scholarly journals Salivary citrullinated proteins in rheumatoid arthritis and associated periodontal disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ildikó Tar ◽  
Éva Csősz ◽  
Edit Végh ◽  
Karin Lundberg ◽  
Nastya Kharlamova ◽  
...  

AbstractPeriodontal disease (PD) can be an important precipitating factor in the production of citrullinated proteins. Its importance is emphasized, but it is not the only way to produce citrullinated proteins. The aim of the current study was to determine the periodontal conditions and the salivary citrullinated protein content in patients with rheumatoid arthritis (RA) compared to healthy controls. We also wished to correlate citrullinated protein levels in the saliva and serum biomarkers with the periodontal status and temporomandibular joint (TMJ) involvement of patients with RA. Twenty-three patients with RA and 17 healthy controls participated the study. Saliva samples were taken: citrulline content of saliva was measured. Blood test results for patients with RA were collected. TMJ disorders were described. Cariological and periodontal indices were registered. Periodontal conditions and periodontal staging were also registered. Comparison of measured values between groups was performed. Intragroup correlation of patients’ values was counted. The prevalence of TMJ complaints was significantly higher in the RA group (8/23) versus controls (1/17). The patients with RA had worse periodontal condition because more patients with RA had gingivitis with a significantly higher bleeding on probing (BOP) (RA: 22.4 ± 25.0%; controls: 6.36 ± 11.6%; p = 0.018). Gingival index (GI) was also significantly higher in the patients than in controls (RA: 0.68 ± 0.58; controls: 0.19 ± 0.38; p = 0.010). The citrullinated protein (relative) content of saliva did not differ significantly (p = 0.147) between patients with RA (1102.2 ± 530.8) and healthy controls (1873.1 ± 1594.9). In RA, the salivary anti-CCP levels positively correlated with PD staging (R = 0.464, p = 0.039) . Control subjects more commonly had healthy gingiva than RA patients. Moreover, in the control group more individuals had intact and reduced height periodontium than periodontitis compared to the RA group. There was no significant difference in the levels of salivary citrulline between patients with RA and controls, despite the significant differences in their periodontal status. Thus, salivary citrulline levels are not associated with RA disease severity.

Author(s):  
Reyhan Köse Çobanoglu ◽  
Taşkın Şentürk

Objectives: This study aims to compare initial albumin-to-globulin ratio (AGR) in patients with rheumatoid arthritis (RA) and primary Sjögren syndrome (pSS) presenting with undifferentiated arthritis (UA) and to investigate whether there was a difference in terms of AGR between the two patient groups and healthy controls. Patients and methods: Between January 2019 and December 2019, a total of 177 patients including 96 RA (10 males, 86 females; mean age: 53.6±10.8 years; range, 21 to 74 years) and 81 pSS (5 males, 76 females; mean age: 53.2±14.1 years; range, 23 to 79 years) and 82 healthy controls (20 males, 62 females; mean age: 50.5±13.6 years; range, 20 to 79 years) were included in this case-control study. Demographic characteristics, albumin, and globulin levels of all participants were recorded. The AGR, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), anti-nuclear antibody (ANA), and anti-citrullinated protein antibodies (ACPA) were assessed. Results: The mean AGR was 1.50±0.16 in the control group, 1.48±0.24 in the RA group, and 1.30±0.23 in the pSS group, indicating a significant difference between the pSS and the other two groups (p<0.001). The receiver operating characteristic analysis revealed that the cut-off value for AGR was 1.39 (area under the curve=0.736) with a sensitivity of 0.642 and a specificity of 0.646 (p<0.001). The ESR and CRP values were higher (p<0.001), and ANA (p<0.001) and RF (p=0.003) positivity were lower in the RA group, compared to the pSS group. Conclusion: This study findings indicate that AGR is a helpful tool in the differential diagnosis of RA and pSS presenting with UA at the time of admission, and Sjögren syndrome should be considered in case of AGR ≤1.39.


Reumatismo ◽  
2020 ◽  
Vol 72 (2) ◽  
pp. 93-102
Author(s):  
N.A.G. Gaafar ◽  
M. Aslani ◽  
Z. Aghazadeh ◽  
S.S. Mortazavi-Jahromi ◽  
A. Razavi ◽  
...  

Rheumatoid arthritis (RA), a form of inflammatory arthritis, is a chronic joint disease characterized by pain and inflammation that affects 0.5% to 1% of the population worldwide. The safety, efficacy, tolerability, and potency of β-D-mannuronic acid (M2000) as a novel NSAID with immunosuppressive property has been reported by several in vitro studies, experimental models and clinical trials phase I/II and III in ankylosing spondylitis and rheumatoid arthritis (RA) patients This research is designed to study the therapeutic efficacy of oral administration of mannuronic acid in RA patients who had inadequate response to conventional drugs and to assess the effect of this drug on gene expression of the signal transducer and activator of transcription (STATs) protein (STAT1, STAT3, STAT4, and STAT6). The study has included 15 RA patients who had an insufficient response to the conventional therapy. The oral dose of mannuronic acid was 1000mg divided into two 500 mg doses per day for 3 months as an addition to conventional therapy. There were 15 healthy volunteer in the control group. Blood samples were collected from both groups, once from healthy controls and twice from RA patients before and after treatment by M2000. The peripheral blood mononuclear cells (PBMCs) were isolated to assess the gene expression level of STAT1, STAT3, STAT4, and STAT6 using the real-time PCR method. Results obtained in this study demonstrated a significant difference in the gene expression level of STAT1 between healthy controls and patients before treatment as well as a significant reduction in RA patients after treatment compared with the level before treatment. In addition, the gene expression level of STAT3 and STAT4 showed a significant reduction in RA patients after treatment compared to patients before treatment, while there was no significant difference between RA patients before treatment and the healthy control group for both molecules. On the other hand, there was no change in the gene expression level of STAT6 among all groups. The outcomes of this study confirmed that β-D-mannuronic acid (M2000) has the ability to control the levels of STAT1, STAT3 and STAT4 in RA patients, and might be beneficial in the management and therapy of RA.


Author(s):  
Frank Faltraco ◽  
Denise Palm ◽  
Adriana Uzoni ◽  
Lena Borchert ◽  
Frederick Simon ◽  
...  

AbstractA link between dopamine levels, circadian gene expression, and attention deficit hyperactivity disorder (ADHD) has already been demonstrated. The aim of this study was to investigate the extent of these relationships by measuring circadian gene expression in primary human-derived dermal fibroblast cultures (HDF) after dopamine exposure. We analyzed circadian preference, behavioral circadian and sleep parameters as well as the circadian gene expression in a cohort of healthy controls and participants with ADHD. Circadian preference was evaluated with German Morningness-Eveningness-Questionnaire (D-MEQ) and rhythms of sleep/wake behavior were assessed via actigraphy. After ex vivo exposure to different dopamine concentrations in human dermal fibroblast (HDF) cultures, the rhythmicity of circadian gene expression (Clock, Bmal1, Per1-3, Cry1) was analyzed via qRT-PCR. We found no statistical significant effect in the actigraphy of both groups (healthy controls, ADHD group) for mid-sleep on weekend days, mid-sleep on weekdays, social jetlag, wake after sleep onset, and total number of wake bouts. D-MEQ scores indicated that healthy controls had no evening preference, whereas subjects with ADHD displayed both definitive and moderate evening preferences. Dopamine has no effect on Per3 expression in healthy controls, but produces a significant difference in the ADHD group at ZT24 and ZT28. In the ADHD group, incubation with dopamine, either 1 µM or 10 µM, resulted in an adjustment of Per3 expression to control levels. A similar effect also was found in the expression of Per2. Statistical significant differences in the expression of Per2 (ZT4) in the control group compared to the ADHD group were found, following incubation with dopamine. The present study illustrates that dopamine impacts on circadian function. The results lead to the suggestion that dopamine may improve the sleep quality as well as ADHD symptoms by adjustment of the circadian gene expression, especially for Per2 and Per3.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 240.2-241
Author(s):  
F. Zekre ◽  
R. Cimaz ◽  
M. Paul ◽  
J. L. Stephan ◽  
S. Paul ◽  
...  

Background:Idiopathic juvenile arthritis (JIA) is a heterogeneous group of pathologies whose origin remains unknown at present (1). They are characterised by a systemic inflammatory and joint disease affecting children under 16 years of age. The current classification groups the different forms of JIA into 7 distinct entities (systemic forms, polyarticular forms with or without rheumatoid factors, oligoarticular forms, inflammatory arthritis associated with enthesopathies (ERA), arthritis associated with psoriasis and unclassifiable arthritis). Exact etiology of JIA is still unknown. To date, the various hypotheses put forward on the occurrence of JIAs integrate the genetic and environmental framework.The link between periodontal disease and rheumatoid arthritis (RA) is largely reported. Recently, Porphyromonas gingivalis (P. gingivalis) infection explained the occurrence of arthritis in rodent and in RA (2). Several studies mention the beneficial effect of P. gingivalis treatment on disease activity.Currently, there are very few studies on the prevalence of P. gingivalis in patients with JIA and the possible involvement of the germ in the development of inflammatory joint diseases in the pediatric population(3)(4).Objectives:The objective of our study is to determine presence of high IgG antibodies against P. gingivalis and Prevotella Intermedia in a cohort of patients with JIA compared to a control population and to determine variation of level according to sub-classes of JIA.Methods:Sera were obtained from 101 patients satisfying the ILAR classification criteria for JIA and in 25 patients with two other dysimmune disorders (type 1 diabetes and juvenile inflammatory bowel disease). Level of IgG antibodies against P. gingivalis and Prevotella Intermedia were obtained by homemade ELISA already used previously (5).Results:In the JIA group, major children were oligarthritis (47.5%), polyarthritis represents 31.7% of JIAs, ERA and systemic forms of JIA are respectively 9 and 11%. For the control group, 10 (40%) children had diabetes and 15 (60%) had IBD.Levels of anti-P. gingivalis anti-Prevotella Intermedia antibodies were higher in AJI group compared at control groups (P<0.01, P<0.05). Theses difference are mainly related to oligoarthritis and ERA subsets for both P. gingivalis and Prevotella Intermedia.Figure 1.Relative titer of antibodies to P. gingivalis and anti Prevotella intermedia. *: P<0.05; **: P<0.01; ***: P<0.001. P. gingivalis (control vs oligoarthritis p= 0.0032. control vs ERA p= 0.0092). Prevotella intermedia (control vs oligoarthritis p= 0.0194. control vs ERA p= 0.0039).Conclusion:We confirmed high level of anti-P. gingivalis and anti-Prevotella intermedia antibodies in JIA compared to other inflammatory disorders. For the first time, we observed that this high level was mainly in oligoarthritis and ERA. Further investigations are required to investigate involvement of oral dysbiosis in AJI pathogenesis. As observed in RA, it could be a new way to integrate in JIA therapy management.References:[1]Thatayatikom A, De Leucio A. Juvenile Idiopathic Arthritis (JIA). StatPearls Publishing; 2020[2]Cheng Z, Meade J, Mankia K, Emery P, Devine DA. Periodontal disease and periodontal bacteria as triggers for rheumatoid arthritis. Best Pract Res Clin Rheumatol. 2017;31(1):19–30.[3]Romero-Sánchez C, Malagón C, Vargas C, Fernanda Torres M, Moreno LC, Rodríguez C, et al. Porphyromonas Gingivalis and IgG1 and IgG2 Subclass Antibodies in Patients with Juvenile Idiopathic Arthritis. J Dent Child Chic Ill. 2017 May 15;84(2):72–9.[4]Lange L, Thiele GM, McCracken C, Wang G, Ponder LA, Angeles-Han ST, et al. Symptoms of periodontitis and antibody responses to Porphyromonas gingivalis in juvenile idiopathic arthritis. Pediatr Rheumatol Online J. 2016 Feb 9[5]Rinaudo-Gaujous M, Blasco-Baque V, Miossec P, Gaudin P, Farge P, Roblin X, et al. Infliximab Induced a Dissociated Response of Severe Periodontal Biomarkers in Rheumatoid Arthritis Patients. J Clin Med. 2019 May 26;8(5).Disclosure of Interests:None declared.


2021 ◽  
Vol 9 ◽  
pp. 205031212110202
Author(s):  
Rgda Mohamed Osman ◽  
Mounkaila Noma ◽  
Abdallah Elssir Ahmed ◽  
Hanadi Abdelbagi ◽  
Rihab Ali Omer ◽  
...  

Objectives: Rheumatoid arthritis is a chronic inflammatory autoimmune disease. This study aimed to determine the association of interleukin-17A-197G/A polymorphism with rheumatoid arthritis in Sudanese patients. Methods: A case–control study was conducted between March and December 2018. Clinical and demographic data of the study participants were collected and analyzed. Polymerase chain reaction restriction fragment length polymorphism molecular technique was done to investigate interleukin-17A-197G/A polymorphisms. All statistical tests were considered statistically significant when p < 0.05. Results: The study population included 266 participants aged between 1 and 85 years, with an average of 40 years, classified into 85 (31.2%) cases (mean age 48.5 ± 11.3 years), and 181 (68.8%) controls (mean age 35.3 ± 15.9 years). The interleukin-17A homozygote AA genotype was more frequent among the control group compared to the case group; 95 (52.5%) and 7 (8.2%), respectively. The homozygote GG and the heterozygote AG genotypes were proportionally not different among the cases and control groups; 13 (54.2%) and 11 (45.8%), and 65 (46.4%) and 75 (53.6%), respectively. According to the distribution of interleukin-17A genotypes, a statistically significant difference was observed among cases with the interleukin-17A AA and AG genotypes, p values 0.001 and 0.004, respectively. For the association interleukin-17A genotypes and family history a negatively significant association was reported (95% confidence interval, –0.219, p value = 0.001). There was also a negatively significant association of interleukin-17A genotypes and anti-cyclic citrullinated peptide (95% confidence interval, −0.141, p value = 0.002). Conclusion: This study is the first study in Sudan established the association between interleukin-17A-197G/A (rs2275913) polymorphisms and susceptibly to rheumatoid arthritis. These findings appeal for further research in Sudan to investigate the exact role of IL-17A in immunopathology and disease severity among Sudanese rheumatoid arthritis


RMD Open ◽  
2021 ◽  
Vol 7 (1) ◽  
pp. e001485
Author(s):  
Johanna M Kroese ◽  
Catherine M C Volgenant ◽  
Wim Crielaard ◽  
Bruno Loos ◽  
Dirkjan van Schaardenburg ◽  
...  

ObjectiveTo evaluate the prevalence of temporomandibular disorders (TMD) in patients with early rheumatoid arthritis (ERA) and individuals at-risk of RA.Methods150 participants were recruited in three groups (50 per group): (1) patients with ERA (2010 EULAR criteria) (2) at-risk individuals and (3) healthy controls. All participants were tested for seropositivity of rheumatoid factor and anticitrullinated protein antibodies. A possible TMD diagnosis was determined according to the standardised and validated diagnostic criteria for TMD (DC/TMD) in five categories: myalgia, arthralgia, articular disc displacement, degenerative joint disease and headache attributed to TMD. Results were tested for the prevalence of TMD (all categories combined) and TMD pain (myalgia and/or arthralgia). To investigate a possible role for bruxism, a probable sleep and/or awake bruxism diagnosis was determined based on self-report and several clinical features.ResultsThe prevalence of any TMD diagnosis did not differ between the three groups. However, at-risk individuals more often had a TMD-pain diagnosis than healthy controls (p=0.046). No such difference was found between the ERA group and the control group. However, within the ERA group, seronegative patients had a TMD-pain diagnosis more often than seropositive patients (4/12 (33%) vs 3/38 (8%), p=0.048). Participants with a TMD-pain diagnosis were more often diagnosed with probable sleep bruxism than those without a TMD-pain diagnosis.ConclusionThe prevalence of TMD pain is increased in individuals at-risk of RA and seronegative ERA patients, and is associated with bruxism signs and symptoms. These results suggest that health professionals should be alert to TMD pain in these groups.


2015 ◽  
Vol 119 (6) ◽  
pp. 663-669 ◽  
Author(s):  
Yi-Yuan Lin ◽  
Shin-Da Lee ◽  
Chia-Ting Su ◽  
Tsung-Lin Cheng ◽  
Ai-Lun Yang

Dysfunction of insulin and insulin-like growth factor-1 (IGF-1) is associated with the pathophysiology of hypertension. The influence of long-term exercise on vascular dysfunction caused by hypertension remains unclear. We investigated whether long-term treadmill training improved insulin- and IGF-1-mediated vasorelaxation in hypertensive rats. Eight-week-old male spontaneously hypertensive rats (SHR) were randomly divided into sedentary and exercise (SHR-EX) groups. The SHR-EX group was trained on a treadmill for 60 min/day, 5 days/wk, for 8 wk. Wistar-Kyoto rats (WKY) were used as the normal control group. After training, aortic insulin- and IGF-1-mediated vasorelaxation was evaluated in organ baths. Additionally, the roles of phosphatidylinositol 3-kinase (PI3K), nitric oxide synthase (NOS), and aortic protein expression were examined in the three groups. Compared with sedentary SHR and WKY groups, insulin- and IGF-1-mediated vasorelaxation was significantly enhanced to a nearly normal level in the SHR-EX group. After endothelial denudation, blunted and comparable vasorelaxation was found among the three groups. Pretreatment with selective PI3K and NOS inhibitors attenuated insulin- and IGF-1-mediated vasorelaxation, and no significant difference was found among the three groups after the pretreatment. The aortic protein levels of the insulin receptor (IR), IGF-1 receptor (IGF-1R), insulin receptor substrate-1 (IRS-1), and endothelial NOS (eNOS) were also significantly increased in the SHR-EX group compared with the other two groups. These results suggested that treadmill training elicited the amelioration of endothelium-dependent insulin/IGF-1-mediated vasorelaxation partly via the increased activation of PI3K and NOS, as well as the enhancement of protein levels of IR, IGF-1R, IRS-1, and eNOS, in hypertension.


2021 ◽  
Vol 48 (1) ◽  
Author(s):  
Eman A. Baraka ◽  
Mona G. Balata ◽  
Shereen H. Ahmed ◽  
Afaf F. Khamis ◽  
Enas A. Elattar

Abstract Background This study aimed to measure the serum and synovial interleukin (IL)-37 levels in rheumatoid arthritis (RA) patients compared to patients with primary knee osteoarthritis (PKOA) and healthy controls and to detect its relation to RA disease activity. Results This cross-sectional study included 50 RA patients with a mean age of 40.24 ± 8.62 years, 50 patients with PKOA with a mean age of 56.69 ± 4.21, and 40 healthy controls with a mean age of 41.75 ± 7.38 years. The mean serum IL-37 level in the RA patients (382.6 ± 73.97 pg/ml) was statistically significantly (P < 0.001) the highest among the studied groups; however, it showed a non-significant difference between the PKOA patients (70.38 ± 27.49 pg/ml) and the healthy controls (69.97 ± 25.12 pg/ml) (P > 0.94). Both serum and synovial IL-37 levels were significantly positively correlated with disease activity scores (r = 0.92, P< 0.001 and r = 0.85, P < 0.001), tender joint counts (r = 0.83, P < 0.001 and r = 0.82, P < 0.001 ), swollen joint counts (r = 0.72, P < 0.001 and r = 0.60, P < 0.001), visual analog scale (r = 0.82, P < 0.001 and r = 0.82, P < 0.001), erythrocyte sedimentation rate (r = 0.75, P < 0.001 and r = 0.65, P < 0.001), and C-reactive protein (r = 0.93, P < 0.001 and r = 0.79, P < 0.001), respectively. Conclusion Serum and synovial IL-37 were significantly elevated in the RA patients, and they were closely correlated. Being less invasive, the serum IL-37 could be a marker of disease activity and could reflect the effective disease control by drugs. Having an anti-inflammatory effect could not suggest IL-37 as the key player to control inflammation alone, but its combination with other anti-proinflammatory cytokines could be investigated.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Makrouhi Sonikian ◽  
Aggeliki Barbatsi ◽  
Eugenia Karakou ◽  
Theodoros Chiras ◽  
Jacob Skarakis ◽  
...  

Abstract Introduction C-reactive protein (CRP) and procalcitonin (PCT) are widely used as markers of inflammation and infection in general population and in chronic hemodialysis (HD) as well. However, in dialysis (D) patients, serum CRP and PCT levels may be elevated even in the absence of inflammatory or infectious disease and diagnostic process is a challenge in such cases. We studied HD patients' laboratory profile concerning CRP and PCT. Subjects and Methods We studied 25 stable HD patients, M/F=22/3, aged 68(44-89) years, dialyzed thrice weekly for 55(6-274) months with a dialysate flow rate of 700 ml/min, with a residual daily diuresis less than 200 ml, Kt/V values of 1,44±0,3 and no signs of infection. Patients were classified in two groups. Group A included 10 patients on pre-dilution online hemodiafiltration (HDF). Group B consisted of 15 patients on conventional HD with low-flux polysulfone membrane. Twenty healthy subjects formed a control group C. Serum CRP and PCT levels were measured in duplicate in A and B groups before and at the end of mid-week dialysis sessions and also in C group. Results Pre-D serum CRP values in the total of patients were higher than those in healthy controls (10,89±19,29 vs 2,54±1,28 mg/L-p=0,004). Compared with group C, pre-D CRP values were higher only in B group (15,98±24,54 mg/L-p=0,001) but not in A group (4,09±3,33 mg/L-p=NS). There was a significant difference in pre-D serum CRP values between A and B groups (p=0,028). At the end of D session serum CRP values showed a tendency to increase in both groups A (5,16±4,81 mg/L) and B (17,00±27,00 mg/L) but differences were not significant. Pre-D serum PCT values in the total of patients were higher than those in healthy controls (0,82±0,9 vs 0,29±0,55 ng/ml-p&lt;0,001). Compared with group C, pre-D PCT values were higher in both A group (0,52±0,15 ng/ml-p&lt;0,001) and B group (1,01±1,13 ng/ml-p=0,006). There was no significant difference in pre-D serum PCT values between A and B groups (p=0,261). At the end of D session serum PCT values decreased in A group (0,32±0,11 ng/ml-p&lt;0,001) and increased in B group (1,12±1,21 ng/ml-p=0,014). Conclusions In patients on both conventional low-flux HD and online HDF pre-D serum CRP and PCT levels were higher than those in healthy subjects. Dialysis modality and membrane flux did not affect post-D serum CRP values, but post-PCT values decreased in online HDF. PCT usefulness might be limited in dialysis with high-flux membranes. Cut-off values have to be established for both markers to eliminate confusion in diagnosis of inflammatory and infectious diseases in hemodialyzed patients.


QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Abeer I Abd Elmagid ◽  
Hala Abdel Al ◽  
Wessam El Sayed Saad ◽  
Seham Kamal Mohamed

Abstract Background Breast cancer is the most common cancer among women and one of the most important causes of death among them.Angiogenesis is an important step for primary tumor growth, invasiveness, and metastases. Angiopoietins are well-recognized endothelial growth factors that are involved in angiogenesis associated with tumors. Aim To explore the diagnostic significance of serum angiopoietin-2 (Ang-2) in breast cancer and to evaluate its prognostic efficacy through studying the degree of its association with the TNM staging of the disease. Patients and Methods This study was conducted on (35) Egyptian female patients who were diagnosed as breast cancer according to histopathological examination of breast biopsy (Group 1, Breast Cancer Patients) and (25) female patients with benign breast diseases (Group II, Pathological Control Patients), in addition to (20) age - matched apparently healthy, free mammogram, females serving as healthy controls (Group III, Healthy Controls). For all participants, measurement of serum Ang-2 was done using enzyme linked immunosorbent assay (ELISA) technique. Results A highly significant increased levels of Ang-2 was observed in breast cancer patients when compared to healthy control group (Z = 4.95, p &lt; 0.01). However, no significant difference was observed in Ang-2 levels between breast cancer patients group and pathological control group (Z = 3.37, p &gt; 0.05). No significant difference was detected in Ang-2 levels in relation to TNM stage and histological grade. No significant correlation was found between Ang-2 levels and serum levels of CA15-3, hormone receptors, HER2/new receptor status (p &gt; 0.05, respectively). Conclusion This study revealed that Ang-2 serum levels were significantly increased in patient with breast cancer compared with healthy controls, indicating that high Ang-2 level is a promising non invasive biomarker for breast cancer diagnosis. However, no significant difference of Ang-2 levels was detected in relation of breast TNM staging in the population studied.


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