Antiarrhythmic drug therapy among patients presenting to emergency department with symptomatic atrial fibrillation - a prospective nationwide cohort

Background: Atrial fibrillation (AF) is a common arrhythmia that causes numerous visits to emergency departments (ED). The aim of the FinFib2 study was to evaluate whether treatment of patients with AF in ED is consistent with the contemporary European Society of Cardiology (ESC) management guidelines. Here we report the results of antiarrhythmic drug therapy (AAD) in ED. Methods: All patients within the two-week study period whose primary reason for the ED visit was symptomatic AF were included into this prospective multicentre study. Comprehensive data on factors contributing to the treatment of AF were collected, including a data of previous use of ADDs, and changes made for them during a visit in ED. Results: The study population consisted of 1013 consecutive patients (mean age 70 +/- 13 years, 47.6% female). The mean European Heart Rhythm Association (EHRA) symptom score was 2.2 +/- 0.8. Rhythm control strategy was opt for 498 (63.8%) and 140 (64.5%) patients with previously and newly diagnosed AF, respectively. In patients with previously diagnosed AF the most frequently used AAD was a beta blocker (80.9%). Prior use of class I (11.4%) and III (9.1%) AADs as well as start or adjustment of their dosage (7.4%) were uncommon. Most of the patients with newly diagnosed AF were prescribed a beta blocker (71.0%) or a calcium channel antagonist (24.0%), and only two of them received class I or class III AADs. Conclusions: Our data demonstrated that in patients presenting to the ED with recurrent symptomatic AF and aimed for rhythm control strategy, the use of class I and class III AADs was rare despite ESC guideline recommendations. It is possible that early adaptation of a more aggressive rhythm control strategy might improve a quality of life for symptomatic patients and alleviate the ED burden associated with AF. Beta blockers were used by majority of patients as rate control therapy both in rate and rhythm control groups.Peer reviewe

Large Lateral Photovoltaic Effect in Metal-(Oxide-) Semiconductor Structures

The lateral photovoltaic effect (LPE) can be used in position-sensitive detectors to detect very small displacements due to its output of lateral photovoltage changing linearly with light spot position. In this review, we will summarize some of our recent works regarding LPE in metal-semiconductor and metal-oxide-semiconductor structures, and give a theoretical model of LPE in these two structures

Identification of Metabolites of Trenbolone Acetate in Androgenic Runoff from a Beef Feedlot

Little is known concerning the potential ecological effects of hormonally active substances associated with discharges from animal feeding operations. Trenbolone acetate is a synthetic anabolic steroid that is widely used in the United States to promote growth of beef cattle. Metabolites of trenbolone acetate include the stereoisomers 17α- and 17β-trenbolone, both of which are stable in animal wastes and are relatively potent androgens in fish and mammals. Our purpose in this study was to evaluate the occurrence of 17α- and 17β-trenbolone in a beef cattle feedlot discharge and in river water upstream and downstream from the discharge. In conjunction with that effort, we measured in vitro androgenic activity of the discharge using CV-1 cells that had been transiently cotransfected with human androgen receptor and reporter gene constructs. Samples were collected on nine different occasions during 2002 and 2003. Whole-water samples from the discharge caused a significant androgenic response in the CV-1 cells and contained detectable concentrations of 17α- and 17β-trenbolone. Further work is needed to ascertain the degree to which synthetic androgens such as trenbolone contribute to androgenic activity of feedlot discharges

Direct Effects, Compensation, and Recovery in Female Fathead Minnows Exposed to a Model Aromatase Inhibitor

BackgroundSeveral chemicals in the environment have the potential to inhibit aromatase, an enzyme critical to estrogen synthesis.ObjectivesThe objective of this study was to provide a detailed characterization of molecular and biochemical responses of female fathead minnows to a model aromatase inhibitor, fadrozole (FAD).MethodsFish were exposed via water to 0, 3, or 30 microg FAD/L for 8 days and then held in clean water for 8 days, with samples collected at four time points during each 8-day period. We quantified ex vivo steroid production, plasma steroids, and plasma vitellogenin (Vtg) concentrations and analyzed relative transcript abundance of 10 key regulatory genes in ovaries and 3 in pituitary tissue by real-time polymerase chain reaction.ResultsEx vivo 17beta-estradiol (E2) production and plasma E2 and Vtg concentrations were significantly reduced after a single day of exposure to 3 microg or 30 microg FAD/L. However, plasma E2 concentrations recovered by the eighth day of exposure in the 3-microg/L group and within 1 day of cessation of exposure in the 30-microg/L group, indicating concentration- and time-dependent physiologic compensation and recovery. Concentration-dependent increases in transcripts coding for aromatase (A isoform), cytochrome P450 side-chain cleavage, steroidogenic acute regulatory protein, and follicle-stimulating hormone receptor all coincided with increased E2 production and recovery of plasma E2 concentrations.ConclusionsResults of this research highlight the need to consider compensation/adaptation and recovery when developing and interpreting short-term bioassays or biomarkers or when trying to predict the effects of chemical exposures based on mode of action

Anti-androgens act jointly in suppressing spiggin concentrations in androgen-primed female three-spined sticklebacks - Prediction of combined effects by concentration addition

This is the post-print version of the final paper published in Aquatic Toxicology. The published article is available from the link below. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. Copyright @ 2013 Elsevier B.V.Increasing attention is being directed at the role played by anti-androgenic chemicals in endocrine disruption of wildlife within the aquatic environment. The co-occurrence of multiple contaminants with anti-androgenic activity highlights a need for the predictive assessment of combined effects, but information about anti-androgen mixture effects on wildlife is lacking. This study evaluated the suitability of the androgenised female stickleback screen (AFSS), in which inhibition of androgen-induced spiggin production provides a quantitative assessment of anti-androgenic activity, for predicting the effect of a four component mixture of anti-androgens. The anti-androgenic activity of four known anti-androgens (vinclozolin, fenitrothion, flutamide, linuron) was evaluated from individual concentration-response data and used to design a mixture containing each chemical at equipotent concentrations. Across a 100-fold concentration range, a concentration addition approach was used to predict the response of fish to the mixture. Two studies were conducted independently at each of two laboratories. By using a novel method to adjust for differences between nominal and measured concentrations, good agreement was obtained between the actual outcome of the mixture exposure and the predicted outcome. This demonstrated for the first time that androgen receptor antagonists act in concert in an additive fashion in fish and that existing mixture methodology is effective in predicting the outcome, based on concentration-response data for individual chemicals. The sensitivity range of the AFSS assay lies within the range of anti-androgenicity reported in rivers across many locations internationally. The approach taken in our study lays the foundations for understanding how androgen receptor antagonists work together in fish and is essential in informing risk assessment methods for complex anti-androgenic mixtures in the aquatic environment.European Commission and Natural Environment Research Council

Embryonic exposure to the fungicide vinclozolin causes virilization of females and alteration of progesterone receptor expression in vivo: an experimental study in mice

BACKGROUND: Vinclozolin is a fungicide that has been reported to have anti-androgenic effects in rats. We have found that in utero exposure to natural or synthetic progesterones can induce hypospadias in mice, and that the synthetic progesterone medroxyprogesterone acetate (MPA) feminizes male and virilizes female genital tubercles. In the current work, we selected a relatively low dose of vinclozolin to examine its in utero effects on the development of the genital tubercle, both at the morphological and molecular levels. METHODS: We gave pregnant dams vinclozolin by oral gavage from gestational days 13 through 17. We assessed the fetal genital tubercles from exposed fetuses at E19 to determine location of the urethral opening. After determination of gonadal sex, either genital tubercles were harvested for mRNA quantitation, or urethras were injected with a plastic resin for casting. We analyzed quantified mRNA levels between treated and untreated animals for mRNA levels of estrogen receptors α and β, progesterone receptor, and androgen receptor using nonparametric tests or ANOVA. To determine effects on urethral length (males have long urethras compared to females), we measured the lengths of the casts and performed ANOVA analysis on these data. RESULTS: Our morphological results indicated that vinclozolin has morphological effects similar to those of MPA, feminizing males (hypospadias) and masculinizing females (longer urethras). Because these results reflected our MPA results, we investigated the effects of in utero vinclozolin exposure on the mRNA expression levels of androgen, estrogen α and β, and progesterone receptors. At the molecular level, vinclozolin down-regulated estrogen receptor α mRNA in females and up-regulated progesterone receptor mRNA. Vinclozolin-exposed males exhibited up-regulated estrogen receptor α and progesterone receptor mRNA, effects we have also seen with exposure to the synthetic estrogen, ethinyl estradiol. CONCLUSION: The results suggest that vinclozolin virilizes females and directly or indirectly affects progesterone receptor expression. It also affects estrogen receptor expression in a sex-based manner. We found no in vivo effect of vinclozolin on androgen receptor expression. We propose that vinclozolin, which has been designated an anti-androgen, may also exert its effects by involving additional steroid-signaling pathways

Satellite observations for detecting and forecasting sea-ice conditions: A summary of advances made in the SPICES Project by the EU's Horizon 2020 Programme

The detection, monitoring, and forecasting of sea-ice conditions, including their extremes, is very important for ship navigation and offshore activities, and for monitoring of sea-ice processes and trends. We summarize here recent advances in the monitoring of sea-ice conditions and their extremes from satellite data as well as the development of sea-ice seasonal forecasting capabilities. Our results are the outcome of the three-year (2015-2018) SPICES (Space-borne Observations for Detecting and Forecasting Sea-Ice Cover Extremes) project funded by the EU's Horizon 2020 programme. New SPICES sea-ice products include pancake ice thickness and degree of ice ridging based on synthetic aperture radar imagery, Arctic sea-ice volume and export derived from multisensor satellite data, and melt pond fraction and sea-ice concentration using Soil Moisture and Ocean Salinity (SMOS) radiometer data. Forecasts of July sea-ice conditions from initial conditions in May showed substantial improvement in some Arctic regions after adding sea-ice thickness (SIT) data to the model initialization. The SIT initialization also improved seasonal forecasts for years with extremely low summer sea-ice extent. New SPICES sea-ice products have a demonstrable level of maturity, and with a reasonable amount of further work they can be integrated into various operational sea-ice services

Environmental chemicals active as human antiandrogens do not activate a stickleback androgen receptor but enhance a feminising effect of oestrogen in roach

AbstractSexual disruption is reported in wild fish populations living in freshwaters receiving discharges of wastewater treatment works (WwTW) effluents and is associated primarily with the feminisation of males by exposure to oestrogenic chemicals. Antiandrogens could also contribute to the feminisation of male fish, but there are far less data supporting this hypothesis and almost nothing is known for the effects of oestrogens in combination with antiandrogens in fish. We conducted a series of in vivo exposures in two fish species to investigate the potency on reproductive-relevant endpoints of the antiandrogenic antimicrobials triclosan (TCS), chlorophene (CP) and dichlorophene (DCP) and the resin, abietic acid (AbA), all found widely in WwTW effluents. We also undertook exposures with a mixture of antiandrogens and a mixture of antiandrogens in combination with the oestrogen 17α-ethinyloestradiol (EE2). In stickleback (Gasterosteus aculeatus), DCP showed a tendency to reduce spiggin induction in females androgenised by dihydrotestosterone (DHT), but these findings were not conclusive. In roach (Rutilus rutilus), exposures to DCP (178 days), or a mixture of TCS, CP and AbA (185 days), or to the model antiandrogen flutamide (FL, 178 days) had no effect on gonadal sex ratio or on the development of the reproductive ducts. Exposure to EE2 (1.5ng/L, 185 days) induced feminisation of the ducts in 17% of the males and in the mixture of antiandrogens (TCS, CP, AbA) in combination with EE2, almost all (96%) of the males had a feminised reproductive ducts. In stickleback androgen receptor (ARα and ARβ) transactivation assays, the model antiandrogens, FL and procymidone inhibited 11-ketotestosterone (11-KT) induced receptor activation, but none of the human antiandrogens, TCS, CP, DCP and AbA had an effect. These data indicate that antimicrobial antiandrogens in combination can contribute to the feminisation process in exposed males, but they do not appear to act through the androgen receptor in fish