Effect of coenzyme Q10 supplementation on heart failure: a meta-analysis123

PubMed Central

Thompson-Paul, Angela M; Bazzano, Lydia A

2013-01-01

Background: Coenzyme Q10 (CoQ10; also called ubiquinone) is an antioxidant that has been postulated to improve functional status in congestive heart failure (CHF). Several randomized controlled trials have examined the effects of CoQ10 on CHF with inconclusive results. Objective: The objective of this meta-analysis was to evaluate the impact of CoQ10 supplementation on the ejection fraction (EF) and New York Heart Association (NYHA) functional classification in patients with CHF. Design: A systematic review of the literature was conducted by using databases including MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and manual examination of references from selected studies. Studies included were randomized controlled trials of CoQ10 supplementation that reported the EF or NYHA functional class as a primary outcome. Information on participant characteristics, trial design and duration, treatment, dose, control, EF, and NYHA classification were extracted by using a standardized protocol. Results: Supplementation with CoQ10 resulted in a pooled mean net change of 3.67% (95% CI: 1.60%, 5.74%) in the EF and −0.30 (95% CI: −0.66, 0.06) in the NYHA functional class. Subgroup analyses showed significant improvement in EF for crossover trials, trials with treatment duration ≤12 wk in length, studies published before 1994, and studies with a dose ≤100 mg CoQ10/d and in patients with less severe CHF. These subgroup analyses should be interpreted cautiously because of the small number of studies and patients included in each subgroup. Conclusions: Pooled analyses of available randomized controlled trials suggest that CoQ10 may improve the EF in patients with CHF. Additional well-designed studies that include more diverse populations are needed. PMID:23221577

The Nitrate-nitrite-NO pathway and its implications for Heart Failure and Preserved Ejection Fraction

PubMed Central

Chirinos, Julio A.; Zamani, Payman

2016-01-01

The pathogenesis of exercise intolerance in patients with heart failure and preserved ejection fraction (HFpEF) is likely multifactorial. In addition to cardiac abnormalities (diastolic dysfunction, abnormal contractile reserve, chronotropic incompetence), several peripheral abnormalities are likely to be involved. These include abnormal pulsatile hemodynamics, abnormal arterial vasodilatory responses to exercise, and abnormal peripheral O2 delivery, extraction and utilization. The nitrate-nitrite-NO pathway is emerging as a potential target to modify key physiologic abnormalities, including late systolic LV load from arterial wave reflections (which has deleterious short- and long-term consequences for the LV), arterial vasodilatory reserve, muscle O2 delivery, and skeletal muscle mitochondrial function. In a recently completed randomized trial, the administration of a single dose of exogenous inorganic nitrate has been shown exert various salutary arterial hemodynamic effects, ultimately leading to enhanced aerobic capacity in patients with HFpEF. These effects have the potential for both immediate improvements in exercise tolerance and for long-term “disease-modifying” effects. In this review, we provide an overview of key mechanistic contributors to exercise intolerance in HFpEF, and of the potential therapeutic role of drugs that target the nitrate-nitrite-NO pathway. PMID:26792295

Alignment of the hydrogen molecule under intense laser fields

DOE PAGES

Lopez, Gary V.; Fournier, Martin; Jankunas, Justin; ...

2017-06-01

Alignment, dissociation and ionization of H 2 molecules in the ground or the electronically excited E,F state of the H 2 molecule are studied and contrasted using the Velocity Mapping Imaging (VMI) technique. Photoelectron images from nonresonant 7-, 8- and 9-photon radiation ionization of H 2 show that the intense laser fields create ponderomotive shifts in the potential energy surfaces and distort the velocity of the emitted electrons that are produced from ionization. Photofragment images of H+ due to the dissociation mechanism that follows the 2-photon excitation into the (E,F; v = 0, J = 0, 1) electronic state showmore » a strong dependence on laser intensity, which is attributed to the high polarizability of the H 2 (E,F) state. For transitions from the J = 0 state, particularly, we observe marked structure in the angular distribution, which we explain as the interference between the prepared J = 0 and Stark-mixed J = 2 rovibrational states of H 2, as the laser intensity increases. Quantification of these effects allows us to extract the molecular polarizability of the H 2 (E,F) state, and yields a value of 103 ± 37 A.U.« less

Alignment of the hydrogen molecule under intense laser fields

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lopez, Gary V.; Fournier, Martin; Jankunas, Justin

Alignment, dissociation and ionization of H 2 molecules in the ground or the electronically excited E,F state of the H 2 molecule are studied and contrasted using the Velocity Mapping Imaging (VMI) technique. Photoelectron images from nonresonant 7-, 8- and 9-photon radiation ionization of H 2 show that the intense laser fields create ponderomotive shifts in the potential energy surfaces and distort the velocity of the emitted electrons that are produced from ionization. Photofragment images of H+ due to the dissociation mechanism that follows the 2-photon excitation into the (E,F; v = 0, J = 0, 1) electronic state showmore » a strong dependence on laser intensity, which is attributed to the high polarizability of the H 2 (E,F) state. For transitions from the J = 0 state, particularly, we observe marked structure in the angular distribution, which we explain as the interference between the prepared J = 0 and Stark-mixed J = 2 rovibrational states of H 2, as the laser intensity increases. Quantification of these effects allows us to extract the molecular polarizability of the H 2 (E,F) state, and yields a value of 103 ± 37 A.U.« less

Effect of the components extracted from the needles of Taxus baccata on protein biosynthesis in a cell-free rat liver system.

PubMed

Sredzińska, K; Gajko, A; Gałasiński, W; Gindzieński, A

1999-01-01

Various species of Taxus contain taxanes that promote polymerization and stabilization of microtubules. They have been reported as antineoplastic compounds with highly effective chemiotherapeutic application. A decrease in incorporation of the radiolabelled precursors into DNA, RNA and proteins in vivo has been reported too. The preliminary results have shown that also the other compounds present in the aqueous extract from Taxus baccata needles, participate in the inhibition of the protein biosynthesis. The binding site of eEF-2 on the ribosome seems to be the target of this inhibition process.

The effects of EF-Ts and bismuth on EF-Tu in Helicobacter pylori: implications for an elegant timing for the introduction of EF-Ts in the elongation and EF-Tu as a potential drug target.

PubMed

Wang, Dongxian; Luo, Benping; Shan, Weiran; Hao, Mingcong; Sun, Xuesong; Ge, Ruiguang

2013-06-01

Helicobacter pylori is a common human pathogen responsible for various gastric diseases. Bismuth can effectively inhibit the growth of this bacterium and is commonly recommended for the treatment of the related diseases. Translation elongation factors EF-Tu and EF-Ts are two important components of the protein translation system. EF-Ts has inhibitory effects on the GTPase activity of EF-Tu and enhances GDP release, a hint that careful timing for the introduction of EF-Ts in the elongation should be accomplished to prevent the complete inhibition of the elongation process. Bismuth inhibits the chaperone activity of EF-Tu, and has opposite effects on the elongation activity: inhibitory effects on the intrinsic GTPase activity and stimulation of GDP release. The present work deepens our understanding of the bacterial elongation process as mediated by EF-Tu and EF-Ts and extends our knowledge about the inhibitory effects of bismuth-based drugs against Helicobacter pylori.

Interaction of plant chimeric calcium/calmodulin-dependent protein kinase with a homolog of eukaryotic elongation factor-1alpha

NASA Technical Reports Server (NTRS)

Wang, W.; Poovaiah, B. W.

1999-01-01

A chimeric Ca2+/calmodulin-dependent protein kinase (CCaMK) was previously cloned and characterized in this laboratory. To investigate the biological functions of CCaMK, the yeast two-hybrid system was used to isolate genes encoding proteins that interact with CCaMK. One of the cDNA clones obtained from the screening (LlEF-1alpha1) has high similarity with the eukaryotic elongation factor-1alpha (EF-1alpha). CCaMK phosphorylated LlEF-1alpha1 in a Ca2+/calmodulin-dependent manner. The phosphorylation site for CCaMK (Thr-257) was identified by site-directed mutagenesis. Interestingly, Thr-257 is located in the putative tRNA-binding region of LlEF-1alpha1. An isoform of Ca2+-dependent protein kinase (CDPK) phosphorylated multiple sites of LlEF-1alpha1 in a Ca2+-dependent but calmodulin-independent manner. Unlike CDPK, CCaMK phosphorylated only one site, and this site is different from CDPK phosphorylation sites. This suggests that the phosphorylation of EF-1alpha by these two kinases may have different functional significance. Although the phosphorylation of LlEF-1alpha1 by CCaMK is Ca2+/calmodulin-dependent, in vitro binding assays revealed that CCaMK binds to LlEF-1alpha1 in a Ca2+-independent manner. This was further substantiated by coimmunoprecipitation of CCaMK and EF-1alpha using the protein extract from lily anthers. Dissociation of CCaMK from EF-1alpha by Ca2+ and phosphorylation of EF-1alpha by CCaMK in a Ca2+/calmodulin-dependent manner suggests that these interactions may play a role in regulating the biological functions of EF-1alpha.

Phytochemical and biological study of callus cultures of Tulbaghia violacea Harv. Cultivated in Egypt.

PubMed

Eid, Hanaa H; Metwally, Ghada F

2017-08-01

As in vitro plant cultures are used extensively to produce bioactive metabolites, our goal was to establish calli from Tulbaghia violacea Harv. flowers and assess the tissue phytochemically and biologically. Murashige & Skoog medium(MS) + 22.6 μM 2,4-dichlorophenoxyacetic acid +2.2 μM benzylaminopurine induced callus from flowers. Gas chromatography/mass spectrometry(GC/MS) analyses of n-hexane extracts of calli(HC) and flowers(HF) revealed 33 and 32 components(92.6 and 98.5%, respectively). Hydrocarbons were predominant in HC (55.0%), whereas a higher percentage of oxygenated compounds was found in HF(74.6%). Trans(E)-anethole(39.1%) and 16-hentriacontanone (30.3%) dominated in HF and HC, respectively. However, sulphur compounds were only detected in HF. Quantitative estimation of thiosulphinates, phenolics, flavonoids and saponins in ethanolic extracts of calli(EC) and flowers(EF) showed much higher contents in EF. Antioxidant, antimicrobial and cytotoxic screening of extracts demonstrated that EF was the most potent, followed by HF and EC; conversely, HC was inactive. Although HC and EC were less biologically active, these calli could be an alternative source of bioactive metabolites.

A multivariate approach to the study of the composting process by means of analytical electrofocusing.

PubMed

Grigatti, Marco; Cavani, Luciano; Ciavatta, Claudio

2007-01-01

Three blends formed by: agro-industrial waste, wastewater sewage sludge, and their mixture, blended with tree pruning as bulking agent, were composted over a 3-month period. During the composting process the blends were monitored for the main physical and chemical characteristics. Electrofocusing (EF) was carried out on the extracted organic matter. The EF profiles were analyzed by principal component analysis (PCA) in order to assess the suitability of EF to evaluate the stabilisation level during the composting process. Throughout the process, the blends showed a general shifting of focused bands, from low to high pH, even though the compost origin affected the EF profiles. If the EF profile is analyzed by dividing it into pH regions, the interpretation of the results can be affected by the origin of compost. A good clustering of compost samples depending on the process time was obtained by analyzing the whole profile by PCA. Analysis of EF results with PCA represents a useful analytical technique to study the evolution and the stabilisation of composted organic matter.

Micro-solid phase extraction of benzene, toluene, ethylbenzene and xylenes from aqueous solutions using water-insoluble β-cyclodextrin polymer as sorbent.

PubMed

Nojavan, Saeed; Yazdanpanah, Mina

2017-11-24

Water-insoluble β-cyclodextrin polymer was synthesized by chemical cross-linking using epichlorohydrin (EPI) as a cross-linker agent. The produced water-insoluble polymer was used as a sorbent for the micro-solid phase extraction (μ-SPE) of benzene, toluene, ethylbenzene and xylenes (BTEX) from water samples. The μ-SPE device consisted of a sealed tea bag envelope containing 15mg of sorbent. For the evaluation of the extraction efficiency, parameters such as extraction and desorption time, desorption solvent and salt concentration were investigated. At an extraction time of 30min in the course of the extraction process, analytes were extracted from a 10mL aqueous sample solution. The analytes were desorbed by ultrasonication in 200μL of acetonitrile for 20min. Analysis of the analytes was done by a gas chromatography-flame ionization detector (GC-FID) system. The enrichment factor (EF) was found to be in the range 23.0-45.4 (EF max =50.0). The method provided linearity ranges of between 0.5 and 500.0ng/mL (depending on the analytes), with good coefficients of determination (r 2 ) ranging between 0.997 and 0.999 under optimized conditions. Detection limits for BTEX were in the range of between 0.15 and 0.60ng/mL, while corresponding recoveries were in the range of 46.0-90.0%. The relative standard deviation of the method for the analytes at 100.0ng/mL concentration level ranged from 5.5 to 11.2% (n=5). The proposed method was concluded to be a cost effective and environmentally-friendly extraction technique with ease of operation and minimal usage of organic solvent. Copyright © 2017 Elsevier B.V. All rights reserved.

Lopinavir Impairs Protein Synthesis and Induces eEF2 Phosphorylation via the Activation of AMP-Activated Protein Kinase

PubMed Central

Hong-Brown, Ly Q.; Brown, C. Randell; Huber, Danuta S.; Lang, Charles H.

2008-01-01

HIV anti-retroviral drugs decrease protein synthesis, although the underlying regulatory mechanisms of this process are not fully established. Therefore, we investigated the effects of the HIV protease inhibitor lopinavir (LPV) on protein metabolism. We also characterized the mechanisms that mediate the effects of this drug on elongation factor-2 (eEF2), a key component of the translational machinery. Treatment of C2C12 myocytes with LPV produced a dose-dependent inhibitory effect on protein synthesis. This effect was observed at 15 min and was maintained for at least 4 h. Mechanistically, LPV increased the phosphorylation of eEF2 and thereby decreased the activity of this protein. Increased phosphorylation of eEF2 was associated with increased activity of its upstream regulators AMP-activated protein kinase (AMPK) and eEF2 kinase (eEF2K). Both AMPK and eEF2K directly phosphorylated eEF2 in an in vitro kinase assay suggesting two distinct paths lead to eEF2 phosphorylation. To verify this connection, myocytes were treated with the AMPK inhibitor compound C. Compound C blocked eEF2K and eEF2 phosphorylation, demonstrating that LPV affects eEF2 activity via an AMPK-eEF2K dependent pathway. In contrast, incubation of myocytes with rottlerin suppressed eEF2K, but not eEF2 phosphorylation, suggesting that eEF2 can be regulated independent of eEF2K. Finally, LPV did not affect PP2A activity when either eEF2 or peptide was used as the substrate. Collectively, these results indicate that LPV decreases protein synthesis, at least in part, via inhibition of eEF2. This appears regulated by AMPK which can act directly on eEF2 or indirectly via the action of eEF2K. PMID:18712774

Effects of Low-Intensity Extracorporeal Shockwave Therapy on Erectile Dysfunction: A Systematic Review and Meta-Analysis.

PubMed

Clavijo, Raul I; Kohn, Taylor P; Kohn, Jaden R; Ramasamy, Ranjith

2017-01-01

Low-intensity extracorporeal shock wave therapy (Li-ESWT) has been proposed as an effective non-invasive treatment option for erectile dysfunction (ED). To use systematic review and meta-analysis to assess the efficacy of Li-ESWT by comparing change in erectile function as assessed by the erectile function domain of the International Index of Erectile Function (IIEF-EF) in men undergoing Li-ESWT vs sham therapy for the treatment of ED. Systematic search was conducted of MEDLINE, EMBASE, and ClinicalTrials.gov for randomized controlled trials that were published in peer-reviewed journals or presented in abstract form of Li-ESWT used for the treatment of ED from January 2010 through March 2016. Randomized controlled trials were eligible for inclusion if they were published in the peer-reviewed literature and assessed erectile function outcomes using the IIEF-EF score. Estimates were pooled using random-effects meta-analysis. Change in IIEF-EF score after treatment with Li-ESWT in patients treated with active treatment vs sham Li-ESWT probes. Data were extracted from seven trials involving 602 participants. The average age was 60.7 years and the average follow-up was 19.8 weeks. There was a statistically significant improvement in pooled change in IIEF-EF score from baseline to follow-up in men undergoing Li-ESWT vs those undergoing sham therapy (6.40 points; 95% CI = 1.78-11.02; I 2  = 98.7%; P < .0001 vs 1.65 points; 95% CI = 0.92-2.39; I 2  = 64.6%; P < .0001; between-group difference, P = .047). Significant between-group differences were found for total treatment shocks received by patients (P < .0001). In this meta-analysis of seven randomized controlled trials, treatment of ED with Li-ESWT resulted in a significant increase in IIEF-EF scores. Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Aphrodisiac effect of aqueous root extract of Lecaniodiscus cupanioides in sexually impaired rats.

PubMed

Ajiboye, Taofeek O; Nurudeen, Quadri O; Yakubu, Musa T

2014-05-01

The phytochemical constituents of the aqueous root extract of Lecaniodiscus cupanioides Planch. Ex Bth. and its aphrodisiac activity on male rat sexual behavior and reproductive hormones in paroxetine-induced sexual dysfunction were evaluated. The extract was screened for the presence of phytochemicals. The extract (25, 50, and 100 mg/kg body weight) and the reference herbal drug PowmaxM (7.14 mg/kg body weight) were administered orally to paroxetine-induced sexually impaired male rats, once daily for 5 days, and their sexual behavior parameters were monitored and computed. The serum hormones (testosterone, follicle-stimulating hormone, and luteinizing hormone) were determined at the end of treatment period. Phytochemical screening revealed the presence of alkaloids, anthraquinones, phenolics, saponins, and tannins. Mount frequency (MF), intromission frequency (IF), ejaculatory frequency (EF), and testosterone, follicle-stimulating hormone, and luteinizing hormone concentrations were reduced significantly (p<0.05) in paroxetine-treated rats. Administration of 25, 50, and 100 mg/kg body weight of the aqueous root extract of L. cupanioides significantly (p<0.05) reversed the paroxetine-mediated alterations in MF, IF, EF, mount latency (ML), intromission latency (IL), ejaculatory latency (EL), postejaculatory interval (PEI), and testosterone, follicle-stimulating hormone, and luteinizing hormone concentrations dose-dependently. The reversal of the male sexual behavior parameters by the extract compared well (p<0.05) with the PowmaxM-treated animals. Data obtained from this study revealed that the aqueous root extract of L. cupanioides restored sexual competence in sexually impaired rats possibly by increasing sexual drive through enhanced reproductive hormones concentration, particularly testosterone, thus supporting the folkloric claim of the plant for the management of sexual disorder in males.

The influence of selected potential oncostatics of plant origin on the protein biosynthesis in vitro.

PubMed

Paszkiewicz-Gadek, A; Chlabicz, J; Gałasiński, W

1988-01-01

Five potential oncostatics of plant origin (reserpine, amphotericin B, rutoside, digoxin, dry aloe extract), and cyclic AMP were investigated for their effect on protein synthesis. The solutions of digoxin and dry aloe extract inhibited protein biosynthesis in vitro. The direct inhibiting effect of digoxin on the ribosomes suggests that this drug forms an inactive complex with this organelle. Therefore it can be concluded that ribosome is the target site of digoxin action. Aloin and aloeemodin are responsible for the inhibitory effect of the solution of dry aloe extract. They inhibit markedly [14C]-leucine incorporation into proteins. Aloin and aloeemodin do not influence directly the ribosomes, but they inhibit elongation factors and peptidyltransferase activities in the complete elongation system. Some preliminary experiments have shown that direct interaction between these substances and elongation factor EF-2 should be taken in account. This observation is the subject of further experiments, in which the characteristics of the inhibitory effect of the components isolated from dry aloe extract will be performed.

Antibacterial activity of crude extracts of prasaprohyai formula and its components against pathogenic bacteria.

PubMed

Sattaponpan, Chisanucha; Kondo, Sumalee

2011-12-01

Prasaprohyai formula is a Thai Traditional Medicine which has been used for reducing feverish in child. Fever is a symptom resulting from various infections and diseases. The major cause of fever is bacterial and viral infections. The Prasaprohyai formula and its components potentially have biological activities including antipyretic and antimicrobial activities. It is in a hope to develop the formula and its components for an alternative medicine of infectious diseases. To study antibacterial activity of Prasaprohyai formula and its components against pathogenic bacteria. Prasaprohyai formula and its components were extracted by different methods, A: maceration with 95% ethanol followed by evaporation (ET), B: ET followed by freeze drying (EF) and C: water distillation (VO). All extracts were tested against clinical isolates from Thammasat University Hospital, Staphylococcus aureus ATCC 25923 and Escherichia coli ATCC 25922. Disk diffusion and broth dilution methods were performed. Crude extracts of ET had higher yield of extraction than other methods. The results showed that the crude extract from different methods of Syzygium aromaticum (Linn) Merr & Perry (Flower) was effective against all bacterial strains with the inhibition zone ranging from 9 to 19 mm. The VO extract of Prasaprohyai formula showed antibacterial activity against most of the pathogenic bacteria in the present study. The activity against Streptococcus pyogenes was found in the VO extract of some components. The ET extracts of Lepidium sativum Linn, Myristica fragrans Houtt (seed) and Myristica fragrans Houtt (aril) had no antibacterial activity against all microorganism. However the EF extracts of this formula and some components were able to mostly inhibit Gram positive bacteria. The results indicated that Prasaprohyai formula and its components were able to inhibit the growth of both Gram positive and Gram negative bacteria including multiresistant strains. The volatile oil extracts seemed to play an important role in antimicrobial activities. The development of Prasaprohyai formula for alternative medicine will be approached in future.

Cinnamon polyphenol extract regulates tristetraprolin and related gene expression in mouse adipocytes

USDA-ARS?s Scientific Manuscript database

Cinnamon (Cinnamomum verum) has been widely used in spices, flavoring agents, and preservatives. Cinnamon polyphenol extract (CPE) may be important in the alleviation of chronic diseases, but the molecular evidence is not substantial. Tristetraprolin (TTP) family proteins have anti-inflammatory ef...

Microencapsulation of Theobroma cacao L. waste extract: optimization using response surface methodology.

PubMed

Gabbay Alves, Taís Vanessa; Silva da Costa, Russany; Aliakbarian, Bahar; Casazza, Alessandro Alberto; Perego, Patrizia; Carréra Silva Júnior, José Otávio; Ribeiro Costa, Roseane Maria; Converti, Attilio

2017-03-01

The cocoa extract (Theobroma cacao L.) has a significant amount of polyphenols (TP) with potent antioxidant activity (AA). This study aims to optimise microencapsulation of the extract of cocoa waste using chitosan and maltodextrin. Microencapsulation tests were performed according to a Box-Behnken factorial design, and the results were evaluated by response surface methodology with temperature, maltodextrin concentration (MD) and extract flowrate (EF) as independent variables, and the fraction of encapsulated TP, TP encapsulation yield, AA, yield of drying and solubility index as responses. The optimum conditions were: inlet temperature of 170 °C, MD of 5% and EF of 2.5 mL/min. HPLC analysis identified epicatechin as the major component of both the extract and microparticles. TP release was faster at pH 3.5 than in water. These results as a whole suggest that microencapsulation was successful and the final product can be used as a nutrient source for aquatic animal feed. Highlights Microencapsulation is optimised according to a factorial design of the Box-Behnken type. Epicatechin is the major component of both the extract and microcapsules. The release of polyphenols from microcapsules is faster at pH 3.5 than in water.

Twitter as a Potential Disaster Risk Reduction Tool. Part II: Descriptive Analysis of Identified Twitter Activity during the 2013 Hattiesburg F4 Tornado.

PubMed

Cooper, Guy Paul; Yeager, Violet; Burkle, Frederick M; Subbarao, Italo

2015-06-29

This article describes a novel triangulation methodological approach for identifying twitter activity of regional active twitter users during the 2013 Hattiesburg EF-4 Tornado. A data extraction and geographically centered filtration approach was utilized to generate Twitter data for 48 hrs pre- and post-Tornado. The data was further validated using six sigma approach utilizing GPS data. The regional analysis revealed a total of 81,441 tweets, 10,646 Twitter users, 27,309 retweets and 2637 tweets with GPS coordinates. Twitter tweet activity increased 5 fold during the response to the Hattiesburg Tornado.  Retweeting activity increased 2.2 fold. Tweets with a hashtag increased 1.4 fold. Twitter was an effective disaster risk reduction tool for the Hattiesburg EF-4 Tornado 2013.

Curcumin analog EF24 induces apoptosis via ROS-dependent mitochondrial dysfunction in human colorectal cancer cells.

PubMed

He, Guodong; Feng, Chen; Vinothkumar, Rajamanickam; Chen, Weiqian; Dai, Xuanxuan; Chen, Xi; Ye, Qingqing; Qiu, Chenyu; Zhou, Huiping; Wang, Yi; Liang, Guang; Xie, Yubo; Wu, Wei

2016-12-01

Colorectal cancer is the most commonly diagnosed malignancy with high mortality rates worldwide. Improved therapeutic strategies with minimal adverse side effects are urgently needed. In this study, the anti-tumor effects of EF24, a novel analog of the natural compound curcumin, were evaluated in colorectal cancer cells. The anti-tumor activity of EF24 on human colon cancer lines (HCT-116, SW-620, and HT-29) was determined by measures of cell cycle arrest, apoptosis, and mitochondrial function. The contribution of ROS in the EF24-induced anti-tumor activity was evaluated by measures of H 2 O 2 and pretreatment with an ROS scavenger, NAC. The findings indicated that EF24 treatment dose-dependently inhibited cell viability and caused cell cycle arrest at G2/M phase in all the tested colon cancer cell lines. Furthermore, we demonstrated that EF24 treatment induced apoptosis effectively via enhancing intracellular accumulation of ROS in both HCT-116 and SW-620 cells, but with moderate effects in HT-29 cells. We found that EF24 treatment decreased the mitochondrial membrane potential in the colon cancer cells, leading to the release of mitochondrial cytochrome c. Also, EF24 induced activation of caspases 9 and 3, causing decreased Bcl-2 protein expression and Bcl-2/Bax ratio. Pretreatment with NAC, a ROS scavenger, abrogated the EF24-induced cell death, apoptosis, cell cycle arrest, and mitochondrial dysfunction, suggesting an upstream ROS generation which was responsible for the anticancer effects of EF24. Our findings support an anticancer mechanism by which EF24 enhanced ROS accumulation in colon cancer cells, thereby resulting in mitochondrial membrane collapse and activated intrinsic apoptotic signaling. Thus, EF24 could be a potential candidate for therapeutic application of colon cancer.

Are the effects of drugs to prevent and to treat heart failure always concordant? The statin paradox and its implications for understanding the actions of antidiabetic medications.

PubMed

Packer, Milton

2018-03-22

Most treatments for chronic heart failure are effective both in preventing its onset and reducing its progression. However, statins prevent the development of heart failure, but they do not decrease morbidity and mortality in those with established heart failure. This apparent discordance cannot be explained by an effect to prevent interval myocardial infarctions. Instead, it seems that the disease that statins were preventing in trials of patients with a metabolic disorder was different from the disease that they were treating in trials of chronic heart failure. The most common phenotype of heart failure in patients with obesity and diabetes is heart failure with a preserved ejection fraction (HFpEF). In this disorder, the anti-inflammatory effects of statins might ameliorate myocardial fibrosis and cardiac filling abnormalities, but these actions may have little relevance to patients with heart failure and a reduced ejection fraction (HFrEF), whose primary derangement is cardiomyocyte loss and stretch. These distinctions may explain why statins were ineffective in trials that focused on HFrEF, but have been reported to produce with favourable effects in observational studies of HFpEF. Similarly, selective cytokine antagonists were ineffective in HFrEF, but have been associated with benefits in HFpEF. These observations may have important implications for our understanding of the effects of antihyperglycaemic medications. Glucagon-like peptide-1 receptor agonists have had neutral effects on heart failure events in people at risk for HFpEF, but have exerted deleterious actions in HFrEF. Similarly, sodium-glucose co-transporter 2 inhibitors, which exert anti-inflammatory effects and reduce heart failure events in patients who are prone to HFpEF, may not be effective in HFrEF. The distinctions between HFrEF and HFpEF may explain why the effects of drugs on heart failure events in diabetes trials may not be relevant to their use in patients with systolic dysfunction. © 2018 The Authors. European Journal of Heart Failure © 2018 European Society of Cardiology.

Spasmogenic and spasmolytic activities of Agastache mexicana ssp. mexicana and A. mexicana ssp. xolocotziana methanolic extracts on the guinea pig ileum.

PubMed

Ventura-Martínez, Rosa; Rodríguez, Rodolfo; González-Trujano, María Eva; Ángeles-López, Guadalupe E; Déciga-Campos, Myrna; Gómez, Claudia

2017-01-20

Agastache mexicana has been used in traditional medicine for relief of abdominal pain and treatment of other diseases. Two subspecies have been identified: A. mexicana ssp. mexicana (AMM) and A. mexicana ssp. xolocotziana (AMX) and both are used traditionally without distinction or in combination. To determine the effect of methanol extracts of A. mexicana ssp. mexicana and A. mexicana ssp. xolocotziana on gut motility and their possible mechanism of action. The effect of AMM and AMX methanol extracts were tested on the spontaneous activity in the isolated guinea pig ileum and on tissues pre-contracted with KCl, electrical field stimulation (EFS) or ACh. In addition, the possible mechanism of action of each subspecies on gut motility was analyzed in the presence of hexametonium, indomethacin, L-NAME, verapamil, atropine or pyrylamine. A comparative chromatographic profile of these extracts was also done to indicate the most abundant flavonoids presents in methanol extracts of both subspecies. AMM, but not AMX, induced a contractile effect in the guinea pig ileum. This spasmogenic effect was partially inhibited by atropine, antagonist of muscarinic receptors; and pyrilamine, antagonist of H 1 receptors. In contrast, AMX, but not AMM, diminished the contractions induced by KCl, EFS or ACh. The spasmolytic activity of AMX was partially inhibited by hexamethonium, ganglionic blocker; and indomethacin, inhibitor of the synthesis of prostaglandins; but not by L-NAME, inhibitor of nitric oxide synthase. In addition, AMX diminished the maximal contraction induced by CaCl 2 in a calcium-free medium. Chromatographic analyses of these methanol extracts showed the presence of acacetin and tilanin in both. These results suggest that in folk medicine only AMX should be used as spasmolytic, and not in combination with AMM as traditionally occurs, due to the spasmogenic effects of the latter. In addition, activation of nicotinic receptors, prostaglandins and calcium channels, but not nitric oxide mechanisms, could be responsible for the spasmolytic activity of AMX. On the other hand, release of ACh and histamine could be involved in the spasmogenic effect induced by AMM. Acacetin and tilanin are present in methanol extracts of both subspecies and both flavonoids were more abundant in AMX than AMM. Our findings contribute to the validation of the traditional use of Agastache mexicana in relieving gastrointestinal disorders, but indicate that the subspecie that should be used for this effect is A. mexicana ssp. xolocotziana. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The altered liver microRNA profile in hepatotoxicity induced by rhizome Dioscorea bulbifera in mice.

PubMed

Yang, Rui; Bai, Qingyun; Zhang, Jiaqi; Sheng, Yuchen; Ji, Lili

2017-08-01

MicroRNA (miRNA) has been reported to play important roles in regulating drug-induced liver injury. Ethyl acetate extract isolated from rhizoma Dioscoreae bulbifera (EF) has been reported to induce hepatotoxicity in our previous studies. This study aims to observe the altered liver miRNA profile and its related signalling pathway involved in EF-induced hepatotoxicity. Serum alanine/aspartate aminotransferase assay showed that EF (450 mg/kg)-induced hepatotoxicity in mice. Results of miRNA chip analysis showed that the expression of eight miRNAs was up-regulated and of other nine miRNAs was down-regulated in livers from EF-treated mice. Further, the altered expression of miR-200a-3p, miR-5132-5p and miR-5130 was validated using real-time polymerase chain reaction (PCR) assay. There were total seven predicted target genes of miR-200a-3p, miR-5132-5p and miR-5130. Only one kyoto encyclopedia genes and genomes pathway was annotated using those target genes, which is protein processing in endoplasmic reticulum (ER). Furthermore, liver expression of DnaJ subfamily A member 1, a key gene involved in protein processing in ER based on the altered miRNAs, was increased in EF-treated mice. In conclusion, the results demonstrated that EF altered the expression of liver miRNA profile and its related signalling pathway, which may be involved in EF-induced hepatotoxicity.

EF24 inhibits tumor growth and metastasis via suppressing NF-kappaB dependent pathways in human cholangiocarcinoma

PubMed Central

Yin, Da-long; Liang, Ying-jian; Zheng, Tong-sen; Song, Rui-peng; Wang, Jia-bei; Sun, Bo-shi; Pan, Shang-ha; Qu, Lian-dong; Liu, Jia-ren; Jiang, Hong-chi; Liu, Lian-xin

2016-01-01

A synthetic monoketone analog of curcumin, termed 3, 5-bis (2-flurobenzylidene) piperidin-4-one (EF24), has been reported to inhibit the growth of a variety of cancer cells both in vitro and in vivo. However, whether EF24 has anticancer effects on cholangiocarcinoma (CCA) cells and the mechanisms remain to be investigated. The aim of our study was to evaluate the molecular mechanisms underlying the anticancer effects of EF24 on CCA tumor growth and metastasis. Cell proliferation, apoptosis, migration, invasion, tumorigenesis and metastasis were examined. EF24 exhibited time- and dose-dependent inhibitory effects on HuCCT-1, TFK-1 and HuH28 human CCA cell lines. EF24 inhibited CCA cell proliferation, migration, and induced G2/M phase arrest. EF24 induced cell apoptosis along with negative regulation of NF-κB- X-linked inhibitor of apoptosis protein (XIAP) signaling pathway. XIAP inhibition by lentivirus mediated RNA interference enhanced EF24-induced apoptosis, while XIAP overexpression reduced it in CCA cells. In vivo, EF24 significantly suppressed the growth of CCA tumor xenografts and tumor metastasis while displaying low toxicity levels. Our findings indicate that EF24 is a potent antitumor agent that inhibits tumor growth and metastasis by inhibiting NF-κB dependent signaling pathways. EF24 may represent a novel approach for CCA treatment. PMID:27571770

EF24 inhibits tumor growth and metastasis via suppressing NF-kappaB dependent pathways in human cholangiocarcinoma.

PubMed

Yin, Da-Long; Liang, Ying-Jian; Zheng, Tong-Sen; Song, Rui-Peng; Wang, Jia-Bei; Sun, Bo-Shi; Pan, Shang-Ha; Qu, Lian-Dong; Liu, Jia-Ren; Jiang, Hong-Chi; Liu, Lian-Xin

2016-08-30

A synthetic monoketone analog of curcumin, termed 3, 5-bis (2-flurobenzylidene) piperidin-4-one (EF24), has been reported to inhibit the growth of a variety of cancer cells both in vitro and in vivo. However, whether EF24 has anticancer effects on cholangiocarcinoma (CCA) cells and the mechanisms remain to be investigated. The aim of our study was to evaluate the molecular mechanisms underlying the anticancer effects of EF24 on CCA tumor growth and metastasis. Cell proliferation, apoptosis, migration, invasion, tumorigenesis and metastasis were examined. EF24 exhibited time- and dose-dependent inhibitory effects on HuCCT-1, TFK-1 and HuH28 human CCA cell lines. EF24 inhibited CCA cell proliferation, migration, and induced G2/M phase arrest. EF24 induced cell apoptosis along with negative regulation of NF-κB- X-linked inhibitor of apoptosis protein (XIAP) signaling pathway. XIAP inhibition by lentivirus mediated RNA interference enhanced EF24-induced apoptosis, while XIAP overexpression reduced it in CCA cells. In vivo, EF24 significantly suppressed the growth of CCA tumor xenografts and tumor metastasis while displaying low toxicity levels. Our findings indicate that EF24 is a potent antitumor agent that inhibits tumor growth and metastasis by inhibiting NF-κB dependent signaling pathways. EF24 may represent a novel approach for CCA treatment.

Twitter as a Potential Disaster Risk Reduction Tool. Part II: Descriptive Analysis of Identified Twitter Activity during the 2013 Hattiesburg F4 Tornado

PubMed Central

Cooper, Guy Paul; Yeager, Violet; Burkle, Frederick M.; Subbarao, Italo

2015-01-01

Background: This article describes a novel triangulation methodological approach for identifying twitter activity of regional active twitter users during the 2013 Hattiesburg EF-4 Tornado. Methodology: A data extraction and geographically centered filtration approach was utilized to generate Twitter data for 48 hrs pre- and post-Tornado. The data was further validated using six sigma approach utilizing GPS data. Results: The regional analysis revealed a total of 81,441 tweets, 10,646 Twitter users, 27,309 retweets and 2637 tweets with GPS coordinates. Conclusions: Twitter tweet activity increased 5 fold during the response to the Hattiesburg Tornado.  Retweeting activity increased 2.2 fold. Tweets with a hashtag increased 1.4 fold. Twitter was an effective disaster risk reduction tool for the Hattiesburg EF-4 Tornado 2013.  PMID:26203396

Bacterial translation elongation factor EF-Tu interacts and colocalizes with actin-like MreB protein.

PubMed

Defeu Soufo, Hervé Joël; Reimold, Christian; Linne, Uwe; Knust, Tobias; Gescher, Johannes; Graumann, Peter L

2010-02-16

We show that translation initiation factor EF-Tu plays a second important role in cell shape maintenance in the bacterium Bacillus subtilis. EF-Tu localizes in a helical pattern underneath the cell membrane and colocalizes with MreB, an actin-like cytoskeletal element setting up rod cell shape. The localization of MreB and of EF-Tu is interdependent, but in contrast to the dynamic MreB filaments, EF-Tu structures are more static and may serve as tracks for MreB filaments. In agreement with this idea, EF-Tu and MreB interact in vivo and in vitro. Lowering of the EF-Tu levels had a minor effect on translation but a strong effect on cell shape and on the localization of MreB, and blocking of the function of EF-Tu in translation did not interfere with the localization of MreB, showing that, directly or indirectly, EF-Tu affects the cytoskeletal MreB structure and thus serves two important functions in a bacterium.

EF-1 alpha is a target site for an inhibitory effect of quercetin in the peptide elongation process.

PubMed

Marcinkiewicz, C; Gałasiński, W; Gindzieński, A

1995-01-01

The effect of quercetin (3,3',4',5,7-pentahydroxyflavone) on the polypeptide elongation system isolated from rat liver cells, was investigated. Quercetin inhibited [14C]leucine incorporation into proteins in vitro and the inhibitory effect is being directed towards the elongation factor eEF-1, but not to eEF-2 and ribosomes. Quercetin was found to form a complex with EF-1 alpha, which was inactive in GTP-dependent binding to ribosomes. It can be suggested that quercetin can block the total or the part of the domain of EF-1 alpha structure that is responsible for formation of the ternary complex EF-1 alpha-GTP-[14C]Phe-tRNA and therefore preventing formation of the quaternary complex with ribosomes.

Revisiting the physiological effects of exercise training on autonomic regulation and chemoreflex control in heart failure: does ejection fraction matter?

PubMed

Andrade, David C; Arce-Alvarez, Alexis; Toledo, Camilo; Díaz, Hugo S; Lucero, Claudia; Quintanilla, Rodrigo A; Schultz, Harold D; Marcus, Noah J; Amann, Markus; Del Rio, Rodrigo

2018-03-01

Heart failure (HF) is a global public health problem that, independent of its etiology [reduced (HFrEF) or preserved ejection fraction (HFpEF)], is characterized by functional impairments of cardiac function, chemoreflex hypersensitivity, baroreflex sensitivity (BRS) impairment, and abnormal autonomic regulation, all of which contribute to increased morbidity and mortality. Exercise training (ExT) has been identified as a nonpharmacological therapy capable of restoring normal autonomic function and improving survival in patients with HFrEF. Improvements in autonomic function after ExT are correlated with restoration of normal peripheral chemoreflex sensitivity and BRS in HFrEF. To date, few studies have addressed the effects of ExT on chemoreflex control, BRS, and cardiac autonomic control in HFpEF; however, there are some studies that have suggested that ExT has a beneficial effect on cardiac autonomic control. The beneficial effects of ExT on cardiac function and autonomic control in HF may have important implications for functional capacity in addition to their obvious importance to survival. Recent studies have suggested that the peripheral chemoreflex may also play an important role in attenuating exercise intolerance in HFrEF patients. The role of the central/peripheral chemoreflex, if any, in mediating exercise intolerance in HFpEF has not been investigated. The present review focuses on recent studies that address primary pathophysiological mechanisms of HF (HFrEF and HFpEF) and the potential avenues by which ExT exerts its beneficial effects.

Hemorrhagic shock-induced cerebral bioenergetic imbalance is corrected by pharmacologic treatment with EF24 in a rat model.

PubMed

Rao, Geeta; Xie, Jun; Hedrick, Andria; Awasthi, Vibhudutta

2015-12-01

Maintenance of cerebral viability and function is an important goal of critical care in victims of injury due to ischemia and hypovolemia. As part of the multiple organ dysfunction syndrome, the brain function after trauma is influenced by the systemic inflammatory response. We investigated the effect of EF24, an anti-inflammatory bis-chalcone, on cerebral bioenergetics in a rat model of 45% hemorrhagic shock. The rats were treated with EF24 (0.4 mg/kg) or EF24 with an artificial oxygen carrier liposome-encapsulated hemoglobin (LEH). The volume of LEH administered was equal to the shed blood. The brain was collected after 6 h of shock for biochemical assays. EF24 treatment showed significant recovery of ATP, phosphocreatine, and NAD/NADH ratio. It also increased citrate synthase activity and cytochrome c oxidase subunit IV expression which were reduced in shock brain. Furthermore, it reduced the shock-induced accumulation of pyruvate and pyruvate dehydrogenase kinase-1 expression, suggesting that EF24 treatment improves cerebral energetics by restoring perturbed pyruvate metabolism in the mitochondria. These effects of EF24 were associated with reduced poly(ADP-ribose) polymerase cleavage and a significant improvement in the levels of nerve growth factor and brain-derived neurotrophic factor in shock brain. Co-administration of LEH with EF24 was only marginally more effective as compared to the treatment with EF24 alone. These results show that EF24 treatment sets up a pro-survival phenotype in shock by resurrecting cerebral bioenergetics. Since EF24 was effective in the absence of accompanying fluid resuscitation, it has potential utility as a pre-hospital pharmacotherapy in shock due to accidental blood loss. Copyright © 2015 Elsevier Ltd. All rights reserved.

Hemorrhagic shock-induced cerebral bioenergetic imbalance is corrected by pharmacologic treatment with EF24 in a rat model

PubMed Central

Rao, Geeta; Xie, Jun; Hedrick, Andria; Awasthi, Vibhudutta

2015-01-01

Maintenance of cerebral viability and function is an important goal of critical care in victims of injury due to ischemia and hypovolemia. As part of the multiple organ dysfunction syndrome, the brain function after trauma is influenced by systemic inflammatory response. We investigated the effect of EF24, an anti-inflammatory bis-chalcone, on cerebral bioenergetics in a rat model of 45% hemorrhagic shock. The rats were treated with EF24 (0.4 mg/kg) or EF24 with an artificial oxygen carrier liposome-encapsulated hemoglobin (LEH). The volume of LEH administered was equal to the shed blood. The brain was collected after 6 h of shock for biochemical assays. EF24 treatment showed significant recovery of ATP, phosphocreatine, and NAD/NADH ratio. It also increased citrate synthase activity and cytochrome c oxidase subunit IV expression which were reduced in shock brain. Furthermore, it reduced the shock-induced accumulation of pyruvate and pyruvate dehydrogenase kinase-1 expression, suggesting that EF24 treatment improves cerebral energetics by restoring perturbed pyruvate metabolism in the mitochondria. These effects of EF24 were associated with reduced poly(ADP-ribose) polymerase cleavage and a significant improvement in the levels of nerve growth factor and brain-derived neurotrophic factor in shock brain. Co-administration of LEH with EF24 was only marginally more effective as compared to the treatment with EF24 alone. These results show that EF24 treatment sets up a pro-survival phenotype in shock by resurrecting cerebral bioenergetics. Since EF24 was effective in the absence of accompanying fluid resuscitation, it has potential utility as a pre-hospital pharmacotherapy in shock due to accidental blood loss. PMID:26232641

N-terminal pro brain natriuretic peptide-guided management in patients with heart failure and preserved ejection fraction: findings from the Trial of Intensified versus standard medical therapy in elderly patients with congestive heart failure (TIME-CHF).

PubMed

Maeder, Micha T; Rickenbacher, Peter; Rickli, Hans; Abbühl, Heidi; Gutmann, Marc; Erne, Paul; Vuilliomenet, André; Peter, Martin; Pfisterer, Matthias; Brunner-La Rocca, Hans-Peter

2013-10-01

To assess the effects of an NT-proBNP-guided medical management on 18-month outcomes in patients with heart failure (HF) and preserved LVEF ( HFpEF). Patients with HFpEF (LVEF >45%; n = 123) and HF with reduced LVEF (HFrEF; LVEF ≤45%; n = 499) with age ≥60 years, NYHA class ≥ II, and elevated NT-proBNP (>400 ng/L or >800 ng/L depending on age) were randomized to medical therapy titrated only to reduce symptoms to NYHA ≤II (symptom-guided) or also to reduce NT-proBNP below the inclusion threshold (NT-proBNP-guided) during a 6-month period. Patients were followed for an additional 12 months. Despite similar treatment escalation, NT-proBNP reduction and symptom relief were less in HFpEF than in HFrEF. Hospitalization-free survival at 18 months was worse in HFpEF than in HFrEF (P = 0.02), while survival and HF hospitalization-free survival did not differ. Among HFpEF patients, NT-proBNP reduction and symptom relief were similar in the symptom-guided (n = 59) and NT-proBNP-guided (n = 64) group despite more aggressive treatment in the NT-proBNP-guided group. In contrast to effects in HFrEF, NT-proBNP-guided management tended to worsen 18-month outcomes in HFpEF, with P-values for the interactions between LVEF stratum and management strategy of 0.2 for hospitalization-free survival, 0.03 for survival, and 0.01 for HF hospitalization-free survival. Outcomes in HFpEF were not better than in HFrEF, and opposite effects of NT-proBNP-guided management were observed in HFpEF compared with HFrEF. These preliminary findings suggest that, in contrast to HFrEF, NT-proBNP-guided therapy may not be beneficial in HFpEF. Trial registration ISRCTN43596477.

Synthetic curcumin analog EF31 inhibits the growth of head and neck squamous cell carcinoma xenografts

PubMed Central

Zhu, Shijun; Moore, Terry W.; Lin, Xiaoqian; Morii, Nao; Mancini, Alessandra; Howard, Randy B.; Culver, Deborah; Arrendale, Richard F.; Reddy, Prabhakar; Evers, Taylor J.; Zhang, Hongzheng; Sica, Gabriel; Chen, Zhuo G.; Sun, Aiming; Fu, Haian; Khuri, Fadlo R.; Shin, Dong M.; Snyder, James P.; Shoji, Mamoru

2013-01-01

Objectives are to examine the efficacy of new synthetic curcumin analogs EF31 in head and neck squamous cell carcinoma in vitro and in vivo, and study their pharmacokinetic and toxicologic effects in vivo. The synthesis of EF31 was described for the first time. Solubility of EF24, EF31 was compared using nephelometric analysis. Human head and neck squamous cell carcinoma Tu212 xenograft tumors were established in athymic nude mice and treated with EF31 i.p. once daily five days a week for about 5 – 6 weeks. The long term effect of EF31 on the NF-κB signaling system in the tumors was examined by Western blot analysis. EF31 at 25 mg/kg, i.p. inhibited tumor growth almost completely. Solubility of EF24 and EF31 are <10, 13 μg/mL or <32, 47 μM, respectively. The serum chemistry profiles of treated mice were within the limits of normal, it revealed a linear increase of Cmax. EF31 decreased the level of phosphorylation of NF-κB p65. In conclusion, the novel synthetic curcumin analogs EF31 is efficacious in inhibiting the growth of Tu212 xenograft tumors and may be useful for treating head and neck squamous cell carcinoma. The long term EF31 treatment inhibited NF-kB p65 phosphorylation in xenografts, implicating downregulation of cancer promoting transcription factors such as angiogenesis and metastasis. PMID:22532032

Chemical profiles and anticancer effects of saponin fractions of different polarity from the leaves of Panax notoginseng.

PubMed

Qian, Mao; Yi, Li; Song-Lin, Li; Jie, Yang; Ping-Hu, Zhang; Qiang, Wang

2014-01-01

To evaluate the chemical profiles and cytotoxic effects among the total saponin fraction (TSF), 25% ethanol fraction (25EF), 50% ethanol fraction (50EF), and 85% ethanol fraction (85EF) prepared by macroporous resin from the leaves of Panax notoginseng. The simultaneous determination of thirteen main saponins, as well as the chemical profiles of saponin fractions of different polarity, was made by HPLC-DAD and LC-ESI-MS(n) analysis. The cytotoxic effects were determined against KP4 cells (human pancreatic cancer), NCI-H727 cells (human lung cancer), HepG2 cells (human hepatocellular cancer), and SGC-7901 cells (human gastric adenocarcinoma). Chemical analysis indicated that 85EF possessed the most abundant cytotoxic protopanaxadiol saponins, including the marker saponins F2, 20(R)-Rg3, 20(S)-Rg3, and Rh2. The MTT assay showed that 85EF also had the strongest cytotoxic effects among the four fractions. 25EF showed no anti-proliferative effects, while 50EF and TSF exhibited weak anti-proliferative activity. From the aspect of comprehensive utilization of resources, 85EF, enriched with low polarity PPD group saponins, is a new alternative source of anticancer saponins, and a promising botanical preparation for further anticancer studies. Copyright © 2014 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Model-based cost-effectiveness analysis of B-type natriuretic peptide-guided care in patients with heart failure.

PubMed

Mohiuddin, Syed; Reeves, Barnaby; Pufulete, Maria; Maishman, Rachel; Dayer, Mark; Macleod, John; McDonagh, Theresa; Purdy, Sarah; Rogers, Chris; Hollingworth, William

2016-12-28

Monitoring B-type natriuretic peptide (BNP) to guide pharmacotherapy might improve survival in patients with heart failure with reduced ejection fraction (HFrEF) or preserved ejection fraction (HFpEF). However, the cost-effectiveness of BNP-guided care is uncertain and guidelines do not uniformly recommend it. We assessed the cost-effectiveness of BNP-guided care in patient subgroups defined by age and ejection fraction. We used a Markov model with a 3-month cycle length to estimate the lifetime health service costs, quality-adjusted life years (QALYs) and incremental net monetary benefits (iNMBs) of BNP-guided versus clinically guided care in 3 patient subgroups: (1) HFrEF patients <75 years; (2) HFpEF patients <75 years; and (3) HFrEF patients ≥75 years. There is no evidence of benefit in patients with HFpEF aged ≥75 years. We used individual patient data meta-analyses and linked primary care, hospital and mortality data to inform the key model parameters. We performed probabilistic analysis to assess the uncertainty in model results. In younger patients (<75 years) with HFrEF, the mean QALYs (5.57 vs 5.02) and costs (£63 527 vs £58 139) were higher with BNP-guided care. At the willingness-to-pay threshold of £20 000 per QALY, the positive iNMB (£5424 (95% CI £987 to £9469)) indicates that BNP-guided care is cost-effective in this subgroup. The evidence of cost-effectiveness of BNP-guided care is less strong for younger patients with HFpEF (£3155 (-£10 307 to £11 613)) and older patients (≥75 years) with HFrEF (£2267 (-£1524 to £6074)). BNP-guided care remained cost-effective in the sensitivity analyses, albeit the results were sensitive to assumptions on its sustained effect. We found strong evidence that BNP-guided care is a cost-effective alternative to clinically guided care in younger patients with HFrEF. It is potentially cost-effective in younger patients with HFpEF and older patients with HFrEF, but more evidence is required, particularly with respect to the frequency, duration and BNP target for monitoring. Cost-effectiveness results from trials in specialist settings cannot be generalised to primary care. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Statistical Modeling of Occupational Exposure to Polycyclic Aromatic Hydrocarbons Using OSHA Data.

PubMed

Lee, Derrick G; Lavoué, Jérôme; Spinelli, John J; Burstyn, Igor

2015-01-01

Polycyclic aromatic hydrocarbons (PAHs) are a group of pollutants with multiple variants classified as carcinogenic. The Occupational Safety and Health Administration (OSHA) provided access to two PAH exposure databanks of United States workplace compliance testing data collected between 1979 and 2010. Mixed-effects logistic models were used to predict the exceedance fraction (EF), i.e., the probability of exceeding OSHA's Permissible Exposure Limit (PEL = 0.2 mg/m3) for PAHs based on industry and occupation. Measurements of coal tar pitch volatiles were used as a surrogate for PAHs. Time, databank, occupation, and industry were included as fixed-effects while an identifier for the compliance inspection number was included as a random effect. Analyses involved 2,509 full-shift personal measurements. Results showed that the majority of industries had an estimated EF < 0.5, although several industries, including Standardized Industry Classification codes 1623 (Water, Sewer, Pipeline, and Communication and Powerline Construction), 1711 (Plumbing, Heating, and Air-Conditioning), 2824 (Manmade Organic Fibres), 3496 (Misc. Fabricated Wire products), and 5812 (Eating Places), and Major group's 13 (Oil and Gas Extraction) and 30 (Rubber and Miscellaneous Plastic Products), were estimated to have more than an 80% likelihood of exceeding the PEL. There was an inverse temporal trend of exceeding the PEL, with lower risk in most recent years, albeit not statistically significant. Similar results were shown when incorporating occupation, but varied depending on the occupation as the majority of industries predicted at the administrative level, e.g., managers, had an estimated EF < 0.5 while at the minimally skilled/laborer level there was a substantial increase in the estimated EF. These statistical models allow the prediction of PAH exposure risk through individual occupational histories and will be used to create a job-exposure matrix for use in a population-based case-control study exploring PAH exposure and breast cancer risk.

Effect of atomic monolayer insertions on electric-field-induced rotation of magnetic easy axis

NASA Astrophysics Data System (ADS)

Tsujikawa, M.; Haraguchi, S.; Oda, T.

2012-04-01

We have investigated the electric field (EF) effect on the magnetic anisotropy energy (MAE) in the thin films MgO/M/Fe/Au(001) and MgO/Fe/M(001) (M = Pd, Pt, and Au) by means of first-principles density-functional calculations. We find that the MAE varies linearly with the EF and investigate the change in slope of the MAE as a function of the EF as the buffer layer is changed. We find that a single monatomic buffer layer may be useful for devices that use EF-modified MAE. We simulate the critical EF for easy-axis rotation and discuss interface effects of Mg/Fe and Fe/Au on MAE.

The effect of pulsed electric fields on the electrotactic migration of human neural progenitor cells through the involvement of intracellular calcium signaling.

PubMed

Hayashi, Hisamitsu; Edin, Fredrik; Li, Hao; Liu, Wei; Rask-Andersen, Helge

2016-12-01

Endogenous electric fields (EFs) are required for the physiological control of the central nervous system development. Application of the direct current EFs to neural stem cells has been studied for the possibility of stem cell transplantation as one of the therapies for brain injury. EFs generated within the nervous system are often associated with action potentials and synaptic activity, apparently resulting in a pulsed current in nature. The aim of this study is to investigate the effect of pulsed EF, which can reduce the cytotoxicity, on the migration of human neural progenitor cells (hNPCs). We applied the mono-directional pulsed EF with a strength of 250mV/mm to hNPCs for 6h. The migration distance of the hNPCs exposed to pulsed EF was significantly greater compared with the control not exposed to the EF. Pulsed EFs, however, had less of an effect on the migration of the differentiated hNPCs. There was no significant change in the survival of hNPCs after exposure to the pulsed EF. To investigate the role of Ca 2+ signaling in electrotactic migration of hNPCs, pharmacological inhibition of Ca 2+ channels in the EF-exposed cells revealed that the electrotactic migration of hNPCs exposed to Ca 2+ channel blockers was significantly lower compared to the control group. The findings suggest that the pulsed EF induced migration of hNPCs is partly influenced by intracellular Ca 2+ signaling. Copyright © 2016 Elsevier B.V. All rights reserved.

Antibacterial activity of synthetic curcumin derivatives: 3,5-bis(benzylidene)-4-piperidone (EF24) and EF24-dimer linked via diethylenetriaminepentacetic acid (EF2DTPA).

PubMed

Vilekar, Prachi; King, Catherine; Lagisetty, Pallavi; Awasthi, Vibhudutta; Awasthi, Shanjana

2014-04-01

Curcumin is well known for its antimicrobial and anti-inflammatory properties. However, since systemic absorption and bioavailability of curcumin from gastrointestinal tract is considerably poor, synthetic curcuminoids are being developed as better alternatives. Two curcumin derivatives: 3,5-bis(benzylidene)-4-piperidone (EF24) and EF24-dimer linked via diethylenetriaminepentacetic acid (EF2DTPA), were included in this study. We investigated the antibacterial activity of EF24 and EF2DTPA against Gram-negative (Escherichia coli) and Gram-positive (Enterococcus faecalis, Staphylococcus aureus) bacteria. We also studied the effects of EF24 and EF2DTPA on uptake and localization of pHrodo-labeled E. coli in the acidic compartments (phagolysosomes) of dendritic cells (DCs) under in vitro conditions. Our results demonstrate that treatment with EF24 and EF2DTPA directly suppresses the bacterial growth. However, these compounds do not affect the bacterial uptake or localization in the DCs.

Glu-Phe from onion (Allium Cepa L.) attenuates lipogenesis in hepatocytes.

PubMed

Lee, Yu Geon; Cho, Jeong-Yong; Hwang, Eom Ji; Jeon, Tae-Il; Moon, Jae-Hak

2017-07-01

A Glu-Phe (EF) was isolated from onion (Allium cepa L. cv. Sunpower). The chemical structure of EF was determined by nuclear magnetic resonance and electrospray ionization-mass (ESI-MS) spectroscopy. We showed that EF reduced lipid accumulation in mouse hepatocytes by inhibiting the expression of sterol regulatory element-binding protein-1c (SREBP-1c) and its lipogenic target genes. We also found that AMP-activated protein kinase (AMPK) was required for the inhibitory effect of EF on lipid accumulation in mouse hepatocytes. Furthermore, EF was qualified in nine onion cultivars by selective multiple reaction-monitoring detection of liquid chromatography-ESI-MS. These results suggest that EF could contribute to the beneficial effect of onion supplement in maintaining hepatic lipid homeostasis.

Additivity rules using similarity models for chemical reactivity: calculation and interpretation of electrofugality and nucleofugality.

PubMed

Bentley, T William

2006-08-25

A recently proposed, multi-parameter correlation: log k (25 degrees C)=s(f) (Ef + Nf), where Ef is electrofugality and Nf is nucleofugality, for the substituent and solvent effects on the rate constants for solvolyses of benzhydryl and substituted benzhydryl substrates, is re-evaluated. A new formula (Ef=log k (RCl/EtOH/25 degrees C) -1.87), where RCl/EtOH refers to ethanolysis of chlorides, reproduces published values of Ef satisfactorily, avoids multi-parameter optimisations and provides additional values of Ef. From the formula for Ef, it is shown that the term (sfxEf) is compatible with the Hammett-Brown (rho+sigma+) equation for substituent effects. However, the previously published values of N(f) do not accurately account for solvent and leaving group effects (e.g. nucleofuge Cl or X), even for benzhydryl solvolyses; alternatively, if the more exact, two-parameter term, (sfxNf) is used, calculated effects are less accurate. A new formula (Nf=6.14 + log k(BX/any solvent/25 degrees C)), where BX refers to solvolysis of the parent benzhydryl as electrofuge, defines improved Nf values for benzhydryl substrates. The new formulae for Ef and Nf are consistent with an assumption that sf=1.00(,) and so improved correlations for benzhydryl substrates can be obtained from the additive formula: log k(RX/any solvent/25 degrees C)=(Ef + Nf). Possible extensions of this approach are also discussed.

Effect of tungsten implantation on the switching parameters in V2O5 films

NASA Astrophysics Data System (ADS)

Burdyukh, S. V.; Berezina, O. Ya.; Pergament, A. L.

2017-11-01

The paper examines the effect of doping with tungsten on switching in hydrated vanadium pentoxide films. The switching effect is associated with the metal-insulator transition in a vanadium dioxide channel that forms in the initial film due to the process of electrical forming (EF). Doping is carried out by the plasma immersion ion implantation method. It is shown that implanting small tungsten doses improves the switching parameters after EF. When implanting large doses, switching is observed without EF, and if EF is applied, the switching effect, on the contrary, disappears.

Development of Hot and Cold Executive Function in Boys and Girls With ADHD.

PubMed

Skogli, Erik Winther; Andersen, Per Normann; Hovik, Kjell Tore; Øie, Merete

2017-02-01

To investigate the development of executive function with pronounced emotional salience (hot EF) and less pronounced emotional salience (cold EF) in boys and girls with ADHD relative to typically developing (TD) children. Seventy-five children with ADHD and 47 TD children were assessed with hot and cold EF tests at baseline and after 2 years. Despite considerable maturation, the ADHD group remained impaired on all cold EF tests relative to TD children after 2 years. There was no effect of gender on cold EF test results. Females with ADHD outperformed TD counterparts on hot EF at baseline. Females with ADHD showed deteriorating hot EF performance, while TD counterparts showed improved hot EF performance across time. Enduring cold EF impairments after 2 years may reflect stable phenotypic traits in children with ADHD. Results indicate divergent developmental trajectories of hot EF in girls with ADHD relative to TD counterparts.

Interaction of apicoplast-encoded elongation factor (EF) EF-Tu with nuclear-encoded EF-Ts mediates translation in the Plasmodiumfalciparum plastid.

PubMed

Biswas, Subir; Lim, Erin E; Gupta, Ankit; Saqib, Uzma; Mir, Snober S; Siddiqi, Mohammad Imran; Ralph, Stuart A; Habib, Saman

2011-03-01

Protein translation in the plastid (apicoplast) of Plasmodium spp. is of immense interest as a target for potential anti-malarial drugs. However, the molecular data on apicoplast translation needed for optimisation and development of novel inhibitors is lacking. We report characterisation of two key translation elongation factors in Plasmodium falciparum, apicoplast-encoded elongation factor PfEF-Tu and nuclear-encoded PfEF-Ts. Recombinant PfEF-Tu hydrolysed GTP and interacted with its presumed nuclear-encoded partner PfEF-Ts. The EF-Tu inhibitor kirromycin affected PfEF-Tu activity in vitro, indicating that apicoplast EF-Tu is indeed the target of this drug. The predicted PfEF-Ts leader sequence targeted GFP to the apicoplast, confirming that PfEF-Ts functions in this organelle. Recombinant PfEF-Ts mediated nucleotide exchange on PfEF-Tu and homology modeling of the PfEF-Tu:PfEF-Ts complex revealed PfEF-Ts-induced structural alterations that would expedite GDP release from PfEF-Tu. Our results establish functional interaction between two apicoplast translation factors encoded by genes residing in different cellular compartments and highlight the significance of their sequence/structural differences from bacterial elongation factors in relation to inhibitor activity. These data provide an experimental system to study the effects of novel inhibitors targeting PfEF-Tu and PfEF-Tu.PfEF-Ts interaction. Our finding that apicoplast EF-Tu possesses chaperone-related disulphide reductase activity also provides a rationale for retention of the tufA gene on the plastid genome. Copyright © 2010 Australian Society for Parasitology Inc. All rights reserved.

9 CFR 205.210 - Effect of EFS outside State in which filed.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Effect of EFS outside State in which filed. 205.210 Section 205.210 Animals and Animal Products GRAIN INSPECTION, PACKERS AND STOCKYARDS... OF FARM PRODUCTS Interpretive Opinions § 205.210 Effect of EFS outside State in which filed. (a) A...

9 CFR 205.210 - Effect of EFS outside State in which filed.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Effect of EFS outside State in which filed. 205.210 Section 205.210 Animals and Animal Products GRAIN INSPECTION, PACKERS AND STOCKYARDS... OF FARM PRODUCTS Interpretive Opinions § 205.210 Effect of EFS outside State in which filed. (a) A...

Clinical efficacy of gamma knife and surgery treatment of mesial temporal lobe epilepsy and their effects on EF-Tumt and EF-Tsmt expression.

PubMed

Wang, X-Q; Zhang, X-D; Han, Y-M; Shi, X-F; Lan, Z-B; Men, X-X; Pan, Y-W

2017-04-01

To study the clinical efficacy of gamma knife and surgery treatment of mesial temporal lobe epilepsy (MTLE) and their effects on EF-Tumt and EF-Tsmt expression. The data of 78 cases of MTLE patients treated in our hospital from April 2011 to March 2013 were retrospectively analyzed. The patients were divided into two groups according to the treatment methods: the surgery group (including 41 cases) and the gamma knife group (including 37 cases). The clinical efficacy, the occurrence and recurrence of complications were evaluated, respectively; meanwhile, the expression of the EF-Tumt protein and EF-Tsmt protein in brain tissue were analyzed. The difference between the efficacy rate of the two groups showed no statistical significance (χ2=0.960, p>0.05). The complication rate of the gamma knife group was significantly lower than that of the control group (χ2=6.430, p<0.05). The recurrence rate of the patients in the gamma knife group was significantly lower than that of the patients in the surgery group (p>0.05). Within the two groups, the positive expression granum of EF-Tsmt protein and EF-Tumt protein of the two groups after treatment were significantly lower than that before treatment (p<0.05). After treatment, the positive expression granum of EF-Tsmt protein of the patients in the gamma knife group was obviously more than that of the patients in the surgery group (p<0.05). The difference between the positive expression granum of EF-Tumt protein of the two groups showed no statistical significance (p>0.05). Before and after treatment within the group, the positive cell of EF-Tsmt protein and EF-Tumt protein of the two groups of patients after treatment were significantly lower than that before treatment (p<0.05). After treatment, the difference between the EF-Tsmt protein positive cell and the EF-Tumt protein positive cell of the two groups of patients showed no statistical significance (p>0.05). Both surgery and gamma knife could treat MTLE effectively, and the efficacy may be related to the ability to reduce the expression of EF-Tsmt protein and EF-Tumt protein in brain tissue.

The substances of plant origin that inhibit protein biosynthesis.

PubMed

Gałasiński, W; Chlabicz, J; Paszkiewicz-Gadek, A; Marcinkiewicz, C; Gindzieński, A

1996-01-01

Some plants were used for a long time in folk medicine as sources of anti-tumour remedies. Their effects on protein biosynthesis in vitro have been examined and described. The separate features of the peptide elongation system, isolated from tumoural cells, have been demonstrated. Some elongation factors or ribosomes have been shown to be a target site for the inhibition of protein biosynthesis caused by the substances isolated from various sources. The glycoside and caffeic acid, isolated from Melissa officinalis leaves, inhibited protein biosynthesis by direct influence the elongation factor eEF-2. The activity of this factor was also inhibited by aloin and aloeemodin. Saponin glycoside and its aglycon, isolated from Verbascum thapsiforme flowers, as well as digoxin, emetine and cepheline directly inactivated ribosomes. "Chagi" fraction, isolated from Inonotus obliquus, is responsible for the inhibitory effect caused by the aqueous tannin--less extract from this fungus. The target site for quercetin has been found to be the subunit form EF-1 alpha. It may be supposed that, the plant inhibitors of protein biosynthesis could be utilized for searching specific antitumoural preparations.

Inhibition of IκB Kinase-Nuclear Factor-κB Signaling Pathway by 3,5-Bis(2-flurobenzylidene)piperidin-4-one (EF24), a Novel Monoketone Analog of Curcumin*

PubMed Central

Kasinski, Andrea L.; Du, Yuhong; Thomas, Shala L.; Zhao, Jing; Sun, Shi-Yong; Khuri, Fadlo R.; Wang, Cun-Yu; Shoji, Mamoru; Sun, Aiming; Snyder, James P.; Liotta, Dennis; Fu, Haian

2009-01-01

The nuclear factor-κB (NF-κB) signaling pathway has been targeted for therapeutic applications in a variety of human diseases, includuing cancer. Many naturally occurring substances, including curcumin, have been investigated for their actions on the NF-κB pathway because of their significant therapeutic potential and safety profile. A synthetic monoketone compound termed 3,5-bis(2-flurobenzylidene)piperidin-4-one (EF24) was developed from curcumin and exhibited potent anticancer activity. Here, we report a mechanism by which EF24 potently suppresses the NF-κB signaling pathway through direct action on IκB kinase (IKK). We demonstrate that 1) EF24 induces death of lung, breast, ovarian, and cervical cancer cells, with a potency about 10 times higher than that of curcumin; 2) EF24 rapidly blocks the nuclear translocation of NF-κB, with an IC50 value of 1.3 μM compared with curcumin, with an IC50 value of 13 μM; 3) EF24 effectively inhibits tumor necrosis factor (TNF)-α-induced IκB phosphorylation and degradation, suggesting a role of this compound in targeting IKK; and 4) EF24 indeed directly inhibits the catalytic activity of IKK in an in vitro-reconstituted system. Our study identifies IKK as an effective target for EF24 and provides a molecular explanation for a superior activity of EF24 over curcumin. The effective inhibition of TNF-α-induced NF-κB signaling by EF24 extends the therapeutic application of EF24 to other NF-κB-dependent diseases, including inflammatory diseases such as rheumatoid arthritis. PMID:18577686

Inhibition of IkappaB kinase-nuclear factor-kappaB signaling pathway by 3,5-bis(2-flurobenzylidene)piperidin-4-one (EF24), a novel monoketone analog of curcumin.

PubMed

Kasinski, Andrea L; Du, Yuhong; Thomas, Shala L; Zhao, Jing; Sun, Shi-Yong; Khuri, Fadlo R; Wang, Cun-Yu; Shoji, Mamoru; Sun, Aiming; Snyder, James P; Liotta, Dennis; Fu, Haian

2008-09-01

The nuclear factor-kappaB (NF-kappaB) signaling pathway has been targeted for therapeutic applications in a variety of human diseases, includuing cancer. Many naturally occurring substances, including curcumin, have been investigated for their actions on the NF-kappaB pathway because of their significant therapeutic potential and safety profile. A synthetic monoketone compound termed 3,5-bis(2-flurobenzylidene)piperidin-4-one (EF24) was developed from curcumin and exhibited potent anticancer activity. Here, we report a mechanism by which EF24 potently suppresses the NF-kappaB signaling pathway through direct action on IkappaB kinase (IKK). We demonstrate that 1) EF24 induces death of lung, breast, ovarian, and cervical cancer cells, with a potency about 10 times higher than that of curcumin; 2) EF24 rapidly blocks the nuclear translocation of NF-kappaB, with an IC(50) value of 1.3 microM compared with curcumin, with an IC(50) value of 13 microM; 3) EF24 effectively inhibits tumor necrosis factor (TNF)-alpha-induced IkappaB phosphorylation and degradation, suggesting a role of this compound in targeting IKK; and 4) EF24 indeed directly inhibits the catalytic activity of IKK in an in vitro-reconstituted system. Our study identifies IKK as an effective target for EF24 and provides a molecular explanation for a superior activity of EF24 over curcumin. The effective inhibition of TNF-alpha-induced NF-kappaB signaling by EF24 extends the therapeutic application of EF24 to other NF-kappaB-dependent diseases, including inflammatory diseases such as rheumatoid arthritis.

Including the spatial variability of metal speciation in the effect factor in life cycle impact assessment: Limits of the equilibrium partitioning method.

PubMed

Tromson, Clara; Bulle, Cécile; Deschênes, Louise

2017-03-01

In life cycle assessment (LCA), the potential terrestrial ecotoxicity effect of metals, calculated as the effect factor (EF), is usually extrapolated from aquatic ecotoxicological data using the equilibrium partitioning method (EqP) as it is more readily available than terrestrial data. However, when following the AMI recommendations (i.e. with at least enough species that represents three different phyla), there are not enough terrestrial data for which soil properties or metal speciation during ecotoxicological testing are specified to account for the influence of soil property variations on metal speciation when using this approach. Alternatively, the TBLM (Terrestrial Biotic Ligand Model) has been used to determine an EF that accounts for speciation, but is not available for metals; hence it cannot be consistently applied to metals in an LCA context. This paper proposes an approach to include metal speciation by regionalizing the EqP method for Cu, Ni and Zn with a geochemical speciation model (the Windermere Humic Aqueous Model 7.0), for 5213 soils selected from the Harmonized World Soil Database. Results obtained by this approach (EF EqP regionalized ) are compared to the EFs calculated with the conventional EqP method, to the EFs based on available terrestrial data and to the EFs calculated with the TBLM (EF TBLM regionalized ) when available. The spatial variability contribution of the EF to the overall spatial variability of the characterization factor (CF) has been analyzed. It was found that the EFs EqP regionalized show a significant spatial variability. The EFs calculated with the two non-regionalized methods (EqP and terrestrial data) fall within the range of the EFs EqP regionalized . The EFs TBLM regionalized cover a larger range of values than the EFs EqP regionalized but the two methods are not correlated. This paper highlights the importance of including speciation into the terrestrial EF and shows that using the regionalized EqP approach is not an acceptable proxy for terrestrial ecotoxicological data even if it can be applied to all metals. Copyright © 2016. Published by Elsevier B.V.

Multiple anticancer activities of EF24, a novel curcumin analog, on human ovarian carcinoma cells.

PubMed

Tan, Xin; Sidell, Neil; Mancini, Alessandra; Huang, Ruo-Pan; Shenming Wang; Horowitz, Ira R; Liotta, Dennis C; Taylor, Robert N; Wieser, Friedrich

2010-10-01

Curcumin, a component of turmeric, has been reported to exhibit potential antitumor activities. This study assessed the effects of a novel synthetic curcumin analog, EF24, on proliferation, apoptosis, and vascular endothelial growth factor (VEGF) regulation in platinum-sensitive (IGROV1) and platinum-resistant (SK-OV-3) human ovarian cancer cells. EF24 time- and dose-dependently suppressed the growth of both cell lines and synergized with cisplatin to induce apoptosis. Although treatment with EF24 had no significant effect on VEGF messenger RNA (mRNA) expression,VEGF protein secretion into conditioned media was dose-dependently reduced with EF24 demonstrating ∼8-fold greater potency than curcumin (P < .05). EF24 significantly inhibited hydrogen peroxide (H(2)O(2))-induced VEGF expression, as did the phenolic antioxidant tert-butylhydroquinone (t-BHQ). EF24 upregulated cellular antioxidant responses as observed by the suppression of reactive oxygen species (ROS) generation and activation of antioxidant response element (ARE)-dependent gene transcription. Given its high potency, EF24 is an excellent lead candidate for further development as an adjuvant therapeutic agent in preclinical models of ovarian cancer.

Major Depressive Disorder is Associated with Broad Impairments on Neuropsychological Measures of Executive Function: A Meta-Analysis and Review

PubMed Central

Snyder, Hannah R.

2012-01-01

Cognitive impairments are now widely acknowledged as an important aspect of major depressive disorder (MDD), and it has been proposed that executive function (EF) may be particularly impaired in patients with MDD. However, the existence and nature of EF impairments associated with depression remain strongly debated. While many studies have found significant deficits associated with MDD on neuropsychological measures of EF, others have not, potentially due to low statistical power, task impurity, and diverse patient samples, and there have been no recent, comprehensive, meta-analyses investigating EF in patients with MDD. The current meta-analysis uses random effects models to synthesize 113 previous research studies that compared participants with MDD to healthy control participants on at least one neuropsychological measure of EF. Results of the meta-analysis demonstrate that MDD is reliably associated with impaired performance on neuropsychological measures of EF, with effect sizes ranging from d = 0.32–0.97. While patients with MDD also have slower processing speed, motor slowing alone cannot account for these results. In addition, some evidence suggests that deficits on neuropsychological measures of EF are greater in patients with more severe current depression symptoms, and those taking psychotropic medications, while evidence for effects of age was weaker. The results are consistent with the theory that MDD is associated with broad impairment in multiple aspects of EF. Implications for treatment of MDD and theories of EF are discussed. Future research is needed to establish the specificity and causal link between MDD and EF impairments. PMID:22642228

EF24 Suppresses Invasion and Migration of Hepatocellular Carcinoma Cells In Vitro via Inhibiting the Phosphorylation of Src

PubMed Central

Tin, Lamtin; Wu, Yiqi; Jin, Yinji; Jin, Xiaoming; Zhang, Fengmin

2016-01-01

Diphenyl difluoroketone (EF24), a curcumin analog, is a promising anticancer compound that exerts its effects by inhibiting cell proliferation and inducing apoptosis. However, the efficacy of EF24 against cancer metastasis, particularly in hepatocellular carcinoma (HCC), remains elusive. In this study, the effect of EF24 on HCCLM-3 and HepG2 cell migration and invasion was detected by wound healing and transwell assay, respectively. The results revealed that EF24 suppressed the migration and invasion of both HCCLM-3 and HepG2 cells. Furthermore, EF24 treatment decreased the formation of filopodia on the cell surface and inhibited the phosphorylation of Src in both cell lines, which may help contribute towards understanding the mechanism underlying the suppressive effect of EF24 on HCC migration and invasion. Additionally, the expression of total- and phosphorylated-Src in primary HCC tissues and their paired lymph node metastatic tissues was detected, and phosphorylated-Src was found to be associated with HCC lymph node metastasis. The results of this study suggest that Src is a novel and promising therapeutic target in HCC and provide evidence to support the hypothesis that EF24 may be a useful therapeutic agent for the treatment of HCC. PMID:27999817

EF24 Suppresses Invasion and Migration of Hepatocellular Carcinoma Cells In Vitro via Inhibiting the Phosphorylation of Src.

PubMed

Zhao, Ran; Tin, Lamtin; Zhang, Yuhua; Wu, Yiqi; Jin, Yinji; Jin, Xiaoming; Zhang, Fengmin; Li, Xiaobo

2016-01-01

Diphenyl difluoroketone (EF24), a curcumin analog, is a promising anticancer compound that exerts its effects by inhibiting cell proliferation and inducing apoptosis. However, the efficacy of EF24 against cancer metastasis, particularly in hepatocellular carcinoma (HCC), remains elusive. In this study, the effect of EF24 on HCCLM-3 and HepG2 cell migration and invasion was detected by wound healing and transwell assay, respectively. The results revealed that EF24 suppressed the migration and invasion of both HCCLM-3 and HepG2 cells. Furthermore, EF24 treatment decreased the formation of filopodia on the cell surface and inhibited the phosphorylation of Src in both cell lines, which may help contribute towards understanding the mechanism underlying the suppressive effect of EF24 on HCC migration and invasion. Additionally, the expression of total- and phosphorylated-Src in primary HCC tissues and their paired lymph node metastatic tissues was detected, and phosphorylated-Src was found to be associated with HCC lymph node metastasis. The results of this study suggest that Src is a novel and promising therapeutic target in HCC and provide evidence to support the hypothesis that EF24 may be a useful therapeutic agent for the treatment of HCC.

Prevalence of left ventricular systolic dysfunction and heart failure with reduced ejection fraction in men and women with type 2 diabetes mellitus: a systematic review and meta-analysis.

PubMed

Bouthoorn, Selma; Gohar, Aisha; Valstar, Gideon; den Ruijter, Hester M; Reitsma, J B; Hoes, Arno W; Rutten, Frans H

2018-04-18

Type 2 diabetes mellitus (T2D) is associated with the development of left ventricular systolic dysfunction (LVSD) and heart failure with reduced ejection fraction (HFrEF). T2D patients with LVSD are at higher risk of mortality and morbidity than patients without LVSD, while progression of LVSD can be delayed or halted by the use of proven therapies. As estimates of the prevalence are scarce and vary considerably, the aim of this study was to retrieve summary estimates of the prevalence of LVSD/HFrEF in T2D and to see if there were any sex differences. A systematic search of Medline and Embase was performed to extract the prevalence of LVSD/HFrEF in T2D (17 studies, mean age 50.1 ± 6.3 to 71.5 ± 7.5), which were pooled using random-effects meta-analysis. The pooled prevalence of LVSD was higher in hospital populations (13 studies, n = 5835, 18% [95% CI 17-19%]), than in the general population (4 studies, n = 1707, 2% [95% CI 2-3%]). Seven studies in total reported sex-stratified prevalence estimates (men: 7% [95% CI 5-8%] vs. women: 1.3% [95% CI 0.0.2.2%]). The prevalence of HFrEF was available in one general population study (5.8% [95% CI 3.7.6%], men: 6.8% vs. women: 3.0%). The summary prevalence of LVSD is higher among T2D patients from a hospital setting compared with from the general population, with a higher prevalence in men than in women in both settings. The prevalence of HFrEF among T2D in the population was only assessed in a single study and again was higher among men than women.

HFpEF and HFrEF Display Different Phenotypes as Assessed by IGF-1 and IGFBP-1.

PubMed

Faxén, Ulrika Ljung; Hage, Camilla; Benson, Lina; Zabarovskaja, Stanislava; Andreasson, Anna; Donal, Erwan; Daubert, Jean-Claude; Linde, Cecilia; Brismar, Kerstin; Lund, Lars H

2017-04-01

Anabolic drive is impaired in heart failure with reduced ejection fraction (HFrEF) but insufficiently studied in heart failure with preserved ejection fraction (HFpEF). Insulin-like growth factor 1 (IGF-1) mediates growth hormone effects and IGF binding protein 1 (IGFBP-1) regulates IGF-1 activity. We tested the hypothesis that HFpEF and HFrEF are similar with regard to IGF-1 and IGFBP-1. In patients with HFpEF (n = 79), HFrEF (n = 85), and controls (n = 136), we analyzed serum IGF-1 and IGFBP-1 concentrations, correlations, and associations with outcome. Age-standardized scores of IGF-1 were higher in HFpEF, median arbitrary units (interquartile range); 1.21 (0.57-1.96) vs HFrEF, 0.09 (-1.40-1.62), and controls, 0.22 (-0.47-0.96), P overall <.001. IGFBP-1 was increased in HFpEF, 48 (28-79), and HFrEF, 65 (29-101), vs controls, 27(14-35) µg/L, P overall <.001. These patterns persisted after adjusting for metabolic and HF severity confounders. IGF-1 was associated with outcomes in HFrEF, hazard ratio per natural logarithmic increase in IGF-1 SD score 0.51 (95% confidence interval 0.32-0.82, P = .005), but not significantly in HFpEF. IGFBP-1 was not associated with outcomes in either HFpEF nor HFrEF. HFpEF and HFrEF phenotypes were similar with regard to increased IGFBP-1 concentrations but differed regarding IGF-1 levels and prognostic role. HFrEF and HFpEF may display different impairment in anabolic drive. Copyright © 2016 Elsevier Inc. All rights reserved.

Mitochondrial Respiration Inhibitors Suppress Protein Translation and Hypoxic Signaling via the Hyperphosphorylation and Inactivation of Translation Initiation Factor eIF2α and Elongation Factor eEF2

PubMed Central

Li, Jun; Mahdi, Fakhri; Du, Lin; Datta, Sandipan; Nagle, Dale G.; Zhou, Yu-Dong

2011-01-01

Over 20000 lipid extracts of plants and marine organisms were evaluated in a human breast tumor T47D cell-based reporter assay for hypoxia-inducible factor-1 (HIF-1) inhibitory activity. Bioassay-guided isolation and dereplication-based structure elucidation of an active extract from the Bael tree (Aegle marmelos) afforded two protolimonoids, skimmiarepin A (1) and skimmiarepin C (2). In T47D cells, 1 and 2 inhibited hypoxia-induced HIF-1 activation with IC50 values of 0.063 µM and 0.068 µM, respectively. Compounds 1 and 2 also suppressed hypoxic induction of the HIF-1 target genes GLUT-1 and VEGF. Mechanistic studies revealed that 1 and 2 inhibited HIF-1 activation by blocking the hypoxia-induced accumulation of HIF-1α protein. At the range of concentrations that inhibited HIF-1 activation, 1 and 2 suppressed cellular respiration by selectively inhibiting the mitochondrial electron transport chain at complex I (NADH dehydrogenase). Further investigation indicated that mitochondrial respiration inhibitors such as 1 and rotenone induced the rapid hyperphosphorylation and inhibition of translation initiation factor eIF2α and elongation factor eEF2. The inhibition of protein translation may account for the short-term exposure effects exerted by mitochondrial inhibitors on cellular signaling, while the suppression of cellular ATP production may contribute to the inhibitory effects following extended treatment periods. PMID:21875114

Evaluation of a teacher training program to enhance executive functions in preschool children.

PubMed

Walk, Laura M; Evers, Wiebke F; Quante, Sonja; Hille, Katrin

2018-01-01

Executive functions (EFs) play a critical role in cognitive and social development. During preschool years, children show not only rapid improvement in their EFs, but also appear sensitive to developmentally appropriate interventions. EMIL is a training program for German preschool teachers that was developed and implemented to improve the EFs of preschoolers. The aim of the present study was to evaluate its effects on the EFs of children between three and six years old. The teacher training (eight sessions, 28.5 hours) was implemented in four preschools. The EFs of children of the intervention group (n = 72, 32 girls, Mage = 48 months) and the control group of four other matched preschools (n = 61, 27 girls, Mage = 48 months) were tested before, during, and after the intervention using different measures assessing working memory, inhibitory control, and cognitive flexibility. The intervention group showed significant gains on three out of seven EF tests (behavioral inhibition, visual-spatial working memory, and combined EFs) compared to the control group. Post hoc analyses for children with low initial EFs scores revealed that participation in the intervention led to significant gains in inhibitory control, visual-spatial working memory, and phonological working memory as well as a marginally significant difference for combined EFs. However, effect sizes were rather small. The results suggest that teacher training can lead to significant improvements in preschooler's EFs. Although preliminary, the results could contribute to the discussion on how teacher training can facilitate the improvement of EFs in preschool children.

Executive function predicts theory of mind but not social verbal communication in school-aged children with autism spectrum disorder.

PubMed

Kouklari, Evangelia-Chrysanthi; Tsermentseli, Stella; Auyeung, Bonnie

2018-05-01

The association between Executive Function (EF) and Theory of Mind (ToM) in autism spectrum disorder (ASD) has been mainly investigated using false belief tasks, whilst less is known about the EF effect on other ToM facets. Furthermore, the role EF plays in social communication in ASD is mainly assessed using parent-report EF ratings rather than direct assessment. The aim of this study was to shed more light on the effect of performance-based EF measures on ToM and social communication in middle childhood in ASD relative to neurotypical controls. Cross-sectional data were collected from 64 matched, school-aged children with and without ASD (8-12 years old), tested on measures of EF (inhibition, working memory, cognitive flexibility), ToM mental state/emotion recognition and social verbal communication. Significant group differences were observed only in selective EF skills (inhibition &cognitive flexibility) and social verbal communication. EF working memory contributed to the explained variance of ToM but not social verbal communication in middle childhood. These findings suggest that EF and ToM are still associated in middle childhood and EF may be a crucial predictor of ToM across childhood in ASD. Implications are discussed regarding the social-cognitive impairment relationship in ASD. Copyright © 2018 Elsevier Ltd. All rights reserved.

5-HT4 receptor agonists enhance both cholinergic and nitrergic activities in human isolated colon circular muscle.

PubMed

Cellek, S; John, A K; Thangiah, R; Dass, N B; Bassil, A K; Jarvie, E M; Lalude, O; Vivekanandan, S; Sanger, G J

2006-09-01

Previous studies have demonstrated mixed inhibitory and facilitatory effects of 5-hydroxytryptamine-4 (5-HT(4)) receptor agonists on electrical field stimulation (EFS)-induced responses in human isolated colon. Here we report three types of responses to EFS in human isolated colon circular muscle: monophasic cholinergic contraction during EFS, biphasic response (nitrergic relaxation during EFS followed by cholinergic contraction after termination of EFS) and triphasic response (cholinergic contraction followed by nitrergic relaxation during EFS and a tachykininergic contraction after EFS). The effects of two 5-HT(4) receptor agonists, prucalopride and tegaserod were then investigated on monophasic responses only. Each compound inhibited contractions during EFS in a concentration-dependent manner. In the presence of N(omega)-nitro-l-arginine methyl ester (l-NAME) however, prucalopride and tegaserod enhanced the contractions in a concentration-dependent manner. In strips where the tone was elevated with substance-P and treated with scopolamine, EFS-induced relaxations were enhanced by the two agonists. The above observed effects by the two agonists were abolished by 5-HT(4) receptor antagonist SB-204070. The two agonists did not alter the tone raised by substance-P in the presence of scopolamine and l-NAME and did not affect carbachol-induced contractions in the presence of tetrodotoxin. These results suggest that in the circular muscle of human colon, 5-HT(4) receptor agonists simultaneously facilitate the activity of neurones which release the inhibitory and excitatory neurotransmitters, nitric oxide and acetylcholine respectively.

Executive Functioning Predicts Academic Achievement in Middle School: A Four-Year Longitudinal Study

ERIC Educational Resources Information Center

Samuels, William Ellery; Tournaki, Nelly; Blackman, Sheldon; Zilinski, Christopher

2016-01-01

Executive functioning (EF) is a strong predictor of children's and adolescents' academic performance. Although research indicates that EF can increase during childhood and adolescence, few studies have tracked the effect of EF on academic performance throughout the middle school grades. EF was measured at the end of Grades 6-9 through 21 teachers'…

Effect of sodium nitroprusside and 8-bromo cyclic GMP on nerve-mediated and acetylcholine-evoked secretory responses in the rat pancreas

PubMed Central

Yago, Maria D; Tapia, Jose A; Salido, Gines M; Adeghate, Ernest; Juma, Lubna M O; Martinez-Victoria, Emilio; Mañas, Mariano; Singh, Jaipaul

2002-01-01

The effects of sodium nitroprusside (SNP) and 8-bromo-guanosine 3′5′ cyclic monophosphate (8-Br-cyclic GMP) on nerve-mediated and acetylcholine (ACh)-evoked amylase secretion, tritiated choline ([3H]-choline) release and on intracellular free calcium concentration ([Ca2+]i) in the isolated rat pancreas were investigated.Electrical field stimulation (EFS; 10 Hz) and ACh (1×10−5 M) caused large increases in amylase output from pancreatic segments. The response to ACh was blocked by atropine (1×10−5 M) whereas the EFS-evoked response was markedly reduced but not abolished. In contrast, pretreatment with tetrodotoxin (1×10−6 M) abolished the secretory effect of EFS.Either SNP (1×10−3 M) or 8-Br-cyclic GMP (1×10−4 M) inhibited amylase secretion compared to basal. Combining either SNP or 8-Br-cyclic GMP with EFS resulted in a marked decrease in amylase output compared to EFS alone. In contrast, either SNP or 8-Br-cyclic GMP had no significant effect on the amylase response to ACh. When extracellular Ca2+ concentration ([Ca2+]o) was elevated from 2.56 mM to 5.12 mM, SNP failed to inhibit the response to EFS.EFS stimulated the release of 3H from pancreatic segments preloaded with [3H]-choline. Either SNP or 8-Br-cyclic GMP had no effect on basal 3H release but significantly reduced the EFS-evoked response.In fura-2 loaded acinar cells, SNP elicited a small decrease in [Ca2+]i compared to basal and had no effect on the ACh-induced [Ca2+]i peak response.Nitric oxide may modulate the release of endogenous neural ACh in response to EFS in the rat pancreas. PMID:11976267

Modulation of spike coding by subthreshold extracellular electric fields and neuronal morphology

NASA Astrophysics Data System (ADS)

Wei, Xile; Li, Bingjie; Lu, Meili; Yi, Guosheng; Wang, Jiang

2015-07-01

We use a two-compartment model, which includes soma and dendrite, to explore how extracellular subthreshold sinusoidal electric fields (EFs) influence the spike coding of an active neuron. By changing the intensity and the frequency of subthreshold EFs, we find that subthreshold EFs indeed affect neuronal coding remarkably within several stimulus frequency windows where the field effects on spike timing are stronger than that on spiking rate. The field effects are maximized at several harmonics of the intrinsic spiking frequency of an active neuron. Our findings implicate the potential resonance mechanism underlying subthreshold field effects. We also discuss how neuronal morphologic properties constrain subthreshold EF effects on spike timing. The morphologic properties are represented by two parameters, gc and p, where gc is the internal conductance between soma and dendrite and geometric factor p characterizes the proportion of area occupied by soma. We find that the contribution to field effects from the variation of p is stronger than that from gc, which suggests that neuronal geometric features play a crucial role in subthreshold field effects. Theoretically, these insights into how subthreshold sinusoidal EFs modulate ongoing neuron behaviors could contribute to uncovering the relevant mechanism of subthreshold sinusoidal EFs effects on neuronal coding. Furthermore, they are useful in rationally designing noninvasive brain stimulation strategies and developing electromagnetic stimulus techniques.

Liposome-encapsulated EF24-HPβCD inclusion complex: a preformulation study and biodistribution in a rat model

NASA Astrophysics Data System (ADS)

Agashe, H.; Lagisetty, P.; Sahoo, K.; Bourne, D.; Grady, B.; Awasthi, V.

2011-06-01

3,5-Bis(2-fluorobenzylidene)-4-piperidone (EF24) is an anti-proliferative diphenyldifluoroketone analog of curcumin with more potent activity. The authors describe a liposome preparation of EF24 using a "drug-in-CD-in liposome" approach. An aqueous solution of EF24 and hydroxypropyl-β-cyclodextrin (HPβCD) inclusion complex (IC) was used to prepare EF24 liposomes. The liposome size was reduced by a combination of multiple freeze-thaw cycles. Co-encapsulation of glutathione inside the liposomes conferred them with the capability of labeling with imageable radionuclide Tc-99m. Phase solubility analysis of EF24-HPβCD mixture provided k 1:1 value of 9.9 M-1. The enhanced aqueous solubility of EF24 (from 1.64 to 13.8 mg/mL) due to the presence of HPβCD helped in the liposome preparation. About 19% of the EF24 IC was encapsulated inside the liposomes (320.5 ± 2.6 nm) by dehydration-rehydration technique. With extrusion technique, the size of 177 ± 6.5 nm was obtained without any effect on encapsulation efficiency. The EF24-liposomes were evaluated for anti-proliferative activity in lung adenocarcinoma H441 and prostate cancer PC-3 cells. The EF24-liposomes demonstrated anti-proliferative activity superior to that of plain EF24 at 10 μM dose. When injected in rats, the Tc-99m-labeled EF24-liposomes cleared from blood with an α- t 1/2 of 21.4 min and β- t 1/2 of 397 min. Tissue radioactivity counting upon necropsy showed that the majority of clearance was due to the uptake in liver and spleen. The results suggest that using "drug-in-CD-in liposome" approach is a feasible strategy to formulate an effective parenteral preparation of EF24. In vitro studies show that the liposomal EF24 remains anti-proliferative, while presenting an opportunity to image its biodistribution.

Liposome-encapsulated EF24-HPβCD inclusion complex: a preformulation study and biodistribution in a rat model

PubMed Central

Agashe, H.; Lagisetty, P.; Sahoo, K.; Bourne, D.; Grady, B.

2011-01-01

3,5-Bis(2-fluorobenzylidene)-4-piperidone (EF24) is an anti-proliferative diphenyldifluoroketone analog of curcumin with more potent activity. The authors describe a liposome preparation of EF24 using a “drug-in-CD-in liposome” approach. An aqueous solution of EF24 and hydroxypropyl-β-cyclodextrin (HPβCD) inclusion complex (IC) was used to prepare EF24 liposomes. The liposome size was reduced by a combination of multiple freeze–thaw cycles. Co-encapsulation of glutathione inside the liposomes conferred them with the capability of labeling with imageable radionuclide Tc-99m. Phase solubility analysis of EF24-HPβCD mixture provided k1:1 value of 9.9 M−1. The enhanced aqueous solubility of EF24 (from 1.64 to 13.8 mg/mL) due to the presence of HPβCD helped in the liposome preparation. About 19% of the EF24 IC was encapsulated inside the liposomes (320.5 ± 2.6 nm) by dehydration–rehydration technique. With extrusion technique, the size of 177 ± 6.5 nm was obtained without any effect on encapsulation efficiency. The EF24-liposomes were evaluated for anti-proliferative activity in lung adenocarcinoma H441 and prostate cancer PC-3 cells. The EF24-liposomes demonstrated anti-proliferative activity superior to that of plain EF24 at 10 μM dose. When injected in rats, the Tc-99m-labeled EF24-liposomes cleared from blood with an α-t1/2 of 21.4 min and β-t1/2 of 397 min. Tissue radioactivity counting upon necropsy showed that the majority of clearance was due to the uptake in liver and spleen. The results suggest that using “drug-in-CD-in liposome” approach is a feasible strategy to formulate an effective parenteral preparation of EF24. In vitro studies show that the liposomal EF24 remains anti-proliferative, while presenting an opportunity to image its biodistribution. PMID:21779150

Liposome-encapsulated EF24-HPβCD inclusion complex: a preformulation study and biodistribution in a rat model.

PubMed

Agashe, H; Lagisetty, P; Sahoo, K; Bourne, D; Grady, B; Awasthi, V

2011-06-01

3,5-Bis(2-fluorobenzylidene)-4-piperidone (EF24) is an anti-proliferative diphenyldifluoroketone analog of curcumin with more potent activity. The authors describe a liposome preparation of EF24 using a "drug-in-CD-in liposome" approach. An aqueous solution of EF24 and hydroxypropyl-β-cyclodextrin (HPβCD) inclusion complex (IC) was used to prepare EF24 liposomes. The liposome size was reduced by a combination of multiple freeze-thaw cycles. Co-encapsulation of glutathione inside the liposomes conferred them with the capability of labeling with imageable radionuclide Tc-99m. Phase solubility analysis of EF24-HPβCD mixture provided k(1:1) value of 9.9 M(-1). The enhanced aqueous solubility of EF24 (from 1.64 to 13.8 mg/mL) due to the presence of HPβCD helped in the liposome preparation. About 19% of the EF24 IC was encapsulated inside the liposomes (320.5 ± 2.6 nm) by dehydration-rehydration technique. With extrusion technique, the size of 177 ± 6.5 nm was obtained without any effect on encapsulation efficiency. The EF24-liposomes were evaluated for anti-proliferative activity in lung adenocarcinoma H441 and prostate cancer PC-3 cells. The EF24-liposomes demonstrated anti-proliferative activity superior to that of plain EF24 at 10 μM dose. When injected in rats, the Tc-99m-labeled EF24-liposomes cleared from blood with an α-t(1/2) of 21.4 min and β-t(1/2) of 397 min. Tissue radioactivity counting upon necropsy showed that the majority of clearance was due to the uptake in liver and spleen. The results suggest that using "drug-in-CD-in liposome" approach is a feasible strategy to formulate an effective parenteral preparation of EF24. In vitro studies show that the liposomal EF24 remains anti-proliferative, while presenting an opportunity to image its biodistribution.

Automated dynamic hollow fiber liquid-liquid-liquid microextraction combined with capillary electrophoresis for speciation of mercury in biological and environmental samples.

PubMed

Li, Pingjing; He, Man; Chen, Beibei; Hu, Bin

2015-10-09

A simple home-made automatic dynamic hollow fiber based liquid-liquid-liquid microextraction (AD-HF-LLLME) device was designed and constructed for the simultaneous extraction of organomercury and inorganic mercury species with the assistant of a programmable flow injection analyzer. With 18-crown-6 as the complexing reagent, mercury species including methyl-, ethyl-, phenyl- and inorganic mercury were extracted into the organic phase (chlorobenzene), and then back-extracted into the acceptor phase of 0.1% (m/v) 3-mercapto-1-propanesulfonic acid (MPS) aqueous solution. Compared with automatic static (AS)-HF-LLLME system, the extraction equilibrium of target mercury species was obtained in shorter time with higher extraction efficiency in AD-HF-LLLME system. Based on it, a new method of AD-HF-LLLME coupled with large volume sample stacking (LVSS)-capillary electrophoresis (CE)/UV detection was developed for the simultaneous analysis of methyl-, phenyl- and inorganic mercury species in biological samples and environmental water. Under the optimized conditions, AD-HF-LLLME provided high enrichment factors (EFs) of 149-253-fold within relatively short extraction equilibrium time (25min) and good precision with RSD between 3.8 and 8.1%. By combining AD-HF-LLLME with LVSS-CE/UV, EFs were magnified up to 2195-fold and the limits of detection (at S/N=3) for target mercury species were improved to be sub ppb level. Copyright © 2015 Elsevier B.V. All rights reserved.

Effect of isothermal dilution on emission factors of organic carbon and n-alkanes in the particle and gas phases of diesel exhaust

NASA Astrophysics Data System (ADS)

Fujitani, Yuji; Saitoh, Katsumi; Fushimi, Akihiro; Takahashi, Katsuyuki; Hasegawa, Shuich; Tanabe, Kiyoshi; Kobayashi, Shinji; Furuyama, Akiko; Hirano, Seishiro; Takami, Akinori

2012-11-01

To investigate the effect of isothermal dilution (30 °C) on emission factors (EFs) of semivolatile and nonvolatile compounds of heavy-duty diesel exhaust, we measured EFs for particulate matter (PM), organic carbon (OC), and elemental carbon (EC) in the particle phase, and EFs for n-alkanes in both the particle phase and the gas phase of exhaust produced under high-idle engine operating conditions at dilution ratios (DRs) ranging from 8 to 1027. The EC EFs did not vary with DR, whereas the OC EFs in the particle phase determined at DR = 1027 were 13% of the EFs determined at DR = 8, owing to evaporation of organic compounds. Using partitioning theory and n-alkane EFs measured at DR = 14 and 238, we calculated the distributions of compounds between the particle and gas phases at DR = 1760, which corresponds to the DR for tailpipe emissions as they move from the tailpipe to the roadside atmosphere. The gas-phase EF of a compound with a vapor pressure of 10-7 Pa was 0.01 μg kg-1-fuel at DR = 14, and this value is 1/330 the value derived at DR = 1760. Our results suggest that the EFs of high-volatility compounds in the particle phase will be overestimated and that the EFs of low-volatility compounds in the gas phase will be underestimated if the estimates are derived from data obtained at the low DRs and they are applied to the real world. Therefore, extrapolation from EFs derived at low DR values to EFs at atmospherically relevant DRs will be a source of error in predictions of the concentrations of particulate matter and gas-phase precursors to secondary organic aerosols in air quality models.

Protocol: Adaptive Implementation of Effective Programs Trial (ADEPT): cluster randomized SMART trial comparing a standard versus enhanced implementation strategy to improve outcomes of a mood disorders program.

PubMed

Kilbourne, Amy M; Almirall, Daniel; Eisenberg, Daniel; Waxmonsky, Jeanette; Goodrich, David E; Fortney, John C; Kirchner, JoAnn E; Solberg, Leif I; Main, Deborah; Bauer, Mark S; Kyle, Julia; Murphy, Susan A; Nord, Kristina M; Thomas, Marshall R

2014-09-30

Despite the availability of psychosocial evidence-based practices (EBPs), treatment and outcomes for persons with mental disorders remain suboptimal. Replicating Effective Programs (REP), an effective implementation strategy, still resulted in less than half of sites using an EBP. The primary aim of this cluster randomized trial is to determine, among sites not initially responding to REP, the effect of adaptive implementation strategies that begin with an External Facilitator (EF) or with an External Facilitator plus an Internal Facilitator (IF) on improved EBP use and patient outcomes in 12 months. This study employs a sequential multiple assignment randomized trial (SMART) design to build an adaptive implementation strategy. The EBP to be implemented is life goals (LG) for patients with mood disorders across 80 community-based outpatient clinics (N = 1,600 patients) from different U.S. regions. Sites not initially responding to REP (defined as < 50% patients receiving ≥ 3 EBP sessions) will be randomized to receive additional support from an EF or both EF/IF. Additionally, sites randomized to EF and still not responsive will be randomized to continue with EF alone or to receive EF/IF. The EF provides technical expertise in adapting LG in routine practice, whereas the on-site IF has direct reporting relationships to site leadership to support LG use in routine practice. The primary outcome is mental health-related quality of life; secondary outcomes include receipt of LG sessions, mood symptoms, implementation costs, and organizational change. This study design will determine whether an off-site EF alone versus the addition of an on-site IF improves EBP uptake and patient outcomes among sites that do not respond initially to REP. It will also examine the value of delaying the provision of EF/IF for sites that continue to not respond despite EF. ClinicalTrials.gov identifier: NCT02151331.

Effects of dietary fat and crude protein on feedlot performance, carcass characteristics, and meat quality in finishing steers fed differing levels of dried distillers grains with solubles.

PubMed

Gunn, P J; Weaver, A D; Lemenager, R P; Gerrard, D E; Claeys, M C; Lake, S L

2009-09-01

The objective of this study was to evaluate the influence of dietary protein and fat from distillers dried grains with solubles (DDGS) on feedlot performance, carcass characteristics, and meat quality in finishing steers. Angus-cross steers (n = 105; 443 +/- 20 kg of BW) were blocked by BW and randomly assigned to 1 of 5 dietary treatments: 1) corn-based diet with DDGS included at 25% of DM (CON), 2) CON with DDGS included at twice the amount of CON (50% of DM; 50DDGS), 3) CON with added corn protein to equal the CP in the 50DDGS diet (CON+CP), 4) CON with added vegetable oil to equal the fat in the 50DDGS diet (CON+VO), and 5) CON with protein and fat added to equal the CP and fat in the 50DDGS diet (CON+CPVO). Steers were fed to a common 12th-rib fat depth endpoint (1.3 +/- 0.2 cm; 68 to 125 d on trial). Loins and rounds were collected from 44 carcasses for Warner-Bratzler shear force (WBSF), ether extract, and case-life analyses. Data were analyzed using the MIXED procedure of SAS. Contrasts between 1) CON vs. elevated CP diets (50DDGS, CON+CP, and CON+CPVO; EP), 2) CON vs. elevated fat diets (50DDGS, CON+VO, and CON+CPVO; EF) and 3) CON vs. diets with elevated CP and fat (50DDGS and CON+CPVO; EPF) were analyzed. There were no differences in days on feed or DMI among treatments. Steers fed CON had greater ADG (P or= 0.06). Steers fed the CON diet had greater marbling scores (P or= 0.44). However, CON steers had greater (P = 0.02) L* values than EF-fed steers and greater b* values than EP, EF, and EPF steers (P

Determination of sugars composition in abscission zone of oil palm fruit

NASA Astrophysics Data System (ADS)

Thang, Y. M.; Ariffin, A. A.; Appleton, D. R.; Asis, A. J.; Mokhtar, M. N.; Yunus, R.

2017-06-01

Fresh oil palm fruit bunches (FFB) arriving at a palm oil mill are graded manually and randomly for ripeness classification by counting the number of empty fruit sockets (EFS) found in each bunch before processing. FFBs with at least ten EFS are classified as ripe bunch, FFBs with less than ten EFS are classified as under-ripe, while bunches without any EFS are classified as unripe. The aim of the present study is to determine the composition of sugars in the abscission of these three groups of FFBs by monitoring their sugars composition. The bunches were grouped according to the number of empty fruit sockets: (i) nil; (ii) 1-9; (iii) ≥10 as unripe, under-ripe and ripe bunches, respectively. Non-structural, structural and water-soluble sugars extracted from the abscission zone were analyzed. The principal component analysis (PCA) based on various sugars compositions revealed some natural clustering among the samples. Bunches with more than one empty fruit sockets were distinguished from the others using glucose, sucrose and oligomers. In conclusion, analysis of sugars composition of the abscission zone could potentially be used as a chemical marker to differentiate those bunches at different stages of ripeness.

Ribosomal elongation factor 4 promotes cell death associated with lethal stress.

PubMed

Li, Liping; Hong, Yuzhi; Luan, Gan; Mosel, Michael; Malik, Muhammad; Drlica, Karl; Zhao, Xilin

2014-12-09

Ribosomal elongation factor 4 (EF4) is highly conserved among bacteria, mitochondria, and chloroplasts. However, the EF4-encoding gene, lepA, is nonessential and its deficiency shows no growth or fitness defect. In purified systems, EF4 back-translocates stalled, posttranslational ribosomes for efficient protein synthesis; consequently, EF4 has a protective role during moderate stress. We were surprised to find that EF4 also has a detrimental role during severe stress: deletion of lepA increased Escherichia coli survival following treatment with several antimicrobials. EF4 contributed to stress-mediated lethality through reactive oxygen species (ROS) because (i) the protective effect of a ΔlepA mutation against lethal antimicrobials was eliminated by anaerobic growth or by agents that block hydroxyl radical accumulation and (ii) the ΔlepA mutation decreased ROS levels stimulated by antimicrobial stress. Epistasis experiments showed that EF4 functions in the same genetic pathway as the MazF toxin, a stress response factor implicated in ROS-mediated cell death. The detrimental action of EF4 required transfer-messenger RNA (tmRNA, which tags truncated proteins for degradation and is known to be inhibited by EF4) and the ClpP protease. Inhibition of a protective, tmRNA/ClpP-mediated degradative activity would allow truncated proteins to indirectly perturb the respiratory chain and thereby provide a potential link between EF4 and ROS. The connection among EF4, MazF, tmRNA, and ROS expands a pathway leading from harsh stress to bacterial self-destruction. The destructive aspect of EF4 plus the protective properties described previously make EF4 a bifunctional factor in a stress response that promotes survival or death, depending on the severity of stress. Translation elongation factor 4 (EF4) is one of the most conserved proteins in nature, but it is dispensable. Lack of strong phenotypes for its genetic knockout has made EF4 an enigma. Recent biochemical work has demonstrated that mild stress may stall ribosomes and that EF4 can reposition stalled ribosomes to resume proper translation. Thus, EF4 protects cells from moderate stress. Here we report that EF4 is paradoxically harmful during severe stress, such as that caused by antimicrobial treatment. EF4 acts in a pathway that leads to excessive accumulation of reactive oxygen species (ROS), thereby participating in a bacterial self-destruction that occurs when cells cannot effectively repair stress-mediated damage. Thus, EF4 has two opposing functions-at low-to-moderate levels of stress, the protein is protective by allowing stress-paused translation to resume; at high-levels of stress, EF4 helps bacteria self-destruct. These data support the existence of a bacterial live-or-die response to stress. Copyright © 2014 Li et al.

Regulation of adipose-tissue-derived stromal cell orientation and motility in 2D- and 3D-cultures by direct-current electrical field.

PubMed

Yang, Gang; Long, Haiyan; Ren, Xiaomei; Ma, Kunlong; Xiao, Zhenghua; Wang, Ying; Guo, Yingqiang

2017-02-01

Cell alignment and motility play a critical role in a variety of cell behaviors, including cytoskeleton reorganization, membrane-protein relocation, nuclear gene expression, and extracellular matrix remodeling. Direct current electric field (EF) in vitro can direct many types of cells to align vertically to EF vector. In this work, we investigated the effects of EF stimulation on rat adipose-tissue-derived stromal cells (ADSCs) in 2D-culture on plastic culture dishes and in 3D-culture on various scaffold materials, including collagen hydrogels, chitosan hydrogels and poly(L-lactic acid)/gelatin electrospinning fibers. Rat ADSCs were exposed to various physiological-strength EFs in a homemade EF-bioreactor. Changes of morphology and movements of cells affected by applied EFs were evaluated by time-lapse microphotography, and cell survival rates and intracellular calcium oscillations were also detected. Results showed that EF facilitated ADSC morphological changes, under 6 V/cm EF strength, and that ADSCs in 2D-culture aligned vertically to EF vector and kept a good cell survival rate. In 3D-culture, cell galvanotaxis responses were subject to the synergistic effect of applied EF and scaffold materials. Fast cell movement and intracellular calcium activities were observed in the cells of 3D-culture. We believe our research will provide some experimental references for the future study in cell galvanotaxis behaviors. © 2017 Japanese Society of Developmental Biologists.

The Probabilistic Efficiency Frontier: A Framework for Cost-Effectiveness Analysis in Germany Put into Practice for Hepatitis C Treatment Options.

PubMed

Mühlbacher, Axel C; Sadler, Andrew

2017-02-01

The German Institute for Quality and Efficiency in Health Care (Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen) adapted the efficiency frontier (EF) approach to conform to statutory provisions on cost-effectiveness analysis of health technologies. EF serves as a framework for evaluating cost-effectiveness and indirectly for pricing and reimbursement decisions. To calculate an EF on the basis of single multidimensional benefit by taking patient preferences and uncertainty into account; to evaluate whether EF is useful to inform decision makers about cost-effectiveness of new therapies; and to find whether a treatment is efficient at given prices demonstrated through a case study on chronic hepatitis C. A single multidimensional benefit was calculated by linear additive aggregation of multiple patient-relevant end points. End points were identified and weighted by patients in a previous discrete-choice experiment (DCE). Aggregation of overall benefit was ascertained using preferences and clinical data. Monte-Carlo simulation was applied. Uncertainty was addressed by price acceptability curve (PAC) and net monetary benefit (NMB). The case study illustrates that progress in benefit and efficiency of hepatitis C virus treatments could be depicted very well with the EF. On the basis of cost, effect, and preference data, the latest generations of interferon-free treatments are shown to yield a positive NMB and be efficient at current prices. EF was implemented taking uncertainty into account. For the first time, a DCE was used with the EF. The study shows how DCEs in combination with EF, PAC, and NMB can contribute important information in the course of reimbursement and pricing decisions. Copyright © 2017 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Simultaneous removal of phosphorus and EfOM using MIEX, coagulation, and low-pressure membrane filtration.

PubMed

Kim, Hyun-Chul; Timmes, Thomas C; Dempsey, Brian A

2015-01-01

The feasibility of using magnetic ion exchange (MIEX) treatment, in-line alum coagulation, and low-pressure membrane filtration was investigated for the simultaneous removal of total phosphorus (TP) and effluent organic matter (EfOM) from biologically treated wastewater. The focus was also placed on minimizing fouling of polyvinylidene fluoride and polyethersulfone membranes, which are the most commonly used low-pressure membranes in new and retrofit wastewater treatment plants. MIEX alone was effective for the removal of EfOM, and MIEX plus a small alum dose was very effective in removing both EfOM and TP. MIEX removed phosphorus, but organic acids in EfOM were preferentially removed, and the effects of competing anions on the removal of EfOM were insignificant. All the pretreatment strategies decreased the resistance to filtration. The greatest decrease in fouling was achieved by using MIEX (15 mL L⁻¹) plus a very low dose of alum (∼0.5 mg Al L⁻¹). Sweep floc coagulation using alum and without MIEX also significantly decreased fouling but did not effectively remove EfOM and produced high floc volume that could be problematic for inside-out hollow-fibre modules. The addition of these reagents into rapid mix followed by membrane filtration would provide operational simplicity and could be easily retrofitted at existing membrane filtration facilities.

Prognostic significance of hemoglobin level in patients with congestive heart failure and normal ejection fraction.

PubMed

Varadarajan, Padmini; Gandhi, Siddharth; Sharma, Sanjay; Umakanthan, Branavan; Pai, Ramdas G

2006-10-01

Previous studies have shown low hemoglobin (Hb) to have an adverse effect on survival in patients with congestive heart failure (CHF) and reduced left ventricular (LV) ejection fraction (EF); but its effect on survival in patients with CHF and normal EF is not known. This study sought to determine whether low Hb has an effect on survival in patients with both CHF and normal EF. Detailed chart reviews were performed by medical residents on 2,246 patients (48% with normal EF) with a discharge diagnosis of CHF in a large tertiary care hospital from 1990 to 1999. The CHF diagnosis was validated using the Framingham criteria. Mortality data were obtained from the National Death Index. Survival analysis was performed using Kaplan-Meier and Cox regression models. By Kaplan-Meier analysis, low Hb (< 12 gm/dl) compared with normal hemoglobin was associated with a lower 5-year survival in patients with CHF and both normal (38 vs. 50%, p = 0.0008) and reduced (35 vs. 48%, p = 0.0009) EF. Using the Cox regression model, low Hb was an independent predictor of mortality after adjusting for age, gender, renal dysfunction, diabetes mellitus, hypertension, and EF in both groups of patients. Low Hb has an independent adverse effect on survival in patients with CHF and both normal and reduced EF in both groups of patients.

Anti-inflammatory activity of bioaccessible fraction from Eryngium foetidum leaves.

PubMed

Dawilai, Suwitcha; Muangnoi, Chawanphat; Praengamthanachoti, Phawachaya; Tuntipopipat, Siriporn

2013-01-01

Eryngium foetidum (EF) has long been used as a medicinal plant and culinary spice in tropical regions. Phytochemicals in its leaves have been proposed to be responsible for the anti-inflammatory and antioxidant activities. The present study used in vitro digestion coupled with Caco-2 cells to assess such activities. Caco-2 cells were incubated with aqueous fraction from simulated digestion (bioaccessible fraction) of EF leaves with/without bile extract prior to stimulation with interleukin-1 beta (IL-1β). Monocyte chemoattractant protein-1 (MCP-1) and IL-8 in culture media and the intracellular reactive oxygen species (ROS) were measured. Approximately 24% β-carotene and 35% lutein of leaves were present in the aqueous fraction. The transfer of caffeic and chlorogenic acids to the aqueous fraction was 76%-81%, while that of kaempferol was 48%. Prior incubation of Caco-2 cells with the bioaccessible fraction suppressed IL-1β activated IL-8 and MCP-1 by 33%, but the fraction lacking mixed micelles decreased IL-8 and MCP-1 levels only by 11%. The pretreatment of Caco-2 cells with the bioaccessible fraction of EF reduced ROS by 34%; the fraction lacking mixed micelles decreased ROS by 28%. These data suggest that bioactive compounds partitioning in mixed micelles play a significant role to suppress the proinflammatory insult but with a modest antioxidant effect.

Anti-Inflammatory Activity of Bioaccessible Fraction from Eryngium foetidum Leaves

PubMed Central

Dawilai, Suwitcha; Muangnoi, Chawanphat; Praengamthanachoti, Phawachaya; Tuntipopipat, Siriporn

2013-01-01

Eryngium foetidum (EF) has long been used as a medicinal plant and culinary spice in tropical regions. Phytochemicals in its leaves have been proposed to be responsible for the anti-inflammatory and antioxidant activities. The present study used in vitro digestion coupled with Caco-2 cells to assess such activities. Caco-2 cells were incubated with aqueous fraction from simulated digestion (bioaccessible fraction) of EF leaves with/without bile extract prior to stimulation with interleukin-1 beta (IL-1β). Monocyte chemoattractant protein-1 (MCP-1) and IL-8 in culture media and the intracellular reactive oxygen species (ROS) were measured. Approximately 24% β-carotene and 35% lutein of leaves were present in the aqueous fraction. The transfer of caffeic and chlorogenic acids to the aqueous fraction was 76%–81%, while that of kaempferol was 48%. Prior incubation of Caco-2 cells with the bioaccessible fraction suppressed IL-1β activated IL-8 and MCP-1 by 33%, but the fraction lacking mixed micelles decreased IL-8 and MCP-1 levels only by 11%. The pretreatment of Caco-2 cells with the bioaccessible fraction of EF reduced ROS by 34%; the fraction lacking mixed micelles decreased ROS by 28%. These data suggest that bioactive compounds partitioning in mixed micelles play a significant role to suppress the proinflammatory insult but with a modest antioxidant effect. PMID:24151629

Phylogenetic structure of soil bacterial communities predicts ecosystem functioning.

PubMed

Pérez-Valera, Eduardo; Goberna, Marta; Verdú, Miguel

2015-05-01

Quantifying diversity with phylogeny-informed metrics helps understand the effects of diversity on ecosystem functioning (EF). The sign of these effects remains controversial because phylogenetic diversity and taxonomic identity may interactively influence EF. Positive relationships, traditionally attributed to complementarity effects, seem unimportant in natural soil bacterial communities. Negative relationships could be attributed to fitness differences leading to the overrepresentation of few productive clades, a mechanism recently invoked to assemble soil bacteria communities. We tested in two ecosystems contrasting in terms of environmental heterogeneity whether two metrics of phylogenetic community structure, a simpler measure of phylogenetic diversity (NRI) and a more complex metric incorporating taxonomic identity (PCPS), correctly predict microbially mediated EF. We show that the relationship between phylogenetic diversity and EF depends on the taxonomic identity of the main coexisting lineages. Phylogenetic diversity was negatively related to EF in soils where a marked fertility gradient exists and a single and productive clade (Proteobacteria) outcompete other clades in the most fertile plots. However, phylogenetic diversity was unrelated to EF in soils where the fertility gradient is less marked and Proteobacteria coexist with other abundant lineages. Including the taxonomic identity of bacterial lineages in metrics of phylogenetic community structure allows the prediction of EF in both ecosystems. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The eukaryotic translation elongation factor eEF1A2 induces neoplastic properties and mediates tumorigenic effects of ZNF217 in precursor cells of human ovarian carcinomas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sun, Yu; Wong, Nicholas; Guan, Yinghui

2008-04-25

Ovarian epithelial carcinomas (OEC) frequently exhibit amplifications at the 20q13 locus which is the site of several oncogenes, including the eukaryotic elongation factor EEF1A2 and the transcription factor ZNF217. We reported previously that overexpressed ZNF217 induces neoplastic characteristics in precursor cells of OEC. Unexpectedly, ZNF217, which is a transcriptional repressor, enhanced expression of eEF1A2. In this study, array comparative genomic hybridization, single nucleotide polymorphism and Affymetrix analysis of ZNF217-overexpressing cell lines confirmed consistently increased expression of eEF1A2 but not of other oncogenes, and revealed early changes in EEF1A2 gene copy numbers and increased expression at crisis during immortalization. We definedmore » the influence of eEF1A2 overexpression on immortalized ovarian surface epithelial cells, and investigated interrelationships between effects of ZNF217 and eEF1A2 on cellular phenotypes. Lentivirally induced eEF1A2 overexpression caused delayed crisis, apoptosis resistance and increases in serum-independence, saturation densities, and anchorage independence. siRNA to eEF1A2 reversed apoptosis resistance and reduced anchorage independence in eEF1A2-overexpressing lines. Remarkably, siRNA to eEF1A2 was equally efficient in inhibiting both anchorage independence and resistance to apoptosis conferred by ZNF217 overexpression. Our data define neoplastic properties that are caused by eEF1A2 in nontumorigenic ovarian cancer precursor cells, and suggest that eEF1A2 plays a role in mediating ZNF217-induced neoplastic progression.« less

Greater impact of acute high-intensity interval exercise on post-exercise executive function compared to moderate-intensity continuous exercise.

PubMed

Tsukamoto, Hayato; Suga, Tadashi; Takenaka, Saki; Tanaka, Daichi; Takeuchi, Tatsuya; Hamaoka, Takafumi; Isaka, Tadao; Hashimoto, Takeshi

2016-03-01

Aerobic moderate-intensity continuous exercise (MCE) can improve executive function (EF) acutely, potentially through the activation of both physiological and psychological factors. Recently, high-intensity interval exercise (HIIE) has been reported to be more beneficial for physical adaptation than MCE. Factors for EF improvement can potentially be more enhanced by HIIE than by MCE; but the effects of HIIE on EF remain unknown. Therefore, we aimed to examine to what extent HIIE impacts post-exercise EF immediately after exercise and during post-exercise recovery, compared with traditional MCE. Twelve healthy male subjects performed cycle ergometer exercise based on either HIIE or MCE protocols in a randomized and counterbalanced order. The HIIE protocol consisted of four 4-min bouts at 90% of peak VO2 with 3-min active recovery at 60% of peak VO2. A volume-matched MCE protocol was applied at 60% of peak VO2. To evaluate EF, a color-words Stroop task was performed pre- and post-exercise. Improvement in EF immediately after exercise was the same for the HIIE and MCE protocols. However, the improvement of EF by HIIE was sustained during 30 min of post-exercise recovery, during which MCE returned to the pre-exercise level. The EF response in the post-exercise recovery was associated with changes in physiological and psychological responses. The present findings showed that HIIE and MCE were capable of improving EF. Moreover, HIIE could prolong improvement in EF during post-exercise recovery. For the first time, we suggest that HIIE may be more effective strategy than MCE for improving EF. Copyright © 2015 Elsevier Inc. All rights reserved.

Eukaryotic polypeptide elongation system and its sensitivity to the inhibitory substances of plant origin.

PubMed

Gałasiński, W

1996-05-01

The structural and functional characteristics of the elongation system (ribosomes and elongation factors) are presented. The immunochemical and diagnostic meaning of the ribosome investigations is considered. Evidence of the participation of ribosomes in the first step of protein glycosylation is presented. The heterogeneous elongation factor eEF-1, isolated from Guerin epithelioma, can be separated into three fractions: one of them functionally corresponds to EF-1 alpha, the second on to EF-1 beta gamma, and the third is an unidentified, active aggregate named EF-1B, which contains the subunit forms EF-1 alpha and EF-1 beta gamma, and other polypeptides showing protein kinase activity. The aggregate EF-1B can be autophosphorylated, while the subunit forms EF-1 alpha and EF-1 beta gamma can neither become autophosphorylated nor phosphorylate other polypeptides. The subunit form EF-beta gamma consists from two polypeptides of 32 and 51 kDa, corresponding to other eukaryotic beta and gamma polypeptides, respectively. EF-1 beta gamma is thermostable and protects against thermal inactivation of EF-1 alpha in the EF-1 alpha-EF-1 beta gamma complex. Pure eEF-2 preparations isolated from normal and neoplastic tissues show different structural features. The existence of eEF-2 in multiple forms, differing in molecular mass, have been found. The eEF-2 with molecular weight of about 100 kDa can be phosphorylated, while eEF-2 of about 65 kDa was not phosphorylated by protein kinase eEF-2. The phosphorylated eEF-2 lost its activity, and this effect was reversed by dephosphorylation. The eEF-2 (65 kDa) was isolated from the active polyribosomes, and it may directly participate in the translocation step of the peptide elongation. It was noted that the components of elongation system can be inhibited, in separate steps, by the substances isolated from various sources of plant origin. Alkaloids emetine and cepheline, cardiac remedy digoxin, saponin glycoside, and its aglycon directly inactivated ribosomes. Quercetin inhibited eEF-1 activity by directly influencing its subunit form EF-1 alpha. eEF-2 was shown to be a target site of the inhibitory action of the glycoside isolated from Melissa officinalis leaves.

Enterococcus faecalis Constitutes an Unusual Bacterial Model in Lysozyme Resistance▿

PubMed Central

Hébert, Laurent; Courtin, Pascal; Torelli, Riccardo; Sanguinetti, Maurizio; Chapot-Chartier, Marie-Pierre; Auffray, Yanick; Benachour, Abdellah

2007-01-01

Lysozyme is an important and widespread compound of the host constitutive defense system, and it is assumed that Enterococcus faecalis is one of the few bacteria that are almost completely lysozyme resistant. On the basis of the sequence analysis of the whole genome of E. faecalis V583 strain, we identified two genes that are potentially involved in lysozyme resistance, EF_0783 and EF_1843. Protein products of these two genes share significant homology with Staphylococcus aureus peptidoglycan O-acetyltransferase (OatA) and Streptococcus pneumoniae N-acetylglucosamine deacetylase (PgdA), respectively. In order to determine whether EF_0783 and EF_1843 are involved in lysozyme resistance, we constructed their corresponding mutants and a double mutant. The ΔEF_0783 mutant and ΔEF_0783 ΔEF_1843 double mutant were shown to be more sensitive to lysozyme than the parental E. faecalis JH2-2 strain and ΔEF_1843 mutant were. However, compared to other bacteria, such as Listeria monocytogenes or S. pneumoniae, the tolerance of ΔEF_0783 and ΔEF_0783 ΔEF_1843 mutants towards lysozyme remains very high. Peptidoglycan structure analysis showed that EF_0783 modifies the peptidoglycan by O acetylation of N-acetyl muramic acid, while the EF_1843 deletion has no obvious effect on peptidoglycan structure under the same conditions. Moreover, the EF_0783 and EF_1843 deletions seem to significantly affect the ability of E. faecalis to survive within murine macrophages. In all, while EF_0783 is currently involved in the lysozyme resistance of E. faecalis, peptidoglycan O acetylation and de-N-acetylation are not the main mechanisms conferring high levels of lysozyme resistance to E. faecalis. PMID:17785473

Targeted predation of extrafloral nectaries by insects despite localized chemical defences

PubMed Central

Gish, Moshe; Mescher, Mark C.; De Moraes, Consuelo M.

2015-01-01

Extrafloral (EF) nectaries recruit carnivorous arthropods that protect plants from herbivory, but they can also be exploited by nectar thieves. We studied the opportunistic, targeted predation (and destruction) of EF nectaries by insects, and the localized chemical defences that plants presumably use to minimize this effect. In field and laboratory experiments, we identified insects that were possibly responsible for EF nectary predation in Vicia faba (fava bean) and determined the extent and accuracy of the feeding damage done to the EF nectaries by these insects. We also performed biochemical analyses of plant tissue samples in order to detect microscale distribution patterns of chemical defences in the area of the EF nectary. We observed selective, targeted feeding on EF nectaries by several insect species, including some that are otherwise not primarily herbivorous. Biochemical analyses revealed high concentrations of l-3,4-dihydroxyphenylalanine, a non-protein amino acid that is toxic to insects, near and within the EF nectaries. These results suggest that plants allocate defences to the protection of EF nectaries from predation, consistent with expectations of optimal defence theory, and that this may not be entirely effective, as insects limit their exposure to these defences by consuming only the secreting tissue of the nectary. PMID:26446809

Birth weight interacts with a functional variant of the oxytocin receptor gene (OXTR) to predict executive functioning in children.

PubMed

Wade, Mark; Prime, Heather; Hoffmann, Thomas J; Schmidt, Louis A; O'Connor, Thomas G; Jenkins, Jennifer M

2018-02-01

Genetic variation in the oxytocin receptor gene (OXTR) is associated with several psychiatric conditions characterized by deficits in executive functioning (EF). A specific OXTR variant, rs2254298, has previously been associated with brain functioning in regions implicated in EF. Moreover, birth weight variation across the entire range is associated with individual differences in cortical structure and function that underlie EF. This is the first study to examine the main and interactive effect between rs2254298 and birth weight on EF in children. The sample consisted of 310 children from an ongoing longitudinal study. EF was measured at age 4.5 using observational tasks indexing working memory, cognitive flexibility, and inhibitory control. A family-based design that controlled for population admixture, stratification, and nongenomic confounds was employed. A significant genetic association between rs2254298 and EF was observed, with more copies of the major allele (G) associated with higher EF. There was also a significant interaction between rs2254298 and birth weight, such that more copies of the major allele in combination with higher birth weight predicted better EF. Findings suggest that OXTR may be associated with discrete neurocognitive abilities in childhood, and these effects may be modulated by intrauterine conditions related to fetal growth and development.

Comparison of Risk of Carpal Tunnel Syndrome in Patients with Distal Radius Fractures After 7 Treatments

PubMed Central

Zhao, Huan-Li; Wang, Gui-Bin; Jia, Yue-Qing; Zhu, Shi-Cai; Zhang, Feng-Fang; Liu, Hong-Mei

2015-01-01

Background To compare risk of carpal tunnel syndrome (CTS) in distal radius fracture (DRF) patients after 7 treatments using bridging external fixation (BrEF), non-bridging external fixation (non-BrEF), plaster fixation, K-wire fixation, dorsal plating fixation, volar plating fixation, and dorsal and volar plating by performing a network meta-analysis. Material/Methods An exhaustive search of electronic databases identified randomized controlled trails (RCTs) closely related to our study topic. The published articles were screened, based on predefined inclusion and exclusion criteria, to select high-quality studies for the present network meta-analysis. Data extracted from the selected studies were analyzed using STATA version 12.0 software. Results The literature search and selection process identified 12 eligible RCTs that contained a total of 1370 DRF patients (394 patients with BrEF, 377 patients with non-BrEF, 89 patients with K-wire fixation, 192 patients with plaster fixation, 42 patients with dorsal plating fixation, 152 patients with volar plating fixation, and 124 patients with dorsal and volar plating fixation). Our network meta-analysis results demonstrated no significant differences in CTS risk among the 7 treatments (P>0.05). The value of surface under the cumulative ranking curve (SUCRA), however, suggested that dorsal plating fixation is the optimal treatment, with the lowest risk of CTS in DRF patients (dorsal plating fixation: 89.2%; dorsal and volar plating: 57.8%; plaster fixation: 50.9%; non-BrEF: 50.6%; volar plating fixation: 39.6%; BrEF: 38.4%; K-wire fixation: 23.6%). Conclusions Our network meta-analysis provides evidence that dorsal plating fixation significantly decreases the risk of CTS and could be the method of choice in DRF patients. PMID:26391617

Effect of Exercise Intensity and Duration on Postexercise Executive Function.

PubMed

Tsukamoto, Hayato; Takenaka, Saki; Suga, Tadashi; Tanaka, Daichi; Takeuchi, Tatsuya; Hamaoka, Takafumi; Isaka, Tadao; Hashimoto, Takeshi

2017-04-01

The effect of exercise volume represented by exercise intensity and duration on postexercise executive function (EF) improvement remains unclear. In the present study, involving two volume-controlled evaluations, we aimed to compare acute exercise protocols with differing intensities and durations to establish an effective exercise protocol for improving EF. In study 1, 12 healthy male subjects performed cycle ergometer exercise, based on a low-intensity (LI) protocol for 20 min (LI20), moderate-intensity (MI) protocol for 20 min (MI20), and MI20 volume-matched LI protocol for 40 min (LI40). The exercise intensities for the LI and MI were set at 30% and 60% of peak oxygen consumption, respectively. In study 2, 15 healthy male subjects performed MI exercise for 10 min (MI10), MI20, and 40 min (MI40). To evaluate the EF, the color-word Stroop task was administrated before exercise, immediately after exercise, and during the 30-min postexercise recovery. In study 1, postexercise EF improvement was sustained for a longer duration after MI20 than after LI40 and was sustained for a longer duration after LI40 than after LI20. In study 2, although there was no significant difference in post-MI exercise EF improvement, the magnitude of difference in the EF between preexercise and 30-min postexercise recovery period was moderately larger in MI40, but not in MI10 and MI20, indicating that the EF improvement during postexercise recovery could be sustained after MI40. The present findings showed that postexercise EF improvement could be prolonged after MI exercise with a moderate duration compared with volume-matched LI exercise with a longer duration. In addition, MI exercise with a relatively long duration may slightly prolong the postexercise EF improvement.

A new photometric study of the triple star system EF Draconis

NASA Astrophysics Data System (ADS)

Yang, Yuan-Gui

2012-04-01

We present new charge-coupled device (CCD) photometry for the triple star EF Draconis, obtained in 2009 and 2011. Using the updated Wilson-Devinney program, the photometric solutions were deduced from two sets of light curves. The results indicate that EF Dra is an A-type W UMa binary with a contact degree of f = 46.7%(±0.6%) and a third light of l3 ≃ 1.5%. Through analyzing the O — C curve, it is found that the orbital period shows a long-time increase with a light-time orbit. The period, semi-amplitude and eccentricity of the third body are Pmod = 17.20(±0.18) yr, A = 0.0039d(±0.0002d) and e = 0.49(±0.02) respectively. This kind of tertiary companion may extract angular momentum from the central system. The orbital period of EF Dra secularly increases at a rate of dP/dt = +3.72(±0.07) × 10-7 d yr-1, which may be interpreted by mass transfer from the less massive to the more massive component. As period increases, the separation between components may increase, which will cause the contact degree to decrease. With mass transferring, the spin angular momentum will increase, while the orbital angular momentum will decrease. Only if the contact configuration would merge at could this kind of deep-contact binary with period increasing, such as EF Dra, evolve into a rapidly-rotating single star.

Effects of Exergame Play on EF in Children and Adolescents at a Summer Camp for Low Income Youth

PubMed Central

Flynn, Rachel M.; Richert, Rebekah A.; Staiano, Amanda E.; Wartella, Ellen; Calvert, Sandra L.

2014-01-01

Past research has suggested exergame play improves adolescents’ executive function (EF) skills. EF change in 70 African American and Hispanic/Latino 10- to 16-year-olds participating in an inner-city summer camp was assessed following five 30-minute exergame play sessions. Children’s EF scores improved from pre- to posttest, and factors related to this change were examined. The number of exergame sessions the participants attended predicted posttest scores. In addition, level of achievement during game play was related to EF scores. Finally, the children’s level of enjoyment was not related to EF; however, frustration and boredom during game play were negatively related to EF. The findings are discussed in terms of their implications for the relationship between exergame play and cognitive benefits for adolescent players. PMID:25328562

Effects of Exergame Play on EF in Children and Adolescents at a Summer Camp for Low Income Youth.

PubMed

Flynn, Rachel M; Richert, Rebekah A; Staiano, Amanda E; Wartella, Ellen; Calvert, Sandra L

2014-01-01

Past research has suggested exergame play improves adolescents' executive function (EF) skills. EF change in 70 African American and Hispanic/Latino 10- to 16-year-olds participating in an inner-city summer camp was assessed following five 30-minute exergame play sessions. Children's EF scores improved from pre- to posttest, and factors related to this change were examined. The number of exergame sessions the participants attended predicted posttest scores. In addition, level of achievement during game play was related to EF scores. Finally, the children's level of enjoyment was not related to EF; however, frustration and boredom during game play were negatively related to EF. The findings are discussed in terms of their implications for the relationship between exergame play and cognitive benefits for adolescent players.

Biological effects of exposure to static electric fields in humans and vertebrates: a systematic review.

PubMed

Petri, Anne-Kathrin; Schmiedchen, Kristina; Stunder, Dominik; Dechent, Dagmar; Kraus, Thomas; Bailey, William H; Driessen, Sarah

2017-04-17

High-voltage direct current (HVDC) lines are the technology of choice for the transport of large amounts of energy over long distances. The operation of these lines produces static electric fields (EF), but the data reviewed in previous assessments were not sufficient to assess the need for any environmental limit. The aim of this systematic review was to update the current state of research and to evaluate biological effects of static EF. Using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) recommendations, we collected and evaluated experimental and epidemiological studies examining biological effects of exposure to static EF in humans (n = 8) and vertebrates (n = 40). There is good evidence that humans and animals are able to perceive the presence of static EF at sufficiently high levels. Hair movements caused by electrostatic forces may play a major role in this perception. A large number of studies reported responses of animals (e.g., altered metabolic, immunologic or developmental parameters) to a broad range of static EF strengths as well, but these responses are likely secondary physiological responses to sensory stimulation. Furthermore, the quality of many of the studies reporting physiological responses is poor, which raises concerns about confounding. The weight of the evidence from the literature reviewed did not indicate that static EF have adverse biological effects in humans or animals. The evidence strongly supported the role of superficial sensory stimulation of hair and skin as the basis for perception of the field, as well as reported indirect behavioral and physiological responses. Physical considerations also preclude any direct effect of static EF on internal physiology, and reports that some physiological processes are affected in minor ways may be explained by other factors. While this literature does not support a level of concern about biological effects of exposure to static EF, the conditions that affect thresholds for human detection and possible annoyance at suprathreshold levels should be investigated.

Effect of aging and long-term erectile function after iodine-125 prostate brachytherapy.

PubMed

Keyes, Mira; Pickles, Tom; Crook, Juanita; McKenzie, Michael; Cheung, Arthur; Spadinger, Ingrid; LaPointe, Vincent; Bachand, W Francois; Morris, James

2015-01-01

To evaluate long-term erectile function (EF) in men treated with iodine-125 prostate brachytherapy (PB) and to determine factors predictive for erectile dysfunction (ED), including natural decline because of aging. Two thousand nine hundred twenty-nine patients (implanted July 1989-June 2012) with baseline EF and greater than 10-month followup (FU) are included. About 78.9% had full and 7.9% had partial EF at baseline. EF was assessed on a physician-reported three-point scale. Poisson regression with generalized estimating equations was used to assess predictors of ED and Kaplan-Meier curves time to ED. The effect of aging was calculated from the declining rate of baseline EF seen in sequential 5-year age cohorts and from the Massachusetts Male Aging Study. The median age was 66 years and median FU 3.5 years (maximum 14 years). About 1142 patients had more than 5 years of FU, and 43% had received 6 months of androgen deprivation therapy (ADT). Significant drop in EF was seen at 6 weeks after PB, with gradual decline thereafter. EF preservation at 5 years for age younger than 55, 56-59, 60-64, 65-69, and 70 year and older was 82%, 73%, 58%, 39%, and 23%, respectively. Comparisons of the 5-year age-related and treatment-related EF decline show that 50% of the long-term EF decline is related to aging. On univariate and multivariate analyses, age at implant, length of FU, hypertension, diabetes, and use of ADT (all p < 0.01) were significant predictors of ED. More than 80% of young men have EF preserved 5 years after PB. Age, ADT, history of hypertension, and the natural decline in EF have negative impact on long-term EF after PB. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

Impressive Suppression of Colon Cancer Growth by Triple Combination SN38/EF24/Melatonin: "Oncogenic" Versus "Onco-Suppressive" Reactive Oxygen Species.

PubMed

Bakalova, Rumiana; Zhelev, Zhivko; Shibata, Sayaka; Nikolova, Biliana; Aoki, Ichio; Higashi, Tatsuya

2017-10-01

The study aimed to investigate the effect of multi-targeted combinations (SN38/EF24; SN38/EF24/melatonin) on the growth of colon cancer in experimental animals and their impact on the ratio "oncogenic"/"onco-suppressive" reactive oxygen species (ROS) - a crucial factor for triggering carcinogenesis, as well as for development of effective therapeutic strategies. The experiments were conducted on colon cancer-grafted mice - non-treated, SN38/EF24-treated and SN38/EF24/melatonin-treated within 22 days. The balance between different types of ROS was measured in vivo by nitroxide-enhanced magnetic resonance imaging (MRI), as well as on isolated tissue specimens by conventional analytical tests. Both combinations significantly suppressed the tumor growth. Impressive anticancer effect was observed in SN38/EF24/melatonin-treated mice - almost complete destruction of the tumor. Both types of ROS (superoxide and hydroperoxides) were elevated in cancer, but the MRI data suggest that the ratio between them tends towards superoxide. SN38/EF24 decreased the level of superoxide, but did not affect the level of hydroperoxides in the cancerous tissue, while SN38/EF24/melatonin decreased the level of superoxide below the control and increased significantly the level of hydroperoxides. The most important observations are that: (i) colon cancer was characterized by a vicious cycle, that ensures a permanent domination of "oncogenic" ROS (as superoxide) over "onco-suppressive" ROS (as hydrogen peroxide); (ii) the anticancer effect of the triple combination EF24/SN38/melatonin was accompanied by decreasing "oncogenic" and increasing "onco-suppressive" ROS; (iii) the ratio between both types of ROS could be a new onco-target for combined therapy; and (iv) nitroxide-enhanced MRI is a valuable tool for analyzing of this ratio. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Synthetic curcumin analog EF31 inhibits the growth of head and neck squamous cell carcinoma xenografts.

PubMed

Zhu, Shijun; Moore, Terry W; Lin, Xiaoqian; Morii, Nao; Mancini, Alessandra; Howard, Randy B; Culver, Deborah; Arrendale, Richard F; Reddy, Prabhakar; Evers, Taylor J; Zhang, Hongzheng; Sica, Gabriel; Chen, Zhuo G; Sun, Aiming; Fu, Haian; Khuri, Fadlo R; Shin, Dong M; Snyder, James P; Shoji, Mamoru

2012-06-01

Objectives are to examine the efficacy, pharmacokinetics, and toxicology of a synthetic curcumin analog EF31 in head and neck squamous cell carcinoma. The synthesis of EF31 was described for the first time. Solubility of EF24 and EF31 was compared using nephelometric analysis. Human head and neck squamous cell carcinoma Tu212 xenograft tumors were established in athymic nude mice and treated with EF31 i.p. once daily five days a week for about 5-6 weeks. The long term effect of EF31 on the NF-κB signaling system in the tumors was examined by Western blot analysis. EF31 at 25 mg kg(-1), i.p. inhibited tumor growth almost completely. Solubilities of EF24 and EF31 are <10 and 13 μg mL(-1) or <32 and 47 μM, respectively. The serum chemistry profiles of treated mice were within the limits of normal, they revealed a linear increase of C(max). EF31 decreased the level of phosphorylation of NF-κB p65. In conclusion, the novel synthetic curcumin analog EF31 is efficacious in inhibiting the growth of Tu212 xenograft tumors and may be useful for treating head and neck squamous cell carcinoma. The long term EF31 treatment inhibited NF-κB p65 phosphorylation in xenografts, implicating downregulation of cancer promoting transcription factors such as angiogenesis and metastasis.

Measuring Executive Function in Early Childhood: A Case for Formative Measurement

PubMed Central

Willoughby, Michael T.; Blair, Clancy B.

2015-01-01

This study tested whether individual executive function (EF) tasks were better characterized as formative (causal) or reflective (effect) indicators of the latent construct of EF. EF data that were collected as part of the Family Life Project (FLP), a prospective longitudinal study of families who were recruited at the birth of a new child (N = 1292), when children were 3, 4, and 5 years old. Vanishing tetrad tests were used to test the relative fit of models in which EF tasks were used as either formative or reflective indicators of the latent construct of EF in the prediction of intellectual ability (at age 3), attention deficit/hyperactivity disorder symptoms (at ages 3–5 years), and academic achievement (at kindergarten). Results consistently indicated that EF tasks were better represented as formative indicators of the latent construct of EF. Next, individual tasks were combined to form an overall measure of EF ability in ways generally consistent with formative (i.e., creating a composite mean score) and reflective (i.e., creating an EF factor score) measurement. The test-retest reliability and developmental trajectories of EF differed substantially, depending on which overall measure of EF ability was used. In general, the across-time stability of EF was markedly higher, perhaps implausibly high, when represented as a factor score versus composite score. Results are discussed with respect to the ways in which the statistical representation of EF tasks can exert a large impact on inferences regarding the developmental causes, course, and consequences of EF. More generally, these results exemplify how some psychological constructs may not conform to conventional measurement wisdom. PMID:26121388

Longitudinal mediators of social problem solving in spina bifida and typical development.

PubMed

Landry, Susan H; Taylor, Heather B; Swank, Paul R; Barnes, Marcia; Juranek, Jenifer

2013-05-01

The current study examined the role of early executive functions (EF) and social language (SL) as well as responsive parenting as mediators of the effect of group on social problem-solving skills at 7 years of age for children with spina bifida and typically developing children. A mediation analysis was used to determine if the effect of having spina bifida on school age social problem-solving skills was mediated through the effect of group on EF/SL at 3 years of age and responsive parenting at 12 and 18 months. As part of a larger longitudinal study, 103 infants (n = 49 with spina bifida; n = 54 typically developing) received measures of EF/SL at 3 years of age and mother-infant play interactions at 12 and 18 months of age were coded for a range of responsive parenting behaviors. Social problem-solving skills were measured with a game-like observational task at 7 years of age. Group had a direct relation with later social problem-solving as well as an indirect relation through early EF/SL skills that, in turn, had a direct relation with later social problem solving. An indirect effect of responsive parenting on later social skills also was found through a direct effect on EF/SL skills. Early precursors of school age difficulties with social problem solving observed for children with spina bifida can be explained, in part, by difficulties in the first 3 years of life with EF/SL. Early responsive parenting appears to positively affect the development of these EF/SL skills. Implications for early intervention are an outcome of this study.

Repeated high-intensity interval exercise shortens the positive effect on executive function during post-exercise recovery in healthy young males.

PubMed

Tsukamoto, Hayato; Suga, Tadashi; Takenaka, Saki; Tanaka, Daichi; Takeuchi, Tatsuya; Hamaoka, Takafumi; Isaka, Tadao; Ogoh, Shigehiko; Hashimoto, Takeshi

2016-06-01

A single bout of aerobic exercise improves executive function (EF), but only for a short period. Compared with a single bout of aerobic exercise, we recently found that high-intensity interval exercise (HIIE) could maintain a longer improvement in EF. However, the mechanism underlying the effect of different exercise modes on the modifications of EF remains unclear. The purpose of the current investigation was to test our hypothesis that the amount of exercise-induced lactate production and its accumulation affects human brain function during and after exercise, thereby affecting post-exercise EF. Ten healthy male subjects performed cycle ergometer exercise. The HIIE protocol consisted of four 4-min bouts at 90% peak VO2 with a 3-min active recovery period at 60% peak VO2. The amount of lactate produced during exercise was manipulated by repeating the HIIE twice with a resting period of 60min between the 1st HIIE and 2nd HIIE. To evaluate EF, a color-word Stroop task was performed, and reverse-Stroop interference scores were obtained. EF immediately after the 1st HIIE was significantly improved compared to that before exercise, and the improved EF was sustained during 40min of the post-exercise recovery. However, for the 2nd HIIE, the improved EF was sustained for only 10min of the post-exercise recovery period, despite the performance of the same exercise. In addition, during and following HIIE, the glucose and lactate accumulation induced by the 2nd HIIE was significantly lower than that induced by the 1st HIIE. Furthermore, there was an inverse relationship between lactate and EF by plotting the changes in lactate levels against changes in EF from pre-exercise during the late phase of post-exercise recovery. These findings suggested the possibility that repeated bouts of HIIE, which decreases lactate accumulation, may dampen the positive effect of exercise on EF during the post-exercise recovery. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Cognitive reserve in Parkinson's disease: the effects of welsh-english bilingualism on executive function.

PubMed

Hindle, John V; Martin-Forbes, Pamela A; Bastable, Alexandra J M; Pye, Kirstie L; Martyr, Anthony; Whitaker, Christopher J; Craik, Fergus I M; Bialystok, Ellen; Thomas, Enlli M; Mueller Gathercole, Virginia C; Clare, Linda

2015-01-01

Objective. Bilingualism has been shown to benefit executive function (EF) and delay the onset of Alzheimer's disease. This study aims at examining whether a bilingual advantage applies to EF in Parkinson's disease (PD). Method. In a cross-sectional outpatient cohort of monolingual English (n = 57) and bilingual Welsh/English (n = 46) speakers with PD we evaluated the effects of bilingualism compared with monolingualism on performance on EF tasks. In bilinguals we also assessed the effects of the degree of daily usage of each language and the degree of bilingualism. Results. Monolinguals showed an advantage in performance of language tests. There were no differences in performance of EF tests in monolinguals and bilinguals. Those who used Welsh less in daily life had better performance on one test of English vocabulary. The degree of bilingualism correlated with one test of nonverbal reasoning and one of working memory but with no other tests of EF. Discussion. The reasons why the expected benefit in EF in Welsh-English bilinguals with PD was not found require further study. Future studies in PD should include other language pairs, analysis of the effects of the degree of bilingualism, and longitudinal analysis of cognitive decline or dementia together with structural or functional neuroimaging.

Cognitive Reserve in Parkinson's Disease: The Effects of Welsh-English Bilingualism on Executive Function

PubMed Central

Hindle, John V.; Martin-Forbes, Pamela A.; Bastable, Alexandra J. M.; Pye, Kirstie L.; Martyr, Anthony; Whitaker, Christopher J.; Craik, Fergus I. M.; Bialystok, Ellen; Thomas, Enlli M.; Mueller Gathercole, Virginia C.; Clare, Linda

2015-01-01

Objective. Bilingualism has been shown to benefit executive function (EF) and delay the onset of Alzheimer's disease. This study aims at examining whether a bilingual advantage applies to EF in Parkinson's disease (PD). Method. In a cross-sectional outpatient cohort of monolingual English (n = 57) and bilingual Welsh/English (n = 46) speakers with PD we evaluated the effects of bilingualism compared with monolingualism on performance on EF tasks. In bilinguals we also assessed the effects of the degree of daily usage of each language and the degree of bilingualism. Results. Monolinguals showed an advantage in performance of language tests. There were no differences in performance of EF tests in monolinguals and bilinguals. Those who used Welsh less in daily life had better performance on one test of English vocabulary. The degree of bilingualism correlated with one test of nonverbal reasoning and one of working memory but with no other tests of EF. Discussion. The reasons why the expected benefit in EF in Welsh-English bilinguals with PD was not found require further study. Future studies in PD should include other language pairs, analysis of the effects of the degree of bilingualism, and longitudinal analysis of cognitive decline or dementia together with structural or functional neuroimaging. PMID:25922786

A pilot study of the efficacy of a computerized executive functioning remediation training with game elements for children with ADHD in an outpatient setting: outcome on parent- and teacher-rated executive functioning and ADHD behavior.

PubMed

van der Oord, S; Ponsioen, A J G B; Geurts, H M; Ten Brink, E L; Prins, P J M

2014-11-01

This pilot study tested the short- and long-term efficacy (9 weeks follow-up) of an executive functioning (EF) remediation training with game elements for children with ADHD in an outpatient clinical setting, using a randomized controlled wait-list design. Furthermore, in a subsample, that is, those treated with methylphenidate, additive effects of the EF training were assessed. A total of 40 children (aged 8-12 years) were randomized to the EF training or wait-list. The training consisted of a 25-session training of inhibition, cognitive flexibility, and working memory. Treatment outcome was assessed by parent- and teacher-rated EF, ADHD, oppositional deviant disorder, and conduct disorder symptoms. Children in the EF training showed significantly more improvement than those in the wait-list condition on parent-rated EF and ADHD behavior in the total sample and in the subsample treated with methylphenidate. Effects were maintained at follow-up. This pilot study shows promising evidence for the efficacy of an EF training with game elements. © 2012 SAGE Publications.

Metacognitive executive function training for young children with ADHD: a proof-of-concept study.

PubMed

Tamm, Leanne; Nakonezny, Paul A

2015-09-01

Executive functions (EF) are impaired in children with attention-deficit/hyperactivity disorder (ADHD). It may be especially critical for interventions to target EF in early childhood given the developmental progression of EF deficits that may contribute to later functional impairments. This proof-of-concept study examined the initial efficacy of an intervention program on EF and ADHD. We also examined child performance on three neurocognitive tasks assessing cognitive flexibility, auditory/visual attention, and sustained/selective attention. Children with ADHD (ages 3-7) and their parents were randomized to receive an intervention targeting metacognitive EF deficits (n = 13) or to a waitlist control condition (n = 12). Linear model analysis of covariance compared groups on parent EF ratings, blinded clinician ratings of ADHD symptoms and improvement, and child performance on neurocognitive measures. Children who received the intervention significantly improved on parent ratings of attention shifting and emotion regulation in addition to clinician ratings of inattention. Moderate effect sizes showed additional intervention effects on parent ratings of inhibition, memory, and planning, and clinician ratings of hyperactivity/impulsivity and overall improvement. Small effect sizes were observed for improvement on child neurocognitive measures. Although replication with a larger sample and an active control group is needed, EF training with a metacognitive focus is a potentially promising intervention for young children with ADHD.

Increased Eating Frequency Is Associated with Lower Obesity Risk, But Higher Energy Intake in Adults: A Meta-Analysis.

PubMed

Wang, Yue-Qiao; Zhang, Yun-Quan; Zhang, Fei; Zhang, Yi-Wen; Li, Rui; Chen, Guo-Xun

2016-06-17

Body weight is regulated by energy intake which occurs several times a day in humans. In this meta-analysis, we evaluated whether eating frequency (EF) is associated with obesity risk and energy intake in adults without any dietary restriction. Experimental and observational studies published before July 2015 were selected through English-language literature searches in several databases. These studies reported the association between EF and obesity risk (odd ratios, ORs) in adults who were not in dietary restriction. R software was used to perform statistical analyses. Ten cross-sectional studies, consisting of 65,742 participants, were included in this analysis. ORs were considered as effect size for the analysis about the effect of EF on obesity risk. Results showed that the increase of EF was associated with 0.83 time lower odds of obesity (i.e., OR = 0.83, 95% confidence intervals (CI) 0.70-0.99, p = 0.040). Analysis about the effect of EF on differences in participants' energy intake revealed that increased EF was associated with higher energy intake (β = 125.36, 95% CI 21.76-228.97, p = 0.017). We conclude that increased EF may lead to lower obesity risk but higher energy intake. Clinical trials are warranted to confirm these results and to assess the clinical practice applicability.

Enhancement effects of nicotine on neurogenic relaxation responses in the corpus cavernosum in rabbits: the role of nicotinic acetylcholine receptor subtypes.

PubMed

Ozturk Fincan, Gokce Sevim; Vural, Ismail Mert; Ercan, Zeynep Sevim; Sarioglu, Yusuf

2010-02-10

Nicotine acts as an agonist of nicotinic acetylcholine receptors, which belong to a superfamily of neurotransmitter-gated ion channels. We previously demonstrated that nicotine increases the electrical field stimulation (EFS)-evoked nitrergic relaxation responses via activation of nicotinic acetylcholine receptors. The aim of the present study is to investigate the subtypes of nicotinic acetylcholine receptors in rabbit corpus cavernosum. EFS-evoked relaxation responses were recorded from corpus cavernosum strips obtained from rabbits with an isometric force displacement transducers. Effects of nicotine on EFS-evoked relaxations were examined in pre-contracted tissues. Then the effect of nicotine on the EFS-evoked relaxations was examined in the presence of hexamethonium, dihydro-beta-erythroidine, mecamylamine or alpha-bungarotoxin. In our study, nicotine (3 x 10(-5), 10(-4)) transiently increased nitrergic relaxations induced by EFS in the rabbit isolated corpus cavernosum. While hexamethonium and mecamylamine near totally inhibited or abolished the neurorelaxation response to nicotine (3 x 10(-5)) on EFS, dihydro-beta-erythroidine and alpha-bungarotoxin partially inhibited these responses. These findings demonstrated that the alpha3-beta4, alpha4-beta2 and alpha7 subunits of nicotinic acetylcholine receptors play role on the nicotine-induced augmentation in EFS-evoked relaxation responses in rabbit corpus cavernosum. Copyright (c) 2009 Elsevier B.V. All rights reserved.

Biomarker Profiles of Acute Heart Failure Patients With a Mid-Range Ejection Fraction.

PubMed

Tromp, Jasper; Khan, Mohsin A F; Mentz, Robert J; O'Connor, Christopher M; Metra, Marco; Dittrich, Howard C; Ponikowski, Piotr; Teerlink, John R; Cotter, Gad; Davison, Beth; Cleland, John G F; Givertz, Michael M; Bloomfield, Daniel M; Van Veldhuisen, Dirk J; Hillege, Hans L; Voors, Adriaan A; van der Meer, Peter

2017-07-01

In this study, the authors used biomarker profiles to characterize differences between patients with acute heart failure with a midrange ejection fraction (HFmrEF) and compare them with patients with a reduced (heart failure with a reduced ejection fraction [HFrEF]) and preserved (heart failure with a preserved ejection fraction [HFpEF]) ejection fraction. Limited data are available on biomarker profiles in acute HFmrEF. A panel of 37 biomarkers from different pathophysiological domains (e.g., myocardial stretch, inflammation, angiogenesis, oxidative stress, hematopoiesis) were measured at admission and after 24 h in 843 acute heart failure patients from the PROTECT trial. HFpEF was defined as left ventricular ejection fraction (LVEF) of ≥50% (n = 108), HFrEF as LVEF of <40% (n = 607), and HFmrEF as LVEF of 40% to 49% (n = 128). Hemoglobin and brain natriuretic peptide levels (300 pg/ml [HFpEF]; 397 pg/ml [HFmrEF]; 521 pg/ml [HFrEF]; p trend  <0.001) showed an upward trend with decreasing LVEF. Network analysis showed that in HFrEF interactions between biomarkers were mostly related to cardiac stretch, whereas in HFpEF, biomarker interactions were mostly related to inflammation. In HFmrEF, biomarker interactions were both related to inflammation and cardiac stretch. In HFpEF and HFmrEF (but not in HFrEF), remodeling markers at admission and changes in levels of inflammatory markers across the first 24 h were predictive for all-cause mortality and rehospitalization at 60 days (p interaction  <0.05). Biomarker profiles in patients with acute HFrEF were mainly related to cardiac stretch and in HFpEF related to inflammation. Patients with HFmrEF showed an intermediate biomarker profile with biomarker interactions between both cardiac stretch and inflammation markers. (PROTECT-1: A Study of the Selective A1 Adenosine Receptor Antagonist KW-3902 for Patients Hospitalized With Acute HF and Volume Overload to Assess Treatment Effect on Congestion and Renal Function; NCT00328692). Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Influence of an electric field on the buoyancy-driven instabilities.

PubMed

Zadrazil, Ales; Sevcíková, Hana

2005-11-01

The influence of dc electric fields (EFs) on the development of buoyancy-driven instabilities of reaction fronts is investigated experimentally in a modified Hele-Shaw cell for the arsenous acid-iodate system. Assessment of effects of external EFs is made both visually and through dispersion curves. It is shown that density fingering, observed on ascending fronts, is suppressed by the EF if the front propagates towards the positive electrode and is enhanced when the front propagates towards the negative electrode. The stabilizing (destabilizing) effects include slower (faster) development of fingers and the decrease (increase) in their numbers. The descending front, stable under no EF conditions, remains stable when an EF is applied with the positive electrode facing the approaching front. When the descending front faces the negative electrode, the tiny fingerlike structure develops after quite a long time.

EF24 suppresses maturation and inflammatory response in dendritic cells.

PubMed

Vilekar, Prachi; Awasthi, Shanjana; Natarajan, Aravindan; Anant, Shrikant; Awasthi, Vibhudutta

2012-07-01

Synthetic curcuminoid EF24 was studied for its effect on the maturation and inflammatory response in murine bone marrow derived immortalized JAWS II dendritic cells (DCs). EF24 reduced the expression of LPS-induced MHC class II, CD80 and CD86 molecules. It also abrogated the appearance of dendrites, a typical characteristic of mature DCs. These effects were accompanied by the inhibition of LPS-induced activation of transcription factor nuclear factor kappa-light-chain enhancer of activated B cells (NF-κB). Simultaneous reduction of pro-inflammatory cytokines [tumor necrosis factor (TNF)-α, IL-6] both at the mRNA and secreted levels was also observed. To investigate the dependency of LPS effects on MyD88 adaptor protein, we transfected JAWS II DCs with dominant negative MyD88 plasmid construct (MyD88-DN). EF24 reduced NF-κB activity and TNF-α secretion in a MyD88-dependent manner. These results suggest that EF24 modulates DCs by suppressing their maturation and reducing the secretion of inflammatory cytokines. Further, it appears that EF24 acts at or upstream of MyD88 in the LPS-TLR4/MyD88/NF-κB pathway.

EF24 suppresses maturation and inflammatory response in dendritic cells

PubMed Central

Vilekar, Prachi; Natarajan, Aravindan; Anant, Shrikant

2012-01-01

Synthetic curcuminoid EF24 was studied for its effect on the maturation and inflammatory response in murine bone marrow derived immortalized JAWS II dendritic cells (DCs). EF24 reduced the expression of LPS-induced MHC class II, CD80 and CD86 molecules. It also abrogated the appearance of dendrites, a typical characteristic of mature DCs. These effects were accompanied by the inhibition of LPS-induced activation of transcription factor nuclear factor kappa-light-chain enhancer of activated B cells (NF-κB). Simultaneous reduction of pro-inflammatory cytokines [tumor necrosis factor (TNF)-α, IL-6] both at the mRNA and secreted levels was also observed. To investigate the dependency of LPS effects on MyD88 adaptor protein, we transfected JAWS II DCs with dominant negative MyD88 plasmid construct (MyD88-DN). EF24 reduced NF-κB activity and TNF-α secretion in a MyD88-dependent manner. These results suggest that EF24 modulates DCs by suppressing their maturation and reducing the secretion of inflammatory cytokines. Further, it appears that EF24 acts at or upstream of MyD88 in the LPS-TLR4/MyD88/NF-κB pathway. PMID:22378503

EF24 (a Curcumin Analog) and ZSTK474 Emphasize the Effect of Cabozantinib in Medullary Thyroid Cancer.

PubMed

Bertazza, Loris; Sensi, Francesca; Cavedon, Elisabetta; Watutantrige-Fernando, Sara; Censi, Simona; Manso, Jacopo; Vianello, Federica; Casal Ide, Eric; Iacobone, Maurizio; Pezzani, Raffaele; Mian, Caterina; Barollo, Susi

2018-06-01

XL184 is a small-molecule kinase inhibitor recently included in first-line systemic therapy for patients with advanced, progressive medullary thyroid cancer (MTC). EF24 is a curcumin analog with a high bioavailability, and ZSTK474 is an inhibitor of the phosphatidylinositol 3-kinase signaling pathway. We investigated the effect of these compounds, alone and in combination, in two rearranged during transfection (RET)-mutated TT and MZ-CRC-1 MTC cell lines and in six mostly RET wild-type human MTC primary cultures. Low IC50 values demonstrated the efficacy of the drugs, whereas the combination index revealed an important synergistic effect of combinations of XL184 + ZSTK474 and XL184 + EF24. Cell-cycle changes and the induction of apoptosis or necrosis were modulated by single compounds or combinations thereof. Both XL184 and EF24, alone or combined, were effective in reducing calcitonin secretion. Western blot and in-cell Western analysis showed that the compounds prompted a decrease in general reactivity to phosphorylated antibodies. Our data confirm XL184 alone as the reference drug for RET-mutated MTC, but we also demonstrated that EF24 alone is effective in inhibiting MTC cell viability. We tested the combinations XL184 + ZSTK474 and XL184 + EF24 too, finding that they act synergistically, irrespective of RET mutation status.

Effects of Tadalafil Once-Daily or On-Demand vs Placebo on Return to Baseline Erectile Function After Bilateral Nerve-Sparing Radical Prostatectomy--Results from a Randomized Controlled Trial (REACTT).

PubMed

Mulhall, John P; Brock, Gerald; Oelke, Matthias; Fode, Mikkel; Probst, Kai A; Henneges, Carsten; d'Anzeo, Gianluca; Rossi, Andrea; Büttner, Hartwig

2016-04-01

The multicenter, randomized, double-blind, double-dummy, placebo-controlled REACTT trial suggested that treatment with tadalafil once daily (OaD) started early after bilateral nerve-sparing radical prostatectomy (nsRP) for prostate cancer may contribute to erectile function (EF)-recovery, which was predefined as achieving an International Index of Erectile Function (IIEF)-EF score ≥22. Here, we report descriptive post-hoc analyses, using the more strict definition for EF-recovery of returning back to the pre-surgery IIEF-EF-level ("back-to-baseline analysis"). REACTT included 422 men <68 years with adenocarcinoma of the prostate and preoperative IIEF-EF ≥22 who underwent nsRP at 50 centers from 9 European countries and Canada. Patients were randomized post-nsRP 1:1:1 to 9-month double-blind treatment (DBT) with tadalafil 5 mg OaD (n = 139), tadalafil 20 mg on-demand (pro-re-nata, PRN; n = 142), or placebo (n = 141), followed by 6-week drug-free washout (DFW) and 3-month open-label tadalafil OaD treatment (OLT). Proportion of patients returning to their preoperative IIEF-EF category (22-25 or ≥26) at the end of DBT, DFW, and OLT. Overall, 92.4% of patients had pre-surgery (baseline) IIEF-EF scores ≥26 (tadalafil OaD 94.2%, PRN 91.6%, placebo 91.5%), 7.4% had IIEF-EF 22-25. At the end of DBT, 22.3% of patients on tadalafil OaD had achieved "back-to-baseline" IIEF-EF, compared with 11.3% on tadalafil PRN and 7.8% on placebo. Of all 58 patients "back-to-baseline" at the end of DBT, only 1 PRN-group patient had started from a baseline IIEF-EF <26. The treatment-group difference at the end of DBT was not maintained after DFW. After 3 months of OLT with tadalafil OaD, the proportion of patients with "back-to-baseline" IIEF-EF had almost doubled in all 3 groups. Changing the definition for EF-recovery from IIEF-EF ≥22 to the more strict definition of "returning back-to-baseline IIEF-EF" had no major impact. Tadalafil OaD started early after nsRP improved drug-assisted EF, but had no effect on unassisted EF following treatment cessation after 9 months. Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Dual Endothelin-A/Endothelin-B Receptor Blockade and Cardiac Remodeling in Heart Failure With Preserved Ejection Fraction

PubMed Central

Valero-Munoz, Maria; Li, Shanpeng; Wilson, Richard M.; Boldbaatar, Batbold; Iglarz, Marc; Sam, Flora

2017-01-01

Background Despite the increasing prevalence of heart failure with preserved ejection fraction (HFpEF) in humans, there remains no evidence-based therapies for HFpEF. Endothelin-1 (ET-1) antagonists are a possibility because elevated ET-1 levels are associated with adverse cardiovascular effects, such as arterial and pulmonary vasoconstriction, impaired left ventricular (LV) relaxation, and stimulation of LV hypertrophy. LV hypertrophy is a common phenotype in HFpEF, particularly when associated with hypertension. Methods and Results In the present study, we found that ET-1 levels were significantly elevated in patients with chronic stable HFpEF. We then sought to investigate the effects of chronic macitentan, a dual ET-A/ET-B receptor antagonist, on cardiac structure and function in a murine model of HFpEF induced by chronic aldosterone infusion. Macitentan caused LV hypertrophy regression independent of blood pressure changes in HFpEF. Although macitentan did not modulate diastolic dysfunction in HFpEF, it significantly reduced wall thickness and relative wall thickness after 2 weeks of therapy. In vitro studies showed that macitentan decreased the aldosterone-induced cardiomyocyte hypertrophy. These changes were mediated by a reduction in the expression of cardiac myocyte enhancer factor 2a. Moreover, macitentan improved adverse cardiac remodeling, by reducing the stiffer cardiac collagen I and titin n2b expression in the left ventricle of mice with HFpEF. Conclusions These findings indicate that dual ET-A/ET-B receptor inhibition improves HFpEF by abrogating adverse cardiac remodeling via antihypertrophic mechanisms and by reducing stiffness. Additional studies are needed to explore the role of dual ET-1 receptor antagonists in patients with HFpEF. PMID:27810862

Dual Endothelin-A/Endothelin-B Receptor Blockade and Cardiac Remodeling in Heart Failure With Preserved Ejection Fraction.

PubMed

Valero-Munoz, Maria; Li, Shanpeng; Wilson, Richard M; Boldbaatar, Batbold; Iglarz, Marc; Sam, Flora

2016-11-01

Despite the increasing prevalence of heart failure with preserved ejection fraction (HFpEF) in humans, there remains no evidence-based therapies for HFpEF. Endothelin-1 (ET-1) antagonists are a possibility because elevated ET-1 levels are associated with adverse cardiovascular effects, such as arterial and pulmonary vasoconstriction, impaired left ventricular (LV) relaxation, and stimulation of LV hypertrophy. LV hypertrophy is a common phenotype in HFpEF, particularly when associated with hypertension. In the present study, we found that ET-1 levels were significantly elevated in patients with chronic stable HFpEF. We then sought to investigate the effects of chronic macitentan, a dual ET-A/ET-B receptor antagonist, on cardiac structure and function in a murine model of HFpEF induced by chronic aldosterone infusion. Macitentan caused LV hypertrophy regression independent of blood pressure changes in HFpEF. Although macitentan did not modulate diastolic dysfunction in HFpEF, it significantly reduced wall thickness and relative wall thickness after 2 weeks of therapy. In vitro studies showed that macitentan decreased the aldosterone-induced cardiomyocyte hypertrophy. These changes were mediated by a reduction in the expression of cardiac myocyte enhancer factor 2a. Moreover, macitentan improved adverse cardiac remodeling, by reducing the stiffer cardiac collagen I and titin n2b expression in the left ventricle of mice with HFpEF. These findings indicate that dual ET-A/ET-B receptor inhibition improves HFpEF by abrogating adverse cardiac remodeling via antihypertrophic mechanisms and by reducing stiffness. Additional studies are needed to explore the role of dual ET-1 receptor antagonists in patients with HFpEF. © 2016 American Heart Association, Inc.

Neural correlates of executive functions in patients with obesity.

PubMed

Ho, Ming-Chou; Chen, Vincent Chin-Hung; Chao, Seh-Huang; Fang, Ching-Tzu; Liu, Yi-Chun; Weng, Jun-Cheng

2018-01-01

Obesity is one of the most challenging problems in human health and is recognized as an important risk factor for many chronic diseases. It remains unclear how the neural systems (e.g., the mesolimbic "reward" and the prefrontal "control" neural systems) are correlated with patients' executive function (EF), conceptualized as the integration of "cool" EF and "hot" EF. "Cool" EF refers to relatively abstract, non-affective operations such as inhibitory control and mental flexibility. "Hot" EF refers to motivationally significant affective operations such as affective decision-making. We tried to find the correlation between structural and functional neuroimaging indices and EF in obese patients. The study population comprised seventeen patients with obesity (seven males and 10 females, BMI = 37.99 ± 5.40, age = 31.82 ± 8.75 year-old) preparing to undergo bariatric surgery. We used noninvasive diffusion tensor imaging, generalized q-sampling imaging, and resting-state functional magnetic resonance imaging to examine the neural correlations between structural and functional neuroimaging indices and EF performances in patients with obesity. We reported that many brain areas are correlated to the patients' EF performances. More interestingly, some correlations may implicate the possible associations of EF and the incentive motivational effects of food. The neural correlation between the left precuneus and middle occipital gyrus and inhibitory control may suggest that patients with a better ability to detect appetitive food may have worse inhibitory control. Also, the neural correlation between the superior frontal blade and affective decision-making may suggest that patients' affective decision-making may be associated with the incentive motivational effects of food. Our results provide evidence suggesting neural correlates of EF in patients with obesity.

Enhance®Fitness Dissemination and Implementation,: 2010-2015: A Scoping Review.

PubMed

Petrescu-Prahova, Miruna G; Eagen, Thomas J; Fishleder, Sarah L; Belza, Basia

2017-03-01

Physical activity has many benefits for older adult physical and mental health. Enhance ® Fitness (EF) is an evidence-based group exercise program delivered by community-based organizations. The purpose of this study was to review recent evidence on the dissemination and implementation of EF. A scoping review of qualitative and quantitative studies with EF as main focus was conducted. CINAHL, PubMed, PubMed Central, SCOPUS, Web of Science, PsycINFO, and Google Scholar were searched between October and November 2015 for data-based studies on EF published in 2010-2015. Two team members abstracted each paper independently using a data abstraction tool. Results were summarized using the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework. Seventeen publications met inclusion criteria. EF has reached and is effective across a broad population base, including individuals with low SES and diverse ethnic/racial backgrounds. EF participation may be associated with reduced risk for falls requiring medical care, and is associated with fewer hospital admissions. Analyses of medical cost savings from EF participation and program implementation costs suggest economic benefits of EF implementation for communities. Organization-level maintenance is facilitated by program-specific and organizational factors, such as instructor training and funding. Individual-level maintenance is facilitated by program structure, absence of pain, and increased quality of life. More-rigorous evidence is needed about the association between participation in EF and conditions such as falls. Evaluation of program fidelity, adaptations, and sustainability is limited; more-systematic examination across population groups and types of organizations would help ensure older adults continue to benefit from EF participation. Copyright © 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

EF24, a novel curcumin analog, disrupts the microtubule cytoskeleton and inhibits HIF-1

PubMed Central

Thomas, Shala L.; Zhong, Diansheng; Zhou, Wei; Malik, Sanna; Liotta, Dennis; Snyder, James P.; Hamel, Ernest; Giannakakou, Paraskevi

2008-01-01

Curcumin, the yellow pigment of the spice turmeric, has emerged as a promising anticancer agent due to its antiproliferative and antiangiogenic properties. However, the molecular mechanism of action of this compound remains a subject of debate. In addition, curcumin’s low bioavailability and efficacy profile in vivo further hinders its clinical development. This study focuses on the mechanism of action of EF24, a novel curcumin analog with greater than curcumin biological activity and bioavailability, but no increased toxicity. Treatment of MDA-MB231 breast and PC3 prostate cancer cells with EF24 or curcumin led to inhibition of HIF-1α protein levels and, consequently, inhibition of HIF transcriptional activity. This drug-induced HIF inhibition occurred in a VHL-dependent but proteasome-independent manner. We found that, while curcumin inhibited HIF-1α gene transcription, EF24 exerted its activity by inhibiting HIF-1α posttranscriptionally. This result suggested that the two compounds are structurally similar but mechanistically distinct. Another cellular effect that further differentiated the two compounds was the ability of EF24, but not curcumin, to induce microtubule stabilization in cells. EF24 had no stabilizing effect on tubulin polymerization in an in vitro assay using purified bovine brain tubulin, suggesting that the EF24-induced cytoskeletal disruption in cells may be the result of upstream signaling events rather than EF24 direct binding to tubulin. In summary, our study identifies EF24 as a novel curcumin-related compound possessing a distinct mechanism of action, which we believe contributes to the potent anticancer activity of this agent and can be further exploited to investigate the therapeutic potential of EF24. PMID:18682687

EF24, a novel curcumin analog, disrupts the microtubule cytoskeleton and inhibits HIF-1.

PubMed

Thomas, Shala L; Zhong, Diansheng; Zhou, Wei; Malik, Sanna; Liotta, Dennis; Snyder, James P; Hamel, Ernest; Giannakakou, Paraskevi

2008-08-01

Curcumin, the yellow pigment of the spice turmeric, has emerged as a promising anticancer agent due to its antiproliferative and antiangiogenic properties. However, the molecular mechanism of action of this compound remains a subject of debate. In addition, curcumin's low bioavailability and efficacy profile in vivo further hinders its clinical development. This study focuses on the mechanism of action of EF24, a novel curcumin analog with greater than curcumin biological activity and bioavailability, but no increased toxicity. Treatment of MDA-MB231 breast and PC3 prostate cancer cells with EF24 or curcumin led to inhibition of HIF-1alpha protein levels and, consequently, inhibition of HIF transcriptional activity. This drug-induced HIF inhibition occurred in a VHL-dependent but proteasome-independent manner. We found that, while curcumin inhibited HIF-1alpha gene transcription, EF24 exerted its activity by inhibiting HIF-1alpha posttranscriptionally. This result suggested that the two compounds are structurally similar but mechanistically distinct. Another cellular effect that further differentiated the two compounds was the ability of EF24, but not curcumin, to induce microtubule stabilization in cells. EF24 had no stabilizing effect on tubulin polymerization in an in vitro assay using purified bovine brain tubulin, suggesting that the EF24-induced cytoskeletal disruption in cells may be the result of upstream signaling events rather than EF24 direct binding to tubulin. In summary, our study identifies EF24 as a novel curcumin-related compound possessing a distinct mechanism of action, which we believe contributes to the potent anticancer activity of this agent and can be further exploited to investigate the therapeutic potential of EF24.

To boost or to CRUNCH? Effect of effortful encoding on episodic memory in older adults is dependent on executive functioning

PubMed Central

Fu, Li; Maes, Joseph H. R.; Kessels, Roy P. C.; Daselaar, Sander M.

2017-01-01

It is essential to develop effective interventions aimed at ameliorating age-related cognitive decline. Previous studies found that effortful encoding benefits episodic memory in older adults. However, to date it is unclear whether this benefit is different for individuals with strong versus weak executive functioning (EF). Fifty-one older adults were recruited and divided into low (N = 26) and high (N = 25) functioning groups, based on their EF capacity. All participants performed a semantic and a perceptual incidental encoding task. Each encoding task was performed under four difficulty levels to establish different effort levels. Encoding was followed by a recognition task. Results showed that the high EF group benefitted from increased effort in both tasks. However, the low EF group only showed a beneficial effect under low levels of effort. Results are consistent with the Compensation-Related Utilization of Neural Circuits Hypothesis (CRUNCH) and suggest that future research directed at developing efficient memory strategies to reduce negative cognitive aging effects should take individual cognitive differences among older adults into account, such as differences in EF. PMID:28328979

Diagnosis and Management of Heart Failure with Preserved Ejection Frac-tion: 10 Key Lessons

PubMed Central

A, Afşin Oktay; Shah, Sanjiv J

2015-01-01

Heart failure with preserved ejection fraction (HFpEF) is a common clinical syndrome associated with high rates of morbidi-ty and mortality. Due to the lack of evidence-based therapies and increasing prevalence of HFpEF, clinicians are often con-fronted with these patients and yet have little guidance on how to effectively diagnose and manage them. Here we offer 10 key lessons to assist with the care of patients with HFpEF: (1) Know the difference between diastolic dysfunction, diastolic heart failure, and HFpEF; (2) diagnosing HFpEF is challenging, so be thorough and consider invasive hemodynamic testing to confirm the diagnosis; (3) a normal B-type natriuretic peptide does not exclude the diagnosis of HFpEF; (4) elevated pul-monary artery systolic pressure on echocardiography in the presence of a normal ejection fraction should prompt considera-tion of HFpEF; (5) use dynamic testing in evaluating the possibility of HFpEF in patients with unexplained dyspnea or exer-cise tolerance; (6) all patients with HFpEF should be systematically evaluated for the presence of coronary artery disease; (7) use targeted treatment for HFpEF patients based on their phenotypic classification; (8) treat HFpEF patients now by treating their comorbidities; (9) understand the importance of heart rate in HFpEF—lower is not always better; and (10) do not forget to consider rare diseases (“zebras”) as causes for HFpEF when evaluating and treating patients. Taken together, these 10 key lessons can help clinicians care for challenging patients with HFpEF while we eagerly await the results of ongoing HFpEF clinical trials and observational studies. PMID:24251461

Sediment quality assessment in a coastal lagoon (Ravenna, NE Italy) based on SEM-AVS and sequential extraction procedure.

PubMed

Pignotti, Emanuela; Guerra, Roberta; Covelli, Stefano; Fabbri, Elena; Dinelli, Enrico

2018-09-01

Sediments from the Pialassa Piomboni coastal lagoon (NE Italy) were studied to assess the degree of contamination and ecological risk related to trace metals by combining a geochemical characterization of bulk sediments with the assessment of the bioavailable forms of trace metals. With this purpose, sediment contamination (Cd, Cu, Hg, Ni, Pb, and Zn) was assessed by Enrichment Factors (EFs), and potential bioavailability by the Simultaneously Extracted Metals and Acid Volatile Sulfides (SEM-AVS) approach (Cd, Cu, Ni, Pb, and Zn), and by Sequential Extraction Procedure (Co, Cr, Cu, Ni, Pb, and Zn). On average, Cr and Ni exhibited no contamination (EF ≤1.5), and a predominance in the residual fraction of the sediment, indicating natural origin for these metals. Cu, Pb and Zn displayed a local contamination, which resulted in a higher proportion of Cu bound to the reducible and oxidizable fractions (~30% and ~40% as median, respectively), and Pb mostly associated with the reducible phase (~60% as median). Hence, Cu and Pb could be mobilized when environmental conditions become reducing or oxidizing. Zn resulted mainly partitioned into the reducible and residual fractions (~50% as median, in both fractions). The Risk Assessment Code (RAC) indicated that approximately 30% of samples had >10% of total Zn weakly bound to the sediment, suggesting a medium risk of exposure for aquatic organisms. RAC results were consistent with the ∑SEM-AVS findings, pointing to possible adverse effects for aquatic biota in ~30% of samples, with Zn mostly accounting for the total metal bioavailability. Hg showed a moderate to very severe enrichment, indicating that a substantial amount of this metal derives from anthropogenic sources and may pose adverse effects on the aquatic biota of the Pialassa Piomboni lagoon. Copyright © 2018 Elsevier B.V. All rights reserved.

Protection of mice from oral Candidiasis by heat-killed enterococcus faecalis, possibly through its direct binding to Candida albicans.

PubMed

Ishijima, Sanae A; Hayama, Kazumi; Ninomiya, Kentaro; Iwasa, Masahiro; Yamazaki, Masatoshi; Abe, Shigeru

2014-01-01

To develop a new therapy against oral candidiasis, a commensal microorganism, Enterococcus faecalis was tested for its ability to modulate Candida growth in vitro and its therapeutic activities against a murine model in vivo. Addition of heat-killed E. faecalis strain EF2001 (EF2001) isolated from healthy human feces to the culture of C. albicans strain TIMM1768 inhibited adherence of the latter to a microtiter plate in a dose dependent manner and Candida cells surrounded by EF2001 were increased. To examine the protective activities of EF2001 in vivo, heat-killed EF2001 was applied orally before and after inoculation of Candida to the tongue of mice previously immunosuppressed. Two days after inoculation this inoculation, both the symptom score and CFU from swabbed-tongue were significantly reduced in the EF2001-treated animals. Histological analysis indicated that EF2001 may potentiate the accumulation of polymorphnuclear cells near a Candida-infected region. These results suggest that oral administration of EF2001 has protective activity against oral candidiasis and that the in vivo activity may be reflected by direct interaction between EF2001 and Candida cells in vitro and the potentiation of an immunostimulatory effect of EF2001.

Influence of activated carbon preloading by EfOM fractions from treated wastewater on adsorption of pharmaceutically active compounds.

PubMed

Hu, Jingyi; Shang, Ran; Heijman, Bas; Rietveld, Luuk

2016-05-01

In this study, the preloading effects of different fractions of wastewater effluent organic matter (EfOM) on the adsorption of trace-level pharmaceutically active compounds (PhACs) onto granular activated carbon (GAC) were investigated. A nanofiltration (NF) membrane was employed to separate the EfOM by size, and two GACs with distinct pore structures were chosen for comparison. The results showed that preloading with EfOM substantially decreased PhAC uptake of the GACs; however, comparable PhAC adsorption capacities were achieved on GACs preloaded by feed EfOM and the NF-permeating EfOM. This indicates that: (1) the NF-rejected, larger EfOM molecules with an expectation to block the PhAC adsorption pores exerted little impact on the adsorbability of PhACs; (2) the smaller EfOM molecules present in the NF permeate contributed mainly to the decrease in PhAC uptake, mostly due to site competition. Of the two examined GACs, the wide pore-size-distributed GAC was found to be more susceptible to EfOM preloading than the microporous GAC. Furthermore, among the fourteen investigated PhACs, the negatively charged hydrophilic PhACs were generally subjected to a greater EfOM preloading impact. Copyright © 2016 Elsevier Ltd. All rights reserved.

The effect of phosphorylation of the EF-2 isolated from rat liver cells on protein biosynthesis in vitro.

PubMed

Gajko, A; Sredzińska, K; Marcinkiewicz, C; Gałasiński, W

1991-01-01

The activity of EF-2 was distinctly decreased after phosphorylation catalysed by a partly purified calmodulin and Ca2+ dependent protein kinase III. At the same time 32P from [gamma-32P]ATP was incorporated into EF-2 molecule. After dephosphorylation of EF-2 catalysed by alkaline phosphatase the activity of this factor was increased. This suggests that the phosphorylation-dephosphorylation of EF-2 is the regulatory process in the elongation step of the translation. Preliminary purification of the kinase III from rat liver resulted in 8-fold purified enzyme with a recovery of 60%.

Core executive functions are associated with success in young elite soccer players.

PubMed

Vestberg, Torbjörn; Reinebo, Gustaf; Maurex, Liselotte; Ingvar, Martin; Petrovic, Predrag

2017-01-01

Physical capacity and coordination cannot alone predict success in team sports such as soccer. Instead, more focus has been directed towards the importance of cognitive abilities, and it has been suggested that executive functions (EF) are fundamentally important for success in soccer. However, executive functions are going through a steep development from adolescence to adulthood. Moreover, more complex EF involving manipulation of information (higher level EF) develop later than simple executive functions such as those linked to simple working memory capacity (Core EF). The link between EF and success in young soccer players is therefore not obvious. In the present study we investigated whether EF are associated with success in soccer in young elite soccer players. We performed tests measuring core EF (a demanding working memory task involving a variable n-back task; dWM) and higher level EF (Design Fluency test; DF). Color-Word Interference Test and Trail Making Test were performed on an exploratory level as they contain a linguistic element. The lower level EF test (dWM) was taken from CogStateSport computerized concussion testing and the higher level EF test (DF) was from Delis-Kaplan Executive Function System test battery (D-KEFS). In a group of young elite soccer players (n = 30; aged 12-19 years) we show that they perform better than the norm in both the dWM (+0.49 SD) and DF (+0.86 SD). Moreover, we could show that both dWM and DF correlate with the number of goals the players perform during the season. The effect was more prominent for dWM (r = 0.437) than for DF (r = 0.349), but strongest for a combined measurement (r = 0.550). The effect was still present when we controlled for intelligence, length and age in a partial correlation analysis. Thus, our study suggests that both core and higher level EF may predict success in soccer also in young players.

Core executive functions are associated with success in young elite soccer players

PubMed Central

Reinebo, Gustaf; Maurex, Liselotte; Ingvar, Martin; Petrovic, Predrag

2017-01-01

Physical capacity and coordination cannot alone predict success in team sports such as soccer. Instead, more focus has been directed towards the importance of cognitive abilities, and it has been suggested that executive functions (EF) are fundamentally important for success in soccer. However, executive functions are going through a steep development from adolescence to adulthood. Moreover, more complex EF involving manipulation of information (higher level EF) develop later than simple executive functions such as those linked to simple working memory capacity (Core EF). The link between EF and success in young soccer players is therefore not obvious. In the present study we investigated whether EF are associated with success in soccer in young elite soccer players. We performed tests measuring core EF (a demanding working memory task involving a variable n-back task; dWM) and higher level EF (Design Fluency test; DF). Color-Word Interference Test and Trail Making Test were performed on an exploratory level as they contain a linguistic element. The lower level EF test (dWM) was taken from CogStateSport computerized concussion testing and the higher level EF test (DF) was from Delis-Kaplan Executive Function System test battery (D-KEFS). In a group of young elite soccer players (n = 30; aged 12–19 years) we show that they perform better than the norm in both the dWM (+0.49 SD) and DF (+0.86 SD). Moreover, we could show that both dWM and DF correlate with the number of goals the players perform during the season. The effect was more prominent for dWM (r = 0.437) than for DF (r = 0.349), but strongest for a combined measurement (r = 0.550). The effect was still present when we controlled for intelligence, length and age in a partial correlation analysis. Thus, our study suggests that both core and higher level EF may predict success in soccer also in young players. PMID:28178738

The effect of deletion of the edema factor on Bacillus anthracis pathogenicity in guinea pigs and rabbits.

PubMed

Levy, Haim; Weiss, Shay; Altboum, Zeev; Schlomovitz, Josef; Rothschild, Nili; Glinert, Itai; Sittner, Assa; Kobiler, David

2012-01-01

Bacillus anthracis secretes three major components, which assemble into two bipartite toxins: lethal toxin (LT), composed of lethal factor (LF) and protective antigen (PA) and edema toxin (ET), composed of edema factor (EF) and PA. EF is a potent calmodulin-dependent adenylate cyclase, which is internalized into the target cell following PA binding. Once inside the cell, EF elevates cAMP levels, interrupting intracellular signaling. Effects of ET were demonstrated on monocytes, neutrophils and T-cells. In an earlier work we demonstrated that a deletion of LF in a fully virulent strain had no effect in guinea pigs and a significant, but not major, effect in the rabbit model. These results suggested that EF might play an important role in the development of infection and mortality following exposure to B. anthracis spores. To evaluate the role of EF in B. anthracis pathogenicity we deleted the cya gene, which encodes the EF protein, in the fully virulent Vollum strain. The Δcya mutant was fully virulent in the guinea pig model as determined by LD(50) experiments. In the rabbit model, when infected subcutaneously, the absence of EF had no effect on the virulence of the mutant. However an increase of two orders of magnitude in the LD(50) was demonstrated when the rabbits were infected by intranasal instillation accompanied with partial mortality and increased mean time to death. These results argue that in the guinea pig model the presence of one of the toxins, ET or LT is sufficient for the development of the infection. In the rabbit model ET plays a role in respiratory infection, most probably mediating the early steps of host colonization. Copyright © 2011 Elsevier Ltd. All rights reserved.

HDAC inhibitors, MS-275 and salermide, potentiates the anticancer effect of EF24 in human pancreatic cancer cells.

PubMed

Yar Saglam, Atiye Seda; Yilmaz, Akin; Onen, Hacer Ilke; Alp, Ebru; Kayhan, Handan; Ekmekci, Abdullah

2016-01-01

Histone deacetylases (HDACs) play a major role in the regulation of chromatin structure and gene expression by changing acetylation status of histone and non-histone proteins. MS-275 (entinostat, MS) is a well-known benzamide-based HDACI and Salermide (SAL), a reverse amide compound HDACI, have antiproliferative effects on several human cancer cells. In this study, we aimed to investigate the effects of HDACIs (MS and SAL) alone and/or combined use with EF24 (EF), a novel synthetic curcumin analog, on human pancreatic cancer cell line (BxPC-3). In vitro, BxPC-3 cells were exposed to varying concentrations of MS, SAL with or without EF, and their effects on cell viability, acetylated Histone H3 and H4 levels, cytotoxicity, and cleaved caspase 3 levels, and cell cycle distribution were measured. The viability of BxPC-3 cells decreased significantly after treatment with EF, MS and SAL treatments. MS and SAL treatment increased the acetylation of histone H3 and H4 in a dose dependent manner. MS and SAL alone or combined with EF were increased the number of cells in G1 phase. In addition, treatment with agents significantly decreased the ratio of cell in G2/M phase. There were significant dose-dependent increases at cleaved Caspase 3 levels after MS treatment but not after SAL treatment. Our results showed that HDAC inhibitors (MS and SAL), when combined with EF, may effectively reduce pancreatic cancer cell (BxPC-3) progression and stop the cell cycle at G1 phase. Further molecular analyses are needed to understand the fundamental molecular consequences of HDAC inhibition in pancreas cancer cells.

Efficacy of actinidin-containing kiwifruit extract Zyactinase on constipation: a randomised double-blinded placebo-controlled clinical trial.

PubMed

Weir, Iona; Shu, Quan; Wei, Nengding; Wei, Chengkai; Zhu, Yi

2018-01-01

Zyactinase® is an extract of green kiwifruit, formulated into the consumer healthcare products marketed as Phloe® and Kivia, used to assist in the relief of the symptoms associated with a range of digestive system dysfunction, including constipation and Irritable Bowel Syndrome (IBS). A randomised, double-blind, placebo-controlled clinical trial was undertaken to determine the ef-fects of the kiwifruit extract on bowel movement, stool formation and IBS associated symptoms amongst a sub-ject group of generally healthy individuals experiencing a period of moderate constipation. Fifty-eight partici-pants were randomized to the kiwifruit extract (28) or placebo (30). Selection criterion was decreased number of bowel movements (<3/week), with increased faecal hardness and IBS associated symptoms. The study ran for three weeks, with participants first undergoing a seven-day wash out period, followed by a seven-day dosing pe-riod, and then a seven-day follow up period. There was a significant increase in the defecation frequency (p<0.001), with a significant improvement in faecal score (p<0.01). There was a significant difference in pain-ful defecation and abdominal pain between the two groups (p<0.01). No side effects, including diarrhoea, urgen-cy or abdominal pain, were observed during the trial. The green kiwifruit extract significantly in-duced normal bowel movements with no adverse effects. The kiwifruit extract relieved constipation and the symptoms of IBS such as bloating, flatulence and abdominal pain.

Diphenyl difluoroketone: a curcumin derivative with potent in vivo anticancer activity.

PubMed

Subramaniam, Dharmalingam; May, Randal; Sureban, Sripathi M; Lee, Katherine B; George, Robert; Kuppusamy, Periannan; Ramanujam, Rama P; Hideg, Kalman; Dieckgraefe, Brian K; Houchen, Courtney W; Anant, Shrikant

2008-03-15

Diphenyl difluoroketone (EF24), a molecule having structural similarity to curcumin, was reported to inhibit proliferation of a variety of cancer cells in vitro. However, the efficacy and in vivo mechanism of action of EF24 in gastrointestinal cancer cells have not been investigated. Here, we assessed the in vivo therapeutic effects of EF24 on colon cancer cells. Using hexosaminidase assay, we determined that EF24 inhibits proliferation of HCT-116 and HT-29 colon and AGS gastric adenocarcinoma cells but not of mouse embryo fibroblasts. Furthermore, the cancer cells showed increased levels of activated caspase-3 and increased Bax to Bcl-2 and Bax to Bcl-xL ratios, suggesting that the cells were undergoing apoptosis. At the same time, cell cycle analysis showed that there was an increased number of cells in the G(2)-M phase. To determine the effects of EF24 in vivo, HCT-116 colon cancer xenografts were established in nude mice and EF24 was given i.p. EF24 significantly suppressed the growth of colon cancer tumor xenografts. Immunostaining for CD31 showed that there was a lower number of microvessels in the EF24-treated animals coupled with decreased cyclooxygenase-2, interleukin-8, and vascular endothelial growth factor mRNA and protein expression. Western blot analyses also showed decreased AKT and extracellular signal-regulated kinase activation in the tumors. Taken together, these data suggest that the novel curcumin-related compound EF24 is a potent antitumor agent that induces caspase-mediated apoptosis during mitosis and has significant therapeutic potential for gastrointestinal cancers.

Spasmolytic effect of aqueous extract of Tagetes erecta L. flowers is mediated through calcium channel blockade on the guinea-pig ileum.

PubMed

Ventura-Martínez, Rosa; Ángeles-López, Guadalupe E; Rodríguez, Rodolfo; González-Trujano, Ma Eva; Déciga-Campos, Myrna

2018-07-01

This study provides pharmacological evidence on the spasmolytic activity of Tagetes erecta L. (marigold or cempasúchil) on the guinea-pig ileum and presents data on its mechanism of action. The relaxant effect on KCl contractions was more marked with aqueous (AqEx) than with ethanol extracts (EtEx) of T. erecta flowers (55.6 ± 11.0 vs 21.1 ± 4.4%, respectively). In addition, the aqueous extract antagonized contractions elicited by EFS, but not by acetylcholine (73.5 ± 1.9 vs 14.5 ± 5.3%, respectively). These effects were not diminished by hexamethonium or L-NAME, but this extract caused a rightward shift in the Ca 2+ concentration-response curves like that of verapamil. Quercetin and rutin, two flavonoids present in this plant, also showed spasmolytic effects (95.7 ± 2.8 and 27.9 ± 7.1%, respectively). Interestingly, in tissues without spasmogens, the extract induced contractions superimposed on their spontaneous activity. These results support the traditional use of T. erecta as a spasmolytic in folk medicine and suggest mainly that quercetin could be partly responsible for this effect. The spasmolytic effect appears to involve voltage-gated calcium channels, but not the nitric oxide pathway or the release of neurotransmitters from enteric neurons. Nevertheless, this plant could produce colic or stomachache as adverse effects in clinical situations in which these symptoms are not originally present. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Diminished but Not Abolished Effect of Two His351 Mutants of Anthrax Edema Factor in a Murine Model

PubMed Central

Zhao, Taoran; Zhao, Xinghui; Liu, Ju; Meng, Yingying; Feng, Yingying; Fang, Ting; Zhang, Jinlong; Yang, Xiuxu; Li, Jianmin; Xu, Junjie; Chen, Wei

2016-01-01

Edema toxin (ET), which is composed of a potent adenylate cyclase (AC), edema factor (EF), and protective antigen (PA), is one of the major toxicity factors of Bacillus anthracis. In this study, we introduced mutations in full-length EF to generate alanine EF(H351A) and arginine EF(H351R) variants. In vitro activity analysis displayed that the adenylyl cyclase activity of both the mutants was significantly diminished compared with the wild-type EF. When the native and mutant toxins were administered subcutaneously in a mouse footpad edema model, severe acute swelling was evoked by wild-type ET, while the symptoms induced by mutant toxins were very minor. Systemic administration of these EF variants caused non-lethal hepatotoxicity. In addition, EF(H351R) exhibited slightly higher activity in causing more severe edema than EF(H351A). Our findings demonstrate that the toxicity of ET is not abolished by substitution of EF residue His351 by alanine or arginine. These results also indicate the potential of the mouse footpad edema model as a sensitive method for evaluating both ET toxicity and the efficacy of candidate therapeutic agents. PMID:26848687

Effect of External Electric Field on Substrate Transport of a Secondary Active Transporter.

PubMed

Zhang, Ji-Long; Zheng, Qing-Chuan; Yu, Li-Ying; Li, Zheng-Qiang; Zhang, Hong-Xing

2016-08-22

Substrate transport across a membrane accomplished by a secondary active transporter (SAT) is essential to the normal physiological function of living cells. In the present research, a series of all-atom molecular dynamics (MD) simulations under different electric field (EF) strengths was performed to investigate the effect of an external EF on the substrate transport of an SAT. The results show that EF both affects the interaction between substrate and related protein's residues by changing their conformations and tunes the timeline of the transport event, which collectively reduces the height of energy barrier for substrate transport and results in the appearance of two intermediate conformations under the existence of an external EF. Our work spotlights the crucial influence of external EFs on the substrate transport of SATs and could provide a more penetrating understanding of the substrate transport mechanism of SATs.

Control of magnetism by electrical charge doping or redox reactions in a surface-oxidized Co thin film with a solid-state capacitor structure

NASA Astrophysics Data System (ADS)

Hirai, T.; Koyama, T.; Chiba, D.

2018-03-01

We have investigated the electric field (EF) effect on magnetism in a Co thin film with a naturally oxidized surface. The EF was applied to the oxidized Co surface through a gate insulator layer made of HfO2, which was formed using atomic layer deposition (ALD). The efficiency of the EF effect on the magnetic anisotropy in the sample with the HfO2 layer deposited at the appropriate temperature for the ALD process was relatively large compared to the previously reported values with an unoxidized Co film. The coercivity promptly and reversibly followed the variation in gate voltage. The modulation of the channel resistance was at most ˜0.02%. In contrast, a dramatic change in the magnetic properties including the large change in the saturation magnetic moment and a much larger EF-induced modulation of the channel resistance (˜10%) were observed in the sample with a HfO2 layer deposited at a temperature far below the appropriate temperature range. The response of these properties to the gate voltage was very slow, suggesting that a redox reaction dominated the EF effect on the magnetism in this sample. The frequency response for the capacitive properties was examined to discuss the difference in the mechanism of the EF effect observed here.

Enhancing ejection fraction measurement through 4D respiratory motion compensation in cardiac PET imaging

NASA Astrophysics Data System (ADS)

Tang, Jing; Wang, Xinhui; Gao, Xiangzhen; Segars, W. Paul; Lodge, Martin A.; Rahmim, Arman

2017-06-01

ECG gated cardiac PET imaging measures functional parameters such as left ventricle (LV) ejection fraction (EF), providing diagnostic and prognostic information for management of patients with coronary artery disease (CAD). Respiratory motion degrades spatial resolution and affects the accuracy in measuring the LV volumes for EF calculation. The goal of this study is to systematically investigate the effect of respiratory motion correction on the estimation of end-diastolic volume (EDV), end-systolic volume (ESV), and EF, especially on the separation of normal and abnormal EFs. We developed a respiratory motion incorporated 4D PET image reconstruction technique which uses all gated-frame data to acquire a motion-suppressed image. Using the standard XCAT phantom and two individual-specific volunteer XCAT phantoms, we simulated dual-gated myocardial perfusion imaging data for normally and abnormally beating hearts. With and without respiratory motion correction, we measured the EDV, ESV, and EF from the cardiac-gated reconstructed images. For all the phantoms, the estimated volumes increased and the biases significantly reduced with motion correction compared with those without. Furthermore, the improvement of ESV measurement in the abnormally beating heart led to better separation of normal and abnormal EFs. The simulation study demonstrated the significant effect of respiratory motion correction on cardiac imaging data with motion amplitude as small as 0.7 cm. The larger the motion amplitude the more improvement respiratory motion correction brought about on the EF measurement. Using data-driven respiratory gating, we also demonstrated the effect of respiratory motion correction on estimating the above functional parameters from list mode patient data. Respiratory motion correction has been shown to improve the accuracy of EF measurement in clinical cardiac PET imaging.

Murine Models of Heart Failure with Preserved Ejection Fraction: a “Fishing Expedition”

PubMed Central

Valero-Muñoz, Maria; Backman, Warren; Sam, Flora

2017-01-01

Summary Heart failure with preserved ejection fraction (HFpEF) is characterized by signs and symptoms of HF in the presence of a normal left ventricular (LV) ejection fraction (EF). Despite accounting for up to 50% of all clinical presentations of HF, the mechanisms implicated in HFpEF are poorly understood, thus precluding effective therapy. The pathophysiological heterogeneity in the HFpEF phenotype also contributes to this disease and likely to the absence of evidence-based therapies. Limited access to human samples and imperfect animal models that completely recapitulate the human HFpEF phenotype have impeded our understanding of the mechanistic underpinnings that exist in this disease. Aging and comorbidities such as atrial fibrillation, hypertension, diabetes and obesity, pulmonary hypertension and renal dysfunction are highly associated with HFpEF. Yet, the relationship and contribution between them remains ill-defined. This review discusses some of the distinctive clinical features of HFpEF in association with these comorbidities and highlights the advantages and disadvantage of commonly used murine models, used to study the HFpEF phenotype. PMID:29333506

Alternating current electric fields of varying frequencies: effects on proliferation and differentiation of porcine neural progenitor cells.

PubMed

Lim, Ji-Hey; McCullen, Seth D; Piedrahita, Jorge A; Loboa, Elizabeth G; Olby, Natasha J

2013-10-01

Application of sinusoidal electric fields (EFs) has been observed to affect cellular processes, including alignment, proliferation, and differentiation. In the present study, we applied low-frequency alternating current (AC) EFs to porcine neural progenitor cells (pNPCs) and investigated the effects on cell patterning, proliferation, and differentiation. pNPCs were grown directly on interdigitated electrodes (IDEs) localizing the EFs to a region accessible visually for fluorescence-based assays. Cultures of pNPCs were exposed to EFs (1 V/cm) of 1 Hz, 10 Hz, and 50 Hz for 3, 7, and 14 days and compared to control cultures. Immunocytochemistry was performed to evaluate the expression of neural markers. pNPCs grew uniformly with no evidence of alignment to the EFs and no change in cell numbers when compared with controls. Nestin expression was shown in all groups at 3 and 7 days, but not at 14 days. NG2 expression was low in all groups. Co-expression of glial fibrillary acidic protein (GFAP) and TUJ1 was significantly higher in the cultures exposed to 10- and 50-Hz EFs than the controls. In summary, sinusoidal AC EFs via IDEs did not alter the alignment and proliferation of pNPCs, but higher frequency stimulation appeared to delay differentiation into mature astrocytes.

Effect of 50 Hz electric field in diacylglycerol acyltransferase mRNA expression level and plasma concentration of triacylglycerol, free fatty acid, phospholipid and total cholesterol

PubMed Central

2012-01-01

Background The effects of exposure to a 50 Hz electric field (EF) on plasma level of triacylglycerol, free fatty acids, total cholesterol and phospholipid and mRNA expression level of diacylglycerol acyltransferase (DGAT) 1 and 2 in liver and intestines from C57BL/6 J mice were studied. Methods The test was based on comparison between mice post treated with 50 Hz EF of 45 kV/m intensity for 30 min per day for 11 days or without EF. DGATs mRNA expression was analyzed by real-time quantitative polymerase chain reaction. Results There was no difference in the gene expression level of DGAT1 in liver and intestines. The DGAT2 gene expression level in liver derived from mice treated with EF was significantly lower than those in the control (P < 0.001). Both plasma total cholesterol (P < 0.01) and phospholipid (P < 0.05) in the group exposed to EF were lower than those in the control, but there was no difference in triacylglycerol or free fatty acid levels. Conclusion Exposure to 50 Hz EF decrease the plasma levels of total cholesterol and phospholipids, and downregulated DGAT2 mRNA expression in liver. The mechanisms for the effects of EF on lipid metabolism are not well understand yet, but altered DGAT2 activity may be involved. PMID:22676350

Effects of electric fields on human mesenchymal stem cell behaviour and morphology using a novel multichannel device.

PubMed

Banks, T A; Luckman, P S B; Frith, J E; Cooper-White, J J

2015-06-01

The intrinsic piezoelectric nature of collagenous-rich tissues, such as bone and cartilage, can result in the production of small, endogenous electric fields (EFs) during applied mechanical stresses. In vivo, these EFs may influence cell migration, a vital component of wound healing. As a result, the application of small external EFs to bone fractures and cutaneous wounds is actively practiced clinically. Due to the significant regenerative potential of stem cells in bone and cartilage healing, and their potential role in the observed improved healing in vivo post applied EFs, using a novel medium throughput device, we investigated the impacts of physiological and aphysiological EFs on human bone marrow-derived mesenchymal stem cells (hBM-MSCs) for up to 15 hours. The applied EFs had significant impacts on hBM-MSC morphology and migration; cells displayed varying degrees of conversion to a highly elongated phenotype dependent on the EF strength, consistent perpendicular alignment to the EF vector, and definitive cathodal migration in response to EF strengths ≥0.5 V cm(-1), with the fastest migration speeds observed at between 1.7 and 3 V cm(-1). We observed variability in hBM-MSC donor-to-donor responses and overall tolerances to applied EFs. This study thus confirms hBM-MSCs are responsive to applied EFs, and their rate of migration towards the cathode is controllable depending on the EF strength, providing new insight into the physiology of hBM-MSCs and possibly a significant opportunity for the utilisation of EFs in directed scaffold colonisation in vitro for tissue engineering applications or in vivo post implantation.

History of Childhood Maltreatment and College Academic Outcomes: Indirect Effects of Hot Execution Function

PubMed Central

Welsh, Marilyn C.; Peterson, Eric; Jameson, Molly M.

2017-01-01

College students who report a history of childhood maltreatment may be at risk for poor outcomes. In the current study, we conducted an exploratory analysis to examine potential models that statistically mediate associations between aspects of maltreatment and aspects of academic outcome, with a particular focus on executive functions (EF). Consistent with contemporary EF research, we distinguished between relatively “cool” EF tasks (i.e., performed in a context relatively free of emotional or motivational valence) and “hot” EF tasks that emphasize performance under more emotionally arousing conditions. Sixty-one male and female college undergraduates self-reported childhood maltreatment history (emotional abuse and neglect, physical abuse and neglect, and sexual abuse) on the Childhood Trauma Questionnaire (CTQ), and were given two EF measures: (1) Go-No-Go (GNG) test that included a Color Condition (cool); Neutral Face Condition (warm); and Emotion Face condition (hot), and (2) Iowa Gambling Task (IGT), a measure of risky decision making that reflects hot EF. Academic outcomes were: (1) grade point average (GPA: first-semester, cumulative, and semester concurrent with testing), and (2) Student Adaptation to College Questionnaire (SACQ). Correlational patterns suggested two EF scores as potential mediators: GNG reaction time (RT) in the Neutral Face condition, and IGT Block 2 adaptive responding. Indirect effects analyses indicated that IGT Block 2 adaptive responding has an indirect effect on the relationship between CTQ Total score and 1st semester GPA, and between CTQ Emotional Abuse and concurrent GPA. Regarding college adaptation, we identified a consistent indirect effect of GNG Neutral Face RT on the relationship between CTQ Emotional Neglect and SACQ total, academic, social, and personal–emotional adaption scores. Our results demonstrate that higher scores on a child maltreatment history self-report negatively predict college academic outcomes as assessed by GPA and by self-reported adaptation. Further, relatively “hot” EF task performance on the IGT and GNG tasks serves as a link between child maltreatment experiences and college achievement and adaptation, suggesting that hot EF skills may be a fruitful direction for future intervention efforts to improve academic outcomes for this population. PMID:28725204

Continuous executive function disruption interferes with application of an information integration categorization strategy.

PubMed

Miles, Sarah J; Matsuki, Kazunaga; Minda, John Paul

2014-07-01

Category learning is often characterized as being supported by two separate learning systems. A verbal system learns rule-defined (RD) categories that can be described using a verbal rule and relies on executive functions (EFs) to learn via hypothesis testing. A nonverbal system learns non-rule-defined (NRD) categories that cannot be described by a verbal rule and uses automatic, procedural learning. The verbal system is dominant in that adults tend to use it during initial learning but may switch to the nonverbal system when the verbal system is unsuccessful. The nonverbal system has traditionally been thought to operate independently of EFs, but recent studies suggest that EFs may play a role in the nonverbal system-specifically, to facilitate the transition away from the verbal system. Accordingly, continuously interfering with EFs during the categorization process, so that EFs are never fully available to facilitate the transition, may be more detrimental to the nonverbal system than is temporary EF interference. Participants learned an NRD or an RD category while EFs were untaxed, taxed temporarily, or taxed continuously. When EFs were continuously taxed during NRD categorization, participants were less likely to use a nonverbal categorization strategy than when EFs were temporarily taxed, suggesting that when EFs were unavailable, the transition to the nonverbal system was hindered. For the verbal system, temporary and continuous interference had similar effects on categorization performance and on strategy use, illustrating that EFs play an important but different role in each of the category-learning systems.

Emulsifier of Arthrobacter RAG-1: specificity of hydrocarbon substrate.

PubMed Central

Rosenberg, E; Perry, A; Gibson, D T; Gutnick, D L

1979-01-01

The purified extracellular emulsifying factor produced by Arthrobacter RAG-1 (EF-RAG) emulsified light petroleum oil, diesel oil, and a variety of crude oils and gas oils. Although kerosine and gasoline were emulsified poorly by EF-RAG, they were converted into good substrates for emulsification by addition of aromatic compounds, such as 2-methylnaphthalene. Neither aromatic nor aliphatic fractions of crude oil were emulsified by EF-RAG; however, mixtures containing both fractions were emulsified. Pure aliphatic or aromatic hydrocarbons were emulsified poorly by EF-RAG. Binary mixtures containing an aliphatic and an aromatic hydrocarbon, however, were excellent substrates for EF-RAG-induced emulsification. Of a variety of alkylcyclohexane and alkylbenzene derivatives tested, only hexyl- or heptylbenzene and octyl- or decylcyclohexane were effectively emulsified by EF-RAG. These data indicate that for EF-RAG to induce emulsification of hydrocarbons in water, the hydrocarbon substrate must contain both aliphatic and cyclic components. With binary mixtures of methylnaphthalene and hexadecane, maximum emulsion was obtained with 25% hexadecane. PMID:453821

Progress in reading and spelling of dyslexic children is not affected by executive functioning.

PubMed

Walda, Sietske A E; van Weerdenburg, Marjolijn; Wijnants, Maarten L; Bosman, Anna M T

2014-12-01

Although poor reading and spelling skills have been associated with weak skills of executive functioning (EF), its role in literacy is not undisputed. Because EF has different theoretical underpinnings, methods of analysis and of assessing, it has led to varying and often contrasting results in its effects in children with dyslexia. The present study has two goals. The first goal is to establish the relationship between a large number of EF tasks and reading and spelling skills in a large number of Dutch dyslexic children (n = 229). More interesting, however, is the second aim. To what extent do EF skills predict progress in reading and spelling in dyslexic children who attended a remediation programme? The results revealed small, but significant relationships between EF and reading and spelling skills, but no relationships between EF and progress in reading and spelling. It is concluded that training EF skills is unlikely to enhance reading and spelling skills. Copyright © 2014 Elsevier Ltd. All rights reserved.

Sorptive extraction using polydimethylsiloxane/metal-organic framework coated stir bars coupled with high performance liquid chromatography-fluorescence detection for the determination of polycyclic aromatic hydrocarbons in environmental water samples.

PubMed

Hu, Cong; He, Man; Chen, Beibei; Zhong, Cheng; Hu, Bin

2014-08-22

In this work, metal-organic frameworks (MOFs, Al-MIL-53-NH₂) were synthesized via the hydrothermal method, and novel polydimethylsiloxane/metal-organic framework (PDMS/MOFs, PDMS/Al-MIL-53-NH₂)-coated stir bars were prepared by the sol-gel technique. The preparation reproducibility of the PDMS/MOFs-coated stir bar was good, with relative standard deviations (RSDs) ranging from 4.8% to 14.9% (n=7) within one batch and from 6.2% to 16.9% (n=6) among different batches. Based on this fact, a new method of PDMS/MOFs-coated stir bar sorptive extraction (SBSE) and ultrasonic-assisted liquid desorption (UALD) coupled with high performance liquid chromatography-fluorescence detection (HPLC-FLD) was developed for the determination of polycyclic aromatic hydrocarbons (PAHs) in environmental water samples. To obtain the best extraction performance for PAHs, several parameters affecting SBSE, such as extraction time, stirring rate, and extraction temperature, were investigated. Under optimal experimental conditions, wide linear ranges and good RSDs (n=7) were obtained. With enrichment factors (EFs) of 16.1- to 88.9-fold (theoretical EF, 142-fold), the limits of detection (LODs, S/N=3) of the developed method for the target PAHs were found to be in the range of 0.05-2.94 ng/L. The developed method was successfully applied to the analysis of PAHs in Yangtze River and East Lake water samples. Copyright © 2014 Elsevier B.V. All rights reserved.

Effect of Play-based Therapy on Meta-cognitive and Behavioral Aspects of Executive Function: A Randomized, Controlled, Clinical Trial on the Students With Learning Disabilities.

PubMed

Karamali Esmaili, Samaneh; Shafaroodi, Narges; Hassani Mehraban, Afsoon; Parand, Akram; Zarei, Masoume; Akbari-Zardkhaneh, Saeed

2017-01-01

Although the effect of educational methods on executive function (EF) is well known, training this function by a playful method is debatable. The current study aimed at investigating if a play-based intervention is effective on metacognitive and behavioral skills of EF in students with specific learning disabilities. In the current randomized, clinical trial, 49 subjects within the age range of 7 to 11 years with specific learning disabilities were randomly assigned into the intervention (25 subjects; mean age 8.5±1.33 years) and control (24 subjects; mean age 8.7±1.03 years) groups. Subjects in the intervention group received EF group training based on playing activities; subjects in the control group received no intervention. The behavior rating inventory of executive function (BRIEF) was administered to evaluate the behavioral and cognitive aspects of EF. The duration of the intervention was 6 hours per week for 9 weeks. Multivariate analysis of covariance was used to compare mean changes (before and after) in the BRIEF scores between the groups. The assumptions of multivariate analysis of covariance were examined. After controlling pre-test conditions, the intervention and control groups scored significantly differently on both the metacognition (P=0.002; effect size=0.20) and behavior regulation indices (P=0.01; effect size=0.12) of BRIEF. Play-based therapy is effective on the metacognitive and behavioral aspects of EF in students with specific learning disabilities. Professionals can use play-based therapy rather than educational approaches in clinical practice to enhance EF skills.

Strong Genetic Overlap Between Executive Functions and Intelligence

PubMed Central

Engelhardt, Laura E.; Mann, Frank D.; Briley, Daniel A.; Church, Jessica A.; Harden, K. Paige; Tucker-Drob, Elliot M.

2016-01-01

Executive functions (EFs) are cognitive processes that control, monitor, and coordinate more basic cognitive processes. EFs play instrumental roles in models of complex reasoning, learning, and decision-making, and individual differences in EFs have been consistently linked with individual differences in intelligence. By middle childhood, genetic factors account for a moderate proportion of the variance in intelligence, and these effects increase in magnitude through adolescence. Genetic influences on EFs are very high, even in middle childhood, but the extent to which these genetic influences overlap with those on intelligence is unclear. We examined genetic and environmental overlap between EFs and intelligence in a racially and socioeconomically diverse sample of 811 twins ages 7-15 years (M = 10.91, SD = 1.74) from the Texas Twin Project. A general EF factor representing variance common to inhibition, switching, working memory, and updating domains accounted for substantial proportions of variance in intelligence, primarily via a genetic pathway. General EF continued to have a strong, genetically-mediated association with intelligence even after controlling for processing speed. Residual variation in general intelligence was influenced only by shared and nonshared environmental factors, and there remained no genetic variance in general intelligence that was unique of EF. Genetic variance independent of EF did remain, however, in a more specific perceptual reasoning ability. These results provide evidence that genetic influences on general intelligence are highly overlapping with those on EF. PMID:27359131

STRESS REGULATION AS A LINK BETWEEN EXECUTIVE FUNCTION AND PRE-FRAILTY IN OLDER ADULTS

PubMed Central

Roiland, R.A.; Lin, F.; Phelan, C.; Chapman, B.P.

2017-01-01

Objectives Both pre-frailty and frailty are linked with impaired executive function (EF) but the mechanism underlying this relationship is not known. Williams and colleagues’ model posits EF affects health outcomes via stress regulation. This model was utlized to test indicators of stress regulation as mediators of the relationship between EF and pre-frailty in older adults. Design Cross-sectional. Setting Academic general clinical research centers. Participants 690 community-dwelling older adults ≥ 50 years of age. Measurements Pre-frailty was measured using a modified form of the Fried Frailty measure. EF was assessed via telephone-based neurocognitive assessments. Indicators of stress regulation included: stress exposure (measured by perceived stress), reactivity and recovery (measured by heart rate) and restoration (measured by serum interleukin-6 and sleep quality). Results 396 individuals were classified as non-frail, 277 as pre-frail, and 17 as frail. Pre-frail and non-frail individuals were included in data analyses. Compared to non-frail individuals, prefrail were older and exhibited poorer EF, higher levels of stress exposure and poorer stress restoration. Poorer EF was associated with greater stress exposure, less stress reactivity, longer stress recovery and poorer stress restoration. The total effect of the relationship between EF and pre-frailty was significant with significant indirect effects supporting stress exposure and restoration as mediators of the relationship. Conclusion Stress exposure and restoration appear to mediate the relationship between EF and pre-frailty. Longitudinal studies are needed to clarify the direction of causality and determine whether stress regulation processes are appropriate targets for interventions aiming to prevent declines in EF and the development of pre-frailty. PMID:26412287

Activation of the p38- pathway by a novel monoketone curcumin analog, EF24, suggests a potential combination strategy

PubMed Central

Thomas, Shala L.; Zhao, Jing; Li, Zijian; Lou, Bin; Du, Yuhong; Purcell, Jamie; Snyder, James P.; Khuri, Fadlo R.; Liotta, Dennis; Fu, Haian

2010-01-01

Increasing attention has been given to the anti-cancer effects of curcumin and the ability of this natural product to inhibit cancer cell proliferation. New curcumin analogs have been developed to optimize the in vitro and in vivo activity of the parent compound yet retain the same safety profile. EF24, a fluorinated synthetic analog, surpasses curcumin in its ability to inhibit cancer cell viability and down-regulate TNFα-induced NF-κB activation. Here we report a critical role of the p38-mediated signaling pathway in the determination of lung cancer cell’s sensitivity to EF24. We have found that EF24-induced decease of lung cancer cell viability was accompanied by upregulated mitogen-activated protein kinases (MAPK) as evidenced by increased phosphorylation of ERK1/2, JNK, and p38. Pharmacological investigation led to our suggestion that EF24 triggers a negative feedback loop through p38 activation. In support of this model, inhibition of p38, either by small molecule inhibitors or through an RNAi-mediated knockdown approach, enhanced the EF24 induced apoptotic death of A549 cells. Thus, inhibition of p38 may boost the EF24 anticancer effect. Indeed, a combination of EF24 and SB203580, a p38 inhibitor, synergistically inhibited clonogenic activity of A549 lung cancer cells and induced their apoptosis as reflected by poly(ADP-ribose) polymerase cleavage, the accumulation of the sub-G1 fraction of cells, and apoptotic cell staining. These studies offer a novel strategy that combines the curcumin analog EF24 with a p38 inhibitor for potentially enhanced therapy in the treatment of lung cancer. PMID:20615389

Activation of the p38 pathway by a novel monoketone curcumin analog, EF24, suggests a potential combination strategy.

PubMed

Thomas, Shala L; Zhao, Jing; Li, Zijian; Lou, Bin; Du, Yuhong; Purcell, Jamie; Snyder, James P; Khuri, Fadlo R; Liotta, Dennis; Fu, Haian

2010-11-01

Increasing attention has been given to the anticancer effects of curcumin and the ability of this natural product to inhibit cancer cell proliferation. New curcumin analogs have been developed to optimize the in vitro and in vivo activity of the parent compound yet retain the same safety profile. EF24, a fluorinated synthetic analog, surpasses curcumin in its ability to inhibit cancer cell viability and down-regulate TNFα-induced NF-κB activation. Here we report a critical role of the p38-mediated signaling pathway in the determination of lung cancer cell's sensitivity to EF24. We have found that EF24-induced decease of lung cancer cell viability was accompanied by upregulated mitogen-activated protein kinases (MAPK) as evidenced by increased phosphorylation of ERK1/2, JNK, and p38. Pharmacological investigation led to our suggestion that EF24 triggers a negative feedback loop through p38 activation. In support of this model, inhibition of p38, either by small molecule inhibitors or through an RNAi-mediated knockdown approach, enhanced the EF24-induced apoptotic death of A549 cells. Thus, inhibition of p38 may boost the EF24 anticancer effect. Indeed, a combination of EF24 and SB203580, a p38 inhibitor, synergistically inhibited clonogenic activity of A549 lung cancer cells and induced their apoptosis as reflected by poly(ADP-ribose) polymerase cleavage, the accumulation of the sub-G(1) fraction of cells, and apoptotic cell staining. These studies offer a novel strategy that combines the curcumin analog EF24 with a p38 inhibitor for potentially enhanced therapy in the treatment of lung cancer. Copyright © 2010 Elsevier Inc. All rights reserved.

Water-compatible graphene oxide/molecularly imprinted polymer coated stir bar sorptive extraction of propranolol from urine samples followed by high performance liquid chromatography-ultraviolet detection.

PubMed

Fan, Wenying; He, Man; You, Linna; Zhu, Xuewei; Chen, Beibei; Hu, Bin

2016-04-22

Due to the high selectivity and stability, molecularly imprinted polymers (MIPs) have been successfully applied in stir bar sorptive extraction (SBSE) as a special coating to improve the selective extraction capability for target analytes. However, traditional MIPs usually suffer from incompatibility in aqueous media and low adsorption capacity, which limit the application of MIP coated stir bar in aqueous samples. To solve these problems, a water-compatible graphene oxides (GO)/MIP composite coated stir bar was prepared in this work by in situ polymerization. The prepared water-compatible GO/MIP coated stir bar presented good mechanical strength and chemical stability, and its recognition ability in aqueous samples was improved due to the polymerization of MIP in water environment, the adsorption capacity for target analytes was also increased by the addition of GO in MIP pre-polymer solution. Based on it, a method of water-compatible GO/MIP coated stir bar sorptive extraction combined with high performance liquid chromatography-ultraviolet detector (HPLV-UV) was proposed for the analysis of propranolol (PRO) in aqueous solution. The influencing factors of SBSE, such as sample pH, salt effect, stirring rate, extraction time, desorption solvent and desorption time, were optimized, and the analytical performance of the developed SBSE-HPLC-UV method was evaluated under the optimized conditions. The limit of detection (LOD) of the proposed method for PRO was about 0.37 μg L(-1), and the enrichment factor (EF) was 59.7-fold (theoretical EF was 100-fold). The reproducibility was also investigated at concentrations of 5 μg L(-1) and the relative standard deviation (RSD) was found to be 7.3% (n=7). The proposed method of GO/MIP coating-SBSE-HPLC-UV was successfully applied for the assay of the interested PRO drug in urine samples, and further extended to the investigation of the excretion of the drugs by monitoring the variation of the concentration of PRO in urine within 10h after drug-taking. Copyright © 2016 Elsevier B.V. All rights reserved.

Inhibition of the NF-κB signaling pathway by the curcumin analog, 3,5-Bis(2-pyridinylmethylidene)-4-piperidone (EF31): anti-inflammatory and anti-cancer properties

PubMed Central

Olivera, Anlys; Moore, Terry W.; Hu, Fang; Brown, Andrew P.; Sun, Aiming; Liotta, Dennis C.; Snyder, James P.; Yoon, Younghyoun; Shim, Hyunsuk; Marcus, Adam I.; Miller, Andrew H.; Pace, Thaddeus W. W.

2012-01-01

Nuclear factor kappa B (NF-κB) is a key signaling molecule in the elaboration of the inflammatory response. Data indicate that curcumin, a natural ingredient of the curry spice turmeric, acts as a NF-κB inhibitor and exhibits both anti-inflammatory and anti-cancer properties. Curcumin analogues with enhanced activity on the NF-κB and other inflammatory signaling pathways have been developed including the synthetic monoketone compound termed 3,5-Bis(2-fluorobenzylidene)-4-piperidone (EF24). 3,5-Bis(2-pyridinylmethylidene)-4-piperidone (EF31) is a structurally-related curcumin analogue whose potency for NF-κB inhibition has yet to be determined. To examine the activity of EF31 compared to EF24 and curcumin, mouse RAW264.7 macrophages were treated with EF31, EF24, curcumin (1–100µM) or vehicle (DMSO 1%) for 1 hour. NF-κB pathway activity was assessed following treatment with lipopolysaccharide (LPS) (1µg/mL). EF31 (IC50 ~5µM) exhibited significantly more potent inhibition of LPS-induced NF-κB DNA binding compared to both EF24 (IC50~35µM) and curcumin (IC50 >50µM). In addition, EF31 exhibited significantly greater inhibition of NF-κB nuclear translocation as well as the induction of downstream inflammatory mediators including pro-inflammatory cytokine mRNA and protein (tumor necrosis factor-α, interleukin-1β, and interleukin-6). Regarding the mechanism of these effects on NF-κB activity, EF31 (IC50~1.92µM) exhibited significantly greater inhibition of IκB kinase β compared to EF24 (IC50~131µM). Finally, EF31 demonstrated potent toxicity in NF-κB-dependent cancer cell lines while having minimal and reversible toxicity in RAW264.7 macrophages. These data indicate that EF31 is a more potent inhibitor of NF-κB activity than either EF24 or curcumin while exhibiting both anti-inflammatory and anticancer activities. Thus, EF31 represents a promising curcumin analogue for further therapeutic development. PMID:22197802

Inhibition of the NF-κB signaling pathway by the curcumin analog, 3,5-Bis(2-pyridinylmethylidene)-4-piperidone (EF31): anti-inflammatory and anti-cancer properties.

PubMed

Olivera, Anlys; Moore, Terry W; Hu, Fang; Brown, Andrew P; Sun, Aiming; Liotta, Dennis C; Snyder, James P; Yoon, Younghyoun; Shim, Hyunsuk; Marcus, Adam I; Miller, Andrew H; Pace, Thaddeus W W

2012-02-01

Nuclear factor kappa B (NF-κB) is a key signaling molecule in the elaboration of the inflammatory response. Data indicate that curcumin, a natural ingredient of the curry spice turmeric, acts as a NF-κB inhibitor and exhibits both anti-inflammatory and anti-cancer properties. Curcumin analogs with enhanced activity on NF-κB and other inflammatory signaling pathways have been developed including the synthetic monoketone compound 3,5-Bis(2-fluorobenzylidene)-4-piperidone (EF24). 3,5-Bis(2-pyridinylmethylidene)-4-piperidone (EF31) is a structurally-related curcumin analog whose potency for NF-κB inhibition has yet to be determined. To examine the activity of EF31 compared to EF24 and curcumin, mouse RAW264.7 macrophages were treated with EF31, EF24, curcumin (1-100 μM) or vehicle (DMSO 1%) for 1h. NF-κB pathway activity was assessed following treatment with lipopolysaccharide (LPS) (1 μg/mL). EF31 (IC(50)~5 μM) exhibited significantly more potent inhibition of LPS-induced NF-κB DNA binding compared to both EF24 (IC(50)~35 μM) and curcumin (IC(50) >50 μM). In addition, EF31 exhibited greater inhibition of NF-κB nuclear translocation as well as the induction of downstream inflammatory mediators including pro-inflammatory cytokine mRNA and protein (tumor necrosis factor-α, interleukin-1β, and interleukin-6). Regarding the mechanism of these effects on NF-κB, EF31 (IC(50)~1.92 μM) exhibited significantly greater inhibition of IκB kinase β compared to EF24 (IC(50)~131 μM). Finally, EF31 demonstrated potent toxicity in NF-κB-dependent cancer cell lines while having minimal and reversible toxicity in RAW264.7 macrophages. These data indicate that EF31 is a more potent inhibitor of NF-κB activity than either EF24 or curcumin while exhibiting both anti-inflammatory and anticancer activities. Thus, EF31 represents a promising curcumin analog for further therapeutic development. Copyright © 2011 Elsevier B.V. All rights reserved.

Regression analysis on the variation in efficiency frontiers for prevention stage of HIV/AIDS.

PubMed

Kamae, Maki S; Kamae, Isao; Cohen, Joshua T; Neumann, Peter J

2011-01-01

To investigate how the cost effectiveness of preventing HIV/AIDS varies across possible efficiency frontiers (EFs) by taking into account potentially relevant external factors, such as prevention stage, and how the EFs can be characterized using regression analysis given uncertainty of the QALY-cost estimates. We reviewed cost-effectiveness estimates for the prevention and treatment of HIV/AIDS published from 2002-2007 and catalogued in the Tufts Medical Center Cost-Effectiveness Analysis (CEA) Registry. We constructed efficiency frontier (EF) curves by plotting QALYs against costs, using methods used by the Institute for Quality and Efficiency in Health Care (IQWiG) in Germany. We stratified the QALY-cost ratios by prevention stage, country of study, and payer perspective, and estimated EF equations using log and square-root models. A total of 53 QALY-cost ratios were identified for HIV/AIDS in the Tufts CEA Registry. Plotted ratios stratified by prevention stage were visually grouped into a cluster consisting of primary/secondary prevention measures and a cluster consisting of tertiary measures. Correlation coefficients for each cluster were statistically significant. For each cluster, we derived two EF equations - one based on the log model, and one based on the square-root model. Our findings indicate that stratification of HIV/AIDS interventions by prevention stage can yield distinct EFs, and that the correlation and regression analyses are useful for parametrically characterizing EF equations. Our study has certain limitations, such as the small number of included articles and the potential for study populations to be non-representative of countries of interest. Nonetheless, our approach could help develop a deeper appreciation of cost effectiveness beyond the deterministic approach developed by IQWiG.

Electromembrane extraction of zwitterionic compounds as acid or base: comparison of extraction behavior at acidic and basic pHs.

PubMed

Nojavan, Saeed; Pourahadi, Ahmad; Hosseiny Davarani, Saied Saeed; Morteza-Najarian, Amin; Beigzadeh Abbassi, Mojtaba

2012-10-01

This study has performed on electromembrane extraction (EME) of some zwitterionic compounds based on their acidic and basic properties. High performance liquid chromatography (HPLC) equipped with UV detection was used for determination of model compounds. Cetirizine (CTZ) and mesalazine (MS) were chosen as model compounds, and each of them was extracted from acidic (as a cation) and basic (as an anion) sample solutions, separately. 1-Octanol and 2-nitrophenyl octylether (NPOE) were used as the common supported liquid membrane (SLM) solvents. EME parameters, such as extraction time, extraction voltage and pH of donor and acceptor solutions were studied in details for cationic and anionic forms of each model compound and obtained results for two ionic forms (cationic and anionic) of each compound were compared together. Results showed that zwitterionic compounds could be extracted in both cationic and anionic forms. Moreover, it was found that the extraction of anionic form of each model compound could be done in low voltages when 1-octanol was used as the SLM solvent. Results showed that charge type was not highly effective on the extraction efficiency of model compounds whereas the position of charge within the molecule was the key parameter. In optimized conditions, enrichment factors (EF) of 27-60 that corresponded to recoveries ranging from 39 to 86% were achieved. Copyright © 2012 Elsevier B.V. All rights reserved.

Catheter ablation of atrial fibrillation in patients with heart failure and preserved ejection fraction.

PubMed

Black-Maier, Eric; Ren, Xinru; Steinberg, Benjamin A; Green, Cynthia L; Barnett, Adam S; Rosa, Normita Sta; Al-Khatib, Sana M; Atwater, Brett D; Daubert, James P; Frazier-Mills, Camille; Grant, Augustus O; Hegland, Donald D; Jackson, Kevin P; Jackson, Larry R; Koontz, Jason I; Lewis, Robert K; Sun, Albert Y; Thomas, Kevin L; Bahnson, Tristam D; Piccini, Jonathan P

2018-05-01

Few studies have examined outcomes of catheter ablation for atrial fibrillation (AF) in patients with heart failure (HF) with preserved ejection fraction (HFpEF). The purpose of this study was to compare outcomes of AF ablation in patients with HFpEF vs HF with reduced ejection fraction (HFrEF). We performed a retrospective study of 230 patients with HF who underwent AF ablation, including 97 (42.2%) with HFrEF and 133 (57.8%) with HFpEF. Outcomes included adverse events, symptoms (Mayo AF Symptom Inventory [MAFSI]), New York Heart Association (NYHA) functional class, and freedom from recurrent atrial arrhythmia at 12 months. Overall, 150 of 230 patients had nonparoxysmal AF (62.8% HFpEF vs 63.0% HFrEF). Patients with HFpEF had a smaller mean left atrial diameter (4.4 ± 0.8 cm vs 4.7 ± 0.7 cm; P = .013) and were less likely to be taking a beta-blocker at baseline (72.9% vs 85.6%; P = .022). Median (Q1, Q3) procedure times (233 minutes [192, 290] vs 233.5 minutes [193.0, 297.5]; P = .780) and adverse events such as acute HF (3.8% vs 6.2%; P = .395) were similar between HFpEF and HFrEF patients. Freedom from recurrent atrial arrhythmia was not significantly different in HFpEF vs HFrEF patients (33.9% vs 32.6%; adjusted hazard ratio 1.47; 95% confidence interval 0.72-3.01), with similar improvements in NYHA functional class (-0.32 vs -0.19; P = .135) and MAFSI symptom severity (-0.23 vs -0.09; P = .116) after ablation. Catheter ablation of AF seems to have similar effectiveness in patients with HF, regardless of presence of systolic dysfunction. There were no significant differences in procedural characteristics, arrhythmia-free recurrence, or functional improvements between patients with HFpEF and those with HFrEF. Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Energy Factor Analysis for Gas Heat Pump Water Heaters

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gluesenkamp, Kyle R

2016-01-01

Gas heat pump water heaters (HPWHs) can improve water heating efficiency with zero GWP and zero ODP working fluids. The energy factor (EF) of a gas HPWH is sensitive to several factors. In this work, expressions are derived for EF of gas HPWHs, as a function of heat pump cycle COP, tank heat losses, burner efficiency, electrical draw, and effectiveness of supplemental heat exchangers. The expressions are used to investigate the sensitivity of EF to each parameter. EF is evaluated on a site energy basis (as used by the US DOE for rating water heater EF), and a primary energy-basismore » energy factor (PEF) is also defined and included. Typical ranges of values for the six parameters are given. For gas HPWHs, using typical ranges for component performance, EF will be 59 80% of the heat pump cycle thermal COP (for example, a COP of 1.60 may result in an EF of 0.94 1.28). Most of the reduction in COP is due to burner efficiency and tank heat losses. Gas-fired HPWHs are theoretically be capable of an EF of up to 1.7 (PEF of 1.6); while an EF of 1.1 1.3 (PEF of 1.0 1.1) is expected from an early market entry.« less

Comparison of fecal DNA extraction kits for the detection of Mycobacterium avium subsp. paratuberculosis by polymerase chain reaction

USDA-ARS?s Scientific Manuscript database

Culture of Mycobacterium avium subsp. paratuberculosis (MAP) from feces has been considered the gold standard for the diagnosis of paratuberculosis for many years. However, direct fecal PCR is becoming more widely used today, demonstrating similar sensitivity and specificity to culture. To ensure ef...

Autonomic regulation therapy to enhance myocardial function in heart failure patients: the ANTHEM‐HFpEF study

PubMed Central

DiCarlo, Lorenzo A.; Libbus, Imad; Kumar, H. Uday; Mittal, Sanjay; Premchand, Rajendra K.; Amurthur, Badri; KenKnight, Bruce H.; Ardell, Jeffrey L.

2017-01-01

Abstract Background Approximately half of the patients presenting with new‐onset heart failure (HF) have HF with preserved left ventricular ejection fraction (HFpEF) and HF with mid‐range left ventricular ejection fraction (HFmrEF). These patients have neurohormonal activation like that of HF with reduced ejection fraction; however, beta‐blockers and angiotensin‐converting enzyme inhibitors have not been shown to improve their outcomes, and current treatment for these patients is symptom based and empiric. Sympathoinhibition using parasympathetic stimulation has been shown to improve central and peripheral aspects of the cardiac nervous system, reflex control, induce myocyte cardioprotection, and can lead to regression of left ventricular hypertrophy. Beneficial effects of autonomic regulation therapy (ART) using vagus nerve stimulation (VNS) have also been observed in several animal models of HFpEF, suggesting a potential role for ART in patients with this disease. Methods The Autonomic Neural Regulation Therapy to Enhance Myocardial Function in Patients with Heart Failure and Preserved Ejection Fraction (ANTHEM‐HFpEF) study is designed to evaluate the feasibility, tolerability, and safety of ART using right cervical VNS in patients with chronic, stable HFpEF and HFmrEF. Patients with symptomatic HF and HFpEF or HFmrEF fulfilling the enrolment criteria will receive chronic ART with a subcutaneous VNS system attached to the right cervical vagus nerve. Safety parameters will be continuously monitored, and cardiac function and HF symptoms will be assessed every 3 months during a post‐titration follow‐up period of at least 12 months. Conclusions The ANTHEM‐HFpEF study is likely to provide valuable information intended to expand our understanding of the potential role of ART in patients with chronic symptomatic HFpEF and HFmrEF. PMID:29283224

Non-Ischemic Heart Failure With Reduced Ejection Fraction Is Associated With Altered Intestinal Microbiota.

PubMed

Katsimichas, Themistoklis; Ohtani, Tomohito; Motooka, Daisuke; Tsukamoto, Yasumasa; Kioka, Hidetaka; Nakamoto, Kei; Konishi, Shozo; Chimura, Misato; Sengoku, Kaoruko; Miyawaki, Hiroshi; Sakaguchi, Taiki; Okumura, Ryu; Theofilis, Konstantinos; Iida, Tetsuya; Takeda, Kiyoshi; Nakamura, Shota; Sakata, Yasushi

2018-05-25

Research suggests that heart failure with reduced ejection fraction (HFrEF) is a state of systemic inflammation that may be triggered by microbial products passing into the bloodstream through a compromised intestinal barrier. However, whether the intestinal microbiota exhibits dysbiosis in HFrEF patients is largely unknown.Methods and Results:Twenty eight non-ischemic HFrEF patients and 19 healthy controls were assessed by 16S rRNA analysis of bacterial DNA extracted from stool samples. After processing of sequencing data, bacteria were taxonomically classified, diversity indices were used to examine microbial ecology, and relative abundances of common core genera were compared between groups. Furthermore, we predicted gene carriage for bacterial metabolic pathways and inferred microbial interaction networks on multiple taxonomic levels.Bacterial communities of both groups were dominated by the Firmicutes and Bacteroidetes phyla. The most abundant genus in both groups wasBacteroides. Although α diversity did not differ between groups, ordination by β diversity metrics revealed a separation of the groups across components of variation.StreptococcusandVeillonellawere enriched in the common core microbiota of patients, whileSMB53was depleted. Gene families in amino acid, carbohydrate, vitamin, and xenobiotic metabolism showed significant differences between groups. Interaction networks revealed a higher degree of correlations between bacteria in patients. Non-ischemic HFrEF patients exhibited multidimensional differences in intestinal microbial communities compared with healthy subjects.

Relation between different metal pollution criteria in sediments and its contribution on assessing toxicity.

PubMed

Alves, Cristina M; Ferreira, Carlos M H; Soares, Helena M V M

2018-05-14

Several tools have been developed and applied to evaluate the metal pollution status of sediments and predict their potential ecological risk assessment. To date, a comprehensive relationship between the information given by these sediment tools for predicting metal bioavailability and the effective toxicity observed is lacking. In this work, the possible inter-correlations between the data outcoming from using several qualitative evaluation tools of the sediment contamination (contamination factor, CF, the enrichment factor, EF, or the geoaccumulation index, Igeo), metal speciation on sediments (evaluated by the modified BCR sequential extraction procedure) and free metal concentrations in pore waters were studied. It was also our aim to evaluate if these assessment tools could be used for predicting the pore waters toxicity data as toxicity proxy. Principal component analysis and cluster analysis revealed that two quality indices used (CF and EF) were highly correlatable with the more labile fractions from BCR sediment speciation. However, neither of these parameters did correlate with the toxicity of pore waters measured by the chronic toxicity (72 h) in Pseudokirchneriella subcapitata. In contrast, the toxic effects of the given total metal load in sediments were better evaluated by using an additive metal approach using pore water free metal concentrations. Copyright © 2018 Elsevier Ltd. All rights reserved.

Electric Field Exposure Improves Subjective Symptoms Related to Sleeplessness in College Students: A Pilot Study of Electric Field Therapy for Sleep Disorder

PubMed Central

Ohtsuki, Takashi; Nabeta, Tomoyuki; Nakanishi, Hiromoto; Kawahata, Hirohisa; Ogihara, Toshio; Morishita, Ryuichi; Aoki, Motokuni

2017-01-01

Background: Sleep disorder is a common health problem in modern days. Estab-lishment of safe, non-invasive, convenient and effective treatment is anticipated in the field of complementary and alternative medicine. Objective: We designed a protocol for a randomized controlled trial to investigate the effect of Electric Field (EF) exposure on sleep disorder. Methods: Nineteen college students with sleep disorder, defined as a score of 8 or higher on the Pitzburg Sleep Quality Index, were divided into two groups; EF intervention and sham treatment. EF exposure (50-Hz, 18 kV) was performed for 30 minutes a day for five con-secutive days. Subjective parameters were obtained by an OSA sleep inventory MA version consisting of five factors, and objective parameters were measured using a sleep-scan. Results: Significant improvement in scores of three factors (sleepiness on rising, refreshing and sleep length) was observed after 5 days of EF exposure intervention, as compared to both before intervention and after 5 days of sham treatment. Moreover, improvement rati-os for these three factors were significantly higher in the EF group than in the sham treat-ment group. Analysis of the sleep-scan demonstrated a high improvement ratio for duration of nocturnal awakening in the EF group. Conclusion: The beneficial effect of electric field therapy on sleep disorder in college stu-dents is considered to be beyond a placebo effect. This study raises the therapeutic possibil-ity of electric field exposure.

Current Perspectives on Systemic Hypertension in Heart Failure with Preserved Ejection Fraction.

PubMed

Tam, Marty C; Lee, Ran; Cascino, Thomas M; Konerman, Matthew C; Hummel, Scott L

2017-02-01

Heart failure with preserved ejection fraction (HFpEF) is a prevalent but incompletely understood syndrome. Traditional models of HFpEF pathophysiology revolve around systemic HTN and other causes of increased left ventricular afterload leading to left ventricular hypertrophy (LVH) and diastolic dysfunction. However, emerging models attribute the development of HFpEF to systemic proinflammatory changes secondary to common comorbidities which include HTN. Alterations in passive ventricular stiffness, ventricular-arterial coupling, peripheral microvascular function, systolic reserve, and chronotropic response occur. As a result, HFpEF is heterogeneous in nature, making it difficult to prescribe uniform therapies to all patients. Nonetheless, treating systemic HTN remains a cornerstone of HFpEF management. Antihypertensive therapies have been linked to LVH regression and improvement in diastolic dysfunction. However, to date, no therapies have definitive mortality benefit in HFpEF. Non-pharmacologic management for HTN, including dietary modification, exercise, and treating sleep disordered breathing, may provide some morbidity benefit in the HFpEF population. Future research is need to identify effective treatments, perhaps in more specific subgroups, and focus may need to shift from reducing mortality to improving exercise capacity and symptoms. Tailoring antihypertensive therapies to specific phenotypes of HFpEF may be an important component of this strategy.

Early applied electric field stimulation attenuates secondary apoptotic responses and exerts neuroprotective effects in acute spinal cord injury of rats.

PubMed

Zhang, C; Zhang, G; Rong, W; Wang, A; Wu, C; Huo, X

2015-04-16

Injury potential, which refers to a direct current voltage between intact and injured nerve ends, is mainly caused by injury-induced Ca2+ influx. Our previous studies revealed that injury potential increased with the onset and severity of spinal cord injury (SCI), and an application of applied electric field stimulation (EFS) with the cathode distal to the lesion could delay and attenuate injury potential formation. As Ca2+ influx is also considered as a major trigger for secondary injury after SCI, we hypothesize that EFS would protect an injured spinal cord from secondary injury and consequently improve functional and pathological outcomes. In this study, rats were divided into three groups: (1) sham group, laminectomy only; (2) control group, subjected to SCI only; and (3) EFS group, received EFS immediately post-injury with the injury potential modulated to 0±0.5 mV by EFS. Functional recovery of the hind limbs was assessed using the Basso, Beattie, and Bresnahan (BBB) locomotor scale. Results revealed that EFS-treated rats exhibited significantly better locomotor function recovery. Luxol fast blue staining was performed to assess the spared myelin area. Immunofluorescence was used to observe the number of myelinated nerve fibers. Ultrastructural analysis was performed to evaluate the size of myelinated nerve fibers. Findings showed that the EFS group rats exhibited significantly less myelin loss and had larger and more myelinated nerve fibers than the control group rats in dorsal corticospinal tract (dCST) 8 weeks after SCI. Furthermore, we found that EFS inhibited the activation of calpain and caspase-3, as well as the expression of Bax, as detected by Western blot analysis. Moreover, EFS decreased cellular apoptosis, as measured by TUNEL, within 4 weeks post-injury. Results suggest that early EFS could significantly reduce spinal cord degeneration and improve functional and historical recovery. Furthermore, these neuroprotective effects may be related to the inhibition of secondary apoptotic responses after SCI. These findings support further investigation of the future clinical application of EFS after SCI. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

The independent and interacting effects of hedonic hunger and executive function on binge eating

PubMed Central

Manasse, Stephanie M.; Espel, Hallie M.; Forman, Evan M.; Ruocco, Anthony C.; Juarascio, Adrienne S.; Butryn, Meghan L.; Zhang, Fengqing; Lowe, Michael R.

2015-01-01

Poor executive function (EF; pre-frontal cognitive control processes governing goal-directed behavior) and elevated hedonic hunger (i.e., preoccupation with palatable foods in the absence of physiological hunger) are theoretical risk and maintenance factors for binge eating (BE) distinct from general obesity. Recent theoretical models posit that dysregulated behavior such as BE may result from a combination of elevated appetitive drive (e.g., hedonic hunger) and decreased EF (e.g., inhibitory control and delayed discounting). The present study sought to test this model in distinguishing BE from general obesity by examining the independent and interactive associations of EF and hedonic hunger with BE group status (i.e., odds of categorization in BE group versus non-BE group). Treatment-seeking overweight and obese women with BE (n = 31) and without BE (OW group; n = 43) were assessed on measures of hedonic hunger and EF (inhibitory control and delay discounting). Elevated hedonic hunger increased the likelihood of categorization in the BE group, regardless of EF. When hedonic hunger was low, poor EF increased the likelihood of categorization in the BE group. Results indicate that the interplay of increased appetitive drives and decreased cognitive function may distinguish BE from overweight/obesity. Future longitudinal investigations of the combinatory effect of hedonic hunger and EF in increasing risk for developing BE are warranted, and may inform future treatment development to target these factors. PMID:25613129

Enhanced jump performance when providing augmented feedback compared to an external or internal focus of attention.

PubMed

Keller, Martin; Lauber, Benedikt; Gottschalk, Marius; Taube, Wolfgang

2015-01-01

Factors such as an external focus of attention (EF) and augmented feedback (AF) have been shown to improve performance. However, the efficacy of providing AF to enhance motor performance has never been compared with the effects of an EF or an internal focus of attention (IF). Therefore, the aim of the present study was to identify which of the three conditions (AF, EF or IF) leads to the highest performance in a countermovement jump (CMJ). Nineteen volunteers performed 12 series of 8 maximum CMJs. Changes in jump height between conditions and within the series were analysed. Jump heights differed between conditions (P < 0.001), resulting in best performance with AF (32.04 ± 7.11 cm), followed by EF (31.21 ± 6.67 cm) and IF (30.77 ± 6.87 cm). Significantly different (P < 0.001) within-series effects of higher jump heights at the end of the series in AF (+1.60%) and lower jump heights at the end of the series in EF (-1.79%) and IF (-1.68%) were observed. Muscle activity did not differ between conditions. The differences between conditions and within the series provide evidence that AF leads to higher performance and better progression within one series than EF and IF. Consequently, AF seems to outperform EF and IF when maximising jump height.

Parasympathetic Nervous System Reactivity Moderates Associations Between Children's Executive Functioning and Social and Academic Competence.

PubMed

McQuade, Julia D; Penzel, Taylor E; Silk, Jennifer S; Lee, Kyung Hwa

2017-10-01

This study examined whether children with poor executive functioning (EF) evidenced less social and academic impairments, compared to other children, if they demonstrated adaptive parasympathetic nervous system (PNS) regulation during experiences of failure. Participants with and without clinical elevations in ADHD symptoms (N = 61; 9-13 years; 48% male; 85% Caucasian) were administered a battery of EF tests and completed manipulated social and cognitive failure tasks. While participants completed failure tasks, respiratory sinus arrhythmia reactivity (RSA-R) was measured as an indicator of PNS reactivity. Children's social and academic impairment in daily life was assessed based on parent and teacher report on multiple measures. RSA-R during social failure moderated the association between poor EF and adult-rated social impairment and RSA-R during cognitive failure moderated the association between poor EF and adult-rated academic impairment. Simple effects indicated that poor EF was significantly associated with impairment when children demonstrated RSA activation (increased PNS activity) but not when children demonstrated RSA withdrawal (decreases in PNS activity). Domain-crossed models (e.g., reactivity to social failure predicting academic impairment) were not significant, suggesting that the moderating effect of RSA-R was domain-specific. Results suggest that not all children with poor EF evidence social and academic impairment; RSA withdrawal during experiences of failure may be protective specifically for children with impaired EF skills.

The joint effect of bilingualism and ADHD on executive functions.

PubMed

Mor, Billy; Yitzhaki-Amsalem, Sarin; Prior, Anat

2015-06-01

The current study investigated the combined effect of ADHD, previously associated with executive function (EF) deficits, and of bilingualism, previously associated with EF enhancement, on EF. Eighty University students, Hebrew monolinguals and Russian Hebrew bilinguals, with and without ADHD participated. Inhibition tasks were a Numeric Stroop task and a Simon arrows task. Shifting tasks were the Trail Making Test (TMT) and a task-switching paradigm. Participants with ADHD performed worse than controls, but we did not find a bilingual advantage in EF. The negative impact of ADHD was more pronounced for bilinguals than for monolinguals, but only in interference suppression tasks. Bilingual participants with ADHD had the lowest performance. Bilingualism might prove to be an added burden for adults with ADHD, leading to reduced EF abilities. Alternatively, the current findings might be ascribed to over- or under-diagnosis of ADHD due to cultural differences between groups. These issues should be pursued in future research. © 2014 SAGE Publications.

The Relations between Television Exposure and Executive Function in Chinese Preschoolers: The Moderated Role of Parental Mediation Behaviors

PubMed Central

Yang, Xiaohui; Chen, Zhe; Wang, Zhenhong; Zhu, Liqi

2017-01-01

The present study examined the relations between preschoolers’ television exposure and executive functions (EF). One hundred and nineteen 3- to 6-year-old children and their parents participated. Parents filled in a questionnaire regarding children’s television viewing time, television content and parental mediation behaviors about their child’s television viewing. The children were asked to finish six EF tasks, including the backward digit span task, the spatial span task, the boy–girl Stroop, the Simon task, the flanker task and the Tower of Hanoi task that assessed working memory, inhibition and planning, respectively. Children’s vocabulary was tested using Peabody Picture Vocabulary Test, and included as control variables in addition to socioeconomic status of the participated families. The results showed that television viewing time and child-directed educational programs were positively associated with EF. In addition, television content fully mediated the effect of television viewing time on EF and parental restrictive approach strategies moderated the effect of television viewing time on EF. PMID:29089912

Predictors and Prognostic Value of Worsening Renal Function During Admission in HFpEF Versus HFrEF: Data From the KorAHF (Korean Acute Heart Failure) Registry.

PubMed

Kang, Jeehoon; Park, Jin Joo; Cho, Young-Jin; Oh, Il-Young; Park, Hyun-Ah; Lee, Sang Eun; Kim, Min-Seok; Cho, Hyun-Jai; Lee, Hae-Young; Choi, Jin Oh; Hwang, Kyung-Kuk; Kim, Kye Hun; Yoo, Byung-Su; Kang, Seok-Min; Baek, Sang Hong; Jeon, Eun-Seok; Kim, Jae-Joong; Cho, Myeong-Chan; Chae, Shung Chull; Oh, Byung-Hee; Choi, Dong-Ju

2018-03-13

Worsening renal function (WRF) is associated with adverse outcomes in patients with heart failure. We investigated the predictors and prognostic value of WRF during admission, in patients with preserved ejection fraction (HFpEF) versus those with reduced ejection fraction (HFrEF). A total of 5625 patients were enrolled in the KorAHF (Korean Acute Heart Failure) registry. WRF was defined as an absolute increase in creatinine of ≥0.3 mg/dL. Transient WRF was defined as recovery of creatinine at discharge, whereas persistent WRF was indicated by a nonrecovered creatinine level. HFpEF and HFrEF were defined as a left ventricle ejection fraction ≥50% and ≤40%, respectively. Among the total population, WRF occurred in 3101 patients (55.1%). By heart failure subgroup, WRF occurred more frequently in HFrEF (57.0% versus 51.3%; P <0.001 in HFrEF and HFpEF). Prevalence of WRF increased as creatinine clearance decreased in both heart failure subgroups. Among various predictors of WRF, chronic renal failure was the strongest predictor. WRF was an independent predictor of adverse in-hospital outcomes (HFrEF: odds ratio; 2.75; 95% confidence interval, 1.50-5.02; P =0.001; HFpEF: odds ratio, 9.48; 95% confidence interval, 1.19-75.89; P =0.034) and 1-year mortality (HFrEF: hazard ratio, 1.41; 95% confidence interval, 1.12-1.78; P =0.004 versus HFpEF: hazard ratio, 1.72; 95% confidence interval, 1.23-2.42; P =0.002). Transient WRF was a risk factor for 1-year mortality, whereas persistent WRF had no additive risk compared to transient WRF. In patients with acute heart failure patients, WRF is an independent predictor of adverse in-hospital and follow-up outcomes in both HFrEF and HFpEF, though with a different effect size. URL: https://www.clinicaltrials.gov. Unique identifier: NCT01389843. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Strong genetic overlap between executive functions and intelligence.

PubMed

Engelhardt, Laura E; Mann, Frank D; Briley, Daniel A; Church, Jessica A; Harden, K Paige; Tucker-Drob, Elliot M

2016-09-01

Executive functions (EFs) are cognitive processes that control, monitor, and coordinate more basic cognitive processes. EFs play instrumental roles in models of complex reasoning, learning, and decision making, and individual differences in EFs have been consistently linked with individual differences in intelligence. By middle childhood, genetic factors account for a moderate proportion of the variance in intelligence, and these effects increase in magnitude through adolescence. Genetic influences on EFs are very high, even in middle childhood, but the extent to which these genetic influences overlap with those on intelligence is unclear. We examined genetic and environmental overlap between EFs and intelligence in a racially and socioeconomically diverse sample of 811 twins ages 7 to 15 years (M = 10.91, SD = 1.74) from the Texas Twin Project. A general EF factor representing variance common to inhibition, switching, working memory, and updating domains accounted for substantial proportions of variance in intelligence, primarily via a genetic pathway. General EF continued to have a strong, genetically mediated association with intelligence even after controlling for processing speed. Residual variation in general intelligence was influenced only by shared and nonshared environmental factors, and there remained no genetic variance in general intelligence that was unique of EF. Genetic variance independent of EF did remain, however, in a more specific perceptual reasoning ability. These results provide evidence that genetic influences on general intelligence are highly overlapping with those on EF. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Derivation of greenhouse gas emission factors for peatlands managed for extraction in the Republic of Ireland and the United Kingdom

NASA Astrophysics Data System (ADS)

Wilson, D.; Dixon, S. D.; Artz, R. R. E.; Smith, T. E. L.; Evans, C. D.; Owen, H. J. F.; Archer, E.; Renou-Wilson, F.

2015-09-01

Drained peatlands are significant hotspots of carbon dioxide (CO2) emissions and may also be more vulnerable to fire with its associated gaseous emissions. Under the United Nations Framework Convention on Climate Change (UNFCCC) and the Kyoto Protocol, greenhouse gas (GHG) emissions from peatlands managed for extraction are reported on an annual basis. However, the Tier 1 (default) emission factors (EFs) provided in the IPCC 2013 Wetlands Supplement for this land use category may not be representative in all cases and countries are encouraged to move to higher-tier reporting levels with reduced uncertainty levels based on country- or regional-specific data. In this study, we quantified (1) CO2-C emissions from nine peat extraction sites in the Republic of Ireland and the United Kingdom, which were initially disaggregated by land use type (industrial versus domestic peat extraction), and (2) a range of GHGs that are released to the atmosphere with the burning of peat. Drainage-related methane (CH4) and nitrous oxide (N2O) emissions as well as CO2-C emissions associated with the off-site decomposition of horticultural peat were not included here. Our results show that net CO2-C emissions were strongly controlled by soil temperature at the industrial sites (bare peat) and by soil temperature and leaf area index at the vegetated domestic sites. Our derived EFs of 1.70 (±0.47) and 1.64 (±0.44) t CO2-C ha-1 yr-1 for the industrial and domestic sites respectively are considerably lower than the Tier 1 EF (2.8 ± 1.7 t CO2-C ha-1 yr-1) provided in the Wetlands Supplement. We propose that the difference between our derived values and the Wetlands Supplement value is due to differences in peat quality and, consequently, decomposition rates. Emissions from burning of the peat (g kg-1 dry fuel burned) were estimated to be approximately 1346 CO2, 8.35 methane (CH4), 218 carbon monoxide (CO), 1.53 ethane (C2H6), 1.74 ethylene (C2H4), 0.60 methanol (CH3OH), 2.21 hydrogen cyanide (HCN) and 0.73 ammonia (NH3), and this emphasises the importance of understanding the full suite of trace gas emissions from biomass burning. Our results highlight the importance of generating reliable Tier 2 values for different regions and land use categories. Furthermore, given that the IPCC Tier 1 EF was only based on 20 sites (all from Canada and Fennoscandia), we suggest that data from another 9 sites significantly expand the global data set, as well as adding a new region.

Antitumor, Antioxidant, and Nitrite Scavenging Effects of Chinese Water Chestnut (Eleocharis dulcis) Peel Flavonoids.

PubMed

Zhan, Ge; Pan, Leiqing; Tu, Kang; Jiao, Shunshan

2016-10-01

The preparation, quantification, and characterization of flavonoid compounds from Chinese water chestnut peel (CWCP) flavonoid extract and ethyl acetate fraction (EF), n-butanol fraction, and water fraction were studied. Among these, EF showed the maximum free radical levels (IC 50 values of 0.36, 0.40, and 0.37 mg/mL for DPPH•, ABTS• + , and •OH, respectively), nitrite scavenging effects (IC 50 = 1.89 mg/mL), and A549 cell inhibitory activities (IC 50 = 776.12 μg/mL) with the highest value of total flavonoid content (TFC, 421.32 mg/g). Moreover, the contents of 8 flavonoids in this fraction were quantified using high-performance liquid chromatography, and fisetin, diosmetin, luteolin, and tectorigenin were the 4 major flavonoids with levels of 31.66, 29.91, 13.69, and 12.41 mg/g, respectively. Luteolin produced a greater inhibition of human lung cancer A549 cells (IC 50 = 59.60 μg/mL) than did fisetin, diosmetin, and tectorigenin. Flow cytometry revealed that the cellular mechanisms of luteolin inhibition of A549 cells were achieved via the induction of cell proliferation arrest at G 1 phase and apoptosis/necrosis. Our findings suggest that flavonoids are closely associated with antitumor, antioxidant, and nitrite scavenging effects of CWCP. © 2016 Institute of Food Technologists®.

Ultrasonically Modified Amended-Cloud Point Extraction for Simultaneous Pre-Concentration of Neonicotinoid Insecticide Residues.

PubMed

Kachangoon, Rawikan; Vichapong, Jitlada; Burakham, Rodjana; Santaladchaiyakit, Yanawath; Srijaranai, Supalax

2018-05-12

An effective pre-concentration method, namely amended-cloud point extraction (CPE), has been developed for the extraction and pre-concentration of neonicotinoid insecticide residues. The studied analytes including clothianidin, imidacloprid, acetamiprid, thiamethoxam and thiacloprid were chosen as a model compound. The amended-CPE procedure included two cloud point processes. Triton™ X-114 was used to extract neonicotinoid residues into the surfactant-rich phase and then the analytes were transferred into an alkaline solution with the help of ultrasound energy. The extracts were then analyzed by high-performance liquid chromatography (HPLC) coupled with a monolithic column. Several factors influencing the extraction efficiency were studied such as kind and concentration of surfactant, type and content of salts, kind and concentration of back extraction agent, and incubation temperature and time. Enrichment factors (EFs) were found in the range of 20⁻333 folds. The limits of detection of the studied neonicotinoids were in the range of 0.0003⁻0.002 µg mL −1 which are below the maximum residue limits (MRLs) established by the European Union (EU). Good repeatability was obtained with relative standard deviations lower than 1.92% and 4.54% for retention time ( t R ) and peak area, respectively. The developed extraction method was successfully applied for the analysis of water samples. No detectable residues of neonicotinoids in the studied samples were found.

EF24 and RAD001 potentiates the anticancer effect of platinum-based agents in human malignant pleural mesothelioma (MSTO-211H) cells and protects nonmalignant mesothelial (MET-5A) cells.

PubMed

Onen, H I; Yilmaz, A; Alp, E; Celik, A; Demiroz, S M; Konac, E; Kurul, I C; Menevse, E S

2015-02-01

The most widespread neoplasm of the pleura is malignant pleural mesothelioma (MPM) with low prevalence rate. The mechanistic target of rapamycin signaling pathway, inhibited by RAD001, was shown to be deregulated in MPM development and considered a novel target for the MPM therapy. The EF24, a curcumin analog, also affects several signaling pathways and kills cancer cells as a single agent or in combination with classical drugs. We aimed to evaluate possible effects of RAD001, EF24, cisplatin, and oxaliplatin treatments on both malignant pleural mesothelioma (MSTO-211H) and nonmalignant mesothelial (Met-5A) cell lines. The effects of the agents on MSTO-211H and Met-5A cells were evaluated in terms of cell viability, cytotoxicity, DNA synthesis rate, quantitation of apoptotic DNA fragmentation, and cleaved caspase 3 levels. Moreover, quantitative messenger RNA (mRNA) analysis of apoptotic (CASP9) and antiapoptotic (BCL2L1 and BCL2) genes were also performed. We found that both EF24 and RAD001 alone treatments decreased only MSTO-211H cell viability, but cisplatin and oxaliplatin affected both cell lines. Pretreatment with EF24 or RAD001 followed by cisplatin increased the effects of cisplatin alone application. EF24 and RAD001 pretreatment decreased DNA fragmentation rate when compared with cisplatin alone treatment in Met-5A cells. Sequential treatments resulted in a significant increase of CASP9 mRNA expression in MSTO-211H cells but not in Met-5A cells. Our preliminary results suggest that pretreatment with EF24 or RAD001 may reduce cytotoxic effect of cisplatin on nonmalignant mesothelial cells and increase cell death response of MPM cells. Further analyses using animal models are needed to confirm these findings in vivo. © The Author(s) 2015.

Effects of vitamin D supplementation on endothelial function: a systematic review and meta-analysis of randomised clinical trials.

PubMed

Hussin, Azizah Mat; Ashor, Ammar W; Schoenmakers, Inez; Hill, Tom; Mathers, John C; Siervo, Mario

2017-04-01

In addition to regulating calcium homoeostasis and bone health, vitamin D influences vascular and metabolic processes including endothelial function (EF) and insulin signalling. This systematic review and meta-analysis of randomised clinical trials (RCTs) were conducted to investigate the effect of vitamin D supplementation on EF and to examine whether the effect size was modified by health status, study duration, dose, route of vitamin D administration, vitamin D status (baseline and post-intervention), body mass index (BMI), age and type of vitamin D. We searched the Medline, Embase, Cochrane Library and Scopus databases from inception until March 2015 for studies meeting the following criteria: (1) RCT with adult participants, (2) vitamin D administration alone, (3) studies that quantified EF using commonly applied methods including ultrasound, plethysmography, applanation tonometry and laser Doppler. Sixteen articles reporting data for 1177 participants were included. Study duration ranged from 4 to 52 weeks. The effect of vitamin D on EF was not significant (SMD: 0.08, 95 % CI -0.06, 0.22, p = 0.28). Subgroup analysis showed a significant improvement of EF in diabetic subjects (SMD: 0.31, 95 % CI 0.05, 0.57, p = 0.02). A non-significant trend was found for diastolic blood pressure (β = 0.02; p = 0.07) and BMI (β = 0.05; p = 0.06). Vitamin D supplementation did not improve EF. The significant effect of vitamin D in diabetics and a tendency for an association with BMI may indicate a role of excess adiposity and insulin resistance in modulating the effects of vitamin D on vascular function. This remains to be tested in future studies.

Grouping and emergent features in vision: toward a theory of basic Gestalts.

PubMed

Pomerantz, James R; Portillo, Mary C

2011-10-01

Gestalt phenomena are often so powerful that mere demonstrations can confirm their existence, but Gestalts have proven hard to define and measure. Here we outline a theory of basic Gestalts (TBG) that defines Gestalts as emergent features (EFs). The logic relies on discovering wholes that are more discriminable than are the parts from which they are built. These wholes contain EFs that can act as basic features in human vision. As context is added to a visual stimulus, a hierarchy of EFs appears. Starting with a single dot and adding a second yields the first two potential EFs: the proximity (distance) and orientation (angle) between the two dots. A third dot introduces two more potential EFs: symmetry and linearity; a fourth dot produces surroundedness. This hierarchy may extend to collinearity, parallelism, closure, and more. We use the magnitude of Configural Superiority Effects to measure the salience of EFs on a common scale, potentially letting us compare the strengths of various grouping principles. TBG appears promising, with our initial experiments establishing and quantifying at least three basic EFs in human vision.

The Effect of Executive Function on Science Achievement Among Normally Developing 10-Year Olds

NASA Astrophysics Data System (ADS)

Lederman, Sheri G.

Executive function (EF) is an umbrella term used to identify a set of discrete but interrelated cognitive abilities that enable individuals to engage in goal-directed, future-oriented action in response to a novel context. Developmental studies indicate that EF is predictive of reading and math achievement in middle childhood. The purpose of this study was to identify the association between EF and science achievement among normally developing 10 year olds. A sample of fifth grade students from a Northeastern suburban community participated in tests of EF, science, and intelligence. Consistent with adult models of EF, principal components analysis identified a three-factor model of EF organization in middle childhood, including cognitive flexibility, working memory, and inhibition. Multiple regression analyses revealed that executive function processes of cognitive flexibility, working memory, and inhibition were all predictive of science performance. Post hoc analyses revealed that high-performing science students differed significantly from low-performing students in both cognitive flexibility and working memory. These findings suggest that complex academic demands specific to science achievement rely on the emergence and maturation of EF components.

Biological and social influences on cognitive control processes dependent on prefrontal cortex

PubMed Central

Diamond, Adele

2014-01-01

Cognitive control functions (“executive functions” [EFs] such as attentional control, self-regulation, working memory, and inhibition) that depend on prefrontal cortex (PFC) are critical for success in school and in life. Many children begin school lacking needed EF skills. Disturbances in EFs occur in many mental health disorders, such as ADHD and depression. This chapter addresses modulation of EFs by biology (genes and neurochemistry) and the environment (including school programs) with implications for clinical disorders and for education. Unusual properties of the prefrontal dopamine system contribute to PFC’s vulnerability to environmental and genetic variations that have little effect elsewhere. EFs depend on a late-maturing brain region (PFC), yet they can be improved even in infants and preschoolers, without specialists or fancy equipment. Research shows that activities often squeezed out of school curricula (play, physical education, and the arts) rather than detracting from academic achievement help improve EFs and enhance academic outcomes. Such practices may also head off problems before they lead to diagnoses of EF impairments, including ADHD. Many issues are not simply education issues or health issues; they are both. PMID:21489397

Catching Fish and Avoiding Sharks: Investigating Factors That Influence Developmentally Appropriate Measurement of Preschoolers' Inhibitory Control.

PubMed

Howard, Steven J; Okely, Anthony D

2015-09-01

Although researchers agree that the first 5 years of life are critical for children's developing executive functions (EFs), further advances are hindered by a lack of consensus on the design and selection of developmentally appropriate EF tasks for young children. Given this debate, well-established adult measures of EF routinely have been adapted for young children. Given young children's comparatively limited cognitive capacities, however, such adaptations do not guarantee that the task's critical EF demands are retained. To investigate this possibility, the current study examined the characteristics that optimize measurement of young children's EFs-specifically, their inhibitory control-using the go/no-go (GNG) task as an exemplar. Sixty preschoolers completed six GNG tasks differing in stimulus animation, presentation time, and response location. Comparison EF tasks were administered to examine concurrent validity of GNG variants. Results indicated effects of stimulus presentation time and response location, with animation further enhancing task validity and reliability. This suggests that current GNG tasks deflate estimates of young children's ability to inhibit, with implications for future design and selection of developmentally appropriate EF tasks.

Isolation and characterization of elongation factor EF-2 from Guerin tumour.

PubMed

Jabłonowska, K; Kopacz-Jodczyk, T; Niedźwiecka, J; Gałasiński, W

1983-01-01

A homogeneous preparation of EF-2 from Guerin tumour cells was obtained. Its Mr (68 000), pI (6.5), optimum pH (7.0) and amino acid composition are very close to those of rat liver elongation factor. EF-2 from Guerin tumour cells is active in the heterologous liver - tumour system, although half as effective as in the homologous system.

Dopamine and executive function: Increased spontaneous eye blink rates correlate with better set-shifting and inhibition, but poorer updating.

PubMed

Zhang, Ting; Mou, Di; Wang, Cuicui; Tan, Fengping; Jiang, Yan; Lijun, Zheng; Li, Hong

2015-06-01

The central dopamine system (DA) has a significant role in the executive function (EF). The spontaneous eye blink rate (EBR) is an effective clinical and non-invasive measure, which is strongly related to the activity of the central dopaminergic system. Previous studies show significant relationships between the two main dimensions of EF (i.e., shifting and inhibition) and the central DA system as measured by EBR. However, most of these studies involve only one EF task for shifting or inhibition; whether or not these relationships are replicated by other EF tasks remains unclear. Besides, the relationship between EBR and another important EF dimension-updating-also remains unknown. The present study examined the correlation between EBR and several EF tasks that captured all the three EF dimensions: shifting, inhibition, and updating. A total of 61 healthy participants were subjected to EBR testing and EF tasks. Results showed that EBR had a different relationship with each of the three tested EF dimensions. An increase in EBR levels was related to an increase in accuracy in shifting and inhibition tasks, a decrease in shifting and inhibition cost, and a decrease in accuracy in updating tasks. These results imply that the role of the central DA system in shifting and inhibition differs from its role in updating. Copyright © 2015 Elsevier B.V. All rights reserved.

Regulation of cellular function via electromagnetic field frequency and extracellular environment: A theoretical- experimental approach

NASA Astrophysics Data System (ADS)

Taghian, Toloo; Sheikh, Abdul; Narmoneva, Daria; Kogan, Andrei

2015-03-01

Application of external electric field (EF) as a non-pharmacological, non-invasive tool to control cell function is of great therapeutic interest. We developed a theoretical-experimental approach to investigate the biophysical mechanisms of EF interaction with cells in electrode-free physiologically-relevant configuration. Our numerical results demonstrated that EF frequency is the major parameter to control cell response to EF. Non-oscillating or low-frequency EF leads to charge accumulation on the cell surface membrane that may mediate membrane initiated cell responses. In contrast, high-frequency EF penetrates the cell membrane and reaches cell cytoplasm, where it may directly activate intracellular responses. The theoretical predictions were confirmed in our experimental studies of the effects of applied EF on vascular cell function. Results show that non-oscillating EF increases vascular endothelial growth factor (VEGF) expression while field polarity controls cell adhesion rate. High-frequency, but not low frequency, EF provides differential regulation of cytoplasmic focal adhesion kinase and VEGF expression depending on the substrate, with increased expression in cells cultured on RGD-rich synthetic hydrogels, and decreased expression for matrigel culture. The authors acknowledge the financial support from the NSF (DMR-1206784 & DMR-0804199 to AK); the NIH (1R21 DK078814-01A1 to DN) and the University of Cincinnati (Interdisciplinary Faculty Research Support Grant to DN and AK).

Comparison of sevelamer and calcium carbonate on endothelial function and inflammation in patients on peritoneal dialysis.

PubMed

Chennasamudram, Sudha P; Noor, Tanjila; Vasylyeva, Tetyana L

2013-06-01

Hyperphosphataemia is a known independent risk factor for cardiovascular mortality. The objective of the study was to compare the effects of two phosphate binders, sevelamer carbonate and calcium carbonate on endothelial function (EF) and inflammation in patients on peritoneal dialysis (PD) with Type 2 diabetes mellitus (T2DM). Fifteen subjects with hyperphosphataemia discontinued all phosphate binders to undergo a two-week washout and were assigned to sevelamer carbonate or calcium carbonate treatments for eight weeks. After a second two-week washout period, subjects crossed over to either of the alternate treatments for another eight weeks. At the beginning and end of each treatment, biomarkers of EF, pro-inflammatory cytokines, serum albumin, calcium, phosphate and lipids were measured. Sevelamer carbonate significantly improved lipid profile compared with calcium carbonate. Amongst the EF and pro-inflammatory biomarkers, sevelamer carbonate decreased serum endothelin-1, plasminogen activator inhibitor-1, C-reactive protein and interleukin-6. Both phosphate binders were effective in decreasing serum phosphate but sevelamer had a positive effect on EF. Treatment with sevelamer carbonate has beneficial effects compared with calcium carbonate in decreasing inflammation and improving EF in patients with T2DM on PD. © 2013 European Dialysis and Transplant Nurses Association/European Renal Care Association.

Transferable Coarse-Grained Models for Ionic Liquids.

PubMed

Wang, Yanting; Feng, Shulu; Voth, Gregory A

2009-04-14

The effective force coarse-graining (EF-CG) method was applied to the imidazolium-based nitrate ionic liquids with various alkyl side-chain lengths. The nonbonded EF-CG forces for the ionic liquid with a short side chain were extended to generate the nonbonded forces for the ionic liquids with longer side chains. The EF-CG force fields for the ionic liquids exhibit very good transferability between different systems at various temperatures and are suitable for investigating the mesoscopic structural properties of this class of ionic liquids. The good additivity and ease of manipulation of the EF-CG force fields can allow for an inverse design methodology of ionic liquids at the coarse-grained level. With the EF-CG force field, the molecular dynamics (MD) simulation at a very large scale has been performed to check the significance of finite size effects on the structural properties. From these MD simulation results, it can be concluded that the finite size effect on the phenomenon of ionic liquid spatial heterogeneity (Wang, Y.; Voth, G. A. J. Am. Chem. Soc. 2005, 127, 12192) is small and that this phenomenon is indeed a nanostructural behavior which leads to the experimentally observed mesoscopic heterogeneous structure of ionic liquids.

Emerging techniques for assisting and accelerating food freezing processes: A review of recent research progresses.

PubMed

Cheng, Lina; Sun, Da-Wen; Zhu, Zhiwei; Zhang, Zi

2017-03-04

Freezing plays an important role in food preservation and the emergence of rapid freezing technologies can be highly beneficial to the food industry. This paper reviews some novel food freezing technologies, including high-pressure freezing (HPF), ultrasound-assisted freezing (UAF), electrically disturbed freezing (EF) and magnetically disturbed freezing (MF), microwave-assisted freezing (MWF), and osmo-dehydro-freezing (ODF). HPF and UAF can initiate ice nucleation rapidly, leading to uniform distribution of ice crystals and the control of their size and shape. Specifically, the former is focused on increasing the degree of supercooling, whereas the latter aims to decrease it. Direct current electric freezing (DC-EF) and alternating current electric freezing (AC-EF) exhibit different effects on ice nucleation. DC-EF can promote ice nucleation and AC-EF has the opposite effect. Furthermore, ODF has been successfully used for freezing various vegetables and fruit. MWF cannot control the nucleation temperature, but can decrease supercooling degree, thus decreasing the size of ice crystals. The heat and mass transfer processes during ODF have been investigated experimentally and modeled mathematically. More studies should be carried out to understand the effects of these technologies on food freezing process.

Effective scheme to determine accurate defect formation energies and charge transition levels of point defects in semiconductors

NASA Astrophysics Data System (ADS)

Yao, Cang Lang; Li, Jian Chen; Gao, Wang; Tkatchenko, Alexandre; Jiang, Qing

2017-12-01

We propose an effective method to accurately determine the defect formation energy Ef and charge transition level ɛ of the point defects using exclusively cohesive energy Ecoh and the fundamental band gap Eg of pristine host materials. We find that Ef of the point defects can be effectively separated into geometric and electronic contributions with a functional form: Ef=χ Ecoh+λ Eg , where χ and λ are dictated by the geometric and electronic factors of the point defects (χ and λ are defect dependent). Such a linear combination of Ecoh and Eg reproduces Ef with an accuracy better than 5% for electronic structure methods ranging from hybrid density-functional theory (DFT) to many-body random-phase approximation (RPA) and experiments. Accordingly, ɛ is also determined by Ecoh/Eg and the defect geometric/electronic factors. The identified correlation is rather general for monovacancies and interstitials, which holds in a wide variety of semiconductors covering Si, Ge, phosphorenes, ZnO, GaAs, and InP, and enables one to obtain reliable values of Ef and ɛ of the point defects for RPA and experiments based on semilocal DFT calculations.

Relationship between soluble microbial products (SMP) and effluent organic matter (EfOM): characterized by fluorescence excitation emission matrix coupled with parallel factor analysis.

PubMed

Yu, Huarong; Qu, Fangshu; Sun, Lianpeng; Liang, Heng; Han, Zhengshuang; Chang, Haiqing; Shao, Senlin; Li, Guibai

2015-02-01

Effluent organic matter (EfOM) originating from wastewater treatment plant (WWTP) is of significant concern, as it not only influences the discharge quality of WWTP but also exerts a significant effect on the efficiency of the downstream advanced treatment facilities. Soluble microbial products (SMP) is a major part of EfOM. In order to further understand the relationship between soluble microbial products (SMP) and EfOM, and in turn, to propose measures for EfOM control, the formation of SMP and EfOM in identical activated sludge sequencing batch reactors (SBR) with different feed water was investigated using fluorescence excitation and emission spectroscopy matrix coupled with parallel factor analysis (EEM-PARAFAC) as well as other organic matter quantification tools. Results showed that EfOM contained not only SMP but also a considerable amount of allochthonous organic matter that derived not merely from natural organic matter (NOM). Four components in EfOM/SMP were identified by EEM-PARAFAC. Tyrosine-like substances in EfOM (Component 3, λex/em=270/316 nm) were mainly originated from utilization associated products (UAP) of SMP. Tryptophan-like substances (Component 2, λex/em=280/336 nm) as well as fulvic-like and humic-like substances in EfOM (Component 1, λex/em=240(290)/392 nm and Component 4, λex/em=260(365)/444 nm) were majorly derived from the refractory substances introduced along with the influent, among which Component 2 was stemmed from sources other than NOM. As solid retention time (SRT) increased, Component 2 and polysaccharides in SMP/EfOM decreased, while Component 4 in SMP increased. Copyright © 2014 Elsevier Ltd. All rights reserved.

Role of Mitochondrial Inheritance on Prostate Cancer Outcome in African American Men

DTIC Science & Technology

2013-10-01

University of Arizona for additional insight. Recommendations have been: 1) to extract only 2-3 10 micron sections per tube with 2 tubes per sample to make...1331. 4. Falk MJ, Pierce EA, Consugar M, Xie MH, Guadalupe M, Hardy O, Rappaport EF, Wallace DC, LeProust E, Gai X. Mitochondrial disease genetic

In Vivo and In Vitro Suppression of Hepatocellular Carcinoma by EF24, a Curcumin Analog

PubMed Central

Wang, Luoluo; Tian, Lantian; Song, Ruipeng; Han, Tianwen; Pan, Shangha; Liu, Lianxin

2012-01-01

The synthetic compound 3,5-bis(2-flurobenzylidene)piperidin-4-one (EF24) is a potent analog of curcumin that exhibits enhanced biological activity and bioavailability without increasing toxicity. EF24 exerts antitumor activity by arresting the cell cycle and inducing apoptosis, suppressing many types of cancer cells in vitro. The antiproliferative and antiangiogenic properties of EF24 provide theoretical support for its development and application to liver cancers. We investigated the in vitro and in vivo activities of EF24 on liver cancer to better understand its therapeutic effects and mechanisms. EF24 induced significant apoptosis and G2/M-phase cell cycle arrest in mouse liver cancer cell lines, Hepa1-6 and H22. The expression levels of G2/M cell cycle regulating factors, cyclin B1 and Cdc2, were significantly decreased, pp53, p53, and p21 were significantly increased in EF24-treated cells. In addition, EF24 treatment significantly reduced Bcl-2 concomitant with an increase in Bax, enhanced the release of cytochrome c from the mitochondria into the cytosol, resulting in an upregulation of cleaved-caspase-3, which promoted poly (ADP-ribose) polymerase cleavage. EF24-treated cells also displayed decreases in phosphorylated Akt, phosphorylated extracellular signal-regulated kinase and vascular endothelial growth factor. Our in vitro protein expression data were confirmed in vivo using a subcutaneous hepatocellular carcinoma (HCC) tumor model. This mouse HCC model confirmed that total body weight was unchanged following EF24 treatment, although tumor weight was significantly decreased. Using an orthotopic HCC model, EF24 significantly reduced the liver/body weight ratio and relative tumor areas compared to the control group. In situ detection of apoptotic cells and quantification of Ki-67, a biomarker of cell proliferation, all indicated significant tumor suppression with EF24 treatment. These results suggest that EF24 exhibits anti-tumor activity on liver cancer cells via mitochondria-dependent apoptosis and inducing cell cycle arrest coupled with antiangiogenesis. The demonstrated activities of EF24 support its further evaluation as a treatment for human liver cancers. PMID:23118928

In vivo and in vitro suppression of hepatocellular carcinoma by EF24, a curcumin analog.

PubMed

Liu, Haitao; Liang, Yingjian; Wang, Luoluo; Tian, Lantian; Song, Ruipeng; Han, Tianwen; Pan, Shangha; Liu, Lianxin

2012-01-01

The synthetic compound 3,5-bis(2-flurobenzylidene)piperidin-4-one (EF24) is a potent analog of curcumin that exhibits enhanced biological activity and bioavailability without increasing toxicity. EF24 exerts antitumor activity by arresting the cell cycle and inducing apoptosis, suppressing many types of cancer cells in vitro. The antiproliferative and antiangiogenic properties of EF24 provide theoretical support for its development and application to liver cancers. We investigated the in vitro and in vivo activities of EF24 on liver cancer to better understand its therapeutic effects and mechanisms. EF24 induced significant apoptosis and G2/M-phase cell cycle arrest in mouse liver cancer cell lines, Hepa1-6 and H22. The expression levels of G2/M cell cycle regulating factors, cyclin B1 and Cdc2, were significantly decreased, pp53, p53, and p21 were significantly increased in EF24-treated cells. In addition, EF24 treatment significantly reduced Bcl-2 concomitant with an increase in Bax, enhanced the release of cytochrome c from the mitochondria into the cytosol, resulting in an upregulation of cleaved-caspase-3, which promoted poly (ADP-ribose) polymerase cleavage. EF24-treated cells also displayed decreases in phosphorylated Akt, phosphorylated extracellular signal-regulated kinase and vascular endothelial growth factor. Our in vitro protein expression data were confirmed in vivo using a subcutaneous hepatocellular carcinoma (HCC) tumor model. This mouse HCC model confirmed that total body weight was unchanged following EF24 treatment, although tumor weight was significantly decreased. Using an orthotopic HCC model, EF24 significantly reduced the liver/body weight ratio and relative tumor areas compared to the control group. In situ detection of apoptotic cells and quantification of Ki-67, a biomarker of cell proliferation, all indicated significant tumor suppression with EF24 treatment. These results suggest that EF24 exhibits anti-tumor activity on liver cancer cells via mitochondria-dependent apoptosis and inducing cell cycle arrest coupled with antiangiogenesis. The demonstrated activities of EF24 support its further evaluation as a treatment for human liver cancers.

Ivabradine: Current and Future Treatment of Heart Failure.

PubMed

Thorup, Lene; Simonsen, Ulf; Grimm, Daniela; Hedegaard, Elise R

2017-08-01

In heart failure (HF), the heart cannot pump blood efficiently and is therefore unable to meet the body's demands of oxygen, and/or there is increased end-diastolic pressure. Current treatments for HF with reduced ejection fraction (HFrEF) include angiotensin-converting enzyme (ACE) inhibitors, angiotension receptor type 1 (AT 1 ) antagonists, β-adrenoceptor antagonists, aldosterone receptor antagonists, diuretics, digoxin and a combination drug with AT 1 receptor antagonist and neprilysin inhibitor. In HF, the risk of readmission for hospital and mortality is markedly higher with a heart rate (HR) above 70 bpm. Here, we review the evidence regarding the use of ivabradine for lowering HR in HF. Ivabradine is a blocker of an I funny current (I(f)) channel and causes rate-dependent inhibition of the pacemaker activity in the sinoatrial node. In clinical trials of HFrEF, treatment with ivabradine seems to improve clinical outcome, for example improved ejection fraction (EF) and less readmission for hospital, but the effect appears most pronounced in patients with HRs above 70 bpm, while the effect on cardiovascular death appears less consistent. The adverse effects of ivabradine include bradycardia, atrial fibrillation and visual disturbances, but ivabradine avoids the negative inotrope effects observed with β-adrenoceptor antagonists. In conclusion, in patients with stable HFrEF with EF<35% and HR above 70 bpm, ivabradine improves the outcome and might be a first choice of therapy, if beta-adrenoceptor antagonists are not tolerated. Further studies must show whether that can be extended to HF patients with preserved EF. © 2017 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Local measurement of error field using naturally rotating tearing mode dynamics in EXTRAP T2R

NASA Astrophysics Data System (ADS)

Sweeney, R. M.; Frassinetti, L.; Brunsell, P.; Fridström, R.; Volpe, F. A.

2016-12-01

An error field (EF) detection technique using the amplitude modulation of a naturally rotating tearing mode (TM) is developed and validated in the EXTRAP T2R reversed field pinch. The technique was used to identify intrinsic EFs of m/n  =  1/-12, where m and n are the poloidal and toroidal mode numbers. The effect of the EF and of a resonant magnetic perturbation (RMP) on the TM, in particular on amplitude modulation, is modeled with a first-order solution of the modified Rutherford equation. In the experiment, the TM amplitude is measured as a function of the toroidal angle as the TM rotates rapidly in the presence of an unknown EF and a known, deliberately applied RMP. The RMP amplitude is fixed while the toroidal phase is varied from one discharge to the other, completing a full toroidal scan. Using three such scans with different RMP amplitudes, the EF amplitude and phase are inferred from the phases at which the TM amplitude maximizes. The estimated EF amplitude is consistent with other estimates (e.g. based on the best EF-cancelling RMP, resulting in the fastest TM rotation). A passive variant of this technique is also presented, where no RMPs are applied, and the EF phase is deduced.

Bioreactor with Ipomoea hederifolia adventitious roots and its endophyte Cladosporium cladosporioides for textile dye degradation.

PubMed

Patil, Swapnil M; Chandanshive, Vishal V; Rane, Niraj R; Khandare, Rahul V; Watharkar, Anuprita D; Govindwar, Sanjay P

2016-04-01

In vitro grown untransformed adventitious roots (AR) culture of Ipomoea hederifolia and its endophytic fungus (EF) Cladosporium cladosporioides decolorized Navy Blue HE2R (NB-HE2R) at a concentration of 20 ppm up to 83.3 and 65%, respectively within 96h. Whereas the AR-EF consortium decolorized the dye more efficiently and gave 97% removal within 36h. Significant inductions in the enzyme activities of lignin peroxidase, tyrosinase and laccase were observed in roots, while enzymes like tyrosinase, laccase and riboflavin reductase activities were induced in EF. Metabolites of dye were analyzed using UV-vis spectroscopy, FTIR and gas chromatography-mass spectrometry. Possible metabolic pathways of NB-HE2R were proposed with AR, EF and AR-EF systems independently. Looking at the superior efficacy of AR-EF system, a rhizoreactor was developed for the treatment of NB-HE2R at a concentration of 1000 ppm. Control reactor systems with independently grown AR and EF gave 94 and 85% NB-HE2R removal, respectively within 36h. The AR-EF rhizoreactor, however, gave 97% decolorization. The endophyte colonization additionally increased root and shoot lengths of candidate plants through mutualism. Combined bioreactor strategies can be effectively used for future eco-friendly remediation purposes. Copyright © 2016 Elsevier Inc. All rights reserved.

Polydimethylsiloxane/MIL-100(Fe) coated stir bar sorptive extraction-high performance liquid chromatography for the determination of triazines in environmental water samples.

PubMed

Lei, Yun; Chen, Beibei; You, Linna; He, Man; Hu, Bin

2017-12-01

Polydimethylsiloxane (PDMS)/MIL-100(Fe) coated stir bar was prepared by sol gel technique, and good preparation reproducibility was achieved with relative standard deviations (RSDs) ranging from 2.6% to 7.5% (n=7) and 3.6% to 10.8% (n=7) for bar-to-bar and batch-to-batch, respectively. Compared with commercial PDMS coated stir bar (Gerstel) and PEG coated stir bar (Gerstel), the prepared PDMS/MIL-100(Fe) stir bar showed better extraction efficiency for target triazines compounds. It also exhibited relatively fast extraction/desorption kinetics and long lifespan. Based on it, a method of PDMS/MIL-100(Fe) coated stir bar sorptive extraction (SBSE)-high performance liquid chromatography-ultraviolet detector (HPLC-UV) was developed for the determination of six triazines (simazine, atrazine, prometon, ametryn, prometryne and prebane) in environmental water samples. Several parameters affecting SBSE of six target triazines including extraction time, stirring rate, sample pH, ionic strength, desorption solvent and desorption time were investigated. Under the optimal experimental conditions, the limits of detection (LODs, S/N=3) were found to be in the range of 0.021-0.079μgL -1 . The repeatability RSDs were in the range of 2.3-6.3% (n=7, c=0.5μgL -1 ) and the enrichment factors (EFs) ranged from 51.1 to 102-fold (theoretical EF was 200-fold). The proposed method was applied to the analysis of target triazines in environmental water samples, with recoveries of 98.0-118% and 94.0-107% for spiked East Lake water and local pond water samples, respectively. Copyright © 2017. Published by Elsevier B.V.

The independent and interacting effects of hedonic hunger and executive function on binge eating.

PubMed

Manasse, Stephanie M; Espel, Hallie M; Forman, Evan M; Ruocco, Anthony C; Juarascio, Adrienne S; Butryn, Meghan L; Zhang, Fengqing; Lowe, Michael R

2015-06-01

Poor executive function (EF; pre-frontal cognitive control processes governing goal-directed behavior) and elevated hedonic hunger (i.e., preoccupation with palatable foods in the absence of physiological hunger) are theoretical risk and maintenance factors for binge eating (BE) distinct from general obesity. Recent theoretical models posit that dysregulated behavior such as BE may result from a combination of elevated appetitive drive (e.g., hedonic hunger) and decreased EF (e.g., inhibitory control and delayed discounting). The present study sought to test this model in distinguishing BE from general obesity by examining the independent and interactive associations of EF and hedonic hunger with BE group status (i.e., odds of categorization in BE group versus non-BE group). Treatment-seeking overweight and obese women with BE (n = 31) and without BE (OW group; n = 43) were assessed on measures of hedonic hunger and EF (inhibitory control and delay discounting). Elevated hedonic hunger increased the likelihood of categorization in the BE group, regardless of EF. When hedonic hunger was low, poor EF increased the likelihood of categorization in the BE group. Results indicate that the interplay of increased appetitive drives and decreased cognitive function may distinguish BE from overweight/obesity. Future longitudinal investigations of the combinatory effect of hedonic hunger and EF in increasing risk for developing BE are warranted, and may inform future treatment development to target these factors. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Influence of the Toxin/Antitoxin mazEF on Growth and Survival of Listeria monocytogenes under Stress.

PubMed

Curtis, Thomas D; Takeuchi, Ippei; Gram, Lone; Knudsen, Gitte M

2017-01-13

A major factor in the resilience of Listeria monocytogenes is the alternative sigma factor B (σ B ). Type II Toxin/Antitoxin (TA) systems are also known to have a role in the bacterial stress response upon activation via the ClpP or Lon proteases. Directly upstream of the σ B operon in L. monocytogenes is the TA system mazEF , which can cleave mRNA at UACMU sites. In this study, we showed that the mazEF TA locus does not affect the level of persister formation during treatment with antibiotics in lethal doses, but exerts different effects according to the sub-inhibitory stress added. Growth of a Δ mazEF mutant was enhanced relative to the wildtype in the presence of sub-inhibitory norfloxacin and at 42 °C, but was decreased when challenged with ampicillin and gentamicin. In contrast to studies in Staphylococcus aureus , we found that the mazEF locus did not affect transcription of genes within the σ B operon, but MazEF effected the expression of the σ B -dependent genes opuCA and lmo0880 , with a 0.22 and 0.05 fold change, respectively, compared to the wildtype under sub-inhibitory norfloxacin conditions. How exactly this system operates remains an open question, however, our data indicates it is not analogous to the system of S. aureus , suggesting a novel mode of action for MazEF in L. monocytogenes.

Direct Nitrous Oxide Emissions From Tropical And Sub-Tropical Agricultural Systems - A Review And Modelling Of Emission Factors.

PubMed

Albanito, Fabrizio; Lebender, Ulrike; Cornulier, Thomas; Sapkota, Tek B; Brentrup, Frank; Stirling, Clare; Hillier, Jon

2017-03-10

There has been much debate about the uncertainties associated with the estimation of direct and indirect agricultural nitrous oxide (N 2 O) emissions in developing countries and in particular from tropical regions. In this study, we report an up-to-date review of the information published in peer-review journals on direct N 2 O emissions from agricultural systems in tropical and sub-tropical regions. We statistically analyze net-N 2 O-N emissions to estimate tropic-specific annual N 2 O emission factors (N 2 O-EFs) using a Generalized Additive Mixed Model (GAMM) which allowed the effects of multiple covariates to be modelled as linear or smooth non-linear continuous functions. Overall the mean N 2 O-EF was 1.2% for the tropics and sub-tropics, thus within the uncertainty range of IPCC-EF. On a regional basis, mean N 2 O-EFs were 1.4% for Africa, 1.1%, for Asia, 0.9% for Australia and 1.3% for Central &South America. Our annual N 2 O-EFs, estimated for a range of fertiliser rates using the available data, do not support recent studies hypothesising non-linear increase N 2 O-EFs as a function of applied N. Our findings highlight that in reporting annual N 2 O emissions and estimating N 2 O-EFs, particular attention should be paid in modelling the effect of study length on response of N 2 O.

Direct Nitrous Oxide Emissions From Tropical And Sub-Tropical Agricultural Systems - A Review And Modelling Of Emission Factors

PubMed Central

Albanito, Fabrizio; Lebender, Ulrike; Cornulier, Thomas; Sapkota, Tek B.; Brentrup, Frank; Stirling, Clare; Hillier, Jon

2017-01-01

There has been much debate about the uncertainties associated with the estimation of direct and indirect agricultural nitrous oxide (N2O) emissions in developing countries and in particular from tropical regions. In this study, we report an up-to-date review of the information published in peer-review journals on direct N2O emissions from agricultural systems in tropical and sub-tropical regions. We statistically analyze net-N2O-N emissions to estimate tropic-specific annual N2O emission factors (N2O-EFs) using a Generalized Additive Mixed Model (GAMM) which allowed the effects of multiple covariates to be modelled as linear or smooth non-linear continuous functions. Overall the mean N2O-EF was 1.2% for the tropics and sub-tropics, thus within the uncertainty range of IPCC-EF. On a regional basis, mean N2O-EFs were 1.4% for Africa, 1.1%, for Asia, 0.9% for Australia and 1.3% for Central & South America. Our annual N2O-EFs, estimated for a range of fertiliser rates using the available data, do not support recent studies hypothesising non-linear increase N2O-EFs as a function of applied N. Our findings highlight that in reporting annual N2O emissions and estimating N2O-EFs, particular attention should be paid in modelling the effect of study length on response of N2O. PMID:28281637

Direct Nitrous Oxide Emissions From Tropical And Sub-Tropical Agricultural Systems - A Review And Modelling Of Emission Factors

NASA Astrophysics Data System (ADS)

Albanito, Fabrizio; Lebender, Ulrike; Cornulier, Thomas; Sapkota, Tek B.; Brentrup, Frank; Stirling, Clare; Hillier, Jon

2017-03-01

There has been much debate about the uncertainties associated with the estimation of direct and indirect agricultural nitrous oxide (N2O) emissions in developing countries and in particular from tropical regions. In this study, we report an up-to-date review of the information published in peer-review journals on direct N2O emissions from agricultural systems in tropical and sub-tropical regions. We statistically analyze net-N2O-N emissions to estimate tropic-specific annual N2O emission factors (N2O-EFs) using a Generalized Additive Mixed Model (GAMM) which allowed the effects of multiple covariates to be modelled as linear or smooth non-linear continuous functions. Overall the mean N2O-EF was 1.2% for the tropics and sub-tropics, thus within the uncertainty range of IPCC-EF. On a regional basis, mean N2O-EFs were 1.4% for Africa, 1.1%, for Asia, 0.9% for Australia and 1.3% for Central & South America. Our annual N2O-EFs, estimated for a range of fertiliser rates using the available data, do not support recent studies hypothesising non-linear increase N2O-EFs as a function of applied N. Our findings highlight that in reporting annual N2O emissions and estimating N2O-EFs, particular attention should be paid in modelling the effect of study length on response of N2O.

Executive functioning before and after onset of alcohol use disorder in adolescence. A TRAILS study.

PubMed

Boelema, Sarai R; Harakeh, Zeena; van Zandvoort, Martine J E; Reijneveld, Sijmen A; Verhulst, Frank C; Ormel, Johan; Vollebergh, Wilma A M

2016-07-01

The aim of the present study was to investigate whether executive functioning (EF) in early adolescence predicted alcohol use disorder (AUD) in late adolescence and whether adolescents with AUD differed in maturation of EF from controls without a diagnosis. We used the data from the Tracking Adolescents' Individual Lives Survey (TRAILS), a cohort of 2230 Dutch adolescents. Working memory, inhibition, and attention were measured at ages 11 and 19. At age 19, lifetime DSM-IV diagnoses were determined, resulting in a control group (n = 1111) and two AUD groups, i.e., alcohol abusers (n = 381) and alcohol dependents (n = 51). Regression analyses assessed whether EF at age 11 predicted the transition to AUD in late adolescence and whether AUD affected maturation of EF from age 11 to 19. EF in early adolescence did not predict AUD in late adolescence. A significant interaction effect emerged between gender and alcohol dependence for shift attention (β = 0.12, SE=0.36), with girls showing smaller maturational rates. This effect remained significant after controlling for alcohol intake (ages 16 and 19) and comorbid psychiatric disorders. Our results do not replicate the finding that EF in early adolescence is a significant predictor of AUD in late adolescence. Furthermore, for the majority of tasks, adolescents with AUD do not differ in EF maturation over the course of adolescence. Alcohol dependent girls however, show less maturation of shift attention. This is independent of the quantity of alcohol intake, which could suggest that non-normative maturation of EF is associated with the behavioural components of AUD. Copyright © 2016 Elsevier Ltd. All rights reserved.

Autophagy and Apoptosis in Hepatocellular Carcinoma Induced by EF25-(GSH)2: A Novel Curcumin Analog

PubMed Central

Zhou, Tao; Ye, Lili; Bai, Yu; Sun, Aiming; Cox, Bryan; Liu, Dahai; Li, Yong; Liotta, Dennis; Snyder, James P.; Fu, Haian; Huang, Bei

2014-01-01

Curcumin, a spice component as well as a traditional Asian medicine, has been reported to inhibit proliferation of a variety of cancer cells but is limited in application due to its low potency and bioavailability. Here, we have assessed the therapeutic effects of a novel and water soluble curcumin analog, 3,5-bis(2-hydroxybenzylidene)tetrahydro-4H-pyran-4-one glutathione conjugate [EF25-(GSH)2], on hepatoma cells. Using the MTT and colony formation assays, we determined that EF25-(GSH)2 drastically inhibits the proliferation of hepatoma cell line HepG2 with minimal cytotoxicity for the immortalized human hepatic cell line HL-7702. Significantly, EF25-(GSH)2 suppressed growth of HepG2 xenografts in mice with no observed toxicity to the animals. Mechanistic investigation revealed that EF25-(GSH)2 induces autophagy by means of a biphasic mechanism. Low concentrations (<5 µmol/L) induced autophagy with reversible and moderate cytoplasmic vacuolization, while high concentrations (>10 µmol/L) triggered an arrested autophagy process with irreversible and extensive cytoplasmic vacuolization. Prolonged treatment with EF25-(GSH)2 induced cell death through both an apoptosis-dependent and a non-apoptotic mechanism. Chloroquine, a late stage inhibitor of autophagy which promoted cytoplasmic vacuolization, led to significantly enhanced apoptosis and cytotoxicity when combined with EF25-(GSH)2. Taken together, these data imply a fail-safe mechanism regulated by autophagy in the action of EF25-(GSH)2, suggesting the therapeutic potential of the novel curcumin analog against hepatocellular carcinoma (HCC), while offering a novel and effective combination strategy with chloroquine for the treatment of patients with HCC. PMID:25268357

Maternal Executive Functioning as a Mechanism in the Intergenerational Transmission of Parenting: Preliminary Evidence

PubMed Central

Bridgett, David J.; Kanya, Meghan J.; Rutherford, Helena J. V.; Mayes, Linda C.

2016-01-01

Multiple lines of inquiry, including experimental animal models, have recently converged to suggest that executive functioning (EF) may be one mechanism by which parenting behavior is transmitted across generations. In the current investigation, we empirically test this notion by examining relations between maternal EF and parenting behaviors during mother-infant interactions, and by examining the role of maternal EF in the intergenerational transmission of parenting behavior. Mother-infant dyads (N=150) in a longitudinal study participated. Mothers were administered measures of EF (working memory and inhibition), reported on the parenting they received from their parents (i.e., the infants’ maternal grandparents), and were observed interacting with their 8-month-old infants. SEM findings indicated that the negative parenting mothers received from their own parents was significantly related to poorer maternal EF, and that poorer maternal EF was significantly related to subsequent engagement in more negative parenting practices with their own infant. A significant indirect effect, through maternal EF, was observed between maternal report of her experiences of negative parenting received while growing up and her own use of negative parenting practices. Our findings make two contributions. First, we add to existing work that has primarily considered relations between parent EF and parenting behavior while interacting with older children by showing that maternal EF affects children, via maternal parenting behavior, beginning very early in life. Second, we provide key evidence of the role of EF in the intergenerational transmission of parenting. Additional implications of these findings, as well as important future directions, are discussed. PMID:27929313

Uniform electric field generation in circular multi-well culture plates using polymeric inserts

NASA Astrophysics Data System (ADS)

Tsai, Hsieh-Fu; Cheng, Ji-Yen; Chang, Hui-Fang; Yamamoto, Tadashi; Shen, Amy Q.

2016-05-01

Applying uniform electric field (EF) in vitro in the physiological range has been achieved in rectangular shaped microchannels. However, in a circular-shaped device, it is difficult to create uniform EF from two electric potentials due to different electrical resistances originated from the length difference between the diameter of the circle and the length of any parallel chord of the bottom circular chamber where cells are cultured. To address this challenge, we develop a three-dimensional (3D) computer-aided designed (CAD) polymeric insert to create uniform EF in circular shaped multi-well culture plates. A uniform EF with a coefficient of variation (CV) of 1.2% in the 6-well plate can be generated with an effective stimulation area percentage of 69.5%. In particular, NIH/3T3 mouse embryonic fibroblast cells are used to validate the performance of the 3D designed Poly(methyl methacrylate) (PMMA) inserts in a circular-shaped 6-well plate. The CAD based inserts can be easily scaled up (i.e., 100 mm dishes) to further increase effective stimulation area percentages, and also be implemented in commercially available cultureware for a wide variety of EF-related research such as EF-cell interaction and tissue regeneration studies.

Pharmacologic Suppression of Inflammation by a Diphenyldifluoroketone, EF24, in a Rat Model of Fixed-Volume Hemorrhage Improves Survival

PubMed Central

Yadav, Vivek R.; Sahoo, Kaustuv; Roberts, Pamela R.

2013-01-01

An exaggerated release of proinflammatory cytokines and accompanying inflammation contributes to the development of multiple organ failure after hemorrhagic shock. Here, we tested the nuclear factor (NF) κ-light-chain-enhancer of activated B cell (NF-κB)–mediated transcriptional control of inflammatory pathways as a target in the management of hemorrhage-induced inflammation. We performed a study in a rat model of fixed-volume hemorrhage to investigate the anti-inflammatory effects of the diphenyldifluoroketone EF24 [3,5-bis(2-fluorobenzylidene)piperidin-4-one], an NF-κB inhibitor, in lung tissue. EF24 treatment (0.4 mg/kg) significantly prevented the upregulation of inflammatory biomarkers in rats subjected to 50% hemorrhage and preserved the pulmonary histology in hemorrhaged rats. The lung tissue from treated rats showed marked suppression of the hemorrhage-mediated induction of Toll-like receptor 4, phospho-p65 NF-κB, inducible nitric-oxide synthase, heme oxygenase–1, and cyclooxygenase-2 (COX-2). The hemorrhage-induced COX-2 activity was also significantly inhibited by the EF24 treatment. At the same time, EF24 induced nuclear factor (erythroid-derived 2)-like 2–mediated protective mechanisms against oxidative stress. EF24 also reduced hemorrhage-induced lung myeloperoxidase activity. The plasma levels of proinflammatory tumor necrosis factor-α, interleukin (IL)-6, IL-1α, and IL-1β were lower in EF24-treated rats than in untreated rats. Moreover, there was a significant reduction in the pulmonary expression of high-mobility group B1 protein. These biochemical effects were accompanied by a significant improvement in the survival of rats administered with EF24 as compared with the rats receiving vehicle control (P < 0.05). Overall, the results suggest that EF24 attenuates hemorrhage-induced inflammation and could serve as a salutary anti-inflammatory agent in resuscitation strategies. PMID:23995597

The Role of Direct Current Electric Field-Guided Stem Cell Migration in Neural Regeneration.

PubMed

Yao, Li; Li, Yongchao

2016-06-01

Effective directional axonal growth and neural cell migration are crucial in the neural regeneration of the central nervous system (CNS). Endogenous currents have been detected in many developing nervous systems. Experiments have demonstrated that applied direct current (DC) electric fields (EFs) can guide axonal growth in vitro, and attempts have been made to enhance the regrowth of damaged spinal cord axons using DC EFs in in vivo experiments. Recent work has revealed that the migration of stem cells and stem cell-derived neural cells can be guided by DC EFs. These studies have raised the possibility that endogenous and applied DC EFs can be used to direct neural tissue regeneration. Although the mechanism of EF-directed axonal growth and cell migration has not been fully understood, studies have shown that the polarization of cell membrane proteins and the activation of intracellular signaling molecules are involved in the process. The application of EFs is a promising biotechnology for regeneration of the CNS.

Interaction between the cellular protein eEF1A and the 3'-terminal stem-loop of West Nile virus genomic RNA facilitates viral minus-strand RNA synthesis.

PubMed

Davis, William G; Blackwell, Jerry L; Shi, Pei-Yong; Brinton, Margo A

2007-09-01

RNase footprinting and nitrocellulose filter binding assays were previously used to map one major and two minor binding sites for the cell protein eEF1A on the 3'(+) stem-loop (SL) RNA of West Nile virus (WNV) (3). Base substitutions in the major eEF1A binding site or adjacent areas of the 3'(+) SL were engineered into a WNV infectious clone. Mutations that decreased, as well as ones that increased, eEF1A binding in in vitro assays had a negative effect on viral growth. None of these mutations affected the efficiency of translation of the viral polyprotein from the genomic RNA, but all of the mutations that decreased in vitro eEF1A binding to the 3' SL RNA also decreased viral minus-strand RNA synthesis in transfected cells. Also, a mutation that increased the efficiency of eEF1A binding to the 3' SL RNA increased minus-strand RNA synthesis in transfected cells, which resulted in decreased synthesis of genomic RNA. These results strongly suggest that the interaction between eEF1A and the WNV 3' SL facilitates viral minus-strand synthesis. eEF1A colocalized with viral replication complexes (RC) in infected cells and antibody to eEF1A coimmunoprecipitated viral RC proteins, suggesting that eEF1A facilitates an interaction between the 3' end of the genome and the RC. eEF1A bound with similar efficiencies to the 3'-terminal SL RNAs of four divergent flaviviruses, including a tick-borne flavivirus, and colocalized with dengue virus RC in infected cells. These results suggest that eEF1A plays a similar role in RNA replication for all flaviviruses.

Zoonotic ectopic fascioliasis: review and discussion.

PubMed

Rashed, Amr A; Khalil, Hazem H M; Morsy, Ayman T A

2010-12-01

Ectopic fascioliasis (EF) has direct and indirect effects on both humans and animals. The phenomenon of EF was individual cases in the period from 1950 up to the end of last century. From the period of 2000 up to 2006, plenty of researches were on EF in the developed and undeveloped countries. Nineteen EF cases infected with the immature and few with the mature worms were 13 females and 6 males. Three cases of lymphatic, pleural and breast fascioliasis reached the adults and laid their eggs in a lymph node in the cervical region pleural cavity and breast tissues. Until recent, knowledge about the ectopic fascioliasis pathway is little. Fasciola hepatica was the commonest species in most cases. The effect of fascioliasis might be direct to liver as ectopic foci or indirect on other organs due to the metabolites and secretory excretory products. All ages and both sexes were EF infected. Watercress topped the list of water plants born encysted metacercariae followed by lettuce, mint, and alfalfa. Nearly 24 million Egyptians at risk and about 800,000 were infected. On the global scale, about 180 million are at risk of infection.

Effects of BRL 38227 on neurally-mediated responses in the guinea-pig isolated bronchus.

PubMed

Good, D M; Clapham, J C; Hamilton, T C

1992-04-01

1. In guinea-pig isolated bronchus treated with indomethacin (2.8 microM), electrical field stimulation (EFS; 10 Hz, 0.5 ms, 60-70 V, for 10 s) evoked a tetrodotoxin (3 microM)-sensitive, biphasic contraction comprising a rapid, atropine (1 microM)-sensitive cholinergic response succeeded by a slowly developing, capsaicin (10 microM)-sensitive, non-adrenergic, non-cholinergic excitatory (NANCe) response. 2. BRL 38227 (0.3-3 microM), salmeterol (0.003-3 microM) and ketotifen (1.0-300 microM) each produced concentration-dependent inhibition of both NANCe and cholinergic responses to EFS in guinea-pig isolated bronchus. 3. Substance P (SP; 1 microM) and neurokinin A (NKA; 0.07 microM) produced contractions equivalent in magnitude to the NANCe response to EFS, which were inhibited by salmeterol (1 microM), but not by BRL 38227 (3 microM) or ketotifen (100 microM). 4. Acetylcholine (ACh; 6 microM) was equi-effective with the electrical activation of cholinergic neurones. BRL 38227 (3 microM) slightly inhibited responses to ACh (6 microM). Salmeterol (1 microM) and ketotifen (100 microM) markedly inhibited responses to ACh (6 microM). 5. In bronchial rings pre-contracted with ACh (100 microM), BRL 38227 (0.1-30 microM), salmeterol (0.001-3 microM) and ketotifen (0.1-100 microM) each produced concentration-dependent relaxation. Unlike ketotifen, BRL 38227 and salmeterol only partially (18.8 +/- 2.1% and 51.8 +/- 3.9% respectively) reversed the ACh-induced contraction. 6. The (+)-analogue of BRL 38227, BRL 38226 (0.3-100 microM), was without effect on responses to EFS and had no effect on the inhibition caused by BRL 38227. The K+-channel activators pinacidil (3.0-30 microM) and RP 52891 (3.0-30 microM) exerted similar inhibitory actions on responses to EFS as BRL 38227, but were less potent. Glibenclamide (0.1-1.O microM) and phentolamine (3 microM) antagonized the inhibitory effects of BRL 38227 on responses to EFS.7. It is concluded that BRL 38227 and ketotifen can inhibit NANCe neuroeffector transmission at concentrations exerting little or no inhibitory effects on responses to exogenously applied tachykinins.By contrast, in addition to suppressing NANCe responses to EFS, salmeterol also markedly inhibits responses to SP and NKA. At concentrations markedly suppressing cholinergic neuroeffector transmission, BRL 38227 has only minor effects on responses to exogenously-applied ACh. Salmeterol and ketotifen both depress responses to ACh within the concentration-range over which they inhibit cholinergic responses to EFS. The inhibitory effects of BRL 38227 on responses to EFS exhibit stereo-specificity and may involve the opening of a neuronal K+-channel. This K+-channel is glibenclamide-and phentolamine-sensitive and appears similar to the smooth muscle K+-channel which is modulated by BRL 38227.

EF24, a novel synthetic curcumin analog, induces apoptosis in cancer cells via a redox-dependent mechanism.

PubMed

Adams, Brian K; Cai, Jiyang; Armstrong, Jeff; Herold, Marike; Lu, Yang J; Sun, Aiming; Snyder, James P; Liotta, Dennis C; Jones, Dean P; Shoji, Mamoru

2005-03-01

In this study, we show that the novel synthetic curcumin analog, EF24, induces cell cycle arrest and apoptosis by means of a redox-dependent mechanism in MDA-MB-231 human breast cancer cells and DU-145 human prostate cancer cells. Cell cycle analysis demonstrated that EF24 causes a G2/M arrest in both cell lines, and that this cell cycle arrest is followed by the induction of apoptosis as evidenced by caspase-3 activation, phosphatidylserine externalization and an increased number of cells with a sub-G1 DNA fraction. In addition, we demonstrate that EF24 induces a depolarization of the mitochondrial membrane potential, suggesting that the compound may also induce apoptosis by altering mitochondrial function. EF24, like curcumin, serves as a Michael acceptor reacting with glutathione (GSH) and thioredoxin 1. Reaction of EF24 with these agents in vivo significantly reduced intracellular GSH as well as oxidized GSH in both the wild-type and Bcl-xL overexpressing HT29 human colon cancer cells. We therefore propose that the anticancer effect of a novel curcumin analog, EF24, is mediated in part by redox-mediated induction of apoptosis.

1H NMR study of the effect of heme insertion on the folding of apomyoglobin

NASA Astrophysics Data System (ADS)

Yamamoto, Yasuhiko; Takemoto, Kenji; Matsuo, Hitomi

2002-01-01

NMR signals arising from His EF5 and His GH1 N ɛH protons of sperm whale myoglobin and apomyoglobin have been assigned, and the protein folding has been studied through the analysis of these signals. His EF5 and His GH1 N ɛH protons participate in the internal hydrogen bonds at the B-GH and EF-H interfaces, respectively, and their signals are remarkably sensitive to local structural alterations at these sites. The shifts of these signals in alkaline pH condition were only slightly affected by the removal of heme, indicating that the overall protein folding is essentially retained in apoprotein. The line width of His EF5 proton signal, however, increased largely in the spectra of apomyoglobin and this result suggests a conformational lability of the EF-H interface in the absence of heme. Furthermore, the His EF5 proton signal was found to be influenced by not only the orientation of heme relative to the protein, but also by the type of hemin used to reconstitute apomyoglobin. These results clearly demonstrate the presence of a long-range structural correlation between the heme active site and the EF-H interface.

Comparative Study of Emission Factors and Mutagenicity of ...

EPA Pesticide Factsheets

Wildfire events produce massive amounts of smoke and thus play an important role in local and regional air quality as well as public health. It is not well understood however if the impacts of wildfire smoke are influenced by fuel types or combustion conditions. Here we developed a novel combustion and sample-collection system that features an automated tube furnace to control combustion conditions and a multistage cryotrap system to efficiently collection particulate and semi-volatile phases of smoke emissions. The furnace sustained stable flaming and smoldering biomass (red oak and peat) burning conditions consistently for ~60 min. The multi-stage cryo-trap system (-10°C followed by -47°C, and ending in -70°C sequential impingers) collected up to 90% (by mass) of the smoke. Condensates were extracted and assessed for mutagenicity (polycyclic aromatic hydrocarbons (PAHs)- and nitroarene-type activity) in Salmonella strains TA100 and TA98+/-S9. Carbon dioxide, carbon monoxide (CO), and particulate matter (PM) concentrations monitored continuously during the combustion process were used to calculate modified combustion efficiency (MCE) and emission factors (EFs). We found that the MCE during smoldering conditions was 74% and 71% and during flaming conditions was 99% and 96% for red oak and peat, respectively. Red oak smoldering EFs for CO and PM were 209 g/kg and 147 g/kg, whereas flaming EFs were 16 g/kg and 0.6 g/kg, respectively. Peat smoldering EF

Associations Between Neutrophil Gelatinase Associated Lipocalin, Neutrophil-to-Lymphocyte Ratio, Atrial Fibrillation and Renal Dysfunction in Chronic Heart Failure

PubMed Central

Argan, Onur; Ural, Dilek; Kozdag, Guliz; Sahin, Tayfun; Bozyel, Serdar; Aktas, Mujdat; Karauzum, Kurtulus; Yılmaz, Irem; Dervis, Emir; Agir, Aysen

2016-01-01

Background Atrial fibrillation (AF) and renal dysfunction are two common comorbidities in patients with chronic heart failure with reduced ejection fraction (HFrEF). This study evaluated the effect of permanent AF on renal function in HFrEF and investigated the associations of atrial fibrillation, neutrophil gelatinase-associated lipocalin (NGAL), and neutrophil-to-lymphocyte ratio (NLR) with adverse clinical outcome. Material/Methods Serum NGAL levels measured by ELISA and NLR were compared between patients with sinus rhythm (HFrEF-SR, n=68), with permanent AF (HFrEF-AF, n=62), and a healthy control group (n=50). Results Mean eGFR levels were significantly lower, and NLR and NGAL levels were significantly higher in the HFrEF patients than in the control patients but the difference between HFrEF-SR and HFrEF-AF was not statistically significant (NGAL: 95 ng/mL in HFrEF-SR, 113 ng/mL in HFrEF-AF and 84 ng/mL in the control group; p<0.001). Independent associates of baseline eGFR were age, hemoglobin, NLR, triiodothyronine, and pulmonary artery systolic pressure. In a mean 16 months follow-up, adverse clinical outcome defined as progression of kidney dysfunction and composite of all-cause mortality and re-hospitalization were not different between HFrEF-SR and HFrEF-AF patients. Although NGAL was associated with clinical endpoints in the univariate analysis, Cox regression analysis showed that independent predictors of increased events were the presence of signs right heart failure, C-reactive protein, NLR, triiodothyronine, and hemoglobin. In ROC analysis, a NLR >3 had a 68% sensitivity and 75% specificity to predict progression of kidney disease (AUC=0.72, 95% CI 0.58–0.85, p=0.001). Conclusions Presence of AF in patients with HFrEF was not an independent contributor of adverse clinical outcome (i.e., all-cause death, re-hospitalization) or progression of renal dysfunction. Renal dysfunction in HFrEF was associated with both NLR and NGAL levels, but systemic inflammation reflected by NLR seemed to be a more important determinant of progression of kidney dysfunction. PMID:27918494

Everyday executive functions in Down syndrome from early childhood to young adulthood: evidence for both unique and shared characteristics compared to youth with sex chromosome trisomy (XXX and XXY).

PubMed

Lee, Nancy Raitano; Anand, Payal; Will, Elizabeth; Adeyemi, Elizabeth I; Clasen, Liv S; Blumenthal, Jonathan D; Giedd, Jay N; Daunhauer, Lisa A; Fidler, Deborah J; Edgin, Jamie O

2015-01-01

Executive functions (EF) are thought to be impaired in Down syndrome (DS) and sex chromosome trisomy (Klinefelter and Trisomy X syndromes; +1X). However, the syndromic specificity and developmental trajectories associated with EF difficulties in these groups are poorly understood. The current investigation (a) compared everyday EF difficulties in youth with DS, +1X, and typical development (TD); and (b) examined relations between age and EF difficulties in these two groups and a TD control group cross-sectionally. Study 1 investigated the syndromic specificity of EF profiles on the Behavior Rating Inventory of Executive Function (BRIEF) in DS (n = 30), +1X (n = 30), and a TD group (n = 30), ages 5-18 years. Study 2 examined age effects on EF in the same cross-sectional sample of participants included in Study 1. Study 3 sought to replicate Study 2's findings for DS by examining age-EF relations in a large independent sample of youth with DS (n = 85) and TD (n = 43), ages 4-24 years. Study 1 found evidence for both unique and shared EF impairments for the DS and +1X groups. Most notably, youth with +1X had relatively uniform EF impairments on the BRIEF scales, while the DS group showed an uneven BRIEF profile with relative strengths and weaknesses. Studies 2 and 3 provided support for fairly similar age-EF relations in the DS and TD groups. In contrast, for the +1X group, findings were mixed; 6 BRIEF scales showed similar age-EF relations to the TD group and 2 showed greater EF difficulties at older ages for +1X. These findings will be discussed within the context of efforts to identify syndrome specific cognitive-behavioral profiles for youth with different genetic syndromes in order to inform basic science investigations into the etiology of EF difficulties in these groups and to develop treatment approaches that are tailored to the needs of these groups.

Everyday executive functions in Down syndrome from early childhood to young adulthood: evidence for both unique and shared characteristics compared to youth with sex chromosome trisomy (XXX and XXY)

PubMed Central

Lee, Nancy Raitano; Anand, Payal; Will, Elizabeth; Adeyemi, Elizabeth I.; Clasen, Liv S.; Blumenthal, Jonathan D.; Giedd, Jay N.; Daunhauer, Lisa A.; Fidler, Deborah J.; Edgin, Jamie O.

2015-01-01

Executive functions (EF) are thought to be impaired in Down syndrome (DS) and sex chromosome trisomy (Klinefelter and Trisomy X syndromes; +1X). However, the syndromic specificity and developmental trajectories associated with EF difficulties in these groups are poorly understood. The current investigation (a) compared everyday EF difficulties in youth with DS, +1X, and typical development (TD); and (b) examined relations between age and EF difficulties in these two groups and a TD control group cross-sectionally. Study 1 investigated the syndromic specificity of EF profiles on the Behavior Rating Inventory of Executive Function (BRIEF) in DS (n = 30), +1X (n = 30), and a TD group (n = 30), ages 5–18 years. Study 2 examined age effects on EF in the same cross-sectional sample of participants included in Study 1. Study 3 sought to replicate Study 2's findings for DS by examining age-EF relations in a large independent sample of youth with DS (n = 85) and TD (n = 43), ages 4–24 years. Study 1 found evidence for both unique and shared EF impairments for the DS and +1X groups. Most notably, youth with +1X had relatively uniform EF impairments on the BRIEF scales, while the DS group showed an uneven BRIEF profile with relative strengths and weaknesses. Studies 2 and 3 provided support for fairly similar age-EF relations in the DS and TD groups. In contrast, for the +1X group, findings were mixed; 6 BRIEF scales showed similar age-EF relations to the TD group and 2 showed greater EF difficulties at older ages for +1X. These findings will be discussed within the context of efforts to identify syndrome specific cognitive-behavioral profiles for youth with different genetic syndromes in order to inform basic science investigations into the etiology of EF difficulties in these groups and to develop treatment approaches that are tailored to the needs of these groups. PMID:26539087

Assessment of In Vivo Antidiabetic Properties of Umbelliferone and Lupeol Constituents of Banana (Musa sp. var. Nanjangud Rasa Bale) Flower in Hyperglycaemic Rodent Model.

PubMed

Ramu, Ramith; S Shirahatti, Prithvi; S, Nanjunda Swamy; Zameer, Farhan; Lakkappa Dhananjaya, Bhadrapura; M N, Nagendra Prasad

2016-01-01

Banana is an extensively cultivated plant worldwide, mainly for its fruit, while its ancillary product, the banana flower is consumed as a vegetable and is highly recommended for diabetics in the traditional Indian medicine system. This study is based on an investigation of the in vivo antihyperglycaemic activity of Umbelliferone (C1) and Lupeol (C2) isolated from the ethanol extract of banana flower (EF) in alloxan induced diabetic rat model. Diabetic rats which were administered with C1, C2 and EF (100 and 200 mg/kg b. wt.) for 4 weeks showed deterioration in fasting hyperglycaemia and reversal of abnormalities in serum/urine protein, urea and creatinine, when compared to the diabetic control group of rats. The diabetic group of rats fed with EF, C1 and C2 (100 mg/kg b. wt.) once daily, for a period of 28 days resulted in a significant reduction of diabetic symptoms viz., polyphagia, polydipsia, polyuria and urine sugar together with an improved body weight. HbA1c extent was reduced whereas levels of insulin and Hb were increased. Both the extract and compounds wielded positive impacts in diabetic rats by reversal of altered activities of hepatic marker enzymes viz., aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP); glycolytic enzyme (hexokinase); shunt enzyme (glucose-6-phosphate dehydrogenase); gluconeogenic enzymes (glucose-6-phosphatase, fructose-1,6-bisphosphatase, lactate dehydrogenase) and pyruvate kinase. The characteristic diabetic complications such as hypercholesterolemia and hypertriacylglycerolemia also significantly reverted to normal in the serum/liver of diabetic rats. Besides these, the treatment increased the activities of enzymatic and non-enzymatic antioxidants in the serum and liver. The histological observations revealed a marked regeneration of the β-cells in the drug treated diabetic rats. In conclusion, the present study illustrates that EF, C1 and C2 enhances the glycolytic activities, besides increasing the hepatic glucose utilization in diabetic rats by stimulating insulin secretion from the remnant β-cells along with potential enzymatic and non-enzymatic antioxidant activities.

Assessment of In Vivo Antidiabetic Properties of Umbelliferone and Lupeol Constituents of Banana (Musa sp. var. Nanjangud Rasa Bale) Flower in Hyperglycaemic Rodent Model

PubMed Central

Ramu, Ramith; S. Shirahatti, Prithvi; S., Nanjunda Swamy; Zameer, Farhan; Lakkappa Dhananjaya, Bhadrapura; M. N., Nagendra Prasad

2016-01-01

Banana is an extensively cultivated plant worldwide, mainly for its fruit, while its ancillary product, the banana flower is consumed as a vegetable and is highly recommended for diabetics in the traditional Indian medicine system. This study is based on an investigation of the in vivo antihyperglycaemic activity of Umbelliferone (C1) and Lupeol (C2) isolated from the ethanol extract of banana flower (EF) in alloxan induced diabetic rat model. Diabetic rats which were administered with C1, C2 and EF (100 and 200 mg/kg b. wt.) for 4 weeks showed deterioration in fasting hyperglycaemia and reversal of abnormalities in serum/urine protein, urea and creatinine, when compared to the diabetic control group of rats. The diabetic group of rats fed with EF, C1 and C2 (100 mg/kg b. wt.) once daily, for a period of 28 days resulted in a significant reduction of diabetic symptoms viz., polyphagia, polydipsia, polyuria and urine sugar together with an improved body weight. HbA1c extent was reduced whereas levels of insulin and Hb were increased. Both the extract and compounds wielded positive impacts in diabetic rats by reversal of altered activities of hepatic marker enzymes viz., aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP); glycolytic enzyme (hexokinase); shunt enzyme (glucose-6-phosphate dehydrogenase); gluconeogenic enzymes (glucose-6-phosphatase, fructose-1,6-bisphosphatase, lactate dehydrogenase) and pyruvate kinase. The characteristic diabetic complications such as hypercholesterolemia and hypertriacylglycerolemia also significantly reverted to normal in the serum/liver of diabetic rats. Besides these, the treatment increased the activities of enzymatic and non-enzymatic antioxidants in the serum and liver. The histological observations revealed a marked regeneration of the β-cells in the drug treated diabetic rats. In conclusion, the present study illustrates that EF, C1 and C2 enhances the glycolytic activities, besides increasing the hepatic glucose utilization in diabetic rats by stimulating insulin secretion from the remnant β-cells along with potential enzymatic and non-enzymatic antioxidant activities. PMID:27003006

Effect of moderate static electric field on the growth and metabolism of Chlorella vulgaris.

PubMed

Nezammahalleh, Hassan; Ghanati, Faezeh; Adams, Thomas A; Nosrati, Mohsen; Shojaosadati, Seyed Abbas

2016-10-01

An electric field (EF) generator device was fabricated and applied to the treatment of Chlorella vulgaris ISC33 at three distinct concentrations before cultivation. The EF of moderate intensity (2.7kVcm(-1)) has a hormetic effect on algal growth. The highest growth stimulation of 51% was observed after 50min treatment of 0.4gL(-1) algal suspension. The influence of EF on the system was then studied from both theoretical and experimental perspectives. The growth rate increased with treatment time up to a maximum because of improved membrane permeability, and then declined afterwards due to peroxide accumulation in the medium. The contents of chlorophylls, carotenoids, soluble carbohydrates, lipids, and proteins were also measured to understand possible changes on algal metabolism. The EF treatment of algal suspension has no observable effect on the cell metabolism while both algal growth and metabolism was significantly affected by the inoculum size. Copyright © 2016 Elsevier Ltd. All rights reserved.

Elucidating the Role of Injury-Induced Electric Fields (EFs) in Regulating the Astrocytic Response to Injury in the Mammalian Central Nervous System

PubMed Central

Baer, Matthew L.; Henderson, Scott C.; Colello, Raymond J.

2015-01-01

Injury to the vertebrate central nervous system (CNS) induces astrocytes to change their morphology, to increase their rate of proliferation, and to display directional migration to the injury site, all to facilitate repair. These astrocytic responses to injury occur in a clear temporal sequence and, by their intensity and duration, can have both beneficial and detrimental effects on the repair of damaged CNS tissue. Studies on highly regenerative tissues in non-mammalian vertebrates have demonstrated that the intensity of direct-current extracellular electric fields (EFs) at the injury site, which are 50–100 fold greater than in uninjured tissue, represent a potent signal to drive tissue repair. In contrast, a 10-fold EF increase has been measured in many injured mammalian tissues where limited regeneration occurs. As the astrocytic response to CNS injury is crucial to the reparative outcome, we exposed purified rat cortical astrocytes to EF intensities associated with intact and injured mammalian tissues, as well as to those EF intensities measured in regenerating non-mammalian vertebrate tissues, to determine whether EFs may contribute to the astrocytic injury response. Astrocytes exposed to EF intensities associated with uninjured tissue showed little change in their cellular behavior. However, astrocytes exposed to EF intensities associated with injured tissue showed a dramatic increase in migration and proliferation. At EF intensities associated with regenerating non-mammalian vertebrate tissues, these cellular responses were even more robust and included morphological changes consistent with a regenerative phenotype. These findings suggest that endogenous EFs may be a crucial signal for regulating the astrocytic response to injury and that their manipulation may be a novel target for facilitating CNS repair. PMID:26562295

Maternal executive functioning as a mechanism in the intergenerational transmission of parenting: Preliminary evidence.

PubMed

Bridgett, David J; Kanya, Meghan J; Rutherford, Helena J V; Mayes, Linda C

2017-02-01

Multiple lines of inquiry, including experimental animal models, have recently converged to suggest that executive functioning (EF) may be one mechanism by which parenting behavior is transmitted across generations. In the current investigation, we empirically test this notion by examining relations between maternal EF and parenting behaviors during mother-infant interactions, and by examining the role of maternal EF in the intergenerational transmission of parenting behavior. Mother-infant dyads (N = 150) in a longitudinal study participated. Mothers were administered measures of EF (working memory and inhibition), reported on the parenting they received from their parents (i.e., the infants' maternal grandparents), and were observed interacting with their 8-month-old infants. SEM findings indicated that the negative parenting mothers received from their own parents was significantly related to poorer maternal EF, and that poorer maternal EF was significantly related to subsequent engagement in more negative parenting practices (e.g., intrusiveness, displays of negativity) with their own infant. A significant indirect effect, through maternal EF, was observed between maternal report of her experiences of negative parenting received while growing up and her own use of negative parenting practices. Our findings make two contributions. First, we add to existing work that has primarily considered relations between parent EF and parenting behavior while interacting with older children by showing that maternal EF affects children, via maternal parenting behavior, beginning very early in life. Second, we provide key evidence of the role of EF in the intergenerational transmission of parenting. Additional implications of these findings, as well as important future directions, are discussed. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

The Association between Parenting Behavior and Executive Functioning in Children and Young Adolescents

PubMed Central

Sosic-Vasic, Zrinka; Kröner, Julia; Schneider, Sibylle; Vasic, Nenad; Spitzer, Manfred; Streb, Judith

2017-01-01

Executive functioning (EF) is associated with various aspects of school achievement and cognitive development in children and adolescents. There has been substantial research investigating associations between EF and other factors in young children, such as support processes and parenting, but less research has been conducted about external factors relating to EF in older children and adolescents. Therefore, the present study investigates one possible factor that could correlate with EF in school-age children and adolescents: parenting behavior. The cross-sectional study design gathered data from 169 children in primary schools, middle-schools, and Gymnasien, and their corresponding parents. All children underwent a standardized task to measure EF, the computer-based Erikson Flanker task, which evaluates EF as a function of error rates and response time. A self-report questionnaire was used to assess parenting behavior. Multilevel analysis was implemented to test the effects of parenting behavior on EF in school-age children. The results show significant associations between various parenting behaviors and children's EF: High scores on parental involvement or parental responsibility are associated with low error rates on the Erikson Flanker task, whereas high parental scores on inconsistent discipline are associated with high error rates. These correlations between parenting behavior and EF remained significant despite controlling for child age, maternal education, family income, and baseline performance (i.e., congruent trials on the Erikson Flanker task). No associations were found between parental behavior and reaction time on the Erikson Flanker task. These results indicate the important association between parenting behaviors and EF skills in school-age children, and foster the necessity to inform parents about ways in which they can optimally support their children's cognitive development. PMID:28424644

Distribution and solid-phase speciation of toxic heavy metals of bed sediments of Bharali tributary of Brahmaputra River.

PubMed

Hoque, Raza Rafiqul; Goswami, K G; Kusre, B C; Sarma, K P

2011-06-01

Heavy metal (Fe, Mn, Zn, Cu, Ni, Pb, and Cd) concentrations and their chemical speciations were investigated for the first time in bed sediments of Bharali River, a major tributary of the Brahmaputra River of the Eastern Himalayas. Levels of Fe, Mn, Pb, and Cd in the bed sediments were much below the average Indian rivers; however, Cu and Zn exhibit levels on the higher side. Enrichment factors (EF) of all metals was greater than 1 and a higher trend of EF was seen in the abandoned channel for most metals. Pb showed maximum EF of 32 at site near an urban center. The geoaccumulation indices indicate that Bharali river is moderately polluted. The metals speciations, done by a sequential extraction regime, show that Cd, Cu, and Pb exhibit considerable presence in the exchangeable and carbonate fraction, thereby showing higher mobility and bioavailability. On the other hand, Ni, Mn, and Fe exhibit greater presence in the residual fraction and Zn was dominant in the Fe-Mn oxide phase. Inter-species correlations at three sites did not show similar trends for metal pairs indicating potential variations in the contributing sources.

A structural equation modeling of executive functions, IQ and mathematical skills in primary students: Differential effects on number production, mental calculus and arithmetical problems.

PubMed

Arán Filippetti, Vanessa; Richaud, María Cristina

2017-10-01

Though the relationship between executive functions (EFs) and mathematical skills has been well documented, little is known about how both EFs and IQ differentially support diverse math domains in primary students. Inconsistency of results may be due to the statistical techniques employed, specifically, if the analysis is conducted with observed variables, i.e., regression analysis, or at the latent level, i.e., structural equation modeling (SEM). The current study explores the contribution of both EFs and IQ in mathematics through an SEM approach. A total of 118 8- to 12-year-olds were administered measures of EFs, crystallized (Gc) and fluid (Gf) intelligence, and math abilities (i.e., number production, mental calculus and arithmetical problem-solving). Confirmatory factor analysis (CFA) offered support for the three-factor solution of EFs: (1) working memory (WM), (2) shifting, and (3) inhibition. Regarding the relationship among EFs, IQ and math abilities, the results of the SEM analysis showed that (i) WM and age predict number production and mental calculus, and (ii) shifting and sex predict arithmetical problem-solving. In all of the SEM models, EFs partially or totally mediated the relationship between IQ, age and math achievement. These results suggest that EFs differentially supports math abilities in primary-school children and is a more significant predictor of math achievement than IQ level.

The Potyviral P3 Protein Targets Eukaryotic Elongation Factor 1A to Promote the Unfolded Protein Response and Viral Pathogenesis1[OPEN

PubMed Central

Shine, M.B.; Cui, Xiaoyan; Chen, Xin; Ma, Na; Kachroo, Pradeep; Zhi, Haijan; Kachroo, Aardra

2016-01-01

The biochemical function of the potyviral P3 protein is not known, although it is known to regulate virus replication, movement, and pathogenesis. We show that P3, the putative virulence determinant of soybean mosaic virus (SMV), targets a component of the translation elongation complex in soybean. Eukaryotic elongation factor 1A (eEF1A), a well-known host factor in viral pathogenesis, is essential for SMV virulence and the associated unfolded protein response (UPR). Silencing GmEF1A inhibits accumulation of SMV and another ER-associated virus in soybean. Conversely, endoplasmic reticulum (ER) stress-inducing chemicals promote SMV accumulation in wild-type, but not GmEF1A-knockdown, plants. Knockdown of genes encoding the eEF1B isoform, which is important for eEF1A function in translation elongation, has similar effects on UPR and SMV resistance, suggesting a link to translation elongation. P3 and GmEF1A promote each other’s nuclear localization, similar to the nuclear-cytoplasmic transport of eEF1A by the Human immunodeficiency virus 1 Nef protein. Our results suggest that P3 targets host elongation factors resulting in UPR, which in turn facilitates SMV replication and place eEF1A upstream of BiP in the ER stress response during pathogen infection. PMID:27356973

Two programmed cell death systems in Escherichia coli: an apoptotic-like death is inhibited by the mazEF-mediated death pathway.

PubMed

Erental, Ariel; Sharon, Idith; Engelberg-Kulka, Hanna

2012-01-01

In eukaryotes, the classical form of programmed cell death (PCD) is apoptosis, which has as its specific characteristics DNA fragmentation and membrane depolarization. In Escherichia coli a different PCD system has been reported. It is mediated by the toxin-antitoxin system module mazEF. The E. coli mazEF module is one of the most thoroughly studied toxin-antitoxin systems. mazF encodes a stable toxin, MazF, and mazE encodes a labile antitoxin, MazE, which prevents the lethal effect of MazF. mazEF-mediated cell death is a population phenomenon requiring the quorum-sensing pentapeptide NNWNN designated Extracellular Death Factor (EDF). mazEF is triggered by several stressful conditions, including severe damage to the DNA. Here, using confocal microscopy and FACS analysis, we show that under conditions of severe DNA damage, the triggered mazEF-mediated cell death pathway leads to the inhibition of a second cell death pathway. The latter is an apoptotic-like death (ALD); ALD is mediated by recA and lexA. The mazEF-mediated pathway reduces recA mRNA levels. Based on these results, we offer a molecular model for the maintenance of an altruistic characteristic in cell populations. In our model, the ALD pathway is inhibited by the altruistic EDF-mazEF-mediated death pathway.

Traffic emission factors of ultrafine particles: effects from ambient air.

PubMed

Janhäll, Sara; Molnar, Peter; Hallquist, Mattias

2012-09-01

Ultrafine particles have a significant detrimental effect on both human health and climate. In order to abate this problem, it is necessary to identify the sources of ultrafine particles. A parameterisation method is presented for estimating the levels of traffic-emitted ultrafine particles in terms of variables describing the ambient conditions. The method is versatile and could easily be applied to similar datasets in other environments. The data used were collected during a four-week period in February 2005, in Gothenburg, as part of the Göte-2005 campaign. The specific variables tested were temperature (T), relative humidity (RH), carbon monoxide concentration (CO), and the concentration of particles up to 10 μm diameter (PM(10)); all indicators are of importance for aerosol processes such as coagulation and gas-particle partitioning. These variables were selected because of their direct effect on aerosol processes (T and RH) or as proxies for aerosol surface area (CO and PM(10)) and because of their availability in local monitoring programmes, increasing the usability of the parameterization. Emission factors are presented for 10-100 nm particles (ultrafine particles; EF(ufp)), for 10-40 nm particles (EF(10-40)), and for 40-100 nm particles (EF(40-100)). For EF(40-100) no effect of ambient conditions was found. The emission factor equations are calculated based on an emission factor for NO(x) of 1 g km(-1), thus the particle emission factors are easily expressed in units of particles per gram of NO(x) emitted. For 10-100 nm particles the emission factor is EF(ufp) = 1.8 × 10(15) × (1 - 0.095 × CO - 3.2 × 10(-3) × T) particles km(-1). Alternative equations for the EFs in terms of T and PM(10) concentration are also presented.

Meta-analysis of the effects of microclimate cooling systems on human performance under thermal stressful environments: potential applications to occupational workers.

PubMed

Chan, Albert P C; Song, Wenfang; Yang, Yang

2015-01-01

This study aims to determine the appropriate microclimate cooling systems (MCSs) to reduce heat stress and improve human performance of occupational workers and their practicality in the occupational field. Meta-analysis was employed to summarize, analyze, and compare the effects of various MCSs on human performance with corresponding physiological and psychological responses, thereby providing solid suggestions for selecting suitable MCSs for occupational workers. Wearing MCSs significantly attenuated the increases in core temperature (-0.34 °C/h) and sweating rate (-0.30 L/h), and significantly improved human performance (+29.9%, effect size [EFS] = 1.1) compared with no cooling condition (CON). Cold air-cooled garments (ACG-Cs; +106.2%, EFS = 2.32) exhibited greater effects on improving human performance among various microclimate cooling garments (MCGs), followed by liquid cooling garments (LCGs; +68.1%, EFS = 1.86) and hybrid cooling garment combining air and liquid cooling (HBCG-AL; +59.1%, EFS=3.38), natural air-cooled garments (ACG-Ns; +39.9%, EFS = 1.12), and phase change material cooling garments (PCMCGs; +19.5%, EFS = 1.2). Performance improvement was observed to be positively and linearly correlated to the differences of core temperature increase rate (r = 0.65, p < 0.01) and sweating rate (r = 0.80, p < 0.001) between MCSs and CON. Considering their application in industrial settings, ACG-Cs, LCGs, and HBCG-AL are practical for work, in which workers do not move frequently, whereas ACG-Ns and PCMCGs are more applicable for the majority of occupational workers. Further enhancement of the cooling efficiency of these two cooling strategies should be initiated. Copyright © 2015 Elsevier Ltd. All rights reserved.

Dissolved effluent organic matter: Characteristics and potential implications in wastewater treatment and reuse applications.

PubMed

Michael-Kordatou, I; Michael, C; Duan, X; He, X; Dionysiou, D D; Mills, M A; Fatta-Kassinos, D

2015-06-15

Wastewater reuse is currently considered globally as the most critical element of sustainable water management. The dissolved effluent organic matter (dEfOM) present in biologically treated urban wastewater, consists of a heterogeneous mixture of refractory organic compounds with diverse structures and varying origin, including dissolved natural organic matter, soluble microbial products, endocrine disrupting compounds, pharmaceuticals and personal care products residues, disinfection by-products, metabolites/transformation products and others, which can reach the aquatic environment through discharge and reuse applications. dEfOM constitutes the major fraction of the effluent organic matter (EfOM) and due to its chemical complexity, it is necessary to utilize a battery of complementary techniques to adequately describe its structural and functional character. dEfOM has been shown to exhibit contrasting effects towards various aquatic organisms. It decreases metal uptake, thus potentially reducing their bioavailability to exposed organisms. On the other hand, dEfOM can be adsorbed on cell membranes inducing toxic effects. This review paper evaluates the performance of various advanced treatment processes (i.e., membrane filtration and separation processes, activated carbon adsorption, ion-exchange resin process, and advanced chemical oxidation processes) in removing dEfOM from wastewater effluents. In general, the literature findings reveal that dEfOM removal by advanced treatment processes depends on the type and the amount of organic compounds present in the aqueous matrix, as well as the operational parameters and the removal mechanisms taking place during the application of each treatment technology. Copyright © 2015 Elsevier Ltd. All rights reserved.

Structural basis for the binding of didemnins to human elongation factor eEF1A and rationale for the potent antitumor activity of these marine natural products.

PubMed

Marco, Esther; Martín-Santamaría, Sonsoles; Cuevas, Carmen; Gago, Federico

2004-08-26

Didemnins and tamandarins are closely related marine natural products with potent inhibitory effects on protein synthesis and cell viability. On the basis of available biochemical and structural evidence and results from molecular dynamics simulations, a model is proposed that accounts for the strong and selective binding of these compounds to human elongation factor eEF1A in the presence of GTP. We suggest that the p-methoxyphenyl ring of these cyclic depsipeptides is inserted into the same pocket in eEF1A that normally lodges either the 3' terminal adenine of aminoacylated tRNA, as inferred from two prokaryotic EF-Tu.GTP.tRNA complexes, or the aromatic side chain of Phe/Tyr-163 from the nucleotide exchange factor eEF1Balpha, as observed in several X-ray crystal structures of a yeast eEF1A:eEF1Balpha complex. This pocket, which has a strong hydrophobic character, is formed by two protruding loops on the surface of eEF1A domain 2. Further stabilization of the bound depsipeptide is brought about by additional crucial interactions involving eEF1A domain 1 in such a way that the molecule fits snugly at the interface between these two domains. In the GDP-bound form of eEF1A, this binding site exists only as two separate halves, which accounts for the much greater affinity of didemnins for the GTP-bound form of this elongation factor. This binding mode is entirely different from those seen in the complexes of the homologous prokaryotic EF-Tu with kirromycin-type antibiotics or the cyclic thiazolyl peptide antibiotic GE2270A. Interestingly, the set of interactions used by didemnins to bind to eEF1A is also distinct from that used by eEF1Balpha or eEF1Bbeta, thus establishing a competition for binding to a common site that goes beyond simple molecular mimicry. The model presented here is consistent with both available biochemical evidence and known structure-activity relationships for these two classes of natural compounds and synthetic analogues and provides fertile ground for future research.

Cardiac diastolic and autonomic dysfunction are aggravated by central chemoreflex activation in heart failure with preserved ejection fraction rats

PubMed Central

Toledo, Camilo; Andrade, David C.; Lucero, Claudia; Arce‐Alvarez, Alexis; Díaz, Hugo S.; Aliaga, Valentín; Schultz, Harold D.; Marcus, Noah J.; Manríquez, Mónica; Faúndez, Marcelo

2017-01-01

Key points Heart failure with preserved ejection fraction (HFpEF) is associated with disordered breathing patterns, and sympatho‐vagal imbalance.Although it is well accepted that altered peripheral chemoreflex control plays a role in the progression of heart failure with reduced ejection fraction (HFrEF), the pathophysiological mechanisms underlying deterioration of cardiac function in HFpEF are poorly understood.We found that central chemoreflex is enhanced in HFpEF and neuronal activation is increased in pre‐sympathetic regions of the brainstem.Our data showed that activation of the central chemoreflex pathway in HFpEF exacerbates diastolic dysfunction, worsens sympatho‐vagal imbalance and markedly increases the incidence of cardiac arrhythmias in rats with HFpEF. Abstract Heart failure (HF) patients with preserved ejection fraction (HFpEF) display irregular breathing, sympatho‐vagal imbalance, arrhythmias and diastolic dysfunction. It has been shown that tonic activation of the central and peripheral chemoreflex pathway plays a pivotal role in the pathophysiology of HF with reduced ejection fraction. In contrast, no studies to date have addressed chemoreflex function or its effect on cardiac function in HFpEF. Therefore, we tested whether peripheral and central chemoreflexes are hyperactive in HFpEF and if chemoreflex activation exacerbates cardiac dysfunction and autonomic imbalance. Sprague‐Dawley rats (n = 32) were subjected to sham or volume overload to induce HFpEF. Resting breathing variability, chemoreflex gain, cardiac function and sympatho‐vagal balance, and arrhythmia incidence were studied. HFpEF rats displayed [mean ± SD; chronic heart failure (CHF) vs. Sham, respectively] a marked increase in the incidence of apnoeas/hypopnoeas (20.2 ± 4.0 vs. 9.7 ± 2.6 events h−1), autonomic imbalance [0.6 ± 0.2 vs. 0.2 ± 0.1 low/high frequency heart rate variability (LF/HFHRV)] and cardiac arrhythmias (196.0 ± 239.9 vs. 19.8 ± 21.7 events h−1). Furthermore, HFpEF rats showed increase central chemoreflex sensitivity but not peripheral chemosensitivity. Accordingly, hypercapnic stimulation in HFpEF rats exacerbated increases in sympathetic outflow to the heart (229.6 ± 43.2% vs. 296.0 ± 43.9% LF/HFHRV, normoxia vs. hypercapnia, respectively), incidence of cardiac arrhythmias (196.0 ± 239.9 vs. 576.7 ± 472.9 events h−1) and diastolic dysfunction (0.008 ± 0.004 vs. 0.027 ± 0.027 mmHg μl−1). Importantly, the cardiovascular consequences of central chemoreflex activation were related to sympathoexcitation since these effects were abolished by propranolol. The present results show that the central chemoreflex is enhanced in HFpEF and that acute activation of central chemoreceptors leads to increases of cardiac sympathetic outflow, cardiac arrhythmogenesis and impairment in cardiac function in rats with HFpEF. PMID:28181258

Children's executive function and high-calorie, low-nutrient food intake: mediating effects of child-perceived adult fast food intake.

PubMed

Tate, Eleanor B; Unger, Jennifer B; Chou, Chih-Ping; Spruijt-Metz, Donna; Pentz, Mary Ann; Riggs, Nathaniel R

2015-04-01

This study tested the relationships among child executive function (EF), child-perceived parent fast food intake, and child self-reported subsequent consumption of high-calorie, low-nutrient (HCLN) food. One year and 6-month longitudinal observation from a larger randomized controlled trial. Southern California elementary schools. Fourth- and fifth-grade children (N = 1,005) participating in the Pathways to Health obesity prevention program. Child EF problems were associated with higher concurrent HCLN intake (B = 0.29, SE = 0.10, p < .001) and had a significant indirect effect through higher perceived frequency of parent fast food intake (indirect effect = 0.17, 95% confidence interval [CI] = [0.11, 0.25], p < .001). Longitudinally, child EF problems did not significantly predict higher HCLN intake a year and a half later (B = 0.01, SE = 0.10, p = .92, n = 848) but did have a significant indirect effect through higher perceived parent fast food intake (indirect effect = 0.05, 95% CI = [0.02, 0.10], p < .001). Children's EF difficulties may increase their perception of parent concurrent fast food intake, contributing to their own unhealthy food intake. However, EF problems may not directly affect HCLN intake across time, except when problems are associated with child perception of more frequent parent consumption of convenience foods. Future research is needed to investigate the possibility that helping children perceive and understand role models' convenience food consumption may improve child dietary consumption patterns. © 2014 Society for Public Health Education.

Suppression of Peripheral Sympathetic Activity Underlies Protease-Activated Receptor 2-Mediated Hypotension

PubMed Central

Kim, Young-Hwan; Ahn, Duck-Sun; Joeng, Ji-Hyun

2014-01-01

Protease-activated receptor (PAR)-2 is expressed in endothelial cells and vascular smooth muscle cells. It plays a crucial role in regulating blood pressure via the modulation of peripheral vascular tone. Although some reports have suggested involvement of a neurogenic mechanism in PAR-2-induced hypotension, the accurate mechanism remains to be elucidated. To examine this possibility, we investigated the effect of PAR-2 activation on smooth muscle contraction evoked by electrical field stimulation (EFS) in the superior mesenteric artery. In the present study, PAR-2 agonists suppressed neurogenic contractions evoked by EFS in endothelium-denuded superior mesenteric arterial strips but did not affect contraction elicited by the external application of noradrenaline (NA). However, thrombin, a potent PAR-1 agonist, had no effect on EFS-evoked contraction. Additionally, ω-conotoxin GVIA (CgTx), a selective N-type Ca2+ channel (ICa-N) blocker, significantly inhibited EFS-evoked contraction, and this blockade almost completely occluded the suppression of EFS-evoked contraction by PAR-2 agonists. Finally, PAR-2 agonists suppressed the EFS-evoked overflow of NA in endothelium-denuded rat superior mesenteric arterial strips and this suppression was nearly completely occluded by ω-CgTx. These results suggest that activation of PAR-2 may suppress peripheral sympathetic outflow by modulating activity of ICa-N which are located in peripheral sympathetic nerve terminals, which results in PAR-2-induced hypotension. PMID:25598663

Influence of anisotropic conductivity in the skull and white matter on transcranial direct current stimulation via an anatomically realistic finite element head model

NASA Astrophysics Data System (ADS)

Suh, Hyun Sang; Lee, Won Hee; Kim, Tae-Seong

2012-11-01

To establish safe and efficient transcranial direct current stimulation (tDCS), it is of particular importance to understand the electrical effects of tDCS in the brain. Since the current density (CD) and electric field (EF) in the brain generated by tDCS depend on various factors including complex head geometries and electrical tissue properties, in this work, we investigated the influence of anisotropic conductivity in the skull and white matter (WM) on tDCS via a 3D anatomically realistic finite element head model. We systematically incorporated various anisotropic conductivity ratios into the skull and WM. The effects of anisotropic tissue conductivity on the CD and EF were subsequently assessed through comparisons to the conventional isotropic solutions. Our results show that the anisotropic skull conductivity significantly affects the CD and EF distribution: there is a significant reduction in the ratio of the target versus non-target total CD and EF on the order of 12-14%. In contrast, the WM anisotropy does not significantly influence the CD and EF on the targeted cortical surface, only on the order of 1-3%. However, the WM anisotropy highly alters the spatial distribution of both the CD and EF inside the brain. This study shows that it is critical to incorporate anisotropic conductivities in planning of tDCS for improved efficacy and safety.

Isolation and properties of the subunit form EF-1C of elongation factor 1 from Guerin epithelioma cells.

PubMed

Marcinkiewicz, C; Gałasiński, W

1993-01-01

EF-1C is a component of the aggregate EF-1B, consisting of the subunit forms EF-1A.EF-1C; it was isolated by dissociation of this aggregate in the presence of GTP. The subunit form EF-1C stimulates binding of aminoacyl-tRNA to ribosomes, catalysed by EF-1A, similarly as EF-1 beta gamma which stimulates the activity of EF-1 in other eukaryotic cells. EF-1C in the presence of 6 M urea was separated into two polypeptides. Polypeptide of molecular mass 32,000 Da is responsible for regeneration of the EF-1A.GTP active complex. Thermal sensitivity of EF-1A was much higher than that of EF-1B, thus a protective role of EF-1C in the EF-1A.EF-1C complex is suggested.

Effects of electrical field on hatchability performance of eggs from a layer-type breeder.

PubMed

Shafey, T M; Al-Batshan, H A; Ghannam, M M

2007-04-01

1. Eggs from a layer-type breeder flock (Baladi, King Saud University) between 50 and 63 weeks of age were used in three trials to study the effects of electrical field (EF) during incubation on albumen and yolk heights, incubation temperature, egg weight loss and hatchability traits. The effects of egg size and eggshell characteristics on hatchability traits of eggs incubated under EF were investigated. 2. Eggs were weighed and graded into three weight classes (small, medium, and large). The physical dimensions, eggshell characteristics, and conductance of eggs were examined. The incubator was divided into two compartments for the control and EF treatments. Two aluminium plates were fitted on the inside walls of the EF compartment, face to face, and connected to a step up electric transformer. Eggs were exposed constantly to the EF during the first 18 d of incubation at the level of 30 kV/m, 60 Hz. 3. Egg size influenced the physical dimensions and eggshell characteristics of eggs. Large eggs had higher egg weight, egg surface area, egg volume, eggshell conductance, and eggshell weight and lower yolk weight percentage than medium or small size eggs. Small eggs had lower egg length and higher egg density than large or medium size eggs. Large eggs had higher eggshell thickness than small size eggs. 4. EF incubation of eggs raised incubation temperature by 0.06 degrees C, and increased the percentage of egg weight loss, hatchability, and weight of hatching chicks and reduced the early embryo deaths, and length of incubation by approximately 9.8, 19.6, 1.7, 62.1 and 2.1%, respectively. 5. There was no significant difference between the two incubation treatments in the heights of albumen and yolk of incubated eggs, percentages of late embryo deaths, and pips with live and dead embryos. Hatchability traits were not significantly influenced by egg size. 6. It was concluded that EF incubation of eggs increased hatchability, chick-hatching weight, and reduced the length of incubation of Baladi eggs. Differences in the physical dimensions and eggshell characteristics of eggs did not influence hatchability traits of eggs under EF incubation.

An activated carbon fiber cathode for the degradation of glyphosate in aqueous solutions by the Electro-Fenton mode: Optimal operational conditions and the deposition of iron on cathode on electrode reusability.

PubMed

Lan, Huachun; He, Wenjing; Wang, Aimin; Liu, Ruiping; Liu, Huijuan; Qu, Jiuhui; Huang, C P

2016-11-15

An activated carbon fiber (ACF) cathode was fabricated and used to treat glyphosate containing wastewater by the Electro-Fenton (EF) process. The results showed that glyphosate was rapidly and efficiently degraded and the BOD 5 /COD ratio was increased to >0.3 implying the feasibility of subsequent treatment of the treated wastewater by biological methods. The results of ion chromatography and HPLC measurements indicated that glyphosate was completely decomposed. Effective OH generation and rapid recycling/recovery of the Fe 2+ ions at the cathode were responsible primarily for the high performance of the ACF-EF process. Factors such as inlet oxygen gas flow rate, Fe 2+ dosage, initial glyphosate concentration, applied current intensity, and solution pH that may affect the efficiency of the ACF-EF process were further studied and the optimum operation condition was established. Results of SEM/EDX, BET and XPS analysis showed the deposition of highly dispersed fine Fe 2 O 3 particles on the ACF surface during the EF reaction. The possibility of using the Fe 2 O 3 -ACF as iron source in the EF process was assessed. Results showed that the Fe 2 O 3 -ACF electrode was effective in degrading glyphosate in the EF process. The deposition of Fe 2 O 3 particles on the ACF electrode had no adverse effect on the reusability of the ACF cathode. Copyright © 2016. Published by Elsevier Ltd.

Spatial Control of Photoacid Diffusion in Chemically Amplified Resist (CAR) via External Electric Field.

PubMed

Kim, Jinok; Yoo, Gwangwe; Park, Jin; Park, Jin-Hong

2018-09-01

We investigated the effect of an electric field-based post exposure bake (EF-PEB) process on photoacid diffusion and pattern formation. To investigate the control of photoacid diffusion experimentally, the EF-PEB processes was performed at various temperatures. Cross sectional images of various EF-PEB processed samples were obtained by scanning electron microscopy (SEM) after ion beam milling. In addition, we conducted a numerical analysis of photoacid distribution and diffusion with following Fick's second law and compared the experimental results with our theoretical model. The drift distance was theoretically predicted by multiplying drift velocity and EF-PEB time, and the experimental values were obtained by finding the difference in pattern depths of PEB/EFPEB samples. Finally, an EF-PEB temperature of 85 °C was confirmed as the optimum condition to maximize photoacid drift distance using the electric field.

A Feline HFpEF Model with Pulmonary Hypertension and Compromised Pulmonary Function.

PubMed

Wallner, Markus; Eaton, Deborah M; Berretta, Remus M; Borghetti, Giulia; Wu, Jichuan; Baker, Sandy T; Feldsott, Eric A; Sharp, Thomas E; Mohsin, Sadia; Oyama, Mark A; von Lewinski, Dirk; Post, Heiner; Wolfson, Marla R; Houser, Steven R

2017-11-29

Heart Failure with preserved Ejection Fraction (HFpEF) represents a major public health problem. The causative mechanisms are multifactorial and there are no effective treatments for HFpEF, partially attributable to the lack of well-established HFpEF animal models. We established a feline HFpEF model induced by slow-progressive pressure overload. Male domestic short hair cats (n = 20), underwent either sham procedures (n = 8) or aortic constriction (n = 12) with a customized pre-shaped band. Pulmonary function, gas exchange, and invasive hemodynamics were measured at 4-months post-banding. In banded cats, echocardiography at 4-months revealed concentric left ventricular (LV) hypertrophy, left atrial (LA) enlargement and dysfunction, and LV diastolic dysfunction with preserved systolic function, which subsequently led to elevated LV end-diastolic pressures and pulmonary hypertension. Furthermore, LV diastolic dysfunction was associated with increased LV fibrosis, cardiomyocyte hypertrophy, elevated NT-proBNP plasma levels, fluid and protein loss in pulmonary interstitium, impaired lung expansion, and alveolar-capillary membrane thickening. We report for the first time in HFpEF perivascular fluid cuff formation around extra-alveolar vessels with decreased respiratory compliance. Ultimately, these cardiopulmonary abnormalities resulted in impaired oxygenation. Our findings support the idea that this model can be used for testing novel therapeutic strategies to treat the ever growing HFpEF population.

Beyond Strength: Participant Perspectives on the Benefits of an Older Adult Exercise Program.

PubMed

Kohn, Marlana; Belza, Basia; Petrescu-Prahova, Miruna; Miyawaki, Christina E

2016-06-01

This study examines the expected and experienced benefits among participants in Enhance®Fitness (EF), an evidence-based group physical activity program for older adults. We also describe the implications for program dissemination (reach, implementation, and maintenance) within the RE-AIM (reach, effectiveness, adoption, implementation, and maintenance) framework. Twenty semistructured interviews were conducted with EF participants enrolled from 2005 to 2012. Interviews were digitally recorded, professionally transcribed, and analyzed using a deductive approach. Participants were motivated to join EF for expected physical benefits and the social environment of a group-based class. Actualized benefits of participation included physical, social, functional, and improved self-image/sense of well-being. Participants valued the practical application of class exercises to daily activities that support independent living, such as lifting objects and completing household chores. Organizations looking to implement EF or improve existing EF classes can improve program reach, implementation, and maintenance by incorporating participants' expressed motivations and valued benefits in program marketing and by improving organizational support to meet participant needs. EF class instructors can tailor their classes to engage participants based on their motivations. Understanding participants' motivations and valued benefits can improve EF dissemination by meeting participant needs with tailored class offerings and organizational needs informed by participant insights that aid program sustainability. © 2015 Society for Public Health Education.

COMMUNICATING THE PARAMETER UNCERTAINTY IN THE IQWIG EFFICIENCY FRONTIER TO DECISION-MAKERS

PubMed Central

Stollenwerk, Björn; Lhachimi, Stefan K; Briggs, Andrew; Fenwick, Elisabeth; Caro, Jaime J; Siebert, Uwe; Danner, Marion; Gerber-Grote, Andreas

2015-01-01

The Institute for Quality and Efficiency in Health Care (IQWiG) developed—in a consultation process with an international expert panel—the efficiency frontier (EF) approach to satisfy a range of legal requirements for economic evaluation in Germany's statutory health insurance system. The EF approach is distinctly different from other health economic approaches. Here, we evaluate established tools for assessing and communicating parameter uncertainty in terms of their applicability to the EF approach. Among these are tools that perform the following: (i) graphically display overall uncertainty within the IQWiG EF (scatter plots, confidence bands, and contour plots) and (ii) communicate the uncertainty around the reimbursable price. We found that, within the EF approach, most established plots were not always easy to interpret. Hence, we propose the use of price reimbursement acceptability curves—a modification of the well-known cost-effectiveness acceptability curves. Furthermore, it emerges that the net monetary benefit allows an intuitive interpretation of parameter uncertainty within the EF approach. This research closes a gap for handling uncertainty in the economic evaluation approach of the IQWiG methods when using the EF. However, the precise consequences of uncertainty when determining prices are yet to be defined. © 2014 The Authors. Health Economics published by John Wiley & Sons Ltd. PMID:24590819

Executive function depletion in children and its impact on theory of mind.

PubMed

Powell, Lindsey J; Carey, Susan

2017-07-01

The current studies provide an experimental, rather than correlational, method for testing hypotheses about the role of executive function (EF) in conceptual development. Previous research has established that adults' tendency to deploy EF can be temporarily diminished by use. Exercising self-control in one context decreases adults' performance on other EF demanding tasks immediately thereafter. Using two different depletion methods, Experiments 1 and 3 extend this finding to preschool-aged children. Experiments 2 and 4 make use of these EF depletion methods to elucidate the role of EF in children's theory of mind reasoning. Experiment 2 shows that EF depletion affects 5-year-olds' ability to predict another's behavior on the basis of that person's false belief, and Experiment 4 shows that this negative effect of depletion extends to 4- and 5-year-olds' ability to explain others' behavior on the basis of their false beliefs. These findings provide direct evidence that EF is required for the expression of an understanding of others' false beliefs across a variety of task demands, even in children who clearly have the capacity to construct such representations. We suggest ways in which depletion may be used as a tool for further investigating the role of executive function in cognitive development. Copyright © 2017. Published by Elsevier B.V.

Arbuscular mycorrhizal fungus inoculation reduces the drought-resistance advantage of endophyte-infected versus endophyte-free Leymus chinensis.

PubMed

Liu, Hui; Chen, Wei; Wu, Man; Wu, Rihan; Zhou, Yong; Gao, Yubao; Ren, Anzhi

2017-11-01

Grasses can be infected simultaneously by endophytic fungi and arbuscular mycorrhizal (AM) fungi. In this study, we tested the hypothesis that endophyte-associated drought resistance of a native grass was affected by an AM fungus. In a greenhouse experiment, we compared the performance of endophyte-infected (EI) and endophyte-free (EF) Leymus chinensis, a dominant species native to the Inner Mongolia steppe, under altered water and AM fungus availability. The results showed that endophyte infection significantly increased drought resistance of the host grass, but the beneficial effects were reduced by AM fungus inoculation. In the mycorrhizal-non-inoculated (MF) treatment, EI plants accumulated significantly more biomass, had greater proline and total phenolic concentration, and lower malondialdehyde concentration than EF plants. In the mycorrhizal-inoculation (MI) treatment, however, no significant difference occurred in either growth or physiological characters measured between EI and EF plants. AM fungus inoculation enhanced drought resistance of EF plants but had no significant effect on drought resistance of EI plants, thus AM fungus inoculation reduced the difference between EI and EF plants. Our findings highlight the importance of interactions among multiple microorganisms for plant performance under drought stress.

Inhibitory effects of botulinum toxin on pyloric and antral smooth muscle.

PubMed

James, Arlene N; Ryan, James P; Parkman, Henry P

2003-08-01

Botulinum toxin injection into the pylorus is reported to improve gastric emptying in gastroparesis. Classically, botulinum toxin inhibits ACh release from cholinergic nerves in skeletal muscle. The aim of this study was to determine the effects of botulinum toxin on pyloric smooth muscle. Guinea pig pyloric muscle strips were studied in vitro. Botulinum toxin type A was added; electric field stimulation (EFS) was performed every 30 min for 6 h. ACh (100 microM)-induced contractile responses were determined before and after 6 h. Botulinum toxin caused a concentration-dependent decrease of pyloric contractions to EFS. At a low concentration (2 U/ml), botulinum toxin decreased pyloric contractions to EFS by 43 +/- 9% without affecting ACh-induced contractions. At higher concentrations (10 U/ml), botulinum toxin decreased pyloric contraction to EFS by 75 +/- 7% and decreased ACh-induced contraction by 79 +/- 9%. In conclusion, botulinum toxin inhibits pyloric smooth muscle contractility. At a low concentration, botulinum toxin decreases EFS-induced contractile responses without affecting ACh-induced contractions suggesting inhibition of ACh release from cholinergic nerves. At higher concentrations, botulinum toxin directly inhibits smooth muscle contractility as evidenced by the decreased contractile response to ACh.

The real factor for polypeptide elongation in Dictyostelium cells is EF-2B, not EF-2A

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yoshino, Tomoko; Maeda, Yasuo; Amagai, Aiko

2007-08-03

Polypeptide elongation factor 2 (EF-2) plays an essential role in protein synthesis and is believed to be indispensable for cell proliferation. Recently, it has been demonstrated that there are two kinds of EF-2 (EF-2A and EF-2B with 76.6% of sequence identity at the amino acid level) in Dictyostelium discoideum. Although the knockout of EF-2A slightly impaired cytokinesis, EF-2A null cells exhibited almost normal protein synthesis and cell growth, suggesting that there is another molecule capable of compensating for EF-2 function. Since EF-2B is the most likely candidate, we examined its function using ef-2b knockdown cells prepared by the RNAi method.more » Our results strongly suggest that EF-2B is required for protein synthesis and cell proliferation, functioning as the real EF-2. Interestingly, the expressions of ef-2a and ef-2b mRNAs during development are reversely regulated, and the ef-2b expression is greatly augmented in ef-2a null cells.« less

Novel synthetic curcumin analogs as potent antiangiogenic agents in colorectal cancer.

PubMed

Rajitha, Balney; Nagaraju, Ganji Purnachandra; Shaib, Walid L; Alese, Olatunji B; Snyder, James P; Shoji, Mamoru; Pattnaik, Subasini; Alam, Afroz; El-Rayes, Bassel F

2017-01-01

The transcription factor NF-κB plays a central role in angiogenesis in colorectal cancer (CRC). Curcumin is a natural dietary product that inhibits NF-κB. The objective of this study is to evaluate the antiangiogenic effects of curcumin and two potent synthetic analogues (EF31 and UBS109) in CRC. IC 50 values for curcumin, EF31, and UBS109 were determined in the HCT116 and HT-29 cell lines. HUVEC tube formation, egg CAM assay, and matrigel plug assays revealed decreased angiogenesis in cell lines treated with curcumin, EF31, or UBS109. Curcumin and its analogues significantly inhibited VEGF-A synthesis and secretion in both cell lines in association with loss of HIF-1α, COX-2, and p-STAT-3 expression. Nuclear NF-κB expression was inhibited by curcumin, EF31, and UBS109. Transfection of p65-NF-κB in HCT116 and HT-29 cells resulted in increased expression of HIF-1α, COX-2, STAT-3, and VEGF-A. Treatment with curcumin, EF31, or UBS109 inhibited these effects in transfected cell lines. In mice carrying HCT116 and HT-29 cell xenografts, EF31 and UBS109 inhibited subcutaneous tumor growth and potentiated the effects of oxaliplatin and 5-FU. Tumors from treated animals revealed inhibition of HIF-1α, COX-2, p-STAT-3, and VEGF expression. Our findings suggest that inhibition of NF-κB leading to decreased transcription and expression of HIF-1α, COX-2, STAT-3, and VEGF is a rational approach for antiangiogenic therapy in CRC. The distinctive properties of EF31 and UBS109 make them promising therapeutic agents for development in CRC as single agents or as part of combination chemotherapy regimens. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Residual Effects of Fertilization History Increase Nitrous Oxide Emissions from Zero-N Controls: Implications for Estimating Fertilizer-Induced Emission Factors.

PubMed

LaHue, Gabriel T; van Kessel, Chris; Linquist, Bruce A; Adviento-Borbe, Maria Arlene; Fonte, Steven J

2016-09-01

Agricultural N fertilization is the dominant driver of increasing atmospheric nitrous oxide (NO) concentrations over the past half-century, yet there is considerable uncertainty in estimates of NO emissions from agriculture. Such estimates are typically based on the amount of N applied and a fertilizer-induced emission factor (EF), which is calculated as the difference in emissions between a fertilized plot and a zero-N control plot divided by the amount of N applied. A fertilizer-induced EF of 1% is currently recognized by the Intergovernmental Panel on Climate Change (IPCC) based on several studies analyzing published field measurements of NO emissions. Although many zero-N control plots used in these measurements received historical N applications, the potential for a residual impact of these inputs on NO emissions has been largely ignored and remains poorly understood. To address this issue, we compared NO emissions under laboratory conditions from soils sampled within zero-N control plots that had historically received N inputs versus soils from plots that had no N inputs for 20 yr. Historical N fertilization of zero-N control plots increased initial NO emissions by roughly one order of magnitude on average relative to historically unfertilized control plots. Higher NO emissions were positively correlated with extractable N and potentially mineralizable N. This finding suggests that accounting for fertilization history may help reduce the uncertainty associated with the IPCC fertilizer-induced EF and more accurately estimate the contribution of fertilizer N to agricultural NO emissions, although further research to demonstrate this relationship in the field is needed. Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.

Aerosol Optical Properties and Trace Gas Emissions From Laboratory-Simulated Western US Wildfires

NASA Astrophysics Data System (ADS)

Selimovic, V.; Yokelson, R. J.; Warneke, C.; Roberts, J. M.; De Gouw, J. A.; Reardon, J.; Griffith, D. W. T.

2017-12-01

Western wildfires have a major impact on air quality in the US. In the fall of 2016, 107 fires were burned in the large-scale combustion facility at the US Forest Service Missoula Fire Sciences Laboratory as part of the Fire Influence on Regional and Global Environments Experiment (FIREX). Canopy, litter, duff, dead wood, and other fuels from various widespread coniferous and chaparral ecosystems were burned in combinations to represent relevant configurations in the field and as pure components to investigate the effects of individual fuels. The smoke emissions were characterized by a large suite of state-of-the-art instruments. In this study we report emission factor (EF, g compound emitted per kg fuel burned) measurements in fresh smoke of a diverse suite of critically-important trace gases measured by open-path Fourier transform infrared spectroscopy (OP-FTIR). We also report aerosol optical properties (absorption EF, single scattering albedo (SSA) and Ångström absorption exponent (AAE)) as well as black carbon (BC) EF measured by photoacoustic extinctiometers (PAX) at 870 and 401 nm. A careful comparison with available field measurements of wildfires confirms that representative data can be extracted from the lab fire data. The OP-FTIR data show that ammonia (1.65 g kg-1), acetic acid (2.44 g kg-1), and other trace gases are significant emissions not previously measured for US wildfires. The PAX measurements show that brown carbon (BrC) absorption is most dominant for combustion of duff (AAE 7.13) and rotten wood (AAE 4.60): fuels that are consumed in greater amounts during wildfires than prescribed fires. We confirm that about 86% of the aerosol absorption at 401 nm in typical fresh wildfire smoke is due to BrC.

Higher Eating Frequency Does Not Decrease Appetite in Healthy Adults12

PubMed Central

Perrigue, Martine M; Drewnowski, Adam; Wang, Ching-Yun; Neuhouser, Marian L

2016-01-01

Background: Consumption of small, frequent meals is suggested as an effective approach to control appetite and food intake and might be a strategy for weight loss or healthy weight maintenance. Despite much speculation on the topic, scientific evidence is limited to support such a relation in the absence of changes to diet composition. Objective: We examined the effects of high compared with low eating frequency (EF) on self-reported appetite as a secondary outcome in a controlled trial. Methods: We conducted a randomized, crossover intervention trial in 12 participants (4 men, 8 women) who completed 2 isocaloric 3-wk intervention phases of low EF (3 eating occasions/d) compared with high EF (8 eating occasions/d). On the last morning of each study phase, participants completed a 4-h appetite testing session. During the appetite testing session, participants completing the low EF phase consumed a meal at 0800. Participants completing the high EF intervention consumed the same meal spread evenly over 2 eating occasions at 0800 and 1030. Standardized ratings of hunger, desire to eat, fullness, thirst, and nausea were completed every 30 min with the use of paper-and-pencil semianchored 100-mm visual analog scales. A composite appetite score was calculated as the mean of hunger, desire to eat, and the inverse of fullness (calculated as 100-fullness rating). Linear regression analysis compared ratings between low EF and high EF conditions. Results: The mean composite appetite score was higher in the high EF condition for the total testing period (baseline through 1200) (P < 0.05) and for the time period from baseline through 1030 (P < 0.001). Conclusion: The results from this study in 12 healthy adults do not support the popularized notion that small, frequent meals help to decrease overall appetite. This trial was registered at clinicaltrials.gov as NCT02548026. PMID:26561409

Higher Eating Frequency Does Not Decrease Appetite in Healthy Adults.

PubMed

Perrigue, Martine M; Drewnowski, Adam; Wang, Ching-Yun; Neuhouser, Marian L

2016-01-01

Consumption of small, frequent meals is suggested as an effective approach to control appetite and food intake and might be a strategy for weight loss or healthy weight maintenance. Despite much speculation on the topic, scientific evidence is limited to support such a relation in the absence of changes to diet composition. We examined the effects of high compared with low eating frequency (EF) on self-reported appetite as a secondary outcome in a controlled trial. We conducted a randomized, crossover intervention trial in 12 participants (4 men, 8 women) who completed 2 isocaloric 3-wk intervention phases of low EF (3 eating occasions/d) compared with high EF (8 eating occasions/d). On the last morning of each study phase, participants completed a 4-h appetite testing session. During the appetite testing session, participants completing the low EF phase consumed a meal at 0800. Participants completing the high EF intervention consumed the same meal spread evenly over 2 eating occasions at 0800 and 1030. Standardized ratings of hunger, desire to eat, fullness, thirst, and nausea were completed every 30 min with the use of paper-and-pencil semianchored 100-mm visual analog scales. A composite appetite score was calculated as the mean of hunger, desire to eat, and the inverse of fullness (calculated as 100-fullness rating). Linear regression analysis compared ratings between low EF and high EF conditions. The mean composite appetite score was higher in the high EF condition for the total testing period (baseline through 1200) (P < 0.05) and for the time period from baseline through 1030 (P < 0.001). The results from this study in 12 healthy adults do not support the popularized notion that small, frequent meals help to decrease overall appetite. This trial was registered at clinicaltrials.gov as NCT02548026. © 2016 American Society for Nutrition.

Elongation factor-2 kinase regulates TG2/β1 integrin/Src/uPAR pathway and epithelial–mesenchymal transition mediating pancreatic cancer cells invasion

PubMed Central

Ashour, Ahmed A; Gurbuz, Nilgun; Alpay, Sultan Neslihan; Abdel-Aziz, Abdel-Aziz H; Mansour, Ahmed M; Huo, Longfei; Ozpolat, Bulent

2014-01-01

Pancreatic ductal adenocarcinoma is one of the lethal cancers with extensive local tumour invasion, metastasis, early systemic dissemination and poorest prognosis. Thus, understanding the mechanisms regulating invasion/metastasis and epithelial–mesenchymal transition (EMT), is the key for developing effective therapeutic strategies for pancreatic cancer (PaCa). Eukaryotic elongation factor-2 kinase (eEF-2K) is an atypical kinase that we found to be highly up-regulated in PaCa cells. However, its role in PaCa invasion/progression remains unknown. Here, we investigated the role of eEF-2K in cellular invasion, and we found that down-regulation of eEF-2K, by siRNA or rottlerin, displays impairment of PaCa cells invasion/migration, with significant decreases in the expression of tissue transglutaminase (TG2), the multifunctional enzyme implicated in regulation of cell attachment, motility and survival. These events were associated with reductions in β1 integrin/uPAR/MMP-2 expressions as well as decrease in Src activity. Furthermore, inhibition of eEF-2K/TG2 axis suppresses the EMT, as demonstrated by the modulation of the zinc finger transcription factors, ZEB1/Snail, and the tight junction proteins, claudins. Importantly, while eEF-2K silencing recapitulates the rottlerin-induced inhibition of invasion and correlated events, eEF-2K overexpression, by lentivirus-based expression system, suppresses such rottlerin effects and potentiates PaCa cells invasion/migration capability. Collectively, our results show, for the first time, that eEF-2K is involved in regulation of the invasive phenotype of PaCa cells through promoting a new signalling pathway, which is mediated by TG2/β1 integrin/Src/uPAR/MMP-2, and the induction of EMT biomarkers which enhance cancer cell motility and metastatic potential. Thus, eEF-2K could represent a novel potential therapeutic target in pancreatic cancer. PMID:25215932

Intake of free sugars and micronutrient dilution in Australian adults.

PubMed

Mok, Angelique; Ahmad, Rabia; Rangan, Anna; Louie, Jimmy Chun Yu

2018-01-01

The negative health effect of excessive intake of free sugars has been gaining increasing public awareness. This secondary analysis aimed to evaluate the impact of free-sugar intake on micronutrient dilution, and estimate a threshold level of free-sugar intake at which a decrease in micronutrient intake becomes evident, based on data from the Australian Health Survey 2011-2012. Dietary data from adult respondents (weighted n = 6150) who had completed two 24-h recalls were analyzed. A published 10-step methodology was adopted and used to estimate the free-sugar intake of the respondents. Six modified cut-offs for percentage of energy of free sugars (%EFS) were created based on recommendations from the WHO and the Institute of Medicine to examine the association between %EFS on micronutrient intakes. Estimated marginal means and SEs were calculated using ANCOVA. Logistic regression was used to calculate the ORs of not meeting the nutrient reference values for Australia and New Zealand for each micronutrient with an increase in free-sugar intake. Analyses were adjusted for age, sex, socioeconomic status, country of birth, whether dieting, smoking status, and remoteness of living area. Peak intake for most micronutrients was observed at %EFS between 5% and <15%. A significant reduction in most micronutrient intakes was observed at >25%EFS. At <5%EFS, some micronutrient intakes were reduced. Only small variations in micronutrient consumptions were observed when %EFS was between 5% and 25%. Core food intake decreased and discretionary food increased with an increase in free-sugar intake. A high free-sugar intake, particularly >25%EFS, was found to have a significant diluting effect on most nutrients. However, a free-sugar intake <5%EFS may increase the risk of undesirably low micronutrient consumption related to inadequate total energy intake. This secondary analysis was registered at anzctr.org.au as ACTRN12617000917336. © 2018 American Society for Nutrition. All rights reserved.

Executive function treatment and intervention in schools.

PubMed

Otero, Tulio M; Barker, Lauren A; Naglieri, Jack A

2014-01-01

This selective review article examines treatment and intervention strategies for executive function (EF) deficits within the school environment. We begin by providing a broad definition of EF. We then examine the scope of EF deficits within the school setting and identify profiles of special populations of students who present with such deficits. A focus is placed on the developmental trajectory that both EF and the frontal lobes follow and how this drives the selection and effectiveness of treatments and interventions at particular "critical periods" throughout a child's academic career. Direct and indirect school-based diagnostic assessment methods to identify EF deficits in students will be briefly reviewed. Against that background, various treatment methods and intervention strategies to remediate both cognitive and affective EF deficits within the confines of the school setting will be presented. Individual and group intervention strategies will be presented as will their current acceptance within the scientific community and applicability to the educational arena. The importance of incorporating school-based neuropsychological assessment methods that aid in the differential diagnosis of academic and behavioral difficulties directly related to EF will also be discussed, as the accurate identification of these impairments is necessary to facilitate data-based decision making when selecting the most appropriate interventions following a developmental model in educational settings. Topics addressing EF treatment modalities and research-based interventions for clinical and school-based practitioners to consider within educational settings will also be presented as suggestions for future research with pediatric populations.

Curcumin analog EF24 induces apoptosis and downregulates the mitogen activated protein kinase/extracellular signal-regulated signaling pathway in oral squamous cell carcinoma.

PubMed

Lin, Chongxiang; Tu, Chengwei; Ma, Yike; Ye, Pengcheng; Shao, Xia; Yang, Zhaoan; Fang, Yiming

2017-10-01

Oral squamous cell carcinoma (OSCC) is one of the most common malignancies worldwide. Diphenyldifluoroketone (EF24) is a curcumin analog that has been demonstrated to improve anticancer activity; however, its therapeutic potential and mechanisms in oral cancer remain unknown. In the present study, the effect of EF24 on apoptosis induction and its potential underlying mechanism in the CAL‑27 human OSCC cell line was investigated. To achieve this, various concentrations of cisplatin or EF24 were administrated to CAL‑27 cells for 24 h, and cell viability, apoptotic DNA fragmentation, and cleaved caspase 3 and 9 levels were evaluated. To investigate the potential underlying mechanism, the levels of mitogen‑activated protein kinase kinase 1 (MEK1) and extracellular signal‑regulated kinase (ERK), two key proteins in the mitogen‑activated protein kinase/ERK signaling pathway, were additionally examined. The results indicated that EF24 and cisplatin treatment decreased cell viability. EF24 treatment increased the levels of activated caspase 3 and 9, and decreased the phosphorylated forms of MEK1 and ERK. Sequential treatments of EF24 and 12‑phorbol‑13‑myristate acetate, a MAPK/ERK activator, resulted in a significant increase of activated MEK1 and ERK, and reversed cell viability. These results suggested that EF24 has potent anti‑tumor activity in OSCC via deactivation of the MAPK/ERK signaling pathway. Further analyses using animal models are required to confirm these findings in vivo.

A superhydrophobic cone to facilitate the xenomonitoring of filarial parasites, malaria, and trypanosomes using mosquito excreta/feces.

PubMed

Cook, Darren A N; Pilotte, Nils; Minetti, Corrado; Williams, Steven A; Reimer, Lisa J

2017-11-06

Background: Molecular xenomonitoring (MX), the testing of insect vectors for the presence of human pathogens, has the potential to provide a non-invasive and cost-effective method for monitoring the prevalence of disease within a community. Current MX methods require the capture and processing of large numbers of mosquitoes, particularly in areas of low endemicity, increasing the time, cost and labour required. Screening the excreta/feces (E/F) released from mosquitoes, rather than whole carcasses, improves the throughput by removing the need to discriminate vector species since non-vectors release ingested pathogens in E/F. It also enables larger numbers of mosquitoes to be processed per pool. However, this new screening approach requires a method of efficiently collecting E/F. Methods: We developed a cone with a superhydrophobic surface to allow for the efficient collection of E/F. Using mosquitoes exposed to either Plasmodium falciparum , Brugia malayi or Trypanosoma brucei brucei, we tested the performance of the superhydrophobic cone alongside two other collection methods. Results: All collection methods enabled the detection of DNA from the three parasites. Using the superhydrophobic cone to deposit E/F into a small tube provided the highest number of positive samples (16 out of 18) and facilitated detection of parasite DNA in E/F from individual mosquitoes. Further tests showed that following a simple washing step, the cone can be reused multiple times, further improving its cost-effectiveness. Conclusions: Incorporating the superhydrophobic cone into mosquito traps or holding containers could provide a simple and efficient method for collecting E/F. Where this is not possible, swabbing the container or using the washing method facilitates the detection of the three parasites used in this study.

Effect of Selective Heart Rate Slowing in Heart Failure With Preserved Ejection Fraction.

PubMed

Pal, Nikhil; Sivaswamy, Nadiya; Mahmod, Masliza; Yavari, Arash; Rudd, Amelia; Singh, Satnam; Dawson, Dana K; Francis, Jane M; Dwight, Jeremy S; Watkins, Hugh; Neubauer, Stefan; Frenneaux, Michael; Ashrafian, Houman

2015-11-03

Heart failure with preserved ejection fraction (HFpEF) is associated with significant morbidity and mortality but is currently refractory to therapy. Despite limited evidence, heart rate reduction has been advocated, on the basis of physiological considerations, as a therapeutic strategy in HFpEF. We tested the hypothesis that heart rate reduction improves exercise capacity in HFpEF. We conducted a randomized, crossover study comparing selective heart rate reduction with the If blocker ivabradine at 7.5 mg twice daily versus placebo for 2 weeks each in 22 symptomatic patients with HFpEF who had objective evidence of exercise limitation (peak oxygen consumption at maximal exercise [o2 peak] <80% predicted for age and sex). The result was compared with 22 similarly treated matched asymptomatic hypertensive volunteers. The primary end point was the change in o2 peak. Secondary outcomes included tissue Doppler-derived E/e' at echocardiography, plasma brain natriuretic peptide, and quality-of-life scores. Ivabradine significantly reduced peak heart rate compared with placebo in the HFpEF (107 versus 129 bpm; P<0.0001) and hypertensive (127 versus 145 bpm; P=0.003) cohorts. Ivabradine compared with placebo significantly worsened the change in o2 peak in the HFpEF cohort (-2.1 versus 0.9 mL·kg(-1)·min(-1); P=0.003) and significantly reduced submaximal exercise capacity, as determined by the oxygen uptake efficiency slope. No significant effects on the secondary end points were discernable. Our observations bring into question the value of heart rate reduction with ivabradine for improving symptoms in a HFpEF population characterized by exercise limitation. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02354573. © 2015 The Authors.

A randomized, double-blind, sham-controlled study of static electric field therapy by high voltage alternating current for active rheumatoid arthritis

PubMed Central

Naito, Yuji; Yamaguchi, Shinnichi; Mori, Yasuhiro; Nakajima, Kouji; Hashimoto, Sanshiro; Tomaru, Masakazu; Satoh, Yoshihiko; Hitomi, Yuji; Karita, Masakazu; Hiwatashi, Tomoaki; Kawahito, Yutaka; Yoshikawa, Toshikazu

2013-01-01

Static electric field therapy by high voltage alternating current (EF-HVAC) is a traditional complementary Japanese medicine used for headache, shoulder stiffness, chronic constipation and insomnia. Open-label studies and clinical experience in Japan have suggested that this electric field therapy is safe and effective in treating chronic arthritis. We evaluated the efficacy of EF-HVAC therapy in a randomized, double-blinded, sham-controlled trial in patients with active rheumatoid arthritis (RA) in community-based general physician centers. Thirty patients fulfilling American College of Rheumatology (ACR) criteria for RA were treated with EF-HVAC therapy with the LEGACIS PLUS System (COCOROCA Corp., Tokyo, Japan) or sham therapy for 12 weeks and followed for 4 weeks without treatment. The disease activity score 28 (DAS28-CRP), visual analogue scale for pain (VAS), modified health assessment questionnaire (MHAQ), and inflammatory parameters were used as the outcome variable. Twenty four patients (n = 12 in each group) were analyzed by a per protocol analysis. Although a significant reduction in DAS28-CRP was observed in EF-HVAC group at 8 and 12 weeks compared to before treatment, there were no significant differences in DAS28-CRP scores during treatment between two groups. The scale of VAS was also significantly decreased by the treatment with EF-HVAC compared to before treatment, in addition, the scale of VAS in EF-HVAC group was significantly lower than sham group at 8 and 12 weeks. Changes in another parameters including MHAQ were not significant between before and after treatment, or by all comparative study between two groups. There were no adverse events related the treatment. In conclusion, the EF-HVAC therapy has a beneficial effect on the improvement to subjective pain of RA. PMID:23874073

A randomized, double-blind, sham-controlled study of static electric field therapy by high voltage alternating current for active rheumatoid arthritis.

PubMed

Naito, Yuji; Yamaguchi, Shinnichi; Mori, Yasuhiro; Nakajima, Kouji; Hashimoto, Sanshiro; Tomaru, Masakazu; Satoh, Yoshihiko; Hitomi, Yuji; Karita, Masakazu; Hiwatashi, Tomoaki; Kawahito, Yutaka; Yoshikawa, Toshikazu

2013-07-01

Static electric field therapy by high voltage alternating current (EF-HVAC) is a traditional complementary Japanese medicine used for headache, shoulder stiffness, chronic constipation and insomnia. Open-label studies and clinical experience in Japan have suggested that this electric field therapy is safe and effective in treating chronic arthritis. We evaluated the efficacy of EF-HVAC therapy in a randomized, double-blinded, sham-controlled trial in patients with active rheumatoid arthritis (RA) in community-based general physician centers. Thirty patients fulfilling American College of Rheumatology (ACR) criteria for RA were treated with EF-HVAC therapy with the LEGACIS PLUS System (COCOROCA Corp., Tokyo, Japan) or sham therapy for 12 weeks and followed for 4 weeks without treatment. The disease activity score 28 (DAS28-CRP), visual analogue scale for pain (VAS), modified health assessment questionnaire (MHAQ), and inflammatory parameters were used as the outcome variable. Twenty four patients (n = 12 in each group) were analyzed by a per protocol analysis. Although a significant reduction in DAS28-CRP was observed in EF-HVAC group at 8 and 12 weeks compared to before treatment, there were no significant differences in DAS28-CRP scores during treatment between two groups. The scale of VAS was also significantly decreased by the treatment with EF-HVAC compared to before treatment, in addition, the scale of VAS in EF-HVAC group was significantly lower than sham group at 8 and 12 weeks. Changes in another parameters including MHAQ were not significant between before and after treatment, or by all comparative study between two groups. There were no adverse events related the treatment. In conclusion, the EF-HVAC therapy has a beneficial effect on the improvement to subjective pain of RA.

Heart Failure with Recovered EF and Heart Failure with Mid-Range EF: Current Recommendations and Controversies.

PubMed

Unkovic, Peter; Basuray, Anupam

2018-04-03

This review explores key features and potential management controversies in two emerging populations in heart failure: heart failure with recovered ejection fraction (HF-recovered EF) and heart failure with mid-range ejection fraction (HFmrEF). While HF-recovered EF patients have better outcomes than heart failure with reduced ejection fraction (HFrEF), they continue to have symptoms, persistent biomarker elevations, and abnormal outcomes suggesting a continued disease process. HFmrEF patients appear to have features of HFrEF and heart failure with preserved ejection fraction (HFpEF), but have a high prevalence of ischemic heart disease and may represent a transitory phase between the HFrEF and HFpEF. Management strategies have insufficient data to warrant standardization at this time. HF-recovered EF and HFmrEF represent new populations with unmet needs and expose the pitfalls of an EF basis for heart failure classification.

Environmental Sustainability in Higher Education: What Do Academics Think?

ERIC Educational Resources Information Center

Christie, Belinda A.; Miller, Kelly K.; Cooke, Raylene; White, John G.

2015-01-01

The slow uptake of Education for Sustainability (EfS) curricula in universities has, partly, been attributed to academics' perceptions that EfS has little relevance within some disciplines. Understanding teaching academics' attitudes, values and experiences of EfS across disciplines can inform future EfS efforts in higher education. This paper…

Effects of a Responsiveness-Focused Intervention in Family Child Care Homes on Children’s Executive Function

PubMed Central

Merz, Emily C.; Landry, Susan H.; Johnson, Ursula Y.; Williams, Jeffrey M.; Jung, Kwanghee

2016-01-01

Caregiver responsiveness has been theorized and found to support children’s early executive function (EF) development. This study examined the effects of an intervention that targeted family child care provider responsiveness on children’s EF. Family child care providers were randomly assigned to one of two intervention groups or a control group. An intervention group that received a responsiveness-focused online professional development course and another intervention group that received this online course plus weekly mentoring were collapsed into one group because they did not differ on any of the outcome variables. Children (N = 141) ranged in age from 2.5 to 5 years (mean age = 3.58 years; 52% female). At pretest and posttest, children completed delay inhibition tasks (gift delay-wrap, gift delay-bow) and conflict EF tasks (bear/dragon, dimensional change card sort), and parents reported on the children’s level of attention problems. Although there were no main effects of the intervention on children’s EF, there were significant interactions between intervention status and child age for delay inhibition and attention problems. The youngest children improved in delay inhibition and attention problems if they were in the intervention rather than the control group, whereas older children did not. These results suggest that improving family child care provider responsive behaviors may facilitate the development of certain EF skills in young preschool-age children. PMID:26941476

Effect of fuels and domestic heating appliance types on emission factors of selected organic pollutants.

PubMed

Šyc, Michal; Horák, Jiří; Hopan, František; Krpec, Kamil; Tomšej, Tomáš; Ocelka, Tomáš; Pekárek, Vladimír

2011-11-01

This study reports on the first complex data set of emission factors (EFs) of selected pollutants from combustion of five fuel types (lignite, bituminous coal, spruce, beech, and maize) in six different domestic heating appliances of various combustion designs. The effect of fuel as well as the effect of boiler type was studied. In total, 46 combustion runs were performed, during which numerous EFs were measured, including the EFs of particulate matter (PM), carbon monoxide, polyaromatic hydrocarbons (PAH), hexachlorobenzene (HxCBz), polychlorinated dibenzo-p-dioxins and furans (PCDD/F), etc. The highest EFs of nonchlorinated pollutants were measured for old-type boilers with over-fire and under-fire designs and with manual stoking and natural draft. Emissions of the above-mentioned pollutants from modern-type boilers (automatic, downdraft) were 10 times lower or more. The decisive factor for emission rate of nonchlorinated pollutants was the type of appliance; the type of fuel plays only a minor role. Emissions of chlorinated pollutants were proportional mainly to the chlorine content in fuel, but the type of appliance also influenced the rate of emissions significantly. Surprisingly, higher EFs of PCDD/F from combustion of chlorinated bituminous coal were observed for modern-type boilers (downdraft, automatic) than for old-type ones. On the other hand, when bituminous coal was burned, higher emissions of HxCBz were found for old-type boilers than for modern-type ones.

Sacubitril/valsartan and short-term changes in the 6-minute walk test: A pilot study.

PubMed

Beltrán, Paola; Palau, Patricia; Domínguez, Eloy; Faraudo, Mercedes; Núñez, Eduardo; Guri, Olga; Mollar, Anna; Sanchis, Juan; Bayés-Genís, Antoni; Núñez, Julio

2018-02-01

Impaired exercise capacity is the most disabling symptom in patients with heart failure with reduced ejection fraction (HFrEF). Despite sacubitril/valsartan showing reduced long-term morbidity and mortality over enalapril in HFrEF, its effects on short-term functional capacity remain uncertain. We sought to evaluate the effects of sacubitril/valsartan on a 30-day six-minute walk test in eligible patients with HFrEF. From November 1, 2016 to February 1, 2017, a total of 58 stable symptomatic patients with HFrEF were eligible for sacubitril/valsartan and underwent 6-MWT before and 30days after initiation of sacubitril/valsartan therapy. A mixed-effects model for repeated-measures was used to analyze the changes. Mean age was 70±11years. 72.4% males, 46.6% with ischemic heart disease, and 51.7% on NYHA functional class III were included. The mean (SD) values of baseline LVEF and 6MWT were 30±7%, and 300±89m, respectively. The median (IQR) of NT-proBNP at baseline was 2701pg/ml (1087-4200). Compared with baseline, the 6-MWT distance increased significantly at 30days by 13.9% (+∆=41.8m (33.4-50.2); p<0.001). In this pilot study, sacubitril/valsartan was associated with an improvement in exercise tolerance in symptomatic patients with HFrEF. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Neutralization of B. anthracis toxins during ex vivo phagocytosis.

PubMed

Tarasenko, Olga; Scott, Ashley; Jones, April; Soderberg, Lee; Alusta, Pierre

2013-07-01

Glycoconjugates (GCs) are recognized as stimulation and signaling agents, affecting cell adhesion, activation, and growth of living organisms. Among GC targets, macrophages are considered ideal since they play a central role in inflammation and immune responses against foreign agents. In this context, we studied the effects of highly selective GCs in neutralizing toxin factors produced by B. anthracis during phagocytosis using murine macrophages. The effects of GCs were studied under three conditions: A) prior to, B) during, and C) following exposure of macrophages to B. anthracis individual toxin (protective antigen [PA], edema factor [EF], lethal factor [LF] or toxin complexes (PA-EF-LF, PA-EF, and PA-LF). We employed ex vivo phagocytosis and post-phagocytosis analysis including direct microscopic observation of macrophage viability, and macrophage activation. Our results demonstrated that macrophages are more prone to adhere to GC-altered PA-EF-LF, PA-EF, and PA-LF toxin complexes. This adhesion results in a higher phagocytosis rate and toxin complex neutralization during phagocytosis. In addition, GCs enhance macrophage viability, activate macrophages, and stimulate nitric oxide (NO) production. The present study may be helpful in identifying GC ligands with toxin-neutralizing and/or immunomodulating properties. In addition, our study could suggest GCs as new targets for existing vaccines and the prospective development of vaccines and immunomodulators used to combat the effects of B. anthracis.

Trastuzumab-induced cardiotoxicity and its risk factors in real-world setting of breast cancer patients.

PubMed

Moilanen, Tiina; Jokimäki, Anna; Tenhunen, Olli; Koivunen, Jussi P

2018-06-05

Cardiotoxicity is the most important side effect of trastuzumab treatment. Heart function monitoring is recommended during the treatment which has led to growing use of resources. The aim of this retrospective study was to determine the frequency and timing of trastuzumab cardiotoxicity and its risk factors in real-world setting. Single institute, retrospective collection of data on HER2+ breast cancer patients (n = 246) was carried out through a pharmacy search for patients who had received trastuzumab in 2006-2014. Clinical and pathological factors, treatment history, EF measurements, cardiac medications, cardiovascular disease history, cardiac symptoms, and survival data were collected from patient records. 32 patients (13%) had EF decline ≥ 10%, eleven (4.5%) had EF decline ≥ 20% within 1 year after trastuzumab initiation, and trastuzumab was discontinued due to suspected cardiotoxicity in six patients (2.4%). 49 patients (19.9%) experienced symptoms related to cardiotoxicity during therapy, which accumulated among those with EF drop. Underlying cardiovascular diseases and multiple (≥ 2) cardiac medications were related to EF drop (≥ 20%) and trastuzumab discontinuation. Majority of EF drops (≥ 10%) and trastuzumab discontinuations were seen within 6months of trastuzumab initiation and recovery of EF drop to < 10% of the baseline was seen in most cases (62.5%). There was no statistically significant difference in the survival of patients according to EF drop. Trastuzumab cardiotoxicity seems to accumulate among patients with underlying cardiac conditions. EF monitoring could be targeted to risk groups without compromising of the cardiac health or survival of HER2-positive breast cancer patients.

Cardiomyocyte Functional Etiology in Heart Failure With Preserved Ejection Fraction Is Distinctive-A New Preclinical Model.

PubMed

Curl, Claire L; Danes, Vennetia R; Bell, James R; Raaijmakers, Antonia J A; Ip, Wendy T K; Chandramouli, Chanchal; Harding, Tristan W; Porrello, Enzo R; Erickson, Jeffrey R; Charchar, Fadi J; Kompa, Andrew R; Edgley, Amanda J; Crossman, David J; Soeller, Christian; Mellor, Kimberley M; Kalman, Jonathan M; Harrap, Stephen B; Delbridge, Lea M D

2018-06-01

Among the growing numbers of patients with heart failure, up to one half have heart failure with preserved ejection fraction (HFpEF). The lack of effective treatments for HFpEF is a substantial and escalating unmet clinical need-and the lack of HFpEF-specific animal models represents a major preclinical barrier in advancing understanding of HFpEF. As established treatments for heart failure with reduced ejection fraction (HFrEF) have proven ineffective for HFpEF, the contention that the intrinsic cardiomyocyte phenotype is distinct in these 2 conditions requires consideration. Our goal was to validate and characterize a new rodent model of HFpEF, undertaking longitudinal investigations to delineate the associated cardiac and cardiomyocyte pathophysiology. The selectively inbred Hypertrophic Heart Rat (HHR) strain exhibits adult cardiac enlargement (without hypertension) and premature death (40% mortality at 50 weeks) compared to its control strain, the normal heart rat. Hypertrophy was characterized in vivo by maintained systolic parameters (ejection fraction at 85%-90% control) with marked diastolic dysfunction (increased E/E'). Surprisingly, HHR cardiomyocytes were hypercontractile, exhibiting high Ca 2+ operational levels and markedly increased L-type Ca 2+ channel current. In HHR, prominent regions of reparative fibrosis in the left ventricle free wall adjacent to the interventricular septum were observed. Thus, the cardiomyocyte remodeling process in the etiology of this HFpEF model contrasts dramatically with the suppressed Ca 2+ cycling state that typifies heart failure with reduced ejection fraction. These findings may explain clinical observations, that treatments considered appropriate for heart failure with reduced ejection fraction are of little benefit for HFpEF-and suggest a basis for new therapeutic strategies. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Strategy-Based Cognitive Training for Improving Executive Functions in Older Adults: a Systematic Review.

PubMed

Mowszowski, L; Lampit, A; Walton, C C; Naismith, S L

2016-09-01

Given projected increases in dementia prevalence, emphasising earlier stages of cognitive impairment in older adults enables targeted early intervention strategies. Strategy-based cognitive training (SCT) is a remedial approach involving guidance and practice in compensatory techniques to improve cognition, including memory and attention. It may also be effective for improving executive functions (EF) integral to everyday tasks. This review systematically evaluates SCT effects on EF in older adults without dementia. Following PRISMA guidelines, we reviewed eligible trials according to pre-defined criteria, differentiating SCT from other cognitive interventions and stipulating total EF-focused intervention time, study design and target population (healthy older adults or mild cognitive decline). We then evaluated trials according to design, methodological quality and outcomes. Unfortunately, with too few studies in mild cognitive impairment, we refocused our review only on healthy older adults. Thirteen studies with 4120 participants in total were included, primarily targeting inductive reasoning. Despite heterogeneous study designs and SCT programs, 11/13 trials reported significant EF improvements, generally of moderate effect size (Hedges' g > 0.3). Four studies reported sustained benefits from one month to 10 years. There was some evidence of far transfer. We conclude that there is promising evidence for SCT as a targeted intervention for EF in healthy older adults and preliminary evidence for maintaining effects over time. Fewer trials have investigated far transfer (e.g. improved everyday functioning) or capacity to delay/prevent dementia, which are most relevant to clinical utility. Limitations include the inability to calculate effect sizes for four studies and absence of statistical meta-analysis.

Exposure to isoflavone-containing soy products and endothelial function: a Bayesian meta-analysis of randomized controlled trials.

PubMed

Beavers, D P; Beavers, K M; Miller, M; Stamey, J; Messina, M J

2012-03-01

To determine whether and to what degree exposure to isoflavone-containing soy products affects EF. Endothelial dysfunction has been identified as an independent coronary heart disease risk factor and a strong predictor of long-term cardiovascular morbidity and mortality. Data on the effects of exposure to isoflavone-containing soy products on EF are conflicting. A comprehensive literature search was conducted using the PUBMED database (National Library of Medicine, Bethesda, MD) inclusively through August 21, 2009 on RCTs using the keywords: soy, isoflavone, phytoestrogen, EF, flow mediated vasodilation, and FMD. A Bayesian meta-analysis was conducted to provide a comprehensive account of the effect of isoflavone-containing soy products on EF, as measured by FMD. A total of 17 RCTs were selected as having sufficient data for study inclusion. The overall mean absolute change in FMD (95% Bayesian CI) for isoflavone-containing soy product interventions was 1.15% (-0.52, 2.75). When the effects of separate interventions were considered, the treatment effect for isolated isoflavones was 1.98% (0.07, 3.97) compared to 0.72% (-1.39, 2.90) for isoflavone-containing soy protein. The models were not improved when considering study-specific effects such as cuff measurement location, prescribed dietary modification, and impaired baseline FMD. Cumulative evidence from the RCTs included in this meta-analysis indicates that exposure to soy isoflavones can modestly, but significantly, improve EF as measured by FMD. Therefore, exposure to isoflavone supplements may beneficially influence vascular health. Copyright © 2010 Elsevier B.V. All rights reserved.

Outcomes of de novo and acute decompensated heart failure patients according to ejection fraction.

PubMed

Choi, Ki Hong; Lee, Ga Yeon; Choi, Jin-Oh; Jeon, Eun-Seok; Lee, Hae-Young; Cho, Hyun-Jai; Lee, Sang Eun; Kim, Min-Seok; Kim, Jae-Joong; Hwang, Kyung-Kuk; Chae, Shung Chull; Baek, Sang Hong; Kang, Seok-Min; Choi, Dong-Ju; Yoo, Byung-Su; Kim, Kye Hun; Park, Hyun-Young; Cho, Myeong-Chan; Oh, Byung-Hee

2018-03-01

There are conflicting results among previous studies regarding the prognosis of heart failure with preserved ejection fraction (HFpEF) compared with heart failure with reduced ejection fraction (HFrEF). This study aimed to compare the outcomes of patients with de novo acute heart failure (AHF) or acute decompensated HF (ADHF) according to HFpEF (EF≥50%), or HFrEF (EF<40%) and to define the prognosis of patients with HF with mid-range EF (HFmrEF, 40≤EF<50%). Between March 2011 and February 2014, 5625 consecutive patients with AHF were recruited from 10 university hospitals. A total of 5414 (96.2%) patients with EF data were enrolled, which consisted of 2867 (53.0%) patients with de novo and 2547 (47.0%) with ADHF. Each of the enrolled group was stratified by EF. In de novo, all-cause death rates were not significantly different between HFpEF and HFrEF (HFpEF vs HFrEF, 206/744 (27.7%) vs 438/1631 (26.9%), HR adj 1.15, 95% CI 0.96 to 1.38, p=0.14). However, among patients with ADHF, HFrEF had a significantly higher mortality rate compared with HFpEF (HFpEF vs HFrEF, 245/613 (40.0%) vs 694/1551 (44.7%), HR adj 1.25, 95% CI 1.06 to 1.47, p=0.007). Also, in ADHF, HFmrEF was associated with a significantly lower mortality rate within 1 year compared with HFrEF (HFmrEF vs HFrEF, 88/383 (23.0%) vs 430/1551 (27.7%), HR adj 1.31, 95% CI 1.03 to 1.65, p=0.03), but a significantly higher mortality rate after 1 year compared with HFpEF (HFmrEF vs HFpEF, 83/295 (28.1%) vs 101/469 (21.5%), HR adj 0.70, 95% CI 0.52 to 0.96, p=0.02). HFpEF may indicate a better prognosis compared with HFrEF in ADHF, but not in de novo AHF. For patients with ADHF, the prognosis associated with HFmrEF was similar to that of HFpEF within the first year following hospitalisation and similar to HFrEF 1  year after hospitalisation. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Effects and moderators of psychosocial interventions on quality of life, and emotional and social function in patients with cancer: An individual patient data meta‐analysis of 22 RCTs

PubMed Central

Kalter, J.; Verdonck‐de Leeuw, I.M.; Sweegers, M.G.; Aaronson, N.K.; Jacobsen, P.B.; Newton, R.U.; Courneya, K.S.; Aitken, J.F.; Armes, J.; Arving, C.; Boersma, L.J.; Braamse, A.M.J.; Brandberg, Y.; Chambers, S.K.; Dekker, J.; Ell, K.; Ferguson, R.J.; Gielissen, M.F.M.; Glimelius, B.; Goedendorp, M.M.; Graves, K.D.; Heiney, S.P.; Horne, R.; Hunter, M.S.; Johansson, B.; Kimman, M.L.; Knoop, H.; Meneses, K.; Northouse, L.L.; Oldenburg, H.S.; Prins, J.B.; Savard, J.; van Beurden, M.; van den Berg, S.W.; Brug, J.

2018-01-01

Abstract Objective This individual patient data (IPD) meta‐analysis aimed to evaluate the effects of psychosocial interventions (PSI) on quality of life (QoL), emotional function (EF), and social function (SF) in patients with cancer, and to study moderator effects of demographic, clinical, personal, and intervention‐related characteristics. Methods Relevant studies were identified via literature searches in 4 databases. We pooled IPD from 22 (n = 4217) of 61 eligible randomized controlled trials. Linear mixed‐effect model analyses were used to study intervention effects on the post‐intervention values of QoL, EF, and SF (z‐scores), adjusting for baseline values, age, and cancer type. We studied moderator effects by testing interactions with the intervention for demographic, clinical, personal, and intervention‐related characteristics, and conducted subsequent stratified analyses for significant moderator variables.Results: PSI significantly improved QoL (β = 0.14,95%CI = 0.06;0.21), EF (β = 0.13,95%CI = 0.05;0.20), and SF (β = 0.10,95%CI = 0.03;0.18). Significant differences in effects of different types of PSI were found, with largest effects of psychotherapy. The effects of coping skills training were moderated by age, treatment type, and targeted interventions. Effects of psychotherapy on EF may be moderated by cancer type, but these analyses were based on 2 randomized controlled trials with small sample sizes of some cancer types. Conclusions PSI significantly improved QoL, EF, and SF, with small overall effects. However, the effects differed by several demographic, clinical, personal, and intervention‐related characteristics. Our study highlights the beneficial effects of coping skills training in patients treated with chemotherapy, the importance of targeted interventions, and the need of developing interventions tailored to the specific needs of elderly patients. PMID:29361206

Developing Therapies for Heart Failure with Preserved Ejection Fraction: Current State and Future Directions

PubMed Central

Butler, Javed; Fonarow, Gregg C.; Zile, Michael R.; Lam, Carolyn S.; Roessig, Lothar; Schelbert, Erik B.; Shah, Sanjiv J.; Ahmed, Ali; Bonow, Robert O.; Cleland, John GF; Cody, Robert J.; Chioncel, Ovidiu; Collins, Sean P.; Dunnmon, Preston; Filippatos, Gerasimos; Lefkowitz, Martin P.; Marti, Catherine N.; McMurray, John J.; Misselwitz, Frank; Nodari, Savina; O’Connor, Christopher; Pfeffer, Marc A.; Pieske, Burkert; Pitt, Bertram; Rosano, Guiseppe; Sabbah, Hani N.; Senni, Michele; Solomon, Scott D.; Stockbridge, Norman; Teerlink, John R.; Georgiopoulou, Vasiliki V.; Gheorghiade, Mihai

2014-01-01

The burden of heart failure with preserved ejection fraction (HFpEF) is considerable and is projected to worsen. To date, there are no approved therapies available for reducing mortality or hospitalizations for these patients. The pathophysiology of HFpEF is complex and includes alterations in cardiac structure and function, systemic and pulmonary vascular abnormalities, end-organ involvement, and comorbidities. There remain major gaps in our understanding of HFpEF pathophysiology. To facilitate a discussion of how to proceed effectively in future with development of therapies for HFpEF, a meeting was facilitated by the FDA and included representatives from academia, industry and regulatory agencies. This document summarizes the proceedings from this meeting. PMID:24720916

Modulation of the magnetic domain size induced by an electric field

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ando, F.; Kakizakai, H.; Yamada, K.

2016-07-11

The electric field (EF) effect on the magnetic domain structure of a Pt/Co system was studied, where an EF was applied to the top surface of the Co layer. The width of the maze domain was significantly modified by the application of the EF at a temperature slightly below the Curie temperature. After a detailed analysis, a change in the microscopic exchange stiffness induced by the EF application was suggested to dominate the modulation of the domain width observed in the experiment. The accumulation of electrons at the surface of the Co layer resulted in an increase in the microscopicmore » exchange stiffness and the Curie temperature. The result was consistent with the recent theoretical prediction.« less

Total and available heavy metal concentrations in soils of the Thriassio plain (Greece) and assessment of soil pollution indexes.

PubMed

Massas, Ioannis; Kalivas, Dionisios; Ehaliotis, Constantions; Gasparatos, Dionisios

2013-08-01

The Thriassio plain is located 25 km west of Athens city, the capital of Greece. Two major towns (Elefsina and Aspropyrgos), heavy industry plants, medium to large-scale manufacturing, logistics plants, and agriculture comprise the main land uses of the studied area. The aim of the present study was to measure the total and available concentrations of Cr, Zn, Ni, Pb, Co, Mn, Ba, Cu, and Fe in the top soils of the plain, and to asses soil contamination by these metals by using the geoaccumulation index (I geo), the enrichment factor (EF), and the availability ratio (AR) as soil pollution indexes. Soil samples were collected from 90 sampling sites, and aqua regia and DTPA extractions were carried out to determine total and available metal forms, respectively. Median total Cr, Zn, Ni, Pb, Co, Mn, Ba, Cu, and Fe concentrations were 78, 155, 81, 112, 24, 321, 834, 38, and 16 × 10(3) mg kg(-1), respectively. The available fractions showed much lower values with medians of 0.4, 5.6, 1.7, 6.9, 0.8, 5.7, 19.8, 2.1, and 2.9 mg kg(-1). Though median total metal concentrations are not considered as particularly high, the I geo and the EF values indicate moderate to heavy soil enrichment. For certain metals such as Cr, Ni, Cu, and Ba, the different distribution patterns between the EFs and the ARs suggest different origin of the total and the available metal forms. The evaluation of the EF and AR data sets for the soils of the two towns further supports the argument that the EFs can well demonstrate the long-term history of soil pollution and that the ARs can adequately portray the recent history of soil pollution.

Production of trans-free margarine with stearidonic acid soybean and high-stearate soybean oils-based structured lipid.

PubMed

Pande, Garima; Akoh, Casimir C; Shewfelt, Robert L

2012-11-01

Omega-3 fatty acids (n-3 FAs) have been positively associated with prevention and treatment of chronic diseases. Intake of high amounts of trans fatty acids (TFAs) is correlated with increased risk of coronary heart disease, inflammation, and cancer. Structured lipid (SL) was synthesized using stearidonic acid (SDA) soybean oil and high-stearate soybean oil catalyzed by Lipozyme(®) TLIM lipase. The SL was compared to extracted fat (EF) from a commercial brand for FA profile, sn-2 positional FAs, triacylglycerol (TAG) profile, polymorphism, thermal behavior, oxidative stability, and solid fat content (SFC). Both SL and EF had similar saturated FA (about 31 mol%) and unsaturated FA (about 68 mol%), but SL had a much lower n-6/n-3 ratio (1.1) than EF (5.8). SL had 10.5 mol% SDA. After short-path distillation, a loss of 53.9% was observed in the total tocopherol content of SL. The tocopherols were lost as free tocopherols. SL and EF had similar melting profile, β' polymorph, and oxidative stability. Margarine was formulated using SL (SLM) and EF (RCM, reformulated commercial margarine). No sensory difference was observed between the 2 margarines. The SL synthesized in this study contained no TFA and possessed desirable polymorphism, thermal properties, and SFC for formulation of soft margarine. The margarine produced with this SL was trans-free and SDA-enriched. The current research increases the food applications of stearidonic acid (SDA) soybean oil. trans-Free SDA containing SL was synthesized with desirable polymorph, thermal properties, and SFC for formulation of soft margarine. The margarine produced with this SL had no trans fat and had a low n-6/n-3 ratio. This may help in reducing trans fat intake in our diet while increasing n-3 FA intake. © 2012 Institute of Food Technologists®

Combination of surfactant enhanced soil washing and electro-Fenton process for the treatment of soils contaminated by petroleum hydrocarbons.

PubMed

Huguenot, David; Mousset, Emmanuel; van Hullebusch, Eric D; Oturan, Mehmet A

2015-04-15

In order to improve the efficiency of soil washing treatment of hydrocarbon contaminated soils, an innovative combination of this soil treatment technique with an electrochemical advanced oxidation process (i.e. electro-Fenton (EF)) has been proposed. An ex situ soil column washing experiment was performed on a genuinely diesel-contaminated soil. The washing solution was enriched with surfactant Tween 80 at different concentrations, higher than the critical micellar concentration (CMC). The impact of soil washing was evaluated on the hydrocarbons concentration in the leachates collected at the bottom of the soil columns. These eluates were then studied for their degradation potential by EF treatment. Results showed that a concentration of 5% of Tween 80 was required to enhance hydrocarbons extraction from the soil. Even with this Tween 80 concentration, the efficiency of the treatment remained very low (only 1% after 24 h of washing). Electrochemical treatments performed thereafter with EF on the collected eluates revealed that the quasi-complete mineralization (>99.5%) of the hydrocarbons was achieved within 32 h according to a linear kinetic trend. Toxicity was higher than in the initial solution and reached 95% of inhibition of Vibrio fischeri bacteria measured by Microtox method, demonstrating the presence of remaining toxic compounds even after the complete degradation. Finally, the biodegradability (BOD₅/COD ratio) reached a maximum of 20% after 20 h of EF treatment, which is not enough to implement a combined treatment with a biological treatment process. Copyright © 2015 Elsevier Ltd. All rights reserved.

Fractionation of trace elements in agricultural soils using ultrasound assisted sequential extraction prior to inductively coupled plasma mass spectrometric determination.

PubMed

Matong, Joseph M; Nyaba, Luthando; Nomngongo, Philiswa N

2016-07-01

The main objectives of this study were to determine the concentration of fourteen trace elements and to investigate their distribution as well as a contamination levels in selected agricultural soils. An ultrasonic assisted sequential extraction procedure derived from three-step BCR method was used for fractionation of trace elements. The total concentration of trace elements in soil samples was obtained by total digestion method in soil samples with aqua regia. The results of the extractable fractions revealed that most of the target trace elements can be transferred to the human being through the food chain, thus leading to serious human health. Enrichment factor (EF), geo-accumulation index (Igeo), contamination factor (CF), risk assessment code (RAC) and individual contamination factors (ICF) were used to assess the environmental impacts of trace metals in soil samples. The EF revealed that Cd was enriched by 3.1-7.2 (except in Soil 1). The Igeo results showed that the soils in the study area was moderately contaminated with Fe, and heavily to extremely polluted with Cd. The soil samples from the unplanted field was found to have highest contamination factor for Cd and lowest for Pb. Soil 3 showed a high risk for Tl and Cd with RAC values of greater than or equal to 50%. In addition, Fe, Ni, Cu, V, As, Mo (except Soil 2), Sb and Pb posed low environmental risk. The modified BCR sequential extraction method provided more information about mobility and environmental implication of studied trace elements in the study area. Copyright © 2016 Elsevier Ltd. All rights reserved.

Polyaniline/cyclodextrin composite coated stir bar sorptive extraction combined with high performance liquid chromatography-ultraviolet detection for the analysis of trace polychlorinated biphenyls in environmental waters.

PubMed

Lei, Yun; He, Man; Chen, Beibei; Hu, Bin

2016-04-01

A novel polyaniline/α-cyclodextrin (PANI/α-CD) composite coated stir bar was prepared by sol-gel process for the analysis of polychlorinated biphenyls (PCBs) in this work. The preparation reproducibility of the PANI/α-CD-coated stir bar was good, with relative standard deviations (RSDs) ranging from 2.3% to 3.7% (n=7) and 2.0% to 3.8% (n=7) for bar to bar and batch to batch, respectively. Based on it, a novel method of PANI/α-CD-coated stir bar sorptive extraction (SBSE) followed by high performance liquid chromatography-ultraviolet (HPLC-UV) detection was developed for the determination of trace PCBs in environmental waters. To obtain the best extraction performance for target PCBs, several parameters affecting SBSE, such as extraction time, stirring rate, and ionic strength were investigated. Under optimal experimental conditions, the limits of detection (LODs) of the proposed method for seven PCBs were in the range of 0.048-0.22 μg/L, and the RSDs were 5.3-9.8% (n=7, c=1 μg/L). Enrichment factors (EFs) ranging from 39.8 to 68.4-fold (theoretical EF, 83.3-fold) for target analytes were achieved. The proposed method was successfully applied for the determination of seven target PCBs in Yangtze River water and East Lake water, and the recoveries were in the range of 73.0-120% for the spiked East Lake water samples and 82.7-121% for the spiked Yangtze River water samples, respectively. Copyright © 2015 Elsevier B.V. All rights reserved.

Stimuli-Responsive Nano-Carrier for Co-delivery of MiR-31 and Doxorubicin to Suppress High MtEF4 Cancer.

PubMed

Wang, Fang; Zhang, Lingyun; Bai, Xiufeng; Cao, Xintao; Jiao, Xiangyu; Huang, Yan; Li, Yansheng; Qin, Yan; Wen, Yongqiang

2018-06-13

Gene interference-based therapeutics represents a fascinating challenge and shows enormous potential for cancer treatment, in which microRNA is used to correct abnormal gene. Based on the above, we introduced microRNA-31 to bind to 3' untranslated region of mtEF4, resulting in the downregulation of its messenger RNA and protein to trigger cancer cells apoptosis through mitochondria-related pathway. To achieve better therapeutic effect, a mesoporous silica nanoparticles-based controlled nanoplatform had been developed. This system was fabricated by conjugation of microRNA-31 onto doxorubicin-loaded mesoporous silica nanoparticles with a PEI/HA coating, and drug release was triggered by acidic environment of tumors. By feat of surface functionalization and tumor-specific conjugation to nanoparticles, our drug delivery system could promote intracellular accumulation of drugs via the active transport at tumor site. More importantly, microRNA-31 not only directly targeted to mtEF4 to promote cells death, but had synergistic effects when used in combination with doxorubicin, and achieved excellent superadditive effects. As such, our research might provide new insights towards detecting high mtEF4 cancer and exploiting highly effective anticancer drugs.

Longitudinal Links between Executive Function, Anger, and Aggression in Middle Childhood.

PubMed

Rohlf, Helena L; Holl, Anna K; Kirsch, Fabian; Krahé, Barbara; Elsner, Birgit

2018-01-01

Previous research has indicated that executive function (EF) is negatively associated with aggressive behavior in childhood. However, there is a lack of longitudinal studies that have examined the effect of deficits in EF on aggression over time and taken into account different forms and functions of aggression at the same time. Furthermore, only few studies have analyzed the role of underlying variables that may explain the association between EF and aggression. The present study examined the prospective paths between EF and different forms (physical and relational) and functions (reactive and proactive) of aggression. The habitual experience of anger was examined as a potential underlying mechanism of the link between EF and aggression, because the tendency to get angry easily has been found to be both a consequence of deficits in EF and a predictor of aggression. The study included 1,652 children (between 6 and 11 years old at the first time point), who were followed over three time points (T1, T2, and T3) covering 3 years. At T1, a latent factor of EF comprised measures of planning, rated via teacher reports, as well as inhibition, set shifting, and working-memory updating, assessed experimentally. Habitual anger experience was assessed via parent reports at T1 and T2. The forms and functions of aggression were measured via teacher reports at all three time points. Structural equation modeling revealed that EF at T1 predicted physical, relational, and reactive aggression at T3, but was unrelated to proactive aggression at T3. Furthermore, EF at T1 was indirectly linked to physical aggression at T3, mediated through habitual anger experience at T2. The results indicate that deficits in EF influence the later occurrence of aggression in middle childhood, and the tendency to get angry easily mediates this relation.

Longitudinal Links between Executive Function, Anger, and Aggression in Middle Childhood

PubMed Central

Rohlf, Helena L.; Holl, Anna K.; Kirsch, Fabian; Krahé, Barbara; Elsner, Birgit

2018-01-01

Previous research has indicated that executive function (EF) is negatively associated with aggressive behavior in childhood. However, there is a lack of longitudinal studies that have examined the effect of deficits in EF on aggression over time and taken into account different forms and functions of aggression at the same time. Furthermore, only few studies have analyzed the role of underlying variables that may explain the association between EF and aggression. The present study examined the prospective paths between EF and different forms (physical and relational) and functions (reactive and proactive) of aggression. The habitual experience of anger was examined as a potential underlying mechanism of the link between EF and aggression, because the tendency to get angry easily has been found to be both a consequence of deficits in EF and a predictor of aggression. The study included 1,652 children (between 6 and 11 years old at the first time point), who were followed over three time points (T1, T2, and T3) covering 3 years. At T1, a latent factor of EF comprised measures of planning, rated via teacher reports, as well as inhibition, set shifting, and working-memory updating, assessed experimentally. Habitual anger experience was assessed via parent reports at T1 and T2. The forms and functions of aggression were measured via teacher reports at all three time points. Structural equation modeling revealed that EF at T1 predicted physical, relational, and reactive aggression at T3, but was unrelated to proactive aggression at T3. Furthermore, EF at T1 was indirectly linked to physical aggression at T3, mediated through habitual anger experience at T2. The results indicate that deficits in EF influence the later occurrence of aggression in middle childhood, and the tendency to get angry easily mediates this relation. PMID:29535615

Proteomic analysis of trichloroethylene-induced alterations in expression, distribution, and interactions of SET/TAF-Iα and two SET/TAF-Iα-binding proteins, eEF1A1 and eEF1A2, in hepatic L-02 cells.

PubMed

Hong, Wen-Xu; Yang, Liang; Chen, Moutong; Yang, Xifei; Ren, Xiaohu; Fang, Shisong; Ye, Jinbo; Huang, Haiyan; Peng, Chaoqiong; Zhou, Li; Huang, Xinfeng; Yang, Fan; Wu, Desheng; Zhuang, Zhixiong; Liu, Jianjun

2012-09-01

Emerging evidence indicates that trichloroethylene (TCE) exposure causes severe hepatotoxicity. However, the mechanisms of TCE hepatotoxicity remain unclear. Recently, we reported that TCE exposure up-regulated the expression of the oncoprotein SET/TAF-Iα and SET knockdown attenuated TCE-induced cytotoxicity in hepatic L-02 cells. To decipher the function of SET/TAF-Iα and its contributions to TCE-induced hepatotoxicity, we employed a proteomic analysis of SET/TAF-Iα with tandem affinity purification to identify SET/TAF-Iα-binding proteins. We identified 42 novel Gene Ontology co-annotated SET/TAF-Iα-binding proteins. The identifications of two of these proteins (eEF1A1, elongation factor 1-alpha 1; eEF1A2, elongation factor 1-alpha 2) were confirmed by Western blot analysis and co-immunoprecipitation (Co-IP). Furthermore, we analyzed the effects of TCE on the expression, distribution and interactions of eEF1A1, eEF1A2 and SET in L-02 cells. Western blot analysis reveals a significant up-regulation of eEF1A1, eEF1A2 and two isoforms of SET, and immunocytochemical analysis reveals that eEF1A1 and SET is redistributed by TCE. SET is redistributed from the nucleus to the cytoplasm, while eFE1A1 is translocated from the cytoplasm to the nucleus. Moreover, we find by Co-IP that TCE exposure significantly increases the interaction of SET with eEF1A2. Our data not only provide insights into the physiological functions of SET/TAF-Iα and complement the SET interaction networks, but also demonstrate that TCE exposure induces alterations in the expression, distribution and interactions of SET and its binding partners. These alterations may constitute the mechanisms of TCE cytotoxicity. Copyright © 2012 Elsevier Inc. All rights reserved.

Purification and properties of the heterogeneous subunits of elongation factor EF-1 from Guerin epithelioma cells.

PubMed

Marcinkiewicz, C; Gajko, A; Gałasiński, W

1991-01-01

Elongation factor EF-1 from Guerin epithelioma was separated into two subunit forms EF-1A and EF-1B by chromatography in the presence of 25% glycerol, successively on CM-Sephadex and DEAE-Sephadex. It was shown that EF-1A is a thermolabile, single polypeptide which catalyses the binding of aminoacyl-tRNA to ribosomes, similarly as eukaryotic EF-1 alpha or prokaryotic EF-Tu. EF-1B was characterized as a complex composed of at least two polypeptides. One of them is EF-1A, the other EF-1C, which stimulates EF-1A activity and protects this elongation factor from thermal inactivation.

Determination of volatile components of green, black, oolong and white tea by optimized ultrasound-assisted extraction-dispersive liquid-liquid microextraction coupled with gas chromatography.

PubMed

Sereshti, Hassan; Samadi, Soheila; Jalali-Heravi, Mehdi

2013-03-08

Ultrasound assisted extraction (UAE) followed by dispersive liquid-liquid microextraction (DLLME) was used for extraction and preconcentration of volatile constituents of six tea plants. The preconcentrated compounds were analyzed by gas chromatography-mass spectrometry (GC-MS). Totally, 42 compounds were identified and caffeine was quantitatively determined. The main parameters (factors) of the extraction process were optimized by using a central composite design (CCD). Methanol and chloroform were selected as the extraction solvent and preconcentration solvent, respectively .The optimal conditions were obtained as 21 in for sonication time; 32°C for temperature; 27 L for volume of extraction solvent and 7.4% for salt concentration (NaCl/H(2)O). The determination coefficient (R(2)) was 0.9988. The relative standard deviation (RSD %) was 4.8 (n=5), and the enhancement factors (EFs) were 4.0-42.6. Copyright © 2013 Elsevier B.V. All rights reserved.

Age-related changes in executive control and their relationships with activity performance in handwriting.

PubMed

Rosenblum, Sara; Engel-Yeger, Batya; Fogel, Yael

2013-04-01

Deterioration in the frontal and prefrontal cortex associated with executive functions (EF) occurs with age and may be associated with changes in daily performance. The aim of the present study was to describe changes occurring with age in Executive Functions (EF) and handwriting activity, as well as to analyze relationships between age, EF and handwriting performance. The study population included 80 healthy participants (aged 31 to 76+) living in the community. After answering five questions about their writing habits, the participants completed the Behavioral Assessment of the Dysexecutive Syndrome (BADS). In addition, they performed a handwriting task on a digitizer included in the Computerized Penmanship Evaluation Tool (ComPET), which provides kinematic measures of the handwriting process. Significant differences were found between the four age groups for both EF and temporal and spatial handwriting measures. A series of regressions indicated that age predicted 35% of the variance of the BADS profile score (EF control) and 32% of the variance of in-air time while writing. The results of this study indicated age effect on both EF control and handwriting performance. Possible implications for further research and clinical evaluation and intervention are discussed. Copyright © 2013 Elsevier B.V. All rights reserved.

Mindfulness Plus Reflection Training: Effects on Executive Function in Early Childhood

PubMed Central

Zelazo, Philip David; Forston, Jessica L.; Masten, Ann S.; Carlson, Stephanie M.

2018-01-01

Executive function (EF) skills are essential for academic achievement, and poverty-related stress interferes with their development. This pre-test, post-test, follow-up randomized-control trial assessed the impact of an intervention targeting reflection and stress reduction on children's EF skills. Preschool children (N = 218) from schools serving low-income families in two U.S. cities were randomly assigned to one of three options delivered in 30 small-group sessions over 6 weeks: Mindfulness + Reflection training; Literacy training; or Business as Usual (BAU). Sessions were conducted by local teachers trained in a literacy curriculum or Mindfulness + Reflection intervention, which involved calming activities and games that provided opportunities to practice reflection in the context of goal-directed problem solving. EF improved in all groups, but planned contrasts indicated that the Mindfulness + Reflection group significantly outperformed the BAU group at Follow-up (4 weeks post-test). No differences in EF were observed between the BAU and Literacy training groups. Results suggest that a brief, small-group, school-based intervention teaching mindfulness and reflection did not improve EF skills more than literacy training but is promising compared to BAU for improving EF in low-income preschool children several weeks following the intervention. PMID:29535661

Phosphorylation decelerates conformational dynamics in bacterial translation elongation factors

PubMed Central

Talavera, Ariel; Hendrix, Jelle; Versées, Wim; Jurėnas, Dukas; Van Nerom, Katleen; Vandenberk, Niels; Singh, Ranjan Kumar; Konijnenberg, Albert; De Gieter, Steven; Castro-Roa, Daniel; Barth, Anders; De Greve, Henri; Sobott, Frank; Hofkens, Johan; Zenkin, Nikolay; Loris, Remy; Garcia-Pino, Abel

2018-01-01

Bacterial protein synthesis is intricately connected to metabolic rate. One of the ways in which bacteria respond to environmental stress is through posttranslational modifications of translation factors. Translation elongation factor Tu (EF-Tu) is methylated and phosphorylated in response to nutrient starvation upon entering stationary phase, and its phosphorylation is a crucial step in the pathway toward sporulation. We analyze how phosphorylation leads to inactivation of Escherichia coli EF-Tu. We provide structural and biophysical evidence that phosphorylation of EF-Tu at T382 acts as an efficient switch that turns off protein synthesis by decoupling nucleotide binding from the EF-Tu conformational cycle. Direct modifications of the EF-Tu switch I region or modifications in other regions stabilizing the β-hairpin state of switch I result in an effective allosteric trap that restricts the normal dynamics of EF-Tu and enables the evasion of the control exerted by nucleotides on G proteins. These results highlight stabilization of a phosphorylation-induced conformational trap as an essential mechanism for phosphoregulation of bacterial translation and metabolism. We propose that this mechanism may lead to the multisite phosphorylation state observed during dormancy and stationary phase. PMID:29546243

Right heart dysfunction and failure in heart failure with preserved ejection fraction: mechanisms and management. Position statement on behalf of the Heart Failure Association of the European Society of Cardiology.

PubMed

Gorter, Thomas M; van Veldhuisen, Dirk J; Bauersachs, Johann; Borlaug, Barry A; Celutkiene, Jelena; Coats, Andrew J S; Crespo-Leiro, Marisa G; Guazzi, Marco; Harjola, Veli-Pekka; Heymans, Stephane; Hill, Loreena; Lainscak, Mitja; Lam, Carolyn S P; Lund, Lars H; Lyon, Alexander R; Mebazaa, Alexandre; Mueller, Christian; Paulus, Walter J; Pieske, Burkert; Piepoli, Massimo F; Ruschitzka, Frank; Rutten, Frans H; Seferovic, Petar M; Solomon, Scott D; Shah, Sanjiv J; Triposkiadis, Filippos; Wachter, Rolf; Tschöpe, Carsten; de Boer, Rudolf A

2018-01-01

There is an unmet need for effective treatment strategies to reduce morbidity and mortality in patients with heart failure with preserved ejection fraction (HFpEF). Until recently, attention in patients with HFpEF was almost exclusively focused on the left side. However, it is now increasingly recognized that right heart dysfunction is common and contributes importantly to poor prognosis in HFpEF. More insights into the development of right heart dysfunction in HFpEF may aid to our knowledge about this complex disease and may eventually lead to better treatments to improve outcomes in these patients. In this position paper from the Heart Failure Association of the European Society of Cardiology, the Committee on Heart Failure with Preserved Ejection Fraction reviews the prevalence, diagnosis, and pathophysiology of right heart dysfunction and failure in patients with HFpEF. Finally, potential treatment strategies, important knowledge gaps and future directions regarding the right side in HFpEF are discussed. © 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.

Diphenyl difluoroketone: a potent chemotherapy candidate for human hepatocellular carcinoma.

PubMed

Liang, Yingjian; Yin, Dalong; Hou, Limin; Zheng, Tongsen; Wang, Jiabei; Meng, Xianzhi; Lu, Zhaoyang; Song, Xuan; Pan, Shangha; Jiang, Hongchi; Liu, Lianxin

2011-01-01

Diphenyl difluoroketone (EF24), a molecule having structural similarity to curcumin, was recently reported to inhibit proliferation of various cancer cells significantly. Here we try to determine the effect and mechanism of EF24 on hepatocellular carcinoma. 2 µM EF24 was found to inhibit the proliferation of PLC/PRF/5, Hep3B, HepG2, SK-HEP-1 and Huh 7 cell lines. However, even 8 µM EF24 treatment did not affect the proliferation of normal liver LO2 cells. Accordingly, 20 mg/kg/d EF24 inhibited the growth of the tumor xenografts conspicuously while causing no apparent change in liver, spleen or body weight. In addition, significant apoptosis and G(2)/M phase cell cycle arrest were found using flow cytometry. Besides, caspases and PARP activation and features typical of apoptosis including fragmented nuclei with condensed chromatin were also observed. Furthermore, the mechanism was targeted at the reduction of nuclear factor kappa b (NF-κB) pathway and the NF-κB-regulated gene products Bcl-2, COX-2, Cyclin B1. Our study has offered a strategy that EF24 being a therapeutic agent for hepatocellular carcinoma.

Diphenyl Difluoroketone: A Potent Chemotherapy Candidate for Human Hepatocellular Carcinoma

PubMed Central

Hou, Limin; Zheng, Tongsen; Wang, Jiabei; Meng, Xianzhi; Lu, Zhaoyang; Song, Xuan; Pan, Shangha; Jiang, Hongchi; Liu, Lianxin

2011-01-01

Diphenyl difluoroketone (EF24), a molecule having structural similarity to curcumin, was recently reported to inhibit proliferation of various cancer cells significantly. Here we try to determine the effect and mechanism of EF24 on hepatocellular carcinoma. 2 µM EF24 was found to inhibit the proliferation of PLC/PRF/5, Hep3B, HepG2, SK-HEP-1 and Huh 7 cell lines. However, even 8 µM EF24 treatment did not affect the proliferation of normal liver LO2 cells. Accordingly, 20 mg/kg/d EF24 inhibited the growth of the tumor xenografts conspicuously while causing no apparent change in liver, spleen or body weight. In addition, significant apoptosis and G2/M phase cell cycle arrest were found using flow cytometry. Besides, caspases and PARP activation and features typical of apoptosis including fragmented nuclei with condensed chromatin were also observed. Furthermore, the mechanism was targeted at the reduction of nuclear factor kappa b (NF-κB) pathway and the NF-κB–regulated gene products Bcl-2, COX-2, Cyclin B1. Our study has offered a strategy that EF24 being a therapeutic agent for hepatocellular carcinoma. PMID:21901145

The effects of deterioration and technological levels on pollutant emission factors for gasoline light-duty trucks.

PubMed

Zhang, Qingyu; Fan, Juwang; Yang, Weidong; Chen, Bixin; Zhang, Lijuan; Liu, Jiaoyu; Wang, Jingling; Zhou, Chunyao; Chen, Xuan

2017-07-01

Vehicle deterioration and technological change influence emission factors (EFs). In this study, the impacts of vehicle deterioration and emission standards on EFs of regulated pollutants (carbon monoxide [CO], hydrocarbon [HC], and nitrogen oxides [NO x ]) for gasoline light-duty trucks (LDTs) were investigated according to the inspection and maintenance (I/M) data using a chassis dynamometer method. Pollutant EFs for LDTs markedly varied with accumulated mileages and emission standards, and the trends of EFs are associated with accumulated mileages. In addition, the study also found that in most cases, the median EFs of CO, HC, and NO x are higher than those of basic EFs in the International Vehicle Emissions (IVE) model; therefore, the present study provides correction factors for the IVE model relative to the corresponding emission standards and mileages. Currently, vehicle emissions are great contributors to air pollution in cities, especially in developing countries. Emission factors play a key role in creating emission inventory and estimating emissions. Deterioration represented by vehicle age and accumulated mileage and changes of emission standards markedly influence emission factors. In addition, the results provide collection factors for implication in the IVE model in the region levels.

Metal contamination of agricultural soils in the copper mining areas of Singhbhum shear zone in India

NASA Astrophysics Data System (ADS)

Giri, Soma; Singh, Abhay Kumar; Mahato, Mukesh Kumar

2017-06-01

The study was intended to investigate the heavy metal contamination in the agricultural soils of the copper mining areas in Singhbhum shear zone, India. The total concentrations of the metals were determined by inductively coupled plasma-mass spectrometer (ICPMS). Pollution levels were assessed by calculating enrichment factor (EF), geo-accumulation index (I_geo), contamination factors (CF), pollution load index ( PLI), Nemerow index and ecological risk index (RI). The metal concentrations in the soil samples exceeded the average shale values for almost all the metals. Principal component analysis resulted in extraction of three factors explaining 82.6% of the data variability and indicated anthropogenic contribution of Cu, Ni, Co, Cr, Mn and Pb. The EF and I_geo values indicated very high contamination with respect to Cu followed by As and Zn in the agricultural soils. The values of PLI, RI and Nemerow index, which considered the overall effect of all the studied metals on the soils, revealed that 50% of the locations were highly polluted with respect to metals. The pollution levels varied with the proximity to the copper mining and processing units. Consequently, the results advocate the necessity of periodic monitoring of the agricultural soils of the area and development of proper management strategies to reduce the metal pollution.

Hot and Cool Executive Functions in Adolescence: Development and Contributions to Important Developmental Outcomes.

PubMed

Poon, Kean

2017-01-01

Despite significant theoretical advancement in the area of child neuropsychology, limited attention has been paid to the developmental features of adolescence. The present study intends to address this issue in relation to executive function (EF). EF refers to the psychological processes that underlie goal-directed behavior; recent studies separate cool EF (psychological process involves pure logic and critical analysis) and hot EF (psychological process driven by emotion). Although neurological findings suggest that adolescence is a sensitive period for EF development, data on comparing the developmental progression in hot or cool EFs is highly missing. Moreover, while evidence has confirmed the relationships between EF and day-to-day functioning, whether and how hot and cool EFs contribute to core developmental outcomes in adolescence is still remained unknown. The current study aims to enhance our understanding of the development and impacts of hot and cool EFs in adolescence. A total of 136 typically developing adolescents from age 12 to 17 completed four cool EF tasks including Backward digit span, Contingency naming test, Stockings of Cambridge, and Stroop Color and Word test, and one hot task on Cambridge gambling task. Data on academic performance and psychological adjustment was also collected. Results showed that cool and hot EF exhibited different patterns of age-related growth in adolescence. Specifically, cool EF ascended with age while hot EF showed a bell-shaped development. Moreover, there were correlations among cool EF measures but no association between cool and hot EFs. Further, cool EF was a better predictor of academic performance, while hot EF uniquely related to emotional problems. The results provide evidence for the association among cool EF tests and the differentiation of hot and cool EFs. The bell-shaped development of hot EF might suggest a period of heightened risk-taking propensity in middle adolescence. Given the plastic nature of EF, especially over adolescence, the current findings may have practical implications for future EF identification and training.

Hot and Cool Executive Functions in Adolescence: Development and Contributions to Important Developmental Outcomes

PubMed Central

Poon, Kean

2018-01-01

Despite significant theoretical advancement in the area of child neuropsychology, limited attention has been paid to the developmental features of adolescence. The present study intends to address this issue in relation to executive function (EF). EF refers to the psychological processes that underlie goal-directed behavior; recent studies separate cool EF (psychological process involves pure logic and critical analysis) and hot EF (psychological process driven by emotion). Although neurological findings suggest that adolescence is a sensitive period for EF development, data on comparing the developmental progression in hot or cool EFs is highly missing. Moreover, while evidence has confirmed the relationships between EF and day-to-day functioning, whether and how hot and cool EFs contribute to core developmental outcomes in adolescence is still remained unknown. The current study aims to enhance our understanding of the development and impacts of hot and cool EFs in adolescence. A total of 136 typically developing adolescents from age 12 to 17 completed four cool EF tasks including Backward digit span, Contingency naming test, Stockings of Cambridge, and Stroop Color and Word test, and one hot task on Cambridge gambling task. Data on academic performance and psychological adjustment was also collected. Results showed that cool and hot EF exhibited different patterns of age-related growth in adolescence. Specifically, cool EF ascended with age while hot EF showed a bell-shaped development. Moreover, there were correlations among cool EF measures but no association between cool and hot EFs. Further, cool EF was a better predictor of academic performance, while hot EF uniquely related to emotional problems. The results provide evidence for the association among cool EF tests and the differentiation of hot and cool EFs. The bell-shaped development of hot EF might suggest a period of heightened risk-taking propensity in middle adolescence. Given the plastic nature of EF, especially over adolescence, the current findings may have practical implications for future EF identification and training. PMID:29367850

Efficient Filtration of Effluent Organic Matter by Polycation-Clay Composite Sorbents: Effect of Polycation Configuration on Pharmaceutical Removal.

PubMed

Shabtai, Itamar A; Mishael, Yael G

2016-08-02

Hybrid polycation-clay composites, based on methylated poly vinylpyridinium, were optimized as sorbents for secondary effluent organic matter (EfOM) including emerging micropollutants. Composite structure was tuned by solution ionic strength and characterized by zeta potential, FTIR, X-ray diffraction, and thermal gravimetric analyses. An increase in ionic strength induced a transition from a train to a loops and tails configuration, accompanied by greater polycation adsorption. Composite charge reversal (zeta potential -18 to 45 mV) increased the adsorption of EfOM and humic acid (HA), moderately and sharply, respectively, suggesting electrostatic and also nonspecific interactions with EfOM. Filtration of EfOM by columns of positively charged composites was superior to that of granular activated carbon (GAC). The overall removal of EfOM was most efficient by the composite with a train configuration. Whereas a composite with a loops and tails configuration was beneficial for the removal of the anionic micropollutants diclofenac, gemfibrozil and ibuprofen from EfOM. These new findings suggest that the loops and tails may offer unique binding sites for small micropollutants which are overseen by the bulk EfOM. Furthermore, they may explain our previous observations that in the presence of dissolved organic matter, micropollutant filtration by GAC columns was reduced, while their filtration by composite columns remained high.

Sacubitril/Valsartan: A Novel Cardiovascular Combination Agent.

PubMed

Sible, Alexandra M; Nawarskas, James J; Alajajian, David; Anderson, Joe R

2016-01-01

Sacubitril/valsartan [LCZ696 (Entresto), Novartis Pharmaceuticals Corp.] is the first in a new class of drugs that combines neprilysin inhibition with angiotensin II receptor antagonism, the combination of which acts to increase endogenous natriuretic peptides while inhibiting the renin-angiotensin-aldosterone system. Sacubitril/valsartan has been studied in the treatment of hypertension, heart failure with reduced ejection fraction (HFrEF), and heart failure with preserved ejection fraction (HFpEF) and has demonstrated clinical efficacy in blood pressure reduction in hypertensive patients with and without HFpEF and a reduction in hospitalizations and mortality for patients with HFrEF. Research to evaluate clinical outcomes in HFpEF is ongoing. Sacubitril/valsartan is approved to reduce hospitalization and risk of cardiovascular death for patients with HFrEF in New York Heart Association (NYHA) functional class II-IV. The product is as well tolerated as an angiotensin-converting enzyme inhibitor, with the most common side effect being hypotension. Expectedly, it is much more costly than generic angiotensin-converting enzyme inhibitors or angiotensin receptor antagonists, which will be a factor in determining how widespread the use of this agent will be. In summary, although the number of published studies evaluating its use is limited, sacubitril/valsartan represents a promising new treatment option for patients with HFrEF. Ongoing studies will continue to refine the role of this agent in clinical practice.

A randomized trial of teen online problem solving for improving executive function deficits following pediatric traumatic brain injury.

PubMed

Wade, Shari L; Walz, Nicolay C; Carey, JoAnne; Williams, Kendra M; Cass, Jennifer; Herren, Luke; Mark, Erin; Yeates, Keith Owen

2010-01-01

To examine the efficacy of teen online problem solving (TOPS) in improving executive function (EF) deficits following traumatic brain injury (TBI) in adolescence. Families of adolescents (aged 11-18 years) with moderate to severe TBI were recruited from the trauma registry of 2 tertiary-care children's hospitals and then randomly assigned to receive TOPS (n = 20), a cognitive-behavioral, skill-building intervention, or access to online resources regarding TBI (Internet resource comparison; n = 21). Parent and teen reports of EF were assessed at baseline and a posttreatment follow-up (mean = 7.88 months later). Improvements in self-reported EF skills were moderated by TBI severity, with teens with severe TBI in the TOPS treatment reporting significantly greater improvements than did those with severe TBI in the Internet resource comparison. The treatment groups did not differ on parent ratings of EF at the follow up. Findings suggest that TOPS may be effective in improving EF skills among teens with severe TBI.

Concurrent production of biodiesel and chemicals through wet in situ transesterification of microalgae.

PubMed

Im, Hanjin; Kim, Bora; Lee, Jae W

2015-10-01

This work addresses an unprecedented way of co-producing biodiesel (FAEE) and valuable chemicals of ethyl levulinate (EL), ethyl formate (EF) and diethyl ether (DEE) from wet in situ transesterification of microalgae. EL, EF, and DEE were significantly produced up to 23.1%, 10.3%, and 52.1% of the maximum FAEE mass with the FAEE yield higher than 90% at 125 °C. Experiments to elucidate a detailed route of EL and EF synthesis were fulfilled and it was found that its main route to the production of EL and EF was the acid hydrolysis of algal cells and esterification with ethanol. To investigate the effect of reaction variables on the products yields, comprehensive experiments were carried out with varying temperatures, solvent and alcohol volumes, moisture contents and catalyst amounts. Coproduction of DEE, EL, EF and FAEE can contribute to elevating the economic feasibility of microalgae-based biodiesel supply chain. Copyright © 2015 Elsevier Ltd. All rights reserved.

Phosphorylation of eukaryotic elongation factor 2 (eEF2) by cyclin A-cyclin-dependent kinase 2 regulates its inhibition by eEF2 kinase.

PubMed

Hizli, Asli A; Chi, Yong; Swanger, Jherek; Carter, John H; Liao, Yi; Welcker, Markus; Ryazanov, Alexey G; Clurman, Bruce E

2013-02-01

Protein synthesis is highly regulated via both initiation and elongation. One mechanism that inhibits elongation is phosphorylation of eukaryotic elongation factor 2 (eEF2) on threonine 56 (T56) by eEF2 kinase (eEF2K). T56 phosphorylation inactivates eEF2 and is the only known normal eEF2 functional modification. In contrast, eEF2K undergoes extensive regulatory phosphorylations that allow diverse pathways to impact elongation. We describe a new mode of eEF2 regulation and show that its phosphorylation by cyclin A-cyclin-dependent kinase 2 (CDK2) on a novel site, serine 595 (S595), directly regulates T56 phosphorylation by eEF2K. S595 phosphorylation varies during the cell cycle and is required for efficient T56 phosphorylation in vivo. Importantly, S595 phosphorylation by cyclin A-CDK2 directly stimulates eEF2 T56 phosphorylation by eEF2K in vitro, and we suggest that S595 phosphorylation facilitates T56 phosphorylation by recruiting eEF2K to eEF2. S595 phosphorylation is thus the first known eEF2 modification that regulates its inhibition by eEF2K and provides a novel mechanism linking the cell cycle machinery to translational control. Because all known eEF2 regulation is exerted via eEF2K, S595 phosphorylation may globally couple the cell cycle machinery to regulatory pathways that impact eEF2K activity.

Phosphorylation of Eukaryotic Elongation Factor 2 (eEF2) by Cyclin A–Cyclin-Dependent Kinase 2 Regulates Its Inhibition by eEF2 Kinase

PubMed Central

Hizli, Asli A.; Chi, Yong; Swanger, Jherek; Carter, John H.; Liao, Yi; Welcker, Markus; Ryazanov, Alexey G.

2013-01-01

Protein synthesis is highly regulated via both initiation and elongation. One mechanism that inhibits elongation is phosphorylation of eukaryotic elongation factor 2 (eEF2) on threonine 56 (T56) by eEF2 kinase (eEF2K). T56 phosphorylation inactivates eEF2 and is the only known normal eEF2 functional modification. In contrast, eEF2K undergoes extensive regulatory phosphorylations that allow diverse pathways to impact elongation. We describe a new mode of eEF2 regulation and show that its phosphorylation by cyclin A–cyclin-dependent kinase 2 (CDK2) on a novel site, serine 595 (S595), directly regulates T56 phosphorylation by eEF2K. S595 phosphorylation varies during the cell cycle and is required for efficient T56 phosphorylation in vivo. Importantly, S595 phosphorylation by cyclin A-CDK2 directly stimulates eEF2 T56 phosphorylation by eEF2K in vitro, and we suggest that S595 phosphorylation facilitates T56 phosphorylation by recruiting eEF2K to eEF2. S595 phosphorylation is thus the first known eEF2 modification that regulates its inhibition by eEF2K and provides a novel mechanism linking the cell cycle machinery to translational control. Because all known eEF2 regulation is exerted via eEF2K, S595 phosphorylation may globally couple the cell cycle machinery to regulatory pathways that impact eEF2K activity. PMID:23184662

Review and analysis of global agricultural N₂O emissions relevant to the UK.

PubMed

Buckingham, S; Anthony, S; Bellamy, P H; Cardenas, L M; Higgins, S; McGeough, K; Topp, C F E

2014-07-15

As part of a UK government funded research project to update the UK N2O inventory methodology, a systematic review of published nitrous oxide (N2O) emission factors was carried out of non-UK research, for future comparison and synthesis with the UK measurement based evidence base. The aim of the study is to assess how the UK IPCC default emission factor for N2O emissions derived from synthetic or organic fertiliser inputs (EF1) compares to international values reported in published literature. The availability of data for comparing and/or refining the UK IPCC default value and the possibility of analysing sufficient auxiliary data to propose a Tier 2 EF1 reporting strategy is evaluated. The review demonstrated a lack of consistency in reporting error bounds for fertiliser-derived EFs and N2O flux data with 8% and 44% of publications reporting EF and N2O flux error bounds respectively. There was also poor description of environmental (climate and soil) and experimental design auxiliary data. This is likely to be due to differences in study objectives, however potential improvements to soil parameter reporting are proposed. The review demonstrates that emission factors for agricultural-derived N2O emissions ranged -0.34% to 37% showing high variation compared to the UK Tier 1 IPCC EF1 default values of 1.25% (IPCC 1996) and 1% (IPPC 2006). However, the majority (83%) of EFs reported for UK-relevant soils fell within the UK IPCC EF1 uncertainty range of 0.03% to 3%. Residual maximum likelihood (REML) analysis of the data collated in the review showed that the type and rate of fertiliser N applied and soil type were significant factors influencing EFs reported. Country of emission, the length of the measurement period, the number of splits, the crop type, pH and SOC did not have a significant impact on N2O emissions. A subset of publications where sufficient data was reported for meta-analysis to be conducted was identified. Meta-analysis of effect sizes of 41 treatments demonstrated that the application of fertiliser has a significant effect on N2O emissions in comparison to control plots and that emission factors were significantly different to zero. However no significant relationships between the quantity of fertiliser applied and the effect size of the amount of N2O emitted from fertilised plots compared to control plots were found. Annual addition of fertiliser of 35 to 557 kg N/ha gave a mean increase in emissions of 2.02 ± 0.28 g N2O/ha/day compared to control treatments (p<0.01). Emission factors were significantly different from zero, with a mean emission factor estimated directly from the meta analysis of 0.17 ± 0.02%. This is lower than the IPCC 2006 Tier 1 EF1 value of 1% but falling within the uncertainty bound for the IPCC 2006 Tier 1 EF1 (0.03% to 3%). As only a small number of papers were viable for meta analysis to be conducted due to lack of reporting of the key controlling factors, the estimates of EF in this paper cannot include the true variability under conditions similar to the UK. Review-derived EFs of 0.34% to 37% and mean EF from meta-analysis of 0.17 ± 0.02% highlight variability in reporting EFs depending on the method applied and sample size. A protocol of systematic reporting of N2O emissions and key auxiliary parameters in publications across disciplines is proposed. If adopted this would strengthen the community to inform IPCC Tier 2 reporting development and reduce the uncertainty surrounding reported UK N2O emissions. Copyright © 2014 Elsevier B.V. All rights reserved.

Children's Executive Function in a CPS-Involved Sample: Effects of Cumulative Adversity and Specific Types of Adversity.

PubMed

Roos, Leslie E; Kim, Hyoun K; Schnabler, Simone; Fisher, Philip A

2016-12-01

Prior research has identified the presence of executive function (EF) deficits in child protective service (CPS) involved (versus non-involved) children but minimal work has examined predictors that might explain individual differences within these CPS-involved children. Here, we sought to characterize EF in a large sample (N=694) of CPS-involved children and examine how specific adversities (physical abuse, neglect, caregiver domestic violence, and caregiver substance dependence) and cumulative adversity (at ages 0-3 and 3-6 years) predict EF (at approximately 5-6 years). It was expected that the sample would exhibit low EF overall based on previous research in maltreated children. Specific adversity and cumulative adversity analyses were largely exploratory given the limited previous work in this area. Results indicated poor EF overall, with 43.5% of children performing worse than chance. Amongst children who performed greater than chance, higher cumulative adversity, physical abuse, and caregiver substance use (at ages 3-6 years) predicted better EF. These findings join literature documenting that, within CPS-involved children, the presence of certain adversities predicts variable cognitive function. Findings highlight the potential relevance of evolutionary psychology to understanding how alterations in behavior linked to harsh and unpredictable early environments may cue accelerated brain development underlying relative cognitive advantages, within at-risk, low performing samples. Longitudinal studies are critical to determine if the relative EF advantages linked to higher adversity persist over time or result in lower EF later on, reflecting a more rapid, but overall limited, trajectory of cognitive development.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Paz-Soldan, C.; La Haye, R. J.; Shiraki, D.

DIII-D plasmas at very low density exhibit onset of n=1 error field (EF) penetration (the `low-density locked mode') not at a critical density or EF, but instead at a critical level of runaway electron (RE) intensity. Raising the density during a discharge does not avoid EF penetration, so long as RE growth proceeds to the critical level. Penetration is preceded by non-thermalization of the electron cyclotron emission, anisotropization of the total pressure, synchrotron emission shape changes, as well as decreases in the loop voltage and bulk thermal electron temperature. The same phenomena occur despite various types of optimal EF correction,more » and in some cases modes are born rotating. Similar phenomena are also found at the low-density limit in JET. These results stand in contrast to the conventional interpretation of the low-density stability limit as being due to residual EFs and demonstrate a new pathway to EF penetration instability due to REs. Existing scaling laws for penetration project to increasing EF sensitivity as bulk temperatures decrease, though other possible mechanisms include classical tearing instability, thermo-resistive instability, and pressure-anisotropy driven instability. Regardless of first-principles mechanism, known scaling laws for Ohmic energy confinement combined with theoretical RE production rates allow rough extrapolation of the RE criticality condition, and thus, the low-density limit to other tokamaks. Furthermore, the extrapolated low-density limit by this pathway decreases with increasing machine size and is considerably below expected operating conditions for ITER. While likely unimportant for ITER, this effect can explain the low-density limit of existing tokamaks operating with small residual EFs.« less

Repetitive Transcranial Magnetic Stimulation for the Treatment of Executive Function Deficits in Autism Spectrum Disorder: Clinical Trial Approach.

PubMed

Ameis, Stephanie H; Daskalakis, Zafiris J; Blumberger, Daniel M; Desarkar, Pushpal; Drmic, Irene; Mabbott, Donald J; Lai, Meng-Chuan; Croarkin, Paul E; Szatmari, Peter

2017-06-01

Executive function (EF) deficits in patients with autism spectrum disorder (ASD) are ubiquitous and understudied. Further, there are no effective, neuroscience-based treatments to address this impairing feature of ASD. Repetitive transcranial magnetic stimulation (rTMS) has demonstrated promise in addressing EF deficits in adult neuropsychiatric disorders. This article will outline the design of a novel randomized-controlled trial of bilateral, 20 Hz, rTMS applied to the dorsolateral prefrontal cortex (DLPFC) for treatment of EF deficits in ASD that is currently ongoing. We describe prior therapeutic rTMS research for ASD and prior rTMS trials targeting EFs in adult neuropsychiatric disorders. A neurophysiological rationale for rTMS treatment of EF deficits in ASD is presented. An ongoing protocol will enroll participants aged 16-35 with ASD and no intellectual disability. Psychotropic medications will be continued during the 4-week trial of active 20 Hz versus sham rTMS applied to the DLPFC. Twenty, active treatment sessions consisting of 25 stimulation trains at a 90% motor threshold will be administered. The primary outcome measure is the Cambridge Neuropsychological Test Automated Battery (CANTAB) spatial working memory task. At present, recruitment, enrollment, and treatment within the described clinical trial are ongoing. EF deficits are common and impairing symptoms of ASD. There are no evidence-based treatments for EF deficits in ASD. The protocol described here will provide important preliminary data on the feasibility and efficacy of 20 Hz rTMS to DLPFC for EF deficits in ASD.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Patil, Swapnil M.; Chandanshive, Vishal V.; Rane, Niraj R.

In vitro grown untransformed adventitious roots (AR) culture of Ipomoea hederifolia and its endophytic fungus (EF) Cladosporium cladosporioides decolorized Navy Blue HE2R (NB-HE2R) at a concentration of 20 ppm up to 83.3 and 65%, respectively within 96 h. Whereas the AR-EF consortium decolorized the dye more efficiently and gave 97% removal within 36 h. Significant inductions in the enzyme activities of lignin peroxidase, tyrosinase and laccase were observed in roots, while enzymes like tyrosinase, laccase and riboflavin reductase activities were induced in EF. Metabolites of dye were analyzed using UV—vis spectroscopy, FTIR and gas chromatography-mass spectrometry. Possible metabolic pathways ofmore » NB-HE2R were proposed with AR, EF and AR-EF systems independently. Looking at the superior efficacy of AR-EF system, a rhizoreactor was developed for the treatment of NB-HE2R at a concentration of 1000 ppm. Control reactor systems with independently grown AR and EF gave 94 and 85% NB-HE2R removal, respectively within 36 h. The AR-EF rhizoreactor, however, gave 97% decolorization. The endophyte colonization additionally increased root and shoot lengths of candidate plants through mutualism. Combined bioreactor strategies can be effectively used for future eco-friendly remediation purposes. - Highlights: • Endophytic fungus on Ipomoea hederifolia promotes root growth and shoot development • Endophytic Cladosporium cladosporioides synergistically degrade Navy Blue-HE2R dye • Endophyte colonized I. hederifolia roots proved superior in dye decolorization • Dye stress and toxicity was efficiently dealt by root-endophyte consortium • Root-endophyte consortium can be used as a sustainable remediation strategy.« less

Flavanol-rich cocoa consumption enhances exercise-induced executive function improvements in humans.

PubMed

Tsukamoto, Hayato; Suga, Tadashi; Ishibashi, Aya; Takenaka, Saki; Tanaka, Daichi; Hirano, Yoshitaka; Hamaoka, Takafumi; Goto, Kazushige; Ebi, Kumiko; Isaka, Tadao; Hashimoto, Takeshi

2018-02-01

Aerobic exercise is known to acutely improve cognitive functions, such as executive function (EF) and memory function (MF). Additionally, consumption of flavanol-rich cocoa has been reported to acutely improve cognitive function. The aim of this study was to determine whether high cocoa flavanol (CF; HCF) consumption would enhance exercise-induced improvement in cognitive function. To test this hypothesis, we examined the combined effects of HCF consumption and moderate-intensity exercise on EF and MF during postexercise recovery. Ten healthy young men received either an HCF (563 mg of CF) or energy-matched low CF (LCF; 38 mg of CF) beverage 70 min before exercise in a single-blind counterbalanced manner. The men then performed moderate-intensity cycling exercise at 60% of peak oxygen uptake for 30 min. The participants performed a color-word Stroop task and face-name matching task to evaluate EF and MF, respectively, during six time periods throughout the experimental session. EF significantly improved immediately after exercise compared with before exercise in both conditions. However, EF was higher after HCF consumption than after LCF consumption during all time periods because HCF consumption improved EF before exercise. In contrast, HCF consumption and moderate-intensity exercise did not improve MF throughout the experiment. The present findings demonstrated that HCF consumption before moderate-intensity exercise could enhance exercise-induced improvement in EF, but not in MF. Therefore, we suggest that the combination of HCF consumption and aerobic exercise may be beneficial for improving EF. Copyright © 2017 Elsevier Inc. All rights reserved.

Impact of penile rehabilitation with low-dose vardenafil on recovery of erectile function in Japanese men following nerve-sparing radical prostatectomy

PubMed Central

Nakano, Yuzo; Miyake, Hideaki; Chiba, Koji; Fujisawa, Masato

2014-01-01

Erectile dysfunction (ED) is a major complication after radical prostatectomy (RP); however, debate continues regarding the efficacy of penile rehabilitation in the recovery of the postoperative erectile function (EF). This study included a total of 103 consecutive sexually active Japanese men with localized prostate cancer undergoing nerve-sparing RP, and analyzed the postoperative EF, focusing on the significance of penile rehabilitation. In this series, 24 and 79 patients underwent bilateral and unilateral nerve-sparing RPs, respectively, and 10 or 20 mg of vardenafil was administered to 35 patients at least once weekly, who agreed to undergo penile rehabilitation. Twelve months after RP, 48 (46.6%) of the 103 patients were judged to have recovered EF sufficient for sexual intercourse without any assistance. The proportion of patients who recovered EF in those undergoing penile rehabilitation (60.0%) was significantly greater than that in those without penile rehabilitation (38.2%). Of several parameters examined, the preoperative International Index of Erectile Function-5 (IIEF-5) score and nerve-sparing procedure were significantly associated with the postoperative EF recovery rates in patients with and without management by penile rehabilitation, respectively. Furthermore, univariate analysis identified the preoperative IIEF-5 score, nerve-sparing procedure and penile rehabilitation as significant predictors of EF recovery, among which the preoperative IIEF-5 score and nerve-sparing procedure appeared to be independently associated with EF recovery. Considering these findings, despite the lack of independent significance, penile rehabilitation with low-dose vardenafil could exert a beneficial effect on EF recovery in Japanese men following nerve-sparing RP. PMID:24994781

Efficiency analysis of the electrocoagulation and electroflotation treatment of poultry slaughterhouse wastewater using aluminum and graphite anodes.

PubMed

Paulista, Larissa Oliveira; Presumido, Pedro Henrique; Theodoro, Joseane Debora Peruço; Pinheiro, Alexei Lorenzetti Novaes

2018-05-08

The application of electrocoagulation (EC) and electroflotation (EF) was investigated for the treatment of poultry slaughterhouse wastewater in a bench scale unit cell electrolyzer with different EC-to-EF ratios at current densities of 3, 9, and 15 mA cm -2 . The EC-to-EF ratio was controlled by current reversal using aluminum and graphite electrodes. The electrochemical treatment showed satisfactory removal efficiencies for Al coagulant loads greater than 51.8 mg L -1 . The 4/5 EC to EF ratio (69.1 mg L -1 Al and 32.2 NmL L -1 additional EF gas) and 3/5 (51.8 mg L -1 Al/64 NmL L -1 additional EF gas) presented the best results for the removal of COD (76-85%), color (93-99%), and turbidity (95-99%), with the additional benefit of reducing the electrode consumption and sludge disposal costs proportionally to the EC-to-EF ratio. The effects of the EC-to-EF ratio and the current density on efficiency of the electrochemical treatment for the removal of COD, apparent color, turbidity, TSS, TSD, and NH 3 -N were discussed in the light of the physicochemical and electrochemical processes underlying the removal mechanism for each parameter. In particular, the blow-off mechanism seems to play an important role in the NH 3 -N removal, whereas indirect electrooxidation mechanism accounts for a fraction of the soluble COD removal for the electrodes configuration used in the treatment.

Electroflotation

NASA Astrophysics Data System (ADS)

Chen, Xueming; Chen, Guohua

Electroflotation (EF) is the flotation using electrolytically generated bubbles of hydrogen and oxygen for separating suspended substances from aqueous phases. This process was first proposed by Elmore in 1905 for flotation of valuable minerals from ores. Compared with the conventional dissolved air flotation (DAF), EF has many advantages, including high flotation efficiency, compact units, easy operation, and less maintenance. Therefore, EF is an attractive alternative to DAF. This technique has been proven very effective in treating oily wastewater or oil-water emulsion, mining wastewater, groundwater, food processing wastewater, restaurant wastewater, industrial sewage, heavy metals containing effluent, and many other water and wastewaters.

Exploratory Decision-Tree Modeling of Data from the Randomized REACTT Trial of Tadalafil Versus Placebo to Predict Recovery of Erectile Function After Bilateral Nerve-Sparing Radical Prostatectomy.

PubMed

Montorsi, Francesco; Oelke, Matthias; Henneges, Carsten; Brock, Gerald; Salonia, Andrea; d'Anzeo, Gianluca; Rossi, Andrea; Mulhall, John P; Büttner, Hartwig

2016-09-01

Understanding predictors for the recovery of erectile function (EF) after nerve-sparing radical prostatectomy (nsRP) might help clinicians and patients in preoperative counseling and expectation management of EF rehabilitation strategies. To describe the effect of potential predictors on EF recovery after nsRP by post hoc decision-tree modeling of data from A Study of Tadalafil After Radical Prostatectomy (REACTT). Randomized double-blind double-dummy placebo-controlled trial in 423 men aged <68 yr with adenocarcinoma of the prostate (Gleason ≤7, normal preoperative EF) who underwent nsRP at 50 centers from nine European countries and Canada. Postsurgery 1:1:1 randomization to 9-mo double-blind treatment with tadalafil 5mg once a day (OaD), tadalafil 20mg on demand, or placebo, followed by a 6-wk drug-free-washout, and a 3-mo open-label tadalafil OaD treatment. Three decision-tree models, using the International Index of Erectile Function-Erectile Function (IIEF-EF) domain score at the end of double-blind treatment, washout, and open-label treatment as response variable. Each model evaluated the association between potential predictors: presurgery IIEF domain and IIEF single-item scores, surgical approach, nerve-sparing score (NSS), and postsurgery randomized treatment group. The first decision-tree model (n=422, intention-to-treat population) identified high presurgery sexual desire (IIEF item 12: ≥3.5 and <3.5) as the key predictor for IIEF-EF at the end of double-blind treatment (mean IIEF-EF: 14.9 and 11.1), followed by high confidence to get and maintain an erection (IIEF item 15: ≥3.5 and <3.5; IIEF-EF: 15.4 and 7.1). For patients meeting these criteria, additional non-IIEF-related predictors included robot-assisted laparoscopic surgery (yes or no; IIEF-EF: 19.3 and 12.6), quality of nerve sparing (NSS: <2.5 and ≥2.5; IIEF-EF: 14.3 and 10.5), and treatment with tadalafil OaD (yes and no; IIEF-EF: 17.6 and 14.3). Additional analyses after washout and open-label treatment identified high presurgery intercourse satisfaction as the key predictor. Exploratory decision-tree analyses identified high presurgery sexual desire, confidence, and intercourse satisfaction as key predictors for EF recovery. Patients meeting these criteria might benefit the most from conserving surgery and early postsurgery EF rehabilitation. Strategies for improving EF after surgery should be discussed preoperatively with all patients; this information may support expectation management for functional recovery on an individual patient level. Understanding how patient characteristics and different treatment options affect the recovery of erectile function (EF) after radical surgery for prostate cancer might help physicians select the optimal treatment for their patients. This analysis of data from a clinical trial suggested that high presurgery sexual desire, sexual confidence, and intercourse satisfaction are key factors predicting EF recovery. Patients meeting these criteria might benefit the most from conserving surgery (robot-assisted surgery, perfect nerve sparing) and postsurgery medical rehabilitation of EF. ClinicalTrials.gov, NCT01026818. Copyright © 2016. Published by Elsevier B.V.

[Construction and expression of recombinant lentiviral vectors of AKT2,PDK1 and BAD].

PubMed

Zhu, Jing; Chen, Bo-Jiang; Huang, Na; Li, Wei-Min

2014-03-01

To construct human protein kinase B (ATK2), phosphoinositide-dependent kinase 1 (PDK1) and bcl-2-associated death protein (BAD) lentiviral expression vector, and to determine their expressions in 293T cells. Total RNA was extracted from lung cancer tissues. The full-length coding regions of human ATK2, BAD and PDK1 cDNA were amplified via RT-PCR using specific primers, subcloned into PGEM-Teasy and then sequenced for confirmation. The full-length coding sequence was cut out with a specific restriction enzyme digest and subclone into pCDF1-MCS2-EF1-copGFP. The plasmids were transfected into 293T cells using the calcium phosphate method. The over expression of AKT2, BAD and PDK1 were detected by Western blot. AKT2, PDK1 and BAD were subcloned into pCDF1-MCS2-EF1-copGFP, with an efficiency of transfection of 100%, 95%, and 90% respectively. The virus titers were 6.7 x 10(6) PFU/mL in the supernatant. After infection, the proteins of AKT2, PDK1 and BAD were detected by Western blot. The lentivial vector pCDF1-MCS2-EF1-copGFP containing AKT2, BAD and PDK1 were successfully constructed and expressed in 293T cells.

Math practice and its influence on math skills and executive functions in adolescents with mild to borderline intellectual disability.

PubMed

Jansen, Brenda R J; De Lange, Eva; Van der Molen, Mariët J

2013-05-01

Adolescents with mild to borderline intellectual disability (MBID) often complete schooling without mastering basic math skills, even though basic math is essential for math-related challenges in everyday life. Limited attention to cognitive skills and low executive functioning (EF) may cause this delay. We aimed to improve math skills in an MBID-sample using computerized math training. Also, it was investigated whether EF and math performance were related and whether computerized math training had beneficial effects on EF. The sample consisted of a total of 58 adolescents (12-15 years) from special education. Participants were randomly assigned to either the experimental group or a treatment as usual (TAU) group. In the experimental condition, participants received 5 weeks of training. Math performance and EF were assessed before and after the training period. Math performance improved equally in both groups. However, frequently practicing participants improved more than participants in the control group. Visuo-spatial memory skills were positively related to addition and subtraction skills. Transfer effects from math training to EF were absent. It is concluded that math skills may increase if a reasonable effort in practicing math skills is made. The relation between visuo-spatial memory skills provides opportunities for improving math performance. Copyright © 2013 Elsevier Ltd. All rights reserved.

Heart rate-induced modifications of concentric left ventricular hypertrophy: exploration of a novel therapeutic concept.

PubMed

Klein, Franziska J; Bell, Stephen; Runte, K Elisabeth; Lobel, Robert; Ashikaga, Takamuru; Lerman, Lilach O; LeWinter, Martin M; Meyer, Markus

2016-10-01

Lowering the heart rate is considered to be beneficial in heart failure (HF) with reduced ejection fraction (HFrEF). In a dilated left ventricle (LV), pharmacological heart rate lowering is associated with a reduction in LV chamber size. In patients with HFrEF, this structural change is associated with better survival. HF with preserved ejection fraction (HFpEF) is increasingly prevalent but, so far, without any evidence-based treatment. HFpEF is typically associated with LV concentric remodeling and hypertrophy. The effects of heart rate on this structural phenotype are not known. Analogous with the benefits of a low heart rate on a dilated heart, we hypothesized that increased heart rates could lead to potentially beneficial remodeling of a concentrically hypertrophied LV. This was explored in an established porcine model of concentric LV hypertrophy and fibrosis. Our results suggest that a moderate increase in heart rate can be used to reduce wall thickness, normalize LV chamber volumes, decrease myocardial fibrosis, and improve LV compliance. Our results also indicate that the effects of heart rate can be titrated, are reversible, and do not induce HF. These findings may provide the rationale for a novel therapeutic approach for HFpEF and its antecedent disease substrate. Copyright © 2016 the American Physiological Society.

Identifying balance and fall risk in community-dwelling older women: the effect of executive function on postural control.

PubMed

Muir-Hunter, Susan W; Clark, Jennifer; McLean, Stephanie; Pedlow, Sam; Van Hemmen, Alysia; Montero Odasso, Manuel; Overend, Tom

2014-01-01

The mechanisms linking cognition, balance function, and fall risk among older adults are not fully understood. An evaluation of the effect of cognition on balance tests commonly used in clinical practice to assess community-dwelling older adults could enhance the identification of at-risk individuals. The study aimed to determine (1) the association between cognition and clinical tests of balance and (2) the relationship between executive function (EF) and balance under single- and dual-task testing. Participants (24 women, mean age of 76.18 [SD 16.45] years) completed six clinical balance tests, four cognitive tests, and two measures of physical function. Poor balance function was associated with poor performance on cognitive testing of EF. In addition, the association with EF was strongest under the dual-task timed up-and-go (TUG) test and the Fullerton Advanced Balance Scale. Measures of global cognition were associated only with the dual-task performance of the TUG. Postural sway measured with the Standing Balance Test, under single- or dual-task test conditions, was not associated with cognition. Decreased EF was associated with worse performance on functional measures of balance. The relationship between EF and balance was more pronounced with dual-task testing using a complex cognitive task combined with the TUG.

Intervention for Executive Functions Development in Early Elementary School Children: Effects on Learning and Behaviour, and Follow-Up Maintenance

ERIC Educational Resources Information Center

Dias, Natália Martins; Seabra, Alessandra Gotuzo

2017-01-01

Executive functions (EF) can be promoted by classroom interventions. Our study investigated whether (a) an intervention conducted by teachers improves EF in children; (b) there are effects on behaviour and academic achievement; and (c) there are stable benefits in a one-year follow-up. Fifty-eight first-graders, divided into experimental (EG = 28)…

Avoiding the side effects of electric current pulse application to electroporated cells in disposable small volume cuvettes assures good cell survival.

PubMed

Grys, Maciej; Madeja, Zbigniew; Korohoda, Włodzimierz

2017-01-01

The harmful side effects of electroporation to cells due to local changes in pH, the appearance of toxic electrode products, temperature increase, and the heterogeneity of the electric field acting on cells in the cuvettes used for electroporation were observed and discussed in several laboratories. If cells are subjected to weak electric fields for prolonged periods, for example in experiments on cell electrophoresis or galvanotaxis the same effects are seen. In these experiments investigators managed to reduce or eliminate the harmful side effects of electric current application. For the experiments, disposable 20 μl cuvettes with two walls made of dialysis membranes were constructed and placed in a locally focused electric field at a considerable distance from the electrodes. Cuvettes were mounted into an apparatus for horizontal electrophoresis and the cells were subjected to direct current electric field (dcEF) pulses from a commercial pulse generator of exponentially declining pulses and from a custom-made generator of double and single rectangular pulses. More than 80% of the electroporated cells survived the dcEF pulses in both systems. Side effects related to electrodes were eliminated in both the flow through the dcEF and in the disposable cuvettes placed in the focused dcEFs. With a disposable cuvette system, we also confirmed the sensitization of cells to a dcEF using procaine by observing the loading of AT2 cells with calceine and using a square pulse generator, applying 50 ms single rectangular pulses. We suggest that the same methods of avoiding the side effects of electric current pulse application as in cell electrophoresis and galvanotaxis should also be used for electroporation. This conclusion was confirmed in our electroporation experiments performed in conditions assuring survival of over 80% of the electroporated cells. If the amplitude, duration, and shape of the dcEF pulse are known, then electroporation does not depend on the type of pulse generator. This knowledge of the characteristics of the pulse assures reproducibility of electroporation experiments using different equipment.

Selection of suitable soybean EF1α genes as internal controls for real-time PCR analyses of tissues during plant development and under stress conditions.

PubMed

Saraiva, Kátia D C; Fernandes de Melo, Dirce; Morais, Vanessa D; Vasconcelos, Ilka M; Costa, José H

2014-09-01

The EF1α genes were stable in the large majority of soybean tissues during development and in specific tissues/conditions under stress. Quantitative real-time PCR (qPCR) analysis strongly depends on transcript normalization using stable reference genes. Reference genes are generally encoded by multigene families and are used in qPCR normalization; however, little effort has been made to verify the stability of different gene members within a family. Here, the expression stability of members of the soybean EF1α gene family (named EF1α 1a1, 1a2, 1b, 2a, 2b and 3) was evaluated in different tissues during plant development and stress exposure (SA and PEG). Four genes (UKN1, SKIP 16, EF1β and MTP) already established as stably expressed were also used in the comparative analysis. GeNorm analyses revealed different combinations of reference genes as stable in soybean tissues during development. The EF1α genes were the most stable in cotyledons (EF1α 3 and EF1α 1b), epicotyls (EF1α 1a2, EF1α 2b and EF1α 1a1), hypocotyls (EF1α 1a1 and EF1β), pods (EF1α 2a and EF1α 2b) and roots (EF1α 2a and UKN1) and less stable in tissues such as trifoliate and unifoliate leaves and germinating seeds. Under stress conditions, no suitable combination including only EF1α genes was found; however, some genes were relatively stable in leaves (EF1α 1a2) and roots (EF1α 1a1) treated with SA as well as in roots treated with PEG (EF1α 2b). EF1α 2a was the most stably expressed EF1α gene in all soybean tissues under stress. Taken together, our data provide guidelines for the selection of EF1α genes for use as reference genes in qPCR expression analyses during plant development and under stress conditions.

Carbon monoxide contributes to the constipating effects of granisetron in rat colon.

PubMed

Nacci, Carmela; Fanelli, Margherita; Potenza, Maria Assunta; Leo, Valentina; Montagnani, Monica; De Salvia, Maria Antonietta

2016-11-14

To investigate the mechanisms underlying the potential contribution of the heme oxygenase/carbon monoxide (HO/CO) pathway in the constipating effects of granisetron. For in vivo studies, gastrointestinal motility was evaluated in male rats acutely treated with granisetron [25, 50, 75 μg/kg/subcutaneous (sc)], zinc protoporphyrin IX [ZnPPIX, 50 μg/kg/intraperitoneal (ip)] and hemin (50 μmol/L/kg/ip), alone or in combination. For in vitro studies, the contractile neurogenic response to electrical field stimulation (EFS, 3, 5, 10 Hz, 14 V, 1 ms, pulse trains lasting 10 s), as well as the contractile myogenic response to acetylcholine (ACh, 0.1-100 μmol/L) were evaluated on colon specimens incubated with granisetron (3 μmol/L, 15 min), ZnPPIX (10 μmol/L, 60 min) or CO-releasing molecule-3 (CORM-3, 100, 200, 400 μmol/L) alone or in combination. These experiments were performed under co-treatment with or without atropine (3 μmol/L, a muscarinic receptor antagonist) or N G -nitro-L-Arginine (L-NNA, 100 μmol/L, a nitric oxide synthase inhibitor). Administration of granisetron (50, 75 μg/kg) in vivo significantly increased the time to first defecation ( P = 0.045 vs vehicle-treated rats), clearly suggesting a constipating effect of this drug. Although administration of ZnPPIX or hemin alone had no effect on this gastrointestinal motility parameter, ZnPPIX co-administered with granisetron abolished the granisetron-induced constipation. On the other hand, co-administration of hemin and granisetron did not modify the increased constipation observed under granisetron alone. When administered in vitro , granisetron alone (3 μmol/L) did not significantly modify the colon's contractile response to either EFS or ACh. Incubation with ZnPPIX alone (10 μmol/L) significantly reduced the colon's contractile response to EFS ( P = 0.016) but had no effect on contractile response to ACh. Co-administration of ZnPPIX and atropine (3 μmol/L) abolished the ZnPPIX-mediated decrease in contractile response to EFS. Conversely, incubation with CORM-3 (400 μmol/L) alone increased both the contractile response to EFS at 10 Hz (10 Hz: 71.02 ± 19.16 vs 116.25 ± 53.70, P = 0.01) and the contractile response to ACh (100 μmol/L) ( P = 0.012). Co-administration of atropine abolished the CORM-3-mediated effects on the EFS-mediated response. When granisetron was co-incubated in vitro with ZnPPIX, the ZnPPIX-mediated decrease in colon contractile response to EFS was lost. On the other hand, co-incubation of granisetron and CORM-3 (400 μmol/L) further increased the colon's contractile response to EFS (at 5 Hz: P = 0.007; at 10 Hz: P = 0.001) and to ACh (ACh 10 μmol/L: P = 0.001; ACh 100 μmol/L: P = 0.001) elicited by CORM-3 alone. L-NNA co-administered with granisetron and CORM-3 abolished the potentiating effect of CORM-3 on granisetron on both the EFS-induced and ACh-induced contractile response. Taken together, findings from in vivo and in vitro studies suggest that the HO/CO pathway is involved in the constipating effects of granisetron.

Carbon monoxide contributes to the constipating effects of granisetron in rat colon

PubMed Central

Nacci, Carmela; Fanelli, Margherita; Potenza, Maria Assunta; Leo, Valentina; Montagnani, Monica; De Salvia, Maria Antonietta

2016-01-01

AIM To investigate the mechanisms underlying the potential contribution of the heme oxygenase/carbon monoxide (HO/CO) pathway in the constipating effects of granisetron. METHODS For in vivo studies, gastrointestinal motility was evaluated in male rats acutely treated with granisetron [25, 50, 75 μg/kg/subcutaneous (sc)], zinc protoporphyrin IX [ZnPPIX, 50 μg/kg/intraperitoneal (ip)] and hemin (50 μmol/L/kg/ip), alone or in combination. For in vitro studies, the contractile neurogenic response to electrical field stimulation (EFS, 3, 5, 10 Hz, 14 V, 1 ms, pulse trains lasting 10 s), as well as the contractile myogenic response to acetylcholine (ACh, 0.1-100 μmol/L) were evaluated on colon specimens incubated with granisetron (3 μmol/L, 15 min), ZnPPIX (10 μmol/L, 60 min) or CO-releasing molecule-3 (CORM-3, 100, 200, 400 μmol/L) alone or in combination. These experiments were performed under co-treatment with or without atropine (3 μmol/L, a muscarinic receptor antagonist) or NG-nitro-L-Arginine (L-NNA, 100 μmol/L, a nitric oxide synthase inhibitor). RESULTS Administration of granisetron (50, 75 μg/kg) in vivo significantly increased the time to first defecation (P = 0.045 vs vehicle-treated rats), clearly suggesting a constipating effect of this drug. Although administration of ZnPPIX or hemin alone had no effect on this gastrointestinal motility parameter, ZnPPIX co-administered with granisetron abolished the granisetron-induced constipation. On the other hand, co-administration of hemin and granisetron did not modify the increased constipation observed under granisetron alone. When administered in vitro, granisetron alone (3 μmol/L) did not significantly modify the colon’s contractile response to either EFS or ACh. Incubation with ZnPPIX alone (10 μmol/L) significantly reduced the colon’s contractile response to EFS (P = 0.016) but had no effect on contractile response to ACh. Co-administration of ZnPPIX and atropine (3 μmol/L) abolished the ZnPPIX-mediated decrease in contractile response to EFS. Conversely, incubation with CORM-3 (400 μmol/L) alone increased both the contractile response to EFS at 10 Hz (10 Hz: 71.02 ± 19.16 vs 116.25 ± 53.70, P = 0.01) and the contractile response to ACh (100 μmol/L) (P = 0.012). Co-administration of atropine abolished the CORM-3-mediated effects on the EFS-mediated response. When granisetron was co-incubated in vitro with ZnPPIX, the ZnPPIX-mediated decrease in colon contractile response to EFS was lost. On the other hand, co-incubation of granisetron and CORM-3 (400 μmol/L) further increased the colon’s contractile response to EFS (at 5 Hz: P = 0.007; at 10 Hz: P = 0.001) and to ACh (ACh 10 μmol/L: P = 0.001; ACh 100 μmol/L: P = 0.001) elicited by CORM-3 alone. L-NNA co-administered with granisetron and CORM-3 abolished the potentiating effect of CORM-3 on granisetron on both the EFS-induced and ACh-induced contractile response. CONCLUSION Taken together, findings from in vivo and in vitro studies suggest that the HO/CO pathway is involved in the constipating effects of granisetron. PMID:27895421

Feasibility of Underwater Friction Stir Welding of Hardenable Alloy Steel

DTIC Science & Technology

2010-12-01

Base Material CNC – Computer Numerical Controlled EDM – Electrical Discharge Machining FSP – Friction Stir Processing FSW – Friction Stir Welding...Hydrogen content was determined through vacuum hot extraction according to ASTM E 146-83. All other components were analyzed by direct current plasma ...emission spectroscopy according to ASTM E 1097-07. C. MICROSTRUCTURE ANALYSIS 1. Specimen Preparation A Charmilles Andrew EF630 CNC Wire EDM

Executive functions in early childhood: the role of maternal and paternal parenting practices.

PubMed

Lucassen, Nicole; Kok, Rianne; Bakermans-Kranenburg, Marian J; Van Ijzendoorn, Marinus H; Jaddoe, Vincent W V; Hofman, Albert; Verhulst, Frank C; Lambregtse-Van den Berg, Mijke P; Tiemeier, Henning

2015-11-01

We investigated the association between mothers' and fathers' harsh parenting and sensitive parenting practices and child's executive functions (EF) in early childhood in 607 families. We focused on three broad dimensions of child EF: Emergent metacognition, inhibitory self-control, and flexibility measured with the parent-reported Behavior Rating Inventory of Executive Function-Preschool Version. Less sensitive parenting of the mother and harsher parenting of the father were related to lower scores of emergent metacognition and inhibitory self-control. Parenting was not associated with child flexibility. This study extends previous research on the association between parenting and EF by the focus on the role of the father and demonstrates independent effects of mother and father on child EF. © 2015 The British Psychological Society.

Electric field-induced suppression of PTEN drives epithelial-to-mesenchymal transition via mTORC1 activation.

PubMed

Yan, Tiantian; Jiang, Xupin; Guo, Xiaowei; Chen, Wen; Tang, Di; Zhang, Junhui; Zhang, Xingyue; Zhang, Dongxia; Zhang, Qiong; Jia, Jiezhi; Huang, Yuesheng

2017-02-01

Naturally occurring electric fields (EFs) are an intrinsic property of wounds. Endogenous EFs in skin wounds play critical roles in the dynamic and well-ordered biological process of wound healing. The epithelial-to-mesenchymal transition (EMT) allows keratinocytes to transition from sedentary cells to motile cells, facilitating wound healing. However, EMT-related studies have been performed without considering endogenous EFs. Thus, the relationship between electrical signals and the EMT remain elusive. Phosphatase and tension homolog (PTEN) and mammalian target of rapamycin complex 1 (mTORC1) are key molecules in sensing electrical cues, and they play significant roles in cellular responses to EFs. In addition, these molecules are closely related to the occurrence of the EMT in other cells. We used primary human keratinocytes to investigate the influence of EFs on the EMT as well as the roles of PTEN and mTORC1 in this process. The effects of EFs on the EMT were investigated by analyzing the levels of specific proteins and transcription factors. The roles of mTORC1 and PTEN and their relationship with each other were studied via pharmacological inhibition or genetic knockdown. A Zeiss imaging system and scratch assays were used to study single-cell motility and monolayer cell migration. EFs induced a range of both biochemical changes (e.g., increased Snail, Slug, vimentin, and N-cadherin expression, decreased E-cadherin expression) and functional changes (e.g., enhanced migratory capacity) that are characteristic of the EMT. EF-stimulated cells exhibited suppressed PTEN expression, and further PTEN downregulation led to the acquisition of more mesenchymal features and the loss of epithelial characteristics, which was accompanied by increased migratory capacity. PTEN overexpression reversed the EF-induced EMT and inhibited the migratory capacity of keratinocytes. EF-induced mTORC1 activation was a required component of the causal relationship between PTEN suppression and the EMT, as mTORC1 inhibition reversed the EMT induced by PTEN downregulation. Our data demonstrate that the EF-induced suppression of PTEN drives the EMT via mTORC1 activation, thereby revealing a new and promising role of EFs in facilitating wound reepithelialization. These results provide a novel perspective regarding the significance of EFs in wound healing; therefore, electrical stimulation offers a new avenue of wound management for improved and accelerated wound healing. Copyright © 2016 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

Non-invasive evaluation of neuroprotective drug candidates for cerebral infarction by PET imaging of mitochondrial complex-I activity

NASA Astrophysics Data System (ADS)

Fukuta, Tatsuya; Asai, Tomohiro; Ishii, Takayuki; Koide, Hiroyuki; Kiyokawa, Chiaki; Hashimoto, Masahiro; Kikuchi, Takashi; Shimizu, Kosuke; Harada, Norihiro; Tsukada, Hideo; Oku, Naoto

2016-07-01

The development of a diagnostic technology that can accurately determine the pathological progression of ischemic stroke and evaluate the therapeutic effects of cerebroprotective agents has been desired. We previously developed a novel PET probe, 2-tert-butyl-4-chloro-5-{6-[2-(2-18F-fluoroethoxy)-ethoxy]-pyridin-3-ylmethoxy}-2H-pyridazin-3-one ([18F]BCPP-EF) for detecting activity of mitochondrial complex I (MC-I). This probe was shown to visualize neuronal damage in the living brain of rodent and primate models of neurodegenerative diseases. In the present study, [18F]BCPP-EF was applied to evaluate the therapeutic effects of a neuroprotectant, liposomal FK506 (FK506-liposomes), on cerebral ischemia/reperfusion (I/R) injury in transient middle cerebral artery occlusion rats. The PET imaging using [18F]BCPP-EF showed a prominent reduction in the MC-I activity in the ischemic brain hemisphere. Treatment with FK506-liposomes remarkably increased the uptake of [18F]BCPP-EF in the ischemic side corresponding to the improvement of blood flow disorders and motor function deficits throughout the 7 days after I/R. Additionally, the PET scan could diagnose the extent of the brain damage accurately and showed the neuroprotective effect of FK506-liposomes at Day 7, at which 2, 3, 5-triphenyltetrazolium chloride staining couldn’t visualize them. Our study demonstrated that the PET technology using [18F]BCPP-EF has a potent capacity to evaluate the therapeutic effect of drug candidates in living brain.

A novel two-dimensional echocardiographic image analysis system using artificial intelligence-learned pattern recognition for rapid automated ejection fraction.

PubMed

Cannesson, Maxime; Tanabe, Masaki; Suffoletto, Matthew S; McNamara, Dennis M; Madan, Shobhit; Lacomis, Joan M; Gorcsan, John

2007-01-16

We sought to test the hypothesis that a novel 2-dimensional echocardiographic image analysis system using artificial intelligence-learned pattern recognition can rapidly and reproducibly calculate ejection fraction (EF). Echocardiographic EF by manual tracing is time consuming, and visual assessment is inherently subjective. We studied 218 patients (72 female), including 165 with abnormal left ventricular (LV) function. Auto EF incorporated a database trained on >10,000 human EF tracings to automatically locate and track the LV endocardium from routine grayscale digital cineloops and calculate EF in 15 s. Auto EF results were independently compared with manually traced biplane Simpson's rule, visual EF, and magnetic resonance imaging (MRI) in a subset. Auto EF was possible in 200 (92%) of consecutive patients, of which 77% were completely automated and 23% required manual editing. Auto EF correlated well with manual EF (r = 0.98; 6% limits of agreement) and required less time per patient (48 +/- 26 s vs. 102 +/- 21 s; p < 0.01). Auto EF correlated well with visual EF by expert readers (r = 0.96; p < 0.001), but interobserver variability was greater (3.4 +/- 2.9% vs. 9.8 +/- 5.7%, respectively; p < 0.001). Visual EF was less accurate by novice readers (r = 0.82; 19% limits of agreement) and improved with trainee-operated Auto EF (r = 0.96; 7% limits of agreement). Auto EF also correlated with MRI EF (n = 21) (r = 0.95; 12% limits of agreement), but underestimated absolute volumes (r = 0.95; bias of -36 +/- 27 ml overall). Auto EF can automatically calculate EF similarly to results by manual biplane Simpson's rule and MRI, with less variability than visual EF, and has clinical potential.

Associations between and development of cool and hot executive functions across early childhood.

PubMed

O'Toole, Sarah; Monks, Claire P; Tsermentseli, Stella

2018-03-01

This study explored the development of cool and hot EF skills across early childhood. Children 4.5- to 5.5-years-old (N = 80) completed performance-based assessments of cool EF (inhibition and working memory), hot EF (affective decision-making and delay of gratification) at three time points across 12 months. Cool EF task performance was consistently correlated with early childhood, but hot EF task performance was not. Performance on cool EF tasks showed significant improvements over early childhood, but performance on hot EF tasks did not. During early childhood performance on delay of gratification and affective decision-making tasks may therefore be unrelated and show limited sensitivity to improvement. Statement of contribution What is already known about cool and hot EF An EF model has been proposed that distinguishes between cool-cognitive and hot-affective skills. Findings regarding whether cool and hot EF are distinct in early childhood are mixed. Hot EF skills, compared to cool EF abilities, are thought to develop more gradually. What the present study adds to understanding of cool and hot EF Performance on cool EF tasks and hot delay of gratification were associated in early childhood. Performance on hot EF tasks was not related, meaning they do not tap the same underlying factor. Age related gains in hot EF were not found, but 5-year-olds had better hot EF than 4-year-olds. © 2017 The British Psychological Society.

Characterisation of Translation Elongation Factor eEF1B Subunit Expression in Mammalian Cells and Tissues and Co-Localisation with eEF1A2

PubMed Central

Janikiewicz, Justyna; Doig, Jennifer; Abbott, Catherine M.

2014-01-01

Translation elongation is the stage of protein synthesis in which the translation factor eEF1A plays a pivotal role that is dependent on GTP exchange. In vertebrates, eEF1A can exist as two separately encoded tissue-specific isoforms, eEF1A1, which is almost ubiquitously expressed, and eEF1A2, which is confined to neurons and muscle. The GTP exchange factor for eEF1A1 is a complex called eEF1B made up of subunits eEF1Bα, eEF1Bδ and eEF1Bγ. Previous studies have cast doubt on the ability of eEF1B to interact with eEF1A2, suggesting that this isoform might use a different GTP exchange factor. We show that eEF1B subunits are all widely expressed to varying degrees in different cell lines and tissues, and at different stages of development. We show that ablation of any of the subunits in human cell lines has a small but significant impact on cell viability and cycling. Finally, we show that both eEF1A1 and eEF1A2 colocalise with all eEF1B subunits, in such close proximity that they are highly likely to be in a complex. PMID:25436608

Effect of the application of cattle urine with or without the nitrification inhibitor DCD, and dung on greenhouse gas emissions from a UK grassland soil.

PubMed

Cardenas, L M; Misselbrook, T M; Hodgson, C; Donovan, N; Gilhespy, S; Smith, K A; Dhanoa, M S; Chadwick, D

2016-11-01

Emissions of nitrous oxide (N 2 O) from soils from grazed grasslands have large uncertainty due to the great spatial variability of excreta deposition, resulting in heterogeneous distribution of nutrients. The contribution of urine to the labile N pool, much larger than that from dung, is likely to be a major source of emissions so efforts to determine N 2 O emission factors (EFs) from urine and dung deposition are required to improve the inventory of greenhouse gases from agriculture. We investigated the effect of the application of cattle urine and dung at different times of the grazing season on N 2 O emissions from a grassland clay loam soil. Methane emissions were also quantified. We assessed the effect of a nitrification inhibitor, dicyandiamide (DCD), on N 2 O emissions from urine application and also included an artificial urine treatment. There were significant differences in N 2 O EFs between treatments in the spring (largest from urine and lowest from dung) but not in the summer and autumn applications. We also found that there was a significant effect of season (largest in spring) but not of treatment on the N 2 O EFs. The resulting EF values were 2.96, 0.56 and 0.11% of applied N for urine for spring, summer and autumn applications, respectively. The N 2 O EF values for dung were 0.14, 0.39 and 0.10% for spring, summer and autumn applications, respectively. The inhibitor was effective in reducing N 2 O emissions for the spring application only. Methane emissions were larger from the dung application but there were no significant differences between treatments across season of application.

RECURRENT STROKE IN THE WARFARIN VERSUS ASPIRIN IN REDUCED EJECTION FRACTION (WARCEF) TRIAL

PubMed Central

Pullicino, Patrick M.; Qian, Min; Sacco, Ralph L.; Freudenberger, Ron; Graham, Susan; Teerlink, John R.; Mann, Douglas; Di Tullio, Marco R.; Ponikowski, Piotr; Lok, Dirk J.; Anker, Stefan D.; Lip, Gregory Y.H.; Estol, Conrado J.; Levin, Bruce; Mohr, J.P.; Thompson, John L. P.; Homma, Shunichi

2014-01-01

Background and Purpose WARCEF randomized 2305 patients in sinus rhythm with ejection fraction (EF) ≤35% to warfarin (INR 2.0–3.5) or aspirin 325 mg. Warfarin reduced the incident ischemic stroke (IIS) hazard rate by 48% over aspirin in a secondary analysis. The IIS rate in heart failure (HF) is too low to warrant routine anticoagulation but epidemiologic studies show that prior stroke increases the stroke risk in HF. We here explore IIS rates in WARCEF patients with and without baseline stroke to look for risk factors for IIS and determine if a subgroup with an IIS rate high enough to give a clinically relevant stroke risk reduction can be identified. Methods We compared potential stroke risk factors between patients with baseline stroke and those without using the exact conditional score test for Poisson variables. We looked for risk factors for IIS, by comparing IIS rates between different risk factors. For EF we tried cutoff points of 10%, 15% and 20%. 15% was used as it was the highest EF that was associated with a significant increase in IIS rate. IIS and EF strata were balanced as to warfarin/aspirin assignment by the stratified randomized design. A multiple Poisson regression examined the simultaneous effects of all risk factors on IIS rate. IIS rates per hundred patient years (/100PY) were calculated in patient groups with significant risk factors. Missing values were assigned the modal value. Results Twenty of 248 (8.1%) patients with baseline stroke and 64 of 2048 (3.1%) without had IIS. IIS rate in patients with baseline stroke (2.37/100PY) was greater than patients without (0.89/100PY)(rate ratio 2.68, p<0.001). Fourteen of 219 (6.4%) patients with ejection fraction (EF)<15% and 70 of 2079 (3.4%) with EF ≥15% had IIS. In the multiple regression analysis stroke at baseline (p<0.001) and EF<15% vs. ≥15% (p=.005) remained significant predictors of IIS. IIS rate was 2.04/100PY in patients with EF<15% and 0.95/100PY in patients with EF ≥15% (p=0.009). IIS rate in patients with baseline stroke and reduced EF was 5.88/100PY with EF<15% decreasing to 2.62/100PY with EF<30%. Conclusions In a WARCEF exploratory analysis, prior stroke and EF<15% were risk factors for IIS. Further research is needed to determine if a clinically relevant stroke risk reduction is obtainable with warfarin in HF patients with prior stroke and reduced EF. PMID:25300706

Mortality associated with heart failure with preserved vs. reduced ejection fraction in a prospective international multi-ethnic cohort study.

PubMed

Lam, Carolyn S P; Gamble, Greg D; Ling, Lieng H; Sim, David; Leong, Kui Toh Gerard; Yeo, Poh Shuan Daniel; Ong, Hean Yee; Jaufeerally, Fazlur; Ng, Tze P; Cameron, Vicky A; Poppe, Katrina; Lund, Mayanna; Devlin, Gerry; Troughton, Richard; Richards, A Mark; Doughty, Robert N

2018-05-21

Whether prevalence and mortality of patients with heart failure with preserved or mid-range (40-49%) ejection fraction (HFpEF and HFmREF) are similar to those of heart failure with reduced ejection fraction (HFrEF), as reported in some epidemiologic studies, remains highly controversial. We determined and compared characteristics and outcomes for patients with HFpEF, HFmREF, and HFrEF in a prospective, international, multi-ethnic population. Prospective multi-centre longitudinal study in New Zealand (NZ) and Singapore. Patients with HF were assessed at baseline and followed over 2 years. The primary outcome was death from any cause. Secondary outcome was death and HF hospitalization. Cox proportional hazards models were used to compare outcomes for patients with HFpEF, HFmrEF, and HFrEF. Of 2039 patients enrolled, 28% had HFpEF, 13% HFmrEF, and 59% HFrEF. Compared with HFrEF, patients with HFpEF were older (62 vs. 72 years), more commonly female (17% vs. 48%), and more likely to have a history of hypertension (61% vs. 78%) but less likely to have coronary artery disease (55% vs. 41%). During 2 years of follow-up, 343 (17%) patients died. Adjusting for age, sex, and clinical risk factors, patients with HFpEF had a lower risk of death compared with those with HFrEF (hazard ratio 0.62, 95% confidence interval 0.46-0.85). Plasma (NT-proBNP) was similarly related to mortality in both HFpEF, HFmrEF, and HFrEF independent of the co-variates listed and of ejection fraction. Results were similar for the composite endpoint of death or HF and were consistent between Singapore and NZ. These prospective multinational data showed that the prevalence of HFpEF within the HF population was lower than HFrEF. Death rate was comparable in HFpEF and HFmrEF and lower than in HFrEF. Plasma levels of NT-proBNP were independently and similarly predictive of death in the three HF phenotypes. Australian New Zealand Clinical Trial Registry (ACTRN12610000374066).

Structural outline of the detailed mechanism for elongation factor Ts-mediated guanine nucleotide exchange on elongation factor Tu.

PubMed

Thirup, Søren S; Van, Lan Bich; Nielsen, Tine K; Knudsen, Charlotte R

2015-07-01

Translation elongation factor EF-Tu belongs to the superfamily of guanine-nucleotide binding proteins, which play key cellular roles as regulatory switches. All G-proteins require activation via exchange of GDP for GTP to carry out their respective tasks. Often, guanine-nucleotide exchange factors are essential to this process. During translation, EF-Tu:GTP transports aminoacylated tRNA to the ribosome. GTP is hydrolyzed during this process, and subsequent reactivation of EF-Tu is catalyzed by EF-Ts. The reaction path of guanine-nucleotide exchange is structurally poorly defined for EF-Tu and EF-Ts. We have determined the crystal structures of the following reaction intermediates: two structures of EF-Tu:GDP:EF-Ts (2.2 and 1.8Å resolution), EF-Tu:PO4:EF-Ts (1.9Å resolution), EF-Tu:GDPNP:EF-Ts (2.2Å resolution) and EF-Tu:GDPNP:pulvomycin:Mg(2+):EF-Ts (3.5Å resolution). These structures provide snapshots throughout the entire exchange reaction and suggest a mechanism for the release of EF-Tu in its GTP conformation. An inferred sequence of events during the exchange reaction is presented. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Effective removal of effluent organic matter (EfOM) from bio-treated coking wastewater by a recyclable aminated hyper-cross-linked polymer.

PubMed

Yang, Wenlan; Li, Xuchun; Pan, Bingcai; Lv, Lu; Zhang, Weiming

2013-09-01

Effluent organic matter (EfOM) is a complex matrix of organic substance mainly from bio-treated sewage effluent and is considered as the main constraint to further advanced treatment. Here a recyclable aminated hyper-cross-linked polymeric adsorbent (NDA-802) featured with aminated functional groups, large specific surface area, and sufficient micropore region was synthesized for effective removal of EfOM from the bio-treated coking wastewater (BTCW), and its removal characteristics was investigated. It was found that hydrophobic fraction was the main constituent (64.8% of DOC) in EfOM of BTCW, and the hydrophobic-neutral fraction had the highest SUVA level (7.06 L mg(-1) m(-1)), which were significantly different from that in the domestic wastewater. Column adsorption experiments showed that NDA-802 exhibited much higher removal efficiency of EfOM than other polymeric adsorbents D-301, XAD-4, and XAD-7, and the efficiency could be readily sustained according to continuous 28-cycle batch adsorption-regeneration experiments. Moreover, dissolved organic matter (DOM) fractionation and excitation-emission matrix (EEM) fluorescence spectroscopy study indicated that NDA-802 showed attractive adsorption preference as well as high removal efficiency of hydrophobic and aromatic compounds. Possibly ascribed to the presence of functional aminated groups, relatively large specific surface area and micropore region of the unique polymer, NDA-802 possesses high and sustained efficiency for the removal of EfOM, and provides a potential alternative for the advanced treatment. Copyright © 2013 Elsevier Ltd. All rights reserved.

Studies of elongation factor Tu in Streptococcus faecium (ATCC 9790)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bourbeau, P.P.

1986-01-01

It has been known for over twenty years that elongation factor Tu (Ef-Tu) is one of the proteins involved in protein synthesis in bacteria. Several years ago, it was proposed that Ef-Tu may, in addition, have other structural functions in bacterial. The author's research has examined the function of Ef-Tu in Streptococcus faecium. Using an antibiotic kirromycin, which specifically inhibits Ef-Tu function, the effects upon a number of cellular parameters were determined. Inhibition of both protein and RNA synthesis was found to be similar to the effect of chloramphenicol. Using the residual division technique for the determination of cell cyclemore » events with both heterogeneous and sucrose gradient fractionated cell populations, a kirromycin sensitive event was detected between 8 min. (Td = 30 min.) and 19 min. (Td = 175 min.) later in the cell cycle than the chloramphenical sensitive event. This suggests that kirromycin is inhibiting a terminal cell cycle event which is in addition to the inhibition of protein synthesis. Purification of Ef-Tu was performed using two different methods: ion exchange and molecular exclusion chromatography; and GDP affinity chromatography. Various schemes were employed to try and obtain optimum cellular fractionation, allowing for both proper separation of ribosomes from the other cellular fractions and retention of enzymatic activity by Ef-Tu as determined by a /sup 3/H-GDP binding assay. Analysis of the cell cycle of S. faecium using the residual division technique was also performed. In addition, certain cell wall antibiotics were used to determine if other cell cycle events could be determined using the residual division technique.« less

Insights into the photo-induced formation of reactive intermediates from effluent organic matter: The role of chemical constituents.

PubMed

Zhou, Huaxi; Lian, Lushi; Yan, Shuwen; Song, Weihua

2017-04-01

In the present study, the formation of triplet states of organic matters ( 3 OM ∗ ) from effluent organic matter (EfOM) under simulated solar irradiation was investigated. EfOM was separated into hydrophobic (HPO), transphilic (TPI), and hydrophilic (HPI) components. The quantum yield coefficients (ƒ TMP ) of 3 OM ∗ were measured for each component and compared to those of reference natural organic matter (NOM). NaBH 4 reduction was performed on the EfOM, and the effect of aromatic ketones moieties on triplet formation was also determined. Furthermore, the apparent quantum yield of 1 O 2 (Φ 1O2 ) and O 2 •- (Φ O2•- ) was measured. Our results suggested that the HPI fraction acted as a sink for 3 OM ∗ . A linear correlation was observed between ƒ TMP and Φ 1O2 for NOM/EfOM, except for NaBH 4 -reduced effluent and HPI components. Both ƒ TMP and Φ 1O2 were positively correlated with the contribution rates of NaBH 4 -reducible moieties (aromatic ketones) toward 3 OM ∗ . Aromatic ketones were primarily responsible for the production of 3 OM ∗ from EfOM, whereas quinone moieties played a key role in the production of 3 OM ∗ in NOM-enriched solutions. Understanding the role of chemical constituents on the photo activity of EfOM/NOM is essential for providing useful insights on their photochemical effects in aquatic systems. Copyright © 2017 Elsevier Ltd. All rights reserved.

Enhancing Food Processing by Pulsed and High Voltage Electric Fields: Principles and Applications.

PubMed

Wang, Qijun; Li, Yifei; Sun, Da-Wen; Zhu, Zhiwei

2018-02-02

Improvements in living standards result in a growing demand for food with high quality attributes including freshness, nutrition and safety. However, current industrial processing methods rely on traditional thermal and chemical methods, such as sterilization and solvent extraction, which could induce negative effects on food quality and safety. The electric fields (EFs) involving pulsed electric fields (PEFs) and high voltage electric fields (HVEFs) have been studied and developed for assisting and enhancing various food processes. In this review, the principles and applications of pulsed and high voltage electric fields are described in details for a range of food processes, including microbial inactivation, component extraction, and winemaking, thawing and drying, freezing and enzymatic inactivation. Moreover, the advantages and limitations of electric field related technologies are discussed to foresee future developments in the food industry. This review demonstrates that electric field technology has a great potential to enhance food processing by supplementing or replacing the conventional methods employed in different food manufacturing processes. Successful industrial applications of electric field treatments have been achieved in some areas such as microbial inactivation and extraction. However, investigations of HVEFs are still in an early stage and translating the technology into industrial applications need further research efforts.

Substance P enhances electrical field stimulation-induced mast cell degranulation in rat trachea.

PubMed

Hua, X Y; Back, S M; Tam, E K

1996-06-01

We previously demonstrated in an ex vivo rat tracheal model that chymotryptic activity is an index of mast cell degranulation and that substance P (SP) and electrical field stimulation (EFS) synergistically degranulate mucosal and connective tissue mast cells. In the current study, we found that the facilitatory effect of SP was apparent at concentrations as low as 10(-9) M. This effect was mimicked by 10(-7) M neurokinin A or by 10(-6) M capsaicin and was blocked by the NK1 receptor antagonist CP-96,345. SP + EFS-induced mast cell secretion was significantly attenuated by 10(-6) M tetrodotoxin. The response was also attenuated in tracheas from rats in which sensory nerves had been depleted by systemic pretreatment with capsaicin or in which sympathetic nerves had been depleted by systemic pretreatment with 6-hydroxy-dopamine. Atropine (10(-6) M) or indomethacin (10(-5) M) also attenuated SP + EFS-induced mast cell secretion. Our findings suggest the importance of a sensitizing rather than a direct stimulating effect of SP on mast cell degranulation. SP may increase the sensitivity of mast cells to EFS-discharged mediators or facilitate the release of mast cell-stimulating mediators from autonomic nerves.

Biomarkers in Acutely Decompensated Heart Failure with Preserved or Reduced Ejection Fraction

PubMed Central

Bishu, Kalkidan; Deswal, Anita; Chen, Horng H.; LeWinter, Martin M.; Lewis, Gregory D.; Semigran, Marc J.; Borlaug, Barry A.; McNulty, Steven; Hernandez, Adrian F.; Braunwald, Eugene; Redfield, Margaret M.

2013-01-01

Background Acute decompensated heart failure (ADHF) occurs with preserved (HFpEF, EF≥50%) or reduced (HFrEF, EF<50%) ejection fraction. Natriuretic peptide (NP) levels are lower in HFpEF than HFrEF. We hypothesized that lower NP levels in HFpEF may be associated with other differences in biomarkers; specifically, renin-angiotensin-aldosterone system (RAAS) activation, oxidative stress and a biomarker that reflects collagen synthesis. Methods In this pre-specified ancillary analysis of ADHF patients enrolled in the Diuretic Optimization Strategies Evaluation (DOSE) study, clinical features and NT-proBNP, cystatin C, plasma renin activity (PRA), aldosterone, oxidative stress (uric acid) and procollagen type III N-terminal peptide (PIIINP) were compared in HFpEF and HFrEF at enrollment and 60 day follow-up. Results Compared to HFrEF (n=219), HFpEF (n=81) patients were older, heavier, more commonly female, less treated with RAAS antagonists, but with similar NYHA class, jugular venous pressure and edema severity. NT-proBNP was lower and systolic blood pressure (BP) and cystatin C were higher in HFpEF. Despite higher systolic BP and less RAAS antagonist use in HFpEF, PRA and aldosterone levels were similar in HFpEF and HFrEF as were uric acid and PIIINP levels. Changes in biomarker levels from enrollment to 60 days were similar between HFrEF (n=149) and HFpEF (n=50). Conclusion Lower NP levels in decompensated HFpEF occur in association with similar ADHF severity, more impaired vascular and renal function but similar elevation of biomarkers that reflect RAAS activation, oxidative stress and collagen synthesis as in HFrEF. PMID:23137508

Mid-range Ejection Fraction Does Not Permit Risk Stratification Among Patients Hospitalized for Heart Failure.

PubMed

Gómez-Otero, Inés; Ferrero-Gregori, Andreu; Varela Román, Alfonso; Seijas Amigo, José; Pascual-Figal, Domingo A; Delgado Jiménez, Juan; Álvarez-García, Jesús; Fernández-Avilés, Francisco; Worner Diz, Fernando; Alonso-Pulpón, Luis; Cinca, Juan; Gónzalez-Juanatey, José Ramón

2017-05-01

European Society of Cardiology heart failure guidelines include a new patient category with mid-range (40%-49%) left ventricular ejection fraction (HFmrEF). HFmrEF patient characteristics and prognosis are poorly defined. The aim of this study was to analyze the HFmrEF category in a cohort of hospitalized heart failure patients (REDINSCOR II Registry). A prospective observational study was conducted with 1420 patients classified according to ejection fraction as follows: HFrEF, < 40%; HFmrEF, 40%-49%; and HFpEF, ≥ 50%. Baseline patient characteristics were examined, and outcome measures were mortality and readmission for heart failure at 1-, 6-, and 12-month follow-up. Propensity score matching was used to compare the HFmrEF group with the other ejection fraction groups. Among the study participants, 583 (41%) had HFrEF, 227 (16%) HFmrEF, and 610 (43%) HFpEF. HFmrEF patients had a clinical profile similar to that of HFpEF patients in terms of age, blood pressure, and atrial fibrillation prevalence, but shared with HFrEF patients a higher proportion of male participants and ischemic etiology, and use of class I drugs targeting HFrEF. All other features were intermediate, and comorbidities were similar among the 3 groups. There were no significant differences in all-cause mortality, cause of death, or heart failure readmission. The similar outcomes were confirmed in the propensity score matched cohorts. The HFmrEF patient group has characteristics between the HFrEF and HFpEF groups, with more similarities to the HFpEF group. No between-group differences were observed in total mortality, cause of death, or heart failure readmission. Copyright © 2016 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Clinical utility of automated assessment of left ventricular ejection fraction using artificial intelligence-assisted border detection.

PubMed

Rahmouni, Hind W; Ky, Bonnie; Plappert, Ted; Duffy, Kevin; Wiegers, Susan E; Ferrari, Victor A; Keane, Martin G; Kirkpatrick, James N; Silvestry, Frank E; St John Sutton, Martin

2008-03-01

Ejection fraction (EF) calculated from 2-dimensional echocardiography provides important prognostic and therapeutic information in patients with heart disease. However, quantification of EF requires planimetry and is time-consuming. As a result, visual assessment is frequently used but is subjective and requires extensive experience. New computer software to assess EF automatically is now available and could be used routinely in busy digital laboratories (>15,000 studies per year) and in core laboratories running large clinical trials. We tested Siemens AutoEF software (Siemens Medical Solutions, Erlangen, Germany) to determine whether it correlated with visual estimates of EF, manual planimetry, and cardiac magnetic resonance (CMR). Siemens AutoEF is based on learned patterns and artificial intelligence. An expert and a novice reader assessed EF visually by reviewing transthoracic echocardiograms from consecutive patients. An experienced sonographer quantified EF in all studies using Simpson's method of disks. AutoEF results were compared to CMR. Ninety-two echocardiograms were analyzed. Visual assessment by the expert (R = 0.86) and the novice reader (R = 0.80) correlated more closely with manual planimetry using Simpson's method than did AutoEF (R = 0.64). The correlation between AutoEF and CMR was 0.63, 0.28, and 0.51 for EF, end-diastolic and end-systolic volumes, respectively. The discrepancies in EF estimates between AutoEF and manual tracing using Simpson's method and between AutoEF and CMR preclude routine clinical use of AutoEF until it has been validated in a number of large, busy echocardiographic laboratories. Visual assessment of EF, with its strong correlation with quantitative EF, underscores its continued clinical utility.

Inhibitory effect of cannabichromene, a major non-psychotropic cannabinoid extracted from Cannabis sativa, on inflammation-induced hypermotility in mice

PubMed Central

Izzo, Angelo A; Capasso, Raffaele; Aviello, Gabriella; Borrelli, Francesca; Romano, Barbara; Piscitelli, Fabiana; Gallo, Laura; Capasso, Francesco; Orlando, Pierangelo; Di Marzo, Vincenzo

2012-01-01

BACKGROUND AND PURPOSE Cannabichromene (CBC) is a major non-psychotropic phytocannabinoid that inhibits endocannabinoid inactivation and activates the transient receptor potential ankyrin-1 (TRPA1). Both endocannabinoids and TRPA1 may modulate gastrointestinal motility. Here, we investigated the effect of CBC on mouse intestinal motility in physiological and pathological states. EXPERIMENTAL APPROACH Inflammation was induced in the mouse small intestine by croton oil. Endocannabinoid (anandamide and 2-arachidonoyl glycerol), palmitoylethanolamide and oleoylethanolamide levels were measured by liquid chromatography-mass spectrometry; TRPA1 and cannabinoid receptors were analysed by quantitative RT-PCR; upper gastrointestinal transit, colonic propulsion and whole gut transit were evaluated in vivo; contractility was evaluated in vitro by stimulating the isolated ileum, in an organ bath, with ACh or electrical field stimulation (EFS). KEY RESULTS Croton oil administration was associated with decreased levels of anandamide (but not 2-arachidonoyl glycerol) and palmitoylethanolamide, up-regulation of TRPA1 and CB1 receptors and down-regulation of CB2 receptors. Ex vivo CBC did not change endocannabinoid levels, but it altered the mRNA expression of TRPA1 and cannabinoid receptors. In vivo, CBC did not affect motility in control mice, but normalized croton oil-induced hypermotility. In vitro, CBC reduced preferentially EFS- versus ACh-induced contractions. Both in vitro and in vivo, the inhibitory effect of CBC was not modified by cannabinoid or TRPA1 receptor antagonists. CONCLUSION AND IMPLICATIONS CBC selectively reduces inflammation-induced hypermotility in vivo in a manner that is not dependent on cannabinoid receptors or TRPA1. PMID:22300105

Noncardiac Comorbidities in Heart Failure With Reduced Versus Preserved Ejection Fraction

PubMed Central

Mentz, Robert J.; Kelly, Jacob P.; von Lueder, Thomas G.; Voors, Adriaan A.; Lam, Carolyn S. P.; Cowie, Martin R.; Kjeldsen, Keld; Jankowska, Ewa A.; Atar, Dan; Butler, Javed; Fiuzat, Mona; Zannad, Faiez; Pitt, Bertram; O’Connor, Christopher M.

2014-01-01

Heart failure patients are classified by ejection fraction (EF) into distinct groups: heart failure with preserved EF (HFpEF) or heart failure with reduced EF (HFrEF). Although patients with heart failure commonly have multiple comorbidities that complicate management and may adversely affect outcomes, their role in the HFpEF and HFrEF groups is not well-characterized. This review summarizes the role of noncardiac comorbidities in patients with HFpEF versus HFrEF, emphasizing prevalence, underlying pathophysiologic mechanisms, and outcomes. Pulmonary disease, diabetes mellitus, anemia, and obesity tend to be more prevalent in HFpEF patients, but renal disease and sleep-disordered breathing burdens are similar. These comorbidities similarly increase morbidity and mortality risk in HFpEF and HFrEF patients. Common pathophysiologic mechanisms include systemic and endomyocardial inflammation with fibrosis. We also discuss implications for clinical care and future HF clinical trial design. The basis for this review was discussions between scientists, clinical trialists, and regulatory representatives at the 10th Global CardioVascular Clinical Trialists Forum. PMID:25456761

Effects of Indoor Air Pollutants on Atopic Dermatitis.

PubMed

Kim, JaKyoung; Kim, HyungJin; Lim, DaeHyun; Lee, Young-Kyu; Kim, Jeong Hee

2016-12-09

The increasing prevalence of atopic dermatitis (AD) is associated with variations in indoor environments. In Korea, many inner walls of homes are covered with wallpaper: such walls emit indoor air pollutants, including volatile organic compounds (VOCs) and formaldehyde. This randomized, double-blind study investigated the effects of wallpaper on indoor air quality and AD. Thirty-one children (aged three to eight years) with moderate AD were assigned to environmentally-friendly (EF) and polyvinyl chloride (PVC) wallpaper groups. Indoor air concentrations of VOCs, natural VOCs (NVOCs), formaldehyde, and total suspended bacteria were measured before and two (W₂) and eight weeks (W₈) after wallpapering. Scoring Atopic Dermatitis (SCORAD) evaluations and blood tests were performed during the same period. The EF wallpaper and PVC wallpaper groups showed similar trends in the changes in total VOCs (TVOC) and formaldehyde content in the indoor air. However, the EF wallpaper group showed more improvement on the SCORAD at W₂ and W₈ than the PVC wallpaper group. The SCORAD index was positively correlated with several indoor air pollutants. Further, the SCORAD index and NVOC % were negatively correlated. Improved SCORAD index and effects of wallpapering on indoor air quality improvements occurred within a short period of time in both groups. We believe that NVOCs in indoor air after EF wallpapering have a beneficial effect on health.

Does Mindfulness Enhance Critical Thinking? Evidence for the Mediating Effects of Executive Functioning in the Relationship between Mindfulness and Critical Thinking.

PubMed

Noone, Chris; Bunting, Brendan; Hogan, Michael J

2015-01-01

Mindfulness originated in the Buddhist tradition as a way of cultivating clarity of thought. Despite the fact that this behavior is best captured using critical thinking (CT) assessments, no studies have examined the effects of mindfulness on CT or the mechanisms underlying any such possible relationship. Even so, mindfulness has been suggested as being beneficial for CT in higher education. CT is recognized as an important higher-order cognitive process which involves the ability to analyze and evaluate evidence and arguments. Such non-automatic, reflective responses generally require the engagement of executive functioning (EF) which includes updating, inhibition, and shifting of representations in working memory. Based on research showing that mindfulness enhances aspects of EF and certain higher-order cognitive processes, we hypothesized that individuals higher in facets of dispositional mindfulness would demonstrate greater CT performance, and that this relationship would be mediated by EF. Cross-sectional assessment of these constructs in a sample of 178 university students was achieved using the observing and non-reactivity sub-scales of the Five Factor Mindfulness Questionnaire, a battery of EF tasks and the Halpern Critical Thinking Assessment. Our hypotheses were tested by constructing a multiple meditation model which was analyzed using Structural Equation Modeling. Evidence was found for inhibition mediating the relationships between both observing and non-reactivity and CT in different ways. Indirect-only (or full) mediation was demonstrated for the relationship between observing, inhibition, and CT. Competitive mediation was demonstrated for the relationship between non-reactivity, inhibition, and CT. This suggests additional mediators of the relationship between non-reactivity and CT which are not accounted for in this model and have a negative effect on CT in addition to the positive effect mediated by inhibition. These findings are discussed in the context of the Default Interventionist Dual Process Theory of Higher-order Cognition and previous studies on mindfulness, self-regulation, EF, and higher-order cognition. In summary, dispositional mindfulness appears to facilitate CT performance and this effect is mediated by the inhibition component of EF. However, this relationship is not straightforward which suggests many possibilities for future research.

Systematic review of biological effects of exposure to static electric fields. Part II: Invertebrates and plants.

PubMed

Schmiedchen, Kristina; Petri, Anne-Kathrin; Driessen, Sarah; Bailey, William H

2018-01-01

The construction of high-voltage direct current (HVDC) lines for the long-distance transport of energy is becoming increasingly popular. This has raised public concern about potential environmental impacts of the static electric fields (EF) produced under and near HVDC power lines. As the second part of a comprehensive literature analysis, the aim of this systematic review was to assess the effects of static EF exposure on biological functions in invertebrates and plants and to provide the basis for an environmental impact assessment of such exposures. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was used to guide the methodological conduct and reporting. Thirty-three studies - 14 invertebrate and 19 plant studies - met the eligibility criteria and were included in this review. The reported behavioral responses of insects and planarians upon exposure strongly suggest that invertebrates are able to perceive the presence of a static EF. Many other studies reported effects on physiological functions that were expressed as, for example, altered metabolic activity or delayed reproductive and developmental stages in invertebrates. In plants, leaf damage, alterations in germination rates, growth and yield, or variations in the concentration of essential elements, for example, have been reported. However, these physiological responses and changes in plant morphology appear to be secondary to surface stimulation by the static EF or caused by concomitant parameters of the electrostatic environment. Furthermore, all of the included studies suffered from methodological flaws, which lowered credibility in the results. At field levels encountered from natural sources or HVDC lines (< 35kV/m), the available data provide reliable evidence that static EF can trigger behavioral responses in invertebrates, but they do not provide evidence for adverse effects of static EF on other biological functions in invertebrates and plants. At far higher field levels (> 35kV/m), adverse effects on physiology and morphology, presumably caused by corona-action, appear to be more likely. Higher quality studies are needed to unravel the role of air ions, ozone, nitric oxide and corona current on alterations in physiological functions and morphology. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Does Mindfulness Enhance Critical Thinking? Evidence for the Mediating Effects of Executive Functioning in the Relationship between Mindfulness and Critical Thinking

PubMed Central

Noone, Chris; Bunting, Brendan; Hogan, Michael J.

2016-01-01

Mindfulness originated in the Buddhist tradition as a way of cultivating clarity of thought. Despite the fact that this behavior is best captured using critical thinking (CT) assessments, no studies have examined the effects of mindfulness on CT or the mechanisms underlying any such possible relationship. Even so, mindfulness has been suggested as being beneficial for CT in higher education. CT is recognized as an important higher-order cognitive process which involves the ability to analyze and evaluate evidence and arguments. Such non-automatic, reflective responses generally require the engagement of executive functioning (EF) which includes updating, inhibition, and shifting of representations in working memory. Based on research showing that mindfulness enhances aspects of EF and certain higher-order cognitive processes, we hypothesized that individuals higher in facets of dispositional mindfulness would demonstrate greater CT performance, and that this relationship would be mediated by EF. Cross-sectional assessment of these constructs in a sample of 178 university students was achieved using the observing and non-reactivity sub-scales of the Five Factor Mindfulness Questionnaire, a battery of EF tasks and the Halpern Critical Thinking Assessment. Our hypotheses were tested by constructing a multiple meditation model which was analyzed using Structural Equation Modeling. Evidence was found for inhibition mediating the relationships between both observing and non-reactivity and CT in different ways. Indirect-only (or full) mediation was demonstrated for the relationship between observing, inhibition, and CT. Competitive mediation was demonstrated for the relationship between non-reactivity, inhibition, and CT. This suggests additional mediators of the relationship between non-reactivity and CT which are not accounted for in this model and have a negative effect on CT in addition to the positive effect mediated by inhibition. These findings are discussed in the context of the Default Interventionist Dual Process Theory of Higher-order Cognition and previous studies on mindfulness, self-regulation, EF, and higher-order cognition. In summary, dispositional mindfulness appears to facilitate CT performance and this effect is mediated by the inhibition component of EF. However, this relationship is not straightforward which suggests many possibilities for future research. PMID:26834669

Developmental Trajectories in Toddlers’ Self-restraint Predict Individual Differences in Executive Functions 14 Years Later: A Behavioral Genetic Analysis

PubMed Central

Friedman, Naomi P.; Miyake, Akira; Robinson, JoAnn L.; Hewitt, John K.

2011-01-01

We examined whether self-restraint in early childhood predicted individual differences in three executive functions (EFs; inhibiting prepotent responses, updating working memory, and shifting task sets) in late adolescence in a sample of ~950 twins. At ages 14, 20, 24, and 36 months, the children were shown an attractive toy and told not to touch it for 30 seconds. Latency to touch the toy increased with age, and latent class growth modeling distinguished two groups of children that differed in their latencies to touch the toy at all 4 time points. Using confirmatory factor analysis, the three EFs (measured with latent variables at age 17 years) were decomposed into a Common EF factor (isomorphic to response inhibition ability) and two factors specific to updating and shifting, respectively. Less restrained children had significantly lower scores on the Common EF factor, equivalent scores on the Updating-specific factor, and higher scores on the Shifting-specific factor than the more restrained children. The less restrained group also had lower IQ scores, but this effect was entirely mediated by the EF components. Twin models indicated that the associations were primarily genetic in origin for the Common EF variable but split between genetics and nonshared environment for the Shifting-specific variable. These results suggest a biological relation between individual differences in self-restraint and EFs, one that begins early in life and persists into late adolescence. PMID:21668099

Mutations in Elongation Factor Ef-1α Affect the Frequency of Frameshifting and Amino Acid Misincorporation in Saccharomyces Cerevisiae

PubMed Central

Sandbaken, M. G.; Culbertson, M. R.

1988-01-01

A mutational analysis of the eukaryotic elongation factor EF-1α indicates that this protein functions to limit the frequency of errors during genetic code translation. We found that both amino acid misincorporation and reading frame errors are controlled by EF-1α. In order to examine the function of this protein, the TEF2 gene, which encodes EF-1α in Saccharomyces cerevisiae, was mutagenized in vitro with hydroxylamine. Sixteen independent TEF2 alleles were isolated by their ability to suppress frameshift mutations. DNA sequence analysis identified eight different sites in the EF-1α protein that elevate the frequency of mistranslation when mutated. These sites are located in two different regions of the protein. Amino acid substitutions located in or near the GTP-binding and hydrolysis domain of the protein cause suppression of frameshift and nonsense mutations. These mutations may effect mistranslation by altering the binding or hydrolysis of GTP. Amino acid substitutions located adjacent to a putative aminoacyl-tRNA binding region also suppress frameshift and nonsense mutations. These mutations may alter the binding of aminoacyl-tRNA by EF-1α. The identification of frameshift and nonsense suppressor mutations in EF-1α indicates a role for this protein in limiting amino acid misincorporation and reading frame errors. We suggest that these types of errors are controlled by a common mechanism or closely related mechanisms. PMID:3066688

Partial degradation of levofloxacin for biodegradability improvement by electro-Fenton process using an activated carbon fiber felt cathode.

PubMed

Gong, Yuexiang; Li, Jiuyi; Zhang, Yanyu; Zhang, Meng; Tian, Xiujun; Wang, Aimin

2016-03-05

Solutions of 500 mL 200 mg L(-1) fluoroquinolone antibiotic levofloxacin (LEVO) have been degraded by anodic oxidation (AO), AO with electrogenerated H2O2 (AO-H2O2) and electro-Fenton (EF) processes using an activated carbon fiber (ACF) felt cathode from the point view of not only LEVO disappearance and mineralization, but also biodegradability enhancement. The LEVO decay by EF process followed a pseudo-first-order reaction with an apparent rate constant of 2.37×10(-2)min(-1), which is much higher than that of AO or AO-H2O2 processes. The LEVO mineralization also evidences the order EF>AO-H2O2>AO. The biodegradability (BOD5/COD) increased from 0 initially to 0.24, 0.09, and 0.03 for EF, AO-H2O2 and AO processes after 360 min treatment, respectively. Effects of several parameters such as current density, initial pH and Fe(2+) concentration on the EF degradation have also been examined. Three carboxylic acids including oxalic, formic and acetic acid were detected, as well as the released inorganic ions NH4(+), NO3(-) and F(-). At last, an ultra-performance liquid chromatography coupled with time-of-flight mass spectrometry was used to identify about eight aromatic intermediates formed in 60 min of EF treatment, and a plausible mineralization pathway for LEVO by EF treatment was proposed. Copyright © 2015 Elsevier B.V. All rights reserved.

Prevalence and Clinical Significance of an E-Reversal Wave in the Left Ventricular Outflow Tract.

PubMed

Pressman, Gregg S; Matejkova, Magdalena; Horrow, Jay C; Pai, Ramdas G

2016-11-15

Diastolic waves are commonly seen in the left ventricular outflow tract on echocardiography. This work focuses on the E-reversal wave (Er) that occurs early in diastole, shortly after the mitral E wave. Factors associated with Er presence and velocity were investigated in a broad patient sample: 100 subjects with normal ejection fraction (EF >55%) and 100 subjects with reduced EF (<45%). Er presence was noted in 58% of the total cohort and correlated inversely with age. It was more common with normal EF (70% vs 45%, p = 0.0005) and was associated with higher mitral E velocity (78.3 ± 23.3 vs 68.4 ± 19.0 cm/s; p = 0.002) and septal e' velocity (6.7 ± 2.5 vs 5.3 ± 2.3 cm/s; p <0.0001). Er velocity was higher in the normal EF group (50 ± 18 vs 34 ± 13 cm/s, p <0.0001) and showed moderate correlation with septal e' velocity (r = 0.43; p <0.0001); 56 subjects experienced major adverse cardiovascular events (MACE) over 1.7 ± 0.3 years of follow-up. Those with an Er had less MACE (particularly heart failure), even after adjustment for multiple clinical and echocardiographic variables (OR 0.28, 95% CI 0.11 to 0.65; p = 0.003). When stratified by EF, the association between Er presence and MACE was significant only in the low EF group. Thus, Er occurs more commonly in younger subjects and those with preserved EF. It is associated with less MACE although this effect appears to be limited to patients with reduced EF. Copyright © 2016 Elsevier Inc. All rights reserved.

Predictors of outcome and methodological issues in children with acute lymphoblastic leukaemia in El Salvador.

PubMed

Bonilla, Miguel; Gupta, Sumit; Vasquez, Roberto; Fuentes, Soad L; deReyes, Gladis; Ribeiro, Raul; Sung, Lillian

2010-12-01

Most children with cancer live in low-income countries (LICs) where risk factors in paediatric acute lymphoblastic leukaemia (ALL) developed in high-income countries may not apply. We describe predictors of survival for children in El Salvador with ALL. We included patients <16 years diagnosed with ALL between January 2001 and July 2007 treated with the El Salvador-Guatemala-Honduras II protocol. Demographic, disease-related, socioeconomic and nutritional variables were examined as potential predictors of event-free survival (EFS) and overall survival (OS). 260/443 patients (58.7%) were classified as standard risk. Standard- and high-risk 5-year EFS were 56.3 ± 4.5% and 48.6 ± 5.5%; 5-year OS were 77.7 ± 3.8% and 61.9 ± 5.8%, respectively. Among standard-risk children, socioeconomic variables such as higher monthly income (hazard ratio [HR] per $100 = 0.84 [95% confidence interval (CI) 0.70-0.99; P=0.04]) and parental secondary education (HR = 0.49, 95% CI 0.29-0.84; P = 0.01) were associated with better EFS. Among high-risk children, higher initial white blood cell (HR per 10×10(9)/L = 1.03, 95% CI 1.02-1.05; P<0.001) predicted worse EFS; socioeconomic variables were not predictive. The difference in EFS and OS appeared related to overestimating OS secondary to poor follow-up after abandonment/relapse. Socioeconomic variables predicted worse EFS in standard-risk children while disease-related variables were predictive in high-risk patients. Further studies should delineate pathways through which socioeconomic status affects EFS in order to design effective interventions. EFS should be the primary outcome in LIC studies. Copyright © 2010 Elsevier Ltd. All rights reserved.

The non-thermal origin of the tokamak low-density stability limit

DOE PAGES

Paz-Soldan, C.; La Haye, R. J.; Shiraki, D.; ...

2016-04-13

DIII-D plasmas at very low density exhibit onset of n=1 error field (EF) penetration (the `low-density locked mode') not at a critical density or EF, but instead at a critical level of runaway electron (RE) intensity. Raising the density during a discharge does not avoid EF penetration, so long as RE growth proceeds to the critical level. Penetration is preceded by non-thermalization of the electron cyclotron emission, anisotropization of the total pressure, synchrotron emission shape changes, as well as decreases in the loop voltage and bulk thermal electron temperature. The same phenomena occur despite various types of optimal EF correction,more » and in some cases modes are born rotating. Similar phenomena are also found at the low-density limit in JET. These results stand in contrast to the conventional interpretation of the low-density stability limit as being due to residual EFs and demonstrate a new pathway to EF penetration instability due to REs. Existing scaling laws for penetration project to increasing EF sensitivity as bulk temperatures decrease, though other possible mechanisms include classical tearing instability, thermo-resistive instability, and pressure-anisotropy driven instability. Regardless of first-principles mechanism, known scaling laws for Ohmic energy confinement combined with theoretical RE production rates allow rough extrapolation of the RE criticality condition, and thus, the low-density limit to other tokamaks. Furthermore, the extrapolated low-density limit by this pathway decreases with increasing machine size and is considerably below expected operating conditions for ITER. While likely unimportant for ITER, this effect can explain the low-density limit of existing tokamaks operating with small residual EFs.« less

Association of eating frequency with anthropometric indices and blood pressure in children and adolescents: the CASPIAN-IV Study.

PubMed

Kelishadi, Roya; Qorbani, Mostafa; Motlagh, Mohammad Esmaeil; Heshmat, Ramin; Ardalan, Gelayol; Bahreynian, Maryam

2016-01-01

This study was conducted to explore the association of eating frequency (EF) with anthropometric indices and blood pressure (BP) in children and adolescents. This nationwide cross-sectional study was performed on a multi-stage sample of 14,880 students, aged 6-18 years, living in 30 provinces in Iran. Parents were asked to report dietary intake of children as frequency of food groups and/or items. EF was defined as the sum of the daily consumption frequency of main meals and snacks. Association of EF with weight disorders, abdominal obesity, and elevated BP was assessed using different logistic regression models adjusted for potential confounding factors. Eating more frequently (≥ 6 vs. ≤ 3) was found among students who were at younger age (11.91 vs. 13.29 years) (p<0.001). Students who reported an EF of 4 (OR: 0.67, CI: 0.57-0.79), 5 (OR: 0.74, CI: 0.62-0.87), and 6 (OR: 0.54, CI: 0.44-0.65) had lower odds of being obese compared to those who had EF ≤ 3. Having EF of 4 (OR: 0.82, CI: 0.71-0.94), 5 (OR: 0.86, CI: 0.74-0.99), and ≥ 6 (OR: 0.73, CI: 0.63-0.85) was related to lower prevalence of abdominal adiposity. Higher EF was associated with lower mean values of anthropometric and BP measures, as well as with lower prevalence of generalized and abdominal obesity in children and adolescents. Longitudinal studies are needed to assess the long-term effects of EF on body composition in the pediatric age group. Copyright © 2016 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Transcatheter Interatrial Shunt Device for the Treatment of Heart Failure: Rationale and Design of the Randomized Trial to REDUCE Elevated Left Atrial Pressure in Heart Failure (REDUCE LAP-HF I).

PubMed

Feldman, Ted; Komtebedde, Jan; Burkhoff, Daniel; Massaro, Joseph; Maurer, Mathew S; Leon, Martin B; Kaye, David; Silvestry, Frank E; Cleland, John G F; Kitzman, Dalane; Kubo, Spencer H; Van Veldhuisen, Dirk J; Kleber, Franz; Trochu, Jean-Noël; Auricchio, Angelo; Gustafsson, Finn; Hasenfuβ, Gerd; Ponikowski, Piotr; Filippatos, Gerasimos; Mauri, Laura; Shah, Sanjiv J

2016-07-01

Heart failure with preserved ejection fraction (HFpEF), a major public health problem with high morbidity and mortality rates, remains difficult to manage because of a lack of effective treatment options. Although HFpEF is a heterogeneous clinical syndrome, elevated left atrial pressure-either at rest or with exertion-is a common factor among all forms of HFpEF and one of the primary reasons for dyspnea and exercise intolerance in these patients. On the basis of clinical experience with congenital interatrial shunts in mitral stenosis, it has been hypothesized that the creation of a left-to-right interatrial shunt to decompress the left atrium (without compromising left ventricular filling or forward cardiac output) is a rational, nonpharmacological strategy for alleviating symptoms in patients with HFpEF. A novel transcatheter interatrial shunt device has been developed and evaluated in patients with HFpEF in single-arm, nonblinded clinical trials. These studies have demonstrated the safety and potential efficacy of the device. However, a randomized, placebo-controlled evaluation of the device is required to further evaluate its safety and efficacy in patients with HFpEF. In this article, we give the rationale for a therapeutic transcatheter interatrial shunt device in HFpEF, and we describe the design of REDUCE Elevated Left Atrial Pressure in Heart Failure (REDUCE LAP-HF I), the first randomized controlled trial of a device-based therapy to reduce left atrial pressure in HFpEF. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02600234. © 2016 American Heart Association, Inc.

ElectroTaxis-on-a-Chip (ETC): an integrated quantitative high-throughput screening platform for electrical field-directed cell migration.

PubMed

Zhao, Siwei; Zhu, Kan; Zhang, Yan; Zhu, Zijie; Xu, Zhengping; Zhao, Min; Pan, Tingrui

2014-11-21

Both endogenous and externally applied electrical stimulation can affect a wide range of cellular functions, including growth, migration, differentiation and division. Among those effects, the electrical field (EF)-directed cell migration, also known as electrotaxis, has received broad attention because it holds great potential in facilitating clinical wound healing. Electrotaxis experiment is conventionally conducted in centimetre-sized flow chambers built in Petri dishes. Despite the recent efforts to adapt microfluidics for electrotaxis studies, the current electrotaxis experimental setup is still cumbersome due to the needs of an external power supply and EF controlling/monitoring systems. There is also a lack of parallel experimental systems for high-throughput electrotaxis studies. In this paper, we present a first independently operable microfluidic platform for high-throughput electrotaxis studies, integrating all functional components for cell migration under EF stimulation (except microscopy) on a compact footprint (the same as a credit card), referred to as ElectroTaxis-on-a-Chip (ETC). Inspired by the R-2R resistor ladder topology in digital signal processing, we develop a systematic approach to design an infinitely expandable microfluidic generator of EF gradients for high-throughput and quantitative studies of EF-directed cell migration. Furthermore, a vacuum-assisted assembly method is utilized to allow direct and reversible attachment of our device to existing cell culture media on biological surfaces, which separates the cell culture and device preparation/fabrication steps. We have demonstrated that our ETC platform is capable of screening human cornea epithelial cell migration under the stimulation of an EF gradient spanning over three orders of magnitude. The screening results lead to the identification of the EF-sensitive range of that cell type, which can provide valuable guidance to the clinical application of EF-facilitated wound healing.

Clinical implications of magnetic resonance imaging in temporomandibular disorders patients presenting ear fullness.

PubMed

Lee, Sang Yeon; Park, Ji Woon; Park, Seo Eun; Nam, Dong Woo; Lim, Hyun Jung; Kim, Young Ho

2017-12-14

The aim of this study was to investigate whether findings detected by temporomandibular joint magnetic resonance imaging (TMJ-MRI) can provide pathognomonic evidence of temporomandibular disorders (TMD) in patients with nonspecific ear fullness (EF). The association of nonspecific EF with clinical characteristics of TMD based on TMJ-MRI findings was examined. Retrospective analysis. Thirty-four subjects (42 ears) who had no detectable otologic problems as a cause of EF were enrolled in this study. Each subject underwent TMJ-MRI to identify pathology of the TMJ as a possible cause of nonspecific EF. All subjects participated in the re-evaluation process following TMD treatment. Anatomical abnormalities in TMJ-MRI, irrespective of TMD signs, were observed in 34 of the 42 ears (80.9%), such as degenerative change of the TMJ (16 ears), articular disc displacement (11 ears), and joint effusion (seven ears). Specific abnormalities of the TMJ were associated with nonspecific EF, and this symptom showed improvement following individualized TMD treatment in those with internal derangement and/or effusion of the TMJ. However, abnormal TMJ-MRI findings were also observed in seven of nine ears with no TMD signs, and there was no significant association between the presence of TMD signs and abnormal TMJ-MRI findings (χ 2 = 0.075, P = .784). Patients presenting with nonspecific EF may have TMD, which can be effectively diagnosed using TMJ-MRI. The present study revealed the causal relationship between nonspecific EF and abnormal TMJ findings based on MRI. Individualized TMD treatments based on TMJ-MRI led to improved treatment outcomes with special regard to nonspecific EF LEVEL OF EVIDENCE: 4 Laryngoscope, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

Causes and Temporal Patterns of 30-Day Readmission Among Older Adults Hospitalized With Heart Failure With Preserved or Reduced Ejection Fraction.

PubMed

Goyal, Parag; Loop, Matthew; Chen, Ligong; Brown, Todd M; Durant, Raegan W; Safford, Monika M; Levitan, Emily B

2018-04-23

It is unknown whether causes and temporal patterns of 30-day readmission vary between heart failure (HF) with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF). We sought to address this question by examining a 5% national sample of Medicare beneficiaries. We included individuals who experienced a hospitalization for HFpEF or HFrEF between 2007 and 2013. We identified causes of 30-day readmission based on primary discharge diagnosis and further classified causes of readmission as HF-related, non-HF cardiovascular-related, and non-cardiovascular-related. We calculated the cumulative incidence of these classifications for HFpEF and HFrEF in a competing risks model and calculated subdistribution hazard ratios of these classifications by comparing those with HFpEF and those with HFrEF. Among 60 640 Medicare beneficiaries, we identified 13 785 unique older adults hospitalized with HFpEF and 15 205 who were hospitalized with HFrEF. Noncardiovascular diagnoses represented the most common causes of 30-day readmission (HFpEF: 59%; HFrEF: 47%), a pattern that was observed for each week of the 30-day study period for both HFpEF and HFrEF participants. In comparing readmission diagnoses in an adjusted model, non-cardiovascular-related diagnoses were more common and HF-related diagnoses were less common in HFpEF participants. Non-cardiovascular-related diagnoses represented the most common causes of 30-day readmission following HF hospitalization for each week of the 30-day postdischarge period. HF diagnoses were less common among those with HFpEF compared with HFrEF. Future interventions aimed at reducing 30-day readmissions following an HF hospitalization would benefit from an increased focus on noncardiovascular comorbidity and interventions that target HFpEF and HFrEF separately. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Exploratory Decision-Tree Modeling of Data from the Randomized REACTT Trial of Tadalafil Versus Placebo to Predict Recovery of Erectile Function After Bilateral Nerve-Sparing Radical Prostatectomy

PubMed Central

Montorsi, Francesco; Oelke, Matthias; Henneges, Carsten; Brock, Gerald; Salonia, Andrea; d’Anzeo, Gianluca; Rossi, Andrea; Mulhall, John P.; Büttner, Hartwig

2017-01-01

Background Understanding predictors for the recovery of erectile function (EF) after nerve-sparing radical prostatectomy (nsRP) might help clinicians and patients in preoperative counseling and expectation management of EF rehabilitation strategies. Objective To describe the effect of potential predictors on EF recovery after nsRP by post hoc decision-tree modeling of data from A Study of Tadalafil After Radical Prostatectomy (REACTT). Design, setting, and participants Randomized double-blind double-dummy placebo-controlled trial in 423 men aged <68 yr with adenocarcinoma of the prostate (Gleason ≤7, normal preoperative EF) who underwent nsRP at 50 centers from nine European countries and Canada. Intervention Postsurgery 1:1:1 randomization to 9-mo double-blind treatment with tadalafil 5 mg once a day (OaD), tadalafil 20 mg on demand, or placebo, followed by a 6-wk drug-free-washout, and a 3-mo open-label tadalafil OaD treatment. Outcome measurements and statistical analysis Three decision-tree models, using the International Index of Erectile Function-Erectile Function (IIEF-EF) domain score at the end of double-blind treatment, washout, and open-label treatment as response variable. Each model evaluated the association between potential predictors: presurgery IIEF domain and IIEF single-item scores, surgical approach, nerve-sparing score (NSS), and postsurgery randomized treatment group. Results and limitations The first decision-tree model (n = 422, intention-to-treat population) identified high presurgery sexual desire (IIEF item 12: ≥3.5 and <3.5) as the key predictor for IIEF-EF at the end of double-blind treatment (mean IIEF-EF: 14.9 and 11.1), followed by high confidence to get and maintain an erection (IIEF item 15: ≥3.5 and <3.5; IIEF-EF: 15.4 and 7.1). For patients meeting these criteria, additional non-IIEF–related predictors included robot-assisted laparoscopic surgery (yes or no; IIEF-EF: 19.3 and 12.6), quality of nerve sparing (NSS: <2.5 and ≥2.5; IIEF-EF: 14.3 and 10.5), and treatment with tadalafil OaD (yes and no; IIEF-EF: 17.6 and 14.3). Additional analyses after washout and open-label treatment identified high presurgery intercourse satisfaction as the key predictor. Conclusions Exploratory decision-tree analyses identified high presurgery sexual desire, confidence, and intercourse satisfaction as key predictors for EF recovery. Patients meeting these criteria might benefit the most from conserving surgery and early postsurgery EF rehabilitation. Strategies for improving EF after surgery should be discussed preoperatively with all patients; this information may support expectation management for functional recovery on an individual patient level. Patient summary Understanding how patient characteristics and different treatment options affect the recovery of erectile function (EF) after radical surgery for prostate cancer might help physicians select the optimal treatment for their patients. This analysis of data from a clinical trial suggested that high presurgery sexual desire, sexual confidence, and intercourse satisfaction are key factors predicting EF recovery. Patients meeting these criteria might benefit the most from conserving surgery (robot-assisted surgery, perfect nerve sparing) and postsurgery medical rehabilitation of EF. Trial registration ClinicalTrials.gov, NCT01026818 PMID:26947602

Heart Failure, Left Ventricular Remodeling, and Circulating Nitric Oxide Metabolites.

PubMed

Chirinos, Julio A; Akers, Scott R; Trieu, Lien; Ischiropoulos, Harry; Doulias, Paschalis-Thomas; Tariq, Ali; Vassim, Izzah; Koppula, Maheswara R; Syed, Amer Ahmed; Soto-Calderon, Haideliza; Townsend, Raymond R; Cappola, Thomas P; Margulies, Kenneth B; Zamani, Payman

2016-10-14

Stable plasma nitric oxide (NO) metabolites (NO M ), composed predominantly of nitrate and nitrite, are attractive biomarkers of NO bioavailability. NO M levels integrate the influence of NO-synthase-derived NO production/metabolism, dietary intake of inorganic nitrate/nitrite, and clearance of NO M . Furthermore, nitrate and nitrite, the most abundant NO M , can be reduced to NO via the nitrate-nitrite-NO pathway. We compared serum NO M among subjects without heart failure (n=126), subjects with heart failure and preserved ejection fraction (HFpEF; n=43), and subjects with heart failure and reduced ejection fraction (HFrEF; n=32). LV mass and extracellular volume fraction were measured with cardiac MRI. Plasma NO M levels were measured after reduction to NO via reaction with vanadium (III)/hydrochloric acid. Subjects with HFpEF demonstrated significantly lower unadjusted levels of NO M (8.0 μmol/L; 95% CI 6.2-10.4 μmol/L; ANOVA P=0.013) than subjects without HF (12.0 μmol/L; 95% CI 10.4-13.9 μmol/L) or those with HFrEF (13.5 μmol/L; 95% CI 9.7-18.9 μmol/L). There were no significant differences in NO M between subjects with HFrEF and subjects without HF. In a multivariable model that adjusted for age, sex, race, diabetes mellitus, body mass index, current smoking, systolic blood pressure, and glomerular filtration rate, HFpEF remained a predictor of lower NO M (β=-0.43; P=0.013). NO M did not correlate with LV mass, or LV diffuse fibrosis. HFpEF, but not HFrEF, is associated with reduced plasma NO M , suggesting greater endothelial dysfunction, enhanced clearance, or deficient dietary ingestion of inorganic nitrate. Our findings may underlie the salutary effects of inorganic nitrate supplementation demonstrated in recent clinical trials in HFpEF. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Marshall N. Rosenbluth Outstanding Doctoral Thesis Award Talk: Control of Non-Axisymmetric Fields With Static and Dynamic Boundary Conditions

NASA Astrophysics Data System (ADS)

Paz-Soldan, C.

2013-10-01

Small deformations of the otherwise axisymmetric field, known as ``error fields'' (EFs), lead to large changes in global MHD stability. This talk will compare results from both 1) a line-tied screw-pinch with rotating conducting walls and 2) the DIII-D tokamak to illustrate that in both devices the EF has greatest effect where it overlaps with the spatial structure of its global kink mode. In both configurations the kink structure in the symmetry direction is well described by a single mode number (azimuthal m = 1 , toroidal n = 1 , respectively) and EF ordering is clear. In the asymmetric direction (axial and poloidal, respectively) the harmonics of the kink are coupled (by line-tying and toroidicity, respectively) and thus EF ordering is not straightforward. In the pinch, the kink is axially localized to the anode region and consequently the anode EF dominates the MHD stability. In DIII-D, the poloidal harmonics of the n = 1 EF whose pitch is smaller than the local field-line pitch are empirically shown to be dominant across a wide breadth of EF optimization experiments. In analogy with the pinch, these harmonics are also where overlap with the kink is greatest and thus where the largest plasma kink response is found. The robustness of the kink structure further enables vacuum-field cost-function minimization techniques to accurately predict optimal EF correction coil currents by strongly weighting the kink-like poloidal harmonics in the minimization. To test the limits of this paradigm recent experiments in DIII-D imposed field structures that lack kink-overlapping harmonics, yielding ~10X less sensitivity. The very different plasmas of the pinch and tokamak thus both demonstrate the dominance of the kink mode in determining optimal EF correction. Supported by US DOE under DE-AC05-06OR23100, DE-FG02-00ER54603, DE-FC02-04ER54698, and NSF 0903900.

The effects of fantastical pretend-play on the development of executive functions: An intervention study.

PubMed

Thibodeau, Rachel B; Gilpin, Ansley T; Brown, Melissa M; Meyer, Brooke A

2016-05-01

Although recent correlational studies have found a relationship between fantasy orientation (FO; i.e., a child's propensity to play in a fantastical realm) and higher order cognitive skills called executive functions (EFs), no work has addressed the causality and directionality of this relationship. The current study experimentally examined the directionality of the observed relationship between FO and EF development in preschool-aged children through an innovative play intervention employing a randomized controlled design. A sample of 110 children between the ages of 3 and 5years were randomly assigned to one of three conditions: fantastical pretend-play intervention, non-imaginative play intervention, or business-as-usual control. Results revealed that children who participated in a 5-week fantastical pretend-play intervention showed improvements in EFs, whereas children in the other two conditions did not. Within the fantastical pretend-play condition, children who were highly engaged in the play and those who were highly fantastical demonstrated the greatest gains in EFs. These data provide evidence for the equifinal relationship between fantasy-oriented play and EF development, such that engaging in fantasy-oriented play may be one of many ways to directly enhance EF development. Copyright © 2016 Elsevier Inc. All rights reserved.

Brain structure and executive functions in children with cerebral palsy: a systematic review.

PubMed

Weierink, Lonneke; Vermeulen, R Jeroen; Boyd, Roslyn N

2013-05-01

This systematic review aimed to establish the current knowledge about brain structure and executive function (EF) in children with cerebral palsy (CP). Five databases were searched (up till July 2012). Six articles met the inclusion criteria, all included structural brain imaging though no functional brain imaging. Study quality was assessed using the STROBE checklist. All articles scored between 58.7% and 70.5% for quality (100% is the maximum score). The included studies all reported poorer performance on EF tasks for children with CP compared to children without CP. For the selected EF measures non-significant effect sizes were found for the CP group compared to a semi-control group (children without cognitive deficits but not included in a control group). This could be due to the small sample sizes, group heterogeneity and lack of comparison of the CP group to typically developing children. The included studies did not consider specific brain areas associated with EF performance. To conclude, there is a paucity of brain imaging studies focused on EF in children with CP, especially of studies that include functional brain imaging. Outcomes of the present studies are difficult to compare as each study included different EF measures and cortical abnormality measures. Copyright © 2013 Elsevier Ltd. All rights reserved.

Short-Lived Buildings in China: Impacts on Water, Energy, and Carbon Emissions.

PubMed

Cai, Wenjia; Wan, Liyang; Jiang, Yongkai; Wang, Can; Lin, Lishen

2015-12-15

This paper has changed the vague understanding that "the short-lived buildings have huge environmental footprints (EF)" into a concrete one. By estimating the annual floor space of buildings demolished and calibrating the average building lifetime in China, this paper compared the EF under various assumptive extended buildings' lifetime scenarios based on time-series environmental-extended input-output model. Results show that if the average buildings' lifetime in China can be extended from the current 23.2 years to their designed life expectancy, 50 years, in 2011, China can reduce 5.8 Gt of water withdrawal, 127.1 Mtce of energy consumption, and 426.0 Mt of carbon emissions, each of which is equivalent to the corresponding annual EF of Belgium, Mexico, and Italy. These findings will urge China to extend the lifetime of existing and new buildings, in order to reduce the EF from further urbanization. This paper also verifies that the lifetime of a product or the replacement rate of a sector is a very important factor that influences the cumulative EF. When making policies to reduce the EF, adjusting people's behaviors to extend the lifetime of products or reduce the replacement rate of sectors may be a very simple and cost-effective option.

Design, synthesis, and biological evaluation of novel EF24 and EF31 analogs as potential IκB kinase β inhibitors for the treatment of pancreatic cancer.

PubMed

Xie, Xuemeng; Tu, Jinfu; You, Heyi; Hu, Bingren

2017-01-01

Given the important role that inhibitory kappa B (IκB) kinase β (IKKβ) plays in pancreatic cancer (PC) development and progression, inhibitors targeting IKKβ are believed to be increasingly popular as novel anti-PC therapies. Two synthetic molecules, named EF24 and EF31 , exhibited favorable potential in terms of inhibition of both IKKβ activity and PC cell proliferation. Aiming to enhance their cellular efficacy and to analyze their structure-activity relationship, four series of EF24 and EF31 analogs were designed and synthesized. Through kinase activity and vitality screening of cancer cells, D6 displayed excellent inhibition of both IKKβ activity and PC cell proliferation. Additionally, multiple biological evaluations showed that D6 was directly bound to IKKβ and significantly suppressed the activation of the IKKβ/nuclear factor κB pathway induced by tumor necrosis factor-α, as well as effectively inducing cancer cell apoptosis. Moreover, molecular docking and molecular dynamics simulation analysis indicated that the dominant force between D6 and IKKβ comprised hydrophobic interactions. In conclusion, D6 may be a promising therapeutic agent for PC treatment and it also provides a structural lead for the design of novel IKKβ inhibitors.

Design, synthesis, and biological evaluation of novel EF24 and EF31 analogs as potential IκB kinase β inhibitors for the treatment of pancreatic cancer

PubMed Central

Xie, Xuemeng; Tu, Jinfu; You, Heyi; Hu, Bingren

2017-01-01

Given the important role that inhibitory kappa B (IκB) kinase β (IKKβ) plays in pancreatic cancer (PC) development and progression, inhibitors targeting IKKβ are believed to be increasingly popular as novel anti-PC therapies. Two synthetic molecules, named EF24 and EF31, exhibited favorable potential in terms of inhibition of both IKKβ activity and PC cell proliferation. Aiming to enhance their cellular efficacy and to analyze their structure–activity relationship, four series of EF24 and EF31 analogs were designed and synthesized. Through kinase activity and vitality screening of cancer cells, D6 displayed excellent inhibition of both IKKβ activity and PC cell proliferation. Additionally, multiple biological evaluations showed that D6 was directly bound to IKKβ and significantly suppressed the activation of the IKKβ/nuclear factor κB pathway induced by tumor necrosis factor-α, as well as effectively inducing cancer cell apoptosis. Moreover, molecular docking and molecular dynamics simulation analysis indicated that the dominant force between D6 and IKKβ comprised hydrophobic interactions. In conclusion, D6 may be a promising therapeutic agent for PC treatment and it also provides a structural lead for the design of novel IKKβ inhibitors. PMID:28553074

Covalent triazine framework-1 as adsorbent for inline solid phase extraction-high performance liquid chromatographic analysis of trace nitroimidazoles in porcine liver and environmental waters.

PubMed

Zhong, Cheng; Chen, Beibei; He, Man; Hu, Bin

2017-02-03

In this study, covalent triazine framework-1 (CTF-1) was adopted as solid phase extraction (SPE) sorbents, and a method of SPE inline coupled with high performance liquid chromatography-ultraviolet (HPLC-UV) detection was developed for trace analysis of three nitroimidazolaes (including metronidazole, ronidazole and dimetridazole) in porcine liver and environmental water samples. CTF-1 has rich π-electron and N containing triazine, thus can form π-π interaction and intermolecular hydrogen bond with three target polar nitroimidazoles, resulting in high extraction efficiency (87%-98%). Besides, CTF-1 has large specific area, which benefits rapid mass transfer and low column pressure, leading to fast adsorption/desorption dynamics. Several parameters affecting inline SPE including pH, sample flow rate, sample volume, desorption reagents, elution flow rate, elution volume, and ionic strength were investigated. Under the optimal experimental conditions, the limits of detection (S/N=3) were found to be in the range of 0.11-0.13μg/L. The enrichment factors (EFs) ranged from 52 to 59 fold (theoretical EF was 60-fold). The relative standard deviations were in the range of 4.3-9.4% (n=7, c=1μg/L), and the linear range was 0.5-500μg/L for three target analytes. The sample throughput is 7/h. The proposed method was successfully applied to the analysis of nitroimidazoles in porcine liver and environmental water samples with good recoveries for the spiked samples. Copyright © 2016 Elsevier B.V. All rights reserved.

The influence of environmental factors on the generalisability of public health research evidence: physical activity as a worked example

PubMed Central

2011-01-01

Background It is rare that decisions about investing in public health interventions in a city, town or other location can be informed by research generated in that specific place. It is therefore necessary to base decisions on evidence generated elsewhere and to make inferences about the extent to which this evidence is generalisable to the place of interest. In this paper we discuss the issues involved in making such inferences, using physical activity as an example. We discuss the ways in which elements of the structural, physical, social and/or cultural environment (environmental factors [EFs]) can shape physical activity (PA) and also how EFs may influence the effectiveness of interventions that aim to promote PA. We then highlight the ways in which EFs may impact on the generalisability of different types of evidence. Discussion We present a framework for thinking about the influence of EFs when assessing the generalisability of evidence from the location in which the evidence was generated (place A) to the location to which the evidence is to be applied (place B). The framework relates to similarities and differences between place A and place B with respect to: a) the distributions of EFs; b) the causal pathways through which EFs or interventions are thought to exert their effect on PA and c) the ways in which EFs interact with each other. We suggest, using examples, how this scheme can be used by public health professionals who are designing, executing, reporting and synthesising research on PA; or designing/implementing interventions. Summary Our analysis and scheme, although developed for physical activity, may potentially be adapted and applied to other evidence and interventions which are likely to be sensitive to influence by elements of the structural, physical, social and/or cultural environment such as the epidemiology of obesity and healthy weight promotion. PMID:22087556

A Wide Band Gap Polymer with a Deep Highest Occupied Molecular Orbital Level Enables 14.2% Efficiency in Polymer Solar Cells.

PubMed

Li, Sunsun; Ye, Long; Zhao, Wenchao; Yan, Hongping; Yang, Bei; Liu, Delong; Li, Wanning; Ade, Harald; Hou, Jianhui

2018-05-21

To simultaneously achieve low photon energy loss ( E loss ) and broad spectral response, the molecular design of the wide band gap (WBG) donor polymer with a deep HOMO level is of critical importance in fullerene-free polymer solar cells (PSCs). Herein, we developed a new benzodithiophene unit, i.e., DTBDT-EF, and conducted systematic investigations on a WBG DTBDT-EF-based donor polymer, namely, PDTB-EF-T. Due to the synergistic electron-withdrawing effect of the fluorine atom and ester group, PDTB-EF-T exhibits a higher oxidation potential, i.e., a deeper HOMO level (ca. -5.5 eV) than most well-known donor polymers. Hence, a high open-circuit voltage of 0.90 V was obtained when paired with a fluorinated small molecule acceptor (IT-4F), corresponding to a low E loss of 0.62 eV. Furthermore, side-chain engineering demonstrated that subtle side-chain modulation of the ester greatly influences the aggregation effects and molecular packing of polymer PDTB-EF-T. With the benefits of the stronger interchain π-π interaction, the improved ordering structure, and thus the highest hole mobility, the most symmetric charge transport and reduced recombination are achieved for the linear decyl-substituted PDTB-EF-T (P2)-based PSCs, leading to the highest short-circuit current density and fill factor (FF). Due to the high Flory-Huggins interaction parameter (χ), surface-directed phase separation occurs in the P2:IT-4F blend, which is supported by X-ray photoemission spectroscopy results and cross-sectional transmission electron microscope images. By taking advantage of the vertical phase distribution of the P2:IT-4F blend, a high power conversion efficiency (PCE) of 14.2% with an outstanding FF of 0.76 was recorded for inverted devices. These results demonstrate the great potential of the DTBDT-EF unit for future organic photovoltaic applications.

A comparison of time taken to return to baseline erectile function following focal and whole gland ablative therapies for localized prostate cancer: A systematic review.

PubMed

Faure Walker, Nicholas A; Norris, Joseph M; Shah, Taimur T; Yap, Tet; Cathcart, Paul; Moore, Caroline M; Ahmed, Hashim U; Emberton, Mark; Minhas, Suks

2018-02-01

To systematically review erectile function (EF) outcomes following primary whole gland (WG) and focal ablative therapies for localized prostate cancer to ascertain whether the treatment modality or intended treatment volume affects the time taken to recover baseline EF. A systematic review was performed according to the preferred reporting items for systematic review and meta-analysis statement. Inclusion criteria were men with localized prostate cancer treated with primary, ablative therapy. Primary outcome was the return to baseline EF measured with objective, validated symptoms scores. Secondary outcome was use of phosphodiesterase inhibitors or erectile aids. Meta-analysis was not performed owing to heterogenous outcome measures. Of 222 articles identified in February 2017, 55 studies which reported EF after ablative therapy were identified but only 17 used validated outcome measures and met inclusion criteria. WG cryotherapy was used in 2 studies, WG high-intensity focused ultrasound (HIFU) in 5, focal cryotherapy in 2, focal HIFU in 3, focal phototherapy or laser therapy in 4, vascular-targeted photodynamic therapy in 3, and irreversible electroporation in 2. WG cryotherapy was associated with a significant decline in EF at 6 months with minimal improvement at 36 months. Baseline IIEF-15 of patients undergoing focal HIFU fell 30 points at 1 month but returned to baseline by 6 months. The remaining focal therapies demonstrated minimal or no effect on EF, but the men in these studies had small foci of disease. The review is limited by lack of randomized studies and heterogenous outcome measures. Most studies assessing the outcomes of focal therapy on sexual function were not of high quality, used heterogenous outcomes, and had relatively short follow up, highlighting the need for more robustly designed studies using validated patient reported outcome measures  for comparison. However, FT in general resulted in less effect on EF than WG ablation. Copyright © 2018 Elsevier Inc. All rights reserved.

A randomized trial of hemodiafiltration and change in cardiovascular parameters.

PubMed

Mostovaya, Irina M; Bots, Michiel L; van den Dorpel, Marinus A; Grooteman, Muriel P C; Kamp, Otto; Levesque, Renée; Ter Wee, Piet M; Nubé, Menso J; Blankestijn, Peter J

2014-03-01

Increased left ventricular mass (LVM), low ventricular ejection fraction (EF), and high pulse-wave velocity (PWV) relate to overall and cardiovascular mortality in patients with ESRD. The aim of this study was to determine the effect of online hemodiafiltration (HDF) versus low-flux hemodialysis (HD) on LVM, EF, and PWV. Echocardiography was used to assess LVM and EF in 342 patients in the CONvective TRAnsport STudy followed for up to 4 years. PWV was measured in 189 patients for up to 3 years. Effect of HDF versus HD on LVM, EF, and PWV was evaluated using linear mixed models. Patients had a mean age of 63 years, and 61% were male. At baseline, median LVM was 227 g (interquartile range [IQR], 183-279 g), and median EF was 65% (IQR, 55%-72%). Median PWV was 9.8 m/s (IQR, 7.5-12.0 m/s). There was no significant difference between the HDF and HD treatment groups in rate of change in LVM (HDF: change, -0.9 g/yr [95% confidence interval (95% CI), -8.9 to 7.7 g]; HD: change, 12.5 g/yr [95% CI, -3.0 to 27.5 g]; P for difference=0.13), EF (HDF: change, -0.3%/yr [95% CI, -2.3% to 1.8%]; HD: change, -3.4%/yr [95% CI, -5.9% to -0.9%]; P=0.17), or PWV (HDF: change, -0.0 m/s per year [95% CI, -0.4 to 0.4 m/s); HD: change, 0.0 m/s per year [95% CI, -0.3 to 0.2 m/s]; P=0.89). No differences in rate of change between treatment groups were observed for subgroups of age, sex, residual kidney function, dialysis vintage, history of cardiovascular disease, diabetes, or convection volume. Treatment with online HDF did not affect changes in LVM, EF, or PWV over time compared with HD.

Biochemical and genetic characterization of the Enterococcus faecalis oxaloacetate decarboxylase complex.

PubMed

Repizo, Guillermo D; Blancato, Víctor S; Mortera, Pablo; Lolkema, Juke S; Magni, Christian

2013-05-01

Enterococcus faecalis encodes a biotin-dependent oxaloacetate decarboxylase (OAD), which is constituted by four subunits: E. faecalis carboxyltransferase subunit OadA (termed Ef-A), membrane pump Ef-B, biotin acceptor protein Ef-D, and the novel subunit Ef-H. Our results show that in E. faecalis, subunits Ef-A, Ef-D, and Ef-H form a cytoplasmic soluble complex (termed Ef-AHD) which is also associated with the membrane. In order to characterize the role of the novel Ef-H subunit, coexpression of oad genes was performed in Escherichia coli, showing that this subunit is vital for Ef-A and Ef-D interaction. Diminished growth of the oadA and oadD single deletion mutants in citrate-supplemented medium indicated that the activity of the complex is essential for citrate utilization. Remarkably, the oadB-deficient strain was still capable of growing to wild-type levels but with a delay during the citrate-consuming phase, suggesting that the soluble Ef-AHD complex is functional in E. faecalis. These results suggest that the Ef-AHD complex is active in its soluble form, and that it is capable of interacting in a dynamic way with the membrane-bound Ef-B subunit to achieve its maximal alkalinization capacity during citrate fermentation.

Reductions in emissions of carbonaceous particulate matter and polycyclic aromatic hydrocarbons from combustion of biomass pellets in comparison with raw fuel burning.

PubMed

Shen, Guofeng; Tao, Shu; Wei, Siye; Zhang, Yanyan; Wang, Rong; Wang, Bin; Li, Wei; Shen, Huizhong; Huang, Ye; Chen, Yuanchen; Chen, Han; Yang, Yifeng; Wang, Wei; Wei, Wen; Wang, Xilong; Liu, Wenxing; Wang, Xuejun; Masse Simonich, Staci L y

2012-06-05

Biomass pellets are emerging as a cleaner alternative to traditional biomass fuels. The potential benefits of using biomass pellets include improving energy utilization efficiency and reducing emissions of air pollutants. To assess the environmental, climate, and health significance of replacing traditional fuels with biomass pellets, it is critical to measure the emission factors (EFs) of various pollutants from pellet burning. However, only a few field measurements have been conducted on the emissions of carbon monoxide (CO), particulate matter (PM), and polycyclic aromatic hydrocarbons (PAHs) from the combustion of pellets. In this study, pine wood and corn straw pellets were burned in a pellet burner (2.6 kW), and the EFs of CO, organic carbon, elemental carbon, PM, and PAHs (EF(CO), EF(OC), EF(EC), EF(PM), and EF(PAH)) were determined. The average EF(CO), EF(OC), EF(EC), and EF(PM) were 1520 ± 1170, 8.68 ± 11.4, 11.2 ± 8.7, and 188 ± 87 mg/MJ for corn straw pellets and 266 ± 137, 5.74 ± 7.17, 2.02 ± 1.57, and 71.0 ± 54.0 mg/MJ for pine wood pellets, respectively. Total carbonaceous carbon constituted 8 to 14% of the PM mass emitted. The measured values of EF(PAH) for the two pellets were 1.02 ± 0.64 and 0.506 ± 0.360 mg/MJ, respectively. The secondary side air supply in the pellet burner did not change the EFs of most pollutants significantly (p > 0.05). The only exceptions were EF(OC) and EF(PM) for pine wood pellets because of reduced combustion temperatures with the increased air supply. In comparison with EFs for the raw pine wood and corn straw, EF(CO), EF(OC), EF(EC), and EF(PM) for pellets were significantly lower than those for raw fuels (p < 0.05). However, the differences in EF(PAH) were not significant (p > 0.05). Based on the measured EFs and thermal efficiencies, it was estimated that 95, 98, 98, 88, and 71% reductions in the total emissions of CO, OC, EC, PM, and PAHs could be achieved by replacing the raw biomass fuels combusted in traditional cooking stoves with pellets burned in modern pellet burners.

Further Analysis of the Effects of Positive Reinforcement on Working Memory in Children with Autism

ERIC Educational Resources Information Center

Baltruschat, Lisa; Hasselhorn, Marcus; Tarbox, Jonathan; Dixon, Dennis R.; Najdowski, Adel C.; Mullins, Ryan D.; Gould, Evelyn R.

2011-01-01

Individuals with autism spectrum disorders (ASD) often exhibit impaired executive function (EF) performance, including difficulty with working memory (WM), in particular. While research has documented the existence of these deficits, surprisingly little research exists that evaluates potential treatment strategies for improving EF or WM. One…

Executive Functioning and Speech-Language Skills Following Long-Term Use of Cochlear Implants

ERIC Educational Resources Information Center

Kronenberger, William G.; Colson, Bethany G.; Henning, Shirley C.; Pisoni, David B.

2014-01-01

Neurocognitive processes such as executive functioning (EF) may influence the development of speech-language skills in deaf children after cochlear implantation in ways that differ from normal-hearing, typically developing children. Conversely, spoken language abilities and experiences may also exert reciprocal effects on the development of EF.…

Minimum energy control for a two-compartment neuron to extracellular electric fields

NASA Astrophysics Data System (ADS)

Yi, Guo-Sheng; Wang, Jiang; Li, Hui-Yan; Wei, Xi-Le; Deng, Bin

2016-11-01

The energy optimization of extracellular electric field (EF) stimulus for a neuron is considered in this paper. We employ the optimal control theory to design a low energy EF input for a reduced two-compartment model. It works by driving the neuron to closely track a prescriptive spike train. A cost function is introduced to balance the contradictory objectives, i.e., tracking errors and EF stimulus energy. By using the calculus of variations, we transform the minimization of cost function to a six-dimensional two-point boundary value problem (BVP). Through solving the obtained BVP in the cases of three fundamental bifurcations, it is shown that the control method is able to provide an optimal EF stimulus of reduced energy for the neuron to effectively track a prescriptive spike train. Further, the feasibility of the adopted method is interpreted from the point of view of the biophysical basis of spike initiation. These investigations are conducive to designing stimulating dose for extracellular neural stimulation, which are also helpful to interpret the effects of extracellular field on neural activity.

Socioeconomic status and oppositional defiant disorder in preschoolers: parenting practices and executive functioning as mediating variables.

PubMed

Granero, Roser; Louwaars, Leonie; Ezpeleta, Lourdes

2015-01-01

To investigate the mediating mechanisms of oppositional defiant disorder (ODD) in preschoolers through pathways analysis, considering the family socioeconomic status (SES) as the independent variable and the parenting style and the children's executive functioning (EF) as the mediating factors. The sample included 622 three-year-old children from the general population. Multi-informant reports from parents and teachers were analyzed. Structural Equation Modeling showed that the associations between SES, EF, parenting style and ODD levels differed by children's gender: (a) for girls, the association of low SES and high ODD scores was partially mediated by difficulties in EF inhibition, and parenting practices defined by corporal punishment and inconsistent discipline obtained a quasi-significant indirect effect into the association between SES and ODD; (b) for boys, SES and EF (inhibition and emotional control) had a direct effect on ODD with no mediation. SES seems a good indicator to identify children at high-risk for prevention and intervention programs for ODD. Girls with ODD in families of low SES may particularly benefit from parent training practices and training in inhibition control.

In vitro Antiproliferative Effect of Earthworm Coelomic Fluid of Eudrilus Eugeniae, Eisenia Foetida, and Perionyx Excavatus on Squamous Cell Carcinoma-9 Cell Line: A Pilot Study.

PubMed

Augustine, Dominic; Rao, Roopa S; Anbu, Jayaraman; Chidambara Murthy, K N

2017-12-01

The earthworm coelomic fluid (ECF) has shown proven antiproliferative effect against breast, liver, gastrointestinal, and brain cancer, but it is least explored in oral cancer. The present in vitro study is an attempt to investigate the antiproliferative activity of ECF on oral cancer cell line squamous cell carcinoma (SCC)-9. ECF was collected from the species Eudrilus eugeniae (EE), Eisenia foetida (EF), and Perionyx excavatus (PE) stored at -80°C. Percentage inhibition of ECF on squamous cell carcinoma-9 cells in vitro was recorded at 24 h. Protein estimation was done using Bradford protein assay validated by the biuret method. Cytotoxicity was tested at 2.5, 5, 10, 20, 40, and 80 μg/ml concentrations by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay in SCC-9 cells in vitro . GraphPad Prism 7.0 software was used to calculate the inhibitory concentration (IC 50 ). Chi-square test was used to analyze the difference between samples. The test samples EE, EF, and PE inhibited the growth of SCC-9 cells significantly in a dose-dependent manner, and the IC 50 values were found to be 4.6, 44.69, and 5.27 μg/ml, respectively. The antiproliferative effect was found to be variable among the three earthworm species with EE showing the most promising effect followed by PE and EF. Establishing the antiproliferative effect of ECF on oral cancer cells could be an initial step toward drug development and future anticancer research. The preliminary investigation has shown that ECF has a promising antiproliferative effect on oral cancer cells in vitro . The present pilot study evaluated the in vitro antiproliferative effect of earthworm coelomic fluid (ECF) of Eudrilus eugeniae (EE), Eisenia foetida (EF), and Perionyx excavatus (PE) on squamous cell carcinoma-9 cell line. The ECF inhibitory activity was promising at inhibitory concentration values of 4.6, 44.69, and 5.27 μg/ml, respectively. Further studies pertaining to antiproliferative mechanism of EE, EF, and PE have been planned. Abbreviations Used: ECF: Earthworm coelomic fluid, EE: Eudrilus eugeniae , EF: Eisenia foetida , PE: Perionyx excavatus , MTT: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, SCC: Squamous cell carcinoma, BSA: Bovine serum albumin, PBS: Phosphored buffered saline, ATCC: American Type Culture Collection.

An evolutionary ‘intermediate state’ of mitochondrial translation systems found in Trichinella species of parasitic nematodes: co-evolution of tRNA and EF-Tu

PubMed Central

Arita, Masashi; Suematsu, Takuma; Osanai, Arihiro; Inaba, Takashi; Kamiya, Haruo; Kita, Kiyoshi; Sisido, Masahiko; Watanabe, Yoh-ichi; Ohtsuki, Takashi

2006-01-01

EF-Tu delivers aminoacyl-tRNAs to ribosomes in the translation system. However, unusual truncations found in some animal mitochondrial tRNAs seem to prevent recognition by a canonical EF-Tu. We showed previously that the chromadorean nematode has two distinct EF-Tus, one of which (EF-Tu1) binds only to T-armless aminoacyl-tRNAs and the other (EF-Tu2) binds to D-armless Ser-tRNAs. Neither of the EF-Tus can bind to canonical cloverleaf tRNAs. In this study, by analyzing the translation system of enoplean nematode Trichinella species, we address how EF-Tus and tRNAs have evolved from the canonical structures toward those of the chromadorean translation system. Trichinella mitochondria possess three types of tRNAs: cloverleaf tRNAs, which do not exist in chromadorean nematode mitochondria; T-armless tRNAs; and D-armless tRNAs. We found two mitochondrial EF-Tu species, EF-Tu1 and EF-Tu2, in Trichinella britovi. T.britovi EF-Tu2 could bind to only D-armless Ser-tRNA, as Caenorhabditis elegans EF-Tu2 does. In contrast to the case of C.elegans EF-Tu1, however, T.britovi EF-Tu1 bound to all three types of tRNA present in Trichinella mitochondria. These results suggest that Trichinella mitochondrial translation system, and particularly the tRNA-binding specificity of EF-Tu1, could be an intermediate state between the canonical system and the chromadorean nematode mitochondrial system. PMID:17012285

Electrostatics effects on Ca(2+) binding and conformational changes in EF-hand domains: Functional implications for EF-hand proteins.

PubMed

Ababou, Abdessamad; Zaleska, Mariola

2015-12-01

Mutations of Gln41 and Lys75 with nonpolar residues in the N-terminal domain of calmodulin (N-Cam) revealed the importance of solvation energetics in conformational change of Ca(2+) sensor EF-hand domains. While in general these domains have polar residues at these corresponding positions yet the extent of their conformational response to Ca(2+) binding and their Ca(2+) binding affinity can be different from N-Cam. Consequently, here we address the charge state of the polar residues at these positions. The results show that the charge state of these polar residues can affect substantially the conformational change and the Ca(2+) binding affinity of our N-Cam variants. Since all the variants kept their conformational activity in the presence of Ca(2+) suggests that the differences observed among them mainly originate from the difference in their molecular dynamics. Hence we propose that the molecular dynamics of Ca(2+) sensor EF-hand domains is a key factor in the multifunctional aspect of EF-hand proteins. Copyright © 2015 Elsevier Inc. All rights reserved.

Safety and Efficacy of Donepezil in Children and Adolescents with Autism: Neuropsychological Measures

PubMed Central

Johnson, Cynthia R.; McAuliffe-Bellin, Sarah; Murray, Patricia Jo; Hardan, Antonio Y.

2011-01-01

Abstract Objective There has been recent interest in the use of cognitive enhancing drugs, such as cholinesterase inhibitors, as a possible treatment for executive functioning (EF) deficits in autism spectrum disorder (ASD). The goal of this study was to assess the tolerability, safety, and efficacy of donepezil on EF in a sample of children and adolescents with ASD. Method Thirty-four children and adolescents with ASD (age range 8–17 years; IQ >75) were enrolled in a 10-week, double-blind, placebo-controlled trial of donepezil (doses of 5 and 10 mg), followed by a 10-week open label trial for placebo nonresponders. Results The effect of donepezil treatment on EF was examined. Despite improvement on a number of EF measures, no statistically significant between-group differences were found (with gains observed for both the placebo and donepezil groups). Conclusions The results suggest that short-term treatment with donepezil may have limited impact on cognitive functioning in ASD. Future controlled trials may need to consider a longer treatment period to detect significant gains on EF measures. PMID:21309696

The Minimal and Short-Lived Effects of Minority Language Exposure on the Executive Functions of Frisian-Dutch Bilingual Children

PubMed Central

Bosma, Evelyn; Hoekstra, Eric; Versloot, Arjen; Blom, Elma

2017-01-01

Various studies have shown that bilingual children need a certain degree of proficiency in both languages before their bilingual experiences enhance their executive functioning (EF). In the current study, we investigated if degree of bilingualism in Frisian-Dutch children influenced EF and if this effect was sustained over a 3-year period. To this end, longitudinal data were analyzed from 120 Frisian-Dutch bilingual children who were 5- or 6-years-old at the first time of testing. EF was measured with two attention and two working memory tasks. Degree of bilingualism was defined as language balance based on receptive vocabulary and expressive morphology scores in both languages. In a context with a minority and a majority language, such as the Frisian-Dutch context, chances for becoming proficient in both languages are best for children who speak the minority language at home. Therefore, in a subsequent analysis, we examined whether minority language exposure predicted language balance and whether there was a relationship between minority language exposure and EF, mediated by language balance. The results showed that intensity of exposure to Frisian at home, mediated by language balance, had an impact on one of the attention tasks only. It predicted performance on this task at time 1, but not at time 2 and 3. This partially confirms previous evidence that the cognitive effects of bilingualism are moderated by degree of bilingualism and furthermore reveals that substantial minority language exposure at home indirectly affects bilingual children’s cognitive development, namely through mediation with degree of bilingualism. However, the findings also demonstrate that the effect of bilingualism on EF is limited and unstable. PMID:28900405

The Minimal and Short-Lived Effects of Minority Language Exposure on the Executive Functions of Frisian-Dutch Bilingual Children.

PubMed

Bosma, Evelyn; Hoekstra, Eric; Versloot, Arjen; Blom, Elma

2017-01-01

Various studies have shown that bilingual children need a certain degree of proficiency in both languages before their bilingual experiences enhance their executive functioning (EF). In the current study, we investigated if degree of bilingualism in Frisian-Dutch children influenced EF and if this effect was sustained over a 3-year period. To this end, longitudinal data were analyzed from 120 Frisian-Dutch bilingual children who were 5- or 6-years-old at the first time of testing. EF was measured with two attention and two working memory tasks. Degree of bilingualism was defined as language balance based on receptive vocabulary and expressive morphology scores in both languages. In a context with a minority and a majority language, such as the Frisian-Dutch context, chances for becoming proficient in both languages are best for children who speak the minority language at home. Therefore, in a subsequent analysis, we examined whether minority language exposure predicted language balance and whether there was a relationship between minority language exposure and EF, mediated by language balance. The results showed that intensity of exposure to Frisian at home, mediated by language balance, had an impact on one of the attention tasks only. It predicted performance on this task at time 1, but not at time 2 and 3. This partially confirms previous evidence that the cognitive effects of bilingualism are moderated by degree of bilingualism and furthermore reveals that substantial minority language exposure at home indirectly affects bilingual children's cognitive development, namely through mediation with degree of bilingualism. However, the findings also demonstrate that the effect of bilingualism on EF is limited and unstable.

Effects of bacterial direct-fed microbials and yeast on site and extent of digestion, blood chemistry, and subclinical ruminal acidosis in feedlot cattle.

PubMed

Beauchemin, K A; Yang, W Z; Morgavi, D P; Ghorbani, G R; Kautz, W; Leedle, J A Z

2003-06-01

Two studies were conducted to determine whether a bacterial direct-fed microbial (DFM) alone or with yeast could minimize the risk of acidosis and improve feed utilization in feedlot cattle receiving high-concentrate diets. Eight ruminally cannulated steers, previously adapted to a high-concentrate diet, were used in crossover designs to study the effects of DFM on feed intake, ruminal pH, ruminal fermentation, blood characteristics, site and extent of digestion, and microbial protein synthesis. Steers were provided ad libitum access to a diet containing steam-rolled barley, barley silage, and a protein-mineral supplement (87, 8, and 5% on a DM basis, respectively). In Exp. 1, treatments were control vs. the lactic-acid producing bacterium Enterococcus faecium EF212 (EF; 6 x 10(9) cfu/d). In Exp. 2, treatments were control vs EF (6 x 10(9) cfu/d) and yeast (Saccharomyces cerevisiae; 6 x 10(9) cfu/d). Supplementing feedlot cattle diets with EF in Exp. 1 increased (P < 0.05) propionate and (P < 0.05) decreased butyrate concentrations, decreased the nadir of ruminal pH (P < 0.05), enhanced the flow of feed N (P < 0.10) to the duodenum but reduced that of microbial N (P < 0.10), reduced (P < 0.10) intestinal digestion of NDF, and increased (P < 0.10) fecal coliform numbers. Other than the increase in propionate concentrations that signify an increase in energy precursors for growth, the other metabolic changes were generally considered to be undesirable. In Exp. 2, providing EF together with yeast abolished most of these undesirable effects. Combining EF with yeast increased the DM digestion of corn grain incubated in sacco, but there were no effects on altering the site or extent of nutrient digestion. The diets used in this study were highly fermentable, and the incidence of subclinical ruminal acidosis, defined as steers with ruminal pH below 5.5 for prolonged periods of time, was high. Supplementing the diet with EF, with or without yeast, had limited effects on reducing ruminal acidosis. It seems that cattle adapted to high-grain diets are able to maintain relatively high feed intake and high fiber digestion despite low ruminal pH. The Enterococcus faecium bacterium and yeast used in this study were of limited value for feedlot cattle already adapted to high-grain diets.

The impact of human activities in soils and sediments on urban and peri-urban areas

NASA Astrophysics Data System (ADS)

Horváth, Adrienn; Szita, Renáta; Bidló, András; Gribovszki, Zoltán

2017-04-01

In this current research we would like to detect the amount of the differences between the natural, the suburb and the urban areas. The aim of the investigation was to determine the impact of human activities on urban and peri-urban soils of Sopron. 72 urban soil samples were collected on 6 sub-catchments for analysing the background pollution of Rák Creek in Sopron. After the analysis of chemical and physical properties of urban soil samples, two element fractions - the total (HNO3+H2O2-extractable) and the available NH4-acetate+EDTA-extractable - were used for element determination. Toxic elements were measured by ICP-OES in the urban soils and the sediments as well. in case of sediment samples from thalweg and dead region. That were collected from the bank of the Rák creek at 6 sampling points to calculate enrichment factors to assess the possible harmful effects of toxic metals. The field and laboratory data were processed using a GIS softver DigiTerraMap. Six elements were selected for analyses Co, Cd, Ni, Cu, Zn, Pb, which are prominent in urban soils. Statistical analysis was carried out with Microsoft Office Excel 2003, STATISTICA 11 and R Studio. C2 program was used for the distribution of toxic elements. Based on results e.g. pH, etc., there were definite differences between natural HAZ, BAN, semi-natural HAJNAL and urbanized FASOR, GYORI, TESCO areas and significant differences in toxic element distribution as well. The toxic elements of sediment showed the following tendency: Pb > Zn > Cu > Ni = Co. The Co and the Ni values were lower than the natural background limits. The Cutotal exceeded the first interventional pollution limit > 75 mg.kg-1 and the available Zn and Pb were higher than the suggested interventional pollution limits Znavailable >40 mg.kg-1; Pbavailable >25 mg.kg-1 at GYORI sub-catchment. The EF values were generally higher in dead region than in thalweg except of GYORI point. Lead had the highest EF values between the five metals investigated and it is followed by Zn strongly. The EFPb > 5, which indicates the moderate degree of Pb contamination inside the town. Co, Cu and Ni exhibited the lowest in our EF values. Summarized, the largest heavy metal values were in sampling point GYORI. The EF values for Pb and Zn increased towards city. The accumulation of Pb was confirmed by moderate enrichment of sediment samples, which are originated from the busiest transport hub of Sopron. The difference between natural and urban areas seemed definite based on our results. Even though the flow characteristic of the dead region and thalweg of the natural part of the stream was different, the heavy metals accumulated in the dead region mainly in the urbanized area.

Structure of the ACF7 EF-Hand-GAR Module and Delineation of Microtubule Binding Determinants.

PubMed

Lane, Thomas R; Fuchs, Elaine; Slep, Kevin C

2017-07-05

Spectraplakins are large molecules that cross-link F-actin and microtubules (MTs). Mutations in spectraplakins yield defective cell polarization, aberrant focal adhesion dynamics, and dystonia. We present the 2.8 Å crystal structure of the hACF7 EF1-EF2-GAR MT-binding module and delineate the GAR residues critical for MT binding. The EF1-EF2 and GAR domains are autonomous domains connected by a flexible linker. The EF1-EF2 domain is an EFβ-scaffold with two bound Ca 2+ ions that straddle an N-terminal α helix. The GAR domain has a unique α/β sandwich fold that coordinates Zn 2+ . While the EF1-EF2 domain is not sufficient for MT binding, the GAR domain is and likely enhances EF1-EF2-MT engagement. Residues in a conserved basic patch, distal to the GAR domain's Zn 2+ -binding site, mediate MT binding. Copyright © 2017 Elsevier Ltd. All rights reserved.

Heat tolerance and expression of protein synthesis elongation factors, EF-Tu and EF-1a, in spring wheat

USDA-ARS?s Scientific Manuscript database

Protein elongation factors, EF-Tu and EF-1a, have been implicated in cell response to heat stress. In spring wheat, EF-Tu displays chaperone activity and reduces thermal aggregation of Rubisco activase. Similarly, in mammalian cells, EF-1a displays chaperone-like activity and regulates the expressio...

Drivers and Blockers: Embedding Education for Sustainability (EfS) in Primary Teacher Education

ERIC Educational Resources Information Center

Wilson, Sue

2012-01-01

The growing emphasis on sustainability in school curricula in Australia reflects international trends in education. Teacher education is a vital strategy for the incorporation of Education for Sustainability (EfS) in school curricula. Research to identify drivers and barriers to embedding EfS across a primary teacher education program in an…

Beliefs and Education for Sustainability in Rural and Regional Australia

ERIC Educational Resources Information Center

Boon, Helen J.

2011-01-01

Few studies have investigated pre-service teachers' beliefs and their knowledge of Education for Sustainability (EfS). Where they have, their perceptions of EfS and the instrumentality of their actions have not been linked to their knowledge of EfS. This matter is particularly important to prepare teachers to teach in Australian rural schools…

The ultrafast dynamics and conductivity of photoexcited graphene at different Fermi energies

PubMed Central

Turchinovich, Dmitry; Kläui, Mathias; Hendry, Euan; Polini, Marco

2018-01-01

For many of the envisioned optoelectronic applications of graphene, it is crucial to understand the subpicosecond carrier dynamics immediately following photoexcitation and the effect of photoexcitation on the electrical conductivity—the photoconductivity. Whereas these topics have been studied using various ultrafast experiments and theoretical approaches, controversial and incomplete explanations concerning the sign of the photoconductivity, the occurrence and significance of the creation of additional electron-hole pairs, and, in particular, how the relevant processes depend on Fermi energy have been put forward. We present a unified and intuitive physical picture of the ultrafast carrier dynamics and the photoconductivity, combining optical pump–terahertz probe measurements on a gate-tunable graphene device, with numerical calculations using the Boltzmann equation. We distinguish two types of ultrafast photo-induced carrier heating processes: At low (equilibrium) Fermi energy (EF ≲ 0.1 eV for our experiments), broadening of the carrier distribution involves interband transitions (interband heating). At higher Fermi energy (EF ≳ 0.15 eV), broadening of the carrier distribution involves intraband transitions (intraband heating). Under certain conditions, additional electron-hole pairs can be created [carrier multiplication (CM)] for low EF, and hot carriers (hot-CM) for higher EF. The resultant photoconductivity is positive (negative) for low (high) EF, which in our physical picture, is explained using solely electronic effects: It follows from the effect of the heated carrier distributions on the screening of impurities, consistent with the DC conductivity being mostly due to impurity scattering. The importance of these insights is highlighted by a discussion of the implications for graphene photodetector applications. PMID:29756035

Inhibitors of neutral endopeptidase potentiate electrically and capsaicin-induced noncholinergic contraction in guinea pig bronchi.

PubMed

Djokic, T D; Nadel, J A; Dusser, D J; Sekizawa, K; Graf, P D; Borson, D B

1989-01-01

To evaluate the role of airway neutral endopeptidase (NEP) in the regulation of contraction of airway smooth muscle in response to endogenous tachykinins, we studied the effects of the NEP inhibitor phosphoramidon on contractions of guinea pig bronchial smooth muscle strips induced by either electrical field stimulation (EFS) or by capsaicin. In the presence of atropine (10(-6) M), propranolol (10(-6) M), phentolamine (10(-5) M), indomethacin (10(-6) M) and pyrilamine (5 x 10(-6) M) EFS (biphasic; pulse width, 1.0 msec; frequency 0.5-5 Hz for 30 sec; intensity, 20 V) produced noncholinergic, nonadrenergic muscle contraction in a frequency-dependent fashion (P less than .001). Phosphoramidon potentiated the contractile responses to EFS (P less than .01). Leucine-thiorphan (10(-5) M), another NEP inhibitor, potentiated EFS-induced contraction in a similar fashion as phosphoramidon (186 and 182% of control, respectively; each comparison, P less than .025). Captopril, bestatin, leupeptin and physostigmine (each drug, 10(-5) M) were without effect (P greater than .5, N = 5). Capsaicin (1.5 x 10(-8) M) produced long-lasting atropine-resistant smooth muscle contraction, an effect potentiated by phosphoramidon (10(-5) M (P less than .001). Removal of the epithelium slightly but significantly (P less than .05) increased the contractile responses to capsaicin and to EFS at impulse frequencies of 2 and 5 Hz, and phosphoramidon substantially increased contractions in tissues without epithelium. The trachea, bronchi and lungs each contained significant NEP activity.(ABSTRACT TRUNCATED AT 250 WORDS)

On the indiscriminate use of imported emission factors in environmental impact assessment: A case study in Chile

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bernal, María Fernanda; Oyarzún, Jorge; Oyarzún, Ricardo, E-mail: royarzun@userena.cl

Environmental Impact Assessment (EIA) aims to determine if the environmental effect of an activity or project complies with standards and regulations. A primary component of the environment to evaluate is air and the effect that various activities can have on its quality. To this end, emission factors (EFs), which are empirical coefficients or mathematical relationships, are normally used. The present research critically analyzes the implications and consequences of using imported EFs in environmental impact studies (EISs), taking as case of study the situation in Chile. Among the main results, the widespread use of EFs in EISs in the country andmore » the lack of assessments of their actual applicability stand out. In addition, the official guidelines related to emissions estimation that are used for EIA in the country mostly include EFs derived elsewhere, without considering the recommendations or restrictions that the original sources indicate for their use. Finally, the broad use of default values defined for the Metropolitan Region in Central Chile, is highly questionable for a country that extends north-south along more than 35° of latitude, with wide variability in climate, traffic conditions, population, soil types, etc. Finally, it is very likely that situations similar to those observed in the present work occurs in other countries with young environmental impact assessment systems, and therefore, that the results herein presented should be of general interest and relevance. - Highlights: • Emission factors are widely used in environmental impact assessment in Chile. • There is a lack of a proper understanding of the limitations of EFs for EIA. • Imported emission factors use requires caution and full understanding. • Misuse of foreign EFs may have serious environmental and economic consequences.« less

Effectiveness of late gadolinium enhancement to improve outcomes prediction in patients referred for cardiovascular magnetic resonance after echocardiography

PubMed Central

2013-01-01

Background Echocardiography (echo) is a first line test to assess cardiac structure and function. It is not known if cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE) ordered during routine clinical practice in selected patients can add additional prognostic information after routine echo. We assessed whether CMR improves outcomes prediction after contemporaneous echo, which may have implications for efforts to optimize processes of care, assess effectiveness, and allocate limited health care resources. Methods and results We prospectively enrolled 1044 consecutive patients referred for CMR. There were 38 deaths and 3 cardiac transplants over a median follow-up of 1.0 years (IQR 0.4-1.5). We first reproduced previous survival curve strata (presence of LGE and ejection fraction (EF) < 50%) for transplant free survival, to support generalizability of any findings. Then, in a subset (n = 444) with contemporaneous echo (median 3 days apart, IQR 1–9), EF by echo (assessed visually) or CMR were modestly correlated (R2 = 0.66, p < 0.001), and 30 deaths and 3 transplants occurred over a median follow-up of 0.83 years (IQR 0.29-1.40). CMR EF predicted mortality better than echo EF in univariable Cox models (Integrated Discrimination Improvement (IDI) 0.018, 95% CI 0.008-0.034; Net Reclassification Improvement (NRI) 0.51, 95% CI 0.11-0.85). Finally, LGE further improved prediction beyond EF as determined by hazard ratios, NRI, and IDI in all Cox models predicting mortality or transplant free survival, adjusting for age, gender, wall motion, and EF. Conclusions Among those referred for CMR after echocardiography, CMR with LGE further improves risk stratification of individuals at risk for death or death/cardiac transplant. PMID:23324403

Design of the effect of adaptive servo-ventilation on survival and cardiovascular hospital admissions in patients with heart failure and sleep apnoea: the ADVENT-HF trial.

PubMed

Lyons, Owen D; Floras, John S; Logan, Alexander G; Beanlands, Robert; Cantolla, Joaquin Durán; Fitzpatrick, Michael; Fleetham, John; John Kimoff, R; Leung, Richard S T; Lorenzi Filho, Geraldo; Mayer, Pierre; Mielniczuk, Lisa; Morrison, Debra L; Ryan, Clodagh M; Series, Frederic; Tomlinson, George A; Woo, Anna; Arzt, Michael; Parthasarathy, Sairam; Redolfi, Stefania; Kasai, Takatoshi; Parati, Gianfranco; Delgado, Diego H; Bradley, T Douglas

2017-04-01

Both types of sleep-disordered breathing (SDB), obstructive and central sleep apnoea (OSA and CSA, respectively), are common in patients with heart failure and reduced ejection fraction (HFrEF). In such patients, SDB is associated with increased cardiovascular morbidity and mortality but it remains uncertain whether treating SDB by adaptive servo-ventilation (ASV) in such patients reduces morbidity and mortality. ADVENT-HF is designed to assess the effects of treating SDB with ASV on morbidity and mortality in patients with HFrEF. ADVENT-HF is a multicentre, multinational, randomized, parallel-group, open-label trial with blinded assessment of endpoints of standard medical therapy for HFrEF alone vs. with the addition of ASV in patients with HFrEF and SDB. Patients with a history of HFrEF undergo echocardiography and polysomnography. Those with a left ventricular ejection fraction ≤45% and SDB (apnoea-hypopnoea index ≥15) are eligible. SDB is stratified into OSA with ≥50% of events obstructive or CSA with >50% of events central. Those with OSA must not have excessive daytime sleepiness (Epworth score of ≤10). Patients are then randomized to receive or not receive ASV. The primary outcome is the composite of all-cause mortality, cardiovascular hospital admissions, new-onset atrial fibrillation requiring anti-coagulation but not hospitalization, and delivery of an appropriate discharge from an implantable cardioverter-defibrillator not resulting in hospitalization during a maximum follow-up time of 5 years. The ADVENT-HF trial will help to determine whether treating SDB by ASV in patients with HFrEF improves morbidity and mortality. © 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.

Socioeconomic status and executive function: developmental trajectories and mediation.

PubMed

Hackman, Daniel A; Gallop, Robert; Evans, Gary W; Farah, Martha J

2015-09-01

Childhood socioeconomic status (SES) predicts executive function (EF), but fundamental aspects of this relation remain unknown: the developmental course of the SES disparity, its continued sensitivity to SES changes during that course, and the features of childhood experience responsible for the SES-EF relation. Regarding course, early disparities would be expected to grow during development if caused by accumulating stressors at a given constant level of SES. Alternatively, they would narrow if schooling partly compensates for the effects of earlier deprivation, allowing lower-SES children to 'catch up'. The potential for later childhood SES change to affect EF is also unknown. Regarding mediating factors, previous analyses produced mixed answers, possibly due to correlation amongst candidate mediators. We address these issues with measures of SES, working memory and planning, along with multiple candidate mediators, from the NICHD Study of Early Childcare (n = 1009). Early family income-to-needs and maternal education predicted planning by first grade, and income-to-needs predicted working memory performance at 54 months. Effects of early SES remained consistent through middle childhood, indicating that the relation between early indicators of SES and EF emerges in childhood and persists without narrowing or widening across early and middle childhood. Changes in family income-to-needs were associated with significant changes in planning and trend-level changes in working memory. Mediation analyses supported the role of early childhood home characteristics in explaining the association between SES and EF, while early childhood maternal sensitivity was specifically implicated in the association between maternal education and planning. Early emerging and persistent SES-related differences in EF, partially explained by characteristics of the home and family environment, are thus a potential source of socioeconomic disparities in achievement and health across development. © 2015 John Wiley & Sons Ltd.

Relationship Between Physical Activity, Body Mass Index, and Risk of Heart Failure

PubMed Central

Pandey, Ambarish; LaMonte, Michael; Klein, Liviu; Ayers, Colby; Psaty, Bruce; Eaton, Charles; Allen, Norrina; de Lemos, James A.; Carnethon, Mercedes; Greenland, Philip; Berry, Jarett D.

2018-01-01

Background Lower leisure-time physical activity (LTPA) and higher body mass index (BMI) are independently associated with risk of heart failure (HF). However, it is unclear if this relationship is consistent for both HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF). Objective This study sought to quantify dose-response associations between LTPA, BMI, and the risk of different HF subtypes. Methods Individual-level data from 3 cohort studies (WHI, MESA, and CHS) were pooled and participants were stratified into guideline-recommended categories of LTPA and BMI. Associations between LTPA, BMI, and risk of overall HF, HFpEF (ejection fraction [EF] ≥45%) and HFrEF (EF <45%) were assessed used multivariable adjusted Cox models and restricted cubic splines. Results The study included 51,451 participants with 3,180 HF events (1,252 HFpEF, 914 HFrEF, 1,014 missing EF). In adjusted analysis, there was a dose-dependent association between higher LTPA levels, lower BMI, and overall HF risk. Among HF subtypes, LTPA in any dose range was not associated with HFrEF risk. In contrast, lower levels of LTPA (<500 metabolic equivalents of task [MET]-min/week) were not associated with HFpEF risk, and dose-dependent associations with lower HFpEF risk were observed at higher levels. Compared with no LTPA, higher than twice the guideline-recommended minimum LTPA levels (>1,000 MET-min/week) were associated with an 19% lower risk of HFpEF (HR: 0.81; 95% CI: 0.68 to 0.97). The dose-response relationship for BMI with HFpEF risk was also more consistent than with HFrEF risk, such that increasing BMI above the normal range (≥ 25 kg/m2) was associated with greater increase in risk of HFpEF than HFrEF. Conclusion Our study findings demonstrate strong, dose-dependent associations between LTPA levels, BMI, and risk of overall HF. Among HF subtypes, higher LTPA levels and lower BMI were more consistently associated with lower risk of HFpEF compared with HFrEF. PMID:28254175

Ventricular-Arterial Coupling and Exercise-Induced Pulmonary Hypertension During Low-Level Exercise in Heart Failure With Preserved or Reduced Ejection Fraction.

PubMed

Obokata, Masaru; Nagata, Yasufumi; Kado, Yuichiro; Kurabayashi, Masahiko; Otsuji, Yutaka; Takeuchi, Masaaki

2017-03-01

Exercise-induced pulmonary hypertension (EIPH) may develop even at low workloads in heart failure (HF) patients. Ventricular-arterial stiffening plays an important role in the pathophysiology of HF with preserved ejection fraction (HFpEF). This study aimed to compare the response of ventricular-arterial coupling and PH during low-level exercise between HFpEF and HF with reduced EF (HFrEF). Echocardiography was performed at rest and during 10 W of bicycle exercise in HFpEF (n = 37) and HFrEF (n = 43). Load-independent contractility (end-systolic elastance [Ees], preload recruitable stroke work [PRSW], and peak power index [PWRI]), arterial afterload (arterial elastance [Ea]), and ventricular-arterial interaction (Ea/Ees) were measured with the use of a noninvasive single-beat technique. EIPH was defined as an estimated pulmonary arterial systolic pressure (PASP) of ≥50 mm Hg at 10 W of exercise. PASP was significantly increased during 10 W of exercise in both HF types, and ~50% of HFpEF patients developed EIPH. Arterial afterload was increased significantly during exercise in both groups. HFrEF and HFpEF patients showed a significant increase in LV contractility assessed by Ees, PRSW, and PWRI during exercise. Although Ea/Ees ratio decreased significantly in HFrEF, reduction in Ea/Ees was attenuated because of blunted Ees increases in patients with HFpEF compared with HFrEF. Even at low-level exercise, ~50% of HFpEF patients developed EIPH. Reduction in Ea/Ees was attenuated owing to less Ees increase in HFpEF compared with HFrEF. Further studies are needed to elucidate the association between ventricular-arterial coupling and EIPH in HFpEF. Copyright © 2016 Elsevier Inc. All rights reserved.

A statistical shape modelling framework to extract 3D shape biomarkers from medical imaging data: assessing arch morphology of repaired coarctation of the aorta.

PubMed

Bruse, Jan L; McLeod, Kristin; Biglino, Giovanni; Ntsinjana, Hopewell N; Capelli, Claudio; Hsia, Tain-Yen; Sermesant, Maxime; Pennec, Xavier; Taylor, Andrew M; Schievano, Silvia

2016-05-31

Medical image analysis in clinical practice is commonly carried out on 2D image data, without fully exploiting the detailed 3D anatomical information that is provided by modern non-invasive medical imaging techniques. In this paper, a statistical shape analysis method is presented, which enables the extraction of 3D anatomical shape features from cardiovascular magnetic resonance (CMR) image data, with no need for manual landmarking. The method was applied to repaired aortic coarctation arches that present complex shapes, with the aim of capturing shape features as biomarkers of potential functional relevance. The method is presented from the user-perspective and is evaluated by comparing results with traditional morphometric measurements. Steps required to set up the statistical shape modelling analyses, from pre-processing of the CMR images to parameter setting and strategies to account for size differences and outliers, are described in detail. The anatomical mean shape of 20 aortic arches post-aortic coarctation repair (CoA) was computed based on surface models reconstructed from CMR data. By analysing transformations that deform the mean shape towards each of the individual patient's anatomy, shape patterns related to differences in body surface area (BSA) and ejection fraction (EF) were extracted. The resulting shape vectors, describing shape features in 3D, were compared with traditionally measured 2D and 3D morphometric parameters. The computed 3D mean shape was close to population mean values of geometric shape descriptors and visually integrated characteristic shape features associated with our population of CoA shapes. After removing size effects due to differences in body surface area (BSA) between patients, distinct 3D shape features of the aortic arch correlated significantly with EF (r = 0.521, p = .022) and were well in agreement with trends as shown by traditional shape descriptors. The suggested method has the potential to discover previously unknown 3D shape biomarkers from medical imaging data. Thus, it could contribute to improving diagnosis and risk stratification in complex cardiac disease.

Effects of supervised exercise and dietary nitrate in older adults with controlled hypertension and/or heart failure with preserved ejection fraction.

PubMed

Shaltout, Hossam A; Eggebeen, Joel; Marsh, Anthony P; Brubaker, Peter H; Laurienti, Paul J; Burdette, Jonathan H; Basu, Swati; Morgan, Ashley; Dos Santos, Patricia C; Norris, James L; Morgan, Timothy M; Miller, Gary D; Rejeski, W Jack; Hawfield, Amret T; Diz, Debra I; Becton, J Thomas; Kim-Shapiro, Daniel B; Kitzman, Dalane W

2017-09-30

Aerobic exercise training is an effective therapy to improve peak aerobic power (peak VO 2 ) in individuals with hypertension (HTN, AHA/ACC class A) and heart failure patients with preserved ejection fraction (HFpEF). High nitrate containing beetroot juice (BRJ) also improves sub-maximal endurance and decreases blood pressure in both HTN and HFpEF. We hypothesized that combining an aerobic exercise and dietary nitrate intervention would result in additive or even synergistic positive effects on exercise tolerance and blood pressure in HTN or HFpEF. We report results from two pilot studies examining the effects of supervised aerobic exercise combined with dietary nitrate in patients with controlled HTN (n = 26, average age 65 ± 5 years) and in patients with HFpEF (n = 20, average age 69 ± 7 years). All patients underwent an aerobic exercise training regimen; half were randomly assigned to consume a high nitrate-containing beet juice beverage (BRJ containing 6.1 mmol nitrate for the HFpEF study consumed three times a week and 8 mmol nitrate for the HTN study consumed daily) while the other half consumed a beet juice beverage with the nitrate removed (placebo). The main result was that there was no added benefit observed for any outcomes when comparing BRJ to placebo in either HTN or HFpEF patients undergoing exercise training (p ≥ 0.14). There were within-group benefits. In the pilot study in patients with HFpEF, aerobic endurance (primary outcome), defined as the exercise time to volitional exhaustion during submaximal cycling at 75% of maximal power output, improved during exercise training within each group from baseline to end of study, 369 ± 149 s vs 520 ± 257 s (p = 0.04) for the placebo group and 384 ± 129 s vs 483 ± 258 s for the BRJ group (p = 0.15). Resting systolic blood pressure in patients with HFpEF also improved during exercise training in both groups, 136 ± 16 mm Hg vs 122 ± 3 mm Hg for the placebo group (p < 0.05) and 132 ± 12 mm Hg vs 119 ± 9 mm Hg for the BRJ group (p < 0.05). In the HTN pilot study, during a treadmill graded exercise test, peak oxygen consumption (primary outcome) did not change significantly, but time to exhaustion (also a primary outcome) improved in both groups, 504 ± 32 s vs 601 ± 38 s (p < 0.05) for the placebo group and 690 ± 38 s vs 772 ± 95 s for the BRJ group (p < 0.05) which was associated with a reduction in supine resting systolic blood pressure in BRJ group. Arterial compliance also improved during aerobic exercise training in both the HFpEF and the HTN patients for both BRJ and placebo groups. Future work is needed to determine if larger nitrate doses would provide an added benefit to supervised aerobic exercise in HTN and HFpEF patients. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of prefrontal tDCS on executive function: Methodological considerations revealed by meta-analysis.

PubMed

Imburgio, Michael J; Orr, Joseph M

2018-05-01

A meta-analysis of studies using single-session transcranial direct current stimulation (tDCS) to target the dorsolateral prefrontal cortex (DLPFC) was undertaken to examine the effect of stimulation on executive function (EF) in healthy samples. 27 studies were included in analyses, yielding 71 effect sizes. The most relevant measure for each task was determined a priori and used to calculate Hedge's g. Methodological characteristics of each study were examined individually as potential moderators of effect size. Stimulation effects on three domains of EF (inhibition of prepotent responses, mental set shifting, and information updating and monitoring) were analyzed separately. In line with previous work, the current study found no significant effect of anodal unilateral tDCS, cathodal unilateral tDCS, or bilateral tDCS on EF. Further moderator and subgroup analyses were only carried out for anodal unilateral montages due to the small number of studies using other montages. Subgroup analyses revealed a significant effect of anodal unilateral tDCS on updating tasks, but not on inhibition or set-shifting tasks. Cathode location significantly moderated the effect of anodal unilateral tDCS. Extracranial cathodes yielded a significant effect on EF while cranial cathodes yielded no effect. Anode size also significantly moderated effect of anodal unilateral tDCS, with smaller anodes being more effective than larger anodes. In summary, anodal DLPFC stimulation is more effective at improving updating ability than inhibition and set-shifting ability, but anodal stimulation can significantly improve general executive function when extracranial cathodes or small anodes are used. Future meta-analyses may examine how stimulation's effects on specific behavioral tasks, rather than broader domains, might be affected by methodological moderators. Copyright © 2018 Elsevier Ltd. All rights reserved.

Cloning and characterization of EF-Tu and EF-Ts from Pseudomonas aeruginosa.

PubMed

Palmer, Stephanie O; Rangel, Edna Y; Montalvo, Alberto E; Tran, Alexis T; Ferguson, Kate C; Bullard, James M

2013-01-01

We have cloned genes encoding elongation factors EF-Tu and EF-Ts from Pseudomonas aeruginosa and expressed and purified the proteins to greater than 95% homogeneity. Sequence analysis indicated that P. aeruginosa EF-Tu and EF-Ts are 84% and 55% identical to E. coli counterparts, respectively. P. aeruginosa EF-Tu was active when assayed in GDP exchange assays. Kinetic parameters for the interaction of EF-Tu with GDP in the absence of EF-Ts were observed to be K M = 33 μM, k cat (obs) = 0.003 s(-1), and the specificity constant k cat (obs)/K M was 0.1 × 10(-3) s(-1) μM(-1). In the presence of EF-Ts, these values were shifted to K M = 2 μM, k cat (obs) = 0.005 s(-1), and the specificity constant k(cat)(obs)/K M was 2.5 × 10(-3) s(-1) μM(-1). The equilibrium dissociation constants governing the binding of EF-Tu to GDP (K GDP) were 30-75 nM and to GTP (K GTP) were 125-200 nM. EF-Ts stimulated the exchange of GDP by EF-Tu 10-fold. P. aeruginosa EF-Tu was active in forming a ternary complex with GTP and aminoacylated tRNA and was functional in poly(U)-dependent binding of Phe-tRNA(Phe) at the A-site of P. aeruginosa ribosomes. P. aeruginosa EF-Tu was active in poly(U)-programmed polyphenylalanine protein synthesis system composed of all P. aeruginosa components.

Linking EfS and Biodiversity? A UK-wide Survey of the Status of Education within Local Biodiversity Action Plans.

ERIC Educational Resources Information Center

Young, Jennifer

2001-01-01

Explores potential for developing education for sustainability (EfS) through biodiversity planning in the UK based on a survey conducted in April 1999. Concludes that biodiversity practitioners have the tools to deliver EfS through implementation of local biodiversity action plans (LBAPs), the concept allowing close links to Local Agenda 21,…

Pre-Service Teachers' Attitudes toward Education for Sustainability and Its Relevance to Their Learning: Implications for Pedagogical Practice

ERIC Educational Resources Information Center

Tomas, Louisa; Girgenti, Sarah; Jackson, Cliff

2017-01-01

The education for sustainability (EfS) literature espouses participatory, praxis-orientated, place-based and holistic approaches to teaching and learning. The introduction of a first-year EfS unit for pre-service teachers at James Cook University provided an opportunity to explore their attitudes toward EfS and their perceptions of the relevant…

Mammalian translation elongation factor eEF1A2: X-ray structure and new features of GDP/GTP exchange mechanism in higher eukaryotes

PubMed Central

Crepin, Thibaut; Shalak, Vyacheslav F.; Yaremchuk, Anna D.; Vlasenko, Dmytro O.; McCarthy, Andrew; Negrutskii, Boris S.; Tukalo, Michail A.; El'skaya, Anna V.

2014-01-01

Eukaryotic elongation factor eEF1A transits between the GTP- and GDP-bound conformations during the ribosomal polypeptide chain elongation. eEF1A*GTP establishes a complex with the aminoacyl-tRNA in the A site of the 80S ribosome. Correct codon–anticodon recognition triggers GTP hydrolysis, with subsequent dissociation of eEF1A*GDP from the ribosome. The structures of both the ‘GTP’- and ‘GDP’-bound conformations of eEF1A are unknown. Thus, the eEF1A-related ribosomal mechanisms were anticipated only by analogy with the bacterial homolog EF-Tu. Here, we report the first crystal structure of the mammalian eEF1A2*GDP complex which indicates major differences in the organization of the nucleotide-binding domain and intramolecular movements of eEF1A compared to EF-Tu. Our results explain the nucleotide exchange mechanism in the mammalian eEF1A and suggest that the first step of eEF1A*GDP dissociation from the 80S ribosome is the rotation of the nucleotide-binding domain observed after GTP hydrolysis. PMID:25326326

Anxious and Depressive Symptomatology Among Male Youth: The Joint and Interactive Contribution of Temperament and Executive Functioning

PubMed Central

Shishido, Yuri; Latzman, Natasha E.; Clark, Lee Anna

2018-01-01

Few studies have investigated the combined effects of temperament and executive functioning (EF) on anxious and depressive symptomatology in youth. The current study is the first to investigate the joint and interactive contribution of mother- and youth self-reported affective dimensions of temperament and EF to the explanation of anxious and depressive symptomatology. Participants included 174 adolescent males (Mage = 13.6 ± 1.35). Results confirmed the joint and interactive contribution of temperament in the explanation of anxious and depressive symptomatology. Further, EF contributed to the explanation of anxious/depressive symptomatology via interaction with youth-, but not mother-reported, temperament; it was not a unique predictor. Results support the need to consider both affective dimensions of temperament and EF in etiological models of anxious and depressive symptomatology, which has implications for identifying at-risk youth and developing early intervention and targeted problem-specific prevention programs. PMID:26754748

Anxious and Depressive Symptomatology Among Male Youth: The Joint and Interactive Contribution of Temperament and Executive Functioning.

PubMed

Latzman, Robert D; Shishido, Yuri; Latzman, Natasha E; Clark, Lee Anna

2016-12-01

Few studies have investigated the combined effects of temperament and executive functioning (EF) on anxious and depressive symptomatology in youth. The current study is the first to investigate the joint and interactive contribution of mother- and youth self-reported affective dimensions of temperament and EF to the explanation of anxious and depressive symptomatology. Participants included 174 adolescent males (M age  = 13.6 ± 1.35). Results confirmed the joint and interactive contribution of temperament in the explanation of anxious and depressive symptomatology. Further, EF contributed to the explanation of anxious/depressive symptomatology via interaction with youth-, but not mother-reported, temperament; it was not a unique predictor. Results support the need to consider both affective dimensions of temperament and EF in etiological models of anxious and depressive symptomatology, which has implications for identifying at-risk youth and developing early intervention and targeted problem-specific prevention programs.

Duplication of Drosophila melanogaster mitochondrial EF-Tu: pre-adaptation to T-arm truncation and exclusion of bulky aminoacyl residues.

PubMed

Sato, Aya; Suematsu, Takuma; Aihara, Koh-Ki; Kita, Kiyoshi; Suzuki, Tsutomu; Watanabe, Kimitsuna; Ohtsuki, Takashi; Watanabe, Yoh-Ichi

2017-03-07

Translation elongation factor Tu (EF-Tu) delivers aminoacyl-tRNA (aa-tRNA) to ribosomes in protein synthesis. EF-Tu generally recognizes aminoacyl moieties and acceptor- and T-stems of aa-tRNAs. However, nematode mitochondrial (mt) tRNAs frequently lack all or part of the T-arm that is recognized by canonical EF-Tu. We previously reported that two distinct EF-Tu species, EF-Tu1 and EF-Tu2, respectively, recognize mt tRNAs lacking T-arms and D-arms in the mitochondria of the chromadorean nematode Caenorhabditis elegans C. elegans EF-Tu2 specifically recognizes the seryl moiety of serylated D-armless tRNAs. Mitochondria of the enoplean nematode Trichinella possess three structural types of tRNAs: T-armless tRNAs, D-armless tRNAs, and cloverleaf tRNAs with a short T-arm. Trichinella mt EF-Tu1 binds to all three types and EF-Tu2 binds only to D-armless Ser-tRNAs, showing an evolutionary intermediate state from canonical EF-Tu to chromadorean nematode (e.g. C. elegans ) EF-Tu species. We report here that two EF-Tu species also participate in Drosophila melanogaster mitochondria. Both D. melanogaster EF-Tu1 and EF-Tu2 bound to cloverleaf and D-armless tRNAs. D. melanogaster EF-Tu1 has the ability to recognize T-armless tRNAs that do not evidently exist in D. melanogaster mitochondria, but do exist in related arthropod species. In addition, D. melanogaster EF-Tu2 preferentially bound to aa-tRNAs carrying small amino acids, but not to aa-tRNAs carrying bulky amino acids. These results suggest that the Drosophila mt translation system could be another intermediate state between the canonical and nematode mitochondria-type translation systems. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

Effect of OFF-state stress induced electric field on trapping in AlGaN/GaN high electron mobility transistors on Si (111)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Anand, M. J., E-mail: anand2@e.ntu.edu.sg, E-mail: eging@ntu.edu.sg; Ng, G. I., E-mail: anand2@e.ntu.edu.sg, E-mail: eging@ntu.edu.sg; Syamal, B.

2015-02-23

The influence of electric field (EF) on the dynamic ON-resistance (dyn-R{sub DS[ON]}) and threshold-voltage shift (ΔV{sub th}) of AlGaN/GaN high electron mobility transistors on Si has been investigated using pulsed current-voltage (I{sub DS}-V{sub DS}) and drain current (I{sub D}) transients. Different EF was realized with devices of different gate-drain spacing (L{sub gd}) under the same OFF-state stress. Under high-EF (L{sub gd} = 2 μm), the devices exhibited higher dyn-R{sub DS[ON]} degradation but a small ΔV{sub th} (∼120 mV). However, at low-EF (L{sub gd} = 5 μm), smaller dyn-R{sub DS[ON]} degradation but a larger ΔV{sub th} (∼380 mV) was observed. Our analysis shows that under OFF-state stress, the gatemore » electrons are injected and trapped in the AlGaN barrier by tunnelling-assisted Poole-Frenkel conduction mechanism. Under high-EF, trapping spreads towards the gate-drain access region of the AlGaN barrier causing dyn-R{sub DS[ON]} degradation, whereas under low-EF, trapping is mostly confined under the gate causing ΔV{sub th}. A trap with activation energy 0.33 eV was identified in the AlGaN barrier by I{sub D}-transient measurements. The influence of EF on trapping was also verified by Silvaco TCAD simulations.« less

Long-Term Results of CCG 5942: A Randomized Comparison of Chemotherapy With and Without Radiotherapy for Children With Hodgkin's Lymphoma—A Report From the Children's Oncology Group

PubMed Central

Wolden, Suzanne L.; Chen, Lu; Kelly, Kara M.; Herzog, Philip; Gilchrist, Gerald S.; Thomson, John; Sposto, Richard; Kadin, Marshall E.; Hutchinson, Raymond J.; Nachman, James

2012-01-01

Purpose In 1995, the Children's Cancer Group (CCG) opened a trial for patients with Hodgkin's lymphoma evaluating whether low-dose involved-field radiation therapy (IFRT) improved event-free survival (EFS) for patients achieving a complete response after chemotherapy. We present the long-term study outcome using final data through March 2007. Patients and Methods Between January 1995 and December 1998, 826 eligible patients were enrolled onto CCG 5942. Four hundred ninety-eight patients achieving an initial complete response to chemotherapy were randomly assigned to receive IFRT or no further therapy. EFS and overall survival (OS) were assessed from the date of study entry or random assignment, as appropriate. Results Ten-year EFS and OS rates for the entire cohort were 83.5% and 92.5%, respectively. In an as-treated analysis for randomly assigned patients, the 10-year EFS and OS rates were 91.2% and 97.1%, respectively, for IFRT and 82.9% and 95.9%, respectively, for no further therapy. For EFS and OS comparisons, P = .004 and P = .50, respectively. Bulk disease, “B” symptoms, and nodular sclerosis histology were risk factors for inferior EFS. Conclusion With a median follow-up of 7.7 years, IFRT produced a statistically significant improvement in EFS but no improvement in OS. For individual patients, the relative risks of relapse versus late effects of IFRT must be considered. Patient and disease characteristics and early response assessment will aid in deciding which patients are most likely to benefit from IFRT. PMID:22649136

Anticancer activity of an imageable curcuminoid 1-[2-aminoethyl-(6-hydrazinopyridine-3-carbamidyl)-3,5-bis-(2-fluorobenzylidene)-4-piperidone (EFAH).

PubMed

Lagisetty, Pallavi; Subramaniam, Dharmalingam; Sahoo, Kaustuv; Anant, Shrikant; Awasthi, Vibhudutta

2012-02-01

3,5-Bis(2-fluorobenzylidine)-4-piperidone or EF24 is a potent anticancer derivative of curcumin. Using an amine derivative of EF24, we synthesized a hydrazinonicotinic acid conjugate, EFAH, for Tc-99m radiolabelling and single photon emission tomography imaging. The aqueous solubility of EFAH (3.5 mg/mL) was significantly more than that of EF24 (1.2 mg/mL); the octanol/water partition coefficient of EFAH was estimated at log P = 0.33. As an antiproliferative agent, EFAH was as effective as EF24 in suppressing the proliferation of H441, MiaPaCa-2 and Panc-1 cells. Daily intraperitoneal injection of EFAH (5 μg) for 3 weeks in mice carrying xenografts of Panc-1 pancreatic cancer showed a mean tumour volume reduction of 79%; the tumour weight decreased by 82% in the treated group. For imaging and biodistribution, EFAH was labelled with Tc-99m (98% RCY) and intravenously administered in rats. Approximately 23.7% and 14.3% of injected dose accumulated in liver and intestine, respectively, suggesting that EFAH is mostly eliminated by hepatobiliary route. The results indicate that HYNIC modification of EF24 for Tc-99m radiolabelling does not affect its antiproliferative efficacy. For the first time, a visual biodisposition of EF24 in a live animal model has been demonstrated. Such knowledge could be of benefit in developing therapeutic curcuminoids, such as EF24. © 2011 John Wiley & Sons A/S.

Pharmacological and morphological characteristics of the muscular system of the giant liver fluke (Fascioloides magna - Bassi 1875).

PubMed

Trailović, Saša M; Marinković, Darko; Trailović, Jelena Nedeljković; Milovanović, Mirjana; Marjanović, Djordje S; Aničić, Milan R

2015-12-01

Motility is required for feeding, reproduction and maintenance of the fluke in the host's liver. According to that, the neuromuscular system can be an attractive drugable target for chemotherapy. Musculature of the Fascioloides magna is organized into three layers, an outer circular layer, beneath this layer the longitudinal layer, and third, the oblique, or diagonal layer underlies the longitudinal layer. In our study, the administration of atropine or caffeine did not cause classic muscle contractions of F. magna muscle strips. However, the Electrical Field Stimulation (EFS) induced stable and repeatable contractions, which enabled us to examine their sensitivity to the various substances. Acetylcholine (ACh) (300 μM and 1 mM), caused only a slight relaxation, without affecting the amplitude of spontaneous contractions or the amplitude of contractions induced by EFS. Contrary to that, atropine (100 μM) caused a significant increase in the basal tone and an increase of EFS-induced contractions. If acetylcholine is an inhibitory neurotransmitter in trematodes, the described effects of atropine are achieved by the blockade of inhibitory neurotransmission. On the other hand, with respect to the process of excitation-contraction coupling, the plant alkaloid ryanodine (30 μM) significantly reduced the basal tone, as well as EFS-induced contractions of F. magna muscle strips. Ryanodine inhibited the potentiating effect of atropine on the basal tone and contractions caused by EFS, which indicates that the contractile effect of atropine is dependent on Ca(++) release from intracellular stores. Caffeine (500 μM) caused relaxation of fluke muscle strips and at the same time significantly enhanced the EFS-induced contractions. Both effects of caffeine can be explained by entry of extracellular Ca(++) into muscle cells. The muscle contractility of F. magna depends both on the entry of extracellular calcium, and calcium release from intracellular stores, which are under the control of RyRs. Our results also suggest that antitrematodal drugs could potentially be developed from substances with selective anti-cholinergic activity. Copyright © 2015 Elsevier Inc. All rights reserved.

Creative Arts-Based Pedagogies in Early Childhood Education for Sustainability (EfS): Challenges and Possibilities

ERIC Educational Resources Information Center

Ward, Kumara S.

2013-01-01

This article showcases a creative approach to early childhood education for sustainability (ECEfS). It reports on the author's doctoral research program, which examined the effectiveness of arts-based pedagogies for exploring and understanding the natural world in an early childhood education program. Motivated by their existing commitment to…

Nutritional values and bioactive components of under-utilised vegetables consumed by indigenous people in Malaysia.

PubMed

Abdul Wahab, Norsuhaila; Ahdan, Rohaina; Ahmad Aufa, Zabidah; Kong, Kin Weng; Johar, Mohd Hafizan; Shariff Mohd, Zalilah; Ismail, Amin

2015-10-01

Diverse plants species in the forest remain under-utilised and they are mainly consumed only by local people. However, increasing issues in food security prompted the present study, which explores the nutritional and antioxidant aspects of Malaysian under-utilised vegetables. The studied vegetables were Paku Nyai (Stenochlaena palustris), Cemperai (Champereia manillana), Maman Pasir (Cleome viscose), Dudung (Erechtites valerianifolia) and Semambuk (Ardisia pendula). Overall, these vegetables exhibited a low proximal content but they were high in vitamin C [7.07-1263 mg kg(-1) edible fresh sample (EFS)] and β-carotene content (18.4-43.9 mg kg(-1) kg(-1) EFS). Cemperai had the highest calcium content (565 mg kg(-1) EFS), whereas Semambuk had the highest total phenolic content [28.21 g gallic acid equivalents kg(-1) edible dried sample (EDS)] and antioxidant activity (86.1%) measured using β-carotene bleaching assay. Maman Pasir contained the highest total flavonoid content (39.99 g CE kg(-1) EDS) and 1,1-diphenyl-2-picryl hydrazyl radical scavenging activity (82.2%). The extracts of these vegetables had significantly prevented the oxidation of haemoglobin and low-density lipoprotein, which yielded a reduced production of malondialdehyde. Semambuk and Maman Pasir are potent to be used as new food and functional food sources as they are rich in nutrients and antioxidants. © 2014 Society of Chemical Industry.

Characterization and cytotoxicity of PAHs in PM2.5 emitted from residential solid fuel burning in the Guanzhong Plain, China.

PubMed

Sun, Jian; Shen, Zhenxing; Zeng, Yaling; Niu, Xinyi; Wang, Jinhui; Cao, Junji; Gong, Xuesong; Xu, Hongmei; Wang, Taobo; Liu, Hongxia; Yang, Liu

2018-05-28

The emission factors (EFs) of polycyclic aromatic hydrocarbons (PAHs) in PM 2.5 were measured from commonly used stoves and fuels in the rural Guanzhong Plain, China. The toxicity of the PM 2.5 also was measured using in vitro cellular tests. EFs of PAHs varied from 0.18 mg kg -1 (maize straw charcoal burning in a clean stove) to 83.3 mg kg -1 (maize straw burning in Heated Kang). The two largest influencing factors on PAH EFs were air supply and volatile matter proportion in fuel. Improvements in these two factors could decrease not only EFs of PAHs but also the proportion of 3-ring to 5-ring PAHs. Exposure to PM 2.5 extracts caused a concentration-dependent decline in cell viability but an increase in reactive oxygen species (ROS), tumor necrosis factor a (TNF-α) and interleukin 6 (IL-6). PM 2.5 emitted from maize burning in Heated Kang showed the highest cytotoxicity, and EFs of ROS and inflammatory factors were the highest as well. In comparison, maize straw charcoal burning in a clean stove showed the lowest cytotoxicity, which indicated a clean stove and fuel treatment were both efficient methods for reducing cytotoxicity of primary PM 2.5 . The production of these bioreactive factors were highly correlated with 3-ring and 4-ring PAHs. Specifically, pyrene, anthracene and benzo(a)anthracene had the highest correlations with ROS production (R = 0.85, 0.81 and 0.80, respectively). This study shows that all tested stoves emitted PM 2.5 that was cytotoxic to human cells; thus, there may be no safe levels of exposure to PM 2.5 emissions from cooking and heating stoves using solid fuels. The study may also provide a new approach for evaluating the cytotoxicity of primary emitted PM 2.5 from solid fuel burning as well as other PM 2.5 sources. Copyright © 2018 Elsevier Ltd. All rights reserved.

Meta-analysis of the effects of carvedilol versus metoprolol on all-cause mortality and hospitalizations in patients with heart failure.

PubMed

Briasoulis, Alexandros; Palla, Mohan; Afonso, Luis

2015-04-15

Long-term treatment with appropriate doses of carvedilol or metoprolol is currently recommended for patients with heart failure with reduced ejection fraction (HFrEF) to decrease the risk of death, hospitalizations, and patients' symptoms. It remains unclear if the β blockers used in patients with HFrEF are equal or carvedilol is superior to metoprolol types. We performed a meta-analysis of the comparative effects of carvedilol versus metoprolol tartrate and succinate on all-cause mortality and/or hospitalization. We conducted an Embase and MEDLINE search for prospective controlled trials and cohort studies of patients with HFrEF who were received to treatment with carvedilol versus metoprolol. We identified 4 prospective controlled and 6 cohort studies with 30,943 patients who received carvedilol and 69,925 patients on metoprolol types (tartrate and succinate) with an average follow-up duration of 36.4 months. All-cause mortality was reduced in prospective studies with carvedilol versus metoprolol tartrate. Neither all-cause mortality nor hospitalizations were significantly different between carvedilol and metoprolol succinate in the cohort studies. In conclusion, in patients with HFrEF, carvedilol and metoprolol succinate have similar effects in reducing all-cause mortality. Copyright © 2015 Elsevier Inc. All rights reserved.

Using an Adoption Design to Separate Genetic, Prenatal, and Temperament Influences on Toddler Executive Function

PubMed Central

Leve, Leslie D.; DeGarmo, David S.; Bridgett, David J.; Neiderhiser, Jenae M.; Shaw, Daniel S.; Harold, Gordon T.; Natsuaki, Misaki N.; Reiss, David

2012-01-01

Poor executive functioning has been implicated in children’s concurrent and future behavioral difficulties, making work aimed at understanding processes related to the development of early executive function (EF) critical for models of developmental psychopathology. Deficits in EF have been associated with adverse prenatal experiences, genetic influences, and temperament characteristics. However, our ability to disentangle the predictive and independent effects of these influences has been limited by a dearth of genetically-informed research designs that also consider prenatal influences. The present study examined EF and language development in a sample of 361 toddlers who were adopted at birth and reared in non-relative adoptive families. Predictors included genetic influences (as inherited from birth mothers), prenatal risk, and growth in child negative emotionality. Structural equation modeling indicated that the effect of prenatal risk on toddler effortful attention at age 27 months became nonsignificant once genetic influences were considered in the model. In addition, genetic influences had unique effects on toddler effortful attention. Latent growth modeling indicated that increases in toddler negative emotionality from 9 to 27 months were associated with poorer delay of gratification and poorer language development. Similar results were obtained in models incorporating birth father data. Mechanisms of intergenerational transmission of EF deficits are discussed. PMID:22799580

Using an adoption design to separate genetic, prenatal, and temperament influences on toddler executive function.

PubMed

Leve, Leslie D; DeGarmo, David S; Bridgett, David J; Neiderhiser, Jenae M; Shaw, Daniel S; Harold, Gordon T; Natsuaki, Misaki N; Reiss, David

2013-06-01

Poor executive functioning has been implicated in children's concurrent and future behavioral difficulties, making work aimed at understanding processes related to the development of early executive function (EF) critical for models of developmental psychopathology. Deficits in EF have been associated with adverse prenatal experiences, genetic influences, and temperament characteristics. However, our ability to disentangle the predictive and independent effects of these influences has been limited by a dearth of genetically informed research designs that also consider prenatal influences. The present study examined EF and language development in a sample of 361 toddlers who were adopted at birth and reared in nonrelative adoptive families. Predictors included genetic influences (as inherited from birth mothers), prenatal risk, and growth in child negative emotionality. Structural equation modeling indicated that the effect of prenatal risk on toddler effortful attention at age 27 months became nonsignificant once genetic influences were considered in the model. In addition, genetic influences had unique effects on toddler effortful attention. Latent growth modeling indicated that increases in toddler negative emotionality from 9 to 27 months were associated with poorer delay of gratification and poorer language development. Similar results were obtained in models incorporating birth father data. Mechanisms of intergenerational transmission of EF deficits are discussed. PsycINFO Database Record (c) 2013 APA, all rights reserved

Agmatine Modulation of Noradrenergic Neurotransmission in Isolated Rat Blood Vessels.

PubMed

Török, Jozef; Zemančíková, Anna

2016-06-30

Agmatine, a vasoactive metabolite of L-arginine, is widely distributed in mammalian tissues including blood vessels. Agmatine binding to imidazoline and α₂-adrenoceptors induces a variety of physiological and pharmacological effects. We investigated the effect of agmatine on contractile responses of the rat pulmonary artery and portal vein induced by electrical stimulation of perivascular nerves and by exogenous adrenergic substances. Experiments were performed on isolated segments of rat main pulmonary artery and its extralobular branches, and portal vein suspended in organ bath containing modified Krebs bicarbonate solution and connected to a force-displacement transducer for isometric tension recording. Electrical field stimulation (EFS) produced tetrodotoxin-sensitive contractile responses of pulmonary artery and portal vein. Besides the well known vasorelaxant actions, we found that agmatine also produced a concentration-dependent inhibition of neurogenic contractions induced by EFS in pulmonary arteries; however, the agmatine treatment did not influence the responses to exogenous noradrenaline. The inhibitory effect on EFS-induced contractions was not abolished by the α₂-adrenoceptor antagonist rauwolscine. In portal vein, in contrast, agmatine increased spontaneous mechanical contractions and enhanced the contractions induced by EFS. The results suggest that agmatine can significantly influence vascular function of pulmonary arteries and portal veins by modulating sympathetically mediated vascular contractions by pre- and postsynaptic mechanisms.

Effects of Indoor Air Pollutants on Atopic Dermatitis

PubMed Central

Kim, JaKyoung; Kim, HyungJin; Lim, DaeHyun; Lee, Young-Kyu; Kim, Jeong Hee

2016-01-01

The increasing prevalence of atopic dermatitis (AD) is associated with variations in indoor environments. In Korea, many inner walls of homes are covered with wallpaper: such walls emit indoor air pollutants, including volatile organic compounds (VOCs) and formaldehyde. This randomized, double-blind study investigated the effects of wallpaper on indoor air quality and AD. Thirty-one children (aged three to eight years) with moderate AD were assigned to environmentally-friendly (EF) and polyvinyl chloride (PVC) wallpaper groups. Indoor air concentrations of VOCs, natural VOCs (NVOCs), formaldehyde, and total suspended bacteria were measured before and two (W2) and eight weeks (W8) after wallpapering. Scoring Atopic Dermatitis (SCORAD) evaluations and blood tests were performed during the same period. The EF wallpaper and PVC wallpaper groups showed similar trends in the changes in total VOCs (TVOC) and formaldehyde content in the indoor air. However, the EF wallpaper group showed more improvement on the SCORAD at W2 and W8 than the PVC wallpaper group. The SCORAD index was positively correlated with several indoor air pollutants. Further, the SCORAD index and NVOC % were negatively correlated. Improved SCORAD index and effects of wallpapering on indoor air quality improvements occurred within a short period of time in both groups. We believe that NVOCs in indoor air after EF wallpapering have a beneficial effect on health. PMID:27941696

Treating Heart Failure with Preserved Ejection Fraction: A Challenge for Clinicians.

PubMed

Howard, Patricia A

2015-06-01

Despite a decline in many forms of cardiovascular disease, heart failure (HF) continues to increase. Heart failure with preserved ejection fraction (HFpEF) is common, especially among persons with multiple comorbidities. HFpEF presents many challenges for clinicians due to the incomplete understanding of the underlying mechanisms and lack of consensus on the most effective strategies for treatment. Angiotensin and beta receptor-blocking drugs, which form the cornerstone for the treatment of systolic HF, have failed to show similar benefits in patients with impaired diastolic function. This article provides an overview of drug therapy for HFpEF, including newer agents now under investigation.

Precision spectroscopy of high rotational states in H2 investigated by Doppler-free two-photon laser spectroscopy in the EF 1Σg+-X 1Σg+ system

NASA Astrophysics Data System (ADS)

Dickenson, G. D.; Salumbides, E. J.; Niu, M.; Jungen, Ch.; Ross, S. C.; Ubachs, W.

2012-09-01

Recently a high precision spectroscopic investigation of the EF1Σg+-X1Σg+ system of molecular hydrogen was reported yielding information on QED and relativistic effects in a sequence of rotational quantum states in the X1Σg+ ground state of the H2 molecule [Salumbides , Phys. Rev. Lett.PRLTAO0031-900710.1103/PhysRevLett.107.043005 107, 043005 (2011)]. The present paper presents a more detailed description of the methods and results. Furthermore, the paper serves as a stepping stone towards a continuation of the previous study by extending the known level structure of the EF1Σg+ state to highly excited rovibrational levels through Doppler-free two-photon spectroscopy. Based on combination differences between vibrational levels in the ground state, and between three rotational branches (O, Q, and S branches) assignments of excited EF1Σg+ levels, involving high vibrational and rotational quantum numbers, can be unambiguously made. For the higher EF1Σg+ levels, where no combination differences are available, calculations were performed using the multichannel quantum defect method, for a broad class of vibrational and rotational levels up to J=19. These predictions were used for assigning high-J EF levels and are found to be accurate within 5 cm-1.

Executive Function Buffers the Association between Early Math and Later Academic Skills.

PubMed

Ribner, Andrew D; Willoughby, Michael T; Blair, Clancy B

2017-01-01

Extensive evidence has suggested that early academic skills are a robust indicator of later academic achievement; however, there is mixed evidence of the effectiveness of intervention on academic skills in early years to improve later outcomes. As such, it is clear there are other contributing factors to the development of academic skills. The present study tests the role of executive function (EF) (a construct made up of skills complicit in the achievement of goal-directed tasks) in predicting 5th grade math and reading ability above and beyond math and reading ability prior to school entry, and net of other cognitive covariates including processing speed, vocabulary, and IQ. Using a longitudinal dataset of N = 1292 participants representative of rural areas in two distinctive geographical parts of the United States, the present investigation finds EF at age 5 strongly predicts 5th grade academic skills, as do cognitive covariates. Additionally, investigation of an interaction between early math ability and EF reveals the magnitude of the association between early math and later math varies as a function of early EF, such that participants who have high levels of EF can "catch up" to peers who perform better on assessments of early math ability. These results suggest EF is pivotal to the development of academic skills throughout elementary school. Implications for further research and practice are discussed.

Myocardial Hypertrophy and Its Role in Heart Failure with Preserved Ejection Fraction

PubMed Central

Heinzel, Frank R.; Hohendanner, Felix; Jin, Ge; Sedej, Simon; Edelmann, Frank

2015-01-01

Left ventricular hypertrophy (LVH) is the most common myocardial structural abnormality associated with heart failure with preserved ejection fraction (HFpEF). LVH is driven by neurohumoral activation, increased mechanical load and cytokines associated with arterial hypertension, chronic kidney disease, diabetes and other co-morbidities. Here we discuss the experimental and clinical evidence that links LVH to diastolic dysfunction and qualifies LVH as one diagnostic marker for HFpEF. Mechanisms leading to diastolic dysfunction in LVH are incompletely understood but may include extracellular matrix changes, vascular dysfunction as well as altered cardiomyocyte mechano-elastical properties. Beating cardiomyocytes from HFpEF patients have not yet been studied, but we and others have shown increased Ca2+ turnover and impaired relaxation in cardiomyocytes from hypertrophied hearts. Structural myocardial remodeling can lead to heterogeneity in regional myocardial contractile function, which contributes to diastolic dysfunction in HFpEF. In the clinical setting of patients with compound co-morbidities, diastolic dysfunction may occur independently of LVH. This may be one explanation why current approaches to reduce LVH have not been effective to improve symptoms and prognosis in HFpEF. Exercise training on the other hand, in clinical trials improved exercise tolerance and diastolic function but did not reduce LVH. Thus, current clinical evidence does not support regression of LVH as a surrogate marker for (short-term) improvement of HFpEF. PMID:26183480

Early Executive Function at Age Two Predicts Emergent Mathematics and Literacy at Age Five

PubMed Central

Mulder, Hanna; Verhagen, Josje; Van der Ven, Sanne H. G.; Slot, Pauline L.; Leseman, Paul P. M.

2017-01-01

Previous work has shown that individual differences in executive function (EF) are predictive of academic skills in preschoolers, kindergartners, and older children. Across studies, EF is a stronger predictor of emergent mathematics than literacy. However, research on EF in children below age three is scarce, and it is currently unknown whether EF, as assessed in toddlerhood, predicts emergent academic skills a few years later. This longitudinal study investigates whether early EF, assessed at two years, predicts (emergent) academic skills, at five years. It examines, furthermore, whether early EF is a significantly stronger predictor of emergent mathematics than of emergent literacy, as has been found in previous work on older children. A sample of 552 children was assessed on various EF and EF-precursor tasks at two years. At age five, these children performed several emergent mathematics and literacy tasks. Structural Equation Modeling was used to investigate the relationships between early EF and academic skills, modeled as latent factors. Results showed that early EF at age two was a significant and relatively strong predictor of both emergent mathematics and literacy at age five, after controlling for receptive vocabulary, parental education, and home language. Predictive relations were significantly stronger for mathematics than literacy, but only when a verbal short-term memory measure was left out as an indicator to the latent early EF construct. These findings show that individual differences in emergent academic skills just prior to entry into the formal education system can be traced back to individual differences in early EF in toddlerhood. In addition, these results highlight the importance of task selection when assessing early EF as a predictor of later outcomes, and call for further studies to elucidate the mechanisms through which individual differences in early EF and precursors to EF come about. PMID:29075209

Early Executive Function at Age Two Predicts Emergent Mathematics and Literacy at Age Five.

PubMed

Mulder, Hanna; Verhagen, Josje; Van der Ven, Sanne H G; Slot, Pauline L; Leseman, Paul P M

2017-01-01

Previous work has shown that individual differences in executive function (EF) are predictive of academic skills in preschoolers, kindergartners, and older children. Across studies, EF is a stronger predictor of emergent mathematics than literacy. However, research on EF in children below age three is scarce, and it is currently unknown whether EF, as assessed in toddlerhood, predicts emergent academic skills a few years later. This longitudinal study investigates whether early EF, assessed at two years, predicts (emergent) academic skills, at five years. It examines, furthermore, whether early EF is a significantly stronger predictor of emergent mathematics than of emergent literacy, as has been found in previous work on older children. A sample of 552 children was assessed on various EF and EF-precursor tasks at two years. At age five, these children performed several emergent mathematics and literacy tasks. Structural Equation Modeling was used to investigate the relationships between early EF and academic skills, modeled as latent factors. Results showed that early EF at age two was a significant and relatively strong predictor of both emergent mathematics and literacy at age five, after controlling for receptive vocabulary, parental education, and home language. Predictive relations were significantly stronger for mathematics than literacy, but only when a verbal short-term memory measure was left out as an indicator to the latent early EF construct. These findings show that individual differences in emergent academic skills just prior to entry into the formal education system can be traced back to individual differences in early EF in toddlerhood. In addition, these results highlight the importance of task selection when assessing early EF as a predictor of later outcomes, and call for further studies to elucidate the mechanisms through which individual differences in early EF and precursors to EF come about.

Metabolomic Fingerprint of Heart Failure with Preserved Ejection Fraction

PubMed Central

Zordoky, Beshay N.; Sung, Miranda M.; Ezekowitz, Justin; Mandal, Rupasri; Han, Beomsoo; Bjorndahl, Trent C.; Bouatra, Souhaila; Anderson, Todd; Oudit, Gavin Y.; Wishart, David S.; Dyck, Jason R. B.

2015-01-01

Background Heart failure (HF) with preserved ejection fraction (HFpEF) is increasingly recognized as an important clinical entity. Preclinical studies have shown differences in the pathophysiology between HFpEF and HF with reduced ejection fraction (HFrEF). Therefore, we hypothesized that a systematic metabolomic analysis would reveal a novel metabolomic fingerprint of HFpEF that will help understand its pathophysiology and assist in establishing new biomarkers for its diagnosis. Methods and Results Ambulatory patients with clinical diagnosis of HFpEF (n = 24), HFrEF (n = 20), and age-matched non-HF controls (n = 38) were selected for metabolomic analysis as part of the Alberta HEART (Heart Failure Etiology and Analysis Research Team) project. 181 serum metabolites were quantified by LC-MS/MS and 1H-NMR spectroscopy. Compared to non-HF control, HFpEF patients demonstrated higher serum concentrations of acylcarnitines, carnitine, creatinine, betaine, and amino acids; and lower levels of phosphatidylcholines, lysophosphatidylcholines, and sphingomyelins. Medium and long-chain acylcarnitines and ketone bodies were higher in HFpEF than HFrEF patients. Using logistic regression, two panels of metabolites were identified that can separate HFpEF patients from both non-HF controls and HFrEF patients with area under the receiver operating characteristic (ROC) curves of 0.942 and 0.981, respectively. Conclusions The metabolomics approach employed in this study identified a unique metabolomic fingerprint of HFpEF that is distinct from that of HFrEF. This metabolomic fingerprint has been utilized to identify two novel panels of metabolites that can separate HFpEF patients from both non-HF controls and HFrEF patients. Clinical Trial Registration ClinicalTrials.gov NCT02052804 PMID:26010610

Risk Factors for Incident Hospitalized Heart Failure With Preserved Versus Reduced Ejection Fraction in a Multiracial Cohort of Postmenopausal Women.

PubMed

Eaton, Charles B; Pettinger, Mary; Rossouw, Jacques; Martin, Lisa Warsinger; Foraker, Randi; Quddus, Abdullah; Liu, Simin; Wampler, Nina S; Hank Wu, Wen-Chih; Manson, JoAnn E; Margolis, Karen; Johnson, Karen C; Allison, Matthew; Corbie-Smith, Giselle; Rosamond, Wayne; Breathett, Khadijah; Klein, Liviu

2016-10-01

Heart failure is an important and growing public health problem in women. Risk factors for incident hospitalized heart failure with preserved ejection fraction (HFpEF) compared with heart failure with reduced ejection fraction (HFrEF) in women and differences by race/ethnicity are not well characterized. We prospectively evaluated the risk factors for incident hospitalized HFpEF and HFrEF in a multiracial cohort of 42 170 postmenopausal women followed up for a mean of 13.2 years. Cox regression models with time-dependent covariate adjustment were used to define risk factors for HFpEF and HFrEF. Differences by race/ethnicity about incidence rates, baseline risk factors, and their population-attributable risk percentage were analyzed. Risk factors for both HFpEF and HFrEF were as follows: older age, white race, diabetes mellitus, cigarette smoking, and hypertension. Obesity, history of coronary heart disease (other than myocardial infarction), anemia, atrial fibrillation, and more than one comorbidity were associated with HFpEF but not with HFrEF. History of myocardial infarction was associated with HFrEF but not with HFpEF. Obesity was found to be a more potent risk factor for African American women compared with white women for HFpEF (P for interaction=0.007). For HFpEF, the population-attributable risk percentage was greatest for hypertension (40.9%) followed by obesity (25.8%), with the highest population-attributable risk percentage found in African Americans for these risk factors. In this multiracial cohort of postmenopausal women, obesity stands out as a significant risk factor for HFpEF, with the strongest association in African American women. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000611. © 2016 American Heart Association, Inc.

Determination of parabens in beverage samples by dispersive liquid-liquid microextraction based on solidification of floating organic droplet.

PubMed

Hou, Fang; Deng, Xiaoying; Jiang, Xinyu; Yu, Jingang

2014-01-01

A simple and efficient method for dispersive liquid-liquid microextraction of methylparaben, ethylparaben, propylparaben and butylparaben in real beverage samples was developed. It is making use of solidified floating organic droplets of 1-dodecanol which has low density and a proper melting point. Parameters influencing the extraction efficiency, such as the type of extraction and dispersive solvent, the volume of extraction and dispersive solvent, salt effect, pH, extraction time, were optimized and resulted in enrichment factors (EFs) of 84 for methylparaben, 103 for ethylparaben, 115 for propylparaben and 126 for butylparaben. The limits of detection for parabens were 1.52, 1.06, 0.32 and 0.17 ng/mL, respectively. Excellent linearity with coefficients of correlation from 0.9970 to 0.9997 was observed in the concentration range of 5-1,000 ng/mL. The repeatability of the proposed method expressed as relative standard deviations (RSDs) ranged from 2.54 to 3.89% (n = 5). The relative recoveries for parabens in beverage samples were good and in the ranges of 89.8-109.9, 90.2-107.3, 90.9-101.7 and 92.3-118.1%, respectively. Thus, the proposed method has excellent potential for the determination of parabens in beverage samples. © The Author [2013]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

CHARACTERIZATION OF PARTICULATE MATTER EMISSION FROM OPEN BURNING OF RICE STRAW

PubMed Central

Oanh, Nguyen Thi Kim; Bich, Thuy Ly; Tipayarom, Danutawat; Manadhar, Bhai R.; Prapat, Pongkiatkul; Simpson, Christopher D.; Liu, L-J Sally

2010-01-01

Emission from field burning of crop residue, a common practice in many parts of the world today, has potential effects on air quality, atmosphere and climate. This study provides a comprehensive size and compositional characterization of particulate matter (PM) emission from rice straw (RS) burning using both in situ experiments (11 spread field burning) and laboratory hood experiments (3 pile and 6 spread burning) that were conducted during 2003–2006 in Thailand. The carbon balance and emission ratio method was used to determine PM emission factors (EF) in the field experiments. The obtained EFs varied from field to hood experiments reflecting multiple factors affecting combustion and emission. In the hood experiments, EFs were found to be depending on the burning types (spread or pile), moisture content and the combustion efficiency. In addition, in the field experiments, burning rate and EF were also influenced by weather conditions, i.e. wind. Hood pile burning produced significantly higher EF (20±8 g kg−1 RS) than hood spread burning (4.7±2.2 g kg−1 RS). The majority of PM emitted from the field burning was PM2.5 with EF of 5.1±0.7 g m−2 or 8.3±2.7 g kg−1 RS burned. The coarse PM fraction (PM10-2.5) was mainly generated by fire attention activities and was relatively small, hence the resulting EF of PM10 (9.4±3.5 g kg−1 RS) was not significantly higher than PM2.5. PM size distribution was measured across 8 size ranges (from <0.4 μm to >9.0 μm). The largest fractions of PM, EC and OC were associated with PM1.1. The most significant components in PM2.5 and PM10 include OC, water soluble ions and levoglucosan. Relative abundance of some methoxyphenols (e.g., acetylsyringone), PAHs (e.g., fluoranthene and pyrene), organochlorine pesticides and PCBs may also serve as additional signatures for the PM emission. Presence of these toxic compounds in PM of burning smoke increases the potential toxic effects of the emission. For illustration, an estimation of the annual RS field burning in Thailand was made using the obtained in situ field burning EFs and preliminary burning activity data. PMID:21243095

Metastable State during Melting and Solid-Solid Phase Transition of [CnMim][NO3] (n = 4-12) Ionic Liquids by Molecular Dynamics Simulation.

PubMed

Cao, Wudi; Wang, Yanting; Saielli, Giacomo

2018-01-11

We simulate the heating process of ionic liquids [C n Mim][NO 3 ] (n = 4, 6, 8, 10, 12), abbreviated as C n , by means of molecular dynamics (MD) simulation starting from a manually constructed triclinic crystal structure composed of polar layers containing anions and cationic head groups and nonpolar regions in between containing cationic alkyl side chains. During the heating process starting from 200 K, each system undergoes first a solid-solid phase transition at a lower temperature, and then a melting phase transition at a higher temperature to an isotropic liquid state (C 4 , C 6 , and C 8 ) or to a liquid crystal state (C 10 and C 12 ). After the solid-solid phase transition, all systems keep the triclinic space symmetry, but have a different set of lattice constants. C 4 has a more significant structural change in the nonpolar regions which narrows the layer spacing, while the layer spacings of other systems change little, which can be qualitatively understood by considering that the contribution of the effective van der Waals interaction in the nonpolar regions (abbreviated as EF1) to free energy becomes stronger with increasing side-chain length, and at the same time the contribution of the effective electrostatic interaction in the polar layers (abbreviated as EF2) to free energy remains almost the same. The melting phase transitions of all systems except C 6 are found to be a two-step process with an intermediate metastable state appeared during the melting from the crystal state to the liquid or liquid crystal state. Because the contribution of EF2 to the free energy is larger than EF1, the metastable state of C 4 has the feature of having higher ordered polar layers and lower ordered side-chain orientation. By contrast, C 8 -C 12 have the feature of having lower ordered polar layers and higher ordered side-chain orientation, because for these systems, the contribution of EF2 to the free energy is smaller than EF1. No metastable state is found for C 6 because the free-energy contribution of EF1 is balanced with EF2.

Impact of Cardiac Progenitor Cells on Heart Failure and Survival in Single Ventricle Congenital Heart Disease.

PubMed

Sano, Toshikazu; Ousaka, Daiki; Goto, Takuya; Ishigami, Shuta; Hirai, Kenta; Kasahara, Shingo; Ohtsuki, Shinichi; Sano, Shunji; Oh, Hidemasa

2018-03-30

Intracoronary administration of cardiosphere-derived cells (CDCs) in patients with single ventricles resulted in a short-term improvement in cardiac function. To test the hypothesis that CDC infusion is associated with improved cardiac function and reduced mortality in patients with heart failure. We evaluated the effectiveness of CDCs using an integrated cohort study in 101 patients with single ventricles, including 41 patients who received CDC infusion and 60 controls treated with staged palliation alone. Heart failure with preserved ejection fraction (EF) or reduced EF was stratified by the cardiac function after surgical reconstruction. The main outcome measure was to evaluate the magnitude of improvement in cardiac function and all-cause mortality at 2 years. Animal studies were conducted to clarify the underlying mechanisms of heart failure with preserved EF and heart failure with reduced EF phenotypes. At 2 years, CDC infusion increased ventricular function (stage 2: +8.4±10.0% versus +1.6±6.4%, P =0.03; stage 3: +7.9±7.5% versus -1.1±5.5%, P <0.001) compared with controls. In all available follow-up data, survival did not differ between the 2 groups (log-rank P =0.225), whereas overall patients treated by CDCs had lower incidences of late failure ( P =0.022), adverse events ( P =0.013), and catheter intervention ( P =0.005) compared with controls. CDC infusion was associated with a lower risk of adverse events (hazard ratio, 0.411; 95% CI, 0.179-0.942; P =0.036). Notably, CDC infusion reduced mortality ( P =0.038) and late complications ( P <0.05) in patients with heart failure with reduced EF but not with heart failure with preserved EF. CDC-treated rats significantly reversed myocardial fibrosis with differential collagen deposition and inflammatory responses between the heart failure phenotypes. CDC administration in patients with single ventricles showed favorable effects on ventricular function and was associated with reduced late complications except for all-cause mortality after staged procedures. Patients with heart failure with reduced EF but not heart failure with preserved EF treated by CDCs resulted in significant improvement in clinical outcome. URL: http://www.clinicaltrials.gov. Unique identifiers: NCT01273857 and NCT01829750. © 2018 American Heart Association, Inc.

Mammalian translation elongation factor eEF1A2: X-ray structure and new features of GDP/GTP exchange mechanism in higher eukaryotes.

PubMed

Crepin, Thibaut; Shalak, Vyacheslav F; Yaremchuk, Anna D; Vlasenko, Dmytro O; McCarthy, Andrew; Negrutskii, Boris S; Tukalo, Michail A; El'skaya, Anna V

2014-11-10

Eukaryotic elongation factor eEF1A transits between the GTP- and GDP-bound conformations during the ribosomal polypeptide chain elongation. eEF1A*GTP establishes a complex with the aminoacyl-tRNA in the A site of the 80S ribosome. Correct codon-anticodon recognition triggers GTP hydrolysis, with subsequent dissociation of eEF1A*GDP from the ribosome. The structures of both the 'GTP'- and 'GDP'-bound conformations of eEF1A are unknown. Thus, the eEF1A-related ribosomal mechanisms were anticipated only by analogy with the bacterial homolog EF-Tu. Here, we report the first crystal structure of the mammalian eEF1A2*GDP complex which indicates major differences in the organization of the nucleotide-binding domain and intramolecular movements of eEF1A compared to EF-Tu. Our results explain the nucleotide exchange mechanism in the mammalian eEF1A and suggest that the first step of eEF1A*GDP dissociation from the 80S ribosome is the rotation of the nucleotide-binding domain observed after GTP hydrolysis. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Does Executive Functioning (EF) Predict Depression in Clinic-Referred Adults?: EF Tests vs. Rating Scales

PubMed Central

Knouse, Laura E.; Barkley, Russell A.; Murphy, Kevin R.

2012-01-01

Background Deficits in executive functioning (EF) are implicated in neurobiological and cognitive-processing theories of depression. EF deficits are also associated with Attention-deficit/hyperactivity disorder (ADHD) in adults, who are also at increased risk for depressive disorders. Given debate about the ecological validity of laboratory measures of EF, we investigated the relationship between depression diagnoses and symptoms and EF as measured by both rating scales and tests in a sample of adults referred for evaluation of adult ADHD. Method Data from two groups of adults recruited from an ADHD specialty clinic were analyzed together: Adults diagnosed with ADHD (N=146) and a clinical control group of adults referred for adult ADHD assessment but not diagnosed with the disorder ADHD (N=97). EF was assessed using a rating scale of EF deficits in daily life and a battery of tests tapping various EF constructs. Depression was assessed using current and lifetime SCID diagnoses (major depression, dysthymia) and self-report symptom ratings. Results EF as assessed via rating scale predicted depression across measures even when controlling for current anxiety and impairment. Self-Management to Time and Self-Organization and Problem-Solving showed the most robust relationships. EF tests were weakly and inconsistently related to depression measures. Limitations Prospective studies are needed to rigorously evaluate EF problems as true risk factors for depressive onset. Conclusions EF problems in everyday life were important predictors of depression. Researchers and clinicians should consistently assess for the ADHD-depression comorbidity. Clinicians should consider incorporating strategies to address EF deficits when treating people with depression. PMID:22858220

Prevalence and Long-Term Survival After Coronary Artery Bypass Grafting in Women and Men With Heart Failure and Preserved Versus Reduced Ejection Fraction.

PubMed

Sun, Louise Y; Tu, Jack V; Bader Eddeen, Anan; Liu, Peter P

2018-06-16

Heart failure (HF) with reduced ejection fraction (rEF) is a widely regarded prognosticator after coronary artery bypass grafting. HF with preserved ejection fraction (pEF) accounts for up to half of all HF cases and is associated with considerable morbidity and mortality in hospitalized cohorts. However, HFpEF outcomes have not been elucidated in cardiac surgical patients. We investigated the prevalence and outcomes of HFpEF and HFrEF in women and men following coronary artery bypass grafting. We conducted a retrospective cohort study in Ontario, Canada, between October 1, 2008, and March 31, 2015, using Cardiac Care Network and Canadian Institute of Health Information data. HF is captured through a validated population-based database of all Ontarians with physician-diagnosed HF. We defined pEF as ejection fraction ≥50% and rEF as ejection fraction <50%. The primary outcome was all-cause mortality. Analyses were stratified by sex. Mortality rates were calculated using Kaplan-Meier method. The relative hazard of death was assessed using multivariable Cox proportional hazard models. Of 40 083 patients (20.6% women), 55.5% had pEF without HF, 25.7% had rEF without HF, 6.9% had HFpEF, and 12.0% had HFrEF. Age-standardized HFpEF mortality rates at 4±2 years of follow-up were similar in women and men. HFrEF standardized HFpEF mortality rates were higher in women than men. We found a higher prevalence and poorer prognosis of HFpEF in women. A history of HF was a more important prognosticator than ejection fraction. Preoperative screening and extended postoperative follow-up should be focused on women and men with HF rather than on rEF alone. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Impact of terrestrial mining and intensive agriculture in pollution of estuarine surface sediments: Spatial distribution of trace metals in the Gulf of Urabá, Colombia.

PubMed

Vallejo Toro, Pedro Pablo; Vásquez Bedoya, Luis Fernando; Correa, Iván Darío; Bernal Franco, Gladys Rocío; Alcántara-Carrió, Javier; Palacio Baena, Jaime Alberto

2016-10-15

The Gulf of Urabá (northwestern Colombia) is a geostrategic region, rich in biodiversity and natural resources. Its economy is mainly based on agribusinesses and mining activities. In this research is determined the impact of these activities in bottom surface sediments of the estuary. Thus, grain size, total organic carbon, total nitrogen, carbonates, Ag, Al, Ca, Cr, Cu, Fe, Hg, Mg, Mn, Ni, Pb and Zn concentrations from 17 surface sediment samples were obtained and enrichment factors (EF) as well as geo-accumulation indices (Igeo) were calculated to determine the contamination level in the gulf. EF and Igeo values revealed that the estuary is extremely contaminated with Ag and moderately contaminated with Zn. Therefore, the observed enrichment of Ag may be explained as a residue of the extraction of gold and platinum-group metals and the enrichment with Zn associated mainly to pesticides used in banana plantations. Copyright © 2016 Elsevier Ltd. All rights reserved.

Preconcentration of Trace Neonicotinoid Insecticide Residues Using Vortex-Assisted Dispersive Micro Solid-Phase Extraction with Montmorillonite as an Efficient Sorbent.

PubMed

Moyakao, Khwankaew; Santaladchaiyakit, Yanawath; Srijaranai, Supalax; Vichapong, Jitlada

2018-04-11

In this work, we investigated montmorillonite for adsorption of neonicotinoid insecticides in vortex-assisted dispersive micro-solid phase extraction (VA-d-μ-SPE). High-performance liquid chromatography with photodiode array detection was used for quantification and determination of neonicotinoid insecticide residues, including thiamethoxam, clothianidin, imidacloprid, acetamiprid, and thiacloprid. In this method, the solid sorbent was dispersed into the aqueous sample solution and vortex agitation was performed to accelerate the extraction process. Finally, the solution was filtered from the solid sorbent with a membrane filter. The parameters affecting the extraction efficiency of the proposed method were optimized, such as amount of sorbent, sample volume, salt addition, type and volume of extraction solvent, and vortex time. The adsorbing results show that montmorillonite could be reused at least 4 times and be used as an effective adsorbent for rapid extraction/preconcentration of neonicotinoid insecticide residues. Under optimum conditions, linear dynamic ranges were achieved between 0.5 and 1000 ng mL -1 with a correlation of determination ( R² ) greater than 0.99. Limit of detection (LOD) ranged from 0.005 to 0.065 ng mL -1 , while limit of quantification (LOQ) ranged from 0.008 to 0.263 ng mL -1 . The enrichment factor (EF) ranged from 8 to 176-fold. The results demonstrated that the proposed method not only provided a more simple and sensitive method, but also can be used as a powerful alternative method for the simultaneous determination of insecticide residues in natural surface water and fruit juice samples.

Comparison of 5-Year Outcomes After Coronary Artery Bypass Grafting in Heart Failure Patients With Versus Without Preserved Left Ventricular Ejection Fraction (from the CREDO-Kyoto CABG Registry Cohort-2).

PubMed

Marui, Akira; Nishiwaki, Noboru; Komiya, Tatsuhiko; Hanyu, Michiya; Tanaka, Shiro; Kimura, Takeshi; Sakata, Ryuzo

2015-08-15

Heart failure (HF) with reduced left ventricular (LV) ejection fraction (HFrEF) is regarded as an independent risk factor for poor outcomes after coronary artery bypass grafting (CABG). However, the impact of HF with preserved EF (HFpEF) still has been unclear. We identified 1,877 patients who received isolated CABG of 15,939 patients who underwent first coronary revascularization enrolled in the CREDO-Kyoto (Coronary REvascularization Demonstrating Outcome Study in Kyoto) Registry Cohort-2. Of them, 1,489 patients had normal LV function (LVEF >50% without a history of HF; Normal group), 236 had HFrEF (LVEF ≤50% with HF), and 152 had HFpEF (LVEF >50% with HF). Preoperative LVEF was the lowest in the HFrEF group (62 ± 12%, 36 ± 9%, and 61 ± 7% for the Normal, HFrEF, and HFpEF groups, respectively; p <0.001). Unadjusted 30-day mortality rate was the highest in the HFrEF group (0.5%, 3.0%, and 0.7%; p = 0.003). However, cumulative incidences of all-cause death at 5-year was the highest in the HFpEF group (14%, 27%, and 32%, respectively; p <0.001). After adjusting confounders, the risk of all-cause death in the HFpEF group was greater than the Normal group (hazard ratio [HR] 1.42; 95% confidence interval [CI] 1.02 to 1.97; p = 0.04). The risk of all-cause death was not different between the HFpEF and the HFrEF groups (HR 0.88; 95% CI 0.61 to 1.29; p = 0.52). In addition, the risks of cardiac death and sudden death in the HFpEF group were greater than the Normal group (HR 2.14, 95% CI 1.32 to 3.49, p = 0.002; and HR 3.60, 95% CI 1.55 to 8.36, p = 0.003, respectively), and the risks of those end points were not different between the HFrEF and the HFpEF groups. Despite low 30-day mortality rate after CABG in patients with HFpEF, HFpEF was associated with high risks of long-term death and cardiovascular events. Patients with HFpEF, as well as HFrEF, should be carefully operated and followed up. Copyright © 2015 Elsevier Inc. All rights reserved.

Hypoxia-mediated sorafenib resistance can be overcome by EF24 through Von Hippel-Lindau tumor suppressor-dependent HIF-1α inhibition in hepatocellular carcinoma.

PubMed

Liang, Yingjian; Zheng, Tongsen; Song, Ruipeng; Wang, Jiabei; Yin, Dalong; Wang, Luoluo; Liu, Haitao; Tian, Lantian; Fang, Xiang; Meng, Xianzhi; Jiang, Hongchi; Liu, Jiaren; Liu, Lianxin

2013-05-01

The increasing incidence of hepatocellular carcinoma (HCC) is of great concern not only in the United States but throughout the world. Although sorafenib, a multikinase inhibitor with antiangiogenic and antiproliferative effects, currently sets the new standard for advanced HCC, tumor response rates are usually quite low. An understanding of the underlying mechanisms for sorafenib resistance is critical if outcomes are to be improved. In this study we tested the hypothesis that hypoxia caused by the antiangiogenic effects of sustained sorafenib therapy could induce sorafenib resistance as a cytoprotective adaptive response, thereby limiting sorafenib efficiency. We found that HCCs, clinically resistant to sorafenib, exhibit increased intratumor hypoxia compared with HCCs before treatment or HCCs sensitive to sorafenib. Hypoxia protected HCC cells against sorafenib and hypoxia-inducible factor 1 (HIF-1α) was required for the process. HCC cells acquired increased P-gp expression, enhanced glycolytic metabolism, and increased nuclear factor kappa B (NF-κB) activity under hypoxia. EF24, a molecule having structural similarity to curcumin, could synergistically enhance the antitumor effects of sorafenib and overcome sorafenib resistance through inhibiting HIF-1α by sequestering it in cytoplasm and promoting degradation by way of up-regulating Von Hippel-Lindau tumor suppressor (VHL). Furthermore, we found that sustained sorafenib therapy led to increased intratumor hypoxia, which was associated with sorafenib sensitivity in HCC subcutaneous mice tumor models. The combination of EF24 and sorafenib showed synergistically effects against metastasis both in vivo and in vitro. Synergistic tumor growth inhibition effects were also observed in subcutaneous and orthotopic hepatic tumors. Hypoxia induced by sustained sorafenib treatment confers sorafenib resistance to HCC through HIF-1α and NF-κB activation. EF24 overcomes sorafenib resistance through VHL-dependent HIF-1α degradation and NF-κB inactivation. EF24 in combination with sorafenib represents a promising strategy for HCC. Copyright © 2013 American Association for the Study of Liver Diseases.

Recovery of Baseline Erectile Function in Men Following Radical Prostatectomy for High-Risk Prostate Cancer: A Prospective Analysis Using Validated Measures.

PubMed

Sridhar, Ashwin N; Cathcart, Paul J; Yap, Tet; Hines, John; Nathan, Senthil; Briggs, Timothy P; Kelly, John D; Minhas, Suks

2016-03-01

Recovery of baseline erectile function (EF) after robotic radical prostatectomy in men with high-risk prostate cancer is under-reported. Published studies have selectively reported on low-risk disease using non-validated and poorly defined thresholds for EF recovery. To assess return to baseline EF in men after robotic radical prostatectomy for high-risk prostate cancer. Five hundred thirty-one men underwent robotic radical prostatectomy for high-risk prostate cancer from February 2010 through July 2014. Pre- and postoperative EF was prospectively assessed using the International Index of Erectile Dysfunction (IIEF-5) questionnaire. Multivariate logistic regression analysis determined the effect of age, preoperative function, comorbidities, body mass index, prostate-specific antigen level, cancer stage or grade, nerve-sparing status, adjuvant therapy, and continence on EF return (defined as postoperative return to baseline EF with or without use of phosphodiesterase type 5 inhibitors). Kaplan-Meier analysis and log-rank test were used to analyze return over time. Mann-Whitney U-test was used to compare IIEF-5 scores. Pre- and postoperative EF was assessed using the IIEF-5 Sexual Health Inventory for Men at 3 months, 6 months, 1 year, 2 years, 3 years, and 4 years postoperatively. Overall, return of EF was seen in 23.5% of patients at 18 months. This was significantly increased in men no older than 60 years (P = .024), with a preoperative IIEF-5 score of at least 22 (P = .042), and after undergoing neurovascular bundle preservation (34.9% of patients, P < .001). There was no significant change in IIEF-5 scores from 3 to 36 months in patients who were treated with phosphodiesterase type 5 inhibitors in the non-neurovascular bundle preservation group (P = .87), although there was significant improvement in those receiving second- or third-line therapies (P = .042). Other than preoperative hypertension (P = .03), none of the other comorbidities predicted return of EF. In this study, 23.5% of men recovered to baseline EF. Of those who underwent bilateral neurovascular bundle preservation robotic radical prostatectomy, 70% recovered baseline EF; however, this accounted for only 9.6% of all patients. Only 4% of men who underwent non-neurovascular bundle preservation had baseline recovery with phosphodiesterase type 5 inhibitors up to 36 months. There was significant improvement after use of second- or third-line therapies, indicating the need for earlier institution of these treatment modalities. Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Importance of individual amino acids in the Switch I region in eEF2 studied by functional complementation in S. cerevisiae.

PubMed

Bartish, Galyna; Nygård, Odd

2008-05-01

Elongation factor 2 (eEF2) is a member of the G-protein super family. G-proteins undergo conformational changes associated with binding of the guanosine nucleotide and hydrolysis of the bound GTP. These structural rearrangements affects the Switch I region (also known as the Effector loop). We have studied the role of individual amino acids in the Switch I region (amino acids 25-73) of S. cerevisiae eEF2 using functional complementation in yeast. 21 point mutations in the Switch I region were created by site-directed mutagenesis. Mutants K49R, E52Q, A53G, F55Y, K60R, Q63A, T68S, I69M and A73G were functional while mutants R54H, F55N, D57A, D57E, D57S, R59K, R59M, Q63E, R65A, R65N, T68A and T68M were inactive. Expression of mutants K49R, A53G, Q63A, I69M and A73G was associated with markedly decreased growth rates and yeast cells expressing mutants A53G and I69M became temperature sensitive. The functional capacity of eEF2 in which the major part Switch I (amino acids T56 to I69) was converted into the homologous sequence found in EF-G from E. coli was also studied. This protein chimera could functionally replace yeast eEF2 in vivo. Yeast cells expressing this mutant grew extremely slowly, showed increased cell death and became temperature sensitive. The ability of the mutant to replace authentic eEF2 in vivo indicates that the structural rearrangement of Switch I necessary for eEF2 function is similar in eukaryotes and bacteria. The effect of two point mutations in the P-loop was also studied. Mutant A25G but not A25V could functionally replace yeast eEF2 even if cells expressing the mutant grew slowly. The A25G mutation converted the consensus sequences AXXXXGK[T/S] in eEF2 to the corresponding motif GXXXXGK[T/S] found in all other G-proteins, suggesting that the alanine found in the P-loop of peptidyltranslocases are not essential for function.

Effect of Linear Low-Intensity Extracorporeal Shockwave Therapy for Erectile Dysfunction-12-Month Follow-Up of a Randomized, Double-Blinded, Sham-Controlled Study.

PubMed

Fojecki, Grzegorz Lukasz; Tiessen, Stefan; Osther, Palle Jørn Sloth

2018-03-01

Short-term data on the effect of low-intensity extracorporeal shockwave therapy (Li-ESWT) on erectile dysfunction (ED) have been inconsistent. The suggested mechanisms of action of Li-ESWT on ED include stimulation of cell proliferation, tissue regeneration, and angiogenesis, which can be processes with a long generation time. Therefore, long-term data on the effect of Li-ESWT on ED are strongly warranted. To assess the outcome at 6 and 12 months of linear Li-ESWT on ED from a previously published randomized, double-blinded, sham-controlled trial. Subjects with ED (N = 126) who scored lower than 25 points in the erectile function domain of the International Index of Erectile Function (IIEF-EF) were eligible for the study. They were allocated to 1 of 2 groups: 5 weekly sessions of sham treatment (group A) or linear Li-ESWT (group B). After a 4-week break, the 2 groups received active treatment once a week for 5 weeks. At baseline and 6 and 12 months, subjects were evaluated by the IIEF-EF, the Erectile Hardness Scale (EHS), and the Sexual Quality of Life in Men. The primary outcome measure was an increase of at least 5 points in the IIEF-EF (ΔIIEF-EF score). The secondary outcome measure was an increase in the EHS score to at least 3 in men with a score no higher than 2 at baseline. Data were analyzed by linear and logistic regressions. Linear regression of the ΔIIEF-EF score from baseline to 12 months included 95 patients (dropout rate = 25%). Adjusted for the IIEF-EF score at baseline, the difference between groups B and A was -1.30 (95% CI = -4.37 to 1.77, P = .4). The success rate based on the main outcome parameter (ΔIIEF-EF score ≥ 5) was 54% in group A vs 47% in group B (odds ratio = 0.67, P = .28). Improvement based on changes in the EHS score in groups A and B was 34% and 24%, respectively (odds ratio = 0.47, P = .82). Exposure to 2 cycles of linear Li-ESWT for ED is not superior to 1 cycle at 6- and 12-month follow-ups. Fojecki GL, Tiessen S, Osther PJS. Effect of Linear Low-Intensity Extracorporeal Shockwave Therapy for Erectile Dysfunction-12-Month Follow-Up of a Randomized, Double-Blinded, Sham-Controlled Study. Sex Med 2018;6:1-7. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Characterization and virulence of Beauveria spp. recovered from emerald ash borer in southwestern Ontario, Canada.

PubMed

Johny, Shajahan; Kyei-Poku, George; Gauthier, Debbie; Frankenhuyzen, Kees van; Krell, Peter J

2012-09-15

The emerald ash borer (EAB), Agrilus planipennis (Coleoptera: Buprestidae), is an invasive wood boring beetle that is decimating North America's ash trees (Fraxinus spp.). To find effective and safe indigenous biocontrol agents to manage EAB, we conducted a survey in 2008-2009 of entomopathogenic fungi (EPF) infecting EAB in five outbreak sites in southwestern Ontario, Canada. A total of 78 Beauveria spp. isolates were retrieved from dead and mycosed EAB cadavers residing in the phloem tissues of dead ash barks, larval frass extracted from feeding galleries under the bark of dead trees. Molecular characterization using sequences of the ITS, 5' end of EF1-α and intergenic Bloc region fragments revealed that Beauveria bassiana and Beauveria pseudobassiana were commonly associated with EAB in the sampled sites. Based on phylogenetic analysis inferred from ITS sequences, 17 of these isolates clustered with B. bassiana, which further grouped into three different sub-clades. However, the combined EF1-α and Bloc sequences detected five genotypes among the three sub-clades. The remaining 61 isolates clustered with B. pseudobassiana, which had identical ITS sequences but were further subdivided into two genotypes by variation in the EF1-α and Bloc regions. Initial virulence screening against EAB adults of 23 isolates representing the different clades yielded 8 that produced more than 90% mortality in a single concentration assay. These isolates differed in virulence based on LC(50) values estimated from multiple concentration bioassay and based on mean survival times at a conidia concentration of 2×10(6) conidia/ml. B. bassiana isolate L49-1AA was significantly more virulent and produced more conidia on EAB cadavers compared to the other indigenous isolates and the commercial strain B. bassiana GHA suggesting that L49-1AA may have potential as a microbiological control agent against EAB. Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.

Inhibition, Updating Working Memory, and Shifting Predict Reading Disability Symptoms in a Hybrid Model: Project KIDS.

PubMed

Daucourt, Mia C; Schatschneider, Christopher; Connor, Carol M; Al Otaiba, Stephanie; Hart, Sara A

2018-01-01

Recent achievement research suggests that executive function (EF), a set of regulatory processes that control both thought and action necessary for goal-directed behavior, is related to typical and atypical reading performance. This project examines the relation of EF, as measured by its components, Inhibition, Updating Working Memory, and Shifting, with a hybrid model of reading disability (RD). Our sample included 420 children who participated in a broader intervention project when they were in KG-third grade (age M = 6.63 years, SD = 1.04 years, range = 4.79-10.40 years). At the time their EF was assessed, using a parent-report Behavior Rating Inventory of Executive Function (BRIEF), they had a mean age of 13.21 years ( SD = 1.54 years; range = 10.47-16.63 years). The hybrid model of RD was operationalized as a composite consisting of four symptoms, and set so that any child could have any one, any two, any three, any four, or none of the symptoms included in the hybrid model. The four symptoms include low word reading achievement, unexpected low word reading achievement, poorer reading comprehension compared to listening comprehension, and dual-discrepancy response-to-intervention, requiring both low achievement and low growth in word reading. The results of our multilevel ordinal logistic regression analyses showed a significant relation between all three components of EF (Inhibition, Updating Working Memory, and Shifting) and the hybrid model of RD, and that the strength of EF's predictive power for RD classification was the highest when RD was modeled as having at least one or more symptoms. Importantly, the chances of being classified as having RD increased as EF performance worsened and decreased as EF performance improved. The question of whether any one EF component would emerge as a superior predictor was also examined and results showed that Inhibition, Updating Working Memory, and Shifting were equally valuable as predictors of the hybrid model of RD. In total, all EF components were significant and equally effective predictors of RD when RD was operationalized using the hybrid model.

Aerobic Exercise Intervention Alters Executive Function and White Matter Integrity in Deaf Children: A Randomized Controlled Study

PubMed Central

Xiong, Xuan; Zhu, Li-Na; Dong, Xiao-xiao; Wang, Wei; Yan, Jun

2018-01-01

This study examined the effects of an 11-week aerobic exercise intervention on executive function (EF) and white matter integrity (WMI). In total, 28 deaf children (aged 9–13 years) were randomly assigned to either an 11-week exercise intervention or the control group. All the children had behavioral assessment and diffusion tensor imaging prior to and following the exercise intervention. The behavioral performance results demonstrated that EF was enhanced by exercise. Relative to the control group, WMI of the exercise intervention group showed (1) lower fractional anisotropy (FA) in the pontine crossing tract (PCT) and right cingulum (hippocampus) (CH), genu of the corpus callosum (gCC), right inferior cerebellar peduncle (ICP), left superior corona radiata (SCR), and left superior frontooccipital fasciculus (SFOF); (2) higher mean diffusivity (MD) in the gCC, right CH, right inferior frontooccipital fasciculus (IFOF), and left anterior limb of the internal capsule (ALIC); and (3) lower MD in the left ICP and left tapetum (TAP). Furthermore, the lower FA in gCC showed a significant negative correlation with improvement in behavioral performance, but the correlation was not significant after FDR correction. These results suggest that exercise can effectively improve deaf children's EF and reshape the WMI in deaf children. The improved EF by exercise is not related to a reshaping of WMI, but more studies on the relationship between EF and WMI by exercise may be needed. PMID:29853843

Dynamic versus isometric electromechanical delay in non-fatigued and fatigued muscle: A combined electromyographic, mechanomyographic, and force approach.

PubMed

Smith, Cory M; Housh, Terry J; Hill, Ethan C; Johnson, Glen O; Schmidt, Richard J

2017-04-01

This study used a combined electromyographic, mechanomyographic, and force approach to identify electromechanical delay (EMD) from the onsets of the electromyographic to force signals (EMD E-F ), onsets of the electromyographic to mechanomyogrpahic signals (EMD E-M ), and onsets of mechanomyographic to force signals (EMD M-F ). The purposes of the current study were to examine: (1) the differences in EMD E-F , EMD E-M , and EMD M-F from the vastus lateralis during maximal, voluntary dynamic (1 repetition maximum [1-RM]) and isometric (maximal voluntary isometric contraction [MVIC]) muscle actions; and (2) the effects of fatigue on EMD E-F , EMD M-F , and EMD E-M . Ten men performed pretest and posttest 1-RM and MVIC leg extension muscle actions. The fatiguing workbout consisted of 70% 1-RM dynamic constant external resistance leg extension muscle actions to failure. The results indicated that there were no significant differences between 1-RM and MVIC EMD E-F , EMD E-M , or EMD M-F. There were, however, significant fatigue-induced increases in EMD E-F (94% and 63%), EMD E-M (107%), and EMD M-F (63%) for both the 1-RM and MVIC measurements. Therefore, these findings demonstrated the effects of fatigue on EMD measures and supported comparisons among studies which examined dynamic or isometric EMD measures from the vastus lateralis using a combined electromyographic, mechanomyographic, and force approach. Copyright © 2017 Elsevier Ltd. All rights reserved.

Advancing understanding of executive function impairments and psychopathology: bridging the gap between clinical and cognitive approaches

PubMed Central

Snyder, Hannah R.; Miyake, Akira; Hankin, Benjamin L.

2015-01-01

Executive function (EF) is essential for successfully navigating nearly all of our daily activities. Of critical importance for clinical psychological science, EF impairments are associated with most forms of psychopathology. However, despite the proliferation of research on EF in clinical populations, with notable exceptions clinical and cognitive approaches to EF have remained largely independent, leading to failures to apply theoretical and methodological advances in one field to the other field and hindering progress. First, we review the current state of knowledge of EF impairments associated with psychopathology and limitations to the previous research in light of recent advances in understanding and measuring EF. Next, we offer concrete suggestions for improving EF assessment. Last, we suggest future directions, including integrating modern models of EF with state of the art, hierarchical models of dimensional psychopathology as well as translational implications of EF-informed research on clinical science. PMID:25859234

Culture-specific links between maternal executive function, parenting, and preschool children's executive function in South Korea.

PubMed

Lee, Min Kyung; Baker, Sara; Whitebread, David

2018-06-01

Research on the relationships between parental factors and children's executive function (EF) has been conducted mainly in Western cultures. This study provides the first empirical test, in a non-Western context, of how maternal EF and parenting behaviours relate to child EF. South Korean mothers and their preschool children (N = 95 dyads) completed EF tasks. Two aspects of parental scaffolding were observed during a puzzle task: contingency (i.e., adjusting among levels of scaffolding according to the child's ongoing evidence of understanding) and intrusiveness (i.e., directive, mother-centred interactions). Maternal EF and maternal contingency each accounted for unique variance in child EF, above and beyond child age, child language and maternal education. Maternal intrusiveness, however, was not significantly related to child EF. Additionally, no mediating role of parenting was found in the maternal and child EF link. However, child language was found to partially mediate the link between maternal contingency and child EF. These results complement prior findings by revealing distinctive patterns in the link between maternal EF, parenting behaviours, and child EF in the Korean context. © 2018 The British Psychological Society.

Frontal Assessment Battery (FAB) is a simple tool for detecting executive deficits in chronic cannabis users.

PubMed

Fontes, Maria Alice; Bolla, Karen I; Cunha, Paulo Jannuzzi; Almeida, Priscila Previato; Jungerman, Flávia; Laranjeira, Ronaldo Ramos; Bressan, Rodrigo A; Lacerda, Acioly L T

2011-06-01

Cannabis is the most used illicit drug in the world, and its use has been associated with prefrontal cortex (PFC) dysfunction, including deficits in executive functions (EF). Considering that EF may influence treatment outcome, it would be interesting to have a brief neuropsychological battery to assess EF in chronic cannabis users (CCU). In the present study, the Frontal Assessment Battery (FAB), a brief, easy to use neuropsychological instrument aimed to evaluate EF, was used to evaluate cognitive functioning of CCU. We evaluated 107 abstinent CCU with the FAB and compared with 44 controls matched for age, estimated IQ, and years of education. CCU performed poorly as compared to controls (FAB total score = 16.53 vs. 17.09, p < .05). CCU had also a poor performance in the Motor Programming subtest (2.47 vs. 2.73, p < .05). This study examined effects of cannabis in executive functioning and showed evidence that the FAB is sensitive to detect EF deficits in early abstinent chronic cannabis users. Clinical significance of these findings remains to be investigated in further longitudinal studies. FAB may be useful as a screening instrument to evaluate the necessity for a complete neuropsychological assessment in this population.

The Effect of Executive Function on Science Achievement among Normally Developing 10-Year Olds

ERIC Educational Resources Information Center

Lederman, Sheri G.

2012-01-01

Executive function (EF) is an umbrella term used to identify a set of discrete but interrelated cognitive abilities that enable individuals to engage in goal-directed, future-oriented action in response to a novel context. Developmental studies indicate that EF is predictive of reading and math achievement in middle childhood. The purpose of this…

Executive Functioning and Prospective Memory in Young Children

ERIC Educational Resources Information Center

Mahy, Caitlin E. V.; Moses, Louis J.

2011-01-01

The current study examined the role of executive functioning (EF) in children's prospective memory (PM) by assessing the effect of delay and number of intentions to-be-remembered on PM, as well as relations between PM and EF. Ninety-six 4-, 5-, and 6-year-olds completed a PM task and two executive function tasks. The PM task required children to…

Working Memory and Cognitive Flexibility-Training for Children with an Autism Spectrum Disorder: A Randomized Controlled Trial

ERIC Educational Resources Information Center

de Vries, Marieke; Prins, Pier J. M.; Schmand, Ben A.; Geurts, Hilde M.

2015-01-01

Background: People with autism spectrum disorders (ASDs) experience executive function (EF) deficits. There is an urgent need for effective interventions, but in spite of the increasing research focus on computerized cognitive training, this has not been studied in ASD. Hence, we investigated two EF training conditions in children with ASD.…

Effects of Fenton treatment on the properties of effluent organic matter and their relationships with the degradation of pharmaceuticals and personal care products.

PubMed

Li, Wei; Nanaboina, Venkateswarlu; Zhou, Qixing; Korshin, Gregory V

2012-02-01

This study examined effects of Fenton oxidation on trace level pharmaceuticals and personal care products (PPCPs) commonly occurring in wastewater. The tested PPCPs included acetaminophen, atenolol, atrazine, carbamazepine, metoprolol, dilantin, DEET, diclofenac, pentoxifylline, oxybenzone, caffeine, fluoxetine, gemfibrozil, ibuprofen, iopromide, naproxen, propranolol, sulfamethoxazole, bisphenol-A and trimethoprim. Transformations of effluent organic matter (EfOM) caused by Fenton oxidation were also quantified. All tested PPCPs, except atrazine and iopromide, were completely removed by Fenton treatment carried out using a 20mg/L Fe (II) concentration and a 2.5 H(2)O(2)/Fe (II) molar ratio. Up to 30% on the total carbon concentration was removed during Fenton treatment which was accompanied by the oxidation of EfOM molecules and formation of oxidation products such as oxalic, formic and acetic acids and, less prominently, formaldehyde, acetaldehyde, propionaldehyde and glycolaldehyde. The absorbance of EfOM treated with Fenton reagent at varying Fe (II) concentration and contact time underwent a consistent decrease. The relative decrease of EfOM absorbance was strongly and unambiguously correlated with the removal of all tested PPCPs. Copyright © 2011 Elsevier Ltd. All rights reserved.

Is xenodontine snake reproduction shaped by ancestry, more than by ecology?

PubMed

Bellini, Gisela P; Arzamendia, Vanesa; Giraudo, Alejandro R

2017-01-01

One of the current challenges of evolutionary ecology is to understand the effects of phylogenetic history (PH) and/or ecological factors (EF) on the life-history traits of the species. Here, the effects of environment and phylogeny are tested for the first time on the reproductive biology of South American xenodontine snakes. We studied 60% of the tribes of this endemic and most representative clade in a temperate region of South America. A comparative method (canonical phylogenetic ordination-CPO) was used to find the relative contributions of EF and PH upon life-history aspects of snakes, comparing the reproductive mode, mean fecundity, reproductive potential, and frequency of nearly 1,000 specimens. CPO analysis showed that PH or ancestry explained most of the variation in reproduction, whereas EF explained little of this variation. The reproductive traits under study are suggested to have a strong phylogenetic signal in this clade, the ancestry playing a big role in reproduction. The EF also influenced the reproduction of South American xenodontines, although to a lesser extent. Our finding provides new evidence of how the evolutionary history is embodied in the traits of living species.

Rationale and design of the PREFERS (Preserved and Reduced Ejection Fraction Epidemiological Regional Study) Stockholm heart failure study: an epidemiological regional study in Stockholm county of 2.1 million inhabitants.

PubMed

Linde, Cecilia; Eriksson, Maria J; Hage, Camilla; Wallén, Håkan; Persson, Bengt; Corbascio, Matthias; Lundeberg, Joakim; Maret, Eva; Ugander, Martin; Persson, Hans

2016-10-01

Heart failure (HF) with preserved (HFpEF) or reduced (HFrEF) ejection fraction is associated with poor prognosis and quality of life. While the incidence of HFrEF is declining and HF treatment is effective, HFpEF is increasing, with no established therapy. PREFERS Stockholm is an epidemiological study with the aim of improving clinical care and research in HF and to find new targets for drug treatment in HFpEF (https://internwebben.ki.se/sites/default/files/20150605_4d_research_appendix_final.pdf). Patients with new-onset HF (n = 2000) will be characterized at baseline and after 1-year follow-up by standardized protocols for clinical evaluation, echocardiography, and ECG. In one subset undergoing elective coronary bypass surgery (n = 100) and classified according to LV function, myocardial biopsies will be collected during surgery, and cardiac magnetic resonance (CMR) imaging will be performed at baseline and after 1 year. Blood and tissue samples will be stored in a biobank. We will characterize and compare new-onset HFpEF and HFrEF patients regarding clinical findings and cardiac imaging, genomics, proteomics, and transcriptomics from blood and cardiac biopsies, and by established biomarkers of fibrosis, inflammation, haemodynamics, haemostasis, and thrombosis. The data will be explored by state-of-the-art bioinformatics methods to investigate gene expression patterns, sequence variation, DNA methylation, and post-translational modifications, and using systems biology approaches including pathway and network analysis. In this epidemiological HF study with biopsy studies in a subset of patients, we aim to identify new biomarkers of disease progression and to find pathophysiological mechanisms to support explorations of new treatment regimens for HFpEF. © 2016 The Authors. European Journal of Heart Failure © 2016 European Society of Cardiology.

Redox Conditions and Related Color Change in Eastern Equatorial Pacific Sediments: IODP Site U1334

NASA Astrophysics Data System (ADS)

Kordesch, W. E.; Gussone, N. C.; Hathorne, E. C.; Kimoto, K.; Delaney, M. L.

2011-12-01

This study was prompted by a 65 m thick brown-green color change in deep-sea sediments of IODP Site U1334 (0-38 Ma, 4799 m water depth) that corresponds to its equatorial crossing (caused by the Northward movement of the pacific plate). Green sediment is a visual indicator of reducing conditions in sediment due to enhanced organic matter deposition and burial. Here we use geochemical redox indicators to characterize the effect of equatorial upwelling on bottom water. The modern redox signal is captured in porewater profiles (nitrate, manganese, iron, sulfate) while trace metal Enrichment Factors (EF) in bulk sediment (manganese, uranium, molybdenum, rhenium) normalized to the detrital component (titanium) record redox state at burial. To measure export productivity we also measure biogenic barium. Porewater profiles reveal suboxic diagenesis; profiles follow the expected sequence of nitrate, manganese oxide, and iron oxide reduction with increasing depth. Constant sulfate (~28 μM) implies anoxia has not occurred. Bulk sediment Mn EF are enriched (EF > 1) throughout the record (Mn EF = 15-200) while U and Mo enrichment corresponds to green color and equatorial proximity (U EF = 4-19; Mo EF = 0-7). Constant Mn enrichment implies continuous oxygenation. Uranium and Mo enrichment near the equator represents suboxic conditions also seen in the porewater. Low Re concentrations (below detection) provide additional evidence against anoxia. A comparison of Mn EF from total digestions to samples treated with an additional reductive cleaning step distinguishes between Mn-oxides and Mn-carbonates, indicating oxygenated and reducing conditions respectively. Mn-carbonate occurrence agrees with U and Mo EF; conditions were more reducing near the equator. Bio-Ba shows significant variability over this interval (22-99 mmol g-1). Our geochemical results indicate that bottom waters became suboxic at the equator as a result of equatorial upwelling-influenced increases in organic matter sedimentation. Comparison of results to Site U1335 (0-26 Ma, 4327 m water depth) will test the relative importance of equatorial proximity.

Cost Recommendation under Uncertainty in IQWiG's Efficiency Frontier Framework.

PubMed

Corro Ramos, Isaac; Lhachimi, Stefan K; Gerber-Grote, Andreas; Al, Maiwenn J

2017-02-01

The National Institute for Quality and Efficiency in Health Care (IQWiG) employs an efficiency frontier (EF) framework to facilitate setting maximum reimbursable prices for new interventions. Probabilistic sensitivity analysis (PSA) is used when yes/no reimbursement decisions are sought based on a fixed threshold. In the IQWiG framework, an additional layer of complexity arises as the EF itself may vary its shape in each PSA iteration, and thus the willingness-to-pay, indicated by the EF segments, may vary. To explore the practical problems arising when, within the EF approach, maximum reimbursable prices for new interventions are sought through PSA. When the EF is varied in a PSA, cost recommendations for new interventions may be determined by the mean or the median of the distances between each intervention's point estimate and each EF. Implications of using these metrics were explored in a simulation study based on the model used by IQWiG to assess the cost-effectiveness of 4 antidepressants. Depending on the metric used, cost recommendations can be contradictory. Recommendations based on the mean can also be inconsistent. Results (median) suggested that costs of duloxetine, venlafaxine, mirtazapine, and bupropion should be decreased by €131, €29, €12, and €99, respectively. These recommendations were implemented and the analysis repeated. New results suggested keeping the costs as they were. The percentage of acceptable PSA outcomes increased 41% on average, and the uncertainty associated to the net health benefit was significantly reduced. The median of the distances between every intervention outcome and every EF is a good proxy for the cost recommendation that would be given should the EF be fixed. Adjusting costs according to the median increased the probability of acceptance and reduced the uncertainty around the net health benefit distribution, resulting in a reduced uncertainty for decision makers.

Tetrodotoxin-insensitive electrical field stimulation-induced contractions on Crotalus durissus terrificus corpus cavernosum.

PubMed

Campos, Rafael; Mónica, Fabíola Z; Rodrigues, Renata Lopes; Rojas-Moscoso, Julio Alejandro; Moreno, Ronilson Agnaldo; Cogo, José Carlos; de Oliveira, Marco Antonio; Antunes, Edson; De Nucci, Gilberto

2017-01-01

Reptiles are the first amniotes to develop an intromitent penis, however until now the mechanisms involved in the electrical field stimulation-induced contraction on corpora cavernosa isolated from Crotalus durissus terrificus were not investigated. Crotalus and rabbit corpora cavernosa were mounted in 10 mL organ baths for isometric tension recording. Electrical field stimulation (EFS)-induced contractions were performed in presence/absence of phentolamine (10 μM), guanethidine (30 μM), tetrodotoxin (1 μM and 1mM), A-803467 (10 μM), 3-iodo-L-Tyrosine (1 mM), salsolinol (3 μM) and a modified Krebs solution (equimolar substitution of NaCl by N-methyl-D-glucamine). Immuno-histochemistry for tyrosine hydroxylase was also performed. Electrical field stimulation (EFS; 8 Hz and 16 Hz) caused contractions in both Crotalus and rabbit corpora cavernosa. The contractions were abolished by previous incubation with either phentolamine or guanethidine. Tetrodotoxin (1 μM) also abolished the EFS-induced contractions of rabbit CC, but did not affect EFS-induced contractions of Crotalus CC. Addition of A-803467 (10 μM) did not change the EFS-induced contractions of Crotalus CC but abolished rabbit CC contractions. 3-iodo-L-Tyrosine and salsolinol had no effect on EFS-induced contractions of Crotalus CC and Rabbit CC. Replacement of NaCl by N- Methyl-D-glucamine (NMDG) abolished EFS-induced contractions of rabbit CC, but did not affect Crotalus CC. The presence of tyrosine hydroxylase was identified in endothelial cells only of Crotalus CC. Since the EFS-induced contractions of Crotalus CC is dependent on catecholamine release, insensitive to TTX, insensitive to A803467 and to NaCl replacement, it indicates that the source of cathecolamine is unlikely to be from adrenergic terminals. The finding that tyrosine hydroxylase is present in endothelial cells suggests that these cells can modulate Crotalus CC tone.

A modeling approach to establish environmental flow threshold in ungauged semidiurnal tidal river

NASA Astrophysics Data System (ADS)

Akter, A.; Tanim, A. H.

2018-03-01

Due to shortage of flow monitoring data in ungauged semidiurnal river, 'environmental flow' (EF) determination based on its key component 'minimum low flow' is always difficult. For EF assessment this study selected a reach immediately after the Halda-Karnafuli confluence, a unique breeding ground for Indian Carp fishes of Bangladesh. As part of an ungauged tidal river, EF threshold establishment faces challenges in changing ecological paradigms with periodic change of tides and hydrologic alterations. This study describes a novel approach through modeling framework comprising hydrological, hydrodynamic and habitat simulation model. The EF establishment was conceptualized according to the hydrologic process of an ungauged semi-diurnal tidal regime in four steps. Initially, a hydrologic model coupled with a hydrodynamic model to simulate flow considering land use changes effect on streamflow, seepage loss of channel, friction dominated tidal decay as well as lack of long term flow characteristics. Secondly, to define hydraulic habitat feature, a statistical analysis on derived flow data was performed to identify 'habitat suitability'. Thirdly, to observe the ecological habitat behavior based on the identified hydrologic alteration, hydraulic habitat features were investigated. Finally, based on the combined habitat suitability index flow alteration and ecological response relationship was established. Then, the obtained EF provides a set of low flow indices of desired regime and thus the obtained discharge against maximum Weighted Usable Area (WUA) was defined as EF threshold for the selected reach. A suitable EF regime condition was obtained within flow range 25-30.1 m3/s i.e., around 10-12% of the mean annual runoff of 245 m3/s and these findings are within researchers' recommendation of minimum flow requirement. Additionally it was observed that tidal characteristics are dominant process in semi-diurnal regime. However, during the study period (2010-2015) the validated model with those reported observations can provide guidance for the decision support system (DSS) to maintain EF range in an ungauged tidal river.

Degradation of tyrosol by a novel electro-Fenton process using pyrite as heterogeneous source of iron catalyst.

PubMed

Ammar, Salah; Oturan, Mehmet A; Labiadh, Lazhar; Guersalli, Amor; Abdelhedi, Ridha; Oturan, Nihal; Brillas, Enric

2015-05-01

Tyrosol (TY) is one of the most abundant phenolic components of olive oil mill wastewaters. Here, the degradation of synthetic aqueous solutions of 0.30 mM TY was studied by a novel heterogeneous electro-Fenton (EF) process, so-called EF-pyrite, in which pyrite powder was the source of Fe(2+) catalyst instead of a soluble iron salt used in classical EF. Experiments were performed with a cell equipped with a boron-doped diamond anode and a carbon-felt cathode, where TY and its products were destroyed by hydroxyl radicals formed at the anode surface from water oxidation and in the bulk from Fenton's reaction between Fe(2+) and H2O2 generated at the cathode. Addition of 1.0 g L(-1) pyrite provided an easily adjustable pH to 3.0 and an appropriate 0.20 mM Fe(2+) to optimize the EF-pyrite treatment. The effect of current on mineralization rate, mineralization current efficiency and specific energy consumption was examined under comparable EF and EF-pyrite conditions. The performance of EF-pyrite was 8.6% superior at 50 mA due to self-regulation of soluble Fe(2+) by pyrite. The TY decay in this process followed a pseudo-first-order kinetics. The absolute rate constant for TY hydroxylation was 3.57 × 10(9) M(-1) s(-1), as determined by the competition kinetics method. Aromatic products like 3,4-dihydroxyphenylethanol, 4-hydroxyphenylacetic acid, 4-hydroxybenzoic acid, 3,4-dihydroxybenzoic acid and catechol, as well as o-benzoquinone, were identified by GC-MS and reversed-phase HPLC. Short-chain aliphatic carboxylic acids like maleic, glycolic, acetic, oxalic and formic were quantified by ion-exclusion HPLC. Oxalic acid was the major and most persistent product found. Based on detected intermediates, a plausible mineralization pathway for TY by EF-pyrite was proposed. Copyright © 2015 Elsevier Ltd. All rights reserved.

Non-adrenergic, non-cholinergic neural activation in guinea-pig bronchi: powerful and frequency-dependent stabilizing effect on tone.

PubMed Central

Lindén, A.; Ullman, A.; Löfdahl, C. G.; Skoogh, B. E.

1993-01-01

1. We examined non-adrenergic, non-cholinergic (NANC) stimulation for its stabilizing effect on bronchial smooth-muscle tone with respect to its regulatory power and the effect of variations in neural impulse frequency. 2. The guinea-pig isolated main bronchus (n = 4-12) was pretreated with indomethacin (10 microM) and incubated with atropine (1 microM) and guanethidine (10 microM). Electrical field stimulation (EFS: 1200 mA, 0.5 ms, 240 s) was applied at various levels of tone prior to EFS: first without tone, then at a moderate tone induced by histamine (0.3 microM) and, finally, at a high tone induced by histamine (6 microM). Three different stimulation frequencies (1, 3 or 10 Hz) were used in order to produce moderate to near-maximum contractile and relaxant NANC neural responses. Both the contractile and the relaxant NANC responses were tetrodotoxin-sensitive in the guinea-pig isolated main bronchus (3 Hz). 3. Without tone prior to EFS, NANC activation (1, 3 or 10 Hz) induced a pronounced contractile response. At a moderate level of tone prior to EFS, NANC activation induced a less pronounced contractile response. At the highest level of tone prior to EFS, NANC activation induced a relaxant response. All these NANC responses adjusted the tone towards a similar level and this 'stabilization level' was 56(6)% at 1 Hz, 65(3)% at 3 Hz and 56(5)% at 10 Hz, expressed as a percentage of the maximum histamine-induced (0.1 mM) tone in each airway preparation. 4. There was a difference of approximately 90% of maximum between the highest and the lowest tone level prior to NANC activation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8358575

A pentapeptide monocyte locomotion inhibitory factor protects brain ischemia injury by targeting the eEF1A1/endothelial nitric oxide synthase pathway.

PubMed

Zhang, Yuefan; Chen, Jun; Li, Fan; Li, Dong; Xiong, Qinhui; Lin, Yang; Zhang, Dazhi; Wang, Xiao-Fan; Yang, Pengyuan; Rui, Yao-Cheng

2012-10-01

Ischemic stroke is a major cause of death worldwide but lacks viable treatment or treatment targets. Monocyte locomotion inhibitory factor (MLIF) is a small heat-stable pentapeptide produced by Entamoeba histolytica in axenic culture, which is supposed to protect the brain from ischemic injury; the mechanism, however, remains unknown. In this study, we further investigated the mechanism underlying the protective role of MLIF in brain ischemia. A middle cerebral artery occlusion model in rats was used for detecting the effect of MLIF in the brain ischemia in vivo. To identify targets of MLIF in brain endothelial cells, we performed immunoprecipitation of biotin-conjugated MLIF and mass spectrometry. MLIF can protect the brain from ischemic injury in vivo, yielding decreased ischemic volume, prolonged survival, and improved neurological outcome. In vitro studies showed that MLIF displayed protective effects through inhibition of expression of pathological inflammatory adhesion molecules and enhancing endothelial nitric oxide synthase expression and nitric oxide release in the cerebrovascular endothelium. The target screening experiments demonstrated binding of MLIF to the ribosomal protein translation elongation factor eEF1A1. MLIF enhanced endothelial nitric oxide synthase expression through stabilization of endothelial nitric oxide synthase mRNA, and eEF1A1 was shown to be necessary for this enhanced expression. Knockdown of eEF1A1 or inhibition of endothelial nitric oxide synthase attenuated MLIF-mediated inhibition of adhesion molecule expression. In this study, we identified a new potential pharmacologically targetable mechanism underlying MLIF's protective effects in brain ischemia through the eEF1A1/endothelial nitric oxide synthase pathway.

Nerve growth factor-enhanced airway responsiveness involves substance P in ferret intrinsic airway neurons.

PubMed

Wu, Z-X; Dey, R D

2006-07-01

Nerve growth factor (NGF), a member of the neurotrophin family, enhances synthesis of neuropeptides in sensory and sympathetic neurons. The aim of this study was to examine the effect of NGF on airway responsiveness and determine whether these effects are mediated through synthesis and release of substance P (SP) from the intrinsic airway neurons. Ferrets were instilled intratracheally with NGF or saline. Tracheal smooth muscle contractility to methacholine and electrical field stimulation (EFS) was assessed in vitro. Contractions of isolated tracheal smooth muscle to EFS at 10 and 30 Hz were significantly increased in the NGF treatment group (10 Hz: 33.57 +/- 2.44%; 30 Hz: 40.12 +/- 2.78%) compared with the control group (10 Hz: 27.24 +/- 2.14%; 30 Hz: 33.33 +/- 2.31%). However, constrictive response to cholinergic agonist was not significantly altered between the NGF treatment group and the control group. The NGF-induced modulation of airway smooth muscle to EFS was maintained in tracheal segments cultured for 24 h, a procedure that causes a significant anatomic and functional loss of SP-containing sensory fibers while maintaining viability of intrinsic airway neurons. The number of SP-containing neurons in longitudinal trunk and superficial muscular plexus and SP nerve fiber density in tracheal smooth muscle all increased significantly in cultured trachea treated with NGF. Pretreatment with CP-99994, an antagonist of neurokinin 1 receptor, attenuated the NGF-induced increased contraction to EFS in cultured segments but had no effect in saline controls. These results show that the NGF-enhanced airway smooth muscle contractile responses to EFS are mediated by the actions of SP released from intrinsic airway neurons.

The moderating effect of ANKK1 on the association of family environment with longitudinal executive function following traumatic brain injury in early childhood: A preliminary study.

PubMed

Smith-Paine, Julia; Wade, Shari L; Treble-Barna, Amery; Zhang, Nanhua; Zang, Huaiyu; Martin, Lisa J; Yeates, Keith Owen; Taylor, H Gerry; Kurowski, Brad G

2018-05-02

This study examined whether the ankyrin repeat and kinase domain containing 1 gene (ANKK1) C/T single-nucleotide polymorphism (SNP) rs1800497 moderated the association of family environment with long-term executive function (EF) following traumatic injury in early childhood. Caregivers of children with traumatic brain injury (TBI) and children with orthopedic injury (OI) completed the Behavior Rating Inventory of Executive Function (BRIEF) at post injury visits. DNA was collected to identify the rs1800497 genotype in the ANKK1 gene. General linear models examined gene-environment interactions as moderators of the effects of TBI on EF at two times post injury (12 months and 7 years). At 12 months post injury, analyses revealed a significant 3-way interaction of genotype with level of permissive parenting and injury type. Post-hoc analyses showed genetic effects were more pronounced for children with TBI from more positive family environments, such that children with TBI who were carriers of the risk allele (T-allele) had significantly poorer EF compared to non-carriers only when they were from more advantaged environments. At 7 years post injury, analyses revealed a significant 2-way interaction of genotype with level of authoritarian parenting. Post-hoc analyses found that carriers of the risk allele had significantly poorer EF compared to non-carriers only when they were from more advantaged environments. These results suggest a gene-environment interaction involving the ANKK1 gene as a predictor of EF in a pediatric injury population. The findings highlight the importance of considering environmental influences in future genetic studies on recovery following TBI and other traumatic injuries in childhood.

Effects of inorganic nitrate and beetroot supplementation on endothelial function: a systematic review and meta-analysis.

PubMed

Lara, Jose; Ashor, Ammar W; Oggioni, C; Ahluwalia, A; Mathers, John C; Siervo, Mario

2016-03-01

Diets rich in inorganic nitrate are associated with lower blood pressure, an effect that may be mediated by an improvement of endothelial function (EF). Therefore, a systematic review and meta-analysis of randomised controlled trials (RCTs) were conducted to examine the effects of inorganic nitrate and beetroot supplementation on measures of EF. MEDLINE, EMBASE and Scopus databases were searched from inception until November 2014. Specific inclusion criteria were as follows: (1) RCTs; (2) trials comparing inorganic nitrate or beetroot supplementation with placebo control groups; and (3) trials reporting effects of these interventions on outcomes of vascular function. Random-effect models were used to assess the pooled effect sizes showed as standardised mean differences (SMD). Nine crossover trials and three parallel trials met our inclusion criteria. The trials were conducted between 2008 and 2014 and included a total of 246 participants with 10-64 participants per study. The duration of each intervention ranged from 1.5 h to 28 days. Inorganic nitrate and beetroot consumption was associated with an improvement in vascular function (SMD 0.36; 95 % CI 0.16, 0.56; P < 0.001). The effect on EF was significantly associated with the dose of inorganic nitrate (β = 0.04, SE = 0.01, P < 0.001), age (β = -0.01, SE = 0.004, P = 0.02), baseline BMI (β = -0.04, SE = 0.02, P = 0.05) and systolic BP (β = -0.01, SE = 0.005, P = 0.02). Inorganic nitrate and beetroot supplementation was associated with beneficial effects on EF. These effects appear to be reduced in older subjects and in subjects with greater cardiometabolic risk.

Combination of alcohol and fructose exacerbates metabolic imbalance in terms of hepatic damage, dyslipidemia, and insulin resistance in rats.

PubMed

Alwahsh, Salamah Mohammad; Xu, Min; Schultze, Frank Christian; Wilting, Jörg; Mihm, Sabine; Raddatz, Dirk; Ramadori, Giuliano

2014-01-01

Although both alcohol and fructose are particularly steatogenic, their long-term effect in the development of a metabolic syndrome has not been studied in vivo. Consumption of fructose generally leads to obesity, whereas ethanol can induce liver damage in the absence of overweight. Here, Sprague-Dawley rats were fed ad libitum for 28 days on five diets: chow (control), liquid Lieber-DeCarli (LDC) diet, LDC +30%J of ethanol (L-Et) or fructose (L-Fr), and LDC combined with 30%J ethanol and 30%J fructose (L-EF). Body weight (BW) and liver weight (LW) were measured. Blood and liver samples were harvested and subjected to biochemical tests, histopathological examinations, and RT-PCR. Alcohol-containing diets substantially reduced the food intake and BW (≤3rd week), whereas fructose-fed animals had higher LW than controls (P<0.05). Additionally, leukocytes, plasma AST and leptin levels were the highest in the fructose-administered rats. Compared to the chow and LDC diets, the L-EF diet significantly elevated blood glucose, insulin, and total-cholesterol levels (also vs. the L-Et group). The albumin and Quick-test levels were the lowest, whereas ALT activity was the highest in the L-EF group. Moreover, the L-EF diet aggravated plasma triglyceride and reduced HDL-cholesterol levels more than 2.7-fold compared to the sum of the effects of the L-Et and L-Fr diets. The decreased hepatic insulin clearance in the L-EF group vs. control and LDC groups was reflected by a significantly decreased C-peptide:insulin ratio. All diets except the control caused hepatosteatosis, as evidenced by Nile red and H&E staining. Hepatic transcription of insulin receptor substrate-1/2 was mainly suppressed by the L-Fr and L-EF diets. The L-EF diet did not enhance the mitochondrial β-oxidation of fatty acids (Cpt1α and Ppar-α expressions) compared to the L-Et or L-Fr diet. Together, our data provide evidence for the coaction of ethanol and fructose with a high-fat-diet on dyslipidemia and insulin resistance-accompanied liver damage.

Structural rationale for the cross-resistance of tumor cells bearing the A399V variant of elongation factor eEF1A1 to the structurally unrelated didemnin B, ternatin, nannocystin A and ansatrienin B

NASA Astrophysics Data System (ADS)

Sánchez-Murcia, Pedro A.; Cortés-Cabrera, Álvaro; Gago, Federico

2017-10-01

At least four classes of structurally distinct natural products with potent antiproliferative activities target the translation elongation factor eEF1A1, which is best known as the G-protein that delivers amino acyl transfer RNAs (aa-tRNAs) to ribosomes during mRNA translation. We present molecular models in atomic detail that provide a common structural basis for the high-affinity binding of didemnin B, ternatin, ansatrienin B and nannocystin A to eEF1A1, as well as a rationale based on molecular dynamics results that accounts for the deleterious effect of replacing alanine 399 with valine. The proposed binding site, at the interface between domains I and III, is eminently hydrophobic and exists only in the GTP-bound conformation. Drug binding at this site is expected to disrupt neither loading of aa-tRNAs nor GTP hydrolysis but would give rise to stabilization of this particular conformational state, in consonance with reported experimental findings. The experimental solution of the three-dimensional structure of mammalian eEF1A1 has proved elusive so far and the highly homologous eEF1A2 from rabbit muscle has been crystallized and solved only as a homodimer in a GDP-bound conformation. Interestingly, in this dimeric structure the large interdomain cavity where the drugs studied are proposed to bind is occupied by a mostly hydrophobic α-helix from domain I of the same monomer. Since binding of this α-helix and any of these drugs to domain III of eEF1A(1/2) is, therefore, mutually exclusive and involves two distinct protein conformations, one intriguing possibility that emerges from our study is that the potent antiproliferative effect of these natural products may arise not only from inhibition of protein synthesis, which is the current dogma, but also from interference with some other non-canonical functions. From this standpoint, this type of drugs could be considered antagonists of eEF1A1/2 oligomerization, a hypothesis that opens up novel areas of research.

A Randomized Trial of Hemodiafiltration and Change in Cardiovascular Parameters

PubMed Central

Bots, Michiel L.; van den Dorpel, Marinus A.; Grooteman, Muriel P.C.; Kamp, Otto; Levesque, Renée; ter Wee, Piet M.; Nubé, Menso J.; Blankestijn, Peter J.

2014-01-01

Background and objective Increased left ventricular mass (LVM), low ventricular ejection fraction (EF), and high pulse-wave velocity (PWV) relate to overall and cardiovascular mortality in patients with ESRD. The aim of this study was to determine the effect of online hemodiafiltration (HDF) versus low-flux hemodialysis (HD) on LVM, EF, and PWV. Design, setting, participants, & measurements Echocardiography was used to assess LVM and EF in 342 patients in the CONvective TRAnsport STudy followed for up to 4 years. PWV was measured in 189 patients for up to 3 years. Effect of HDF versus HD on LVM, EF, and PWV was evaluated using linear mixed models. Results Patients had a mean age of 63 years, and 61% were male. At baseline, median LVM was 227 g (interquartile range [IQR], 183–279 g), and median EF was 65% (IQR, 55%–72%). Median PWV was 9.8 m/s (IQR, 7.5–12.0 m/s). There was no significant difference between the HDF and HD treatment groups in rate of change in LVM (HDF: change, −0.9 g/yr [95% confidence interval (95% CI), −8.9 to 7.7 g]; HD: change, 12.5 g/yr [95% CI, −3.0 to 27.5 g]; P for difference=0.13), EF (HDF: change, −0.3%/yr [95% CI, −2.3% to 1.8%]; HD: change, −3.4%/yr [95% CI, −5.9% to −0.9%]; P=0.17), or PWV (HDF: change, −0.0 m/s per year [95% CI, −0.4 to 0.4 m/s); HD: change, 0.0 m/s per year [95% CI, −0.3 to 0.2 m/s]; P=0.89). No differences in rate of change between treatment groups were observed for subgroups of age, sex, residual kidney function, dialysis vintage, history of cardiovascular disease, diabetes, or convection volume. Conclusions Treatment with online HDF did not affect changes in LVM, EF, or PWV over time compared with HD. PMID:24408114

Elongation factor Ts directly facilitates the formation and disassembly of the Escherichia coli elongation factor Tu·GTP·aminoacyl-tRNA ternary complex.

PubMed

Burnett, Benjamin J; Altman, Roger B; Ferrao, Ryan; Alejo, Jose L; Kaur, Navdep; Kanji, Joshua; Blanchard, Scott C

2013-05-10

Aminoacyl-tRNA (aa-tRNA) enters the ribosome in a ternary complex with the G-protein elongation factor Tu (EF-Tu) and GTP. EF-Tu·GTP·aa-tRNA ternary complex formation and decay rates are accelerated in the presence of the nucleotide exchange factor elongation factor Ts (EF-Ts). EF-Ts directly facilitates the formation and disassociation of ternary complex. This system demonstrates a novel function of EF-Ts. Aminoacyl-tRNA enters the translating ribosome in a ternary complex with elongation factor Tu (EF-Tu) and GTP. Here, we describe bulk steady state and pre-steady state fluorescence methods that enabled us to quantitatively explore the kinetic features of Escherichia coli ternary complex formation and decay. The data obtained suggest that both processes are controlled by a nucleotide-dependent, rate-determining conformational change in EF-Tu. Unexpectedly, we found that this conformational change is accelerated by elongation factor Ts (EF-Ts), the guanosine nucleotide exchange factor for EF-Tu. Notably, EF-Ts attenuates the affinity of EF-Tu for GTP and destabilizes ternary complex in the presence of non-hydrolyzable GTP analogs. These results suggest that EF-Ts serves an unanticipated role in the cell of actively regulating the abundance and stability of ternary complex in a manner that contributes to rapid and faithful protein synthesis.

Molecular Mechanism for the Control of Eukaryotic Elongation Factor 2 Kinase by pH: Role in Cancer Cell Survival

PubMed Central

Xie, Jianling; Mikolajek, Halina; Pigott, Craig R.; Hooper, Kelly J.; Mellows, Toby; Moore, Claire E.; Mohammed, Hafeez; Werner, Jörn M.; Thomas, Gareth J.

2015-01-01

Acidification of the extracellular and/or intracellular environment is involved in many aspects of cell physiology and pathology. Eukaryotic elongation factor 2 kinase (eEF2K) is a Ca2+/calmodulin-dependent kinase that regulates translation elongation by phosphorylating and inhibiting eEF2. Here we show that extracellular acidosis elicits activation of eEF2K in vivo, leading to enhanced phosphorylation of eEF2. We identify five histidine residues in eEF2K that are crucial for the activation of eEF2K during acidosis. Three of them (H80, H87, and H94) are in its calmodulin-binding site, and their protonation appears to enhance the ability of calmodulin to activate eEF2K. The other two histidines (H227 and H230) lie in the catalytic domain of eEF2K. We also identify His108 in calmodulin as essential for activation of eEF2K. Acidification of cancer cell microenvironments is a hallmark of malignant solid tumors. Knocking down eEF2K in cancer cells attenuated the decrease in global protein synthesis when cells were cultured at acidic pH. Importantly, activation of eEF2K is linked to cancer cell survival under acidic conditions. Inhibition of eEF2K promotes cancer cell death under acidosis. PMID:25776553

Virtual multiple errands test (VMET): a virtual reality-based tool to detect early executive functions deficit in Parkinson’s disease

PubMed Central

Cipresso, Pietro; Albani, Giovanni; Serino, Silvia; Pedroli, Elisa; Pallavicini, Federica; Mauro, Alessandro; Riva, Giuseppe

2014-01-01

Introduction: Several recent studies have pointed out that early impairment of executive functions (EFs) in Parkinson’s Disease (PD) may be a crucial marker to detect patients at risk for developing dementia. The main objective of this study was to compare the performances of PD patients with mild cognitive impairment (PD-MCI) with PD patients with normal cognition (PD-NC) and a control group (CG) using a traditional assessment of EFs and the Virtual Multiple Errands Test (VMET), a virtual reality (VR)-based tool. In order to understand which subcomponents of EFs are early impaired, this experimental study aimed to investigate specifically which instrument best discriminates among these three groups. Materials and methods: The study included three groups of 15 individuals each (for a total of 45 participants): 15 PD-NC; 15 PD-MCI, and 15 cognitively healthy individuals (CG). To assess the global neuropsychological functioning and the EFs, several tests (including the Mini Mental State Examination (MMSE), Clock Drawing Test, and Tower of London test) were administered to the participants. The VMET was used for a more ecologically valid neuropsychological evaluation of EFs. Results: Findings revealed significant differences in the VMET scores between the PD-NC patients vs. the controls. In particular, patients made more errors in the tasks of the VMET, and showed a poorer ability to use effective strategies to complete the tasks. This VMET result seems to be more sensitive in the early detection of executive deficits because these two groups did not differ in the traditional assessment of EFs (neuropsychological battery). Conclusion: This study offers initial evidence that a more ecologically valid evaluation of EFs is more likely to lead to detection of subtle executive deficits. PMID:25538578

Impact of primary and secondary air supply intensity in stove on emissions of size-segregated particulate matter and carbonaceous aerosols from apple tree wood burning

NASA Astrophysics Data System (ADS)

Sun, Jian; Shen, Zhenxing; Zhang, Leiming; Zhang, Qian; Lei, Yali; Cao, Junji; Huang, Yu; Liu, Suixin; Zheng, Chunli; Xu, Hongmei; Liu, Hongxia; Pan, Hua; Liu, Pingping; Zhang, Renjian

2018-04-01

In order to assess emission factors (EF) more accurately from household biomass burning, a series of laboratory-controlled apple tree wood burning tests were conducted to measure the EFs of size-segregated particulate matter (PM) and carbonaceous aerosols. The controlled burning experiments were conducted with designed primary air (PA) and secondary air (SA) supply intensity. An optimum value of 7 m3·h- 1 was found for SA, resulting the highest modified combustion efficiency (92.4 ± 2.5%) as well as the lowest EFs of PM2.5 (0.13 ± 0.01 g·MJ- 1), OC (0.04 ± 0.03 g·MJ- 1) and EC (0.03 ± 0.01 g·MJ- 1). SA values of 7 and 10 m3·h- 1 resulted the lowest EFs for all the different PM sizes. In a test with PA of 6 m3·h- 1 and SA of 7 m3·h- 1, very low EFs were observed for OC1 (8.2%), OC2 (11.2%) and especially OP (Pyrolyzed OC) (0%, not detected), indicating nearly complete combustion under this air supply condition. Besides SA, higher PA was proved to have positive effects on PM and carbonaceous fraction emission reduction. For example, with a fixed SA of 1.5 m3·h- 1, EFs of PM2.5 decreased from 0.64 to 0.27 g·MJ- 1 when PA increased from 6 to 15 m3·h- 1 (P < 0.05). Similar reductions were also observed in EFs of OC, EC and size segregated PM.

Heart Failure With Preserved Ejection Fraction in Diabetes: Mechanisms and Management.

PubMed

Meagher, Patrick; Adam, Mohamed; Civitarese, Robert; Bugyei-Twum, Antoinette; Connelly, Kim A

2018-05-01

Diabetes mellitus (DM) is a major cause of heart failure in the Western world, either secondary to coronary artery disease or from a distinct entity known as "diabetic cardiomyopathy." Furthermore, heart failure with preserved ejection fraction (HFpEF) is emerging as a significant clinical problem for patients with DM. Current clinical data suggest that between 30% and 40% of patients with HFpEF suffer from DM. The typical structural phenotype of the HFpEF heart consists of endothelial dysfunction, increased interstitial and perivascular fibrosis, cardiomyocyte stiffness, and hypertrophy along with advanced glycation end products deposition. There is a myriad of mechanisms that result in the phenotypical HFpEF heart including impaired cardiac metabolism and substrate utilization, altered insulin signalling leading to protein kinase C activation, advanced glycated end products deposition, prosclerotic cytokine activation (eg, transforming growth factor-β activation), along with impaired nitric oxide production from the endothelium. Moreover, recent investigations have focused on the role of endothelial-myocyte interactions. Despite intense research, current therapeutic strategies have had little effect on improving morbidity and mortality in patients with DM and HFpEF. Possible explanations for this include a limited understanding of the role that direct cell-cell communication or indirect cell-cell paracrine signalling plays in the pathogenesis of DM and HFpEF. Additionally, integrins remain another important mediator of signals from the extracellular matrix to cells within the failing heart and might play a significant role in cell-cell cross-talk. In this review we discuss the characteristics and mechanisms of DM and HFpEF to stimulate potential future research for patients with this common, and morbid condition. Copyright © 2018 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Impact of Perinatally Acquired HIV Disease Upon Longitudinal Changes in Memory and Executive Functioning.

PubMed

Malee, Kathleen M; Chernoff, Miriam C; Sirois, Patricia A; Williams, Paige L; Garvie, Patricia A; Kammerer, Betsy L; Harris, Lynnette L; Nozyce, Molly L; Yildirim, Cenk; Nichols, Sharon L

2017-08-01

Little is known regarding effects of perinatally acquired HIV infection (PHIV) on longitudinal change in memory and executive functioning (EF) during adolescence despite the importance of these skills for independence in adulthood. PHIV (n = 144) and perinatally HIV-exposed uninfected youth (PHEU, n = 79), ages 12-17, completed standardized tests of memory and EF at baseline and 2 years later. Changes from baseline for each memory and EF outcome were compared between PHEU and PHIV youth with (PHIV/C, n = 39) and without (PHIV/non-C, n = 105) history of CDC class C (AIDS-defining) diagnoses. Among PHIV youth, associations of baseline and past disease severity with memory and EF performance at follow-up were evaluated using adjusted linear regression models. Participants were primarily black (79%); 16% were Hispanic; 55% were female. Mean memory and EF scores at follow-up generally fell in the low-average to average range. Pairwise comparison of adjusted mean change from baseline to follow-up revealed significantly greater change for PHIV/non-C compared with PHEU youth in only one verbal recognition task, with a difference in mean changes for PHIV/non-C versus PHEU of -0.99 (95% CI: -1.80 to -0.19; P = 0.02). Among youth with PHIV, better immunologic status at baseline was positively associated with follow-up measures of verbal recall and recognition and cognitive inhibition/flexibility. Past AIDS-defining diagnoses and higher peak viral load were associated with lower performance across multiple EF tasks at follow-up. Youth with PHIV demonstrated stable memory and EF during a 2-year period of adolescence, allowing cautious optimism regarding long-term outcomes.

Evolution of molecular weight and fluorescence of effluent organic matter (EfOM) during oxidation processes revealed by advanced spectrographic and chromatographic tools.

PubMed

Chen, Zhiqiang; Li, Mo; Wen, Qinxue; Ren, Nanqi

2017-11-01

Effluent organic matter (EfOM) is an emerging concern to receiving aquatic environment due to its refractory property. The degradation of EfOM in ozonation and other two advanced oxidation processes (AOPs), UV/H 2 O 2 and UV/persulfate (PS), was investigated in this study. Fluorescence spectra coupled with parallel factor analysis (PARAFAC) and two-dimensional correlation gel permeation chromatography (2D-GPC) were used to track the evolution of EfOM during each oxidation process. Results showed that the degradation of EfOM indicated by dissolved organic carbon (DOC), UV 254 and fluorescence components, fitted well with pseudo-first-order kinetic model during the oxidation processes. Ozonation showed higher degradation efficiency than AOPs, while UV/PS was more effective than UV/H 2 O 2 with equimolar oxidants dosage. Ozone and SO· 4 - were more reactive with terrestrial humic-like substances, while hydroxyl radical preferentially reacted with protein-like substances. Organic molecules with higher molecular weight (MW) were susceptible to ozone or radicals. Ozonation could transform higher MW (MW of 3510 and 575) organic matters into lower MW organic matters (MW of 294), while reductions of all the organics were observed in both AOPs. Due to the higher reaction rates between ozone and EfOM, ozonation maybe serve as a pre-treatment for AOPs to reduce the radical and energy consumption and improve mineralization of EfOM by AOPs. The decline in DOC, UV 254 , fluorescence and reduction in oxidants increased with the increase of oxidants dosage, and linear correlations among them were found during the ozonation and AOPs. Copyright © 2017. Published by Elsevier Ltd.

Association of COMT and PRODH gene variants with intelligence quotient (IQ) and executive functions in 22q11.2DS subjects.

PubMed

Carmel, Miri; Zarchi, Omer; Michaelovsky, Elena; Frisch, Amos; Patya, Miriam; Green, Tamar; Gothelf, Doron; Weizman, Abraham

2014-09-01

The 22q11.2 deletion syndrome (22q11.2DS) carries the highest genetic risk factor for the development of schizophrenia. We investigated the association of genetic variants in two schizophrenia candidate genes with executive function (EF) and IQ in 22q11.2DS individuals. Ninety two individuals with 22q11.2 deletion were studied for the genetic association between COMT and PRODH variants and EF and IQ. Subjects were divided into children (under 12 years old), adolescents (between 12 and 18 years old) and adults (older than 18 years), and genotyped for the COMT Val158Met (rs4680) and PRODH Arg185Trp (rs4819756) polymorphisms. The participants underwent psychiatric evaluation and EF assessment. Our main finding is a significant influence of the COMT Val158Met polymorphism on both IQ and EF performance. Specifically, 22q11.2DS subjects with Met allele displayed higher IQ scores in all age groups compared to Val carriers, reaching significance in both adolescents and adults. The Met allele carriers performed better than Val carriers in EF tasks, being statistically significant in the adult group. PRODH Arg185Trp variant did not affect IQ or EF in our 22q11.2DS cohort. In conclusion, functional COMT variant, but not PRODH, affects IQ and EF in 22q11.2DS subjects during neurodevelopment with a maximal effect at adulthood. Future studies should monitor the cognitive performance of the same individuals from childhood to old age. Copyright © 2014 Elsevier Ltd. All rights reserved.

Virtual multiple errands test (VMET): a virtual reality-based tool to detect early executive functions deficit in Parkinson's disease.

PubMed

Cipresso, Pietro; Albani, Giovanni; Serino, Silvia; Pedroli, Elisa; Pallavicini, Federica; Mauro, Alessandro; Riva, Giuseppe

2014-01-01

Several recent studies have pointed out that early impairment of executive functions (EFs) in Parkinson's Disease (PD) may be a crucial marker to detect patients at risk for developing dementia. The main objective of this study was to compare the performances of PD patients with mild cognitive impairment (PD-MCI) with PD patients with normal cognition (PD-NC) and a control group (CG) using a traditional assessment of EFs and the Virtual Multiple Errands Test (VMET), a virtual reality (VR)-based tool. In order to understand which subcomponents of EFs are early impaired, this experimental study aimed to investigate specifically which instrument best discriminates among these three groups. The study included three groups of 15 individuals each (for a total of 45 participants): 15 PD-NC; 15 PD-MCI, and 15 cognitively healthy individuals (CG). To assess the global neuropsychological functioning and the EFs, several tests (including the Mini Mental State Examination (MMSE), Clock Drawing Test, and Tower of London test) were administered to the participants. The VMET was used for a more ecologically valid neuropsychological evaluation of EFs. Findings revealed significant differences in the VMET scores between the PD-NC patients vs. the controls. In particular, patients made more errors in the tasks of the VMET, and showed a poorer ability to use effective strategies to complete the tasks. This VMET result seems to be more sensitive in the early detection of executive deficits because these two groups did not differ in the traditional assessment of EFs (neuropsychological battery). This study offers initial evidence that a more ecologically valid evaluation of EFs is more likely to lead to detection of subtle executive deficits.

Ca2+ Binding to EF Hands 1 and 3 Is Essential for the Interaction of Apoptosis-Linked Gene-2 with Alix/AIP1 in Ocular Melanoma†

PubMed Central

Subramanian, Lalita; Polans, Arthur S.; Walker, Teresa M.; van Ginkel, Paul R.; Bhattacharya, Saswati; Dellaria, Julia M.; Crabb, John W.; Cox, Jos; Durussel, Isabelle; Palczewski, Krzysztof

2005-01-01

Apoptosis-linked gene-2 (ALG-2) encodes a 22 kDa Ca2+-binding protein of the penta EF-hand family that is required for programmed cell death in response to various apoptotic agents. Here, we demonstrate that ALG-2 mRNA and protein are down-regulated in human uveal melanoma cells compared to their progenitor cells, normal melanocytes. The down regulation of ALG-2 may provide melanoma cells with a selective advantage. ALG-2 and its putative target molecule, Alix/AIP1, are localized primarily in the cytoplasm of melanocytes and melanoma cells independent of the intracellular Ca2+ concentration or the activation of apoptosis. Cross-linking and analytical centrifugation studies support a single-species dimer conformation of ALG-2, also independent of Ca2+ concentration. However, binding of Ca2+ to both EF-1 and EF-3 is necessary for ALG-2 interaction with Alix/AIP1 as demonstrated using surface plasmon resonance spectroscopy. Mutations in EF-5 result in reduced target interaction without alteration in Ca2+ affinity. The addition of N-terminal ALG-2 peptides, residues 1–22 or residues 7–17, does not alter the interaction of ALG-2 or an N-terminal deletion mutant of ALG-2 with Alix/AIP1, as might be expected from a model derived from the crystal structure of ALG-2. Fluorescence studies of ALG-2 demonstrate that an increase in surface hydrophobicity is primarily due to Ca2+ binding to EF-3, while Ca2+ binding to EF-1 has little effect on surface exposure of hydrophobic residues. Together, these data indicate that gross surface hydrophobicity changes are insufficient for target recognition. PMID:15366927

75 FR 27986 - Electronic Filing System-Web (EFS-Web) Contingency Option

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-19

...] Electronic Filing System--Web (EFS-Web) Contingency Option AGENCY: United States Patent and Trademark Office... availability of its patent electronic filing system, Electronic Filing System--Web (EFS-Web) by providing a new contingency option when the primary portal to EFS-Web has an unscheduled outage. Previously, the entire EFS...

Study of phosphorylation of translation elongation factor 2 (EF-2) from wheat germ.

PubMed

Smailov, S K; Lee, A V; Iskakov, B K

1993-04-26

Phosphorylation of elongation factor 2 (EF-2) by specific Ca2+/calmodulin-dependent kinase is considered as a possible mechanism of regulation of protein biosynthesis in animal cells at the level of polypeptide chain elongation. In this report we show that wheat germ EF-2 can be intensively phosphorylated by the rabbit reticulocyte EF-2 kinase. Phosphorylation results in inhibition of the activity of plant EF-2 in poly(U)-dependent cell-free translation system. Thus, the activity of EF-2 in plant cells can be potentially regulated by phosphorylation. However, we could not detect endogenous EF-2 kinase activity in wheat germ either in vitro or in vivo. Furthermore, EF-2 kinase activity is not displayed in different organs of wheat and other higher plants.

Temporal trends and factors associated with diabetes mellitus among patients hospitalized with heart failure: Findings from Get With The Guidelines-Heart Failure registry.

PubMed

Echouffo-Tcheugui, Justin B; Xu, Haolin; DeVore, Adam D; Schulte, Phillip J; Butler, Javed; Yancy, Clyde W; Bhatt, Deepak L; Hernandez, Adrian F; Heidenreich, Paul A; Fonarow, Gregg C

2016-12-01

The contribution of diabetes to the burden of heart failure (HF) remains largely undescribed. Assessing diabetes temporal trends among US patients hospitalized with HF and their relation with quality measures in real-world practice can help to define this burden. Using data from the Get With the Guidelines-Heart Failure registry, we assessed temporal trends in diabetes prevalence among patients with HF and in subgroups with reduced ejection fraction (HFrEF; EF < 40%), borderline EF (HFbEF; 40%≤EF <50%), or preserved EF (HFpEF; EF ≥ 50%), hospitalized between 2005 and 2015. Logistic regression was used to assess whether in-hospital outcomes and HF quality of care were related to trends. Among 364,480 HF hospitalizations, 160,171 had diabetes (44.0% overall, 41.8% in HFrEF, 46.7% in HFbEF, 45.5% in HFpEF). There was a temporal increase in diabetes frequency in HF patients (43.2%-45.8%; P trend <.0001), including among those with HFrEF (42.0%-43.6%; P trend <.0001), HFbEF (46.0%-49.2%; P trend <.0001), or HFpEF (43.6%-46.8%, P trend <.0001). Diabetic patients had a longer hospital stay (adjusted odds ratio 1.14, 95% CI 1.12-1.16), but lower in-hospital mortality (adjusted odds ratio 0.93 [0.89-0.97]) compared with those without diabetes, with limited differences in quality measures. Temporal trends in diabetes were not associated with in-hospital mortality or length of stay. There were no temporal interactions of most HF quality measures with diabetes status. Approximately 44% of hospitalized HF patients have diabetes, and this proportion has been increasing over the past 10years, particularly among those patients with new-onset HFpEF. Copyright © 2016 Elsevier Inc. All rights reserved.

A comparison of HFrEF vs HFpEF's clinical workload and cost in the first year following hospitalization and enrollment in a disease management program.

PubMed

Murphy, T M; Waterhouse, D F; James, S; Casey, C; Fitzgerald, E; O'Connell, E; Watson, C; Gallagher, J; Ledwidge, M; McDonald, K

2017-04-01

Admission with heart failure (HF) is a milestone in the progression of the disease, often resulting in higher intensity medical care and ensuing readmissions. Whilst there is evidence supporting enrolling patients in a heart failure disease management program (HF-DMP), not all reported HF-DMPs have systematically enrolled patients with HF with preserved ejection fraction (HFpEF) and there is a scarcity of literature differentiating costs based on HF-phenotype. 1292 consenting, consecutive patients admitted with a primary diagnosis of HF were enrolled in a hospital based HF-DMP and categorized as HFpEF (EF≥45%) or HFrEF (EF<45%). Hospitalizations, primary care, medications, and DMP workload with associated costs were evaluated assessing DMP clinic-visits, telephonic contact, medication changes over 1year using a mixture of casemix and micro-costing techniques. The total average annual cost per patient was marginally higher in patients with HFrEF €13,011 (12,011, 14,078) than HFpEF, €12,206 (11,009, 13,518). However, emergency non-cardiovascular admission rates and average cost per patient were higher in the HFpEF vs HFrEF group (0.46 vs 0.31 per patient/12months) & €655 (318, 1073) vs €584 (396, 812). In the first 3months of the outpatient HF-DMP the HFrEF population cost more on average €791 (764, 819) vs €693 (660, 728). There are greater short-term (3-month) costs of HFrEF versus HFpEF as part of a HF-DMP following an admission. However, long-term (3-12month) costs of HFpEF are greater because of higher non-cardiovascular rehospitalisations. As HFpEF becomes the dominant form of HF, more work is required in HF-DMPs to address prevention of non-cardiovascular rehospitalisations and to integrate hospital based HF-DMPs into primary healthcare structures. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Comparing emission rates derived from a model with a plume-based approach and quantifying the contribution of vehicle classes to on-road emissions and air quality.

PubMed

Xu, Junshi; Wang, Jonathan; Hilker, Nathan; Fallah-Shorshani, Masoud; Saleh, Marc; Tu, Ran; Wang, An; Minet, Laura; Stogios, Christos; Evans, Greg; Hatzopoulou, Marianne

2018-06-05

This study presents a comparison of fleet averaged emission factors (EFs) derived from a traffic emission model with EFs estimated using plume-based measurements, including an investigation of the contribution of vehicle classes to carbon monoxide (CO), nitrogen oxides (NO x ), and elemental carbon (EC) along an urban corridor. To this end, a field campaign was conducted over one week in June 2016 on an arterial road in Toronto, Canada. Traffic data were collected using a traffic camera and a radar, while air quality was characterized using two monitoring stations: one located at ground-level and another at the rooftop of a four-storey building. A traffic simulation model was calibrated and validated and sec-by-sec speed profiles for all vehicle trajectories were extracted to model emissions. In addition, dispersion modelling was conducted to identify the extent to which differences in emissions translate to differences in near-road concentrations. Our results indicate that modelled EFs for CO and NO x are twice as high as plume-based EFs. Besides, modelled results indicate that transit bus emissions accounted for 60% and 70% of the total emissions of NO x and EC. Transit bus emission rates in g/passenger.km for NO x and EC were up to 8 and 22 times the emission rates of passenger cars. In contrast, the Toronto streetcars, which are electrically fuelled, were found to improve near-road air quality despite their negative impact on traffic speeds. Finally, we observe that the difference in estimated concentrations derived from the two methods is not as large as the difference in estimated emissions due to the influence of meteorology and of the urban background given that the study network is located in a busy downtown area. Implications This study presents a comparison of fleet averaged emission factors (EFs) derived from a traffic emission model with EFs estimated using plume-based measurements, including an investigation of the contribution of vehicle classes to various pollutants. Besides, dispersion modelling was conducted to identify the extent to which differences in emissions translate to differences in near-road concentrations. We observe that the difference in estimated concentrations derived from the two methods is not as large as the difference in estimated emissions due to the influence of meteorology and of the urban background as the study network is located in a busy downtown area.

Determination of amantadine in biological fluids using simultaneous derivatization and dispersive liquid-liquid microextraction followed by gas chromatography-flame ionization detection.

PubMed

Farajzadeh, Mir Ali; Nouri, Nina; Alizadeh Nabil, Ali Akbar

2013-12-01

A one-step derivatization and microextraction technique for the determination of amantadine in the human plasma and urine samples is presented. An appropriate mixture of methanol (disperser solvent), 1,2-dibromoethane (extraction solvent), and butylchloroformate (derivatization agent) is rapidly injected into samples. After centrifuging, the sedimented phase is analyzed by gas chromatography-flame ionization detection (GC-FID). The kind of extraction and disperser solvents and their volumes, amount of derivatization agent and reaction/extraction time which are effective in derivatization/dispersive liquid-liquid microextraction (DLLME) procedure are optimized. Under the optimal conditions, the enrichment factor (EF) of the target analyte was obtained to be 408 and 420, and limit of detection (LOD) 4.2 and 2.7ngmL(-1), in plasma and urine respectively. The linear range is 14-5000 and 8.7-5000ng/mL for plasma and urine, respectively (squared correlation coefficient≥0.990). The relative recoveries obtained for the spiked plasma and urine samples are between 72% and 93%. Moreover, the inter- and intra-day precisions are acceptable at all spiked concentrations (relative standard deviation <7%). Finally the method was successfully applied to determine amantadine in biological samples. Copyright © 2013 Elsevier B.V. All rights reserved.

Nitric oxide-induced vasorelaxation in response to PnTx2-6 toxin from Phoneutria nigriventer spider in rat cavernosal tissue.

PubMed

Nunes, Kenia P; Cordeiro, Marta N; Richardson, Michael; Borges, Marcia N; Diniz, Simone O F; Cardoso, Valbert N; Tostes, Rita; De Lima, Maria Elena; Webb, Robert Clinton; Leite, Romulo

2010-12-01

Priapism is one of several symptoms observed in accidental bites by the spider Phoneutria nigriventer. The venom of this spider is comprised of many toxins, and the majority has been shown to affect excitable ion channels, mainly sodium (Na(+) ) channels. It has been demonstrated that PnTx2-6, a peptide extracted from the venom of P. nigriventer, causes erection in anesthetized rats and mice. We investigated the mechanism by which PnTx2-6 evokes relaxation in rat corpus cavernosum. PnTx2-6 toxin potentiates nitric oxide (NO)-dependent cavernosal relaxation. Rat cavernosal strips were incubated with bretylium (3 × 10(-5) M) and contracted with phenylephrine (PE; 10(-5) M). Relaxation responses were evoked by electrical field stimulation (EFS) or sodium nitroprusside (SNP) before and after 4 minutes of incubation with PnTx2-6 (10(-8) M). The effect of PnTx2-6 on relaxation induced by EFS was also tested in the presence of atropine (10(-6) M), a muscarinic receptor antagonist, N-type Ca(2+) channel blockers (ω-conotoxin GVIA, 10(-6) M) and sildenafil (3 × 10(-8) M). Technetium99m radiolabeled PnTx2-6 subcutaneous injection was administrated in the penis. Whereas relaxation induced by SNP was not affected by PnTx2-6, EFS-induced relaxation was significantly potentiated by this toxin as well as PnTx2-6 plus SNP. This potentiating effect was further increased by sildenafil, not altered by atropine, however was completely blocked by the N-type Ca(2+) channels. High concentrated levels of radiolabeled PnTx2-6 was specifically found in the cavernosum tissue, suggesting PnTx2-6 is an important toxin responsible for P. nigriventer spider accident-induced priapism. We show that PnTx2-6 slows Na(+) channels inactivation in nitrergic neurons, allowing Ca(2+) influx to facilitate NO/cGMP signalling, which promotes increased NO production. In addition, this relaxation effect is independent of phosphodiesterase enzyme type 5 inhibition. Our data displays PnTx2-6 as possible pharmacological tool to study alternative treatments for erectile dysfunction. © 2010 International Society for Sexual Medicine.

Draft Whole-Genome Sequences of Escherichia fergusonii Strains Isolated from Beef Trim (GTA-EF02), Ground Beef (GTA-EF03), and Chopped Kale (GTA-EF04).

PubMed

Manninger, Paul; Koziol, Adam; Carrillo, Catherine D

2016-04-14

Escherichia fergusoniiis a Gram-negative, rod-shaped, non-spore-forming member of theEnterobacteriaceaefamily and is a bacterium with both biotechnological applications and implication in human clinical disease. Here, we report the draft genome sequences of three isolates ofE. fergusoniifrom beef trim (GTA-EF02), ground beef (GTA-EF03), and chopped kale (GTA-EF04). Copyright © 2016 Manninger et al.

Empirically Defined Patterns of Executive Function Deficits in Schizophrenia and Their Relation to Everyday Functioning: A Person-Centered Approach

PubMed Central

Iampietro, Mary; Giovannetti, Tania; Drabick, Deborah A. G.; Kessler, Rachel K.

2013-01-01

Executive function (EF) deficits in schizophrenia (SZ) are well documented, although much less is known about patterns of EF deficits and their association to differential impairments in everyday functioning. The present study empirically defined SZ groups based on measures of various EF abilities and then compared these EF groups on everyday action errors. Participants (n=45) completed various subtests from the Delis–Kaplan Executive Function System (D-KEFS) and the Naturalistic Action Test (NAT), a performance-based measure of everyday action that yields scores reflecting total errors and a range of different error types (e.g., omission, perseveration). Results of a latent class analysis revealed three distinct EF groups, characterized by (a) multiple EF deficits, (b) relatively spared EF, and (c) perseverative responding. Follow-up analyses revealed that the classes differed significantly on NAT total errors, total commission errors, and total perseveration errors; the two classes with EF impairment performed comparably on the NAT but performed worse than the class with relatively spared EF. In sum, people with SZ demonstrate variable patterns of EF deficits, and distinct aspects of these EF deficit patterns (i.e., poor mental control abilities) may be associated with everyday functioning capabilities. PMID:23035705

Impairment in Occupational Functioning and Adult ADHD: The Predictive Utility of Executive Function (EF) Ratings Versus EF Tests

PubMed Central

Barkley, Russell A.; Murphy, Kevin R.

2010-01-01

Attention deficit hyperactivity disorder (ADHD) is associated with deficits in executive functioning (EF). ADHD in adults is also associated with impairments in major life activities, particularly occupational functioning. We investigated the extent to which EF deficits assessed by both tests and self-ratings contributed to the degree of impairment in 11 measures involving self-reported occupational problems, employer reported workplace adjustment, and clinician rated occupational adjustment. Three groups of adults were recruited as a function of their severity of ADHD: ADHD diagnosis (n = 146), clinical controls self-referring for ADHD but not diagnosed with it (n = 97), and community controls (n = 109). Groups were combined and regression analyses revealed that self-ratings of EF were significantly predictive of impairments in all 11 measures of occupational adjustment. Although several tests of EF also did so, they contributed substantially less than did the EF ratings, particularly when analyzed jointly with the ratings. We conclude that EF deficits contribute to the impairments in occupational functioning that occur in conjunction with adult ADHD. Ratings of EF in daily life contribute more to such impairments than do EF tests, perhaps because, as we hypothesize, each assesses a different level in the hierarchical organization of EF as a meta-construct. PMID:20197297

Intraindividual Variability in Executive Functions but Not Speed of Processing or Conflict Resolution Predicts Performance Differences in Gait Speed in Older Adults

PubMed Central

Mahoney, Jeannette; Verghese, Joe

2014-01-01

Background. The relationship between executive functions (EF) and gait speed is well established. However, with the exception of dual tasking, the key components of EF that predict differences in gait performance have not been determined. Therefore, the current study was designed to determine whether processing speed, conflict resolution, and intraindividual variability in EF predicted variance in gait performance in single- and dual-task conditions. Methods. Participants were 234 nondemented older adults (mean age 76.48 years; 55% women) enrolled in a community-based cohort study. Gait speed was assessed using an instrumented walkway during single- and dual-task conditions. The flanker task was used to assess EF. Results. Results from the linear mixed effects model showed that (a) dual-task interference caused a significant dual-task cost in gait speed (estimate = 35.99; 95% CI = 33.19–38.80) and (b) of the cognitive predictors, only intraindividual variability was associated with gait speed (estimate = −.606; 95% CI = −1.11 to −.10). In unadjusted analyses, the three EF measures were related to gait speed in single- and dual-task conditions. However, in fully adjusted linear regression analysis, only intraindividual variability predicted performance differences in gait speed during dual tasking (B = −.901; 95% CI = −1.557 to −.245). Conclusion. Among the three EF measures assessed, intraindividual variability but not speed of processing or conflict resolution predicted performance differences in gait speed. PMID:24285744

Mutation/SNP analysis in EF-hand calcium binding domain of mitochondrial Ca[Formula: see text] uptake 1 gene in bipolar disorder patients.

PubMed

Safari, Roghaiyeh; Salimi, Reza; Tunca, Zeliha; Ozerdem, Aysegul; Ceylan, Deniz; Sakizli, Meral

2016-06-01

Calcium signaling is important for synaptic plasticity, generation of brain rhythms, regulating neuronal excitability, data processing and cognition. Impairment in calcium homeostasis contributed to the development of psychiatric disorders such as bipolar disorder (BP). MCU is the most important calcium transporter in mitochondria inner membrane responsible for influx of Ca[Formula: see text]. MICU1 is linked with MCU and has two canonical EF hands that are vital for its activity and regulates MCU-mediated Ca[Formula: see text] influx. In the current study, we aimed to investigate the role of genetic alteration of EF hand calcium binding motifs of MICU1 on the development of BP. We examined patients with BP, first degree relatives of these patients and healthy volunteers for mutations and polymorphisms in EF hand calcium binding motifs of MICU1. The result showed no SNP/mutation in BP patients, in healthy subjects and in first degree relatives. Additionally, alignment of the EF hand calcium binding regions among species (Gallus-gallus, Canis-lupus-familiaris, Bos-taurus, Mus-musculus, Rattus-norvegicus, Pan-troglodytes, Homosapiens and Danio-rerio) showed exactly the same amino acids (DLNGDGEVDMEE and DCDGNGELSNKE) except in one of the calcium binding domain of Danio-rerio that there was only one difference; leucine instead of Methionine. Our results showed that the SNP on EF-hand Ca[Formula: see text] binding domains of MICU1 gene had no effect in phenotypic characters of BP patients.