Varying Patterns of Biomarkers of Mineral and Bone Metabolism After Kidney Transplantation

2017 ◽  
Vol 49 (08) ◽  
pp. 618-624
Author(s):  
Agnieszka Makówka ◽  
Maciej Głyda ◽  
Ewa-Rutkowska Majewska ◽  
Michał Nowicki
Keyword(s):  
Kidney Transplantation ◽  
Bone Metabolism ◽  
Mineral Metabolism ◽  
Fibroblast Growth Factor 23 ◽  
Serum Markers ◽  
Creatinine Ratio ◽  
Bone Specific Alkaline Phosphatase ◽  
Calcium Phosphorus ◽  
25 Oh Vitamin D ◽  
Fgf 23

AbstractSclerostin inhibits Wnt/β-catenin signaling pathway, thereby decreasing bone formation. Osteoblast stimulating actions of parathyroid hormone (PTH) are mediated by suppression of sclerostin. Thus, sclerostin may reflect both bone metabolism and parathyroid function. The study was aimed to analyze the patterns of the changes of mineral and bone biomarkers for 9 months following kidney transplantation (KTx). Thirty-five patients after KTx were included into a 9-month observational study. Serum creatinine, calcium, phosphorus, 25-OH vitamin D, PTH, fibroblast growth factor 23 (FGF-23), sclerostin, and bone-specific alkaline phosphatase (BAP) were measured before KTx, and 1, 2 weeks, and 1, 2, 3, 4, 5, 6, and 9 months thereafter. Urine sclerostin/creatinine ratio was assessed in parallel from month 1 after KTx. Following KTx most serum markers significantly decreased till the end of observation including PTH (by 58%), phosphorus (37%), sclerostin (31%), BAP (28%), and FGF-23 (82%). Most of the decrease was observed during first 2 months after KTx. Serum calcium was increased by 17%. Urine sclerostin/creatinine ratio increased from month 1 till month 6. At KTx serum FGF-23 correlated only with phosphate (r=0.62, p=0.01) and PTH with BAP (r=0.49, p=0.04) but not with sclerostin. At the end of the study neither serum sclerostin nor FGF-23 correlated with other parameters of mineral and bone metabolism. Sclerostin shows the limited utility as the marker of the resolution of bone and mineral metabolism after KTx.

MO476EFFECT OF ESTROGEN DEFICIENCY ON THE STATE OF BONE AND MINERAL METABOLISM IN WOMEN WITH STAGE III-V CHRONIC KIDNEY DISEASE

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
НИНА МАЛАХОВА ◽  
Fatima Dzgoeva
Keyword(s):  
Cardiovascular System ◽  
Bone Metabolism ◽  
Sex Hormones ◽  
Bone Mineral ◽  
Solid Phase ◽  
Mineral Metabolism ◽  
Fibroblast Growth Factor 23 ◽  
Estrogen Deficiency ◽  
The State ◽  
Drug Induced

Abstract Background and Aims Clinical studies in recent years have revealed a close relationship between hormonal disorders in women with CKD and the duration and quality of life, bone mineral and related disorders of the cardiovascular system. In individual studies, there is a tendency to improve the indicators of mineral and bone metabolism and the state of the cardiovascular system in hormonal or other drug-induced correction of hormonal dysfunctions in women. - Aims to study the effect of estrogen deficiency on bone and mineral metabolism in a population of women suffering from CKD stages III-V Method The study included 52 women who met the clinical criteria for the possible appointment of hormone therapy (both replacement and combined oral contraceptives) for the purpose of a detailed examination of the state of their cardiovascular system and bone-mineral metabolism in dynamics (with an interval of 10-12 months) in order to assess the degree of influence of estrogen-deficient conditions on the course of such common complications of CKD as cardiovascular diseases and pathology of the bone system. The age of the patients ranged from 26 to 61 years (mean age-50.65±9.17 years). The duration of CPN averaged 77.02 months.. The stages of CKD were determined according to the K/DOQI (2012) criteria, and the glomerular filtration rate was calculated using the CKD-EPI formula. The following parameters were evaluated: the concentration of sclerostin, osteoprotegerin, fibroblast growth factor 23 (FGF-23), parathyroid hormone, total calcium, phosphorus, alkaline phosphatase, creatinine, and urea. Follicle-stimulating hormone( FSH), luteinizing hormone(LH) and estradiol were determined by solid-phase chemiluminescent enzyme immunoassay (commercial sets of Alkor-Bio, St. Petersburg). Serum concentrations of sclerostin, sRANKL (soluble RANKL), and osteoprotegerin were determined by the enzyme-linked immunoassay using Biomedica gruppe test systems. Results The examined patients showed hormonal dysfunctions (82%), accompanied by changes in the content of sex hormones: the concentration of estradiol was below normal: 123.4±72.5 pmol/l and 150.0-450.0 pmol/l, respectively, in patients and in normal (p<0.01), which confirms the presence of estrogen deficiency in the examined patients . Concentrations of FSH and LH exceeded the norm in the group of patients as a whole: 91.6±46.1 IU/l and 3.0-8.0 IU/l FSH content in patients and normal; 51.8±32.1 IU/l and 3.0-10.0 IU/l LH in patients and normal. In the group of patients as a whole, an increase in the level of sclerostin to 28.5 ± 9.2 pmol/l was detected ( norm 12±33.45 pmol/l), an increase in the level of osteoprotegerin to 6.9±0.4 pmol/l (norm 2.7 pmol/l). Positive and negative correlations were found between the levels of morphogenetic proteins, sex hormones, and characteristic parameters of hormonal dysfunctions Conclusion Pre-and postmenopausal women with CKD have hormonal dysfunctions, including disorders of sexual and reproductive function, menstrual cycle, decreased fertility, increased risks of miscarriage at its onset, the basis of hormonal dysfunctions is the absence of LH peaks and changes in the concentration of estradiol depending on the phase of the cycle, hypoestrogenemia. It is assumed that there is a pathogenetic link between hormonal dysfunctions and disorders in the system of bone metabolism regulatory proteins in patients with CKD.

scholarly journals Impact of Race on the Association of Mineral Metabolism With Heart Failure: the Multi-Ethnic Study of Atherosclerosis

2019 ◽  
Vol 105 (4) ◽  
pp. e1144-e1151
Author(s):  
Cassianne Robinson-Cohen ◽  
Michael Shlipak ◽  
Mark Sarnak ◽  
Ronit Katz ◽  
Carmen Peralta ◽  
...  
Keyword(s):  
Risk Factors ◽  
Heart Failure ◽  
African Americans ◽  
Ethnic Groups ◽  
Mineral Metabolism ◽  
Fibroblast Growth Factor 23 ◽  
Cox Models ◽  
Ethnic Study ◽  
Potential Risk Factors ◽  
Fgf 23

Abstract Background Alterations in mineral metabolism, such as high phosphorus, high parathyroid hormone (PTH), and high fibroblast growth factor-23 (FGF-23) have been identified as potential risk factors for heart failure (HF). Important differences in the prevalence of mineral metabolism abnormalities and in the risk of HF have been reported across race and/or ethnic groups. In this study, we evaluated whether the associations of mineral metabolism markers with HF differed by race and/or ethnicity. Methods We included participants free of cardiovascular disease from the Multi-Ethnic Study of Atherosclerosis to quantify rates of HF overall and across race and/or ethnic groups. Using Cox models, we tested associations of baseline higher phosphorus (>4 mg/dL), PTH greater than 65 pg/mL, and FGF-23 greater than 46.5 pg/mL with incident HF, and for interactions by race and/or ethnicity, adjusting for sociodemographic and cardiovascular risk factors. Results Among the 6413 participants, median follow-up time was 14.9 years. The incidence rate for HF was highest for African Americans and lowest for Chinese (4.71 and 2.42 per 1000 person-years, respectively). The prevalence of elevated PTH (18.8% vs 7.4%) but not FGF-23 (23.1% vs 28.8%) was higher in African Americans vs Whites. In multivariable models, the associations of elevated PTH (hazard ratio [HR] 1.50, 95% CI: 1.13-1.99) and FGF-23 (HR 1.37, 95% CI: 1.07-1.75) with incident HF were statistically significant. However, the interactions by race and/or ethnicity were not statistically significant. Conclusions In a multiethnic population, higher PTH and FGF-23 were associated with risk of HF in African American and Hispanic individuals. There is no evidence that race and/or ethnicity modifies the association of altered mineral metabolism with risk of HF.

scholarly journals Calcium Regulates FGF-23 Expression in Bone

Endocrinology ◽  
2013 ◽  
Vol 154 (12) ◽  
pp. 4469-4482 ◽  
Author(s):  
Valentin David ◽  
Bing Dai ◽  
Aline Martin ◽  
Jinsong Huang ◽  
Xiaobin Han ◽  
...  
Keyword(s):  
Culture Media ◽  
Fibroblast Growth Factor 23 ◽  
Dihydroxyvitamin D3 ◽  
Pooled Data ◽  
Calcium Diet ◽  
High Calcium ◽  
High Calcium Diet ◽  
Calcium Phosphorus ◽  
Serum Pth ◽  
Fgf 23

Calcium has recently been shown to regulate fibroblast growth factor 23 (FGF-23), a bone-derived phosphate and vitamin D-regulating hormone. To better understand the regulation of FGF-23 by calcium, phosphorus, 1,25 dihydroxyvitamin D3 [1,25(OH)2D], and PTH, we examined FGF-23 expression under basal conditions and in response to PTH, doxercalciferol, or high-calcium diet treatment in Gcm2−/− and Cyp27b1−/− mutant mice. Gcm2−/− mice exhibited low serum PTH and 1,25(OH)2D concentrations, hypocalcemia, and hyperphosphatemia, whereas Cyp27b1−/− mice had high PTH, undetectable 1,25(OH)2D, hypocalcemia, and hypophosphatemia. Serum FGF-23 levels were decreased in both mutant models. Doxercalciferol administration increased serum FGF-23 levels in both mutant models. PTH administration to Gcm2−/− mice also increased serum FGF-23 levels, in association with an increase in both 1,25(OH)2D and calcium concentrations. Multiple regression analysis of pooled data indicated that changes in FGF-23 were positively correlated with serum calcium and 1,25(OH)2D but not related to changes in serum phosphate concentrations. A high-calcium diet also increased serum FGF-23 concentrations in Cyp27b1−/− mice in the absence of 1,25(OH)2D and in Gcm2−/− mice with low PTH. The addition of calcium to the culture media also stimulated FGF-23 message expression in MC3T3-E1 osteoblasts. In addition, FGF-23 promoter activity in cultured osteoblasts was inhibited by the L-calcium-channel inhibitor nifedipine and stimulated by calcium ionophores. The effects of chronic low calcium to prevent 1,25(OH)2D and PTH stimulation of FGF-23 in these mutant mouse models suggest that suppression of FGF-23 plays an important physiological adaptive response to hypocalcemia.

THE ROLE OF FBROBLAST GROWTH FACTOR 23 (FGF 23) IN THE MINERAL AND BONE DISORDER (MBD) OF THE PATENTS WITH CHRONIC KIDNEY DISEASE

2016 ◽  
pp. 9-14
Author(s):  
Huu Vu Quang Nguyen ◽  
Tam Vo
Keyword(s):  
Chronic Kidney Disease ◽  
Growth Factor ◽  
Kidney Disease ◽  
Kidney Function ◽  
Mineral Metabolism ◽  
Fibroblast Growth Factor 23 ◽  
Normal Kidney ◽  
Mineral And Bone Disorder ◽  
Normal Kidney Function ◽  
Fgf 23

Fibroblast growth factor 23 (FGF23) is a key regulator of phosphorus metabolism whose effects in patients with chronic kidney disease (CKD) have only recently begun to be appreciated. Recent study of this phosphaturic hormone has revealed new path-ways of mineral regulation in both individuals with normal kidney function and in patients with CKD. While the effects of FGF23 on mineral metabolism in CKD appears to be similar to its effects in individuals with normal kidney function, elevated levels of the protein in the CKD population have also been linked to kidney disease progression, altered skeletal histology, and increased mortality rates, relationships that have not been examined in the general population.Thus, potential differences in FGF23 metabolism accompany the elevated levels found in CKD patients and, although the exact pathophysiological consequences remain mostly unknown, elevated FGF23 levels appear to contribute to major complications of CKD that plague both adults and children. Key words: FGF23, chronic kidney

scholarly journals FGF-23 Levels before and after Renal Transplantation

2009 ◽  
Vol 2009 ◽  
pp. 1-5 ◽  
Author(s):  
Domniki Economidou ◽  
Spyros Dovas ◽  
Aikaterini Papagianni ◽  
Panagiotis Pateinakis ◽  
Dimitrios Memmos
Keyword(s):  
Renal Transplantation ◽  
Mineral Metabolism ◽  
Fibroblast Growth Factor 23 ◽  
Renal Transplant Recipients ◽  
Vitamin D Metabolism ◽  
Before And After ◽  
Stage Renal Disease ◽  
End Stage ◽  
A Prospective Study ◽  
Fgf 23

Phosphatonin fibroblast growth factor-23 (FGF-23) is involved in phosphate (P) excretion and vitamin D metabolism. Recently, FGF-23 has been suggested to be responsible for the hypophosphatemia and inappropriately low calcitriol levels observed after renal transplantation. We performed a prospective study to investigate FGF-23 levels in patients with end-stage renal disease before and after renal transplantation and their probable association with markers of bone and mineral metabolism. Intact FGF-23 levels were determined before and at 3, 6, and 12 months posttransplantation in 18 renal transplant recipients. Intact parathyroid hormone (iPTH), calcium (Ca), P, 25(OH)VitD, and 1,25VitD levels were measured at the same time periods. Renal threshold phosphate concentration (/GFR) was also calculated at 3, 6, and 12 months posttransplantation. The results showed that FGF-23 levels decreased by 89% 3 months posttransplantation (346 146 versus 37 9 pg/mL, ) and remained stable throughout the study period. iPTH and P levels also decreased significantly after renal transplantation, while Ca and 1,25VitD increased. Pretransplantation FGF-23 was significantly correlated with P levels at 3 months posttransplantation (). In conclusion, FGF-23 levels decrease dramatically after successful renal transplantation. Pre-transplantation FGF-23 correlate with P levels 3 months posttransplantation.

scholarly journals Early and Sustained Changes in Bone Metabolism After Severe Burn Injury

2016 ◽  
Vol 101 (4) ◽  
pp. 1506-1515 ◽  
Author(s):  
Gabriela Katharina Muschitz ◽  
Elisabeth Schwabegger ◽  
Roland Kocijan ◽  
Andreas Baierl ◽  
Hervé Moussalli ◽  
...  
Keyword(s):  
Bone Metabolism ◽  
Burn Injury ◽  
Fibroblast Growth Factor 23 ◽  
Type I ◽  
Severe Burn ◽  
Bone Specific Alkaline Phosphatase ◽  
Type I Procollagen ◽  
Male Patients ◽  
Severe Burn Injury

Abstract Context: Severe burn injury causes a massive stress response, consecutively heightened serum levels of acute phase proteins, cortisol, and catecholamines with accompanying disturbance in calcium metabolism. Objective: Evaluation of early and prolonged changes of serum bone turnover markers (BTMs) and regulators of bone metabolism. Design: Longitudinal observational design. Setting: University clinic. Patients: A total of 32 male patients with a median age of 40.5 years and a median burned total body surface area of 40% (83% patients with full thickness burn injury). Interventions: None. Main Outcome Measures: Comparison of changes of BTM/regulators of bone metabolism in the early (d 2–7) and prolonged (d 7–56) phases after trauma. Results: All investigated BTM/regulators significantly changed. During the early phase, pronounced increases were observed for serum type 1 collagen cross-linked C-telopeptide, intact N-terminal propeptide of type I procollagen, sclerostin, Dickkopf-1, bone-specific alkaline phosphatase, fibroblast growth factor 23, and intact parathyroid hormone levels, whereas 25-hydroxyvitamin D, albumin, serum, and ionized calcium levels decreased. Changes of osteoprotegerin, osteocalcin, and phosphate were less pronounced but remained significant. In the prolonged phase, changes of intact N-terminal propeptide of type I procollagen were most pronounced, followed by elevated sclerostin, osteocalcin, bone-specific alkaline phosphatase, and lesser changes for albumin levels. Calcium and ionized calcium levels tardily increased and remained within the limit of normal. In contrast, levels of intact parathyroid hormone, fibroblast growth factor 23, C-reactive protein, and to a lesser extent serum type 1 collagen cross-linked C-telopeptide and phosphate levels declined significantly during this phase of investigation. Conclusions: Ongoing changes of BTM and regulators of bone metabolism suggest alterations in bone metabolism with a likely adverse influence on bone quality and structure in male patients with severe burn injuries.

scholarly journals Kidney transplantation and bone disease: risk factors of development and diagnostics

2017 ◽  
Vol 19 (1) ◽  
pp. 111-121
Author(s):  
O. N. Vetchinnikova
Keyword(s):  
Risk Factors ◽  
Kidney Transplantation ◽  
Bone Disease ◽  
Disease Risk ◽  
Mineral Metabolism ◽  
Fibroblast Growth Factor 23 ◽  
Diagnostic Algorithm ◽  
Dynamic Monitoring ◽  
Bone Disorders ◽  
Osteoporosis Risk Factors

Bone disease is a serious and common condition in patients after kidney transplantation. The review analyzed the causes of bone disorders in the early and late postoperative period that are associated with renal transplantation: fibroblast growth factor 23, parathyroid hormone, vitamin D, immunosuppressive therapy and imbalance of mineral metabolism. It shows the most common clinical variant of the post-transplant bone disease – secondary osteoporosis, risk factors of its development and complications. It presents the diagnostic algorithm for dynamic monitoring and evaluating the effectiveness of the treatment of bone disorders

scholarly journals Prognostic Importance of Fibroblast Growth Factor-23 in Dialysis Patients

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Nilgül Akalin ◽  
Yıldız Okuturlar ◽  
Özlem Harmankaya ◽  
Asuman Gedıkbaşi ◽  
Selçuk Sezıklı ◽  
...  
Keyword(s):  
Mineral Metabolism ◽  
Binding Capacity ◽  
Fibroblast Growth Factor 23 ◽  
High Serum ◽  
Phosphate Binders ◽  
Dialysis Patients ◽  
Dialysis Adequacy ◽  
Positive Correlation ◽  
Fgf 23 ◽  
Iron Binding Capacity

Introduction. In this study, we aimed to demonstrate the correlation of FGF-23 levels with bone-mineral metabolism, anemia, and the treatment in dialysis patients.Methods. Eighty-nine patients with similar age, gender, dialysis duration, and dialysis adequacy who were receiving hemodialysis replacement therapy for at least 6 months were included in the study. Serum iron, iron binding capacity, ferritin, hemoglobin (Hb), hematocrit (Htc), calcium (Ca), phosphorus (P), intact parathormone (iPTH), and FGF-23 levels were studied. In addition, active vitamin D and phosphate binders calcimimetic therapies that patients have received in the last 6 months were recorded.Results. It was determined that there was a positive correlation between serum FGF-23 values and PTH values (P<0,01) and Ca*P values (P<0,01). A positive correlation was found between serum FGF-23 values and Ca values at a rate of 24,6% (P<0,05) and betweenPvalues at a rate of 59,1% (P<0,01). A positive correlation was determined between serum FGF-23 values and hemoglobin (Hb) values (P<0,05) and hematocrit (Htc) values (P<0,05). In multivariate analysis, no significant correlation was found between serum FGF-23 levels and Hb and Htc.Conclusion. The effects of high serum FGF-23 levels on different parameters may be correlated with the development of refractory secondary hyperparathyroidism.

scholarly journals 0002 Decreased Concentration of Klotho and Increased Concentration of FGF-23 in the Cerebrospinal Fluid of Patients with Narcolepsy

SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A1-A1
Author(s):  
G P Oliveira ◽  
R M Elias ◽  
G B Fernandes ◽  
R Moyses ◽  
S Tufik ◽  
...  
Keyword(s):  
Mineral Metabolism ◽  
Fibroblast Growth Factor 23 ◽  
Enzyme Linked Immunosorbent Assay ◽  
Aging Properties ◽  
The Status ◽  
Csf Levels ◽  
Fgf 23 ◽  
Csf Concentration ◽  
Hypocretin 1

Abstract Introduction Narcolepsy is a disorder characterized by hypersomnolence, cataplexy, sleep paralysis, hallucinations and sleep fragmentation. Patients with type 1 narcolepsy have cataplexy and/or hypocretin-1 deficiency. Klotho is a protein expressed by kidneys and choroid plexus, with anti-aging properties. Fibroblast growth factor 23 (FGF-23) is a hormone secreted by osteocytes with actions on mineral metabolism. The purpose of study was to explore the status of concentration of klotho and FGF23 in the cerebrospinal fluids (CSF) of patients with narcolepsy. Methods 59 patients with narcolepsy and 17 individuals were enrolled. We used a radioimmunoassay technique, human klotho enzyme-linked immunosorbent assay (ELISA), human intact FGF23 ELISA and spectrophotometry to measure hypocretin-1, klotho, FGF-23 and phosphorus, respectively. T-Student Test was used to compare klotho and phosphate concentrations and Mann-Whitney U Test was used to compare FGF-23 levels between groups. ANOVA Test was used to compare klotho and phosphate CSF concentrations among narcolepsy patients with CSF hypocretin-1 &lt;110pg/ml (HCRT-) and narcolepsy patients with CSF hypocretin-1 &gt;110pg/ml (HCRT+) versus control subjects. Results Klotho and phosphorus CSF levels were lower in narcoleptic patients than in control (908.18 ± 405.51 versus 1265.78 ± 523.26 pg/ml; p=0.004 and 1.34 ± 0.25 versus 1.58 ± 0.23 mg/dl; p= 0.001, respectively). We found higher median FGF-23 levels in narcoleptic patients (5.51 versus 4.00 RU/ml; p= 0.001). Klotho and phosphorus CSF levels were lower in both HCRT-/HCRT+ than controls (892.63 ± 388.34/ 925.95 ± 430.76 versus 1265.78 ± 523.26 pg/ml; p=0.014 and 1.35 ± 0.28/ 1.33 ± 0.22 versus 1.58 ± 0.23 mg/dl; p= 0.004). Moreover, we found higher median FGF-23 levels in both HCRT-/HCRT+ groups versus controls (5.51/ 6.02 versus 4.00 RU/ml in controls), p= 0.009. Conclusion Patients with narcolepsy have decreased CSF concentration of klotho and increased CSF levels of FGF-23. These findings may play a role in understanding the pathogenesis of narcolepsy. Support  

scholarly journals Gla-Rich Protein (GRP) as an Early and Novel Marker of Vascular Calcification and Kidney Dysfunction in Diabetic Patients with CKD: A Pilot Cross-Sectional Study

2020 ◽  
Vol 9 (3) ◽  
pp. 635 ◽  
Author(s):  
Ana P. Silva ◽  
Carla S.B. Viegas ◽  
Filipa Mendes ◽  
Ana Macedo ◽  
Patrícia Guilherme ◽  
...  
Keyword(s):  
Vascular Calcification ◽  
Mineral Metabolism ◽  
Fibroblast Growth Factor 23 ◽  
Positive Association ◽  
Serum Levels ◽  
Diabetic Patients ◽  
Mineral And Bone Disorder ◽  
Cross Sectional ◽  
Low Levels ◽  
Fgf 23

Vascular calcification (VC) is one of the strongest predictors of cardiovascular risk in chronic kidney disease (CKD) patients. New diagnostic/prognostic tools are required for early detection of VC allowing interventional strategies. Gla-rich protein (GRP) is a cardiovascular calcification inhibitor, whose clinical utility is here highlighted. The present study explores, for the first time, correlations between levels of GRP in serum with CKD developmental stage, mineral metabolism markers, VC and pulse pressure (PP), in a cohort of 80 diabetic patients with mild to moderate CKD (stages 2–4). Spearman’s correlation analysis revealed a positive association of GRP serum levels with estimated glomerular filtration rate (eGFR) and α-Klotho, while a negative correlation with phosphate (P), fibroblast growth factor 23 (FGF-23), vascular calcification score (VCS), PP, calcium (x) phosphate (CaxP) and interleukin 6 (IL-6). Serum GRP levels were found to progressively decrease from stage 2 to stage 4 CKD. Multivariate analysis identified low levels of eGFR and GRP, and high levels of FGF-23 associated with both the VCS and PP. These results indicate an association between GRP, renal dysfunction and CKD-mineral and bone disorder. The relationship between low levels of GRP and vascular calcifications suggests a future, potential utility for GRP as an early marker of vascular damage in CKD.

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