Mindful Coping Power: Comparative Effects on Children's Reactive Aggression and Self-Regulation.

Coping Power (CP) is an evidence-based preventive intervention for youth with disruptive behavior problems. This study examined whether Mindful Coping Power (MCP), a novel adaptation which integrates mindfulness into CP, enhances program effects on children's reactive aggression and self-regulation. A pilot randomized design was utilized to estimate the effect sizes for MCP versus CP in a sample of 102 child participants (fifth grade students, predominantly low-middle income, 87% Black). MCP produced significantly greater improvement in children's self-reported dysregulation (emotional, behavioral, cognitive) than CP, including children's perceived anger modulation. Small to moderate effects favoring MCP were also observed for improvements in child-reported inhibitory control and breath awareness and parent-reported child attentional capacity and social skills. MCP did not yield a differential effect on teacher-rated reactive aggression. CP produced a stronger effect than MCP on parent-reported externalizing behavior problems. Although MCP did not enhance program effects on children's reactive aggression as expected, it did have enhancing effects on children's internal, embodied experiences (self-regulation, anger modulation, breath awareness). Future studies are needed to compare MCP and CP in a large scale, controlled efficacy trial and to examine whether MCP-produced improvements in children's internal experiences lead to improvements in their observable behavior over time.

Nutrition Support Therapies on the Medication Administration Record: Impacts on Staff Perception of Nutrition Care.

BACKGROUND: It has been reported that many hospitals in the United States have fragmented and ineffective ordering, administration, documentation, and evaluation/monitoring of nutrition therapies. This paper reports on a project to investigate if perceived hospital staff awareness and documentation of nutrition support therapies (NSTs) improves by including them as part of the medication administration record (MAR). METHODS: Surveys were conducted with nursing staff, physicians, and dietitians before and after adding NSTs to the MAR to evaluate the perceived impact on the outcome of interest. The outcomes of interest include nurses' perception of ease of finding information, awareness of an order, and ability to assess administration and documentation and dietitian, nurse, and physician staff perceptions of impact of intervention on aspects of the nutrition care process. RESULTS: After adding NST to the MAR, nursing staff perceived improvement in knowing that their patient had an oral nutritional supplement (ONS) order (P = .01), when and how much product was last administered (P = .01), and documentation of the type of product consumed (P = .01) and volume of product consumed (P = .01). The majority of dietitian and nurses surveyed reported perceived improvement in placing and finding ONS orders, in administration of ONS, in ability to evaluate patient nutrition status, and in ONS intake and a positive impact on clinical practice. CONCLUSION: Inclusion of NST in the MAR presents an innovative solution to enhance staff awareness of ordered therapies and perception of improved documentation of nutrition interventions for hospitalized patients.

Effect of Broccoli Sprouts and Live Attenuated Influenza Virus on Peripheral Blood Natural Killer Cells: A Randomized, Double-Blind Study.

UNLABELLED: Enhancing antiviral host defense responses through nutritional supplementation would be an attractive strategy in the fight against influenza. Using inoculation with live attenuated influenza virus (LAIV) as an infection model, we have recently shown that ingestion of sulforaphane-containing broccoli sprout homogenates (BSH) reduces markers of viral load in the nose. To investigate the systemic effects of short-term BSH supplementation in the context of LAIV-inoculation, we examined peripheral blood immune cell populations in non-smoking subjects from this study, with a particular focus on NK cells. We carried out a randomized, double-blinded, placebo-controlled study measuring the effects of BSH (N = 13) or placebo (alfalfa sprout homogenate, ASH; N = 16) on peripheral blood mononuclear cell responses to a standard nasal vaccine dose of LAIV in healthy volunteers. Blood was drawn prior to (day-1) and post (day2, day21) LAIV inoculation and analyzed for neutrophils, monocytes, macrophages, T cells, NKT cells, and NK cells. In addition, NK cells were enriched, stimulated, and assessed for surface markers, intracellular markers, and cytotoxic potential by flow cytometry. Overall, LAIV significantly reduced NKT (day2 and day21) and T cell (day2) populations. LAIV decreased NK cell CD56 and CD158b expression, while significantly increasing CD16 expression and cytotoxic potential (on day2). BSH supplementation further increased LAIV-induced granzyme B production (day2) in NK cells compared to ASH and in the BSH group granzyme B levels appeared to be negatively associated with influenza RNA levels in nasal lavage fluid cells. We conclude that nasal influenza infection may induce complex changes in peripheral blood NK cell activation, and that BSH increases virus-induced peripheral blood NK cell granzyme B production, an effect that may be important for enhanced antiviral defense responses. TRIAL REGISTRATION: ClinicalTrials.gov NCT01269723.

Effect of broccoli sprouts on nasal response to live attenuated influenza virus in smokers: a randomized, double-blind study.

BACKGROUND: Smokers have increased susceptibility and altered innate host defense responses to influenza virus infection. Broccoli sprouts are a source of the Nrf2 activating agentsulforaphane, and short term ingestion of broccoli sprout homogenates (BSH) has been shown to reduce nasal inflammatory responses to oxidant pollutants. OBJECTIVES: Assess the effects of BSH on nasal cytokines, virus replication, and Nrf2-dependent enzyme expression in smokers and nonsmokers. METHODS: We conducted a randomized, double-blind, placebo-controlled trial comparing the effects of BSH on serially sampled nasal lavage fluid (NLF) cytokines, viral sequence quantity, and Nrf2-dependent enzyme expression in NLF cells and biopsied epithelium. Healthy young adult smokers and nonsmokers ingested BSH or placebo (alfalfa sprout homogenate) for 4 days, designated Days -1, 0, 1, 2. On Day 0 they received standard vaccine dose of live attenuated influenza virus (LAIV) intranasally. Nasal lavage fluids and nasal biopsies were collected serially to assess response to LAIV. RESULTS: In area under curve analyses, post-LAIV IL-6 responses (P = 0.03) and influenza sequences (P = 0.01) were significantly reduced in NLF from BSH-treated smokers, while NAD(P)H: quinoneoxidoreductasein NLF cells was significantly increased. In nonsmokers, a similar trend for reduction in virus quantity with BSH did not reach statistical significance. CONCLUSIONS: In smokers, short term ingestion of broccoli sprout homogenates appears to significantly reduce some virus-induced markers of inflammation, as well as reducing virus quantity. Nutritional antioxidant interventions have promise as a safe, low-cost strategy for reducing influenza risk among smokers and other at risk populations. TRIAL REGISTRATION: ClinicalTrials.gov NCT01269723.

A dihydroflavonol glucoside from Commiphora africana that mediates DNA strand scission.

A crude CH(2)Cl(2)-MeOH extract prepared from Commiphora africana was found to mediate Cu(2+)-dependent relaxation of supercoiled plasmid DNA. Bioassay-guided fractionation of this extract was carried out and was monitored by the use of an in vitro DNA strand scission assay. The dihydroflavonol glucoside phellamurin (1) was identified as the active principle responsible for the DNA cleavage activity of the crude extract.

DNA topoisomerase I inhibitors from Rinorea anguifera.

An organic extract prepared from Rinorea anguifera was investigated in order to identify the natural principle(s) responsible for stabilization of a topoisomerase I-DNA covalent binary complex. Bioassay-guided fractionation resulted in the isolation of mauritianin and (+)-syringaresinol as new topoisomerase I inhibitors, and also of the known inhibitor camptothecin.

DNA polymerase beta lyase inhibitors from Maytenus putterlickoides.

During a survey of plant secondary metabolites for DNA polymerase beta lyase inhibitors, we found that a crude methyl ethyl ketone extract prepared from Maytenus putterlickoides showed strong inhibition of the lyase activity of DNA polymerase beta in an in vitro assay. Bioassay-guided fractionation of the extract, using an in vitro assay, resulted in the discovery of a new active principle, 30-(4'-hydroxybenzoyloxy)-11alpha-hydroxylupane-20(29)-en-3-one (1), as well as a known compound, (-)-epicatechin (2). Compounds 1 and 2 exhibited DNA polymerase beta lyase inhibitory activity with IC50 values of 62.8 and 18.5 microM, respectively. Compound 2 was capable of potentiating the action of the monofunctional methylating agent methyl methanesulfonate in cultured human cancer cells, consistent with the possible utility of inhibitors of this type in vivo.

A coumarin from Mallotus resinosus that mediates DNA cleavage.

A crude extract prepared from roots of Mallotus resinosus exhibited significant Cu(2+)-dependent DNA strand scission activity and was thus selected for bioassay-guided fractionation. Scopoletin (1), a simple coumarin, was identified as the active principle responsible for DNA cleavage activity of the crude extract. The DNA strand scission activity of 1, as well as that of three structural analogues, is reported.

Plant sterols as selective DNA polymerase beta lyase inhibitors and potentiators of bleomycin cytotoxicity.

In a survey of crude plant extracts for DNA polymerase beta lyase inhibitors, the hexanes extracts of Cladogynus orientalis, Hymenache donacifolia, and Heteropsis integerrima, and the methyl ethyl ketone extract of Acacia pilispina were found to exhibit good inhibition of the dRP lyase activity of DNA polymerase beta. Bioassay-guided fractionation of these extracts led to the isolation of three DNA polymerase beta lyase inhibitory phytosterols, namely stigmasterol (1) and beta-sitosterol (2), isolated from the hexanes extracts, and beta-sitosterol-beta-d-glucoside (3), isolated from the methyl ethyl ketone extract. Compounds 1-3 inhibited the DNA polymerase beta lyase activity with IC(50) values of 43.6, 43.3, and 72.4 microM, respectively. Compounds 1 and 2 were found capable of potentiating the action of bleomycin in cultured human tumor cells, consistent with the possibility that lyase inhibitors may find utility in vivo.

A DNA-damaging oxoaporphine alkaloid from Piper caninum.

Bioassay-guided fractionation of an active organic extract of Piper caninum, using a sensitive yeast assay to monitor putative double-strand DNA-damaging activity, resulted in the isolation of the 4,5-dioxoaporphine alkaloid cepharadione A (1). Compound 1 exhibited potent inhibitory activity in a yeast cytotoxicity assay with IC(50) values of 50.2 nM toward RS321NpRAD52 grown on glucose versus 293 nM toward the same yeast strain grown on galactose.

New neolignans that inhibit DNA polymerase beta lyase.

Bioassay-directed fractionation of a methyl ethyl ketone extract of the roots of Endlicheria aff. resulted in the isolation of four new neolignans (1-4) and eight known compounds, namely, canellin A (5), canellin C (6), 3'-methoxyguianin (7), (7S,8R,1'S,5'S,6'R)-Delta(2',8')-3',6'-dihydroxy-5'-methoxy-3,4-methylenedioxy-4'-oxo-8.1',7.5'-neolignan (8), armenin-B (9), dillapiole (10), 1-allyl-2,6-dimethoxy-3,4-methylenedioxybenzene (11), and omega-hydroxyisodillapiole (12). The structures of the new compounds (1-4) were established as (7S,8R,1'S,5'S,6'R)-Delta(2',8')-5',6'-dihydroxy-3'-methoxy-3,4-methylenedioxy-4'-oxo-8.1',7.5'-neolignan, (7S,8R,1'S,5'S,6'R)-Delta(2',8')-3',5',6'-trihydroxy-3,4-methylenedioxy-4'-oxo-8.1',7.5'-neolignan, 2,4-dimethoxy-5,6-methylenedioxy-1-(2-propenyl)benzene, and 2,6-dimethoxy-3,4-methylenedioxycinnamyl alcohol, respectively, on the basis of spectroscopic interpretation.

Phenolic acid amides: a new type of DNA strand scission agent from Piper caninum.

In a survey of the active components of crude plant extracts for their ability to cleave DNA, a crude extract prepared from Piper caninum was found to induce the relaxation of supercoiled pBR322 plasmid DNA in the presence of Cu(2+). Bioassay-guided fractionation was carried out on this extract, guided by an in vitro DNA strand scission assay. Three active principles were isolated and identified as N-cis-feruloyl tyramine (1),N-trans-feruloyl tyramine (2), and 1-cinnamoylpyrrolidine (3). Compounds 1-3 represent a structurally new type of DNA strand scission agent.

A new ursane triterpene from Monochaetum vulcanicum that inhibits DNA polymerase beta lyase.

Bioassay-directed fractionation of a butanone extract of Monochaetum vulcanicum resulted in the isolation of a new triterpene (1) and four known compounds, ursolic acid (2), 2alpha-hydroxyursolic acid (3), 3-(p-coumaroyl)ursolic acid (4), and beta-sitosteryl-beta-d-galactoside (5). The structure of the new compound 1 was established as 3beta-acetoxy-2alpha-hydroxyurs-12-en-28-oic acid on the basis of extensive 1D and 2D NMR spectroscopic interpretation and chemical derivatization. Compounds 1-3 and 5 exhibited polymerase beta lyase activity.

A new acylated oleanane triterpenoid from Couepia polyandra that inhibits the lyase activity of DNA polymerase beta.

Bioassay-directed fractionation of a n-hexane extract of Couepia polyandra using an assay to detect inhibitors of the lyase activity of DNA polymerase beta resulted in the isolation of the new triterpene 3beta,16beta,23-triacetoxyolean-12-en-28-oic acid (1) and four known compounds, oleanolic acid, betulinic acid, stigmasterol, and beta-sitosterol. The structure of the new compound was established on the basis of extensive 1D and 2D NMR spectroscopic interpretation. All five compounds inhibited DNA polymerase beta lyase activity.

Luotonin A. A naturally occurring human DNA topoisomerase I poison.

Luotonin A is a pyrroloquinazolinoquinoline alkaloid isolated from the Chinese herbal medicinal plant Peganum nigellastrum. Although previously shown to exhibit cytotoxicity against the murine leukemia P-388 cell line, the mechanism of action of luotonin A is unknown. Presently, we demonstrate that luotonin A stabilizes the human DNA topoisomerase I-DNA covalent binary complex, affording the same pattern of cleavage as the structurally related topoisomerase I inhibitor camptothecin. Luotonin A also mediated topoisomerase I-dependent cytotoxicity toward Saccharyomyces cerevisiae lacking yeast topoisomerase I, but harboring a plasmid having the human topoisomerase I gene under the control of a galactose promoter. This finding identifies a putative biochemical locus for the cytotoxic action of luotonin A and has important implications for the mechanism of action of camptothecin and the design of camptothecin analogues.

DNA damaging activity of ellagic acid derivatives.

A strain of yeast rendered repair deficient by the conditional expression of the RAD52 locus was used to search for natural products capable of damaging DNA. Four ellagic acid derivatives, namely 3,3'-dimethyl-4'-O-beta-D-glucopyranosyl ellagic acid (1), 3,3',4-trimethyl-4'-O-beta-D-glucopyranosyl ellagic acid (2), 3'-methyl-3,4-O,O-methylidene ellagic acid (3) and 3'-methyl-3,4-O,O-methylidene-4'-O-beta-D-glucopyranosyl ellagic acid (4), were identified by this assay as DNA damaging natural principles from several plants, including Alangium javanicum, Anisophyllea apetala, Crypteronia paniculata, Mouririi sp. and Scholtzia parviflora. Although none of the isolated principles mediated frank strand scission of DNA in vitro, all of them potently inhibited the growth of yeast in the absence of expression of RAD52.

DNA-damaging agents from Crypteronia paniculata.

A survey of crude plant extracts using a new yeast strain designed to identify DNA-damaging agents resulted in the identification of an extract prepared from Crypteronia paniculata. Bioassay-guided fractionation resulted in the isolation of three active compounds. Two of these were ellagic acid derivatives, namely, 3,3'-di-O-methylellagic acid 4'-O-beta-d-xylopyranoside (1) and 3'-O-methyl-3,4-methylenedioxyellagic acid 4'-O-beta-d-glucopyranoside (2). The third was identified as kaempferol-3-O-alpha-l-rhamnoside (3). The three principles exhibited strong, selective cytotoxity toward the RAD52 repair-deficient yeast strain.