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Individuals were assigned to ranges of energy intake from added sugars based on unadjusted Day 1 intakes buy amantadine with amex hiv infection rate haiti. Medians buy genuine amantadine online antiviral resistance mechanisms, standard errors buy amantadine with a mastercard antiviral nasal spray, and percents below or above the Dietary Reference Intakes were obtained using C-Side. When ranges of intakes do not share the same letter, they are significantly different (p < 0. Individuals were assigned to ranges of energy intake from added sugars based on unadjusted Day 1 intakes. Medians, standard errors, and percents below or above the Dietary Reference Intakes were obtained using C-Side. When ranges of intakes do not share the same letter, they are significantly different (p < 0. Individuals were assigned to ranges of energy intake from added sugars based on unadjusted Day 1 intakes. Medians, standard errors, and percents below or above the Dietary Reference Intakes were obtained using C-Side. When ranges of intakes do not share the same letter, they are significantly different (p < 0. Individuals were assigned to ranges of energy intake from added sugars based on unadjusted Day 1 intakes. Medians, standard errors, and percents below or above the Dietary Reference Intakes were obtained using C-Side. When ranges of intakes do not share the same letter, they are significantly different (p < 0. Individuals were assigned to ranges of energy intake from added sugars based on unadjusted Day 1 intakes. Medians, standard errors, and percents below or above the Dietary Reference Intakes were obtained using C-Side. When ranges of intakes do not share the same letter, they are significantly different (p < 0. Individuals were assigned to ranges of energy intake from added sugars based on unadjusted Day 1 intakes. Medians, standard errors, and percents below or above the Dietary Reference Intakes were obtained using C-Side. When ranges of intakes do not share the same letter, they are significantly different (p < 0. Individuals were assigned to ranges of energy intake from added sugars based on unadjusted Day 1 intakes. Medians, standard errors, and percents below or above the Dietary Reference Intakes were obtained using C-Side. Individuals were assigned to ranges of energy intake from carbohydrates based on unadjusted 2-day average intakes. Estimates of nutrient intake were adjusted using the Iowa State University method to provide estimates of usual intake. Children fed human milk or who reported no food intake for a day were excluded from the analysis. Individuals were assigned to ranges of energy intake from carbohydrates based on unadjusted 2-day average intakes. Estimates of nutrient intake were adjusted using the Iowa State University method to provide estimates of usual intake. Children fed human milk or who reported no food intake for a day were excluded from the analysis. Individuals were assigned to ranges of energy intake from carbohydrates based on unadjusted 2-day average intakes. Estimates of nutrient intake were adjusted using the Iowa State University method to provide estimates of usual intake. Individuals were assigned to ranges of energy intake from carbohydrates based on unadjusted 2-day average intakes. Estimates of nutrient intake were adjusted using the Iowa State University method to provide estimates of usual intake. Individuals were assigned to ranges of energy intake from carbohydrates based on unadjusted 2-day average intakes. Estimates of nutrient intake were adjusted using the Iowa State University method to provide estimates of usual intake. Individuals were assigned to ranges of energy intake from carbohydrates based on unadjusted 2-day average intakes. Estimates of nutrient intake were adjusted using the Iowa State University method to provide estimates of usual intake. Individuals were assigned to ranges of energy intake from carbohydrates based on unadjusted 2-day average intakes. Estimates of nutrient intake were adjusted using the Iowa State University method to provide estimates of usual intake. Individuals were assigned to ranges of energy intake from carbohydrates based on unadjusted 2-day average intakes. Estimates of nutrient intake were adjusted using the Iowa State University method to provide estimates of usual intake. L Options for Dealing with Uncertainties Methods for dealing with uncertainties in scientific data are generally understood by working scientists and require no special discussion here except to point out that such uncertainties should be explicitly acknowl- edged and taken into account whenever a risk assessment is undertaken. More subtle and difficult problems are created by uncertainties associated with some of the inferences that must be made in the absence of directly applicable data; much confusion and inconsistency can result if they are not recognized and dealt with in advance of undertaking a risk assessment. At least partial, empirically based answers to some of these questions may be available for some of the nutrients under review, but in no case is scientific information likely to be sufficient to provide a highly certain answer; in many cases there will be no relevant data for the nutrient in question. It should be recognized that for several of these questions, certain infer- ences have been widespread for long periods of time; thus, it may seem unnecessary to raise these uncertainties anew. When several sets of animal toxicology data are available, for example, and data are not sufficient for identifying the set (i. In the absence of definitive empirical data applicable to a specific case, it is generally assumed that there will not be more than a tenfold variation in response among members of the human population. In the absence of absorption data, it is generally assumed that humans will absorb the chemi- cal at the same rate as the animal species used to model human risk. In the absence of complete understanding of biological mechanisms, it is gener- ally assumed that, except possibly for certain carcinogens, a threshold dose must be exceeded before toxicity is expressed. The use of defaults to fill knowledge and data gaps in risk assessment has the advantage of ensuring consistency in approach (the same defaults are used for each assessment) and minimizing or eliminating case-by-case manipulations of the conduct of risk assessment to meet predetermined risk management objectives. The major disadvantage of the use of defaults is the potential for displacement of scientific judgment by excessively rigid guidelines. The risk assessors’ obligation in such cases is to provide explicit justification for any such departure. The use of preselected defaults is not the only way to deal with model uncertainties.
Chapter 8: Connective tissue disorders 367 Management Clinical features r Most patients with mild disease are treated conserva- r Thrombosis: Venous thromboses are more common tively discount amantadine hiv transmission risk statistics. These occur mainly in the r Nonsteroidal anti-inﬂammatory drugs are ﬁrst-line deepveinsofthecalf safe 100mg amantadine antiviral drugs for shingles. Arterialthrombosisinthe r Antimalarials are used for systemic symptoms purchase 100mg amantadine with amex hiv infection to symptom timeline, refrac- cerebral vessels, coronary, renal and mesenteric arter- tory arthritis and skin disease. Cyclophosphamide is more toxic but may be used in severe diffuse proliferative nephritis or severe neu- Investigations ropsychiatric lupus. Prognosis Generally a good prognosis, chronic forms of the disease Management are seen. Patients with renal or neuropsychiatric involve- Anticoagulation with aspirin for mild cases and war- ment have a worse prognosis. During the ﬁrst and third trimester of pregnancy low-molecular-weight heparin is used due to the terato- genicity of warfarin and risks of bleeding in labour. Antiphospholipid syndrome Deﬁnition A disorder characterised by the presence of autoantibod- Systemic sclerosis and scleroderma ies directed against phospholipids or plasma proteins bound to phospholipids. Deﬁnition Sclerosis (hardening due to excessive production of con- nective tissue) of collagen affecting the skin (sclero- Aetiology/pathophysiology derma) and the internal organs (systemic sclerosis). The condition causes a thrombotic ten- Incidence dency due to loss of phospholipid dependent coagula- Rare, 3 per million. Pro-thrombotic stimuli such as preg- nancy, surgery, cigarette smoking, hypertension and Age the use of oral contraceptives further exacerbate this Anyage, mean onset at 40 years. Antibodies include the lupus anti-coagulant (anti-coagulant in vitro but procoagulant in vivo), anti β2glycoprotein-I antibodies and anticardiolipin Sex antibodies. A scleroderma like disor- eration and thickening of the intima and ﬁbrosis of the der is seen following exposure to silica, vinyl chlo- adventitia is seen. Morphoea are patches of sclerotic skin on the trunk r Raynaud’s phenomenon is treated by avoiding cold, andlimbs,whichmaybelocalisedormoregeneralised. Malabsorp- r Limited cutaneous systemic sclerosis begins with tion may require changes in diet. Notreatmenthasbeenshowntoalter r Overlap syndromes have combinations of the features the long-term progression of scleroderma. Diffuse dis- of systemic sclerosis, systemic lupus erythematosus, ease with severe visceral involvement carries the worst dermatomyositis or rheumatoid arthritis. Chapter 8: Connective tissue disorders 369 Nervous system: Cardiovascular system: Ischaemic changes in central and Pericarditis, myocardial fibrosis peripheral nervous system. Peripheral causing a restrictive cardiomyopathy, neuropathy may occur due to conduction tissue fibrosis causes perineural vascular sclerosis. Respiratory system: Pulmonary fibrosis especially in lower Gastrointestinal system: lobes and pulmonary hypertension. Motility disorders including gastro- oesophageal reflux with oesophagitis, ulceration and aspiration pneumonia, malabsorption secondary to bacterial Genitourinary system: overgrowth. Sjogren’s¨ syndrome Pathophysiology There is lymphocytic inﬁltration of salivary glands and Deﬁnition other exocrine glands in the respiratory and gastroin- Achronic inﬂammatory disorder of the lacrimal and testinal tract, the skin and the vagina. Sex 9F : 1M Clinical features Aetiology r Ocular manifestations: Sensation of persistent grit- Sjogren’s¨ syndrome may be primary, or secondary to tiness, photosensitivity, tiredness and an inability to rheumatoid arthritis, systemic lupus erythematosus, produce tears (keratoconjunctivitis sicca). There is r Gastrointestinal system: Lack of saliva (xerostomia) an association with non-Hogkin B cell lymphoma. There 370 Chapter 8: Musculoskeletal system may be oral ulcers, dental caries and ﬁrm non-tender age of 40 years. The skin shows collagenous thicken- phenomenon and an association with other organ ing of the dermis with chronic inﬂammatory cell inﬁl- speciﬁc autoimmune disorders in primary Sjogren’s¨ trates. Occasionally there are systemic features including vasculitis and renal tubu- Clinical features lar defects. Gradual onset of non-speciﬁc systemic features followed by symmetrical, progressive, proximal muscle weakness. Occasionally there is cardiac r Schirmer’s test for keratoconjunctivitis sicca measures involvement leading to heart failure, respiratory involve- tear production. An edge of a strip of ﬁlter paper is ment, including nonspeciﬁc interstitial pneumonia, and placed in the lower eyelid and the length that becomes oesophageal involvement, which may be sufﬁciently se- wetismeasured. Management Sex Acute phases are treated with corticosteroids, which 2F: 1M should be reduced gradually to a low-maintenance dose. Methotrexate, azathioprine or cyclophosphamide are Aetiology/pathophysiology used in resistant cases. Dermatomyositis is associated with malignancy of variable severity, and spontaneous remissions can (e. Chapter 8: Crystal arthropathies 371 Marfan’s syndrome Management r β-blockers have been shown to slow aortic dilata- Deﬁnition tion, and lifelong therapy is recommended by the Inherited condition resulting in abnormalities of con- European Society of Cardiology. The under- r Musculokeletal: Patients have elongated and asym- lyingpathologyisanabnormalityinskin,jointandblood metrical faces with a high arched palate. Some of the reduced upper to lower body segment ratio and an subtypes have been mapped to mutations in the collagen arm span that exceeds the patient’s height. Clinical features r Cardiovascular system: There is degeneration of the There is hyperextensible skin with normal elastic recoil, media of blood vessel walls: hypermobile joints, and fragility of blood vessels causing 1 Dilation of the aortic valve ring producing regurgi- bruising and occasionally aortic dissection and rupture. Hypermobility can lead to early osteoarthritic changes 2 Mitral valve prolapse and associated mitral valve and damage to the joints. The diagnosis is clinical and can be based on clinical cri- r Calcium pyrophosphate causes pseudogout. Once diagnosed patients require periodic r Crystallised injected corticosteroids may result in ia- aortic imaging to detect early dilation. Typically pyrosphosphate crystals are seen Xanthine Hypoxanthine within a phagolysosomal sac, whereas urate crystals are Xanthine Oxidase not conﬁned. Phagocytosis induces Uric Acid cytokine release leading to chemotaxis and further in- ﬂammation. An acute inﬂammatory arthritis resulting from urate An acuteepisodeofgoutmaybeprecipitatedbyasudden crystal deposition secondary to hyperuricaemia. Risk factors include surgery, infection, dehydration, severe illness, Prevalence/incidence starvation, diuretics and alcohol. Pathophysiology r Injointsanacutesynovitismayoccurwhenuratecrys- Age tals have been phagocytosed. Sex r If chronic, the crystals accumulate in the synovium 10M:1F and sites such as the ear cartilage forming lumps termed tophi. Theresultof urate damage is either tubulointerstitial disease (urate Aetiology nephropathy) or acute tubular necrosis. High levels of uric acid cause gout but not all individuals with hyperuricaemia will develop gout.
Arthritis may involve a ated features such as joint instability should be enquired single joint (monoarticular) order amantadine american express hiv infection after 1 week, less than four joints (oligo about order genuine amantadine on line hiv infection symptoms rash. The relationship to exercise may be important 100mg amantadine visa an antiviral agent quizlet, as inﬂamma- tory disorders are often worse after periods of inactivity Joint stiffness and relieved by rest, whereas mechanical disorders tend Joint stiffness is another presentation usually associated to be worse on exercise and relieved by rest. A full systems enquiry is necessary as are characteristic of rheumatoid arthritis but may oc- many disorders have multisystem involvement. Less than 10 minutes in sensation including tingling or numbness are often of stiffness is common in osteoarthritis compared with due to abnormalities in nerve function. Establishment of iacstiffnessisaparticularfeatureofankylosingspondyli- the distribution helps to differentiate peripheral nerve tis. Locking of a joint is a sudden inability to complete damage from nerve root damage. Loss of function is im- amovement, such as extension at the knee caused by a portant as therapy aims to both relieve pain and establish mechanical block such as a foreign body in the joint or necessary function for daily activities. Seropositivity allows prediction of severity and the need for earlier aggressive therapy and Although some of the available tests used in diagnosis increases the likelihood of extra-articular features. Combin- ing tests may allow a clinical diagnosis to be conﬁmed Joint aspiration (see Table 8. Rheumatoid factor: These are antibodies of any class Unexplained joint swelling may require aspiration to directed against the Fc portion of immunoglobulins. The aspiration itself may be of therapeu- The routine laboratory test detects only IgM antibodies, tic value lowering the pressure and relieving pain. It is which agglutinate latex particles or red cells opsonised often coupled with intra-articular washout or instilla- with IgG. It is the presence of these IgM rheumatoid tion of steroid or antibiotic as appropriate. Examina- factor antibodies that is used to describe a patient as tion of the synovial ﬂuid may be of diagnostic value (see seropositive or seronegative. Local spread from a soft tissue infection atively birefringent, whereas the crystals of pseudogout may also occur. Previously Haemophilus inﬂuenzae was seen in young children, Many modalities of joint imaging and direct visualisa- but it is now rare due to vaccination. Patients with tion are used to diagnose and follow the course of mus- sickle cell anaemia are prone to osteomyelitis due to culoskeletaldisordersandareoftenusedincombination. The ﬁndings in individual conditions will be described r Direct spread from local infection may occur with later. Streptococcus, Staphylococcus, anaerobes and gram- r X-ray: Many musculoskeletal disorders have charac- negative organisms. Pathophysiology Comparison of X-ray changes over time is especially In children the long bones are most often involved; in useful in monitoring disorders that have a degenera- adults, vertebral, sternoclavicular and sacroiliac bones tive course. In- r Ulrasound is of value in examining the joint and sur- fections from a distant focus spread via the blood stream rounding soft tissue. In children the organisms usually diagnosing the cause of a painful hip not amenable to settle in the metaphysis because the growth disc (physis) palpation. Acute inﬂammation occurs accompanied by a rise in It can demonstrate both bone and soft tissue disor- pressure leading to pain and disruption of blood ﬂow. In children infectious conditions prior to X-ray changes, it is of the physis acts as a physical barrier to intra-articular great value in identifying malignant bone inﬁltration spread. Bone and joint infections Clinical features Presentationrangesfromanacuteillnesswithpain,fever, swelling and acute tenderness over the affected bone, to Acute osteomyelitis an insidious onset of non-speciﬁc dull aching and vague Deﬁnition systemic illness. Complications Age r As thebonehealsandnewboneisformed,infectedtis- Normally seen in children and adults over 50 years. Chapter 8: Bone and joint infections 355 Sinuses form in the presence of continuing infection, Chronic osteomyelitis resulting in a chronic osteomyelitis. Aetiology Investigations Previously, chronic osteomyelitis resulted from poorly r The X-ray ﬁnding may take 2–3 weeks to develop. It now occurs more fre- raised periostium is an early sign that may be seen quentlyinpost-traumaticosteomyelitis. With healing there is sclerosis and seques- Pathophysiology trated bone fragments may be visible. Blood cultures are positive in the bone may remain dormant for years giving rise to 50%. Clinical features The clinical course is typically ongoing chronic pain Management r and low-grade fever following an episode of acute os- Surgical drainage should be used if there is a subpe- teomyelitis. There may be pus discharging through a si- riosteal abscess, if systemic upset is refractory to an- nus. However, if the pus is retained within the bone or tibiotic treatment or if there is suspected adjacent join the sinus becomes obstructed, rising pressure leads to an involvement. Par- enteral treatment is often required for a prolonged period (2–4 weeks) prior to a long course of oral an- Investigations tibiotics to ensure eradication. Theperiostiummayberaisedwithunderlying with a third-generation cephalosporin to cover for new bone formation. Management r Adequate analgesia is essential and may be improved Discharging sinuses require dressing, and if an abscess with splints to immobilise the limb (which also helps persists despite antibiotic therapy it should be incised to avoid contractures). Prolonged combined parenteral antibiotics to reduce associated muscle disuse atrophy and to are required. In early stages the joint space is preserved, but later there is narrowing and ir- Tuberculous bone infection regularity with bone erosion and calciﬁcation within adjacent soft tissue. Incidence Patients with tuberculosis have a 5% lifetime risk of Management developing bone disease. Chemotherapy with combination anti-tuberculous agents for 12–18 months (see page 105). Rest and trac- tion may be useful; if the articular surfaces are damaged, Age arthrodesis or joint replacement may be required. Geography Septic arthritis Major illness in developing countries, with increasing Deﬁnition incidence in the developed world. Aetiology Tuberculous osteomyelitis is usually due to haematoge- Aetiology nous spread from a primary focus in the lungs or gas- Joint infection arises most commonly from haematoge- trointestinal tract (see pages 105 and 154). Other mechanisms include local trauma or creased the incidence of tuberculosis and tuberculous an adjacent infective focus such as osteomyelitis. The patient complains of pain and later swelling due to Pathophysiology pus collection. Muscle spasm and wasting occur with Bacteriaareinitiallyfoundinthesynovialmembranebut limitation of movement and rigidity. Cytokine-mediated losis, pain may be mild and presentation delayed until inﬂammationandariseinintra-articularpressurefollow thereisavisibleabscessorvertebralcollapsecausingpain the spread of bacteria. Erosion of the articular cartilage results from the In previously healthy children and adults, penicillin release of proteolytic enzymes from neutrophils within (Streptococcus cover) and ﬂucloxacillin (Staphylococ- the inﬂammatory exudate. A third-generation cephalosporin enzymes can result in chondrocyte and bone damage. If the hip The classical features of septic arthritis are a red, hot, is infected it should be held abducted and 30◦ ﬂexed. Overall the Drainage of pus and arthroscopic joint washout under knee is the most commonly affected joint, but hips are anaesthesia can be performed.
Ten minutes of light jogging cheapest amantadine antiviral resistance mechanisms, cycling buy on line amantadine hiv infection vdrl, or calisthenics before practice will increase circulation to cold muscles trusted amantadine 100 mg hiv infection, making them more pliable so that they put less stress and tension on their attachment sites (apophyses). The heel portion of the shoe should not be too tight and there should be good padding in the heel. The result is shorter healing time and faster return to sport Stretching exercises for calcaneal apophysitis To be done 2-3 times daily 1. Standing calf stretch Facing a wall, put your hands against the wall at about eye level. With the back knee straight, push the heel of the back leg down on the floor and slowly lean into the wall, until you can feel a stretch in the back of your calf muscle. Towel stretch Sit on the floor with your injured leg stretched out in front of you. Using kidney rather than renal improves understanding by patients, families, healthcare workers, and the lay public. Designations 5D and 5T indicate end-stage renal disease patients who undergo chronic dialysis (5D) treatment or have undergone kidney transplantation (5T). Recently, insulin resistance, obesity, and the metabolic syndrome have been implicated as risk factors. The increased utilization of pharmaceuticals has increased the frequency of immune-mediated (allergic) tubulointerstitial nephritis, particularly from antibiotics. Lastly, volume depleted patients are more susceptible to radiocontrast-induced nephropathy. Comprehensive systems targeting early recognition, prevention and management, and treatment by primary care physicians and physician extenders are required at this critical stage in collaboration with nephrologists. Their opinions also differed from nephrologists regarding evaluations by and expectations of nephrologists. Certain conditions such as malignancy, dementia, multiple comorbidities, or an advanced directive may preclude referral to a nephrologist. Electrolyte Abnormalities Na <130 mEq/L or >147 mEq/L in absence of diuretics K <3. In a prospective German study, the 5-yr survival rate was <10% in elderly type 2 diabetics and <40% in the younger type 1 cohort. The elderly, including patients 75 yr, are less likely to survive long enough to receive a deceased donor kidney transplant compared with non-diabetic patients. However, if left untreated, there is progression through phases of asymptomatic mesangial extracellular matrix accumulation, microalbuminuria, macro- albuminuria, and finally, overt proteinuric nephropathy. During the asymptomatic phase, glomerular hyperfiltration occurs with mesangial scarring. Due to the hyperglycemia-induced2 accumulation of matrix, diabetic kidneys are frequently normally sized when examined by ultrasound (normal: 10–12 cm). In some series, diabetic nephropathy may be accompanied by another non-hypertension-related kidney disorder in 5–15% of cases. The 24-h urine protein is considered the gold standard of urine protein determination as protein excretion may vary with the circadian rhythm, particularly in patients with glomerular disease. Benign proteinuria that occurs due to fever, intense exercise, postural changes, volume depletion, or acute illnesses should be reevaluated during stable conditions. Because several factors may cause transient increases in microalbuminuria, the diagnosis requires at least 2 serial first-morning urine specimens over 2–3 weeks. For example, African Americans typically display earlier and more rapid declines in renal function. The presence of one or more of these clinical scenarios should prompt urgent patient referral to a nephrologist for confirmatory and/or additional diagnoses. Clinical remission of renal disease has taken place when proteinuria declines to <1 g/24-h, and regression is defined by a decline in proteinuria to <0. A reduction in insulin and/or other antihyperglycemiant medications (not metformin) may be required to prevent hypoglycemia. Aging and obesity are the two most important reasons behind this increasing prevalence. However, ethnicity-related differences in therapeutic response are usually nullified by concomitant diuretic therapy. Therefore, no particular agent should be avoided in patients of African American ethnicity. Greater elevations should be thoroughly investigated and may require nephrological consultation. High sodium intake reduces effectiveness of antihypertensive therapies and is determined best by a 24-h urine sodium collection. The prevalence of proteinuria is 4–8% worldwide and 10–20% in hypertensive, obese, and/or diabetic populations. The presence of even small amounts of albuminuria (>10 mg/g) is associated with adverse cardiovascular outcomes. Types of Proteinuria Traditionally, normal urinary protein excretion is considered to be <150 mg/24-h; total urinary proteins measured are comprised of immunoglobulins, assorted globulins, and Tamm-Horsfall mucoprotein. Persistently elevated total urinary protein signifies: a) defect(s) in the glomerular basement membrane b) impaired tubular protein reabsorption, eg, tubulointerstitial nephritis c) increased filtration of low molecular weight protein(s), ie, “overflow proteinuria” as may occur with light chains. Persistent proteinuria is defined as two or more positive quantitative tests of protein excretion, separated by at least 2 weeks. Common, benign sources of albuminuria/proteinuria include orthostatic proteinuria, intense activity/exercise, and fever. The urinalysis dipstick may not register proteinuria when the urine is highly dilute, (ie, specific gravity 1. Notably, a new classification system that eschews the terms micro- and macroalbuminuria may be established in the near future. The urine dipstick favors albumin detection and is relatively insensitive for tubular proteinuria, eg, immunoglobulin light chains. If tubular proteinuria is suspected, specific qualitative and quantitative examinations may be required, eg, serum free light chain analysis (Freelite™) and serum and urine immunofixation. For screening purposes, a 24-h urine is unnecessary, but if a serum monoclonal protein is detected, a 24-h urine collection for immunofixation is indicated. Consultation with a clinical laboratory expert is advised to optimize diagnostic yield in such cases. Patients with stable, persistent proteinuria of <1 g/24-h have a very small risk of progression to kidney failure compared to individuals with greater proteinuria. Inflammation upregulates hepcidin, a liver-synthesized protein that reduces gut iron absorption and impedes iron release from the reticuloendothelial system to the developing erythron. To correct iron deficiency, oral iron should always be tried initially, and multiple iron salt preparations are available.
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