Retaining nurses in a changing health care environment: The role of job embeddedness and self-efficacy.

BACKGROUND: Because nurses are on the front lines of care delivery, they are subject to frequent changes to their work practices. This change-laden environment puts nurses at higher risk for turnover. Given the frequent disruption to the way nurses perform their jobs, change-related self-efficacy (CSE), or confidence that one can handle change, may be vital to their retention. PURPOSE: The purpose of this article is to examine the roles of CSE and job embeddedness in reducing turnover intentions among nurses. Specifically, this article tests a model in which CSE is the intervening mechanism through which job embeddedness influences turnover intentions. METHODS: Drawing on a sample of 207 nurses working in the medical/surgical unit of a major metropolitan hospital in the United States, this study employs OLS regression to test for direct effects of job embeddedness and CSE on turnover intentions and bias-corrected bootstrapping to test for the indirect effects of job embeddedness on turnover intentions through CSE. FINDINGS: Results show that CSE is directly linked to turnover intentions, and the effects of job embeddedness on turnover intentions become fully manifest through CSE. PRACTICE IMPLICATIONS: Improved nurse retention may lead to stable patient care and less disruption in service delivery. Improved retention also benefits health care organizations financially, as costs of replacing a nurse can exceed 100% of the salary for the position. Given the shortage of nurses in some geographic areas, retention remains an important goal.

Endophytic fungi associated with Taxus fuana (West Himalayan Yew) of Pakistan: potential bio-resources for cancer chemopreventive agents.

CONTEXT: Endophytic fungi, being a prolific source of bioactive secondary metabolites, are of great interest for natural product discovery. OBJECTIVE: Isolation and partial characterization of endophytic fungi inhabiting the leaves and woody parts of Taxus fuana Nan Li & R.R. Mill. (Taxaceae) and evaluation of biological activity. MATERIALS AND METHODS: Endophytic fungal isolates were identified by molecular analysis of internal transcribed spacer (ITS) regions of 18S rDNA. Extracts of the endophytic fungi cultured on potato dextrose agar and modified medium were evaluated using cancer chemoprevention bioassays [inhibition of TNF-α-induced NFκB, aromatase and inducible nitric oxide synthase (iNOS); induction of quinone reductase 1 (QR1)] and growth inhibition with MCF-7 cells. RESULTS: Nine of 15 fungal isolates were identified as belonging to Epicoccum, Mucor, Penicillium, Chaetomium, Paraconiothriym, Plectania or Trichoderma. Five of the 15 extracts inhibited NFκB activity (IC50 values ranging between 0.18 and 17 µg/mL) and five inhibited iNOS (IC50 values ranging between 0.32 and 12.9 µg/mL). In the aromatase assay, only two isolates mediated inhibition (IC50 values 12.2 and 10.5 µg/mL). With QR1 induction, three extracts exhibited significant activity (concentrations to double activity values ranging between 0.20 and 5.5 µg/mL), and five extracts inhibited the growth of MCF-7 cells (IC50 values ranging from 0.56 to 17.5 µg/mL). Six active cultures were derived from woody parts of the plant material. CONCLUSION: The endophytic fungi studied are capable of producing pharmacologically active natural compounds. In particular, isolates derived from the wood of Taxus fuana should be prioritized for the isolation and characterization of bioactive constituents.

Preliminary evaluation for cancer chemopreventive and cytotoxic potential of naturally growing ethnobotanically selected plants of Pakistan.

CONTEXT: Natural products are a very productive source of leads for the development of medicines. Six Pakistani plants were chosen for study based on ethnobotanical data. OBJECTIVE: Exploration of important medicinal plants of Pakistan for cancer treatment. MATERIALS AND METHODS: The crude extracts of the six plants and their fractions were tested for inhibition of nuclear factor κB (NFκB), aromatase, and nitric oxide (NO) production in lipopolysaccharide (LPS)-activated murine macrophage RAW 264.7 cells, induction of quinone reductase 1 (QR1), agonism of retinoid X receptor, and growth inhibition with MCF-7, LU-1 and MDA-MB-231 cancer cells. RESULTS: Two samples of Withania coagulans (Stocks) Dunal (Solanaceae) demonstrated inhibition of TNF-α induced activity of NFκB with IC50 values of 2.6 and 4.3 µg/mL, respectively. Two fractions from W. coagulans and Euphorbia wallichii Hook F. (Euphorbiaceae) aerial parts inhibited aromatase with IC50 values of 17.0 and 17.7 µg/mL, respectively. A total of 13 samples (five from E. wallichii, one from Acer oblongifolium Hort. ex Dippel (Aceraceae), one from Aster thomsonii C. B. Clarke (Asteraceae) and six from W. coagulans aerial parts with fruits) inhibited NO production with IC50 values ranging from 1.3 to 15.6 µg/mL. Fourteen samples demonstrated induction of QR1 with CD ranging from 1.0 to 20.6 µg/mL, and a total of eight extracts and fractions inhibited the proliferation of cancer cells in culture with IC50 values ranging from 1.2 to 7.8 µg/mL. DISCUSSION AND CONCLUSION: Selected plants can be a valuable source of chemopreventive and anticancer products. W. coagulans aerial parts showed the strongest activity.

Neoflavonoids and tetrahydroquinolones as possible cancer chemopreventive agents.

Several lactone- and lactam-based neoflavonoids and tetrahydroquinolones were synthesized and evaluated for cancer chemopreventive studies using cell and molecular target-based in vitro bioassays, namely NFκB, aromatase, and quinone reductase 1. These analogs blocked TNF-α-induced NFκB activation in a dose-dependent manner with IC50 values in the range of 0.11-3.2 µM. In addition, compound 8 inhibited aromatase activity with an IC50 value of 12.12 µM, and compound 10 affected quinone reductase 1 induction (IR, 3.6; CD, 19.57 µM). Neoflavonoids 8 and 10 exhibiting good results can further be optimized for improved therapeutic profiles. However, investigations into the actions of neoflavonoids and tetrahydroquinolones, especially those related to the NFκB signaling pathway, aromatase inhibition, induction of quinone reductase 1 expression, and in vivo studies could provide new insights into the cancer chemopreventive ability of these molecules.

Suppression of tumor necrosis factor-α-induced nuclear factor κB activation and aromatase activity by capsaicin and its analog capsazepine.

Target-specific drugs, including natural products, offer promise for the amelioration of cancer and other human ailments. Capsaicin, the pungent ingredient present in chilies (Capsicum annuum L.), and capsazepine, a synthetic analog of capsaicin (collectively referred to as vanilloids), are known to possess a variety of pharmacological and physiological properties. In our continuous effort to discover and characterize cancer chemopreventive agents from natural products, we investigated the effect of vanilloids on nuclear factor κ-light-chain-enhancer of activated B cells (NFκB) activation using stably transfected 293/NFκB-Luc human embryonic kidney cells induced by treatment with tumor necrosis factor-α (TNFα) and on aromatase activity. Capsaicin and capsazepine blocked TNFα-induced NFκB activation in a dose-dependent manner with 50% inhibitory concentration (IC(50)) values of 0.68 and 4.2 µM, respectively. No significant cytotoxicity was observed at the highest concentrations tested (53.1 µM for capsazepine and 65.5 µM for capsaicin). In addition, these vanilloids inhibited aromatase activity with IC(50) values of 13.6 and 8.8 µM, respectively. Computer-aided molecular docking studies showed docking scores indicative of good binding affinity of vanilloids with aromatase and NFκB. The highly conserved residues for capsaicin and capsazepine binding with NFκB p50 were Ser299 and Ile278 (H-bond 2.81Å) and with NFκB p100 were Ser6, Arg82, Val86, Arg90 (H-bond 2.89Å), Gly4, and Ser2 (H-bond 2.81Å). The amino acids Trp224, Arg435, and Val373 (H-bond 2.80Å) were found to be important for the binding of capsaicin and capsazepine with aromatase. Based on these findings, aromatase and NFκB are suggested as valid targets for these compounds; additional investigation of chemopreventive or chemotherapeutic potential is required.

Resveratrol derivatives as promising chemopreventive agents with improved potency and selectivity.

SCOPE: Despite scores of investigations, the actual impact of resveratrol (3,5,4'-trihydroxy-trans-stilbene) on human health, as a dietary component or supplement, remains moot. This is due to many factors, such as relatively low potency, pleiotropic mechanisms, and rapid metabolism. Nonetheless, as a promiscuous molecule that interacts with numerous targets, resveratrol can be viewed as a scaffold for designing structural relatives potentially capable of mediating more intense responses with greater mechanistic stringency. METHODS AND RESULTS: We currently report the synthesis and biological evaluation of 92 stilbene analogs. The compounds were tested with in vitro assays for activation of quinone reductase 1, inhibition of quinone reductase 2, nitric oxide production, aromatase, NFκB, 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ornithine decarboxylase, or cyclooxygenase-1 and -2, quenching of 2,2-diphenyl-1-picrylhydrazyl free radical, interaction with estrogen receptors, and as antiproliferative agents. Several compounds were found to mediate responses with much greater potency than resveratrol; some mediated pleiotropic responses, as is the case with the parent molecule, but others were highly specific or totally inactive. When administered to rats, higher serum concentrations and greater stability was demonstrated with prototype lead molecules. CONCLUSION: Owing to structural simplicity, facile syntheses are available for large-scale production. These data support the promise of more advanced development of novel resveratrol derivatives as drug entities.

Bioactive compounds from the fern Lepisorus contortus.

Phytochemical investigation of the whole plant of Lepisorus contortus (Christ) Ching led to the isolation of five new phenylethanoid glycosides (1-5), each containing a caffeoyl group, a new flavonoid glycoside (10), and 14 known compounds (6-9 and 11-15, syringic acid, vanillic acid, phloretic acid, diplopterol, and ß-sitosterol). This is the first report of phenylethanoid glycosides from the family Polypodiaceae. Compounds 1-15 were evaluated for their cancer chemopreventive potential based on their ability to inhibit tumor necrosis factor alpha (TNF-α)-induced NF-κB activity, nitric oxide (NO) production, and aromatase, quinone reductase 2 (QR-2), and COX-1/-2 activities. Quercetin-3-O-ß-d-glucoside (15) demonstrated inhibition against QR2 with an IC(50) value of 3.84 µM, which confirmed kaempferol/quercetin glycosides as the active compounds to inhibit QR2. The compound also demonstrated NF-κB activity with an IC(50) value of 33.6 µM. In addition, compounds 1, 2, 4, and 6 showed aromatase activity with IC(50) values of 30.7, 32.3, 26.8, and 35.3 µM, respectively.

Fijiolides A and B, inhibitors of TNF-alpha-induced NFkappaB activation, from a marine-derived sediment bacterium of the genus Nocardiopsis.

Fijiolide A, a potent inhibitor of TNF-alpha-induced NFkappaB activation, along with fijiolide B, were isolated from a marine-derived bacterium of the genus Nocardiopsis. The planar structures of fijiolides A (1) and B (2) were elucidated by interpretation of 2D NMR spectroscopic data, while the absolute configurations of these compounds were defined by interpretation of circular dichroism and 2D NMR data combined with application of the advanced Mosher's method. Fijiolides A and B are related to several recently isolated chloroaromatic compounds, which appear to be the Bergman cyclization products of enediyne precursors. Fijiolide A reduced TNF-alpha-induced NFkappaB activation by 70.3%, with an IC(50) value of 0.57 micro-M. Fijiolide B demonstrated less inhibition, only 46.5%, without dose dependence. The same pattern was also observed with quinone reductase (QR) activity: fijiolide A was found to induce quinone reductase-1 (QR1) with an induction ratio of 3.5 at a concentration of 20 microg/mL (28.4 microM). The concentration required to double the activity was 1.8 microM. Fijiolide B did not affect QR1 activity, indicating the importance of the nitrogen substitution pattern for biological activity. On the basis of these data, fijiolide A is viewed as a promising lead for more advanced anticancer testing.

Cancer chemopreventive activity and metabolism of isoliquiritigenin, a compound found in licorice.

Isoliquiritigenin (2',4',4-trihydroxychalcone; ILG), a chalcone found in licorice root and many other plants, has shown potential chemopreventive activity through induction of phase II enzymes such as quinone reductase-1 in murine hepatoma cells. In this study, the in vivo metabolism of ILG was investigated in rats. In addition, ILG glucuronides and ILG-glutathione adducts were observed in human hepatocytes and in livers from rats treated with ILG. ILG glucuronides were detected in both plasma and rat liver tissues. In addition, in a full-term cancer chemoprevention study conducted with 7,12-dimethylbenz(a)anthracene-treated female Sprague-Dawley rats, dietary administration of ILG slightly increased tumor latency but had a negative effect on the incidence of mammary tumors starting at approximately 65 days after 7,12-dimethylbenz(a)anthracene administration. Further, no significant induction of phase II enzymes was found in mammary glands, which is consistent with the low level of ILG observed in these tissues. However, ILG significantly induced quinone reductase-1 activity in the colon, and glutathione as well as glutathione S-transferase in the liver. Analysis of mRNA expression in tissues of rats treated with ILG supported these findings. These results suggest that ILG should be tested for chemopreventive efficacy in nonmammary models of cancer.

Isolation and evaluation of kaempferol glycosides from the fern Neocheiropteris palmatopedata.

Kaempferol glycosides, named palmatosides A (1), B (2) and C (3), together with three known kaempferol glycosides, multiflorins A (4) and B (5), and afzelin (6), were isolated from the roots of the fern Neocheiropteris palmatopedata. Palmatosides A (1) and B (2) each possessed an unusual sugar moiety containing a 4,4-dimethyl-3-oxo-butoxy substituent group. The isolated compounds were evaluated for their cancer chemopreventive potential based on their ability to inhibit tumor necrosis factor alpha (TNF-alpha)-induced NF-kappaB activity, nitric oxide (NO) production, aromatase, quinone reductase 2 (QR2) and COX-1/-2 activities. Palmatosides B (2) and C (3) inhibited TNF-alpha-induced NF-kappaB activity with IC(50) values of 15.7 and 24.1 microM, respectively; multiflorin A (4) inhibited aromatase enzyme with an IC(50) value of 15.5 microM; afzelin (6) showed 68.3% inhibition against QR2 at a concentration of 11.5 microg/ml; palmatoside A (1) showed 52% inhibition against COX-1 enzyme at a concentration of 10 microg/ml; and multiflorin B (5) showed 52% inhibition against nitric oxide production at a concentration of 20 microg/ml. In addition, compounds 3-6 were shown to bind QR2 enzyme using LC-MS ultrafiltration binding assay.