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1.
Inflammation plays a role in the pathogenesis of immune-mediated epilepsy, but also in epilepsy of other etiology such as hippocampal sclerosis. This study aimed to characterize immune cell signatures in the peripheral blood (PB) and cerebrospinal fluid (CSF) in temporal lobe epilepsy (TLE) of different etiologies. We retrospectively evaluated CSF routine parameters and immune cell profiles using flow cytometry in a cohort of 51 patients and 45 age-matched controls with functional disorders. Groups were comprised of patients with nonlesional TLE (n = 26), TLE due to hippocampal sclerosis (n = 14), or limbic encephalitis with antibodies against the 65-kDa isoform of glutamic acid decarboxylase (GAD65-LE; n = 11). TLE patients showed increased proportions of human leukocyte antigen–DR isotype (HLA-DR)-expressing CD4+ T lymphocytes in the CSF. Furthermore, they were characterized by a shift in monocyte subsets toward immature CD14lowCD16+ cells in the PB and blood/CSF-barrier dysfunction. Whereas TLE patients in general showed similar immune cell profiles, patients with GAD65-LE differed from other TLE patients by increased proportions of HLA-DR–expressing CD8+ T lymphocytes and type 2/3 oligoclonal bands. These findings point to a role of innate and adaptive immunity in TLE. CSF parameters may help to discriminate epilepsy patients from controls and different forms of TLE from each other.  相似文献   

2.
We have reported previously that moderate intensity aerobic exercise training attenuates airway inflammation in a murine asthma model. Recent studies implicate regulatory T (Treg) cells in decreasing asthma-related airway inflammation; as such, the current study examined the effect of exercise on Treg cell function in a murine asthma model. Mice were sensitized with ovalbumin (OVA) prior to the start of exercise training at a moderate intensity 3×/week for 4 weeks; exercise was performed as treadmill running (13.5 m/min, 0% grade). Mice were OVA challenged repeatedly throughout the exercise protocol. At protocol completion, mice were analyzed for changes in the number and suppressive function of CD4+CD25+Foxp3+ cells isolated from lungs, mediastinal lymph nodes, and spleens. Results show that exercise increased significantly the number of Foxp3+ cells within the lungs and mediastinal lymph nodes, but not the spleens, of OVA-treated mice as compared with sedentary controls. Exercise also enhanced the suppression function of CD4+CD25+Foxp3+ Treg cells derived from OVA-treated mice as compared with sedentary controls. Specifically, Treg cells from exercised, OVA-treated mice more effectively suppressed CD4+CD25? cell proliferation and Th2 cytokine production in vitro. Enhanced suppression was associated with increased protein levels of TGF-β and lesser amounts of IL-10 and IL-17; however, blocking TGF-β had no effect on suppressive functions. These data demonstrate that exercise-mediated increases in Treg cell function may play a role in the attenuation of airway inflammation. Further, these results indicate that moderate intensity aerobic exercise training may alter the Treg cell function within the asthmatic airway.  相似文献   

3.
The present study evaluated associations between the percentages of T cell immunoglobulin and mucin domain 3 (Tim3)-positive T cells and related cytokines and multiple sclerosis (MS). We collected peripheral blood samples from 30 MS patients and 30 healthy controls. Flow cytometry was used to determine the proportions of CD3+Tim3+, CD4+Tim3+, and CD4+CD25+Tim3+ in peripheral blood mononuclear cells (PBMCs) and related cell subsets. The serum concentrations of galectin-9, IL-17, and IFN-γ also were determined using enzyme-linked immunosorbent assays (ELISA). The percentages of Tim3-positive T cells in CD4+ and CD4+CD25+ T cell subsets were significantly lower among MS patients than among controls. This difference was particularly evident in the CD4+CD25(high) T cell subset. The proportions of CD4+Tim3+ and CD4+CD25+Tim3+ cells in PBMCs were significantly lower in the MS group than in the control group, whereas no significant differences were detected regarding the percentages of CD3+Tim3+ in PBMCs and T cell subsets. The serum concentrations of galectin-9, IL-17, and IFN-γ all were increased in MS patients compared with healthy controls. Our results support that Tim3 and related cytokines may be involved in the onset of MS.  相似文献   

4.
Epilepsy is a nervous system disorder characterized by recurrent seizures. Among several types of epilepsy, which accounts for a significant portion of the disease worldwide, temporal lobe epilepsy (TLE) is one of the most common types of intractable epilepsy in adulthood. It has been suggested that complex febrile seizures in early life are associated with the development of TLE later in life; however, cellular and molecular links between febrile seizures and TLE remain unclear because of the lack of an appropriate in vitro system. Using rat hippocampal slice cultures, in which many features of native organotypic organization are retained, we found that the dentate granule cells exhibit aberrant migration in the dentate hilus via enhanced excitatory GABAA receptor (GABAA‐R) signaling, which results in granule cell ectopia that persists into adulthood. We further found that the granule cell ectopia is associated with spontaneous limbic seizures in adulthood. Importantly, both of these phenomena were prevented by inhibiting Na+K+2Cl? co‐transporter (NKCC1) which mediates the excitatory action of GABA.  相似文献   

5.
Autism spectrum disorders (ASD) are characterized by impairment in social interactions, communication deficits, and restricted repetitive interests and behaviors. A potential etiologic role for immune dysfunction in ASD has been suggested. Dynamic adaptive cellular immune function was investigated in 66 children with a confirmed diagnosis of ASD and 73 confirmed typically developing (TD) controls 2-5 years-of-age. In vitro stimulation of peripheral blood mononuclear cells with PHA and tetanus was used to compare group-associated cellular responses. The production of GM-CSF, TNFα, and IL-13 were significantly increased whereas IL-12p40 was decreased following PHA stimulation in ASD relative to TD controls. Induced cytokine production was associated with altered behaviors in ASD children such that increased pro-inflammatory or TH1 cytokines were associated with greater impairments in core features of ASD as well as aberrant behaviors. In contrast, production of GM-CSF and TH2 cytokines were associated with better cognitive and adaptive function. Following stimulation, the frequency of CD3+, CD4+ and CD8+ T cells expressing activation markers CD134 and CD25 but not CD69, HLA-DR or CD137 were significantly reduced in ASD, and suggests an altered activation profile for T cells in ASD. Overall these data indicate significantly altered adaptive cellular immune function in children with ASD that may reflect dysfunctional immune activation, along with evidence that these perturbations may be linked to disturbances in behavior and developmental functioning. Further longitudinal analyzes of cellular immunity profiles would delineate the relationship between immune dysfunction and the progression of behavioral and developmental changes throughout the course of this disorder.  相似文献   

6.
Interferon-ß (IFN-ß) is an immunomodulatory drug of choice to control relapsing–remitting multiple sclerosis (RR-MS), although its function is still unclear. A reduced suppressive function of CD4+CD25+ regulatory T cells (Treg) has been shown in RR-MS patients. In this study, to understand the effect of IFN-ß on CD4+CD25+ regulatory T cells, we analyzed the frequency and function of these cells and Foxp3 gene expression before and after treatment.We evaluated the frequency and function of CD4+CD25+Foxp3+ regulatory T cells by flow cytometry and co-culture inhibition test respectively and gene expression of Foxp3 by real-time PCR in a longitudinal follow-up study in 18 relapsing–remitting MS patients. Our data revealed that IFN-ß significantly improved frequency and suppressive function of Treg cells (P < 0.05) without any significant effect on gene expression of Foxp3 after 6 months. The results of the present study indicate that IFN-ß therapy in some of patients with RR-MS may restore function of regulatory T cells and control the unchecked immune cascade activity. Larger longitudinal studies on more MS patients are required to confirm our findings.  相似文献   

7.

Objectives

We recently described a monocyte pro-inflammatory state in patients with bipolar disorder (BD). We hypothesized that the CD4+T cell system is also activated and determined percentages of Th1, Th2, Th17 and CD4+CD25highFoxP3+ regulatory T cells.

Methods

We carried out a detailed FACS analysis to determine the various T cell subsets and used frozen stored peripheral blood mononuclear cells (PBMC) of 38 BD patients (of whom we previously had tested monocytes for pro-inflammatory gene expression ( [Drexhage et al., 2010a] and [Padmos et al., 2008])) and of 22 age/gender matched healthy controls (HC). In addition the cytokines CCL2, IL-1β, IL-6, TNF-α, PTX3, IL-10, IFN-γ, IL-17A, IL-4, IL-5 and IL-22 were measured in serum.

Results

(a) Serum sCD25 levels and percentages of anti-inflammatory CD4+CD25highFoxP3+ regulatory T cells were higher, the latter in BD patients <40 years of age. Percentages of Th1, Th2 and Th17 cells were normal.(b) Of the pro-inflammatory monocyte cytokines CCL2 and PTX3 were raised in serum.(c) The monocyte pro-inflammatory state and the raised percentages of CD4+CD25highFoxP3+ regulatory T cells occurred independently from each other.(d) In BD patients positive for thyroid autoimmune disease a significantly reduced percentage of CD4+CD25highFoxP3+ regulatory T cells was found as compared to BD patients without AITD.

Conclusion

Our data show an enhancement of pro-inflammatory monocyte and anti-inflammatory T cell forces in BD patients. A lack of anti-inflammatory T cell forces co-occurred with AITD in BD patients.  相似文献   

8.
Objectives – To determine whether percentages of CD4+CD25high T cells (a group of regulatory T cells, Treg) differ in patients with multiple sclerosis (MS) in relapse vs remission after glucocorticoid treatment and whether treatment for relapses changes Treg population and the expression of Foxp3, a key Treg‐associated molecule. Materials and methods – Peripheral blood mononuclear cells (PBMC) were obtained from 20 patients with MS during relapse, just before and 2 days after starting steroid treatment (i.v. methylprednisolone 1 g/day for 3 days) and then 6 weeks after treatment. CD4+CD25hi cells were analysed by using flow cytometry. Cytokines were measured by using an ELISA and Foxp3, CD3 and CD25 expression by using quantitative real‐time PCR. Results – The percentage of CD4+CD25hi cells, plasma IL‐10 and Foxp3/CD3 ratio increased 48 h after methylprednisolone initiation and returned to baseline values by 6 weeks post‐treatment. Conclusions – Results suggest that glucocorticoids increase Treg cell functional molecules and percentages. This may be a mechanism whereby steroids expedite recovery from MS relapses.  相似文献   

9.
Infection with viral or bacterial pathogens has been linked with the development of multiple sclerosis (MS), while infection with helminth parasites has been associated protection against MS and other autoimmune diseases. Here we have used a murine model of MS, experimental autoimmune encephalomyelitis (EAE), to examine the effect of infection with the respiratory pathogen Bordetella pertussis infection on development of CNS inflammation. The data demonstrate that infection of mice with B. pertussis significantly attenuates the clinical course of EAE induced by active immunization or cell transfer. This was reflected in a significant reduction in VLA-4 and LFA-1 expression on T cells and infiltration of IL-17+, IFN-γ+ and IFN-γ+IL-17+ CD4 T cells into the CNS. Infection with B. pertussis induced IL-10 production from dendritic cells in vitro and enhanced the frequency of IL-10-producing CD25-Foxp3+/− CD4+ T cells in vivo. Furthermore, the suppressive effects of B. pertussis infection on EAE were lost in IL-10−/− mice. Our findings demonstrate that a bacterial infection of the respiratory tract can attenuate EAE by promoting production of the anti-inflammatory cytokine IL-10 that may suppress licensing of autoaggressive T cells in the lungs, thereby preventing their migration into the CNS.  相似文献   

10.
BackgroundSurgery renders patients susceptible to life-threatening complications, including infections, multiple organ failure, and presumably cancer metastases. Surgery-induced immune perturbations were suggested to contribute to such deleterious effects, but also to facilitate post-injury healing. Preoperative psychological and physiological stress responses may contribute to these immune perturbations, and could thus jeopardize patients even before surgery. The current study assessed the effects of various operations on an array of immune indices during the perioperative period. To qualify immune changes before surgery, patients’ immune status was also compared to that of healthy controls.MethodsA total of 81 subjects (operated patients and healthy controls) provided up to five daily blood samples during the perioperative period, for assessment of leukocyte subtypes (granulocytes, monocytes, Tc, Th, NK, NKT, CD4+CD25+, CD8brightCD4dim, and B cells) and their surface markers (HLA-DR and LFA-1).ResultsEven before surgery patients displayed immune perturbations, including reduced lymphocyte HLA-DR expression and increased monocyte LFA-1 expression. Following surgery, we recorded a reduction in lymphocyte numbers that was subtype specific, increased granulocyte numbers, and reduced expression of HLA-DR by lymphocytes and monocytes. Finally, no significant associations were found between alteration in leukocyte numbers and cell surface markers (although these indices showed high correlations with other variables), implying differential mediating mechanisms.ConclusionSeveral immune alterations are manifested prior to surgery, and contribute to the marked postoperative changes, which are commonly interpreted as immune suppression. We discuss the possible adaptive and maladaptive nature of these perturbations in the context of natural injury, stress, and surgery.  相似文献   

11.
Inflammatory mediators such as cytokines are likely to contribute to the pathophysiology of epilepsy. Proinflammatory cytokines are also associated with mood disorders, such as major depression. As people with temporal lobe epilepsy (TLE) are at an increased risk of mood disorders, we attempted to evaluate peripheral levels of IL-1β in people with TLE with depression and people with TLE without depression and in healthy controls. In a cross-sectional study, we compared three groups: 21 people with TLE without depression (TLE D −), 18 people with TLE with depression (TLE D +), and 31 controls without depression. A structured clinical interview (MINI-Plus) was used to diagnose current depression, and the Hamilton Depression Rating Scale (HAM-D) was used to quantify depressive symptoms. Plasma levels of IL-1β were significantly higher in people with TLE with depression than in controls (p = 0.004) or people with TLE without depression (p = 0.006). Interleukin-1beta levels positively correlated with HAM-D scores (Spearman's rho = 0.381, p = 0.017) in people with TLE. Higher levels of IL-1β in TLE seem to be associated with depression.  相似文献   

12.
Study objectivesEvidence suggests a cell-mediated autoimmune pathogenesis for narcolepsy type 1 (NT1), but it is not clear whether the disease is associated with overall changes in T cell subsets. The increase in NT1 incidence after H1N1 vaccination campaign with the Pandemrix™ vaccine suggests that disease-relevant changes in the immune system following this vaccination were important. In this study, we aimed to investigate differentiated T cell subsets and levels of CD25 and CD69 activation markers in a cohort of mainly Pandemrix™-vaccinated NT1 patients compared with their vaccinated and unvaccinated siblings.MethodsPeripheral blood mononuclear cells were collected in parallel and analysed with flow cytometry in 31 NT1 patients with disease onset after the 2009 influenza A (H1N1) pandemic and/or Pandemrix™ vaccination and 45 of their non-narcoleptic siblings (29/31 and 34/45 vaccinated, respectively).ResultsWe observed significantly lower effector memory CD4+ T cell levels in NT1 patients compared to their siblings, when controlling for HLA DQB1106:02 and vaccination status. Further, within the sibling group, vaccination status significantly affected frequencies of central memory and CD8+CD25+ T cells, and HLA DQB1106:02 status significantly affected frequencies of CD4+CD25+ T cells.ConclusionWe confirm that NT1 is associated with lower levels of effector memory CD4+ T cells in peripheral blood. Importantly, this finding was only significant when controlling for vaccination and HLA status in both patients and controls. We thus demonstrate the importance of characterizing such factors (eg HLA and vaccination) when studying T cell subsets in NT1. This might explain earlier conflicting results.  相似文献   

13.
The incidence of cardiovascular disease, including inflammatory heart diseases like myocarditis, is increased in men. Similarly, male BALB/c mice infected with coxsackievirus B3 (CVB3) develop more severe acute inflammation in the heart compared to females. To better understand the effect of male sex hormones on cardiac inflammation, we gonadectomized (Gdx) male BALB/c mice and examined acute CVB3-induced myocarditis compared to sham controls. Viral replication in the heart was not significantly altered between Gdx and sham mice. However, gonadectomy significantly reduced testosterone levels and inflammation in the heart. FACS analysis of cell populations isolated from the heart revealed that CD11b+ cells were significantly reduced in Gdx males. However, a GR1+F4/80+ subset of CD11b+ cells was significantly increased. Because this subset also expressed the interleukin (IL)-4R and IL-10, we refer to these cells as “alternatively activated” or M2 macrophages. A greater percentage of M2 macrophages in Gdx males expressed the inhibitory receptor Tim-3, while fewer expressed IL-1β and IL-10. Only M2 macrophages upregulated TLR4 and Tim-3, whereas GR1?IL-4Rlo macrophages did not. Additionally, IL-4+CD4+ Th2 cells, Foxp3+ regulatory T (Treg) cells and Tim-3+CD4+ T cells were significantly increased in the heart following Gdx. Thus, we report for the first time that the inhibitory receptor Tim-3 is expressed on M2 macrophages. Our findings show that sex hormones and/or other mediators released from the testes inhibit anti-inflammatory populations in the heart including Tim-3+ M2, Tim-3+CD4+ T cells, Th2 and Treg resulting in more severe acute cardiac inflammation in males following CVB3 infection.  相似文献   

14.
《Epilepsy research》2007,73(2-3):89-96
PurposeTo assess the possible cognitive alterations in epilepsy patients compared with controls over 5 years, and to investigate the clinical variables mainly implied in mental impairment.MethodsIn our longitudinal single-center study, 50 patients with temporal lobe epilepsy (TLE) and 50 controls were administered the same battery of comprehensive neuropsychological tests at baseline and after 5 years.ResultsTLE patients showed a significant impairment in attention and psychomotor speed compared with controls after 5 years, while the other cognitive domains did not exhibit any important changes. This worsening was mainly related to the duration of epilepsy, the age at onset, a history of tonic–clonic seizures and a low educational level.ConclusionsWe believe that tapping the attention and psychomotor speed decline in TLE patients should be considered relevant for future research, in order to achieve a deeper understanding of the cognitive dimensions of this field.  相似文献   

15.
Abstract. Objective: The aim of the study was to find out whether INF--1a influences the immune profile of peripheral blood (PB) leukocytes in MS patients. Method: We have studied 20 patients with relapsing-remitting form of MS treated with INF--1a using twocolor cytometry. We determined immune cells phenotypes and production of some cytokines: IL-4, IL-10, IL-12, IFN-, before drug administration and after starting the treatment. Results: In MS patients an increased percentage of CD14+CD86+ cells and CD3+CD25+ cells was noticed after 6, 9 and 12 months of INF--1a therapy. Among cytokine-producing cells we noted an increased fraction of CD3+IL-4, CD14+IL-10 and CD14+IL-12 cells after 12 months, which decreased to the level observed before treatment after 24-month therapy. Conclusions: IFN--1a treatment was associated with significant changes in immune response. This effect was mostly evident within the first year of treatment.  相似文献   

16.
To study whether cerebral mycobacterial infection induces granuloma and protective immunity similar to systemic infection, we intracerebrally infected mice with Mycobacterium bovis bacilli Calmette–Guerin. Granuloma and IFN-γ+CD4+ T cell responses are induced in the central nervous system (CNS) similar to periphery, but the presence of IFN-γIL-17 double-positive CD4+ T cells is unique to the CNS. The major CNS source of TNF-α is microglia, with modest production by CD4+ T cells and macrophage. Protective immunity is accompanied by accumulation of Foxp3+CD4+ T cells and PD-L2+ dendritic cells, suggesting that both inflammatory and anti-inflammatory responses develop in the CNS following mycobacterial infection.  相似文献   

17.
Previous studies have reported activation of inflammatory cytokines in seizures, but clinical characteristics of epilepsy associated with cytokine activation have not been well established. In this study, serum levels of interleukin-6 (IL-6) and interleukin-1 receptor antagonist (IL-1RA) were measured, and clinical characteristics of epilepsy were assessed in 86 well-evaluated patients with refractory focal epilepsy and in 5 patients with controlled focal epilepsy. Epilepsy was evaluated based on patient histories, electroclinical findings, and high-resolution brain MRI scans. Sixty-three healthy blood donors served as controls. IL-6 concentrations were chronically increased in epilepsy patients (11%) compared with healthy controls (0%) (P = 0.007). Increased levels of IL-6 were more prevalent in patients with temporal lobe epilepsy (TLE) compared to patients with extra-TLE (P = 0.028). Also the mean and the median serum levels of IL-6 were higher in patients with TLE than in patients with extra-TLE (P = 0.042). Concentrations of IL-1RA were not significantly different in patients compared with controls. Indicated by increased levels of IL-6 in TLE, epilepsy type is important in determining chronic overproduction of cytokines in refractory focal epilepsy. The results may reflect a chronic immunological process in the brain in patients with refractory epilepsy.  相似文献   

18.
The distribution of lymphocyte subpopulations in cerebrospinal fluid (CSF) and their phenotypic characteristics were extensively investigated in a group of 18 healthy individuals using two- and three-color flow cytometry. Generally, CDS+ T lymphocytes constituted the vast majority of CSF lymphocytes while the number of B lymphocytes and NK cells were low. Most T lymphocytes exhibited the phenotype of memory /primed cells in both the CD4+ and CD8+ subpopulations. Two markers for recent activation, HLA-DR and interleukin-2 receptor (CD25) were not upregulated when compared with peripheral blood (PB) in the majority of CSF T lymphocytes. However, a fraction of T lymphocytes co-expressing the NK cell markers CD56 and/or CD16 showed a pronounced upregulation of HLA-DR in CSF as compared with PB. This study documents that the cellular composition of the normal CSF differs profoundly from PB regarding all major lymphocyte subpopulations. This has to be taken into account in studies addressing questions regarding cellular immune reactions in the central nervous system under pathological conditions.  相似文献   

19.
ObjectiveThe objective of this study was to compare the seizure characteristics and treatment outcomes in patient groups with temporal lobe epilepsy (TLE) identified with isolated amygdala enlargement (AE) on magnetic resonance imaging studies.MethodsPubMed, Embase, and the Cochrane Library were searched for relevant studies using the keywords ‘amygdala enlargement’, ‘epilepsy’, and ‘seizures’ in April 2015. Human studies, written in English, that investigated cohorts of patients with TLE and AE were included.ResultsOf 204 abstracts initially identified using the search strategy, 14 studies met the inclusion criteria (11 epilepsy studies and 3 psychiatry studies). Ultimately, 8 full studies on AE and TLE involving 107 unique patients were analyzed. Gender distribution consisted of 50 males and 57 females. Right amygdala enlargement was seen in 39 patients, left enlargement in 58 patients, and bilateral enlargement in 7 patients. Surgical resection was performed in 28 patients, with the most common finding being dysplasia/hamartoma or focal cortical dysplasia. Most studies involved small samples of less than 12 patients. There was a wide discrepancy in the methods used to measure amygdala volume, in both patients and controls, hindering comparisons. Most TLE with AE studies observed a later age of seizure onset (mean: 32.2 years) compared with studies involving TLE with HS (mean of mid- to late childhood). A higher frequency of complex partial seizures compared with that of convulsive seizures is seen in patients with AE (67–100% vs. 26–47%), and they have an excellent response to antiepileptic drugs (81.8%–100% of seizure-free patients). All studies that included controls also found a significant difference in frequency of seizure types between their cases and controls.ConclusionsReliable assessment of amygdala volume remains a critical issue hindering better understanding of the clinical management and research of this focal epilepsy syndrome. Within these limitations, the literature suggests characteristics of an older age of epilepsy onset, a greater tendency to nonconvulsive seizures, and a good response to antiepileptic drugs in this interesting group of epilepsies.  相似文献   

20.
Macrophages have been found histologically to be activated in multiple sclerosis. We analyzed the expression of CD23 and CD25 on monocytes/macrophages in peripheral blood obtained from patients with multiple sclerosis (MS) to investigate their role in the demyelinating process. Peripheral blood mononuclear cells were obtained from 30 patients with MS including for Baló's diseases (24 with acute relapsing type disease, six with chronic progressive type disease) and 12 healthy controls. The percentage of CD14+ CD23+ monocytes/macrophages and CD14+ CD25+ monocytes/macrophages were determined by two-color flow cytometry. The percentage of CD14+ CD23+ monocytes was significantly higher in patients with MS in the active phase as compared with controls (P < 0.01). Six patients with acute relapsing MS, who had received no therapy, had higher CD14+ CD23+ cells than did controls (P < 0.0001). CD14+ CD25+ monocytes/macrophages were not detected in peripheral blood monocytes/macrophages of patients with MS except Baló's concentric sclerosis. The four patients with Baló's concentric sclerosis had markedly elevated levels of CD14+ CD25+ monocytes/macrophages. Our findings suggest that monocytes/macrophages are activated during an exacerbatiion of MS. and that they may play an important role in the process of demyelination.  相似文献   

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