Cholecalciferol
Hydroxycholecalciferols
Calcifediol
Ergocalciferols
Vitamin D Deficiency
Vitamin D
Rickets
24,25-Dihydroxyvitamin D 3
Vitamins
25-Hydroxyvitamin D 2
Phosphorus
Calcitriol
Dietary Supplements
Steroid Hydroxylases
Hydroxylation
Cholestanetriol 26-Monooxygenase
Trichosurus
Chickens
Calcium, Dietary
Parathyroid Hormone
25-Hydroxyvitamin D3 1-alpha-Hydroxylase
Pest Control
Receptors, Calcitriol
Calcium
Bone Density Conservation Agents
Food, Fortified
Bone and Bones
Duodenum
Tromethamine
Calcium Radioisotopes
Double-Blind Method
Seasons
Minerals
S100 Calcium Binding Protein G
Ethacrynic Acid
Bread
Bone Density
Apoptosis inhibitory activity of cytoplasmic p21(Cip1/WAF1) in monocytic differentiation. (1/960)
p21(Cip1/WAF1) inhibits cell-cycle progression by binding to G1 cyclin/CDK complexes and proliferating cell nuclear antigen (PCNA) through its N- and C-terminal domains, respectively. The cell-cycle inhibitory activity of p21(Cip1/WAF1) is correlated with its nuclear localization. Here, we report a novel cytoplasmic localization of p21(Cip1/WAF1) in peripheral blood monocytes (PBMs) and in U937 cells undergoing monocytic differentiation by in vitro treatment with vitamin D3 or ectopic expression of p21(Cip1/WAF1), and analyze the biological consequences of this cytoplasmic expression. U937 cells which exhibit nuclear p21(Cip1/WAF1) demonstrated G1 cell-cycle arrest and subsequently differentiated into monocytes. The latter event was associated with a cytoplasmic expression of nuclear p21(Cip1/WAF1), concomitantly with a resistance to various apoptogenic stimuli. Biochemical analysis showed that cytoplasmic p21(Cip1/WAF1) forms a complex with the apoptosis signal-regulating kinase 1 (ASK1) and inhibits stress-activated MAP kinase cascade. Expression of a deletion mutant of p21(Cip1/WAF1) lacking the nuclear localization signal (DeltaNLS-p21) did not induce cell cycle arrest nor monocytic differentiation, but led to an apoptosis-resistant phenotype, mediated by binding to and inhibition of the stress-activated ASK1 activity. Thus, cytoplasmic p21(Cip1/WAF1) itself acted as an inhibitor of apoptosis. Our findings highlight the different functional roles of p21(Cip1/WAF1), which are determined by its intracellular distribution and are dependent on the stage of differentiation. (+info)1Alpha,25dihydroxyvitamin D3 and platinum drugs act synergistically to inhibit the growth of prostate cancer cell lines. (2/960)
The majority of men who die from prostate cancer (PC) have hormone-refractory disease. To date, chemotherapeutic agents have had little or no impact on the survival of such patients. To explore a new approach for the treatment of hormone-refractory PC, we examined the combination effects of cis- or carboplatin with vitamin D. 1alpha,25-Dihydroxyvitamin D3 (1alpha,25(OH)2D3) and its synthetic analogue, Ro 25-6760, have an antiproliferative effect on some prostate cancer cell lines. Consequently, the growth-inhibitory effects of the drugs were measured, both singularly and in combination with cis- or carboplatin, on PC cells. Our results show that although each of the drugs alone displayed antiproliferative activity, the growth inhibition of PC cells was further enhanced by the combination of 1alpha,25(OH)2D3 or Ro 25-6760 and either platinum agent. The greatest enhancement of inhibition occurred using smaller concentrations of the platinum compound in combination with higher concentrations of 1alpha,25(OH)2D3. Isobologram analysis revealed that 1alpha,25(OH)2D3 and platinum acted in a synergistic manner to inhibit the growth of PC cells. Our findings suggest that there is potential clinical value in combining 1alpha,25(OH)2D3 with platinum compounds for the treatment of advanced-stage human PC. (+info)Plasma 25-hydroxyvitamin D in growing kittens is related to dietary intake of cholecalciferol. (3/960)
Vitamin D synthesis by growing kittens exposed to ultraviolet light is ineffective. Concentration of 25-hydroxyvitamin D (25-OHD) in plasma (the most useful index of vitamin D status) was measured in six groups each of seven kittens given a purified diet (12 g calcium and 8 g phosphorus/kg, calculated metabolizable energy = 20 kJ/g) that contained either 0.0, 3.125, 6.25, 12.5, 18.75 or 25 microg of cholecalciferol/kg diet. All kittens received these diets from 9 to 22 wk of age, and the two groups given the 0.0 and 3.125 microg cholecalciferol/kg treatments continued to receive the diets until they were 34 wk old. Total and ionizable calcium and phosphorus in plasma were not affected by treatments. No adverse clinical changes were observed or found on radiographic examination of the kittens at 22 or 34 wk of age. Plasma concentration of 25-OHD was linearly related (r2 = 0.99, P < 0.001) to dietary intake of cholecalciferol. Plasma concentration of 25-OHD in kittens given the diet without added vitamin D was significantly less at 22 wk than at 9 wk, whereas kittens receiving the diet containing 3.125 microg cholecalciferol/kg had significantly higher 25-OHD concentrations at 22 and 34 wk than at 9 wk of age. Kittens given the 6.25 microg cholecalciferol/kg diet had plasma 25-OHD concentrations at 22 wk > 50 nmol/L which is considered replete for humans. An allowance of 6. 25 microg (250 IU) of cholecalciferol/kg diet is suggested to provide a margin of safety. (+info)Structure-function studies of new C-20 epimer pairs of vitamin D3 analogs. (4/960)
A growing number of calcitriol (1alpha,25-dihydroxyvitamin D3) analogs have become available in recent years. Many of these analogs exhibit lower calcemic effects than calcitriol and inhibit cell proliferation and enhance cell differentation more efficiently than calcitriol. We have compared structure-function relationships of a series of new C-20 epimer (20-epi) vitamin D3 analogs with their natural C-20 counterparts. In human MG-63 osteosarcoma cells, quantification of cellular osteocalcin mRNA levels by Northern blot analysis and osteocalcin biosynthesis by radioimmunoassay indicated that most studied analogs at a concentration of 10 nm induced osteocalcin gene expression more efficiently than the parent compound, calcitriol. Interestingly, when the biological responses were compared with the binding affinities of the analogs to in-vitro translated human vitamin D receptor and with their ability to protect the receptor against partial proteolytic digestion, significant correlations were not observed. Further, molecular modelling of the compounds by energy minimization did not reveal marked differences in the three-dimensional structures of the analogs. These results suggest that higher than normal ligand binding affinity or 'natural' conformation of the ligand-receptor complex are not necessarily required for the 'superagonist' transactivation activity. The mechanism of action of the efficient analogs may involve stabilization and/or differential binding of transcriptional coactivators or transcription intermediary factors to the hVDR during transactivation. (+info)1alpha,25-dihydroxy-3-epi-vitamin D3: in vivo metabolite of 1alpha,25-dihydroxyvitamin D3 in rats. (5/960)
We recently identified 1alpha,25-dihydroxy-3-epi-vitamin D3 as a major in vitro metabolite of 1alpha,25-dihydroxyvitamin D3, produced in primary cultures of neonatal human keratinocytes. We now report the isolation of 1alpha,25-dihydroxy-3-epi-vitamin D3 from the serum of rats treated with pharmacological doses of 1alpha,25-dihydroxyvitamin D3. 1alpha,25-dihydroxy-3-epi-vitamin D3 was identified through its co-migration with synthetic 1alpha,25-dihydroxy-3-epi-vitamin D3 on both straight and reverse phase high performance liquid chromatography systems and by mass spectrometry. Along with 1alpha,25-dihydroxy-3-epi-vitamin D3, other previously known metabolites, namely, 1alpha,24(R),25-trihydroxyvitamin D3, 1alpha,25-dihydroxy-24-oxo-vitamin D3 and 1alpha,25-dihydroxyvitamin D3-26,23-lactone, were also identified. Thus, our study for the first time provides direct evidence to indicate that 1alpha,25-dihydroxy-3-epi-vitamin D3 is an in vivo metabolite of 1alpha,25-dihydroxyvitamin D3 in rats. (+info)Cloning of porcine 25-hydroxyvitamin D3 1alpha-hydroxylase and its regulation by cAMP in LLC-PK1 cells. (6/960)
The 25-hydroxyvitamin D3 1alpha-hydroxylase, also referred to as CYP27B1, is a mitochondrial cytochrome P450 enzyme that catalyzes the biosynthesis of 1alpha, 25-dihydroxyvitamin D3 (1alpha,25(OH)2D3) from 25-hydroxyvitamin D3 in renal proximal tubular cells. Recently, human, mouse, and rat CYP27B1 cDNA have been cloned, however the gene regulation has not been fully elucidated. In the present study, porcine CYP27B cDNA was cloned, and the effects of cAMP and vitamin D3 on the regulation of CYP27B1 mRNA expression in LLC-PK1 cells were examined. PCR cloning revealed that porcine CYP27B1 cDNA consisted of 2316 bp, encoding a protein of 504 amino acids. The deduced amino acid sequence showed over 80% identity to the human, mouse, and rat enzyme. LLC-PK1 cells were incubated with humoral factors, and expression of CYP27B1 mRNA was measured by a quantitative reverse transcription-PCR. At the completion of 3-, 6-, 12-, and 24-h incubations, 500 micromol/L 8-bromo-cAMP had significantly increased CYP27B1 mRNA expression (260 to 340%). The adenylate cyclase activator forskolin at 50 micromol/L also had a stimulatory effect at 6 h (190%). Moreover, the protein kinase A inhibitor H-89 reduced the cAMP effect. On the other hand, 1alpha,25(OH)2D3 had no effect on CYP27B1 mRNA expression at 10 and 100 nmol/L, whereas expression of 25-hydroxyvitamin D3 24-hydroxylase (CYP24) mRNA was markedly increased by 1alpha,25(OH)2D3. These findings suggest that LLC-PK1 cells express CYP27B1 mRNA, and that cAMP is an upregulating factor of the CYP27B1 gene in vitro. (+info)Vitamin D3 supplementation of beef steers increases longissimus tenderness. (7/960)
The objectives of these experiments were to determine 1) the effectiveness of supplemental vitamin D3 (VITD) on altering plasma and muscle calcium levels, 2) whether VITD supplementation improves Warner-Bratzler shear force (WBS) values of steaks from feedlot beef steers, and 3) the tenderness response curve of longissimus steaks from steers supplemented with VITD. In Exp. 1, 20 crossbred steers were assigned randomly to one of four treatment diets consisting of either 0, 2.5, 5.0, or 7.5 x 106 IU of VITD per day for 10 d. Blood samples were obtained daily during this supplementation period and 5 d thereafter (d 11 to 15). Between d 6 and 13, a linear increase (P < .01) in ionized plasma calcium concentrations was observed in steers supplemented with VITD. Compared to unsupplemented steers, serum calcium concentrations of the steers receiving 7.5 x 106 IU of VITD per day were increased 8 to 48%. In Exp. 2, longissimus samples from crossbred steers (n = 118) that were supplemented with either 0 or 5 x 106 IU of VITD per day for 7 d were obtained and aged for 7, 14, or 21 d. Following the initial 7-d postmortem aging period, VITD supplementation lowered (P < .01) WBS (.58 kg) and increased sensory tenderness rating (.6 units) compared to cuts originating from unsupplemented steers. In Exp. 3, 44 steers were supplemented with either 0 or 7.5 x 106 IU of VITD per day for 10 d immediately prior to slaughter. Results indicated that plasma and longissimus calcium concentration were higher (P < .05) for steers that received supplemental VITD. Compared with unsupplemented cuts, VITD supplementation improved WBS of cuts aged for either 7 or 14 d (P = .02 and P = .07, respectively). Sensory panelists rated samples from VITD supplemented steers as more tender than their unsupplemented counterparts. Activation of calpain proteases could be responsible for the observed tenderization due to the supplementation of VITD. (+info)A two-hit mechanism for vitamin D3-mediated transcriptional repression of the granulocyte-macrophage colony-stimulating factor gene: vitamin D receptor competes for DNA binding with NFAT1 and stabilizes c-Jun. (8/960)
We previously described a control element in the granulocyte-macrophage colony-stimulating factor (GM-CSF) enhancer that is necessary and sufficient to mediate both transcriptional activation in response to T-cell stimuli and transcriptional repression by 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] through the vitamin D3 receptor (VDR). This DNA element is a composite site that is recognized by both Fos-Jun and NFAT1; it is directly bound by VDR in the absence of a retinoid X receptor as an apparent monomer, and it is bound in a unique tertiary conformation. We describe here the mechanism by which VDR elicits its transcriptional inhibitory effect. Firstly, VDR outcompetes NFAT1 for binding to the composite site. Overexpression of NFAT1 in vivo by transient transfection is able to relieve the 1,25(OH)2D3-dependent repression. Secondly, VDR stabilizes the binding of a Jun-Fos heterodimer to the adjacent AP-1 portion of the element. This appears to occur through a direct interaction between VDR and c-Jun, as demonstrated in vitro by direct glutathione S-transferase coprecipitation assays. In vivo, overexpression of c-Jun, but not c-Fos, leads to a rescue of the 1, 25(OH)2D3-mediated repression. Transfected FLAG-VDR bound to the NFAT1-AP-1 DNA binding element can be selectively precipitated from nuclear extracts that are made from cells treated with activating agents in the presence of 1,25(OH)2D3. VDR is not detected in the complex in the absence of the ligand. Thus, VDR acts selectively on the two components required for activation of this promoter/enhancer: it competes with NFAT1 for binding to the composite site, positioning itself adjacent to Jun-Fos on the DNA. Co-occupancy apparently leads to an inhibitory effect on c-Jun's transactivation function. These two events mediated by VDR effectively block the NFAT1-AP-1 activation complex, resulting in an attenuation of activated GM-CSF transcription. (+info)Vitamin D deficiency can occur due to several reasons, including:
1. Limited sun exposure: Vitamin D is produced in the skin when it is exposed to sunlight. People who live in regions with limited sunlight, such as far north or south latitudes, may experience vitamin D deficiency.
2. Poor dietary intake: Vitamin D is found in few foods, such as fatty fish, egg yolks, and fortified dairy products. People who follow a restrictive diet or do not consume enough of these foods may develop vitamin D deficiency.
3. Inability to convert vitamin D: Vitamin D undergoes two stages of conversion in the body before it becomes active. The first stage occurs in the skin, and the second stage occurs in the liver. People who have a genetic disorder or certain medical conditions may experience difficulty converting vitamin D, leading to deficiency.
4. Certain medications: Some medications, such as anticonvulsants and glucocorticoids, can interfere with vitamin D metabolism and lead to deficiency.
5. Increased demand: Vitamin D deficiency can occur in people who have high demands for vitamin D, such as pregnant or lactating women, older adults, and individuals with certain medical conditions like osteomalacia or rickets.
Vitamin D deficiency can cause a range of health problems, including:
1. Osteomalacia (softening of the bones)
2. Rickets (a childhood disease that causes softening of the bones)
3. Increased risk of fractures
4. Muscle weakness and pain
5. Fatigue and malaise
6. Depression and seasonal affective disorder
7. Autoimmune diseases, such as multiple sclerosis, type 1 diabetes, and rheumatoid arthritis
8. Cardiovascular disease
9. Certain types of cancer, such as colorectal, breast, and prostate cancer
If you suspect you may have a vitamin D deficiency, it's important to speak with your healthcare provider, who can diagnose the deficiency through a blood test and recommend appropriate treatment. Treatment for vitamin D deficiency typically involves taking supplements or increasing exposure to sunlight.
Rickets is caused by a deficiency of vitamin D, usually due to inadequate sunlight exposure, breastfeeding, or a diet that is low in calcium and vitamin D. It can also be caused by certain medical conditions, such as kidney disease, or by taking certain medications that interfere with vitamin D production.
Symptoms of rickets may include:
* Bowed legs or other deformities of the bones
* Pain in the bones and joints
* Softening of the bones (osteomalacia)
* Difficulty walking or standing
* delayed tooth development
* Frequent infections
If rickets is suspected, a doctor may perform a physical examination, take a medical history, and order diagnostic tests such as X-rays or blood tests to confirm the diagnosis. Treatment typically involves correcting any underlying nutritional deficiencies and managing any related health issues. In severe cases, surgery may be necessary to repair damaged bones.
Prevention is key in avoiding rickets, so it's important for parents to ensure their children are getting enough vitamin D and calcium through a balanced diet and adequate sunlight exposure. In regions with limited sunlight, fortified foods such as milk and cereal can be helpful. Breastfeeding mothers may need to supplement their diets with vitamin D to ensure their babies are getting enough.
Cholecalciferol
Vitamin D
Endocrine gland
Rodenticide
Median lethal dose
Cat food
Dog food
Ergocalciferol
Vitamin D toxicity
Diphenadione
1080 usage in New Zealand
Cefoxitin
Endocrine bone disease
Calcifediol
Vitamin D deficiency
Michael F. Holick
Carotenoid complex
Osteomalacia
Previtamin D3
Vegetarian and vegan dog diet
D-CON
Rickets
Ultraviolet
Butylated hydroxyanisole
Hypercalcaemia
Dog health
Calcitriol
Prehormone
Glossary of medicine
Vegan nutrition
DailyMed - X- cholecalciferol powder
MedlinePlus - Search Results for: CHOLECALCIFEROL
CHOLECALCIFEROL - Books - NCBI
Cholecalciferol (Vitamin D3): MedlinePlus Drug Information
Vitacost Vitamin D3 as Cholecalciferol 10000 IU, 365 ct - Ralphs
CHOLECALCIFEROL/PD - Search Results - PubMed
Cholecalciferol (Vitamin D3) - Side Effects, Interactions, Uses, Dosage, Warnings | Everyday Health
Is calcifediol better than cholecalciferol for vitamin D supplementation? - PubMed
Liquid Vitamin D3 (Cholecalciferol) Natural Orange Flavor 5000 IU - 2 fl. oz (59 ml) - Solgar Vitamin and Herb | Pureformulas
Solgar Liquid Vitamin D3 (Cholecalciferol) 125 mcg (5000IU) Natural Or - VitaminLife
An in-vitro-in-vivo model for the transdermal delivery of cholecalciferol for the purposes of rodent management - Fingerprint
...
Standard Process Cataplex D - Whole Food Immune Support, Digestive Health, Bone Strength and Bone Health with Cholecalciferol,...
Cholecalciferol 25mcg - athenacompanyltd
Vitamin D3 Cholecalciferol Drops
Common and Rare Side Effects for VITAMIN D3
DailyMed - DECARA K VEGICAPS- cholecalciferol, phytonadione capsule
Menaquinone - brand name list from Drugs.com
60L IU Cholecalciferol Drop Manufacturer,Exporter,Supplier
Vitamin D3 (25-Hydroxy-Cholecalciferol) - MedLab Bochum
CHOLECALCIFEROL 60,000 IU SACHET Manufacturer Supplier | PCD Franchise
Cholecalciferol Archives - Medical Weight Loss And Hormone Clinic
Bio-Tech D3-5 Cholecalciferol 100 Caps - Free Shipping
Solgar Vitamin D3 (Cholecalciferol) 5,000 IU 240 Veg Capsules
Nutrients | Free Full-Text | Evaluation of Vitamin D Metabolism in Patients with Type 1 Diabetes Mellitus in the Setting of...
A randomized placebo-controlled, double-blind study to investigate the effect of a high oral loading dose of cholecalciferol in...
Solgar Vitamin D3 (Cholecalciferol) 400 IU Softgels - Locatel Health & Wellness Online Store
Cholecalciferol Vit D3 Injections Manufacturers Suppliers - WHO:GMP Third Party Contract Manufacturers
10003
- MAVIDOS was a randomized, double-blind, placebo-controlled trial of 1000 IU/day cholecalciferol from 14 weeks' gestation until delivery. (bvsalud.org)
- Half of the participants were randomly assigned to receive cholecalciferol 1000 IU/day from around 14 weeks' gestation until delivery, and half were assigned to receive placebo. (medscape.com)
- Using logistic regression, the researchers analyzed links between maternal cholecalciferol 1000 IU/day supplements or placebo and atopic eczema risk in their offspring. (medscape.com)
Effect of antenatal2
- We assessed the effect of antenatal cholecalciferol supplementation on the incidence of preterm birth , delivery mode and post-partum haemorrhage (PPH). (bvsalud.org)
- Our data provide the first randomized controlled trial evidence of a protective effect of antenatal cholecalciferol supplementation on risk of infantile atopic eczema, with the effect only seen in infants that were breastfed for more than 1 month," write lead study author Sarah El-Heis, MRCP, DM, and colleagues. (medscape.com)
Antenatal cholecalciferol supplementation2
- Does antenatal cholecalciferol supplementation affect the mode or timing of delivery? (bvsalud.org)
- Antenatal cholecalciferol supplementation did not alter timing of birth or prevalence of preterm birth but demonstrated a possible effect on the likelihood of SVD. (bvsalud.org)
5,0001
- BIO-TECH D3-5 Cholecalciferol 100 Capsules Anti-Oxidants / Vitamins Vitamin D D3-5 Cholecalciferol Each capsule supplies Vitamin D3 Cholecalciferol 5,000 IU Inactive ingredients: Pharmaceutical grade microcrystalline cellulose, Fumed silica. (hmherbs.com)
Vitamin13
- Cholecalciferol (vitamin D 3 ) is used as a dietary supplement when the amount of vitamin D in the diet is not enough. (medlineplus.gov)
- Cholecalciferol (vitamin D 3 ) is also used along with calcium to prevent and treat bone diseases such as rickets (softening and weakening of bones in children caused by lack of vitamin D), osteomalacia (softening and weakening of bones in adults caused by lack of vitamin D), and osteoporosis (a condition in which the bones become thin and weak and break easily). (medlineplus.gov)
- Cholecalciferol (vitamin D 3 ) is in a class of medications called vitamin D analogs. (medlineplus.gov)
- Cholecalciferol (vitamin D 3 ) comes as a capsule, gel capsule, chewable gel (gummy), tablet, and liquid drops to take by mouth. (medlineplus.gov)
- Check with your doctor or pharmacist before taking a cholecalciferol (vitamin D) supplement. (medlineplus.gov)
- If you become pregnant while taking cholecalciferol (vitamin D 3 ), call your doctor. (medlineplus.gov)
- When cholecalciferol (vitamin D 3 ) is used to treat and prevent bone diseases, you should eat and drink of foods and drinks that are rich in calcium. (medlineplus.gov)
- Cholecalciferol (vitamin D 3 ) may cause side effects. (medlineplus.gov)
- People with adequate access to sunlight usually do not need dietary vitamin D because ultraviolet light converts 7-dehydrocholesterol abundant in skin to vitamin D3 cholecalciferol. (hmherbs.com)
- Cholecalciferol better known as Vitamin D3 is a form of Vitamin D. It transforms into a hormone in the blood stream and helps in the absorption of calcium and phosphate. (portea.com)
- Vitamin D3 (25-OH Cholecalciferol) Test is also referred to as 25-OH vitamin D test, Calcidiol test and 25-hydroxycholecalciferol test. (portea.com)
- You can also choose to get your cholecalciferol vitamin d3 test done at your home that too at an economical price with the help of Portea. (portea.com)
- One rodenticide, cholecalciferol (Vitamin D 3 ), has been registered for use in New Mexico, and holds great promise for the control of field rodents involved in plague epizootics. (cdc.gov)
Calcium1
- In addition to this, clients can avail this Calcium Citraate Maleale, cholecalciferol And Folic Acid Tablet from us in different packaging options. (sunestalifesciences.com)
Hydroxy1
- anthropometric measurements were made to determine nutritional status and estimation of 25- hydroxy cholecalciferol (25OHD) done for all those studied. (bvsalud.org)
Zinc1
- Other poisons that are not anticoagulants are cholecalciferol and zinc phosphide. (sccf.org)
Ingredients1
- tell your doctor and pharmacist if you are allergic to cholecalciferol, any other medications, or any of the ingredients in cholecalciferol products. (medlineplus.gov)
Placebo2
- Gestation at birth and incidence of preterm birth ( cholecalciferol 5.7%, placebo 4.5%, P = 0.43) were similar between the two treatment groups. (bvsalud.org)
- PPH was less common in women randomized to cholecalciferol [32.1% compared with placebo (38.1%, P = 0.054) overall], but similar when stratified by delivery mode. (bvsalud.org)
Supplements1
- Cholecalciferol supplements are available alone and in combination with vitamins, and in combination with medications. (medlineplus.gov)
Healthy1
- Cholecalciferol is needed by the body for healthy bones, muscles, nerves, and to support the immune system. (medlineplus.gov)