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PBL PY2 Fall > Diabetes Type 1 Therapeutics > Flashcards

Diabetes Type 1 Therapeutics Flashcards

1
Q

approximately __% of cases of diabetes are type 1

A

10

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2
Q

what are the 2 principle fuel of the body?

A

glucose and free fatty acids (stored as glycogen & triglycerides)

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3
Q

the brain can only use what form of fuel?

A

glucose

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4
Q

glucogenesis occurs in what organs?

A

liver and kidneys

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5
Q

insulin is secreted by the ___ cells of the pancreas

A

beta

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6
Q

insulin is secreted in high concentrations of ____ and suppressed in low concentrations

A

glucose

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7
Q

meals cause what type of release of insulin?

A

biphasic relase (a large burst in the first 30 min and the the rest over 1-2 hrs post meal)

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8
Q

how does insulin decrease blood glucose?

A

allows glucose to enter the cells to be used

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9
Q

what is the effect of insulin of FFA?

A

helps them be stored as triglycerides

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10
Q

what is the effect of insulin on glycogen?

A

helps the liver and muscles store glycogen for future use

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11
Q

what causes GLP-1 to be released?

A

food (glucose)

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12
Q

GLP-1 is secreted from ___

A

the intesting

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13
Q

GLP-1 stimulates the release of ___

A

insulin from beta cells

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14
Q

GLP-1 suppresses the release of ____

A

glucagon

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15
Q

what is the effect of GLP-1 on food intake?

A

reduces it (why patients have significant weight loss)

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16
Q

what is the effect of GLP-1 on gastric emptying?

A

slows

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17
Q

what enzyme causes the degradation of GLP-1?

A

DPP-4

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18
Q

what is glucagon?

A

hormone that increases the amount of glucose/fuel in the blood

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19
Q

how does glucagon increase the amount of glucagon in the blood?

A

causes breakdown/release of stored glycogen in the muscle/liver (glucogenesis)

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20
Q

glucagon converts FFAs into the ____ after prolonged starvation

A

ketone bodies

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21
Q

type 1DM involves the autoimmune destruction of ____, which lead to insulin deficiency

A

beta cells

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22
Q

t/f T1DM can be idiopathic, or there can be detectable antibodies to diagnose

A

t

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23
Q

what are 3 classic symptoms of T1DM?

A

polydipsia, polyuria, polyphagia

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24
Q

t/f the onset of T1DM is typically acute/severe

A

t, most patients are diagnosed by a DKA episode

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25
Q

what is the typical body type of T1DM?

A

usually lean, may have significant weight loss before diagnosis

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26
Q

t/f the malfunction of beta cells is progressive in T2DM

A

t

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27
Q

the rate of beta cell dysfunction in T2DM may be affected by the level of ___ control

A

glucose

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28
Q

in T2DM, impaired glucose may be present for ____ years before diagnosis

A

5-8

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29
Q

ketosis is rare in T2DM, but ____ is more common in poorly controlled T2 patients

A

hyperosmolar hyperglycemic state (HHS)

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30
Q

what is Latent Autoimmune Diabetes in Adults (LADA)?

A

when antibodies attack the pancreatic beta cells

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31
Q

LADA shares ___ aspects of both Type 1 and Type 2 diabetes

A

genetic

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32
Q

what is the therapy for LADA?

A

patients may not require insulin at diagnosis, but may progress to insulin over months to years

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33
Q

what do the BMI and antibody titers of LADA patients look like?

A

variable

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34
Q

what FPG is diagnostic of diabetes?

A

7.0 mmol/L or greater

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35
Q

what A1C is diagnostic of diabetes?

A

6.5% or more

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36
Q

what 2 hour PG in a 75g load OGTT is diagnostic of diabetes?

A

11.1 mmol/L or greater

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37
Q

what random PG is diagnostic of diabetes?

A

11.1 mmol/L or more

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38
Q

what are 2 acute complications of diabetes?

A

hypoglycemia and DKA

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39
Q

what are some microvascular complications of diabetes?

A

retinopathy, neuropathy, nephropathy

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40
Q

what are macrovascular complications of diabetes?

A

CVD, cerebrovascular dx, peripheral arterial dx, amputation

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41
Q

what are the ABCDESSS of diabetes?

A 
A1C targets
BP targets
Cholesterol targets 
Drugs for CVD risk reduction 
Exercise & diet 
Screening complications
Smoking cessation
Self-management, stress
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42
Q

hypoglycemia typically occurs when the BG is ___mmol/L

A

less than 4.0

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43
Q

what are the symptoms of mild hypoglycemia?

A

tremors, palpitations, sweating, anxiety, tingling, nausea, exercessive hunger

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44
Q

what are the symptoms of moderate hypoglycemia?

A

headache, mood changes, irritability, visual disturbances, dizziness

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45
Q

what are the symptoms of severe hypoglycemia?

A

unresponsive, unconscious, seizures, coma

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46
Q

hypoglycemia should be treated with ___

A

15g of carbs

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47
Q

give examples of 15g of carbs to treat hypoglycemia

A
  1. glucose tabs
  2. 3/4 cup of juice or reg soft drink
  3. 6 lifesavers
  4. 15ml honey
  5. 15ml or 3 packs table sugar in water
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48
Q

if treating hypoglycemia, how long do you wait after taking the 15g of carbs to test BG?

A

15 minutes

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49
Q

if BG is above 4 15min after treating a low and the next meal is within an hour away, what do you do next?

A

you are good, can wait until next meal to eat, just be mindful of Sx

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50
Q

if BG is above 4 15min after treating a low and the next meal is more than 1hr away, what should be done?

A

eat a starch and protein snack

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51
Q

give 2 examples of starch/protein snacks that can be eaten between meals to prevent lows

A

7 crackers and 1 piece of cheese; 1 piece of bread and 2 tabs of peanut butter (can also mix and match the carb/protein)

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52
Q

what is the A1C target for most patients with type 1 or 2 diabetics?

A

7.0 or below

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53
Q

what is the typical A1C target for type 2 patients to reduce risk of CKD and retinopathy if patients are at low risk for hypoglycemia?

A

6.5 or less

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54
Q

what is the A1C target for patients who are functionally dependent?

A

7.1-8.0

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55
Q

what is the A1C target for patients with recurrent severe hypoglycemia and or hypoglycemia unawareness?

A

7.1-8.5%

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56
Q

what is the A1C target for patients with limited life expectancy?

A

7.1-8.5%

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57
Q

what is the A1C target for patients who are frail elderly w/wo dementia?

A

7.1-8.5%

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58
Q

you should not target an A1C higher than ___% to minimize hyperglycemia and acute/chronic complications

A

8.5%

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59
Q

what is the target FPG?

A

4.0-7.0

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60
Q

what is the target 2hr PPG?

A

5.0-10.0

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61
Q

what is the target 2hr PPG if the A1C targets are not being met?

A

5.0-8.0

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62
Q

what is the target LDL in diabetic patients?

A

2.0 mmol/L or less

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63
Q

what is the target BP for diabetic patients?

A

<130/80 mmHg

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64
Q

what bloodwork tests can be used to diagnose diabetes?

A

c-peptide, fasting insulin & antibody tests, urinalysis, electrolytes, TSH, CBC, ACR, SCr, eGFR

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65
Q

how often should A1C be monitored?

A

every 3 months; can be every 6 months if normal

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66
Q

how often should SCr and eGFR be tested?

A

periodically unless indicated

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67
Q

what are the benefits of exercise in diabetes?

A
  1. improve comorbidities/complications
  2. decrease insulin resistance
  3. decrease development of peripheral neuropathy
  4. weight management
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68
Q

t/f both aerobic and resistance exercise can be beneficial in diabetes

A

t

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69
Q

the recommended exercise regimen is ___minutes of aerobic exercise per week and ___ sessions of resistance training

A

150; 2

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70
Q

t/f all patients with diabetes should see a dietitian

A

t

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71
Q

t/f diabetic patients should eat 3 regular meals a day

A

t

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72
Q

what foods should be reduced in diabetic patients?

A
  1. sugar-containing drinks
  2. cream/sugar in coffee
  3. fried foods
  4. desserts and “unhealthy” snacks
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73
Q

what dietary elements should be increased in diabetic patients?

A

water, fruits and veg

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74
Q

what does the glycemic index of food mean?

A

refers to the amount of increase in BG the consumption of carbs when compared to glucose or white bread

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75
Q

foods with ____(lower or higher) glycemic index may help with BG control

A

lower

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76
Q

what is the effect of alcohol on BG?

A

can cause hypoglycemia

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77
Q

if a patient is on insulin or secretagogues, the hypoglycemia caused by alcohol can occur up to ___hrs after consumption

A

24

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78
Q

what are acceptable alcohol intakes for diabetic patients (once their BG levels are controlled) for women and men?

A

2 standard drinks/day or 10/week for women and 3/day or 15/week in men

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79
Q

t/f adequate food/carb intake is important before, during and after alcohol

A

t

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80
Q

what are some safety recommendations for alcohol consumption in diabetic patients?

A
  1. monitor for lows through the night & early morning (set an alarm)
  2. tell someone to look out for you
  3. GLUCAGON MAY NOT WORK, call 911
  4. wear medic alert bracelet
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81
Q

insulin reduces A1c by ___%

A

1.5-2.5%

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82
Q

is there a max insulin dose?

A

no

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83
Q

what are the side effects of insulin?

A

hypoglycemia, weight gain, hypokalemia

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84
Q

where can insulin be injected?

A

abdomen, upper arms, anterior.lateral thigh, butt

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85
Q

you should not inject insulin (or anything else) within __ cm of the belly button

A

5cm

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86
Q

is it recommended to wipe skin with alcohol before injecting insulin?

A

no (evidence does not suggest benefit and may cause stinging, but you can use alcohol on the catridge before placing the needle)

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87
Q

basal insulins are also called ____ insulin

A

background

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88
Q

basal insulins include ___ and ___ acting insulins

A

intermediate and long

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89
Q

what is an example of intermediate acting insulin?

A

NPH

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90
Q

what is the brand name of NPH insulin?

A

Humulin-N and Novolin ge NPH

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91
Q

what is the onset time for NPH (intermediate acting insulin)?

A

1-3hrs

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92
Q

what is the peak time for NPH (intermediate-acting) insulin?

A

5-8hrs

93
Q

what is the duration for NPH (intermediate acting) insulin?

A

up to 18hrs

94
Q

what are the types of long-acting insulin?

A

detemir (Levemir), Glargine U-100 (Lantus), Glargine U-300 (Tuojeo), Glargine biosimilar (Basaglar), Degludec U-100, U-200 (Tresiba)

95
Q

what is the brand name of detemir?

A

levemir

96
Q

what is the brand name of glargine U-100?

A

lantus

97
Q

what is the brand name of glargine U-300?

A

tuojeo

98
Q

what is the brand name of the glargine biosimilar?

A

basaglar

99
Q

what is the brand name for degludec U-200?

A

tresiba

100
Q

what is the onset time of long-acting insulins?

A

1.5hrs

101
Q

what is the peak time of long acting insulins?

A

they have no peak

102
Q

what is the duration of detemir?

A

16-24hrs

103
Q

what is the duration of Lantus?

A

24hrs

104
Q

what is the duration of tuojeo?

A

> 30hrs

105
Q

what is the duration of degludec?

A

42hrs

106
Q

bolus insulin is also called ____ insulin

A

prandial/mealtime; short-acting, rapid-acting

107
Q

regular insulin, aspart, faster-acting insulin aspart, lisipro, and glulisine fall under what category of insulin?

A

bolus

108
Q

what are the 2 categories of bolus insulin?

A

Rapid-acting and short-acting

109
Q

which insulins are rapid acting?

A

Aspart (Nove-Rapid), Gluisine (Apidra), Lispro U-100, U-200 (Humalog), faster-acting insulin aspart (Fiasp)

110
Q

what is the brand name for Aspart?

A

Novo-rapid

111
Q

what is the brand name for Glulisine?

A

Apidra

112
Q

what is the brand name for Lispro U-200?

A

Humalog

113
Q

what is the brand name for Faster acting insulin aspart?

A

Fiasp

114
Q

what is the onset time of Aspart (Novo-Rapid)?

A

9-20min

115
Q

what is the peak time for Apsart (Novo-Rapid)?

A

1-1.5hrs

116
Q

what is the duration of Aspasrt (Novo-Rapid)?

A

3-5hrs

117
Q

what is the onset time for Glulisine (Apidra)?

A

10-15min

118
Q

what is the peak time of Glulisine (Apidra)?

A

1-1.5hrs

119
Q

what is the duration of Glulisine (Apidra)?

A

3.5-5hrs

120
Q

what is the onset time of Lispro U-100, U-200 (Humalog)?

A

10-15min

121
Q

what is the peak time of lispro U-100, U-200 (humalog)?

A

1-2 hrs

122
Q

what is the duration of lispro U-100, U-200?

A

3-4.75hrs

123
Q

what is the onset time of FIASP?

A

4 min

124
Q

what is the peak time of FIASP?

A

0.5-1.5hr

125
Q

what is the duration of FIASP?

A

3-5hrs

126
Q

insulin regular (Humulin R, Novolin ge Toronto) and Insulin regular (Entuzity U-500) are examples of what type of bolus insulin?

A

short-acting

127
Q

what is the onset time of insulin regular (Humulin R, Novolin ge Toronto)?

A

30

128
Q

what is the peak time of Insulin regular (Humulin R, Novolin ge Toronto)?

A

2-3hrs

129
Q

what is the duration of Insulin regular (Humulin R, Novolin ge Toronto)?

A

6.5hrs

130
Q

what is the onset time of Insulin regular (entuzity U-500)?

A

15min

131
Q

what is the peak time of insulin regular entuzity U-500?

A

4-8hrs

132
Q

what is the duration of Insulin regular entuzity U-500?

A

17-24hrs

133
Q

what is premixed insulin?

A

short or rapid acting insulin mixed with intermediate acting insulin in various percentages (30/70, 40/60, 50/50)

134
Q

when can pre-mixed insulin be useful?

A

in patients with less stringent A1C targets and those who dont want to (or cant) give more than 2 injections per day

135
Q

how long does it take for Insulin glargine U-300 (Tuojeo) to reach steady state?

A

3-4 days

136
Q

a ____% higher dose of insulin glargine U-300 (tuojeo) is required compared to insulin glargine

A

10-15%

137
Q

when changing from U-300 glargine to U-100 glargine, how do you adjust the dose?

A

reduce the dose by 20%

138
Q

how long does it take insulin degludec (tresiba) to reach steady state?

A

3-4 days

139
Q

in insulin naive type 2 patients, what is the starting dose of insulin degludec (tresiba)?

A

10 units

140
Q

in type 1 diabetes, how should the dose of tresiba be adjusted comapred to the dose of T2?

A

reduce by 20%

141
Q

how often is tresiba titrated?

A

once weekly or every 4 days

142
Q

insulin regular humulin R U-500 (Entuzity) provides both ___ and ____ coverage

A

basal & bolus

143
Q

the insulin regular Humulin R U-500 (Entuzity) has pen increments of __Units

A

5

144
Q

when dosing Insulin regular humulin R U-500 (Entuzity) BID, ___% is given before breakfast and ___% is given before dinner

A

60; 40

145
Q

when insulin regular humulin R U-500 (Entuzity) is dosed TID, __% is given before breakfast, ___% before lunch and ___% before dinner

A

40%, 30%, 30%

146
Q

insulin regular humulin R U-500 (Entuzity) should be given how soon before a meal?

A

30 min

147
Q

when starting insulin in type 1 patients, what is the starting dose?

A

0.3–1.0 U/kg/day in divided doses (basal and bolus) –> usually 0.5u/kg/day

148
Q

what doses of insulin may be appropriate in Type 1 patients in their honeymoon phase?

A

0.2–06 u/kg/day

149
Q

___% of the daily insulin should be given as basal

A

40-60%

150
Q

carb counting is usually started prior to starting what type of device?

A

insulin pump

151
Q

how is an insulin carb ratio calculated?

A

total daily carbs / total daily bolus insulin

152
Q

insulin carb ratios are adjusted based on what glucose reading?

A

2hr post-meal

153
Q

what is the role of an insulin pump?

A

provides continuous infusion and allows for flexible timing of meals, exercise etc.

154
Q

when a patient has an insulin pump, do they still need to give themselves a bolus at meals and/or snacks?

A

yes

155
Q

what type of insulin do insulin pumps use?

A

rapid acting insulin

156
Q

Using an insulin pump requires one injection every ___ days

A

3

157
Q

t/f insulin pumps may have reduced frequency of severity of hypoglycemia

A

t

158
Q

on sick days, how often should patients check their BG?

A

every 2-3 hours

159
Q

should patients omit insulin on sick days?

A

NO! They may even need more insulin (monitor)

160
Q

how often should patients check their ketones on sick days?

A

every 2-3 hours or when using the washroom

161
Q

how should patients adjust their food intake on sick days?

A

try to keep carb intake as normal as possible using small meals and liquids containing carbs

162
Q

when should patients call 811 or a healthcare provider during sick days?

A

if moderate to large ketones, cant keep BG above 4, vommiting/diarrhea for more than 24hors, signs of DKA, unable to manage insulin or take care of self

163
Q

what happens in DKA?

A

a lack of insulin stimulates an accelerated starvation process with lipolysis and the formation of ketone bodies

164
Q

when does DKA typically happen?

A

when patient is undiagnosed or newly diagnosed or if insulin has been omitted

165
Q

what are the effects of DKA?

A

volume depletion, dehydration, decreased GFR, electrolyte depletion, and acidosis

166
Q

what is the treatment regimen for DKA?

A
  1. IV fluids (watch osmolarity –> rapid decrease can cause cerebral edema)
  2. IV insulin (0.1u/kg/hr)
  3. K to avoid hypokalemia
167
Q

in DKA, what type of insulin needs to be given?

A

short acting (regular)

168
Q

in DKA, insulin shoul be held until the K is greater than ___mmol/L

A

3.3

169
Q

when managing glucose issues based on trends in a patient, you treat lows first and then you target what reading to fix next?

A

the first high glucose reading of the day

170
Q

t/f sometimes you may need to adjust more than one insulin dose at a time, but try to only change one at a time

A

t

171
Q

what is the Dawn phenomenon?

A

release of hormones in the early morning hours that cause rise in BG (cortisol is the hromone that causes this)

172
Q

what is the Symogi effect?

A

rebound hyperglycemia caused by an episode of hypoglycemia, usually between 1 and 3 am

173
Q

how can Dawn and symogi effect be diagnosed?

A

testing BG at bedtime and through the night and early moring

174
Q

how often should BG be tested in type 1 diabetics?

A

at least as often as insulin is injected (before each meal and before bed)

175
Q

in continuous glucose monitoring, how long can a sensor be worn?

A

6-7 days

176
Q

Can continuous glucose monitoring completely eliminate finger-prick testing?

A

no

177
Q

continuous glucose monitoring takes readings from what fluid?

A

interstitial fluid

178
Q

how long can the freestyle libre sensor be worn?

A

14 days

179
Q

can the freestyle libre give readings if you scan through clothing

A

yes

180
Q

flash glucose monitoring (freestyle libre) provides glucose readings from what fluid?

A

interstitial fluid

181
Q

what is the MOA of SGLT2 in diabetes?

A

decrease renal glucose resorption and decrease renal threshold for glucose

182
Q

SGLT2 can decrease A1C in what timeframe?

A

3-6 months

183
Q

what are the side effects of SGLT2 inhibitors?

A

increased yeast infections and UTI, increased BUN and SCR, decreased BP and hypovolemia

184
Q

what is the effect of SGLT2 on weight?

A

weight loss

185
Q

how much do SGLT2 decrease A1C?

A

0.5-0.8%

186
Q

what are risk factors for DKA with SGLT2?

A

low carb intake/fasting, acute serious illness, elderly, surgery, decreased insulin dose, excessive alcohol intake

187
Q

you should not drive if your BG is less than

A

4

188
Q

when on long car trips, you should check you BG every __hrs

A

4

189
Q

after a low, it may take ___minutes for your brain to recover

A

40

190
Q

once you have treated a low, dont drive until your BG is above ____mmol/L

A

5.0

191
Q

what type of insulin is “cloudy”

A

NPH

192
Q

what needs to be done to NPH insulin before using?

A

inverted 10 times until it is uniform

193
Q

if BG reaches ___mmol/L, you need to start checking your ketones

A

14

194
Q

the optimal response of SGLT2 on A1C may take how long?

A

up to 6 months

195
Q

what is the chemical rxn that occurs in a glucometer?

A

glucose in blood reacts with glucose oxidase to form glucuronic acid which then reacts with ferricyanide to form ferrocyanide which gets oxidized by an electrode that generates a current directly proportional to the glucose concentration

196
Q

endogenous insulin is mostly broken down by the ___, exogenous insulin is mostly broken down by the ___

A

liver; kidenys

197
Q

what are some situations when a patient needs to test their BG more?

A
  1. pregnancy
  2. sickness
  3. exercise
  4. hospitalization
  5. when starting out on new dose
198
Q

how is insulin stored?

A

fridge until opened, once opened keep at room temp for 1 month (will help prevent stinging)

199
Q

how long can levemir and tuojeo be kept at room temp?

A

42 days

200
Q

what affect does massaging a muscle have on insulin absorption?

A

increases it

201
Q

order the injection sites of insulin in order of most to least well absorbed

A
  1. abdomen
  2. back or arms
  3. thighs
  4. butt
202
Q

what is the effect of heat on insulin absorption?

A

increases

203
Q

what is the effect of dehydration on insulin absorption?

A

slows

204
Q

what is the effect of lipohypertrophy on insulin absorption?

A

decreases

205
Q

what is the effect of insulin concentration on its absorption?

A

more dilute are absorbed faster than highly concentrated

206
Q

what is the effect of renal impairment on insulin PK?

A

lowers insulin clearance and may prolong and intensify the action of endogenous and exogenous insulin

207
Q

what is the effect of insulin antibodies on insulin PK?

A

IgG antibodies bind insulin as it is absorbed and release it slowly which delays or prolongs its effect

208
Q

what is the effect of hyperthyroidism on insulin PK?

A

increases the clearance of insulin and increases the action of insulin making control difficult

209
Q

what is the effect of hepatic impairment on insulin PK?

A

hepatic impairment puts patients at higher risk for hypoglycemia

210
Q

when do you need to do a finger prick to test BG and CANNOT do it from alternate sites?

A

in hypoglycemia, sickness, not stable glucose levels

211
Q

what is the effect of echinacea in diabetes?

A

some sources say it can lower BG by having an effect on insulin-induced adipocyte differentiation

212
Q

what is the effect of pseudoephedrine on diabetes?

A

can raise BG, do not recommend taking it

213
Q

what type of respirations in DKA cause CO2 levels to be low and O2 to be high?

A

Kussmaul’s breathing

214
Q

why is bicarb not frequently given to DKA patients?

A

there is not enough evidence to suggest using it and it can cause ADRs like increased hospitalization duration, worsening ketoenemia etc. and likely has no benefit over traditional therapy

215
Q

why does hypokalemia occur in DKA?

A

hyperglycemia causes osmotic loss of fluid and electrolytes

216
Q

why does the treatment of DKA cause hypokalemia?

A

insulin causes glucose to move into cells, which draws up more fluid, which also causes K to leave the blood and move into cells

217
Q

why is D5W given to DKA patients?

A

too much glucose moving into the cells of the brain bringing water with it can cause cerebral edema, so they give D5W which cant cross membranes so it will keep some water in the blood

218
Q

what is the screening test for diabetic retinopathy?

A

dilated eye exam

219
Q

what is the screening test for diabetic neuropathy?

A

filament testing

220
Q

what are the lon-term effects of diabetic retinopathy?

A

vision impairment, blurred vision, floaters, blindness, glaucoma

221
Q

what are the possible treatments for diabetic retinopathy?

A
  1. retinal photocoagulation (laser therapy_
  2. vitrectomy
  3. anti-vascular endothelial factor (VEGF) like ranibizumab
  4. steroids
  5. aldose reductase inhibitors
222
Q

what are the 2 types of diabetic retinopathy?

A

proliferative and non-proliferative

223
Q

how often should screening for complications occur in Type 1 and Type 2?

A

Type 1: within 5 years of diagnosis and then annually

Type 2: on diagnosis and then yearly

224
Q

what are the two classes of diabetic Neuropathy?

A
  1. peripheral

2. autonomic

225
Q

what are some treatments for diabetic neuropathy?

A
  1. anticonvulsants (gabapentin, preganalin, valproate)
  2. Antidepressants (amitriptyline, duoloxetine and venlafaxine)
  3. dopamine agonists to promote gastric motility: metaclopramide & azithromycin
  4. topicals (capsaicin and nitrates)
226
Q

what are treatment options for diabetic nephroptahy?

A
  1. SGLT2 inhibitors
  2. RAAS blockers for BP
  3. neurologic botanicals and anticholinergic to prevent retention
227
Q

what are the screening tests for diabetic nephropathy?

A

ACR and eGFR

228
Q

what ACR may indicate kidney damage?

A

2.0 or higher

PBL PY2 Fall (21 decks)

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