In vitro combination effects of plant-derived quercetin with synthetic bicalutamide on prostate cancer and normal cell lines: in silico comparison.

Prostate cancer is the second most frequent and the fifth greatest cause of death in men. Although diet has been connected to the prevalence of cancer in addition to other factors, the relation between cancer and prevention is weak. Treatment options are at risk due to cell resistance. To identify new combinations, we tried plant-derived quercetin with bicalutamide on cell lines. To determine the cytotoxicity and apoptotic potential of plant-derived quercetin and its combination, MTT [3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide] and dual stain assays were performed. In silico protein-ligand interaction was performed to support the in vitro findings. A thin layer, column, and high-performance chromatography were used to purify quercetin along with an authentic sample. In the cytotoxic study, quercetin was minimized by 80% similar to bicalutamide and a combination of quercetin and bicalutamide by 50% when compared to controls by 2%. Quercetin and bicalutamide showed a similar binding affinity for androgen receptors (9.7 and 9.8), hub genes (10.8 and 10.0), and a few other PCa-related genes (9.4 and 9.1). We propose to conclude that the combination of quercetin plus bicalutamide can be used for chemotherapy if additional in vivo studies are conducted. The intake of foods high in polyphenolic compounds can help to prevent prostate cancer. Examination of quercetin on several cell lines will provide a definite conclusion to combat cancers.

Two Randomized Trials of Low-Dose Calcium Supplementation in Pregnancy.

BACKGROUND: The World Health Organization recommends 1500 to 2000 mg of calcium daily as supplementation, divided into three doses, for pregnant persons in populations with low dietary calcium intake in order to reduce the risk of preeclampsia. The complexity of the dosing scheme, however, has led to implementation barriers. METHODS: We conducted two independent randomized trials of calcium supplementation, in India and Tanzania, to assess the noninferiority of a 500-mg daily dose to a 1500-mg daily dose of calcium supplementation. In each trial, the two primary outcomes were preeclampsia and preterm birth, and the noninferiority margins for the relative risks were 1.54 and 1.16, respectively. RESULTS: A total of 11,000 nulliparous pregnant women were included in each trial. The cumulative incidence of preeclampsia was 3.0% in the 500-mg group and 3.6% in the 1500-mg group in the India trial (relative risk, 0.84; 95% confidence interval [CI], 0.68 to 1.03) and 3.0% and 2.7%, respectively, in the Tanzania trial (relative risk, 1.10; 95% CI, 0.88 to 1.36) - findings consistent with the noninferiority of the lower dose in both trials. The percentage of live births that were preterm was 11.4% in the 500-mg group and 12.8% in the 1500-mg group in the India trial (relative risk, 0.89; 95% CI, 0.80 to 0.98), which was within the noninferiority margin of 1.16; in the Tanzania trial, the respective percentages were 10.4% and 9.7% (relative risk, 1.07; 95% CI, 0.95 to 1.21), which exceeded the noninferiority margin. CONCLUSIONS: In these two trials, low-dose calcium supplementation was noninferior to high-dose calcium supplementation with respect to the risk of preeclampsia. It was noninferior with respect to the risk of preterm live birth in the trial in India but not in the trial in Tanzania. (Funded by the Bill and Melinda Gates Foundation and others; ClinicalTrials.gov number, NCT03350516; Clinical Trials Registry-India number, CTRI/2018/02/012119; and Tanzania Medicines and Medical Devices Authority Trials Registry number, TFDA0018/CTR/0010/5).

Assessment of workplace integration of migrant nurses and midwives within international health care settings: a scoping review protocol.

OBJECTIVE: The objective of this scoping review is to map the available evidence on the assessment of workplace integration of migrant nurses and midwives in international health care settings. INTRODUCTION: Internationally, migrant nurses and midwives are an increasingly important resource in government strategy for addressing the current and predicted workforce shortages in health care. Much has been documented about the orientation stages of their transition to foreign workplaces but few sources have considered the workplace integration of this population. INCLUSION CRITERIA: The review will include all studies involving migrant nurses and midwives who are working outside their country of initial nurse or midwife registration for at least one year. The context will be all hospital, community, and residential care home settings, including the mental health, intellectual disability, and maternity care sectors. METHODS: The JBI methodology for scoping reviews and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews will be used to conduct this review. The databases to be searched will include CINAHL, MEDLINE, Embase, CENTRAL, and Google Scholar. Gray literature will also be searched and a hand search will be conducted of sources that fall outside these database searches. Two reviewers will independently screen titles, abstracts, and full-text articles. The extracted data will be presented in a tabulated chart accompanied by a narrative summary that aligns with the objectives and scope of this review.

Synthesis, characterization and biological evaluation of mononuclear Co(II), Ni(II), Cu(II) and Pd(II) complexes with new N2O2 Schiff base ligands.

New tetradentate N(2)O(2) donor Schiff bases and their mononuclear Co(II), Ni(II), Cu(II), and Pd(II) complexes were synthesized and characterized extensively by IR, (1)H-, (13)C-NMR, mass, ESR, conductivity measurements, elemental and thermal analysis. Specifically the magnetic and electronic spectral measurements demonstrate the octahedral structures of cobalt(II), nickel(II) complexes and square planar geometries of copper(II), palladium(II) complexes. All the ligands and complexes were screened for their in vitro antibacterial activity against two gram-positive bacteria (Bacillus subtilis, Staphylococcus aureus) and two gram-negative bacteria (Escherichia coli, Klebsiella pneumonia). In this study, Pd(II) complexes exhibited potent antibacterial activity against B. subtilis, S. aureus whereas other metal complexes also exerted good activity towards all tested strains even than standard drugs streptomycin and ampicillin.

Pregnancy interceptive activity of the roots of Calotropis gigantea Linn. in rats.

OBJECTIVE: We conducted this study to evaluate the pregnancy interceptive activity of the roots of Calotropis gigantea Linn. in colony-bred adult Sprague-Dawley rats when administered during the preimplantation and/or peri-implantation periods. METHODS: The ethanolic extract of the roots of C. gigantea Linn. and its hexane, chloroform, n-butanol-soluble and n-butanol-insoluble fractions were administered to rats on Day 1, Days 1-5, Days 1-7 or Days 5-7 postcoitum. Rats from the control group received an equal volume of the vehicle (Tween 80 in glass distilled water) only. At autopsy on Day 10 postcoitum, the final body weight and number as well as status of the corpora lutea and implantations in each animal were recorded. For estrogen agonistic and antagonistic activities, 21-day-old immature rats ovariectomized 7 days earlier were treated orally with the test agent or the vehicle for 3 days. In the case of estrogen antagonistic activity, the rats also received 0.05 mg/kg of 17alpha-ethinyl estradiol for 3 days. At autopsy 24 h after the last treatment, uterine fresh weight was taken and premature opening of the vagina as well as the extent of vaginal cornification, if any, were recorded. RESULTS: The ethanolic extract of the roots of C. gigantea Linn. exhibited 100% pregnancy interceptive activity in rats when administered as a single oral dose of 100 mg/kg on Day 1 postcoitum. The extract also exhibited 100% efficacy at the dose of 12.5 mg/kg when administered in the Days 1-5 and 1-7 postcoitum schedules. When administered during the peri-cum-early postimplantation period (i.e., Days 5-7 postcoitum at 250 mg/kg), most of the implantations showed signs of resorption. On fractionation, the chloroform fraction showed 100% activity at 100 mg/kg in the single-day (Day 1 postcoitum) schedule, whereas the hexane, n-butanol-soluble and n-butanol-insoluble fractions were found to be inactive at this dose. At autopsy on Day 10 postcoitum, 7-25% loss in body weight was recorded at the minimum effective contraceptive dose (MED) in rats treated with the ethanolic extract as well as its chloroform-soluble fraction on Days 1-7, 1-5 and 1 postcoitum, in comparison with the 6-7% increase in body weight observed in vehicle control rats. There was however no mortality in any of the treatment groups. The active ethanolic extract and its chloroform fraction were devoid of any estrogen agonistic or antagonistic activity at their respective MEDs in the ovariectomized immature rat bioassay. Efforts are being made to isolate the active principles devoid of effect on body weight. CONCLUSIONS: The findings suggest the potential for developing products of this plant as contraceptives for human use and welfare. In addition, characterization of the agents responsible for body weight decrease and evaluation of their mechanism of action and safety profile, with or without contraceptive efficacy, might have added advantage for the management of obesity.

Evaluation of contraceptive activity of a mineralo-herbal preparation in Sprague-Dawley rats.

OBJECTIVE: This study was aimed to evaluate a marketed mineralo-herbal preparation containing plants known to have potent contraceptive activity, or contraindicated for use during pregnancy in folklore/ancient Indian literature and recommended for use as an appetizer and headache, hyperacidity and chronic constipation reliever for effect on spermatogenesis and implantation-cum-early postimplantation events in adult Sprague-Dawley rats. METHODS: The preparation, suspended in distilled water with the addition of sterile gum acacia, was administered at 1 g/kg daily dose (extrapolated from human dose on surface area basis) to male rats covering one spermatogenic cycle and to female rats during the entire preimplantation and early postimplantation period by oral route. Fertility performance of male rats was tested following mating with untreated fertile females. RESULTS: Findings of this study indicate that the mineralo-herbal preparation at this dose and schedule produced no discernible effect on weight of testis, epididymis and accessory glands, spermatogenesis, vasal sperm picture or mating rate in male rats when administered during the period covering one spermatogenic cycle, but caused significant reduction in number of implantations in females mated with these male rats as well as in female rats treated during the postcoital period. CONCLUSIONS: Any adverse effect on fertility/reproductive health following administration over longer periods/at higher doses in humans habituated to continuous use of this preparation cannot be completely ruled out from this limited study. Findings also suggest caution in indiscriminate use of this and other such preparations containing varying amounts of plants/plant products reported to possess contraceptive property and available for other pharmacological indications over-the-counter in most countries.