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Anti-insulin Antibodies Type 1 Diabetes

The Importance Of Anti-insulin Antibody In Patients With Type 1 Diabetes Mellitus Treated With Continuous Subcutaneous Insulin Infusion Or Multiple Daily Insulin Injections Therapy.

The Importance Of Anti-insulin Antibody In Patients With Type 1 Diabetes Mellitus Treated With Continuous Subcutaneous Insulin Infusion Or Multiple Daily Insulin Injections Therapy.

Abstract To investigate the influence of two insulin administration modalities, continuous subcutaneous insulin infusion (CSII) and multiple daily insulin injections (MDI) therapy with insulin analogues, on the development of insulin antibodies (IAs) in patients with type 1 diabetes mellitus and to assess the impact of IAs on glucose control and hypoglycaemia. 96 patients with type 1 diabetes mellitus treated with CSII (n = 48) or MDI (n = 48) were included in the study. Age, duration of diabetes, A1c, preprandial and postprandial blood glucose and hypoglycaemic events were compared between IA positive and negative patients. IA levels were higher in the CSII group (% 24.6 ± 14.2) than the MDI group (% 13.2 ± 9.9). Duration of diabetes and age were not associated with IA positiveness. While A1c, preprandial blood glucose and the frequency of hypoglycaemic events were similar in two groups, postprandial blood glucose was lower in IA positive group (P = 0.03). Patients with type 1 diabetes mellitus treated with CSII with insulin analogues had higher IA levels when compared to MDI therapy. However, the development of IAs did not impair the glycaemic control. Continue reading >>

Pro-insulin; A “primary” Target Of Autoantibodies In Type 1 Diabetes

Pro-insulin; A “primary” Target Of Autoantibodies In Type 1 Diabetes

Insulin autoantibodies (IAA) were first convincingly demonstrated by Palmer and co-workers in 1983. These autoantibodies appear prior to insulin treatment and are present in approximately 70% of children and adolescents at the diagnosis of type 1 diabetes. The levels of IAA show a strong inverse correlation with age, being found in more than 90% of children under the age of 5 years at diagnosis. The early appearance of IAA makes them particularly useful for diabetes prediction in young children. Induction of insulin antibodies to exogenous insulin means that IAA measurement is no longer informative once insulin therapy has been given for more than 2 weeks. Of the major islet antigens, proinsulin and glutamate decarboxylase (GAD) are currently the best candidates as primary autoantigens; i.e. those that could play a role in the initiation of the autoimmune response that leads to beta cell destruction and type 1 diabetes. Proinsulin is favoured by many, since autoantibodies to insulin are often the first to be detected in young children at increased genetic risk of type 1 diabetes. Proinsulin, unlike GAD is expressed almost exclusively in beta cells, which is consonant with the specific targeting of beta cells by T-cells infiltrating the pancreatic islets. The very high frequency of insulin autoantibodies (IAA) found in young children at diabetes onset shows that loss of tolerance to proinsulin is common in those who progress rapidly [1][2]. Insulin autoantibodies are also found in the non-obese diabetic (NOD) mouse model of spontaneous autoimmune diabetes [3], which further supports a role for proinsulin as a primary autoantigen. Age effects Birth cohort studies have shown that IAA can be detected from 6 months of age in children at increased genetic risk of type 1 diabe Continue reading >>

Autoantibodies Against Islet Cells (ica), Gad, Ia2, Insulin

Autoantibodies Against Islet Cells (ica), Gad, Ia2, Insulin

Detection of antibodies against islet cells of the pancreas (ICA). Indication: Type I diabetes mellitus, differentiation between late manifestation of type 1 diabetes mellitus (latent autoimmune diabetes in adulthood, LADA) from type 2 diabetes. For a reliable determination of antibodies against islet cells an extended incubation time of 18 hours for the patient serum must be observed. The incubation time may be reduced to 2 hours but this will lead to a decrease in the sensitivity of the antibody detection test. Standardised control with JDF units available (order number CA 1021-0101-1). With indirect immunofluorescence autoantibodies against pancreas islets (ICA) can be detected in 80% of patients with new-onset diabetes type 1. Characteristic target antigens of ICA are the enzyme glutamic acid decarboxylase (GAD) and tyrosine phosphatase (IA2). This BIOCHIP can be supplemented by further substrates, e.g., primate cerebellum for detection of autoantibodies against GAD. The use of small BIOCHIPs (1 x 1 mm) considerably facilitates the microscopic evaluation (order number FA 1020-1). The BIOCHIPS are virtually completely visible in the field of view, simplifying the location of the islet cells and, particularly for negative samples, eliminating the need for time-intensive examination. Continue reading >>

The Importance Of Anti-insulin Antibody In Patients With Type 1 Diabetes Mellitus Treated With Continuous Subcutaneous Insulin Infusion Or Multiple Daily Insulin Injections Therapy

The Importance Of Anti-insulin Antibody In Patients With Type 1 Diabetes Mellitus Treated With Continuous Subcutaneous Insulin Infusion Or Multiple Daily Insulin Injections Therapy

Abstract To investigate the influence of two insulin administration modalities, continuous subcutaneous insulin infusion (CSII) and multiple daily insulin injections (MDI) therapy with insulin analogues, on the development of insulin antibodies (IAs) in patients with type 1 diabetes mellitus and to assess the impact of IAs on glucose control and hypoglycaemia. 96 patients with type 1 diabetes mellitus treated with CSII (n = 48) or MDI (n = 48) were included in the study. Age, duration of diabetes, A1c, preprandial and postprandial blood glucose and hypoglycaemic events were compared between IA positive and negative patients. IA levels were higher in the CSII group (% 24.6 ± 14.2) than the MDI group (% 13.2 ± 9.9). Duration of diabetes and age were not associated with IA positiveness. While A1c, preprandial blood glucose and the frequency of hypoglycaemic events were similar in two groups, postprandial blood glucose was lower in IA positive group (P = 0.03). Patients with type 1 diabetes mellitus treated with CSII with insulin analogues had higher IA levels when compared to MDI therapy. However, the development of IAs did not impair the glycaemic control. Continue reading >>

The Importance Of Anti-insulin Antibody In Patients With Type 1 Diabetes Mellitus Treated With Continuous Subcutaneous Insulin Infusion Or Multiple Daily Insulin Injections Therapy

The Importance Of Anti-insulin Antibody In Patients With Type 1 Diabetes Mellitus Treated With Continuous Subcutaneous Insulin Infusion Or Multiple Daily Insulin Injections Therapy

Abstract To investigate the influence of two insulin administration modalities, continuous subcutaneous insulin infusion (CSII) and multiple daily insulin injections (MDI) therapy with insulin analogues, on the development of insulin antibodies (IAs) in patients with type 1 diabetes mellitus and to assess the impact of IAs on glucose control and hypoglycaemia. 96 patients with type 1 diabetes mellitus treated with CSII (n = 48) or MDI (n = 48) were included in the study. Age, duration of diabetes, A1c, preprandial and postprandial blood glucose and hypoglycaemic events were compared between IA positive and negative patients. IA levels were higher in the CSII group (% 24.6 ± 14.2) than the MDI group (% 13.2 ± 9.9). Duration of diabetes and age were not associated with IA positiveness. While A1c, preprandial blood glucose and the frequency of hypoglycaemic events were similar in two groups, postprandial blood glucose was lower in IA positive group (P = 0.03). Patients with type 1 diabetes mellitus treated with CSII with insulin analogues had higher IA levels when compared to MDI therapy. However, the development of IAs did not impair the glycaemic control. Received: 5 January 2010 / Accepted: 31 August 2010 / Published online: 15 September 2010 A1c (%) 7.4 ±1.6 7.9 ±2 0.17 Duration of CSII therapy (years) 5.7 ±4.4 4.1 ±3.3 0.37 of the prolonging duration of insulin action [24,28,29]. postprandial hyperglycaemia [30,31] and average glyca- emia [12,13,32], but most of the others showed no cor- measured as A1c [14–17,29,33–37] or average glycaemia between IAs and decreasing in insulin dosage [13–15,17, 33,35,39,41]. In our study, total daily insulin dose was reports [44–46]. However, it was not supported by the studies of large populations [15,29,35,37,47]. In Continue reading >>

Immunological Hypoglycemia Associated With Insulin Antibodies Induced By Exogenous Insulin In 11 Chinese Patients With Diabetes

Immunological Hypoglycemia Associated With Insulin Antibodies Induced By Exogenous Insulin In 11 Chinese Patients With Diabetes

Journal of Diabetes Research Volume 2015 (2015), Article ID 746271, 9 pages Department of Endocrinology and Metabolism, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, China Academic Editor: Mitsuhiko Noda Copyright © 2015 Heng Quan et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Aims. To investigate the characteristics of immunological hypoglycemia associated with insulin antibodies (IAbs) induced by exogenous insulin in Chinese patients with diabetes. Methods. The clinical data of patients with immunological hypoglycemia due to IAbs were retrospectively analyzed by screening patients with diabetes discharged from West China Hospital from 2007 to 2013. Results. A total of 11 patients (eight men and three women) were identified. Insulin-C-peptide separation was found in all patients via insulin and C-peptide release test. Previous insulin use was ceased after admission and was switched to oral hypoglycemic agents (OHAs) (8/11), lifestyle modification only (2/11), or regular human insulin (1/11). Hypoglycemia was ameliorated after a median of 20 days (interquartile range [IQR], 11–40), while IAbs turned negative after a median of 17 months (IQR, 4–19), and serum immunoreactive insulin (IRI) levels dropped substantially after a median of 22 months (IQR, 9–32) in these cases. Conclusions. In insulin-treated patients with unexpected and refractory hypoglycemia even after insulin therapy was gradually reduced or even withdrawn, IAbs induced by exogenous insulin should be considered, and insulin withdrawal might be promptly needed. The course of immunological hypoglycemia was Continue reading >>

Islet Autoantibodies And Type 1 Diabetes: Does The Evidence Support Screening?

Islet Autoantibodies And Type 1 Diabetes: Does The Evidence Support Screening?

Type 1 diabetes (T1D)3 is a chronic progressive autoimmune disorder with complex polygenic susceptibility, usually associated with certain HLA alleles (IDDM1 locus). Environmental factors, which are poorly defined, also contribute to the pathogenesis. T1D is characterized by lymphocyte infiltration into the islets of Langerhans in the pancreas, leading to inflammation and selective destruction of the insulin-producing β-cells, resulting in hyperglycemia (1). Patients with T1D fail to produce insulin and are dependent on exogenous insulin to maintain life. Although it is considerably less common than type 2 diabetes, the worldwide prevalence of T1D is increasing by approximately 3% per annum. The incidence varies widely among countries. In Americans under the age of 20 years, the prevalence of T1D rose by 23% between 2001 and 2009, and >30 000 people are diagnosed annually in the US with T1D. Progression to T1D is typically marked by the presence of islet-specific autoantibodies in the serum. In humans, autoantibodies are present months to years before disease onset, and a similar trend is seen in the nonobese diabetic (NOD) mouse model of autoimmune diabetes (2). The rate of T1D development varies among individuals, possibly due to non-HLA genetic factors and/or environmental factors beyond the initial trigger. Most of the current information on the pathogenesis of T1D from the initial triggers to the final effector stages of β-cell destruction has been derived from animal models that mimic the human disease (3). T lymphocytes are central determinants for β-cell destruction in T1D. Nevertheless, autoantibodies and B lymphocytes are components of some autoimmune diseases and may contribute to the pathogenesis of T1D. Multiple studies have documented the role of autoan Continue reading >>

Anti-insulin Antibodies And Retinopathy In Juvenile Onset Type-1 Diabetes

Anti-insulin Antibodies And Retinopathy In Juvenile Onset Type-1 Diabetes

Dr. Rajendra Prasad Centre for Ophthalmic Sciences, Department of Medicine, Department of Anatomy, All Institute of Medical Sciences, New Delhi, India Correspondence Address: K Sharma Department of Neuro-Ophthalmology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Post Box 375, Lucknow - 226001 India Source of Support: None, Conflict of Interest: None PMID: 1810880 Juvenile diabetics have severe loss of beta cell function and require replacement therapy with insulin. Insulin antigenicity can produce anti-insulin antibodies resulting in allergic reactions and insulin resistance. The role of insulin-anti-insulin antibody complexes in the development and progress of chronic diabetic complications like microangiopathy is not very clear. In the present study, there was statistically a significant trend of higher insulin antibody binding levels in IDDM patients who developed retinopathy. Though there was a trend of higher insulin antibody in IDDM patients with retinopathy, there was no association between insulin antibody and HLA antigen which some authors have reported. How to cite this article: Sharma K, Khosla P K, Tiwari H K, Sharma R K, Bajaj J S. Anti-insulin antibodies and retinopathy in juvenile onset type-1 diabetes. Indian J Ophthalmol 1991;39:174-5 Juvenile diabetics have severe loss of beta cell function and require replacement therapy with insulin. Insulin antigenicity can produce anti-insulin antibodies resulting in allergic reactions [1] and insulin resistance [2] The role of insulin-anti-insulin antibody complexes in the development and progress of chronic diabetic complications like microangiopathy is not very clear. The present study investigates the relationship between anti-insulin antibody and retinopathy in insulin dependent Continue reading >>

Anti-insulin Antibody Test

Anti-insulin Antibody Test

Insulin antibodies - serum; Insulin Ab test; Insulin resistance - insulin antibodies; Diabetes - insulin antibodies The anti-insulin antibody test checks to see if your body has produced antibodies against insulin. Antibodies are proteins the body produces to protect itself when it detects anything "foreign," such as a virus or transplanted organ. How the Test is Performed How to Prepare for the Test No special preparation is necessary. How the Test will Feel When the needle is inserted to draw blood, some people feel moderate pain. Others feel only a prick or stinging. Afterward, there may be some throbbing or a slight bruise. This soon goes away. Why the Test is Performed This test may be performed if: Normal Results Normally, there are no antibodies against insulin in your blood. Normal value ranges may vary slightly among different laboratories. Some labs use different measurements or test different samples. Talk to your health care provider about the meaning of your specific test results. What Abnormal Results Mean If you have IgG and IgM antibodies against insulin, your body reacts as if the insulin in your body is a foreign protein that needs to be removed. This may make insulin less effective, or not effective at all. This is because the antibody prevents the insulin from working the right way in your cells. As a result, your blood sugar can be unusually high. The antibodies can also prolong the effect of insulin by releasing some insulin long after your meal has been absorbed. This can put you at risk for low blood sugar. If the test shows a high level of IgE antibody against insulin, your body has developed an allergic response to the insulin. This could put you at risk for skin reactions where you inject insulin. You can also develop more severe reactions tha Continue reading >>

Test Id: Inab Insulin Antibodies, Serum

Test Id: Inab Insulin Antibodies, Serum

Predicting the future development of type 1 diabetes in asymptomatic children, adolescents, and young adults, when used in conjunction with family history, HLA-typing, and other autoantibodies, including GD65S/81596 Glutamic Acid Decarboxylase (GAD65) Antibody Assay, Serum and islet cell antigen 2 (IA-2) antibodies Differential diagnosis of type 1 versus type 2 diabetes Evaluating diabetics with insulin resistance in patients with established diabetes (type 1 or type 2) Investigation of hypoglycemia in nondiabetic subjects The onset of autoimmune diabetes mellitus (type 1 diabetes mellitus) is preceded (and accompanied) by the appearance of autoantibodies to a variety of pancreatic islet cell antigens in serum, including insulin. The level of these autoantibodies is generally low and may even fall during follow-up. In genetically predisposed, but disease-free, individuals (first degree relatives of patients with type 1 diabetes or individuals with permissive HLA alleles), detection of multiple islet cell autoantibodies is a strong predictor for subsequent development of type I diabetes. Once type 1 diabetes has become fully manifest, insulin autoantibody levels usually fall to low or undetectable levels. However, after insulin therapy is initiated, autoantibody production may recur as a memory response. Insulin autoantibody production is more common when therapeutic insulin of animal origin is used (rarely used in contemporary practice). Larger therapeutic doses may be required because of antibody-induced insulin resistance. Insulin antibodies may be found in nondiabetic individuals complaining of hypoglycemic attacks. In this setting their presence can be an indicator of "factitious hypoglycemia" due to the surreptitious injection of insulin, rather than to a clinical Continue reading >>

Anti-insulin Receptor Antibodies Related To Hypoglycemia In A Previously Diabetic Patient

Anti-insulin Receptor Antibodies Related To Hypoglycemia In A Previously Diabetic Patient

We report the case of a 47-year-old woman who was referred to our unit for hypoglycemia. She was diagnosed with diabetes at age 30 years and was previously treated with metformin, sulfonylureas, and glucagon-like peptide 1 agonists. Despite interruption of her treatments, she had for 1 month clinical features evoking hypoglycemic spells, with adrenergic and neuroglycopenic symptoms subsiding after glucose administration. Her BMI was 23.8 kg/m2. She had axillary acanthosis nigricans but no lipodystrophy. Continuous glucose monitoring showed hypoglycemia down to 2.1 mmol/L, mostly during fasting periods, and hyperglycemia up to 13.7 mmol/L in the absence of any treatment. HbA1c was 15%. During a fasting test, venous glucose concentration dropped to 2.5 mmol/L with concomitant low serum levels of C-peptide, insulinemia, and proinsulinemia: <1.40, <3, and 3.6 pmol/L, respectively (reference ranges in healthy subjects 17.8–173, 370–1,470, and 3.3–28 pmol/L, respectively). Plasma levels of cortisol, somatostatin, IGF-1, and Western blot analysis of IGF-2 and its precursors were normal. Thoraco-abdominal computed tomography and whole-body F-18-fluorodeoxyglucose positron emission tomography scan did not reveal any abnormality. We evaluated the presence of anti-insulin receptor antibodies (AIRAs) using a radioreceptor assay (1). The patient’s total serum and purified immunoglobulin fractions inhibited the binding of a tracer concentration of radiolabeled insulin, consistent with significant titers of AIRAs. Patient’s serum and purified immunoglobulins activated proximal (tyrosine phosphorylation of insulin receptor β-subunit and insulin receptor substrate-1) and distal (phosphorylation of Akt/PKB) insulin-signaling pathways in vitro in a dose-dependant manner, mimick Continue reading >>

Autoantibodies In Type 1 Diabetes

Autoantibodies In Type 1 Diabetes

Diabetes mellitus is a disorder characterized by hyperglycemia in both the fasting and post-prandial states. The two most common forms of diabetes mellitus, type 1 and type 2 (previously called juvenile-onset and adult-onset, respectively), comprise the vast majority of cases. Type 1 diabetes (T1DM) has been shown to be a disease characterized by immune-mediated destruction of the insulin-secreting cells of the pancreas; it comprises the majority of cases of diabetes seen in childhood and approximately, 5–10% of all cases of diabetes mellitus in the USA and perhaps accounts for an even higher percentage in those nations with lower rates of obesity. The process of beta-cell destruction, marked by the production of autoantibodies to the beta-cell, occurs over many years and ultimately results in metabolic abnormalities first manifested as impaired glucose tolerance and then progressing to symptomatic hyperglycemia. It has been reported that approximately 50% of the genetic risk for T1DM can be attributed to the HLA region. The highest risk HLA-DR3/4 DQ8 genotype has been shown to be highly associated with beta-cell autoimmunity. The first antibodies described in association with the development of T1DM were islet cell autoantibodies (ICA). Subsequently, antibodies to insulin (IAA), glutamic acid decarboxylase (GAA or GAD) and protein tyrosine phosphatase (IA2 or ICA512) have all been defined. The number of antibodies, rather than the individual antibody, is thought to be most predictive of progression to overt diabetes. Continue reading >>

Prediction Of Type 1 Diabetes Mellitus

Prediction Of Type 1 Diabetes Mellitus

INTRODUCTION Type 1 diabetes mellitus is an autoimmune disease arising through a complex interaction of both genetic and immunologic factors [1]. The increase in understanding of the pathogenesis of type 1 diabetes mellitus has made it possible to consider intervention to delay the autoimmune disease process in an attempt to delay or even prevent the onset of hyperglycemia (figure 1). Although no successful strategy for the prevention of type 1 diabetes has yet been identified, subjects who are at high risk for type 1 diabetes can be identified using a combination of immune, genetic, and metabolic markers. This topic will review the use of genetic, immunologic, and metabolic markers to predict type 1 diabetes. The definition, epidemiology, pathogenesis, and prevention of type 1 diabetes are discussed in detail elsewhere. (See "Classification of diabetes mellitus and genetic diabetic syndromes" and "Epidemiology, presentation, and diagnosis of type 1 diabetes mellitus in children and adolescents" and "Pathogenesis of type 1 diabetes mellitus" and "Prevention of type 1 diabetes mellitus".) OVERVIEW OF TYPE 1 DIABETES Type 1 diabetes mellitus is an autoimmune disease arising through a complex interaction of both genetic and immunologic factors [1]. It is usually caused by an immune-mediated destruction of the insulin-producing beta cells in the islets of Langerhans [2]. Immune-mediated type 1 diabetes is called type 1A to distinguish it from some rarer cases in which an autoimmune etiology cannot be determined (type 1B); the latter are said to be idiopathic [3]. The term type 1 diabetes used here refers to type 1A, or autoimmune diabetes. (See "Classification of diabetes mellitus and genetic diabetic syndromes".) Genetic – Type 1 diabetes occurs in genetically susceptibl Continue reading >>

Autoantibodies In Diabetes

Autoantibodies In Diabetes

Islet cell autoantibodies are strongly associated with the development of type 1 diabetes. The appearance of autoantibodies to one or several of the autoantigens—GAD65, IA-2, or insulin—signals an autoimmune pathogenesis of β-cell killing. A β-cell attack may be best reflected by the emergence of autoantibodies dependent on the genotype risk factors, isotype, and subtype of the autoantibodies as well as their epitope specificity. It is speculated that progression to β-cell loss and clinical onset of type 1 diabetes is reflected in a developing pattern of epitope-specific autoantibodies. Although the appearance of autoantibodies does not follow a distinct pattern, the presence of multiple autoantibodies has the highest positive predictive value for type 1 diabetes. In the absence of reliable T-cell tests, dissection of autoantibody responses in subjects of genetic risk should prove useful in identifying triggers of islet autoimmunity by examining seroconversion and maturation of the autoantibody response that may mark time to onset of type 1 diabetes. The complexity of the disease process is exemplified by multiple clinical phenotypes, including autoimmune diabetes masquerading as type 2 diabetes in youth and adults. Autoantibodies may also provide prognostic information in clinically heterogeneous patient populations when examined longitudinally. ISLET CELL AUTOANTIBODIES Autoantibodies are created by the immune system when it fails to distinguish between “self” and “nonself.” It is normally trained to recognize and ignore the body’s own cells and to not overreact to nonthreatening substances in the environment. At the same time, the immune system must be able to create antibodies that target and fight specific foreign substances that do pose a threat. Continue reading >>

Gad Antibodies And Diabetes

Gad Antibodies And Diabetes

What Are GAD Antibodies? Your pancreas needs the enzyme glutamic acid decarboxylase (GAD) to function normally. Antibodies that target this enzyme are called GAD antibodies. An antibody is a protein that your immune system uses to attack foreign objects. Those foreign objects are often potentially harmful, such as viruses or bacteria. Sometimes, the immune system makes antibodies that mistakenly attack normal, cells that aren’t harmful. When that happens, it’s called an autoimmune disorder. About 70 percent of people with type 1 diabetes have GAD antibodies in their blood. Once other diagnostic tools, such as glucose tolerance tests, indicate you have diabetes, the next step is to determine if it’s type 1 or 2. This is important because although they have a lot in common, these are two distinct conditions. Each requires a specific approach to management and treatment. Your doctor may order a GAD test to learn more. You might also hear it called GADA or anti-GAD. Instead of a specific GAD test, you can also have an antibody panel to test for GAD and other antibodies as well. Other antibodies associated with type 1 diabetes include: islet cell cytoplasmic autoantibodies (ICAs) insulinoma-associated-2 autoantibodies (IA-2As) insulin autoantibodies (IAAs), which are more common in children than adults All of these tests are done with the use of a simple blood test. You won’t need to fast or do anything else to prepare. A healthcare professional will take blood from a vein in your arm and send it to a laboratory for analysis. If GAD or any of these other antibodies are found, it means you most likely have type 1 diabetes. If no GAD antibodies are found, you probably have type 2. Learn more: Type 1 diabetes: Causes, symptoms, and more » Type 1 diabetes is the result Continue reading >>

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