Iron Metabolism

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Which trace element is essential for oxygen transport and participation in biochemical processes?

Iron

What are the common oxidation states of iron?

Ferrous (Fe2+) and ferric (Fe3+)

What can free iron catalyze, resulting in reactive and damaging free radicals?

Oxidative reactions

Which proteins bind iron for storage and transport?

Transferrin, Ferritin, Lactoferrin

Where is the majority of total body iron found in human adults?

In the heme moiety of erythrocytes (haemoglobin)

What are the dietary sources of iron?

Liver, meat, egg yolk, green leafy vegetables and whole grain cereals

In which form does iron occur in animal sources like meat, fish, and poultry?

Heme iron

What is the total body iron content in human adults?

3-4 g

What percentage of total body iron is found in mobilizable 'ferritin' stores?

20-25%

What is the main function of iron binding proteins?

To hold iron for functional activity or for its storage and transport

What is the primary function of iron in the body?

To transport oxygen

Which type of iron is most easily absorbed by the body?

Heme iron

Where is iron stored in the body when it is not immediately needed?

Liver and spleen

What is the protein responsible for transporting iron throughout the body?

Transferrin

Which protein is responsible for storing oxygen in muscle cells?

Myoglobin

What is the name of the storage protein that releases iron when the body needs it?

Ferritin

What is the term for a condition characterized by a lack of iron in the body?

Iron deficiency anemia

What is the term for a condition characterized by an excess of iron in the body?

Iron overload

Which foods are good sources of iron?

All of the above

What is the role of iron in energy production?

It produces ATP

Which vitamin can improve the absorption of non-heme iron?

Vitamin C

What is the function of transferrin in the body?

Transferrin transports iron to the cells

Which protein is responsible for storing iron when it is not immediately needed?

Ferritin

What is the main function of hemoglobin in the body?

Carrying oxygen from the lungs to the tissues

What is the main function of myoglobin in the body?

Storing oxygen in muscle cells

What are the symptoms of iron deficiency anemia?

Fatigue, weakness, and shortness of breath

What can happen if the body has too much iron?

Damage to the liver, heart, and other organs

What is the term for a condition characterized by a lack of iron in the body?

Iron deficiency anemia

What is the role of iron in producing hemoglobin and myoglobin?

Iron binds to the proteins to enable oxygen transport

What organs are primarily affected by iron overload?

Liver and heart

Which type of iron is easily absorbed by the body?

Heme iron

What are good dietary sources of iron?

All of the above

Which group of people is at a higher risk of iron deficiency?

Vegetarians

What is the main function of iron in the body?

All of the above

What is the term for a condition characterized by a lack of iron in the body?

Iron deficiency anemia

What is the role of transferrin in the body?

Transporting iron throughout the body

What is the function of myoglobin in the body?

Storing iron in muscle cells

Which organ is the primary physiologic source of reserve iron in the body?

Liver

How much iron is contained in the hemoglobin needed to carry oxygen through the blood?

4 g

How is iron primarily excreted from the body?

Through sloughing of tissues

What is the term for a condition characterized by a lack of iron in the body?

Iron deficiency anemia

What is the main cause of iron deficiency?

Increased demand for iron

What is the main cause of iron overload?

Excessive iron absorption

What is the management approach for severe iron deficiency?

Therapeutic phlebotomy

Which part of the small intestine is responsible for the largest amount of iron absorption?

Duodenum

What is the enzyme responsible for reducing ferric iron to ferrous iron in the small intestine?

Dcytb

Which protein transports iron across the enterocyte's cell membrane?

DMT1

Which substance enhances the absorption of non-heme iron?

Ascorbic acid

What is the main protein involved in the storage of iron?

Ferritin

What is the most convenient laboratory test to estimate iron stores in the body?

Serum ferritin

What is the normal transferrin saturation range in the body?

20-30%

Which therapy forms a complex with iron and is commonly used to eliminate iron via urine?

Desferrioxamine

In individuals overloaded with iron, small amounts of free serum iron can be available due to what factor?

Saturation of serum transferrin

Under iron overload conditions, which microorganisms can become pathogenic due to their iron dependency?

Pathogenic microorganisms

Which marine bacteria can cause a rapidly progressive infection in iron overloaded individuals after ingestion of contaminated food?

Vibrio vulnificus

What is the outcome of a rapidly progressive Vibrio vulnificus infection in iron overloaded individuals?

Death within 24 hours

Which protein can be close to saturation in individuals overloaded with iron?

Serum transferrin

Which protein is responsible for storing iron when it is not immediately needed?

Ferritin

Which microorganism can become pathogenic under iron overload conditions?

Vibrio vulnificus

What is the cause of death in iron overloaded individuals infected with Vibrio vulnificus?

Rapidly progressive infection

What are the two broad categories of disorders of iron metabolism?

Iron Deficiency and Iron Overload

What are the causes of iron deficiency?

Increased demand for iron, increased loss of iron, nutritional deficiency, inability to absorb iron, damage to the intestinal lining, and inflammation

What are the symptoms of iron deficiency anemia?

Microcytic and hypochromic red blood cells, low hemoglobin levels, and low serum ferritin values

What is the management approach for iron deficiency?

Examination for the cause and source of bleeding, iron supplementation, and transfusion with packed red blood cells if the deficiency is severe

What are the causes of iron overload?

Genetic mutations, secondary factors such as blood transfusions or overdosing on iron pills or injections

What are the complications of iron overload?

Cirrhosis and liver tumors, diabetes mellitus, and cardiac failure

How is iron overload managed?

Dietary changes, therapeutic phlebotomy (periodic withdrawals of large amounts of blood), and avoiding iron supplements, iron-rich foods, alcohol, and raw or undercooked fish and shellfish.

What are the dietary sources of iron?

Liver, meat, egg yolk, green leafy vegetables, and whole grain cereals.

What is the main function of iron?

Key role in synthesis of oxygen transporting and oxygen storage proteins. Formation of heme enzymes and other iron-containing enzymes involved in electron transfer and oxidation-reductions. DNA synthesis and repair.

What is the difference between heme iron and non-heme iron?

Heme iron is found in animal sources like meat, fish, and poultry, and is easily absorbed (high bioavailability). Non-heme iron is found in plant sources like dried beans, peas, fruits, and vegetables, and has relatively lower bioavailability.

Who are at higher risk of iron deficiency?

Vegetarians.

What are the main functions of iron?

Key role in synthesis of oxygen transporting and oxygen storage proteins. Formation of heme enzymes and other iron-containing enzymes involved in electron transfer and oxidation-reductions. DNA synthesis and repair.

What is the function of heme iron?

Heme iron is responsible for synthesis of oxygen transporting and oxygen storage proteins.

What is the function of non-heme iron?

Non-heme iron is involved in electron transfer and oxidation-reductions, as well as DNA synthesis and repair.

What is the purpose of iron chelating therapy?

To eliminate excess iron from the body

Which therapy forms a complex with iron and is commonly used to eliminate iron via urine?

Desferrioxamine

What role does transferrin play in iron overload and infection?

Transferrin can be close to saturation, making small amounts of free serum iron available

Under what circumstances can usually nonpathogenic microorganisms become pathogenic?

When an individual is overloaded with iron

Which marine bacteria can cause a rapidly progressive infection in iron overloaded individuals after ingestion of contaminated food?

Vibrio vulnificus

What is the outcome of a rapidly progressive Vibrio vulnificus infection in iron overloaded individuals?

Death within 24 hours

How is iron primarily excreted from the body?

Via urine

What is the management approach for severe iron deficiency?

Iron supplementation

What are good dietary sources of iron?

Meat, fish, poultry

What is the major site of iron absorption in the body?

The small intestine (largest amount absorbed in the duodenum by enterocytes of the duodenal lining)

What are the two forms of iron that can enter the mucosal cell in the small intestine?

The free ion (ferrous form) or as heme iron (iron is split off from the porphyrin ring in the mucosal cytoplasm)

What enzyme reduces ferric iron (Fe3+) to ferrous iron (Fe2+) in the small intestine?

Ferric reductase enzyme on the enterocytes’ brush border, duodenal cytochrome B (Dcytb)

What protein transports iron across the enterocyte’s cell membrane into the cell?

Divalent metal transporter 1 (DMT1)

What are the increasing factors that enhance iron absorption?

Ascorbic acid, HCl, iron deficiency

What are the inhibitory factors that reduce iron absorption?

Phytates (storage form of phosphates - abundant in cereals), tannins and other polyphenol compounds in fruits, tea coffee, red wine cocoa, achlorhydra GI disease, antacids, iron overload, gastric bypass surgery

What is the protein responsible for storing iron in intestinal lining cells?

Ferritin

What is the only known iron exporter in mammals?

Ferroportin

True or false: Iron from animal sources is more easily absorbed than iron from plant sources.

True

True or false: Vegetarians have a higher risk of iron deficiency.

True

True or false: Iron plays a key role in the synthesis of oxygen transporting and oxygen storage proteins.

True

True or false: Iron is involved in DNA synthesis and repair.

True

True or false: Heme iron is found in plant sources like dried beans and peas.

False

True or false: Iron deficiency can lead to anemia.

True

True or false: Iron overload can lead to organ damage.

True

True or false: Most of the iron in the body is contained in hemoglobin?

True

True or false: Iron is lost from the body through usual excretory routes?

False

True or false: Iron deficiency can be caused by increased demand for iron?

True

True or false: Iron overload can be caused by genetic mutations?

True

True or false: Hemochromatosis is more commonly seen in women than men?

False

True or false: Iron overload can lead to cirrhosis and liver tumors?

True

True or false: Therapeutic phlebotomy involves withdrawing small amounts of blood?

False

True or false: Iron is primarily absorbed in the small intestine.

True

True or false: Iron can enter the mucosal cell as either the free ion or as heme iron.

True

True or false: Phytates and polyphenol compounds inhibit iron absorption.

True

True or false: Hephaestin is a ferroxidase found mainly in the small intestine.

True

True or false: Transferrin is the protein involved in the transport of iron in the blood.

True

True or false: Serum ferritin is an indirect marker of total body iron stores.

True

True or false: Ferritin is the major protein involved in the storage of iron.

True

True or false: Iron chelating therapy forms a complex with iron and is commonly used to eliminate iron via urine?

True

True or false: Individuals overloaded with iron may have a close to saturation serum transferrin value, making small amounts of free serum iron available?

True

True or false: Microorganisms that are usually nonpathogenic can become pathogenic under iron overload conditions?

True

True or false: Vibrio vulnificus, a marine bacteria found in oysters and commercial shellfish, can cause a rapidly progressive infection in iron overloaded individuals?

True

True or false: Normal individuals consuming the same food are entirely free of symptoms when infected with Vibrio vulnificus?

True

True or false: Iron overload can lead to a rapidly progressive infection with death ensuing within 24 hours after ingestion of contaminated food?

True

True or false: Iron overload can lead to a rapidly progressive infection with death ensuing within 24 hours after ingestion of contaminated food?

True

True or false: Iron overload can lead to a rapidly progressive infection with death ensuing within 24 hours after ingestion of contaminated food?

True

True or false: Iron overload can lead to a rapidly progressive infection with death ensuing within 24 hours after ingestion of contaminated food?

True

Match the following types of iron with their bioavailability:

Heme iron = Easily absorbed (high bioavailability) Non-heme iron = Relatively lower bioavailability

Match the following sources of iron with their types:

Liver, meat, egg yolk, green leafy vegetables and whole grains cereals = Dietary Meat, fish and poultry = Animal sources Dried beans, peas fruits and vegetables = Plant sources

Match the following functions of iron with their descriptions:

Synthesis of oxygen transporting and oxygen storage proteins = Key role in oxygen transportation Formation of heme enzymes and other iron-containing enzymes = Involved in electron transfer and oxidation-reductions DNA synthesis and repair = Important for genetic processes

Match the following iron-related terms with their definitions:

Iron deficiency = Condition characterized by a lack of iron in the body Heme iron = Iron from animal sources which is easily absorbed Ferritin = Protein responsible for storing iron when it is not immediately needed Transferrin = Protein responsible for transporting iron throughout the body

Match the following iron-related conditions with their descriptions:

Iron overload = Can lead to cirrhosis and liver tumors Iron deficiency anemia = Caused by insufficient iron levels in the body Vibrio vulnificus infection in iron overloaded individuals = Can be rapidly progressive with high mortality

Match the following iron-related topics with their true or false statements:

Iron from animal sources is more easily absorbed than iron from plant sources = True Most of the iron in the body is contained in hemoglobin = True Hephaestin is a ferroxidase found mainly in the small intestine = True Heme iron is found in plant sources like dried beans and peas = False

Match the following iron-related enzymes with their functions:

Ferroportin = Only known iron exporter in mammals Hephaestin = Ferroxidase that oxidizes Fe2+ to Fe3+ Cytochrome P450 = Reduces ferric iron (Fe3+) to ferrous iron (Fe2+) in the small intestine

Match the following terms with their correct descriptions:

Iron Absorption = Major site of absorption is the small intestine Iron Transport = The protein involved in the transport of iron is transferrin Iron Storage = The major protein involved in the storage of iron is ferritin Iron Overload = Saturation above 50% of transferrin is indicative of this condition

Match the following factors with their effects on iron absorption:

Ascorbic acid = Increases iron absorption Phytates = Inhibits iron absorption Tannins = Inhibits iron absorption Iron deficiency = Increases synthesis of DMT1, Dcytb, and ferroportin

Match the following components with their roles in iron metabolism:

Dcytb = Reduces ferric iron (Fe3+) to ferrous (Fe2+) DMT1 = Transports iron across the enterocyte’s cell membrane Ferroportin = The only known iron exporter in mammals Hephaestin = Oxidizes Fe2+ to Fe3+

Match the following forms of iron with their correct descriptions:

Ferric Iron = Reduced to ferrous iron in the small intestine Heme Iron = Iron is split off from the porphyrin ring in the mucosal cytoplasm Non-Heme Iron = Inhibited by phytates and polyphenol compounds Transferrin-Bound Iron = Delivered mainly to bone marrow and liver

Match the following conditions with their effects on iron metabolism:

Iron Deficiency = Increases transferrin synthesis Inflammation = Less iron is absorbed to deprive bacteria of iron Achlorhydra = Causes decreased absorption of iron Liver Disease = May lead to increased transferrin saturation

Match the following proteins with their functions in iron metabolism:

Transferrin = Involved in the transport of iron in the blood Ferritin = The major protein involved in the storage of iron Hephaestin = Can oxidize Fe2+ to Fe3+ Apoferritin = Regulates iron absorption in response to the body’s needs

Match the following forms of iron with their correct descriptions:

Ferric Iron = Reduced to ferrous iron in the small intestine Heme Iron = Iron is split off from the porphyrin ring in the mucosal cytoplasm Non-Heme Iron = Inhibited by phytates and polyphenol compounds Transferrin-Bound Iron = Delivered mainly to bone marrow and liver

Match the following substances with their role in iron metabolism:

Desferrioxamine = Forms a complex with iron and is eliminated via urine Transferrin = Binds iron for transport Ferritin = Stores iron when it is not immediately needed Hephaestin = Ferroxidase found mainly in the small intestine

Match the following conditions with their characteristic features:

Iron overload = Serum transferrin value can be close to saturation, making small amounts of free serum iron available Iron deficiency = Lack of iron in the body Thalassemias = Bleeding is not an option Vibrio vulnificus infection in iron overloaded individuals = Rapidly progressive infection, with death ensuing within 24 h after ingestion of the meal

Match the following microorganisms with their characteristic features:

Vibrio vulnificus = Marine bacteria, found in a small percentage of oysters and commercial shellfish Nonpathogenic microorganisms = Iron dependent and cannot compete against partially saturated transferrin in the normal individual Pathogenic microorganisms in iron overloaded individuals = Usually nonpathogenic microorganisms that can now become pathogenic due to iron overload Microorganisms in normal individuals = Entirely free of symptoms after consuming the same food as iron overloaded individuals

Match the following terms with their definitions:

Iron chelating therapy = Use of Desferrioxamine to eliminate excess iron from the body Iron overload = Condition characterized by an excess of iron in the body Ferrioxamine = Complex formed between Desferrioxamine and iron Thalassemias = Conditions where bleeding is not an option

Match the following iron-related concepts with their characteristic features:

Iron absorption = Enhanced by factors such as vitamin C and acidic environment Iron excretion = Occurs via urine in iron chelating therapy Iron storage = Role of ferritin when iron is not immediately needed Iron transport = Role of transferrin

Match the following conditions with their potential complications:

Iron overload = Rapidly progressive infection with Vibrio vulnificus after ingestion of contaminated food Iron deficiency = Anemia Thalassemias = Complications arising when bleeding is not an option Infection in normal individuals = Entirely free of symptoms after consuming the same food as iron overloaded individuals

Match the following iron-related proteins with their functions:

Transferrin = Binds iron for transport Ferritin = Stores iron when it is not immediately needed Hephaestin = Ferroxidase found mainly in the small intestine Desferrioxamine = Forms a complex with iron for elimination

Match the following conditions with their characteristic symptoms:

Iron overload = No specific symptoms, but may lead to complications like infection Iron deficiency = Fatigue, weakness, shortness of breath Thalassemias = Complications when bleeding is not an option Vibrio vulnificus infection in iron overloaded individuals = Rapidly progressive infection, with death ensuing within 24 h after ingestion of the meal

Match the following iron-related complications with their associated conditions:

Rapidly progressive infection = Iron overload with Vibrio vulnificus infection Anemia = Iron deficiency Nonpathogenic microorganisms becoming pathogenic = Iron overload Lack of energy = Thalassemias

Match the following conditions with their corresponding iron status:

Iron Deficiency Anemia = Hemoglobin < 13 g/dl (male), 12 g/dl (female) Iron Overload = Iron content of the body can be elevated to values as high as 100 g in patients due to excessive absorption Iron Deficiency = The serum transferrin value (expressed as the total iron binding capacity) will be elevated with a serum iron saturation of less than 16 % Normal Iron Level = A loss of about 1 mg day–1 occurs in a healthy adult

Match the following conditions with their corresponding causes:

Iron Deficiency = Inability to absorb iron (use of acid reducing medications like proton pump inhibitors) Iron Overload = Overdosing on iron pills or injections

Match the following conditions with their corresponding management options:

Iron Deficiency = Management: a careful examination for the cause and source of bleeding Iron Overload = Therapeutic phlebotomy: Periodic withdrawals of large amounts of blood, where the iron is contained in the hemoglobin

Match the following conditions with their corresponding symptoms:

Iron Deficiency Anemia = Microscopic examination of blood shows characteristic microcytic (small in size) and hypochromic (under-pigmented) RBCs Iron Overload = The accumulation of iron in the liver, pancreas, and heart can lead to cirrhosis and liver tumors, diabetes mellitus, and cardiac failure respectively Iron Deficiency = Damage to the intestinal lining. (surgery involving the duodenum, which severely reduce the surface area available for absorption)

Match the following conditions with their corresponding facts:

Iron Deficiency = Functional or actual iron deficiency may be caused by Increased demand for iron, which the diet cannot accommodate Iron Overload = Iron overload also referred to as Hemochromatosis may be caused by; Genetic mutation (HFE gene) – associated with a marked inappropriate increase in iron absorption

Match the following conditions with their corresponding effects on the body:

Iron Deficiency Anemia = The liver produces more transferrin, presumably attempting to maximize use of the little iron that is available (thereby increasing overall binding capacity) Iron Overload = Often used to describe hemochromatosis because it can lead to darkening of the skin and hyperglycemia Iron Deficiency = Microscopic examination of blood shows characteristic microcytic (small in size) and hypochromic (under-pigmented) RBCs

Match the following conditions with their corresponding iron levels:

Iron Deficiency Anemia = Bone marrow aspiration will reveal no storage iron to be present and serum ferritin values are virtually zero Iron Overload = Iron content of the body can be elevated to values as high as 100 g in patients due to excessive absorption Iron Deficiency = The serum transferrin value (expressed as the total iron binding capacity) will be elevated with a serum iron saturation of less than 16 % Normal Iron Level = A loss of about 1 mg day–1 occurs in a healthy adult

Study Notes

Iron Metabolism and Functions

  • Iron functions include:
    • Synthesis of oxygen transporting and oxygen storage proteins
    • Formation of heme enzymes and other iron-containing enzymes
    • DNA synthesis and repair
  • Dietary sources of iron:
    • Animal sources (meat, fish, poultry) containing heme iron with high bioavailability
    • Plant sources (dried beans, peas, fruits, and vegetables) containing non-heme iron with relatively lower bioavailability
  • Vegetarians are at higher risk of iron deficiency due to lower bioavailability of non-heme iron

Iron Absorption

  • Major site of absorption: small intestine (duodenum)
  • Iron enters mucosal cells as free ion (ferrous form) or heme iron
  • Ferric reductase enzyme (duodenal cytochrome B) reduces ferric iron (Fe3+) to ferrous iron (Fe2+)
  • Divalent metal transporter 1 (DMT1) transports iron across the enterocyte's cell membrane
  • Factors increasing iron absorption: ascorbic acid, HCl
  • Factors inhibiting iron absorption: phytates, tannins, polyphenol compounds, achlorhydria, GI disease, antacids, iron overload, gastric bypass surgery

Iron Transport and Distribution

  • Protein involved in iron transport: transferrin (glycoprotein synthesized in liver)
  • Transferrin binds iron absorbed from the intestine and recycled from aging red blood cells
  • Transferrin binds to specific cell surface receptors to deliver iron mainly to bone marrow and liver
  • Distribution of iron:
    • 0.1% in plasma
    • 2.5 g in hemoglobin
    • Rest in ferritin complexes (bone marrow, liver, and spleen)

Iron Storage

  • Ferritin: major protein involved in iron storage
  • Hemosiderin: iron storage complex composed of partially digested ferritin and iron
  • Iron storage occurs in hepatocytes and reticuloendothelial cells
  • Serum ferritin concentrations correlate with total body iron stores
  • Serum ferritin is used as a diagnostic test for iron deficiency anemia

Iron Excretion

  • Iron is conserved and not readily lost from the body
  • "Excretion" occurs through the normal sloughing of tissues that are not reutilized (e.g., epidermis and gastrointestinal mucosal cells)
  • Loss of about 1 mg/day occurs in a healthy adult
  • Higher losses in premenopausal women (menses, parturition, etc.)

Disorders of Iron Metabolism

  • Two broad categories:
    • Iron Deficiency
    • Iron Overload

Iron Deficiency

  • Causes:
    • Increased demand for iron
    • Increased loss of iron (bleeding, excessive menstrual flow)
    • Nutritional deficiency (lack of dietary iron or consumption of foods that inhibit iron absorption)
    • Inability to absorb iron (use of acid-reducing medications)
    • Damage to the intestinal lining (surgery, inflammation)
  • Characteristics:
    • Serum transferrin value elevated with serum iron saturation < 16%
    • Liver produces more transferrin to maximize iron use
  • Management:
    • Careful examination for cause and source of bleeding
    • Supplementation with iron (oral ferrous sulfate tablets or IV iron therapy)
    • Transfusion with packed red blood cells may be indicated in severe cases

Iron Overload

  • Causes:
    • Genetic mutation (HFE gene) – hereditary hemochromatosis
    • Secondary factors (blood transfusions, iron supplements or injections) – secondary hemochromatosis
  • Characteristics:
    • Iron content of the body can be elevated to values as high as 100 g
    • Iron toxicity results when circulating iron exceeds transferrin availability
  • Management:
    • Dietary changes (avoiding iron-rich foods, alcohol, and vitamin C restriction)
    • Therapeutic phlebotomy: periodic withdrawals of large amounts of blood### Iron Chelating Therapy
  • Desferrioxamine is a commonly used iron chelating therapy that forms a complex with iron, called ferrioxamine, which is eliminated through urine.
  • This therapy is particularly useful in cases where bleeding is not an option, such as in thalassemias.

Iron Overload and Infection

  • Iron overload can lead to an increased risk of infection, as excess iron can make small amounts of free serum iron available.
  • Iron-dependent microorganisms, which are usually non-pathogenic, can become pathogenic in individuals with iron overload.
  • Iron overload can impair the body's ability to compete against partially saturated transferrin, allowing microorganisms to thrive.

Vibrio Vulnificus Infection

  • Vibrio vulnificus is a marine bacteria found in a small percentage of oysters and commercial shellfish.
  • Individuals with iron overload can develop a rapidly progressive infection with Vibrio vulnificus after consuming contaminated food.
  • This infection can be fatal, with death occurring within 24 hours after ingestion of the meal.
  • In contrast, normal individuals who consume the same food are typically free of symptoms.

Test your knowledge of iron metabolism with this quiz! Learn about the role of iron in oxygen transport and its participation in biochemical processes. Explore the different oxidation states of iron and how they contribute to energy metabolism.

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