In vitro metacestodicidal activities of genistein and other isoflavones against Echinococcus multilocularis and Echinococcus granulosus

Echinococcus multilocularis and Echinococcus granulosus metacestode infections in humans cause alveolar echinococcosis and cystic echinococcosis, respectively, in which metacestode development in visceral organs often results in particular organ failure. Further, cystic hydatidosis in farm animals causes severe economic losses. Although benzimidazole derivatives such as mebendazole and albendazole are being used as therapeutic agents, there is often no complete recovery after treatment. Hence, in searching for novel treatment options, we examined the in vitro efficacies of a number of isoflavones against Echinococcus metacestodes and protoscoleces. The most prominent isoflavone, genistein, exhibits significant metacestodicidal activity in vitro. However, genistein binds to the estrogen receptor and can thus induce estrogenic effects, which is a major concern during long-term chemotherapy. We have therefore investigated the activities of a number of synthetic genistein derivatives carrying a modified estrogen receptor binding site. One of these, Rm6423, induced dramatic breakdown of the structural integrity of the metacestode germinal layer of both species within 5 to 7 days of in vitro treatment. Further, examination of the culture medium revealed increased leakage of parasite proteins into the medium during treatment, but zymography demonstrated a decrease in the activity of metalloproteases. Moreover, two of the genistein derivatives, Rm6423 and Rm6426, induced considerable damage in E. granulosus protoscoleces, rendering them nonviable. These findings demonstrate that synthetic isoflavones exhibit distinct in vitro effects on Echinococcus metacestodes and protoscoleces, which could potentially be exploited further for the development of novel chemotherapeutical tools against larval-stage Echinococcus infection.

Leakage of the arterial prosthesis of an Impella RVAD

Seromas occurring around a vascular graft are a rare complication. We report a life-threatening plasma leakage that occurred through the polytetrafluoroethylene vascular prosthesis of an Impella right ventricular assist device (Impella RD [Impella Cardiosystems GmbH, Aachen, Germany]) implanted in a 62-year-old patient with acute right ventricular failure after cardiac transplantation. The leakage became progressively massive. Weaning the patient from the right ventricular assist device was not possible. The prosthesis was thus wrapped within a pericardial patch to contain the leakage. Three days later the patient could be successfully weaned and the pump was removed. The clinical evolution was favorable.

Losses of chromosome arms 4q, 8p, 13q and gain of 8q are correlated with increasing chromosomal instability in hepatocellular carcinoma

OBJECTIVE: Chromosomal instability is a key feature in hepatocellular carcinoma (HCC). Array comparative genomic hybridization (aCGH) revealed recurring structural aberrations, whereas fluorescence in situ hybridization (FISH) indicated an increasing number of numerical aberrations in dedifferentiating HCC. Therefore, we examined whether there was a correlation between structural and numerical aberrations of chromosomal instability in HCC. METHODS AND RESULTS: 27 HCC (5 well, 10 moderately, 12 lower differentiated) already cytogenetically characterized by aCGH were analyzed. FISH analysis using probes for chromosomes 1, 3, 7, 8 and 17 revealed 1.46-4.24 signals/nucleus, which correlated with the histological grade (well vs. moderately,p < 0.0003; moderately vs. lower, p < 0.004). The number of chromosomes to each other was stable with exceptions only seen for chromosome 8. Loss of 4q and 13q, respectively, were correlated with the number of aberrations detected by aCGH (p < 0.001, p < 0.005; Mann-Whitney test). Loss of 4q and gain of 8q were correlated with an increasing number of numerical aberrations detected by FISH (p < 0.020, p < 0.031). Loss of 8p was correlated with the number of structural imbalances seen in aCGH (p < 0.048), but not with the number of numerical changes seen in FISH. CONCLUSION: We found that losses of 4q, 8p and 13q were closely correlated with an increasing number of aberrations detected by aCGH, whereas a loss of 4q and a gain of 8q were also observed in the context of polyploidization, the cytogenetic correlate of morphological dedifferentiation.

Vaginal voiding: a common cause of daytime urinary leakage in girls

STUDY OBJECTIVE: To estimate the frequency of vaginal voiding as the cause of daytime urinary leakage in girls, and to study the effect of instructions intended to alleviate the problem. SETTING: Girls with vaginal voiding were identified in a group of girls referred because of daytime urinary leakage. They were evaluated by a noninvasive screening protocol. Girls with vaginal voiding were instructed on how to achieve better toilet habits. PARTICIPANTS: Twelve girls with vaginal voiding. RESULTS: Vaginal voiding was found in 12 of 39 girls with daytime urinary leakage. Their age ranged between 8.5 and 13.9 years. They all had history of small leakage immediately after voiding. A body mass index greater than the corresponding 85th percentile was noted in 5 girls, and labial fusion was noted in 2 girls. The complaint disappeared in 10 girls and improved in the remaining 2 girls after instructions on how to achieve better toilet habits. CONCLUSIONS: Vaginal voiding is common in girls. It occurs in girls at risk of overweight, in girls with labial fusion, and in girls adopting a hairpin posture while sitting on the toilet. The diagnosis is obtained by an adequate history. Proper voiding instructions resolve the problem.

Contrast-enhanced MR myelography in spontaneous intracranial hypotension: description of an artefact imitating CSF leakage

In contrast-enhanced (CE) MR myelography, hyperintense signal outside the intrathecal space in T1-weighted sequences with spectral presaturation inversion recovery (SPIR) is usually considered to be due to CSF leakage. We retrospectively investigated a hyperintense signal at the apex of the lung appearing in this sequence in patients with SIH (n = 5), CSF rhinorrhoea (n = 2), lumbar spine surgery (n = 1) and in control subjects (n = 6). Intrathecal application of contrast agent was performed in all patients before MR examination, but not in the control group. The reproducible signal increase was investigated with other fat suppression techniques and MR spectroscopy. All patients and controls showed strongly hyperintense signal at the apex of the lungs imitating CSF leakage into paraspinal tissue. This signal increase was identified as an artefact, caused by spectroscopically proven shift and broadening of water and lipid resonances (1-2 ppm) in this anatomical region. Only patients with SIH showed additional focal enhancement along the spinal nerve roots and/or in the spinal epidural space. In conclusion CE MR myelography with spectral selective fat suppression shows a reproducible cervicothoracic artefact, imitating CSF leakage. Selective water excitation technique as well as periradicular and epidural contrast collections may be helpful to discriminate between real pathological findings and artefacts.

Tropical cyclone-related socio-economic losses in the western North Pacific region

The western North Pacific (WNP) is the area of the world most frequently affected by tropical cyclones (TCs). However, little is known about the socio-economic impacts of TCs in this region, probably because of the limited relevant loss data. Here, loss data from Munich RE's NatCatSERVICE database is used, a high-quality and widely consulted database of natural disasters. In the country-level loss normalisation technique we apply, the original loss data are normalised to present-day exposure levels by using the respective country's nominal gross domestic product at purchasing power parity as a proxy for wealth. The main focus of our study is on the question of whether the decadal-scale TC variability observed in the Northwest Pacific region in recent decades can be shown to manifest itself economically in an associated variability in losses. It is shown that since 1980 the frequency of TC-related loss events in the WNP exhibited, apart from seasonal and interannual variations, interdecadal variability with a period of about 22 yr – driven primarily by corresponding variations of Northwest Pacific TCs. Compared to the long-term mean, the number of loss events was found to be higher (lower) by 14% (9%) in the positive (negative) phase of the decadal-scale WNP TC frequency variability. This was identified for the period 1980–2008 by applying a wavelet analysis technique. It was also possible to demonstrate the same low-frequency variability in normalised direct economic losses from TCs in the WNP region. The identification of possible physical mechanisms responsible for the observed decadal-scale Northwest Pacific TC variability will be the subject of future research, even if suggestions have already been made in earlier studies.

Clinical signs of deformed wing virus infection are predictive markers for honey bee colony losses.

The ectoparasitic mite Varroa destructor acting as a virus vector constitutes a central mechanism for losses of managed honey bee, Apis mellifera, colonies. This creates demand for an easy, accurate and cheap diagnostic tool to estimate the impact of viruliferous mites in the field. Here we evaluated whether the clinical signs of the ubiquitous and mite-transmitted deformed wing virus (DWV) can be predictive markers of winter losses. In fall and winter 2007/2008, A.m. carnica workers with apparent wing deformities were counted daily in traps installed on 29 queenright colonies. The data show that colonies which later died had a significantly higher proportion of workers with wing deformities than did those which survived. There was a significant positive correlation between V. destructor infestation levels and the number of workers displaying DWV clinical signs, further supporting the mite's impact on virus infections at the colony level. A logistic regression model suggests that colony size, the number of workers with wing deformities and V. destructor infestation levels constitute predictive markers for winter colony losses in this order of importance and ease of evaluation.

Legal Implications of the Use of Export Taxes in Addressing Carbon Leakage: Competing Border Adjustment Measures

The prevailing uncertainties about the future of the post-Kyoto international legal framework for climate mitigation and adaptation increase the likelihood of unilateral trade interventions that aim to address climate policy concerns, as exemplified by the controversial European Union initiative to include the aviation industry in its emissions trading system. The emerging literature suggests that border carbon adjustment (BCA) measures imposed by importing countries would lead to substantial legal complications in relation to World Trade Organization law and hence to possible trade disputes. Lack of legal clarity on BCAs is exacerbated by potential counter or pre-emptive export restrictions that exporting countries might impose on carbon-intensive products. In this context, this paper investigates the interface between legal and welfare implications of competing unilateral BCA measures. It argues that carbon export taxes will be an inevitable part of the future climate change regime in the absence of a multilateral agreement. It also describes the channels through which competing BCAs may lead to trade conflicts and political complications as a result of their distributional and welfare impacts at the domestic and global levels.

Hohlraum Target for Overcoming Refractive Losses in Plasma X-ray Lasers

Refractive losses in laser-produced plasmas used as gain media are caused by electron density gradients, and limit the energy transport range. The pump pulse is thus deflected from the high-gain region and the short wavelength laser signal also steers away, causing loss of collimation. A Hohlraum used as a target makes the plasma homogeneous and can mitigate refractive losses by means of wave-guiding. A computational study combining a hydrodynamics code and an atomic physics code is presented, which includes a ray-tracing modeling based on the eikonal theory of the trajectory equation. This study presents gain calculations based on population inversion produced by free-electron collisions exciting bound electrons into metastable levels in the 3d94d1(J = 0) → 3d94p1(J = 1) transition of Ni-like Sn. Further, the Hohlraum suggests a dramatic enhancement of the conversion efficiency of collisionally excited x-ray lasing for Ni-like Sn.