scholarly journals Changes in Antigen-Specific Cytokine and Chemokine Responses to Plasmodium falciparum Antigens in a Highland Area of Kenya after a Prolonged Absence of Malaria Exposure

2014 ◽  
Vol 82 (9) ◽  
pp. 3775-3782 ◽  
Author(s):  
Lyticia A. Ochola ◽  
Cyrus Ayieko ◽  
Lily Kisia ◽  
Ng'wena G. Magak ◽  
Estela Shabani ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Severe Disease ◽  
Clinical Malaria ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Highland Area ◽  
Cytokine Responses ◽  
Increased Risk ◽  
Tnf Α ◽  
Ifn Γ

ABSTRACTIndividuals naturally exposed toPlasmodium falciparumlose clinical immunity after a prolonged lack of exposure.P. falciparumantigen-specific cytokine responses have been associated with protection from clinical malaria, but the longevity ofP. falciparumantigen-specific cytokine responses in the absence of exposure is not well characterized. A highland area of Kenya with low and unstable malaria transmission provided an opportunity to study this question. The levels of antigen-specific cytokines and chemokines associated in previous studies with protection from clinical malaria (gamma interferon [IFN-γ], interleukin-10 [IL-10], and tumor necrosis factor alpha [TNF-α]), with increased risk of clinical malaria (IL-6), or with pathogenesis of severe disease in malaria (IL-5 and RANTES) were assessed by cytometric bead assay in April 2008, October 2008, and April 2009 in 100 children and adults. During the 1-year study period, none had an episode of clinicalP. falciparummalaria. Two patterns of cytokine responses emerged, with some variation by antigen: a decrease at 6 months (IFN-γ and IL-5) or at both 6 and 12 months (IL-10 and TNF-α) or no change over time (IL-6 and RANTES). These findings document thatP. falciparumantigen-specific cytokine responses associated in prior studies with protection from malaria (IFN-γ, TNF-α, and IL-10) decrease significantly in the absence ofP. falciparumexposure, whereas those associated with increased risk of malaria (IL-6) do not. The study findings provide a strong rationale for future studies of antigen-specific IFN-γ, TNF-α, and IL-10 responses as biomarkers of increased population-level susceptibility to malaria after prolonged lack ofP. falciparumexposure.

scholarly journals Similar Cytokine Responses and Degrees of Anemia in Patients with Plasmodium falciparum and Plasmodium vivax Infections in the Brazilian Amazon Region

2008 ◽  
Vol 15 (4) ◽  
pp. 650-658 ◽  
Author(s):  
Andréa Aparecida Morais Fernandes ◽  
Leonardo José de Moura Carvalho ◽  
Graziela Maria Zanini ◽  
Ana Maria Revorêdo da Silva Ventura ◽  
José Maria Souza ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Plasmodium Vivax ◽  
Brazilian Amazon ◽  
Immunoglobulin M ◽  
Interleukin 12 ◽  
Necrosis Factor Alpha ◽  
Cytokine Responses ◽  
Tnf Α ◽  
Brazilian Amazon Region ◽  
Ifn Γ

ABSTRACT The mechanisms of malarial anemia induction are poorly understood, but cytokines and autoantibodies are considered to play important roles. This work aimed at evaluating the degree of anemia and the plasmatic profile of the cytokines tumor necrosis factor alpha (TNF-α), gamma interferon (IFN-γ), interleukin-12 (IL-12), migration inhibitory factor (MIF), and IL-10 and the monocyte chemotactic protein-1 (MCP-1) chemokine, as well as evaluating the presence of antibodies directed to components of the normal erythrocyte membrane and to cardiolipin in individuals with malaria from the Brazilian Amazon. No difference was observed in the frequency of anemia between patients infected by Plasmodium vivax and those infected by Plasmodium falciparum, and there was no relationship between the levels of parasitemia and the manifestations of anemia in P. vivax and P. falciparum patients. Significant increases in the concentrations of TNF-α, IFN-γ, MIF, and MCP-1 were observed in patients with P. falciparum and P. vivax malaria, whereas the concentrations of IL-10 was increased only in patients with P. vivax infection. Higher concentrations of IL-12 and IL-10 were observed in the P. falciparum anemic patients, while for TNF-α this profile was observed in the nonanemic ones. P. vivax-infected and P. falciparum-infected patients with positive immunoglobulin M (IgM) or IgM and IgG responses, respectively, against blood-stage forms of the parasites had significantly lower hemoglobin levels than did those with negative responses. There was no correlation between the presence of anti-erythrocyte and anti-cardiolipin antibodies and the presence or intensity of the anemia. Our data suggest that in areas of low endemicity and unstable transmission of malaria, P. vivax and P. falciparum infections present similar characteristics in terms of the induction of anemia and cytokine responses.

scholarly journals CXC Ligand 9 Response to Malaria during Pregnancy Is Associated with Low-Birth-Weight Deliveries

2012 ◽  
Vol 80 (9) ◽  
pp. 3034-3038 ◽  
Author(s):  
Shu Dong ◽  
Jonathan D. Kurtis ◽  
Sunthorn Pond-Tor ◽  
Edward Kabyemela ◽  
Patrick E. Duffy ◽  
...  
Keyword(s):  
Birth Weight ◽  
Low Birth Weight ◽  
Strong Association ◽  
Placental Malaria ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Tnf Α ◽  
Malaria During Pregnancy ◽  
Placental Blood ◽  
Ifn Γ

ABSTRACTPlacental infection withPlasmodium falciparumis associated with increased levels of proinflammatory cytokines, including tumor necrosis factor alpha (TNF-α) and gamma interferon (IFN-γ), and previous studies have associated increased levels of these cytokines with low birth weight (LBW), especially for malaria-infected primigravidae. To define the contribution of TNF-α and IFN-γ networks to placental-malaria-associated LBW, we measured chemokines induced by TNF-α and IFN-γ and related them to birth weight in a birth cohort of 782 mother-infant pairs residing in an area ofP. falciparumholoendemicity in Tanzania. Among primigravidae, levels of CCL2, CXC ligand 9 (CXCL9), and CXCL13 were significantly higher during malaria infection in both the placenta and peripheral blood. Placental CXCL9 and CXCL13 levels were also higher in placental blood from secundigravidae and multigravidae. In multivariate analyses adjusted for known predictors of birth weight, malaria-infected primigravidae with placental CXCL9 levels in the lowest tertile gave birth to babies who weighed 610 g more than babies born to mothers with high CXCL9 levels. CXCL9 expression is induced by IFN-γ, and the strong association between birth weight and placental CXCL9 is consistent with previous observations relating IFN-γ to poor pregnancy outcomes.

scholarly journals Complex T Cell Interactions Contribute to Helicobacter pylori Gastritis in Mice

2012 ◽  
Vol 81 (3) ◽  
pp. 740-752 ◽  
Author(s):  
Brian M. Gray ◽  
Clinton A. Fontaine ◽  
Sara A. Poe ◽  
Kathryn A. Eaton
Keyword(s):  
T Cells ◽  
Helicobacter Pylori ◽  
T Cell ◽  
Published Data ◽  
Proinflammatory Response ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Tnf Α ◽  
Ifn Γ ◽  
H Pylori

ABSTRACTDisease due to the gastric pathogenHelicobacter pylorivaries in severity from asymptomatic to peptic ulcer disease and cancer. Accumulating evidence suggests that one source of this variation is an abnormal host response. The goal of this study was to use a mouse model ofH. pylorigastritis to investigate the roles of regulatory T cells (Treg) as well as proinflammatory T cells (Th1 and Th17) in gastritis, gastric T cell engraftment, and gastric cytokine production. Our results support published data indicating that severe gastritis in T cell recipient mice is due to failure of Treg engraftment, that Treg ameliorate gastritis, and that the proinflammatory response is attributable to interactions between several cell subsets and cytokines. We confirmed that gamma interferon (IFN-γ) is essential for induction of gastritis but showed that IFN-γ-producing CD4 T cells are not necessary. Interleukin 17A (IL-17A) also contributed to gastritis, but to a lesser extent than IFN-γ. Tumor necrosis factor alpha (TNF-α) and IL-17F were also elevated in association with disease. These results indicate that whileH. pylori-specific CD4+T cells and IFN-γ are both essential for induction of gastritis due toH. pylori, IFN-γ production by T cells is not essential. It is likely that other proinflammatory cytokines, such as IL-17F and TNF-α, shown to be elevated in this model, also contribute to the induction of disease. We suggest that gastritis due toH. pyloriis associated with loss of immunoregulation and alteration of several cytokines and cell subsets and cannot be attributed to a single immune pathway.

scholarly journals Specific CD4+T-Cell Reactivity and Cytokine Release in Different Clinical Presentations of Leptospirosis

2015 ◽  
Vol 22 (12) ◽  
pp. 1276-1284 ◽  
Author(s):  
Magdalena Sarah Volz ◽  
Verena Moos ◽  
Kristina Allers ◽  
Enno Luge ◽  
Anne Mayer-Scholl ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Severe Disease ◽  
Clinical Manifestations ◽  
Cytokine Release ◽  
Cell Reactivity ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Tnf Α ◽  
T Cell Reactivity

ABSTRACTClinical manifestations of leptospirosis are highly variable: from asymptomatic to severe and potentially fatal. The outcome of the disease is usually determined in the immunological phase, beginning in the second week of symptoms. The underlying mechanisms, predictive factors, and individual immune responses that contribute to clinical variations are not well understood. The aim of this study was to determine the specifics of CD4+T-cell reactivity and cytokine release after stimulation with leptospiral antigens in patients with leptospirosis of different disease severities (patients with mild and severe symptoms) and in control subjects (with and without proven exposure toLeptospira). Whole-blood specimens were stimulated withLeptospiraantigensin vitro. Subsequently, intracellular staining of cytokines was performed, and flow cytometry was used to assess the expression of CD40 ligand (CD40L) and the production of gamma interferon (IFN-γ), interleukin-10 (IL-10), IL-2, and tumor necrosis factor alpha (TNF-α) by CD4+T cells. The production of inflammatory cytokines such as TNF-α by CD4+T cells after stimulation with leptospiral antigens was highest in patients with severe disease. In contrast, the ratio of IL-10 production to TNF-α production was higher in exposed subjects than in patients with mild and severe disease. Levels of proinflammatory cytokines such as TNF-α may be useful markers of the severity of the immunological phase of leptospirosis. IL-10 production by T cells after antigen-specific stimulation may indicate a more successful downregulation of the inflammatory response and may contribute to an asymptomatic course of the disease.

scholarly journals Discrimination between Active and Latent Tuberculosis Based on Ratio of Antigen-Specific to Mitogen-Induced IP-10 Production

2014 ◽  
Vol 53 (2) ◽  
pp. 504-510 ◽  
Author(s):  
Yun Hee Jeong ◽  
Yun-Gyoung Hur ◽  
Hyejon Lee ◽  
Sunghyun Kim ◽  
Jang-Eun Cho ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Interleukin 2 ◽  
Induced Responses ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Monocyte Chemoattractant Protein 1 ◽  
Tnf Α ◽  
Release Assay ◽  
Ltbi Group ◽  
Ifn Γ

Mycobacterium tuberculosisis the major causative agent of tuberculosis (TB). The gamma interferon (IFN-γ) release assay (IGRA) has been widely used to diagnose TB by testing cell-mediated immune responses but has no capacity for distinguishing between active TB and latent TB infection (LTBI). This study aims to identify a parameter that will help to discriminate active TB and LTBI. Whole-blood samples from 33 active TB patients, 20 individuals with LTBI, and 26 non-TB controls were applied to the commercial IFN-γ release assay, QuantiFERON-TB Gold In-Tube, and plasma samples were analyzed for interleukin-2 (IL-2), IL-6, IL-8, IL-10, IL-13, tumor necrosis factor-alpha (TNF-α), IFN-γ, monokine induced by IFN-γ (MIG), interferon gamma inducible protein 10 (IP-10), interferon-inducible T cell alpha chemoattractant (I-TAC), and monocyte chemoattractant protein 1 (MCP-1) by using a commercial cytometric bead array. TheMycobacterium tuberculosisantigen-specific production of most of the assayed cytokines and chemokines was higher in the active TB than in the LTBI group. The mitogen-induced responses were lower in the active TB than in the LTBI group. When the ratio of TB-specific to mitogen-induced responses was calculated, IL-2, IL-6, IL-10, IL-13, TNF-α, IFN-γ, MIG, and IP-10 were more useful in discriminating active TB from LTBI. In particular, most patients showed higher IP-10 production toMycobacterium tuberculosisantigens than to mitogen at the individual level, and the ratio for IP-10 was the strongest indicator of active infection versus LTBI with 93.9% sensitivity and 90% specificity. In conclusion, the ratio of the TB-specific to the mitogen-induced IP-10 responses showed the most promising accuracy for discriminating active TB versus LTBI and should be further studied to determine whether it can serve as a biomarker that might help clinicians administer appropriate treatments.

scholarly journals Coexistent Malnutrition Is Associated with Perturbations in Systemic and Antigen-Specific Cytokine Responses in Latent Tuberculosis Infection

2016 ◽  
Vol 23 (4) ◽  
pp. 339-345 ◽  
Author(s):  
Rajamanickam Anuradha ◽  
Saravanan Munisankar ◽  
Yukthi Bhootra ◽  
Nathalla Pavan Kumar ◽  
Chandrakumar Dolla ◽  
...  
Keyword(s):  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Interleukin 4 ◽  
Cytokine Responses ◽  
Increased Risk ◽  
Tnf Α ◽  
Latent Tb ◽  
Low Bmi ◽  
Ifn Γ

ABSTRACTMalnutrition, as defined by low body mass index (BMI), is a major risk factor for the development of active tuberculosis (TB), although the biological basis underlying this susceptibility remains poorly characterized. To verify whether malnutrition affects the systemic and antigen-specific cytokine levels in individuals with latent TB (LTB), we examined circulating and TB antigen-stimulated levels of cytokines in individuals with LTB and low BMI (LBMI) and compared them with those in individuals with LTB and normal BMI (NBMI). Coexistent LBMI with LTB was characterized by diminished circulating levels of type 1 (gamma interferon [IFN-γ] and tumor necrosis factor alpha [TNF-α]), type 2 (interleukin-4 [IL-4]), type 17 (IL-22), and other proinflammatory (IL-1α, IL-1β, and IL-6) cytokines but elevated levels of other type 2 (IL-5 and IL-13) and regulatory (IL-10 and transforming growth factor beta [TGF-β]) cytokines. In addition, LBMI with LTB was associated with diminished TB antigen-induced IFN-γ, TNF-α, IL-6, IL-1α, and IL-1β levels. Finally, there was a significant positive correlation between BMI values and TNF-α and IL-1β levels and a significant negative correlation between BMI values and IL-2, IL-10, and TGF-β levels in individuals with LTB. Therefore, our data reveal that latent TB with a coexistent low BMI is characterized by diminished protective cytokine responses and heightened regulatory cytokine responses, providing a potential biological mechanism for the increased risk of developing active TB.

scholarly journals Cytokine Responses to Plasmodium falciparumLiver-Stage Antigen 1 Vary in Rainy and Dry Seasons in Highland Kenya

2000 ◽  
Vol 68 (9) ◽  
pp. 5198-5204 ◽  
Author(s):  
C. C. John ◽  
P. O. Sumba ◽  
J. H. Ouma ◽  
B. L. Nahlen ◽  
C. L. King ◽  
...  
Keyword(s):  
Rainy Season ◽  
Mononuclear Cells ◽  
Age Groups ◽  
Dry Season ◽  
Peripheral Blood Mononuclear ◽  
Necrosis Factor Alpha ◽  
Liver Stage ◽  
Cytokine Responses ◽  
Tnf Α ◽  
Ifn Γ

ABSTRACT Seasonal epidemics of malaria occur in highland areas of western Kenya where transmission intensity varies according to rainfall. This study describes the seasonal changes in cytokine responses toPlasmodium falciparum liver-stage antigen 1 (LSA-1) by children (≤17 years old) and adults (≥18 years old) living in such a highland area. Fourteen- to 24-mer peptides corresponding to the N- and C-terminal nonrepeat regions of LSA-1 stimulated production of interleukin-5 (IL-5), interleukin-10 (IL-10), gamma interferon (IFN-γ), and tumor necrosis factor alpha (TNF-α) by peripheral blood mononuclear cells (PBMC) from 17 to 73% of individuals in both age groups in both seasons. IL-10 and TNF-α responses were more frequent during the high-transmission, rainy season than during the low-transmission, dry season (73 and 67% versus 17 and 25% response rates, respectively). In contrast, there was no seasonal change in the proportion of LSA-1-driven IFN-γ and IL-5 responses. Children produced less IFN-γ than adults, but IL-5, IL-10, and TNF-α levels were similar for both age groups. Depletion of CD8+ cells from PBMC decreased IFN-γ but increased IL-10 production. Individuals with LSA-1-stimulated IL-10 responses in the dry season were less likely to become reinfected in the subsequent rainy season than those without IL-10 responses (25% versus 49%;P = 0.083). These data support the notion that maintenance of LSA-1-driven IL-10 and TNF-α responses requires repeated and sustained exposure to liver-stage P. falciparum. In contrast, IFN-γ responses increase slowly with age but persist once acquired. CD8+ T cells are the major source of IFN-γ but may suppress production or secretion of IL-10.

scholarly journals The Predominant CD4+ Th1 Cytokine Elicited to Chlamydia trachomatis Infection in Women Is Tumor Necrosis Factor Alpha and Not Interferon Gamma

2017 ◽  
Vol 24 (4) ◽  
Author(s):  
Stephen J. Jordan ◽  
Kanupriya Gupta ◽  
Brian M. O. Ogendi ◽  
Rakesh K. Bakshi ◽  
Richa Kapil ◽  
...  
Keyword(s):  
T Cells ◽  
Chlamydia Trachomatis ◽  
Tumor Necrosis ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Tnf Α ◽  
Th1 Cytokine ◽  
Factor Alpha ◽  
Ifn Γ ◽  
Necrosis Factor

ABSTRACT Chlamydia trachomatis infection is the most prevalent bacterial sexually transmitted infection and can cause significant reproductive morbidity in women. There is insufficient knowledge of C. trachomatis-specific immune responses in humans, which could be important in guiding vaccine development efforts. In contrast, murine models have clearly demonstrated the essential role of T helper type 1 (Th1) cells, especially interferon gamma (IFN-γ)-producing CD4+ T cells, in protective immunity to chlamydia. To determine the frequency and magnitude of Th1 cytokine responses elicited to C. trachomatis infection in humans, we stimulated peripheral blood mononuclear cells from 90 chlamydia-infected women with C. trachomatis elementary bodies, Pgp3, and major outer membrane protein and measured IFN-γ-, tumor necrosis factor alpha (TNF-α)-, and interleukin-2 (IL-2)-producing CD4+ and CD8+ T-cell responses using intracellular cytokine staining. The majority of chlamydia-infected women elicited CD4+ TNF-α responses, with frequency and magnitude varying significantly depending on the C. trachomatis antigen used. CD4+ IFN-γ and IL-2 responses occurred infrequently, as did production of any of the three cytokines by CD8+ T cells. About one-third of TNF-α-producing CD4+ T cells coproduced IFN-γ or IL-2. In summary, the predominant Th1 cytokine response elicited to C. trachomatis infection in women was a CD4+ TNF-α response, not CD4+ IFN-γ, and a subset of the CD4+ TNF-α-positive cells produced a second Th1 cytokine.

scholarly journals Malaria Modifies Neonatal and Early-Life Toll-Like Receptor Cytokine Responses

2013 ◽  
Vol 81 (8) ◽  
pp. 2686-2696 ◽  
Author(s):  
Komi Gbédandé ◽  
Stefania Varani ◽  
Samad Ibitokou ◽  
Parfait Houngbegnon ◽  
Sophie Borgella ◽  
...  
Keyword(s):  
Immune Responses ◽  
Early Life ◽  
In Utero ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Toll Like Receptor ◽  
Content Type ◽  
Cytokine Responses ◽  
Increased Risk ◽  
Tnf Α

ABSTRACTProtection from infections in early life relies extensively on innate immunity, but it is unknown whether and how maternal infections modulate infants' innate immune responses, thereby altering susceptibility to infections.Plasmodium falciparumcauses pregnancy-associated malaria (PAM), and epidemiological studies have shown that PAM enhances infants' susceptibility to infection withP. falciparum. We investigated how PAM-mediated exposuresin uteroaffect innate immune responses and their relationship with infection in infancy. In a prospective study of mothers and their babies in Benin, we investigated changes in Toll-like receptor (TLR)-mediated cytokine responses related toP. falciparuminfections. Whole-blood samples from 134 infants at birth and at 3, 6, and 12 months of age were stimulated with agonists specific for TLR3, TLR4, TLR7/8, and TLR9. TLR-mediated interleukin 6 (IL-6) and IL-10 production was robust at birth and then stabilized, whereas tumor necrosis factor alpha (TNF-α) and gamma interferon (IFN-γ) responses were weak at birth and then increased. In multivariate analyses, maternalP. falciparuminfections at delivery were associated with significantly higher TLR3-mediated IL-6 and IL-10 responses in the first 3 months of life (P< 0.05) and with significantly higher TLR3-, TLR7/8-, and TLR9-mediated TNF-α responses between 6 and 12 months of age (P< 0.05). Prospective analyses showed that higher TLR3- and TLR7/8-mediated IL-10 responses at birth were associated with a significantly higher risk ofP. falciparuminfection in infancy (P< 0.05). Neonatal and infant intracellular TLR-mediated cytokine responses are conditioned byin uteroexposure through PAM late in pregnancy. Enhanced TLR-mediated IL-10 responses at birth are associated with an increased risk ofP. falciparuminfection, suggesting a compromised ability to combat infection in early life.

scholarly journals Specific Human and Candida Cellular Interactions Lead to Controlled or Persistent Infection Outcomes during Granuloma-Like Formation

2016 ◽  
Vol 85 (1) ◽  
Author(s):  
Barbara Misme-Aucouturier ◽  
Marjorie Albassier ◽  
Nidia Alvarez-Rueda ◽  
Patrice Le Pape
Keyword(s):  
Immune Cells ◽  
Immune Cell ◽  
Human Peripheral Blood ◽  
Cell Interaction ◽  
Cellular Interactions ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Tnf Α ◽  
Ifn Γ

ABSTRACT A delayed type of multicellular process could be crucial during chronic candidiasis in determining the course of infection. This reaction, consisting of organized immune cells surrounding the pathogen, initiates an inflammatory response to avoid fungal dissemination. The goal of the present study was to examine, at an in vitro cellular scale, Candida and human immune cell interaction dynamics during a long-term period. By challenging human peripheral blood immune cells from 10 healthy donors with 32 Candida albicans and non-albicans (C. glabrata, C. tropicalis, C. parapsilosis, C. dubliniensis, C. lusitaniae, C. krusei, and C. kefyr) clinical isolates, we showed that Candida spp. induced the formation of granuloma-like structures within 6 days after challenge, but their sizes and the respective fungal burdens differed according to the Candida species. These two parameters are positively correlated. Phenotypic characteristics, such as hypha formation and higher axenic growth rate, seem to contribute to yeast persistence within granuloma-like structures. We showed an interindividual variability of the human response against Candida spp. Higher proportions of neutrophils and elevated CD4+/CD8+ T cell ratios during the first days after challenge were correlated with early production of gamma interferon (IFN-γ) and associated with controlled infection. In contrast, the persistence of Candida could result from upregulation of proinflammatory cytokines such as interleukin-6 (IL-6), IFN-γ, and tumor necrosis factor alpha (TNF-α) and a poor anti-inflammatory negative feedback (IL-10). Importantly, regulatory subsets of NK cells and CD4lo CD8hi doubly positive (DP) lymphocytes at late stage infiltrate granuloma-like structures and could correlate with the IL-10 and TNF-α production. These data offer a base frame to explain cellular events that guide infection control or fungal persistence.

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