Anti-Obesity Drugs

ANTI-OBESITY DRUGS

Q. 1 In morbid obesity BMI is greater than?
 A 30
 B 35
 C 40
 D 45
Q. 1 In morbid obesity BMI is greater than?
 A 30
 B 35
 C 40
 D 45
Ans. C

Explanation:

40 REF: Sabiston Textbook of Surgery, 18th ed chapter 17

Morbid obesity is defined as being either 100 lb above ideal body weight, twice ideal body weight, or a body mass index (BMI, measured as weight in kilograms divided by height in meters squared) of 40 kg/m2. The latter definition is more accepted internationally and has essentially replaced the former ones for all practical and scientific purposes.


Q. 2

Appetite is stimulated by all except

 A

Agouti related peptide

 B

Melanocyte concentrating hormone

 C

Melanocyte stimulating hormone

 D

Neuropeptide Y

Q. 2

Appetite is stimulated by all except

 A

Agouti related peptide

 B

Melanocyte concentrating hormone

 C

Melanocyte stimulating hormone

 D

Neuropeptide Y

Ans. C

Explanation:

Melanocyte stimulating hormone [Ref: Ganong 22/e, p 238t; Guyton physiology 11/e, p 869t; Harrison 17/e, p 255, 463, 464; Obesity: Mechanisms & Clinical Management by Robert H. Eckel 2003 – p 129]

a..Melanocyte stimulating hormone (a-MSH) depresses appetite by acting centrally on satiety centre.

Neurotransmitters & Hormones that influence feeding and satiety centres in the hypothalamus

Increase Feeding (Orexigenic)

Decrease Feeding (Anorexigenic)

Neuropeptide Y (NPY)

a-Melanocyte-stimulating hormone (a-MSH)

Agouti-related protein (AGRP)

Leptin

Melanin-concentrating hormone (MCH)

Serotonin

Orexins A and B

Norepinephrine

Endorphins

Corticotropin-releasing hormone (CRH)

Galanin (GAL)

Insulin

Amino acids (glutamate and 7-aminobutyric

Cholecystokinin (CCK)*

acid)

Glucagon-like peptide (GLP)

Cortisol

Cocaine- and amphetamine-regulated transcript (CART)

Ghrelin

Peptide YY (PYY)*

Growth hormone releasing hormone (GHRH)

Bombesin

*CCK & PYY are mentioned as orexigenic in Harrison 17/e, p 464 but in Ganong & Guyton these are mentioned under anorexigenic peptides.

 



Q. 3 Appetite is stimulated by all of the following peptides, Except:
 A Agouti — Related Peptide (AGRP)
 B Melanocyte Stimulating Hormone (MSH)
 C Melanin Concentrating Hormone (MCH)
 D Neuropeptide Y
Q. 3 Appetite is stimulated by all of the following peptides, Except:
 A Agouti — Related Peptide (AGRP)
 B Melanocyte Stimulating Hormone (MSH)
 C Melanin Concentrating Hormone (MCH)
 D Neuropeptide Y
Ans. B

Explanation:

Melanocyte Stimulating Hormone (MSH)

Quiz In Between


Q. 4 Drugs used for obesity reduction are:
 A Sibutarmine
 B Olestra
 C Fenfluramine
 D All of the above
Q. 4 Drugs used for obesity reduction are:
 A Sibutarmine
 B Olestra
 C Fenfluramine
 D All of the above
Ans. D

Explanation:

All of the above


Q. 5

The following drugs are used in obesity, except:

 A

Orlistat

 B

Sibutramine

 C

Olestra

 D

Neuropeptide Y Agonist

Q. 5

The following drugs are used in obesity, except:

 A

Orlistat

 B

Sibutramine

 C

Olestra

 D

Neuropeptide Y Agonist

Ans. D

Explanation:

Neuropeptide Y Antagonist are used in the medical management of obesity; Neuropeptide Y Agonist are not anti-obesity drugs.

While Orlistat, Silbutramine and Olestra are used in the treatment of obesity.

Ref: K D Tripathi Textbook of Pharmacology, 5th Edition, Pages 117-18; Obesity: Pathophysiology, Psychology and Treatment By George L. Blackburn, Beatrice Stefannie Kanders, Pages 283-99
3. Concise Dictionary of Pharmacological Agents: Properties and Synonyms By Dr. Ian Morton, Ian K. M. Morton, Judith M. Hall, Dr. Judith Hall, Page 192


Q. 6

Drugs used in the treatment of obesity in a 36 year old man is/are which of the following?

 A

Orlistat

 B

Sibutramine

 C

Rimonabant

 D

All of the above

Q. 6

Drugs used in the treatment of obesity in a 36 year old man is/are which of the following?

 A

Orlistat

 B

Sibutramine

 C

Rimonabant

 D

All of the above

Ans. D

Explanation:

Orlistat is the saturated derivative of lipstatin, a potent natural inhibitor of pancreatic lipases isolated from the bacterium Streptomyces toxytricini.

Its primary function is preventing the absorption of fats from the human diet, thereby reducing caloric intake.

It is intended for use in conjunction with a physician-supervised reduced-calorie diet.

Sibutramine is a centrally-acting serotonin-nor epinephrine reuptake inhibitor, structurally related to amphetamines.

It reduces the reuptake of serotonin, nor epinephrine, and dopamine, thereby increasing the levels of these substances in synaptic clefts and helping enhance satiety.

Rimonabant is an anorectic antiobesity drug that has been withdrawn from the market. It is an inverse agonist for the cannabinoid receptor CB1. Its main effect is reduction in appetite.

Quiz In Between


Q. 7

Sibutramine belongs to which group of drugs according to it’s indication of use?

 A

Antipsychotic

 B

Antihypertensive

 C

Anti-Obesity

 D

Anti-Diabetic

Q. 7

Sibutramine belongs to which group of drugs according to it’s indication of use?

 A

Antipsychotic

 B

Antihypertensive

 C

Anti-Obesity

 D

Anti-Diabetic

Ans. C

Explanation:

Sibutramine is a centrally acting anorectic drug which was used as anti obesity drug. 

  • The target site of action is ventromedial and lateral hypothalamic regions in the CNS.
  • It functions as a serotonin and nor epinephrine reuptake inhibitor.
  • It was withdrawn from US market in October 2010, due to an increased risk of non fatal myocardial infarction and non fatal stroke among individuals with pre existing cardiovascular disease.
Ref: Harrison’s Principles of Internal Medicine, 18th edn, Chapter 78

Q. 8

What should be the value of BMI for it to be classified as obesity?

 A

> 50

 B

> 40

 C

> 30

 D

> 20

Q. 8

What should be the value of BMI for it to be classified as obesity?

 A

> 50

 B

> 40

 C

> 30

 D

> 20

Ans. C

Explanation:

BMI stands for the Body Mass Index which is used to predict weight for the respective height.

It is defined as the weight in kilograms divided by the square of height in metres and is expressed as kg/m2.

A value  of BMI > 30 is classified as obesity and a BMI of > 40 is classified under class III obesity. A BMI > 20 up to 30 will include those who are pre-obese and the overweight.

RefPark’s Textbook of Preventive and Social Medicine 19th Edition; Pages 332 – 335; 515.


Q. 9

What should be the value of BMI for it to be classified as obesity?

 A

> 50

 B

> 40

 C

> 30

 D

> 20

Q. 9

What should be the value of BMI for it to be classified as obesity?

 A

> 50

 B

> 40

 C

> 30

 D

> 20

Ans. C

Explanation:

BMI stands for the Body Mass Index which is used to predict weight for the respective height.

It is defined as the weight in kilograms divided by the square of height in metres and is expressed as kg/m2.

A value  of BMI > 30 is classified as obesity and a BMI of > 40 is classified under class III obesity.

A BMI > 20 up to 30 will include those who are pre-obese and the overweight.

RefPark’s Textbook of Preventive and Social Medicine 19th Edition; Pages 332 – 335; 515.

Quiz In Between


Q. 10

Orexins play an important role in people with eating disorders. All of the following are orexins, EXCEPT:

 A

Leptin

 B

Orexin-A

 C

Hypocretin 1

 D

Hypocretin 2

Q. 10

Orexins play an important role in people with eating disorders. All of the following are orexins, EXCEPT:

 A

Leptin

 B

Orexin-A

 C

Hypocretin 1

 D

Hypocretin 2

Ans. A

Explanation:

Orexins (A and B) or Hypocretins (1 and 2):

  • They are produced by neurons in the lateral hypothalamus perifornical area. 
  • Regulated by glucose, leptin, neuropeptide Y, and POMC neurons. 
  • They stimulate food intake.
Leptin:
  • It is produced in adipose tissue. 
  • Acts on neuropeptide Y, AgRP-containing neurons, and -MSH neurons in the arcuate nucleus of the hypothalamus to decrease food intake.
 
Ref: Molina P.E. (2010). Chapter 10. Endocrine Integration of Energy & Electrolyte Balance. In P.E. Molina (Ed), Endocrine Physiology, 3e.

 


Q. 11

The primary action of leptin is:

 A

To increase food intake

 B

To decrease food intake

 C

To increase gastric contraction

 D

To increase intestinal motility

Q. 11

The primary action of leptin is:

 A

To increase food intake

 B

To decrease food intake

 C

To increase gastric contraction

 D

To increase intestinal motility

Ans. B

Explanation:

LEPTIN
 
It is a 167 aa peptide secreted from adipocytes, blood leptin level reflects total body fat.
Its primary action: To decrease food intake. It in CNS decreases NPY and alpha MSH.
Leptin deficiency may lead to obesity.
 
Ref: Sleisenger and Fordtran’s, Edition-9, Page-8.

Q. 12

Mechanism of action of Orlistat used to treat obesity is which of the following?

 A

Central reuptake inhibitor of both norepinephrine and serotonin

 B

Intestinal lipase inhibitor

 C

Central reuptake facilitator of serotonin

 D

Intestinal amylase inhibitor

Q. 12

Mechanism of action of Orlistat used to treat obesity is which of the following?

 A

Central reuptake inhibitor of both norepinephrine and serotonin

 B

Intestinal lipase inhibitor

 C

Central reuptake facilitator of serotonin

 D

Intestinal amylase inhibitor

Ans. B

Explanation:

Sibutramine is central reuptake inhibitor of Noradrenaline and serotonin. Orlistat is a intestinal lipase inhibitor.

Quiz In Between


Q. 13

Appetite is stimulated by all of the following peptides, EXCEPT:

 A

Neuropeptide Y

 B

Agouti – Related Peptide (AGRP)

 C

Melanocyte Stimulating hormone (MSH)

 D

Melanin Concentrating Hormone (MCH)

Q. 13

Appetite is stimulated by all of the following peptides, EXCEPT:

 A

Neuropeptide Y

 B

Agouti – Related Peptide (AGRP)

 C

Melanocyte Stimulating hormone (MSH)

 D

Melanin Concentrating Hormone (MCH)

Ans. C

Explanation:

Pro-opiomelanocortin (POMC) derivatives, particularly alpha MSH decrease food intake. These derivatives have four receptors MC1-R is involved in skin pigmentation, MC2-R is involved in adrenal glucocorticoid production, MC3-R is associated with control of sebaceous gland secretion and MC4-R mediates effects on apetite. Alpha MSH activates the melanocortin 4 receptor and mediates anorexigenic effects.

Ref: Textbook of Medical Physiology By Guyton and Hall, 10th Edition, Page 805 ; Harrison’s Principles of Internal Medicine, 16th Edition, Page 233


Q. 14

Which of the following inhibits appetite by counteracting the effects of neuropeptide Y?

 A

Orexins

 B

Neuropeptide Y

 C

Ghrelin

 D

Leptin

Q. 14

Which of the following inhibits appetite by counteracting the effects of neuropeptide Y?

 A

Orexins

 B

Neuropeptide Y

 C

Ghrelin

 D

Leptin

Ans. D

Explanation:

Leptin acts on receptors in the hypothalamus of the brain where it inhibits appetite by (1) counteracting the effects of neuropeptide Y (a potent feeding stimulant secreted by cells in the gut and in the hypothalamus); (2) counteracting the effects of anandamide (another potent feeding stimulant that binds to the same receptors as THC), and (3) promoting the synthesis of α-MSH, an appetite suppressant.

Ghrelin is a hormone produced mainly by P/D1 cells lining the fundus of the human stomach and epsilon cells of the pancreas that stimulates hunger.

Neuropeptide Y is a natural substance that acts on the brain to stimulate eating.Leptin reduces the output of NPY from the hypothalamus, a major production center.

Orexins (hypocretins) are neuropeptides primarily localized in the hypothalamus and are implicated in the regulation of a variety of activities, including feeding behavior and energy balance.


Q. 15

The principal polypeptide that increases food intake are the following, EXCEPT:

 A

Neuropeptide-Y

 B

Leptin

 C

Orexin-A

 D

Endocannabinoid

Q. 15

The principal polypeptide that increases food intake are the following, EXCEPT:

 A

Neuropeptide-Y

 B

Leptin

 C

Orexin-A

 D

Endocannabinoid

Ans. B

Explanation:

The major afferent signal allowing the brain to sense the level of energy stores is the hormone leptin. Circulating leptin levels are proportionate to the amount of body fat. Higher circulating leptin levels generally reduce, while lower levels generally increase, appetite. 
 
Factors that increases the appetite:
  • Neuropeptide Y
  • Melanin-concentrating hormone
  • Agouti-related peptide
  • Orexin
  • Endocannabinoid
Ref: Paulsen D.F. (2010). Chapter 6. Adipose Tissue. In D.F. Paulsen (Ed), Histology & Cell Biology: Examination & Board Review, 5e.

Quiz In Between


Q. 16

Appetite is stimulated by all of the following, EXCEPT:

 A

Agouti related peptide

 B

Melanocyte concentrating hormone

 C

Melanocyte stimulating hormone

 D

Neuropeptide Y

Q. 16

Appetite is stimulated by all of the following, EXCEPT:

 A

Agouti related peptide

 B

Melanocyte concentrating hormone

 C

Melanocyte stimulating hormone

 D

Neuropeptide Y

Ans. C

Explanation:

Appetite is influenced by many factors that are integrated by the brain, most importantly within the hypothalamus. Signals that impinge on the hypothalamic center include neural afferents, hormones, and metabolites. Vagal inputs are particularly important, bringing information from viscera, such as gut distention. Hormonal signals include leptin, insulin, cortisol, and gut peptides.

Appetite is increased by:
  • NPY, neuropeptide Y
  • Melanin-concentrating hormone (MCH)
  • Agouti-related peptide (AgRP)
  • Orexin
  • Endocannabinoid
Appetite is decreased by:
  • MSH, melanocyte-stimulating hormone
  • CART, cocaine- and amphetamine-related transcript
  • GLP-1,glucagon-related peptide-1
  • CCK, cholecystokinin

Q. 17

All of the following factors increases appetite, EXCEPT:

 A

Neuropeptide Y

 B

Melanin concentrating hormone

 C

Melanocyte stimulating hormone

 D

Agouti related peptide

Q. 17

All of the following factors increases appetite, EXCEPT:

 A

Neuropeptide Y

 B

Melanin concentrating hormone

 C

Melanocyte stimulating hormone

 D

Agouti related peptide

Ans. C

Explanation:

Melanocyte stimulating hormone decreases the appetite.
 
The factors that regulate appetite through effects on central neural circuits:
 
Factors that increases the appetite:
  • Neuropeptide Y
  • Melanin-concentrating hormone
  • Agouti-related peptide
  • Orexin
  • Endocannabinoid
Factors that decreases the appetite:
  • Alpha-melanocyte-stimulating hormone
  • Cocaine- and amphetamine-related transcript
  • Glucagon-related peptide-1
  • Cholecystokinin
Ref: Flier J.S., Maratos-Flier E. (2012). Chapter 77. Biology of Obesity. In D.L. Longo, A.S. Fauci, D.L. Kasper, S.L. Hauser, J.L. Jameson, J. Loscalzo (Eds), Harrison’s Principles of Internal Medicine, 18e.

Q. 18

Appetite is stimulated by all of the following peptides, Except:

 A

Agouti – Related Peptide (AGRP)

 B

Melanocyte Stimulating hormone (MSH)

 C

Melanin Concentrating Hormone (MCH)

 D

Neuropeptide Y

Q. 18

Appetite is stimulated by all of the following peptides, Except:

 A

Agouti – Related Peptide (AGRP)

 B

Melanocyte Stimulating hormone (MSH)

 C

Melanin Concentrating Hormone (MCH)

 D

Neuropeptide Y

Ans. B

Explanation:

B i.e. Melanocyte Stimulating hormone (MSH)

MSH (a-melanocyte stimulating hormone) and CART (cocaine & amphetamine regulated transcript) releasing POMC (pro-opio-melano-cortin) neurons are anorexigenic/anti-orexigenic (i.e. produce satiety & decrease appetite). Whereas, AGRP (agouti-related-peptide) and NPY (neuropeptide Y) releasing neurons of arcuate nuclei of hypothalamus are orexigenic (i.e. increase appetite & cause obesity).

Regulation of Food Intake

– Hypothalmus contains hunger (feeding) and satiety centers. The lateral nuclei of hypothalamus serve as a feeding (hunger) center and ventromedial nuclei of hypothalamus serve as the satiety center. Stimulation of feeding center & /or destruction of satiety center cause voracious appetite (hyperphagia) & obesity. Whereas, destruction of feeding center & /or stimulation of satiety center cause anorexia (complete satiety Rack of desire for food) & progressive inanition (weight loss).

– Lesions of paraventricular nuclei of hypothalamus cause excessive eating and lesions of dorsomedial nuclei usually depress eating behaviour.

– Arcuate nuclei of hypothalamus, are the sites where multiple hormones released from gastrointestinal tract and adiose tissue converge to regulate food intake & energy expenditure. It has 2 types of neurons.

Quiz In Between


Q. 19

Antilipidemic drugs that prevent hypercholestero­lemia by inhibiting absorption –

 A

Ezetimibe

 B

Orlistat

 C

Cholestyramine

 D

Statins

Q. 19

Antilipidemic drugs that prevent hypercholestero­lemia by inhibiting absorption –

 A

Ezetimibe

 B

Orlistat

 C

Cholestyramine

 D

Statins

Ans. A

Explanation:

Ans. is ‘a’ i.e., Ezetimibe

Ezetimibe inhibits the absorption of cholesterol by bidning to transporter [NPC-1L1 (Niemann Pick Cl, likel) SR­Bl, 145 KDa] located in intestinal brush border.

Note:

Orlistat also reduces cholesterol absorption, but it is an anti-obesity drug (not an antilipidemic drug).


Q. 20

All of the following agents are used in obesity except-

 A

Orlistat

 B

Sibutramine

 C

Olestra

 D

Neuropeptide Y analogues

Q. 20

All of the following agents are used in obesity except-

 A

Orlistat

 B

Sibutramine

 C

Olestra

 D

Neuropeptide Y analogues

Ans. D

Explanation:

Ans. is `d’ i.e., Neuropeptide Y analogues

PHARMACOLOGICAL TREATMENT OF OBESITY

o Antiobesity drugs act in either of two ways:‑

a)       Reduce food intake (anorectic)

b)       Reduce absorption

a) Reduce food intake

1. ↑ Norepinephrine and serotonin in CNS (Central anorexients)

o Augmentation of neurotransmission of norepinephrine and serotonin (5-HT, receptors) reduce caloric intake without a sense of deprivation.

o Amphetamines, fenfluramine, dexfenfluramine, diethylpropion, mazindal, phenteramine and phendimetrazine increase release of norepinephrine in CNS.

o Sibutramine blocks reuptake of both norephrine and serotonine resulting activation of 5-HT, receptrs.

o Sibutramine is the only anorexiant that is currently approved by FDA for long term use.

2. NPY and AgRP antagonsits

3. MSH and CART agonists

4. Cannabinoid receptrs antagonist (Rimonabant)

5. Leptin analogues

b) Reduce absorption 

Orlistat


Q. 21

Drugs used in the treatment of obesity is/are?

 A

Orlistat

 B

Sibutramine

 C

Rimonabant

 D

All of the above

Q. 21

Drugs used in the treatment of obesity is/are?

 A

Orlistat

 B

Sibutramine

 C

Rimonabant

 D

All of the above

Ans. D

Explanation:

Ans. is `d’ i.e., All of the above

Quiz In Between


Q. 22

An oral hypoglycemic agent used to treat obesity is:

September 2008

 A

Tolbutamide

 B

Glipizide

 C

Gliclazide

 D

Metformin

Q. 22

An oral hypoglycemic agent used to treat obesity is:

September 2008

 A

Tolbutamide

 B

Glipizide

 C

Gliclazide

 D

Metformin

Ans. D

Explanation:

Ans. D: Metformin

Agents used for treating obesity

  • Orlistat reduces intestinal fat absorption by inhibiting pancreatic lipase. Orlistat may cause frequent, oily bowel movements (steatorrhea), but if fat in the diet is reduced, symptoms often improve.
  • Sibutramine is an anorectic or appetite suppressant, reducing the desire to eat. Sibutramine may increase blood pressure and may cause dry mouth, constipation, headache, and insomnia.
  • Rimonabant is a recently developed anti-obesity medication. It is cannabinoid (CB1) receptor antagonist that acts centrally on the brain thus decreasing appetite. It may also act peripherally by increasing thermogenesis and therefore increasing energy expenditure.
  • In people with Diabetes mellitus type 2, the drug metformin can reduce weight.
  • olestra is a sucrose polyester which can be used as a cooking medium in place of fat.
  • Leptin analogues are under investigation.

Q. 23

Sibutramine is used for:

September 2009, March 2013

 A

Hemorrhage

 B

Nasal decongestant

 C

Diabetes

 D

Obesity

Q. 23

Sibutramine is used for:

September 2009, March 2013

 A

Hemorrhage

 B

Nasal decongestant

 C

Diabetes

 D

Obesity

Ans. D

Explanation:

Ans. D: Obesity

It is a centrally-acting serotonin-norepinephrine reuptake inhibitor structurally related to amphetamines. Sibutramine is an appetite suppressant that is administered orally for the treatment of obesity.

Sibutramine has a number of clinically significant interactions. The concomitant use of sibutramine and monoamine oxidase inhibitors (MAOIs, such as selegiline) is not indicated, as it may increase the risk of serotonin syndrome. Taking both sibutramine and certain medications used in the treatment of migraines—such as ergolines and triptans, as well as opioids, may also increase the risk for serotonin syndrome, as may the use of more than one serotonin reuptake inhibitor at the same time.

The concomitant use of sibutramine and drugs which inhibit CYP3A4, such as ketoconazole and erythromycin, may increase plasma levels of sibutramine.


Q. 24

Appetite is increased by ‑

 A

α-MHS

 B

Leptin

 C

Serotonin

 D

Neuropeptide Y

Q. 24

Appetite is increased by ‑

 A

α-MHS

 B

Leptin

 C

Serotonin

 D

Neuropeptide Y

Ans. D

Explanation:

Ans. is ‘d’ i.e., Neuropeptide Y

Quiz In Between


Q. 25

Which of the following increases appetite

 A

Insulin

 B

Leptin

 C

α-MSH

 D

Neuropeptide Y

Q. 25

Which of the following increases appetite

 A

Insulin

 B

Leptin

 C

α-MSH

 D

Neuropeptide Y

Ans. D

Explanation:

Ans. is ‘d’ i.e., Neuropeptide Y


Q. 26

Side effect of topiramate is ‑

 A

Weight loss

 B

Visual impairement

 C

Insomnia

 D

Hemolysis

Q. 26

Side effect of topiramate is ‑

 A

Weight loss

 B

Visual impairement

 C

Insomnia

 D

Hemolysis

Ans. A

Explanation:

Ans. is ‘a’ i.e., Weight loss

Topiramate

  • Weak carbonic anhydrase inhibitor with broad spectrum anticonvulsant activity.
  • Acts via – prolongation of Na+ channel inactivation, GABA potentiation, gultamate receptor antagonism, neuronal hyperpolarisation via K+ channels.
  • Used in SPS, CPS, GTCS, myoclonic epilepsy, prophylaxis of migraine.
  • Readily absorbed orally and mainly excreted in urine. T1/2 – 24hrs.
  • Adverse effects impairment of attention, sedation, ataxia, word finding difficulties, poor memory, weight loss, paresthesias, and renal stones.

Q. 27

Sibutramine is ‑

 A

Antithyroid drug

 B

Antiobesity drug

 C

Antimalarial drug

 D

Antitubercoulous drug

Q. 27

Sibutramine is ‑

 A

Antithyroid drug

 B

Antiobesity drug

 C

Antimalarial drug

 D

Antitubercoulous drug

Ans. A

Explanation:

Ans. is ‘a’ i.e., Endorphines 

  • Endorphins have major action on receptors.
  • Enkephalins have major action on a receptors.
  • Dynorphins have major action on c receptors.

Quiz In Between



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