Ecotoxicological threshold levels of a mixture of herbicides (atrazine, diuron and metolachlor) in freshwater microcosms

Twelve indoor, plankton-dominated, freshwater microcosms (600 l) were used to study the effect of a mixture of herbicides on structural and functional aspects of these ecosystems. The EC50, 72 h values of the most susceptible standard test alga Selenastrum capricornutum (EC50, atrazine=54 μg l−1, EC50, diuron=15 μg l−1, EC50, metolachlor=56 μg l−1) were used as a starting point for the dosage applied in the microcosms (dosages: 0, 0.01, 0.03, 0.1, 0.3, 1× EC50). The microcosms were exposed to chronic levels for 28 days and subsequently monitored for 4 more weeks. The following effects were observed: (1) direct effects became apparent from an initial drop in photosynthesis efficiency, pH and oxygen concentration and a decrease in the abundance of several phytoplankton taxa at the 0.3 × EC50 treatment level and higher. (2) Fourteen days post application an increase in the abundance of several phytoplankton taxa (Chlamydomonas sp. and Stephanodiscus/Cyclotella) was observed; oxygen concentrations recovered while alkalinity, conductivity and total inorganic nitrogen were elevated. (3) Effects on fauna were minor. Daphnia galeata showed a decreasing trend and the cyclopoid copepods an increasing trend at the end of the experiment. Multivariate statistical analyses demonstrated no effects of any treatment level on the zooplankton community. Effects were reported for the phytoplankton community at dose levels of 0.3 × EC50 and higher. On species level the most sensitive taxon was Chlorophyceae coccales. For this taxon a NOEC at the dose level of 0.01 × EC50 was calculated. This effect however was relatively small in magnitude and merely based on an increase in numbers in the control and lowest treated microcosms rather than a decrease in numbers in all other treatments. The standards based on algal toxicity data, as adopted by the Uniform Principles, consist of a safety factors of 0.1 to be multiplied with the EC50. The NOEC of coccales was lower than 0.1 × EC50. All other observed variables in this aquatic ecosystem were sufficiently protected against the mixture of herbicides by the safety factor as proposed in the Uniform Principles. This revised version was published online in August 2006 with corrections to the Cover Date.     

Uprooting and Burial of Invasive Alien Plants: A New Tool in Coastal Restoration?

Invasive alien plants are a problem for conservation management, and control of these species can be combined with habitat restoration. Subsoil burial of uprooted plants is a new method of mechanical control, which might be suitable in disturbed habitats. The method was tested in Rosa rugosa (Japanese Rose), an invasive shrub in north‐western Europe with negative effects on coastal biodiversity. Two months after uprooting and burial in dunes of north‐eastern Denmark, 89% of the 58 shrubs resprouted from roots and rhizomes; on average 41 resprouts per shrub. Resprout density was twice as high at former shrub margins compared with the center; resprouts were taller and originated from more superficial soil layers at the margin than in the center. Resprouting was negatively correlated with fragment depth, and no resprouts were observed from greater than 15 cm depth. The number of resprouts increased with fragment dry mass (0.5–168.5 g). After 18 months with harrowing the species was still resprouting, flowering, and fruiting, albeit with no difference between shrub margin and center. Resprouts were taller (26 cm) and coverage was higher (0–4%) after two compared with three times harrowing, whereas no difference was found in cover of native dune species (1–5%). The results show that even small fragments of R. rugosa resprout, and that resprouting persists despite repeated harrowing. Thus, careful subsoil burial of all fragments is necessary, special attention should be paid to the shrub margin, and follow‐up treatments are needed. The effectiveness of the burial method is discussed for restoration of coastal dunes.     

The Cx26-G45E mutation displays increased hemichannel activity in a mouse model of the lethal form of keratitis-ichthyosis-deafness syndrome

Mutations in the GJB2 gene (Cx26) cause deafness in humans. Most are loss-of-function mutations and cause nonsyndromic deafness. Some mutations produce a gain of function and cause syndromic deafness associated with skin disorders, such as keratitis-ichthyosis-deafness syndrome (KIDS). Cx26-G45E is a lethal mutation linked to KIDS that forms constitutively active connexin hemichannels. The pathomechanism(s) by which mutant Cx26 hemichannels perturb normal epidermal cornification are poorly understood. We created an animal model for KIDS by generating an inducible transgenic mouse expressing Cx26-G45E in keratinocytes. Cx26-G45E mice displayed reduced viability, hyperkeratosis, scaling, skin folds, and hair loss. Histopathology included hyperplasia, acanthosis, papillomatosis, increased cell size, and osteal plugging. These abnormalities correlated with human KIDS pathology and were associated with increased hemichannel currents in transgenic keratinocytes. These results confirm the pathogenic nature of the G45E mutation and provide a new model for studying the role of aberrant connexin hemichannels in epidermal differentiation and inherited connexin disorders.     

Adults with Down syndrome have reduced cardiac response after light exercise testing

Objective

Physical fitness is reduced in adults with Down syndrome (DS). The present study was conducted to elucidate the exercise response in adults with DS.

Design

Case controlled before-after trial.

Setting

Residential centre for people with intellectual disabilities.

Participants

96 Adults with DS, 25 non-DS adults with an intellectual disability, 33 controls.

Interventions

Echocardiography to exclude heart defects and to measure cardiac index (CI) in the supine position, supine position with raised legs, and following ten knee bends.

Main outcome measure

Exercise testing

Results

At rest, mean CI was not significantly different between persons with DS and controls (2.3 vs. 2.4 l/min/m², p = 0.3). However, mean CI after exercise was significantly lower in DS (2.9 vs. 3.7 l/min/m², p < 0.001) and mean CI increase from rest to exercise was more than 50% lower in DS. On the contrary, CI after exercise was similar among controls and non-DS adults with an intellectual disability. Significantly lower stroke volumes in DS were found with insufficient heart rate response.

Conclusions

CI at rest was similar in adults with DS and controls; however persons with DS have a diminished cardiac response to exercise. Stroke volumes were significantly lower in DS during exercise and a compensated heightened heart rate was absent.     

Prophylactic veno-arterial extracorporeal membrane oxygenation in patients undergoing high-risk percutaneous coronary intervention

Netherlands Heart Journal - Complex high-risk percutaneous coronary intervention (PCI) is challenging and frequently accompanied by haemodynamic instability. Veno-arterial extracorporeal membrane...     

A Systematic Review of the Level of Evidence in Economic Evaluations of Medical Devices: The Example of Vertebroplasty and Kyphoplasty

Context

Economic evaluations are far less frequently reported for medical devices than for drugs. In addition, little is known about the quality of existing economic evaluations, particularly for innovative devices, such as those used in vertebroplasty and kyphoplasty.

Objective

To assess the level of evidence provided by the available economic evaluations for vertebroplasty and kyphoplasty.

Data Sources

A systematic review of articles in English or French listed in the MEDLINE, PASCAL, COCHRANE and National Health Service Economic Evaluation databases, with limits on publication date (up to the date of the review, March 2014).

Study Selection

We included only economic evaluations of vertebroplasty or kyphoplasty. Editorial and methodological articles were excluded.

Data Extraction

Data were extracted from articles by two authors working independently and using two analysis grids to measure the quality of economic evaluations.

Data Synthesis

Twenty-one studies met our inclusion criteria. All were published between 2008 and 2014. Eighteen (86%) were full economic evaluations. Cost-effectiveness analysis (CEA) was the most frequent type of economic evaluation, and was present in 11 (52%) studies. Only three CEAs complied fully with the British Medical Journal checklist. The quality of the data sources used in the 21 studies was high, but the CEAs conforming to methodological guidelines did not use high-quality data sources for all components of the analysis.

Conclusions

This systematic review shows that the level of evidence in economic evaluations of vertebroplasty and kyphoplasty is low, despite the recent publication of a large number of studies. This finding highlights the challenges to be faced to improve the quality of economic evaluations of medical devices.     

Construction and characterization of two infectious molecular clones of encephalomyocarditis virus.

We constructed and characterized two infectious molecular clones of encephalomyocarditis (EMC) virus. Both constructs, pDL and pDA, were assembled from five overlapping cDNA clones derived from the diabetogenic variant of EMC virus (EMC-D) and from two synthetic oligonucleotide cartridges. pDA contained a single point mutation at position 1720 within the "puff" region of capsid protein 1AB that was derived from the nondiabetogenic variant of EMC virus (EMC-B). This point mutation resulted in an amino acid substitution of arginine (EMC-B) for lysine (EMC-D). Our construction illustrates two novel findings: (i) that the problem of stably cloning long poly(C) tracts of EMC virus can be circumvented by the use of a shortened, synthetic, poly(dC-dG) oligonucleotide cartridge, and (ii) that a single point mutation in the puff region of the capsid protein 1AB leads to change in its electrophoretic mobility and to a change in the plaque size of recombinant virus.     

Veno-arterial extracorporeal membrane oxygenation in addition to primary PCI in patients presenting with ST-elevation myocardial infarction

Introduction

Primary percutaneous coronary intervention (pPCI) in ST-elevation myocardial infarction (STEMI) can cause great haemodynamic instability. Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) can provide haemodynamic support in patients with STEMI but data on outcome and complications are scarce.

Methods

An in-hospital registry was conducted enrolling all patients receiving VA-ECMO. Patients were analysed for medical history, mortality, neurological outcome, complications and coronary artery disease.

Results

Between 2011 and 2016, 12 patients underwent pPCI for STEMI and received VA-ECMO for haemodynamic support. The majority of the patients were male (10/12) with a median age of 63 (47–75) years and 4 of the 12 patients had a history of coronary artery disease. A cardiac arrest was witnessed in 11 patients. The left coronary artery was compromised in 8 patients and 4 had right coronary artery disease. All patients were in Killip class IV. Survival to discharge was 67% (8/12), 1?year survival was 42% (5/12), 2 patients have not yet reached the 1?year survival point but are still alive and 1 patient died within a year after discharge. All-cause mortality was 42% (5/12) of which mortality on ECMO was 33% (4/12). Patient-related complications occurred in 6 of the 12 patients: 1 patient suffered major neurological impairment, 2 patients suffered haemorrhage at the cannula site, 2 patients had limb ischaemia and 1 patient had a haemorrhage elsewhere. There were no VA-ECMO hardware malfunctions.

Conclusion

VA-ECMO in pPCI for STEMI has a high survival rate and neurological outcome is good, even when the patient is admitted with a cardiac arrest.

     

Clonal variants of differentiated P19 embryonal carcinoma cells exhibit epidermal growth factor receptor kinase activity

Differentiated clonal cell lines were isolated from pluripotent P19 embryonal carcinoma (EC) cells treated as aggregates with retinoic acid. Two were characterized in detail. The lines differ in morphology, proliferation rate, the production of plasminogen activator, and in their mitogenic response to insulin but both produce extracellular matrix proteins and can be serially passaged over extended periods, in contrast to differentiated derivatives of many other EC lines. Further, both lines have receptors for and respond mitogenically to epidermal growth factor (EGF). Endogenous phosphorylation of several proteins, including the EGF receptor (150 kDa) and a 38-kDa protein, is induced by EGF in membranes isolated from these cells. Preincubation of membranes with EGF renders them able to catalyze phosphorylation of tyrosine residues in exogenously added peptide substrates. High voltage electrophoresis confirmed the tyrosine specificity of the phosphorylation on the 150- and 38-kDa bands. By contrast, similar experiments in undifferentiated cells showed that intact P19 EC neither bind nor respond to EGF mitogenically and EGF induces no changes in phosphorylation in isolated membranes.