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PHARMACEUTICALS 1. NAME 1.1 SubstanceRetinol 1.2 GroupVitamin A 1.3 Synonyms15- apo-B-caroten-15-ol (3,7-dimethyl-9-(2,6, 6-trimethylcyclohex-1-enyl) nona- 2 anti-infective vitamin Anti-xerophthalmic vitamin Axerophtholum Biosterol Oleovitamin A Retinal (vitamin A aldehyde) vitamin A1 1.4 Identification numbers 1.4.1 CAS number 1.4.2 Other numbers 68-26-8 Martindale online monograph link no. 7823-k 1.5 Brand names, Trade namesTo be completed by each centre. 1.6 Manufacturers, ImportersA 313 (Chabre, France) 2. SUMMARY 2.1 Main risks and target organsAcaren (Belgium) Afaxin (Canada) AFI-A diagnostikum (Nyco, Norway) Alfa Monovit (Italy) Alfatar (Arnaldi, Italy) Alphalin (Lilly, USA) Amirale (IDI, Italy) Amplex-A (Spain) A-Muslin (Mucos, Germany) Anol Standard (Belgium) A-OM (Spain) Aquasol A (Argentina, Rover Canada, Armour USA) Ariovit (Roche, Denmark) Arovit (Belgium; Roche in France, Germany, Italy, Netherland, South Africa, Spain, Sweden, Switzerland) Astrapin, oily form (Germany) Atunol (Argentina) Auxina A Masiva (Gayoso Wellcome, Spain) Avibon (Theraplix, France) A-Vicotrat (Heyl, Germany) Avimin (Ferrosan, Denmark) Avita (South Africa) Avitam Masivo (Spain) A-vitamin (DAK, Denmark) Avitina (CT, Italy) Axerol (Wander, Switzerland). Isotretinoil (CAPS, South Africa). Medox, Vitamin A tablet (CAPS, Zimbabwe) To be completed by the centre. The main risk is hypervitaminosis A which occurs both in young children and adults receiving more than 100,000 units/daily over several months or in acute poisoning. 2.2 Summary of clinical effects Target organs are the skin, CNS, bone and liver. Chronic vitamin A intoxication produces musculo-skeletal and skin disorders, dry hair, alopesia, anemia, headache, hepatomegaly, fever and gastrointestinal disturbanaces in the adult. Headache, nausea, vomiting and irritability have been observed after excessive consumption of animal liver containing vitamin A or one dose of 1,500,000 IU. Toxicity is reversible on withdrawal of vitamin A, but in children, premature closure of epipyses of long bones may arrest bone growth. 2.3 Diagnosis Infants aged 3-7 months who ingested 350,000 IU developed vomiting, irritability, bulging fontanelles and elevated cerebrospinal fluid pressure (Ellenhorn & Barceloux, 1988). Toxicity usually occurs about 6 h after ingestion in acute poisoning with vitamin A. Acute overdose also results in hydrocephalus in infants and increased intracranial pressure (pseudotumor cerebri) in older children and adults. Symptoms of acute overdose include bleeding from gums or sore mouth and a bulging soft spot on head. In babies, confusion or unusual excitement, diarrhoea, dizziness, or drowsiness, double vision, severe headache, severe irritability, peeling of skin, especially on lips and palms, seizures, and severe vomiting have been reported. The diagnosis is made by history of exposure to vitamin A and the presence of nausea, vomiting, anorexia, headache, irritability, engthema, prurities, fever, features of acute vitamin A poisoning. There may be fatigue hepatosplenomegaly, visual disturbances, skin lesions, dry hair, bleeding and haematological abnormalities in chronic exposure. 2.4 First aid measures and management principles In children raised intracranial pressure with bulging fontanelles, papilloedema and diplopia may be symptoms of chronic toxicity. Laboratory analyses may show raised serum aspartate transaminase (SGOT), alanine transaminase (SGPT), erythrocyte sedimentation rate, serum calcium and alkaline phosphatase in blood. Complete blood count may reveal haematological abnormalities such as anaemia, leucopenia or leucocytosis, and thrombocytopenia. In acute poisoning by ingestion, induce emesis or perform gastric lavage and administer activated charcoal. 3. PHYSICO-CHEMICAL PROPERTIES 3.1 Origin of the substance In cases of eye contact, immediately irrigate with copious amounts of water. In severe overdoses, maintain clear airway, establish and monitor breathing and circulatory functions. Reduce intracranial pressure with mannitol or corticosteroids. Monitor blood pressure, fluids, electrolytes, papilledema and CNS status. Vitamin A ester concentrate (natural) consists of a natural ester, or mixture of natural esters of retinol, or of a solution of ester, or mixture of esters in arachis oil or other suitable vegetable oil. It contains in 1 g not less than 485,000 units of vitamin A and not less than 97.0% of the number of units of vitamin A stated on the label. It may contain a suitable antioxidant or mixture of antioxidants (BP 1988). 3.2 Chemical structure Synthetic vitamin A concentrate (oily form) consists of an ester or mixture of esters of retinol (the acetate, propionate or palmitate) prepared by synthesis. It may be diluted with a suitable vegetable oil. It contains in 1 g not less than 500, 000 units of vitamin A and not less than 95.0% and not more than 110.0% of the number of units of vitamin A stated on the label. It may contain suitable stabilizing agents such as antioxidants (BP 1988). Synthetic vitamin A concentrate (powder form) consists of an ester or mixture of esters of retinol (the acetate, propionate or palmitate) prepared by synthesis and dispersed in a matrix of gelatin, acacia or other suitable material. It contains in 1 g not less than 250,000 units of vitamin A and not less than 95.0% and not more than 115.0% of the number of units of vitamin A stated on the label. It may contain suitable stabilizing agents such as antioxidants (BP 1988). Synthetic vitamin A concentrate (water-dispersible form) consists of an ester or mixture of esters of retinol (the acetate, propionate or palmitate) prepared by synthesis to which suitable solubilizers have been added. It contains in 1 g not less than 100,000 units of vitamin A and not less than 95.0% and not more than 115.0% of the number of units of vitamin A stated on the label. It may contain suitable stabilizing agents such as antimicrobial preservatives and antioxidants (BP 1988). Structural formula: C20H3O 3.3 Physical properties 3.3.1 Properties of the substance Molecular weight: 286.5 - Vitamin A Ester Concentrate (Natural) 3.3.2 Properties of the locally available formulation Characteristics: A yellow oil or mixture of oil and crystalline material which yields an homogenous yellow oil on warming with a faint odour. Solubility: Practically insoluble in water; soluble or partly soluble in ethanol (96%); miscible with chloroform, with ether and petroleum spirit. - Synthetic Vitamin A Concentrate (Oily Form) Characteristics: A yellow to brownish-yellow oily liquid with a faint and characteristic odour. Solubility: Practically insoluble in water; soluble or partly soluble in absolute ethanol; miscible with organic solvents. Partial crystallization may occur in highly concentrated solutions. - Synthetic Vitamin A Concentrate (Water-dispersible Form) Characteristics: a yellow or yellowish liquid of variable opalescence and viscosity and a characteristic odour. Highly concentrated solutions may become cloudy at low temperatures or take the form of a gel at room temperature. Solubility: Soluble in water. Melting points: Vitamin A acetate about 57 °C Vitamin A palmitate 28-30 °C. To be completed by each centre. 3.4 Other characteristics 3.4.1 Shelf-life of the substanceUp to 2 years depending on the preparation. 3.4.2 Shelf-life of the locally available formulationTo be completed by each centre. 3.4.3 Storage conditionsVitamin A ester concentrate (natural), synthetic Vitamin A concentrates (oily, powder and water-miscible forms) should be kept in an airtight container, protected from light and stored at a temperature of 8°C to 15°C. Once the container has been opened its contents should be used as soon as possible; any part of the contents not used at once should be protected by an atmosphere of an inert gas. 3.4.4 BioavailabilityTo be completed by each centre. 3.4.5 Specific properties and compositionTo be completed by each centre. 4. USES 4.1 Indications- Vitamin A deficiency (prophylaxis and treatment). 4.2 Therapeutic dosage 4.2.1 Adults Vitamin A is indicated only for prevention or treatment of Vitamin A deficiency states, which may occur as a result of inadequate nutrition or intestinal malabsorption in patients receiving an adequate balanced diet. Dietary improvement is preferred over supplementation whenever possible. Deficiency of vitamin A may lead to keratomalacia, xerophthalmia, and nyctalopia (night blindness). Requirements of vitamin A may be increased and/or supplementation may be necessary in the following persons or conditions (although clinical deficiencies are usually rare) (Reynolds, 1989; USP DI, 1989; McEvoy, 1988; Speight, 1987; Vanderveen, 1980). - During prolonged stress or infection or chronic fever In malabsorption syndromes associated with pancreatic insufficiency (pancreatic disease, cystic fibrosis); hepatic biliary tract disease (hepatic function impairment, cirrhosis, obstructive jaundice); diseases of the small intestine (coeliac disease, tropical sprue, regional enteritis, persistent diarrhoea); or postgastrectomy in patients with diabetes mellitus, hyperthyroidism, or severe protein deficiency. In general, Vitamin A absorption will be impaired in any condition in which fat malabsorption (steatorrhoea) occurs. In addition, conversion of dietary beta-carotene to vitamin A may be impaired in diabetes mellitus and hyperthyroidism. Supplementation with vitamin A is necessary in patients receiving total parenteral nutrition (TPN); undergoing rapid weight loss regimes; or in those with malnutrition, because of inadequate dietary intake. Requirements of all vitamins are increased during pregnancy and breast-feeding. However, high doses of vitamin A are teratogenic and there are few indications for supplementation during pregnancy. Requirements may be increased by the following medications: cholestyramine, colestipol, mineral oil, neomycin and sucralfate. Vitamin A is not appropriate for the treatment of dry or wrinkled skin, eye problems, or prevention or treatment of infections not related to vitamin A deficiency. Vitamin A dietary intake has been reported in a population-based case-control study to have reduced the risk of cervical cancer (Verreault et al, 1989). - Dermatological disorders The oral retinoids, or synthetic derivatives of vitamin A, are used in the treatment of various dermatoses. The most useful drugs are isotretinoin (13-cis-retinoic acid) for nodulocystic acne and etretinate for refractory psoriasis vulgaris. Retinoids are also effective in the treatment of papulomatous dermatoses other than psoriasis (e.g., inherited disorders of keratinization), cutaneous T-cell lymphoma and in the chemotherapy of cancer (Pasterino et al, 1988, Caffery & Josephson, 1988). However, systemic administration of these compounds is frequently associated with liver toxicity, abnormalities of serum lipid profiles, teratogenic effects and adverse mucocutaneous effects (David et al, 1988). A potential role of vitamin A in prevention of treatment of cancer has been suggested but efficacy has not been proven. A daily dietary intake of about 750 µg of vitamin A is recommended for healthy adults. Dietary vitamin A is derived from 2 sources: retinol is provided by dairy products, eggs and fish liver oils (the most concentrated natural source); pro-vitamin carotenoids can be obtained from many plants. 4.2.2 ChildrenIn the treatment of xerophthalmia: Vitamin A palmitate 110 mg or vitamin A acetate 66 mg (200,000 units of vitamin A) administered orally. The dose should be repeated the next day followed by an additional dose administered 1 to 2 weeks later. When there is repeated vomiting or severe diarrhoea. a water-miscible vitamin A palmitate 55 mg (100,000 units) should be given by intramuscular injection instead of the first oral dose. In the prophylaxis of blinding xerophthalmia vitamin A palmitate 110 mg of vitamin A acetate 66 mg (100,000 units) may be given by mouth every 4 to 6 months. Note: Vitamin A injection should not be administered intravenously because of the risk of anaphylactic shock and death. The recommended daily intake in children aged 6 - 12 months is 300 µg. 4.3 Contraindications Treatment of xerophthalmia: as adults, except in children younger than 12 months for whom the dose is halved. In the prophylaxis of blinding xerophthalmia in children less than 12 months old, vitamin A palmitate 55 mg or vitamin A acetate 33 mg (100,000 units of vitamin A) should be given by mouth. The dose should be repeated every 4 to 6 months. In children under 12 months, water miscible vitamin A palmitate 27.5 mg (50,000 units) should be given by intramuscular injection instead of the first oral dose when this latter is not acceptable - for example in nausea, diarrhoea, pre-operative and post-operative conditions, in malabsorption syndromes or when ocular damage is severe. Note: Vitamin A injection should not be administered intravenously because of the risk of anaphylactic shock and death. Caution is recommended in young children, who are usually more sensitive to the effects of high doses of vitamin A. Normal daily requirements vary according to age. Adequate and well- controlled studies have not been done. 5. ROUTES OF ENTRY 5.1 Oral Excessive doses of vitamin A should be avoided in pregnancy beccause of potential teratogenic effects (Reynolds, 1993). This is the most important route of entry. 5.2 InhalationNo data available. 5.3 DermalAbsorption of the retinoid tretinoin is minimal after application of commercial 5.4 Eyeformulations to the skin. No data available. 5.5 ParenteralThis route is used for patients with absorption problems, e.g: coeliac disease and sprue. 5.6 OtherNo data available. 6. KINETICS 6.1 Absorption by route of exposureIn oral doses that do not greatly exceed the physiological requirements, vitamin A is readily and easily absorbed provided fat absorption is normal. Absorption is incomplete on administration of larger doses and in patients with fat malabsorption, low protein intake or hepatic or pancreatic disease. Water-miscible preparations of retinol or its esters are absorbed more rapidly from the GI tract than oil solutions. Retinol esters are hydrolysed in the GI lumen by pancreatic enzymes. Retinol is absorbed and re-esterified mainly to retinal palmitate. Fatty acid esters of retinol enter the circulation by transport in chylomicrons of lymph. Peak plasma concentrations of retinol esters occur about 4 - 5 hours after oral administration of retinol in an oil solution and 3 - 4 hours after administration of a water miscible retinol; higher plasma concentrations are obtained after administration of a water miscible preparation of vitamin A than after an oily solution. Normal serum concentrations of retinol range from 300 to 700 ng/l adults and from 200 to 500 ng/l in infants (McEvoy, 1988). 6.2 Distribution by route of exposureRetinal palmitate and small amounts of retinol and retinal are stored in the liver. Small amounts of retinal palmitate are stored in the kidney, lung, adrenal glands, retina and intraperitoneal fat. Normal body stores of vitamin A are sufficient to meet the body's requirements for several months. Vitamin A passes into milk. Retinol in circulation is bound to a specific globulin, retinol binding protein (RPB). Release of retinol from the liver depends on several factors including protein and zinc. RPB circulates as a complex with a prealbumin protein and concentrations of RPB may be decreased in patients with protein malnutrition. However, the serum concentration of retinol is not a good index of hepatic stores as these may be depleted. After taking a meal deficient in vitamin A, normal serum concentrations are maintained until the liver stores are depleted. On administration to a patient deficient in vitamin A, vitamin A correction occurs in the retina followed by accumulation in the liver; serum concentrations remain normal until the liver stores are saturated. Patients with glomerulonephritis or lipoid nephrosis may have increased serum concentrations of vitamin A because of RBP or storage abnormalities. If large doses of vitamin A are administered after saturation of storage sites, the binding capacity of RBP may be exceeded and unbound retinol carried by lipoproteins may enter the circulation. This unbound retinol may bring about many of the toxic effects on cellular membranes from hypervitaminosis A (McEvoy, 1988). 6.3 Biological half-life by route of exposureBy ingestion, 1.9 hours. 6.4 MetabolismRetinol is conjugated with glucuronic acid; the B-glucuronide undergoes enterohepatic circulation and oxidation to retinol and retinoic acid. Retinoic acid undergoes decarboxylation and conjugation with glucuronic acid. 6.5 Elimination by route of exposureRetinol, retinoic acid and water-soluble metabolites are excreted in faeces and urine. Normally no unchanged retinol is excreted in urine. However, in patients with pneumonia or chronic nephritis, unchanged vitamin A may be excreted (McEvoy, 1988). 7. PHARMACOLOGY AND TOXICOLOGY 7.1 Mode of action 7.1.1 Toxicodynamics 20% to 50% of the absorbed retinol is eliminated in faeces and urine as conjugation or oxidation products. Approximately 20% is not absorbed and is eliminated in faeces (Hathcock et al, 1990). Toxicity from a large dose of vitamin A is more common in young children than in adults. A few hours after administration of vitamin A at a dose of about 75,000 units/kg, irritability, drowsiness, vertigo, delirium, coma, vomiting and diarrhoea may occur. Increased intracranial pressure with bulging fontanelles in infants, headache, papilloedema, exophthalmos and visual disturbances have been reported. Erythema and general peeling of the skin may occur a few days later and may persist for several weeks. However, symptoms usually disappear within a few days after the drug has been discontinued. 7.1.2 PharmacodynamicsVitamin A is required for growth and bone development, vision, reproduction and the integrity of mucosal and epithelial surfaces. In the retina, retinol is converted to the aldehyde, cis-retinal, which combines with opsin to form rhodopsin, the visual pigment. Vitamin A has been reported to act as a co-factor in various reactions including mucopolysaccharide synthesis, cholesterol synthesis and hydroxysteroid metabolism. The retinoid tretinoin increases cell turnover. Vitamin A deficiency leads to xerophthalmia, Bitot's spots, keratomalacia, night blindness (nyctalopia), hyperkeratosis of the skin, epithelial metaplasia of mucous membranes and decreased resistance to infections. Administration of vitamin A completely reverses signs of vitamin A deficiency unless keratomalacia has resulted in irreversible ocular damage. 7.2 Toxicity 7.2.1 Human data 184.108.40.206 Adults Retinol esters are hydrolysed in the gastrointestinal tract, absorbed as retinol and re-esterified mainly to retinal palmitate. This is transported by chylomicrons to the relevant tissues, including the retina, liver, mucosa and epithelia. Retinol is metabolized by conjugation pathways and excreted. There have been reports of papilloedema associated with vitamin A. Nodular liver cirrhosis and portal hypertension occurred in a 36-year-old man 3.5 years after receiving vitamin A 70 million units by mouth over 7 weeks for psoriasis. Peripheral neuritis and pain developed in 2 leprotic patients treated with thiambutosine when vitamin A 15,000 and 120,000 units daily respectively were taken; nerve pain stopped when the excess vitamin A was withdrawn. Hypercalcaemia and skeletal changes occurred in 5 patients who had taken excess amounts of vitamin A (David et al, 1986). 126.96.36.199 Children Congenital malformations associated with maternal over-use of high doses of vitamin A have also recently been reported (Bendich and Langseth, 1989). However, no cause and effect relationship has been established. Deficiency of the vitamin during pregnancy has also been associated with congenital abnormalities. Reported cases of vitamin A toxicity are rare. Administration of more than 50,000 to 500,000 UI daily for months has produced hepatosplenomegaly (Babb & Kieraldo, 1978) and other effects. 7.2.2 Relevant animal data Allergy to vitamin A especially in children, has been reported and confirmed. There is no evidence that vitamin A at any dose is lethal to animals. However, both deficiency and excess of vitamin A in pregnant animals are teratogenic. 7.2.3 Relevant in vitro dataNo data available. 7.3 Carcinogenicity- Animal data 7.4 Teratogenicity In rats (and probably in man), vitamin A appears to play a role in testosterone synthesis. If vitamin A increases endogenous levels of this hormone, which may mediate the development of prostatic cancer, this effect may be more significant in older animals (and man) whose natural levels of testosterone are declining (Dukes & Beeley, 1989). - Human data Although epidemiological studies have demonstrated a reduced risk of certain cancers with increasing consumption of vitamin A, there is strong evidence that vitamin A has the opposite effect with regard to prostatic cancer. The risk increases directly with the intake of vitamin A in men at all ages, but the trend was strong in those of 70 years and older. Vitamin A seems to influence tumour progression rather than the early stages of carcinogenesis. The mechanism by which vitamin A may enhance carcinogenesis is not yet established (Dukes & Beeley, 1989). The teratogenicity of vitamin A in both high and low doses is well established in animals. However, it is uncertain whether vitamin A is teratogenic in man. A 1983 case report suggested that a multivitamin product containing vitamin A may have caused a cleft palate in one infant; there may be an association between the birth of two malformed children to mothers who had taken excess vitamin A and the birth of 120 malformed children with deficiency of vitamin A; there has been a case of a baby born with congenital xerophthalmia and bilateral cleft because of deficiency of vitamin A in the mother; excess intake in some mothers resulted in defects of the urinary tract, urogenital system and microcephaly in the infants (Briggs et al, 1986). There are few documented reports in humans which link teratogenic consequences to high intakes of supplemental retinol taken either acutely or chronically. Until more is known about the mechanisms of placental transfer and control as well as about the dose-related teratogenicity of vitamin A at different stages of gestation, there are few justifications for routine ingestion by fertile women of supplemental vitamin A in excess of 8,000 to 10,000 IU. Exceptions occur when clinical signs are evident and hospital diets are unusually deficient (Underwood, 1989). 7.5 Mutagenicity 7.6 Interactions 7.7 Main adverse effects 8. TOXICOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS 8.1 Material sampling plan 8.1.1 Sampling and specimen collection 126.96.36.199 Toxicological analyses 220.127.116.11 Biomedical analyses 220.127.116.11 Arterial blood gas analysis 22.214.171.124 Haematological analyses 18.104.22.168 Other (unspecified) analyses 8.1.2 Storage of laboratory samples and specimens 126.96.36.199 Toxicological analyses 18.104.22.168 Biomedical analyses 188.8.131.52 Arterial blood gas analysis 18.104.22.168 Haematological analyses 18.104.22.168 Other (unspecified) analyses 8.1.3 Transport of laboratory samples and specimens 188.8.131.52 Toxicological analyses 18.104.22.168 Biomedical analyses 126.96.36.199 Arterial blood gas analysis 126.96.36.199 Haematological analyses 22.214.171.124 Other (unspecified) analyses 8.2 Toxicological Analyses and Their Interpretation 8.2.1 Tests on toxic ingredient(s) of material 126.96.36.199 Simple Qualitative Test(s) 18.104.22.168 Advanced Qualitative Confirmation Test(s) 220.127.116.11 Simple Quantitative Method(s) 184.108.40.206 Advanced Quantitative Method(s) 8.2.2 Tests for biological specimens 220.127.116.11 Simple Qualitative Test(s) 22.214.171.124 Advanced Qualitative Confirmation Test(s) 220.127.116.11 Simple Quantitative Method(s) 188.8.131.52 Advanced Quantitative Method(s) 184.108.40.206 Other Dedicated Method(s) 8.2.3 Interpretation of toxicological analyses 8.3 Biomedical investigations and their interpretation 8.3.1 Biochemical analysis 18.104.22.168 Blood, plasma or serum 18.104.22.168 Urine 188.8.131.52 Other fluids 8.3.2 Arterial blood gas analyses 8.3.3 Haematological analyses 8.3.4 Interpretation of biomedical investigations 8.4 Other biomedical (diagnostic) investigations and their interpretation 8.5 Overall Interpretation of all toxicological analyses and toxicological investigations 8.6 References 9. CLINICAL EFFECTS 9.1 Acute poisoning 9.1.1 Ingestion By contrast, the retinoids isotretinoin and etretinate are highly teratogenic in man. Their use is contraindicated during pregnancy and conception must be prevented for at least 4 weeks after use of isotretinoin and for at least 2 years after use of etretinate. Doses of vitamin A that do not exceed the physiologic requirements are not usually toxic (McEvoy, 1988). However, acute intoxication has generally been observed following ingestion of vitamin A-rich liver from the polar bear, halibut or shark. The doses have been in the range of one million units of vitamin A, but as low as 30,000 IU in children. The symptoms occur 6 to24 h after ingestion and are characterized by acute onset of drowsiness, irritability, vertigo, headache, delirium and convulsions, diarrhoea and intolerance to food. Long- term administration of as little as 10,000 IU daily may be sufficient to cause chronic hypervitaminosis A. The main symptoms of chronic intoxication include malaise, gastrointestinal complaints, changes in the skin and mucous membranes, headache, tenderness and pain in the bone and joints, and fever (Helsing, 1988). Hypersensitivity reactions do not seem to occur. 9.1.2 Inhalation Toxicity from large doses of vitamin A is more common in young children than in adults. A few hours after administration of 25,000 units/kg, severe irritability, drowsiness, or vertigo, delirium, coma, vomiting and diarrhoea may occur. Increased intracranial pressure with bulging fontanelles in infants, headache, papilloedema, exophthalmos, and visual disturbances have been reported. Erythema and generalized peeling of the skin occur a few days later and may persist for several weeks. However, symptoms usually disappear within a few days after the drug is discontinued (McEvoy, 1988; Speight, 1987). No data available. 9.1.3 Skin exposureSkin reactions are more common after topical application of the retinoids 9.1.4 Eye contactetretinate, isotretinoin and tretinoin. The most common cutaneous side effects are xerosis of the skin associated with pruritus and sometimes with erythema, skin hyperfragility and desquamation of the skin, particularly of the palms and soles (David et al, 1988); hair loss from scalp, eyebrows and/or eyelashes. No data available. 9.1.5 Parenteral exposureThe same as for oral exposure. 9.1.6 OtherNo data available. 9.2 Chronic poisoning 9.2.1 IngestionChronic overdose results in hepatotoxicity, papilloedema, intracranial hypertension, hypomenorrhoea, portal hypertension, haemolysis and anaemia, radiographic bone changes and, in children, premature closure of the epiphyses. Toxicity is slowly reversible on withdrawal of vitamin A, but may persist for several weeks. Bone or joint pain fever, general feeling of bodily discomfort or weakness, headache, increase in the volume and frequency of urination, especially at night, irritability, loss of appetite, stomach pain, unusual tiredness and vomiting are also reported (David et al, 1988; USP DI 1989; McEvoy, 1988). 9.2.2 InhalationNo data available. 9.2.3 Skin exposureAfter repeated administration to the skin, the retinoid tretinoin may cause drying or cracking of skin or lips, increased sensitivity of skin to sunlight, loss of hair, yellow-orange patches on soles of feet, palms of hands or skin around nose and lips. 9.2.4 Eye contactNo data available. 9.2.5 Parenteral exposureAs for oral exposure. 9.2.6 OtherNo data available. 9.3 Course, prognosis, cause of deathToxicity in both acute and chronic vitamin A is reversible on withdrawal of vitamin A. In chronic overdose, toxicity may persist for several weeks. In children, the premature closure of ephphyses of the long bones may result in arrested bone growth (Reynolds, 1993). 9.4 Systematic description of clinical effects 9.4.1 Cardiovascular In general, most signs and symptoms of overdoes rsolve within one week after withdrawal of vitamin A and appropriate symptomatic treatment. Benign intracranial hypertension resolves usually after symptomatic treatment. However, papilloedema and skeletal abnormalities may persist for several months and visual impairement (blindness) due to optic atcoply may remain as a permanent sequela (Goldfrank, 1986). Tachycardia, possibly secondary to fever (Helsing, 1988). 9.4.2 RespiratoryNo information available. 9.4.3 Neurological 220.127.116.11 CNSAcute symptoms of vitamin A poisoning include drowsiness, sluggishness, irritability and somnolence, severe headache and papilloedema. In young children, raised intracranial pressure with bulging of the fontanelles, papilloedema and diplopia have been observed. Intracranial hypertension may sometimes occur together with skin and hair changes, pain in musculoskeletal system and fatigue. Chronic daily doses of 3, 000,000 IU of vitamin A have induced central nervous symptoms such as psychosis, with pathological changes in the cerebrospinal fluid (Helsing, 1988; USP DI 1989). Pseudotumour cerebri (benign intracranial hypertension), vertigo and papilloedema have occurred following the daily intake of 10,000 - 20,000 IU for 2 years in adults; in children even few months of treatment may suffice (Helsing, 1988; USP DI, 1989). Similar effects have been reported for retinoids for both acute and chronic intoxication (David et al, 1988; Reynolds, 1989). 126.96.36.199 Peripheral nervous systemNo data available. 22.214.171.124 Autonomic nervous systemNo data available. 220.127.116.11 Skeletal and smooth muscleNo data available. 9.4.4 GastrointestinalNausea, vomiting and anorexia are common symptoms of acute vitamin A intoxication, as are dryness and scaling of the lips, gingivitis and bleeding from the gums (USP DI, 1989, Helsing, 1988). 9.4.5 HepaticEnlargement of the liver, spleen and lymph nodes have been reported in adults (Helsing, 1988). Liver damage due to vitamin A and its derivatives occurs after acute poisoning; whether liver toxicity occurs after chronic poisoning is still uncertain (David et al, 1988). Excessive administration of vitamin A and its derivatives can lead to fibrosis in the Disse space and obstruction of sinusoidal blood flow, causing non- cirrhotic portal hypertension and hepatocellular dysfunction (Reynolds, 1989). Elevated serum concentrations of aspartate transaminase (AST, SGOT), alanine transaminase (ALT, SGPT) and occasionally lactic dehydrogenase (GGT) and alkaline phosphatase have been reported (David et al, 1988; McEvoy, 1988; Krishnaswany, 1987). 9.4.6 Urinary 126.96.36.199 RenalIn chronic intoxication, polyuria, increased frequency of micturition, urinary incontinence, enuresis and acute renal failure due to tubular necrosis may occur (Dukes, 1984; USP DI, 1989). Patients with renal dysfunction, in chronic dialysis and haemodialyzed patients appear to have increased circulating vitamin A levels. 188.8.131.52 OtherNo data available. 9.4.7 Endocrine and reproductive systemsHypomenorrhoea may be an early symptom of chronic intoxication. 9.4.8 DermatologicalIn acute intoxication, peeling of the entire skin can occur as a delayed symptom. Among the early and most commonly reported symptoms of chronic poisoning with vitamin A and its derivatives are pruritus; erythema; hyperkeratosis; dryness, haemorrhage and fissures of the lips (Krishnaswany, 1987; McEvoy, 1988; USP DI, 1989; Reynolds, 1989). A yellow to yellow-orange discoloration of the skin, decreased tolerance to sunlight, changes in pigmentation, hair loss and brittle nails can occur (USP DI, 1989; Reynolds, 1989; Helsing, 1988). Spider angiomas and palmar erythema in patients with serious hepatic damage due to chronic use of vitamin A have also been reported. 9.4.9 Eye, ear, nose, throat: local effectsEye: ocular toxicities involve the conjunctival membrane, cornea and retina manifested by photophobia, palsy of the ocular muscle, retinal haemorrhage and protrusio bulbi, nystagmus, diplopia, dryness, irritation and pain. These are due to raised intracranial pressure. Intoxication can also lead to papilloedema, which in some cases may be the only symptom (Helsing, 1988; David et al, 1988). Anterior segment inflammation, contact lens intolerance and altered refraction have also been reported with the retinoid isotretinoin (Caffery & Josephson, 1988). 9.4.10 Haematological Ear, nose, and throat: no data available. High doses of vitamin A reduce the stability of the hypoprotein boundary layer of erythrocytes, which can lead to haemolysis and anaemia. Neutropenia or leucocytosis, thrombocytopenia, aplastic anaemia and increased sedimentation rate have been reported after high doses of vitamin A (McEvoy, 1988; USP DI, 1989; Dukes, 1984). 9.4.11 ImmunologicalNo data available. 9.4.12 Metabolic 126.96.36.199 Acid-base disturbancesNo data available. 184.108.40.206 Fluid and electrolyte disturbancesOedema and ascites are sometimes seen in patients with chronic intoxication (Helsing, 1988). Polydipsia may also occur. 126.96.36.199 OthersChronic intoxication with vitamin A has been reported to cause hyperglycaemia, increased alkaline phosphatase, hypoproteinuria, hypoprothrombinaemia, increased sulphobromphthalein retention, elevated serum transaminases, low serum ascorbic acid, decreased protein content of cerebrospinal fluid, elevated urinary hydroxyproline, and hypercalciuria. Continued vitamin A administration or accumulation is associated with an increase in serum cholesterol and consequently might be linked with atherosclerosis (Helsing, 1988). 9.4.13 Allergic reactionsHyperlipidaemia: As a result of liver damage, vitamin A and its derivatives produce a rise in serum triglycerides and, in particular, in very low density lipoproteins. The changes are reversible on stopping treatment (Krishnaswamy, 1987; David et al, 1988). Hypersensitivity reactions do not seem to occur (Hellriegel, 1984). 9.4.14 Other clinical effectsExcessive intake of vitamin A leads to accelerated resorption of trabecular and cortical bone due to increased osteoclast activity. Pain in bones and joints is a common symptom. Bone tenderness with complications such as periosteum, hyperostosis and, in children, premature closure of the epiphyses of the long bones causing growth arrest (Reynolds, 1989, USP DI, 1989; Helsing, 1988). Similar effects have been reported for vitamin A derivatives (David et al, 1988). Skeletal deformities involving the lower limbs and the spine were seen in a 15-month old girl who had received during the previous few months a total dose of 10.5 million IU of vitamin A (Helsing, 1988). 9.4.15 Special risksPregnancy: Vitamin A in high doses induces congenital abnormalities in the offspring of rats and has been reported to impair learning ability in rat offspring. In man, epidemiological data on teratogenicity is lacking. However, human teratogenicity of synthetic vitamin A derivatives such as isotretinoin is now well accepted. Results from an epidemiological case-control study on prenatal exposure to vitamin A alone or in combination with other vitamins have indicated that a teratogenic effect could exist for exposures to high doses of vitamin A. Urinary tract malformations, growth retardations, and early epiphyseal closure have been reported in children whose mothers took excessive amounts during pregnancy (Krishnaswany, 1987; USP DI, 1989; Rosa et al, 1986). 9.5 Other Breast-feeding: Problems in humans have not been documented with intake of normal daily requirements; however, vitamin A is excreted in breast milk (USP DI, 1989). Enzyme deficiencies: No data available. No data available. 9.6 Summary 10. MANAGEMENT 10.1 General principlesTreatment is mainly supportive. Make a proper assessment of the airway, breathing and neurological status of the patient. Reduce intracranial pressure with mannitol or corticosteroids. 10.2 Relevant laboratory analyses 10.2.1 Sample collection After oral exposure, gastric lavage is indicated if more than the therapeutic doses is ingested. Alternatively, emesis is indicated unless the victim is comatose. A cathartic may be administered. Wash contaminated skin thoroughly with soap and water. If the eyes are affected, irrigate with copious amounts of water for 10 to 15 minutes and consult ophthalmologist if pain persists. Monitor patient for dark adaptation tests, electronystagmogram, electroretinogram and plasma vitamin A determinations. Hepatic and renal status should be evaluated, especially in chronic exposure. Blood sample and 24 h urine collection. 10.2.2 Biomedical analysisRoutine blood and urine analysis of retinol and metabolites may confirm the severity of poisoning. 10.2.3 Toxicological analysis Monitor for haematologic effects, including haemolysis, anaemia, thrombocytopenia and leucopenia. Monitor serum AST (SGOT) and ALT (SGPT) concentrations (McEvoy, 1988). Analysis of vitamin A in blood and urine may be done by colorimetric or gas chromatography. 10.2.4 Other investigations 10.3 Life supportive procedures and symptomatic/specific treatmentMaintain clear airway, establish and monitor breathing and circulation. 10.4 Decontamination Control seizures with IV diazepam or phenobarbital. Reduce intracranial pressure with mannitol or corticostreoids. Support other CNS functions. Neuroleptics may be required to control psychotic reactions. Monitor hepatic function. Correct anaemia and other haematological abnormalities, if necessary. Ingestion: Gastric lavage and emesis are indicated if large amounts are ingested. 10.5 Elimination Activated charcoal should be administered in usual doses of 30 to 100 g in adults and 15-30 g in children. A saline cathartic (e.g. sodium sulphate) may be given in doses of 20 to 30 g in adults and 150 mg/kg in children over 2 years. However, saline cathartics are contraindicated in patients with impaired renal function. Skin: wash exposed areas thoroughly with soap and water. Eyes: irrigate eyes copious amounts of water for at least 15 min. Consult an ophthalmologist, if pain persists. Since the volume or frequency of urination may be increased, especially at night, osmotic diuresis or haemodialysis has been suggested. 10.6 Antidote treatment 10.6.1 AdultsThere is no specific antidote available. 10.6.2 ChildrenThere is no specific antidote available. 10.7 Management discussionVitamin E may increase the absorption, utilization and storage of vitamin A and may protect against hypervitaminosis A; however, these effects are controversial (McEvoy, 1988). 11. ILLUSTRATIVE CASES 11.1 Case reports from literature- Hypercalcaemia caused by vitamin A toxicity was observed in a 16-year-old patient. Diagnosis was difficult because she denied recent ingestion of vitamin A and was thought to be bulimic. Symptoms included vomiting, diarrhoea, thirst and polyuria. She also developed a dry scaly skin rash on her back, face and extremities. The findings on physical examination were normal except for multiple excoriations on her extremities, a dry scaly rash over her upper arms, fissures at the corners of her mouth and dry mucous membranes. Intravenous fluids and loop diuretics lowered the serum calcium and ameliorated the symptoms of nausea and vomiting temporarily. During the 10 days of this therapy, the serum calcium never fell below 11.5 mg/dl. Oral prednisone was then started and produced a prompt and lasting reduction of the serum calcium to normal (Bergman et al, 1988). 11.2 Internally extracted data on cases - Plasma retinol levels and toxicity were evaluated in thirteen metastatic breast cancer patients treated orally with high dose (300,000 IU/day) retinal acetate in combination with tamoxifen. During the first 2 months of treatment, a cumulative increase of plasma retinol occurred; long-term systemic toxicity was acceptable and included gastrointestinal symptoms, skin toxicity and headache. These symptoms could be related to the long-term increase of retinol systemic concentrations (Ressasco et al, 1988). - The teratogenicity of vitamin A has been repeatedly reported in the literature and confirmed on the basis of several cases of adverse pregnancy outcome associated with maternal isotretinoin exposure. Teratogenic effects have been reported after normal supplementation with vitamin A during pregnancy (Lungarotti et al, 1987). - A 7-year-old girl, a 13-year-old boy and a 26-year-old woman, all with renal failure, developed biochemical and clinical findings of vitamin A toxicity (hypervitaminosis A) while receiving a total parenteral nutrition regime containing vitamin A; the symptoms improved after withdrawal of vitamin A from the regime. These cases demonstrate that patients with renal failure may be at risk for symptomatic vitamin A toxicity, if given standard supplementation (Gleghorn et al, 1986). - A 29-year-old man developed hepatic cirrhosis as a manifestation of vitamin A toxicity induced by the ingestion of 6 to 8 ounces of beef liver per week for 8 to 9 years. However, a history of infectious mononucleosis was probably a contributing factor. A 41-year-old woman developed chronichypervitaminosis A due to long-term use of special regimen utilizing an emulsified vitamin A product containing 15,000 IU per drop (Inkeles et al, 1986). - Vitamin A intake was assessed from dietary histories of 452 men with prostate cancer and 899 population controls in Hawaii during the period 1977-1983. In the group of men less than 70 years of age, there was no significant association between vitamin A and the risk of prostate cancer. In the men aged 70 or older, the risk correlated directly with the amount of vitamin A consumed. The findings were consistent across the 5 ethnic groups and similar for the various components of vitamin A and its metabolites but were somewhat stronger for total carotenes than for total retinol. These data suggest possible mechanisms for this risk enhancement by vitamin A in the elderly men (Kolonel et al, 1987). To be completed by each centre. 11.3 Internal casesTo be completed by each centre. 12. Additional information 12.1 Availability of antidotesNo antidotes are available. 12.2 Specific preventive measuresNo data available. 12.3 Other 13. REFERENCESBabb RR, Kieraldo JH (1978). Cirrhosis due to hypervitaminosis. A. West J Med 128:244-248. 14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE ADDRESS(ES) Bendich A & Langseth L (1989) Safety of vitamin A. American Journal of Clinical Nutrition 49(2): 357-371 (February). Bergman SM, O'Mailia J, Krane NK, Wallin JD (1988) Vitamin A- induced hypercalcaemia: response to corticosteroids. Nephron, 50(4): 362-364. Briggs GG, Freeman RK & Yaffe SJ (1986) Vitamin A. In: Drugs in pregnancy and lactation. A reference guide to fetal and neonatal risk. Second edition. Williams and Wilkins, Baltimore, Maryland, USA, 473/v-476/v. Caffery BE & Josephson JE (1988) Ocular side effects of isotretinoin therapy. Journal of the American Optometric Association, 59(3): 221-224. British Pharmacopoeia 1988, Volume I. Department of Health and Social Security, Scottish Home and Health Department (1988). Vitamin A: 596-598. David M, Hodak E & Lowe NJ (1988) Adverse effects of retinoids. Medical Toxicology, 3: 273-288. Dukes MNG & Beeley L (1989) Vitamin A and prostatic cancer. Side effects of drugs. Annual 13, Elsevier, Amsterdam - New York, 346-347. Gleghorn EE, Eisenberg LD, Hack S, Parton P, Merritt RJ (1986) Observations of vitamin A toxicity in 3 patients with renal failure receiving parenteral alimentation. American Journal of Clinical Nutrition 44(1): 107-112 (June). Goldfrank LR, Flomenbaum NE, Lewin NA, Weisman RS, Howland NA, and Kulberg AG: Goldfrank's Toxicologic Emergencies (1988) 3rd Ed. Appleton-Century-Crofts/Norwalk Connecticut. Hathcock JN, Hattan DG, Jenkins NY et al (1990) Evaluation of vitamin A toxicity. Am. J. Clin. Nutri. 52: 183 - 202. Hellriegel KP (1984) Vitamins: Vitamin A (Retinol). In Dukes MNG, Meyler's side effect of drugs. Tenth edition, Elsevier, 715- 726. Helsing E (1988) Vitamins in: Dukes MNG. Meyler's side effects of drugs. 11th edition, Elsevier, Amsterdam, 799-805. Inkeles SR, Connor WE, Illingworth DR (1986) Hepatic and dermatologic manifestations of chronic hypervitaminosis A in adults. Reports of two cases. American Journal of Medicine, 80(3): 491-496. Kolonel LN, Haukin JH, Yoshizawa CN (1987) Vitamin A and prostate cancer in elderly men: enhancement of risk. Cancer Research 47(11): 2982-2985 (June). Krishnaswany K (1987) Diseases of a tropical environment. In: Speight TN. Avery's drug treatment. Principles and practice of clinical pharmacology and therapeutics. Third edition, Williams and Wilkins, Baltimore, Maryland, USA, 1273-1315. Lungarotti MS, Marinelli D, Mariano T, Calobro A (1987) Multiple congenital anomalies associated with apparently normal maternal intake of vitamin A: a photocopy of isotretinoin syndrome? American Journal of Medical Genetics 27(2): 245-248 (June). McEvoy GK (1988) Vitamin A. Drug information 88. American Hospital Formulary Service. The American Society of Hospital Pharmacists, Montgomery Avenue, Bethesda, Maryland, USA, 2090- 2093. Pastorino U, Soresi E, Clerici M, Chiesa G, Belloni PA, Ongari M, Valente M, Ravassi G (1988) Lung cancer chemoprevention with retinol palmitate. Preliminary data from a randomized rial on stage Ia non small-cell lung cancer. Acta Oncologica 27(6b): 773- 782. Ressasco M, Canobbio L, Trave F, Valenti G, Mazzoni A, Gauti G, Roccardo F, Nicolin A (1988) Plasma retinol levels and side effects following high-dose retinal acetate in breast cancer patients. Anticancer Research, 8(6): 1319-1323. Reynolds JEF (1989) Nutritional agents and vitamins: Martindale, The Extra Pharmacopoeia, 29th edition, The Pharmaceutical Press, London, 1250-1290. Rosa FW, Wilk AL, Kelsey FO (1986) Teratogen update: vitamin A congeners. Teratology 33(3): 355-356. Underwood BA (1989) Teratogenicity of vitamin A. International Journal for Vitamin & Nutrition Research Supplement, 30: 42-55. USP DI. The United States Pharmacopoeial Convention Inc. (1989) Vitamin A (Systemic). Drug information for the health care professional. 10th Edition, USA, 2415-2417. Vanderveen E (1980) Vitamins and other nutrients. In: Osol Arthur, Remington's Pharmaceutical Sciences. Mack Publishing Company, Easton, Pennsylvania, 945-977. Verreault R, Chu J, Mandelson M, Shy K (1989) A case-control study of diet and invasive cervical cancer. International Journal of Cancer, 43(6): 1050-1054 (June 15). Dr O.J. Kasilo Drug and Toxicology Information Service Department of Pharmacy University of Zimbabwe Medical School P.O.Box A178 Avondale Harare, Zimbabwe Dr C.F.B. Nhachi Department of Clinical Pharmacology and Toxicology University of Zimbabwe Medical School (address as above). Tel: 263-4-790233 or 791631, Ext. 117/172 Telex: 2526801 UNIVZ ZW Fax: 263-4-303 292 Date: December 1989.
See Also: Toxicological Abbreviations


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Artist: → Attilah Tha Hun
{Attilah Tha Hun}
Attention, I'm the Jefferson Thomas new invention
I am Muhammad and Nastrodamus' new prediction
I'm the addiction to religion that keeps you from sinning
The viper hissin, tellin eve to eat the fruits of wisdom
I'm the incision in your tendons that keep you imprisoned-
In mid-evil dungeons. I'm the vision of the 9th dimension
I am encrypted inscriptions in the Egyptian Kremlins
With goddesses on mount Olympus call it higher livin
On arrival I am a rival with revolvers spinnin
Im a rifle take a life when ever get risen
But not bodies listens, im an orphan missin
I am satan I am hell im a schorchin prison
I am jesus don't believe it I support forgivness
Im a fetus im the mother who aborts tha mission
Im a corpse that's livin, a beeting heart that isn't
Im a sword incision, im a pain infliction
Times tickin, pen's scrbblin lyrics in
I like words with rhythm, I lke rhymes and women
I want dimonds denim I want cars and riches
I love art tradition, I want smarts and wisdom
Im a griffin flyin with the pidgeons
Psychotic symptom im a victim you could hear me screaming
Im a wild being, im a child dreaming
Im a deconstructive rebel with a deeper meening
Face eatin bathsalts
Fresh out the oven spread the ash in the asfalt
You sleep with the fishes while im flowin like a mad shark
Heart is mad dark better run when the wrath start
Listens when the wraiths talk
You goin down game over thats my 8ball
Fuck the law, we face off. If the shotty had a face
Its nose is sawed off sneezin out buckshots
Pusyy niggas hide thier balls take the cup off
Slapped back criss cross getcha tung slit off
I have to thrive all i want to do is fly
Lets acend with the gods and be closer to the sky
Pain merged with the words like the rhythm hurts
Bit my tung once and fainted cause the venom serged
Bone breakin bars bitch lets see how much your tung is worth-
I be in the jungle and I slither were the serpents lurk
Light it up like jackolanterns, spread it out like aids and cancer
Eyes are what the ravens after blindin all you fuckin bastards
Nigguh im a fuckin panther my nigguhs a fuckin raptor
Blood is what the dragons aftr princesses we fuckin capture
Ain't trynta make a couple bills im trynta make a kill-
Slap bangers hard like they fuckin made of stainless steel
Barley survive all i want to do is fly
Lets acend with the gods and be closer to the sky
(Excerpt from Hitlers speech on «Triumph of the will»)
«Today, we ourselves must remove undesirable elements which have proven to be bad. It is our wish and will that this State and Reich will endure for millennia to come. We are happy in the knowledge that this fortune belongs to us completely. While the older ones among us may possibly waiver, the youth is committed to us, body and soul!»

subset: commoncrawl


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Worldwide surveillance of self-reported sitting time (2020)
a scoping review
This study provides an updated collation of self-report sitting time globally. The daily sitting time findings should be interpreted cautiously. Sitting time data were collected in 62 of 215 countries, representing 47% of the global adult population. Daily sitting time was on average 4.7 h. There was particularly a lack of data in low- and middle-income countries, but data that were available suggested they reported less daily sitting time than higher-income countries.
Literatuurverwijzing: Mclaughlin, M., Atkin, A.J., Starr, L., & Hall, A. (2020). Worldwide surveillance of self-reported sitting time: a scoping review. International journal of behavioral nutrition and physical activity 17


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Suffolk face at Assembly
Published 6:37 pm Saturday, January 2, 2010
When the Virginia General Assembly convenes for its 2010 session on Jan. 13, there will be a new Suffolk face among those moving in and out of the legislative chambers and offices.
But when Fletcher Stephens heads to Richmond, he won't be there to vote on legislation or meet with lobbyists. As a page in the General Assembly, the 14-year-old will have more basic duties — delivering messages, running paperwork between offices, running errands and the like.
For some of the young participants in the page program, it will be their first exposure to the political process.
But Fletcher, known as Kyle to parents Robert and Karen Stephens, has been around politics all his life. Photos of Fletcher and his dad with state and national political figures adorn the walls of both his bedroom and his father's study.
"It's fun and inspiring to meet famous people," the young teen says. "It kind of tells me that if they can do it, I can, too."
And that's the message he wants to send to his friends and others from his peer group as he prepares to leave home for a two-month stay in Richmond: "If you go for something and if you want to do it as much as you say you want to do it, then you can do it."
Confidence and the power of positive thinking — not to mention hard work — are among the foundational ideals of the Stephens household. There's also an awareness that God is ultimately the one in control of the family members' lives.
That awareness is summed up in a question Robert Stephens said he has taught his son to ask himself as he has become involved in everything from community politics to Hollywood movie productions in recent years: "If God has a plan for you, why do you have one?"
Robert Stephens worked in the Clinton White House for years, and the former president keeps in touch with him, maintaining an avid interest in the younger Stephens' studies and aspirations.
After the elder Stephens suffered a heart attack and he realized he needed to make some lifestyle changes and reduce his level of stress, the family moved to Chuckatuck from Lauren, Md., in 2006, and Fletcher is now a ninth-grade student at King's Fork High School.
Here, they have attempted to adopt what Robert Stephens calls "a lifestyle of surrender."
"Sometimes, if we get ourselves out of the way, it's amazing what can come into your life," he said.
Fletcher Stephens is a great example of that philosophy in action. Two years ago, he told a reporter he thought he'd like to be the first pro basketball player to become president of the United States. Since then, he has adjusted his goals, leaving the possibility of either former dream open while pursuing a newly developed interest in the law.
Serving as a General Assembly page could be steps toward achieving at least two of those three potential goals, but he still wasn't sure it was something he wanted to do until he was accepted for the program. He really had hoped to play JV basketball this winter, but he didn't make the team, so the door opened up to the experience in Richmond, and he decided to surrender to the opportunity.
Leaving school and friends for Richmond would be hard, he said. "But then I had to think about my future and my priorities. This will teach me independence and taking on new responsibilities on a different level."
There also will be some political and social connections to be made, and it's likely that a new photograph or two — showing Fletcher with more smiling politicians — will show up on the Stephens walls by the end of the winter.
Nobody knows where this experience might lead. But Fletcher and his parents have resolved to surrender to whatever is in store for them and to take advantage of the opportunities as they arise.


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Novafast has secured a Borefields piping program of works which will require a continual supply of Novaflo piping over the next five years. Pipe sizes will range from 50mm-250mm with burst pressure requirements to exceed 12 MPa and temperature ratings up to 93 degrees celsius.
Business Manager David Figallo says "By securing this new contract this will allow Novafast to create local multi-disciplined employment opportunities at its Adelaide facilities. The contract is also key to supporting Novafast's local growth and expansion plans forecast for 2021. We would like to thank our customers who support our Australian business which facilitates these great growth opportunities, particularly in a time where COVID has made local business all that more important."
Novafast is on track to deliver its two first deliveries of pipe for mid-late February.
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Happily Ever After
BHLDN's first-ever wedding fairytale store comes to life: From playful shoes tothe Lingerie Room
It was love at first sight.
BHLDN's first-ever brick-and-mortar store anywhere enchanted from the sidewalk and wooed me just steps into its Highland Village door. Forgive me for gushing, but the bridal (and special occasion) boutique is simultaneously beautiful, quirky, whimsical, simple and lush.
And this is from someone who got her happily ever after back in 1996.
Cut from the same creative cloth as Anthropologie, BHLDN's sister store is a head-to toe location for a modern bride who still wants to get caught up in the fairytale. BHLDN isn't just about weddings though. It embraces the art of celebration.
This is a museum where you are invited to touch the art and try it on for size. Brides and their parties can slip away in the private areas complete with comfy seating and separate dressing rooms.
The interiors are cohesive and yet individual to the purpose of each room. The front of the store is filled with light and a showcase for the bridesmaids and cocktail dresses, many of which can serve the same purpose. Brides who fall in love with a look can get it for their wedding party within 24 hours; a wedding gown can be ordered on a Wednesday for a Saturday event.
BHLDN's in-house designers create both special occasion and wedding gowns, but the store also works with designers such as Tracy Reese.
Down a wide hallway, lit with fixtures taking flight, is the Décor Room, a colorful and demure spot Martha Stewart would most definitely approve of. A large marble table sits in the middle of the dark-paneled room, surrounded by shelves laden with stationery, books, table decorations, handmade cake toppers, sparkles, ribbons and other creative doo-dads. Items in the Décor Room are often one-of-a-kind, so shoppers would be wise to purchase what they like.
The shoe salon and accessory space is a playful nod to the "something blue" so often associated with weddings. Bright blue walls surround the shoes that range from traditional bridal to fun eye-catchers. The groom gets a few special pieces exclusive to Houston in the form of cufflinks, wedding bands, bow ties and boutonnieres. Pop from the shoes to the array of fascinators, jewelry and toppers ranging from lacy wraps to chunky crocheted numbers.
Slip away into the Lingerie Room, a warmly lit space filled with seductively sweet lingerie, coffee table books and little touches like ivory parasols. Each department within BHLDN has its own manager and stylist, which is especially important for lingerie.
The store is designed to pull shoppers to the back of the boutique and into the bridal gown gallery. It's magical in here, with high ceilings, soft light and gowns of all kinds displayed on slate-hued mannequins. This is a museum where you are invited to touch the art and try it on for size. Brides and their parties can slip away in the private areas complete with comfy seating and separate dressing rooms.
Considering how wedding gowns fetch thousands of dollars, the BHLDN selection is moderately priced starting at $600 for a tea-length day gown and topping out at $6,000 for a full-length handmade dress. Gowns range from a zero to 12 and BHLDN staff say they are true to size and are sewn with alterations in mind if necessary. The Houston store will have a tailor on hand by appointment or will refer women to a BHLDN-approved tailor.
BHLDN has wisely introduced a line of separates that go beyond the aisle and into holiday like the Frolicking Feather skirt ($850) that is available in black or white. Little touches abound such as hair accessories and gloves with a vintage flair.
It's easy to be swept away by romance of BHLDN. The name is inspired by the Dutch word "To Keep" sans the vowels and it seems likely that's just what brides will do with this new Houston boutique.


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Are you curious to know what is garlic classified as? You have come to the right place as I am going to tell you everything about garlic classified as in a very simple explanation. Without further discussion let's begin to know what is garlic classified as?
What Is Garlic Classified As?
Garlic, with its distinct aroma and pungent flavor, is a beloved ingredient in cuisines around the world. Beyond its culinary uses, garlic has also been recognized for its potential health benefits. In this blog post, we will explore the classification of garlic, its culinary significance, and its nutritional value. Prepare to uncover the wonders of this versatile and flavorful bulb.
Classification Of Garlic
Garlic, scientifically known as Allium sativum, belongs to the Alliaceae family, which includes other notable plants like onions, leeks, and shallots. It is a perennial herbaceous plant that grows from a bulb, consisting of individual cloves enclosed in a papery skin. While garlic is commonly associated with the Allium genus, it is often classified as its own species due to its unique characteristics.
Culinary Significance
Garlic has been an integral part of culinary traditions across various cultures for centuries. Its potent flavor adds depth and complexity to a wide range of dishes. From Mediterranean cuisine to Asian stir-fries and Latin American salsas, garlic is a fundamental ingredient that enhances the taste profile of many recipes. Whether used raw, roasted, sautéed, or minced, garlic imparts a distinct and aromatic essence to savory dishes.
Nutritional Value
Garlic is not only prized for its culinary attributes but also for its potential health benefits. This versatile bulb is low in calories and rich in essential nutrients. Here are some key nutritional components found in garlic:
- Allicin: Allicin is a sulfur compound found in garlic that is believed to contribute to its characteristic aroma and potential health benefits. It has been studied for its antimicrobial, antioxidant, and anti-inflammatory properties.
- Vitamins and Minerals: Garlic contains various vitamins and minerals, including vitamin C, vitamin B6, manganese, and selenium. These nutrients play vital roles in supporting immune function, cellular health, and overall well-being.
- Phytochemicals: Garlic is rich in phytochemicals, such as flavonoids and organosulfur compounds, which have been associated with potential health benefits. These compounds may have antioxidant and anti-inflammatory effects, promoting cardiovascular health and potentially reducing the risk of certain diseases.
- Fiber: Garlic contains dietary fiber, which is important for digestive health and maintaining healthy cholesterol levels.
- Low in Calories: Garlic is a low-calorie food, making it a great addition to a balanced and calorie-conscious diet.
Incorporating Garlic Into Your Diet
Adding garlic to your culinary repertoire is easy and can elevate the flavors of your dishes. Here are a few simple ways to incorporate garlic into your diet:
- Sauteed or Roasted: Sauté garlic in olive oil for a fragrant base to many recipes. Roasting whole cloves can also yield a sweet and mellow flavor.
- Minced or Crushed: Finely mince or crush garlic cloves to release their flavor and incorporate them into sauces, dressings, marinades, or dips.
- Seasonings and Spices: Garlic powder or granules can be used as a convenient alternative when fresh garlic is not available.
- Flavor Booster: Enhance the taste of your favorite soups, stews, stir-fries, or roasted vegetables by adding a few cloves of garlic.
Garlic's classification as Allium sativum highlights its unique qualities and importance in the culinary world. Its rich flavor, distinct aroma, and potential health benefits make it a versatile ingredient that enhances a wide array of dishes. Incorporating garlic into your diet not only adds a delightful taste but also introduces valuable nutrients and potential health-promoting properties. So, embrace the culinary power of garlic and explore the myriad ways it can elevate your meals while contributing to a well-rounded and flavorful lifestyle.
On Zoconnects you will get to know much more about similar topics.
What Category Is Garlic?
Garlic is a vegetable that belongs to the onion family. It has a pungent, spicy flavor that mellows and sweetens with cooking. Although garlic is a vegetable, it is more commonly used to flavor foods.
What Food Category Is Garlic Or Onion?
vegetable group
Selection of food groups
In the vegetable group, the frequently consumed species—onion (Allium cepa var. cepa), garlic (Allium sativum), leek (Allium ampeloprasum), chives (Allium schoenoprasum), shallots (Allium cepa var.
What Is Garlic Technically?
Garlic is an allium, which means it's a vegetable from the same family as onion, leek, shallot, and chives. Although it is technically a vegetable because the stem, leaves, and bulb can be consumed, it's more commonly used like a spice or herb would be, rather than a vegetable.
Is Garlic A Root Vegetable?
Root vegetables are grown underground and include onions, garlic, carrots, potatoes, and beets, among others. They offer a variety of flavors and can be prepared in many ways.
I Have Covered All The Following Queries And Topics In The Above Article
Is Garlic A Vegetable Or Herb
Is Garlic A Root
Why Is Garlic A Vegetable
Is Garlic Good For You
Is Garlic A Spice
Is Garlic One Of Your Five A Day
Garlic Scientific Name
Garlic Origin
What Is Garlic Classified As


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Here is a cute Mega Bloks table for your toddlers. My nephew has this and his mother loved it for him.
Mega Bloks Big Builders Build 'N Learn Table 30-Piece Block Set for $26.99 (Reg.$44.99)
- Age Range: 1 – 5Y
- Portable, folding table building set
- 30 pieces include building blocks and special parts
- Build a town with market, gas station, traffic light, and more
- Match and count to learn colors and numbers
- Comes with 2 rolling vehicles
- Tabletop track for rolling fun
- Perfect for little hands
- Hands-on play for early childhood development
- Combine with other Mega Bloks preschool toys and build them up!
Score free 2-day shipping on most orders of $35 or more! You can also select free store pickup on many items, which might even be available the same day. Shipping starts at $5.99 for orders under $35.
Be sure to check out the other Walmart Deals we are finding.


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Freeze Sculpting Cryolipolysis Fat Freezing Weight Loss Machine Slimming Beauty Equipment
Product name | 4 cryo handle cryolipolysis machine |
Technical Principle | Fat Freezing |
Display screen | 10.4 inch large LCD |
Cooling temperature | 1-5 files (cooling temperature 0℃ to -11℃) |
Heating temperate | 0-4 gears (preheating for 3 minutes, heating temperature 37 to 45 ℃) |
Vacuum suction | 1-5 files (10-50Kpa) |
Input voltage | 110V/220v |
Output Power | 300-500w |
Fuse | 20A |
Does lipolysis require general anesthesia or only local anesthesia?
According to the treatment area: For large-area lipolysis, the operation time is long, and general anesthesia can be selected, which can not only avoid the discomfort caused by the operation, but also reduce the fear of the operation. For example, for local lipolysis, the operation time is short, and local anesthesia can be used, which generally does not cause too much pain. The specific method can be determined by the patient according to the individual's circumstances by consulting the doctor.
How many days does it take after double chin surgery?
Regarding double chin liposuction: the sutures can be removed generally within seven days after the operation, but if the normal care is not done, the recovery time will be prolonged. If you take care of it properly, it will fully recover in about 7 days, which seems natural. In the early stages of surgery, it is also important to avoid foods such as peppers, because these foods can affect local healing. At the same time, wear a mask on time as recommended by your doctor to prevent local sagging. In addition, if there is severe swelling, it can be reduced by wet compresses, but be careful not to contaminate the wound.
Fat freezing
Weight loss
Body slimming and shaping
Cellulite removal
Cryolipo,commonly referred to as fat freezing, is a nonsurgical fat reduction procedure that uses cold temperature to reduce fat deposits in certain areas of the body. The procedure is designed to reduce localized fat deposits or bulges that do not respond to diet and exercise.but the effect takes several months to be seen.in general 4 months.this technology is based on the finding that fat cells are more susceptible to damage from cold temperatures than other cells, such as skin cells. The cold temperature injures the fat cells. The injury triggers an inflammatory response by the body, which results in the death of the fat cells. Macrophages, a type of white blood cells and part of the body's immune system, is "called to the injury location," to rid the dead fat cells and debris from the body.


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The Tragic Death of Vijay Antony's Daughter Brings Attention to Mental Health
2 min readThe Tragic Death of Vijay Antony's Daughter Brings Attention to Mental Health
Shockwaves from this terrible news have reverberated across the local community and the movie business.
The tragic news of Meera's demise shocked the globe on a tragic Wednesday in Chennai. The 16-year-old was discovered dead in their Chennai home and was the adored daughter of famous actor and musician Vijay Antony.
A heartfelt message from Meera's mother and father, Vijay Antony, confirmed the news of her departure. Meera's mother replied to an older tweet that served as a melancholy memory of a better time when Meera had accomplished a big academic milestone. She had voiced her utter excitement in March, calling Meera the "root of my courage, my source of joy amidst my tears, and my incentive to persevere." They had no idea that such would become one of their final treasured recollections of their dear daughter.
Meera attended an institution in Chennai in addition to being the child of a well-known person in the film business. Her unexpected death took place inside the confines of a hospital in Chennai, leaving her loved ones in the dark.
Vijay Antony has lately experienced tragedy prior to this devastating defeat. He experienced a serious injury while filming "Pichaikkaran 2." The brilliant Tamil film director suffered wounds to his head and nose while working on a special effects project.
The tragic news of Meera's demise serves as a sobering reminder of the value of help and education for mental health issues. Nobody can comprehend the depths of suffering and hopelessness that motivated Meera to make such a sad choice. It is a sobering reminder that real people battle with real-life difficulties, especially the expectations and pressures associated with celebrity, behind the sparkle and glitter of the entertainment business.
There is optimism that Meera's terrible story will spark discussions about psychological health and urge people to seek treatment when necessary as the film industry and everyone else grieve the loss of her young life. Her family will always feel the sadness of her passing, but maybe her narrative will spur us all to become more understanding, compassionate, and conscious of the challenges that others could be going through behind their outward appearances.


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The Utah Jazz beat the Charlotte Hornets on Friday night but through most of the second half they were without one of their most integral players.
Mike Conley subbed out of the game during a timeout at the 6:58 mark of the third and later headed to the locker room. The Jazz announced during the fourth quarter that Conley would not return because of tightness in his right hamstring.
There was no immediate update after the game as to the severity of Conley's hamstring issue or his availability for Sunday's game on the road against the Indiana Pacers.
"We'll have to wait to get an assessment on where he is from our health and performance staff," Jazz head coach Quin Snyder said.
Conley is no stranger to hamstring injuries, which can be nagging and hard to manage for anyone. Conley missed 19 games before last season's All-Star break because of strained left hamstring, an injury that he's had to deal with before.
Last season during Conley's absence, the Jazz went on a 10-game win streak, and Conley has admitted time and time again that he struggled through most of the 2019-20 campaign. This season however, Conley has been playing some of the best basketball of his career and has been a difference-maker for the Jazz.
"Mike just has a way of being out there and kind of calming stuff," Donovan Mitchell said of his teammate after the game on Friday. "We definitely missed that presence on the offensive end, the offensive mind that he has. That was definitely one thing we definitely missed coming down the stretch, just to kind of settle this down in certain instances."
The Jazz were playing on the second night of a back-to-back against Charlotte, one of three back-to-back sets on their schedule between now and the March 5-10 All-Star break.
Conley has not missed a game this season and was averaging 16.5 points, six assists and 3.6 rebounds this season heading into Friday's contest, while shooting 40.3% from beyond the arc.


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Atletico Madrid have reportedly enquired about William Saliba, who will return to Arsenal in the summer from his loan spell at Marseille.
According to L'Equipe, La Liga champions Atletico Madrid are interested in William Saliba and could look to approach him in the summer when he returns to Arsenal. The French international has been sensational during his loan spell at Marseille as he enters a crucial phase in his career.
Many Arsenal fans remain puzzled over Mikel Arteta's handling of William Saliba. The Spanish manager decided to spend £50 million on Ben White in the summer while letting a promising prospect like Saliba leave the club on loan.
The decision was praised by some, as Saliba continues to perform well at Marseille, becoming an important part of Jorge Sampaoli's defensive unit. Be it a back-three or back-four, the young defender has found a place in the starting lineup, making 45 appearances across all competitions.
Marseille have been exploring the possibility to keep Saliba beyond his loan spell, but Arsenal are unwilling to sell him, despite interest from some big clubs. There seems to be a plan for the Frenchman under Arteta, who continues to count on the 21-year-old.
On the other hand, Saliba's recent comments indicated he will be looking at regular game time wherever he may be playing next season. His rise within the Marseille setup while being called up to the French national squad in the most recent international break has given him more confidence. Saliba also remains open to remaining at the French club beyond the current season.
At Arsenal, White and Gabriel Magalhaes are the first-choice centre-backs, although the possibility of the north Londoners playing in Europe will allow Saliba the opportunity to play regularly. The Gunners are already planning to hand him a new deal when he returns in the summer.
However, with two years left on his contract, it is a period when the player can explore other opportunities, with Arsenal having limited powers to keep hold of his services. It will be a testing summer for Arsenal in their resolve to retain Saliba as some big clubs continue to circle.
Atletico Madrid are the latest club to express an interest, as Diego Simeone explores signing Saliba in the summer transfer window to shore up his backline. The reigning La Liga champions have very little left to play for this season, and they are already planning moves for the next campaign.
They would like to mount a challenge for La Liga and the UEFA Champions League next term and are looking at essential players who could shore up their squad for the long-term. Saliba is understood to be one such player, and hence Atletico Madrid could approach Arsenal over a potential move.
What Arsenal do with the defender will play a crucial role in determining his future. Whether Saliba agrees to sign a new deal or not, remains a question for the summer, which could open the floodgates for interested clubs, like Atletico Madrid, to swoop in and explore signing the 21-year-old in the summer.


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- Location / Mosborough, Sheffield, ENGLAND
- Venue / Westfield School
- Event / School Dance
The first ever public performance by Def Leppard at a local school in Mosborough, Sheffield.
The first time at this venue.
The venue was located around 4 miles from the city centre and a cafeteria within Westfield School.
The school was closed in December 2006 and later demolished.
The band played as part of a school end of term dance event.
According to the 1987 biography Animal Instinct they were paid five pounds by a teacher, played for around fifty minutes and smuggled in some beer in the bass drum.
The band line-up was: Joe Elliott, Rick Savage, Steve Clark, Pete Willis and Tony Kenning.
The first song they played was an unreleased original called 'World Beyond The Sky'.
The only other confirmed track was an encore cover of Thin Lizzy song 'Jailbreak'.
An audience recording of this show exists on cassette but it has not been circulated and it's tracklisting/quality is also unknown.
The show was hastily arranged by a local band friend and promoter called Bootleg Bill after Steve Clark had threatened to quit unless they actually played a concert.
This had happened a few days earlier on a band holiday in the Norfolk Broads when they travelled to Ipswich to see a UFO gig.
Joe Elliott returned to Westfield in 1989 for the taping of a scene in the UK BBC TV documentary 'Rock Of Ages - The Def Leppard Story'. He was shown talking about the concert in the hall where it took place. The original building was demolished after a fire in 2007 and rebuilt as the Westfield Sports College about three quarters of a mile away in Beighton.
Read more about this show in the Lep History section.
show intro
- n/a
setlist - (Full list not confirmed/About 6 songs played)
- 01 - World Beyond The Sky - (Confirmed First Song)
- 00 - Beyond The Temple - (Possible Song)
- 00 - Misty Dreamer/Tomorrow Seems Like Yesterday - (Possible Song)
- 00 - Beyond The Temple - (Possible Song)
- 00 - (Got To) See The Lights - (Possible Song)
- 00 - Heat Street - (Possible Song)
- encore
- 00 - Jailbreak (Thin Lizzy cover) - (Confirmed Encore)
- Full setlist unknown.
- Add Setlist (If you attended this show)
- View - All Songs Played 1978
songs by album
- n/a
show info
- Tour - Def Leppard Early Years Tour 1978
- Fan Recorded - Yes (Audio) - (Un-circulated)
- Venue - Website
- Venue Address - Westfield Crescent, Mosborough, Sheffield S20 5AQ
- English County - South Yorkshire
- District - Mosborough
- Area Map - Google
- Last Show Here - December 1977 (Private Show at rehearsal space)
- Capacity - n/a
- Attendance - 150-200
- Headliner - Def Leppard
- 01 - Joe Elliott - Lead Vocals
- 02 - Steve Clark - Guitars
- 03 - Pete Willis - Guitars
- 04 - Rick Savage - Bass
- 05 - Tony Kenning - Drums
band members
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venue street view
A view looking towards where the venue/school used to be.
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Stay in touch with the latest updates.
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The 35 would like to make sure that the public understands these five main points:
- The bottle found was not confirmed to have been alcohol – The nearly empty (very few oz.) vitamin water bottle was found by the bus driver and allegedly "smelled" like alcohol. The employee told Principal Barsotti the bottle smelled like alcohol, but whether or not alcohol was in the bottle is unknown, it was never tested or turned over to authorities.


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The Federal Bureau of Investigation (FBI) is now helping local authorities monitor the "autonomous zone" that has popped up around George Floyd Square in Minneapolis, Fox News reported.
The autonomous zone has reportedly brought record levels of gun violence and other violent crime since last May, according to Fox News.
Reporter @BrianEntin tried to document what's happening at the growing "George Floyd Autonomous Zone" in Minneapolis. He was confronted by #antifa militants. Like in CHAZ & Portland, drivers & police are not allowed inside. Press are threatened. pic.twitter.com/xMJx74tHnk
— Andy Ngô (@MrAndyNgo) March 10, 2021
Members of the community have pleaded with law enforcement to step in and put an end to the scourge of crime.
George Floyd Square has been set up around where the video of former Minneapolis Police Officer Derek Chauvin kneeling on the neck of Floyd while police tried to detain him was first recorded, according to Fox News. The square became a memorial and a popular demonstration spot in the immediate aftermath of Floyd's death, Fox News reported. To protect demonstrators from traffic, the city of Minneapolis put concrete barriers in place, but now those barricades are being used by certain armed members of the autonomous zone to keep law enforcement out, according to Fox News. (RELATED: 2 Jurors In George Floyd Case Dismissed After Media Coverage Of Settlement)
Within the autonomous zone limits, gang activity, drug dealing, and gun violence are plaguing residents and local businesses, Fox News reported.
"The current situation at 38th and Chicago is unacceptable and will not and must not be tolerated," Minneapolis Police Chief Medaria Arradondo proclaimed at a Wednesday press conference, according to Fox News. Arrandondo also announced that the FBI Minneapolis Field Office, U.S. Attorney's Office District of Minnesota, and the Bureau of Alcohol, Tobacco, Firearms and Explosives (ATF), St. Paul Field Division will be helping local authorities out an end to the autonomous zone, according to Fox News.
"Violence in any part of our city must be addressed and those contributing to the harm of our neighborhoods have to be held accountable," Arradondo added, Fox News reported. Previously, the Minneapolis City Council has cut police department funding, as well as settled a civil suit with Floyd's family to the tune of $27 million.
A George Floyd autonomous zone in Minneapolis is blocked off by barricades & checkpoints. A business owner within zone was violently beaten unconcious by a man who demanded money. Responding police & ambulance were stopped by aggressive protesters. #BLM https://t.co/8FJduWFC50 pic.twitter.com/yKCwgaRRac
— Andy Ngô (@MrAndyNgo) September 18, 2020
The police cuts have diverted resources away from the autonomous zone, and the National Police Association has taken legal action on behalf of the residents and businesses located in the autonomous zone in order to get law enforcement to patrol the neighborhood again, Fox News reported.
"We are going to restore peace and safety to that neighborhood, and we're going to do it collectively with the help and a force multiplier by our partners. And we will not tolerate that any longer, and that intersection must be reopened." Arrandono said Wednesday, Fox News reported.


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Determined to address challenges posed by the outbreak of the coronavirus, underwriting firms have begun to adopt the use of Unstructured Supplementary Service Data (USSD), to reach out to more Nigerians to increase market penetration.
With the federal and state governments encouraging physical and social distance to limit human contacts to curb the spread of the virus, the underwriters chose to advance digital awareness, leveraging technology to give insurance a facelift.
Under the arrangement, a prospective policyholder will have an easy, quick and convenient channel to buy new products and policies, renew existing policies and make payments for Value Added Services.
The general idea is for the USSD code is to improve customer experience, and reduce turnaround time for all transactions, says the Head of Sales and Corporate Communications for Sovereign Trust Insurance Plc, Segun Bankole, who told The Guardian at the weekend, that his firm identified technology as a veritable game-changer in the insurance industry.
According to him, there is a need for underwriters to take the bull by the horn to latch onto opportunities of advancing her retail products and services with the Mobile App and the USSD code.
The Executive Director and Divisional Head, Technical, Jude Modilim enumerated the benefits of the Mobile App and assured the insuring public that they are in for a good time and a memorable insurance experience within the confines of their homes anywhere in the world.
Support InfoStride News' Credible Journalism: Only credible journalism can guarantee a fair, accountable and transparent society, including democracy and government. It involves a lot of efforts and money. We need your support. Click here to Donate


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Say goodbye to FOMO. With fully immersive, user-generated, 360-degree videos and photos, SOAK users can capture more than a moment, but an entire atmosphere.
Imagine being able to experience places, parties and moments you might never otherwise experience, via VR. SOAK users could finally be there, without actually being there.
Our challenge was to communicate the one-of-a-kind features offered by this app, ensuring it became an unmissable download for those unmissable moments.
The team took inspiration from the immersive name and the idea of a way to 'soak up the sun', 'soak in the atmosphere' and all the playful ideas those ideas represent.
We added depth to the mark to highlight the 360 dimensions of the app's features. And combined playful, retro colours of west coast sunsets with the contemporary feel of an east coast lifestyle.


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Table of Contents
Federal Withholding Tables 2021 – The IRS has just lately released the newly publicized Federal Income Tax Withholding Methods utilization in 2021. This publication, called Publication 15-T, is utilized to publicize the difference in tax rate and to supply employers the techniques to figure out how much wage they ought to withhold through the workers. To show how much they need to withhold from your employees, the IRS has also well prepared the IRS 2021 Withholding Tables because file.
This publication can be difficult to understand. But still, it is a great way to know about how the tax is counted according to the latest method.
What Are Federal Income Tax Withholding Tables?
IRS 2021 Withholding Tables, They are the set of tables that can help employers to discover the amount of withheld tax that needs to be extracted from the employees' salary. These tables can be found in the most recent publication 15-T. In order to work out how significantly tax needs to be withheld from your employees' salary, the tables can be utilized after the employers compile and make use of the data identified from your W-4 form, the employees' processing statuses, as well as the tax consistency.
How Exactly Does the Federal Income Tax Work?
IRS 2021 Withholding Tables is described as the tax that is certainly withheld from income– nevertheless of what kind of income is. This sort of income' includes wage, wage, tips, incentives and bonuses , wagering money, and even joblessness reward.
Inside the United States, the taxation system utilizes a intensifying level. To be described simply: the better you get, the more you pay the tax. In 2021, seven percentage classes are still applied since the tax rates, beginning from 10%, 12%, 22%, 24%, 32%, 35%, to the greatest one, 37%.
Federal Income Tax Withholding Method: Wage Bracket Technique
The IRS 2021 Withholding Tables can be used after you follow the method to determine the federal tax withholding. This technique is a 4-step method in order to find the final amount of tax withheld.
- Obtain the quantity of modified wage, the ways are printed in Step 1 (a-h).
- Find out the tentative withholding amount (Step 2a).
- Account for tax credits (Step 3a-3c).
- Lastly, figure out the final amount to withhold for a pay period (step 4a-4b).
Federal Income Tax Withholding Method: Percentage Method
Unlike the wage bracket, this method is applicable for any amount of wages. To use this method, you still need to collect the W-4 form and filing statuses from each employee.
Along with the tables provided inside the publication 15-T, the step-by-step tax checking method is additionally accessible there for types of W-4 forms: 2019 and previously types, and also the 2020 and afterwards variations.
Whilst completing the worksheet offered in the file, you need to look for the info shown in IRS 2021 Withholding Tables. This worksheet used to add up tax withholding with W-4 form dated 2019 and previously can vary with the worksheet utilized for W-4 form in 2020 model and later inspite of the minor variation.


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Kurt Gray is the co-author of "The Mind Club: Who Thinks, What Feels, and Why It Matters," a newly-released book that examines mind perception and human behavior.
An award-winning psychologist, Gray runs the Mind Perception and Morality Lab at UNC, which investigates the behavior behind religion, politics and other aspects of society. Staff writer Zoe Hazerjian spoke to Gray about mind perception, his research and Donald Trump.
The Daily Tar Heel: How did the idea for this book come about?
Kurt Gray: As Daniel (M. Wegner, co-author) and I looked around the world, we realized that much of our disagreement seems to rely upon mind perception. We looked at all the various kinds of minds in the book.
DTH: Who is the audience for this book?
KG: Anyone interested in the workings of the mind and moral disagreements.
DTH: Does this book appeal to students, specifically UNC students?


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3D Creator
What Do Fishing, Backpacking, Building Motorcycles and 3DEXPERIENCE World Have in Common?
Meet three engineers on the SOLIDWORKS portfolio management team who are as passionate about bringing SOLIDWORKS products to market as they are about pursuing their adventurous hobbies.
... ContinuedModel Mania SOLIDWORKS Cloud Challenge 2023 is Now Open!
Returning for its fourth year, the Model Mania® SOLIDWORKS Cloud Challenge is now open to all 3DEXPERIENCE World attendees, in-person and virtual. Learn how you can participate this year.
... ContinuedGet it Done Faster with SOLIDWORKS Browser-based Role Enhancements
I'm excited to announce the latest updates to the SOLIDWORKS browser-based design roles, including improved collaboration and notifications, Soft Selection for sub-division surfaces, Miter Flange, assembly balloons and much more.
... ContinuedThe Top Ten List – 3DEXPERIENCE World 2023 is now open for idea submissions!
The Top Ten List – 3DEXPERIENCE World 2023 is now open for idea submission and discussion. This is your chance to submit enhancement ideas for SOLIDWORKS products and vote on your favorite ideas. We are gathering Top Ten List ideas
... ContinuedMusic is Magic: Base Building
Learn how the SOLIDWORKS Magic Wheelchair build team designed and fabricated Savannah's epic costume. With 3D Creator and xDesign, they were able to create their smallest frame ever.
... ContinuedThis Year's Top 10 Enhancements in SOLIDWORKS Browser-based Roles
The latest enhancements in the SOLIDWORKS browser-based roles include 2D drawing improvements, smart mates, net surfacing, and more to help you be as productive as possible, in addition to improving downstream communication for manufacturing.
... ContinuedCatch Up on Key Browser-based 3DEXPERIENCE Works Role Enhancements in 2022
Each quarter, the SOLIDWORKS R&D team transforms your feedback into enhancements for the 3DEXPERIENCE Works design and engineering browser-based roles. Get caught up on key enhancements in 2022 so far.
... ContinuedExpand Your Toolset and Reduce Time to Market – Discover Design in the Cloud
Learn how SOLIDWORKS users can expand their skillsets and get products to market faster with 3DEXPERIENCE Works solutions.
... ContinuedJason Pohl: Creating a Mini Monster Truck with SOLIDWORKS and xShape
Industrial Designer and SOLIDWORKS Champion Jason Pohl partners with Sean O'Neill to create a mini monster truck for his kids' sandbox with SOLIDWORKS and xShape.
... ContinuedThe July 2022 Update is Here – What's Hot in the SOLIDWORKS Browser-based Design Roles
The latest 3DEXPERIENCE® Works release of browser-based design roles, R2022x FD03, is here and it's full of productivity enhancements to help you do your job better and faster.
... ContinuedSmooth Like That— New Switch App
Using the roles in the SOLIDWORKS® Cloud Offer just got better with a new option to our browser-based design and engineering roles that offer another fast and easy way to access your favorite design apps.
... ContinuedPrincess Power: Creating a Castle in the Clouds
What does it take to design an epic princess castle? Check out how the SOLIDWORKS Magic Wheelchair Build Team took Freyja's passions and turned them into her dream costume!
... ContinuedWhat's New with xDesign, xShape, and More!
Join SOLIDWORKS LIVE for a closer look at xDesign and xShape apps—with superheroes! Host Sean O'Neill welcomes a team of experts to show the power and flexibility of cloud-based solutions.
... ContinuedSpring Forward with Productivity— The 3DEXPERIENCE Works Design and Engineering April Update is Here!
Find out what's new in the latest release of our 3DEXPERIENCE® Works browser-based roles for design and engineering.
... ContinuedModel Mania SOLIDWORKS Cloud Challenge is Back at the All-Virtual 3DEXPERIENCE World
This blog explains what the Model Mania SOLIDWORKS Cloud Challenge is all about, how you can participate, and some tips for bringing your entry to the next level for a better chance at winning.
... Continued


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One of the primary missions of West Slope Foundation is to identify and meet the immediate and long-term needs of the Caldor Fire Survivors. We wish we could help everyone who was impacted by the wildland fire, but unfortunately there is not sufficient funding, so certain requirements have to be met to qualify for assistance. The requirements are outlined below.
Applying for Survivor's Assistance
To qualify for West Slope Foundation Aid* Programs or Disaster Case Management assistance, all these requirements must be met:
Disaster Related
50% or more loss to home due to direct impact of the disaster (this does not include smoke, ash, or any other damage outside of fire) or your home was completely destroyed. This is verified by the El Dorado County Caldor Fire Structure Status map provided by the El Dorado County Sheriff's Department.
Home lost was primary residence.
Live(d) within the burn scar.
Submit one application per household. You only need to fill out this application once. If you have already filled out this form and need immediate assistance, please fill out the Immediate Needs Application. A link is provided below.


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With bright chords, pumping rhythms, and gripping bass lines, the fast-rising talent Aldonna emerges from Melbourne's underground with her 'Morph' EP, including remixes from Alex Kassian and Marli, set for release via the always reliable HOMAGE label.
Having cut her teeth in Melbourne's lively community with her party series Re-Leaf and as a fixture on the Australian club circuit, Aldonna's sound is clearly supercharged with dancefloor energy. And her passion hasn't gone unnoticed. Cosigns from the likes of BICEP, who tapped her to contribute to their acclaimed 'Feel My Bicep' mix series, prove she's been an artist to watch for some time. Now with her debut EP, she introduces her own distinct sound which traverses seamlessly through nostalgic trance motifs and hyper ravey breaks. Aldonna is clearly making a push to be an unstoppable force in clubland.
The EP leads off with 'Nights In Shizuoka' and a rugged rhythm laying the foundation for arpeggiated synths building until a mystical pan flute carries the ballad to heavenly heights. Throughout the release, Aldonna showcases a knack for playing with a multitude of sonic textures, and the next track titled 'Air Sign' possesses layers of immersive textures, from tight acid lines to bubbling ambiance, haunting vocal chops, and warm emotive melodies layered over pumping breaks for an ecstatic anthem. The a-side concludes with 'For All That We Know' as a tight bass line sets the stage for Aldonna to build on her playful aesthetic with a shimmering and exuberant melody.
On the flip side, Aldonna goes full rave mode with 'The Empress' Acid Line', leading with chopped breaks before an infectious acid riff creeps and builds with seductive vocals, delivering massive energy that is palpable. Following the originals is a remix by Berlin-based Love On The Rocks mainstay Alex Kassian who aims his version of 'The Empress' Acid Line' at the most euphoric dancefloor moments and delivers a tried and true trancey euro-house weapon not to be overlooked. Rounding out the release is Melbourne's own Marli who flips 'Air Sign' with a rumbling bass line to reveal a bumping house cut that will satisfy the most vibrant crowds in the dance.


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A gorgeous assortment of pink blooms including pink roses, peonies and gladiolas makes this soft and feminine piece a perfect pledge to your loved one's grave. Multiple sizes shown- choose your favorite! Dimensions may vary.
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2022 Husqvarna Z454XS
Speed forward max: 17 km/h
Cutting width: 137 cm
Cutting height: 38 mm-114 mm
Zero Turn
Husqvarna's XS Series starts with all the benefits of the standard Z400 and takes it to the next level. Upgrades include a suspended seat platform for added comfort, Parker HTE12 transmissions with 23" tires for increased ground speed, premium FX class Kawasaki engines, deeper cutting decks and twin fuel tanks for extended run time.
Although every attempt is made to ensure the accuracy of the information above, due to the possibility of human error, we cannot guarantee the accuracy of the displayed information, the availability of any unit, or the accuracy of its photo or stock photo. Please contact C & P Motorsports for verification or if you would like more information. Specifications subject to change. *Prices exclude dealer-installed accessories, optional equipment physically attached to the vehicle, transportation charges and any applicable taxes and fees ^unless otherwise stated. All discounts are subject to change without prior notice. All prices are in Canadian Dollars unless otherwise stated. All financing offers are subject to change and are O.A.C. Please contact our dealership for more information.