Advanced Practice Registered Nurse Full Practice Authority, Provider Supply, and Health Outcomes: A Border Analysis.

Due to a growing physician shortage, patients have difficulty accessing primary care. In an effort to expand access and support patient health, many states are reducing barriers for advanced practice registered nurses to provide primary care without physician collaboration. Maryland provides an interesting case study. We leverage Maryland's policy change to explore the effects of full practice authority (FPA), focusing on the number of professionals and health outcomes for patients. Employing a border county comparison between Maryland and Pennsylvania, we estimate the effect of FPA. Our analysis of health outcomes focuses on three county-level health outcomes: poor or fair health, poor mental health days, and preventable hospital stays. We find that FPA is associated with increases in the number of certified nurse midwives by 0.6 per 100,000 residents and nurse practitioners by 22.4 per 100,000 residents. We also find evidence of an association of FPA with reductions in the share of residents who report being in poor or fair health by 2.8 percentage points and poor mental health days per month by 0.354 days per person. Combined, our results provide suggestive evidence that moving to FPA improves access to care and leads to improved health outcomes for Maryland residents. Removing regulatory barriers that prevent certified nurse midwives and nurse practitioners from working to the full extent of their training may increase access to primary care and improve patient outcomes.

Tamoxifen Pharmacovigilance: Implications for Safe Use in the Future.

OBJECTIVE: To survey the status of current tamoxifen pharmacovigilance documentation reflecting tamoxifen use in an academic outpatient multispecialty practice in older adults. This data will help provide information to develop improved pharmacovigilance for a growing cohort of older adult users. The data will be utilized by an interdisciplinary team developing new methods of identifying factors for individualized pharmacovigilance in older adults. DESIGN: Retrospective chart review to gather descriptive and quantitative data on tamoxifen pharmacovigilance. SETTING: Multi-specialty clinic. PATIENTS: Ninety-three patients 60 years of age and older. MAIN OUTCOME MEASURES: Quantitative report of tamoxifen monitoring as well as descriptive analysis of individual cases. RESULTS: We found 19 cases of serious adverse events possibly related to tamoxifen (thrombi, uterine malignancies). There were 15 cases with no documentation of pharmacovigilance. All cases had incomplete pharmacovigilance documented. There were two cases of hypercalcemia. There was one case of tamoxifen discontinuation resulting from muscle pain and with chronic muscle pain complaints while receiving tamoxifen. We observed a correlation in older age or high comorbidity burden patients and adverse events patients. CONCLUSION: Some studies direct the important pharmacovigilance toward prevention of thrombi, uterine malignancies, and hypercalcemia; however, it is not easy to identify recommendations for frequency or focus of monitoring to prevent adverse events for individual older adults based on existing recommendations. The data collected and presented in this study serve to heighten awareness of tamoxifen pharmacovigilance and as a starting point for the application of machine learning techniques and modeling to identify high-risk patients and individualized pharmacovigilance recommendations.

Palbinone from Paeonia suffruticosa protects hepatic cells via up-regulation of heme oxygenase-1.

Paeonia suffruticosa has been traditionally employed for vitalizing blood circulation and alleviating liver and inflammatory diseases. The pathways by which palbinone (PB) isolated from P. suffruticosa mediates heme oxygenase-1 (HO-1) induction were investigated using the specific inhibitors for PI3K and mitogen activated protein kinases pathways. The effect of PB-treatment on Nrf2 translocalization and HO-1-antioxidant response element (ARE) regulation was examined employing Western blot and luciferase assays. PB induced HO-1 expression via the activation of Nrf2 in the hepatic cells, and ARE-dependent genes were stimulated via the PB-mediated Nrf2 activation. PB-mediated HO-1 expression could be involved with PI3K/Akt and ERK1/2 pathways. Our study suggests the mechanism by which PB induces HO-1 expression in the hepatic cells. This might substantiate the traditional applications of P. suffruticosa for the treatment of oxidative stress-related diseases including oxidant and inflammatory-mediated vascular and liver diseases.

Honokiol inhibits vascular vessel formation of mouse embryonic stem cell-derived endothelial cells via the suppression of PECAM and MAPK/mTOR signaling pathway.

Embryonic stem cells, which are characterized by pluripotency and self-renewal, have recently been highlighted in drug discovery. In particular, the potential of ES cells to differentiate into specific-cell types make them an extremely useful tool in the evaluation of the biological activity of test compounds. Honokiol, a major neolignan derived from the bark of Magnolia obovata, has been shown an anti-tumor activity. However, the precise mechanism of action in the anti-tumor activity of honokiol is still poorly understood. Here, we evaluated the antiangiogenic activity of honokiol using mouse ES cell-derived embryoid bodies. mES-derived EBs were formed using hanging drop cultures and vascular formation was induced on gelatincoated plates in EGM-2 medium. The growth inhibition of honokiol was found to be more sensitive in the differentiated EB-derived endothelial cells compared to the undifferentiated EB-derived cells. Honokiol also inhibited the vascular formation of mES cells on 3-D collagen gel and decreased the expression of endothelial biomarkers VEGFR2 and PECAM in the differentiated EB-derived endothelial cells. In addition, honokiol suppressed the MAPK and mTOR signaling pathways in the EB-derived endothelial cells. Therefore, the anti-angiogenic activity of honokiol is associated in part with the suppression of PECAM and MAPK/mTOR pathways in EB-derived endothelial cells.

Xanthine oxidase inhibitory activity of constituents of Cinnamomum cassia twigs.

A methanol extract of the twigs of Cinnamomum cassia was found to inhibit xanthine oxidase. Purification of the methanol extract afforded three new phenolic glycosides, cinnacasolide A-C (11-13), together with 10 known compounds (1-10). The structures of the three new compounds were determined by interpretation of spectroscopic data. Cinnamaldehyde derivatives 1-5 and 7 were significant inhibitors of xanthine oxidase, with IC(50) values ranging from 7.8 to 36.3 µg/mL. The results indicate that the acyl group of these cinnamaldehyde derivatives plays an important role in the inhibition of xanthine oxidase.

Selective cholinesterase inhibition by lanostane triterpenes from fruiting bodies of Ganoderma lucidum.

Two new lanostane triterpenes, named methyl ganoderate A acetonide (1) and n-butyl ganoderate H (2), were isolated from the fruiting bodies of Ganoderma lucidum together with 16 known compounds (3-18). Extensive spectroscopic and chemical studies established the structures of these compounds as methyl 7ß,15α-isopropylidenedioxy-3,11,23-trioxo-5α-lanost-8-en-26-oate (1) and n-butyl 12ß-acetoxy-3ß-hydroxy-7,11,15,23-tetraoxo-5α-lanost-8-en-26-oate (2). Because new compounds exhibiting specific anti-acetylcholinesterase activity are being sought as possible drug candidates for the treatment of Alzheimer's and related neurodegenerative diseases, compounds 1-18 were examined for their inhibitory activities against acetylcholinesterase and butyrylcholinesterase. All of the compounds exhibited moderate acetylcholinesterase-inhibitory activity, with IC(50) values ranging from 9.40 to 31.03µM. In contrast, none of the compounds except lucidadiol (13) and lucidenic acid N (14) exhibited butyrylcholinesterase-inhibitory activity at concentrations up to 200µM. These results indicate that these lanostane triterpenes are preferential inhibitors of acetylcholinesterase and may be suitable drug candidates.

Anti-inflammatory activity of constituents from Glechoma hederacea var. longituba.

Rosmarinic acid, its analogues, and a phenolic compound were obtained from G. hederacea var. longituba. There were two new compounds, methyl isoferuloyl-7-(3,4-dihydroxyphenyl) lactate (1) and benzyl-4'-hydroxy-benzoyl-3'-O-ß-D-glucopyranoside (4), and four known compounds (2, 3, 5 and 6). The structures of these compounds were determined on the basis of spectroscopic methods. Each compound was tested by NF-κB luciferase assay and three rosmarinic acid analogues inhibited NF-κB production and the induction of COX-2 and iNOS mRNA in HepG2 cells.

New sesquiterpene lactones from Glechoma hederacea L. and their cytotoxic effects on human cancer cell lines.

Three new sesquiterpene lactones, 1 α,10 ß-epoxy-4-hydroxy-glechoma-5-en-olide (1), 1 ß,10 α-epoxy-4,8-dihydroxy-glechoma-5-en-olide (2), and 1 ß,10 α;4 α,5 ß-diepoxy-8-methoxy-glechoman-8 α,12-olide (3), were isolated from the whole plant of Glechoma hederacea, together with four known sesquiterpene lactones. The structures of the three new sesquiterpene lactones were determined by spectroscopic evidence. Cytotoxic effects of the isolated compounds were examined against MDA-MB-231 (breast), HCT116 (colon), SW620 (colon), and DU145 (prostate) human cancer cell lines.

Biphenyl and biphenyl ether quinolizidine N-oxide alkaloids from Lagerstroemia indica L.

Four new biphenyl and biphenyl ether quinolizidine N-oxide alkaloids, 5- EPI-dihydrolyfoline N-oxide (1), decamine N-oxide (2), lagerstroemine N-oxide (3), and lagerine N-oxide (4), were isolated from the aerial parts of Lagerstroemia indica, and their structures were established by extensive spectroscopic studies. In addition, the inhibitory effects of isolated compounds on rat lens aldose reductase (RLAR) were examined.

Two new lignans from the roots of Pulsatilla koreana.

Two new lignans, (2 R,3 R)-2 ß-(4''-hydroxy-3''-methoxybenzyl)-3 α-(4'-hydroxy-3'-methoxybenzyl)-γ-butyrolactone 2-O-( ß-D-glucopyranoside) (1) and (1 S,2 R,3 S)-dimethyl-1,2,3,4-tetrahydro-3,6,7-trihydroxy-1-(3',4'-dihydroxyphenyl)naphthalene-2,3-dicarboxylate (2) together with nine known compounds (3-11) were isolated from the ethyl acetate fraction of the roots of Pulsatilla koreana. Their chemical structures were established based on physicochemical and spectroscopic data analyses. All isolates were investigated for their inhibition effects against the classical pathway of the complement system. Among them, compound 6 showed significant inhibitory activity with an IC (50) value of 75.9 µM, compounds 8 and 9 had moderate effects with IC (50) values of 182.2 and 166.5 µM, respectively.

Inhibition of experimental atopic dermatitis by rhubarb (rhizomes of Rheum tanguticum) and 5-lipoxygenase inhibition of its major constituent, emodin.

The antiallergic activity of rhubarb and its constituents, anthraquinones, has been reported previously. For further evaluation of the antiallergic activity, a 70% ethanol extract of the rhizomes of Rheum tanguticum (RTE) was prepared and its inhibitory activity on an animal model of atopic dermatitis (AD) was examined for the first time. Oral administration of RTE (30-300 mg/kg/day) for 5 weeks significantly inhibited hapten-induced dermatitis in NC/Nga mice based on the skin severity score. In addition, treatment with RTE at 100 mg/kg/day also reduced the numbers of white blood cells, neutrophils and eosinophils in the blood, and led to a significant reduction in the IgE concentration in the serum. In rat basophilic leukemia (RBL)-1 cells, RTE inhibited 5-lipoxygenase (5-LOX)-catalysed leukotriene production (IC(50) = 43.6 µg/mL). Among the anthraquinone derivatives isolated, emodin strongly inhibited this parameter (IC(50) = 4.3 µM). Taken together, these findings suggest that rhubarb exerts inhibitory activity against AD, and that the 5-LOX inhibitory activity of its major constituent, emodin, may contribute to this inhibitory action.

Ergosta-7,22-diene-2ß,3α,9α-triol from the fruit bodies of Ganoderma lucidum induces apoptosis in human myelocytic HL-60 cells.

Ganoderma lucidum is known as a medicinal mushroom used in traditional medicine. In our study, the cytotoxic activities of 17 compounds (1-17) isolated from the fruiting bodies of G. lucidum were investigated. Among them, ergosta-7,22-diene-2ß,3α,9α-triol (EGDT) induced apoptosis in HL-60 human premyelocytic leukemia cells. EGDT activated the apoptotic process, including DNA fragmentation and caspase-3 activity. In immunoblotting analysis, treatment with EGDT resulted in the cleavage of procaspase-3 and poly(ADP-ribose) polymerase (PARP) into active forms. In the in vivo study, the administration (i.p.) of EGDT to Lewis lung carcinoma (LLC)-inoculated mice evidenced a significant inhibition of tumor growth. These results indicate that EGDT was one of the apoptotic constituents of G. lucidum, and might be an antitumor agent.

A new flavan-3-ol and the anti-inflammatory effect of flavonoids from the fruit peels of Wisteria floribunda.

A new flavan-3-ol, (+)-afzelechin 5-O-ß-d-glucopyranoside (2), together with 13 known flavonoids (1, 3-14), was isolated from the fruit peels of Wisteria floribunda. Their structures were assigned by detailed interpretation of NMR, MS, and CD spectroscopic data, as well as by comparing with published reports. The in vitro anti-inflammatory activity of the isolated compounds (1-14) was examined. Among them, compounds 3, 6, and 9 produced highest inhibitory effects on tumor necrosis factor alpha (TNF-α)-induced nuclear factor kappa-B activation in HepG2 cells with IC(50) values of 14.1, 16.5, and 11.9 µM, respectively. With the exception of compound 6, the compounds significantly inhibited the accumulation of pro-inflammatory inducible nitric oxide synthase and cyclooxygenase-2 proteins in TNF-α-stimulated HepG2 cells at a concentration as low as 0.1 µM.

The selected flavonol glycoside derived from Sophorae Flos improves glucose uptake and inhibits adipocyte differentiation via activation AMPK in 3T3-L1 cells.

Among nine flavonols (1-9) obtained from Sophorae Flos, we first isolated compounds 4, 5, 8, and 9. These isolates (1-9) were evaluated for the phosphorylation of AMPK and ACC. Administered at 10 µM, 9 possessed high potent activity. Compound 9 displayed a dose-dependent stimulation of glucose uptake in 3T3-L1 cells, and this increase was obviously attenuated by compound C, an AMPK inhibitor. In addition, 9 also phosphorylated AMPK and its downstream substrate ACC in 3T3-L1 cells in a time- and dose-dependent manner. Moreover, we discovered that compound C inhibits 9-stimulated ACC phosphorylation and motivated the 9-inhibited C/EBPα and PPARγ, and FAS gene expression, significantly. These results revealed the role of the AMPK downstream signaling pathway in 9-improved glucose metabolism in 3T3-L1 cells and 9-inhibited adipocyte differentiation. Differentiation was investigated by Oil Red O staining activity after 9 administration (0-20 µM) in 6 days. Compound 9 decreased mean droplet size in a dose-dependent manner. The results revealed that 9 blocked adipogenic conversion in 3T3-L1 cells together with several significant downregulating adipocyte-specific transcription factors, including PPARγ, C/EBPα, and SREBP1. It also reduced FAS gene expression in a dose-dependent manner, which is crucial for adipogenesis in vitro.

Lanostane triterpenes from Ganoderma lucidum suppress the adipogenesis in 3T3-L1 cells through down-regulation of SREBP-1c.

Several lanostane triterpenes [butyl ganoderate A (1), butyl ganoderate B (2), butyl lucidenate N (3), and butyl lucidenate A (4)] bearing a butyl ester side chain from the fruiting bodies of Ganoderma lucidum exhibited considerable inhibitory effects on adipogenesis in 3T3-L1 cells. The inhibitory mechanism of 1 and 3 on adipogenesis in 3T3-L1 cells was investigated; we found that the mRNA and protein expression levels of SREBP-1c were reduced by treatment with 1 and 3 versus the untreated control. Furthermore, compounds 1 and 3 suppressed the mRNA expression levels of FAS and ACC. These results demonstrate that inhibition of adipogenesis in 3T3-L1 cells by treatment with 1 and 3 may be mediated in part through down-regulation of the adipogenic transcription factor SREBP-1c and its target genes, such as FAS and ACC.

The antimicrobial activity of compounds from the leaf and stem of Vitis amurensis against two oral pathogens.

Nine compounds isolated from the leaf and stem of Vitis amurensis Rupr. (Vitaceae) were evaluated for their antimicrobial activity against two oral pathogens, Streptococcus mutans and Streptococcus sanguis, which are associated with caries and periodontal disease, respectively. The results of several antimicrobial tests, including MIC, MBC, and TBAI, showed that three compounds inhibited the growth of the test bacteria at concentrations ranging from 12.5 to 50 microg/mL. Among these compounds, compound 5, trans-epsilon-viniferin, displayed the strongest activity against S. mutans and S. sanguis with MIC values of 25 and 12.5 microg/mL, respectively. This is the first report on the antimicrobial activity of stilbenes and oligostilbenes isolated from the leaf and stem of V. amurensis. Thus, this result suggests that natural antimicrobial compounds derived from V. amurensis may benefit oral health as plaque-control agents for the prevention of dental caries and periodontal disease.

Inhibition of neuraminidase activity by polyphenol compounds isolated from the roots of Glycyrrhiza uralensis.

We isolated 18 polyphenols with neuraminidase inhibitory activity from methanol extracts of the roots of Glycyrrhiza uralensis. These polyphenols consisted of four chalcones (1-4), nine flavonoids (5-13), four coumarins (14-17), and one phenylbenzofuran (18). When we tested the effects of these individual compounds and analogs thereof on neuraminidase activation, we found that isoliquiritigenin (1, IC(50)=9.0 microM) and glycyrol (14, IC(50)=3.1 microM) had strong inhibitory activity. Structure-activity analysis showed that the furan rings of the polyphenols were essential for neuraminidase inhibitory activity, and that this activity was enhanced by the apioside group on the chalcone and flavanone backbone. In addition, the presence of a five-membered ring between C-4 and C-2' in coumestan was critical for neuraminidase inhibition. All neuraminidase inhibitors screened were found to be reversible noncompetitive inhibitors.

Homoisoflavonoid derivatives from the roots of Ophiopogon japonicus and their in vitro anti-inflammation activity.

Three new homoisoflavonoids (1-3) were isolated from the roots of Ophiopogon japonicus (Liliaceae). The structures of new metabolites were determined on the basis of spectroscopic analyses including 2D NMR. The anti-inflammatory activities of new compounds (1-3) were investigated by their effects on the release of the inflammatory chemokine eotaxin, stimulated by IL-4 and the combination of IL-4 and TNF-alpha in BEAS-2B cells, which mimics the in vivo conditions in bronchial allergic asthma.

WITHDRAWN: Anti-proliferative effects of compounds from the fruit peel of Wisteria floribunda on vascular smooth muscle cells.

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Lanostane triterpenes from the fruiting bodies of Ganoderma lucidum and their inhibitory effects on adipocyte differentiation in 3T3-L1 Cells.

Four new lanostane triterpenes, butyl ganoderate A (1), butyl ganoderate B (2), butyl lucidenate N (3), and butyl lucidenate A (4), were isolated from the fruiting bodies of Ganoderma lucidum together with 14 known compounds (5-18). The structures of the new triterpenes were established by extensive spectroscopic studies and chemical evidence. In addition, the inhibitory effect of isolated compounds on adipocyte differentiation in 3T3-L1 cells was examined.