participants included in the study. Oure study adhered to the Declaration of Helsinki.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePermission to Reproduce Material:\u003c/strong\u003e All figures, tables, or textual materials reproduced from other sources have been appropriately cited, and necessary permissions were obtained from the original copyright holders.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to Publish\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;All authors have read and approved the final version of the manuscript and consent to its submission for publication. The authors affirm that the work is original, has not been published previously, and is not currently under consideration for publication elsewhere. There are no legal, ethical, or financial conflicts that would prevent publication of this work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments:\u0026nbsp;\u003c/strong\u003eThis research forms part of a thesis aimed at achieving a professional doctorate degree in dentistry. We are grateful to the Ethics Committee of the Research Vice-Chancellor at Ilam University of Medical Sciences and Shahid Beheshti University of Medical Sciences, under the number 123, for approving this study. We would like to extend our sincere thanks and appreciation to all those who collaborated with us in conducting this research.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors contribution:\u003c/strong\u003e All authors contributed to the writing of this article, and the details of each author\u0026apos;s work are as follows:\u003c/p\u003e\n\u003cp\u003eParisa Kazemi: Conceptualization, Methodology, Supervision, Writing \u0026ndash; Original Draft.\u003c/p\u003e\n\u003cp\u003eMohammad Reza Soltani: conceptualization,Data Curation, Writing \u0026ndash; Review \u0026amp; Editing.\u003c/p\u003e\n\u003cp\u003eMehrnaz Moradinezhad: Methodology, Validation, Formal Analysis, Supervision, Laboratory Procedures.\u003c/p\u003e\n\u003cp\u003eMinou Najar Nobari: Visualization. Writing, Review and editing\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMina Ahmadianghalehsorkh: Conceptualization, Literature Review, Resources, Writing \u0026ndash; Review \u0026amp; Editing.\u003c/p\u003e\n\u003cp\u003eSeyed Reza Mousavianfard: preparing for submit, submitting, writing some parts of the article, Laboratory Procedures.\u003c/p\u003e\n\u003cp\u003eSeyed Mehdi Hosseini: Project Administration, Laboratory Procedures, Data Collection, investigation\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication:\u003c/strong\u003e Not Applicable\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eBabaei Hatkehlouei M, Dadgar S, Shokrzadeh M, Mousavi J, Sobouti F. A review of the release of cytotoxic ions from fixed orthodontic wires in laboratory environments. Clin Excell. 2020;10(3):56\u0026ndash;63.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTahmasbi S, Ghorbani M, Sheikh T, Yaghoubnejad Y. Galvanic corrosion and ion release from different orthodontic brackets and wires in acidic artificial saliva. J Dent SCH Shahid Beheshti Univ Med Sci. 2019;32(1):37\u0026ndash;44.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChaturvedi T, Upadhayay S. An overview of orthodontic material degradation in oral Cavity. Indian J Dent Res. 2010;21(2):275.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMirhashemi SA, Jahangiri S, Moghaddam MM, Bahrami R. ASSeSSment of the rate of orthodontic appliances ion release in different mouthwashes: An overview. J Dent Med. 2020;4(32):255\u0026ndash;64.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMikulewicz M, Wo\\lowiec P, Janeczek M, Gedrange T, Chojnacka K. The release of metal ions from orthodontic appliances animal tests. Angle Orthos. 2014;84(4):673\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNatarajan M, Padmanabhan S, Chitharanjan A, Narasimhan M. Evaluation of the genotoxic effects of fixed appliances on oral mucosal cells and the relationship to nickel and chromium concentrations: an in-vivo study. Am J Orthos Dentofac Orthop. 2011;140(3):383\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAmini F, Borzabadi Farahani A, Jafari A, Rabbani M. In vivo study of metal content of oral mucosa cells in patients with and without fixed orthodontic appliances. Ortho CraniofacRes. 2008;11(1):51\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHafez HS, Selim EMN, Eid FHK, Tawfik WA, Al-Ashkar EA, Mostafa YA. Cytotoxicity, genotoxicity, and metal release in patients with fixed orthodontic appliances: A longitudinal in-vivo study. Am J Orthos Dentofac Orthos. 2011;140(3):298\u0026ndash;308.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDownarowicz P, Mikulewicz M. Trace metal ions release from fixed orthodontic appliances and DNA damage in oral mucosa cells by in-vivo studies: A literature review. Adv Clin Exp Med Off Organ Wroclaw Med Univ. 2017;26(7):1155\u0026ndash;62.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWendl B, Wiltsche H, Lankmayr E, Winsauer H, Walter A, Muchitsch A, et al. Metal release profiles of orthodontic bands, brackets, and wires: An in-vitro study. J Orofac Orthos Kieferorthop\u0026auml;die. 2017;78(6):494\u0026ndash;503.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCortizo MC, De Mele MFL, Cortizo AM. Metallic dental material biocompatibility inosteoblast like cells. Biol Trace Elem Res. 2004;100(2):151\u0026ndash;68.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOrtiz AJ, Fern\u0026aacute;ndez E, Vicente A, Calvo JL, Ortiz C. Metallic ions released from stainless steel, nickel-free, and titanium orthodontic alloys: Toxicity and DNA damage. Am J Orthod Dentofac Orthop. 2011;140(3):e115\u0026ndash;22.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOlszewska A, Hanć A, Bara\\lkiewicz D, Rzymski P. Metals and metalloids release from orthodontic elastomeric and stainless-steel ligatures: In-vitro risk assessment of human exposure. Biol Trace Elem Res. 2020;196(2):646\u0026ndash;53.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHuang H-H. Variation in corrosion resistance of nickel-titanium wires from different manufacturers. Angle Orthod. 2005;75(4):661\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSchumacher H-A, Bourauel C, Drescher D. Frictional forces when rectangular guiding arches with varying edge bevels are employed. J Orofac Orthop Kieferorthop\u0026auml;die. 1998;59(3):139\u0026ndash;49.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCantarella D, Lombardo L, Siciliani G. The dynforce archwire. Ann Stomatol (Roma). 2013;4(2):204.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSecchi AG, Puente JA. Contemporary straight wire biomechanics. Orthod-Inkling enhance E-Book Curr Princ Tech. 2016; 437.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNayak RS, Khanna B, Pasha A, Vinay K, Narayan A, Chaitra K. Evaluation of nickel and chromium ion release during fixed orthodontic treatment using inductively coupled plasma-mass spectrometer: An in-vivo study. J Int Oral Health JIOH. 2015;7(8):14.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eParashar S, Maurya R, Gupta A, Hegde C, Anand N. Estimation of release of Nickel and Chromium by Indian Made Orthodontic Appliance in Saliva. J Clin Diagn Res JCDR. 2015;9(9):ZC75.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMikulewicz M, Chojnacka K, Wo\\lowiec P. Release of metal ions from fixed orthodontic appliance: an in vitro study of continuous flow systems. Angle Orthod. 2014;84(1):140\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKuhta M, Pavlin D, Slaj M, Varga S, Lapter-Varga M, Slaj M. Type of archwire and level of acidity: effects on the release of metal ions from orthodontic appliances. Angle Orthod. 2009;79(1):102\u0026ndash;10.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJamilian A, Moghaddas O, Toopchi S, Perillo L. Comparison of nickel and chromium ions released from stainleSS steel and Miti wires after immersion in Oral B\u0026reg;, Orthokin\u0026reg; and artificial saliva. J Contemp Dent Pract. 2014;15(4):403\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1. Grouping test samples.\u003c/p\u003e\n\u003cdiv\u003e\n \u003ctable dir=\"rtl\" border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 398px;\"\u003e\n \u003cp dir=\"LTR\"\u003e6 pieces of scratched American Orthodontics wire are\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp dir=\"LTR\"\u003eA group\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 398px;\"\u003e\n \u003cp dir=\"LTR\"\u003e6 pieces of unscratched American Orthodontics wire\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp dir=\"LTR\"\u003eB group\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 398px;\"\u003e\n \u003cp dir=\"LTR\"\u003e6 pieces of scratched ortho organizer wire\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp dir=\"LTR\"\u003eC group\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 398px;\"\u003e\n \u003cp dir=\"LTR\"\u003e6 pieces of unscratched ortho organizer wire\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp dir=\"LTR\"\u003eD group\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 2. Soluble compounds of artificial saliva.\u003c/p\u003e\n\u003cdiv\u003e\n \u003ctable dir=\"rtl\" border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 143px;\"\u003e\n \u003cp dir=\"LTR\"\u003egrams per liter\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 143px;\"\u003e\n \u003cp dir=\"LTR\"\u003eContents\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 143px;\"\u003e\n \u003cp dir=\"LTR\"\u003e0.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 143px;\"\u003e\n \u003cp dir=\"LTR\"\u003eNaCl\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 143px;\"\u003e\n \u003cp dir=\"LTR\"\u003e0.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 143px;\"\u003e\n \u003cp dir=\"LTR\"\u003eKCl\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 143px;\"\u003e\n \u003cp dir=\"LTR\"\u003e0.\u003cspan dir=\"RTL\"\u003e795\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 143px;\"\u003e\n \u003cp dir=\"LTR\"\u003eCaCl\u003csub\u003e2\u003c/sub\u003e.2H\u003csub\u003e2\u003c/sub\u003eO\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 143px;\"\u003e\n \u003cp dir=\"LTR\"\u003e0.\u003cspan dir=\"RTL\"\u003e005\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 143px;\"\u003e\n \u003cp dir=\"LTR\"\u003eNa\u003csub\u003e2\u003c/sub\u003eS.9H\u003csub\u003e2\u003c/sub\u003eO\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 143px;\"\u003e\n \u003cp dir=\"LTR\"\u003e0.\u003cspan dir=\"RTL\"\u003e69\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 143px;\"\u003e\n \u003cp dir=\"LTR\"\u003eNaH\u003csub\u003e2\u003c/sub\u003ePO\u003csub\u003e4\u003c/sub\u003e.2H\u003csub\u003e2\u003c/sub\u003eO\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 143px;\"\u003e\n \u003cp dir=\"LTR\"\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 143px;\"\u003e\n \u003cp dir=\"LTR\"\u003eUrea\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003eTable 3. Comparison of 4 groups in terms of the amount of chromium ion release (in ppm) in the first, second and third measurement.\u003c/p\u003e\n\u003cdiv\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"657\" class=\"fr-table-selection-hover\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 88px;\"\u003e\n \u003cp\u003eMeasurement time\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003eGroup\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003ePipe number\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e1\u003csup\u003est\u003c/sup\u003e analysis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e2\u003csup\u003end\u003c/sup\u003e analysis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e3\u003csup\u003erd\u003c/sup\u003e analysis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003eTotal average\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003eTotal standard deviation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003eTest statistics\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003eDegrees of freedom\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51px;\"\u003e\n \u003cp\u003eP-value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"12\" style=\"width: 88px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e24 hours after the start of the intervention\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e1\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.0\u003cspan dir=\"RTL\"\u003e6\u003c/span\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.0\u003cspan dir=\"RTL\"\u003e55\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.0\u003cspan dir=\"RTL\"\u003e59\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e0.016\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e0.002\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e6.130\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e16\u003c/span\u003e\u003c/p\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026gt;0.001\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.0\u003cspan dir=\"RTL\"\u003e49\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.0\u003cspan dir=\"RTL\"\u003e56\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.0\u003cspan dir=\"RTL\"\u003e49\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e3\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.0\u003cspan dir=\"RTL\"\u003e52\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.0\u003cspan dir=\"RTL\"\u003e53\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.0\u003cspan dir=\"RTL\"\u003e58\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003eB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e1\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.0\u003cspan dir=\"RTL\"\u003e30\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.0\u003cspan dir=\"RTL\"\u003e27\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.0\u003cspan dir=\"RTL\"\u003e35\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e0.010\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e0.012\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.0\u003cspan dir=\"RTL\"\u003e40\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.0\u003cspan dir=\"RTL\"\u003e41\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.0\u003cspan dir=\"RTL\"\u003e36\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e3\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.0\u003cspan dir=\"RTL\"\u003e29\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.0\u003cspan dir=\"RTL\"\u003e33\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.0\u003cspan dir=\"RTL\"\u003e39\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003eC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e1\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.0\u003cspan dir=\"RTL\"\u003e62\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.0\u003cspan dir=\"RTL\"\u003e65\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.0\u003cspan dir=\"RTL\"\u003e60\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e0.021\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e0.003\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e8.141\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e16\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026gt;0.001\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.059\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.065\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.066\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e3\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.073\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.071\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.065\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003eD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e1\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.047\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.050\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.053\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e0.012\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e0.001\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.048\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.047\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.041\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e3\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.045\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.045\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.048\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"12\" valign=\"top\" style=\"width: 88px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eTwo weeks after the start of the intervention\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e1\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.060\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.055\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.059\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e0.054\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e0.004\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e9.276\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e16\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026gt;0.001\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.049\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.056\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.049\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e3\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.052\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.053\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.058\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003eB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e1\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.030\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.027\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.035\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e0.034\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e0.005\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.040\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.041\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.036\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e3\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.029\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.033\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.039\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003eC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e1\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.062\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.065\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.060\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e0.065\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e0.004\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e440.9\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e16\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026gt;0.001\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.059\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.065\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.066\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e3\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.073\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.071\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.045\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003eD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e1\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.047\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.050\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.053\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e0.047\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e0.003\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.048\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.047\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.041\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e3\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.045\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.045\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.048\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"12\" valign=\"top\" style=\"width: 88px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eFour weeks after the start of the intervention\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e1\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.028\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.032\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.035\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e0.0333\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e0.00339\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e5.159\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e16\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026gt;0.001\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.038\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.036\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.031\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e3\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.033\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.030\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.037\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003eB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e1\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.023\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.025\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.026\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e0.02511\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e0.00337\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.025\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.031\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.029\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e3\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.020\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n 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\u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51px;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Chromium ion release, orthodontic wire, surface scratching, artificial saliva","lastPublishedDoi":"10.21203/rs.3.rs-6680924/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6680924/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eIntroduction\u003c/strong\u003e: Placing orthodontic wires in the oral cavity, exposing them to saliva, can cause corrosion and the release of metal ions, such as chromium. If this release of metal ions exceeds a certain amount, it could lead to cell toxicity and other complications. This study aimed to determine the chromium ion release rate from stainless steel orthodontic wires in an artificial saliva solution.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods and Materials\u003c/strong\u003e: In this laboratory study, we selected 24 sections of stainless-steel orthodontic wires from two brands: American Orthodontics and Ortho Organizer. The wires from each brand were then divided into two groups, one with scratches and one without. In each group, we placed three pairs of upper and lower jaw orthodontic wires into Falcon tubes filled with 50cc of artificial saliva solution. After ensuring complete sealing, we incubated the samples at 37 degrees Celsius. The concentration of chromium ions released in each sample was measured using an ICP-OES device at three intervals: 1, 14, and 28 days. We analyzed the obtained data using SPSS version 24 software.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: The study results demonstrate a significant difference (P\u0026lt;0.001) in the amount of chromium ion released between wires without surface scratches and those with surface scratches for both brands. On average, the release of chromium ions was higher in wires with surface scratches. Additionally, a significant difference (P\u0026lt;0.001) in chromium ion release was observed between the two brands. In this case, the Ortho Organizer brand exhibited a higher average release of chromium ions, both in wires with surface scratches and those without.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eThis study demonstrates that chromium ions are released at a faster rate from stainless steel (SS) orthodontic wires with surface scratches. Nevertheless, it's important to note that the maximum amount of chromium ion released remains below the toxic threshold for the human body.\u003c/p\u003e","manuscriptTitle":"Comparing the chromium ion release rate from stainless steel orthodontic wires with and without surface abrasion in an artificial saliva solution: An in-vitro study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-06-16 10:39:20","doi":"10.21203/rs.3.rs-6680924/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"b61cced2-a538-4ebe-9acf-c3d7a1c92a58","owner":[],"postedDate":"June 16th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-06-19T07:39:13+00:00","versionOfRecord":[],"versionCreatedAt":"2025-06-16 10:39:20","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6680924","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6680924","identity":"rs-6680924","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}