Disaggregated N2O emission factors in China based on cropping parameters create a robust approach to the IPCC Tier 2 methodology

NASA Astrophysics Data System (ADS)

Shepherd, Anita; Yan, Xiaoyuan; Nayak, Dali; Newbold, Jamie; Moran, Dominic; Dhanoa, Mewa Singh; Goulding, Keith; Smith, Pete; Cardenas, Laura M.

2015-12-01

China accounts for a third of global nitrogen fertilizer consumption. Under an International Panel on Climate Change (IPCC) Tier 2 assessment, emission factors (EFs) are developed for the major crop types using country-specific data. IPCC advises a separate calculation for the direct nitrous oxide (N2O) emissions of rice cultivation from that of cropland and the consideration of the water regime used for irrigation. In this paper we combine these requirements in two independent analyses, using different data quality acceptance thresholds, to determine the influential parameters on emissions with which to disaggregate and create N2O EFs. Across China, the N2O EF for lowland horticulture was slightly higher (between 0.74% and 1.26% of fertilizer applied) than that for upland crops (values ranging between 0.40% and 1.54%), and significantly higher than for rice (values ranging between 0.29% and 0.66% on temporarily drained soils, and between 0.15% and 0.37% on un-drained soils). Higher EFs for rice were associated with longer periods of drained soil and the use of compound fertilizer; lower emissions were associated with the use of urea or acid soils. Higher EFs for upland crops were associated with clay soil, compound fertilizer or maize crops; lower EFs were associated with sandy soil and the use of urea. Variation in emissions for lowland vegetable crops was closely associated with crop type. The two independent analyses in this study produced consistent disaggregated N2O EFs for rice and mixed crops, showing that the use of influential cropping parameters can produce robust EFs for China.

Integrating Ecological and Water Footprint Accounting in a Multi-Regional Input-Output Framework

EPA Science Inventory

Carbon, ecological, and water footprints (CF, EF, and WF) are accounting tools that can be used to understand the connection between consumption activities and environmental pressures on the Earth?s atmosphere, bioproductive areas, and freshwater resources. These indicators have ...

Differential Improvement of Executive Functions During Abstinence in Cocaine-Dependent Patients: A Longitudinal Study.

PubMed

Inozemtseva, Olga; Pérez-Solís, Lina; Matute, Esmeralda; Juárez, Jorge

2016-09-18

In substance abusers, deficits in executive functioning (EF) are relevant to understanding the behavioral regulation of substance consumption and the failure to remain abstinent. To determine the course of EF impairment, measured with traditional and ecological instruments, after 1 and 3 months of abstinence in patients with cocaine dependence. 26 cocaine-only-dependent in-patients (cocaine-dependent group, CDG) and 24 nondependent controls (control group, CG) recruited from a typical population were assessed using several EF tests and questionnaires [Stroop, verbal and graphic fluency, Wisconsin Card-Sorting Test (WCST), Tower of London (TOL), and Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A)] after three periods of abstinence: 1 week, 1 month, and 3 months. At 1 week (baseline), CDG underperformed CG on most EF measures (WCST categories completed; TOL-total number of moves, execution time, and rule violations; and various BRIEF-A subscales). At 1 month, CDG moderately improved its performance on several measures, meanwhile the improvement in the 12 patients who would eventually complete the 3-month abstinence proved particularly significant when compared to their baseline values. In the a posteriori comparison of the baseline values of noncompleters versus completers, scores for the former were lower on the EF tasks, but higher on the BRIEF-A. Both groups, showed significantly worse scores than CG on both instruments. Cocaine-dependent patients showed marked difficulties in the EF associated mainly with adaptive behavior to their environment. Cocaine-dependent patients with better EF at baseline improved significantly during abstinence and had better treatment adherence. Results suggest that executive improvement and treatment adherence in cocaine abusers in abstinence is related to intrinsic cognitive characteristics of patients.

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.

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.

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.

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.

Depressed heart rate variability as an independent predictor of death in chronic congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy.

PubMed

Ponikowski, P; Anker, S D; Chua, T P; Szelemej, R; Piepoli, M; Adamopoulos, S; Webb-Peploe, K; Harrington, D; Banasiak, W; Wrabec, K; Coats, A J

1997-06-15

After acute myocardial infarction, depressed heart rate variability (HRV) has been proven to be a powerful independent predictor of a poor outcome. Although patients with chronic congestive heart failure (CHF) have also markedly impaired HRV, the prognostic value of HRV analysis in these patients remains unknown. The aim of this study was to investigate whether HRV parameters could predict survival in 102 consecutive patients with moderate to severe CHF (90 men, mean age 58 years, New York Heart Association [NYHA] class II to IV, CHF due to idiopathic dilated cardiomyopathy in 24 patients and ischemic heart disease in 78 patients, ejection fraction [EF], 26%; peak oxygen consumption, 16.9 ml/kg/min) after exclusion of patients in atrial fibrilation with diabetes or with chronic renal failure. In the prognostic analysis (Cox proportional-hazards model, Kaplan-Meier survival analysis), the following factors were investigated: age, CHF etiology, NYHA class, EF, peak oxygen consumption, presence of ventricular tachycardia on Holter monitoring, and HRV measures derived from 24-hour electrocardiography monitoring, calculated in the time (standard deviation of all normal RR intervals [SDNN], standard deviation of 5-minute RR intervals [SDANN], mean of all 5-minute standard deviations of RR intervals [SD], root-mean-square of difference of successive RR intervals [rMSSD], and percentage of adjacent RR intervals >50 ms different [pNN50]) and frequency domain (total power [TP], power within low-frequency band [LF], and power within high-frequency band [HF]). During follow-up of 584 +/- 405 days (365 days in all who survived), 19 patients (19%) died (mean time to death: 307 +/- 315 days, range 3 to 989). Cox's univariate analysis identified the following factors to be predictors of death: NYHA (p = 0.003), peak oxygen consumption (p = 0.01), EF (p = 0.02), ventricular tachycardia on Holter monitoring (p = 0.05), and among HRV measures: SDNN (p = 0.004), SDANN (p = 0.003), SD (p = 0.02), and LF (p = 0.003). In multivariate analysis, HRV parameters (SDNN, SDANN, LF) were found to predict survival independently of NYHA functional class, EF, peak oxygen consumption, and ventricular tachycardia on Holter monitoring. The Kaplan-Meier survival curves revealed SDNN < 100 ms to be a useful risk factor; 1-year survival in patients with SDNN < 100 ms was 78% when compared with 95% in those with SDNN > 100 ms (p = 0.008). The coexistence of SDNN < 100 ms and a peak oxygen consumption < 14 ml/kg/min allowed identification of a group of 18 patients with a particularly poor prognosis (1-year survival 63% vs 94% in the remaining patients, p <0.001). We conclude that depressed HRV on 24-hour ambulatory electrocardiography monitoring is an independent risk factor for a poor prognosis in patients with CHF. Whether analysis of HRV could be recommended in the risk stratification for better management of patients with CHF needs further investigation.

Base de linhas moleculares para síntese espectral estelar

NASA Astrophysics Data System (ADS)

Milone, A.; Sanzovo, G.

2003-08-01

A análise das abundâncias quí micas fotosféricas em estrelas do tipo solar ou tardia, através do cálculo teórico de seus espectros, emprega a espectroscopia de alta resolução e necessita de uma base representativa de linhas atômicas e moleculares com suas respectivas constantes bem determinadas. Nesse trabalho, utilizamos como ponto de partida as extensas listas de linhas espectrais de sistemas eletrônicos de algumas moléculas diatômicas compiladas por Kurucz para a construção de uma base de linhas moleculares para a sí ntese espectral estelar. Revisamos as determinações dos fatores rotacionais de Honl-London das forças de oscilador das linhas moleculares, para cada banda vibracional de alguns sistemas eletrônicos, seguindo a regra usual de normalização. Usamos as forças de oscilador eletrônicas da literatura. Os fatores vibracionais de Franck-Condon de cada banda foram especialmente recalculados empregando-se novas constantes moleculares. Reproduzimos, com êxito, as absorções espectrais de determinadas bandas eletrônicas-vibracionais das espécies moleculares C12C12, C12N14 e Mg24H em espectros de estrelas de referência como o Sol e Arcturus.

Impaired chronotropic and vasodilator reserves limit exercise capacity in patients with heart failure and a preserved ejection fraction.

PubMed

Borlaug, Barry A; Melenovsky, Vojtech; Russell, Stuart D; Kessler, Kristy; Pacak, Karel; Becker, Lewis C; Kass, David A

2006-11-14

Nearly half of patients with heart failure have a preserved ejection fraction (HFpEF). Symptoms of exercise intolerance and dyspnea are most often attributed to diastolic dysfunction; however, impaired systolic and/or arterial vasodilator reserve under stress could also play an important role. Patients with HFpEF (n=17) and control subjects without heart failure (n=19) generally matched for age, gender, hypertension, diabetes mellitus, obesity, and the presence of left ventricular hypertrophy underwent maximal-effort upright cycle ergometry with radionuclide ventriculography to determine rest and exercise cardiovascular function. Resting cardiovascular function was similar between the 2 groups. Both had limited exercise capacity, but this was more profoundly reduced in HFpEF patients (exercise duration 180+/-71 versus 455+/-184 seconds; peak oxygen consumption 9.0+/-3.4 versus 14.4+/-3.4 mL x kg(-1) x min(-1); both P<0.001). At matched low-level workload, HFpEF subjects displayed approximately 40% less of an increase in heart rate and cardiac output and less systemic vasodilation (all P<0.05) despite a similar rise in end-diastolic volume, stroke volume, and contractility. Heart rate recovery after exercise was also significantly delayed in HFpEF patients. Exercise capacity correlated with the change in cardiac output, heart rate, and vascular resistance but not end-diastolic volume or stroke volume. Lung blood volume and plasma norepinephrine levels rose similarly with exercise in both groups. HFpEF patients have reduced chronotropic, vasodilator, and cardiac output reserve during exercise compared with matched subjects with hypertensive cardiac hypertrophy. These limitations cannot be ascribed to diastolic abnormalities per se and may provide novel therapeutic targets for interventions to improve exercise capacity in this disorder.

Long-Term Preservation of Left Ventricular Systolic Function in Patients With Refractory Angina Pectoris and Inducible Myocardial Ischemia on Optimal Medical Therapy.

PubMed

Slavich, Massimo; Maranta, Francesco; Fumero, Andrea; Godino, Cosmo; Giannini, Francesco; Oppizzi, Michele; Colombo, Antonio; Fragasso, Gabriele; Margonato, Alberto

2016-05-15

Refractory angina pectoris (RAP) represents a clinical condition characterized by frequent episodes of chest pain despite therapy optimization. According to myocardial stunning and myocardial hibernation definitions, RAP should represent the ideal condition for systolic dysfunction development. We aim to investigate the evolution of left ventricular (LV) function in patients with RAP. A retrospective study which encompasses 144 patients with RAP referred to our institution from 1999 to December 2014 was performed. Of them, 88 met the inclusion criteria, and LV function was assessed by echocardiography. All of them had persistent angina episodes on top of optimal medical therapy and evidence of significant inducible myocardial ischemia and no further revascularization options. Nitrates consumption rate, time of angina duration, and the number of angina attacks were evaluated. In the whole population, ejection fraction (EF) was 44% ± 2. EF was significantly lower in patients with previous myocardial infarction (41% ± 1.5 vs 51% ± 1.8, p <0.0001). The duration time and the number of angina attacks did not correlate with EF in the whole population and in patients without previous myocardial infarction. In patients with previous myocardial infarction, the number of anginal attacks did not correlate with EF, but EF appeared higher in patients with angina duration >5 years (<5 years EF 37% ± 1 [n = 26]; >5 years 44% ± 2 [n = 44]; p 0.02). Long-term LV function in patients with RAP is generally preserved. A previous history of myocardial infarction is the only determinant in the development of systolic dysfunction. In conclusion, frequent angina attacks and a long-term history of angina are not apparently associated to worse LV function. Copyright © 2016 Elsevier Inc. All rights reserved.

Promising technological innovations in cognitive training to treat eating-related behavior.

PubMed

Forman, Evan M; Goldstein, Stephanie P; Flack, Daniel; Evans, Brittney C; Manasse, Stephanie M; Dochat, Cara

2018-05-01

One potential reason for the suboptimal outcomes of treatments targeting appetitive behavior, such as eating and alcohol consumption, is that they do not target the implicit cognitive processes that may be driving these behaviors. Two groups of related neurocognitive processes that are robustly associated with dysregulated eating and drinking are attention bias (AB; selective attention to specific stimuli) and executive function (EF; a set of cognitive control processes such as inhibitory control, working memory, set shifting, that govern goal-directed behaviors). An increasing body of work suggests that EF and AB training programs improve regulation of appetitive behaviors, especially if trainings are frequent and sustained. However, several key challenges, such as adherence to the trainings in the long term, and overall potency of the training, remain. The current manuscript describes five technological innovations that have the potential to address difficulties related to the effectiveness and feasibility of EF and AB trainings: (1) deployment of training in the home, (2) training via smartphone, (3) gamification, (4) virtual reality, and (5) personalization. The drawbacks of these innovations, as well as areas for future research, are also discussed. The above-mentioned innovations are likely to be instrumental in the future empirical work to develop and evaluate effective EF and AB trainings for appetitive behaviors. Copyright © 2017 Elsevier Ltd. All rights reserved.

Development of Hot Exhaust Emission Factors for Iranian-Made Euro-2 Certified Light-Duty Vehicles.

PubMed

Banitalebi, Ehsan; Hosseini, Vahid

2016-01-05

Emission factors (EFs) are fundamental, necessary data for air pollution research and scenario implementation. With the vision of generating national EFs of the Iranian transportation system, a portable emission measurement system (PEMS) was used to develop the basic EFs for a statistically significant sample of Iranian gasoline-fueled privately owned light duty vehicles (LDVs) operated in Tehran. A smaller sample size of the same fleet was examined by chassis dynamometer (CD) bag emission measurement tests to quantify the systematic differences between the PEMS and CD methods. The selected fleet was tested over four different routes of uphill highways, flat highways, uphill urban streets, and flat urban streets. Real driving emissions (RDEs) and fuel consumption (FC) rates were calculated by weighted averaging of the results from each route. The activity of the fleet over each route type was assumed as a weighting factor. The activity data were obtained from a Tehran traffic model. The RDEs of the selected fleet were considerably higher than the certified emission levels of all vehicles. Differences between Tehran real driving cycles and the New European Driving Cycle (NEDC) was attributed to the lower loading of NEDC. A table of EFs based on RDEs was developed for the sample fleet.

Exercise Training in Group 2 Pulmonary Hypertension: Which Intensity and What Modality.

PubMed

Arena, Ross; Lavie, Carl J; Borghi-Silva, Audrey; Daugherty, John; Bond, Samantha; Phillips, Shane A; Guazzi, Marco

2016-01-01

Pulmonary hypertension (PH) due to left-sided heart disease (LSHD) is a common and disconcerting occurrence. For example, both heart failure (HF) with preserved and reduced ejection fraction (HFpEF and HFrEF) often lead to PH as a consequence of a chronic elevation in left atrial filling pressure. A wealth of literature demonstrates the value of exercise training (ET) in patients with LSHD, which is particularly robust in patients with HFrEF and growing in patients with HFpEF. While the effects of ET have not been specifically explored in the LSHD-PH phenotype (i.e., composite pathophysiologic characteristics of patients in this advanced disease state), the overall body of evidence supports clinical application in this subgroup. Moderate intensity aerobic ET significantly improves peak oxygen consumption, quality of life and prognosis in patients with HF. Resistance ET significantly improves muscle strength and endurance in patients with HF, which further enhance functional capacity. When warranted, inspiratory muscle training and neuromuscular electrical stimulation are becoming recognized as important components of a comprehensive rehabilitation program. This review will provide a detailed account of ET programing considerations in patients with LSHD with a particular focus on those concomitantly diagnosed with PH. Copyright © 2015 Elsevier Inc. All rights reserved.

Children's Executive Function and High-Calorie, Low-Nutrient Food Intake: Mediating Effects of Child-Perceived Adult Fast Food Intake

ERIC Educational Resources Information Center

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

2015-01-01

Objective: 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. Design: One year and 6-month longitudinal observation from a larger randomized controlled trial. Setting. Southern California…

Experimental evaluation and thermodynamic system modeling of thermoelectric heat pump clothes dryer

DOE PAGES

Patel, Viral K.; Gluesenkamp, Kyle R.; Goodman, Dakota; ...

2018-02-28

Electric clothes dryers consume about 6% of US residential electricity consumption. Using a solid-state technology without refrigerant, thermoelectric (TE) heat pump dryers have the potential to be more efficient than units based on electric resistance and less expensive than units based on vapor compression. This study presents a steady state TE dryer model, and validates the model against results from an experimental prototype. The system model is composed of a TE heat pump element model coupled with a psychrometric dryer sub-model. Experimental results had energy factors (EFs) of up to 2.95 kg of dry cloth per kWh (6.51 lb c/kWh),more » with a dry time of 159 min. A faster dry time of 96 min was also achieved at an EF of 2.54 kg c/kWh (5.60 lb c/kWh). The model was able to replicate the experimental results within 5% of EF and 5% of dry time values. Finally, the results are used to identify important parameters that affect dryer performance, such as relative humidity of air leaving the drum.« less

Experimental evaluation and thermodynamic system modeling of thermoelectric heat pump clothes dryer

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

Patel, Viral K.; Gluesenkamp, Kyle R.; Goodman, Dakota

Electric clothes dryers consume about 6% of US residential electricity consumption. Using a solid-state technology without refrigerant, thermoelectric (TE) heat pump dryers have the potential to be more efficient than units based on electric resistance and less expensive than units based on vapor compression. This study presents a steady state TE dryer model, and validates the model against results from an experimental prototype. The system model is composed of a TE heat pump element model coupled with a psychrometric dryer sub-model. Experimental results had energy factors (EFs) of up to 2.95 kg of dry cloth per kWh (6.51 lb c/kWh),more » with a dry time of 159 min. A faster dry time of 96 min was also achieved at an EF of 2.54 kg c/kWh (5.60 lb c/kWh). The model was able to replicate the experimental results within 5% of EF and 5% of dry time values. Finally, the results are used to identify important parameters that affect dryer performance, such as relative humidity of air leaving the drum.« less

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.

Degradation of pharmaceutical beta-blockers by electrochemical advanced oxidation processes using a flow plant with a solar compound parabolic collector.

PubMed

Isarain-Chávez, Eloy; Rodríguez, Rosa María; Cabot, Pere Lluís; Centellas, Francesc; Arias, Conchita; Garrido, José Antonio; Brillas, Enric

2011-08-01

The degradation of the beta-blockers atenolol, metoprolol tartrate and propranolol hydrochloride was studied by electro-Fenton (EF) and solar photoelectro-Fenton (SPEF). Solutions of 10 L of 100 mg L⁻¹ of total organic carbon of each drug in 0.1 M Na₂SO₄ with 0.5 mM Fe²⁺ of pH 3.0 were treated in a recirculation flow plant with an electrochemical reactor coupled with a solar compound parabolic collector. Single Pt/carbon felt (CF) and boron-doped diamond (BDD)/air-diffusion electrode (ADE) cells and combined Pt/ADE-Pt/CF and BDD/ADE-Pt/CF cells were used. SPEF treatments were more potent with the latter cell, yielding 95-97% mineralization with 100% of maximum current efficiency and energy consumptions of about 0.250 kWh g TOC⁻¹. However, the Pt/ADE-Pt/CF cell gave much lower energy consumptions of about 0.080 kWh g TOC⁻¹ with slightly lower mineralization of 88-93%, then being more useful for its possible application at industrial level. The EF method led to a poorer mineralization and was more potent using the combined cells by the additional production of hydroxyl radicals (•OH) from Fenton's reaction from the fast Fe²⁺ regeneration at the CF cathode. Organics were also more rapidly destroyed at BDD than at Pt anode. The decay kinetics of beta-blockers always followed a pseudo first-order reaction, although in SPEF, it was accelerated by the additional production of •OH from the action of UV light of solar irradiation. Aromatic intermediates were also destroyed by hydroxyl radicals. Ultimate carboxylic acids like oxalic and oxamic remained in the treated solutions by EF, but their Fe(III) complexes were photolyzed by solar irradiation in SPEF, thus explaining its higher oxidation power. NO₃⁻ was the predominant inorganic ion lost in EF, whereas the SPEF process favored the production of NH₄⁺ ion and volatile N-derivatives. Copyright © 2011 Elsevier Ltd. All rights reserved.

Global time trends in PAH emissions from motor vehicles

NASA Astrophysics Data System (ADS)

Shen, Huizhong; Tao, Shu; Wang, Rong; Wang, Bin; Shen, Guofeng; Li, Wei; Su, Shenshen; Huang, Ye; Wang, Xilong; Liu, Wenxin; Li, Bengang; Sun, Kang

2011-04-01

Emission from motor vehicles is the most important source of polycyclic aromatic hydrocarbons (PAHs) in urban areas. Emission factors of individual PAHs for motor vehicles reported in the literature varied 4 to 5 orders of magnitude, leading to high uncertainty in emission inventory. In this study, key factors affecting emission factors of PAHs (EF PAH) for motor vehicles were evaluated quantitatively based on thousands of EF PAH measured in 16 countries for over 50 years. The result was used to develop a global emission inventory of PAHs from motor vehicles. It was found that country and vehicle model year are the most important factors affecting EF PAH, which can be quantified using a monovariate regression model with per capita gross domestic production (purchasing power parity) as a sole independent variable. On average, 29% of variation in log-transformed EF PAH could be explained by the model, which was equivalent to 90% reduction in overall uncertainty on arithmetic scale. The model was used to predict EF PAH and subsequently PAH emissions from motor vehicles for various countries in the world during a period from 1971 to 2030. It was estimated that the global emission reached its peak value of approximate 101 Gg in 1978 and decreased afterwards due to emission control in developed countries. The annual emission picked up again since 1990 owing to accelerated energy consumption in China and other developing countries. With more and more rigid control measures taken in the developing world, global emission of PAHs is currently passing its second peak. It was predicted that the emission would decrease from 77 Gg in 2010 to 42 Gg in 2030.

Multiprofissional electronic protocol in ophtalmology with enfasis in strabismus.

PubMed

Ribeiro, Christie Graf; Moreira, Ana Tereza Ramos; Pinto, José Simão DE Paula; Malafaia, Osvaldo

2016-01-01

to create and validate an electronic database in ophthalmology focused on strabismus, to computerize this database in the form of a systematic data collection software named Electronic Protocol, and to incorporate this protocol into the Integrated System of Electronic Protocols (SINPE(c)). this is a descriptive study, with the methodology divided into three phases: (1) development of a theoretical ophthalmologic database with emphasis on strabismus; (2) computerization of this theoretical ophthalmologic database using SINPE(c) and (3) interpretation of the information with demonstration of results to validate the protocol. We inputed data from the charts of fifty patients with known strabismus through the Electronic Protocol for testing and validation. the new electronic protocol was able to store information regarding patient history, physical examination, laboratory exams, imaging results, diagnosis and treatment of patients with ophthalmologic diseases, with emphasis on strabismus. We included 2,141 items in this master protocol and created 20 new specific electronic protocols for strabismus, each with its own specifics. Validation was achieved through correlation and corroboration of the symptoms and confirmed diagnoses of the fifty included patients with the diagnostic criteria for the twenty new strabismus protocols. a new, validated electronic database focusing on ophthalmology, with emphasis on strabismus, was successfully created through the standardized collection of information, and computerization of the database using proprietary software. This protocol is ready for deployment to facilitate data collection, sorting and application for practitioners and researchers in numerous specialties. criar uma base eletrônica de dados em oftalmologia com ênfase em estrabismo através da coleta padronizada de informações. Informatizar esta base sob a forma de software para a coleta sistemática de dados chamado "Protocolo Eletrônico" e incorporar este "Protocolo Eletrônico" da Oftalmologia ao Sistema Integrado de Protocolos Eletrônicos (SINPE(c)). este é um estudo descritivo e a metodologia aplicada em seu desenvolvimento está didaticamente dividida em três fases: 1) criação da base teórica de dados clínicos de oftalmologia com ênfase em estrabismo; 2) informatização da base teórica dos dados utilizando o SINPE(c); e 3) interpretação das informações com demonstração dos resultados. A informatização da base de dados foi realizada pela utilização da concessão de uso do SINPE(c). Foram incluídos neste protocolo 50 pacientes com estrabismo para validação do protocolo. o protocolo eletrônico desenvolvido permitiu armazenar informações relacionadas à anamnese, exame físico, exames complementares, diagnóstico e tratamento de pacientes com doenças oftalmológicas, com ênfase em estrabismo. Foram incluídos neste trabalho 2141 itens no protocolo mestre e foram criados 20 protocolos específicos de estrabismo, cada um com suas particularidades. Os 50 pacientes que foram incluídos nos protocolos específicos demonstraram a eficácia do método empregado. foi criada uma base eletrônica de dados em oftalmologia com ênfase em estrabismo através da coleta padronizada de informações. Esta base de dados foi informatizada sob a forma de software onde os futuros usuários poderão utilizar o protocolo eletrônico multiprofissional de doenças oftalmológicas com ênfase em estrabismo para a coleta de seus dados.

Age and sex differences in cerebral glucose consumption measured by pet using (18-F) fluorodeoxyglucose (FDG)

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

Duara, R.; Barker, W.; Chang, J.

1985-05-01

Resting cerebral glucose metabolic rates (CMRglc) were measured in 23 subjects by PET using FDG. Subjects were divided into several groups (mean age +- S.D.) 5 young males (YM) (27 +- 6); 6 young females (YF)(33 +9); 5 elderly males (EM)(73 +- 5); 7 elderly females (EF)(69 +- 7). Additionally, from these groups 4 YM, 3YF, 5EM and 4EF were studied again within 6 weeks under identical conditions. CMRglc in the YF group again was significantly hider than YM (p 0.05). No obvious relationships of CMRglc to the phase of the menstrual cycle was found in this small group. Theremore » was a trend (p=0.06) toward a higher CMRglc in YF than EF. These results support the findings of higher CBF in YF versus YM. The differences between the results of Kuhl et al (J. Cereb. and a reduction of CMRglc with age was found in a mixed group of males and females (58and female), and where no age effect was found the males, are also resolved by these findings. The authors suggest that the apparent age effect, in females in this study, is principally a hormonal one.« less

Optimization of the electro-Fenton and solar photoelectro-Fenton treatments of sulfanilic acid solutions using a pre-pilot flow plant by response surface methodology.

PubMed

El-Ghenymy, Abdellatif; Garcia-Segura, Sergi; Rodríguez, Rosa María; Brillas, Enric; El Begrani, Mohamed Soussi; Abdelouahid, Ben Ali

2012-06-30

A central composite rotatable design and response surface methodology were used to optimize the experimental variables of the electro-Fenton (EF) and solar photoelectro-Fenton (SPEF) degradations of 2.5L of sulfanilic acid solutions in 0.05M Na(2)SO(4). Electrolyses were performed with a pre-pilot flow plant containing a Pt/air diffusion reactor generating H(2)O(2). In SPEF, it was coupled with a solar photoreactor under an UV irradiation intensity of ca. 31Wm(-2). Optimum variables of 100mAcm(-2), 0.5mM Fe(2+) and pH 4.0 were determined after 240min of EF and 120min of SPEF. Under these conditions, EF gave 47% of mineralization, whereas SPEF was much more powerful yielding 76% mineralization with 275kWh kg(-1) total organic carbon (TOC) energy consumption and 52% current efficiency. Sulfanilic acid decayed at similar rate in both treatments following a pseudo-first-order kinetics. The final solution treated by EF contained a stable mixture of tartaric, acetic, oxalic and oxamic acids, which form Fe(III) complexes that are not attacked by hydroxyl radicals formed from H(2)O(2) and added Fe(2+). The quick photolysis of these complexes by UV light of sunlight explains the higher oxidation power of SPEF. NH(4)(+) was the main inorganic nitrogen ion released in both processes. Copyright © 2012 Elsevier B.V. All rights reserved.

Multi-scale research of time and space differences about ecological footprint and ecological carrying capacity of the water resources

NASA Astrophysics Data System (ADS)

Li, Jiahong; Lei, Xiaohui; Fu, Qiang; Li, Tianxiao; Qiao, Yu; Chen, Lei; Liao, Weihong

2018-03-01

A multi-scale assessment framework for assessing and comparing the water resource sustainability based on the ecological footprint (EF) is introduced. The study aims to manage the water resource from different views in Heilongjiang Province. First of all, from the scale of each city, the water ecological carrying capacity (ECC) was calculated from 2000 to 2011, and map the spatial distribution of the recent 3 years which show that, the water ecological carrying capacity (ECC) is uneven and has a downward trend year by year. Then, from the perspective of the five secondary partition basins in Heilongjiang Province, the paper calculated the ecological carrying capacity (ECC), the ecological footprint (EF) and ecological surplus and deficit (S&D) situation of water resources from 2000 to 2011, which show that the ecological deficit situation is more prominent in Nenjiang and Suifenhe basins which are in an unsustainable development state. Finally, from the perspective of the province, the paper calculated the ecological carrying capacity (ECC), the ecological footprint (EF) and ecological S&D of water resources from 2000 to 2011 in Heilongjiang Province, which show that the ecological footprint (EF) is in the rising trend, and the correlation coefficient between the ecological carrying capacity (ECC) and the precipitation is 0.8. There are 5 years of unsustainable development state in Heilongjiang. The proposed multi-scale assessment of WEF aims to evaluate the complex relationship between water resource supply and consumption in different spatial scales and time series. It also provides more reasonable assessment result which can be used by managers and regulators.

Evaluating Sustainability of Cropland Use in Yuanzhou County of the Loess Plateau, China Using an Emergy-Based Ecological Footprint

PubMed Central

Bai, Xiaomei; Wen, Zhongming; An, Shaoshan; Li, Bicheng

2015-01-01

Evaluating the sustainability of cropland use is essential for guaranteeing a secure food supply and accomplishing agriculture sustainable development. This study was conducted in the ecologically vulnerable Loess Plateau region of China to evaluate the sustainability of cropland use based on an ecological footprint model that integrates emergy analysis. One modified method proposed in 2005 is known as the emergetic ecological footprint (EEF). We enhanced the method by accounting for both the surface soil energy in the carrying capacity calculation and the net topsoil loss for human consumption in the EF calculation. This paper evaluates whether the cropland of the study area was overloaded or sustainably managed during the period from 1981 to 2009. Toward this end, the final results obtained from EEF were compared to conventional EF and previous methods. The results showed that the cropland of Yuanzhou County has not been used sustainably since 1983, and the conventional EF analysis provided similar results. In contrast, a deficit did not appear during this time period when previous calculation methods of others were used. Additionally, the ecological sustainable index (ESI) from three models indicated that the recently used cropland system is unlikely to be unsustainable. PMID:25738289

Effects of bilingualism on the age of onset and progression of MCI and AD: evidence from executive function tests.

PubMed

Bialystok, Ellen; Craik, Fergus I M; Binns, Malcolm A; Ossher, Lynn; Freedman, Morris

2014-03-01

Previous articles have reported that bilingualism is associated with a substantial delay in the onset of both Alzheimer's disease (AD) and Mild Cognitive Impairment (MCI). The present study reports results from 74 MCI patients and 75 AD patients; approximately half of the patients in each group were bilingual. All patients were interviewed to obtain details of their language use, onset of their condition, and lifestyle habits. Patients performed three executive function (EF) tests from the D-KEFS battery (Trails, Color-Word Interference, Verbal Fluency) on 3 occasions over a period of approximately 1 year. Results replicated the finding that bilingual patients are several years older than comparable monolinguals at both age of symptom onset and date of first clinic visit. This result could not be attributed to language group differences in such lifestyle variables as diet, smoking, alcohol consumption, physical activity, or social activity. On the first testing occasion, performance on the EF tasks was generally comparable between the language groups, contesting arguments that bilinguals wait longer before attending the clinic. Finally, EF performance tended to decline over the 3 sessions, but no differences were found between monolinguals and bilinguals in the rate of decline. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Removal of fluoride, SDS, ammonia and turbidity from semiconductor wastewater by combined electrocoagulation-electroflotation.

PubMed

Aoudj, S; Khelifa, A; Drouiche, N

2017-08-01

Semiconductor industry effluents contain organic and inorganic pollutants, such as sodium dodecyl sulfate (SDS), fluoride and ammonia, at high levels which consists a major environmental issue. A combined EC-EF process is proposed as a post-treatment after precipitation for simultaneous clarification and removal of pollutants. In EC step, a hybrid Fe-Al was used as the soluble anode in order to avoid supplementary EC step. EC-Fe is more suitable for SDS removal; EC-Al is more suitable for fluoride removal, while EC with hybrid Al-Fe makes a good compromise. Clarification and ammonia oxidation were achieved in the EF step. Effects of anodic material, initial pH, current, anion nature, chloride concentration and initial pollutant concentration were studied. The final concentrations may reach 0.27, 6.23 and 0.22 mg L -1 for SDS, fluoride and ammonia respectively. These concentrations are far lower than the correspondent discharge limits. Similarly, the final turbidity was found 4.35 NTU which is lower than 5NTU and the treated water does not need further filtration before discharge. Furthermore, the EC-EF process proves to be sufficiently energy-efficient with less soluble electrode consumption. Copyright © 2017 Elsevier Ltd. All rights reserved.

Galectin-3 in heart failure with preserved ejection fraction. A RELAX trial substudy (Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Diastolic Heart Failure).

PubMed

AbouEzzeddine, Omar F; Haines, Phillip; Stevens, Susanna; Nativi-Nicolau, Jose; Felker, G Michael; Borlaug, Barry A; Chen, Horng H; Tracy, Russell P; Braunwald, Eugene; Redfield, Margaret M

2015-03-01

This study hypothesized that elevated galectin-3 (Gal-3) levels would identify patients with more advanced heart failure (HF) with preserved ejection fraction (HFpEF) as assessed by key pathophysiological domains. Gal-3 is implicated in the pathogenesis of cardiac fibrosis but is also increased with normal aging and renal dysfunction. Cardiac fibrosis may contribute to cardiac dysfunction, exercise intolerance, and congestion in HFpEF. Two hundred eight patients from the RELAX (Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Diastolic Heart Failure) trial of sildenafil in HFpEF had Gal-3 measured at enrollment. Pathophysiological domains assessed included biomarkers of neurohumoral activation, fibrosis, inflammation and myocardial necrosis, congestion severity and quality of life, cardiac structure and function, and exercise performance. Analysis adjusted for age, sex, and/or cystatin-C levels. Potential interaction between baseline Gal-3 and treatment (sildenafil) effect on the RELAX study primary endpoint (change in peak oxygen consumption) was tested. Gal-3 levels were associated with age and severity of renal dysfunction. Adjusting for age, sex, and/or cystatin-C, Gal-3 was not associated with biomarkers of neurohumoral activation, fibrosis, inflammation or myocardial necrosis, congestion or quality-of-life impairment, cardiac remodeling or dysfunction, or exercise intolerance. Gal-3 did not identify patients who responded to phosphodiesterase type 5 (PDE-5) inhibitors (interaction p = 0.53). In overt HFpEF, Gal-3 was related to severity of renal dysfunction and accounting for this, was not independently associated with severity of pathophysiological derangements or response PDE-5 inhibition. These findings underscore the need to adjust for renal function when interpreting Gal-3 levels, and call into question the value of Gal-3 to quantify disease severity in overt HFpEF. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Rational Engineering of a Cold-Adapted α-Amylase from the Antarctic Ciliate Euplotes focardii for Simultaneous Improvement of Thermostability and Catalytic Activity

PubMed Central

Yang, Guang; Yao, Hua; Mozzicafreddo, Matteo; Ballarini, Patrizia; Pucciarelli, Sandra

2017-01-01

ABSTRACT The α-amylases are endo-acting enzymes that hydrolyze starch by randomly cleaving the 1,4-α-d-glucosidic linkages between the adjacent glucose units in a linear amylose chain. They have significant advantages in a wide range of applications, particularly in the food industry. The eukaryotic α-amylase isolated from the Antarctic ciliated protozoon Euplotes focardii (EfAmy) is an alkaline enzyme, different from most of the α-amylases characterized so far. Furthermore, EfAmy has the characteristics of a psychrophilic α-amylase, such as the highest hydrolytic activity at a low temperature and high thermolability, which is the major drawback of cold-active enzymes in industrial applications. In this work, we applied site-directed mutagenesis combined with rational design to generate a cold-active EfAmy with improved thermostability and catalytic efficiency at low temperatures. We engineered two EfAmy mutants. In one mutant, we introduced Pro residues on the A and B domains in surface loops. In the second mutant, we changed Val residues to Thr close to the catalytic site. The aim of these substitutions was to rigidify the molecular structure of the enzyme. Furthermore, we also analyzed mutants containing these combined substitutions. Biochemical enzymatic assays of engineered versions of EfAmy revealed that the combination of mutations at the surface loops increased the thermostability and catalytic efficiency of the enzyme. The possible mechanisms responsible for the changes in the biochemical properties are discussed by analyzing the three-dimensional structural model. IMPORTANCE Cold-adapted enzymes have high specific activity at low and moderate temperatures, a property that can be extremely useful in various applications as it implies a reduction in energy consumption during the catalyzed reaction. However, the concurrent high thermolability of cold-adapted enzymes often limits their applications in industrial processes. The α-amylase from the psychrophilic Antarctic ciliate Euplotes focardii (named EfAmy) is a cold-adapted enzyme with optimal catalytic activity in an alkaline environment. These unique features distinguish it from most α-amylases characterized so far. In this work, we engineered a novel EfAmy with improved thermostability, substrate binding affinity, and catalytic efficiency to various extents, without impacting its pH preference. These characteristics can be considered important properties for use in the food, detergent, and textile industries and in other industrial applications. The enzyme engineering strategy developed in this study may also provide useful knowledge for future optimization of molecules to be used in particular industrial applications. PMID:28455329

Rational Engineering of a Cold-Adapted α-Amylase from the Antarctic Ciliate Euplotes focardii for Simultaneous Improvement of Thermostability and Catalytic Activity.

PubMed

Yang, Guang; Yao, Hua; Mozzicafreddo, Matteo; Ballarini, Patrizia; Pucciarelli, Sandra; Miceli, Cristina

2017-07-01

The α-amylases are endo-acting enzymes that hydrolyze starch by randomly cleaving the 1,4-α-d-glucosidic linkages between the adjacent glucose units in a linear amylose chain. They have significant advantages in a wide range of applications, particularly in the food industry. The eukaryotic α-amylase isolated from the Antarctic ciliated protozoon Euplotes focardii ( Ef Amy) is an alkaline enzyme, different from most of the α-amylases characterized so far. Furthermore, Ef Amy has the characteristics of a psychrophilic α-amylase, such as the highest hydrolytic activity at a low temperature and high thermolability, which is the major drawback of cold-active enzymes in industrial applications. In this work, we applied site-directed mutagenesis combined with rational design to generate a cold-active Ef Amy with improved thermostability and catalytic efficiency at low temperatures. We engineered two Ef Amy mutants. In one mutant, we introduced Pro residues on the A and B domains in surface loops. In the second mutant, we changed Val residues to Thr close to the catalytic site. The aim of these substitutions was to rigidify the molecular structure of the enzyme. Furthermore, we also analyzed mutants containing these combined substitutions. Biochemical enzymatic assays of engineered versions of Ef Amy revealed that the combination of mutations at the surface loops increased the thermostability and catalytic efficiency of the enzyme. The possible mechanisms responsible for the changes in the biochemical properties are discussed by analyzing the three-dimensional structural model. IMPORTANCE Cold-adapted enzymes have high specific activity at low and moderate temperatures, a property that can be extremely useful in various applications as it implies a reduction in energy consumption during the catalyzed reaction. However, the concurrent high thermolability of cold-adapted enzymes often limits their applications in industrial processes. The α-amylase from the psychrophilic Antarctic ciliate Euplotes focardii (named Ef Amy) is a cold-adapted enzyme with optimal catalytic activity in an alkaline environment. These unique features distinguish it from most α-amylases characterized so far. In this work, we engineered a novel Ef Amy with improved thermostability, substrate binding affinity, and catalytic efficiency to various extents, without impacting its pH preference. These characteristics can be considered important properties for use in the food, detergent, and textile industries and in other industrial applications. The enzyme engineering strategy developed in this study may also provide useful knowledge for future optimization of molecules to be used in particular industrial applications. Copyright © 2017 Yang et al.

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.

Estimation of methane emission from California natural gas industry.

PubMed

Kuo, Jeff; Hicks, Travis C; Drake, Brian; Chan, Tat Fu

2015-07-01

Energy generation and consumption are the main contributors to greenhouse gases emissions in California. Natural gas is one of the primary sources of energy in California. A study was recently conducted to develop current, reliable, and California-specific source emission factors (EFs) that could be used to establish a more accurate methane emission inventory for the California natural gas industry. Twenty-five natural gas facilities were surveyed; the surveyed equipment included wellheads (172), separators (131), dehydrators (17), piping segments (145), compressors (66), pneumatic devices (374), metering and regulating (M&R) stations (19), hatches (34), pumps (2), and customer meters (12). In total, 92,157 components were screened, including flanges (10,101), manual valves (10,765), open-ended lines (384), pressure relief valves (358), regulators (930), seals (146), threaded connections (57,061), and welded connections (12,274). Screening values (SVs) were measured using portable monitoring instruments, and Hi-Flow samplers were then used to quantify fugitive emission rates. For a given SV range, the measured leak rates might span several orders of magnitude. The correlation equations between the leak rates and SVs were derived. All the component leakage rate histograms appeared to have the same trend, with the majority of leakage rates<0.02 cubic feet per minute (cfm). Using the cumulative distribution function, the geometric mean was found to be a better indicator than the arithmetic mean, as the mean for each group of leakage rates found. For most component types, the pegged EFs for SVs of ≥10,000 ppmV and of ≥50,000 ppmV are relatively similar. The component-level average EFs derived in this study are often smaller than the corresponding ones in the 1996 U.S. Environmental Protection Agency/Gas Research Institute (EPA/GRI) study. Twenty-five natural gas facilities in California were surveyed to develop current, reliable, and California-specific source emission factors (EFs) for the natural gas industry. Screening values were measured by using portable monitoring instruments, and Hi-Flow samplers were then used to quantify fugitive emission rates. The component-level average EFs derived in this study are often smaller than the corresponding ones in the 1996 EPA/GRI study. The smaller EF values from this study might be partially attributable to the employment of the leak detection and repair program by most, if not all, of the facilities surveyed.

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.

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.

Estudo da região HII galática NGC 2579

NASA Astrophysics Data System (ADS)

Riffel, R.; Copetti, M. V. F.

2003-08-01

Desde a descoberta dos gradientes de abundância química em galáxias espirais, as regiões HII galáticas têm sido intensamente estudadas com o objetivo de determinar a forma do gradiente de abundância química na Via-Láctea. Entretanto, a forma do gradiente galático continua controversa e existem muitas regiões HII que continuam inexploradas. A região HII galática NGC 2579 é um objeto que aparece em imagens Ha, como uma pequena mancha brilhante de aproximadamente 2 segundos de arco de diâmetro a 20 segundos de arco ao leste de RCW 20, sendo NGC 2579 muitas vezes confundida com esta última. Apesar de seu alto brilho superficial, NGC 2579 é um objeto pouco estudado provavelmente por problemas de identificação deste objeto. Como parte de um projeto de reavaliação dos gradientes de abundância química das regiões HII na Via-Láctea, estamos realizando um estudo extensivo das propriedades físicas básicas como temperatura eletrônica, densidade eletrônica e composição química da região HII galática NGC 2579. Analisamos dados espectrofotométricos de fenda longa na faixa de 3700Å a 7750Å obtidos com o telescópio de 1.52 m do ESO, Chile, em 2002. Determinamos a temperatura eletrônica usando a razão entre as linhas do [OIII] (l4959+l5007/l4363) e a densidade eletrônica pela razão entre as linhas do [SII] (l6716/l6731). As abundâncias químicas do O, N, Cl, S, Ne e He foram determinadas. Realizamos um estudo de imagens fotométricas nas bandas UBVRI obtidas em 2000 no observatório astronômico San Pedro Mártir, México, para identificar e classificar as estrelas ionizantes de NGC 2579 e determinar a distância deste objeto.

Quantitative analysis of ecological effects for land use planning based on ecological footprint method: a case research in Nanyang City

NASA Astrophysics Data System (ADS)

Zhang, Jing; Liu, Yaolin; Chen, Xinming

2008-10-01

The research of coordinated development between land use and ecological building is a new problem with the development of country economy, whose intention is to improve economy development and protect eco-environment in order to realize regional sustainable development. Evaluating human effects on the ecosystem by a comprehensive, scientific and quantitative method is a critical issue in the process of general land use planning. At present, ecological footprint methodology, as an excellent educational tool applicable to global issues, is essential for quantifying humanity's consumption of natural capital, for overall assessments of human impact on earth as well as for general land use planning. However, quantitative studies on the development trends of ecological footprint (EF) time series and biological capacity (BC) time series in a given region are still rare. Taking Nanyang City as a case study, this paper presents two quantitative estimate indices over time scale called the change rate and scissors difference to quantitatively analyze the trends of EF and BC over the planning period in general land use planning form 1997-2004 and to evaluate the ecological effects of the land use general planning form 1997 to.2010. The results showed that: 1 In Nanyang city, trends of the per capita EF and BC were on the way round, and the ecological deficit enhanced from 1997 to 2010. 2 The difference between the two development trends of per capita EF and BC had been increasing rapidly and the conflict between the EF and BC was aggravated from 1997 to 2010. 3 The general land use planning (1997 - 2010) of Nanyang city had produced some positive effects on the local ecosystem, but the expected biological capacity in 2010 can hardly be realized following this trend. Therefore, this paper introduces a "trinity" land use model in the guidelines of environment- friendly land use pattern and based on the actual situation of Nanyang city, with the systemic synthesis of land utilization of the cities, the village and the suburb as a principal part and the land development reorganization and the ecological environment construction as the key point.

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

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…

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.

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.

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.

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

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.

Left ventricular volume analysis as a basic tool to describe cardiac function.

PubMed

Kerkhof, Peter L M; Kuznetsova, Tatiana; Ali, Rania; Handly, Neal

2018-03-01

The heart is often regarded as a compression pump. Therefore, determination of pressure and volume is essential for cardiac function analysis. Traditionally, ventricular performance was described in terms of the Starling curve, i.e., output related to input. This view is based on two variables (namely, stroke volume and end-diastolic volume), often studied in the isolated (i.e., denervated) heart, and has dominated the interpretation of cardiac mechanics over the last century. The ratio of the prevailing coordinates within that paradigm is termed ejection fraction (EF), which is the popular metric routinely used in the clinic. Here we present an insightful alternative approach while describing volume regulation by relating end-systolic volume (ESV) to end-diastolic volume. This route obviates the undesired use of metrics derived from differences or ratios, as employed in previous models. We illustrate basic principles concerning ventricular volume regulation by data obtained from intact animal experiments and collected in healthy humans. Special attention is given to sex-specific differences. The method can be applied to the dynamics of a single heart and to an ensemble of individuals. Group analysis allows for stratification regarding sex, age, medication, and additional clinically relevant covariates. A straightforward procedure derives the relationship between EF and ESV and describes myocardial oxygen consumption in terms of ESV. This representation enhances insight and reduces the impact of the metric EF, in favor of the end-systolic elastance concept advanced 4 decades ago.

Field Measurements of Trace Gases and Aerosols Emitted by Undersampled Combustion Sources Including Wood and Dung Cooking Fires, Garbage and Crop Residue Burning, and Indonesian Peat Fires

NASA Astrophysics Data System (ADS)

Stockwell, C.; Jayarathne, T. S.; Goetz, D.; Simpson, I. J.; Selimovic, V.; Bhave, P.; Blake, D. R.; Cochrane, M. A.; Ryan, K. C.; Putra, E. I.; Saharjo, B.; Stone, E. A.; DeCarlo, P. F.; Yokelson, R. J.

2017-12-01

Field measurements were conducted in Nepal and in the Indonesian province of Central Kalimantan to improve characterization of trace gases and aerosols emitted by undersampled combustion sources. The sources targeted included cooking with a variety of stoves, garbage burning, crop residue burning, and authentic peat fires. Trace gas and aerosol emissions were studied using a land-based Fourier transform infrared spectrometer, whole air sampling, photoacoustic extinctiometers (405 and 870nm), and filter samples that were analyzed off-line. These measurements were used to calculate fuel-based emission factors (EFs) for up to 90 gases, PM2.5, and PM2.5 constituents. The aerosol optical data measured included EFs for the scattering and absorption coefficients, the single scattering albedo (at 870 and 405 nm), as well as the absorption Ångström exponent. The emissions varied significantly by source, although light absorption by both brown and black carbon (BrC and BC, respectively) was important for all non-peat sources. For authentic peat combustion, the emissions of BC were negligible and absorption was dominated by organic aerosol. The field results from peat burning were in reasonable agreement with recent lab measurements of smoldering Kalimantan peat and compare well to the limited data available from other field studies. The EFs can be used with estimates of fuel consumption to improve regional emissions inventories and assessments of the climate and health impacts of these undersampled sources.

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

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.

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

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.

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.

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

Combined electrocoagulation and electroflotation for removal of fluoride from drinking water.

PubMed

Zuo, Qianhai; Chen, Xueming; Li, Wei; Chen, Guohua

2008-11-30

A combined electrocoagulation (EC) and electroflotation (EF) process was proposed to remove fluoride from drinking water. Its efficacy was investigated under different conditions. Experimental results showed that the combined process could remove fluoride effectively. The total hydraulic retention time required was only 30 min. After treatment, the fluoride concentration was reduced from initial 4.0-6.0mg/L to lower than 1.0mg/L. The influent pH value was found to be a very important variable that affected fluoride removal significantly. The optimal influent pH range is 6.0-7.0 at which not only can effective defluoridation be achieved, but also no pH readjustment is needed after treatment. In addition, it was found that SO(4)(2-) had negative effect; Ca(2+) had positive effect; while Cl(-) had little effect on the fluoride removal. The EC charge loading, EF charge loading and energy consumption were 3.0 Faradays/m(3), 1.5 Faradays/m(3), and 1.2 kWh/m(3), respectively, under typical conditions where fluoride was reduced from initial 4.0 to 0.87 mg/L.

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.

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.

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

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.

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.

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.

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

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.

Do Optimal Prognostic Thresholds in Continuous Physiological Variables Really Exist? Analysis of Origin of Apparent Thresholds, with Systematic Review for Peak Oxygen Consumption, Ejection Fraction and BNP

PubMed Central

Leong, Tora; Rehman, Michaela B.; Pastormerlo, Luigi Emilio; Harrell, Frank E.; Coats, Andrew J. S.; Francis, Darrel P.

2014-01-01

Background Clinicians are sometimes advised to make decisions using thresholds in measured variables, derived from prognostic studies. Objectives We studied why there are conflicting apparently-optimal prognostic thresholds, for example in exercise peak oxygen uptake (pVO2), ejection fraction (EF), and Brain Natriuretic Peptide (BNP) in heart failure (HF). Data Sources and Eligibility Criteria Studies testing pVO2, EF or BNP prognostic thresholds in heart failure, published between 1990 and 2010, listed on Pubmed. Methods First, we examined studies testing pVO2, EF or BNP prognostic thresholds. Second, we created repeated simulations of 1500 patients to identify whether an apparently-optimal prognostic threshold indicates step change in risk. Results 33 studies (8946 patients) tested a pVO2 threshold. 18 found it prognostically significant: the actual reported threshold ranged widely (10–18 ml/kg/min) but was overwhelmingly controlled by the individual study population's mean pVO2 (r = 0.86, p<0.00001). In contrast, the 15 negative publications were testing thresholds 199% further from their means (p = 0.0001). Likewise, of 35 EF studies (10220 patients), the thresholds in the 22 positive reports were strongly determined by study means (r = 0.90, p<0.0001). Similarly, in the 19 positives of 20 BNP studies (9725 patients): r = 0.86 (p<0.0001). Second, survival simulations always discovered a “most significant” threshold, even when there was definitely no step change in mortality. With linear increase in risk, the apparently-optimal threshold was always near the sample mean (r = 0.99, p<0.001). Limitations This study cannot report the best threshold for any of these variables; instead it explains how common clinical research procedures routinely produce false thresholds. Key Findings First, shifting (and/or disappearance) of an apparently-optimal prognostic threshold is strongly determined by studies' average pVO2, EF or BNP. Second, apparently-optimal thresholds always appear, even with no step in prognosis. Conclusions Emphatic therapeutic guidance based on thresholds from observational studies may be ill-founded. We should not assume that optimal thresholds, or any thresholds, exist. PMID:24475020

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…

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.

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

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

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.

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.

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

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.

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.

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.

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

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.

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.

An urban metabolism and ecological footprint assessment of Metro Vancouver.

PubMed

Moore, Jennie; Kissinger, Meidad; Rees, William E

2013-07-30

As the world urbanizes, the role of cities in determining sustainability outcomes grows in importance. Cities are the dominant form of human habitat, and most of the world's resources are either directly or indirectly consumed in cities. Sustainable city analysis and management requires understanding the demands a city places on a wider geographical area and its ecological resource base. We present a detailed, integrated urban metabolism of residential consumption and ecological footprint analysis of the Vancouver metropolitan region for the year 2006. Our overall goal is to demonstrate the application of a bottom-up ecological footprint analysis using an urban metabolism framework at a metropolitan, regional scale. Our specific objectives are: a) to quantify energy and material consumption using locally generated data and b) to relate these data to global ecological carrying capacity. Although water is the largest material flow through Metro Vancouver (424,860,000 m(3)), it has the smallest ecological footprint (23,100 gha). Food (2,636,850 tonnes) contributes the largest component to the ecological footprint (4,514,400 gha) which includes crop and grazing land as well as carbon sinks required to sequester emissions from food production and distribution. Transportation fuels (3,339,000 m(3)) associated with motor vehicle operation and passenger air travel comprises the second largest material flow through the region and the largest source of carbon dioxide emissions (7,577,000 tonnes). Transportation also accounts for the second largest component of the EF (2,323,200 gha). Buildings account for the largest electricity flow (17,515,150 MWh) and constitute the third largest component of the EF (1,779,240 gha). Consumables (2,400,000 tonnes) comprise the fourth largest component of the EF (1,414,440 gha). Metro Vancouver's total Ecological Footprint in 2006 was 10,071,670 gha, an area approximately 36 times larger than the region itself. The EFA reveals that cropland and carbon sinks (forested land required to sequester carbon dioxide emissions) account for 90% of Metro Vancouver's overall demand for biocapacity. The per capita ecological footprint is 4.76 gha, nearly three times the per capita global supply of biocapacity. Note that this value excludes national government services that operate outside the region and could account for up to an additional 2 gha/ca. Copyright © 2013 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.

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

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.

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.

Field accumulation risks of heavy metals in soil and vegetable crop irrigated with sewage water in western region of Saudi Arabia.

PubMed

Balkhair, Khaled S; Ashraf, Muhammad Aqeel

2016-01-01

Wastewater irrigated fields can cause potential contamination with heavy metals to soil and groundwater, thus pose a threat to human beings . The current study was designed to investigate the potential human health risks associated with the consumption of okra vegetable crop contaminated with toxic heavy metals. The crop was grown on a soil irrigated with treated wastewater in the western region of Saudi Arabia during 2010 and 2011. The monitored heavy metals included Cd, Cr, Cu, Pb and Zn for their bioaccumulation factors to provide baseline data regarding environmental safety and the suitability of sewage irrigation in the future. The pollution load index (PLI), enrichment factor (EF) and contamination factor (CF) of these metals were calculated. The pollution load index of the studied soils indicated their level of metal contamination. The concentrations of Ni, Pb, Cd and Cr in the edible portions were above the safe limit in 90%, 28%, 83% and 63% of the samples, respectively. The heavy metals in the edible portions were as follows: Cr > Zn > Ni > Cd > Mn > Pb > Cu > Fe. The Health Risk Index (HRI) was >1 indicating a potential health risk. The EF values designated an enhanced bio-contamination compared to other reports from Saudi Arabia and other countries around the world. The results indicated a potential pathway of human exposure to slow poisoning by heavy metals due to the indirect utilization of vegetables grown on heavy metal-contaminated soil that was irrigated by contaminated water sources. The okra tested was not safe for human use, especially for direct consumption by human beings. The irrigation source was identified as the source of the soil pollution in this study.

Field accumulation risks of heavy metals in soil and vegetable crop irrigated with sewage water in western region of Saudi Arabia

PubMed Central

Balkhair, Khaled S.; Ashraf, Muhammad Aqeel

2015-01-01

Wastewater irrigated fields can cause potential contamination with heavy metals to soil and groundwater, thus pose a threat to human beings . The current study was designed to investigate the potential human health risks associated with the consumption of okra vegetable crop contaminated with toxic heavy metals. The crop was grown on a soil irrigated with treated wastewater in the western region of Saudi Arabia during 2010 and 2011. The monitored heavy metals included Cd, Cr, Cu, Pb and Zn for their bioaccumulation factors to provide baseline data regarding environmental safety and the suitability of sewage irrigation in the future. The pollution load index (PLI), enrichment factor (EF) and contamination factor (CF) of these metals were calculated. The pollution load index of the studied soils indicated their level of metal contamination. The concentrations of Ni, Pb, Cd and Cr in the edible portions were above the safe limit in 90%, 28%, 83% and 63% of the samples, respectively. The heavy metals in the edible portions were as follows: Cr > Zn > Ni > Cd > Mn > Pb > Cu > Fe. The Health Risk Index (HRI) was >1 indicating a potential health risk. The EF values designated an enhanced bio-contamination compared to other reports from Saudi Arabia and other countries around the world. The results indicated a potential pathway of human exposure to slow poisoning by heavy metals due to the indirect utilization of vegetables grown on heavy metal-contaminated soil that was irrigated by contaminated water sources. The okra tested was not safe for human use, especially for direct consumption by human beings. The irrigation source was identified as the source of the soil pollution in this study. PMID:26858563

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

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

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.

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

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

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.

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.

Determination of the kinetics of guanine nucleotide exchange on EF-Tu and EF-Ts: continuing uncertainties.

PubMed

Manchester, Keith L

2004-01-30

An analysis is made of the rate constants for the reactions involving the interactions of EF-Tu, EF-Ts, GDP, and GTP recently derived by Gromadski et al. [Biochemistry 41 (2002) 162]. Though their measured values appear to allow a reasonable rate of nucleotide exchange sufficient to support rates of protein synthesis in vivo, their data underestimate the thermodynamic barrier involved in nucleotide exchange and therefore cannot be considered definitive. A kinetic scheme consistent with the thermodynamic barrier can be achieved by modification of various rate constants, particularly of those involving the release of EF-Ts from EF-Tu.GTP.EF-Ts, but such constants are markedly different from what are experimentally observed. It thus remains impossible at present satisfactorily to model guanine nucleotide exchange on EF-Tu, catalysed by EF-Ts by a double displacement mechanism, with experimentally derived rate constants. Metabolic control analysis has been applied to determine the degree of flux control of the different steps in the pathway.

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.

Pathophysiological understanding of HFpEF: microRNAs as part of the puzzle.

PubMed

Rech, Monika; Barandiarán Aizpurua, Arantxa; van Empel, Vanessa; van Bilsen, Marc; Schroen, Blanche

2018-05-01

Half of all heart failure patients have preserved ejection fraction (HFpEF). Comorbidities associated with and contributing to HFpEF include obesity, diabetes and hypertension. Still, the underlying pathophysiological mechanisms of HFpEF are unknown. A preliminary consensus proposes that the multi-morbidity triggers a state of systemic, chronic low-grade inflammation, and microvascular dysfunction, causing reduced nitric oxide bioavailability to adjacent cardiomyocytes. As a result, the cardiomyocyte remodels its contractile elements and fails to relax properly, causing diastolic dysfunction, and eventually HFpEF. HFpEF is a complex syndrome for which currently no efficient therapies exist. This is notably due to the current one-size-fits-all therapy approach that ignores individual patient differences. MicroRNAs have been studied in relation to pathophysiological mechanisms and comorbidities underlying and contributing to HFpEF. As regulators of gene expression, microRNAs may contribute to the pathophysiology of HFpEF. In addition, secreted circulating microRNAs are potential biomarkers and as such, they could help stratify the HFpEF population and open new ways for individualized therapies. In this review, we provide an overview of the ever-expanding world of non-coding RNAs and their contribution to the molecular mechanisms underlying HFpEF. We propose prospects for microRNAs in stratifying the HFpEF population. MicroRNAs add a new level of complexity to the regulatory network controlling cardiac function and hence the understanding of gene regulation becomes a fundamental piece in solving the HFpEF puzzle.

Heart rate response and functional capacity in patients with chronic heart failure with preserved ejection fraction.

PubMed

Domínguez, Eloy; Palau, Patricia; Núñez, Eduardo; Ramón, José María; López, Laura; Melero, Joana; Bellver, Alejandro; Santas, Enrique; Chorro, Francisco J; Núñez, Julio

2018-03-24

The mechanisms of exercise intolerance in heart failure with preserved ejection fraction (HFpEF) are not yet elucidated. Chronotropic incompetence has emerged as a potential mechanism. We aimed to evaluate whether heart rate (HR) response to exercise is associated to functional capacity in patients with symptomatic HFpEF. We prospectively studied 74 HFpEF patients [35.1% New York Heart Association Class III, 53% female, age (mean ± standard deviation) 72.5 ± 9.1 years, and 59.5% atrial fibrillation]. Functional performance was assessed by peak oxygen consumption (peak VO 2 ). The mean (standard deviation) peak VO 2 was 10 ± 2.8 mL/min/kg. The following chronotropic parameters were calculated: Delta-HR (HR at peak exercise - HR at rest), chronotropic index (CI) = (HR at peak exercise - resting HR)/[(220 - age) - resting HR], and CI according to the equation developed by Keteyian et al. (CIK) (HR at peak exercise - HR at rest)/[119 + (HR at rest/2) - (age/2) - 5 - HR at rest]. In a bivariate setting, peak VO 2 was positively and significantly correlated with Delta-HR (r = 0.35, P = 0.003), CI (r = 0.27, P = 0.022), CIK (r = 0.28, P = 0.018), and borderline with HR at peak exercise (r = 0.22, P = 0.055). In a multivariable linear regression analysis that included clinical, analytical, echocardiographic, and functional capacity covariates, the chronotropic parameters were positively associated with peak VO 2 . We found a linear relationship between Delta-HR and peak VO 2 (β coefficient of 0.03; 95% confidence interval: 0.004-0.05; P = 0.030); conversely, the association among CIs and peak VO 2 was exponentially shaped. In patients with chronic HFpEF, the HR response to exercise was positively associated to patient's functional capacity. © 2018 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

The C-terminal Helix of Pseudomonas aeruginosa Elongation Factor Ts Tunes EF-Tu Dynamics to Modulate Nucleotide Exchange.

PubMed

De Laurentiis, Evelina Ines; Mercier, Evan; Wieden, Hans-Joachim

2016-10-28

Little is known about the conservation of critical kinetic parameters and the mechanistic strategies of elongation factor (EF) Ts-catalyzed nucleotide exchange in EF-Tu in bacteria and particularly in clinically relevant pathogens. EF-Tu from the clinically relevant pathogen Pseudomonas aeruginosa shares over 84% sequence identity with the corresponding elongation factor from Escherichia coli Interestingly, the functionally closely linked EF-Ts only shares 55% sequence identity. To identify any differences in the nucleotide binding properties, as well as in the EF-Ts-mediated nucleotide exchange reaction, we performed a comparative rapid kinetics and mutagenesis analysis of the nucleotide exchange mechanism for both the E. coli and P. aeruginosa systems, identifying helix 13 of EF-Ts as a previously unnoticed regulatory element in the nucleotide exchange mechanism with species-specific elements. Our findings support the base side-first entry of the nucleotide into the binding pocket of the EF-Tu·EF-Ts binary complex, followed by displacement of helix 13 and rapid binding of the phosphate side of the nucleotide, ultimately leading to the release of EF-Ts. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Precision Medicine for Heart Failure with Preserved Ejection Fraction: An Overview.

PubMed

Shah, Sanjiv J

2017-06-01

There are few proven therapies for heart failure with preserved ejection fraction (HFpEF). The lack of therapies, along with increased recognition of the disorder and its underlying pathophysiology, has led to the acknowledgement that HFpEF is heterogeneous and is not likely to respond to a one-size-fits-all approach. Thus, HFpEF is a prime candidate to benefit from a precision medicine approach. For this reason, we have assembled a compendium of papers on the topic of precision medicine in HFpEF in the Journal of Cardiovascular Translational Research. These papers cover a variety of topics relevant to precision medicine in HFpEF, including automated identification of HFpEF patients; machine learning, novel molecular approaches, genomics, and deep phenotyping of HFpEF; and clinical trial designs that can be used to advance precision medicine in HFpEF. In this introductory article, we provide an overview of precision medicine in HFpEF with the hope that the work described here and in the other papers in this special theme issue will stimulate investigators and clinicians to advance a more targeted approach to HFpEF classification and treatment.

Precision Medicine for Heart Failure with Preserved Ejection Fraction: An Overview

PubMed Central

Shah, Sanjiv J.

2017-01-01

There are few proven therapies for heart failure with preserved ejection fraction (HFpEF). The lack of therapies, along with increased recognition of the disorder and its underlying pathophysiology, has led to the acknowledgement that HFpEF is heterogeneous and is not likely to respond to a one-size-fits-all approach. Thus, HFpEF is a prime candidate to benefit from a precision medicine approach. For this reason, we have assembled a compendium of papers on the topic of precision medicine in HFpEF in the Journal of Cardiovascular Translational Research. These papers cover a variety of topics relevant to precision medicine in HFpEF, including automated identification of HFpEF patients; machine learning, novel molecular approaches, genomics, and deep phenotyping of HFpEF; and clinical trial designs that can be used to advance precision medicine in HFpEF. In this introductory article, we provide an overview of precision medicine in HFpEF with the hope that the work described here and in the other papers in this special theme issue will stimulate investigators and clinicians to advance a more targeted approach to HFpEF classification and treatment. PMID:28585183

Evaluation of compatibility between different types of adhesives and dual-cured resin cement.

PubMed

Franco, Eduardo B; Lopes, Lawrence G; D'alpino, Paulo H P; Pereira, José C; Mondelli, Rafael F L; Navarro, Maria F L

2002-01-01

The objective of this in vitro study was to evaluate the bonding compatibility between different adhesives and a dual-cured resin cement, using a conventional tensile bond test. The adhesives used were: Prime & Bond (PB) (Dentsply) (PB), Scotchbond Multi Purpose (SB) (3M), and the activator Self Cure (SC) (Dentsply). The dual-curing resin cement used was Enforce (EF) (Dentsply). Six groups with five specimens in each were tested: G1: EF/PB/EF (light cured); G2: EF/SB/EF (light cured); G3: EF/PB+SC/EF (light cured); G4: EF/PB+SC/EF (only chemically cured); G5: EF/EF (light cured); G6: EF/EF (only chemically cured). The resin cement was applied in two stainless steel molds with a cone-shaped perforation measuring 4 mm in diameter and 1 mm in thickness, and the adhesive was applied between them. Ten minutes after specimens were cured, the tensile strength was measured in a universal testing machine at a crosshead speed of 0.5 mm/min. The mean values (MPa) +/- SD obtained in each experimental group were: G1: 1.4 +/- 0.2; G2: 1.3 +/- 0.2; G3: 1.2 +/- 0.4; G4: 0.8 +/- 0.2; G5: 1.2 +/- 0.1; G6: 0.7 +/- 0.1. The results were statistically evaluated using nonparametric Kruskal-Wallis and Dunn tests (p < or = 0.05). Statistically significant differences among groups were found only between G1 and G4, and G1 and G6. There was no incompatibility among the different adhesives used with dual-cured resin cement. The lowest tensile bond strength values occurred in the absence of photoactivation.

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.

Application of electrochemical advanced oxidation processes to the mineralization of the herbicide diuron.

PubMed

Pipi, Angelo R F; Sirés, Ignasi; De Andrade, Adalgisa R; Brillas, Enric

2014-08-01

Here, solutions with 0.185mM of the herbicide diuron of pH 3.0 have been treated by electrochemical advanced oxidation processes (EAOPs) like electrochemical oxidation with electrogenerated H2O2 (EO-H2O2), electro-Fenton (EF) and UVA photoelectro-Fenton (PEF) or solar PEF (SPEF). Trials were performed in stirred tank reactors of 100mL and in a recirculation flow plant of 2.5L using a filter-press reactor with a Pt or boron-doped diamond (BDD) anode and an air-diffusion cathode for H2O2 electrogeneration. Oxidant hydroxyl radicals were formed from water oxidation at the anode and/or in the bulk from Fenton's reaction between added Fe(2+) and generated H2O2. In both systems, the relative oxidation ability of the EAOPs increased in the sequence EO-H2O2

Modification of rat detrusor muscle contraction by ascorbic acid and citric acid involving enhanced neurotransmitter release and Ca2+ influx.

PubMed

Dasgupta, Jaydip; Elliott, Ruth A; Tincello, Douglas G

2009-01-01

Consumption of carbonated soft drinks is independently associated with the development of overactive bladder (OR 1.41, 95% Cl 1.02-1.95). We have shown previously that artificial sweeteners, present in carbonated soft drinks, enhanced detrusor muscle contraction. Other constituents of soft drinks are preservatives and antioxidants, we evaluated the effects of two of these, ascorbic acid and citric acid, on the contractile response of isolated rat bladder muscle strips. Detrusor muscle strips were suspended in a perfusion organ bath. We determined the effect of ascorbic acid and citric acid on the contractile responses to electrical field stimulation (EFS) in the absence and presence of atropine, carbachol, alpha, beta methylene ATP, potassium and calcium. Ascorbic acid and citric acid (10(-7) M to 10(-3) M) enhanced the contractile response to 10 Hz EFS compared to control (P < 0.01). The frequency and amplitude of spontaneous bladder contractions were enhanced in the presence of ascorbic acid and citric acid by 14%, 21%, 21%, and 11% respectively. Ascorbic acid 10(-4) M significantly increased the atropine resistant response to EFS 5 Hz by 37% (P < 0.01) and inhibited contraction in response to carbachol 10(-4) M by 24%, (P < 0.05). Both ascorbic acid 10(-4) M and citric acid 10(-5) M significantly enhanced maximum contractile responses to alpha, beta methylene ATP, KCI and calcium compared to control. Ascorbic acid and citric acid augmented bladder muscle contraction possibly by enhanced Ca(2+) influx. Presynaptic neurotransmitter release was enhanced by ascorbic acid. Carbonated beverages containing preservatives may aggravate symptoms of OAB. (c) 2009 Wiley-Liss, Inc.

Emission characteristics of NOx, CO, NH3 and VOCs from gas-fired industrial boilers based on field measurements in Beijing city, China

NASA Astrophysics Data System (ADS)

Yue, Tao; Gao, Xiang; Gao, Jiajia; Tong, Yali; Wang, Kun; Zuo, Penglai; Zhang, Xiaoxi; Tong, Li; Wang, Chenlong; Xue, Yifeng

2018-07-01

In the past decade, due to the management policies and coal combustion controls in Beijing, the consumption of natural gas has increased gradually. Nevertheless, the research on the emission characteristics of gaseous pollutants emitted from gas-fired industrial boilers, especially considering the influence of low nitrogen (low-NOx) retrofit policy of gas boilers, is scarcely. In this study, based on literature and field investigations, onsite measurements of NOx, CO, NH3 and VOCs (Volatile Organic Compounds) emissions from gas-fired industrial boilers as well as the key factors that affected the emission of gaseous pollutants were discussed. Category-specific emission factors (EFs) of NOx, CO, NH3 and VOCs were obtained from the field measurements of 1107 "low-NOx" retrofitted and unabated gas-fired industrial boilers. Our results showed that operating load and control measures were the two key factors affecting the formation of gaseous pollutants. The EFs of NOx (EFNOx) and CO (EFCO) of atmospheric combustion boilers (ACBs) were much higher than the EFs of chamber combustion boilers (CCBs). The total emissions of NOx, CO, NH3 and VOCs from gas-fired industrial boilers in Beijing in the year of 2015 were estimated at 10489.6 t, 3272.8 t, 196.4 t and 235.4 t, respectively. Alkanes, BTEX, oxygenated VOCs and non-reactive organic matter were the four main chemical components of VOCs. As for the spatial distributions, the emissions of NOx, CO, NH3 and VOCs from gas-fired industrial boilers in Beijing were predominantly concentrated in central six urban districts. In the future, more detailed investigation and field tests for all kinds of gas-fired industrial boilers are still greatly needed to achieve more reliable estimations of atmospheric pollutants from gas-fired industrial boilers.

The reciprocal relationship between executive function and theory of mind in middle childhood: a 1-year longitudinal perspective.

PubMed

Austin, Gina; Groppe, Karoline; Elsner, Birgit

2014-01-01

There is robust evidence showing a link between executive function (EF) and theory of mind (ToM) in 3- to 5-year-olds. However, it is unclear whether this relationship extends to middle childhood. In addition, there has been much discussion about the nature of this relationship. Whereas some authors claim that ToM is needed for EF, others argue that ToM requires EF. To date, however, studies examining the longitudinal relationship between distinct subcomponents of EF [i.e., attention shifting, working memory (WM) updating, inhibition] and ToM in middle childhood are rare. The present study examined (1) the relationship between three EF subcomponents (attention shifting, WM updating, inhibition) and ToM in middle childhood, and (2) the longitudinal reciprocal relationships between the EF subcomponents and ToM across a 1-year period. EF and ToM measures were assessed experimentally in a sample of 1,657 children (aged 6-11 years) at time point one (t1) and 1 year later at time point two (t2). Results showed that the concurrent relationships between all three EF subcomponents and ToM pertained in middle childhood at t1 and t2, respectively, even when age, gender, and fluid intelligence were partialled out. Moreover, cross-lagged structural equation modeling (again, controlling for age, gender, and fluid intelligence, as well as for the earlier levels of the target variables), revealed partial support for the view that early ToM predicts later EF, but stronger evidence for the assumption that early EF predicts later ToM. The latter was found for attention shifting and WM updating, but not for inhibition. This reveals the importance of studying the exact interplay of ToM and EF across childhood development, especially with regard to different EF subcomponents. Most likely, understanding others' mental states at different levels of perspective-taking requires specific EF subcomponents, suggesting developmental change in the relations between EF and ToM across childhood.

Measuring executive function in Indian mothers and their 4-year-old daughters.

PubMed

von Suchodoletz, Antje; Slot, Pauline L; Shroff, Delshad M

2017-03-01

Executive function (EF), including cognitive flexibility, attention shifting, and inhibitory control, has been linked to a range of outcomes across the lifespan, such as school readiness and academic functioning, job performance, health, and social-emotional well-being. Yet, research investigating links between parent EF and child EF is still limited. This is partly due to challenges in measuring the same EF abilities in parents and their children. The current study investigated the applicability of a computer-based battery of various EF tasks for use with both mothers and children. The battery included the following EF tasks: Dimensional Change Card Sort, Hearts and Flowers, and Fish Flanker. Participants were 80 Indian mothers and their 4-year-old daughters. EF was measured with regard to accuracy scores, response time, and inverse efficiency (IE) scores of the most complex blocks of each task. Scoring patterns indicated that children's task performance appeared to be determined by their ability to recognize the cue indicating which task to perform at any given trial and to inhibit an incorrect response. In contrast, mothers' performance appeared to be determined by response time, that is, their ability to be quick in giving the correct response. However, for both children and mothers, IE scores best captured individual differences in EF performance between participants. Furthermore, confirmatory factor analyses found that, for both children and mothers, all EF measures loaded on a latent factor, suggesting that the measures shared common variance in EF. There appeared to be no significant association between mothers' and children's EF scores, controlling for several background variables. Directions for further research include examining the applicability of the EF task battery to reliably describe developmental trajectories of EF abilities over time, and further examining variability in the parent-child EF association across the lifespan. © 2017 The Institute of Psychology, Chinese Academy of Sciences and John Wiley & Sons Australia, Ltd.

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.

Heart Failure With Improved Ejection Fraction: Clinical Characteristics, Correlates of Recovery, and Survival: Results From the Valsartan Heart Failure Trial.

PubMed

Florea, Viorel G; Rector, Thomas S; Anand, Inder S; Cohn, Jay N

2016-07-01

Heart failure with recovered or improved ejection fraction (HFiEF) has been proposed as a new category of HF. Whether HFiEF is clinically distinct from HF with persistently reduced ejection fraction remains to be validated. Of the 5010 subjects enrolled in the Valsartan Heart Failure Trial (Val-HeFT), 3519 had a baseline left ventricular EF of <35% and a follow-up echocardiographic assessment of EF at 12 months. Of these, 321 (9.1%) patients who had a 12-month EF of >40% constituted the subgroup with HFiEF. EF improved from 28.7±5.6% to 46.5±5.6% in the subgroup with HFiEF and remained reduced (25.2±6.2% and 27.5±7.1%) in the subgroup with HF with reduced ejection fraction. The group with HFiEF had a less severe hemodynamic, biomarker, and neurohormonal profile, and it was treated with a more intense HF medication regimen. Subjects who had higher blood pressure and those treated with a β-blocker or randomized to valsartan had greater odds of being in the HFiEF group, whereas those with an ischemic pathogenesis, a more dilated left ventricle, and a detectable hs-troponin had lower odds of an improvement in EF. Recovery of the EF to >40% was associated with a better survival compared with persistently reduced EF. Our data support HFiEF as a stratum of HF with reduced ejection fraction with a more favorable outcome, which occurs in a minority of patients with HF with reduced ejection fraction who have a lower prevalence of ischemic heart disease, a less severe hemodynamic, biomarker, and neurohormonal profile, and who are treated with a more intense HF medication regimen. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00336336. © 2016 American Heart Association, Inc.

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.

Hot and Cool Executive Functions in Children with Attention-Deficit/Hyperactivity Disorder and Comorbid Oppositional Defiant Disorder.

PubMed

Antonini, Tanya N; Becker, Stephen P; Tamm, Leanne; Epstein, Jeffery N

2015-09-01

While neuropsychological deficits in both "hot" and "cool" executive functions (EFs) have been documented among individuals with attention-deficit/hyperactivity disorder (ADHD), these EF deficits are not universal across all individuals with this diagnosis. One potential moderator of executive dysfunction may be the presence of comorbid oppositional defiant disorder (ODD). This study examined the association between "hot" and "cool" EFs and comorbid ODD in children with ADHD. Thirty-three children with ADHD and comorbid ODD (ADHD+ODD), 67 with ADHD without ODD (ADHD-ODD), and 30 typically developing controls participated. Children were 7-12 years of age. "Cool" EFs were assessed with a spatial span task and a card sorting test. "Hot" EFs were assessed using a delay discounting task and a gambling task. ADHD-ODD and ADHD+ODD groups performed more poorly on "cool" EF tasks than controls, but did not differ from each other. Furthermore, the number of ADHD symptoms, but not ODD symptoms, was associated with "cool" EF scores. The three groups did not differ on "hot" EF tasks and the number of ADHD or ODD symptoms was unrelated to "hot" EF scores. In sum, children with ADHD presented with "cool" EF deficits which appear to be unrelated to ODD comorbidity. However, "hot" EF deficits were not present among children with ADHD, irrespective of comorbid ODD status.

Maximizing Performance: Augmented Feedback, Focus of Attention, and/or Reward?

PubMed

Wälchli, Michael; Ruffieux, Jan; Bourquin, Yann; Keller, Martin; Taube, Wolfgang

2016-04-01

Different approaches like providing augmented feedback (aF), applying an external focus of attention (EF), or rewarding participants with money (RE) have been shown to instantly enhance motor performance. So far, these approaches have been tested either in separate studies or directly against each other. However, there is no study that combined aF, EF, and/or RE to test whether this provokes additional benefits. The aim of the present study was therefore to identify the most powerful combination. Eighteen participants performed maximal countermovement jumps in six different conditions: neutral (NE), aF, RE, aF + EF, aF + RE, and aF + EF + RE. Participants demonstrated the highest jump heights with aF + EF, followed by aF + EF + RE, aF + RE, aF, RE, and finally, NE. Activity of the M. rectus femoris differed significantly between conditions resulting in lower muscular activity in aF + EF and aF + EF + RE compared with NE. All other parameters, such as ground reaction forces and joint angles, were comparable across conditions. This is the first study showing superior performance when combining aF with EF. As reduced muscular activity was found only in conditions with EF, it is argued in line with the constrained action hypothesis that adopting an EF improves movement efficiency. In contrast, aF seems to rather enhance (intrinsic) motivation. However, monetary reward did not further amplify performance.

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.

Developmental trends of hot and cool executive function in school-aged children with and without autism spectrum disorder: Links with theory of mind.

PubMed

Kouklari, Evangelia-Chrysanthi; Tsermentseli, Stella; Monks, Claire P

2018-03-26

The development of executive function (EF) in autism spectrum disorder (ASD) has been investigated using only "cool"-cognitive EF tasks while there is limited knowledge regarding the development of "hot"-affective EF. Although cool EF development and its links to theory of mind (ToM) have been widely examined, understanding of the influence of hot EF to ToM mechanisms is minimal. The present study introduced a longitudinal design to examine the developmental changes in cool and hot EF of children with ASD (n = 45) and matched (to age and IQ) controls (n = 37) as well as the impact of EF on ToM development over a school year. For children with ASD, although selective cool (working memory and inhibition) and hot (affective decision making) EF domains presented age-related improvements, they never reached the performance level of the control group. Early cool working memory predicted later ToM in both groups but early hot delay discounting predicted later ToM only in the ASD group. No evidence was found for the reverse pattern (early ToM predicting later EF). These findings suggest that improvements in some EF aspects are evident in school age in ASD and highlight the crucial role that both cool and hot EF play in ToM development.

Possibility of the transformation of eEF-2 (100 kDa) to eEF-2 (65 kDa) in the peptide elongation process in vitro.

PubMed

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

1999-02-16

Two active eEF-2 polypeptides of approximately 100 and 65 kDa were copurified from rat liver cells and separated. The fate of eEF-2 (100 kDa) during its binding to ribosomes and in the translocation step of the peptide elongation process was investigated. It was shown that eEF-2 (100 kDa) did not change its form during the process of binding to the ribosomes. In the postribosomal supernatant, obtained from the postincubation mixture of the elongation process, only eEF-2 (65 kDa) was found. These results suggest that the form of eEF-2 (100 kDa), when bound to the ribosome during the elongation process, is transformed to eEF-2 (65 kDa). Copyright 1999 Academic Press.

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.

Differential Responses of Post-Exercise Recovery of Leg Blood Flow and Oxygen Uptake Kinetics in HFpEF versus HFrEF.

PubMed

Thompson, Richard B; Pagano, Joseph J; Mathewson, Kory W; Paterson, Ian; Dyck, Jason R; Kitzman, Dalane W; Haykowsky, Mark J

2016-01-01

The goals of the current study were to compare leg blood flow, oxygen extraction and oxygen uptake (VO2) after constant load sub-maximal unilateral knee extension (ULKE) exercise in patients with heart failure with reduced ejection fraction (HFrEF) compared to those with preserved ejection fraction (HFpEF). Previously, it has been shown that prolonged whole body VO2 recovery kinetics are directly related to disease severity and all-cause mortality in HFrEF patients. To date, no study has simultaneously measured muscle-specific blood flow and oxygen extraction post exercise recovery kinetics in HFrEF or HFpEF patients; therefore it is unknown if muscle VO2 recovery kinetics, and more specifically, the recovery kinetics of blood flow and oxygen extraction at the level of the muscle, differ between HF phenotypes. Ten older (68±10yrs) HFrEF (n = 5) and HFpEF (n = 5) patients performed sub-maximal (85% of maximal weight lifted during an incremental test) ULKE exercise for 4 minutes. Femoral venous blood flow and venous O2 saturation were measured continuously from the onset of end-exercise, using a novel MRI method, to determine off-kinetics (mean response times, MRT) for leg VO2 and its determinants. HFpEF and HFrEF patients had similar end-exercise leg blood flow (1.1±0.6 vs. 1.2±0.6 L/min, p>0.05), venous saturation (42±12 vs. 41±11%, p>0.05) and VO2 (0.13±0.08 vs. 0.11±0.05 L/min, p>0.05); however HFrEF had significantly delayed recovery MRT for flow (292±135sec. vs 105±63sec., p = 0.004) and VO2 (95±37sec. vs. 47±15sec., p = 0.005) compared to HFpEF. Impaired muscle VO2 recovery kinetics following ULKE exercise differentiated HFrEF from HFpEF patients and suggests distinct underlying pathology and potential therapeutic approaches in these populations.

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.

Social Skills and Executive Function Among Youth With Sickle Cell Disease: A Preliminary Investigation

PubMed Central

Wolfe, Kelly; Lebensburger, Jeffrey; Nieman, Jilian; Barnes, Margaux; Nolan, William; King, Allison; Madan-Swain, Avi

2014-01-01

Objectives To explore the relationship between executive function (EF) and social skills in youth with sickle cell disease (SCD). Methods 20 youth with SCD completed objective tests of EF (Tasks of Executive Control; Animal Sorting subtest from the Developmental Neuropsychological Assessment-Second Edition), an IQ screener, and paper-and-pencil measures of social skills (Social Skills Improvement System [SSIS]). Primary caregivers completed paper-and-pencil measures of EF (Behavior Rating Inventory of Executive Function) and social skills (SSIS). Results EF scores from the Behavior Rating Inventory of Executive Function related to parent- and child-reported social skills such that EF deficits correlated with poorer overall and domain-specific social skills. Similarly, EF scores from the Animal Sorting test related to child-reported social skills. Worse parent-reported EF predicted worse parent-reported social skills above the variance accounted for by IQ. Conclusions EF is related to social skills and may be necessary for successful social interaction among youth with SCD. These results provide rationale and guidance for future larger-scale investigations of EF and social skills among children with SCD. PMID:24431467

Aortic flow conditions predict ejection efficiency in the NHLBI-Sponsored Women's Ischemia Syndrome Evaluation (WISE).

PubMed

Doyle, Mark; Pohost, Gerald M; Bairey Merz, C Noel; Farah, Victor; Shaw, Leslee J; Sopko, George; Rogers, William J; Sharaf, Barry L; Pepine, Carl J; Thompson, Diane V; Rayarao, Geetha; Tauxe, Lindsey; Kelsey, Sheryl F; Biederman, Robert W W

2017-06-01

The Windkessel model of the cardiovascular system, both in its original wind-chamber and flow-pipe form, and in its electrical circuit analog has been used for over a century to modeled left ventricular ejection conditions. Using parameters obtained from aortic flow we formed a Flow Index that is proportional to the impedance of such a "circuit". We show that the impedance varies with ejection fraction (EF) in a manner characteristic of a resonant circuit with multiple resonance points, with each resonance point centrally located in a small range of EF values, i.e., corresponding to multiple contiguous EF bands. Two target populations were used: (I) a development group comprising male and female subjects (n=112) undergoing cardiovascular magnetic resonance (CMR) imaging for a variety of cardiac conditions. The Flow Index was developed using aortic flow data and its relationship to left ventricular EF was shown. (II) An illustration group comprised of female subjects from the Women's Ischemia Syndrome Evaluation (WISE) (n=201) followed for 5 years for occurrence of major adverse cardiovascular events (MACE). Flow data was not available in this group but since the Flow Index was related to the EF we noted the MACE rate with respect to EF. The EFs of the development population covered a wide range (9%-76%) traversing six Flow Index resonance bands. Within each Flow Index resonance band the impedance varied from highly capacitive at the lower range of EF through minimal impedance at resonance, to highly inductive at the higher range of EF, which is characteristic of a resonant circuit. When transitioning from one EF band to a higher band, the Flow Index made a sudden transition from highly inductive to capacitive impedance modes. MACE occurred in 26 (13%) of the WISE (illustration) population. Distance in EF units (Delta center ) from the central location between peaks of MACE activity was derived from EF data and was predictive of MACE rate with an area under the receiver operator curve of 0.73. Of special interest, Delta center was highly predictive of MACE in the sub-set of women with EF >60% (AUC 0.79) while EF was no more predictive than random chance (AUC 0.48). A Flow Index that describes impedance conditions of left ventricular ejection can be calculated using data obtained completely from the ascending aorta. The Flow Index exhibits a periodic variation with EF, and in a separate illustration population the occurrence of MACE was observed to exhibit a similar periodic variation with EF, even in cases of normal EF.

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.

The role of arterial hypertension in development heart failure with preserved ejection fraction: just a risk factor or something more?

PubMed

Tadic, Marijana; Cuspidi, Cesare; Frydas, Athanasios; Grassi, Guido

2018-04-04

Heart failure with preserved ejection fraction (HFpEF) is an entity that still raises many questions. The agreement about definition, pathophysiology, and therapeutic approach is still missing. Arterial hypertension is present in majority of patients with HFpEF, and it is still not clear if it represent a risk factor or "sine qua non" condition for HFpEF development. The underlying mechanisms of hypertension and HFpEF involve the same biohumoral systems: renin-angiotensin-aldosterone, sympathetic nervous system, and oxidative stress. However, not all hypertensive patients have HFpEF. The predisposition of some hypertensive patients to develop HFpEF needs to be resolved. Large randomized controlled trials did not prove the usefulness of renin-angiotensin-aldosterone inhibitors, diuretics, calcium channel blockers, and beta-blockers in HFpEF patients. The majority of studies did not succeed to demonstrate the reduction of cardiovascular and all-cause mortality in HFpEF individuals. One of the major limitations in these investigations was the inconsistency of HFpEF definition, which mainly refers to left ventricular ejection fraction (LVEF) cut-off that ranged from 40 to 50% in different studies. This review article provides the available data about pathophysiology and mechanisms that connect hypertension and HFpEF, investigations and therapy used in both conditions.

Heterogeneity of executive functions among comorbid neurodevelopmental disorders

PubMed Central

Dajani, Dina R.; Llabre, Maria M.; Nebel, Mary Beth; Mostofsky, Stewart H.; Uddin, Lucina Q.

2016-01-01

Executive functions (EFs) are used to set goals, plan for the future, inhibit maladaptive responses, and change behavior flexibly. Although some studies point to specific EF profiles in autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) — prevalent and often highly comorbid neurodevelopmental disorders — others have not differentiated them. The objective of the current study was to identify distinct profiles of EF across typically developing (TD) children and children with ASD and ADHD. We employed a latent profile analysis using indicators of EF (e.g., working memory, inhibition, and flexibility) in a mixed group of 8–13 year-olds including TD children (n = 128), children with ASD without ADHD (n = 30), children with ADHD (n = 93), and children with comorbid ASD and ADHD (n = 66). Three EF classes emerged: “above average,” “average,” and “impaired.” EF classes did not reproduce diagnostic categories, suggesting that differences in EF abilities are present within the ASD and ADHD groups. Further, greater EF dysfunction predicted more severe socioemotional problems, such as anxiety/depression. These results highlight the heterogeneity of current diagnostic groups and identify an “impaired” EF group, consisting of children with both ASD and ADHD, which could specifically be targeted for EF intervention. PMID:27827406

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.

EF24 induces ROS-mediated apoptosis via targeting thioredoxin reductase 1 in gastric cancer cells

PubMed Central

Chen, Weiqian; Chen, Xi; Ying, Shilong; Feng, Zhiguo; Chen, Tongke; Ye, Qingqing; Wang, Zhe; Qiu, Chenyu; Yang, Shulin; Liang, Guang

2016-01-01

Gastric cancer (GC) is one of the leading causes of cancer mortality in the world, and finding novel agents for the treatment of advanced gastric cancer is of urgent need. Diphenyl difluoroketone (EF24), a molecule having structural similarity to curcumin, exhibits potent anti-tumor activities by arresting cell cycle and inducing apoptosis. Although EF24 demonstrates potent anticancer efficacy in numerous types of human cancer cells, the cellular targets of EF24 have not been fully defined. We report here that EF24 may interact with the thioredoxin reductase 1 (TrxR1), an important selenocysteine (Sec)-containing antioxidant enzyme, to induce reactive oxygen species (ROS)-mediated apoptosis in human gastric cancer cells. By inhibiting TrxR1 activity and increasing intracellular ROS levels, EF24 induces a lethal endoplasmic reticulum stress in human gastric cancer cells. Importantly, knockdown of TrxR1 sensitizes cells to EF24 treatment. In vivo, EF24 treatment markedly reduces the TrxR1 activity and tumor cell burden, and displays synergistic lethality with 5-FU against gastric cancer cells. Targeting TrxR1 with EF24 thus discloses a previously unrecognized mechanism underlying the biological activity of EF24, and reveals that TrxR1 is a good target for gastric cancer therapy. PMID:26919110

Acanthamoeba migration in an electric field.

PubMed

Rudell, Jolene Chang; Gao, Jing; Sun, Yuxin; Sun, Yaohui; Chodosh, James; Schwab, Ivan; Zhao, Min

2013-06-21

We investigated the in vitro response of Acanthamoeba trophozoites to electric fields (EFs). Acanthamoeba castellanii were exposed to varying strengths of an EF. During EF exposure, cell migration was monitored using an inverted microscope equipped with a CCD camera and the SimplePCI 5.3 imaging system to capture time-lapse images. The migration of A. castellanii trophozoites was analyzed and quantified with ImageJ software. For analysis of cell migration in a three-dimensional culture system, Acanthamoeba trophozoites were cultured in agar, exposed to an EF, digitally video recorded, and analyzed at various Z focal planes. Acanthamoeba trophozoites move at random in the absence of an EF, but move directionally in response to an EF. Directedness in the absence of an EF is 0.08 ± 0.01, while in 1200 mV/mm EF, directedness is significantly higher at -0.65 ± 0.01 (P < 0.001). We find that the trophozoite migration response is voltage-dependent, with higher directionality with higher voltage application. Acanthamoeba move directionally in a three-dimensional (3D) agar system as well when exposed to an EF. Acanthamoeba trophozoites move directionally in response to an EF in a two-dimensional and 3D culture system. Acanthamoeba trophozoite migration is also voltage-dependent, with increased directionality with increasing voltage. This may provide new treatment modalities for Acanthamoeba keratitis.

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.

Toward a Comprehensive Understanding of Executive Cognitive Function in Implicit Racial Bias

PubMed Central

Ito, Tiffany A.; Friedman, Naomi P.; Bartholow, Bruce D.; Correll, Joshua; Loersch, Chris; Altamirano, Lee J.; Miyake, Akira

2014-01-01

Although performance on laboratory-based implicit bias tasks often is interpreted strictly in terms of the strength of automatic associations, recent evidence suggests that such tasks are influenced by higher-order cognitive control processes, so-called executive functions (EFs). However, extant work in this area has been limited by failure to account for the unity and diversity of EFs, focus on only a single measure of bias and/or EF, and relatively small sample sizes. The current study sought to comprehensively model the relation between individual differences in EFs and the expression of racial bias in three commonly used laboratory measures. Participants (N=485) completed a battery of EF tasks (session 1) and three racial bias tasks (session 2), along with numerous individual difference questionnaires. The main findings were as follows: (1) measures of implicit bias were only weakly intercorrelated; (2) EF and estimates of automatic processes both predicted implicit bias and also interacted, such that the relation between automatic processes and bias expression was reduced at higher levels of EF; (3) specific facets of EF were differentially associated with overall task performance and controlled processing estimates across different bias tasks; (4) EF did not moderate associations between implicit and explicit measures of bias; and (5) external, but not internal, motivation to control prejudice depended on EF to reduce bias expression. Findings are discussed in terms of the importance of global and specific EF abilities in determining expression of implicit racial bias. PMID:25603372

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.

Evidence of Microvascular Dysfunction in Heart Failure with Preserved Ejection Fraction

PubMed Central

Lee, Joshua F.; Barrett-O’Keefe, Zachary; Garten, Ryan S.; Nelson, Ashley D.; Ryan, John J.; Nativi, Jose N.; Richardson, Russell S.; Wray, D. Walter

2015-01-01

Objective While vascular dysfunction is well-defined in HF patients with reduced ejection fraction (HFrEF), disease-related alterations in the peripheral vasculature of HF patients with preserved ejection fraction (HFpEF) are not well characterized. Thus, we sought test the hypothesis that HFpEF patients would demonstrate reduced vascular function, at both the conduit artery and microvascular levels, compared to controls. Methods We examined both conduit artery function via brachial artery flow-mediated dilation (FMD) and microvascular function via reactive hyperemia (RH) following 5 min of ischemia in 24 Class II–IV HFpEF patients and 24 healthy controls matched for age, sex, and brachial artery diameter. Results FMD was reduced in HFpEF patients compared to controls (HFpEF: 3.1 ± 0.7%; Controls: 5.1 ± 0.5%; P = 0.03). However, shear rate at time of peak brachial artery dilation was lower in HFpEF patients compared to controls (HFpEF: 42,070 ± 4,018 s−1; Controls: 69,018 ± 9,509 s−1; P = 0.01), and when brachial artery FMD was normalized for the shear stimulus, cumulative area-under-the-curve (AUC) at peak dilation, the between-group differences were eliminated (HFpEF: 0.11 ± 0.03 %/AUC; Controls: 0.09 ± 0.01 %/AUC; P = 0.58). RH, assessed as AUC, was lower in HFpEF patients (HFpEF: 454 ± 35 mL; Controls: 660 ± 63 mL; P < 0.01). Conclusions Collectively, these data suggest that maladaptations at the microvascular level contribute to the pathophysiology of HFpEF, while conduit artery vascular function is not diminished beyond that which occurs with healthy aging. PMID:26567228

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.

Anthrax Vaccine Precipitated Induces Edema Toxin-Neutralizing, Edema Factor-Specific Antibodies in Human Recipients

PubMed Central

Dumas, Eric K.; Gross, Timothy; Larabee, Jason; Pate, Lance; Cuthbertson, Hannah; Charlton, Sue; Hallis, Bassam; Engler, Renata J. M.; Collins, Limone C.; Spooner, Christina E.; Chen, Hua; Ballard, Jimmy; James, Judith A.

2017-01-01

ABSTRACT Edema toxin (ET), composed of edema factor (EF) and protective antigen (PA), is a virulence factor of Bacillus anthracis that alters host immune cell function and contributes to anthrax disease. Anthrax vaccine precipitated (AVP) contains low but detectable levels of EF and can elicit EF-specific antibodies in human recipients of AVP. Active and passive vaccination of mice with EF can contribute to protection from challenge with Bacillus anthracis spores or ET. This study compared humoral responses to ET in recipients of AVP (n = 33) versus anthrax vaccine adsorbed (AVA; n = 66), matched for number of vaccinations and time postvaccination, and further determined whether EF antibodies elicited by AVP contribute to ET neutralization. AVP induced higher incidence (77.8%) and titer (229.8 ± 58.6) of EF antibodies than AVA (4.2% and 7.8 ± 8.3, respectively), reflecting the reported low but detectable presence of EF in AVP. In contrast, PA IgG levels and ET neutralization measured using a luciferase-based cyclic AMP reporter assay were robust and did not differ between the two vaccine groups. Multiple regression analysis failed to detect an independent contribution of EF antibodies to ET neutralization in AVP recipients; however, EF antibodies purified from AVP sera neutralized ET. Serum samples from at least half of EF IgG-positive AVP recipients bound to nine decapeptides located in EF domains II and III. Although PA antibodies are primarily responsible for ET neutralization in recipients of AVP, increased amounts of an EF component should be investigated for the capacity to enhance next-generation, PA-based vaccines. PMID:28877928

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.

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

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.

Not just a sum of its parts: How tasks of the theory of mind scale relate to executive function across time.

PubMed

Doenyas, Ceymi; Yavuz, H Melis; Selcuk, Bilge

2018-02-01

There is a well-established relationship between theory of mind (ToM) and executive function (EF) during the preschool years. However, less is known about the concurrent and longitudinal relations between EF and specific tasks tapping different aspects of ToM. The current study investigated the ToM-EF relationship across 1 year in 3- to 5-year-old Turkish children using the ToM battery of Wellman and Liu (2004), which measures understanding of diverse desires (DD), diverse beliefs (DB), knowledge access (KA), contents false belief (CFB), explicit false belief (EFB), and hidden emotion (HE). This battery has not yet been used in its entirety to test the predictive relations between ToM and EF. We used peg-tapping and day-night tasks to measure EF. Our sample comprised 150 Turkish preschool children (69 girls) aged 36-60 months at Time 1 (T1) and 49-73 months at Time 2 (T2). Using the ToM composite with all six tasks, when child's age, receptive language, and T1 ability level (EF or ToM) were controlled, T1 EF significantly predicted T2 ToM, whereas T1 ToM did not predict T2 EF. Among DD, DB, KA, false belief understanding (FBU: the composite score of CFB and EFB), and HE, only KA and FBU were significantly associated with EF at T1 and T2. Further regression analyses showed that KA did not have a predictive relationship with EF. Instead, FBU drove the predictive EF-ToM relationship across time. Thus, in Turkish children, earlier EF predicts later ToM, but especially the FBU component, in this well-validated battery. Copyright © 2017. Published by Elsevier Inc.

Heart failure with recovered ejection fraction: clinical characteristics, determinants and prognosis. CARDIOCHUS-CHOP registry.

PubMed

Agra Bermejo, Rosa; Gonzalez Babarro, Eva; López Canoa, J Nicolás; Varela Román, Alfonso; Gómez Otero, Inés; Oro Ayude, Marcos; Parada Vazquez, Pablo; Gómez Rodríguez, Isabel; Díaz Castro, Oscar; González Juanatey, Jose Ramón

2017-10-05

The magnitude and the prognostic impact of recovering left ventricular ejection fraction (LVEF) in patients with heart failure (HF) and systolic dysfunction is unclear. The aim of this study was to evaluate the clinical characteristics and prognosis of patients with HFrecEF in an HF population. 449 consecutive patients were selected with the diagnosis of HF and an evaluation of LVEF in the 6 months prior to selection who were referred to two HF units. Patients with systolic dysfunction were only considered if a second echocardiogram was performed during the follow-up. At the time of diagnosis, 207 patients had LVEF > 40% (HFpEF) and 242 had LVEF ≤ 40% (HFrEF). After 1 year, the LVEF was re-evaluated in all 242 patients with a LVEF ≤ 40%: in 126 (52%), the second LVEF was > 40% (HFrecEF), and the remaining 116 (48%) had LVEF ≤ 40% (HFrEF). After 1800 ± 900 days of follow-up patients with recovered LVEF had a significantly lower mortality rate (HFpEF vs. HFrecEF: hazard ratio (HR) = 2.286, 95% confidence interval (95% CI) 1.264-4.145, p = 0.019; HFrEF vs. HFrecEF: HR = 2.222, 95% CI 1.189-4.186, p < 0.001) and hospitalization rate (HFpEF vs. HFrecEF: HR = 1.411, 95% CI 1.046-1.903, p = 0.024; HFrEF vs. HFrecEF: HR = 1.388, 95% CI 1.002-1.924, p = 0.049). The following are predictors of LVEF recovery: younger age, lower functional class, treatment with renin-angiotensin-aldosterone system inhibitors and beta-blockers, absence of defibrillator use, and non-ischemic aetiology. Patients with HF and reduced LVEF who were re-evaluated after 1 year, had significant improvement in their LVEF and had a more favourable prognosis than HF with preserved and reduced ejection fraction.

Relations between executive function and emotionality in preschoolers: Exploring a transitive cognition-emotion linkage.

PubMed

Ferrier, David E; Bassett, Hideko H; Denham, Susanne A

2014-01-01

Emotions play a crucial role in appraisal of experiences and environments and in guiding thoughts and actions. Moreover, executive function (EF) and emotion regulation (ER) have received much attention, not only for positive associations with children's social-emotional functioning, but also for potential central roles in cognitive functioning. In one conceptualization of ER (Campos etal., 2004), processes of ER, and those of emotional expression and experience (hereafter referred to as emotionality) are highly related and reciprocal; yet, there has been little research on young children's EF that focuses on emotionality, although it is easily observed within a classroom. The two goals of the study were to: (1) investigate the relatively unexplored role of emotionality in the development of EF in early childhood and (2) assess the relations between an observational rating of EF obtained after direct assessment with a standardized EF rating scale. We predicted that observed emotionality and EF would both demonstrate stability and predict one another within and across time. 175 children aged 35-60 months were recruited from Head Start and private childcare centers. Using partial least squares modeling, we chose T1 emotionality as the exogenous variable and tested pathways between emotionality and EF across two time points, 6 months apart. Results showed that both T1 observed EF and emotionality predicted their respective T2 counterparts, supporting the idea that both constructs build upon existing systems. Further, T1 emotionality predicted T1 observed EF and the T2 BRIEF-P composite. In turn, T1 observed EF predicted emotionality and the T2 BRIEF-P composite. These findings fit with literature on older populations in which EF and emotionality have been related, yet are the first to report such relations in early childhood. Last, T1 observed EF's positive prediction of the T2 BRIEF-P composite lends credence to the use of both EF measures in applied and research settings.

The contribution of children's time-specific and longitudinal expressive language skills on developmental trajectories of executive function.

PubMed

Kuhn, Laura J; Willoughby, Michael T; Vernon-Feagans, Lynne; Blair, Clancy B

2016-08-01

To investigate whether children's early language skills support the development of executive functions (EFs), the current study used an epidemiological sample (N=1121) to determine whether two key language indicators, vocabulary and language complexity, were predictive of EF abilities over the preschool years. We examined vocabulary and language complexity both as time-varying covariates that predicted time-specific indicators of EF at 36 and 60 months of age and as time-invariant covariates that predicted children's EF at 60 months and change in EF from 36 to 60 months. We found that the rate of change in children's vocabulary between 15 and 36 months was associated with both the trajectory of EF from 36 to 60 months and the resulting abilities at 60 months. In contrast, children's language complexity had a time-specific association with EF only at 60 months. These findings suggest that children's early gains in vocabulary may be particularly relevant for emerging EF abilities. Copyright © 2016 Elsevier Inc. All rights reserved.

Solitary Active Videogame Play Improves Executive Functioning More Than Collaborative Play for Children with Special Needs.

PubMed

Flynn, Rachel M; Colon, Nirmaliz

2016-12-01

This pilot study examined the impact of playing an active videogame on executive functioning (EF) skills for children with special needs, who typically have lower EF skills. Acute EF change was measured in 36 children with a range of special needs, including mental health disorders and developmental disabilities. Participants were assigned to one of two active videogame conditions: playing alone and playing with a peer. Two different EF tasks were conducted pre- and postplay. Children who played alone increased their accuracy performance more than children in the paired-play condition on two measures of EF. The study explored potential covariates of prior videogame experience, age, and enjoyment, but none of these variables related to EF change. This study's findings support active videogame play as an activity that can boost EF skills for children with special needs when they play alone. Future research should continue to examine the relationships between EF and active videogame play with a peer to elucidate the contributions of social interactions.

Similarity and diversity of translational GTPase factors EF-G, EF4, and BipA: From structure to function.

PubMed

Ero, Rya; Kumar, Veerendra; Chen, Yun; Gao, Yong-Gui

2016-12-01

EF-G, EF4, and BipA are members of the translation factor family of GTPases with a common ribosome binding mode and GTPase activation mechanism. However, topological variations of shared as well as unique domains ensure different roles played by these proteins during translation. Recent X-ray crystallography and cryo-electron microscopy studies have revealed the structural basis for the involvement of EF-G domain IV in securing the movement of tRNAs and mRNA during translocation as well as revealing how the unique C-terminal domains of EF4 and BipA interact with the ribosome and tRNAs contributing to the regulation of translation under certain conditions. EF-G, EF-4, and BipA are intriguing examples of structural variations on a common theme that results in diverse behavior and function. Structural studies of translational GTPase factors have been greatly facilitated by the use of antibiotics, which have revealed their mechanism of action.

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

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.

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.

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

Translation Control of Swarming Proficiency in Bacillus subtilis by 5-Amino-pentanolylated Elongation Factor P.

PubMed

Rajkovic, Andrei; Hummels, Katherine R; Witzky, Anne; Erickson, Sarah; Gafken, Philip R; Whitelegge, Julian P; Faull, Kym F; Kearns, Daniel B; Ibba, Michael

2016-05-20

Elongation factor P (EF-P) accelerates diprolyl synthesis and requires a posttranslational modification to maintain proteostasis. Two phylogenetically distinct EF-P modification pathways have been described and are encoded in the majority of Gram-negative bacteria, but neither is present in Gram-positive bacteria. Prior work suggested that the EF-P-encoding gene (efp) primarily supports Bacillus subtilis swarming differentiation, whereas EF-P in Gram-negative bacteria has a more global housekeeping role, prompting our investigation to determine whether EF-P is modified and how it impacts gene expression in motile cells. We identified a 5-aminopentanol moiety attached to Lys(32) of B. subtilis EF-P that is required for swarming motility. A fluorescent in vivo B. subtilis reporter system identified peptide motifs whose efficient synthesis was most dependent on 5-aminopentanol EF-P. Examination of the B. subtilis genome sequence showed that these EF-P-dependent peptide motifs were represented in flagellar genes. Taken together, these data show that, in B. subtilis, a previously uncharacterized posttranslational modification of EF-P can modulate the synthesis of specific diprolyl motifs present in proteins required for swarming motility. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Do executive functions explain the covariance between internalizing and externalizing behaviors?

PubMed

Hatoum, Alexander S; Rhee, Soo Hyun; Corley, Robin P; Hewitt, John K; Friedman, Naomi P

2017-11-16

This study examined whether executive functions (EFs) might be common features of internalizing and externalizing behavior problems across development. We examined relations between three EF latent variables (a common EF factor and factors specific to updating working memory and shifting sets), constructed from nine laboratory tasks administered at age 17, to latent growth intercept (capturing stability) and slope (capturing change) factors of teacher- and parent-reported internalizing and externalizing behaviors in 885 individual twins aged 7 to 16 years. We then estimated the proportion of intercept-intercept and slope-slope correlations predicted by EF as well as the association between EFs and a common psychopathology factor (P factor) estimated from all 9 years of internalizing and externalizing measures. Common EF was negatively associated with the intercepts of teacher-rated internalizing and externalizing behavior in males, and explained 32% of their covariance; in the P factor model, common EF was associated with the P factor in males. Shifting-specific was positively associated with the externalizing slope across sex. EFs did not explain covariation between parent-rated behaviors. These results suggest that EFs are associated with stable problem behavior variation, explain small proportions of covariance, and are a risk factor that that may depend on gender.

Calcium-independent metal-ion catalytic mechanism of anthrax edema factor

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

Shen, Yuequan; Zhukovskaya, Natalia L.; Guo, Qing

2009-11-18

Edema factor (EF), a key anthrax exotoxin, has an anthrax protective antigen-binding domain (PABD) and a calmodulin (CaM)-activated adenylyl cyclase domain. Here, we report the crystal structures of CaM-bound EF, revealing the architecture of EF PABD. CaM has N- and C-terminal domains and each domain can bind two calcium ions. Calcium binding induces the conformational change of CaM from closed to open. Structures of the EF-CaM complex show how EF locks the N-terminal domain of CaM into a closed conformation regardless of its calcium-loading state. This represents a mechanism of how CaM effector alters the calcium affinity of CaM andmore » uncouples the conformational change of CaM from calcium loading. Furthermore, structures of EF-CaM complexed with nucleotides show that EF uses two-metal-ion catalysis, a prevalent mechanism in DNA and RNA polymerases. A histidine (H351) further facilitates the catalysis of EF by activating a water to deprotonate 3'OH of ATP. Mammalian adenylyl cyclases share no structural similarity with EF and they also use two-metal-ion catalysis, suggesting the catalytic mechanism-driven convergent evolution of two structurally diverse adenylyl cyclases.« less

Education for Sustainability (EfS): Practice and Practice Architectures

ERIC Educational Resources Information Center

Kemmis, Stephen; Mutton, Rebecca

2012-01-01

This paper reports some findings from an investigation of educational practice in ten (formal and informal) education for sustainability (EfS) initiatives, to characterise exemplary practice in school and community education for sustainability, considered crucial to Australia's future. The study focused on rural/regional Australia, specifically…

75 FR 41894 - Wapakoneta Machine Company, Currently Known as EF Industrial Technologies, Inc., Wapakoneta, OH...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-19

... Company, Currently Known as EF Industrial Technologies, Inc., Wapakoneta, OH; Amended Certification... of early 2010, Wapakoneta Machine Company is currently known as EF Industrial Technologies, Inc. Some... Wapakoneta Machine Company, currently known as EF Industrial Technologies, Inc., Wapakoneta, Ohio became...

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.

EF1A1/HSC70 Cooperatively Suppress Brain Endothelial Cell Apoptosis via Regulating JNK Activity.

PubMed

Liu, Ying; Jiang, Shu; Yang, Peng-Yuan; Zhang, Yue-Fan; Li, Tie-Jun; Rui, Yao-Cheng

2016-10-01

In our previous study, eEF1A1 was identified to be a new target for protecting brain ischemia injury, but the mechanism remains largely unknown. In this study, we screened the downstream cellular protein molecules interacted with eEF1A1 and found mechanism of eEF1A1 in brain ischemia protection. Through co-immunoprecipitation and mass spectrometry for searching the interaction of proteins with eEF1A1 in bEnd3 cells, HSC70 was identified to be a binding protein of eEF1A1, which was further validated by Western blot and immunofluorescence. eEF1A1 or HSC70 knockdown, respectively, increased OGD-induced apoptosis of brain vascular endothelial cells, which was detected by Annexin V-FITC/PI staining. HSC70 or eEF1A1 knockdown enhances phosphorylated JNK, phosphorylation of c-JUN (Ser63, Ser73), cleaved caspase-9, and cleaved caspase-3 expression, which could be rescued by JNK inhibitor. In summary, our data suggest that the presence of chaperone forms of interaction between eEF1A1 and HSC70 in brain vascular endothelial cells, eEF1A1 and HSC70 can play a protective role in the process of ischemic stroke by inhibiting the JNK signaling pathway activation. © 2016 John Wiley & Sons Ltd.

Relations Between Self-reported Executive Functioning and Speech Perception Skills in Adult Cochlear Implant Users.

PubMed

Moberly, Aaron C; Patel, Tirth R; Castellanos, Irina

2018-02-01

As a result of their hearing loss, adults with cochlear implants (CIs) would self-report poorer executive functioning (EF) skills than normal-hearing (NH) peers, and these EF skills would be associated with performance on speech recognition tasks. EF refers to a group of high order neurocognitive skills responsible for behavioral and emotional regulation during goal-directed activity, and EF has been found to be poorer in children with CIs than their NH age-matched peers. Moreover, there is increasing evidence that neurocognitive skills, including some EF skills, contribute to the ability to recognize speech through a CI. Thirty postlingually deafened adults with CIs and 42 age-matched NH adults were enrolled. Participants and their spouses or significant others (informants) completed well-validated self-reports or informant-reports of EF, the Behavior Rating Inventory of Executive Function - Adult (BRIEF-A). CI users' speech recognition skills were assessed in quiet using several measures of sentence recognition. NH peers were tested for recognition of noise-vocoded versions of the same speech stimuli. CI users self-reported difficulty on EF tasks of shifting and task monitoring. In CI users, measures of speech recognition correlated with several self-reported EF skills. The present findings provide further evidence that neurocognitive factors, including specific EF skills, may decline in association with hearing loss, and that some of these EF skills contribute to speech processing under degraded listening conditions.

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

In-Plume Emission Test Stand 2: emission factors for 10- to 100-kW U.S. military generators.

PubMed

Zhu, Dongzi; Nussbaum, Nicholas J; Kuhns, Hampden D; Chang, M-C Oliver; Sodeman, David; Uppapalli, Sebastian; Moosmüller, Hans; Chow, Judith C; Watson, John G

2009-12-01

Although emissions of air pollutants from some military tactical equipment are not subject to the emissions standards, local communities near military bases must conform to the National Ambient Air Quality Standards. Military diesel generators are widely used in training. A portable in-plume system was used to measure fuel-based emission factors (EFs) for particulate matter (PM), carbon monoxide (CO), nitrogen oxides (NOx), and hydrocarbons (HCs) for 30-, 60-, and 100-kW generators at five load levels and for cold starts. It was found that EFs depend on multiple parameters including engine size, engine load, unit age, and total running hours. The average CO EF of generators tested was 5% lower, and the average NOx EF was 63% lower than AP-42 estimates; average PM EF was 80% less than the AP-42 estimates. A 2002 model-year 60-kW engine produced 25% less PM than a 1995 engine of the same family with similar running hours. CO EFs decrease with increasing engine load, NOx EFs increase up to mid-loads and decrease slightly at high loads, PM EFs increase with loads for 30- and 60-kW engines. CO and PM have higher EFs and NOx has a lower EF during cold starts than during hot-stabilized operation. PM chemical source profiles were also examined.

EF24 induces ROS-mediated apoptosis via targeting thioredoxin reductase 1 in gastric cancer cells.

PubMed

Zou, Peng; Xia, Yiqun; Chen, Weiqian; Chen, Xi; Ying, Shilong; Feng, Zhiguo; Chen, Tongke; Ye, Qingqing; Wang, Zhe; Qiu, Chenyu; Yang, Shulin; Liang, Guang

2016-04-05

Gastric cancer (GC) is one of the leading causes of cancer mortality in the world, and finding novel agents for the treatment of advanced gastric cancer is of urgent need. Diphenyl difluoroketone (EF24), a molecule having structural similarity to curcumin, exhibits potent anti-tumor activities by arresting cell cycle and inducing apoptosis. Although EF24 demonstrates potent anticancer effïcacy in numerous types of human cancer cells, the cellular targets of EF24 have not been fully defined. We report here that EF24 may interact with the thioredoxin reductase 1 (TrxR1), an important selenocysteine (Sec)-containing antioxidant enzyme, to induce reactive oxygen species (ROS)-mediated apoptosis in human gastric cancer cells. By inhibiting TrxR1 activity and increasing intracellular ROS levels, EF24 induces a lethal endoplasmic reticulum stress in human gastric cancer cells. Importantly, knockdown of TrxR1 sensitizes cells to EF24 treatment. In vivo, EF24 treatment markedly reduces the TrxR1 activity and tumor cell burden, and displays synergistic lethality with 5-FU against gastric cancer cells. Targeting TrxR1 with EF24 thus discloses a previously unrecognized mechanism underlying the biological activity of EF24, and reveals that TrxR1 is a good target for gastric cancer therapy.

MicroRNA-33b, upregulated by EF24, a curcumin analog, suppresses the epithelial-to-mesenchymal transition (EMT) and migratory potential of melanoma cells by targeting HMGA2.

PubMed

Zhang, Pu; Bai, Huiyuan; Liu, Gentao; Wang, Heyong; Chen, Feng; Zhang, Baoshun; Zeng, Panying; Wu, Chengxiang; Peng, Cong; Huang, Changjin; Song, Yang; Song, Erqun

2015-05-05

Diphenyl difluoroketone (EF24), a curcumin analog, exhibits potent anti-tumor activities by arresting cell cycle and inducing apoptosis. However, the efficacy and modes of action of EF24 on melanoma metastasis remain elusive. In this study, we found that at non-cytotoxic concentrations, EF24 suppressed cell motility and epithelial-to-mesenchymal Transition (EMT) of melanoma cell lines, Lu1205 and A375. EF24 also suppressed HMGA2 expression at mRNA and protein levels. miR-33b directly bound to HMGA2 3' untranslated region (3'-UTR) to suppress its expression as measured by dual-luciferase assay. EF24 increased expression of E-cadherin and decreased STAT3 phosphorylation and expression of the mesenchymal markers, vimentin and N-cadherin. miR-33b inhibition or HMGA2 overexpression reverted EF24-mediated suppression of EMT phenotypes. In addition, EF24 modulated the HMGA2-dependent actin stress fiber formation, focal adhesion assembly and FAK, Src and RhoA activation by targeting miR-33b. Thus, the results suggest that EF24 suppresses melanoma metastasis via upregulating miR-33b and concomitantly reducing HMGA2 expression. The observed activities of EF24 support its further evaluation as an anti-metastatic agent in melanoma therapy. Copyright © 2015. Published by Elsevier Ireland Ltd.

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.

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.

Relationship Between Executive Functioning and Symptoms of Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder in 6-8 Year Old Children.

PubMed

Neely, Rachel Jane; Green, Jessica Leigh; Sciberras, Emma; Hazell, Philip; Anderson, Vicki

2016-10-01

This study examined relationships between executive functioning (EF) and ADHD/ASD symptoms in 339 6-8 year-old children to characterise EF profiles associated with ADHD and ADHD + ASD. ADHD status was assessed using screening surveys and diagnostic interviews. ASD symptoms were measured using the Social Communication Questionnaire, and children completed assessments of EF. We found the EF profile of children with ADHD + ASD did not differ from ADHD-alone and that lower-order cognitive skills contributed significantly to EF. Dimensionally, ASD and inattention symptoms were differentially associated with EF, whereas hyperactivity symptoms were unrelated to EF. Differences between categorical and dimensional findings suggest it is important to use both diagnostic and symptom based approaches in clinical settings when assessing these children's functional abilities.

Toward a comprehensive understanding of executive cognitive function in implicit racial bias.

PubMed

Ito, Tiffany A; Friedman, Naomi P; Bartholow, Bruce D; Correll, Joshua; Loersch, Chris; Altamirano, Lee J; Miyake, Akira

2015-02-01

Although performance on laboratory-based implicit bias tasks often is interpreted strictly in terms of the strength of automatic associations, recent evidence suggests that such tasks are influenced by higher-order cognitive control processes, so-called executive functions (EFs). However, extant work in this area has been limited by failure to account for the unity and diversity of EFs, focus on only a single measure of bias and/or EF, and relatively small sample sizes. The current study sought to comprehensively model the relation between individual differences in EFs and the expression of racial bias in 3 commonly used laboratory measures. Participants (N = 485) completed a battery of EF tasks (Session 1) and 3 racial bias tasks (Session 2), along with numerous individual difference questionnaires. The main findings were as follows: (a) measures of implicit bias were only weakly intercorrelated; (b) EF and estimates of automatic processes both predicted implicit bias and also interacted, such that the relation between automatic processes and bias expression was reduced at higher levels of EF; (c) specific facets of EF were differentially associated with overall task performance and controlled processing estimates across different bias tasks; (d) EF did not moderate associations between implicit and explicit measures of bias; and (e) external, but not internal, motivation to control prejudice depended on EF to reduce bias expression. Findings are discussed in terms of the importance of global and specific EF abilities in determining expression of implicit racial bias. PsycINFO Database Record (c) 2015 APA, all rights reserved.

Up-regulation of eEF1A2 promotes proliferation and inhibits apoptosis in prostate cancer.

PubMed

Sun, Yue; Du, Chengli; Wang, Bo; Zhang, Yanling; Liu, Xiaoyan; Ren, Guoping

2014-07-18

eEF1A2 is a protein translation factor involved in protein synthesis, which possesses important function roles in cancer development. This study aims at investigating the expression pattern of eEF1A2 in prostate cancer and its potential role in prostate cancer development. We examined the expression level of eEF1A2 in 30 pairs of prostate cancer tissues by using RT-PCR and immunohistochemical staining (IHC). Then we applied siRNA specifically targeting eEF1A2 to down-regulate its expression in DU-145 and PC-3 cells. Flow cytometer was used to explore apoptosis and Western-blot was used to detect the pathway proteins of apoptosis. Our results showed that the expression level of eEF1A2 in prostate cancer tissues was significantly higher compared to their corresponding normal tissues. Reduction of eEF1A2 expression in DU-145 and PC-3 cells led to a dramatic inhibition of proliferation accompanied with enhanced apoptosis rate. Western blot revealed that apoptosis pathway proteins (caspase3, BAD, BAX, PUMA) were significantly up-regulated after suppression of eEF1A2. More importantly, the levels of eEF1A2 and caspase3 were inversely correlated in prostate cancer tissues. Our data suggests that eEF1A2 plays an important role in prostate cancer development, especially in inhibiting apoptosis. So eEF1A2 might serve as a potential therapeutic target in prostate cancer. Copyright © 2014 Elsevier Inc. All rights reserved.

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.

Executive Functions after Age 5: Changes and Correlates

ERIC Educational Resources Information Center

Best, John R.; Miller, Patricia H.; Jones, Lara L.

2009-01-01

Research and theorizing on executive function (EF) in childhood has been disproportionately focused on preschool age children. This review paper outlines the importance of examining EF throughout childhood, and even across the lifespan. First, examining EF in older children can address the question of whether EF is a unitary construct. The…

A new soil water and bulk eletrical conductivity sensor technology for irrigation and salinity management

USDA-ARS?s Scientific Manuscript database

Many soil water sensors, especially those based on electromagnetic (EM) properties of soils, have been shown to be unsuitable in salt-affected or clayey soils. Most available soil water content sensors are of this EM type, particularly the so-called capacitance sensors. They often over estimate and ...

Are executive function and impulsivity antipodes? A conceptual reconstruction with special reference to addiction

PubMed Central

Bickel, Warren K.; Jarmolowicz, David P.; Mueller, E. Terry; Gatchalian, Kirstin M.; McClure, Samuel M.

2014-01-01

Rationale Although there is considerable interest in how either executive function (EF) or impulsivity relate to addiction, there is little apparent overlap between these research areas. Objectives The present paper aims to determine if components of these two constructs are conceptual antipodes—widely separated on a shared continuum. Methods EFs and impulsivities were compared and contrasted. Specifically, the definitions of the components of EF and impulsivity, the methods used to measure the various components, the populations of drug users that show deficits in these components, and the neural substrates of these components were compared and contrasted. Results Each component of impulsivity had an antipode in EF. EF, however, covered a wider range of phenomena, including compulsivity. Conclusions Impulsivity functions as an antipode of certain components of EF. Recognition of the relationship between EF and impulsivity may inform the scientific inquiry of behavioral problems such as addiction. Other theoretical implications are discussed. PMID:22441659

EFS: an ensemble feature selection tool implemented as R-package and web-application.

PubMed

Neumann, Ursula; Genze, Nikita; Heider, Dominik

2017-01-01

Feature selection methods aim at identifying a subset of features that improve the prediction performance of subsequent classification models and thereby also simplify their interpretability. Preceding studies demonstrated that single feature selection methods can have specific biases, whereas an ensemble feature selection has the advantage to alleviate and compensate for these biases. The software EFS (Ensemble Feature Selection) makes use of multiple feature selection methods and combines their normalized outputs to a quantitative ensemble importance. Currently, eight different feature selection methods have been integrated in EFS, which can be used separately or combined in an ensemble. EFS identifies relevant features while compensating specific biases of single methods due to an ensemble approach. Thereby, EFS can improve the prediction accuracy and interpretability in subsequent binary classification models. EFS can be downloaded as an R-package from CRAN or used via a web application at http://EFS.heiderlab.de.

Executive function predicts artificial language learning

PubMed Central

Kapa, Leah L.; Colombo, John

2017-01-01

Previous research suggests executive function (EF) advantages among bilinguals compared to monolingual peers, and these advantages are generally attributed to experience controlling two linguistic systems. However, the possibility that the relationship between bilingualism and EF might be bidirectional has not been widely considered; while experience with two languages might improve EF, better EF skills might also facilitate language learning. In the current studies, we tested whether adults’ and preschool children’s EF abilities predicted success in learning a novel artificial language. After controlling for working memory and English receptive vocabulary, adults’ artificial language performance was predicted by their inhibitory control ability (Study 1) and children’s performance was predicted by their attentional monitoring and shifting ability (Study 2). These findings provide preliminary evidence suggesting that EF processes may be employed during initial stages of language learning, particularly vocabulary acquisition, and support the possibility of a bidirectional relationship between EF and language acquisition. PMID:29129958

Executive Function and Magnitude Skills in Preschool Children

PubMed Central

Prager, Emily O.; Sera, Maria D.; Carlson, Stephanie M.

2016-01-01

Executive Function (EF) has been highlighted as a potentially important factor for mathematical understanding. The relation has been well established in school-aged children but has been less explored at younger ages. The current study investigated the relation between EF and mathematics in preschool aged children. Participants were 142 typically developing 3- and 4-year-olds. Controlling for verbal ability, a significant positive correlation was found between EF and general math abilities in this age group. Importantly, we further examined this relation causally by varying the EF load on a magnitude comparison task. Results suggested a developmental pattern wherein 3-year-olds’ performance on the magnitude comparison task was worst when EF was taxed the most. Conversely, 4-year-olds performed well on the magnitude task despite varying EF demands, suggesting that EF might play a critical role in the development of math concepts. PMID:27082019

Sustainable and safe design of footwear integrating ecological footprint and risk criteria.

PubMed

Herva, Marta; Álvarez, Antonio; Roca, Enrique

2011-09-15

The ecodesign of a product implies that different potential environmental impacts of diverse nature must be taken into account considering its whole life cycle, apart from the general design criteria (i.e. technical, functional, ergonomic, aesthetic or economic). In this sense, a sustainability assessment methodology, ecological footprint (EF), and environmental risk assessment (ERA), were combined for the first time to derive complementary criteria for the ecodesign of footwear. Four models of children's shoes were analyzed and compared. The synthetic shoes obtained a smaller EF (6.5 gm(2)) when compared to the leather shoes (11.1 gm(2)). However, high concentrations of hazardous substances were detected in the former, even making the Hazard Quotient (HQ) and the Cancer Risk (CR) exceed the recommended safety limits for one of the synthetic models analyzed. Risk criteria were prioritized in this case and, consequently, the design proposal was discarded. For the other cases, the perspective provided by the indicators of different nature was balanced to accomplish a fairest evaluation. The selection of fibers produced under sustainable criteria and the reduction of the materials consumption was recommended, since the area requirements would be minimized and the absence of hazardous compounds would ensure safety conditions during the use stage. Copyright © 2011 Elsevier B.V. All rights reserved.

Urinary Iodine Concentrations in Cancer Patients

PubMed Central

Kargar, Saeed; Shiryazdi, Seyed Mostafa; Atashi, Seyed Reza; Neamatzadeh, Hossein; Kamali, Mahdieh

2017-01-01

Background: It has been suggested that incidence of some cancers, especially examples in the breast and stomach may be influenced by the iodine intake. However, only few studies are available at present. Therefore, we have conducted the present assessment of iodine status in Iranian patients diagnosed with a malignancy. Materials and Methods: This cross-sectional study was conducted in 85 patients diagnosed with different types of cancer at Shahid Sadoughi Hospital, Yazd, Iran. The method used was based on the Sandell–Kolthoff reaction. Results: The median urinary iodine concentration (UIC) was 17.4 μg/L, with ≤20 μg/L indicative of severe iodine deficiency. According to the WHO/IC C IDD/UNIC EF classification, 88.1%, 7.1% and 2.4% of patients had a UIC <20 (severe), 20–49 (mild), and 50–99 μg/L (moderate), respectively. There was no statistically significant differences in UIC between men and women. Conclusion: The UIC values indicate that Iranian cancer patients were seriously iodine deficient according to WHO/UNIC EF/IC C IDD, and that this is a suitable index to assess iodine status in Iranians. Daily consumption of salt fortified with iodine or other approaches to increase intake might be effective strategies for prevention or reduction of malignancies. PMID:28441792

A study of assessment indicators for environmental sustainable development of science parks in Taiwan.

PubMed

Chen, Han-Shen; Chien, Li-Hsien; Hsieh, Tsuifang

2013-08-01

This study adopted the ecological footprint calculation structure to calculate the ecological footprints of the three major science parks in Taiwan from 2008 to 2010. The result shows that the ecological footprints of the Hsinchu Science Park, the Central Taiwan Science Park, and the Southern Taiwan Science Park were about 3.964, 2.970, and 4.165 ha per capita. The ecological footprint (EF) of the Central Taiwan Science Park was the lowest, meaning that the influence of the daily operations in the Central Taiwan Science Park on the environment was rather low. Secondly, the population density was relatively high, and the EF was not the highest of the Hsinchu Science Park, meaning that, while consuming ecological resources, the environmental management done was effective. In addition, the population density in Southern Taiwan Science Park is 82.8 units, lower than that of Hsinchu Science Park, but its ecological footprint per capita is 0.201 units, higher than Hsinchu, implying its indicator management has space for improvement. According to the analysis result above, in the science parks, the percentages of high-energy-consuming industries were rather high. It was necessary to encourage development of green industries with low energy consumption and low pollution through industry transformation.

Education for Sustainability in Universities: Challenges and Opportunities for Change

ERIC Educational Resources Information Center

Higgins, Blanche; Thomas, Ian

2016-01-01

Education for sustainability (EfS) is widely supported and researched; however, the broad and deep implementation of EfS in universities that is needed lags behind the goals of change agents. This article reviews literature on change procedures; in particular, curriculum change in universities. Our aim was to develop insights into strategies…

Supporting the Sustainability Journey of Tertiary International Students in Australia

ERIC Educational Resources Information Center

Sidiropoulos, Liz; Wex, Irene; Sibley, Jonathan

2013-01-01

This article reports the findings of a pilot Education for Sustainability (EfS) program implemented in 2011 for international students in a multi-campus distributed learning environment at an Australian university. It outlines the context of the pilot EfS program and reports survey findings of the environmental attitudes and sustainability…

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

EXECUTIVE FUNCTION PROFILES IN CHILDREN WITH AND WITHOUT SPECIFIC LANGUAGE IMPAIRMENT

PubMed Central

Marton, Klara; Campanelli, Luca; Scheuer, Jessica; Yoon, Jungmee; Eichorn, Naomi

2013-01-01

We present findings from a study that focused on specific executive functions (EF) in children with and without specific language impairment (SLI). We analyzed performance patterns and EF profiles (spatial working memory, inhibition control, and sustained attention) in school-age SLI children and two control groups: age-matched and language matched. Our main research goal was to identify those EFs that show a weakness in children with SLI. Our specific aims were to: (1) examine whether the EF problems in children with SLI are domain-general; (2) examine whether deficits in EF in children with SLI can be explained by the general slowness hypothesis or by an overall delay in development; (3) compare EF profiles to examine whether children with SLI show a distinct pattern of performance from their peers. Our findings showed different EF profiles for the groups. We observed differences in performance patterns related to age (e.g., reaction time in response inhibition) and differences related to language status (e.g., sensitivity to interference). The findings show interesting associations in EFs that play a crucial role in language processing. PMID:25302062

Understanding the EF-hand closing pathway using non-biased interatomic potentials.

PubMed

Dupuis, L; Mousseau, Normand

2012-01-21

The EF-hand superfamily of proteins is characterized by the presence of calcium binding helix-loop-helix structures. Many of these proteins undergo considerable motion responsible for a wide range of properties upon binding but the exact mechanism at the root of this motion is not fully understood. Here, we use an unbiased accelerated multiscale simulation scheme, coupled with two force fields - CHARMM-EEF1 and the extended OPEP - to explore in details the closing pathway, from the unbound holo state to the closed apo state, of two EF-hand proteins, the Calmodulin and Troponin C N-terminal nodules. Based on a number of closing simulations for these two sequences, we show that the EF-hand β-scaffold, identified as crucial by Grabarek for the EF-hand opening driven by calcium binding, is also important in closing the EF-hand. We also show the crucial importance of the phenylalanine situated at the end of first EF-hand helix, and identify an intermediate state modulating its behavior, providing a detailed picture of the closing mechanism for these two representatives of EF-hand proteins. © 2012 American Institute of Physics

Riser Pattern: Another Determinant of Heart Failure With Preserved Ejection Fraction.

PubMed

Komori, Takahiro; Eguchi, Kazuo; Saito, Toshinobu; Hoshide, Satoshi; Kario, Kazuomi

2016-10-01

Paradoxical increase in blood pressure (BP) during sleep, exceeding those of awake BP, is called the "riser" BP pattern, and known as an abnormal circadian BP rhythm, has been reported to be associated with adverse cardiovascular prognoses. However, the significance of ambulatory BP in heart failure patients with preserved ejection fraction (HFpEF) has never been reported. Here, we tested our hypothesis that abnormal circadian BP rhythm is associated with HFpEF. The authors enrolled 508 patients with hospitalized HF (age 68±13 years; 315 men, 193 women). There were 232 cases of HFpEF and 276 cases of heart failure with reduced ejection fraction (HFrEF). The riser BP pattern was significantly more frequent in the HFpEF (28.9%) group compared with the HFrEF group (19.9%). In a multivariable logistic regression analysis, the riser BP pattern was associated with HFpEF (odds ratio, 1.73; 95% confidence interval, 1.02-2.91; P=.041) independent of the other covariates. In conclusion, the riser BP pattern was associated with HFpEF. ©2016 Wiley Periodicals, Inc.

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.

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

Assessment of executive functioning in children and young adults treated for frontal lobe tumours using ecologically valid tests.

PubMed

Longaud-Valès, A; Chevignard, M; Dufour, C; Grill, J; Puget, S; Sainte-Rose, C; Valteau-Couanet, D; Dellatolas, G

2016-08-01

There is a lack of studies assessing executive functions (EF) using ecologically valid tests in children with frontal lobe lesions. This study aimed to (1) evaluate EF in children, adolescents and young adults treated for childhood frontal lobe tumours, (2) identify factors influencing performance, such as age at diagnosis or type of treatment, and (3) examine correlations between intellectual ability and classical and ecological tests of EF. Twenty-one patients, aged 8-27 years, treated for a childhood benign or malignant frontal lobe tumour, and 42 healthy controls (matched for gender, age and socio-economic status) were assessed using classical tests of EF, and the BADS-C ecological battery. Patients also underwent assessment of intellectual ability and parent and teacher ratings of the BRIEF questionnaire. IQ scores ranged from 45 to 125 (mean FSIQ = 84) and were lower in case of epilepsy, hydrocephalus and lower parental education. Patients displayed deficits in most, but not all measures of EF. Most classical and ecological measures of EF were strongly correlated to IQ. This study confirms the frequency of EF deficits in this population; it also highlights the utility of ecological measures of EF and some limitations of classical tests of EF in children.

Formation of ethyl ferulate from feruloylated oligosaccharide by transesterification of rice koji enzyme under sake mash conditions.

PubMed

Suzuki, Nobukazu; Ito, Toshihiko; Hiroshima, Kai; Tokiwano, Tetsuo; Hashizume, Katsumi

2016-03-01

Formation of ethyl ferulate (EF) and ferulic acid (FA) under sake mash conditions was studied using feruloylated oligosaccharide (FO), prepared from rice grains, as the substrate for rice koji enzyme. EF and FA were produced from FO over six times faster than from alkyl ferulates however, under the same ethanol concentration, only small differences were observed between the EF/FA ratios when either FO or methyl ferulate were used as substrates. Esterification and hydrolysis of FO or methyl ferulate showed similar pH dependencies and similar EF/FA ratios for each substrate in all of the pH ranges tested. Ethanol concentration clearly affected the EF/FA ratio; the ratio increased as ethanol concentration increased. Formation of EF and FA in the sake mash simulated rice digest was accelerated by addition of exogenous FO. These results indicated that supply of FO to sake mash is a crucial step for EF and FA formation, and ethanol is an influencing factor in the EF/FA ratio. The rice koji enzyme reaction suggested that EF and FA are formed through a common feruloylated enzyme intermediate complex by transesterification or hydrolysis, and these reactions occur competitively. Copyright © 2015 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Social skills and executive function among youth with sickle cell disease: a preliminary investigation.

PubMed

Hensler, Molly; Wolfe, Kelly; Lebensburger, Jeffrey; Nieman, Jilian; Barnes, Margaux; Nolan, William; King, Allison; Madan-Swain, Avi

2014-06-01

To explore the relationship between executive function (EF) and social skills in youth with sickle cell disease (SCD).   20 youth with SCD completed objective tests of EF (Tasks of Executive Control; Animal Sorting subtest from the Developmental Neuropsychological Assessment-Second Edition), an IQ screener, and paper-and-pencil measures of social skills (Social Skills Improvement System [SSIS]). Primary caregivers completed paper-and-pencil measures of EF (Behavior Rating Inventory of Executive Function) and social skills (SSIS).   EF scores from the Behavior Rating Inventory of Executive Function related to parent- and child-reported social skills such that EF deficits correlated with poorer overall and domain-specific social skills. Similarly, EF scores from the Animal Sorting test related to child-reported social skills. Worse parent-reported EF predicted worse parent-reported social skills above the variance accounted for by IQ.   EF is related to social skills and may be necessary for successful social interaction among youth with SCD. These results provide rationale and guidance for future larger-scale investigations of EF and social skills among children with SCD. © The Author 2014. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Adaptive alterations of elastic fibers in the bilaminar zone of rabbit temporomandibular joint following disc displacement.

PubMed

Gu, Zhiyuan; Wu, Huiling; Feng, Jianying; Shibata, Takanori; Hu, Ji'an; Zhang, Yinkai; Xie, Zhijian

2002-12-01

To study the adaptive alterations of elastic fibers in the bilaminar zone (BZ) of rabbit temporomandibular joint (TMJ) following disc displacement. Twenty-eight Japanese white rabbits were used in this study. The right temporomandibular joints of 20 of 28 rabbits were subjected to the surgical procedure of anterior disc displacement (ADD). Four rabbits in the surgical group were sacrificed at 2, 4, 6, 8 and 12 weeks after operation. Their temporomandibular joints were studied histochemically. Elastic fibers were reduced in number and ran irregularly in the superior lamina of BZ from ADD rabbits. The jungly elastic fibers (EFs) could still be seen at 2 weeks after operation. At 4 weeks, the number of EFs decreased significantly; EFs lost their jungly arrangement and were shaped like rough dots, of which the arrangement and the lengths were different. Six weeks after operation, many EFs were replaced by distorted, uneven, non-oriented fine EFs, distributed unevenly and some thick or fine EFs that ran irregularly. The number of EFs decreased further and their arrangement was more deranged at 8 weeks. At 10 and 12 weeks, EFs in the superior lamina of BZ were similar to those at 8 weeks. Our results show that EFs lost their function as well as their distribution and arrangement after disc displacement.

Fluid intelligence and executive functioning more alike than different?

PubMed

van Aken, Loes; Kessels, Roy P C; Wingbermühle, Ellen; van der Veld, William M; Egger, Jos I M

2016-02-01

Fluid intelligence (Gf) has been related to executive functioning (EF) in previous studies, and it is also known to be correlated with crystallized intelligence (Gc). The present study includes representative measures of Gf, Gc, and EF frequently used in clinical practice to examine this Gf-EF relation. It is hypothesised that the Gf-EF relation is higher than the Gc-EF relation, and that working memory in particular (as a measure of EF) shows a high contribution to this relation. Confirmatory factor analysis was performed on a mixed neuropsychiatric and non-clinical sample consisting of 188 participants, using the Kaufman Adolescent and Adult Intelligence Test, and three executive tasks of the Cambridge Neuropsychological Test Automated Battery, covering working memory, planning skills, and set shifting. The model fitted the data well [χ²(24)=35.25, p=0.07, RMSEA=0.050]. A very high correlation between Gf and EF was found (0.91), with working memory being the most profound indicator. A moderate to high correlation between Gc and EF was present. Current results are consistent with findings of a strong relation between Gf and working memory. Gf and EF are highly correlated. Gf dysfunction in neuropsychiatric patients warrants further EF examination and vice versa. It is discussed that results confirm the need to distinguish between specific versus general fluid/executive functioning, the latter being more involved when task complexity and novelty increase. This distinction can provide a more refined differential diagnosis and improve neuropsychiatric treatment indication.

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).

Hypertension and Heart Failure with Preserved Ejection Fraction: Connecting the Dots.

PubMed

Tsioufis, Costas; Georgiopoulos, Georgios; Oikonomou, Dimitrios; Thomopoulos, Costas; Katsiki, Niki; Kasiakogias, Alexandros; Chrysochoou, Christina; Konstantinidis, Dimitrios; Kalos, Theodoros; Tousoulis, Dimitrios

2017-01-01

Heart failure (HF) with preserved ejection fraction (EF) (HFpEF) accounts for approximately 50% of HF cases and its prevalence relative to HF with reduced EF is rising. Hypertension (HT) is the most common co-morbidity in HFpEF patients and it is implicated in both the pathogenesis and the prognosis of the disease. Therefore, HT is a modifiable risk factor of high yield in HFpEF. We reviewed the literature for epidemiologic data supporting the co-aggregation of the two entities as well as patho-physiologic mechanisms linking HT to HFpEF. Most importantly, we focused on treatment options targeting HT as a preventive strategy for delaying the progression of diastolic dysfunction or decreasing the odds for developing HFpEF. Along this line, we summarized the evidence and efficacy associated with different classes of antihypertensive medications in HFpEF patients. Finally, non-pharmacological approaches, including renal denervation and lifestyle modifications, to achieve optimal blood pressure (BP) control in HFpEF patients are reported. Unfortunately, no specific antihypertensive treatment has established a major survival benefit in this high risk subjects. Until the results of the efficacy of the novel drug LCZ696 (valsartan/ sacubitril) are available, the continuous monitoring and lowering of the BP by pharmacological and non-pharmacological means should be considered the major preventive and treatment strategy in HFpEF patients. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Pharmacokinetics and tissue distribution of enrofloxacin after single intramuscular injection in Pacific white shrimp.

PubMed

Fang, X; Zhou, J; Liu, X

2018-02-01

The pharmacokinetic properties and tissue distribution of enrofloxacin (EF) were investigated after single intramuscular (i.m.) dose of 10 mg/kg body weight (b.w.) in Pacific white shrimp at 22 to 25°C. EF and its metabolite ciprofloxacin (CF) were determined by high-performance liquid chromatography. After i.m. administration, EF was absorbed quickly, and the peak of EF concentration (C max ) reached at first time point in hemolymph. The volume of distribution V d(area) of EF was 3.84 L/kg, indicating that the distribution of EF was good. The area under the concentration-time curve (AUC) of EF was 90.1 and 274.2 μg hr/ml in muscle and hepatopancreas, respectively, which was higher than 75.8 μg hr/ml in hemolymph. The EF elimination was slow in muscle and hepatopancreas with the half-life (T 1/2β ) of 52.3 and 75.8 hr, respectively. CF, the mainly metabolite of EF, was detected in hemolymph, muscle and hepatopancreas. The C max was 0.030, 0.013 and 0.218 μg/ml, respectively. Based on a minimum inhibitory concentration (MIC) of 0.006-0.032 μg/ml for susceptible strains, EF i.m. injected at a dose 10 mg/kg could be efficacious against common pathogenic bacteria of Pacific white shrimp. © 2017 John Wiley & Sons Ltd.

P2X and P2Y Receptors Mediate Contraction Induced by Electrical Field Stimulation in Feline Esophageal Smooth Muscle.

PubMed

Cho, Young Rae; Jang, Hyeon Soon; Kim, Won; Park, Sun Young; Sohn, Uy Dong

2010-10-01

It is well-known that electrical field stimulation (EFS)-induced contraction is mediated by a cholinergic mechanism and other neurotransmitters. NO, ATP, calcitonin gene-related peptide (CGRP), and substance P are released by EFS. To investigate the purinergic mechanism involved in the EFS-induced contraction, purinegic receptors antagonists were used. Suramine, a non-selective P2 receptor antagonist, reduced the contraction induced by EFS. NF023 (10(-7)~10(-4) M), a selective P2X antagonist, inhibited the contraction evoked by EFS. Reactive blue (10(-6)~10(-4) M), selective P2Y antagonist, also blocked the contraction in a dose-dependent manner. In addition, P2X agonist α,β-methylene 5'-adenosine triphosphate (αβMeATP, 10(-7)~10(-5) M) potentiated EFS-induced contraction in a dose-dependent manner. P2Y agonist adenosine 5'-[β-thio]diphosphate trilithium salt (ADPβS, 10(-7)~10(-5) M) also potentiated EFS-induced contractions in a dose-dependent manner. Ecto-ATPase activator apyrase (5 and 10 U/ml) reduced EFS-induced contractions. Inversely, 6-N,N-diethyl-D-β,γ-dibromomethylene 5'-triphosphate triammonium (ARL 67156, 10(-4) M) increased EFS-induced contraction. These data suggest that endogenous ATP plays a role in EFS-induced contractions which are mediated through both P2X-receptors and P2Y-receptors stimulation in cat esophageal smooth muscle.

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.

Conclusions about Interventions, Programs, and Approaches for Improving Executive Functions that appear Justified and those that, despite much hype, do not

PubMed Central

Diamond, Adele; Ling, Daphne S.

2015-01-01

The ‘Executive Functions’ (EFs) of inhibitory control, working memory, and cognitive flexibility enable us to think before we act, resist temptations or habitual reactions, stay focused, mentally play with ideas, reason, problem-solve, flexibly adjust to changed demands or priorities, and see things from new and different perspectives. These skills are critical for success in all life’s aspects. They are sometimes more predictive than even IQ or socioeconomic status. Understandably, there is great interest in improving EFs. It’s now clear they can be improved at any age through training and practice, much as physical exercise hones physical fitness. It also appears though, despite claims to the contrary, that wide transfer does not seem to occur and aerobic exercise per se does little to improve EFs. Important questions remain including: Are benefits just ephemeral and superficial? How much can EFs be improved and how long can benefits be sustained? What are the best methods for improving EFs? What about an approach accounts for its success? Do the answers to any of these differ by individual characteristics such as age or gender? Since stress, sadness, loneliness, or poor health impair EFs, and the reverse enhances EFs, I predict that approaches that not only directly train EFs but also indirectly support EFs by addressing emotional, social, and physical needs will be the most successful at improving EFs. PMID:26749076

Purification and Characterization of Tagless Recombinant Human Elongation Factor 2 Kinase (eEF-2K) Expressed in Escherichia coli

PubMed Central

Abramczyk, Olga; Tavares, Clint D. J.; Devkota, Ashwini K.; Ryazanov, Alexey G.; Turk, Benjamin E.; Riggs, Austen F.; Ozpolat, Bulent; Dalby, Kevin N.

2012-01-01

The eukaryotic elongation factor 2 kinase (eEF-2K) modulates the rate of protein synthesis by impeding the elongation phase of translation by inactivating the eukaryotic elongation factor 2 (eEF-2) via phosphorylation. eEF-2K is known to be activated by calcium and calmodulin, whereas the mTOR and MAPK pathways are suggested to negatively regulate kinase activity. Despite its pivotal role in translation regulation and potential role in tumor survival, the structure, function and regulation of eEF-2K have not been described in detail. This deficiency may result from the difficulty of obtaining the recombinant kinase in a form suitable for biochemical analysis. Here we report the purification and characterization of recombinant human eEF-2K expressed in the Escherichia coli strain Rosetta-gami 2(DE3). Successive chromatography steps utilizing Ni-NTA affinity, anion-exchange and gel filtration columns accomplished purification. Cleavage of the thioredoxin-His6-tag from the N-terminus of the expressed kinase with TEV protease yielded 9 mg of recombinant (G-D-I)-eEF-2K per liter of culture. Light scattering shows that eEF-2K is a monomer of ~ 85 kDa. In vitro kinetic analysis confirmed that recombinant human eEF-2K is able to phosphorylate wheat germ eEF-2 with kinetic parameters comparable to the mammalian enzyme. PMID:21605678

Analysis of serum chemokine levels in patients with HIV-associated eosinophilic folliculitis.

PubMed

Yokobayashi, H; Sugaya, M; Miyagaki, T; Kai, H; Suga, H; Yamada, D; Minatani, Y; Watanabe, K; Kikuchi, Y; Tamaki, T; Sato, S

2013-02-01

Patients with human immunodeficiency virus (HIV) infection exhibit various skin diseases. HIV-associated eosinophilic folliculitis (EF) and pruritic papular eruption (PPE) are frequently seen. To understand the mechanisms underlying HIV-associated EF and PPE. In order to know frequencies of EF and PPE among patients with HIV infection, we first collected HIV(+) patients who visited dermatology clinic in National Center for Global Health and Medicine during February 2007. We next collected 25 serum samples from HIV(+) patients with skin diseases from May 2008 to May 2010. Eight of 25 patients had EF (EF group), four had PPE (PPE group) and others had non-itchy skin problems such as condyloma acuminatum (no itch group). We first confirmed high frequencies of EF (10.7%) and PPE (5.3%) among 75 HIV(+) patients who visited our clinic during one month. We then measured serum levels of CCL11, CCL17, CCL26 and CCL27. Serum CCL17 levels in EF were significantly higher than those of PPE and no itch group. Serum CCL26 and CCL27 levels in EF were higher than those of no itch group. The number of CD4(+) cells in EF was significantly lower than that in no itch group. High serum levels of CCL17, CCL26 and CCL27, and low CD4(+) cell counts may account for the development of HIV-associated EF. © 2012 The Authors. Journal of the European Academy of Dermatology and Venereology © 2012 European Academy of Dermatology and Venereology.

Emerging Executive Functioning and Motor Development in Infants at High and Low Risk for Autism Spectrum Disorder.

PubMed

St John, Tanya; Estes, Annette M; Dager, Stephen R; Kostopoulos, Penelope; Wolff, Jason J; Pandey, Juhi; Elison, Jed T; Paterson, Sarah J; Schultz, Robert T; Botteron, Kelly; Hazlett, Heather; Piven, Joseph

2016-01-01

Existing evidence suggests executive functioning (EF) deficits may be present in children with autism spectrum disorder (ASD) by 3 years of age. It is less clear when, prior to 3 years, EF deficits may emerge and how EF unfold over time. The contribution of motor skill difficulties to poorer EF in children with ASD has not been systematically studied. We investigated the developmental trajectory of EF in infants at high and low familial risk for ASD (HR and LR) and the potential associations between motor skills, diagnostic group, and EF performance. Participants included 186 HR and 76 LR infants. EF (A-not-B), motor skills (Fine and Gross Motor), and cognitive ability were directly assessed at 12 months and 24 months of age. Participants were directly evaluated for ASD at 24 months using DSM-IV-TR criteria and categorized as HR-ASD, HR-Negative, and LR-Negative. HR-ASD and HR-Negative siblings demonstrated less improvement in EF over time compared to the LR-Negative group. Motor skills were associated with group and EF performance at 12 months. No group differences were found at 12 months, but at 24 months, the HR-ASD and HR-Negative groups performed worse than the LR-Negative group overall after controlling for visual reception and maternal education. On reversal trials, the HR-ASD group performed worse than the LR-Negative group. Motor skills were associated with group and EF performance on reversal trials at 24 months. Findings suggest that HR siblings demonstrate altered EF development and that motor skills may play an important role in this process.

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

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.

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.

Improving substance use prevention efforts with executive function training.

PubMed

Pentz, Mary Ann; Riggs, Nathaniel R; Warren, Christopher M

2016-06-01

Executive function (EF) includes emotional regulation, planning and decision-making, and behavioral impulse control. Improving youth substance use (SU) prevention by targeting EF poses challenges including determining whether specific sub-domains of EF are more associated with SU than others, whether EF is related to some types of SU more than others, and whether EF programs might be enhanced by inclusion of mindfulness training. Data were drawn from two studies from the Pathways to Health project: a randomized controlled trial of 4th-6th graders and a cross-sectional pilot study of the relationship of EF to specific types of SU in a sample of 7th graders. Survey measures included assessment of the EF subdomains of inhibitory control (IC), emotional control, working memory, organization/planning, lifetime SU (tobacco and alcohol use), and mindfulness. Analyses included multivariate and multiple group path analysis. Results suggested that the EF sub-domain of IC was the strongest and most consistent predictor of SU, particularly cigarette and e-cigarette use, though emotional control was predictive of alcohol use among late-elementary school students. In the 7th grade sample, IC was predictive of alcohol, cigarette, and e-cigarette use only among students in the low 75% of mindfulness. Findings from the present studies suggest that improvements in SU prevention efforts may result from increased curricular emphasis on IC and its application to multiple substance use prevention, and systematically integrating mindfulness with EF skills training. Future research should examine whether EF-SU relationships vary across patterns of SU and types of measures used to assess EF. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

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.

Heart failure with preserved ejection fraction and systolic dysfunction in the community.

PubMed

Moutinho, Marco Aurélio Esposito; Colucci, Flávio Augusto; Alcoforado, Veronica; Tavares, Leandro Reis; Rachid, Mauricio Bastos Freitas; Rosa, Maria Luisa Garcia; Ribeiro, Mário Luiz; Abdalah, Rosemery; Garcia, Juliana Lago; Mesquita, Evandro Tinoco

2008-02-01

In developed countries, heart failure with preserved ejection fraction (HFpEF) is more prevalent than heart failure with reduced ejection fraction (HFrEF) in the community. However, it has not been completely established if this fact is also observed within our community. To determine the most prevalent form of heart failure (HFpEF or HFrEF) and whether the prevalence of HFpEF is higher in the community. This is a cross-sectional study conducted with patients clinically diagnosed with HF who were seen in community-based health care centers from January to December 2005. Echodopplercardiograms were performed for all patients. The form of HF was stratified according to the presence of abnormalities and the shortening fraction observed on the echodopplercardiogram. The study evaluated 170 patients (61.0 +/- 13.3 years of age), most of them women and elderly. HFpEF was the more prevalent form of HF (64.2%, p<0.001), affecting mostly elderly women (62%, p = 0.07), whereas the opposite condition, HFrEF, was observed mostly in elderly men (63.6%, p = 0.07). Patients with no HF represented one-third of the cases (27.6%). HFrEF patients had more lower-limb edema, coronary disease, diabetes, chronic renal failure, higher Boston scores and hospital readmissions. Use of alcoholic beverages and smoking were also more common among HFrEF patients. HFpEF is the most prevalent form of HF in the community especially among elderly women, whereas HFrEF affects mostly elderly men and is associated with greater clinical severity, main risk factors and no changes in lifestyle. Despite the signs and symptoms of HF, this condition was not confirmed for one-third of the cases.

Left ventricular remodeling and change of systolic function after closure of patent ductus arteriosus in adults: device and surgical closure.

PubMed

Jeong, Young-Hoon; Yun, Tae-Jin; Song, Jong-Min; Park, Jung-Jun; Seo, Dong-Man; Koh, Jae-Kon; Lee, Se-Whan; Kim, Mi-Jeong; Kang, Duk-Hyun; Song, Jae-Kwan

2007-09-01

Left ventricular (LV) remodeling and predictors of LV systolic function late after closure of patent ductus arteriosus (PDA) in adults remain to be clearly demonstrated. In 45 patients with PDA, including 28 patients who received successful occlusion using the Amplatzer device (AD group) (AGA, Golden Valley, MN) and 17 patients who received surgical closure (OP group), echocardiography studies were performed before closure and 1 day (AD group) or within 7 days (OP group) after closure, and then were repeated at > or = 6 months (17 +/- 13 months). In both groups, LV ejection fraction (EF) and end-diastolic volume index were significantly decreased immediately after closure, whereas end-systolic volume index did not change. During the long-term follow-up period, end-systolic as well as end-diastolic volume indices decreased significantly in both groups and LV EF recovered compared to the immediate postclosure state. However, LV EF remained low compared to the preclosure state. Five patients (11.1%) including 3 patients in the AD group and 2 patients in the OP group showed persistent late LV systolic dysfunction (EF <50%). In stepwise, multiple logistic regression analysis, preclosure EF was the only independent predictor of late normal postclosure EF (odds ratio, 1.230; 95% CI, 1.054-1.434; P = .008). Receiver operating characteristic curve analysis showed that preclosure EF > or = 62% had a sensitivity of 72% and a specificity of 83% for predicting late normal LV EF after closure. Left ventricular EF remains low late after PDA closure compared with preclosure state in adults. Preclosure LV EF is the best index to predict late postclosure LV EF.

Emerging Executive Functioning and Motor Development in Infants at High and Low Risk for Autism Spectrum Disorder

PubMed Central

St. John, Tanya; Estes, Annette M.; Dager, Stephen R.; Kostopoulos, Penelope; Wolff, Jason J.; Pandey, Juhi; Elison, Jed T.; Paterson, Sarah J.; Schultz, Robert T.; Botteron, Kelly; Hazlett, Heather; Piven, Joseph

2016-01-01

Existing evidence suggests executive functioning (EF) deficits may be present in children with autism spectrum disorder (ASD) by 3 years of age. It is less clear when, prior to 3 years, EF deficits may emerge and how EF unfold over time. The contribution of motor skill difficulties to poorer EF in children with ASD has not been systematically studied. We investigated the developmental trajectory of EF in infants at high and low familial risk for ASD (HR and LR) and the potential associations between motor skills, diagnostic group, and EF performance. Participants included 186 HR and 76 LR infants. EF (A-not-B), motor skills (Fine and Gross Motor), and cognitive ability were directly assessed at 12 months and 24 months of age. Participants were directly evaluated for ASD at 24 months using DSM-IV-TR criteria and categorized as HR-ASD, HR-Negative, and LR-Negative. HR-ASD and HR-Negative siblings demonstrated less improvement in EF over time compared to the LR-Negative group. Motor skills were associated with group and EF performance at 12 months. No group differences were found at 12 months, but at 24 months, the HR-ASD and HR-Negative groups performed worse than the LR-Negative group overall after controlling for visual reception and maternal education. On reversal trials, the HR-ASD group performed worse than the LR-Negative group. Motor skills were associated with group and EF performance on reversal trials at 24 months. Findings suggest that HR siblings demonstrate altered EF development and that motor skills may play an important role in this process. PMID:27458411

Influence of fuel mass load, oxygen supply and burning rate on emission factor and size distribution of carbonaceous particulate matter from indoor corn straw burning.

PubMed

Shen, Guofeng; Xue, Miao; Wei, Siye; Chen, Yuanchen; Wang, Bin; Wang, Rong; Shen, Huizhong; Li, Wei; Zhang, Yanyan; Huang, Ye; Chen, Han; Wei, Wen; Zhao, Qiuyue; Li, Bin; Wu, Haisuo; Tao, Shu

2013-03-01

The uncertainty in emission estimation is strongly associated with the variation in emission factor (EF), which could be influenced by a variety of factors such as fuel properties, stove type, fire management and even methods used in measurements. The impacts of these factors are complicated and often interact with each other. Controlled burning experiments were conducted to investigate the influences of fuel mass load, air supply and burning rate on the emissions and size distributions of carbonaceous particulate matter (PM) from indoor corn straw burning in a cooking stove. The results showed that the EFs of PM (EF(PM)), organic carbon (EFoc) and elemental carbon (EF(EC)) were independent of the fuel mass load. The differences among them under different burning rates or air supply amounts were also found to be insignificant (p > 0.05) in the tested circumstances. PM from the indoor corn straw burning was dominated by fine PM with diameter less than 2.1 microm, contributing 86.4% +/- 3.9% of the total. The size distribution of PM was influenced by the burning rate and air supply conditions. On average, EF(PM), EF(OC) and EF(EC) for corn straw burned in a residential cooking stove were (3.84 +/- 1.02), (0.846 +/- 0.895) and (0.391 +/- 0.350) g/kg, respectively. EF(PM), EF(OC) and EF(EC) were found to be positively correlated with each other (p < 0.05), but they were not significantly correlated with the EF of co-emitted CO, suggesting that special attention should be paid to the use of CO as a surrogate for other incomplete combustion pollutants.

The curcumin analog EF24 targets NF-κB and miRNA-21, and has potent anticancer activity in vitro and in vivo.

PubMed

Yang, Chuan He; Yue, Junming; Sims, Michelle; Pfeffer, Lawrence M

2013-01-01

EF24 is a curcumin analog that has improved anticancer activity over curcumin, but its therapeutic potential and mechanism of action is unknown, which is important to address as curcumin targets multiple signaling pathways. EF24 inhibits the NF-κB but not the JAK-STAT signaling pathway in DU145 human prostate cancer cells and B16 murine melanoma cells. EF24 induces apoptosis in these cells apparently by inhibiting miR-21 expression, and also enhances the expression of several miR-21 target genes, PTEN and PDCD4. EF24 treatment significantly suppressed the growth of DU145 prostate cancer xenografts in immunocompromised mice and resulted in tumor regression. EF24 enhanced the expression of the miR-21 target PTEN in DU145 tumor tissue, but suppressed the expression of markers of proliferating cells (cyclin D1 and Ki67). In syngeneic mice injected with B16 cells, EF24 treatment inhibited the formation of lung metastasis, prolonged animal survival, inhibited miR-21 expression and increased the expression of miR-21 target genes. Expression profiling of miRNAs regulated by EF24 in vitro and in vivo showed that the antitumor activity of EF24 reflected the enhanced expression of potential tumor suppressor miRNAs as well as the suppressed expression of oncogenic miRNAs, including miR-21. Taken together, our data suggest that EF24 is a potent anticancer agent and selectively targets NF-κB signaling and miRNA expression, indicating that EF24 has significant potential as a therapeutic agent in various cancers.

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.

The Curcumin Analog EF24 Targets NF-κB and miRNA-21, and Has Potent Anticancer Activity In Vitro and In Vivo

PubMed Central

Yang, Chuan He; Yue, Junming; Sims, Michelle; Pfeffer, Lawrence M.

2013-01-01

EF24 is a curcumin analog that has improved anticancer activity over curcumin, but its therapeutic potential and mechanism of action is unknown, which is important to address as curcumin targets multiple signaling pathways. EF24 inhibits the NF-κB but not the JAK-STAT signaling pathway in DU145 human prostate cancer cells and B16 murine melanoma cells. EF24 induces apoptosis in these cells apparently by inhibiting miR-21 expression, and also enhances the expression of several miR-21 target genes, PTEN and PDCD4. EF24 treatment significantly suppressed the growth of DU145 prostate cancer xenografts in immunocompromised mice and resulted in tumor regression. EF24 enhanced the expression of the miR-21 target PTEN in DU145 tumor tissue, but suppressed the expression of markers of proliferating cells (cyclin D1 and Ki67). In syngeneic mice injected with B16 cells, EF24 treatment inhibited the formation of lung metastasis, prolonged animal survival, inhibited miR-21 expression and increased the expression of miR-21 target genes. Expression profiling of miRNAs regulated by EF24 in vitro and in vivo showed that the antitumor activity of EF24 reflected the enhanced expression of potential tumor suppressor miRNAs as well as the suppressed expression of oncogenic miRNAs, including miR-21. Taken together, our data suggest that EF24 is a potent anticancer agent and selectively targets NF-κB signaling and miRNA expression, indicating that EF24 has significant potential as a therapeutic agent in various cancers. PMID:23940701

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

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.

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.

Relations between executive function and emotionality in preschoolers: Exploring a transitive cognition–emotion linkage

PubMed Central

Ferrier, David E.; Bassett, Hideko H.; Denham, Susanne A.

2014-01-01

Emotions play a crucial role in appraisal of experiences and environments and in guiding thoughts and actions. Moreover, executive function (EF) and emotion regulation (ER) have received much attention, not only for positive associations with children’s social–emotional functioning, but also for potential central roles in cognitive functioning. In one conceptualization of ER (Campos etal., 2004), processes of ER, and those of emotional expression and experience (hereafter referred to as emotionality) are highly related and reciprocal; yet, there has been little research on young children’s EF that focuses on emotionality, although it is easily observed within a classroom. The two goals of the study were to: (1) investigate the relatively unexplored role of emotionality in the development of EF in early childhood and (2) assess the relations between an observational rating of EF obtained after direct assessment with a standardized EF rating scale. We predicted that observed emotionality and EF would both demonstrate stability and predict one another within and across time. 175 children aged 35–60 months were recruited from Head Start and private childcare centers. Using partial least squares modeling, we chose T1 emotionality as the exogenous variable and tested pathways between emotionality and EF across two time points, 6 months apart. Results showed that both T1 observed EF and emotionality predicted their respective T2 counterparts, supporting the idea that both constructs build upon existing systems. Further, T1 emotionality predicted T1 observed EF and the T2 BRIEF-P composite. In turn, T1 observed EF predicted emotionality and the T2 BRIEF-P composite. These findings fit with literature on older populations in which EF and emotionality have been related, yet are the first to report such relations in early childhood. Last, T1 observed EF’s positive prediction of the T2 BRIEF-P composite lends credence to the use of both EF measures in applied and research settings. PMID:24904500

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

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.

Interpreting the paleo-redox record: Mn enrichment factors

NASA Astrophysics Data System (ADS)

Chun, C. O.; Delaney, M. L.

2006-12-01

Redox-sensitive metal enrichment factors (EF), have the ability to describe the redox chemistry of the overlying water and marine sediments at time of burial. Manganese (Mn) precipitates as Mn-rich oxyhydroxides in oxic environments, leading to sedimentary EF > 1 calculated relative to average continental crust as the presumed detrital source. Mn EF can also occur from source changes that are unrelated to redox changes. We compared bulk sediment digestions to sample splits treated with a reductive cleaning step prior to sediment digestion, to test whether the Mn EF are from oxyhydroxides. We measured sedimentary Mn EF for the past 30 m.y. for a Nazca Ridge site in the southeast Pacific (ODP Site 1237). The site is marked by a pronounced color change at 162 mcd, within an interval dominated by calcareous-rich lithology, prompting questions of source versus paleo-redox changes. Mn EF were measured across the Paleocene-Eocene Thermal Maximum (PETM) at three sites on Walvis Ridge in the southeast Atlantic (ODP Sites 1262, 1266, and 1263). The PETM global warming event leads to questions of redox changes. At Nazca Ridge Mn EF range from 10-70 prior to the change with decrease to crustal averages after the boundary. After two reductive cleanings on sediments exhibiting Mn EF >1, Mn EF were at crustal averages. Mn EF prior to the color change are oxyhydroxides and not a major input of detrital material. We suggest the color change represents a paleo-redox boundary, more oxygenated depositional setting prior to the change and more reducing depositional setting afterwards. Walvis Ridge PETM sections exhibit Mn EF values ranging between 4 and 12 prior to the warming, values at crustal averages during the warming, return to pre-event values in the recovery period. After the reductive cleaning procedure the deep (1262) and intermediate (1266) sites with Mn EF >1 before and after the warming event reduced to crustal averages with no change to Mn EF during the event. Bottom waters at those two sites were most likely oxygenated prior to the event, reducing at the onset of the warming, and returned to pre-event conditions in the recovery. Future studies of Mn EF as a paleo-redox indicator should include the reductive cleaning procedure to verify Mn-oxyhydroxides.

Physiological dead space and arterial carbon dioxide contributions to exercise ventilatory inefficiency in patients with reduced or preserved ejection fraction heart failure.

PubMed

Van Iterson, Erik H; Johnson, Bruce D; Borlaug, Barry A; Olson, Thomas P

2017-12-01

Patients with heart failure (HF) with reduced (HFrEF) or preserved (HFpEF) ejection fraction demonstrate an increased ventilatory equivalent for carbon dioxide (V̇ E /V̇CO 2 ) slope. The physiological correlates of the V̇ E /V̇CO 2 slope remain unclear in the two HF phenotypes. We hypothesized that changes in the physiological dead space to tidal volume ratio (V D /V T ) and arterial CO 2 tension (PaCO 2 ) differentially contribute to the V̇ E /V̇CO 2 slope in HFrEF vs. HFpEF. Adults with HFrEF (n = 32) and HFpEF (n = 27) [mean ± standard deviation (SD) left ventricular ejection fraction: 22 ± 7% and 61 ± 9%, respectively; mean ± SD body mass index: 28 ± 4 kg/m 2 and 33 ± 6 kg/m 2 , respectively; P < 0.01] performed cardiopulmonary exercise testing with breath-by-breath ventilation and gas exchange measurements. PaCO 2 was measured via radial arterial catheterization. We calculated the V̇ E /V̇CO 2 slope via linear regression, and V D /V T  = 1 - [(863 × V̇CO 2 )/(V̇ E  × PaCO 2 )]. Resting V D /V T (0.48 ± 0.08 vs. 0.41 ± 0.11; P = 0.04), but not PaCO 2 (38 ± 5 mmHg vs. 40 ± 3 mmHg; P = 0.21) differed between HFrEF and HFpEF. Peak exercise V D /V T (0.39 ± 0.08 vs. 0.32 ± 0.12; P = 0.02) and PaCO 2 (33 ± 6 mmHg vs. 38 ± 4 mmHg; P < 0.01) differed between HFrEF and HFpEF. The V̇ E /V̇CO 2 slope was higher in HFrEF compared with HFpEF (44 ± 11 vs. 35 ± 8; P < 0.01). Variance associated with the V̇ E /V̇CO 2 slope in HFrEF and HFpEF was explained by peak exercise V D /V T (R 2  = 0.30 and R 2  = 0.50, respectively) and PaCO 2 (R 2  = 0.64 and R 2  = 0.28, respectively), but the relative contributions of each differed (all P < 0.01). Relationships between the V̇ E /V̇CO 2 slope and both V D /V T and PaCO 2 are robust, but differ between HFpEF and HFrEF. Increasing V̇ E /V̇CO 2 slope appears to be strongly explained by mechanisms influential in regulating PaCO 2 in HFrEF, which contrasts with the strong role of increased V D /V T in HFpEF. © 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.

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'…

Embedding EfS in Teacher Education through a Multi-Level Systems Approach: Lessons from Queensland

ERIC Educational Resources Information Center

Evans, Neus; Ferreira, Jo-Anne; Davis, Julie; Stevenson, Robert B.

2016-01-01

This article reports on the fourth stage of an evolving study to develop a systems model for embedding education for sustainability (EfS) into preservice teacher education. The fourth stage trialled the extension of the model to a comprehensive state-wide systems approach involving representatives from all eight Queensland teacher education…

Education for Sustainability Using a Campus Eco-Garden as a Learning Environment

ERIC Educational Resources Information Center

Cheang, Chi Chiu; So, Wing-Mui Winnie; Zhan, Ying; Tsoi, Kwok Ho

2017-01-01

Purpose: This paper aims to explore stakeholder perspectives of the role of a campus eco-garden in education for sustainability (EfS). It will combine the perspectives to highlight a powerful learning environment (PLE) for university students to realize the concept of EfS. Design/methodology/approach: Semi-structured interviews were conducted to…

Executive Functioning Predicts School Readiness and Success: Implications for Assessment and Intervention

ERIC Educational Resources Information Center

Cantin, Rachelle H.; Mann, Trisha D.; Hund, Alycia M.

2012-01-01

In recent years, executive functioning (EF) has received increasing attention from researchers and practitioners focusing on how EF predicts important outcomes such as success at school and in life. For example, EF has been described as the single best predictor of school readiness (Blair & Razza, 2007). Moreover, EF has been implicated in…

Education for Sustainability in University Curricula: Policies and Practice in Victoria

ERIC Educational Resources Information Center

Leihy, Peodair; Salazar, Jose

2011-01-01

Education for sustainability (EfS) refers to education that builds the knowledge, skills and dispositions for living sustainably. It is bringing sustainability--for some time a prominent concern within higher education--firmly within the fold of teaching and learning, a key aspect of universities' core business. Is EfS an unstoppable juggernaut in…

Socio-Scientific Issues in Education: Innovative Practices and Contending Epistemologies

ERIC Educational Resources Information Center

Robottom, Ian

2012-01-01

In the past decade, we have seen the well-established discourse of environmental education (EE) supplanted by that of education for sustainability (EfS). In some ways this change in terminology has been no more than a slogan change, with the actual educational practices associated with EfS little changed from those qualified by EE (Campbell and…

Multiformity of elongation factor eEF-2 isolated from rat liver cells.

PubMed

Gajko, A; Gałasiński, W; Gindzieński, A

1994-07-29

Two fractions of eEF-2 (M(r) approx. 100,000 and M(r) approx. 65,000) were isolated from post-ribosomal supernatant of the rat liver cells. Only eEF-2, with mol. weight of about 100,000 Da, can be phosphorylated, but only eEF-2, with mol. weight of about 65,000 Da, was isolated from the active polyribosomes. The existence of two eEF-2 forms with different properties in the rat liver cells is striking and uncovers new aspects for the cellular function of this protein.

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.

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

Eukaryotic elongation factor 2 is a prognostic marker and its kinase a potential therapeutic target in HCC

PubMed Central

Pott, Leona L; Hagemann, Sascha; Reis, Henning; Lorenz, Kristina; Bracht, Thilo; Herold, Thomas; Skryabin, Boris V; Megger, Dominik A; Kälsch, Julia; Weber, Frank; Sitek, Barbara; Baba, Hideo A

2017-01-01

Hepatocellular carcinoma is a cancer with increasing incidence and largely refractory to current anticancer drugs. Since Sorafenib, a multikinase inhibitor has shown modest efficacy in advanced hepatocellular carcinoma additional treatments are highly needed. Protein phosphorylation via kinases is an important post-translational modification to regulate cell homeostasis including proliferation and apoptosis. Therefore kinases are valuable targets in cancer therapy. To this end we performed 2D differential gel electrophoresis and mass spectrometry analysis of phosphoprotein-enriched lysates of tumor and corresponding non-tumorous liver samples to detect differentially abundant phosphoproteins to screen for novel kinases as potential drug targets. We identified 34 differentially abundant proteins in phosphoprotein enriched lysates. Expression and distribution of the candidate protein eEF2 and its phosphorylated isoform was validated immunohistochemically on 78 hepatocellular carcinoma and non-tumorous tissue samples. Validation showed that total eEF2 and phosphorylated eEF2 at threonine 56 are prognostic markers for overall survival of HCC-patients. The activity of the regulating eEF2 kinase, compared between tumor and non-tumorous tissue lysates by in vitro kinase assays, is more than four times higher in tumor tissues. Functional analyzes regarding eEF2 kinase were performed in JHH5 cells with CRISPR/Cas9 mediated eEF2 kinase knock out. Proliferation and growth is decreased in eEF2 kinase knock out cells. Conclusion eEF2 and phosphorylated eEF2 are prognostic markers for survival of hepatocellular carcinoma patients and the regulating eEF2 kinase is a potential drug target for tumor therapy. PMID:28060762

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

Eukaryotic elongation factor 2 is a prognostic marker and its kinase a potential therapeutic target in HCC.

PubMed

Pott, Leona L; Hagemann, Sascha; Reis, Henning; Lorenz, Kristina; Bracht, Thilo; Herold, Thomas; Skryabin, Boris V; Megger, Dominik A; Kälsch, Julia; Weber, Frank; Sitek, Barbara; Baba, Hideo A

2017-02-14

Hepatocellular carcinoma is a cancer with increasing incidence and largely refractory to current anticancer drugs. Since Sorafenib, a multikinase inhibitor has shown modest efficacy in advanced hepatocellular carcinoma additional treatments are highly needed. Protein phosphorylation via kinases is an important post-translational modification to regulate cell homeostasis including proliferation and apoptosis. Therefore kinases are valuable targets in cancer therapy. To this end we performed 2D differential gel electrophoresis and mass spectrometry analysis of phosphoprotein-enriched lysates of tumor and corresponding non-tumorous liver samples to detect differentially abundant phosphoproteins to screen for novel kinases as potential drug targets. We identified 34 differentially abundant proteins in phosphoprotein enriched lysates. Expression and distribution of the candidate protein eEF2 and its phosphorylated isoform was validated immunohistochemically on 78 hepatocellular carcinoma and non-tumorous tissue samples. Validation showed that total eEF2 and phosphorylated eEF2 at threonine 56 are prognostic markers for overall survival of HCC-patients. The activity of the regulating eEF2 kinase, compared between tumor and non-tumorous tissue lysates by in vitro kinase assays, is more than four times higher in tumor tissues. Functional analyzes regarding eEF2 kinase were performed in JHH5 cells with CRISPR/Cas9 mediated eEF2 kinase knock out. Proliferation and growth is decreased in eEF2 kinase knock out cells. eEF2 and phosphorylated eEF2 are prognostic markers for survival of hepatocellular carcinoma patients and the regulating eEF2 kinase is a potential drug target for tumor therapy.

Executive Function is Associated with Social Competence in Preschool-Aged Children Born Preterm or Full Term

PubMed Central

Alduncin, Nidia; Huffman, Lynne C.; Feldman, Heidi M.; Loe, Irene M.

2014-01-01

Background Executive function (EF), defined as higher-order cognitive processes used in planning and organizing actions and emotions, is often impaired in children born preterm. Few studies have assessed social competence, the processes and resources required to meet social demands and achieve social goals, in children born preterm. The relations between EF and social competence in preterm and full term preschoolers have not been well characterized. Aims To characterize social competence and assess the relationship between EF and social competence in preschool-aged children born preterm or full term. Study design Cross-sectional study. Subjects Study subjects had a history of preterm birth (≤ 34 weeks gestation) and birth weight < 2500 g (n = 70). Controls were born full term (≥ 37 weeks) (n = 79). Outcome measures Children completed a battery of EF tasks; a mean age-adjusted z-score for the battery was generated for each child. Parents rated child EF on one scale and child social competence on two standardized scales. Results Compared to full term children, preterm children showed a lower mean EF battery z-score, poorer parent-rated EF, and poorer scores on the two social competence scales. In hierarchical multiple regression models, EF battery z-score and parent-rated EF made independent contributions to both measures of social competence. Preterm birth explained additional variance for one measure of social competence. Conclusions Standard assessment of EF skills and social competence in young preschool children, including children born preterm, may identify at-risk children for long-term social difficulties and may also provide targets for intervention. PMID:24661446

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.

Ratings of Everyday Executive Functioning (REEF): A parent-report measure of preschoolers' executive functioning skills.

PubMed

Nilsen, Elizabeth S; Huyder, Vanessa; McAuley, Tara; Liebermann, Dana

2017-01-01

Executive functioning (EF) facilitates the development of academic, cognitive, and social-emotional skills and deficits in EF are implicated in a broad range of child psychopathologies. Although EF has clear implications for early development, the few questionnaires that assess EF in preschoolers tend to ask parents for global judgments of executive dysfunction and thus do not cover the full range of EF within the preschool age group. Here we present a new measure of preschoolers' EF-the Ratings of Everyday Executive Functioning (REEF)-that capitalizes on parents' observations of their preschoolers' (i.e., 3- to 5-year-olds) behavior in specific, everyday contexts. Over 4 studies, items comprising the REEF were refined and the measure's reliability and validity were evaluated. Factor analysis of the REEF yielded 1 factor, with items showing strong internal reliability. More important, children's scores on the REEF related to both laboratory measures of EF and another parent-report EF questionnaire. Moreover, reflecting divergent validity, the REEF was more strongly related to measures of EF as opposed to measures of affective styles. The REEF also captured differences in children's executive skills across the preschool years, and norms at 6-month intervals are reported. In summary, the REEF is a new parent-report measure that provides researchers with an efficient, valid, and reliable means of assessing preschoolers' executive functioning. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Family demographic profiles and their relationship with the quality of executive functioning subcomponents in kindergarten.

PubMed

Vandenbroucke, Loren; Verschueren, Karine; Ceulemans, Eva; De Smedt, Bert; De Roover, Kim; Baeyens, Dieter

2016-06-01

Executive functioning (EF), needed for goal-oriented behaviour, thoughts, and emotions, is important for various life domains. This study examined the relationship between family demographics and EF subcomponents. A kindergarten sample was tested on subcomponents of working memory, inhibition, and cognitive flexibility. Parents provided information on demographic variables. For 78 children both EF and demographic data were available. First, demographic profiles were identified within the sample. Two profiles were found: A low-risk profile of mainly two-biological-parent, high-income families with a highly educated mother who did not smoke during pregnancy and a high-risk profile of low-income families with a young, low-educated mother who more often smoked during pregnancy. Second, children with different demographic profiles were compared on EF subcomponents. Results indicate differential relations between family demographics and EF subcomponents: Whereas for most EF subcomponents no association with family demographics was found, high-risk children performed better on response shifting and tended to perform worse on verbal memory than low-risk children. Parenting stress decreased performance only for high-risk children. Although this study found limited impact of family demographics for EF, further longitudinal research can provide nuanced insights about which factors influence specific EF subcomponents during which developmental periods and guide targeted prevention of EF difficulties. © 2015 The British Psychological Society.

Assembly of Q{beta} viral RNA polymerase with host translational elongation factors EF-Tu and -Ts.

PubMed

Takeshita, Daijiro; Tomita, Kozo

2010-09-07

Replication and transcription of viral RNA genomes rely on host-donated proteins. Qbeta virus infects Escherichia coli and replicates and transcribes its own genomic RNA by Qbeta replicase. Qbeta replicase requires the virus-encoded RNA-dependent RNA polymerase (beta-subunit), and the host-donated translational elongation factors EF-Tu and -Ts, as active core subunits for its RNA polymerization activity. Here, we present the crystal structure of the core Qbeta replicase, comprising the beta-subunit, EF-Tu and -Ts. The beta-subunit has a right-handed structure, and the EF-Tu:Ts binary complex maintains the structure of the catalytic core crevasse of the beta-subunit through hydrophobic interactions, between the finger and thumb domains of the beta-subunit and domain-2 of EF-Tu and the coiled-coil motif of EF-Ts, respectively. These hydrophobic interactions are required for the expression and assembly of the Qbeta replicase complex. Thus, EF-Tu and -Ts have chaperone-like functions in the maintenance of the structure of the active Qbeta replicase. Modeling of the template RNA and the growing RNA in the catalytic site of the Qbeta replicase structure also suggests that structural changes of the RNAs and EF-Tu:Ts should accompany processive RNA polymerization and that EF-Tu:Ts in the Qbeta replicase could function to modulate the RNA folding and structure.

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).

Student Teachers' Workplace-Based Learning in Sweden on Early Childhood Education for Sustainability: Experiences in Practice Settings

ERIC Educational Resources Information Center

Ärlemalm-Hagsér, Eva

2017-01-01

Workplace-based learning experiences are integral to early childhood teacher education. In Sweden, the objectives of early childhood teacher education programmes require students to develop knowledge and skills about education for sustainability (EfS), in accordance with national policy documents. This includes how to work with EfS in everyday…

Integrating Education for Sustainability in Preservice Teacher Education: A Case Study from a Regional Australian University

ERIC Educational Resources Information Center

Mills, Reece; Tomas, Louisa

2013-01-01

Education for Sustainability (EfS) has been prioritised in the School of Education at James Cook University (JCU), Townsville, Australia. This article presents a case study that explores the ways in which teacher educators integrate EfS in their teaching in the Bachelor of Education (BEd) (Primary) at JCU, and their perceptions of enablers and…

The I3E Model for Embedding Education for Sustainability within Higher Education Institutions

ERIC Educational Resources Information Center

Cebrián, Gisela

2018-01-01

This paper presents an evidence-based model (the I3E model) for embedding education for sustainability (EfS) within a higher education institution. This model emerged from a doctoral research that examined organisational learning and change processes at the University of Southampton to build EfS into the university curriculum. The researcher aimed…

Food matrix and cooking process affect mineral bioaccessibility of enteral nutrition formulas.

PubMed

Galán, María Gimena; Drago, Silvina Rosa

2014-02-01

When enteral formulas (EF) are administered orally as a supplement to the normal diet, they are often mixed with conventional foods or included in recipes in order to seek new flavors and textures and avoid monotony. The aims of this work were to study the bioaccessibility of Fe, Zn and Ca from commercial EF and the impact upon their incorporation into sweet preparations. Twenty commercial EF, before and after inclusion in sweet food (rice pudding, RP; banana smoothie, BS; tea, T; chocolate dessert, CD) were evaluated regarding Fe, Zn and Ca dialyzability (%DFe , %DZn , %DCa ) as an estimator of mineral bioaccessibility. Fe, Zn and Ca dialyzability from EF was variable and generally low. Heating during EF-sweet food preparation (T and CD) lowered values to 44.1 %DFe , possibly due to degradation of vitamin C, and 52.7 %DZn and 25.3 %DCa , due to the interaction with food components. EF and EF-sweet foods did not represent a good supply of Fe, Zn and Ca as recommended. This study demonstrated how the bioaccessibility of these minerals is affected by the food matrix in which EF is included as well as heating during food preparation. © 2013 Society of Chemical Industry.

Transformation of chiral polychlorinated biphenyls (PCBs) in a stream food web

USGS Publications Warehouse

Dang, V.D.; Walters, D.M.; Lee, C.M.

2010-01-01

The enantiomeric composition of chiral PCB congeners was determined in Twelvemile Creek (Clemson, SC) to examine potential mechanisms of biotransformation in a stream food web. We measured enantiomeric fractions (EFs) of six PCB atropisomers (PCBs 84, 91, 95, 136, 149, and 174) in surface sediment, fine benthic organic matter (FBOM), coarse particulate organic matter (CPOM), periphyton, Asian clam, mayflies, yellowfin shiner, and semipermeable membrane devices (SPMDs) using gas chromatography (GC-ECD). Nonracemic EFs of PCBs 91, 95, 136, and 149 were measured in almost all samples. Enantiomeric compositions of PCBs 84 and 174 were infrequently detected with racemic EFs measured in samples except for a nonracemic EF of PCB 84 in clams. Nonracemic EFs of PCBs 91, 136, and 149 in SPMDs may be due to desorption of nonracemic residues from FBOM. EFs for some atropisomers were significantly different among FBOM, CPOM, and periphyton, suggesting that their microbial communities have different biotransformation processes. Nonracemic EFs in clams and fish suggest both in vivo biotransformation and uptake of nonracemic residues from their food sources. Longitudinal variability in EFs was generally low among congeners observed in matrices. ?? 2010 American Chemical Society.

The translation elongation factor eEF1A1 couples transcription to translation during heat shock response

PubMed Central

Vera, Maria; Pani, Bibhusita; Griffiths, Lowri A; Muchardt, Christian; Abbott, Catherine M; Singer, Robert H; Nudler, Evgeny

2014-01-01

Translation elongation factor eEF1A has a well-defined role in protein synthesis. In this study, we demonstrate a new role for eEF1A: it participates in the entire process of the heat shock response (HSR) in mammalian cells from transcription through translation. Upon stress, isoform 1 of eEF1A rapidly activates transcription of HSP70 by recruiting the master regulator HSF1 to its promoter. eEF1A1 then associates with elongating RNA polymerase II and the 3′UTR of HSP70 mRNA, stabilizing it and facilitating its transport from the nucleus to active ribosomes. eEF1A1-depleted cells exhibit severely impaired HSR and compromised thermotolerance. In contrast, tissue-specific isoform 2 of eEF1A does not support HSR. By adjusting transcriptional yield to translational needs, eEF1A1 renders HSR rapid, robust, and highly selective; thus, representing an attractive therapeutic target for numerous conditions associated with disrupted protein homeostasis, ranging from neurodegeneration to cancer. DOI: http://dx.doi.org/10.7554/eLife.03164.001 PMID:25233275

The ecological and construct validity of a newly developed measure of executive function: the Virtual Library Task.

PubMed

Renison, Belinda; Ponsford, Jennie; Testa, Renee; Richardson, Barry; Brownfield, Kylie

2012-05-01

Virtual reality (VR) assessment paradigms have the potential to address the limited ecological validity of pen and paper measures of executive function (EF) and the pragmatic and reliability issues associated with functional measures. To investigate the ecological validity and construct validity of a newly developed VR measure of EF, the Virtual Library Task (VLT); a real life analogous task--the Real Library Task (RLT); and five neuropsychological measures of EF were administered to 30 patients with traumatic brain injury (TBI) and 30 healthy Controls. Significant others for each participant also completed the Dysexecutive Questionnaire (DEX), which is a behavioral rating scale of everyday EF. Performances on the VLT and the RLT were significantly positively correlated indicating that VR performance is similar to real world performance. The TBI group performed significantly worse than the Control group on the VLT and the Modified Six Elements Test (MSET) but the other four neuropsychological measures of EF failed to differentiate the groups. Both the MSET and the VLT significantly predicted everyday EF suggesting that they are both ecologically valid tools for the assessment of EF. The VLT has the advantage over the MSET of providing objective measurement of individual components of EF.

Myostatin inhibits eEF2K-eEF2 by regulating AMPK to suppress protein synthesis.

PubMed

Deng, Zhao; Luo, Pei; Lai, Wen; Song, Tongxing; Peng, Jian; Wei, Hong-Kui

2017-12-09

Growth of skeletal muscle is dependent on the protein synthesis, and the rate of protein synthesis is mainly regulated in the stage of translation initiation and elongation. Myostatin, a member of the transforming growth factor-β (TGF-β) superfamily, is a negative regulator of protein synthesis. C2C12 myotubes was incubated with 0, 0.01, 0.1, 1, 2, 3 μg/mL myostatin recombinant protein, and then we detected the rates of protein synthesis by the method of SUnSET. We found that high concentrations of myostatin (2 and 3 μg/mL) inhibited protein synthesis by blocking mTOR and eEF2K-eEF2 pathway, while low concentration of myostatin (0.01, 0.1 and 1 μg/mL) regulated eEF2K-eEF2 pathway activity to block protein synthesis without affected mTOR pathway, and myostatin inhibited eEF2K-eEF2 pathway through regulating AMPK pathway to suppress protein synthesis. It provided a new mechanism for myostatin regulating protein synthesis and treating muscle atrophy. Copyright © 2017. Published by Elsevier Inc.

Revisiting the continuum hypothesis: toward an in-depth exploration of executive functions in korsakoff syndrome.

PubMed

Brion, Mélanie; Pitel, Anne-Lise; Beaunieux, Hélène; Maurage, Pierre

2014-01-01

Korsakoff syndrome (KS) is a neurological state mostly caused by alcohol-dependence and leading to disproportionate episodic memory deficits. KS patients present more severe anterograde amnesia than Alcohol-Dependent Subjects (ADS), which led to the continuum hypothesis postulating a progressive increase in brain and cognitive damages during the evolution from ADS to KS. This hypothesis has been extensively examined for memory but is still debated for other abilities, notably executive functions (EF). EF have up to now been explored by unspecific tasks in KS, and few studies explored their interactions with memory. Exploring EF in KS by specific tasks based on current EF models could thus renew the exploration of the continuum hypothesis. This paper will propose a research program aiming at: (1) clarifying the extent of executive dysfunctions in KS by tasks focusing on specific EF subcomponents; (2) determining the differential EF deficits in ADS and KS; (3) exploring EF-memory interactions in KS with innovative tasks. At the fundamental level, this exploration will test the continuum hypothesis beyond memory. At the clinical level, it will propose new rehabilitation tools focusing on the EF specifically impaired in KS.

Revisiting the Continuum Hypothesis: Toward an In-Depth Exploration of Executive Functions in Korsakoff Syndrome

PubMed Central

Brion, Mélanie; Pitel, Anne-Lise; Beaunieux, Hélène; Maurage, Pierre

2014-01-01

Korsakoff syndrome (KS) is a neurological state mostly caused by alcohol-dependence and leading to disproportionate episodic memory deficits. KS patients present more severe anterograde amnesia than Alcohol-Dependent Subjects (ADS), which led to the continuum hypothesis postulating a progressive increase in brain and cognitive damages during the evolution from ADS to KS. This hypothesis has been extensively examined for memory but is still debated for other abilities, notably executive functions (EF). EF have up to now been explored by unspecific tasks in KS, and few studies explored their interactions with memory. Exploring EF in KS by specific tasks based on current EF models could thus renew the exploration of the continuum hypothesis. This paper will propose a research program aiming at: (1) clarifying the extent of executive dysfunctions in KS by tasks focusing on specific EF subcomponents; (2) determining the differential EF deficits in ADS and KS; (3) exploring EF-memory interactions in KS with innovative tasks. At the fundamental level, this exploration will test the continuum hypothesis beyond memory. At the clinical level, it will propose new rehabilitation tools focusing on the EF specifically impaired in KS. PMID:25071526

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.

A Complex Distribution of Elongation Family GTPases EF1A and EFL in Basal Alveolate Lineages

PubMed Central

Mikhailov, Kirill V.; Janouškovec, Jan; Tikhonenkov, Denis V.; Mirzaeva, Gulnara S.; Diakin, Andrei Yu.; Simdyanov, Timur G.; Mylnikov, Alexander P.; Keeling, Patrick J.; Aleoshin, Vladimir V.

2014-01-01

Translation elongation factor-1 alpha (EF1A) and the related GTPase EF-like (EFL) are two proteins with a complex mutually exclusive distribution across the tree of eukaryotes. Recent surveys revealed that the distribution of the two GTPases in even closely related taxa is frequently at odds with their phylogenetic relationships. Here, we investigate the distribution of EF1A and EFL in the alveolate supergroup. Alveolates comprise three major lineages: ciliates and apicomplexans encode EF1A, whereas dinoflagellates encode EFL. We searched transcriptome databases for seven early-diverging alveolate taxa that do not belong to any of these groups: colpodellids, chromerids, and colponemids. Current data suggest all seven are expected to encode EF1A, but we find three genera encode EFL: Colpodella, Voromonas, and the photosynthetic Chromera. Comparing this distribution with the phylogeny of alveolates suggests that EF1A and EFL evolution in alveolates cannot be explained by a simple horizontal gene transfer event or lineage sorting. PMID:25179686

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

Elongation Factor Ts Directly Facilitates the Formation and Disassembly of the Escherichia coli Elongation Factor Tu·GTP·Aminoacyl-tRNA Ternary Complex*

PubMed Central

Burnett, Benjamin J.; Altman, Roger B.; Ferrao, Ryan; Alejo, Jose L.; Kaur, Navdep; Kanji, Joshua; Blanchard, Scott C.

2013-01-01

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. PMID:23539628

Targeting Endothelial Function to Treat Heart Failure with Preserved Ejection Fraction: The Promise of Exercise Training

PubMed Central

Lemmens, Katrien; Vrints, Christiaan J.

2017-01-01

Although the burden of heart failure with preserved ejection fraction (HFpEF) is increasing, there is no therapy available that improves prognosis. Clinical trials using beta blockers and angiotensin converting enzyme inhibitors, cardiac-targeting drugs that reduce mortality in heart failure with reduced ejection fraction (HFrEF), have had disappointing results in HFpEF patients. A new “whole-systems” approach has been proposed for designing future HFpEF therapies, moving focus from the cardiomyocyte to the endothelium. Indeed, dysfunction of endothelial cells throughout the entire cardiovascular system is suggested as a central mechanism in HFpEF pathophysiology. The objective of this review is to provide an overview of current knowledge regarding endothelial dysfunction in HFpEF. We discuss the molecular and cellular mechanisms leading to endothelial dysfunction and the extent, presence, and prognostic importance of clinical endothelial dysfunction in different vascular beds. We also consider implications towards exercise training, a promising therapy targeting system-wide endothelial dysfunction in HFpEF. PMID:28706575

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.

eEF2K/eEF2 Pathway Controls the Excitation/Inhibition Balance and Susceptibility to Epileptic Seizures

PubMed Central

Heise, Christopher; Taha, Elham; Murru, Luca; Ponzoni, Luisa; Cattaneo, Angela; Guarnieri, Fabrizia C.; Montani, Caterina; Mossa, Adele; Vezzoli, Elena; Ippolito, Giulio; Zapata, Jonathan; Barrera, Iliana; Ryazanov, Alexey G.; Cook, James; Poe, Michael; Stephen, Michael Rajesh; Kopanitsa, Maksym; Benfante, Roberta; Rusconi, Francesco; Braida, Daniela; Francolini, Maura; Proud, Christopher G.; Valtorta, Flavia; Passafaro, Maria; Sala, Mariaelvina; Bachi, Angela; Verpelli, Chiara; Rosenblum, Kobi; Sala, Carlo

2017-01-01

Abstract Alterations in the balance of inhibitory and excitatory synaptic transmission have been implicated in the pathogenesis of neurological disorders such as epilepsy. Eukaryotic elongation factor 2 kinase (eEF2K) is a highly regulated, ubiquitous kinase involved in the control of protein translation. Here, we show that eEF2K activity negatively regulates GABAergic synaptic transmission. Indeed, loss of eEF2K increases GABAergic synaptic transmission by upregulating the presynaptic protein Synapsin 2b and α5-containing GABAA receptors and thus interferes with the excitation/inhibition balance. This cellular phenotype is accompanied by an increased resistance to epilepsy and an impairment of only a specific hippocampal-dependent fear conditioning. From a clinical perspective, our results identify eEF2K as a potential novel target for antiepileptic drugs, since pharmacological and genetic inhibition of eEF2K can revert the epileptic phenotype in a mouse model of human epilepsy. PMID:27005990

Developmental differences in relations between parent-reported executive function and unitized and non-unitized memory representations during childhood

PubMed Central

Blankenship, Sarah L.; Riggins, Tracy

2015-01-01

Previous research has documented an association between executive functioning (EF) and memory for bound details. However, it is unknown if this relation varies as a function of the type of bound information (i.e., unitized versus non-unitized) and whether this association changes as a function of age during childhood, when both EF and memory undergo rapid development. The current study sought to address these gaps by examining whether relations between parent-reported EF differed for unitized versus non-unitized memory representations and if these relations differed between children who were 4, 6, or 8 years of age. Results revealed that EF was selectively associated with non-unitized associative memory in 8-year-old children; no significant relations between EF and either memory condition were evident in 4- or 6-year-olds. These results suggest relations between EF and memory may be specific to non-unitized representations and that this association may emerge across childhood as both EF and memory abilities develop. PMID:26347683

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.

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.

The Role of the Y-Located TSPY Gene in Prostatic Oncogenesis

DTIC Science & Technology

2007-02-01

to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data ...from CIS to invasive germ cell tumors [7, 31]. To validate the microarray data , we had selected 4 up-regulated (RGC32, PDGFC, WNT5A and CCND2) and 4...on selection medium ( data not shown). eEF1A1 is one of two isoforms (eEF1A1 and eEF1A2) of translation elongation factor alpha (eEF1A). eEF1A1 is

Update of Aircraft Profile Data for the Integrated Noise Model Computer Program. Volume 1. Final Report

DTIC Science & Technology

1992-03-01

general aviation 53 Cop. Fleet 1985 BUSINESS JET 1i F turbojet & turbofan 55 Gates LEAR 25 CJ610-8 1 E,F 54 Gates LEAR 36 TFE731 -2 3 E,F...Cessna CI1 3 TFE731 -3-1005 3 * E,F 60 Mitsubishi MU300-10 J3I1D-4 3 E,F 58 Canadair CL600 ALFSO2L 3 E, 61 Canadair CL601 CF34-3A 3 E,F 62 Israel A/C ASIRA...1125 TFE731 -3A 3 EF S.. ... .. ... ... .. . .. ... .............. - - - - - - - - - - - - - - - --I.....- -- --- -- - - -------.-- -- - - -- - 4

Erectile dysfunction and lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH) combined responders to tadalafil after 12 weeks of treatment.

PubMed

Roehrborn, Claus G; Egan, Kathryn B; Miner, Martin M; Ni, Xiao; Wong, David G; Rosen, Raymond C

2016-07-01

To analyse the proportion of men taking tadalafil 5 mg once daily who experience a combined improvement in symptoms of both erectile dysfunction (ED) and lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH). The data from men aged ≥45 years randomized to tadalafil 5 mg once daily or placebo enrolled in one of four randomized, placebo-controlled LUTS/BPH clinical trials were analysed (N = 927). A novel classification of 'combined responders' to ED and LUTS/BPH treatment was defined, based on published criteria for men who showed improvement in both International Index of Erectile Function - Erectile Function domain (IIEF-EF) score and total International Prostate Symptom Score (IPSS). Descriptive analyses assessed the covariate distribution by responder status. Unadjusted and adjusted logistic regressions provided odds ratios with 95% confidence intervals comparing combined responders with all others (partial and non-responders). Among men randomized to tadalafil 5 mg, 40.5% were combined responders (n = 189). Among placebo randomized men, 18.3% were combined responders (n = 84). Combined responders, in the total population, had the highest baseline IPSS and lowest baseline IIEF-EF scores, corresponding to the highest level of dysfunction. The majority of men were aged ≤65 years, white, non-obese, non-smokers, and regular alcohol consumers. Only treatment, baseline IPSS, baseline IIEF-EF, obesity and psychoactive medication use were significantly associated with responder status (P ≤ 0.05). Tadalafil-treated men had 2.8 times significantly increased adjusted odds of being combined responders vs non-responders (P < 0.001). For each unit decrease in baseline IIEF-EF or alcoholic drink consumption per week there was a 4% significant increase in the adjusted odds of being a combined responder to tadalafil therapy. This novel measure of combined response is useful in differentiating patients with clinically relevant symptom improvement for both ED and LUTS/BPH after treatment with tadalafil 5 mg once daily vs placebo. This combined responder measure may be useful in future assessment of treatment benefits across patient groups after various types of treatment intervention (e.g. surgical vs pharmacotherapy vs non-pharmacological intervention). © 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.

Measure Guideline: Heat Pump Water Heaters in New and Existing Homes

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

Shapiro, C.; Puttagunta, S.; Owens, D.

2012-02-01

This Building America Measure Guideline is intended for builders, contractors, homeowners, and policy-makers. This document is intended to explore the issues surrounding heat pump water heaters (HPWHs) to ensure that homeowners and contractors have the tools needed to appropriately and efficiently install HPWHs. Heat pump water heaters (HPWHs) promise to significantly reduce energy consumption for domestic hot water (DHW) over standard electric resistance water heaters (ERWHs). While ERWHs perform with energy factors (EFs) around 0.9, new HPWHs boast EFs upwards of 2.0. High energy factors in HPWHs are achieved by combining a vapor compression system, which extracts heat from themore » surrounding air at high efficiencies, with electric resistance element(s), which are better suited to meet large hot water demands. Swapping ERWHs with HPWHs could result in roughly 50% reduction in water heating energy consumption for 35.6% of all U.S. households. This Building America Measure Guideline is intended for builders, contractors, homeowners, and policy-makers. While HPWHs promise to significantly reduce energy use for DHW, proper installation, selection, and maintenance of HPWHs is required to ensure high operating efficiency and reliability. This document is intended to explore the issues surrounding HPWHs to ensure that homeowners and contractors have the tools needed to appropriately and efficiently install HPWHs. Section 1 of this guideline provides a brief description of HPWHs and their operation. Section 2 highlights the cost and energy savings of HPWHs as well as the variables that affect HPWH performance, reliability, and efficiency. Section 3 gives guidelines for proper installation and maintenance of HPWHs, selection criteria for locating HPWHs, and highlights of important differences between ERWH and HPWH installations. Throughout this document, CARB has included results from the evaluation of 14 heat pump water heaters (including three recently released HPWH products) installed in existing homes in the northeast region of the United States.« less

An Integrated Leadership Model for Leading Education for Sustainability in Higher Education and the Vital Role of Students as Change Agents

ERIC Educational Resources Information Center

Warwick, Paul

2016-01-01

This paper explores the leadership of education for sustainability (EfS) in higher education, focusing specifically on the key role students can play as internal catalysts for change. It presents a case study of Plymouth University, a higher education institution with an international reputation for EfS leadership. The paper outlines the…

Executive Dysfunctions among Boys with Attention Deficit Hyperactivity Disorder (ADHD): Performance-Based Test and Parents Report

ERIC Educational Resources Information Center

Shimoni, Ma'ayan; Engel-Yeger, Batya; Tirosh, Emanuel

2012-01-01

Difficulty in executive functions (EF) is a core symptom of ADHD. Yet, the EF assessments are still in controversy. It is still unclear whether the everyday implementation of EF can be assessed under laboratory conditions. Therefore, the purposes of the present study are: (a) to examine EF among boys with ADHD both in everyday behavior (as…

The Long-Term Impact of an Education for Sustainability Course on Israeli Science and Technology Teachers' Pro-Environment Awareness, Commitment and Behaviour

ERIC Educational Resources Information Center

Abramovich, Anat; Loria, Yahavit

2015-01-01

The impact of an Education for Sustainability (EfS) course for science and technology junior high school teachers on the intentional and actual environmental behaviour of participants was studied by researching the EfS implementation of 13 science and technology teachers within their family, community, and work environment. The research was…

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.

Systematic Observation: Relevance of This Approach in Preschool Executive Function Assessment and Association with Later Academic Skills.

PubMed

Escolano-Pérez, Elena; Herrero-Nivela, Maria Luisa; Blanco-Villaseñor, Angel; Anguera, M Teresa

2017-01-01

Executive functions (EFs) are high-level cognitive processes that allow us to coordinate our actions, thoughts, and emotions, enabling us to perform complex tasks. An increasing number of studies have highlighted the role of EFs in building a solid foundation for subsequent development and learning and shown that EFs are associated with good adjustment and academic skills. The main objective of this study was to analyze whether EF levels in 44 Spanish children in the last year of preschool were associated with levels of literacy and math skills the following year, that is, in the first year of compulsory education. We used a multi-method design, which consisted of systematic observation to observe preschool children during play and selective methodology to assess their reading, writing, and math skills in the first year of compulsory primary education. General linear modeling was used to estimate the percentage of variability in academic skills in the first year of primary school that was explained by preschool EF abilities. The results showed that preschool EF level, together with participants and the instrument used to assess academic skills, explained 99% of the variance of subsequent academic performance. Another objective was to determine whether our findings were generalizable to the reference population. To make this determination, we estimated the optimal sample size for assessing preschool EFs. To do this, we performed a generalizability analysis. The resulting generalizability coefficient showed that our sample of 44 students was sufficient for assessing preschool EFs. Therefore, our results are generalizable to the reference population. Our results are consistent with previous reports that preschool EF abilities may be associated with subsequent literacy and math skills. Early assessment of EFs may therefore contribute to identifying children who are likely to experience later learning difficulties and guide the design of suitable interventions for the optimization of EFs.

Systematic Observation: Relevance of This Approach in Preschool Executive Function Assessment and Association with Later Academic Skills

PubMed Central

Escolano-Pérez, Elena; Herrero-Nivela, Maria Luisa; Blanco-Villaseñor, Angel; Anguera, M. Teresa

2017-01-01

Executive functions (EFs) are high-level cognitive processes that allow us to coordinate our actions, thoughts, and emotions, enabling us to perform complex tasks. An increasing number of studies have highlighted the role of EFs in building a solid foundation for subsequent development and learning and shown that EFs are associated with good adjustment and academic skills. The main objective of this study was to analyze whether EF levels in 44 Spanish children in the last year of preschool were associated with levels of literacy and math skills the following year, that is, in the first year of compulsory education. We used a multi-method design, which consisted of systematic observation to observe preschool children during play and selective methodology to assess their reading, writing, and math skills in the first year of compulsory primary education. General linear modeling was used to estimate the percentage of variability in academic skills in the first year of primary school that was explained by preschool EF abilities. The results showed that preschool EF level, together with participants and the instrument used to assess academic skills, explained 99% of the variance of subsequent academic performance. Another objective was to determine whether our findings were generalizable to the reference population. To make this determination, we estimated the optimal sample size for assessing preschool EFs. To do this, we performed a generalizability analysis. The resulting generalizability coefficient showed that our sample of 44 students was sufficient for assessing preschool EFs. Therefore, our results are generalizable to the reference population. Our results are consistent with previous reports that preschool EF abilities may be associated with subsequent literacy and math skills. Early assessment of EFs may therefore contribute to identifying children who are likely to experience later learning difficulties and guide the design of suitable interventions for the optimization of EFs. PMID:29375409

Characterising the Profile of Everyday Executive Functioning and Relation to IQ in Adults with Williams Syndrome: Is the BRIEF Adult Version a Valid Rating Scale?

PubMed Central

Porter, Melanie A.

2015-01-01

Although there is evidence of a distinct profile of executive dysfunction in Williams syndrome (WS), a rare genetically based neurodevelopmental disorder, the utility of informant reports of everyday executive function (EF) impairments and their relation to intelligence is not yet clear. Here we aimed to evaluate the functional impact of executive dysfunction in adults with WS and to establish the validity of child and adult versions of the most commonly used rating scale for EF assessment, the Behaviour Rating Inventory of Executive Function (BRIEF). We were also interested in whether distinct components of everyday EF relate to intelligence in WS. Parent report child (BRIEF-C) and adult (BRIEF-A) ratings were collected on 20 adults with WS (aged 18.5 to 53 years), with a mean IQ of 60.95 (SD = 17.67). Neuropsychological measures of EF included: The Shape School Test (Espy, 2007); select subdomains of EF from the Woodcock-Johnson III Tests of Cognitive Abilities, Australian Adaptation (WJ III COG); and select subdomains from the Vineland Adaptive Behaviour Scales, Second Edition—Parent Survey (Vineland-II). Results showed that the BRIEF-A, but not the BRIEF-C, was the most highly correlated with neuropsychological measures of EF, suggesting that it was a valid measure of the profile of EF impairments in adults with WS. The profile of everyday EF dysfunction revealed relative impairments in monitoring, working memory, planning and organisation in WS. In addition, both neuropsychological and rating scale measures showed an association between the shifting component of EF and intelligence. These findings indicate that the BRIEF-A is a valid measure of the multidimensional nature of real-world impairments in EF, and highlight its utility as a less labor intensive and low-cost screening tool for measuring specific EF impairments that could become the focus of targeted intervention in adults with WS. PMID:26355600

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

Distribution and Phylogeny of EFL and EF-1α in Euglenozoa Suggest Ancestral Co-Occurrence Followed by Differential Loss

PubMed Central

Gile, Gillian H.; Faktorová, Drahomíra; Castlejohn, Christina A.; Burger, Gertraud; Lang, B. Franz; Farmer, Mark A.; Lukeš, Julius; Keeling, Patrick J.

2009-01-01

Background The eukaryotic elongation factor EF-1α (also known as EF1A) catalyzes aminoacyl-tRNA binding by the ribosome during translation. Homologs of this essential protein occur in all domains of life, and it was previously thought to be ubiquitous in eukaryotes. Recently, however, a number of eukaryotes were found to lack EF-1α and instead encode a related protein called EFL (for EF-Like). EFL-encoding organisms are scattered widely across the tree of eukaryotes, and all have close relatives that encode EF-1α. This intriguingly complex distribution has been attributed to multiple lateral transfers because EFL's near mutual exclusivity with EF-1α makes an extended period of co-occurrence seem unlikely. However, differential loss may play a role in EFL evolution, and this possibility has been less widely discussed. Methodology/Principal Findings We have undertaken an EST- and PCR-based survey to determine the distribution of these two proteins in a previously under-sampled group, the Euglenozoa. EF-1α was found to be widespread and monophyletic, suggesting it is ancestral in this group. EFL was found in some species belonging to each of the three euglenozoan lineages, diplonemids, kinetoplastids, and euglenids. Conclusions/Significance Interestingly, the kinetoplastid EFL sequences are specifically related despite the fact that the lineages in which they are found are not sisters to one another, suggesting that EFL and EF-1α co-occurred in an early ancestor of kinetoplastids. This represents the strongest phylogenetic evidence to date that differential loss has contributed to the complex distribution of EFL and EF-1α. PMID:19357788

The development of executive function and language skills in the early school years.

PubMed

Gooch, Debbie; Thompson, Paul; Nash, Hannah M; Snowling, Margaret J; Hulme, Charles

2016-02-01

The developmental relationships between executive functions (EF) and early language skills are unclear. This study explores the longitudinal relationships between children's early EF and language skills in a sample of children with a wide range of language abilities including children at risk of dyslexia. In addition, we investigated whether these skills independently predict children's attention/behaviour skills. Data are presented from 243 children at four time points. Children were selected for being at risk of reading difficulties either because of a family history of dyslexia (FR; N = 90) or because of concerns regarding their language development (LI; N = 79) or as typically developing controls (TD; N = 74). The children completed tasks to assess their executive function and language skills at ages 4, 5 and 6 years. At 6 (T4) and 7 years (T5) parents and teachers rated the children's attention/behaviour skills. There was a strong concurrent relationship between language and EF at each assessment. Longitudinal analyses indicated a considerable degree of stability in children's language and EF skills: the influence of language on later EF skills (and vice versa) was weak and not significant in the current sample. Children's EF, but not language, skills at T3 predicted attention/behaviour ratings at T4/T5. There is a strong concurrent association between language and EF skills during the preschool and early school years, when children with language impairment show persistent EF deficits. Latent variables measuring language and EF show high longitudinal stability with little evidence of significant or strong reciprocal influences between these constructs. EF, but not language, skills predict later ratings of children's attention and behaviour. © 2015 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.

Characterization of the 1st and 2nd EF-hands of NADPH oxidase 5 by fluorescence, isothermal titration calorimetry, and circular dichroism

PubMed Central

2012-01-01

Background Superoxide generated by non-phagocytic NADPH oxidases (NOXs) is of growing importance for physiology and pathobiology. The calcium binding domain (CaBD) of NOX5 contains four EF-hands, each binding one calcium ion. To better understand the metal binding properties of the 1st and 2nd EF-hands, we characterized the N-terminal half of CaBD (NCaBD) and its calcium-binding knockout mutants. Results The isothermal titration calorimetry measurement for NCaBD reveals that the calcium binding of two EF-hands are loosely associated with each other and can be treated as independent binding events. However, the Ca2+ binding studies on NCaBD(E31Q) and NCaBD(E63Q) showed their binding constants to be 6.5 × 105 and 5.0 × 102 M-1 with ΔHs of -14 and -4 kJ/mol, respectively, suggesting that intrinsic calcium binding for the 1st non-canonical EF-hand is largely enhanced by the binding of Ca2+ to the 2nd canonical EF-hand. The fluorescence quenching and CD spectra support a conformational change upon Ca2+ binding, which changes Trp residues toward a more non-polar and exposed environment and also increases its α-helix secondary structure content. All measurements exclude Mg2+-binding in NCaBD. Conclusions We demonstrated that the 1st non-canonical EF-hand of NOX5 has very weak Ca2+ binding affinity compared with the 2nd canonical EF-hand. Both EF-hands interact with each other in a cooperative manner to enhance their Ca2+ binding affinity. Our characterization reveals that the two EF-hands in the N-terminal NOX5 are Ca2+ specific. Graphical abstract PMID:22490336

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

Validation of ultrasound imaging for Achilles entheseal fibrocartilage in bovines and description of changes in humans with spondyloarthritis.

PubMed

Aydin, Sibel Zehra; Bas, Emine; Basci, Onur; Filippucci, Emilio; Wakefield, Richard J; Celikel, Cigdem; Karahan, Mustafa; Atagunduz, Pamir; Benjamin, Mike; Direskeneli, Haner; McGonagle, Dennis

2010-12-01

Entheseal fibrocartilage (EF) derangement is hypothesised to be pivotal to the pathogenesis of spondyloarthritis. Ultrasound is useful for visualisation of the enthesis but its role in EF visualisation is uncertain. This work aimed to demonstrate face and content validity of ultrasound for EF visualisation both by bovine histological evaluation and EF imaging in spondyloarthritis. Achilles enthesis of 18 bovine hindfeet was visualised using a MyLab 70 ultrasound machine. The presence of tissue with EF characteristics was documented and histological confirmation was performed on five randomly selected sections using Masson trichrome staining. Ultrasound of the Achilles tendon (AT) was performed in 19 patients with spondyloarthritis and 21 healthy controls (HC). The bovine EF could be visualised in all cases and seen as a thin, uncompressible, well-defined, anechoic layer between the hyperechoic bone and the hyperechoic fibrils of the enthesis both in longitudinal and transverse scans. This region corresponded to EF on histological examination. The same pattern of low signal corresponding to EF location was seen in 17/19 patients and all HC. Discontinuities of the anechoic layer around the erosions and enthesophytes were observed in the spondyloarthritis group. The thickness of the anechoic layer was not significantly different in spondyloarthritis and HC (0.5 ± 0.1 vs 0.5 ± 0.2 mm, p=0.9) whereas the thickness of the EF was greater in men (0.6 ± 0.2 vs 0.5 ± 0.1 mm; p=0.009) compared with women. Ultrasound can visualise EF of the AT insertion, which can be abnormal in cases of spondyloarthritis. This has implications for a better understanding of enthesopathy.

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.

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

Eating frequency is inversely associated with BMI, waist circumference and the proportion of body fat in Korean adults when diet quality is high, but not when it is low: analysis of the Fourth Korea National Health and Nutrition Examination Survey (KNHANES IV).

PubMed

Kim, Sunmi; Yang, Jeong Hee; Park, Gyeong-Hun

2018-04-01

The role of eating frequency (EF) in obesity development has been debated, and few studies have investigated Asian populations. Diet quality might affect the association between EF and obesity. Therefore, we investigated the association between EF and obesity indicators in a representative sample of Korean adults with consideration to diet quality. This cross-sectional study used data of 6951 participants aged 19-93 years (male 49·8 %, female 50·2 %) from the Fourth Korean National Health and Nutrition Examination Survey. EF was assessed using a questionnaire, and diet quality was defined as mean adequacy ratio (MAR). To explore the association between EF and obesity indicators, we used multiple linear regression analyses with and without interaction terms between diet quality and EF. EF was inversely associated with each obesity indicator, including body fat percentage (BF%), BMI and waist circumference (WC), showing a significant linear trend (P<0·001 for BF%, WC and BMI). In addition, the association between EF and each obesity indicator was significantly altered according to diet quality (P value of the interaction term EF×diet quality=0·008 in the regression model for BF%, <0·001 for BMI and 0·043 for WC). In the stratified analyses according to diet quality, EF had a significant inverse association with BF%, WC and BMI in the high diet quality groups, but not in the low diet quality groups. This study suggests that EF is inversely associated with the obesity indicators when diet quality is high, but not when it is low in Korean adults.

Executive functioning deficits in preschool children with Fetal Alcohol Spectrum Disorders

PubMed Central

Fuglestad, Anita J.; Whitley, Marisa L.; Carlson, Stephanie M.; Boys, Christopher J.; Eckerle, Judith K.; Fink, Birgit A.; Wozniak, Jeffrey R.

2014-01-01

Executive function (EF) deficit is a hallmark of Fetal Alcohol Spectrum Disorders (FASD), but the vast majority of available evidence comes from school-age children and adolescents. Very little is known about EF during the critical developmental period prior to 6 years of age in FASD. We evaluated EF in 39 children with FASD (3.0 – 5.5 years) and a comparison group of 50 age-matched, non-exposed controls. Measures included the EF Scale for Early Childhood and a Delay of Gratification task. Compared to age-matched controls, pre-school children with FASD had impairments on the EF Scale and showed more impulsivity on the Delay of Gratification task. To confirm the EF Scale finding, FASD group performance was compared to a separate normative dataset (N=1,400). Those with FASD performed below normal (M= −0.57, SD=0.92). Within the FASD group, IQ was correlated with the EF Scale (partial r=.60, p=.001) and Delay of Gratification (partial r=.58, p=.005). EF Scale performance did not differ significantly across levels of FASD severity [fetal alcohol syndrome (FAS), partial FAS, or alcohol-related neurobehavioral disorder (ARND)]. However, compared to normative data, those with FAS had the largest deficits (M= −0.91 SD, SE=0.23), followed by partial FAS (M= −0.66 SD, SE=0.26), then ARND (M= −0.36 SD, SE=0.20). These novel data show that EF deficits manifest well before the age of 6 years in children with FASD, that they occur across the spectrum, and that EF may be most impaired in children with more severe forms of FASD and/or lower IQs. PMID:25011516

Infant motor and cognitive abilities and subsequent executive function.

PubMed

Wu, Meng; Liang, Xi; Lu, Shan; Wang, Zhengyan

2017-11-01

Although executive function (EF) is widely considered crucial to several aspects of life, the mechanisms underlying EF development remain largely unexplored, especially for infants. From a behavioral or neurodevelopmental perspective, motor and general cognitive abilities are linked with EF. EF development is a multistage process that starts with sensorimotor interactive behaviors, which become basic cognitive abilities and, in turn, mature EF. This study aims to examine how infant motor and general cognitive abilities are linked with their EF at 3 years of age. This work also aims to explore the potential processes of EF development from early movement. A longitudinal study was conducted with 96 infants (55 girls and 41 boys). The infants' motor and general cognitive abilities were assessed at 1 and 2 years of age with Bayley Scales of Infant and Toddler Development, Second and Third Editions, respectively. Infants' EFs were assessed at 3 years of age with Working Memory Span task, Day-Night task, Wrapped Gift task, and modified Gift-in-Bag task. Children with higher scores for cognitive ability at 2 years of age performed better in working memory, and children with higher scores for gross motor ability at 2 years performed better in cognitive inhibitory control (IC). Motor ability at 1 year and fine/gross motor ability at 2 years indirectly affected cognitive IC via general cognitive ability at 2 years and working memory. EF development is a multistage process that originates from physical movement to simple cognitive function, and then to complex cognitive function. Infants and toddlers can undergo targeted motor training to promote EF development. Copyright © 2017 Elsevier Inc. All rights reserved.

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).

Emission factors of air pollutants from CNG-gasoline bi-fuel vehicles: Part II. CO, HC and NOx.

PubMed

Huang, Xiaoyan; Wang, Yang; Xing, Zhenyu; Du, Ke

2016-09-15

The estimation of emission factors (EFs) is the basis of accurate emission inventory. However, the EFs of air pollutants for motor vehicles vary under different operating conditions, which will cause uncertainty in developing emission inventory. Natural gas (NG), considered as a "cleaner" fuel than gasoline, is increasingly being used to reduce combustion emissions. However, information is scarce about how much emission reduction can be achieved by motor vehicles burning NG (NGVs) under real road driving conditions, which is necessary for evaluating the environmental benefits for NGVs. Here, online, in situ measurements of the emissions from nine bi-fuel vehicles were conducted under different operating conditions on the real road. A comparative study was performed for the EFs of black carbon (BC), carbon monoxide (CO), hydrocarbons (HCs) and nitrogen oxides (NOx) for each operating condition when the vehicles using gasoline and compressed NG (CNG) as fuel. BC EFs were reported in part I. The part II in this paper series reports the influence of operating conditions and fuel types on the EFs of CO, HC and NOx. Fuel-based EFs of CO showed good correlations with speed when burning CNG and gasoline. The correlation between fuel-based HC EFs and speed was relatively weak whether burning CNG or gasoline. The fuel-based NOx EFs moderately correlated with speed when burning CNG, but weakly correlated with gasoline. As for HC, the mileage-based EFs of gasoline vehicles are 2.39-12.59 times higher than those of CNG vehicles. The mileage-based NOx EFs of CNG vehicles are slightly higher than those of gasoline vehicles. These results would facilitate a detailed analysis of the environmental benefits for replacing gasoline with CNG in light duty vehicles. Copyright © 2016 Elsevier B.V. All rights reserved.

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.

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

Trends in the use of echocardiography and left ventriculography to assess left ventricular ejection fraction in patients hospitalized with acute myocardial infarction

PubMed Central

Joffe, Samuel W.; Chalian, Armen; Tighe, Dennis A.; Aurigemma, Gerard P.; Yarzebski, Jorge; Gore, Joel M.; Lessard, Darleen; Goldberg, Robert J.

2009-01-01

Background While current guidelines strongly recommend the measurement of ejection fraction (EF) in all patients hospitalized with acute myocardial infarction (AMI), there are little data available describing trends in the use of diagnostic modalities to assess EF in these patients. The purpose of this study was to evaluate trends in the use of ventriculography and echocardiography to measure EF in a community sample of patients hospitalized with AMI. Methods The medical records of 5,380 residents of the Worcester (MA) metropolitan area hospitalized with AMI at 11 greater Worcester medical centers between 1997 and 2005 were reviewed. Results Between 1997 and 2005, the proportion of patients hospitalized with AMI undergoing measurement of EF by both ventriculography and echocardiography increased from 11% to 18%, while the percentage of patients who did not receive an evaluation of EF by either modality decreased from 37% to 27%. The percentage of patients undergoing measurement of EF by ventriculography alone increased from 14% to 20%, while the percentage of patients undergoing measurement of EF by echocardiography alone remained stable at 37%. In 1997, echocardiography was performed prior to ventriculography in approximately two-thirds of hospitalized patients, while in 2005, ventriculography was performed prior to echocardiography in approximately two-thirds of patients with AMI. Conclusions The use of left ventriculography, and the concurrent use of both ventriculography and echocardiography, to assess EF in patients with AMI is increasing. While the proportion of patients who do not have their EF assessed has declined during recent years, many still do not receive a determination of their EF. PMID:19619693

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

A liposomal formulation of the synthetic curcumin analog EF24 (Lipo-EF24) inhibits pancreatic cancer progression: towards future combination therapies.

PubMed

Bisht, Savita; Schlesinger, Martin; Rupp, Alexander; Schubert, Rolf; Nolting, Jens; Wenzel, Jörg; Holdenrieder, Stefan; Brossart, Peter; Bendas, Gerd; Feldmann, Georg

2016-07-11

Pancreatic cancer is one of the most lethal of human malignancies known to date and shows relative insensitivity towards most of the clinically available therapy regimens. 3,5-bis(2-fluorobenzylidene)-4-piperidone (EF24), a novel synthetic curcumin analog, has shown promising in vitro therapeutic efficacy in various human cancer cells, but insufficient water solubility and systemic bioavailability limit its clinical application. Here, we describe nano-encapsulation of EF24 into pegylated liposomes (Lipo-EF24) and evaluation of these particles in preclinical in vitro and in vivo model systems of pancreatic cancer. Transmission electron microscopy and size distribution studies by dynamic light scattering confirmed intact spherical morphology of the formed liposomes with an average diameter of less than 150 nm. In vitro, treatment with Lipo-EF24 induced growth inhibition and apoptosis in MIAPaCa and Pa03C pancreatic cancer cells as assessed by using cell viability and proliferation assays, replating and soft agar clonogenicity assays as well as western blot analyses. Lipo-EF24 potently suppressed NF-kappaB nuclear translocation by inhibiting phosphorylation and subsequent degradation of its inhibitor I-kappa-B-alpha. In vivo, synergistic tumor growth inhibition was observed in MIAPaCa xenografts when Lipo-EF24 was given in combination with the standard-of-care cytotoxic agent gemcitabine. In line with in vitro observations, western blot analysis revealed decreased phosphorylation of I-kappa-B-alpha in excised Lipo-EF24-treated xenograft tumor tissues. Due to its promising therapeutic efficacy and favorable toxicity profile Lipo-EF24 might be a promising starting point for development of future combinatorial therapeutic regimens against pancreatic cancer.

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.

Impaired associative taste learning and abnormal brain activation in kinase-defective eEF2K mice.

PubMed

Gildish, Iness; Manor, David; David, Orit; Sharma, Vijendra; Williams, David; Agarwala, Usha; Wang, Xuemin; Kenney, Justin W; Proud, Chris G; Rosenblum, Kobi

2012-02-24

Memory consolidation is defined temporally based on pharmacological interventions such as inhibitors of mRNA translation (molecular consolidation) or post-acquisition deactivation of specific brain regions (systems level consolidation). However, the relationship between molecular and systems consolidation are poorly understood. Molecular consolidation mechanisms involved in translation initiation and elongation have previously been studied in the cortex using taste-learning paradigms. For example, the levels of phosphorylation of eukaryotic elongation factor 2 (eEF2) were found to be correlated with taste learning in the gustatory cortex (GC), minutes following learning. In order to isolate the role of the eEF2 phosphorylation state at Thr-56 in both molecular and system consolidation, we analyzed cortical-dependent taste learning in eEF2K (the only known kinase for eEF2) ki mice, which exhibit reduced levels of eEF2 phosphorylation but normal levels of eEF2 and eEF2K. These mice exhibit clear attenuation of cortical-dependent associative, but not of incidental, taste learning. In order to gain a better understanding of the underlying mechanisms, we compared brain activity as measured by MEMRI (manganese-enhanced magnetic resonance imaging) between eEF2K ki mice and WT mice during conditioned taste aversion (CTA) learning and observed clear differences between the two but saw no differences under basal conditions. Our results demonstrate that adequate levels of phosphorylation of eEF2 are essential for cortical-dependent associative learning and suggest that malfunction of memory processing at the systems level underlies this associative memory impairment. © 2012 Cold Spring Harbor Laboratory Press

Heart Failure with Preserved Ejection Fraction - Concept, Pathophysiology, Diagnosis and Challenges for Treatment.

PubMed

Miljkovik, Lidija Veterovska; Spiroska, Vera

2015-09-15

Heart failure (HF) with preserved left ventricular (LV) ejection fraction (HFpEF) occurs in 40 to 60% of the patients with HF, with a prognosis which is similar to HF with reduced ejection fraction (HFrEF). HFpEF pathophysiology is different from that of HFrEF, and has been characterized with diastolic dysfunction. Diastolic dysfunction has been defined with elevated left ventricular stiffness, prolonged iso-volumetric LV relaxation, slow LV filing and elevated LV end-diastolic pressure. Arterial hypertension occurs in majority cases with HFpEF worldwide. Patients are mostly older and obese. Diabetes mellitus and atrial fibrillation appear proportionally in a high frequency of patients with HFpEF. The HFpEF diagnosis is based on existence of symptoms and signs of heart failure, normal or approximately normal ejection and diagnosing of LV diastolic dysfunction by means of heart catheterization or Doppler echocardiography and/or elevated concentration of plasma natriuretic peptide. The present recommendations for HFpEF treatment include blood pressure control, heart chamber frequency control when atrial fibrillation exists, in some situations even coronary revascularization and an attempt for sinus rhythm reestablishment. Up to now, it is considered that no medication or a group of medications improve the survival of HFpEF patients. Due to these causes and the bad prognosis of the disorder, rigorous control is recommended of the previously mentioned precipitating factors for this disorder. This paper presents a universal review of the most important parameters which determine this disorder.

The pretranslocation ribosome is targeted by GTP-bound EF-G in partially activated form

PubMed Central

Hauryliuk, Vasili; Mitkevich, Vladimir A.; Eliseeva, Natalia A.; Petrushanko, Irina Yu.; Ehrenberg, Måns; Makarov, Alexander A.

2008-01-01

Translocation of the tRNA·mRNA complex through the bacterial ribosome is driven by the multidomain guanosine triphosphatase elongation factor G (EF-G). We have used isothermal titration calorimetry to characterize the binding of GDP and GTP to free EF-G at 4°C, 20°C, and 37°C. The binding affinity of EF-G is higher to GDP than to GTP at 4°C, but lower at 37°C. The binding enthalpy and entropy change little with temperature in the case of GDP binding but change greatly in the case of GTP binding. These observations are compatible with a large decrease in the solvent-accessible hydrophobic surface area of EF-G on GTP, but not GDP, binding. The explanation we propose is the locking of the switch 1 and switch 2 peptide loops in the G domain of EF-G to the γ-phosphate of GTP. From these data, in conjunction with previously reported structural data on guanine nucleotide-bound EF-G, we suggest that EF-G enters the pretranslocation ribosome as an “activity chimera,” with the G domain activated by the presence of GTP but the overall factor conformation in the inactive form typical of a GDP-bound multidomain guanosine triphosphatase. We propose that the active overall conformation of EF-G is attained only in complex with the ribosome in its “ratcheted state,” with hybrid tRNA binding sites. PMID:18836081

Kirromycin, an Inhibitor of Protein Biosynthesis that Acts on Elongation Factor Tu

PubMed Central

Wolf, Heinz; Chinali, Gianni; Parmeggiani, Andrea

1974-01-01

Kirromycin, a new inhibitor of protein synthesis, is shown to interfere with the peptide transfer reaction by acting on elongation factor Tu (EF-Tu). All the reactions associated with this elongation factor are affected. Formation of the EF-Tu·GTP complex is strongly stimulated. Peptide bond formation is prevented only when Phe-tRNAPhe is bound enzymatically to ribosomes, presumably because GTP hydrolysis associated with enzymatic binding of Phe-tRNAPhe is not followed by release of EF-Tu·GDP from the ribosome. This antibiotic also enables EF-Tu to catalyze the binding of Phe-tRNAPhe to the poly(U)·ribosome complex even in the absence of GTP. EF-Tu activity in the GTPase reaction is dramatically affected by kirromycin: GTP hydrolysis, which normally requires ribosomes and aminoacyl-tRNA, takes place with the elongation factor alone. This GTPase shows the same Km for GTP as the one dependent on Phe-tRNAPhe and ribosomes in the absence of the antibiotic. Ribosomes and Phe-tRNAPhe, but not tRNAPhe or Ac-Phe-tRNAPhe, stimulate the kirromycin-induced EF-Tu GTPase. These results indicate that the catalytic center of EF-Tu GTPase that is dependent upon aminoacyl-tRNA and ribosomes is primarily located on the elongation factor. In conclusion, kirromycin can substitute for GTP, aminoacyl-tRNA, or ribosomes in various reactions involving EF-Tu, apparently by affecting the allosteric controls between the sites on the EF-Tu molecule interacting with these components. PMID:4373734

Toroidal modeling of the n = 1 intrinsic error field correction experiments in EAST

NASA Astrophysics Data System (ADS)

Yang, Xu; Liu, Yueqiang; Sun, Youwen; Wang, Huihui; Gu, Shuai; Jia, Manni; Li, Li; Liu, Yue; Wang, Zhirui; Zhou, Lina

2018-05-01

The m/n = 2/1 resonant vacuum error field (EF) in the EAST tokamak experiments, inferred from the compass coil current amplitude and phase scan for mode locking, was found to depend on the parity between the upper and lower rows of the EF correction (EFC) coils (Wang et al 2016 Nucl. Fusion 56 066011). Here m and n are the poloidal and toroidal harmonic numbers in a torus, respectively. This experimental observation implies that the compass scan results cannot be simply interpreted as reflecting the true intrinsic EF. This work aims at understanding this puzzle, based on toroidal modeling of the EFC plasma discharge in EAST using the MARS-F code (Liu et al 2000 Phys. Plasmas 7 3681). By varying the amplitude and phase of the assumed n = 1 intrinsic vacuum EF with different poloidal spectra, and by computing the plasma response to the assumed EF, the compass scan predicted 2/1 EF, based on minimizing the computed resonant electromagnetic torque, can be made to match well with that of the EFC experiments using both even and odd parity coils. Moreover, the compass scan predicted vacuum EFs are found to be significantly differing from the true intrinsic EF used as input to the MARS-F code. While the puzzling result remains to be fully resolved, the results from this study offer an improved understanding of the EFC experiments and the compass scan technique for determining the intrinsic resonant EF.

Exploring the differential associations between components of executive functioning and reactive and proactive aggression.

PubMed

Hecht, Lisa K; Latzman, Robert D

2018-02-01

A large body of literature confirms the importance of executive functioning (EF) in the explanation of aggressive and antisocial behaviors. However, the common and specific associations between subtypes of aggression, such as reactive (RA), proactive aggression (PA), and EF are unclear. The current study explored the nuanced associations between components of EF and subtypes of aggression, using a latent variable approach. Participants were 384 racially diverse undergraduate students (ages 18-52 years) who completed a self-report measure of RA and PA, and traditional neuropsychological tasks of EF. The appropriateness of using a nested bifactor model of EF was confirmed, and this bifactor model of EF was then used to examine the specific associations between components of EF and RA and PA. Results revealed that components of EF are differentially associated with RA and PA. Specifically, impulsive, provoked aggression (i.e., RA) was associated with lower levels of goal-oriented inhibition and higher levels of flexibility, whereas planned, goal-oriented aggression (i.e., PA) was associated with higher levels of working memory. Findings from the current study underscore the importance of considering the multidimensional nature of EF, as well as the heterogeneity within aggression, rather than considering either construct as a single monolithic construct. The current study suggests that potentially unique brain-based pathways from aspects of EF to subtypes of aggression may exist, and points toward potential avenues through which to intervene.

The Temporal Association Between Executive Function and Life-Space Mobility in Old Age.

PubMed

Poranen-Clark, Taina; von Bonsdorff, Mikaela B; Rantakokko, Merja; Portegijs, Erja; Eronen, Johanna; Pynnönen, Katja; Eriksson, Johan G; Viljanen, Anne; Rantanen, Taina

2018-05-09

Life-space mobility, an indicator of community mobility, describes person's movements in terms of the distance from home, the frequency of movement, and the need of assistance for movement. Executive function (EF) is a higher-order cognitive function that supervises motor control and plays a key role in a person's ability to function independently. Cognitive impairment often co-occurs with restricted life-space mobility; however, the direction of the longitudinal associations between EF and life-space mobility is unclear. The aim of this study was to investigate the temporal associations between EF and life-space mobility among community-dwelling older people. One hundred eight community-dwelling persons aged 76 to 91 years participated in the 2 year follow-up study. EF was measured with the Trail Making Test. The Life-Space Assessment (range 0-120, higher scores indicate more mobility) was used to assess life-space mobility. Cross-lagged model design was used to examine longitudinal relationship between EF and life-space mobility. The model was adjusted for age and gender. Average age of participants at baseline was 82.2 (SD 4.1) years and 59% were women. Better EF at baseline predicted higher life-space mobility at follow-up (path coefficient = 3.81, 95% confidential interval; 0.84, 6.78, p = .012), whereas baseline life-space mobility did not predict EF at follow-up. EF was a determinant of life-space mobility. Supporting EF may enhance maintaining independence and active participation in old age.

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.

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.

Potentiation of Schaffer-Collateral CA1 Synaptic Transmission by eEF2K and p38 MAPK Mediated Mechanisms.

PubMed

Weng, Weiguang; Chen, Ying; Wang, Man; Zhuang, Yinghan; Behnisch, Thomas

2016-01-01

The elongation factor 2 kinase (eEF2K), likewise known as CaMKIII, has been demonstrated to be involved in antidepressant responses of NMDA receptor antagonists. Even so, it remains open whether direct inhibition of eEF2K without altering up-stream or other signaling pathways affects hippocampal synaptic transmission and neuronal network synchrony. Inhibition of eEF2K by the selective and potent eEF2K inhibitor A-484954 induced a fast pre-synaptically mediated enhancement of synaptic transmission and synchronization of neural network activity. The eEF2K-inhibition mediated potentiation of synaptic transmission of hippocampal CA1 neurons is most notably independent of protein synthesis and does not rely on protein kinase C, protein kinase A or mitogen-activated protein kinase (MAPK)/extracellular signal-regulated protein kinase 1/2. Moreover, the strengthening of synaptic transmission in the response to the inhibition of eEF2K was strongly attenuated by the inhibition of p38 MAPK. In addition, we show the involvement of barium-sensitive and more specific the TWIK-related potassium-1 (TREK-1) channels in the eEF2K-inhibition mediated potentiation of synaptic transmission. These findings reveal a novel pathway of eEF2K mediated regulation of hippocampal synaptic transmission. Further research is required to study whether such compounds could be beneficial for the development of mood disorder treatments with a fast-acting antidepressant response.

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.

Characterization of Mexican coriander (Eryngium foetidum) essential oil and its inactivation of Listeria monocytogenes in vitro and during mild thermal pasteurization of pineapple juice.

PubMed

Ngang, Jean J Essia; Nyegue, Maximilienne A; Ndoye, Foe C; Tchuenchieu Kamgain, Alex D; Sado Kamdem, Sylvain L; Lanciotti, Rosalba; Gardini, Fausto; Etoa, François-Xavier

2014-03-01

The aim of this work was to characterize the essential oil (EO) of Eryngium foetidum (EfEO) and assess its activity toward Listeria monocytogenes in broth and during thermal inactivation of the pathogen in pineapple juice. In this respect, EfEO was chemically characterized, and its antilisteria potential in broth as a function of pH, cell load, and EfEO concentration was assessed through a central composite design. Furthermore, the inactivation kinetics of L. monocytogenes in the juice were assessed by combining EfEO and low pasteurization temperatures. A total of 81 compounds were identified from EfEO. The reduction of pH and cell load increased EO activity. The use of only 15 ppm of EfEO during pasteurization of pineapple juice at 60°C reduced the time required for a 4-log reduction in L. monocytogenes CFU/ml by 74.9% (i.e., from 8.5 to 2.1 min) compared with treatment without EfEO. It could be concluded that EfEO activity toward L. monocytogenes increases with the reduction of pH and that it can be used at sublethal concentrations in combination with low temperatures in pineapple juice pasteurization. This study demonstrates that EO-assisted pasteurization is a promising strategy for the reduction of thermal impact during juice production. EfEO is easily available and compatible with many juices and is thus promising for industrial application.

Interfering With Lipid Raft Association: A Mechanism to Control Influenza Virus Infection By Sambucus Nigra

PubMed Central

Shahsavandi, Shahla; Ebrahimi, Mohammad Majid; Hasaninejad Farahani, Ameneh

2017-01-01

Sambucus nigra (elder) are broadly used species to treat microbial infections. The potential antiviral activity and mechanism action of elder fruit (EF) in human epithelium cell (A549) cultures infected with H9N2 influenza virus were determined. The effect of various concentrations of EF on influenza virus replication was examined by using virus titration, quantitative real time RT-PCR, fusion and lipid raft assays following two treatment procedures: A) pre-treated H9N2 virus with each concentration of EF extract and transfection of A549 cell cultures, and B) each concentrations of EF was added to H9N2 virus infected-cell cultures following virus adsorption. In both treatments with lower doses of EF increased viral titer as well as synthesized viral nucleoprotein as indicating the herb had no inhibitory effects on virus replication. In (B) trial with higher doses, 40 and 80 μg/mL of EF, a significant decrease in virus titer and viral protein synthesis were shown in EF treated cells indicating the herb affect either entry of viruses or inhibition virus particle release. The results suggest that EF treatment of the influenza virus infected-human epithelial cells may involve in lipid raft association which function as platform for formation of viral membrane fusion and budding. Differencesin treatment time and dose of EF extract in infected cells with influenza virus have a marked effect on the efficacy of the herb. PMID:29201101

The Role of Executive Function in Children’s Competent Adjustment to Middle School

PubMed Central

Jacobson, Lisa A.; Williford, Amanda P.; Pianta, Robert C.

2012-01-01

Executive function (EF) skills play an important role in children’s cognitive and social functioning. These skills develop throughout childhood, concurrently with a number of developmental transitions and challenges. One of these challenges is the transition from elementary into middle-level schools, which has the potential to significantly disrupt children’s academic and social trajectories. However, little is known about the role of EF in children’s adjustment during this transition. This study investigated the relation between children’s EF skills, assessed both before and during elementary school, and sixth grade academic and social competence. In addition, the influences of the type of school setting attended in sixth grade on children’s academic and behavioral outcomes were examined. EF assessed prior to and during elementary school significantly predicted sixth grade competence, as rated by teachers and parents, in both academic and social domains, after controlling for background characteristics. The interactions between type of school setting and EF skills were significant: parents tended to report more behavioral problems and less regulatory control in children with weaker EF skills who were attending middle school. In contrast, teachers reported greater academic and behavioral difficulty in students with poorer EF attending elementary school settings. In conclusion, children’s performance-based EF skills significantly affect adjustment to the academic and behavioral demands of sixth grade, with parent report suggesting greater difficulty for children with poorer EF in settings where children are provided with less external supports (e.g., middle school). PMID:21246422

9 CFR 205.102 - Name of person subjecting a farm product to a security interest, on EFS and master list-format.

Code of Federal Regulations, 2010 CFR

2010-01-01

... product to a security interest, on EFS and master list-format. 205.102 Section 205.102 Animals and Animal... of person subjecting a farm product to a security interest, on EFS and master list—format. On an EFS, and on a master list, the name of the person subjecting a farm product to a security interest must...

9 CFR 205.102 - Name of person subjecting a farm product to a security interest, on EFS and master list-format.

Code of Federal Regulations, 2012 CFR

2012-01-01

... product to a security interest, on EFS and master list-format. 205.102 Section 205.102 Animals and Animal... of person subjecting a farm product to a security interest, on EFS and master list—format. On an EFS, and on a master list, the name of the person subjecting a farm product to a security interest must...

9 CFR 205.102 - Name of person subjecting a farm product to a security interest, on EFS and master list-format.

Code of Federal Regulations, 2014 CFR

2014-01-01

... product to a security interest, on EFS and master list-format. 205.102 Section 205.102 Animals and Animal... of person subjecting a farm product to a security interest, on EFS and master list—format. On an EFS, and on a master list, the name of the person subjecting a farm product to a security interest must...

9 CFR 205.102 - Name of person subjecting a farm product to a security interest, on EFS and master list-format.

Code of Federal Regulations, 2013 CFR

2013-01-01

... product to a security interest, on EFS and master list-format. 205.102 Section 205.102 Animals and Animal... of person subjecting a farm product to a security interest, on EFS and master list—format. On an EFS, and on a master list, the name of the person subjecting a farm product to a security interest must...

9 CFR 205.102 - Name of person subjecting a farm product to a security interest, on EFS and master list-format.

Code of Federal Regulations, 2011 CFR

2011-01-01

... product to a security interest, on EFS and master list-format. 205.102 Section 205.102 Animals and Animal... of person subjecting a farm product to a security interest, on EFS and master list—format. On an EFS, and on a master list, the name of the person subjecting a farm product to a security interest must...

Direct evidence of an elongation factor-Tu/Ts·GTP·Aminoacyl-tRNA quaternary complex.

PubMed

Burnett, Benjamin J; Altman, Roger B; Ferguson, Angelica; Wasserman, Michael R; Zhou, Zhou; Blanchard, Scott C

2014-08-22

During protein synthesis, elongation factor-Tu (EF-Tu) bound to GTP chaperones the entry of aminoacyl-tRNA (aa-tRNA) into actively translating ribosomes. In so doing, EF-Tu increases the rate and fidelity of the translation mechanism. Recent evidence suggests that EF-Ts, the guanosine nucleotide exchange factor for EF-Tu, directly accelerates both the formation and dissociation of the EF-Tu-GTP-Phe-tRNA(Phe) ternary complex (Burnett, B. J., Altman, R. B., Ferrao, R., Alejo, J. L., Kaur, N., Kanji, J., and Blanchard, S. C. (2013) J. Biol. Chem. 288, 13917-13928). A central feature of this model is the existence of a quaternary complex of EF-Tu/Ts·GTP·aa-tRNA(aa). Here, through comparative investigations of phenylalanyl, methionyl, and arginyl ternary complexes, and the development of a strategy to monitor their formation and decay using fluorescence resonance energy transfer, we reveal the generality of this newly described EF-Ts function and the first direct evidence of the transient quaternary complex species. These findings suggest that EF-Ts may regulate ternary complex abundance in the cell through mechanisms that are distinct from its guanosine nucleotide exchange factor functions. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

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.

Verbal Processing Speed and Executive Functioning in Long-Term Cochlear Implant Users

PubMed Central

Pisoni, David B.; Kronenberger, William G.

2015-01-01

Purpose The purpose of this study was to report how verbal rehearsal speed (VRS), a form of covert speech used to maintain verbal information in working memory, and another verbal processing speed measure, perceptual encoding speed, are related to 3 domains of executive function (EF) at risk in cochlear implant (CI) users: verbal working memory, fluency-speed, and inhibition-concentration. Method EF, speech perception, and language outcome measures were obtained from 55 prelingually deaf, long-term CI users and matched controls with normal hearing (NH controls). Correlational analyses were used to assess relations between VRS (articulation rate), perceptual encoding speed (digit and color naming), and the outcomes in each sample. Results CI users displayed slower verbal processing speeds than NH controls. Verbal rehearsal speed was related to 2 EF domains in the NH sample but was unrelated to EF outcomes in CI users. Perceptual encoding speed was related to all EF domains in both groups. Conclusions Verbal rehearsal speed may be less influential for EF quality in CI users than for NH controls, whereas rapid automatized labeling skills and EF are closely related in both groups. CI users may develop processing strategies in EF tasks that differ from the covert speech strategies routinely employed by NH individuals. PMID:25320961

Cognitive, Parent and Teacher Rating Measures of Executive Functioning: Shared and Unique Influences on School Achievement

PubMed Central

Dekker, Marielle C.; Ziermans, Tim B.; Spruijt, Andrea M.; Swaab, Hanna

2017-01-01

Very little is known about the relative influence of cognitive performance-based executive functioning (EF) measures and behavioral EF ratings in explaining differences in children's school achievement. This study examined the shared and unique influence of these different EF measures on math and spelling outcome for a sample of 84 first and second graders. Parents and teachers completed the Behavior Rating Inventory of Executive Function (BRIEF), and children were tested with computer-based performance tests from the Amsterdam Neuropsychological Tasks (ANT). Mixed-model hierarchical regression analyses, including intelligence level and age, showed that cognitive performance and teacher's ratings of working memory and shifting concurrently explained differences in spelling. However, teacher's behavioral EF ratings did not explain any additional variance in math outcome above cognitive EF performance. Parent's behavioral EF ratings did not add any unique information for either outcome measure. This study provides support for the ecological validity of performance- and teacher rating-based EF measures, and shows that both measures could have a complementary role in identifying EF processes underlying spelling achievement problems. The early identification of strengths and weaknesses of a child's working memory and shifting capabilities, might help teachers to broaden their range of remedial intervention options to optimize school achievement. PMID:28194121

Associations between early life adversity and executive function in children adopted internationally from orphanages

PubMed Central

Hostinar, Camelia E.; Stellern, Sarah A.; Schaefer, Catherine; Carlson, Stephanie M.; Gunnar, Megan R.

2012-01-01

Executive function (EF) abilities are increasingly recognized as an important protective factor for children experiencing adversity, promoting better stress and emotion regulation as well as social and academic adjustment. We provide evidence that early life adversity is associated with significant reductions in EF performance on a developmentally sensitive battery of laboratory EF tasks that measured cognitive flexibility, working memory, and inhibitory control. Animal models also suggest that early adversity has a negative impact on the development of prefrontal cortex-based cognitive functions. In this study, we report EF performance 1 y after adoption in 2.5- to 4-y-old children who had experienced institutional care in orphanages overseas compared with a group of age-matched nonadopted children. To our knowledge, this is the youngest age and the soonest after adoption that reduced EF performance has been shown using laboratory measures in this population. EF reductions in performance were significant above and beyond differences in intelligence quotient. Within the adopted sample, current EF was associated with measures of early deprivation after controlling for intelligence quotient, with less time spent in the birth family before placement in an institution and lower quality of physical/social care in institutions predicting poorer performance on the EF battery. PMID:23047689

Associations between early life adversity and executive function in children adopted internationally from orphanages.

PubMed

Hostinar, Camelia E; Stellern, Sarah A; Schaefer, Catherine; Carlson, Stephanie M; Gunnar, Megan R

2012-10-16

Executive function (EF) abilities are increasingly recognized as an important protective factor for children experiencing adversity, promoting better stress and emotion regulation as well as social and academic adjustment. We provide evidence that early life adversity is associated with significant reductions in EF performance on a developmentally sensitive battery of laboratory EF tasks that measured cognitive flexibility, working memory, and inhibitory control. Animal models also suggest that early adversity has a negative impact on the development of prefrontal cortex-based cognitive functions. In this study, we report EF performance 1 y after adoption in 2.5- to 4-y-old children who had experienced institutional care in orphanages overseas compared with a group of age-matched nonadopted children. To our knowledge, this is the youngest age and the soonest after adoption that reduced EF performance has been shown using laboratory measures in this population. EF reductions in performance were significant above and beyond differences in intelligence quotient. Within the adopted sample, current EF was associated with measures of early deprivation after controlling for intelligence quotient, with less time spent in the birth family before placement in an institution and lower quality of physical/social care in institutions predicting poorer performance on the EF battery.

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.

Executive functions in adults with developmental dyslexia.

PubMed

Smith-Spark, James H; Henry, Lucy A; Messer, David J; Edvardsdottir, Elisa; Zięcik, Adam P

2016-01-01

Executive functioning (EF) deficits are well recognized in developmental dyslexia, yet the majority of studies have concerned children rather than adults, ignored the subjective experience of the individual with dyslexia (with regard to their own EFs), and have not followed current theoretical perspectives on EFs. The current study addressed these shortfalls by administering a self-report measure of EF (BRIEF-A; Roth, Isquith, & Gioia, 2005) and experimental tasks to IQ-matched groups of adults with and without dyslexia. The laboratory-based tasks tested the three factors constituting the framework of EF proposed by Miyake et al. (2000). In comparison to the group without dyslexia, the participants with dyslexia self-reported more frequent EF problems in day-to-day life, with these difficulties centering on metacognitive processes (working memory, planning, task monitoring, and organization) rather than on the regulation of emotion and behaviour. The participants with dyslexia showed significant deficits in EF (inhibition, set shifting, and working memory). The findings indicated that dyslexia-related problems have an impact on the daily experience of adults with the condition. Further, EF difficulties are present in adulthood across a range of laboratory-based measures, and, given the nature of the experimental tasks presented, extend beyond difficulties related solely to phonological processing. Copyright © 2016 Elsevier Ltd. All rights reserved.

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.

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.

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%.

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

Engineering Forum Strategic Plan

EPA Pesticide Factsheets

This Strategic Plan highlights the purpose, mission, goals, and objectives of the U.S. Environmental Protection Agency (EPA) Engineering Forum (EF). It sets forth the principles that guide the EF's decision-making, helps clarify the EF's priorities, and...

Performance-based measures and behavioral ratings of executive function in diagnosing attention-deficit/hyperactivity disorder in children.

PubMed

Tan, Alexander; Delgaty, Lauren; Steward, Kayla; Bunner, Melissa

2018-04-16

Deficits in real-world executive functioning (EF) are a frequent characteristic of attention-deficit/hyperactivity disorder (ADHD). However, the predictive value of using performance-based and behavioral rating measures of EF when diagnosing ADHD remains unclear. The current study investigates the use of performance-based EF measures and a parent-report questionnaire with established ecological validity and clinical utility when diagnosing ADHD. Participants included 21 healthy controls, 21 ADHD-primary inattentive, and 21 ADHD-combined type subjects aged 6-15 years. A brief neuropsychological battery was administered to each subject including common EF assessment measures. Significant differences were not found between groups on most performance-based EF measures, whereas significant differences (p < 0.05) were found on most parent-report behavioral rating scales. Furthermore, performance-based measures did not predict group membership above chance levels. Results further support differences in predictive value of EF performance-based measures compared to parent-report questionnaires when diagnosing ADHD. Further research must investigate the relationship between performance-based and behavioral rating measures when assessing EF in ADHD.

eEF2K/eEF2 Pathway Controls the Excitation/Inhibition Balance and Susceptibility to Epileptic Seizures.

PubMed

Heise, Christopher; Taha, Elham; Murru, Luca; Ponzoni, Luisa; Cattaneo, Angela; Guarnieri, Fabrizia C; Montani, Caterina; Mossa, Adele; Vezzoli, Elena; Ippolito, Giulio; Zapata, Jonathan; Barrera, Iliana; Ryazanov, Alexey G; Cook, James; Poe, Michael; Stephen, Michael Rajesh; Kopanitsa, Maksym; Benfante, Roberta; Rusconi, Francesco; Braida, Daniela; Francolini, Maura; Proud, Christopher G; Valtorta, Flavia; Passafaro, Maria; Sala, Mariaelvina; Bachi, Angela; Verpelli, Chiara; Rosenblum, Kobi; Sala, Carlo

2017-03-01

Alterations in the balance of inhibitory and excitatory synaptic transmission have been implicated in the pathogenesis of neurological disorders such as epilepsy. Eukaryotic elongation factor 2 kinase (eEF2K) is a highly regulated, ubiquitous kinase involved in the control of protein translation. Here, we show that eEF2K activity negatively regulates GABAergic synaptic transmission. Indeed, loss of eEF2K increases GABAergic synaptic transmission by upregulating the presynaptic protein Synapsin 2b and α5-containing GABAA receptors and thus interferes with the excitation/inhibition balance. This cellular phenotype is accompanied by an increased resistance to epilepsy and an impairment of only a specific hippocampal-dependent fear conditioning. From a clinical perspective, our results identify eEF2K as a potential novel target for antiepileptic drugs, since pharmacological and genetic inhibition of eEF2K can revert the epileptic phenotype in a mouse model of human epilepsy. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

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.

Prospective relations between maternal autonomy support and child executive functioning: investigating the mediating role of child language ability.

PubMed

Matte-Gagné, Célia; Bernier, Annie

2011-12-01

Although emerging evidence suggests that parental behavior is related to the development of child executive functioning (EF), the mechanisms through which parenting affects child EF have yet to be investigated. The goal of this study was to examine the potential mediating role of child language in the prospective relation between maternal autonomy support and child EF. A total of 53 mother-infant dyads took part in three home visits at 15months, 2years, and 3years, allowing for the assessment of maternal autonomy support (T1), child expressive vocabulary (T2), and child EF (T3). The results suggested that child language played a mediating role in the relation between maternal autonomy support and child performance on EF tasks entailing a strong impulse control component above and beyond child previous EF and family socioeconomic status (SES). In contrast, no such mediating role of language was found with EF tasks tapping mostly into working memory and set shifting. Thus, this study highlights one pathway through which parenting can affect child executive control. Copyright © 2011 Elsevier Inc. All rights reserved.

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

Activation of Elongation Factor G by Phosphate Analogues

PubMed Central

Salsi, Enea; Farah, Elie

2016-01-01

EF-G is a universally conserved translational GTPase that promotes the translocation of tRNA and mRNA through the ribosome. EF-G binds to the ribosome in a GTP-bound form and subsequently catalyzes GTP hydrolysis. The contribution of the ribosome-stimulated GTP hydrolysis by EF-G to tRNA/mRNA translocation remains debated. Here, we show that while EF-G•GDP does not stably bind to the ribosome and induce translocation, EFG• GDP in complex with phosphate group analogues BeF3− and AlF4− promotes the translocation of tRNA and mRNA. Furthermore, the rates of mRNA translocation induced by EF-G in the presence of GTP and a non-hydrolysable analogue of GTP, GDP•BeF3−are similar. Our results are consistent with the model suggesting that GTP hydrolysis is not directly coupled to mRNA/tRNA translocation. Hence, GTP binding is required to induce the activated, translocation-competent conformation of EF-G while GTP hydrolysis triggers EF-G release from the ribosome. PMID:27063503

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.

Links between theory of mind and executive function in young children with autism: clues to developmental primacy.

PubMed

Pellicano, Elizabeth

2007-07-01

There has been much theoretical discussion of a functional link between theory of mind (ToM) and executive function (EF) in autism. This study sought to establish the relationship between ToM and EF in young children with autism (M = 5 years, 6 months) and to examine issues of developmental primacy. Thirty children with autism and 40 typically developing children, matched on age and ability, were assessed on a battery of tasks measuring ToM (1st- and 2nd-order false belief) and components of EF (planning, set shifting, inhibition). A significant correlation emerged between ToM and EF variables in the autism group, independent of age and ability, while ToM and higher order planning ability remained significantly related in the comparison group. Examination of the pattern of ToM-EF impairments in the autism group revealed dissociations in 1 direction only: impaired ToM with intact EF. These findings support the view that EF may be 1 important factor in the advancement of ToM understanding in autism. The theoretical implications of these findings are discussed. Copyright 2007 APA.

Ca2+-independent Binding of Anionic Phospholipids by Phospholipase C δ1 EF-hand Domain*

PubMed Central

Cai, Jingfei; Guo, Su; Lomasney, Jon W.; Roberts, Mary F.

2013-01-01

Recombinant EF-hand domain of phospholipase C δ1 has a moderate affinity for anionic phospholipids in the absence of Ca2+ that is driven by interactions of cationic and hydrophobic residues in the first EF-hand sequence. This region of PLC δ1 is missing in the crystal structure. The relative orientation of recombinant EF with respect to the bilayer, established with NMR methods, shows that the N-terminal helix of EF-1 is close to the membrane interface. Specific mutations of EF-1 residues in full-length PLC δ1 reduce enzyme activity but not because of disturbing partitioning of the protein onto vesicles. The reduction in enzymatic activity coupled with vesicle binding studies are consistent with a role for this domain in aiding substrate binding in the active site once the protein is transiently anchored at its target membrane. PMID:24235144

Super-resolution imaging and tracking of protein-protein interactions in sub-diffraction cellular space

NASA Astrophysics Data System (ADS)

Liu, Zhen; Xing, Dong; Su, Qian Peter; Zhu, Yun; Zhang, Jiamei; Kong, Xinyu; Xue, Boxin; Wang, Sheng; Sun, Hao; Tao, Yile; Sun, Yujie

2014-07-01

Imaging the location and dynamics of individual interacting protein pairs is essential but often difficult because of the fluorescent background from other paired and non-paired molecules, particularly in the sub-diffraction cellular space. Here we develop a new method combining bimolecular fluorescence complementation and photoactivated localization microscopy for super-resolution imaging and single-molecule tracking of specific protein-protein interactions. The method is used to study the interaction of two abundant proteins, MreB and EF-Tu, in Escherichia coli cells. The super-resolution imaging shows interesting distribution and domain sizes of interacting MreB-EF-Tu pairs as a subpopulation of total EF-Tu. The single-molecule tracking of MreB, EF-Tu and MreB-EF-Tu pairs reveals intriguing localization-dependent heterogonous dynamics and provides valuable insights to understanding the roles of MreB-EF-Tu interactions.

Super-resolution imaging and tracking of protein–protein interactions in sub-diffraction cellular space

PubMed Central

Liu, Zhen; Xing, Dong; Su, Qian Peter; Zhu, Yun; Zhang, Jiamei; Kong, Xinyu; Xue, Boxin; Wang, Sheng; Sun, Hao; Tao, Yile; Sun, Yujie

2014-01-01

Imaging the location and dynamics of individual interacting protein pairs is essential but often difficult because of the fluorescent background from other paired and non-paired molecules, particularly in the sub-diffraction cellular space. Here we develop a new method combining bimolecular fluorescence complementation and photoactivated localization microscopy for super-resolution imaging and single-molecule tracking of specific protein–protein interactions. The method is used to study the interaction of two abundant proteins, MreB and EF-Tu, in Escherichia coli cells. The super-resolution imaging shows interesting distribution and domain sizes of interacting MreB–EF-Tu pairs as a subpopulation of total EF-Tu. The single-molecule tracking of MreB, EF-Tu and MreB–EF-Tu pairs reveals intriguing localization-dependent heterogonous dynamics and provides valuable insights to understanding the roles of MreB–EF-Tu interactions. PMID:25030837

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

Interactions among predators and plant specificity protect herbivores from top predators.

PubMed

Bosc, Christopher; Pauw, Anton; Roets, Francois; Hui, Cang

2018-05-04

The worldwide loss of top predators from natural and agricultural systems has heightened the need to understand how important they are in controlling herbivore abundance. The effect of top predators on herbivore species is likely to depend on 1) the importance of the consumption of intermediate predators by top predators (intra-guild predation; IGP), but also on 2) plant specificity by herbivores, because specialists may defend themselves better (enemy-free space; EFS). Insectivorous birds, as top predators, are generally known to effectively control herbivorous insects, despite also consuming intermediate predators such as spiders, but how this effect varies among herbivore species in relation to the cascading effects of IGP and EFS is not known. To explore this, we excluded birds from natural fynbos vegetation in South Africa using large netted cages and recorded changes in abundance relative to control plots for 199 plant-dwelling intermediate predator and 341 herbivore morpho-species that varied in their estimated plant specificity. We found a strong negative effect of birds on the total abundance of all intermediate predators, with especially clear effects on spiders (strong IGP). In contrast with previous studies, which document a negative effect of birds on herbivores, we found an overall neutral effect of birds on herbivore abundance, but the effect varied among species: some species were negatively affected by birds, suggesting that they were mainly consumed by birds, whereas others, likely released from spiders by IGP, were positively affected. Some species were also effectively neutrally affected by birds. These tended to be more specialized to plants compared to the other species, which may imply that some plant specialists benefited from protection provided by EFS from both birds and spiders. These results suggest that the response of herbivore species to top predators may depend on cascading effects of interactions among predators and on their degree of plant specificity. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

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

Dasgupta, Jaydip; Elliott, Ruth A.; Doshani, Angie

Introduction: Consumption of carbonated soft drinks has been shown to be independently associated with the development of overactive bladder symptoms (OR 1.62, 95% CI 1.18, 2.22) [Dallosso, H.M., McGrother, C.W., Matthews, R.J., Donaldson, M.M.K., 2003. The association of diet and other lifestyle factors with overactive bladder and stress incontinence: a longitudinal study in women. BJU Int. 92, 69-77]. We evaluated the effects of three artificial sweeteners, acesulfame K, aspartame and sodium saccharin, on the contractile response of isolated rat detrusor muscle strips. Methods: Strips of detrusor muscle were placed in an organ bath and stimulated with electrical field stimulation (EFS)more » in the absence and presence of atropine, and with {alpha},{beta} methylene ATP, potassium, calcium and carbachol. Results: Sweeteners 10{sup -7} M to 10{sup -2} M enhanced the contractile response to 10 Hz EFS compared to control (p < 0.01). The atropine-resistant response to EFS was marginally increased by acesulfame K 10{sup -6} M, aspartame 10{sup -7} M and sodium saccharin 10{sup -7} M. Acesulfame K 10{sup -6} M increased the maximum contractile response to {alpha},{beta} methylene ATP by 35% ({+-} 9.6%) (p < 0.05) and to KCl by 12% ({+-} 3.1%) (p < 0.01). Sodium saccharin also increased the response to KCl by 37% ({+-} 15.2%) (p < 0.05). These sweeteners shifted the calcium concentration-response curves to the left. Acesulfame K 10{sup -6} M increased the log EC{sub 5} from -2.79 ({+-} 0.037) to -3.03 ({+-} 0.048, p < 0.01) and sodium saccharin 10{sup -7} M from -2.74 ({+-} 0.03) to 2.86 ({+-} 0.031, p < 0.05). The sweeteners had no significant effect on the contractile response to carbachol but they did increase the amplitude of spontaneous bladder contractions. Discussion: These results suggest that low concentrations of artificial sweeteners enhanced detrusor muscle contraction via modulation of L-type Ca{sup +2} channels.« less

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.

Quality of life questionnaire predicts poor exercise capacity only in HFpEF and not in HFrEF.

PubMed

Ahmeti, Artan; Henein, Michael Y; Ibrahimi, Pranvera; Elezi, Shpend; Haliti, Edmond; Poniku, Afrim; Batalli, Arlind; Bajraktari, Gani

2017-10-17

The Minnesota Living with Heart Failure Questionnaire (MLHFQ) is the most widely used measure of quality of life (QoL) in HF patients. This prospective study aimed to assess the relationship between QoL and exercise capacity in HF patients. The study subjects were 118 consecutive patients with chronic HF (62 ± 10 years, 57 females, in NYHA I-III). Patients answered a MLHFQ questionnaire in the same day of complete clinical, biochemical and echocardiographic assessment. They also underwent a 5 min walk test (6-MWT), in the same day, which grouped them into; Group I: ≤ 300 m and Group II: >300 m. In addition, left ventricular (LV) ejection fraction (EF), divided them into: Group A, with preserved EF (HFpEF) and Group B with reduced EF (HFrEF). The mean MLHFQ total scale score was 48 (±17). The total scale, and the physical and emotional functional MLHFQ scores did not differ between HFpEF and HFpEF. Group I patients were older (p = 0.003), had higher NYHA functional class (p = 0.002), faster baseline heart rate (p = 0.006), higher prevalence of smoking (p = 0.015), higher global, physical and emotional MLHFQ scores (p < 0.001, for all), larger left atrial (LA) diameter (p = 0.001), shorter LV filling time (p = 0.027), higher E/e' ratio (0.02), shorter isovolumic relaxation time (p = 0.028), lower septal a' (p = 0.019) and s' (p = 0.023), compared to Group II. Independent predictors of 6-MWT distance for the group as a whole were increased MLHFQ total score (p = 0.005), older age (p = 0.035), and diabetes (p = 0.045), in HFpEF were total MLHFQ (p = 0.007) and diabetes (p = 0.045) but in HFrEF were only LA enlargement (p = 0.005) and age (p = 0.013. A total MLHFQ score of 48.5 had a sensitivity of 67% and specificity of 63% (AUC on ROC analysis of 72%) for limited exercise performance in HF patients. Quality of life, assessment by MLHFQ, is the best correlate of exercise capacity measured by 6-MWT, particularly in HFpEF patients. Despite worse ejection fraction in HFrEF, signs of raised LA pressure independently determine exercise capacity in these patients.

Mouse pharmacokinetics and metabolism of the curcumin analog, 4-piperidinone,3,5-bis[(2-fluorophenyl)methylene]-acetate(3E,5E) (EF-24; NSC 716993).

PubMed

Reid, Joel M; Buhrow, Sarah A; Gilbert, Judith A; Jia, Lee; Shoji, Mamoru; Snyder, James P; Ames, Matthew M

2014-06-01

Curcumin, a keto-enol constituent of turmeric, has in vitro and in vivo antitumor activity. However, in vivo potency is low due to poor oral absorption. The mono-carbonyl analog, 3,5-bis[(2-fluorophenyl)methylene]-4-piperidinone acetate (EF-24, NSC 716993), exhibited broad-spectrum activity in the NCI anticancer cell line screen and potent antiangiogenesis activity in a HUVEC cell migration assay. The purpose of this study was to characterize the preclinical pharmacology of EF-24 in mice. EF-24 plasma stability, protein binding, pharmacokinetics, and metabolism were characterized utilizing an LC/MS/MS assay. An LC/MS/MS assay incorporated protein precipitation with methanol, reverse-phase HPLC separation under gradient elution using an aqueous methanol mobile phase containing 0.1 % formic acid, and positive electrospray ionization detection of the m/z 312 > 149 transition for EF-24. The assay was linear over the range 7.8-1,000 nM. Plasma protein binding was >98 % with preferential binding to albumin. EF-24 plasma disposition in mice after i.v. administration of a 10 mg/kg dose was best fit to a 3-compartment open model. The terminal elimination half-life and plasma clearance values were 73.6 min and 0.482 L/min/kg, respectively. EF-24 bioavailability was 60 and 35 % after oral and i.p. administration, respectively. NADPH-dependent metabolism of EF-24 loss in liver microsomal preparations yielded several metabolites consistent with EF-24 hydroxylation and reduction.

Translation elongation factor EF-Tu modulates filament formation of actin-like MreB protein in vitro.

PubMed

Defeu Soufo, Hervé Joël; Reimold, Christian; Breddermann, Hannes; Mannherz, Hans G; Graumann, Peter L

2015-04-24

EF-Tu has been shown to interact with actin-like protein MreB and to affect its localization in Escherichia coli and in Bacillus subtilis cells. We have purified YFP-MreB in an active form, which forms filaments on glass slides in vitro and was active in dynamic light-scattering assays, polymerizing in milliseconds after addition of magnesium. Purified EF-Tu enhanced the amount of MreB filaments, as seen by sedimentation assays, the speed of filament formation and the length of MreB filaments in vitro. EF-Tu had the strongest impact on MreB filaments in a 1:1 ratio, and EF-Tu co-sedimented with MreB filaments, revealing a stoichiometric interaction between both proteins. This was supported by cross-linking assays where 1:1 species were well detectable. When expressed in E. coli cells, B. subtilis MreB formed filaments and induced the formation of co-localizing B. subtilis EF-Tu structures, indicating that MreB can direct the positioning of EF-Tu structures in a heterologous cell system. Fluorescence recovery after photobleaching analysis showed that MreB filaments have a higher turnover in B. subtilis cells than in E. coli cells, indicating different filament kinetics in homologous or heterologous cell systems. The data show that MreB can direct the localization of EF-Tu in vivo, which in turn positively affects the formation and dynamics of MreB filaments. Thus, EF-Tu is a modulator of the activity of a bacterial actin-like protein. Copyright © 2015. Published by Elsevier Ltd.

Development of methane emission factors for enteric fermentation in cattle from Benin using IPCC Tier 2 methodology.

PubMed

Kouazounde, J B; Gbenou, J D; Babatounde, S; Srivastava, N; Eggleston, S H; Antwi, C; Baah, J; McAllister, T A

2015-03-01

The objective of this study was to develop emission factors (EF) for methane (CH4) emissions from enteric fermentation in cattle native to Benin. Information on livestock characteristics and diet practices specific to the Benin cattle population were gathered from a variety of sources and used to estimate EF according to Tier 2 methodology of the 2006 Intergovernmental Panel on Climate Change (IPCC) Guidelines for National Greenhouse Gas Inventories. Most cattle from Benin are Bos taurus represented by Borgou, Somba and Lagune breeds. They are mainly multi-purpose, being used for production of meat, milk, hides and draft power and grazed in open pastures and crop lands comprising tropical forages and crops. Estimated enteric CH4 EFs varied among cattle breeds and subcategory owing to differences in proportions of gross energy intake expended to meet maintenance, production and activity. EFs ranged from 15.0 to 43.6, 16.9 to 46.3 and 24.7 to 64.9 kg CH4/head per year for subcategories of Lagune, Somba and Borgou cattle, respectively. Average EFs for cattle breeds were 24.8, 29.5 and 40.2 kg CH4/head per year for Lagune, Somba and Borgou cattle, respectively. The national EF for cattle from Benin was 39.5 kg CH4/head per year. This estimated EF was 27.4% higher than the default EF suggested by IPCC for African cattle with the exception of dairy cattle. The outcome of the study underscores the importance of obtaining country-specific EF to estimate global enteric CH4 emissions.

The impact of extubation failure in patients with good-grade subarachnoid hemorrhage.

PubMed

Wojak, Jann F; Ditz, Claudia; Abusamha, Abdulkareem; Smith, Emma; Gliemroth, Jan; Tronnier, Volker; Küchler, Jan

2018-06-13

The aim of this study was to analyze the clinical impact of extubation failure (EF) in with good grade subarachnoid hemorrhage (SAH), in which a good clinical course is usually expected. We reviewed the clinical data from 141 patients with SAH and i. initial Hunt & Hess grade 1-3 ii. induction of general anesthesia for intervention and iii. the presence of data about the functional outcome. Patients were divided into three groups: 1. Primary tracheotomized patients (PT), 2. Patients with successful extubation (ES) and 3. Patients with EF (reintubation within 48 h). EF occurred with a rate of 0.12. The leading cause of EF was respiratory insufficiency (n=7), followed by impaired consciousness (n=5). Multivariate logistic regression did not show any neurological predictor of EF. Patients with ES showed an excellent outcome after 6 months (favorable outcome: 95.7 %), whereas the outcome of EF and PT patients was significantly (p<0.05) poorer. The case fatality rate was non-significantly higher in the EF group (0.15 vs 0.03). Hospitalization was significantly reduced for patients with ES, while the occurrence of symptomatic cerebral vasospasms and vasospastic cerebral infarction was similar between Patients with EF, ES or PT. We showed that EF is a frequent condition in good grade SAH, but is not predictable using common neurological parameters. Regarding the functional outcome, we were able to show that the result of an extubation trial clearly delineates the patients in two distinct groups, in which ES predicts an excellent outcome. Copyright © 2018 Elsevier Inc. All rights reserved.

In Situ Tropical Peatland Fire Emission Factors and Their Variability, as Determined by Field Measurements in Peninsula Malaysia

NASA Astrophysics Data System (ADS)

Smith, T. E. L.; Evers, S.; Yule, C. M.; Gan, J. Y.

2018-01-01

Fires in tropical peatlands account for >25% of estimated total greenhouse gas emissions from deforestation and degradation. Despite significant global and regional impacts, our understanding of specific gaseous fire emission factors (EFs) from tropical peat burning is limited to a handful of studies. Furthermore, there is substantial variability in EFs between sampled fires and/or studies. For example, methane EFs vary by 91% between studies. Here we present new fire EFs for the tropical peatland ecosystem; the first EFs measured for Malaysian peatlands, and only the second comprehensive study of EFs in this crucial environment. During August 2015 (under El Niño conditions) and July 2016, we embarked on field campaigns to measure gaseous emissions at multiple peatland fires burning on deforested land in Southeast Pahang (2015) and oil palm plantations in North Selangor (2016), Peninsula Malaysia. Gaseous emissions were measured using open-path Fourier transform infrared spectroscopy. The IR spectra were used to retrieve mole fractions of 12 different gases present within the smoke (including carbon dioxide and methane), and these measurements used to calculate EFs. Peat samples were taken at each burn site for physicochemical analysis and to explore possible relationships between specific physicochemical properties and fire EFs. Here we present the first evidence to indicate that substrate bulk density affects methane fire EFs reported here. This novel explanation of interplume, within-biome variability, should be considered by those undertaking greenhouse gas accounting and haze forecasting in this region and is of importance to peatland management, particularly with respect to artificial compaction.

Left ventricular strain and twisting in heart failure with preserved ejection fraction: an updated review.

PubMed

Tadic, Marijana; Pieske-Kraigher, Elisabeth; Cuspidi, Cesare; Genger, Martin; Morris, Daniel A; Zhang, Kun; Walther, Nina Alexandra; Pieske, Burket

2017-05-01

Despite the high prevalence of the patients with heart failure with preserved ejection fraction (HFpEF), our knowledge about this entity, from diagnostic tools to therapeutic approach, is still not well established. The evaluation of patients with HFpEF is mainly based on echocardiography, as the most widely accepted tool in cardiac imaging. Identification of left ventricular (LV) diastolic dysfunction has long been considered as the only responsible for HFpEF, and its evaluation is still "sine qua non" of HFpEF diagnostics. However, one should be aware of the fact that identifying cardiac dysfunction in HFpEF might be very challenging and often needs more complex evaluation of cardiac structure and function. New echocardiographic modalities such as 2D and 3D speckle tracking imaging could help in the diagnosis of HFpEF and provide further information regarding LV function and mechanics. Early diagnosis, medical management, and adequate monitoring of HFpEF patients are prerequisites of modern medical treatment. New healthcare approaches require individualized patient care, which is why clinicians should have all clinical, laboratory, and diagnostic data before making final decisions about the treatment of any patients. This is particularly important for HFpEF that often remains undiagnosed for quite a long time, which further prolongs the beginning of adequate treatment and brings into question outcome of these patients. The aim of this article is to provide the overview of the main principles of LV mechanics and summarize recent data regarding LV strain in patients with HFpEF.

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.

Mouse pharmacokinetics and metabolism of the curcumin analog, 4-Piperidione,3,5-bis[(2-fluorophenyl)methylene]-acetate(3E,5E) (EF-24; NSC 716993)

PubMed Central

Reid, Joel M.; Buhrow, Sarah A.; Gilbert, Judith A.; Jia, Lee; Shoji, Mamoru; Snyder, James P.; Ames, Matthew M.

2015-01-01

Purpose Curcumin, a keto-enol constituent of turmeric, has in vitro and in vivo antitumor activity. However, in vivo potency is low due to poor oral absorption. The mono-carbonyl analog, 3,5-bis[(2-fluorophenyl)methylene]-4-piperidinone acetate (EF-24, NSC 716993), exhibited broad spectrum activity in the NCI anti-cancer cell line screen and potent anti-angiogenesis activity in a HUVEC cell migration assay. The purpose of this study was to characterize the preclinical pharmacology of EF-24 in mice. Methods EF-24 plasma stability, protein binding, pharmacokinetics and metabolism were characterized utilizing an LC/MS/MS assay. Results An LC/MS/MS assay that incorporated protein precipitation with methanol, reverse-phase HPLC separation under gradient elution using an aqueous methanol mobile phase containing 0.1% formic acid and positive electrospray ionization detection of the m/z 312 > 149 transition for EF-24. The assay was linear over the range 7.8-1000 nM. Plasma protein binding was > 98% with preferential binding to albumin. EF-24 plasma disposition in mice after i.v. administration of a 10 mg/kg dose was best fit to a 3-compartment open model. The terminal elimination half-life and plasma clearance values were 73.6 min and 0.482 L/min/kg, respectively. EF-24 bioavailability was 60% and 35% after oral and i.p. administration, respectively. NADPH-dependent metabolism of EF-24 loss in liver microsomal preparations yielded several metabolites consistent with EF-24 hydroxylation and reduction. PMID:24760417

Objective Versus Subjective Measures of Executive Functions: Predictors of Participation and Quality of Life in Parkinson Disease?

PubMed

Vlagsma, Thialda T; Koerts, Janneke; Tucha, Oliver; Dijkstra, Hilde T; Duits, Annelien A; van Laar, Teus; Spikman, Jacoba M

2017-11-01

To determine whether objective (neuropsychological tests) and subjective measures (questionnaires) of executive functions (EFs) are associated in patients with Parkinson disease (PD), and to determine to what extent level of participation and quality of life (QoL) of patients with PD can be predicted by these measures of EFs. Correlational research design (case-control and prediction design). Departments of neuropsychology of 3 medical centers. A sample (N=136) of patients with PD (n=42) and their relatives, and controls without PD (n=94). Not applicable. A test battery measuring EFs. In addition, patients, their relatives, and controls completed the Dysexecutive Questionnaire, Brock Adaptive Functioning Questionnaire, and Barkley Deficits in Executive Functioning Scale - time management questionnaires measuring complaints about EFs. Participation and QoL were measured with the Impact on Participation and Autonomy scale and the Parkinson's Disease Questionnaire-39, respectively. Patients with PD showed impairments in EFs on objective tests and reported significantly more complaints about EFs than did controls without PD. No associations were found between patients' performances on objective and subjective measures of EFs. However, both objective and subjective measures predicted patients' level of participation. In addition, subjective measures of EFs predicted QoL in patients with PD. These findings show that objective and subjective measures of EFs are not interchangeable and that both approaches predict level of participation and QoL in patients with PD. However, within this context, sex needs to be taken into account. Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

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.

Computer Systems Acquisition Metrics Handbook. Volume II. Quality Factor Modules.

DTIC Science & Technology

1982-05-01

are unable to evil .mte) IPAW BrY: APFD If: i Ef-24 EFFICICYe: EfPDF.l L C1E PHASE: Sota S): PRELINARY DESIGN EfP. 1 EfDC. 2 = StSM NAM:. I. CUM...unable to evaluate) Iv. D6PB=’S C3#rm: PWAPM BY:______ APFD N _______ Po-30 MACHM NDE WM4 MEASE SO= Go&e:. PoII4LS LIM P E PHAiSE: SJRMCs): IMPLEME

Comorbidity and ventricular and vascular structure and function in heart failure with preserved ejection fraction: a community-based study.

PubMed

Mohammed, Selma F; Borlaug, Barry A; Roger, Véronique L; Mirzoyev, Sultan A; Rodeheffer, Richard J; Chirinos, Julio A; Redfield, Margaret M

2012-11-01

Patients with heart failure and preserved ejection fraction (HFpEF) display increased adiposity and multiple comorbidities, factors that in themselves may influence cardiovascular structure and function. This has sparked debate as to whether HFpEF represents a distinct disease or an amalgamation of comorbidities. We hypothesized that fundamental cardiovascular structural and functional alterations are characteristic of HFpEF, even after accounting for body size and comorbidities. Comorbidity-adjusted cardiovascular structural and functional parameters scaled to independently generated and age-appropriate allometric powers were compared in community-based cohorts of HFpEF patients (n=386) and age/sex-matched healthy n=193 and hypertensive, n=386 controls. Within HFpEF patients, body size and concomitant comorbidity-adjusted cardiovascular structural and functional parameters and survival were compared in those with and without individual comorbidities. Among HFpEF patients, comorbidities (obesity, anemia, diabetes mellitus, and renal dysfunction) were each associated with unique clinical, structural, functional, and prognostic profiles. However, after accounting for age, sex, body size, and comorbidities, greater concentric hypertrophy, atrial enlargement and systolic, diastolic, and vascular dysfunction were consistently observed in HFpEF compared with age/sex-matched normotensive and hypertensive. Comorbidities influence ventricular-vascular properties and outcomes in HFpEF, yet fundamental disease-specific changes in cardiovascular structure and function underlie this disorder. These data support the search for mechanistically targeted therapies in this disease.

The Benefits of Executive Control Training and the Implications for Language Processing

PubMed Central

Hussey, Erika K.; Novick, Jared M.

2012-01-01

Recent psycholinguistics research suggests that the executive function (EF) skill known as conflict resolution – the ability to adjust behavior in the service of resolving among incompatible representations – is important for several language processing tasks such as lexical and syntactic ambiguity resolution, verbal fluency, and common-ground assessment. Here, we discuss work showing that various EF skills can be enhanced through consistent practice with working-memory tasks that tap these EFs, and, moreover, that improvements on the training tasks transfer across domains to novel tasks that may rely on shared underlying EFs. These findings have implications for language processing and could launch new research exploring if EF training, within a “process-specific” framework, could be used as a remediation tool for improving general language use. Indeed, work in our lab demonstrates that EF training that increases conflict-resolution processes has selective benefits on an untrained sentence-processing task requiring syntactic ambiguity resolution, which relies on shared conflict-resolution functions. Given claims that conflict-resolution abilities contribute to a range of linguistic skills, EF training targeting this process could theoretically yield wider performance gains beyond garden-path recovery. We offer some hypotheses on the potential benefits of EF training as a component of interventions to mitigate general difficulties in language processing. However, there are caveats to consider as well, which we also address. PMID:22661962

A secure base from which to regulate: Attachment security in toddlerhood as a predictor of executive functioning at school entry.

PubMed

Bernier, Annie; Beauchamp, Miriam H; Carlson, Stephanie M; Lalonde, Gabrielle

2015-09-01

In light of emerging evidence suggesting that the affective quality of parent-child relationships may relate to individual differences in young children's executive functioning (EF) skills, the aim of this study was to investigate the prospective associations between attachment security in toddlerhood and children's EF skills in kindergarten. Mother-child dyads (N = 105) participated in 2 toddlerhood visits in their homes, when children were 15 months and 2 years of age. Mother-child attachment security was assessed with the Attachment Q-Sort during both these visits. When children were in kindergarten (ages 5-6), they were administered a battery of EF tasks, and their teachers completed the Behavior Rating Inventory of Executive Function to assess children's EF problems. The results indicated that kindergarteners who were more securely attached to their mothers in toddlerhood showed better performance on all EF tasks, and were considered by their teachers to present fewer EF problems in everyday school situations. These results held above family socioeconomic status (SES) and child age, sex, and general cognitive functioning. The fact that early attachment security uniquely predicted both teacher reports and children's objective EF task performance suggests that parent-child attachment may be a promising factor to consider in the continuing search for the social antecedents of young children's EF. (c) 2015 APA, all rights reserved).

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.

Left ventricular ejection fraction to predict early mortality in patients with non-ST-segment elevation acute coronary syndromes.

PubMed

Bosch, Xavier; Théroux, Pierre

2005-08-01

Improvement in risk stratification of patients with non-ST-segment elevation acute coronary syndrome (ACS) is a gateway to a more judicious treatment. This study examines whether the routine determination of left ventricular ejection fraction (EF) adds significant prognostic information to currently recommended stratifiers. Several predictors of inhospital mortality were prospectively characterized in a registry study of 1104 consecutive patients, for whom an EF was determined, who were admitted for an ACS. Multiple regression models were constructed using currently recommended clinical, electrocardiographic, and blood marker stratifiers, and values of EF were incorporated into the models. Age, ST-segment shifts, elevation of cardiac markers, and the Thrombolysis in Myocardial Infarction (TIMI) risk score all predicted mortality (P < .0001). Adding EF into the model improved the prediction of mortality (C statistic 0.73 vs 0.67). The odds of death increased by a factor of 1.042 for each 1% decrement in EF. By receiver operating curves, an EF cutoff of 48% provided the best predictive value. Mortality rates were 3.3 times higher within each TIMI risk score stratum in patients with an EF of 48% or lower as compared with those with higher. The TIMI risk score predicts inhospital mortality in a broad population of patients with ACS. The further consideration of EF adds significant prognostic information.

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

Fresh and Oxidized Emissions from In-Use Transit Buses Running on Diesel, Biodiesel, and CNG.

PubMed

Watne, Ågot K; Psichoudaki, Magda; Ljungström, Evert; Le Breton, Michael; Hallquist, Mattias; Jerksjö, Martin; Fallgren, Henrik; Jutterström, Sara; Hallquist, Åsa M

2018-06-26

The potential effect of changing to a nonfossil fuel vehicle fleet was investigated by measuring primary emissions (by extractive sampling of bus plumes) and secondary mass formation, using a Gothenburg Potential Aerosol Mass (Go:PAM) reactor, from 29 in-use transit buses. Regarding fresh emissions, diesel (DSL) buses without a diesel particulate filter (DPF) emitted the highest median mass of particles, whereas compressed natural gas (CNG) buses emitted the lowest ( Md EF PM 514 and 11 mg kg fuel -1 , respectively). Rapeseed methyl ester (RME) buses showed smaller Md EF PM and particle sizes than DSL buses. DSL (no DPF) and hybrid-electric RME (RME HEV ) buses exhibited the highest particle numbers ( Md EF PN 12 × 10 14 # kg fuel -1 ). RME HEV buses displayed a significant nucleation mode ( D p < 20 nm). EF PN of CNG buses spanned the highest to lowest values measured. Low Md EF PN and Md EF PM were observed for a DPF-equipped DSL bus. Secondary particle formation resulting from exhaust aging was generally important for all the buses (79% showed an average EF PM:AGED /EF PM:FRESH ratio >10) and fuel types tested, suggesting an important nonfuel dependent source. The results suggest that the potential for forming secondary mass should be considered in future fuel shifts, since the environmental impact is different when only considering the primary emissions.

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.

Association between sleep-disordered breathing and arterial stiffness in heart failure patients with reduced or preserved ejection fraction.

PubMed

Suzuki, Satoshi; Yoshihisa, Akiomi; Sato, Yu; Watanabe, Shunsuke; Yokokawa, Tetsuro; Sato, Takamasa; Oikawa, Masayoshi; Kobayashi, Atsushi; Yamaki, Takayoshi; Kunii, Hiroyuki; Nakazato, Kazuhiko; Suzuki, Hitoshi; Saitoh, Shu-Ichi; Ishida, Takafumi; Takeishi, Yasuchika

2018-06-01

Sleep-disordered breathing (SDB) is associated with arterial stiffness, which may be one of the factors that lead to heart failure (HF). We examined the relationship between pulse wave velocity (PWV) and SDB in patients who have HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). We measured the apnoea-hypopnoea index (AHI) by polysomnography, echocardiographic parameters, and PWV in 221 HF patients. Age, blood pressure, and PWV were higher in HFpEF (ejection fraction > 50%, n = 70) patients than in HFrEF (ejection fraction < 50%, n = 151) patients. All HF patients were divided into three groups according to AHI: none-to-mild SDB group (AHI < 15 times/h, n = 77), moderate SDB group (15 < AHI < 30 times/h, n = 59), and severe SDB group (AHI > 30 times/h, n = 85). Although blood pressure and echocardiographic parameters did not differ among the three groups, PWV was significantly higher in the severe SDB group than in the none-to-mild and moderate SDB groups (P = 0.002). When the HFrEF and HFpEF patients were analysed separately, PWV was significantly higher in the severe SDB group than in the none-to-mild and moderate SDB groups in patients with HFpEF (P = 0.002), but not in those with HFrEF (P = 0.068). In the multiple regression analysis to determine PWV, the presence of severe SDB was found to be an independent predictor of high PWV in HFpEF (β = 0.234, P = 0.005), but not in HFrEF patients. Severe SDB is associated with elevated arterial stiffness and may be related to the pathophysiology of HF, especially in HFpEF patients. © 2018 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

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.

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.

Natural Surfactant Enrichments in the Atlantic Ocean Between 50°N and 50°S: Data from the Atlantic Meridional Transect, Oct-Nov 2014

NASA Astrophysics Data System (ADS)

Sabbaghzadeh, B.; Upstill-Goddard, R. C.; Nightingale, P. D.; Beale, R.

2016-02-01

Surfactants that decrease air-sea gas exchange by suppressing the gas transfer velocity (kw) show variable enrichments in the sea surface microlayer (SML) relative to the underlying water. This reflects variability in the rates of surfactant production and consumption. Total surfactant activity (SA: equivalent to Triton-X-100, mgL -1) was determined daily between the UK and the Falkland Islands, during cruise 24 of the Atlantic Meridional Transect programme (AMT 24). Samples were simultaneously obtained from the SML (Garrett screen), from the ship's underway system (inlet at 7m) and in hydrocasts to 500m. SA analysis was by hanging mercury drop electrode polarography (Metrohm 797 VA Computrace). SA enrichment factors (EF: SML SA / underlying water SA) >1 were observed at most locations, showing the SML to be consistently SA-enriched along the entire cruise transect. The persistence of these enrichments up to wind speeds 12m s-¹ support previous conclusions regarding the stability of the SML under high winds. More specifically, SA in the SML was up to four-fold higher in the Atlantic Northern Hemisphere than in the Atlantic Southern Hemisphere. Even so, EF values were not significantly different between the two hemispheres (p >0.05). These various findings have potentially important implications for kw variability across ocean basin scales.

Improvement of a Global High-Resolution Ammonia Emission Inventory for Combustion and Industrial Sources with New Data from the Residential and Transportation Sectors.

PubMed

Meng, Wenjun; Zhong, Qirui; Yun, Xiao; Zhu, Xi; Huang, Tianbo; Shen, Huizhong; Chen, Yilin; Chen, Han; Zhou, Feng; Liu, Junfeng; Wang, Xinming; Zeng, Eddy Y; Tao, Shu

2017-03-07

There is increasing evidence indicating the critical role of ammonia (NH 3 ) in the formation of secondary aerosols. Therefore, high quality NH 3 emission inventory is important for modeling particulate matter in the atmosphere. Unfortunately, without directly measured emission factors (EFs) in developing countries, using data from developed countries could result in an underestimation of these emissions. A series of newly reported EFs for China provide an opportunity to update the NH 3 emission inventory. In addition, a recently released fuel consumption data product has allowed for a multisource, high-resolution inventory to be assembled. In this study, an improved global NH 3 emission inventory for combustion and industrial sources with high sectorial (70 sources), spatial (0.1° × 0.1°), and temporal (monthly) resolutions was compiled for the years 1960 to 2013. The estimated emissions from transportation (1.59 Tg) sectors in 2010 was 2.2 times higher than those of previous reports. The spatial variation of the emissions was associated with population, gross domestic production, and temperature. Unlike other major air pollutants, NH 3 emissions continue to increase, even in developed countries, which is likely caused by an increased use of biomass fuel in the residential sector. The emissions density of NH 3 in urban areas is an order of magnitude higher than in rural areas.

Efficiency of energy recovery from municipal solid waste and the resultant effect on the greenhouse gas balance.

PubMed

Gohlke, Oliver

2009-11-01

Global warming is a focus of political interest and life-cycle assessment of waste management systems reveals that energy recovery from municipal solid waste is a key issue. This paper demonstrates how the greenhouse gas effects of waste treatment processes can be described in a simplified manner by considering energy efficiency indicators. For evaluation to be consistent, it is necessary to use reasonable system boundaries and to take the generation of electricity and the use of heat into account. The new European R1 efficiency criterion will lead to the development and implementation of optimized processes/systems with increased energy efficiency which, in turn, will exert an influence on the greenhouse gas effects of waste management in Europe. Promising technologies are: the increase of steam parameters, reduction of in-plant energy consumption, and the combined use of heat and power. Plants in Brescia and Amsterdam are current examples of good performance with highly efficient electricity generation. Other examples of particularly high heat recovery rates are the energy-from-waste (EfW) plants in Malmö and Gothenburg. To achieve the full potential of greenhouse gas reduction in waste management, it is necessary to avoid landfilling combustible wastes, for example, by means of landfill taxes and by putting incentives in place for increasing the efficiency of EfW systems.

Getting the right grasp on executive function

PubMed Central

Gonzalez, Claudia L. R.; Mills, Kelly J.; Genee, Inge; Li, Fangfang; Piquette, Noella; Rosen, Nicole; Gibb, Robbin

2014-01-01

Executive Function (EF) refers to important socio-emotional and cognitive skills that are known to be highly correlated with both academic and life success. EF is a blanket term that is considered to include self-regulation, working memory, and planning. Recent studies have shown a relationship between EF and motor control. The emergence of motor control coincides with that of EF, hence understanding the relationship between these two domains could have significant implications for early detection and remediation of later EF deficits. The purpose of the current study was to investigate this relationship in young children. This study incorporated the Behavioral Rating Inventory of Executive Function (BRIEF) and two motor assessments with a focus on precision grasping to test this hypothesis. The BRIEF is comprised of two indices of EF: (1) the Behavioral Regulation Index (BRI) containing three subscales: Inhibit, Shift, and Emotional Control; (2) the Metacognition Index (MI) containing five subscales: Initiate, Working Memory, Plan/Organize, Organization of Materials, and Monitor. A global executive composite (GEC) is derived from the two indices. In this study, right-handed children aged 5–6 and 9–10 were asked to: grasp-to-construct (Lego® models); and grasp-to-place (wooden blocks), while their parents completed the BRIEF questionnaire. Analysis of results indicated significant correlations between the strength of right hand preference for grasping and numerous elements of the BRIEF including the BRI, MI, and GEC. Specifically, the more the right hand was used for grasping the better the EF ratings. In addition, patterns of space-use correlated with the GEC in several subscales of the BRIEF. Finally and remarkably, the results also showed a reciprocal relationship between hand and space use for grasping and EF. These findings are discussed with respect to: (1) the developmental overlap of motor and executive functions; (2) detection of EF deficits through tasks that measure lateralization of hand and space use; and (3) the possibility of using motor interventions to remediate EF deficits. PMID:24778624

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.

Executive function and falls in older adults: new findings from a five-year prospective study link fall risk to cognition.

PubMed

Mirelman, Anat; Herman, Talia; Brozgol, Marina; Dorfman, Moran; Sprecher, Elliot; Schweiger, Avraham; Giladi, Nir; Hausdorff, Jeffrey M

2012-01-01

Recent findings suggest that executive function (EF) plays a critical role in the regulation of gait in older adults, especially under complex and challenging conditions, and that EF deficits may, therefore, contribute to fall risk. The objective of this study was to evaluate if reduced EF is a risk factor for future falls over the course of 5 years of follow-up. Secondary objectives were to assess whether single and dual task walking abilities, an alternative window into EF, were associated with fall risk. We longitudinally followed 256 community-living older adults (age: 76.4±4.5 yrs; 61% women) who were dementia free and had good mobility upon entrance into the study. At baseline, a computerized cognitive battery generated an index of EF, attention, a closely related construct, and other cognitive domains. Gait was assessed during single and dual task conditions. Falls data were collected prospectively using monthly calendars. Negative binomial regression quantified risk ratios (RR). After adjusting for age, gender and the number of falls in the year prior to the study, only the EF index (RR: .85; CI: .74-.98, p = .021), the attention index (RR: .84; CI: .75-.94, p = .002) and dual tasking gait variability (RR: 1.11; CI: 1.01-1.23; p = .027) were associated with future fall risk. Other cognitive function measures were not related to falls. Survival analyses indicated that subjects with the lowest EF scores were more likely to fall sooner and more likely to experience multiple falls during the 66 months of follow-up (p<0.02). These findings demonstrate that among community-living older adults, the risk of future falls was predicted by performance on EF and attention tests conducted 5 years earlier. The present results link falls among older adults to cognition, indicating that screening EF will likely enhance fall risk assessment, and that treatment of EF may reduce fall risk.

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.

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.

Clinical outcome of extended-field irradiation vs. pelvic irradiation using intensity-modulated radiotherapy for cervical cancer.

PubMed

Ouyang, Yi; Wang, Yanhong; Chen, Kai; Cao, Xinping; Zeng, Yiming

2017-12-01

The aim of the present study was to evaluate the distinctions in survival and toxicity between patients with cervical cancer with common iliac node or para-aortic node involvement, who were treated with extended-field intensity-modulated radiotherapy (EF-IMRT) and patients with or without lower involved pelvic nodes, who were treated with pelvic IMRT. A total of 55 patients treated with EF-IMRT and 52 patients treated with pelvic IMRT at the Sun Yat-Sen University Cancer Center (Guangzhou, China) were retrospectively analyzed. Patients treated with EF-IMRT had the highest level of lymph node involvement to the para-aortic or common iliac nodes, while patients treated with pelvic IMRT had no para-aortic or common iliac nodes involved (P<0.001). The median follow-up time was 29.5 months. The 3-year overall survival (OS) rates of EF-IMRT and pelvic IMRT were 79.4 and 82.3% (P=0.45), respectively, and the 3-year disease-free survival (DFS) rates of EF-IMRT and pelvic IMRT were 61.0 and 73.7% (P=0.55), respectively. Cox's regression analysis revealed that EF irradiation was a protective prognostic factor for OS and DFS. A total of 16 patients in the EF-IMRT group and 13 patients in the pelvic IMRT group experienced treatment failure (P=0.67), with the patterns of failure being the same for the two groups (P=0.88). The cumulative incidence of grade 3 and 4 acute toxicities in the EF-IMRT group was 34.5%, in comparison with 19.2% in the pelvic group (P=0.048). The results of the present study suggest that patients with cervical cancer with grossly involved common iliac or para-aortic nodes should be electively subjected to EF irradiation to improve the survival and alter patterns of recurrence. Notably, EF irradiation delivered via IMRT exhibits an increased toxicity incidence, however, this remains within an acceptable range.

Clinical outcome of extended-field irradiation vs. pelvic irradiation using intensity-modulated radiotherapy for cervical cancer

PubMed Central

Ouyang, Yi; Wang, Yanhong; Chen, Kai; Cao, Xinping; Zeng, Yiming

2017-01-01

The aim of the present study was to evaluate the distinctions in survival and toxicity between patients with cervical cancer with common iliac node or para-aortic node involvement, who were treated with extended-field intensity-modulated radiotherapy (EF-IMRT) and patients with or without lower involved pelvic nodes, who were treated with pelvic IMRT. A total of 55 patients treated with EF-IMRT and 52 patients treated with pelvic IMRT at the Sun Yat-Sen University Cancer Center (Guangzhou, China) were retrospectively analyzed. Patients treated with EF-IMRT had the highest level of lymph node involvement to the para-aortic or common iliac nodes, while patients treated with pelvic IMRT had no para-aortic or common iliac nodes involved (P<0.001). The median follow-up time was 29.5 months. The 3-year overall survival (OS) rates of EF-IMRT and pelvic IMRT were 79.4 and 82.3% (P=0.45), respectively, and the 3-year disease-free survival (DFS) rates of EF-IMRT and pelvic IMRT were 61.0 and 73.7% (P=0.55), respectively. Cox's regression analysis revealed that EF irradiation was a protective prognostic factor for OS and DFS. A total of 16 patients in the EF-IMRT group and 13 patients in the pelvic IMRT group experienced treatment failure (P=0.67), with the patterns of failure being the same for the two groups (P=0.88). The cumulative incidence of grade 3 and 4 acute toxicities in the EF-IMRT group was 34.5%, in comparison with 19.2% in the pelvic group (P=0.048). The results of the present study suggest that patients with cervical cancer with grossly involved common iliac or para-aortic nodes should be electively subjected to EF irradiation to improve the survival and alter patterns of recurrence. Notably, EF irradiation delivered via IMRT exhibits an increased toxicity incidence, however, this remains within an acceptable range. PMID:29344136

The Drosophila mitochondrial translation elongation factor G1 contains a nuclear localization signal and inhibits growth and DPP signaling.

PubMed

Trivigno, Catherine; Haerry, Theodor E

2011-02-25

Mutations in the human mitochondrial elongation factor G1 (EF-G1) are recessive lethal and cause death shortly after birth. We have isolated mutations in iconoclast (ico), which encodes the highly conserved Drosophila orthologue of EF-G1. We find that EF-G1 is essential during fly development, but its function is not required in every tissue. In contrast to null mutations, missense mutations exhibit stronger, possibly neomorphic phenotypes that lead to premature death during embryogenesis. Our experiments show that EF-G1 contains a secondary C-terminal nuclear localization signal. Expression of missense mutant forms of EF-G1 can accumulate in the nucleus and cause growth and patterning defects and animal lethality. We find that transgenes that encode mutant human EF-G1 proteins can rescue ico mutants, indicating that the underlying problem of the human disease is not just the loss of enzymatic activity. Our results are consistent with a model where EF-G1 acts as a retrograde signal from mitochondria to the nucleus to slow down cell proliferation if mitochondrial energy output is low.

The Drosophila Mitochondrial Translation Elongation Factor G1 Contains a Nuclear Localization Signal and Inhibits Growth and DPP Signaling

PubMed Central

Trivigno, Catherine; Haerry, Theodor E.

2011-01-01

Mutations in the human mitochondrial elongation factor G1 (EF-G1) are recessive lethal and cause death shortly after birth. We have isolated mutations in iconoclast (ico), which encodes the highly conserved Drosophila orthologue of EF-G1. We find that EF-G1 is essential during fly development, but its function is not required in every tissue. In contrast to null mutations, missense mutations exhibit stronger, possibly neomorphic phenotypes that lead to premature death during embryogenesis. Our experiments show that EF-G1 contains a secondary C-terminal nuclear localization signal. Expression of missense mutant forms of EF-G1 can accumulate in the nucleus and cause growth and patterning defects and animal lethality. We find that transgenes that encode mutant human EF-G1 proteins can rescue ico mutants, indicating that the underlying problem of the human disease is not just the loss of enzymatic activity. Our results are consistent with a model where EF-G1 acts as a retrograde signal from mitochondria to the nucleus to slow down cell proliferation if mitochondrial energy output is low. PMID:21364917

Executive Function, Self-Regulated Learning, and Reading Comprehension: A Training Study.

PubMed

Cirino, Paul T; Miciak, Jeremy; Gerst, Elyssa; Barnes, Marcia A; Vaughn, Sharon; Child, Amanda; Huston-Warren, Emily

The goal of this study was to evaluate the extent to which training that emphasizes the process of executive function (EF) and self-regulated learning (SRL) would result in increased reading comprehension; we also evaluated interrelationships of EF, SRL, and reading. We report an experiment ( N = 75 fourth graders) that contrasted two researcher-implemented conditions (text-based reading [TB] and text-based reading plus executive function [TB+EF]) to a control. We also evaluated relationships among measures of SRL, EF, and reading. Both the TB and TB+EF groups outperformed the control group for proximal text comprehension (where the topic was similar to that covered in training) and background knowledge related to it, but the two researcher-led groups performed similarly. There were no significant differences for less proximal text, and again similar performance for both TB and TB+EF. Correlations among measures were weak in general, although the pattern was similar to that found in the extant literature. The findings speak to the difficulty in separating these components from those of strong instruction more generally. The relationships of these constructs to reading comprehension will likely be enhanced by more sensitive measurement of EF and reading comprehension, particularly where tied to active treatment components.

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.

Riser Pattern Is a Novel Predictor of Adverse Events in Heart Failure Patients With Preserved Ejection Fraction.

PubMed

Komori, Takahiro; Eguchi, Kazuo; Saito, Toshinobu; Hoshide, Satoshi; Kario, Kazuomi

2017-01-25

The cardiovascular prognosis of heart failure with preserved ejection fraction (HFpEF) has been shown to be similar to that of heart failure with reduced ejection fraction (HFrEF). It is unknown which factors predict cardiovascular outcome in HFpEF. We tested the hypothesis that the abnormal pattern of circadian blood pressure (BP) rhythm known as the riser BP pattern is associated with adverse outcomes in HFpEF.Methods and Results:We performed a prospective, observational cohort study of hospitalized HF patients who underwent ambulatory BP monitoring (ABPM). Five hundred and sixteen hospitalized HF patients (age, 69±13 years; male, n=321 [62%]; female, n=195 [38%]) were followed up for a median 20.9 months. The composite outcome consisting of all-cause mortality and cardiovascular events was observed in 220 patients. On Kaplan-Meier analysis, the riser BP pattern subgroup had a significantly higher incidence of the composite outcome than the other subgroups of HFpEF patients (HR, 3.01; 95% CI: 1.54-6.08, P<0.01), but not the HFrEF patients. The riser BP pattern was found to be a novel predictor of cardiovascular outcome in HFpEF patients.

Formation of ethyl ferulate by rice koji enzyme in sake and mirin mash conditions.

PubMed

Hashizume, Katsumi; Ito, Toshihiko; Ishizuka, Takahiro; Takeda, Naoki

2013-08-01

Formation mechanism of ethyl ferulate (EF) in sake and mirin mash conditions was investigated to understand EF level control in the manufacturing process. Rice koji formed EF from ferulic acid (FA) and ethanol and decomposed EF to FA. This did not occur in sake yeast and chemical esterification was rare. Esterification of FA and hydrolysis of EF by rice koji might be due to feruloyl esterase(s). The rice koji enzyme showed normal Michaelis-Menten kinetics for FA in ethyl esterification and for EF in hydrolysis, but not for ethanol in the esterification reaction. Substrate specificity of the rice koji enzyme for hydroxycinnamic acids suggested that the main enzyme involved might be similar to type A feruloyl esterase. We studied the rice koji enzyme properties, short-term digestion of steamed rice grains with exogenous ethanol and small scale mirin making with pH adjustment. Our results suggested differences in the esterification and hydrolysis properties of the enzyme, in particular, different pH dependencies and different behaviors under high ethanol conditions; these factors might cause the differing EF levels in sake and mirin mashes. Copyright © 2013 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Complete kinetic mechanism for recycling of the bacterial ribosome

PubMed Central

Borg, Anneli; Pavlov, Michael

2016-01-01

How EF-G and RRF act together to split a post-termination ribosomal complex into its subunits has remained obscure. Here, using stopped-flow experiments with Rayleigh light scattering detection and quench-flow experiments with radio-detection of GTP hydrolysis, we have clarified the kinetic mechanism of ribosome recycling and obtained precise estimates of its kinetic parameters. Ribosome splitting requires that EF-G binds to an already RRF-containing ribosome. EF-G binding to RRF-free ribosomes induces futile rounds of GTP hydrolysis and inhibits ribosome splitting, implying that while RRF is purely an activator of recycling, EF-G acts as both activator and competitive inhibitor of RRF in recycling of the post-termination ribosome. The ribosome splitting rate and the number of GTPs consumed per splitting event depend strongly on the free concentrations of EF-G and RRF. The maximal recycling rate, here estimated as 25 sec−1, is approached at very high concentrations of EF-G and RRF with RRF in high excess over EF-G. The present in vitro results, suggesting an in vivo ribosome recycling rate of ∼5 sec−1, are discussed in the perspective of rapidly growing bacterial cells. PMID:26527791

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.

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

The Role of Protein Elongation Factor eEF1A2 in Breast Cancer

DTIC Science & Technology

2006-09-01

serve as regulators of multiple signaling pathways (15-18). PIs are composed of an inositol ring covalently bound to a lipid phosphatidic acid ...mouse model of aristolochic acid nephropathy, and human kidney-proximal tubule cells. Satisfyingly, one of these targets is Dishevelled 2 (DVL2...Rho signaling proteins together. The two human eEF1A isoforms (eEF1A2 and eEF1A2) are very similar proteins (92% amino acid identity). The two

Gene expression of human lung cancer cell line CL1-5 in response to a direct current electric field.

PubMed

Huang, Ching-Wen; Chen, Huai-Yi; Yen, Meng-Hua; Chen, Jeremy J W; Young, Tai-Horng; Cheng, Ji-Yen

2011-01-01

Electrotaxis is the movement of adherent living cells in response to a direct current (dc) electric field (EF) of physiological strength. Highly metastatic human lung cancer cells, CL1-5, exhibit directional migration and orientation under dcEFs. To understand the transcriptional response of CL1-5 cells to a dcEF, microarray analysis was performed in this study. A large electric-field chip (LEFC) was designed, fabricated, and used in this study. CL1-5 cells were treated with the EF strength of 0 mV/mm (the control group) and 300 mV/mm (the EF-treated group) for two hours. Signaling pathways involving the genes that expressed differently between the two groups were revealed. It was shown that the EF-regulated genes highly correlated to adherens junction, telomerase RNA component gene regulation, and tight junction. Some up-regulated genes such as ACVR1B and CTTN, and some down-regulated genes such as PTEN, are known to be positively and negatively correlated to cell migration, respectively. The protein-protein interactions of adherens junction-associated EF-regulated genes suggested that platelet-derived growth factor (PDGF) receptors and ephrin receptors may participate in sensing extracellular electrical stimuli. We further observed a high percentage of significantly regulated genes which encode cell membrane proteins, suggesting that dcEF may directly influence the activity of cell membrane proteins in signal transduction. In this study, some of the EF-regulated genes have been reported to be essential whereas others are novel for electrotaxis. Our result confirms that the regulation of gene expression is involved in the mechanism of electrotactic response.

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.

Interaction of the Left Dorsolateral Prefrontal Cortex (l-DLPFC) and Right Orbitofrontal Cortex (OFC) in Hot and Cold Executive Functions: Evidence from Transcranial Direct Current Stimulation (tDCS).

PubMed

Nejati, Vahid; Salehinejad, Mohammad Ali; Nitsche, Michael A

2018-01-15

An organizing principle which has recently emerged proposes that executive functions (EF) can be divided into cognitive (cold) and affective/reward-related (hot) processes related to the dorsolateral prefrontal cortex (DLPFC) and orbitofrontal cortex (OFC) respectively. A controversial question is whether cold and hot EF are functionally and structurally independent or not. This study investigated how the left DLPFC (l-DLPFC) and right OFC (r-OFC) interact in hot and cold EF using transcranial direct current stimulation (tDCS). Twenty-four healthy male subjects received anodal, cathodal and sham tDCS (20 min, 1.5 mA) over the l-DLPFC (F3) and r-OFC (Fp2) with a 72-h interval between each stimulation condition. After five minutes of stimulation, participants underwent a series of cold and hot EF tasks including the Go/No-Go and Tower of Hanoi (TOH) as measures of cold EF and the BART and temporal discounting tasks as measures of hot EF. Inhibitory control mostly benefited from anodal l-DLPFC/cathodal r-OFC tDCS. Planning and problem solving were more prominently affected by anodal l-DLPFC/cathodal r-OFC stimulation, although the reversed electrode position with the anode positioned over the r-OFC also affected some aspects of task performance. Risk-taking behavior and risky decision-making decreased under both anodal l-DLPFC/cathodal r-OFC and anodal r-OFC/cathodal l-DLPFC tDCS. Cold EF rely on DLPFC activation while hot EF rely on both, DLPFC and OFC activation. Results suggest that EF are placed on continuum with lateral and mesial prefrontal areas contributing to cold and hot aspects respectively. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Clinical significance of a presystolic wave on Doppler examination of the left ventricular outflow tract.

PubMed

Joshi, Kamal R; Kabirdas, Deepa; Romero-Corral, Abel; Shah, Mahek; Figueredo, Vincent M; Pressman, Gregg S

2014-11-15

A presystolic wave (PSW) is commonly seen on Doppler examination of the left ventricular outflow tract (LVOT), but is little studied. We conducted a retrospective study to assess the prevalence of the PSW, correlations with various Doppler parameters, and its clinical significance. Two hundred echocardiograms, 100 with ejection fraction (EF) >55% and 100 with EF <45%, were reviewed. Mitral inflow velocities, septal annular velocities, LVOT, and PSW velocities were measured. Major adverse cardiovascular events (MACE [death, heart failure hospitalization, atrial fibrillation, and stroke]) were compared between those with and without a PSW, in both EF groups. Mean age was 58 ± 15 years; 56% were men and 69% were African-American. PSW prevalence was similar between normal (68%) and reduced EF groups (62%). However, its velocity was less in the low EF group (37 ± 10 vs 48 ± 16 cm/s, p <0.0001). In subjects with normal EF PSW velocity correlated with mitral A velocity (rho = 0.43, p = 0.0003). In subjects with reduced EF the association with A velocity was not significant (rho = 0.22, p = 0.09), but there was a significant association with annular a' velocity (rho = 0.38, p = 0.002). Over a mean follow-up of 1.7 ± 0.3 years, 57 subjects (28%) experienced MACE. Those without a PSW had more MACE (39% vs 23%, p = 0.02); PSW absence remained predictive of MACE after adjustment for multiple variables, especially in patients with reduced EF. In conclusion, PSW is common in the LVOT. Its presence and magnitude are associated with measures of atrial contraction. Its absence is associated with increased rates of adverse events, especially in patients with low EF. Copyright © 2014 Elsevier Inc. All rights reserved.

Enhanced pulmonary vasodilator reserve and abnormal right ventricular: pulmonary artery coupling in heart failure with preserved ejection fraction.

PubMed

Andersen, Mads J; Hwang, Seok-Jae; Kane, Garvan C; Melenovsky, Vojtech; Olson, Thomas P; Fetterly, Kenneth; Borlaug, Barry A

2015-05-01

Pulmonary hypertension and right ventricular (RV) dysfunction are common in patients with advanced heart failure with preserved ejection fraction (HFpEF), yet their underlying mechanisms remain poorly understood. We sought to examine RV-pulmonary artery (PA) functional reserve responses and RV-PA coupling at rest and during β-adrenergic stimulation in subjects with earlier stage HFpEF. In a prospective trial, subjects with HFpEF (n=39) and controls (n=18) underwent comprehensive invasive and noninvasive hemodynamic assessment using high fidelity micromanometer catheters, echocardiography, and expired gas analysis at rest and during dobutamine infusion. HFpEF subjects displayed similar RV structure but significantly impaired RV systolic (lower RV dP/dtmax/IP and s') and diastolic function (higher RV τ) coupled with more severe pulmonary vascular disease, manifest by higher PA pressures, higher PA resistance, and lower PA compliance compared with controls. Dobutamine infusion caused greater pulmonary vasodilation in HFpEF compared with controls, with enhanced reductions in PA resistance, greater increase in PA compliance, and a more negative slope in the PA pressure-flow relationship when compared with controls (all P<0.001). RV-PA coupling analysis revealed that dobutamine improved RV ejection in HFpEF subjects through afterload reduction alone, rather than through enhanced contractility, indicating RV systolic reserve dysfunction. Pulmonary hypertension in early stage HFpEF is related to partially reversible pulmonary vasoconstriction coupled with RV systolic and diastolic dysfunction, even in the absence of RV structural remodeling. Pulmonary vascular tone is more favorably responsive to β-adrenergic stimulation in HFpEF than controls, suggesting a potential role for β-agonists in the treatment of patients with HFpEF and pulmonary hypertension. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01418248. © 2015 American Heart Association, Inc.

Comparison of Predictors of Heart Failure-related Hospitalization or Death in Patients with versus without Preserved Left Ventricular Ejection Fraction

PubMed Central

Mangla, Ashvarya; Kane, John; Beaty, Elijah; Richardson, DeJuran; Powell, Lynda H.; Calvin, James E.

2013-01-01

Heart failure with preserved ejection fraction (HFpEF) is recognized as a major cause of cardiovascular morbidity and mortality. An ability to identify patients with HFpEF who are at increased risk for adverse outcome can facilitate their more careful management. We studied the patients having heart failure (HF) using data from the Heart Failure Adherence and Retention Trial (HART). HART enrolled 902 NYHA Class II or III patients who had been recently hospitalized for HF to study the impact of self-management counseling on the primary outcome of death or HF hospitalization. In HART 208 patients had HFpEF and 692 had HFrEF (heart failure with reduced ejection fraction), and were followed for median of 1080 days. Two final multivariate models were developed. In patients having HFpEF, predictors of primary outcome were: male sex (OR 3.45, p=0.004), NYHA class III (OR 3.05, p=0.008), distance covered on 6-minute walk test (6-MWT) of< 620 feet (OR 2.81, p=0.013), and <80% adherence to prescribed medications (OR 2.61, p=0.018). In patients having HFrEF, the predictors were: being on diuretics (OR 3.06, p=0.001), having ≥ 3 comorbidities (OR 2.11, p=0.0001), distance covered on 6-MWT of < 620 feet (OR 1.94, p=0.001), NYHA class III (OR 1.90, p=0.001) and age > 65 years (OR 1.63, p=0.01). In conclusion, indicators of functional status(6-MWT and NYHA class) were common to both HFpEF and HFrEF patients while gender and adherence to prescribed therapy were unique to patients having HFpEF in predicting death or HF hospitalization. PMID:24063842

Assessing the dysexecutive syndrome in dementia.

PubMed

Gansler, David A; Huey, Edward D; Pan, Jessica J; Wasserman, Eric; Grafman, Jordan H

2017-03-01

We compared performance on tests of dysexecutive behaviour (DB) and executive function (EF) in patients with behavioural variant frontotemporal dementia (bvFTD), primary progressive aphasia (PPA) and corticobasal syndrome (CBS). Patients diagnosed with bvFTD (n=124), PPA (n=34) and CBS (n=85) were recruited. EF was measured with the Delis-Kaplan Executive Function System (DKEFS: performance based), and DB was measured with the Frontal Systems Behavior Scale (FrSBe: caregiver-report based). Confirmatory factor analysis characterised the relationship between EF and DB, binary logistic regression evaluated the incremental diagnostic utility of the measures and neuroimaging data from 110 patients identified neural correlates. EF was lowest and DB was highest in bvFTD participants. EF and DB were distinct but related (r=-0.48). Measures correctly classified 89% of bvFTD from CBS patients and 93% of bvFTD from PPA patients-30% and 13% above base rates (59%, 80%), respectively. All modalities were useful in identifying CBS and PPA, whereas DB alone was useful for identifying bvFTD. EF was uniquely associated with caudal left dorsolateral prefrontal and lateral temporo-parietal cortices. DB was uniquely associated with the cingulate (R>L), right subcallosal and right anterior frontal cortex. EF and DB were associated with the rostral dorsolateral prefrontal cortex bilaterally. EF and DB measures displayed criterion and construct validity, had incremental utility at low DB levels (CBS and PPA) and were associated with overlapping and distinct neural correlates. EF and DB procedures can conjointly provide useful diagnostic and descriptive information in identifying and ruling out the dysexecutive syndrome. 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/.

Linking Resting-State Networks in the Prefrontal Cortex to Executive Function: A Functional Near Infrared Spectroscopy Study.

PubMed

Zhao, Jia; Liu, Jiangang; Jiang, Xin; Zhou, Guifei; Chen, Guowei; Ding, Xiao P; Fu, Genyue; Lee, Kang

2016-01-01

Executive function (EF) plays vital roles in our everyday adaptation to the ever-changing environment. However, limited existing studies have linked EF to the resting-state brain activity. The functional connectivity in the resting state between the sub-regions of the brain can reveal the intrinsic neural mechanisms involved in cognitive processing of EF without disturbance from external stimuli. The present study investigated the relations between the behavioral executive function (EF) scores and the resting-state functional network topological properties in the Prefrontal Cortex (PFC). We constructed complex brain functional networks in the PFC from 90 healthy young adults using functional near infrared spectroscopy (fNIRS). We calculated the correlations between the typical network topological properties (regional topological properties and global topological properties) and the scores of both the Total EF and components of EF measured by computer-based Cambridge Neuropsychological Test Automated Battery (CANTAB). We found that the Total EF scores were positively correlated with regional properties in the right dorsal superior frontal gyrus (SFG), whereas the opposite pattern was found in the right triangular inferior frontal gyrus (IFG). Different EF components were related to different regional properties in various PFC areas, such as planning in the right middle frontal gyrus (MFG), working memory mainly in the right MFG and triangular IFG, short-term memory in the left dorsal SFG, and task switch in the right MFG. In contrast, there were no significant findings for global topological properties. Our findings suggested that the PFC plays an important role in individuals' behavioral performance in the executive function tasks. Further, the resting-state functional network can reveal the intrinsic neural mechanisms involved in behavioral EF abilities.

Coronary microvascular rarefaction and myocardial fibrosis in heart failure with preserved ejection fraction.

PubMed

Mohammed, Selma F; Hussain, Saad; Mirzoyev, Sultan A; Edwards, William D; Maleszewski, Joseph J; Redfield, Margaret M

2015-02-10

Characterization of myocardial structural changes in heart failure with preserved ejection fraction (HFpEF) has been hindered by the limited availability of human cardiac tissue. Cardiac hypertrophy, coronary artery disease (CAD), coronary microvascular rarefaction, and myocardial fibrosis may contribute to HFpEF pathophysiology. We identified HFpEF patients (n=124) and age-appropriate control subjects (noncardiac death, no heart failure diagnosis; n=104) who underwent autopsy. Heart weight and CAD severity were obtained from the autopsy reports. With the use of whole-field digital microscopy and automated analysis algorithms in full-thickness left ventricular sections, microvascular density (MVD), myocardial fibrosis, and their relationship were quantified. Subjects with HFpEF had heavier hearts (median, 538 g; 169% of age-, sex-, and body size-expected heart weight versus 335 g; 112% in controls), more severe CAD (65% with ≥1 vessel with >50% diameter stenosis in HFpEF versus 13% in controls), more left ventricular fibrosis (median % area fibrosis, 9.6 versus 7.1) and lower MVD (median 961 versus 1316 vessels/mm(2)) than control (P<0.0001 for all). Myocardial fibrosis increased with decreasing MVD in controls (r=-0.28, P=0.004) and HFpEF (r=-0.26, P=0.004). Adjusting for MVD attenuated the group differences in fibrosis. Heart weight, fibrosis, and MVD were similar in HFpEF patients with CAD versus without CAD. In this study, patients with HFpEF had more cardiac hypertrophy, epicardial CAD, coronary microvascular rarefaction, and myocardial fibrosis than controls. Each of these findings may contribute to the left ventricular diastolic dysfunction and cardiac reserve function impairment characteristic of HFpEF. © 2014 American Heart Association, Inc.

Investigation of Antihyperglycaemic Activity of Banana (Musa sp. Var. Nanjangud rasa bale) Flower in Normal and Diabetic Rats.

PubMed

Ramu, Ramith; Shirahatti, Prithvi S; Dhanabal, S P; Zameer, Farhan; Dhananjaya, B L; Nagendra Prasad, M N

2017-10-01

The vital enzymes of starch digestion and absorption are intestinal α-glucosidases and their inhibition improves postprandial hyperglycaemia, constituting an effective mode of therapy in diabetes. The present study was designed to assess the inhibitory potential of ethanol extract of banana flower (EF) on mammalian α-glucosidases and its pharmacological effects on postprandial hyperglycaemia in normal and alloxan-induced diabetic rats. EF was evaluated for its inhibitory potential and mode of inhibition on mammalian α-glucosidases. Further, the role of EF and its constituents Umbelliferone (C1) and Lupeol (C2) on glucose uptake using isolated rat hemi-diaphragm and insulinotropic activity using RINm5F (rat insulinoma) cell lines were determined. The phytocomponents in EF were also evaluated using GC-MS. EF illustrated a dose-dependent inhibition for rat intestinal sucrase, maltase and p -nitrophenyl-α-D-glucopyranoside (pNPG) hydrolysis (IC 50 values: 18.76±0.22, 25.54±0.10 and 76.42±1.12 µg/ml, respectively) and the mode of inhibition was non-competitive with low Ki values. Oral administration (100-200 mg/kg b.wt.) of EF significantly improved the maltose/glucose-induced postprandial hyperglycaemia in normal and alloxan-induced diabetic rats. EF, C1 and C2 exhibited stimulation of glucose uptake and a dose-dependent glucose-induced insulin secretion at both 4.5 and 16.7 mM glucose concentrations. Further, GC-MS analysis revealed significant levels of steroids (25.61%), diazoprogesterone (21.31%), sesquiterpene (11.78%) and other phytocomponents. EF inhibited α-glucosidases besides promoting glucose uptake and insulin secretion, resulting in antihyperglycaemic effect determining EF as a potent anti-diabetic agent. Abbreviations used: mg/dl: milligramsper deciliter, mM: millimolar, b.wt.: body weight.

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

Rationale, Design, and Methodology of the APOLLON trial: A comPrehensive, ObservationaL registry of heart faiLure with midrange and preserved ejectiON fraction.

PubMed

Özlek, Bülent; Özlek, Eda; Çelik, Oğuzhan; Çil, Cem; Doğan, Volkan; Tekinalp, Mehmet; Zencirkıran Ağuş, Hicaz; Kahraman, Serkan; Ösken, Altuğ; Rencüzoğulları, İbrahim; Tanık, Veysel Ozan; Bekar, Lütfü; Çakır, Mustafa Ozan; Kaya, Bedri Caner; Tibilli, Hakan; Çelik, Yunus; Başaran, Özcan; Mert, Kadir Uğur; Sevinç, Samet; Demirci, Erkan; Dondurmacı, Engin; Biteker, Murat

2018-05-01

Although almost half of chronic heart failure (HF) patients have mid-range (HFmrEF) and preserved left-ventricular ejection fraction (HFpEF), no studies have been carried out with these patients in our country. This study aims to determine the demographic characteristics and current status of the clinical background of HFmrEF and HFpEF patients in a multicenter trial. A comPrehensive, ObservationaL registry of heart faiLure with mid range and preserved ejectiON fraction (APOLLON) trial will be an observational, multicenter, and noninterventional study conducted in Turkey. The study population will include 1065 patients from 12 sites in Turkey. All data will be collected at one point in time and the current clinical practice will be evaluated (ClinicalTrials.gov number NCT03026114). We will enroll all consecutive patients admitted to the cardiology clinics who were at least 18 years of age and had New York Heart Association class II, III, or IV HF, elevated brain natriuretic peptide levels within the last 30 days, and an left ventricular ejection fraction (LVEF) of at least 40%. Patients fulfilling the exclusion criteria will not be included in the study. Patients will be stratified into two categories according to LVEF: mid-range EF (HFmrEF, LVEF 40%-49%) and preserved EF (HFpEF, LVEF ≥50%). Regional quota sampling will be performed to ensure that the sample was representative of the Turkish population. Demographic, lifestyle, medical, and therapeutic data will be collected by this specific survey. The APOLLON trial will be the largest and most comprehensive study in Turkey evaluating HF patients with a LVEF ≥40% and will also be the first study to specifically analyze the recently designated HFmrEF category.

Electromagnetic enhancement of ordered silver nanorod arrays evaluated by discrete dipole approximation.

PubMed

Wei, Guoke; Wang, Jinliang; Chen, Yu

2015-01-01

The enhancement factor (EF) of surface-enhanced Raman scattering (SERS) from two-dimensional (2D) hexagonal silver nanorod (AgNR) arrays were investigated in terms of electromagnetic (EM) mechanism by using the discrete dipole approximation (DDA) method. The dependence of EF on several parameters, i.e., structure, length, excitation wavelength, incident angle and polarization, and gap size has been investigated. "Hotspots" were found distributed in the gaps between adjacent nanorods. Simulations of AgNR arrays of different lengths revealed that increasing the rod length from 374 to 937 nm (aspect ratio from 2.0 to 5.0) generated more "hotspots" but not necessarily increased EF under both 514 and 532 nm excitation. A narrow lateral gap (in the incident plane) was found to result in strong EF, while the dependence of EF on the diagonal gap (out of the incident plane) showed an oscillating behavior. The EF of the array was highly dependent on the angle and polarization of the incident light. The structure of AgNR and the excitation wavelength were also found to affect the EF. The EF of random arrays was stronger than that of an ordered one with the same average gap of 21 nm, which could be explained by the exponential dependence of EF on the lateral gap size. Our results also suggested that absorption rather than extinction or scattering could be a good indicator of EM enhancement. It is expected that the understanding of the dependence of local field enhancement on the structure of the nanoarrays and incident excitations will shine light on the optimal design of efficient SERS substrates and improved performance.

Contributions to Executive Dysfunction in Operation Enduring Freedom/Operation Iraqi Freedom Veterans With Posttraumatic Stress Disorder and History of Mild Traumatic Brain Injury.

PubMed

Jurick, Sarah M; Crocker, Laura D; Sanderson-Cimino, Mark; Keller, Amber V; Trenova, Liljana S; Boyd, Briana L; Twamley, Elizabeth W; Rodgers, Carie S; Schiehser, Dawn M; Aupperle, Robin L; Jak, Amy J

Posttraumatic stress disorder (PTSD), history of mild traumatic brain injury (mTBI), and executive function (EF) difficulties are prevalent in Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) Veterans. We evaluated the contributions of injury variables, lower-order cognitive component processes (processing speed/attention), and psychological symptoms to EF. OEF/OIF Veterans (N = 65) with PTSD and history of mTBI were administered neuropsychological tests of EF and self-report assessments of PTSD and depression. Those impaired on one or more EF measures had higher PTSD and depression symptoms and lower processing speed/attention performance than those with intact performance on all EF measures. Across participants, poorer attention/processing speed performance and higher psychological symptoms were associated with worse performance on specific aspects of EF (eg, inhibition and switching) even after accounting for injury variables. Although direct relationships between EF and injury variables were equivocal, there was an interaction between measures of injury burden and processing speed/attention such that those with greater injury burden exhibited significant and positive relationships between processing speed/attention and inhibition/switching, whereas those with lower injury burden did not. Psychological symptoms as well as lower-order component processes of EF (attention and processing speed) contribute significantly to executive dysfunction in OEF/OIF Veterans with PTSD and history of mTBI. However, there may be equivocal relationships between injury variables and EF that warrant further study. Results provide groundwork for more fully understanding cognitive symptoms in OEF/OIF Veterans with PTSD and history of mTBI that can inform psychological and cognitive interventions in this population.

[Course of ejection fraction, regurgitation fraction and ventricular volumes during exertion in chronic aortic insufficiency. Study using technetium 99m gamma-cineangiography].

PubMed

Bassand, J P; Faivre, R; Berthout, P; Cardot, J C; Verdenet, J; Bidet, R; Maurat, J P

1985-06-01

Previous studies have shown that variations of the ejection fraction (EF) during exercise were representative of the contractile state of the left ventricle: an increased EF on effort is considered to be physiological, whilst a decrease would indicate latent LV dysfunction unmasked during exercise. This hypothesis was tested by performing Technetium 99 gamma cineangiography at equilibrium under basal conditions and at maximal effort in 8 healthy subjects and 44 patients with pure, severe aortic regurgitation to measure the ejection and regurgitant fractions and the variations in end systolic and end diastolic LV volume. In the control group the EF increased and end systolic volume decreased significantly on effort whilst the regurgitant fraction and end diastolic volume were unchanged. In the 44 patients with aortic regurgitation no significant variations in EF, end systolic and end diastolic volumes were observed because the individual values were very dispersed. Variations of the EF and end systolic volume were inversely correlated. The regurgitant fraction decreased significantly on effort. Based on the variations of the EF and end systolic volume three different types of response to effort could be identified: in 7 patients, the EF increased on effort and end systolic volume decreased without any significant variation in the end diastolic volume, as in the group of normal control subjects; in 22 patients, a reduction in EF was observed on effort, associated with an increased end systolic volume. These changes indicated latent IV dysfunction inapparent at rest and unmasked by exercise; in a third group of 15 patients, the EF decreased on effort despite a physiological decrease in end systolic volume due to a greater decrease in end diastolic volume.(ABSTRACT TRUNCATED AT 250 WORDS)

Ejection fraction in myocardial perfusion imaging assessed with a dynamic phantom: comparison between IQ-SPECT and LEHR.

PubMed

Hippeläinen, Eero; Mäkelä, Teemu; Kaasalainen, Touko; Kaleva, Erna

2017-12-01

Developments in single photon emission tomography instrumentation and reconstruction methods present a potential for decreasing acquisition times. One of such recent options for myocardial perfusion imaging (MPI) is IQ-SPECT. This study was motivated by the inconsistency in the reported ejection fraction (EF) and left ventricular (LV) volume results between IQ-SPECT and more conventional low-energy high-resolution (LEHR) collimation protocols. IQ-SPECT and LEHR quantitative results were compared while the equivalent number of iterations (EI) was varied. The end-diastolic (EDV) and end-systolic volumes (ESV) and the derived EF values were investigated. A dynamic heart phantom was used to produce repeatable ESVs, EDVs and EFs. Phantom performance was verified by comparing the set EF values to those measured from a gated multi-slice X-ray computed tomography (CT) scan (EF True ). The phantom with an EF setting of 45, 55, 65 and 70% was imaged with both IQ-SPECT and LEHR protocols. The data were reconstructed with different EI, and two commonly used clinical myocardium delineation software were used to evaluate the LV volumes. The CT verification showed that the phantom EF settings were repeatable and accurate with the EF True being within 1% point from the manufacture's nominal value. Depending on EI both MPI protocols can be made to produce correct EF estimates, but IQ-SPECT protocol produced on average 41 and 42% smaller EDV and ESV when compared to the phantom's volumes, while LEHR protocol underestimated volumes by 24 and 21%, respectively. The volume results were largely similar between the delineation methods used. The reconstruction parameters can greatly affect the volume estimates obtained from perfusion studies. IQ-SPECT produces systematically smaller LV volumes than the conventional LEHR MPI protocol. The volume estimates are also software dependent.

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.

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.

23 CFR Appendixes E-F to Subpart A... - [Reserved

Code of Federal Regulations, 2010 CFR

2010-04-01

... 23 Highways 1 2010-04-01 2010-04-01 false [Reserved] E Appendixes E-F to Subpart A of Part 230 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION CIVIL RIGHTS EXTERNAL PROGRAMS Equal...) Appendixes E-F to Subpart A of Part 230 [Reserved] ...

Performance evaluation of structure based and ligand based virtual screening methods on ten selected anti-cancer targets.

PubMed

Ramasamy, Thilagavathi; Selvam, Chelliah

2015-10-15

Virtual screening has become an important tool in drug discovery process. Structure based and ligand based approaches are generally used in virtual screening process. To date, several benchmark sets for evaluating the performance of the virtual screening tool are available. In this study, our aim is to compare the performance of both structure based and ligand based virtual screening methods. Ten anti-cancer targets and their corresponding benchmark sets from 'Demanding Evaluation Kits for Objective In silico Screening' (DEKOIS) library were selected. X-ray crystal structures of protein-ligand complexes were selected based on their resolution. Openeye tools such as FRED, vROCS were used and the results were carefully analyzed. At EF1%, vROCS produced better results but at EF5% and EF10%, both FRED and ROCS produced almost similar results. It was noticed that the enrichment factor values were decreased while going from EF1% to EF5% and EF10% in many cases. Published by Elsevier Ltd.

Social Maturity and Executive Function Among Deaf Learners

PubMed Central

Marschark, Marc; Kronenberger, William G.; Rosica, Mark; Borgna, Georgianna; Convertino, Carol; Durkin, Andreana; Machmer, Elizabeth; Schmitz, Kathryn L.

2017-01-01

Two experiments examined relations among social maturity, executive function, language, and cochlear implant (CI) use among deaf high school and college students. Experiment 1 revealed no differences between deaf CI users, deaf nonusers, and hearing college students in measures of social maturity. However, deaf students (both CI users and nonusers) reported significantly greater executive function (EF) difficulties in several domains, and EF was related to social maturity. Experiment 2 found that deaf CI users and nonusers in high school did not differ from each other in social maturity or EF, but individuals who relied on sign language reported significantly more immature behaviors than deaf peers who used spoken language. EF difficulties again were associated with social maturity. The present results indicate that EF and social maturity are interrelated, but those relations vary in different deaf subpopulations. As with academic achievement, CI use appears to have little long-term impact on EF or social maturity. Results are discussed in terms of their convergence with findings related to incidental learning and functioning in several domains. PMID:27686092

A Longitudinal Assessment of the Relation between Executive Function and Theory of Mind at 3, 4, and 5 Years

PubMed Central

Marcovitch, Stuart; O’Brien, Marion; Calkins, Susan D.; Leerkes, Esther M.; Weaver, Jennifer M.; Levine, Douglas W.

2014-01-01

This longitudinal study contributes to the growing literature on the predictive nature of the relation between executive function (EF) and theory of mind (ToM). A latent variable model was fit to the data acquired from 226 socioeconomically and racially diverse children (52% female) at 3, 4, and 5 years of age on a number of age-appropriate tasks designed to assess EF and ToM. After controlling for sex, income-to-needs, and receptive language ability, there was substantial stability within each construct as children aged. In addition, EF at 3 years predicted ToM at 4 years but ToM did not predict EF, replicating earlier results. This pattern also appeared from 4 to 5 years of age, suggesting that the developmental precedence of EF persists later in development. Implications of these findings are discussed in terms of contemporary cognitive development theories, as well as the relation between EF and social reasoning in general. PMID:25642021

Fluctuations between multiple EF-G-induced chimeric tRNA states during translocation on the ribosome

NASA Astrophysics Data System (ADS)

Adio, Sarah; Senyushkina, Tamara; Peske, Frank; Fischer, Niels; Wintermeyer, Wolfgang; Rodnina, Marina V.

2015-06-01

The coupled translocation of transfer RNA and messenger RNA through the ribosome entails large-scale structural rearrangements, including step-wise movements of the tRNAs. Recent structural work has visualized intermediates of translocation induced by elongation factor G (EF-G) with tRNAs trapped in chimeric states with respect to 30S and 50S ribosomal subunits. The functional role of the chimeric states is not known. Here we follow the formation of translocation intermediates by single-molecule fluorescence resonance energy transfer. Using EF-G mutants, a non-hydrolysable GTP analogue, and fusidic acid, we interfere with either translocation or EF-G release from the ribosome and identify several rapidly interconverting chimeric tRNA states on the reaction pathway. EF-G engagement prevents backward transitions early in translocation and increases the fraction of ribosomes that rapidly fluctuate between hybrid, chimeric and posttranslocation states. Thus, the engagement of EF-G alters the energetics of translocation towards a flat energy landscape, thereby promoting forward tRNA movement.

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.

Induced seasonal reproductive performance in two breeds of sheep.

PubMed

de Nicolo, G; Morris, S T; Kenyon, P R; Morel, P C H; Parkinson, T J

2008-01-30

The objective of the present experiment was to determine whether failure to become pregnant through out-of-season reproductive management regimes is attributable to a failure to stimulate normal corpora lutea (CL) production. Romney ewes and East Friesian Composite (EF) ewes were mated in summer, autumn, winter, and early and late spring after administration of intravaginal progesterone inserts (plus eCG in spring and summer) in a factorial (two breedsxfive mating periods) experimental design. Oestrus rate was determined from mating data, and the numbers of CL were determined by laparoscopy 9 days after ram introduction. Conception rate, pregnancy rate and litter size were determined by transabdominal ultrasonography 62 days after ram introduction. Proportions of ewes displaying oestrus did not differ significantly (75-100%) between seasons or breeds, except for the Romney ewes in summer (67%; P<0.05). Numbers of CL on Day 9 for EF ewes was lowest in autumn (1.5) and winter (1.5), and highest in late spring (2.1; P<0.05). In contrast, Romney ewes had the lowest CL count in summer (1.3), and the highest in autumn (1.8) and winter (1.6; P<0.05). Only in summer was there a difference between breeds (EF 1.8; Romney 1.3; P<0.01). The proportion of ewes that failed to conceive despite having one or more CL present was highest in late spring (EF 41%, Romney 43%), and lowest in autumn (EF 9%, Romney 4%) and winter (EF 14%, Romney 4%; P<0.05). Conception and pregnancy rates followed similar patterns with values for autumn (EF 91%, 91%; Romney 96%, 96%) and June (EF 86%, 82%; Romney 91%, 83%) being significantly (P<0.05) higher than in early (EF 50%, 40%; Romney 54%, 50%) and late spring (EF 44%, 36%; Romney 42%, 36%). Pregnancy rate in summer was higher for EF ewes (60%) than for Romney ewes (39%) but conception rates were not statistically different (EF 68%; Romney 60%). Numbers of foetuses identified at scanning was highest in autumn (1.5) and lowest in late spring (0.5 P<0.001): Litter size in pregnant EF ewes was highest in early spring and lowest in winter (1.8 versus 1.2; P<0.01), but for pregnant Romney ewes was highest in winter and lowest in early spring (1.9 versus 1.3; P<0.001). It was concluded that seasonal differences in the ability of ewes to conceive are not the consequence of failure to display oestrus or to ovulate, but probably are a result of failure of fertilisation or the establishment of pregnancy.

Structure of a novel antibacterial toxin that exploits elongation factor Tu to cleave specific transfer RNAs

DOE PAGES

Michalska, Karolina; Gucinski, Grant C.; Garza-Sanchez, Fernando; ...

2017-08-11

Contact-dependent growth inhibition (CDI) is a mechanism of inter-cellular competition in which Gram-negative bacteria exchange polymorphic toxins using type V secretion systems. Here, we present structures of the CDI toxin from Escherichia coli NC101 in ternary complex with its cognate immunity protein and elongation factor Tu (EF-Tu). The toxin binds exclusively to domain 2 of EF-Tu, partially overlapping the site that interacts with the 3'-end of aminoacyl-tRNA (aa-tRNA). The toxin exerts a unique ribonuclease activity that cleaves the single-stranded 3'-end from tRNAs that contain guanine discriminator nucleotides. EF-Tu is required to support this tRNase activity in vitro, suggesting the toxinmore » specifically cleaves substrate in the context of GTP·EF-Tu·aa-tRNA complexes. However, superimposition of the toxin domain onto previously solved GTP·EF-Tu·aa-tRNA structures reveals potential steric clashes with both aa-tRNA and the switch I region of EF-Tu. Further, the toxin induces conformational changes in EF-Tu, displacing a β-hairpin loop that forms a critical salt-bridge contact with the 3'-terminal adenylate of aa-tRNA. Altogether, these observations suggest that the toxin remodels GTP·EF-Tu·aa-tRNA complexes to free the 3'-end of aa-tRNA for entry into the nuclease active site.« less

Structure of a novel antibacterial toxin that exploits elongation factor Tu to cleave specific transfer RNAs

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

Michalska, Karolina; Gucinski, Grant C.; Garza-Sanchez, Fernando

Contact-dependent growth inhibition (CDI) is a mechanism of inter-cellular competition in which Gram-negative bacteria exchange polymorphic toxins using type V secretion systems. Here, we present structures of the CDI toxin from Escherichia coli NC101 in ternary complex with its cognate immunity protein and elongation factor Tu (EF-Tu). The toxin binds exclusively to domain 2 of EF-Tu, partially overlapping the site that interacts with the 3'-end of aminoacyl-tRNA (aa-tRNA). The toxin exerts a unique ribonuclease activity that cleaves the single-stranded 3'-end from tRNAs that contain guanine discriminator nucleotides. EF-Tu is required to support this tRNase activity in vitro, suggesting the toxinmore » specifically cleaves substrate in the context of GTP·EF-Tu·aa-tRNA complexes. However, superimposition of the toxin domain onto previously solved GTP·EF-Tu·aa-tRNA structures reveals potential steric clashes with both aa-tRNA and the switch I region of EF-Tu. Further, the toxin induces conformational changes in EF-Tu, displacing a β-hairpin loop that forms a critical salt-bridge contact with the 3'-terminal adenylate of aa-tRNA. Altogether, these observations suggest that the toxin remodels GTP·EF-Tu·aa-tRNA complexes to free the 3'-end of aa-tRNA for entry into the nuclease active site.« less

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.

Epicardial fat thickness: threshold values and lifestyle association in male adolescents.

PubMed

Cena, H; Fonte, M L; Casali, P M; Maffoni, S; Roggi, C; Biino, G

2015-04-01

Obese adolescents with high proportion of visceral fat are at higher risk of developing the metabolic syndrome. The study aims to investigate if echocardiographic epicardial fat thickness (EF) could be predictive of visceral obesity (VO) early in life and to provide EF threshold values specific for male adolescents. Further aim was to investigate the association between EF, lifestyle and metabolic disease familiarity. Anthropometric data were collected from 102 normal weight and overweight, healthy male adolescents (mean age: 14.91 ±  1.98 years); bioelectrical impedance analysis and transthoracic echocardiogram were performed in the same sample. Each participant fulfilled a validated self-administered lifestyle questionnaire. We found higher EF values in sedentary adolescents (P < 0.05), in those who never eat fruit and vegetables (P < 0.05), and in those with overweight mothers (P < 0.05). The strongest independent predictor of EF was waist circumference (P < 0.0001). Using the waist to height ratio as a marker of VO, logistic regression analysis revealed that 1 mm EF gain is responsible for seven times higher VO risk (P < 0.0001). Receiver Operating Characteristic (ROC) analysis showed that the optimal cut-off for EF thickness associated to youth VO is 3.2 mm. Ultrasonography EF measurement might be a second-level assessment tool, useful to detect early cardiometabolic damage stage. © 2014 The Authors. Pediatric Obesity © 2014 World Obesity.

The role of resting-state EEG localized activation and central nervous system arousal in executive function performance in children with Attention-Deficit/Hyperactivity Disorder.

PubMed

Zhang, Da-Wei; Johnstone, Stuart J; Roodenrys, Steven; Luo, Xiangsheng; Li, Hui; Wang, Encong; Zhao, Qihua; Song, Yan; Liu, Lu; Qian, Qiujin; Wang, Yufeng; Sun, Li

2018-06-01

This study explored the relationships between resting-state electroencephalogram (RS-EEG) localized activation and two important types of executive functions (EF) to extend the prognostic utilization of RS-EEG in children with Attention-Deficit/Hyperactivity Disorder (AD/HD). Also, the role of central nervous system (CNS) arousal in the relationships was examined. Fifty-eight children with AD/HD participated in the study. RS-EEG localized activation was derived from spectral power differences between EEG in eyes-closed and eyes-open conditions. CNS arousal was measured based on alpha band power. Common and everyday EF scores were obtained as EF outcomes. Frontal delta activation predicted common EF ability and posterior alpha activation predicted everyday EF. A serial mediation analysis found that lower CNS baseline arousal was related to greater arousal and delta activation in series, which in turn related to worse common EF. A follow-up study found that baseline arousal was related to larger interference cost. RS-EEG is indicative of individual differences in two important types of EF in children with AD/HD. Lower CNS arousal may be a driving force for the poorer common EF performance. The current study supports prognostic utilization of RS-EEG and AD/HD models that take resting brain activity into consideration in children with AD/HD. Copyright © 2018 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Eosinophilic folliculitis occurring after stem cell transplant for acute lymphoblastic leukemia: a case report and review.

PubMed

Zitelli, Kristine; Fernandes, Neil; Adams, Brian B

2015-07-01

Eosinophilic folliculitis (EF) comprises classic eosinophilic pustular folliculitis (EPF), human immunodeficiency virus (HIV)-related EF, and infantile EPF subtypes. A fourth proposed subtype describes EF associated with hematologic malignancy. Recently, EF has occurred after bone marrow or stem cell transplantation (SCT). We report a unique case of EF after haploidentical allogeneic SCT for acute lymphoblastic leukemia (ALL) and review the literature for similar cases. A 56-year-old, HIV-negative ALL patient presented with an intensely pruritic papulopustular eruption. He had undergone haploidentical allogeneic SCT 65 days earlier, which he had tolerated well. Histopathology revealed a moderately dense perifollicular and perivascular lymphocytic infiltrate with many eosinophils extending from the superficial dermis to the subcutaneous fat. Fungal stains were negative. These findings were highly consistent with EF. Therapy with a class II topical corticosteroid ointment, oral doxepin, and emollients achieved near-resolution of the lesions within eight weeks. Transition to topical tacrolimus 0.1% ointment applied twice daily to residual lesions yielded complete clearance by 12 weeks with mild post-inflammatory hyperpigmentation. The patient's ALL remains in remission. A fourth proposed subtype of EF is associated with HIV-negative hematologic disease. This subtype is distinguished by a predictable timeframe to presentation and a relatively rapid response to therapy. Although EF is an important consideration in all patients with hematologic malignancy, clinically heightened suspicion is warranted during the 2-3 months after transplant. © 2014 The International Society of Dermatology.

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.

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/.

Delayed Repolarization Underlies Ventricular Arrhythmias in Rats With Heart Failure and Preserved Ejection Fraction.

PubMed

Cho, Jae Hyung; Zhang, Rui; Kilfoil, Peter J; Gallet, Romain; de Couto, Geoffrey; Bresee, Catherine; Goldhaber, Joshua I; Marbán, Eduardo; Cingolani, Eugenio

2017-11-21

Heart failure with preserved ejection fraction (HFpEF) represents approximately half of heart failure, and its incidence continues to increase. The leading cause of mortality in HFpEF is sudden death, but little is known about the underlying mechanisms. Dahl salt-sensitive rats were fed a high-salt diet (8% NaCl) from 7 weeks of age to induce HFpEF (n=38). Rats fed a normal-salt diet (0.3% NaCl) served as controls (n=13). Echocardiograms were performed to assess systolic and diastolic function from 14 weeks of age. HFpEF-verified and control rats underwent programmed electrical stimulation. Corrected QT interval was measured by surface ECG. The mechanisms of ventricular arrhythmias (VA) were probed by optical mapping, whole-cell patch clamp to measure action potential duration and ionic currents, and quantitative polymerase chain reaction and Western blotting to investigate changes in ion channel expression. After 7 weeks of a high-salt diet, 31 of 38 rats showed diastolic dysfunction and preserved ejection fraction along with signs of heart failure and hence were diagnosed with HFpEF. Programmed electric stimulation demonstrated increased susceptibility to VA in HFpEF rats ( P <0.001 versus controls). The arrhythmogenicity index was increased ( P <0.001) and the corrected QT interval on ECG was prolonged ( P <0.001) in HFpEF rats. Optical mapping of HFpEF hearts demonstrated prolonged action potentials ( P <0.05) and multiple reentry circuits during induced VA. Single-cell recordings of cardiomyocytes isolated from HFpEF rats confirmed a delay of repolarization ( P =0.001) and revealed downregulation of transient outward potassium current ( I to ; P <0.05). The rapid components of the delayed rectifier potassium current ( I Kr ) and the inward rectifier potassium current ( I K1 ) were also downregulated ( P <0.05), but the current densities were much lower than for I to . In accordance with the reduction of I to , both Kcnd3 transcript and Kv4.3 protein levels were decreased in HFpEF rat hearts. Susceptibility to VA was markedly increased in rats with HFpEF. Underlying abnormalities include QT prolongation, delayed repolarization from downregulation of potassium currents, and multiple reentry circuits during VA. Our findings are consistent with the hypothesis that potassium current downregulation leads to abnormal repolarization in HFpEF, which in turn predisposes to VA and sudden cardiac death. © 2017 American Heart Association, Inc.

The fsr Quorum-Sensing System and Cognate Gelatinase Orchestrate the Expression and Processing of Proprotein EF_1097 into the Mature Antimicrobial Peptide Enterocin O16.

PubMed

Dundar, Halil; Brede, Dag A; La Rosa, Sabina Leanti; El-Gendy, Ahmed Osama; Diep, Dzung B; Nes, Ingolf F

2015-07-01

A novel antimicrobial peptide designated enterocin O16 was purified from Enterococcus faecalis. Mass spectrometry showed a monoisotopic mass of 7,231 Da, and N-terminal Edman degradation identified a 29-amino-acid sequence corresponding to residues 90 to 119 of the EF_1097 protein. Bioinformatic analysis showed that enterocin O16 is composed of the 68 most C-terminal residues of the EF_1097 protein. Introduction of an in-frame isogenic deletion in the ef1097 gene abolished the production of enterocin O16. Enterocin O16 has a narrow inhibitory spectrum, as it inhibits mostly lactobacilli. Apparently, E. faecalis is intrinsically resistant to the antimicrobial peptide, as no immunity connected to the production of enterocin O16 could be identified. ef1097 has previously been identified as one of three loci regulated by the fsr quorum-sensing system. The introduction of a nonsense mutation into fsrB consistently impaired enterocin O16 production, but externally added gelatinase biosynthesis-activating pheromone restored the antimicrobial activity. Functional genetic analysis showed that the EF_1097 proprotein is processed extracellularly into enterocin O16 by the metalloprotease GelE. Thus, it is evident that the fsr quorum-sensing system constitutes the regulatory unit that controls the expression of the EF_1097 precursor protein and the protease GelE and that the latter is required for the formation of enterocin O16. On the basis of these results, this study identified antibacterial antagonism as a novel aspect related to the function of fsr and provides a rationale for why ef1097 is part of the fsr regulon. The fsr quorum-sensing system modulates important physiological functions in E. faecalis via the activity of GelE. The present study presents a new facet of fsr signaling. The system controls the expression of three primary target operons (fsrABCD, gelE-sprE, and ef1097-ef1097b). We demonstrate that the concerted expression of these operons constitutes the elements necessary for the production of a bacteriocin-type peptide and that antimicrobial antagonism is an intrinsic function of fsr. The bacteriocin enterocin O16 consists of the 68 most C-terminal residues of the EF_1097 secreted proprotein. The GelE protease processes the EF_1097 proprotein into enterocin O16. In this manner, fsr signaling enables E. faecalis populations to express antimicrobial activity in a cell density-dependent manner. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

The fsr Quorum-Sensing System and Cognate Gelatinase Orchestrate the Expression and Processing of Proprotein EF_1097 into the Mature Antimicrobial Peptide Enterocin O16

PubMed Central

Dundar, Halil; Brede, Dag A.; La Rosa, Sabina Leanti; El-Gendy, Ahmed Osama; Diep, Dzung B.

2015-01-01

ABSTRACT A novel antimicrobial peptide designated enterocin O16 was purified from Enterococcus faecalis. Mass spectrometry showed a monoisotopic mass of 7,231 Da, and N-terminal Edman degradation identified a 29-amino-acid sequence corresponding to residues 90 to 119 of the EF_1097 protein. Bioinformatic analysis showed that enterocin O16 is composed of the 68 most C-terminal residues of the EF_1097 protein. Introduction of an in-frame isogenic deletion in the ef1097 gene abolished the production of enterocin O16. Enterocin O16 has a narrow inhibitory spectrum, as it inhibits mostly lactobacilli. Apparently, E. faecalis is intrinsically resistant to the antimicrobial peptide, as no immunity connected to the production of enterocin O16 could be identified. ef1097 has previously been identified as one of three loci regulated by the fsr quorum-sensing system. The introduction of a nonsense mutation into fsrB consistently impaired enterocin O16 production, but externally added gelatinase biosynthesis-activating pheromone restored the antimicrobial activity. Functional genetic analysis showed that the EF_1097 proprotein is processed extracellularly into enterocin O16 by the metalloprotease GelE. Thus, it is evident that the fsr quorum-sensing system constitutes the regulatory unit that controls the expression of the EF_1097 precursor protein and the protease GelE and that the latter is required for the formation of enterocin O16. On the basis of these results, this study identified antibacterial antagonism as a novel aspect related to the function of fsr and provides a rationale for why ef1097 is part of the fsr regulon. IMPORTANCE The fsr quorum-sensing system modulates important physiological functions in E. faecalis via the activity of GelE. The present study presents a new facet of fsr signaling. The system controls the expression of three primary target operons (fsrABCD, gelE-sprE, and ef1097-ef1097b). We demonstrate that the concerted expression of these operons constitutes the elements necessary for the production of a bacteriocin-type peptide and that antimicrobial antagonism is an intrinsic function of fsr. The bacteriocin enterocin O16 consists of the 68 most C-terminal residues of the EF_1097 secreted proprotein. The GelE protease processes the EF_1097 proprotein into enterocin O16. In this manner, fsr signaling enables E. faecalis populations to express antimicrobial activity in a cell density-dependent manner. PMID:25733609

Risk of Heart Failure With Preserved Ejection Fraction in Older Women After Contemporary Radiotherapy for Breast Cancer.

PubMed

Saiki, Hirofumi; Petersen, Ivy A; Scott, Christopher G; Bailey, Kent R; Dunlay, Shannon M; Finley, Randi R; Ruddy, Kathryn J; Yan, Elizabeth; Redfield, Margaret M

2017-04-11

Cardiomyocytes are resistant to radiation. However, cardiac radiation exposure causes coronary microvascular endothelial inflammation, a perturbation implicated in the pathogenesis of heart failure (HF) and particularly HF with preserved ejection fraction (HFpEF). Radiotherapy for breast cancer results in variable cardiac radiation exposure and may increase the risk of HF. We conducted a population-based case-control study of incident HF in 170 female residents of Olmsted County, Minnesota (59 cases and 111 controls), who underwent contemporary (1998-2013) radiotherapy for breast cancer with computed tomography-assisted radiotherapy planning. Controls were matched to cases for age, tumor side, chemotherapy use, diabetes mellitus, and hypertension. Mean cardiac radiation dose (MCRD) in each patient was calculated from the patient's computed tomography images and radiotherapy plan. Mean age at radiotherapy was 69±9 years. Of HF cases, 38 (64%) had EF≥50% (HFpEF), 18 (31%) had EF<50% (HF with reduced EF), and 3 (5%) did not have EF measured. The EF was ≥40% in 50 of the 56 HF cases (89%) with an EF measurement. The mean interval from radiotherapy to HF was 5.8±3.4 years. The odds of HF was higher in patients with a history of ischemic heart disease or atrial fibrillation. The MCRD was 2.5 Gy (range, 0.2-13.1 Gy) and higher in cases (3.3±2.7 Gy) than controls (2.1±2.0 Gy; P =0.004). The odds ratio (95% confidence interval) for HF per log MCRD was 9.1 (3.4-24.4) for any HF, 16.9 (3.9-73.7) for HFpEF, and 3.17 (0.8-13.0) for HF with reduced EF. The increased odds of any HF or HFpEF with increasing MCRD remained significant after adjustment for HF risk factors and in sensitivity analyses matching by cancer stage rather than tumor side. Only 18.6% of patients experienced new or recurrent ischemic events between radiotherapy and the onset of HF. The relative risk of HFpEF increases with increasing cardiac radiation exposure during contemporary conformal breast cancer radiotherapy. These data emphasize the importance of radiotherapy techniques that limit MCRD during breast cancer treatment. Moreover, these data provide further support for the importance of coronary microvascular compromise in the pathophysiology of HFpEF. © 2017 American Heart Association, Inc.

Executive Functions and Attachment Relationships in Children With ADHD: Links to Externalizing/Internalizing Problems, Social Skills, and Negative Mood Regulation.

PubMed

Al-Yagon, Michal; Forte, Dovrat; Avrahami, Lital

2017-09-01

Theoretical models suggest multiple underlying pathways for ADHD and multiple risk factors' co-occurrence as impairing this population's affective, interpersonal, and behavioral adjustment. After comparing groups' executive functioning (EF) difficulties and attachment security with each parent, this study primarily aimed to examine four risk factors (ADHD, child-father attachment, child-mother attachment, EF) as possibly explaining children's socioemotional/behavioral measures (externalizing/internalizing behavior, social skills, negative mood regulation). Participants were 100 children in Grades 5-6 (ages 11-12 years; M=11.45 years, SD=.50): 50 with formally diagnosed ADHD, and 50 with typical development (TD). Instruments were children's self-report measures and teachers' evaluation. Significant group differences emerged on all EF measures and attachment relationships, and most socioemotional/behavioral measures. Findings demonstrated the significant contribution of children's ADHD, parental attachments, and, partially, EF difficulties in explaining children's socioemotional/behavioral adjustment. Children with ADHD, compared to children with TD, reported significantly larger EF deficits and a significantly higher incidence of insecure attachment to the father as well as a lower sense of trust and closeness to the mother. Outcomes highlighted the role of children's four risk factors (ADHD, child-father attachment, child-mother attachment, EF) in explaining their socioemotional/behavioral adjustment. The EF deficits contributed only to intrapersonal maladjustment.

Self-assessed symptoms in chronic heart failure--important information for clinical management.

PubMed

Ekman, Inger; Kjörk, Ewa; Andersson, Bert

2007-04-01

To compare the patients' self-assessment of the severity of their symptoms with a physicians assessment and to evaluate the ability of self-assessed symptoms and ejection fraction (EF) to predict long-term survival in heart failure patients. Patients (n=332) evaluated symptoms using a self-administered functional classification scale (Specific Activity Scale, SAS), which is equivalent to the NYHA scale. EF and NYHA functional class was also recorded. All patients were followed over a 3-year period. Approximately 50% of patients classified themselves into SAS class I. In contrast, the cardiologists classified only 9% of the patients as NYHA class I. In patients with severe left ventricular dysfunction (EF

Electric Field Comparison between Microelectrode Recording and Deep Brain Stimulation Systems—A Simulation Study

PubMed Central

Johansson, Johannes; Wårdell, Karin; Hemm, Simone

2018-01-01

The success of deep brain stimulation (DBS) relies primarily on the localization of the implanted electrode. Its final position can be chosen based on the results of intraoperative microelectrode recording (MER) and stimulation tests. The optimal position often differs from the final one selected for chronic stimulation with the DBS electrode. The aim of the study was to investigate, using finite element method (FEM) modeling and simulations, whether lead design, electrical setup, and operating modes induce differences in electric field (EF) distribution and in consequence, the clinical outcome. Finite element models of a MER system and a chronic DBS lead were developed. Simulations of the EF were performed for homogenous and patient-specific brain models to evaluate the influence of grounding (guide tube vs. stimulator case), parallel MER leads, and non-active DBS contacts. Results showed that the EF is deformed depending on the distance between the guide tube and stimulating contact. Several parallel MER leads and the presence of the non-active DBS contacts influence the EF distribution. The DBS EF volume can cover the intraoperatively produced EF, but can also extend to other anatomical areas. In conclusion, EF deformations between stimulation tests and DBS should be taken into consideration as they can alter the clinical outcome. PMID:29415442

Executive Functioning Skills in Preschool-Age Children With Cochlear Implants

PubMed Central

Beer, Jessica; Kronenberger, William G.; Castellanos, Irina; Colson, Bethany G.; Henning, Shirley C.; Pisoni, David B.

2014-01-01

Purpose The purpose of this study was to determine whether deficits in executive functioning (EF) in children with cochlear implants (CIs) emerge as early as the preschool years. Method Two groups of children ages 3 to 6 years participated in this cross-sectional study: 24 preschoolers who had CIs prior to 36 months of age and 21 preschoolers with normal hearing (NH). All were tested on normed measures of working memory, inhibition-concentration, and organization-integration. Parents completed a normed rating scale of problem behaviors related to EF. Comparisons of EF skills of children with CIs were made to peers with NH and to published nationally representative norms. Results Preschoolers with CIs showed significantly poorer performance on inhibition-concentration and working memory compared with peers with NH and with national norms. No group differences were found in visual memory or organization-integration. When data were controlled for language, differences in performance measures of EF remained, whereas differences in parent-reported problems with EF were no longer significant. Hearing history was generally unrelated to EF. Conclusions This is the first study to demonstrate that EF deficits found in older children with CIs begin to emerge as early as preschool years. The ability to detect these deficits early has important implications for early intervention and habilitation after cochlear implantation. PMID:24686747

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.

The Relationship Between Executive Functions and Language Abilities in Children: A Latent Variables Approach

PubMed Central

Park, Ji Sook; Gangopadhyay, Ishanti; Davidson, Meghan M.; Weismer, Susan Ellis

2017-01-01

Purpose We aimed to outline the latent variables approach for measuring nonverbal executive function (EF) skills in school-age children, and to examine the relationship between nonverbal EF skills and language performance in this age group. Method Seventy-one typically developing children, ages 8 through 11, participated in the study. Three EF components, inhibition, updating, and task-shifting, were each indexed using 2 nonverbal tasks. A latent variables approach was used to extract latent scores that represented each EF construct. Children were also administered common standardized language measures. Multiple regression analyses were conducted to examine the relationship between EF and language skills. Results Nonverbal updating was associated with the Receptive Language Index on the Clinical Evaluation of Language Fundamentals–Fourth Edition (CELF-4). When composites denoting lexical–semantic and syntactic abilities were derived, nonverbal inhibition (but not shifting or updating) was found to predict children's syntactic abilities. These relationships held when the effects of age, IQ, and socioeconomic status were controlled. Conclusions The study makes a methodological contribution by explicating a method by which researchers can use the latent variables approach when measuring EF performance in school-age children. The study makes a theoretical and a clinical contribution by suggesting that language performance may be related to domain-general EFs. PMID:28306755

Executive Function, Self-Regulated Learning, and Reading Comprehension: A Training Study

PubMed Central

Cirino, Paul T.; Miciak, Jeremy; Gerst, Elyssa; Barnes, Marcia A.; Vaughn, Sharon; Child, Amanda; Huston-Warren, Emily

2016-01-01

The goal of this study was to evaluate the extent to which training that emphasizes the process of executive function (EF) and self-regulated learning (SRL) would result in increased reading comprehension; we also evaluated interrelationships of EF, SRL, and reading. We report an experiment (N = 75 fourth graders) that contrasted two researcher-implemented conditions (text-based reading [TB] and text-based reading plus executive function [TB+EF]) to a control. We also evaluated relationships among measures of SRL, EF, and reading. Both the TB and TB+EF groups outperformed the control group for proximal text comprehension (where the topic was similar to that covered in training) and background knowledge related to it, but the two researcher-led groups performed similarly. There were no significant differences for less proximal text, and again similar performance for both TB and TB+EF. Correlations among measures were weak in general, although the pattern was similar to that found in the extant literature. The findings speak to the difficulty in separating these components from those of strong instruction more generally. The relationships of these constructs to reading comprehension will likely be enhanced by more sensitive measurement of EF and reading comprehension, particularly where tied to active treatment components. PMID:26746314

The Relationship Between Executive Functions and Language Abilities in Children: A Latent Variables Approach.

PubMed

Kaushanskaya, Margarita; Park, Ji Sook; Gangopadhyay, Ishanti; Davidson, Meghan M; Weismer, Susan Ellis

2017-04-14

We aimed to outline the latent variables approach for measuring nonverbal executive function (EF) skills in school-age children, and to examine the relationship between nonverbal EF skills and language performance in this age group. Seventy-one typically developing children, ages 8 through 11, participated in the study. Three EF components, inhibition, updating, and task-shifting, were each indexed using 2 nonverbal tasks. A latent variables approach was used to extract latent scores that represented each EF construct. Children were also administered common standardized language measures. Multiple regression analyses were conducted to examine the relationship between EF and language skills. Nonverbal updating was associated with the Receptive Language Index on the Clinical Evaluation of Language Fundamentals-Fourth Edition (CELF-4). When composites denoting lexical-semantic and syntactic abilities were derived, nonverbal inhibition (but not shifting or updating) was found to predict children's syntactic abilities. These relationships held when the effects of age, IQ, and socioeconomic status were controlled. The study makes a methodological contribution by explicating a method by which researchers can use the latent variables approach when measuring EF performance in school-age children. The study makes a theoretical and a clinical contribution by suggesting that language performance may be related to domain-general EFs.

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.

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.

Scaling from instantaneous remote-sensing-based latent heat flux to daytime integrated value with the help of SiB2

NASA Astrophysics Data System (ADS)

Song, Yi; Ma, Mingguo; Li, Xin; Wang, Xufeng

2011-11-01

This research dealt with a daytime integration method with the help of Simple Biosphere Model, Version 2 (SiB2). The field observations employed in this study were obtained at the Yingke (YK) oasis super-station, which includes an Automatic Meteorological Station (AMS), an eddy covariance (EC) system and a Soil Moisture and Temperature Measuring System (SMTMS). This station is located in the Heihe River Basin, the second largest inland river basin in China. The remotely sensed data and field observations employed in this study were derived from Watershed Allied Telemetry Experimental Research (WATER). Daily variations of EF in temporal and spatial scale would be detected by using SiB2. An instantaneous midday EF was calculated based on a remote-sensing-based estimation of surface energy budget. The invariance of daytime EF was examined using the instantaneous midday EF calculated from a remote-sensing-based estimation. The integration was carried out using the constant EF method in the intervals with a steady EF. Intervals with an inconsistent EF were picked up and ET in these intervals was integrated separately. The truth validation of land Surface ET at satellite pixel scale was carried out using the measurement of eddy covariance (EC) system.

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

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.

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.

[The contribution of endogenous vasodilators to the control of glomerular hemodynamics].

PubMed

Arima, S; Ito, S; Abe, K

1994-06-01

Preglomerular afferent (Af-) and postglomerular efferent arterioles (Ef-Arts) are crucial vascular segments in the control of glomerular hemodynamics. However, their vascular reactivity is not fully understood. We examined: 1) their responses to angiotensin II (AII) or norepinephrine (NE), and 2) the possible modulatory roles of nitric oxide (NO) and prostaglandins (PGs) in these responses. Rabbit Af- or Ef-Arts were microperfused in vitro. Ef-Arts were perfused in either the orthograde direction from the distal end of Af-Arts through the glomerulus (OP) or the retrograde direction from its distal end to eliminate the influence of the glomerulus (RP). Although AII and NE constricted both arterioles in a dose-dependent manner, sensitivity to AII was higher in Ef-Arts. AII began to cause significant (P < 0.01) constriction from 10(-9) M (11 +/- 3%, n = 11) in Af-Arts, and from 10(-11) M in Ef-Arts (OP; 11 +/- 4%, n = 9. RP; 10 +/- 2%, n = 5). In addition, both AII and NE produced stronger constriction of Ef-Arts in RP than OP; AII at 10(-8) M or NE at 10(-6) M decreased the diameter by 35 +/- 4% or 25 +/- 4% in OP and 74 +/- 4% or 62 +/- 7% in RP. NO synthesis inhibitor nitro-L-arginine (L-NAME; 10(-4) M) increased the sensitivity of Af-Art to AII without affecting the reactivity of Ef-Art; in L-NAME-pretreated Af-Arts, AII began to cause significant constriction from 10(-10) M (14 +/- 4%, n = 9, P < 0.01). Thus, L-NAME-pretreatment significantly decreased the differences in sensitivity to AII between Af- and Ef-Arts without affecting different vascular responses between OP and RP. Indomethacin (5 x 10(-5) M) significantly augmented the AII- or NE-induced Ef-Art constriction only in OP; AII at 10(-8) M or NE at 10(-6) M decreased the diameter by 72 +/- 5% (n = 8) or 48 +/- 3% (n = 7). Thus, indomethacin-pretreatment markedly diminished the differences in responses between OP and RP. These results suggest that 1) NO modulates AII action only in the Af-Art, contributing to the difference in sensitivity to AII between Af- and Ef-Art, and 2) the glomerulus controls vascular reactivity of the downstream Ef-Art by releasing PGs.

Pattern of executive functioning in adolescents with epilepsy: A multimethod measurement approach.

PubMed

Modi, Avani C; Vannest, Jennifer; Combs, Angela; Turnier, Luke; Wade, Shari L

2018-03-01

Youth with epilepsy demonstrate deficits in executive functioning (EF), the skills necessary for goal-directed behavior (e.g., problem-solving, initiating, monitoring, organization, planning, and working memory). Despite 30-50% of youth with epilepsy demonstrating EF deficits, no extant studies have utilized both performance and questionnaire-based measures to examine the pattern of EF deficits in adolescents with epilepsy. Study aims were to 1) identify the pattern of EF deficits in adolescents with epilepsy and 2) identify which assessment tools are most sensitive to EF deficits in this population (adolescents, ages 13-17, with epilepsy). An exploratory aim was to examine group differences on measures of EF by epilepsy type. Standard performance-based neuropsychological measures (Wechsler Intelligence Scale for Children - Version V or Wechsler Adult Intelligence Scale Working Memory Index-Version IV, Delis Kaplan Executive Functioning System, NIH Toolbox, Test of Everyday Attention for Children) and the Behavior Rating Inventory of Executive Functioning (BRIEF) comprised the multimethod assessment battery. Depending on the measure, 30% of adolescents with epilepsy had deficits in working memory, 17% in cognitive flexibility/problem solving, 6% in inhibition, and 18% in planning/organization. Attention was a significant problem for 15% of adolescents with epilepsy. Correlations among the various EF measures were quite poor. Across various EF domains, results indicated that adolescents with localization-related epilepsy demonstrated better EF skills compared to adolescents with unclassified epilepsy. Overall, our findings suggest that executive functioning deficits are selective and different from those observed in other neurological populations (e.g., attention deficit hyperactivity disorder (ADHD), traumatic brain injury) where problems with self-regulation (i.e., inhibition, planning/organization) are more pronounced. These findings support utilizing multiple measures, including both performance-based neuropsychological tests and parent- and self-reports, to assess executive functioning difficulties in adolescents with epilepsy as they are uniquely sensitive to executive functioning domains. Adolescents with unclassified epilepsy also appear to be at higher risk for EF deficits and thus represent an important group to target for intervention. Copyright © 2018 Elsevier Inc. All rights reserved.

Executive Function and Falls in Older Adults: New Findings from a Five-Year Prospective Study Link Fall Risk to Cognition

PubMed Central

Mirelman, Anat; Herman, Talia; Brozgol, Marina; Dorfman, Moran; Sprecher, Elliot; Schweiger, Avraham; Giladi, Nir; Hausdorff, Jeffrey M.

2012-01-01

Background Recent findings suggest that executive function (EF) plays a critical role in the regulation of gait in older adults, especially under complex and challenging conditions, and that EF deficits may, therefore, contribute to fall risk. The objective of this study was to evaluate if reduced EF is a risk factor for future falls over the course of 5 years of follow-up. Secondary objectives were to assess whether single and dual task walking abilities, an alternative window into EF, were associated with fall risk. Methodology/Main Results We longitudinally followed 256 community-living older adults (age: 76.4±4.5 yrs; 61% women) who were dementia free and had good mobility upon entrance into the study. At baseline, a computerized cognitive battery generated an index of EF, attention, a closely related construct, and other cognitive domains. Gait was assessed during single and dual task conditions. Falls data were collected prospectively using monthly calendars. Negative binomial regression quantified risk ratios (RR). After adjusting for age, gender and the number of falls in the year prior to the study, only the EF index (RR: .85; CI: .74–.98, p = .021), the attention index (RR: .84; CI: .75–.94, p = .002) and dual tasking gait variability (RR: 1.11; CI: 1.01–1.23; p = .027) were associated with future fall risk. Other cognitive function measures were not related to falls. Survival analyses indicated that subjects with the lowest EF scores were more likely to fall sooner and more likely to experience multiple falls during the 66 months of follow-up (p<0.02). Conclusions/Significance These findings demonstrate that among community-living older adults, the risk of future falls was predicted by performance on EF and attention tests conducted 5 years earlier. The present results link falls among older adults to cognition, indicating that screening EF will likely enhance fall risk assessment, and that treatment of EF may reduce fall risk. PMID:22768271

Black carbon, particle number concentration and nitrogen oxide emission factors of random in-use vehicles measured with the on-road chasing method

NASA Astrophysics Data System (ADS)

Ježek, I.; Katrašnik, T.; Westerdahl, D.; Močnik, G.

2015-10-01

The chasing method was used in an on-road measurement campaign, and emission factors (EF) of black carbon (BC), particle number (PN) and nitrogen oxides (NOx) were determined for 139 individual vehicles of different types encountered on the roads. The aggregated results provide EFs for BC, NOx and PN for three vehicle categories: goods vehicles, gasoline and diesel passenger cars. This is the first on-road measurement study where BC EFs of numerous individual diesel cars were determined in real-world driving conditions. We found good agreement between EFs of goods vehicles determined in this campaign and the results of previous studies that used either chasing or remote-sensing measurement techniques. The composition of the sampled car fleet determined from the national vehicle registry information is reflective of Eurostat statistical data on the Slovenian and European vehicle fleet. The median BC EF of diesel and gasoline cars that were in use for less than 5 years decreased by 60 and 47 % from those in use for 5-10 years, respectively; the median NOx and PN EFs of goods vehicles that were in use for less than 5 years decreased from those in use for 5-10 years by 52 and 67 %, respectively. Surprisingly, we found an increase of BC EFs in the newer goods vehicle fleet compared to the 5-10-year old one. The influence of engine maximum power of the measured EFs showed an increase in NOx EF from least to more powerful vehicles with diesel engines. Finally, a disproportionate contribution of high emitters to the total emissions of the measured fleet was found; the top 25 % of emitting diesel cars contributed 63, 47 and 61 % of BC, NOx and PN emissions respectively. With the combination of relatively simple on-road measurements and sophisticated post processing, individual vehicle EF can be determined and useful information about the fleet emissions can be obtained by exactly representing vehicles which contribute disproportionally to vehicle fleet emissions; and monitor how the numerous emission reduction approaches are reflected in on-road driving conditions.

Theory-of-mind in individuals with Alström syndrome is related to executive functions, and verbal ability.

PubMed

Frölander, Hans-Erik; Möller, Claes; Rudner, Mary; Mishra, Sushmit; Marshall, Jan D; Piacentini, Heather; Lyxell, Björn

2015-01-01

This study focuses on cognitive prerequisites for the development of theory-of-mind (ToM), the ability to impute mental states to self and others in young adults with Alström syndrome (AS). AS is a rare and quite recently described recessively inherited ciliopathic disorder which causes progressive sensorineural hearing loss and juvenile blindness, as well as many other organ dysfunctions. Two cognitive abilities were considered; Phonological working memory (WM) and executive functions (EF), both of importance in speech development. Ten individuals (18-37 years) diagnosed with AS, and 20 individuals with no known impairment matched for age, gender, and educational level participated. Sensory functions were measured. Information about motor functions and communicative skills was obtained from responses to a questionnaire. ToM was assessed using Happés strange stories, verbal ability by a vocabulary test, phonological WM by means of an auditory presented non-word serial recall task and EF by tests of updating and inhibition. The AS group performed at a significantly lower level than the control group in both the ToM task and the EF tasks. A significant correlation was observed between recall of non-words and EF in the AS group. Updating, but not inhibition, correlated significantly with verbal ability, whereas both updating and inhibition were significantly related to the ability to initiate and sustain communication. Poorer performance in the ToM and EF tasks were related to language perseverance and motor mannerisms. The AS group displayed a delayed ToM as well as reduced phonological WM, EF, and verbal ability. A significant association between ToM and EF, suggests a compensatory role of EF. This association may reflect the importance of EF to perceive and process input from the social environment when the social interaction is challenged by dual sensory loss. We argue that limitations in EF capacity in individuals with AS, to some extent, may be related to early blindness and progressive hearing loss, but maybe also to gene specific abnormalities.

Theory-of-mind in individuals with Alström syndrome is related to executive functions, and verbal ability

PubMed Central

Frölander, Hans-Erik; Möller, Claes; Rudner, Mary; Mishra, Sushmit; Marshall, Jan D.; Piacentini, Heather; Lyxell, Björn

2015-01-01

Objective: This study focuses on cognitive prerequisites for the development of theory-of-mind (ToM), the ability to impute mental states to self and others in young adults with Alström syndrome (AS). AS is a rare and quite recently described recessively inherited ciliopathic disorder which causes progressive sensorineural hearing loss and juvenile blindness, as well as many other organ dysfunctions. Two cognitive abilities were considered; Phonological working memory (WM) and executive functions (EF), both of importance in speech development. Methods: Ten individuals (18–37 years) diagnosed with AS, and 20 individuals with no known impairment matched for age, gender, and educational level participated. Sensory functions were measured. Information about motor functions and communicative skills was obtained from responses to a questionnaire. ToM was assessed using Happés strange stories, verbal ability by a vocabulary test, phonological WM by means of an auditory presented non-word serial recall task and EF by tests of updating and inhibition. Results: The AS group performed at a significantly lower level than the control group in both the ToM task and the EF tasks. A significant correlation was observed between recall of non-words and EF in the AS group. Updating, but not inhibition, correlated significantly with verbal ability, whereas both updating and inhibition were significantly related to the ability to initiate and sustain communication. Poorer performance in the ToM and EF tasks were related to language perseverance and motor mannerisms. Conclusion: The AS group displayed a delayed ToM as well as reduced phonological WM, EF, and verbal ability. A significant association between ToM and EF, suggests a compensatory role of EF. This association may reflect the importance of EF to perceive and process input from the social environment when the social interaction is challenged by dual sensory loss. We argue that limitations in EF capacity in individuals with AS, to some extent, may be related to early blindness and progressive hearing loss, but maybe also to gene specific abnormalities. PMID:26441796

Left Atrial Remodeling and Atrioventricular Coupling in a Canine Model of Early Heart Failure With Preserved Ejection Fraction

PubMed Central

Zakeri, Rosita; Moulay, Gilles; Chai, Qiang; Ogut, Ozgur; Hussain, Saad; Takahama, Hiroyuki; Lu, Tong; Wang, Xiao-Li; Linke, Wolfgang A.; Lee, Hon-Chi; Redfield, Margaret M.

2016-01-01

Background Left atrial (LA) compliance and contractility influence left ventricular (LV) stroke volume. We hypothesized that diminished LA compliance and contractile function occur early during development of heart failure with preserved ejection fraction (HFpEF) and impair overall cardiac performance. Method and Results Cardiac magnetic resonance imaging, echocardiography, LV and LA pressure-volume studies, and tissue analyses were performed in a model of early HFpEF (elderly dogs, renal wrap-induced hypertension, exogenous aldosterone; n=9) and young control dogs (sham surgery; n=13). Early HFpEF was associated with LA enlargement, cardiomyocyte hypertrophy and enhanced LA contractile function (median active emptying fraction 16% [95% CI 13–24] vs 12[10–14]%, p=0.008; end-systolic pressure-volume relationship slope 2.4[1.9–3.2]mmHg/mL HFpEF vs 1.5[1.2–2.2]mmHg/mL controls, p=0.01). However, atrioventricular coupling was impaired and the curvilinear LA end-reservoir pressure-volume relationship was shifted upward/leftward in HFpEF (LA stiffness constant, βLA, 0.16[0.11–0.18]mmHg/mL vs 0.06[0.04–0.10]mmHg/mL controls, p=0.002) indicating reduced LA compliance. Impaired atrioventricular coupling and lower LA compliance correlated with lower LV stroke volume. Total fibrosis and titin isoform composition were similar between groups, however titin was hyperphosphorylated in HFpEF and correlated with βLA. LA microvascular reactivity was diminished in HFpEF versus controls. LA microvascular density tended to be lower in HFpEF and inversely correlated with βLA. Conclusions In early-stage hypertensive HFpEF, LA cardiomyocyte hypertrophy, titin hyperphosphorylation and microvascular dysfunction occur in association with increased systolic and diastolic LA chamber stiffness, impaired atrioventricular coupling and decreased LV stroke volume. These data indicate that maladaptive LA remodeling occurs early during HFpEF development, supporting a concept of global myocardial remodeling. PMID:27758811

Parent ratings of executive function in young preschool children with symptoms of attention-deficit/-hyperactivity disorder.

PubMed

Skogan, Annette Holth; Zeiner, Pål; Egeland, Jens; Urnes, Anne-Grethe; Reichborn-Kjennerud, Ted; Aase, Heidi

2015-04-15

Recent research has demonstrated that deficits in basic, self-regulatory processes, or executive function (EF), may be related to symptoms of attention-deficit/hyperactivity disorder (ADHD) already during the preschool period. As the majority of studies investigating these relations in young children have been based primarily on clinically administered tests, it is not clear how early symptoms of ADHD may be related to observations of EF in an everyday context. The preschool version of the Behavior Rating Inventory of Executive Function (BRIEF-P) was developed to provide information about EF through observable, behavioral manifestations of self-regulation, and is the most commonly used rating scale for EF assessment in children. Relations between symptoms of ADHD reported in the Preschool Age Psychiatric Assessment interview (PAPA), and EF as measured by the BRIEF-P (parent form), were investigated in a large, nonreferred sample of preschool children (37-47 months, n = 1134) recruited from the Norwegian Mother and Child Cohort Study (MoBa) at the Norwegian Institute of Public Health. The inventory's discriminative ability was examined in a subsample consisting of children who met the diagnostic criteria for either ADHD, oppositional defiant disorder (ODD) or anxiety disorder, and typically developing controls (n = 308). The four groups were also compared with regard to patterns of EF difficulties reported in the BRIEF-P. Of the five BRIEF-P subscales, Inhibit and Working Memory were the two most closely related to ADHD symptoms, together explaining 38.5% of the variance in PAPA symptom ratings. Based on their scores on the Inhibit and Working Memory subscales (combined), 86.4% of the children in the ADHD and TD groups were correctly classified. ADHD symptoms were associated with more severe difficulties across EF domains, and a different EF profile in comparison to children with other symptoms (anxiety, ODD) and to typically developing controls. Early symptoms of ADHD were linked to parent-reported difficulties primarily within inhibition and working memory, suggesting that deficiencies within these two EF domains characterize early forms of ADHD. Our findings support the clinical utility of the BRIEF-P as a measure of EF in young preschool children with symptoms of ADHD.

18F-EF5 PET-based Imageable Hypoxia Predicts Local Recurrence in Tumors Treated With Highly Conformal Radiation Therapy.

PubMed

Qian, Yushen; Von Eyben, Rie; Liu, Yufei; Chin, Frederick T; Miao, Zheng; Apte, Sandeep; Carter, Justin N; Binkley, Michael S; Pollom, Erqi L; Harris, Jeremy P; Prionas, Nicolas D; Kissel, Madelyn; Simmons, Amanda; Diehn, Maximilian; Shultz, David B; Brown, J Martin; Maxim, Peter G; Koong, Albert C; Graves, Edward E; Loo, Billy W

2018-04-18

Tumor hypoxia contributes to radiation resistance. A noninvasive assessment of tumor hypoxia would be valuable for prognostication and possibly selection for hypoxia-targeted therapies. 18 F-pentafluorinated etanidazole ( 18 F-EF5) is a nitroimidazole derivative that has demonstrated promise as a positron emission tomography (PET) hypoxia imaging agent in preclinical and clinical studies. However, correlation of imageable hypoxia by 18 F-EF5 PET with clinical outcomes after radiation therapy remains limited. Our study prospectively enrolled 28 patients undergoing radiation therapy for localized lung or other tumors to receive pretreatment 18 F-EF5 PET imaging. Depending on the level of 18 F-EF5 tumor uptake, patients underwent functional manipulation of tumor oxygenation with either carbogen breathing or oral dichloroacetate followed by repeated 18 F-EF5 PET. The hypoxic subvolume of tumor was defined as the proportion of tumor voxels exhibiting higher 18 F-EF5 uptake than the 95th percentile of 18 F-EF5 uptake in the blood pool. Tumors with a hypoxic subvolume ≥ 10% on baseline 18 F-EF5 PET imaging were classified as hypoxic by imaging. A Cox model was used to assess the correlation between imageable hypoxia and clinical outcomes after treatment. At baseline, imageable hypoxia was demonstrated in 43% of all patients (12 of 28), including 6 of 16 patients with early-stage non-small cell lung cancer treated with stereotactic ablative radiation therapy and 6 of 12 patients with other cancers. Carbogen breathing was significantly associated with decreased imageable hypoxia, while dichloroacetate did not result in a significant change under our protocol conditions. Tumors with imageable hypoxia had a higher incidence of local recurrence at 12 months (30%) than those without (0%) (P < .01). Noninvasive hypoxia imaging by 18 F-EF5 PET identified imageable hypoxia in about 40% of tumors in our study population. Local tumor recurrence after highly conformal radiation therapy was higher in tumors with imageable hypoxia. Copyright © 2018 Elsevier Inc. All rights reserved.

Early executive function deficit in preterm children and its association with neurodevelopmental disorders in childhood: a literature review.

PubMed

Sun, Jing; Buys, Nicholas

2012-01-01

The purpose of this study is to examine the association of deficits of executive function (EF) and neurodevelopmental disorders in preterm children and the potential of assessing EF in infants as means of early identification. EF refers to a collection of related but somewhat discrete abilities, the main ones being working memory, inhibition, and planning. There is a general consensus that EF governs goal-directed behavior that requires holding those plans or programs on-line until executed, inhibiting irrelevant action and planning a sequence of actions. EF plays an essential role in cognitive development and is vital to individual social and intellectual success. Most researchers believe in the coordination and integrate cognitive-perceptual processes in relation to time and space, thus regulating higher-order cognitive processes, such as problem solving, reasoning, logical and flexible thinking, and decision-making. The importance of the maturation of the frontal lobe, particularly the prefrontal cortex, to the development of EF in childhood has been emphasized. Therefore, any abnormal development in the prefrontal lobes of infants and children could be expected to result in significant deficits in cognitive functioning. As this is a late-maturing part of the brain, various neurodevelopmental disorders, such as autism spectrum disorders, attention deficit hyperactivity disorder, language disorders, and schizophrenia, as well as acquired disorders of the right brain (and traumatic brain injury) impair EF, and the prefrontal cortex may be particularly susceptible to delayed development in these populations. The deficits of EF in infants are persistent into childhood and related to neurodevelopmental disorders in childhood and adolescence.

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.

Hydrogen-Deuterium Exchange Mass Spectrometry Reveals Calcium Binding Properties and Allosteric Regulation of Downstream Regulatory Element Antagonist Modulator (DREAM).

PubMed

Zhang, Jun; Li, Jing; Craig, Theodore A; Kumar, Rajiv; Gross, Michael L

2017-07-18

Downstream regulatory element antagonist modulator (DREAM) is an EF-hand Ca 2+ -binding protein that also binds to a specific DNA sequence, downstream regulatory elements (DRE), and thereby regulates transcription in a calcium-dependent fashion. DREAM binds to DRE in the absence of Ca 2+ but detaches from DRE under Ca 2+ stimulation, allowing gene expression. The Ca 2+ binding properties of DREAM and the consequences of the binding on protein structure are key to understanding the function of DREAM. Here we describe the application of hydrogen-deuterium exchange mass spectrometry (HDX-MS) and site-directed mutagenesis to investigate the Ca 2+ binding properties and the subsequent conformational changes of full-length DREAM. We demonstrate that all EF-hands undergo large conformation changes upon calcium binding even though the EF-1 hand is not capable of binding to Ca 2+ . Moreover, EF-2 is a lower-affinity site compared to EF-3 and -4 hands. Comparison of HDX profiles between wild-type DREAM and two EF-1 mutated constructs illustrates that the conformational changes in the EF-1 hand are induced by long-range structural interactions. HDX analyses also reveal a conformational change in an N-terminal leucine-charged residue-rich domain (LCD) remote from Ca 2+ -binding EF-hands. This LCD domain is responsible for the direct interaction between DREAM and cAMP response element-binding protein (CREB) and regulates the recruitment of the co-activator, CREB-binding protein. These long-range interactions strongly suggest how conformational changes transmit the Ca 2+ signal to CREB-mediated gene transcription.

Elongation factor Tu resistant to kirromycin in an Esherichia coli mutant altered in both tuf genes

PubMed Central

Fischer, Eckhard; Wolf, Heinz; Hantke, Klaus; Parmeggiani, Andrea

1977-01-01

A mutant of Escherichia coli is described that displays kirromycin resistance in a cell-free system by virtue of an altered elongation factor Tu (EF-Tu). In poly(U)-directed poly(Phe) synthesis the kirromycin resistance of the crystallized enzyme ranged between a factor of 80 and 700, depending on temperature. Similarly, kirromycin-induced EF-Tu GTPase activity uncoupled from ribosomes and aminoacyl-tRNA required correspondingly higher concentrations of the antibiotic. Resistance of EF-Tu to kirromycin is a consequence of a modified enzyme structure as indicated by its altered fingerprint pattern. P1 transduction experiments showed that the kirromycin-resistant EF-Tu is coded by an altered tufB gene (tufB1). The known existence of two genes coding for EF-Tu would interfere with the recognition of a mutant altered in only one of those genes, if the mutation were recessive. Because kirromycin blocks EF-Tu release from the ribosome, kirromycin sensitivity is dominant, as shown by the failure of a mixed EF-Tu population to express resistance in vitro. Therefore, phenotypic expression of kirromycin resistance in vivo appears to be only possible if the EF-Tu mutant lacks an active tufA gene, a property likely to be inherited from the parental D22 strain. The observations that introduction of a tufA+ region makes the resistant strain sensitive to the antibiotic and that transduction of tufB1 into a recipient other than E. coli D22 yields kirromycin-sensitive progeny support these conclusions. Images PMID:337296

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

Enteral Feeding Set Handling Techniques.

PubMed

Lyman, Beth; Williams, Maria; Sollazzo, Janet; Hayden, Ashley; Hensley, Pam; Dai, Hongying; Roberts, Cristine

2017-04-01

Enteral nutrition therapy is common practice in pediatric clinical settings. Often patients will receive a pump-assisted bolus feeding over 30 minutes several times per day using the same enteral feeding set (EFS). This study aims to determine the safest and most efficacious way to handle the EFS between feedings. Three EFS handling techniques were compared through simulation for bacterial growth, nursing time, and supply costs: (1) rinsing the EFS with sterile water after each feeding, (2) refrigerating the EFS between feedings, and (3) using a ready-to-hang (RTH) product maintained at room temperature. Cultures were obtained at baseline, hour 12, and hour 21 of the 24-hour cycle. A time-in-motion analysis was conducted and reported in average number of seconds to complete each procedure. Supply costs were inventoried for 1 month comparing the actual usage to our estimated usage. Of 1080 cultures obtained, the overall bacterial growth rate was 8.7%. The rinse and refrigeration techniques displayed similar bacterial growth (11.4% vs 10.3%, P = .63). The RTH technique displayed the least bacterial growth of any method (4.4%, P = .002). The time analysis in minutes showed the rinse method was the most time-consuming (44.8 ± 2.7) vs refrigeration (35.8 ± 2.6) and RTH (31.08 ± 0.6) ( P < .0001). All 3 EFS handling techniques displayed low bacterial growth. RTH was superior in bacterial growth, nursing time, and supply costs. Since not all pediatric formulas are available in RTH, we conclude that refrigerating the EFS between uses is the next most efficacious method for handling the EFS between bolus feeds.

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.

Enantiomer fractions of chlordane components in sediment from U.S. Geological Survey sites in lakes and rivers

USGS Publications Warehouse

Ulrich, E.M.; Foreman, W.T.; Van Metre, P.C.; Wilson, J.T.; Rounds, S.A.

2009-01-01

Spatial, temporal, and sediment-type trends in enantiomer signatures were evaluated for cis- and trans-chlordane (CC, TC) in archived core, suspended, and surficial-sediment samples from six lake, reservoir, and river sites across the United States. The enantiomer fractions (EFs) measured in these samples are in good agreement with those reported for sediment, soil, and air samples in previous studies. The chlordane EFs were generally close to the racemic value of 0.5, with CC values ranging from 0.493 to 0.527 (usually >0.5) and TC values from 0.463 to 0.53 (usually <0.5). EF changes with core depth were detected for TC and CC in some cores, with the most non-racemic values near the top of the core. Surficial and suspended sediments generally have EF values similar to the top core layers but are often more non-racemic, indicating that enantioselective degradation is occurring before soils are eroded and deposited into bottom sediments. We hypothesize that rapid losses (desorption or degradation) from suspended sediments of the more bioavailable chlordane fraction during transport and initial deposition could explain the apparent shift to more racemic EF values in surficial and top core sediments. Near racemic CC and TC in the core profiles suggest minimal alteration of chlordane from biotic degradation, unless it is via non-enantioselective processes. EF values for the heptachlor degradate, heptachlor epoxide (HEPX), determined in surficial sediments from one location only were always non-racemic (EF ??? 0.66), were indicative of substantial biotic processing, and followed reported EF trends.

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

Hemodynamic responses to small muscle mass exercise in heart failure patients with reduced ejection fraction

PubMed Central

Barrett-O'Keefe, Zachary; Lee, Joshua F.; Berbert, Amanda; Witman, Melissa A. H.; Nativi-Nicolau, Jose; Stehlik, Josef; Richardson, Russell S.

2014-01-01

To better understand the mechanisms responsible for exercise intolerance in heart failure with reduced ejection fraction (HFrEF), the present study sought to evaluate the hemodynamic responses to small muscle mass exercise in this cohort. In 25 HFrEF patients (64 ± 2 yr) and 17 healthy, age-matched control subjects (64 ± 2 yr), mean arterial pressure (MAP), cardiac output (CO), and limb blood flow were examined during graded static-intermittent handgrip (HG) and dynamic single-leg knee-extensor (KE) exercise. During HG exercise, MAP increased similarly between groups. CO increased significantly (+1.3 ± 0.3 l/min) in the control group, but it remained unchanged across workloads in HFrEF patients. At 15% maximum voluntary contraction (MVC), forearm blood flow was similar between groups, while HFrEF patients exhibited an attenuated increase at the two highest intensities compared with controls, with the greatest difference at the highest workload (352 ± 22 vs. 492 ± 48 ml/min, HFrEF vs. control, 45% MVC). During KE exercise, MAP and CO increased similarly across work rates between groups. However, HFrEF patients exhibited a diminished leg hyperemic response across all work rates, with the most substantial decrement at the highest intensity (1,842 ± 64 vs. 2,675 ± 81 ml/min; HFrEF vs. control, 15 W). Together, these findings indicate a marked attenuation in exercising limb perfusion attributable to impairments in peripheral vasodilatory capacity during both arm and leg exercise in patients with HFrEF, which likely plays a role in limiting exercise capacity in this patient population. PMID:25260608

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