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Clinical Chemistry

Transcript: • reaction between the molecules and reagent in the curvette produce new molecules that absorb the wavelength of light energy Left lobe Indicator electrode WEAKNESS FATIGUE Definition C.Significance of Spectrophotometry • a technique that allows scientists to identify substances without having a close contact • useful for toxic and volatile substances • used for identifying gases • used to determine the seriousness of a diseases through comparison with the standard curve 2. Blood Urea Nitrogen Eye Damage Heart Attack % transmittance (T) = x 100 Absorbance (A) = -log = -log (T) common lab tests used to evaluate how well the kidneys are working • electrolytes are unequally distributed between intracellular (inside the cell) and extracellular (outside the cell) • concentrations in (mmol/L) a hallow muscular organ has 4 chambers circulates blood throughout the body to distribute amount of nutrients needed Clinical Chemistry SHAKING c. Serum Cholesterol (HDL + LDL + Tryglycerides = Total Cholesterol) d. Prothrombin time is a test of plasma clotting activity reflects the activity of vitamin K-dependent clotting factors synthesized by the liver increase - denatureofacute liver disease vitamin K deficiency Impotence Difficulty passing urine Analyte solution Glucose stored in the body as glycogen in the liver. Glucogenesis: Glycogen mobilized then converted to glucose when blood glucose concentration is low roduce glucose from non-carbohydrate precursors (pyruvate, amino acids, glycerol) maintains blood glucose concentrations BUN test measures the surplus of amino acids which are converted to urea and excreted by the kidneys. (amount of urea nitrogen) • Urea nitrogen is what forms when protein breaks down. • BUN concentration is influenced by diet, hormones, and kidney function but not a recommended test for kidney disease • Low BUN levels - starvation, pregnancy, and low-protein diet • High BUN levels - high protein diet, after administration of steroids and kidney disease 1. Serum Creatinine • test that measures the level of creatinine in the blood Creatinine • waste product of creatine phosphate • substance stored in muscle, used for energy • excreted by the kidney • not affected by diet or hormone levels • Increased due to impairment of urine formation or excretion which occurs in renal disease, shock, water imbalance, or ureter blockage brownish yellow substance found in bile produced when the liver breaks down old red blood cells removed from the body through the stool gives stool its normal color 1. Troponin a. Liver enzyme tests (Bile Function) d. Chloride HEADACHE Right atrium Principle of the Beer-Lambert Law that relates the concentration of a saple to the passed light path length. Techniques used in measuring concentrations of molecules in body fluids: 1. O- Toludine Method 2. Glucose Oxidase Method 3. Quick Screen of Blood Glucose 2. Electrolyte References 1. O- Toluidine Method b. Total Serum Protein Test • a branch of medical science • analysis of biological materials, usually bodily fluids • diagnosis on the state of the human body • physical, chemical, and microscopic examination of urine • detect and measure compounds that pass through the urine • routine medical exam to screen for early signs of diabetes or kidney disease, check for blood in the urine, or diagnoseurinary tract infection Recommended to: Aspartate aminotransferase (AST) • formerly called SGOT • AST enzyme also found in muscles and other tissues besides the liver Alanine aminotransferase (ALT) • formerly called SGPT • almost exclusively found in the liver If ALT and AST are found together in elevated amounts in the blood, liver damage is most likely present. C. Kidney (Renal) Function Tests Heart • determined electrochemically • potentiometric method • samples are applied to disposable biosensors which contain an electrochemical sensor (electrode) • When sample interacts with the reagents in the biosensor strips, the current generated is detected by the meter and converted into glucose units. 4. Significance urine sample III.Biochemical Test Profiles Low blood glucose • Plasma Glucose ≤ 45 mg⁄dl • insufficient supply of glucose --> may develop Impaired Mentation, Drowsiness or Coma • Diagnosis based on the following criteria: 1. Identification of low blood glucose 2. Compatible symptoms with hypoglycemia 3. Resolution of symptoms with administration of glucose (glycolysis) • Symptoms: • total CO2 content • part of blood buffer system which maintains blood pH level at 7.4 • Acidosis - pH level < 7.35 and is caused by decreasing HCO3- concentrations • Alkalosis - pH level > 7.45 and is caused by increase in HCO3- concentration Using Test Strip – plastic reagent strip with glucose testing spot is convenient IMPAIRED VISION 1. Lipid profile – cholesterol Gallbladder Reference electrode Bilirubin circulates in the bloodstream in 2 forms: a. Indirect (or unconjugated) bilirubin • form of bilirubin insoluble in water • travels through

Clinical Chemistry

Transcript: Introduction to Kinetics Hyperthyrodism General Chemistry Urinalysis Clinical Chemistry Special Chemistry Arjay Dave Deypalan Clinical Endocrinology -mostly for detection of gastrointestinal disorder -help diagnose certain conditions affecting digestive tract - the stool will be checked for color, consistency, amount, shape, odor and presence of mucus -Commonly ordered blood chemistries -has a broad introduction to a variety of concepts in chemistry -physical, chemical, and microscopic examination of urine. -urine is examined under a microscope to look at cells, urine crystals, mucus and other substances in the sample -to identify any bacteria or other germs that might be present in the urine Erica Nikki Jancee Pasaol -Generally concerned with body fluids and analysis -closely monitored for quality control in hospitals sample preparation Toxicology -includes 6 types of main sections. -provides testing on a variety of specimens and serves as key provider when focusing myeloma diseases Conclusion -study of hormones -branch of science that deals with endocrine system -concerned with the study of the fucnctions of hormones -measurement of therapeutic medications blood levels to optimize dosage - its main focus is on drugs with a narrow therapeutic range Fecal/ Stool Analysis Clinical Chemistry Definition -concerned with the study of the adverse effects of chemicals on living organism -studies harmful effects of chemical, biological, and physical agents that establishes extent damages on living organisms Gel electrophoresis Therapeutic Drug Monitoring 62 ECG bpm

Clinical Chemistry

Transcript: What is Clinical Chemistry? INtroduction its the branch of laboratory medicine that uses chemical anlaysis to study the levels of various body constituents during health and disease. These tests are usually performed on blood samples, but urine and other body fluids are analyzed Chemistry Panels/Profiles A grouping of tests that are used to reflect the state of an individuals general health OR used to evaluate a particular body system Types of specimens: Most common: blood & urine Less common: CSF, pleural, peritoneal, synovial Examples of panels Renal: glucose, BUN, creatinine, electrolytes LIPID: Triglycerides, total cholesterol, LDL, HDL Thyroid: T3, T4, TSH Cardiac: Creatine kinase Liver: Total protein, albumin, bilirubin, liver enzymrs (AST, ALT, LD, AP, GGT) Serum Proteins - formed from chains of amino acids 2 major groups: albumins (60%) and globulins (40%) Total serum protein and albumin are measured in a sample and globulin is computed from the difference (total protein - albumin = globulin) albumins serve as transport proteins globulins are comprised of antibodies, coag proteins, enzymes Albumin/globulin ratio should be 2:1; in liver and kidney disease it will be reversed; WHY? liver makes albumin, so its decreased in liver disease and in kidney disease, you lose albumin in your urine. Total serum protein provides info on state of hydration, nutrition and liver function Hypoalbuminemia occurs in liver disease, starvation, increased protein breakdown, and increased protein loss thru skin, kidneys or GI tract ELECTROLYTES refer to cations Na+, K+ and anions Cl-, HCO3- Effect hydration acid-base balance heart and muscle function MINERAL METABOLISM Calcium: bone & tooth formation; blood coagulation & neuromuscular excitation Phosphorus: bone & tooth formation Iron: Hgb production 90% is bound in calcium complexes in skeleton; only unbound is measured in lab Hypercalcemia occurs in parathyroidism, bone malignancies,hormone disorders Hypocalcemia - life threatening; due to hypoparathyroidism, vit D3 deficiency, poor Ca absorption due to intestinal disease Iron deficiency can lead to anemia; caused by iron poor diet, poor iron absorption, bleeding, impaired release of iron stores Increased serum iron levels can be due to hemolytic anemia, increased iron intake, blocked synthesis (lead posioning) Proper Kidney Function needed for water & electrolyte balance; serum & plasma creatinine, uric acid and BUN can be altered in kidney disease Creatinine is a waste product of creatine phosphate (stored in muscle for energy) If renal fucntion is impaired, serum creatinine levels increase BUN - surplus amino acids are converted to urea & excreted by kidneys Low levels: starvation, pregnancy, low-protein diet High levels: high-protein diet, after steroid use, kidney disease URIC ACID - formed from breakdown of nucleic acids & excreted by kidneys Tends to precipitate into crystals or urates Used to diagnose gout (uric acid precipitates in tissue - painful) LIVER FUNCTION Carb metabolism; produces plasma proteins; involed in lipid metabolism; source of cholesterol; storage site for vitamins, iron, glycogen; detoxifies BILIRUBIN - waste product from breakdon of Hgb; formed in liver & excreted in bile Most bili becomes bound & is called conjugated or direct; remaining is indirect Serum bili assays measure total & direct (Total - direct = indirect) Only increased levels are significant: hemolytic anemia, gall bladder disease; biliary obstruction LIVER ENZYMES - a rise typically reflects injury to liver tissue AP (alkaline phosphatase) - found thru out body, especially bone & liver ducts; increased levels w/ liver tumors & lesions ALT (alanine aminotransferase) - found in low levels in cardiac tissue and high levels in liver tissue; highly elevated in toxic and viral hepatitis AST (aspartate aminotransferase) - found in cardiac, muscle & liver tissue; elevated after MI and in liver disease GGT (gamma glutamyl transferase) - found in pancreas, kideny, liver & prostate; used to monitor recovery from hepatitis LD/LDH (lactate dehydrogenase) - throughout most of body tissue; increased after an MI and in liver disease CARDIAC FUNCTION Creatine kinase enzyme found in muscle & brain Following a heart attack, its released from heart muscle THYROID FUNCTION - thyroid gland makes hormones that stimulate metabolsim Hyperthyroidism (Graves) - excess secretion of thyroid hormones Hypothyroidism (myxedema) - decreased thyroid function T3 (triiodothyronine) - thyroid hormone T4 (thyroxine) - thyroid hormone TSH - anterior pituitary hormone that regulates thyroid gland Specimen Collection & Processing SERUM: used for most clinical chem tests Fluid that remains after blood has clottted No fibrinogen (clotting factors) in serum No anticoagulant is used in tube Gel separator; tiger or red top PLASMA: Fluid that remains after blood has not been allowed to clot Anitcoagulant is in tube Purple (heme), blue (coag tests), greent top (blood chems)

Clinical Chemistry

Transcript: plasma vs. serum analyzer Spectrophotometry determines concentration of apolipoproteins apolipoproteins are used to bind lipids in order to form lipoproteins calibration curve is created to determine unknown concentration determined risk factor for dyslipidemia, CVD, and neurodegenerative disease Spectrofluorometer Clinical Chemistry measures ions in sample potassium, calcium, sodium, fluoride, ammonium (urine sample) set up ion related diseases previously discussed can help diagnose Reye's syndrome, evaluate metabolism, response to treatment for liver disease, liver function Immunochromatography assay types description used to isolate antibodies strips are used to "trap" analyte strip components application pad conjugate pad test line absorbent pad colorimetry three different types sandwich competitive multiple detection sandwich labeled antibodies immoblized after the test line to capture any excess analyte that did not get trapped at the test line competitive labeled analyte and analyte from solution is in competition to bind with labeled conjugate on test strip multiple detection number of test lines are equivalent to the number of analytes being tested Immunoturbidimetric assay Background ELISA Sample Preparation measures fluorescence emitted from analyte how it works calibration curve created light source at the same wavelength of the analyte is passed through the sample wavelength excites analyte, causing it to emit light containing fluorescence photometer measures fluorescence amount of fluorescence is proportional to the concentration of analyte measures the transmittance and absorbance of light passing through a sample Beer-Lambert's law calibration curve blood glucose, iron-deficiency anemia, alcohol toxicity, lead toxicity, renal failure, hemolytic anemia determines total amount of protein in sample Various dilutions of bovine serum albumin to create calibration curve absorbance measured can diagnose kidney disease, liver disease, and multiple myeloma Overview Colorimetry Enzyme-linked immunosorbent assay concentration of peptides, proteins, antibodies, and hormones reaction process uses colorimetry can diagnose pancreatic function, renal failure, ovarian disease, risk of spontaneous abortion, metastatic prostate cancer, jaundice, small MI's Flame photometry most advanced can analyze multiple samples simultaneously Creatine phophokinase MI/heart attack Bilirubin viral hepatitis, cirrhosis, mononucleosis, jaundice, hemolytic anemias ISE Sample preparation photometry colorimetry flame photometers spectrophotometers Ion-selective electrodes (ISE) Assay immunoturbidmetric Bradford ELISA immunochromatography determines ion concentration sodium, potassium, and lithium Abnormal results for these could mean impaired absorption due to an alteration of the enzyme controlling that particular electrolyte, an issue with the parathyroid gland, cancer, multiple organ failure, toxic shock syndrome, pancreatitis, vitamin deficiencies, cystic fibrosis, congestive heart failure, etc Bradford assay Immunochromatography started in the 19th & 20th century animal chemistry William Prout Otto Folin & Donald Van Slyke used to prevent lawsuits misuse of clinical chemistry

Clinical Chemistry

Transcript: Meet the Pituitary -Small bean shaped gland at the base of the brain -Controls function of most of the endocrine glands -Separated into an anterior lobe [Adenohypophysis] and a posterior lobe [neurohypophysis] -Lobes are connected to the hypothalamus by a stalk that contains blood vessels and nerve cell projections Pituitary The Pituitary Gland TSH Thyroid Stimulating Hormone Function: Stimulate T3 and T4 release Stimulate thyroid gland growth -ANTERIOR PITUITARY- Stimulant Cold Stress TSH Bradycardia Stimulant TRH from the hypothalamus Target Thyroid Gland Hypometabolic states Structure Structure Same as LH and FSH Alpha Beta Unique to TSH Synthesis TRH Synthesis TRH to TSH TRH release TRH binding to pituitary Phosphokinase C pathway TSH gene activation and expression TSH to T3 & T4 TSH release TSH binds to thyroid gland Increase iodine uptake Increase tyrosine synthesis T3 & T4 synthesis and release TSH T3 & T4 ACTH -ANTERIOR PITUITARY- Adrenocorticotropic hormone Function: Endocrine stress response Stimulate cortisol synthesis Stimulant and Target ACTH Stimulant CRH from the hypothalamus Target Zona fasciculata Emotional Physiological Perceived Structure and Synthesis Synthesis ACTH CRH to ACTH CRH binding Proopiomelanocortin production and cleavage ACTH release ACTH to Cortisol MRAP activates binding of ACTH to MCR2 LDL receptor generation LDL uptake and breakdown Cortisol synthesis and release CRH Cortisol GH The Growth Hormone Function: Stimulates cell growth and division by accelerating the rate of protein synthesis -ANTERIOR PITUITARY- Synthesis and Structure Synthesis and Structure Polypeptide chain 190 Amino Acid Residues 2 Disulphide Bridges 4 alpha helices arranged in an anti-parallel manner Stimulant and Target Stimulant Target Stress Bone Muscle All other tissues Exercise Sleep High protein diet LH -ANTERIOR PITUITARY- Luteinizing Hormone Function: Stimulates sexual development and function Females: induce ovulation Males: produce sex hormones Function and Target LH Stimulant GnRH from hypothalamus Target Testes and ovaries Synthesis and Structure Structure Synthesis Glycoprotein molecule made of alpha 1 and beta 1 subunit Produced by gonadotropic cells and regulated by GnRH Similar to TSH, FSH, hCG FSH -ANTERIOR PITUITARY- Follicle-stimulating Hormone Function: Females: promotes follicle development, stimulates estrogen secretion Males: sperm maturation, inhibin production Stimulant and Target FSH Stimulant GnRH from hypothalamus Target Testes and ovaries Synthesis and Structure Synthesis Structure Produced in pituitary gland Regulated by GnRH Polypeptide units: alpha and beta Alpha same as TSH, hCG, LH Beta more unique to TSH PRL -ANTERIOR PITUITARY- Prolactin Hormone Function 2 primary responsibilities: milk production promotes growth of mammary alveoli Stimulant & Target Stimulant Stimulation of the nipples Suckling Target Mammary glands Synthesis & Structure Synthesis & Structure Lactotrophs Peptide hormone 198 amino acids Small protein MSH -ANTERIOR PITUITARY- Melanocyte-stimulating hormone Function: MSH Stimulates the melanocytes of the skin to increase the production of melanin Structure & Target Made by... Target: The pituitary Melanocytes Hypothalamus Skin Structure MSH is a group of peptide hormones and is the only hormone that is found in the pars intermedia Synthesis & Stimulant Stimulant Pars intermedia is only stimulated to secrete MSH... -During pregnancy -During fetal development -In very young children -Some diseases Skin is stimulated by the sun & UV light Oxt Oxytocin Hormone Function: Child birth and breast feeding Contract uterine muscle Movement of sperm -POSTERIOR PITUITARY- Synthesis and Structure Synthesis and Structure Oxytocin is composed of nine amino acids with a sulfur bridge between the two cysteines. The hormone is released into the blood from the posterior lobe Stimulant and Target Target Stimulant Labor Breast Feeding Females: Uterine Smooth Muscle Mammary Gland Males: Smooth muslce in ductus Prostate gland Sexual Activity Low Intensity stimulation ADH -POSTERIOR PITUITARY- Anti-Diuretic Hormone Function: Osmotic balance Kidneys Regulates blood pressure Blood volume Synthesis & Structure Synthesis Nerve cells Occurs in nuclei in hypothalamus Structure Structure Peptide hormone 9 amino acids Short Stimulant & Target Target Drugs Decrease in effective plasma volume Exercise Decrease in arterial pressure Stimulant Increase in serum osmolality Kidneys Pain, stress, sleep References References Al-Chalabi, M., Bass, A. N., & Alsalman, I. (2020). Physiology, prolactin. Statpearls. https://www.ncbi.nlm.nih.gov/books/NBK507829/#:~:text=Prolactin%20contributes%20to%20hundreds%20of,actual%20production%20of%20milk%20occurs. Angelousi, A., Margioris, A. N., & Tsatsanis, C. (2020). ACTH action on the adrenals. NCBI Bookshelf.https://www.ncbi.nlm.nih.gov/books/NBK279118/ Brinkman, J. E., Tariq, M. A., Leavitt, J., & Sharma, S. (2021). Physiology, growth hormone. Stat Pearls.

Clinical Chemistry

Transcript: Thank You! The Chemistry of MAID (Medical Assistance in Dying) Introduction Introduction Brief History Federal government passed the Bill C-14 on June 17th Pathway of MAID eligibility, meeting with Physicians and Nurse practitioners, witnesses, 10-day window period Voluntary euthanasia : euthanasia is conducted with consent - A doctor is allowed by law to end a person’s life by a painless means Assisted suicide: a doctor assists a patient to commit suicide if they request it Delivery Order of IV medication Medications 1. Saline 10ml 2. Midazolam 10mg 3. Saline 10ml 4. Lidocaine 40mg 5. Propofol 1000mg 6. Saline 10ml 7. Rocuronium 200mg 9. Saline 10ml Additional Antiemetic Medications: Metoclopramide 20mg PO and Ondansetron 8mg PO 1 hour prior to adminserting MAID Midazolam Midazolam Water soluble benzodiazepine Anxiolytic & sedative Changes respiratory pattern Short half life (T1/2: 15 minutes) Elimination: hepatic perfusion Bound to plasma proteins Reduces adrenergic but not cortisol or renin response Blood flow to kidneys and liver decreases, no changes in myocardial or cerebral oxygen consumption alpha-hydroxymidazolam --> hydroxylation ---> glucuronide Dose for MAID: 10mg Local Anesthetic Lidocaine Purpose: Given to reduce possible burning in a peripheral vein due to propofol. Mechanism of action: Lidocaine is an amide local anesthetic that works by stopping sodium ions from passing through voltage gated channels into cells on nerve cell membranes. This stops the sodium-potassium pump from becoming active and allowing pain stimulus to reach the central nervous system ( Beecham, Bansal, Goyal., 2020) Adverse Effects No sodium-potassium pump results in: - vasodilation -hypotension -irregular heart rate. Adverse Effects image: https://biology.stackexchange.com/questions/53750/sodium-concentration-during-action-potential-generation Medication and Pain Transmission Medication & Pain Transmission image: https://napaanesthesia.com/blog-pre-emptive-pain-management/ Propofol Propofol • Propofol, also recognized as 2,6-diisopropylphenol, and "milk of amnesia" due to it's opaque, milky colour, is a hypotonic, induction agent used as an IV delivered anesthetic and sedation drug • The unique properties allow for minimal side effects, a short half life of only 2 to 4 minutes, and does not have any known reversal agents • Propofol inhibits the neurotransmitter g-aminobutyric acid (GABA) through the GABA A receptors Effects of Propofol on Body Systems Central Nervous System: Propofol decreases cerebral metabolism, the blood flow and intracranial pressure; as the dose is increased it can also begin to significantly lower arterial pressures Respiratoy System: similar to many other CNS depressants, Propofol contains respiratory depressants allowing it to effectively decrease a patient's respirations, and acts to a greater effect than that of benzodiazepines Cardiovascular System: Propofol has much greater and profound effects than other anesthetics which is why it is preferred in most sedation procedures; it is also known to decrease systemic vascular resistance which in turn, lowers the cardiac output of the left ventricle, as well slows down the systolic and diastolic functions of the heart causing myocardial depressions Use of Propofol in MAiD • Propofol is the third drug used in medically assisted death via intravenous injection • Known to be painful to the patient entering the vein, so Lidocaine is first administered in order to provide comfort measures to the patient • Propofol is administered at a dose of 10mg/mL and each patient must be fully evaluated and assessed prior to injecting the last portion of drugs which are the neuromuscular blockers as full and sufficient sedation needs to be reached prior to carrying on with the procedure; the overall dose for propofol can vary for each patient Rocuronium Rocuronium 200 mg given IV Last step Used after a coma is induced by propofol as a non-depolarizing neuromuscular blocker or muscle relaxant Mechanism of Action: Rocuronium acts by competitively binding to nicotinic cholinergic receptors, preventing depolarization and the release of calcium ions stopping muscle contraction This stops breathing with no need to breathe (air hunger)/ gasping and distress After administration cardiac death is expected within 5-20 minutes and cyanosis may occur References References Beecham, Bansal, Goyal. (2020). Lidocaine. StatPearls Publishing. Retrieved from: https://www.ncbi.nlm.nih.gov/books/NBK539881 Byrne, M. F., Chiba, N., Singh, H., Sadowski, D. C., & Clinical Affairs Committee of the Canadian Association of Gastroenterology (2008). Propofol use for sedation during endoscopy in adults: a Canadian Association of Gastroenterology position statement. Canadian journal of gastroenterology. 22(5), 457–459. https://doi.org/10.1155/2008/268320, Jain, A., & Maani, C.V. (2019). Rocuronium. StatPearls Publishing. Retrieved from: https://www.ncbi.nlm.nih.gov/books/NBK539888/ J.W., Halliday,

Clinical Chemistry

Transcript: Clinical History 1 8 References Laboratory Testing 2 https://path.upmc.edu/cases/case825.html Contributed by Daniel D. Rhoads, MD and Octavia M. Peck Palmer, PhD Approxamentaly a month after debulking surgery, a 66-year-old female with metastatic colon cancer is brought to the emergency department. She reports weakness, fecal impaction, diarrhea, decreased oral intake, and weight loss. She says she has been taking docusate sodium, senna, polyethylene glycol, and milk of magnesia as instructed. 7 Conclusions Clinical Chemistry Result Interpretation 3 In order to treat this patient, she recieved fluid resusitation to improve the function of her kidneys so that she could begin to filter out the excess and establish balance. It was also discovered that she had been taking 3 times the recommended dose of milk of magnesia. This was promptly discontinued. She was able to leave the hospital after 9 days of treatment. While she has a lot of abnormal values, most of these can be attributed to an acute kidney injury, volume depletion, or tumor lysis syndrome. What stands out the most would be the magnesium of 11.5 mg/dL which would explain her muscle weakness. Complaints of Weakness Mackenzie Easter Hypermagnesemia 4 6 Other Tests to Conduct This patient has very classic signs and history: excess intake from docusate sodium, senna, polyethylene glycol, and milk of magnesia elderly (66) metastatic colon cancer (debulking) acute kidney injury (increased BUN, creatinine, urine protein) With hypermagnesemia, there should be additional measures taken to assess her parathyroid hormones because increases in magnesium can cause hyperparathyroidism. This is caused by low levels of PTH and would contribute the high phosphorus levels she has.

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