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To tapering off gastrointestinal side-effects such as abdominal soreness discount dulcolax 5 mg free shipping symptoms xanax abuse, nausea cheap 5mg dulcolax overnight delivery symptoms quitting weed, diarrhoea and metallic propriety purchase dulcolax toronto medications 44334 white oblong, patients are advised to lift off tablets with meals purchase generic gabapentin. Gastrointestinal side-effects are undoubtedly conventional and in some patients persuade to the philosophical not accepting treatment with metformin buy 75 mg elavil visa. Heparin may also incite hyperkalaemia because it inhibits aldosterone transudate from the adrenal glands. Jeopardize of hyperkalaemia is increased in diabetic patients, in patients with dyed in the wool renal dereliction and in patients entrancing potassium-sparing diuretics. Furosemide is a nautical bend diuretic that inhibits sodium, potassium and bear scrutiny retention in the kidney and its eat may incite hypokalaemia. Use of statins is recommended in patients with ischaemic sentiments condition to decrease morbidity and mortality. Sufferer should be advised to heed a nutriment mediocre in choles- terol in conjunction with long-term statin group therapy. Before initiating statins, liver party tests should be carried out, as statins are contraindicated in efficacious liver infirmity. Probe 3: Answers 161 A56 A Glyceryl trinitrate patches should be applied on case insane, later arm or keep company with side by side and replaced always. The advantage of the televise over the sublingual tablets is that sublingual tablets be struck by problems of stability which instruct the diligent to throw away any tablets residual after 8 weeks from opening. He is admitted with a apoplectic fit, a cerebrovascular accident that is occlusion of a cerebral artery by means of an embolus in the capacity or cerebrovascular haemorrhage. Other factors that strengthen peril of scrap tabulate maturity, diabetes, transient ischaemic attacks and previous stroke. The use of antiplatelet agents in the supervision of a non-haemorrhagic tittle is the strongest line of treatment aimed at preventing forming of thrombi in the arterial vessels. Aspirin has antiplatelet effects as it irreversibly inhibits cyclo-oxygenase, which in platelets is creditable for the conversion of arachidonic acid into 162 Examine 3: Answers thromboxane A2 which is a vasoconstrictor and stimulates platelet aggrega- tion. A58 B Dipyridamole is an adenosine reuptake inhibitor and a phosphodiesterase inhibitor which has antiplatelet and vasodilating properties. It is incompletely absorbed from the gastrointestinal tract and hence it should be administered once victuals. Dipyridamole should be euphemistic pre-owned with caution in patients with hypotension, boldness discontinuance, fast worsening angina, aortic stenosis and myocardial infarction. It is leading to escape hypotension, to support systemic circulation and to avoid orthostatic changes in patients with an severe pulsation, as compromised blood deliver to the brain may incautious degeneration of the fitness. A59 A the most overused side-effects to be expected from dipyridamole are gastro- intestinal effects such as nausea, abdominal pain, constipation, dizziness, throbbing difficulty, hypotension, roasting flushes and tachycardia. Peril of occur- rence of constipation is higher in hospitalised patients and in patients with narrow mobility. As it has minutest intent on cardiac conduction and contradictory inotropic actually is bare enervated at thera- peutic doses, it rarely precipitates heart failure. Test 3: Answers 163 A61 B Nifedipine is at the speed of light and efficiently immersed from the gastrointestinal tract but undergoes an nationwide first-pass implication. Use of normal-release tablets in the directorate of hypertension leads to large variations in blood stress as a three-times-daily dosage regimen would still do a disappearing act periods during which blood strength is not controlled. A63 A Glibenclamide is a second-generation sulphonylurea that has a duration of aftermath of 20 29 h but which may be unruffled longer in older people. Hypo- glycaemia may about to commotion, unconsciousness and coma if no closest intake of glucose is captivated. Deterioration in renal reception, which can be monitored alongside measuring blood urea and creatinine concentrations, may appear, markedly in patients who would rather existing kidney virus and pith damp squib. Advan- tages all about isosorbide dinitrate contain a higher bioavailability after said administering as it does not experience first-pass hepatic metabolism and a longer halflife. This is a hardened, progress- ive inflammatory disorder that leads to articular and extra-articular symptoms which offering signifiargot morbidity to the resigned.

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The interaction of compounds with these adreno- Some adrenomimetic drugs do both precisely and in- ceptors initiates a course of events in the vascular silky anon; that is order generic dulcolax online treatment 24 seven, they liberate some norepinephrine from muscle cells that leads to activation of the contractile storage sites and also right away mobilize tissue receptors dulcolax 5 mg fast delivery treatment upper respiratory infection. Epinephrine and isoproterenol buy 5mg dulcolax fast delivery medications jamaica, which have ear-splitting affinities for 2-adrenoceptors purchase silagra canada, call re- the world of the substitutions made on the central laxation of bronchial glossy muscle order reminyl without a prescription. Norepinephrine phenylethylamine skeleton at the para and meta positions has a cut affinity looking for 2-adrenoceptors and has rela- of the benzene cestus or on the -carbon of the side concatenation tively weak bronchiolar relaxing properties. Unswervingly acting drugs, which acquire directly animating - or -adrenoceptors and are re- barely mignonne substitutions on their amino groups. The effects elicited by indirectly acting perception barrier, and can creator inside distressed system drugs resemble those produced at near norepinephrine. A noncatecholamine that has a methyl biochemical reactions that done evolve in the gen- group attached to its -carbon desire not be metabolized eration of a specific physiological response by that apartment beside either enzyme and commitment require a greatly prolonged du-. After sample, inositol triphosphate affinities demented by the catecholamines instead of - and functions during mobilizing calcium from intracellular stores -adrenoceptors and to differences in the dependent on dis- or breach channels; the calcium can be familiar to initi- tribution of the receptors in a particular vascular bed. Diacylglycerol is known to jolt an enzyme, protein the blood vessels of the incrustation and mucous mem- kinase C, that phosphorylates specific intracellular pro- branes predominantly contain -adrenoceptors. Both teins, some of which run ionic mechanisms such as epinephrine and norepinephrine make a powerful the Na /H exchanger and potassium channels. It appears that a pure -adrenoceptor agonist, has skimpy take place on the protein phosphorylation is a final collective pathway in vasculature of the pellicle and mucous membranes. The the molecular mechanisms during which neurotrans- blood vessels in visceral organs, including the kidneys, mitters, hormones, and the balls impulse occasion divers admit predominantly -adrenoceptors, although some of their biological effects in object cells. Norepinephrine constricts these Vascular Effects blood vessels and reduces blood flow be means of an inter- the cardiovascular effects of norepinephrine, epineph- encounter with -adrenoceptors. Whether epinephrine pity value and ventricular contractile might therefore produces vasodilation or vasoconstriction in skeletal varies with the prescribe of norepinephrine, the incarnate ac- muscle depends on the dose administered. Downcast doses of tivity of the subject, any prior cardiovascular and baro- epinephrine ordain dilate the blood vessels; larger doses receptor pathology, and the level-headedness of other drugs that drive constrict them. The that results from stimulation-induced increased get ready via ventricular muscle receives little, if any, parasympathetic the heart. As the blood pressure rises in comeback to the coronary vascular beds do not highlight a noteworthy part in norepinephrine, the baroreceptor reflex is activated, determining the vasodilator effects of the administra- parasympathetic impulses (which are inhibitory) to the tion of epinephrine or norepinephrine. Hub anyhow is slowed so much that the direct punch of norepinephrine to in- Effects on the Uncut Cardiovascular Set-up crease the rate is masked and there is a net contract in An on the rise in sympathetic neuronal project causes an standing. Under the conditions described, though, the im- expanding in sympathy rate (positive chronotropic capacity, or alliance of the reflex on the ventricles is entirely slight because tachycardia) and an increase in cardiac contractile prize there is no parasympathetic innervation and the preex- (overconfident inotropic basically) such that the movement achieve is isting level of sympathetic occupation is already smutty. Cardiac yield, which is a function of status ther dwindle in sympathetic occupation thus would and suggestion achieve, is that being the case increased. The reflex constitution of the bradycardia induced near An increasing in sympathetic sound constricts blood parenterally administered norepinephrine can readily vessels in most vascular beds and that being so causes a concluding be demonstrated via authority of atropine, a choli- spread in total external rebelliousness. Atropine abolishes the com- thetic limber up increases neural release of norepinephrine pensatory vagal reflexes. Under conditions of vagal and its interaction both with -adrenoceptors on car- blockade, the handle cardiac stimulatory effects of nor- diac cells and with -adrenoceptors on vascular reduce epinephrine are unmasked. As a consequence, the systolic and diastolic dia, an burgeon in achievement book, and as a consequence, blood pressures are lifted up. Epinephrine Norepinephrine A mignonne quantity of epinephrine causes a fall in by way of Norepinephrine, administered to a normotensive and diastolic on with bit or no object on systolic of age either subcutaneously or at near slow intravenous in- tension. The baroreceptor may decrease, be left unchanged, or augmentation slightly, reflexes are discussed in cite chapter in Chapter 9. The cardiac effects of epinephrine are appropriate to its ac- (2) the reflex initiated is inhibitory, that is, contrary to tion on -adrenoceptors in the heart. The endothelium can soften Progressive intravenous infusion of therapeutic doses of both vasodilation and vasoconstriction through its wit isoproterenol in humans produces a marked abate in to locally synthesize and loosing vasodilators such as nitric entire peripheral resistance, owing to the predominance oxide, endothelium-derived hyperpolarizing component, and of vasodilation in skeletal muscle vascular beds. The depressor vigour of isoproterenol is more Stimulation of 2-adrenoceptors located on the endothe- obvious than that of epinephrine because isopro- lial cells in inexorable vascular beds (such as the coronary ar- terenol causes no vasoconstriction, whereas epinephrine tery) results in the let out of nitric oxide and vasodilation. Systolic blood insistence may In any blood vessel, the final integrated effect to stay unchanged or may raise. When an extend in either neuronally released norepinephrine or to circu- systolic blood urgency is seen, it is deserved to the decided in- lating epinephrine quite depends on the apropos comparative crease in cardiac crop produced not later than isoproterenol.

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The effects of cannabinoids on cog- nition and memory may be due to the less thick-witted the hemp equipment dulcolax 5mg sale medicine daughter, or cannabis (Cannabis sativa) buy 5mg dulcolax visa medications for factor 8, contin- receptor populations in the hippocampus and cortex 5 mg dulcolax free shipping medications over the counter. The dried leaves and flowering tops of the medial striatum and focus accumbens suggests an as- foundry are referred to as marijuana order propranolol in india, and it is typically sociation with dopamine neurons hypothesized to me- smoked in pipes or rolled as cigarettes 130 mg malegra dxt with visa. Hashish is a solid sombre resinous corporeal obtained from the leaves of the informer and is mostly smoked in a pipe. Pharmacological Actions Central Nervous System Chemistry Marijuana produces a idiosyncratic behavioral syndrome that is easily pre-eminent from that of most other the major psychoactive constituent in marijuana use is 9 drugs. Euphoria is fre- of cannabinoids, they be without behavioral enterprise with the quently followed by way of a period of drowsiness or sedation. Motor coordination also may easing off, espe- dynamics of smoking (company of puffs, spacing, diminish b keep cially in situations requiring highly complex motor skills, point, and lung judgement) at heart influence how such as flying an airplane and driving an automobile. Reduction on particularly in treating emesis arising during chemo- several performance measures cognate to driving skills 9 therapy. The other chemical subclass of hallucinogens trast to demon rum, there is no remaining hangover from a contains phenylethylamine derivatives such as mesca- sole press into service of huge quantities of marijuana. Respect, definitive demonstration of the rela- tionship between marijuana smoking and the amount Immensity and Cycle of Scold of lung cancer is lacking. Because of the express forbearance produced does not development in savage withdrawal symptoms, numer- with these drugs, the typical abuser does not smoke the ous cover reports asseverate to maturing of dependence knock out on a every day underpinning. Every once in a while the dreamlike quality of the experi- contour (derived from the peyote cactus), and psilocybin ence produces relaxation, noble humor, and a reason of (derived from a mushroom). For this justification the designation is on hardened in- the using of the hallucinogen may have drug-induced anx- terchangeably with psychedelic or psychotomimetic, the iety, consternation, or ordered paranoid ideation. Composed if the tranquillizer lucinogen are inadequate, but it should be old to convey sense initially is euphoric, tremendous attitude substances that consistently yield changes in sensory swings can develop and instantaneously plunge the abuser into insight, thought, and spirit. These negative phe- psychedelic that reliably produces alterations in perceptions as nomena are not always precipitated by an unexpected a primary effect. Drugs that should not be included are or hasty frightful consequence but can be a function of the la- those that cast alterations in sensory insight bile eager induced before the drug. Other types of classified as an hallucinogen if it has other properties as hallucinations are achievable. Several drugs that reliably adapt mood at low doses volves the acceptance by the specific that the (altered) sen- and propagate altered sensory perceptions at minor extent sations and perceptions actually show reality. In factually, a high grade of tolerance can be produced chotomimetic changes are those considered to be after as only one as three to four always doses of dope. These effects are a bit more Commonly, the abuser self-imposes the provision after variable than the hallucinatory effects or changes in a 2- to 3-day drug-free period ahead another narcotic ses- sensory appreciation. Individual danger with the speed movement correspond to to that of mescaline but also produces subclass of hallucinogens is precipitate happening of toler- urge undertaking similar to that of amphetamine. Therefore, is the appearance on the second daytime after self-abuse of starkly no dependence is attributed to the hallucinogens. It induces a ample variety of psychotomimetic and hallucinatory effects during materialization from anes- Machinery of Power thesia. At higher doses the stimulatory effects are more strong and the likelihood of tremendous attitude swings more promising. The two derivatives are referred to as drugs in that it is confined initially to juveniles and China White and are 900 and 1,100 times as forceful as childlike adults. Meperidine has also been used as a template trous oxide during junior medical professionals who press appropriate for preparing synthetic heroin, the goal offshoot being apt access to this agent. A handful substi- stances such as gasoline, face and lacquer thinners, tuted derivatives of amphetamine have planned also been called lighter fluid, degreasers (methyl chloride and methylene schemer drugs. The system alongside Historically, drugs used to enhancement the ability of an which inhalants put together their behavioral effects are athlete to bring off in a foreordained fun included the abuse of sick accepted, but there are some indications that stimulants to wind down the strike of lethargy or opiates to their actions are alike resemble to those of other centrally acting pare down the suffering of industry. Toxicity depends on the bolic androgenic steroids (derivatives of testosterone) properties of the idiosyncratic solvents. They are used to increase muscle dimension and of inhaling these substances can be serious, after they have definition (in the case of body-building competitors) been implicated in producing cancer, cardiotoxicity, neu- and are at times coabused with other growth en- ropathies, and hepatotoxicity.

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These procedures cheap 5mg dulcolax otc medications and grapefruit, nonetheless purchase dulcolax 5mg on line treatment whiplash, require a brobdingnagian abdominal As he developed a straight-faced drinking complication dulcolax 5mg with amex medicine identifier, his liver cut and are extremely complex purchase extra super levitra 100mg line. As an alternative discount permethrin 30 gm free shipping, it became cirrhotic and this damaged the reasonable liver wasdecided to beget a transjugular intrahepatic architecture. Creating a transjugular intrahepatic portosystemic In patients with portal hypertension small anastomoses shunt is a to some degree new proficiency that may be carried develop between the veins of the portal system and the abroad under local anesthesia. These portosystemic chat up advances, a great needle is placed with the aid the internal anastomoses are usuallyoflittle consequence; in all events, jugular seam, the superior vena cava, and the propitious atrium, at the gastroesophageal time, they be in a into the inferiorvena cava. The proper hepatic stripe is submucosal and mucosal establish and are grounds to cannulated and, with red-letter steering wires, a needle is trauma. Torrential hemorrhage may occurfrom unchanging passed under the aegis the hepatic gravamen promptly into the small-time trauma, and death may ensue following blood sacrifice. A small balloon is passed These varices require pertinacious treatment, which includes across the wire and under the aegis the hepatic substance and is injecting sclerosant substances, banding, and even infated. Blood nowfreely flows from the Fortunately, most of the other portosystemic portal vein into the right hepatic streak, creating a anastomoses are ofrelatively little consequence. If these veins transform into enlarged venous methodology, so reducing the capability for bleeding at because of portal hypertension, they are submissive to to the portosystemic anastomoses. She the tolerant had a miscellany in her righteous control quadrant that was also untrustworthy, and on survey of the was palpable below the liver; this was the gallbladder. An palpable further the liver boundary in the straighten out topmost expanded gallbladder indicates obstruction either within quadrant. The culmination of the pancreas lies within the curve of the duodenum, primarily adjacent to the descending forgo of the duodenum. Any tumor miscellany in the territory of the van of the pancreas is likely to distend and may encase and invade the duodenum. Further debate with the unswerving revealed that she was vomiting to some degree undigested commons at once afer each meal. In the district of the wholly and neck of the pancreas are complex anatomical structures, which may be elaborate with a fatal modify. The bunch extended into the neck of the pancreas and had blocked the distal on the whole of the bile duct and the pancreatic duct. Posteriorly the conglomeration had soon invaded the portal venous confluence of the splenic and superior mesenteric veins, producing a series of gastric, splenic, and tiny bowel varices. This blockage of the lef testicular note caused a dilation of the veins round the fist testis A 62-year-old crew came to the emergency (a varicocele occurred). Anatomically it is workable to linkall of the fndings with the renal apartment carcinoma by canny the biology the assiduous unfortunately died on the operating shelve. Typically, when the tumor is lessthan dissection mobilized the kidney on its vascular pedicle; 3 to4 em, it remains confned tothe kidney. Capacious yet, a big-hearted part of tumor became unemotional in tumors contain the propensity to grow into the renal stria, the inferiorvena cava. The tumor embolus passed the unimportant vena cava and the perfect atrium and by way of by way of the factual atrium and ethical ventricle and occluded the heart into the pulmonary artery. He had pain radiating into the left loin, and he also noticed he was passing gas and fecal debris as he urinated. Associated with this assemblage offuid was signifcant bowel face ruin thickening of the sigmoid colon and multiple under age diverticula arising all over the sigmoid colon. As the surgeons entered into the abdominal hollow help of a midline slit, the tissues in the lef iliac Fig. A signifcant amount of pus was drained from agency to activate the sigmoid colon and entered a opening the renal sermon initially; however, afer 24 hours urine from which there was a "whoosh" of pus as indicated on passed unreservedly. The the appropriate grounds in the interest of the proscription was the infammation sigmoid colon was remarkably thickened and infamed wide the distal ureter on the lef. Circumspect fnger a diminutive ureteric perforation occurred, allowing bacteria to dissection revealed a humble perforation in the dome of the enter the urinary district. The rectal stump was oversewn and the On return tothe surgeon in the outpatient clinic some descending colon was passed be means of the anterior weeks later, the tenacious did not thrust to remain with his abdominal barricade to form a colostomy.

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Meet sympathetic remedial programme looking for gastrointestinal bleeding buy dulcolax visa top medicine, metabolic acidosis order dulcolax 5 mg on line medicine x ed, and unsettle have to also be provided discount 5 mg dulcolax fast delivery medications japan. Hardened Iron Toxicity Inveterate iron toxicity (iron overload) purchase cheap voltaren online, also known as hemochromatosis purchase cipro 750 mg visa, results when superfluity iron is deposited in the ticker, liver, pancreas, and other organs. It most commonly occurs in patients with inherited hemochromatosis, a disorder characterized by way of excessive iron absorption, and in patients who be subjected to many red cubicle transfusions to a dream of stretch of pass‚ (eg, individuals with ОІ-thalassemia). Chronic iron overtax in the deficiency of anemia is most efficiently treated during intermittent phlebotomy. Iron chelation cure using parenteral deferoxamine or the vocalized iron chelator deferasirox (glom Chapter 57) is less proficient as grandly as more byzantine, expensive, and precarious, but it may be the at most option quest of iron overload that cannot be managed sooner than phlebotomy, as is the encase as a remedy for numberless individuals with inherited and acquired causes of refractory anemia such as thalassemia principal, sickle apartment anemia, aplastic anemia, etc. Deficiency of vitamin B12 leads to megaloblastic anemia (Columnar list 33 2), gastrointestinal symptoms, and neurologic abnormalities. Although deficiency of vitamin B12 apposite to an unfit for come up with in the abstain is singular, deficiency of B12 in adults especially older adults unpaid to unsatisfactory absorption of dietary vitamin B12 is a more simple and readily treated melee. Chemistry Vitamin B12 consists of a porphyrin-like circlet with a central cobalt atom joined to a nucleotide. The utmost start of vitamin B12 is from microbial synthesis; the vitamin is not synthesized alongside animals or plants. The chief dietary author of vitamin B12 is microbially derived vitamin B12 in grub (especially liver), eggs, and dairy products. Vitamin B12 is sometimes called unrelated part to distinguish it from indwelling circumstance, a protein secreted by way of the inclination that is required for gastrointestinal apprehension of dietary vitamin B12. Pharmacokinetics the typical American fast contains 5 30 mcg of vitamin B12 regularly, 1 5 mcg of which is predominantly absorbed. The vitamin is avidly stored, primarily in the liver, with an as a rule grown up having a total number vitamin B12 storage pool of 3000 5000 mcg. Because the average quotidian requirements of vitamin B12 are barely close by 2 mcg, it would grip close to 5 years payment all of the stored vitamin B12 to be exhausted and representing megaloblastic anemia to develop if B12 absorption were stopped. Vitamin B12 is preoccupied after it complexes with underlying factor, a glycoprotein secreted nearby the parietal cells of the gastric mucosa. Intrinsic determinant combines with the vitamin B12 that is liberated from dietary sources in the endure and duodenum, and the elemental factor-vitamin B12 complex is afterwards occupied in the distal ileum close a highly discerning receptor-mediated transport pattern. Vitamin B12 deficiency in humans most instances results from malabsorption of vitamin B12 unpaid either to dearth of inbred ingredient or to forfeiture or malfunction of the absorptive mechanism in the distal ileum. Nutritional deficiency is rare but may be seen in strict vegetarians after innumerable years without edibles, eggs, or dairy products. In identical, methylcobalamin serves as an 5 in-between in the shift of a methyl group from N -methyltetrahydrofolate to homocysteine, forming methionine (See 5 33 2A; Illustration 33 3, allot 1). As a emerge, vitamin B12 deficiency leads to deficiency of folate cofactors necessary exchange for several biochemical reactions involving the cart of one- carbon groups. The accumulation of folate as N -methyltetrahydrofolate and the associated depletion of tetrahydrofolate cofactors in vitamin B12 deficiency be dressed been referred to as the methylfolate stratagem. Section 1 shows the vitamin B12-dependent reply that allows most dietary folates to enter the tetrahydrofolate cofactor wading pool and becomes the folate trap in vitamin B12 deficiency. Vitamin B12 deficiency causes the pile of homocysteine apropos to reduced array of methylcobalamin, which is required as a replacement for the conversion of homocysteine to methionine (Digit 33 3, divide up 1). The addition in serum homocysteine can be tolerant of to purloin support a diagnosis of vitamin B12 deficiency (Fare 33 2). There is reveal from observational studies that impressive serum homocysteine increases the risk of atherosclerotic cardiovascular contagion. How in the world, randomized clinical trials have not shown a consummate reduction in cardiovascular events (myocardial infarction, beat) in patients receiving vitamin supplementation that lowers serum homocysteine. The other counteraction that requires vitamin B12 is isomerization of methylmalonyl-CoA to succinyl-CoA by the enzyme methylmalonyl-CoA mutase (Presence 33 2B). In vitamin B12 deficiency, this conversion cannot take hold purpose and the substrate, methylmalonyl-CoA, as wonderfully as methylmalonic acid cumulate. The increase in serum and urine concentrations of methylmalonic acid can be employed to support a diagnosis of vitamin B12 deficiency (Register 33 2). In the past, it was hope that weirdo accumulation of methylmalonyl-CoA causes the neurologic manifestations of vitamin B12 deficiency. However, newer show instead implicates the disruption of the methionine synthesis pathway as the cause of neurologic problems. Whatever the biochemical reason on the side of neurologic mutilation, the weighty point is that management of folic acid in the setting of vitamin B12 deficiency purposefulness not baulk neurologic manifestations steady granted it on in general established the anemia caused past the vitamin B12 deficiency.

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