Investigation of the Relationship Between Serum Trace Elements and MSFC Levels in Multiple Sclerosis

Investigation of the Relationship Between Serum Trace Elements and MSFC Levels in Multiple Sclerosis | 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 Investigation of the Relationship Between Serum Trace Elements and MSFC Levels in Multiple Sclerosis Cihat Ozguncu¹, Serefnur Ozturk¹, Haluk Gumus¹, Gokhan Ozdemir¹, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6277424/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 05 May, 2025 Read the published version in Biological Trace Element Research → Version 1 posted 9 You are reading this latest preprint version Abstract The effects of heavy metals have been investigated in the etiology of multiple sclerosis(MS) for years. However, common results have yet to be obtained in previous studies. So, we aimed to examine the relationship between heavy metals and MS around the province of Konya, where air pollution is intense. Study participants with MS were investigated regarding the expanded disability status (EDSS) and multiple sclerosis functional composite (MSFC) scales. All study participants were also evaluated concerning the Beck's Depression Inventory (BDI), Facit Fatigue Scale (FFS), Fatigue Severity Scale (FSS) and levels of blood chromium (Cr), manganese (Mn), copper (Cu), zinc (Zn), selenium (Se), cadmium (Cd), and lead (Pb). While were 49 people in the MS group, 51 individuals constituted the controls. Levels of Mn, Zn, Cd, and Pb were significantly higher in controls (p < .001, 0.002, < .001, <.001, respectively). There was no significant difference between MS and control groups regarding depression and fatigue scores. MSFC parameters, depression and fatigue scale scores were statistically higher with increasing EDSS in MS patients. A significant correlation was also observed between the scores of the timed 25-foot walk (T25FW) and dominant hand 9-hole peg test (9HPT) and Cr levels (p = 0.014, 0.004). A relationship was also observed between Mn levels and T25FW (p = 0.047). Heavy metal and trace element levels can be seen at different levels in MS patients. While a correlation was observed between some MSFC parameters and Cr and Mn levels, no relationship was observed between heavy metal levels, depression, fatigue, and EDSS. depression fatigue multiple sclerosis trace element chromium manganese 1. Introduction Multiple sclerosis (MS) is a chronic disease that can cause significant morbidity at a young age, causing inflammation, demyelination, and loss of axons involving the central nervous system. After the identification of MS, various studies have commenced investigating the etiology of MS rapidly. Although environmental, genetic, and autoimmune factors are emphasized to be effective in its etiology, how MS starts and what causes the progression has yet to be clearly understood [ 1 ]. Therefore, a definitive treatment for the disease has not yet been found. Regarding environmental factors, mining areas, active volcano regions, and industrial zones with intense air pollution are rich in heavy metals and trace elements [ 2 ]. The accumulation of heavy metals and trace elements is known to be directly related to various disease groups. Different heavy metals and trace elements can lead to diseases by acting through different pathways or play an important role in cellular functions by participating in the structure of enzymes. In case of heavy metal imbalance in the cerebrospinal fluid (CSF), the condition can lead to pathological lesions that may result in the involvement of the blood-brain barrier, accumulation of heavy metals and neurodegeneration [ 3 ]. Zinc (Zn) is vital in regulating the immune system, showing its effect through the tumor necrosis factor (TNF)-alpha inhibitors. The deficiency of Zn can lead to the weakness of the immune system and contributes to the pathogenesis of MS by causing an imbalance between the functions of T helper-1 (Th1) and T helper-2 (Th2) cells, and the failure of Th17 downregulation [ 4 ]. Copper (Cu) plays a key role in the synthesis of myelin. The deficiency of Cu can potentially lead to myelinopathy, and Cu also shows its effectiveness by binding to vital enzymes such as cytochrome oxidase and superoxide dismutase [ 5 ]. In addition, when the CSF of MS patients was examined, the levels of Cu were observed to be significantly increased compared to the normal population [ 6 ]. After exposure to lead (Pb), the production of autoantibodies was observed against the proteins of the central nervous system (CNS), such as myelin basic protein (MBP) and glial fibrillary acidic protein (GFAB). These antibodies are predicted to also play a role in demyelination [ 7 ]. Given that cadmium (Cd) is known as a neurotoxic metal upon exposure to high levels, polyneuropathy is observed, and Cd is also considered to have effects on the blood-brain barrier [ 8 , 9 ]. Another element, selenium (Se), is a trace element found in a narrow range in the body. In studies, Se has been suggested to be associated with the neurodegenerative diseases of CNS [ 10 ]. Additionally, Se can also bring on mitochondrial damage by leading to the formation of reactive oxygen radicals and inhibiting antioxidant reactions. It is anticipated that the effects of Se may lead to neuro-toxication [ 11 , 12 ]. Acting as a cofactor in many enzymes, manganese (Mn) is another trace element known to have important functions in the proper functioning of the immune system [ 13 , 14 ]. Finally, chromium (Cr) is a rare transition metal, and it has been reported that Cr can be stored in the body and may cause neurotoxicity [ 15 ]. Such features as its geographical structure spreading on a broad plateau in Central Anatolia, climate, and proximity to the industrial zones are among the factors causing the province of Konya to rank first in Turkey regarding air pollution [ 16 ]. Our study will compare the findings of MS patients with those of the controls, and the relationship between the specified elements and MS will be investigated. The effects of these elements on the prognosis and diagnosis of MS will be evaluated. 2. Methods Planned prospectively, our study was performed between August and November 2021 with approval from the Local Ethics Committee of the Faculty of Medicine at Selcuk University (Reg. number: 2019/81). Patients over 18 years of age, diagnosed with MS under the 2017 McDonald criteria [ 17 ] and those with no rheumatological disease, pregnancy, and not being in an attack period were included in the study after obtaining informed written consent. For all patients, such features as age, gender, comorbid diseases, duration and subtype of MS, medications administered to treat MS, living in proximal homes to the city center, frequency of fish consumption, smoking status, and educational status were recorded. The values of the expanded disability status scale (EDSS) were calculated by performing neurological examinations of the patients [ 18 ]. The timed 25-foot walk test (T25FW), the 9-hole peg test (9HPT), and the paced auditory serial addition test (2 seconds and 3 seconds versions) (PASAT2 and PASAT3) making up the multiple sclerosis functional composite (MSFC) were carried out to evaluate the relationships between the scales in MS patient group [ 19 ]. In addition, we also evaluated the levels of fatigue and depression, the most common complaints witnessed in MS patients from the early stages of the study period. The fatigue severity (FSS) [ 18 , 20 , 21 ] and the facit fatigue scales (FFS) [ 22 , 23 ], used to evaluate the validity and reliability of MS, were performed to assess the complaints under the self-reporting by each patient. A score of 36 > on FSS was evaluated as fatigue. Similarly, each patient was asked to complete the Beck Depression Inventory (BDI) [ 24 , 25 ], which is a widely used test to evaluate depression all over the world. A score of 17 or higher acquired in BDI was considered depression. Patients (n = 51) over 18 with no pregnancy and not diagnosed with any diseases on admission to our polyclinic were also included in the study as the control group after informed written consent was obtained. In the control group, the features such as age, gender, distance from the homes to the city center, smoking status, and fish consumption were recorded, and the scales of BDI, FSS, and FFS were also carried out in the control group. Drawn from the entire study population and kept in blood sample tubes, the samples were transferred to tubes of trace elements. The serum obtained by centrifugation at 5000 rpm for five minutes was taken into an Eppendorf tube and stored at -80°C until the investigation. After sampling was completed, the samples were first dried by exposing them to high heat in a microwave oven in our university's advanced technology laboratory. The levels of Zn, Mn, Cu, Pb, Se, Cr, and Cd were determined with the inductively coupled plasma mass spectrometry (ICP-MS) device (Perkin Elmer / ICP MS ELAN DRC-E, PerkinElmer Inc, Wellesley, United States ). 2.1 Statistical Analysis All statistical analysis was performed using the R version 3.6.0 (The R Foundation for Statistical Computing, Vienna, Austria; https://www.r-project.org ). Shapiro-Wilk’s normality test and Q-Q plots were used to assess the normality of the data. Also, the Levene test was performed to check the homogeneity of the variances. The numerical variables were presented as mean ± standard deviation (SD) (range: minimum-maximum) or median (interquartile range [IQR]: 25th percentile-75th percentile) as appropriate. Even so, the categorical variables were described as number (n) and percentage (%). T25FW was converted to Z-score as Z-LEG to calculate multiple sclerosis functional composite. Similarly, 9HPT was converted to Z-ARM and PASAT-3 was converted to Z-COG. MSFC score was calculated with Z-ARM, Z-LEG and Z-COG [ 26 ]. Reference values from the literature were used during the calculation [ 19 ]. An independent samples t-test, the Welch’s t-test, the Mann-Whitney U test, the Yates continuity correction chi-square test, and the Fisher-Freeman-Halton test was conducted to determine whether there was a statistically significant difference or association between the study groups regarding the demographical and clinical characteristics, and laboratory findings. The Spearman-rho ranked-order correlation coefficients were used to examine the relationship between numerical variables. A two-tailed p-value of < 5% was considered statistically significant. 3. Results While there were 49 patients with a mean age of 35.08±11.36 years in the MS group, the control group was composed of 51 individuals with a mean age of 31.41±10.71 years. The male-to-female (M/F) ratios were 32/17 and 31/20 in the MS and control groups, respectively. The mean duration of MS was detected as five years (1-27), and the mean EDSS score was calculated as 2.81 (0.5-5.5). The distributions of the MS subtypes among the patients were as follows: 41 patients with relapsing-remitting multiple sclerosis (RRMS), four with primary progressive multiple sclerosis (PPMS), and four with secondary progressive multiple sclerosis (SPMS). The findings are presented in Table 1. The levels of Mn, Zn, Cd, and Pb were significantly higher in the control group (p<.001, 0.002, <.001, <.001, respectively). There was no significant difference between the MS and control groups in terms of depression and fatigue scores, and the comparisons are given in Table 2. Given the evaluation of MSFC of MS patients, the parameters of MSFC and depression and fatigue scales were observed to be statistically higher, as well as the increase in EDSS. A significant correlation was also observed between T25FW and 9HPT scores and Cr levels (p= 0.014, 0.004, respectively ). Similarly, a significant correlation was observed between manganese level and T25FW and Z score. (p= 0.047) (Table 3). In addition, the values of the elements, +Mn (26.59 [IQR, 22.84-42.13] vs. 52.91 [IQR, 35.80-74.96], p <.001), Zn (868.96±190.56 vs. 1067.38±322.79, p=.002), Cd (0 [IQR, 0-0.03] vs. 0.17 [IQR, 0-0.39], p<.001), and Pb (7.5 [IQR, 0-25.55] vs. 28 [IQR, 17.08-65.5], p<.001) were determined to be lower in the MS patient group, compared to the healthy controls. When the correlations among trace elements were evaluated, it was observed that there was a significant correlation between Mn level and Cr, Cd, Pb (p= 0.021, <0.001, <0.001 respectively), a significant correlation between Se levels and Cr, Zn, Cd (p= 0.002, 0.014, 0.048 respectively), a correlation between Cr and Cu and a correlation between Cd and Pb (p= 0.012, <0.001 respectively) (table 4). 4. Discussion Although many studies are investigating the association between MS and heavy metals based on the literature, various points remain unexplained, and there are also studies reporting conflicting findings regarding the relationship between MS and heavy metals. The relationship between the severity of MS and exposure to higher levels of heavy metals is one of the challenges to be clarified. In light of the literature, in a systematic review evaluating the effects of heavy metals on MS, it was reported that no difference was observed between the MS and control groups regarding Se and Cu levels, and Zn was found lower, as consistent with our study findings. On the other hand, the Mn levels were higher in MS patients [ 14 ]. In a similar meta-analysis, the levels of Cd were stated to be higher in MS patients. Although the levels of Pb were higher in MS patients, the difference was considered statistically insignificant [ 27 ]. Another meta-analysis evaluating only the Zn levels showed that the Zn levels were significantly lower in the MS population than in the controls, which is in line with our study results [ 28 ]. In two different studies conducted in Iran, where air pollution is intense, as in the province of Konya, the levels of Pb were found to be similar between the MS patient and control groups. Another study also evaluated the levels of Cu and Se within patients with MS. It detected that the levels of both elements were at a similar rate between the MS and control groups, consistent with our study findings [ 29 ]. In the study carried out by Aliomrani et al., the level of Cd was determined to be higher in the MS group [ 30 ]. In a study published in 2017 that included findings similar to our study, the levels of Cd, Zn, and Mn were observed to be decreased in MS patients compared to those in the control group [ 31 ]. In the literature, there are also results complying with our study findings, revealing that the levels of Pb and Zn are lower in MS patients [ 32 ]. In a study carried out in Brazil and including completely different findings from those in our study, it was stated that the levels of Cu and Cr were lower, the level of Pb was higher, and there was no difference concerning Zn levels in MS patients [ 33 ]. Such differences suggested that the results in different studies could vary considerably according to regions and geographical features where the studies were conducted. Although the results in the literature and our study are generally compatible, some studies report conflicting results regarding the levels of Pb and Cd in MS patients. It is unlikely that any comments will be made about whether such a situation plays a role as a by-product in the pathophysiology of MS but has no direct effect on the issue or whether MS has an unknown mechanism yet. Our study observed that, along with the increase in EDSS, the parameters of MSFC, depression, and fatigue scales were also statistically higher. Those findings are supported by more than one study in the literature [ 34 , 35 ]. In many studies, it is stated that there is an increase in depression and fatigue scores in MS patients compared to the controls [ 36 , 37 ]. Even so, an increase was observed in the depression and fatigue scores in our MS patients; the difference displayed no statistical significance. Therefore, it is likely to make different inferences, and we consider that the entity deserves further evaluation. Although our study revealed a statistically significant relationship between the scores of T25FW and 9HPT-dominant and the levels of Cr, no publications supporting or contradicting such a finding were encountered in the literature. The levels of Cr were within normal limits in our samples, and there was no finding suggestive of toxicity. In a placebo-controlled double-anonymized study investigating the effects of Cr supplementation on neuronal functions, it was reported that Cr supplementation could increase cognitive inhibitory control and cerebral function in older adults at risk for neurodegeneration [ 38 ]. The effect of Cr can explain the findings in our study. Further studies should elucidate the necessity and importance of Cr supplementation in MS patients. In our study, a correlation is observed between T25FW and Mn levels. No publication in the literature clearly explains the effect of Mn levels on walking function. However, publications indicate that cows whose diets contain trace elements (zinc, manganese, copper and cobalt) positively increase their kinematic walking parameters. In this publication, it was reported that no difference was observed between the zinc and copper levels in the blood of the control group and the experimental group. However, there was a significant increase in manganese levels in those receiving supplementary food [ 39 ]. More research needs to be done on this issue. The present study also has several limitations. First, no national and geographical characteristics could be evaluated since the data obtained from a single center were utilized. Secondly, the levels of heavy metals and trace elements evaluated in the study may be affected by many clinical and structural conditions; in other words, nutritional supplements and lifestyle habits can alter the levels of serum elements. Additionally, no occupational details were evaluated in the population studied; some occupations are known to be risky due to exposure to heavy metals. Finally, although depression and fatigue are known to be affected by many conditions, those conditions have been ignored. It is recommended that those conditions be considered and investigated in studies that include larger populations. As a result of the findings in our study and previous studies, it still seems unlikely that a clear relationship between MS and the levels of heavy metals and trace elements can be established. However, the lower levels of certain elements, especially in MS patients, support the hypothesis that those elements and their levels may be a distinguishing factor in MS. In particular, the relationship between Cr and Mn levels and MSFC parameters needs to be re-evaluated and confirmed by further studies. With novel tests and methods, the etiology and pathophysiology of MS will be enlightened more clearly, and the question marks will be eliminated as a result of such studies. 5. Conclusion The Mn, Zn, Cd, and Pb levels were lower in the MS group compared to the control, while the Se, Cr, and Cu levels were similar. No correlation was observed between the levels of heavy metals and trace elements and the scores of depression, fatigue, and EDSS. Declarations Data Availability Statement The raw data supporting the outcomes of this article will be made available by the authors without undue reservation. Authorship Contribution Statement CO: planning, organization, data collection, writing, and editing. SO: organization, writing, and editing HG: planning and organization. BO, GÖ, GO, IG: data collection. All authors contributed to the article and approved the submitted version. Ethics Statement The study involving human participants was carried out under the principles of the 1964 Declaration of Helsinki and its later amendments, and the study protocol was also reviewed and approved by the Local Ethics Committee for Clinical Researches of Selcuk University (Approval number: 2019/81). Conflict of Interest The authors declare that the research was conducted without commercial or financial relationships construed as a potential conflict of interest. Financial Support This study was supported by the Scientific Research Projects Coordinatorship of Selcuk University (Project number: 20401145). Disclosure Our study began in 2019 after receiving ethical approval. Due to the difficulty obtaining financial support for the project and the subsequent pandemic, it was necessary to start recruiting patients later. Our study was presented as an oral presentation at the 12th Clinical Neuroimmunology Symposium held in Antalya, Turkiye, between 12-15 May 2022. References Kamińska, J., et al., Multiple sclerosis - etiology and diagnostic potential. Postepy Hig Med Dosw (Online), 2017. 71 (0): p. 551-563. https://doi.org/10.5604/01.3001.0010.3836 Hansell, A.L., C.J. Horwell, and C. Oppenheimer, The health hazards of volcanoes and geothermal areas. Occup Environ Med, 2006. 63 (2): p. 149-56, 125. https://doi.org/10.1136/oem.2005.022459 Madeddu, R., et al., Heavy metals and multiple sclerosis in Sardinian population (Italy). 2011. 44 (9): p. 1699-1712. https://doi.org/10.1080/00032719.2010.520396 Mezzaroba, L., et al., The role of zinc, copper, manganese and iron in neurodegenerative diseases. Neurotoxicology, 2019. 74 : p. 230-241. https://doi.org/10.1016/j.neuro.2019.07.007 De Riccardis, L., et al., Copper and ceruloplasmin dyshomeostasis in serum and cerebrospinal fluid of multiple sclerosis subjects. Biochim Biophys Acta Mol Basis Dis, 2018. 1864 (5 Pt A): p. 1828-1838. https://doi.org/10.1016/j.bbadis.2018.03.007 Melø, T.M., et al., Manganese, copper, and zinc in cerebrospinal fluid from patients with multiple sclerosis. Biol Trace Elem Res, 2003. 93 (1-3): p. 1-8. https://doi.org/10.1385/BTER:93:1-3:1 El-Fawal, H.A., et al., Neuroimmunotoxicology: humoral assessment of neurotoxicity and autoimmune mechanisms. Environ Health Perspect, 1999. 107 Suppl 5 (Suppl 5): p. 767-75. https://doi.org/10.1289/ehp.99107s5767 Viaene, M.K., et al., Cadmium: a possible etiological factor in peripheral polyneuropathy. Neurotoxicology, 1999. 20 (1): p. 7-16. Méndez-Armenta, M., et al., Brain regional lipid peroxidation and metallothionein levels of developing rats exposed to cadmium and dexamethasone. Toxicol Lett, 2003. 144 (2): p. 151-7. https://doi.org/10.1016/S0378-4274(03)00199-1 Filippini, T., et al. Selenium Neurotoxicity and Amyotrophic Lateral Sclerosis: An Epidemiologic Perspective . 2018. https://doi.org/10.1007/978-3-319-95390-8_12 Oliveira, C.S., et al., Chemical Speciation of Selenium and Mercury as Determinant of Their Neurotoxicity. Adv Neurobiol, 2017. 18 : p. 53-83. https://doi.org/10.1007/978-3-319-60189-2_4 Mandrioli, J., et al., Elevated Levels of Selenium Species in Cerebrospinal Fluid of Amyotrophic Lateral Sclerosis Patients with Disease-Associated Gene Mutations. Neurodegener Dis, 2017. 17 (4-5): p. 171-180. https://doi.org/10.1159/000460253 Erikson, K.M. and M. Aschner, Manganese neurotoxicity and glutamate-GABA interaction. Neurochem Int, 2003. 43 (4-5): p. 475-80. https://doi.org/10.1016/S0197-0186(03)00037-8 Nirooei, E., et al., Blood Trace Element Status in Multiple Sclerosis: a Systematic Review and Meta-analysis. Biol Trace Elem Res, 2022. 200 (1): p. 13-26. https://doi.org/10.1007/s12011-021-02621-5 Wise, J.P., Jr., et al., Current understanding of hexavalent chromium [Cr(VI)] neurotoxicity and new perspectives. Environ Int, 2022. 158 : p. 106877. https://doi.org/10.1016/j.envint.2021.106877 Yahaya, N., et al. Air Quality Status in Konya City Centre, Konya, Turkey during Pandemic Covid-19 . in IOP Conference Series: Earth and Environmental Science . 2022. IOP Publishing. https://doi.org/10.1088/1755-1315/1013/1/012006 Thompson, A.J., et al., Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol, 2018. 17 (2): p. 162-173. https://doi.org/10.1016/S1474-4422(17)30470-2 Kurtzke, J.F., Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology, 1983. 33 (11): p. 1444-52. https://doi.org/10.1212/WNL.33.11.1444 Cutter, G.R., et al., Development of a multiple sclerosis functional composite as a clinical trial outcome measure. Brain, 1999. 122 ( Pt 5) : p. 871-82. https://doi.org/10.1093/brain/122.5.871 Armutlu, K., et al., The validity and reliability of the Fatigue Severity Scale in Turkish multiple sclerosis patients. Int J Rehabil Res, 2007. 30 (1): p. 81-5. https://doi.org/10.1097/MRR.0b013e3280146ec4 Krupp, L.B., et al., The fatigue severity scale. Application to patients with multiple sclerosis and systemic lupus erythematosus. Arch Neurol, 1989. 46 (10): p. 1121-3. https://doi.org/10.1001/archneur.1989.00520460115022 Delgado-Álvarez, A., et al., Validation of two new scales for the assessment of fatigue in Multiple Sclerosis: F-2-MS and FACIT-F. Mult Scler Relat Disord, 2022. 63 : p. 103826. https://doi.org/10.1016/j.msard.2022.103826 Webster, K., D. Cella, and K. Yost, The Functional Assessment of Chronic Illness Therapy (FACIT) Measurement System: properties, applications, and interpretation. Health Qual Life Outcomes, 2003. 1 : p. 79. https://doi.org/10.1037/t77273-000 Beck, A.T., R.A. Steer, and G.K. Brown, Beck depression inventory. 1996. https://doi.org/10.1037/t00742-000 Kapci, E.G., et al., Beck Depression Inventory II: evaluation of the psychometric properties and cut-off points in a Turkish adult population. Depress Anxiety, 2008. 25 (10): p. E104-10. https://doi.org/10.1002/da.20371 Tiftikçioğlu, B., Multiple Sclerosis Functional Composite (MSFC): Scoring Instructions. Noro Psikiyatr Ars, 2018. 55 (Suppl 1): p. S46-s48. https://doi.org/10.29399/npa.23330 Sarihi, S., et al., Toxic heavy metal concentrations in multiple sclerosis patients: A systematic review and meta-analysis. Excli j, 2021. 20 : p. 1571-1584. Bredholt, M. and J.L. Frederiksen, Zinc in Multiple Sclerosis: A Systematic Review and Meta-Analysis. ASN Neuro, 2016. 8 (3). https://doi.org/10.1177/1759091416651511 Alizadeh, A., et al., Comparison of serum Concentration of Se, Pb, Mg, Cu, Zn, between MS patients and healthy controls. Electron Physician, 2016. 8 (8): p. 2759-2764. https://doi.org/10.19082/2759 Aliomrani, M., et al., Blood Concentrations of Cadmium and Lead in Multiple Sclerosis Patients from Iran. Iran J Pharm Res, 2016. 15 (4): p. 825-833. Janghorbani, M., et al. Trace Elements in Serum Samples of Patients with Multiple Sclerosis . 2017. https://doi.org/10.30958/ajh.4-2-3 Forte, G., et al., Quantification of chemical elements in blood of patients affected by multiple sclerosis. Ann Ist Super Sanita, 2005. 41 (2): p. 213-6. de Oliveira, M., et al., A preliminary study of the concentration of metallic elements in the blood of patients with multiple sclerosis as measured by ICP-MS. Sci Rep, 2020. 10 (1): p. 13112. https://doi.org/10.1038/s41598-020-69979-9 Yigit, P., et al., The relationship between cognition, depression, fatigue, and disability in patients with multiple sclerosis. Ir J Med Sci, 2021. 190 (3): p. 1129-1136. https://doi.org/10.1007/s11845-020-02377-2 Patti, F., et al., Cognitive impairment and its relation with disease measures in mildly disabled patients with relapsing-remitting multiple sclerosis: baseline results from the Cognitive Impairment in Multiple Sclerosis (COGIMUS) study. Mult Scler, 2009. 15 (7): p. 779-88. https://doi.org/10.1177/1352458509105544 Boeschoten, R.E., et al., Prevalence of depression and anxiety in Multiple Sclerosis: A systematic review and meta-analysis. J Neurol Sci, 2017. 372 : p. 331-341. https://doi.org/10.1016/j.jns.2016.11.067 Brenner, P. and F. Piehl, Fatigue and depression in multiple sclerosis: pharmacological and non-pharmacological interventions. Acta Neurol Scand, 2016. 134 Suppl 200 : p. 47-54. https://doi.org/10.1111/ane.12648 Krikorian, R., et al., Improved cognitive-cerebral function in older adults with chromium supplementation. Nutr Neurosci, 2010. 13 (3): p. 116-22. https://doi.org/10.1179/147683010X12611460764084 Yamamoto, S., et al., Kinematic gait analysis and lactation performance in dairy cows fed a diet supplemented with zinc, manganese, copper and cobalt. Anim Sci J, 2014. 85 (3): p. 330-5. https://doi.org/10.1111/asj.12141 Tables Table 1. Demographical and clinical characteristics of multiple sclerosis patients and controls MS n (%) Controls n (%) p -value Demographical characteristics Age (years) 35.08±11.36 31.41±10.71 .100 1 Gender (F/M) 32 (65.3)/17 (34.7) 31 (60.8)/20 (39.2) .794 2 Duration of MS 5 (1-27) MS Scores EDSS 2.81±1.58 (0.5-5.5) T25FW 7.17±2.70 (4.4-16.1) 9HPT-Dominant 23.39±8.70 (13.9-52.8) 9HPT-Non-Dominant 27.19±11.29 (16-58.3) PASAT 3-Seconds Version 27.67±5.57 (9-48) PASAT 2-Seconds Version 25.54±6.71 (2-43) Z-ARM 0,02 ± 1,11 (-2,53 – 2,31) Z-LEG 0,21 ± 0,24 (-0,58 – 0,45) Z-COGNITIVE -1,48 ± 0,56 (-3,73 – 0,25) MSFC -0,42 ± 0,53 (-1,77 – 0,46) Type of MS RRMS 41 (83.7) SPMS 4 (8.2) PPMS 4 (8.2) Drugs Administered Glatiramer acetate 1 (2) Interferon beta-1a 5 (10.2) Teriflunomide 2 (4.1) Dimethyl Fumarate 8 (16.3) Fingolimod 13 (26.5) Ocrelizumab 10 (20.4) Rituximab 2 (4.1) Cladribine 2 (4.1) No drugs 6 (12.2) EDSS: Expanded disability status scale, MS: Multiple sclerosis, 9HPT: Dominant hand 9-hole peg test, PASAT: Paced auditory serial addition test, PPMS: Primary progressive multiple sclerosis, RRMS: Relapsing-remitting multiple sclerosis, SPMS: Secondary progressive multiple sclerosis, T25FW: Timed 25-foot walk test, MSFC: Multiple Sclerosis Functional Composite Table 2. Comparisons between multiple sclerosis patients and controls in the study MS n (%) Controls n (%) p -value Laboratory findings Cr 733.66±157.24 725.10±217.60 .839 1 Mn 26.59 (22.84-42.13) 52.91 (35.80-74.96) <.001 2 Cu 1708±388.58 1699.39±447.40 .927 1 Zn 868.96±190.56 1067.38±322.79 .002 3 Se 159.71±74.85 155.79±26.78 .518 1 Cd 0 (0-0.03) 0.17 (0-0.39) <.001 2 Pb 7.5 (0-25.55) 28 (17.08-65.5) <.001 2 Scales BDI 17.39±12.88 13.55±9.59 .098 3 Beck (≥17) 22 (44.9) 16 (32.7) .300 4 FFS 23.47±13.83 21.29±10.06 .374 3 FSS 41.70±18.30 36.18±14.82 .109 1 FSS (≥36) 30 (65.2) 26 (53.1) .320 4 Smoking Status 13 (26.5) 22 (43.1) .126 4 Fish consumption .893 5 About 1 per week 5 (10.2) 7 (13.7) About 1 per month 29 (59.2) 30 (58.8) About 1 per year 13 (26.5) 11 (21.6) None 2 (4.1) 3 (5.9) Residence Area .036 5 Province 38 (77.6) a 48 (94.1) b County 9 (18.4) 3 (5.9) Others 2 (4.1) 0 (0) Employment Status .005 4 Employed 17 (34.7) 33 (64.7) Unemployed 32 (65.3) 18 (35.3) Data were expressed as mean ± standard deviation (SD), median (interquartile range: 25 th percentile-75 th percentile), or number ( n ) and percentage (%). 1 Independent samples t- test, 2 Mann-Whitney U test, 3 Welch’s t -test, 4 Yates continuity correction chi-square test, 5 Fisher-Freeman-Halton test. BDI: Beck depression inventory, FFS: Facit fatigue scale, FSS: Fatigue severity scale, Cd: Cadmium, Cr: Chromium, Cu: Copper, Mn: Manganese, MS: Multiple sclerosis, Pb: Lead, Se: Selenium, Zn: Zinc, Table 3. Evaluation of the relationship between the scales in patients with multiple sclerosis EDSS T25FW 9HPT Dominant 9HPT Non-Dominant PASAT 3 Z ARM Z LEG Z COG MSFC T25FW 0.866 <0.001 - - - - 9HPT Dominant 0.763* <0.001 0.782* <0.001 - - - 9HPT Non-Dominant 0.738* <0.001 0.678* <0.001 0.690* <0.001 - - PASAT 3-Seconds Version 0.446* <0.001 0.526* <0.001 0.516* <0.001 0.360* 0.012 - PASAT 2-Seconds Version 0.364* 0.011 0.454* <0.001 0.486* <0.001 0.363* 0.011 0.857* <0.001 0,857* <0,001 0,454* 0,001 0,857* <0,001 0,630* <0,001 BDI 0.551* <0.001 0.491* <0.001 0.491* <0.001 0.512* <0.001 0.295* 0.042 -0,585* <0,001 -0,514* <0,001 -0,283* 0,049 -0,582* <0,001 FFS 0.697* <0.001 0.609* <0.001 0.509* <0.001 0.560* <0.001 0.287* 0.048 -0,410* 0,005 -0,519* <0,001 -0,104 0,479 -0,496* <0,001 FSS 0.643* <0.001 0.493* <0.001 0.399* 0.006 0.447* 0.002 -0,161 0,289 -0,410 0,005 -0,408* 0,005 -0,15 0,923 -0,352* 0,016 Level of Cr 0,187 0,199 0.368* 0.014 0.426* 0.004 0,154 0,291 0,024 0,869 -0,141 0,335 -0,006 0,965 0,220 0,129 -0,020 0,893 Level of Mn 0,176 0,253 0,301* 0,047 0,057 0,711 0,010 0,951 -0,188 0,222 -0,08 0,606 -0,301* 0,047 -0,273 0,073 -0,192 0,211 Z ARM -0,801* <0,001 -0,685* <0,001 -0,890* <0,001 -0,886* <0,001 0,471* 0,001 - - - - Z LEG 0,791* <0,001 -1* <0,001 -0,607* <0,001 -0,525* <0,001 0,526* <0,001 0,685* <0,001 - - - Z COG -0,400* 0,004 -0,476* 0,001 -0,313* 0,028 -0,221 0,127 1 0,368* 0,009 0,476* 0,001 - - MSFC -0,817* <0,001 -0,791* <0,001 -0,818* <0,001 -0,771* <0,001 0,684* <0,001 0,924* <0,001 0,791* <0,001 0,681* <0,001 - BDI: Beck depression inventory, Cr: Chromium, EDSS: Expanded disability status scale, FFS: Facit fatigue scale, FSS: Fatigue severity scale, 9HPT: Dominant hand 9-hole peg test, PASAT: Paced auditory serial addition test, T25FW: Timed 25-foot walk test , Z COG: Cognitive Z Score, MSFC: Multiple Sclerosis Functional Composite, Cr:cromium, Mn: manganese Table 4. Evaluation of the relationship between the trace elements Cr Mn Cu Zn Se Cd Mn 0,258* 0,021 - Cu 0,280* 0,012 0,034 0,768 - Zn -0,101 0,372 0,194 0,085 0,168 0,137 - Se 0,342* 0,002 -0,102 0,366 0,213 0,058 0,275* 0,014 - Cd -0,051 0,650 0,414* <0,001 -0,123 0,275 0,146 0,197 -0,222* 0,048 - Pb -0,130 0,252 0,503* <0,001 -0,210 0,061 0,117 0,301 -0,194 0,085 0,580* <0,001 Mn: manganese, Cu: copper, Zn: zinc, Se: selenium, Cd: cadmium, Pb:lead, Cr:cromium Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 05 May, 2025 Read the published version in Biological Trace Element Research → Version 1 posted Editorial decision: Revision requested 06 Apr, 2025 Reviews received at journal 02 Apr, 2025 Reviewers agreed at journal 24 Mar, 2025 Reviews received at journal 23 Mar, 2025 Reviewers agreed at journal 23 Mar, 2025 Reviewers invited by journal 22 Mar, 2025 Editor assigned by journal 21 Mar, 2025 Submission checks completed at journal 21 Mar, 2025 First submitted to journal 21 Mar, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6277424","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":433369397,"identity":"5b215980-9482-4908-8a9c-f70ba295aed2","order_by":0,"name":"Cihat Ozguncu¹","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA6klEQVRIiWNgGAWjYDACZh4kzgcgZmMnRssBKJtxBkgLM0FrkLRAbCSkhb+d9+DnDxV1dhtuNz+Ttvm1TZ6PmYHxw8cc3FokDvMlSxw4w5a84c4xM+ncvtuGbcwMzJIzt+HWYsDMYyBxsI0n2eBGDpt0bs9tRqAWNmZe/FqMfxxsk4Bosey5bU+MFjOgLQZ2YC0MP24nEtQicZjHzOLMmYQEyRtpxpa9DbeT25gZm/H6hb//jPGNioo6e74byQ9v/Phz23Z+e/PBDx/xaIGBxAYQydgGJhsIqwcCewj1hyjFo2AUjIJRMMIAAIRgTB2EMM5aAAAAAElFTkSuQmCC","orcid":"","institution":"Selcuk University","correspondingAuthor":true,"prefix":"","firstName":"Cihat","middleName":"","lastName":"Ozguncu¹","suffix":""},{"id":433369399,"identity":"656b8667-c132-4acd-9d5a-2881e0d0c729","order_by":1,"name":"Serefnur Ozturk¹","email":"","orcid":"","institution":"Selcuk University","correspondingAuthor":false,"prefix":"","firstName":"Serefnur","middleName":"","lastName":"Ozturk¹","suffix":""},{"id":433369401,"identity":"b268b8ec-d588-4912-97ba-b303ab6733db","order_by":2,"name":"Haluk Gumus¹","email":"","orcid":"","institution":"Selcuk University","correspondingAuthor":false,"prefix":"","firstName":"Haluk","middleName":"","lastName":"Gumus¹","suffix":""},{"id":433369405,"identity":"f1dd913a-a0d8-45fb-b115-95c9da20b06b","order_by":3,"name":"Gokhan Ozdemir¹","email":"","orcid":"","institution":"Selcuk University","correspondingAuthor":false,"prefix":"","firstName":"Gokhan","middleName":"","lastName":"Ozdemir¹","suffix":""},{"id":433369406,"identity":"d05a4dbe-6c78-4e0b-ab3a-61a58cc0e50a","order_by":4,"name":"Bahadır Ozturk²","email":"","orcid":"","institution":"Selcuk University","correspondingAuthor":false,"prefix":"","firstName":"Bahadır","middleName":"","lastName":"Ozturk²","suffix":""},{"id":433369408,"identity":"edc33b1a-84fa-490c-95d3-f9c3943aaae8","order_by":5,"name":"Ilkay Guzel²","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Ilkay","middleName":"","lastName":"Guzel²","suffix":""},{"id":433369409,"identity":"c6a0a921-e42c-4407-93d3-3bfbb5788229","order_by":6,"name":"Gozde Ongun³","email":"","orcid":"","institution":"Medicalpark Hospital","correspondingAuthor":false,"prefix":"","firstName":"Gozde","middleName":"","lastName":"Ongun³","suffix":""}],"badges":[],"createdAt":"2025-03-21 12:08:10","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6277424/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6277424/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s12011-025-04643-9","type":"published","date":"2025-05-05T15:57:45+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":82537552,"identity":"041190ea-3982-4460-b614-2a4ae58541c1","added_by":"auto","created_at":"2025-05-12 16:08:30","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1393719,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6277424/v1/0e2b31b2-3eb7-41f6-bc8d-d576636899f7.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Investigation of the Relationship Between Serum Trace Elements and MSFC Levels in Multiple Sclerosis","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eMultiple sclerosis (MS) is a chronic disease that can cause significant morbidity at a young age, causing inflammation, demyelination, and loss of axons involving the central nervous system. After the identification of MS, various studies have commenced investigating the etiology of MS rapidly. Although environmental, genetic, and autoimmune factors are emphasized to be effective in its etiology, how MS starts and what causes the progression has yet to be clearly understood [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Therefore, a definitive treatment for the disease has not yet been found. Regarding environmental factors, mining areas, active volcano regions, and industrial zones with intense air pollution are rich in heavy metals and trace elements [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. The accumulation of heavy metals and trace elements is known to be directly related to various disease groups. Different heavy metals and trace elements can lead to diseases by acting through different pathways or play an important role in cellular functions by participating in the structure of enzymes. In case of heavy metal imbalance in the cerebrospinal fluid (CSF), the condition can lead to pathological lesions that may result in the involvement of the blood-brain barrier, accumulation of heavy metals and neurodegeneration [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eZinc (Zn) is vital in regulating the immune system, showing its effect through the tumor necrosis factor (TNF)-alpha inhibitors. The deficiency of Zn can lead to the weakness of the immune system and contributes to the pathogenesis of MS by causing an imbalance between the functions of T helper-1 (Th1) and T helper-2 (Th2) cells, and the failure of Th17 downregulation [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Copper (Cu) plays a key role in the synthesis of myelin. The deficiency of Cu can potentially lead to myelinopathy, and Cu also shows its effectiveness by binding to vital enzymes such as cytochrome oxidase and superoxide dismutase [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. In addition, when the CSF of MS patients was examined, the levels of Cu were observed to be significantly increased compared to the normal population [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. After exposure to lead (Pb), the production of autoantibodies was observed against the proteins of the central nervous system (CNS), such as myelin basic protein (MBP) and glial fibrillary acidic protein (GFAB). These antibodies are predicted to also play a role in demyelination [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Given that cadmium (Cd) is known as a neurotoxic metal upon exposure to high levels, polyneuropathy is observed, and Cd is also considered to have effects on the blood-brain barrier [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Another element, selenium (Se), is a trace element found in a narrow range in the body. In studies, Se has been suggested to be associated with the neurodegenerative diseases of CNS [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Additionally, Se can also bring on mitochondrial damage by leading to the formation of reactive oxygen radicals and inhibiting antioxidant reactions. It is anticipated that the effects of Se may lead to neuro-toxication [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Acting as a cofactor in many enzymes, manganese (Mn) is another trace element known to have important functions in the proper functioning of the immune system [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Finally, chromium (Cr) is a rare transition metal, and it has been reported that Cr can be stored in the body and may cause neurotoxicity [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eSuch features as its geographical structure spreading on a broad plateau in Central Anatolia, climate, and proximity to the industrial zones are among the factors causing the province of Konya to rank first in Turkey regarding air pollution [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Our study will compare the findings of MS patients with those of the controls, and the relationship between the specified elements and MS will be investigated. The effects of these elements on the prognosis and diagnosis of MS will be evaluated.\u003c/p\u003e"},{"header":"2. Methods","content":"\u003cp\u003e Planned prospectively, our study was performed between August and November 2021 with approval from the Local Ethics Committee of the Faculty of Medicine at Selcuk University (Reg. number: 2019/81). Patients over 18 years of age, diagnosed with MS under the 2017 McDonald criteria [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e] and those with no rheumatological disease, pregnancy, and not being in an attack period were included in the study after obtaining informed written consent. For all patients, such features as age, gender, comorbid diseases, duration and subtype of MS, medications administered to treat MS, living in proximal homes to the city center, frequency of fish consumption, smoking status, and educational status were recorded. The values of the expanded disability status scale (EDSS) were calculated by performing neurological examinations of the patients [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. The timed 25-foot walk test (T25FW), the 9-hole peg test (9HPT), and the paced auditory serial addition test (2 seconds and 3 seconds versions) (PASAT2 and PASAT3) making up the multiple sclerosis functional composite (MSFC) were carried out to evaluate the relationships between the scales in MS patient group [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn addition, we also evaluated the levels of fatigue and depression, the most common complaints witnessed in MS patients from the early stages of the study period. The fatigue severity (FSS) [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] and the facit fatigue scales (FFS) [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e], used to evaluate the validity and reliability of MS, were performed to assess the complaints under the self-reporting by each patient. A score of 36\u0026thinsp;\u0026gt;\u0026thinsp;on FSS was evaluated as fatigue. Similarly, each patient was asked to complete the Beck Depression Inventory (BDI) [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e], which is a widely used test to evaluate depression all over the world. A score of 17 or higher acquired in BDI was considered depression. Patients (n\u0026thinsp;=\u0026thinsp;51) over 18 with no pregnancy and not diagnosed with any diseases on admission to our polyclinic were also included in the study as the control group after informed written consent was obtained. In the control group, the features such as age, gender, distance from the homes to the city center, smoking status, and fish consumption were recorded, and the scales of BDI, FSS, and FFS were also carried out in the control group. Drawn from the entire study population and kept in blood sample tubes, the samples were transferred to tubes of trace elements. The serum obtained by centrifugation at 5000 rpm for five minutes was taken into an Eppendorf tube and stored at -80\u0026deg;C until the investigation. After sampling was completed, the samples were first dried by exposing them to high heat in a microwave oven in our university's advanced technology laboratory. The levels of Zn, Mn, Cu, Pb, Se, Cr, and Cd were determined with the inductively coupled plasma mass spectrometry (ICP-MS) device (Perkin Elmer / ICP MS ELAN DRC-E, PerkinElmer Inc, Wellesley, United States ).\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Statistical Analysis\u003c/h2\u003e \u003cp\u003eAll statistical analysis was performed using the R version 3.6.0 (The R Foundation for Statistical Computing, Vienna, Austria; \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.r-project.org\u003c/span\u003e\u003cspan address=\"https://www.r-project.org\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e). Shapiro-Wilk\u0026rsquo;s normality test and Q-Q plots were used to assess the normality of the data. Also, the Levene test was performed to check the homogeneity of the variances. The numerical variables were presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD) (range: minimum-maximum) or median (interquartile range [IQR]: 25th percentile-75th percentile) as appropriate. Even so, the categorical variables were described as number (n) and percentage (%). T25FW was converted to Z-score as Z-LEG to calculate multiple sclerosis functional composite. Similarly, 9HPT was converted to Z-ARM and PASAT-3 was converted to Z-COG. MSFC score was calculated with Z-ARM, Z-LEG and Z-COG [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Reference values from the literature were used during the calculation [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. An independent samples t-test, the Welch\u0026rsquo;s t-test, the Mann-Whitney U test, the Yates continuity correction chi-square test, and the Fisher-Freeman-Halton test was conducted to determine whether there was a statistically significant difference or association between the study groups regarding the demographical and clinical characteristics, and laboratory findings. The Spearman-rho ranked-order correlation coefficients were used to examine the relationship between numerical variables. A two-tailed p-value of \u0026lt;\u0026thinsp;5% was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Results","content":"\u003cp\u003eWhile there were 49 patients with a mean age of 35.08\u0026plusmn;11.36 years in the MS group, the control group was composed of 51 individuals with a mean age of 31.41\u0026plusmn;10.71 years. The male-to-female (M/F) ratios were 32/17 and 31/20 in the MS and control groups, respectively. The mean duration of MS was detected as five years (1-27), and the mean EDSS score was calculated as 2.81 (0.5-5.5). The distributions of the MS subtypes among the patients were as follows: 41 patients with relapsing-remitting multiple sclerosis (RRMS), four with primary progressive multiple sclerosis (PPMS), and four with secondary progressive multiple sclerosis (SPMS). The findings are presented in Table 1.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe levels of Mn, Zn, Cd, and Pb were significantly higher in the control group (p\u0026lt;.001, 0.002, \u0026lt;.001, \u0026lt;.001, respectively). There was no significant difference between the MS and control groups in terms of depression and fatigue scores, and the comparisons are given in Table 2.\u003c/p\u003e\n\u003cp\u003eGiven the evaluation of MSFC of MS patients, the parameters of MSFC and depression and fatigue scales were observed to be statistically higher, as well as the increase in EDSS. A significant correlation was also observed between T25FW and 9HPT scores and Cr levels (p= 0.014, 0.004, respectively ). Similarly, a significant correlation was observed between manganese level and T25FW and Z score. (p= 0.047) (Table 3).\u003c/p\u003e\n\u003cp\u003eIn addition, the values of the elements, +Mn (26.59 [IQR, 22.84-42.13] vs. 52.91 [IQR, 35.80-74.96], p \u0026lt;.001), Zn (868.96\u0026plusmn;190.56 vs. 1067.38\u0026plusmn;322.79, p=.002), Cd (0 [IQR, 0-0.03] vs. 0.17 [IQR, 0-0.39], p\u0026lt;.001), and Pb (7.5 [IQR, 0-25.55] vs. 28 [IQR, 17.08-65.5], p\u0026lt;.001) were determined to be lower in the MS patient group, compared to the healthy controls.\u003c/p\u003e\n\u003cp\u003eWhen the correlations among trace elements were evaluated, it was observed that there was a significant correlation between Mn level and Cr, Cd, Pb (p= 0.021, \u0026lt;0.001, \u0026lt;0.001 respectively), a significant correlation between Se levels and Cr, Zn, Cd (p= 0.002, 0.014, 0.048 respectively), a correlation between Cr and Cu and a correlation between Cd and Pb (p= 0.012, \u0026lt;0.001 respectively) (table 4).\u003c/p\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eAlthough many studies are investigating the association between MS and heavy metals based on the literature, various points remain unexplained, and there are also studies reporting conflicting findings regarding the relationship between MS and heavy metals. The relationship between the severity of MS and exposure to higher levels of heavy metals is one of the challenges to be clarified.\u003c/p\u003e \u003cp\u003eIn light of the literature, in a systematic review evaluating the effects of heavy metals on MS, it was reported that no difference was observed between the MS and control groups regarding Se and Cu levels, and Zn was found lower, as consistent with our study findings. On the other hand, the Mn levels were higher in MS patients [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. In a similar meta-analysis, the levels of Cd were stated to be higher in MS patients. Although the levels of Pb were higher in MS patients, the difference was considered statistically insignificant [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Another meta-analysis evaluating only the Zn levels showed that the Zn levels were significantly lower in the MS population than in the controls, which is in line with our study results [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn two different studies conducted in Iran, where air pollution is intense, as in the province of Konya, the levels of Pb were found to be similar between the MS patient and control groups. Another study also evaluated the levels of Cu and Se within patients with MS. It detected that the levels of both elements were at a similar rate between the MS and control groups, consistent with our study findings [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. In the study carried out by Aliomrani et al., the level of Cd was determined to be higher in the MS group [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. In a study published in 2017 that included findings similar to our study, the levels of Cd, Zn, and Mn were observed to be decreased in MS patients compared to those in the control group [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. In the literature, there are also results complying with our study findings, revealing that the levels of Pb and Zn are lower in MS patients [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. In a study carried out in Brazil and including completely different findings from those in our study, it was stated that the levels of Cu and Cr were lower, the level of Pb was higher, and there was no difference concerning Zn levels in MS patients [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. Such differences suggested that the results in different studies could vary considerably according to regions and geographical features where the studies were conducted.\u003c/p\u003e \u003cp\u003eAlthough the results in the literature and our study are generally compatible, some studies report conflicting results regarding the levels of Pb and Cd in MS patients. It is unlikely that any comments will be made about whether such a situation plays a role as a by-product in the pathophysiology of MS but has no direct effect on the issue or whether MS has an unknown mechanism yet.\u003c/p\u003e \u003cp\u003eOur study observed that, along with the increase in EDSS, the parameters of MSFC, depression, and fatigue scales were also statistically higher. Those findings are supported by more than one study in the literature [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. In many studies, it is stated that there is an increase in depression and fatigue scores in MS patients compared to the controls [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e, \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]. Even so, an increase was observed in the depression and fatigue scores in our MS patients; the difference displayed no statistical significance. Therefore, it is likely to make different inferences, and we consider that the entity deserves further evaluation. Although our study revealed a statistically significant relationship between the scores of T25FW and 9HPT-dominant and the levels of Cr, no publications supporting or contradicting such a finding were encountered in the literature.\u003c/p\u003e \u003cp\u003eThe levels of Cr were within normal limits in our samples, and there was no finding suggestive of toxicity. In a placebo-controlled double-anonymized study investigating the effects of Cr supplementation on neuronal functions, it was reported that Cr supplementation could increase cognitive inhibitory control and cerebral function in older adults at risk for neurodegeneration [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. The effect of Cr can explain the findings in our study. Further studies should elucidate the necessity and importance of Cr supplementation in MS patients.\u003c/p\u003e \u003cp\u003eIn our study, a correlation is observed between T25FW and Mn levels. No publication in the literature clearly explains the effect of Mn levels on walking function. However, publications indicate that cows whose diets contain trace elements (zinc, manganese, copper and cobalt) positively increase their kinematic walking parameters. In this publication, it was reported that no difference was observed between the zinc and copper levels in the blood of the control group and the experimental group. However, there was a significant increase in manganese levels in those receiving supplementary food [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]. More research needs to be done on this issue.\u003c/p\u003e \u003cp\u003eThe present study also has several limitations. First, no national and geographical characteristics could be evaluated since the data obtained from a single center were utilized. Secondly, the levels of heavy metals and trace elements evaluated in the study may be affected by many clinical and structural conditions; in other words, nutritional supplements and lifestyle habits can alter the levels of serum elements. Additionally, no occupational details were evaluated in the population studied; some occupations are known to be risky due to exposure to heavy metals. Finally, although depression and fatigue are known to be affected by many conditions, those conditions have been ignored. It is recommended that those conditions be considered and investigated in studies that include larger populations.\u003c/p\u003e \u003cp\u003eAs a result of the findings in our study and previous studies, it still seems unlikely that a clear relationship between MS and the levels of heavy metals and trace elements can be established. However, the lower levels of certain elements, especially in MS patients, support the hypothesis that those elements and their levels may be a distinguishing factor in MS. In particular, the relationship between Cr and Mn levels and MSFC parameters needs to be re-evaluated and confirmed by further studies. With novel tests and methods, the etiology and pathophysiology of MS will be enlightened more clearly, and the question marks will be eliminated as a result of such studies.\u003c/p\u003e"},{"header":"5. Conclusion","content":"\u003cp\u003eThe Mn, Zn, Cd, and Pb levels were lower in the MS group compared to the control, while the Se, Cr, and Cu levels were similar. No correlation was observed between the levels of heavy metals and trace elements and the scores of depression, fatigue, and EDSS.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eData Availability Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe raw data supporting the outcomes of this article will be made available by the authors without undue reservation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthorship Contribution Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCO: planning, organization, data collection, writing, and editing. SO: organization, writing, and editing HG: planning and organization. BO, G\u0026Ouml;, GO, IG: data collection. All authors contributed to the article and approved the submitted version.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study involving human participants was carried out under the principles of the 1964 Declaration of Helsinki and its later amendments, and the study protocol was also reviewed and approved by the Local Ethics Committee for Clinical Researches of Selcuk University (Approval number: 2019/81).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that the research was conducted without commercial or financial relationships construed as a potential conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFinancial Support\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by the Scientific Research Projects Coordinatorship of Selcuk University (Project number: 20401145).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDisclosure\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOur study began in 2019 after receiving ethical approval. Due to the difficulty obtaining financial support for the project and the subsequent pandemic, it was necessary to start recruiting patients later. Our study was presented as an oral presentation at the 12th Clinical Neuroimmunology Symposium held in Antalya, Turkiye, between 12-15 May 2022.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eKamińska, J., et al., \u003cem\u003eMultiple sclerosis - etiology and diagnostic potential.\u003c/em\u003e Postepy Hig Med Dosw (Online), 2017. \u003cstrong\u003e71\u003c/strong\u003e(0): p. 551-563. https://doi.org/10.5604/01.3001.0010.3836\u003c/li\u003e\n\u003cli\u003eHansell, A.L., C.J. Horwell, and C. Oppenheimer, \u003cem\u003eThe health hazards of volcanoes and geothermal areas.\u003c/em\u003e Occup Environ Med, 2006. \u003cstrong\u003e63\u003c/strong\u003e(2): p. 149-56, 125. https://doi.org/10.1136/oem.2005.022459\u003c/li\u003e\n\u003cli\u003eMadeddu, R., et al., \u003cem\u003eHeavy metals and multiple sclerosis in Sardinian population (Italy).\u003c/em\u003e 2011. \u003cstrong\u003e44\u003c/strong\u003e(9): p. 1699-1712. https://doi.org/10.1080/00032719.2010.520396\u003c/li\u003e\n\u003cli\u003eMezzaroba, L., et al., \u003cem\u003eThe role of zinc, copper, manganese and iron in neurodegenerative diseases.\u003c/em\u003e Neurotoxicology, 2019. \u003cstrong\u003e74\u003c/strong\u003e: p. 230-241. https://doi.org/10.1016/j.neuro.2019.07.007\u003c/li\u003e\n\u003cli\u003eDe Riccardis, L., et al., \u003cem\u003eCopper and ceruloplasmin dyshomeostasis in serum and cerebrospinal fluid of multiple sclerosis subjects.\u003c/em\u003e Biochim Biophys Acta Mol Basis Dis, 2018. \u003cstrong\u003e1864\u003c/strong\u003e(5 Pt A): p. 1828-1838. https://doi.org/10.1016/j.bbadis.2018.03.007\u003c/li\u003e\n\u003cli\u003eMel\u0026oslash;, T.M., et al., \u003cem\u003eManganese, copper, and zinc in cerebrospinal fluid from patients with multiple sclerosis.\u003c/em\u003e Biol Trace Elem Res, 2003. \u003cstrong\u003e93\u003c/strong\u003e(1-3): p. 1-8. https://doi.org/10.1385/BTER:93:1-3:1\u003c/li\u003e\n\u003cli\u003eEl-Fawal, H.A., et al., \u003cem\u003eNeuroimmunotoxicology: humoral assessment of neurotoxicity and autoimmune mechanisms.\u003c/em\u003e Environ Health Perspect, 1999. \u003cstrong\u003e107 Suppl 5\u003c/strong\u003e(Suppl 5): p. 767-75. https://doi.org/10.1289/ehp.99107s5767\u003c/li\u003e\n\u003cli\u003eViaene, M.K., et al., \u003cem\u003eCadmium: a possible etiological factor in peripheral polyneuropathy.\u003c/em\u003e Neurotoxicology, 1999. \u003cstrong\u003e20\u003c/strong\u003e(1): p. 7-16.\u003c/li\u003e\n\u003cli\u003eM\u0026eacute;ndez-Armenta, M., et al., \u003cem\u003eBrain regional lipid peroxidation and metallothionein levels of developing rats exposed to cadmium and dexamethasone.\u003c/em\u003e Toxicol Lett, 2003. \u003cstrong\u003e144\u003c/strong\u003e(2): p. 151-7. https://doi.org/10.1016/S0378-4274(03)00199-1\u003c/li\u003e\n\u003cli\u003eFilippini, T., et al. \u003cem\u003eSelenium Neurotoxicity and Amyotrophic Lateral Sclerosis: An Epidemiologic Perspective\u003c/em\u003e. 2018. https://doi.org/10.1007/978-3-319-95390-8_12\u003c/li\u003e\n\u003cli\u003eOliveira, C.S., et al., \u003cem\u003eChemical Speciation of Selenium and Mercury as Determinant of Their Neurotoxicity.\u003c/em\u003e Adv Neurobiol, 2017. \u003cstrong\u003e18\u003c/strong\u003e: p. 53-83. https://doi.org/10.1007/978-3-319-60189-2_4\u003c/li\u003e\n\u003cli\u003eMandrioli, J., et al., \u003cem\u003eElevated Levels of Selenium Species in Cerebrospinal Fluid of Amyotrophic Lateral Sclerosis Patients with Disease-Associated Gene Mutations.\u003c/em\u003e Neurodegener Dis, 2017. \u003cstrong\u003e17\u003c/strong\u003e(4-5): p. 171-180. https://doi.org/10.1159/000460253\u003c/li\u003e\n\u003cli\u003eErikson, K.M. and M. Aschner, \u003cem\u003eManganese neurotoxicity and glutamate-GABA interaction.\u003c/em\u003e Neurochem Int, 2003. \u003cstrong\u003e43\u003c/strong\u003e(4-5): p. 475-80. https://doi.org/10.1016/S0197-0186(03)00037-8\u003c/li\u003e\n\u003cli\u003eNirooei, E., et al., \u003cem\u003eBlood Trace Element Status in Multiple Sclerosis: a Systematic Review and Meta-analysis.\u003c/em\u003e Biol Trace Elem Res, 2022. \u003cstrong\u003e200\u003c/strong\u003e(1): p. 13-26. https://doi.org/10.1007/s12011-021-02621-5\u003c/li\u003e\n\u003cli\u003eWise, J.P., Jr., et al., \u003cem\u003eCurrent understanding of hexavalent chromium [Cr(VI)] neurotoxicity and new perspectives.\u003c/em\u003e Environ Int, 2022. \u003cstrong\u003e158\u003c/strong\u003e: p. 106877. https://doi.org/10.1016/j.envint.2021.106877\u003c/li\u003e\n\u003cli\u003eYahaya, N., et al. \u003cem\u003eAir Quality Status in Konya City Centre, Konya, Turkey during Pandemic Covid-19\u003c/em\u003e. in \u003cem\u003eIOP Conference Series: Earth and Environmental Science\u003c/em\u003e. 2022. IOP Publishing. https://doi.org/10.1088/1755-1315/1013/1/012006\u003c/li\u003e\n\u003cli\u003eThompson, A.J., et al., \u003cem\u003eDiagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria.\u003c/em\u003e Lancet Neurol, 2018. \u003cstrong\u003e17\u003c/strong\u003e(2): p. 162-173. https://doi.org/10.1016/S1474-4422(17)30470-2\u003c/li\u003e\n\u003cli\u003eKurtzke, J.F., \u003cem\u003eRating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS).\u003c/em\u003e Neurology, 1983. \u003cstrong\u003e33\u003c/strong\u003e(11): p. 1444-52. https://doi.org/10.1212/WNL.33.11.1444\u003c/li\u003e\n\u003cli\u003eCutter, G.R., et al., \u003cem\u003eDevelopment of a multiple sclerosis functional composite as a clinical trial outcome measure.\u003c/em\u003e Brain, 1999. \u003cstrong\u003e122 ( Pt 5)\u003c/strong\u003e: p. 871-82. https://doi.org/10.1093/brain/122.5.871\u003c/li\u003e\n\u003cli\u003eArmutlu, K., et al., \u003cem\u003eThe validity and reliability of the Fatigue Severity Scale in Turkish multiple sclerosis patients.\u003c/em\u003e Int J Rehabil Res, 2007. \u003cstrong\u003e30\u003c/strong\u003e(1): p. 81-5. https://doi.org/10.1097/MRR.0b013e3280146ec4\u003c/li\u003e\n\u003cli\u003eKrupp, L.B., et al., \u003cem\u003eThe fatigue severity scale. Application to patients with multiple sclerosis and systemic lupus erythematosus.\u003c/em\u003e Arch Neurol, 1989. \u003cstrong\u003e46\u003c/strong\u003e(10): p. 1121-3. https://doi.org/10.1001/archneur.1989.00520460115022\u003c/li\u003e\n\u003cli\u003eDelgado-\u0026Aacute;lvarez, A., et al., \u003cem\u003eValidation of two new scales for the assessment of fatigue in Multiple Sclerosis: F-2-MS and FACIT-F.\u003c/em\u003e Mult Scler Relat Disord, 2022. \u003cstrong\u003e63\u003c/strong\u003e: p. 103826. https://doi.org/10.1016/j.msard.2022.103826\u003c/li\u003e\n\u003cli\u003eWebster, K., D. Cella, and K. Yost, \u003cem\u003eThe Functional Assessment of Chronic Illness Therapy (FACIT) Measurement System: properties, applications, and interpretation.\u003c/em\u003e Health Qual Life Outcomes, 2003. \u003cstrong\u003e1\u003c/strong\u003e: p. 79. https://doi.org/10.1037/t77273-000\u003c/li\u003e\n\u003cli\u003eBeck, A.T., R.A. Steer, and G.K. Brown, \u003cem\u003eBeck depression inventory.\u003c/em\u003e 1996. https://doi.org/10.1037/t00742-000\u003c/li\u003e\n\u003cli\u003eKapci, E.G., et al., \u003cem\u003eBeck Depression Inventory II: evaluation of the psychometric properties and cut-off points in a Turkish adult population.\u003c/em\u003e Depress Anxiety, 2008. \u003cstrong\u003e25\u003c/strong\u003e(10): p. E104-10. https://doi.org/10.1002/da.20371\u003c/li\u003e\n\u003cli\u003eTiftik\u0026ccedil;ioğlu, B., \u003cem\u003eMultiple Sclerosis Functional Composite (MSFC): Scoring Instructions.\u003c/em\u003e Noro Psikiyatr Ars, 2018. \u003cstrong\u003e55\u003c/strong\u003e(Suppl 1): p. S46-s48. https://doi.org/10.29399/npa.23330\u003c/li\u003e\n\u003cli\u003eSarihi, S., et al., \u003cem\u003eToxic heavy metal concentrations in multiple sclerosis patients: A systematic review and meta-analysis.\u003c/em\u003e Excli j, 2021. \u003cstrong\u003e20\u003c/strong\u003e: p. 1571-1584.\u003c/li\u003e\n\u003cli\u003eBredholt, M. and J.L. Frederiksen, \u003cem\u003eZinc in Multiple Sclerosis: A Systematic Review and Meta-Analysis.\u003c/em\u003e ASN Neuro, 2016. \u003cstrong\u003e8\u003c/strong\u003e(3). https://doi.org/10.1177/1759091416651511\u003c/li\u003e\n\u003cli\u003eAlizadeh, A., et al., \u003cem\u003eComparison of serum Concentration of Se, Pb, Mg, Cu, Zn, between MS patients and healthy controls.\u003c/em\u003e Electron Physician, 2016. \u003cstrong\u003e8\u003c/strong\u003e(8): p. 2759-2764. https://doi.org/10.19082/2759\u003c/li\u003e\n\u003cli\u003eAliomrani, M., et al., \u003cem\u003eBlood Concentrations of Cadmium and Lead in Multiple Sclerosis Patients from Iran.\u003c/em\u003e Iran J Pharm Res, 2016. \u003cstrong\u003e15\u003c/strong\u003e(4): p. 825-833.\u003c/li\u003e\n\u003cli\u003eJanghorbani, M., et al. \u003cem\u003eTrace Elements in Serum Samples of Patients with Multiple Sclerosis\u003c/em\u003e. 2017. https://doi.org/10.30958/ajh.4-2-3\u003c/li\u003e\n\u003cli\u003eForte, G., et al., \u003cem\u003eQuantification of chemical elements in blood of patients affected by multiple sclerosis.\u003c/em\u003e Ann Ist Super Sanita, 2005. \u003cstrong\u003e41\u003c/strong\u003e(2): p. 213-6.\u003c/li\u003e\n\u003cli\u003ede Oliveira, M., et al., \u003cem\u003eA preliminary study of the concentration of metallic elements in the blood of patients with multiple sclerosis as measured by ICP-MS.\u003c/em\u003e Sci Rep, 2020. \u003cstrong\u003e10\u003c/strong\u003e(1): p. 13112. https://doi.org/10.1038/s41598-020-69979-9\u003c/li\u003e\n\u003cli\u003eYigit, P., et al., \u003cem\u003eThe relationship between cognition, depression, fatigue, and disability in patients with multiple sclerosis.\u003c/em\u003e Ir J Med Sci, 2021. \u003cstrong\u003e190\u003c/strong\u003e(3): p. 1129-1136. https://doi.org/10.1007/s11845-020-02377-2\u003c/li\u003e\n\u003cli\u003ePatti, F., et al., \u003cem\u003eCognitive impairment and its relation with disease measures in mildly disabled patients with relapsing-remitting multiple sclerosis: baseline results from the Cognitive Impairment in Multiple Sclerosis (COGIMUS) study.\u003c/em\u003e Mult Scler, 2009. \u003cstrong\u003e15\u003c/strong\u003e(7): p. 779-88. https://doi.org/10.1177/1352458509105544\u003c/li\u003e\n\u003cli\u003eBoeschoten, R.E., et al., \u003cem\u003ePrevalence of depression and anxiety in Multiple Sclerosis: A systematic review and meta-analysis.\u003c/em\u003e J Neurol Sci, 2017. \u003cstrong\u003e372\u003c/strong\u003e: p. 331-341. https://doi.org/10.1016/j.jns.2016.11.067\u003c/li\u003e\n\u003cli\u003eBrenner, P. and F. Piehl, \u003cem\u003eFatigue and depression in multiple sclerosis: pharmacological and non-pharmacological interventions.\u003c/em\u003e Acta Neurol Scand, 2016. \u003cstrong\u003e134 Suppl 200\u003c/strong\u003e: p. 47-54. https://doi.org/10.1111/ane.12648\u003c/li\u003e\n\u003cli\u003eKrikorian, R., et al., \u003cem\u003eImproved cognitive-cerebral function in older adults with chromium supplementation.\u003c/em\u003e Nutr Neurosci, 2010. \u003cstrong\u003e13\u003c/strong\u003e(3): p. 116-22. https://doi.org/10.1179/147683010X12611460764084\u003c/li\u003e\n\u003cli\u003eYamamoto, S., et al., \u003cem\u003eKinematic gait analysis and lactation performance in dairy cows fed a diet supplemented with zinc, manganese, copper and cobalt.\u003c/em\u003e Anim Sci J, 2014. \u003cstrong\u003e85\u003c/strong\u003e(3): p. 330-5. https://doi.org/10.1111/asj.12141\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u0026nbsp;\u003cstrong\u003eTable 1.\u003c/strong\u003e Demographical and clinical characteristics of multiple sclerosis patients and controls\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"631\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMS\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eControls\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ep\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eDemographical characteristics\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eAge (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e35.08\u0026plusmn;11.36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e31.41\u0026plusmn;10.71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e.100\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eGender (F/M)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e32 (65.3)/17 (34.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e31 (60.8)/20 (39.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e.794\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eDuration of MS\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e5 (1-27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMS Scores\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eEDSS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2.81\u0026plusmn;1.58 (0.5-5.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eT25FW\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e7.17\u0026plusmn;2.70 (4.4-16.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e9HPT-Dominant\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e23.39\u0026plusmn;8.70 (13.9-52.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e9HPT-Non-Dominant\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e27.19\u0026plusmn;11.29 (16-58.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePASAT 3-Seconds Version\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e27.67\u0026plusmn;5.57 (9-48)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePASAT 2-Seconds Version\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e25.54\u0026plusmn;6.71 (2-43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eZ-ARM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0,02 \u0026plusmn; 1,11 (-2,53 \u0026ndash; 2,31)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eZ-LEG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0,21 \u0026plusmn; 0,24 (-0,58 \u0026ndash; 0,45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eZ-COGNITIVE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e-1,48 \u0026plusmn; 0,56 (-3,73 \u0026ndash; 0,25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMSFC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e-0,42 \u0026plusmn; 0,53 (-1,77 \u0026ndash; 0,46)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eType of MS\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eRRMS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e41 (83.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eSPMS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e4 (8.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePPMS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e4 (8.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eDrugs Administered\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;Glatiramer acetate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;Interferon beta-1a\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e5 (10.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;Teriflunomide\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2 (4.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;Dimethyl Fumarate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e8 (16.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;Fingolimod\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e13 (26.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;Ocrelizumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e10 (20.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;Rituximab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2 (4.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;Cladribine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2 (4.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;No drugs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e6 (12.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eEDSS: Expanded disability status scale, MS: Multiple sclerosis, 9HPT: Dominant hand 9-hole peg test, PASAT: Paced auditory serial addition test, PPMS: Primary progressive multiple sclerosis, RRMS: Relapsing-remitting multiple sclerosis, SPMS: Secondary progressive multiple sclerosis, T25FW: Timed 25-foot walk test, MSFC: Multiple Sclerosis Functional Composite\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2.\u003c/strong\u003e Comparisons between multiple sclerosis patients and controls in the study\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 168px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMS\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eControls\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ep\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 168px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLaboratory findings\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 168px;\"\u003e\n \u003cp\u003eCr\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e733.66\u0026plusmn;157.24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e725.10\u0026plusmn;217.60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e.839\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 168px;\"\u003e\n \u003cp\u003eMn\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e26.59 (22.84-42.13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e52.91 (35.80-74.96)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026lt;.001\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 168px;\"\u003e\n \u003cp\u003eCu\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e1708\u0026plusmn;388.58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e1699.39\u0026plusmn;447.40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e.927\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 168px;\"\u003e\n \u003cp\u003eZn\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e868.96\u0026plusmn;190.56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e1067.38\u0026plusmn;322.79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e.002\u003csup\u003e3\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 168px;\"\u003e\n \u003cp\u003eSe\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e159.71\u0026plusmn;74.85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e155.79\u0026plusmn;26.78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e.518\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 168px;\"\u003e\n \u003cp\u003eCd\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e0 (0-0.03)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e0.17 (0-0.39)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026lt;.001\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 168px;\"\u003e\n \u003cp\u003ePb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e7.5 (0-25.55)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e28 (17.08-65.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026lt;.001\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 168px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eScales\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 168px;\"\u003e\n \u003cp\u003eBDI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e17.39\u0026plusmn;12.88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e13.55\u0026plusmn;9.59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e.098\u003csup\u003e3\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 168px;\"\u003e\n \u003cp\u003eBeck (\u0026ge;17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e22 (44.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e16 (32.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e.300\u003csup\u003e4\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 168px;\"\u003e\n \u003cp\u003eFFS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e23.47\u0026plusmn;13.83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e21.29\u0026plusmn;10.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e.374\u003csup\u003e3\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 168px;\"\u003e\n \u003cp\u003eFSS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e41.70\u0026plusmn;18.30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e36.18\u0026plusmn;14.82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e.109\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 168px;\"\u003e\n \u003cp\u003eFSS (\u0026ge;36)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e30 (65.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e26 (53.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e.320\u003csup\u003e4\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 168px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSmoking Status\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e13 (26.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e22 (43.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e.126\u003csup\u003e4\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 168px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFish consumption\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e.893\u003csup\u003e5\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 168px;\"\u003e\n \u003cp\u003eAbout 1 per week\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e5 (10.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e7 (13.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 168px;\"\u003e\n \u003cp\u003eAbout 1 per month\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e29 (59.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e30 (58.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 168px;\"\u003e\n \u003cp\u003eAbout 1 per year\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e13 (26.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e11 (21.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 168px;\"\u003e\n \u003cp\u003eNone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e2 (4.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e3 (5.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 168px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eResidence Area\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e.036\u003csup\u003e5\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 168px;\"\u003e\n \u003cp\u003eProvince\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e38 (77.6)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e48 (94.1)\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 168px;\"\u003e\n \u003cp\u003eCounty\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e9 (18.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e3 (5.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 168px;\"\u003e\n \u003cp\u003eOthers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e2 (4.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 168px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eEmployment Status\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e.005\u003csup\u003e4\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 168px;\"\u003e\n \u003cp\u003eEmployed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e17 (34.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e33 (64.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 168px;\"\u003e\n \u003cp\u003eUnemployed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e32 (65.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e18 (35.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eData were expressed as mean \u0026plusmn; standard deviation (SD), median (interquartile range: 25\u003csup\u003eth\u003c/sup\u003e percentile-75\u003csup\u003eth\u003c/sup\u003e percentile), or number (\u003cem\u003en\u003c/em\u003e) and percentage (%).\u003csup\u003e1\u003c/sup\u003eIndependent samples \u003cem\u003et-\u003c/em\u003etest, \u003csup\u003e2\u003c/sup\u003eMann-Whitney \u003cem\u003eU\u003c/em\u003e test, \u003csup\u003e3\u003c/sup\u003eWelch\u0026rsquo;s \u003cem\u003et\u003c/em\u003e-test, \u003csup\u003e4\u003c/sup\u003eYates continuity correction chi-square test, \u003csup\u003e5\u003c/sup\u003eFisher-Freeman-Halton test. BDI:\u0026nbsp;Beck depression inventory, FFS: Facit fatigue scale, FSS: Fatigue severity scale, Cd: Cadmium, Cr: Chromium, Cu: Copper, Mn: Manganese, MS: Multiple sclerosis, Pb: Lead, Se: Selenium, Zn: Zinc,\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3.\u003c/strong\u003e Evaluation of the relationship between the scales in patients with multiple sclerosis\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"604\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eEDSS\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eT25FW\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e9HPT Dominant\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e9HPT\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;Non-Dominant\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePASAT 3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eZ ARM\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eZ LEG\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eZ COG\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMSFC\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eT25FW\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.866\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e9HPT Dominant\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.763*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.782*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e9HPT\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eNon-Dominant\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.738*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.678*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.690*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePASAT 3-Seconds Version\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.446*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.526*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.516*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.360*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e0.012\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePASAT 2-Seconds Version\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.364*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e0.011\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.454*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.486*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.363*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e0.011\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.857*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0,857*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0,001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0,454*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e0,001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0,857*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0,001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0,630*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0,001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eBDI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.551*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.491*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.491*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.512*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.295*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e0.042\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e-0,585*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0,001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e-0,514*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0,001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e-0,283*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e0,049\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e-0,582*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0,001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eFFS\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.697*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.609*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.509*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.560*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.287*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e0.048\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e-0,410*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e0,005\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e-0,519*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0,001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e-0,104\u003c/p\u003e\n \u003cp\u003e0,479\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e-0,496*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0,001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eFSS\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.643*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.493*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.399*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e0.006\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.447*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e0.002\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e-0,161\u003c/p\u003e\n \u003cp\u003e0,289\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e-0,410\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e0,005\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e-0,408*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e0,005\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e-0,15\u003c/p\u003e\n \u003cp\u003e0,923\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e-0,352*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e0,016\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eLevel of Cr\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e0,187\u003c/p\u003e\n \u003cp\u003e0,199\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.368*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e0.014\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.426*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e0.004\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e0,154\u003c/p\u003e\n \u003cp\u003e0,291\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0,024\u003c/p\u003e\n \u003cp\u003e0,869\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e-0,141\u003c/p\u003e\n \u003cp\u003e0,335\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e-0,006\u003c/p\u003e\n \u003cp\u003e0,965\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e0,220\u003c/p\u003e\n \u003cp\u003e0,129\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e-0,020\u003c/p\u003e\n \u003cp\u003e0,893\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLevel of Mn\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e0,176\u003c/p\u003e\n \u003cp\u003e0,253\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0,301*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e0,047\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e0,057\u003c/p\u003e\n \u003cp\u003e0,711\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e0,010\u003c/p\u003e\n \u003cp\u003e0,951\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e-0,188\u003c/p\u003e\n \u003cp\u003e0,222\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e-0,08\u003c/p\u003e\n \u003cp\u003e0,606\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e-0,301*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e0,047\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e-0,273\u003c/p\u003e\n \u003cp\u003e0,073\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e-0,192\u003c/p\u003e\n \u003cp\u003e0,211\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eZ ARM\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e-0,801*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0,001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e-0,685*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0,001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e-0,890*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0,001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e-0,886*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0,001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0,471*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e0,001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eZ LEG\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0,791*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0,001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e-1*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0,001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e-0,607*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0,001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e-0,525*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0,001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0,526*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0,001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0,685*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0,001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eZ COG\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e-0,400*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e0,004\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e-0,476*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e0,001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e-0,313*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e0,028\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e-0,221\u003c/p\u003e\n \u003cp\u003e0,127\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0,368*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e0,009\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0,476*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e0,001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMSFC\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e-0,817*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0,001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e-0,791*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0,001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e-0,818*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0,001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e-0,771*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0,001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0,684*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0,001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0,924*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0,001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0,791*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0,001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0,681*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0,001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eBDI: Beck depression inventory, Cr: Chromium, EDSS: Expanded disability status scale, FFS: Facit fatigue scale, FSS: Fatigue severity scale, 9HPT: Dominant hand 9-hole peg test, PASAT: Paced auditory serial addition test, T25FW: Timed 25-foot walk test , Z COG: Cognitive Z Score, MSFC: Multiple Sclerosis Functional Composite, Cr:cromium, Mn: manganese\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4.\u003c/strong\u003e Evaluation of the relationship between the trace elements\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"539\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003eCr\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003eMn\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003eCu\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003eZn\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003eSe\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003eCd\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003eMn\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0,258*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e0,021\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003eCu\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0,280*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e0,012\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003e0,034\u003c/p\u003e\n \u003cp\u003e0,768\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003eZn\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003e-0,101\u003c/p\u003e\n \u003cp\u003e0,372\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003e0,194\u003c/p\u003e\n \u003cp\u003e0,085\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003e0,168\u003c/p\u003e\n \u003cp\u003e0,137\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003eSe\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0,342*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e0,002\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003e-0,102\u003c/p\u003e\n \u003cp\u003e0,366\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003e0,213\u003c/p\u003e\n \u003cp\u003e0,058\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0,275*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e0,014\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003eCd\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003e-0,051\u003c/p\u003e\n \u003cp\u003e0,650\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0,414*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0,001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003e-0,123\u003c/p\u003e\n \u003cp\u003e0,275\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003e0,146\u003c/p\u003e\n \u003cp\u003e0,197\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e-0,222*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e0,048\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003ePb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003e-0,130\u003c/p\u003e\n \u003cp\u003e0,252\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0,503*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0,001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003e-0,210\u003c/p\u003e\n \u003cp\u003e0,061\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003e0,117\u003c/p\u003e\n \u003cp\u003e0,301\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003e-0,194\u003c/p\u003e\n \u003cp\u003e0,085\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0,580*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0,001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eMn: manganese, Cu: copper, Zn: zinc, Se: selenium, Cd: cadmium, Pb:lead, Cr:cromium\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"biological-trace-element-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bter","sideBox":"Learn more about [Biological Trace Element Research](https://www.springer.com/journal/12011)","snPcode":"12011","submissionUrl":"https://submission.nature.com/new-submission/12011/3","title":"Biological Trace Element Research","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"depression, fatigue, multiple sclerosis, trace element, chromium, manganese","lastPublishedDoi":"10.21203/rs.3.rs-6277424/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6277424/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThe effects of heavy metals have been investigated in the etiology of multiple sclerosis(MS) for years. However, common results have yet to be obtained in previous studies. So, we aimed to examine the relationship between heavy metals and MS around the province of Konya, where air pollution is intense. Study participants with MS were investigated regarding the expanded disability status (EDSS) and multiple sclerosis functional composite (MSFC) scales. All study participants were also evaluated concerning the Beck's Depression Inventory (BDI), Facit Fatigue Scale (FFS), Fatigue Severity Scale (FSS) and levels of blood chromium (Cr), manganese (Mn), copper (Cu), zinc (Zn), selenium (Se), cadmium (Cd), and lead (Pb). While were 49 people in the MS group, 51 individuals constituted the controls. Levels of Mn, Zn, Cd, and Pb were significantly higher in controls (p\u0026thinsp;\u0026lt;\u0026thinsp;.001, 0.002, \u0026lt;\u0026thinsp;.001, \u0026lt;.001, respectively). There was no significant difference between MS and control groups regarding depression and fatigue scores. MSFC parameters, depression and fatigue scale scores were statistically higher with increasing EDSS in MS patients. A significant correlation was also observed between the scores of the timed 25-foot walk (T25FW) and dominant hand 9-hole peg test (9HPT) and Cr levels (p\u0026thinsp;=\u0026thinsp;0.014, 0.004). A relationship was also observed between Mn levels and T25FW (p\u0026thinsp;=\u0026thinsp;0.047). Heavy metal and trace element levels can be seen at different levels in MS patients. While a correlation was observed between some MSFC parameters and Cr and Mn levels, no relationship was observed between heavy metal levels, depression, fatigue, and EDSS.\u003c/p\u003e","manuscriptTitle":"Investigation of the Relationship Between Serum Trace Elements and MSFC Levels in Multiple Sclerosis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-03-31 13:15:29","doi":"10.21203/rs.3.rs-6277424/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-04-07T00:23:27+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-04-02T13:55:52+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"98232325118754120709933306342472314574","date":"2025-03-24T18:57:00+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-03-23T17:13:38+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"207666650300481952546725377987075174646","date":"2025-03-23T12:24:22+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-03-22T18:11:36+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-03-21T13:21:49+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-03-21T13:16:51+00:00","index":"","fulltext":""},{"type":"submitted","content":"Biological Trace Element Research","date":"2025-03-21T11:53:35+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"biological-trace-element-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bter","sideBox":"Learn more about [Biological Trace Element Research](https://www.springer.com/journal/12011)","snPcode":"12011","submissionUrl":"https://submission.nature.com/new-submission/12011/3","title":"Biological Trace Element Research","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"c4a018a8-8fe5-4ff9-b263-f46e4b6035a3","owner":[],"postedDate":"March 31st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-05-12T16:03:38+00:00","versionOfRecord":{"articleIdentity":"rs-6277424","link":"https://doi.org/10.1007/s12011-025-04643-9","journal":{"identity":"biological-trace-element-research","isVorOnly":false,"title":"Biological Trace Element Research"},"publishedOn":"2025-05-05 15:57:45","publishedOnDateReadable":"May 5th, 2025"},"versionCreatedAt":"2025-03-31 13:15:29","video":"","vorDoi":"10.1007/s12011-025-04643-9","vorDoiUrl":"https://doi.org/10.1007/s12011-025-04643-9","workflowStages":[]},"version":"v1","identity":"rs-6277424","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6277424","identity":"rs-6277424","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}