scholarly journals Correlation Between Quantitative MRI and Muscle Histopathology in Muscle Biopsies from Healthy Controls and Patients with IBM, FSHD and OPMD

2020 ◽  
Vol 7 (4) ◽  
pp. 495-504
Author(s):  
Saskia Lassche ◽  
Benno Küsters ◽  
Arend Heerschap ◽  
Maxime V.P. Schyns ◽  
Coen A.C. Ottenheijm ◽  
...  
Keyword(s):  
Tibialis Anterior ◽  
Vastus Lateralis ◽  
Fatty Infiltration ◽  
Quantitative Mri ◽  
Muscle Disease ◽  
Healthy Controls ◽  
Muscle Mri ◽  
Severity Grading ◽  
Scale Range ◽  
Muscle Biopsies

Background: Muscle MRI is increasingly used as a diagnostic and research tool in muscle disorders. However, the correlation between MRI abnormalities and histopathological severity is largely unknown. Objective: To investigate correlations between muscle MRI abnormalities and histopathological severity in healthy controls and patients with muscle disease. Methods: We performed quantitative MRI and histopathological analysis in 35 patients with inclusion body myositis, facioscapulohumeral muscular dystrophy or oculopharyngeal muscular dystrophy and 12 healthy controls. Participants contributed needle biopsies of the vastus lateralis and/or tibialis anterior, yielding 77 muscle biopsies with matched T1, T2 and TIRM MRI imaging. Muscle biopsies were evaluated with a semi-quantitative histopathology severity grading scale (range 0–12) and an inflammation severity grading scale (range 0–3). Results: In muscle disease, histopathology sum scores ranged from 0 to 11 and correlated significantly with fat percentage as measured on MRI (Spearman’s rho = 0.594, p < 0.001). Muscle edema on muscle MRI was associated with increased amounts of inflammation (p < 0.001). Mild abnormalities occured in 95% of control biopsies and were more pronounced in tibialis anterior (median sum score of 1±1 in vastus lateralis and 2±1 in tibialis anterior (p = 0.048)). Conclusion: In muscle disease, fatty infiltration on MRI correlates moderately with muscle histopathology. Histopathological abnormalities can occur prior to the onset of fatty infiltration. In middle-aged controls, almost all biopsies showed some histopathological abnormalities. The findings from this study may facilitate the choice for appropriate imaging sequences as outcome measures in therapeutic trials.

Thigh and Leg Muscle MRI Findings in GNE Myopathy

2021 ◽  
pp. 1-8
Author(s):  
Farzad Fatehi ◽  
Soroor Advani ◽  
Ali Asghar Okhovat ◽  
Bentolhoda Ziaadini ◽  
Hosein Shamshiri ◽  
...  
Keyword(s):  
Tibialis Anterior ◽  
Vastus Lateralis ◽  
Fatty Infiltration ◽  
Muscular Dystrophies ◽  
Tibialis Posterior ◽  
Muscle Mri ◽  
Muscle Involvement ◽  
Fat Infiltration ◽  
Gne Myopathy ◽  
Adductor Magnus

Background: Muscle MRI protocols have been developed to assess muscle involvement in a wide variety of muscular dystrophies. Different muscular dystrophies can involve muscle groups in characteristic patterns. These patterns can be identified in muscle MRI in the form of fatty infiltration. Objective: This study was conducted to add the existing knowledge of muscle MRI in GNE myopathy and evaluate the correlation of muscular involvement with different gene mutations. Methods: The MRI scans of the 18 GNE patients were analyzed retrospectively. Cluster analysis was done for grouping the muscles and patients. Results: The four muscles with the highest fat infiltration were adductor magnus, tibialis anterior, semitendinosus, and semimembranosus. Furthermore, three clusters of muscle involvement were found, including cluster 1, typical muscle involvement indicating muscles with the highest infiltration: extensor digitorum longus, gracilis, biceps femoris, soleus, gastrocnemius medial, adductor longus, tibialis anterior, adductor magnus, semimembranosus, semitendinosus; cluster 2, less typical muscle involvement indicating muscles with intermediate fat infiltration, peroneus longus, gastrocnemius lateral, and minimal fat infiltration in most of the patients, i.e., tibialis posterior; and cluster 3, atypical muscle involvement with low-fat infiltration: rectus femoris, sartorius, vastus intermedius, vastus medialis, and vastus lateralis. Conclusions: This study found three clusters of muscle involvement and three groups of patients among GNE patients. Hamstring muscles and the anterior compartment of the lower leg were the muscles with the highest fat infiltration. Moreover, a weak genotype-muscle MRI association was found in which tibialis posterior was more involved in patients with the most frequent mutation, i.e., C.2228T >  C (p.M743T) mutation; however, this finding may be related to longer disease duration.

scholarly journals Preserved single muscle fiber specific force in facioscapulohumeral muscular dystrophy

Neurology ◽  
2020 ◽  
Vol 94 (11) ◽  
pp. e1157-e1170 ◽  
Author(s):  
Saskia Lassche ◽  
Nicol C. Voermans ◽  
Robbert van der Pijl ◽  
Marloes van den Berg ◽  
Arend Heerschap ◽  
...  
Keyword(s):  
Muscle Fiber ◽  
Vastus Lateralis ◽  
Muscle Fibers ◽  
Fatty Infiltration ◽  
Facioscapulohumeral Muscular Dystrophy ◽  
Single Muscle ◽  
Healthy Controls ◽  
Specific Force ◽  
Single Muscle Fiber ◽  
Muscle Biopsies

ObjectiveTo investigate single muscle fiber contractile performance in muscle biopsies from patients with facioscapulohumeral muscular dystrophy (FSHD), one of the most common hereditary muscle disorders.MethodsWe collected 50 muscle biopsies (26 vastus lateralis, 24 tibialis anterior) from 14 patients with genetically confirmed FSHD and 12 healthy controls. Single muscle fibers (n = 547) were isolated for contractile measurements. Titin content and titin phosphorylation were examined in vastus lateralis muscle biopsies.ResultsSingle muscle fiber specific force was intact at saturating and physiologic calcium concentrations in all FSHD biopsies, with (FSHDFAT) and without (FSHDNORMAL) fatty infiltration, compared to healthy controls. Myofilament calcium sensitivity of force is increased in single muscle fibers obtained from FSHD muscle biopsies with increased fatty infiltration, but not in FSHD muscle biopsies without fatty infiltration (pCa50: 5.77–5.80 in healthy controls, 5.74–5.83 in FSHDNORMAL, and 5.86–5.90 in FSHDFAT single muscle fibers). Cross-bridge cycling kinetics at saturating calcium concentrations and myofilament cooperativity did not differ from healthy controls. Development of single muscle fiber passive tension was changed in all FSHD vastus lateralis and in FSHDFAT tibialis anterior, resulting in increased fiber stiffness. Titin content was increased in FSHD vastus lateralis biopsies; however, titin phosphorylation did not differ from healthy controls.ConclusionMuscle weakness in patients with FSHD is not caused by reduced specific force of individual muscle fibers, even in severely affected tissue with marked fatty infiltration of muscle tissue.

scholarly journals Advanced MRI Techniques for Muscle Imaging

2017 ◽  
Vol 21 (04) ◽  
pp. 459-469 ◽  
Author(s):  
Doris Leung ◽  
Darryl Sneag ◽  
Filippo Grande ◽  
John Carrino ◽  
Vivek Kalia
Keyword(s):  
Magnetic Resonance ◽  
Fatty Infiltration ◽  
Sampling Bias ◽  
Disease Diagnosis ◽  
Quantitative Mri ◽  
Muscle Disease ◽  
Whole Body ◽  
Resonance Spectroscopy ◽  
Capillary Perfusion ◽  
Complete Evaluation

AbstractAdvanced magnetic resonance imaging (MRI) techniques can evaluate a wide array of muscle pathologies including acute or chronic muscle injury, musculotendinous response to injury, intramuscular collections and soft tissue masses, and others. In recent years, MRI has played a more important role in muscle disease diagnosis and monitoring. MRI provides excellent spatial and contrast resolution and helps direct optimal sites for muscle biopsy. Whole-body MRI now helps identify signature patterns of muscular involvement in large anatomical regions with relative ease. Quantitative MRI has advanced the evaluation and disease tracking of muscle atrophy and fatty infiltration in entities such as muscular dystrophies. Multivoxel magnetic resonance spectroscopy (MRS) now allows a more thorough, complete evaluation of a muscle of interest without the inherent sampling bias of single-voxel MRS or biopsy. Diffusion MRI allows quantification of muscle inflammation and capillary perfusion as well as muscle fiber tracking.

Hyperthyroidism and cation pumps in human skeletal muscle

2005 ◽  
Vol 288 (6) ◽  
pp. E1265-E1269 ◽  
Author(s):  
Anne Lene Dalkjær Riis ◽  
Jens Otto Lunde Jørgensen ◽  
Niels Møller ◽  
Jørgen Weeke ◽  
Torben Clausen
Keyword(s):  
Skeletal Muscle ◽  
Human Skeletal Muscle ◽  
Vastus Lateralis ◽  
Vastus Lateralis Muscle ◽  
Healthy Controls ◽  
Thyroid Status ◽  
Before And After ◽  
Muscle Biopsies ◽  
Hyperthyroid Patients ◽  
Major Target

Skeletal muscle constitutes the major target organ for the thermogenic action of thyroid hormone. We examined the possible relation between energy expenditure (EE), thyroid status, and the contents of Ca2+-ATPase and Na+-K+-ATPasein human skeletal muscle. Eleven hyperthyroid patients with Graves' disease were studied before and after medical treatment with methimazole and compared with eight healthy subjects. Muscle biopsies were taken from the vastus lateralis muscle, and EE was determined by indirect calorimetry. Before treatment, the patients had two- to fivefold elevated total plasma T3 and 41% elevated EE compared with when euthyroidism had been achieved. In hyperthyroidism, the content of Ca2+-ATPase was increased: (mean ± SD) 6,555 ± 604 vs. 5,212 ± 1,580 pmol/g in euthyroidism ( P = 0.04) and 4,523 ± 1,311 pmol/g in healthy controls ( P = 0.0005). The content of Na+-K+-ATPase showed 89% increase in hyperthyroidism: 558 ± 101 vs. 296 ± 34 pmol/g ( P = 0.0001) in euthyroidism and 278 ± 52 pmol/g in healthy controls ( P < 0.0001). In euthyroidism, the contents of both cation pumps did not differ from those of healthy controls. The Ca2+-ATPase content was significantly correlated to plasma T3 and resting EE. This provides the first evidence that, in human skeletal muscle, the capacity for Ca2+ recycling and active Na+-K+ transport are correlated to EE and thyroid status.

Z-line degradation and phagocytosis of sarcomeric fragments in myonecrosis

1983 ◽  
Vol 41 ◽  
pp. 790-791
Author(s):  
Melinda L. Estes ◽  
Samuel M. Chou
Keyword(s):  
Vastus Lateralis ◽  
Inflammatory Myopathy ◽  
Muscle Disease ◽  
White Female ◽  
Inflammatory Cell Infiltrate ◽  
Limb Weakness ◽  
Muscle Diseases ◽  
History Of ◽  
The Right ◽  
Mononuclear Inflammatory Cell

Many muscle diseases show common pathological features although their etiology is different. In primary muscle diseases a characteristic finding is myofiber necrosis. The mechanism of myonecrosis is unknown. Polymyositis is a primary muscle disease characterized by acute and subacute degeneration as well as regeneration of muscle fibers coupled with an inflammatory infiltrate. We present a case of polymyositis with unusual ultrastructural features indicative of the basic pathogenetic process involved in myonecrosis.The patient is a 63-year-old white female with a one history of proximal limb weakness, weight loss and fatigue. Examination revealed mild proximal weakness and diminished deep tendon reflexes. Her creatine kinase was 1800 mU/ml (normal < 140 mU/ml) and electromyography was consistent with an inflammatory myopathy which was verified by light microscopy on biopsy muscle. Ultrastructural study of necrotizing myofiber, from the right vastus lateralis, showed: (1) degradation of the Z-lines with preservation of the adjacent Abands including M-lines and H-bands, (Fig. 1), (2) fracture of the sarcomeres at the I-bands with disappearance of the Z-lines, (Fig. 2), (3) fragmented sarcomeres without I-bands, engulfed by invading phagocytes, (Fig. 3, a & b ), and (4) mononuclear inflammatory cell infiltrate in the endomysium.

scholarly journals SAT0332 ANTIBODIES AGAINST CYTOSOLIC 5’-NUCLEOTIDASE 1A IN SPORADIC INCLUSION BODY MYOSITIS: ASSOCIATION WITH CLINICAL AND MRI FEATURES

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1112.1-1112
Author(s):  
R. Dejthevaporn ◽  
S. Shah ◽  
S. Wastling ◽  
J. Thornton ◽  
T. Yousry ◽  
...  
Keyword(s):  
Inclusion Body ◽  
Inclusion Body Myositis ◽  
Rating Scale ◽  
Fatty Infiltration ◽  
Connective Tissue Diseases ◽  
Diagnostic Process ◽  
Antibody Testing ◽  
Muscle Mri ◽  
Mri Features ◽  
Sporadic Inclusion Body Myositis

Background:Autoantibodies directed against cytosolic 5´-nucleotidase 1A (cN1A) have been identified in sporadic inclusion body myositis (sIBM) and other connective tissue diseases. Anti-cN1A antibodies may support the diagnostic process for sIBM as well as potentially provide clues for disease pathogenesis. Nevertheless, the utility of anti-cN1A autoantibody testing in clinical practice remains unclear and requires validation.Objectives:To investigate the association between anti-cN1A antibody status and clinical and MRI features in patients with sIBM.Methods:Data for patients fulfilling European Neuromuscular Centre (ENMC) 2011 criteria for sIBM were obtained from a natural history study database. Demographic, clinical, functional assessment, and muscle MRI data in patients with sIBM who had anti-cN1A autoantibody testing were collected and analysed. Comparisons between subgroups with anti-cN1A antibody status were performed with the Mann-Whitney or Fisher’s exact tests, as appropriate.Results:Forty-nine patients with sIBM had anti-cN1A autoantibody testing, of whom 17 (34.7%) were positive. Twelve patients had muscle MRI performed (seropositivity=5). Demographics, disease duration at antibody testing and overall disease pattern were closely matched in antibody positive and negative cohorts. Dysphagia was more common in the seropositive subgroup (77% vs 47%, p=0.070). Antibody positive patients were more severely affected with a trend to lower IBM functional rating scale (IBMFRS) scores (22.4±8.4 vs 26.7±6.4, p=0.09) with significantly worse ability to climb stairs (0.9±0.9, 1.7±1.1, p=0.02). On T1-weighted MRI more fatty infiltration was found in seropositive patients (Mercuri score: 3.0±0.8 vs 1.7±0.7, p=0.03). Short tau inversion recovery (STIR) hyperintensity was more conspicuous in seropositive patients (STIR extent score: 2.4±0.6 vs 1.4±0.7, p=0.04).Conclusion:There was a trend for more dysphagia and severity of dysphagia in seropositive patients. Differences in upper limb involvement were not seen according to IBMFRS and Medical Research Council (MRC) strength grades. Seropositive patients were more severely affected at the lower limb level, in terms of muscle weakness, physical function, MRI fatty infiltration and muscle inflammation. These results suggest positive antibody status is associated with a worse phenotype. These results have potential implications in clinical trials: whether antibody status influences treatment response should be assessed.Disclosure of Interests:Revadee Dejthevaporn: None declared, Sachit Shah: None declared, Stephen Wastling: None declared, John Thornton: None declared, Tarek Yousry: None declared, Jasper M Morrow: None declared, Pedro M Machado Consultant of: PMM: Abbvie, Celgene, Janssen, Lilly, MSD, Novartis, Pfizer, Roche and UCB, Speakers bureau: PMM: Abbvie, BMS, Lilly, MSD, Novartis, Pfizer, Roche and UCB

scholarly journals AB0156 NMR-BASED MUSCLE METABOLOMICS IN INFLAMMATORY MYOSITIS- UNDERSTANDING CHANGES IN SERUM AS A REFLECTION OF THE MUSCLE

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1378.2-1379
Author(s):  
L. Gupta ◽  
U. Kumar ◽  
A. Anuja ◽  
P. Sharma ◽  
A. Guleria ◽  
...  
Keyword(s):  
Statistical Significance ◽  
Muscle Disease ◽  
P Value ◽  
Healthy Controls ◽  
Inflammatory Myositis ◽  
Activity Assessment ◽  
Muscle Tissues ◽  
Low Levels ◽  
Serum Metabolomics ◽  
Research Grant

Background:We have previously found promise in NMR as a tool to distinguish sera of active from inactive inflammatory myositis (IIM)1. To understand the changes previously found in sera and urine we studied muscle tissue of patients with myositis.Objectives:To identify differences in metabolome on inflamed muscle tissues of patients with active myositis from that of healthy controls and infectious polymyositis.Methods:Muscle (n=17) from patients classifiable as myositis by the ACR-EULAR criteria [34 years (23.5 - 50.5 IQR), M/F 1:3] were compared with healthy controls [n=11, age= 44 (35-50) years, M/F-1:1]. Two disease controls with infectious polymyositis were also compared. Findings were applied to muscle biopsy tissues of two patients with established myositis and superadded infections (HBV, Histoplasmosis) to assess discriminatory potential.Metabolic profiles were obtained at 800 MHZ NMR spectrometer and compared using multivariate partial least-squares discriminant analysis (PLS-DA). The discriminatory metabolites were identified based on variable importance in projection (VIP) statistics and further evaluated for statistical significance (p-value <0.05). Paired T tests, ANNOVA and correlation of individual metabolites were done after normalizing for formate.Results:Metabolomics profiles in IIM were distinct from healthy controls (Fig. 1A).Of the various discriminatory metabolites (Fig. 1B), Succinate had the highest discriminatory potential (AUC 0.8, P=0.01) followed by citrate, glycine, glycerol, glucose, creatine and lactate. (Fig. 1C) Both glucose and creatine were decreased in IIM (Fig. 1D,E) and this was uniform across all types of IIM. However, glycine levels differed across different myositis subsets supporting the fact that they might differ in pathogenesis. (Fig. 1E) Amongst various serum biomarkers of muscle disease and damage, serum Aspartate Transaminase correlated with glutamate (r=0.6, p=0.01), and serum creatinine correlated negatively with glycerol (r-0.8, p=0.04),Biopsies of infectious polymyositis suggested difference in spectra from IIM (Fig. 2A). Trends were observed towards lower succinate and higher citrate levels suggesting metabolomics could possibly be useful to differentiate the two. Muscle of both patients with IIM with superadded infectious polymyositis also exhibited low succinate and elevated citrate.Conclusion:Muscle metabolomics of active myositis is distinctive. Amino acids and creatine are lower in diseases muscle suggesting active breakdown and loss, in turn explaining previous findings of low levels in serum in active disease. Certain metabolite composition differ in different types of myositis supporting different pathogenesis.Infectious polymyositis might exhibit different metabolome from IIM with potential as a biomarker though this needs to be confirmed in larger numbers.Disclosures:Funded by APLAR research grant 2017 awarded to Dr Latika Gupta.References:[1]Gupta L, Kumar D, Gulerai A, Kumar U, Misra R. “NMR-Based Serum, Urine and Muscle Metabolomics in Inflammatory Myositis for Diagnosis and Activity Assessment: Serum Metabolomics Can Differentiate Active from Inactive Myositis” Oral presentation at the ACR, Atlanta 2019.Acknowledgments:MSA and metabolomics supported by APLAR research grant.Disclosure of Interests:None declared

scholarly journals VASTUS LATERALIS OBLIQUE ACTIVITY DURING GAIT OF SUBJECTS WITH PATELLOFEMORAL PAIN

2017 ◽  
Vol 23 (2) ◽  
pp. 88-92
Author(s):  
Gilmar Moraes Santos ◽  
Karina Gramani Say ◽  
Flávio Pulzatto ◽  
Thiele de Cássia Libardoni ◽  
Larissa Milani Brognoli Sinhorim ◽  
...  
Keyword(s):  
Knee Joint ◽  
Vastus Lateralis ◽  
Pain Syndrome ◽  
Patellofemoral Pain Syndrome ◽  
Patellofemoral Pain ◽  
Flexion Angle ◽  
Oblique Muscle ◽  
Electromyographic Activity ◽  
Healthy Controls ◽  
Patellar Stability

ABSTRACT Introduction: So far, little is known about the behavior of electromyographic activity of vastus lateralis oblique muscle during treadmill gait in subjects with and without patellofemoral pain syndrome. Objective: The purpose of this study was to investigate the electromyographic activity of the patellar stabilizers muscles and the angle of the knee joint flexion in subjects with and without patellofemoral pain syndrome. Method: Fifteen subjects without (21 ± 3 years) and 12 with patellofemoral pain syndrome (20 ± 2 years) were evaluated. The electromyographic activity and flexion angle of the knee joint were obtained during gait on the treadmill with a 5 degree inclination. Results: The knee flexion angle was significantly lower in the subjects with patellofemoral pain syndrome when compared with the healthy controls. The electromyographic activity of vastus lateralis longus was significantly greater during gait on the treadmill with inclination in subjects with patellofemoral pain syndrome. The results also showed that the electromyographic activity of vastus lateralis oblique and vastus medialis oblique were similar in both groups, regardless of the condition (with/without inclination). Conclusion: We have shown that knee kinematics during gait differs among patients with and without patellofemoral pain syndrome and healthy controls and that a different motor strategy persists even when the pain is no longer present. In addition, the findings suggested that the vastus lateralis oblique has a minor role in patellar stability during gait.

LIMB-GIRDLE MUSCULAR DYSTROPHY: ITS LARGER SIGNIFICANCE

PEDIATRICS ◽  
1968 ◽  
Vol 41 (2) ◽  
pp. 382-384
Author(s):  
S. C.
Keyword(s):  
Peripheral Nerves ◽  
Neuromuscular Disorders ◽  
Serum Enzymes ◽  
Muscle Disease ◽  
Muscular Dystrophies ◽  
Muscular Weakness ◽  
Conduction Velocities ◽  
Clinical Awareness ◽  
Muscle Biopsies

The current literature reflects the interest of pediatricians, neurologists, and internists in the neuromuscular disorders of childhood.1-5 Clinical awareness and the availability and refinement of ancillary procedures, such as electromyography, measurement of nerve conduction velocities, determination of serum enzymes and muscle biopsies, have made it possible to differentiate many of these conditions and correctly localize the pathology of these lower motor neuron disorders to the anterior horn cells, the peripheral nerves, and/or the muscles.1 Primary muscle disease is the most frequent cause of progressive muscular weakness in children with neuromuscular disorders.2 The primary myopathies are either hereditary or acquired. The muscular dystrophies and the myotonic syndrome are representative of the genetic variety, while the acquired disorders are recognized clinically as polymyositis and dermatomyositis.

Enhanced sarcoplasmic reticulum Ca2+ release following intermittent sprint training

2000 ◽  
Vol 279 (1) ◽  
pp. R152-R160 ◽  
Author(s):  
Niels Ørtenblad ◽  
Per K. Lunde ◽  
Klaus Levin ◽  
Jesper L. Andersen ◽  
Preben K. Pedersen
Keyword(s):  
Sarcoplasmic Reticulum ◽  
High Intensity ◽  
Vastus Lateralis ◽  
Ryanodine Receptors ◽  
Vastus Lateralis Muscle ◽  
Sprint Training ◽  
High Intensity Training ◽  
Before And After ◽  
Muscle Biopsies ◽  
Intensity Training

To evaluate the effect of intermittent sprint training on sarcoplasmic reticulum (SR) function, nine young men performed a 5 wk high-intensity intermittent bicycle training, and six served as controls. SR function was evaluated from resting vastus lateralis muscle biopsies, before and after the training period. Intermittent sprint performance (ten 8-s all-out periods alternating with 32-s recovery) was enhanced 12% ( P < 0.01) after training. The 5-wk sprint training induced a significantly higher ( P < 0.05) peak rate of AgNO3-stimulated Ca2+ release from 709 (range 560–877; before) to 774 (596–977) arbitrary units Ca2+ ⋅ g protein− 1 ⋅ min− 1(after). The relative SR density of functional ryanodine receptors (RyR) remained unchanged after training; there was, however, a 48% ( P < 0.05) increase in total number of RyR. No significant differences in Ca2+ uptake rate and Ca2+-ATPase capacity were observed following the training, despite that the relative density of Ca2+-ATPase isoforms SERCA1 and SERCA2 had increased 41% and 55%, respectively ( P < 0.05). These data suggest that high-intensity training induces an enhanced peak SR Ca2+ release, due to an enhanced total volume of SR, whereas SR Ca2+ sequestration function is not altered.

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