Dynamics of Diplostomum spathaceum infection in snail hosts at a fish farm

Ecologically sustainable disease prevention in intensive monocultures, such as fish farming, is based on the knowledge of the ecology of parasites and the identification of the key proportion of host populations for parasite life cycles. In this paper, we examined the life cycle dynamics of the pathogenic trematode Diplostomum spathaceum at a fish farm during a period of 1 year, focusing especially on the pattern of infection in the snail host (Lymnaea stagnalis) population, which is the key phase in the parasite life cycle regarding preventative actions. We found that (1) the infection varied seasonally in snails, being highest in late August; (2) the prevalence of infection and the proportion of individuals releasing cercariae were strongly dependent on snail size; (3) the parasite over-wintered in snails as dormant sporocysts and 4) the mortality of infected snails was not likely to differ from uninfected individuals during winter. Furthermore, the seasonality and development of the infection in the snails corresponded to the pattern of infection observed in the tracer rainbow trout caged in the farm area. This pattern of infection also indicated strong spatiality of the infection, probably because of differences in the size of the snail population between the ponds rather than differences in the prevalence of infection. Overall, present results indicate a possibility for late-summer outbreaks of D. spathaceum, but also that snail prevention at farms could be conducted more efficiently by considering both size-dependent infection and the timing of cercarial release.     

Eight-Row Multidetector Computed Tomography Coronary Angiography Evaluation of Significant Coronary Artery Disease in Patients with Severe Aortic Valve Stenosis

Background The aim of this study was to evaluate whether 8-row multidetector computed tomography coronary angiography (MDCT-CA) could replace invasive conventional coronary angiography (CCA) in patients with acquired severe aortic valve stenosis (AS). Coronary artery disease (CAD) diagnosis should be obtained with a noninvasive method in patients with AS undergoing valvular replacement. We evaluated the diagnostic accuracy of MDCT-CA in detecting high-grade (≥50%) stenoses in the main coronary arteries in patients with AS.Methods Twenty-three patients with acquired severe AS underwent both CCA and MDCT-CA. We calculated the total and volumetric calcium scores and evaluated the image quality of each coronary segment as assessable or nonassessable for stenosis. The images of the arteries were evaluated for the occurrence of artifacts and the presence of high-grade stenoses (≥50%) by visual estimation and comparison with that of CCA.Results Of the 322 segments screened 224 were assessable for stenosis. Heavy calcium load rendered 37 (38%) of the 98 coronary segments nonassessable.Compared to CCA, MDCT-CA had a sensitivity of 63%, a specificity of 96%, a positive predictive value of 52%, and a negative predictive value of 98% for ≥50% stenoses in the main coronary arteries.Conclusions Eight-row MDCT-CA revealed a low sensitivity in detecting significant coronary artery disease in patients with acquired severe AS. High calcium burden decreased visualization of the lumen and complicated most often a correct assessment. In this patient group, CCA should still remain the primary pre-surgical test to rule out coronary lesions requiring revascularization.     

Usefulness of T-wave loop and QRS complex loop to predict mortality after acute myocardial infarction

The aim of the study was to assess whether parameters based on the T-wave loop and QRS loop predict mortality, and cardiac mortality in particular, during follow-up of consecutive survivors of acute myocardial infarction (AMI). Patients with AMI (n = 437), treated according to contemporary guidelines, underwent digital high-resolution electrocardiography in orthogonal Frank leads (X, Y, Z) 5 to 14 days after AMI. Several T-wave and QRS loop parameters, such as the width and height of the loops and their ratio, T-wave loop dispersion (TWLD), QRS loop dispersion, and co-sine of the angle between the main vectors of the T-wave and QRS loops (TCRT), were calculated using a custom-made software package. During an average follow-up period of 43 +/- 14 months, 53 patients (12%) died. Of these 53 deaths, 35 were cardiac. TWLD and TCRT were the T-wave loop/QRS loop parameters that best predicted for cardiac mortality on univariate comparison (35.4 +/- 5.62 vs 32.8 +/- 2.87 for TWLD, p < 0.001 and -0.135 +/- 0.665 vs -0.657 +/- 0.518 for TCRT, p < 0.001, alive vs cardiac death, respectively). After adjustment for clinical risk markers in the Cox regression analysis, TWLD still significantly predicted for cardiac mortality (p < 0.05); however, TCRT had lost its predictive power. TWLD did not have significant univariate or multivariate association with noncardiac mortality. In conclusion, TWLD that describes the shape of the T-wave loop is a specific predictor of cardiac death and independent of the clinical risk markers in the current treatment era of patients with AMI.     

Effect of surface chemistry of porous silicon microparticles on glucagon-like peptide-1 (GLP-1) loading,release and biological activity

Recently, mesoporous silicon (PSi) microparticles have been shown to extend the duration of action of peptides, reducing the need for frequent injections. Glucagon-like peptide 1 (GLP-1) is a potential novel treatment for type 2 diabetes.     

Tocopherols and tocotrienols plasma levels are associated with cognitive impairment

Vitamin E includes 8 natural compounds (4 tocopherols, 4 tocotrienols) with potential neuroprotective activity. α-Tocopherol has mainly been investigated in relation to cognitive impairment. We examined the relation of all plasma vitamin E forms and markers of vitamin E damage (α-tocopherylquinone, 5-nitro-γ-tocopherol) to mild cognitive impairment (MCI) and Alzheimer's disease (AD). Within the AddNeuroMed-Project, plasma tocopherols, tocotrienols, α-tocopherylquinone, and 5-nitro-γ-tocopherol were assessed in 168 AD cases, 166 MCI, and 187 cognitively normal (CN) people. Compared with cognitively normal subjects, AD and MCI had lower levels of total tocopherols, total tocotrienols, and total vitamin E. In multivariable-polytomous-logistic regression analysis, both MCI and AD cases had 85% lower odds to be in the highest tertile of total tocopherols and total vitamin E, and they were, respectively, 92% and 94% less likely to be in the highest tertile of total tocotrienols than the lowest tertile. Further, both disorders were associated with increased vitamin E damage. Low plasma tocopherols and tocotrienols levels are associated with increased odds of MCI and AD.     

Genetic polymorphism of cytochrome P450 2D6 determines oestrogen receptor activity of the major infertility drug clomiphene via its active metabolites

Clomiphene citrate is the most used drug for the treatment of female infertility, a common condition in western societies and developing countries. Despite dose escalation, up to 30% of women do not respond. Since clomiphene shares structural similarities with tamoxifen, which is predominantly bioactivated by the polymorphic cytochrome P450 (CYP) 2D6, we systematically explored clomiphene metabolism and action in vitro and in vivo by pharmacogenetic, -kinetic and -dynamic investigations. Human liver microsomes were incubated with clomiphene citrate and nine metabolites were identified by mass spectrometry and tested at the oestrogen receptor for their antagonistic capacity. (E)-4-hydroxyclomiphene and (E)-4-hydroxy-N-desethylclomiphene showed strongest inhibition of the oestrogen receptor activity with 50% inhibitory concentrations of 2.5 and 1.4 nm, respectively. CYP2D6 has been identified as the major enzyme involved in their formation using recombinant CYP450 isozymes as confirmed by inhibition experiments with CYP monoclonal antibodies. We correlated the CYP2D6 genotype of 30 human liver donors with the microsomal formation rate of active metabolites and observed a strong gene-dose effect. A healthy female volunteer study confirmed our in vitro data that the CYP2D6 polymorphism substantially determines the formation of the active clomiphene metabolites. Comparison of the C(max) of (E)-4-hydroxyclomiphene and (E)-4-hydroxy-N-desethylclomiphene showed 8 and 12 times lower concentrations in subjects with non-functional CYP2D6 alleles. Our results highlight (E)-4-hydroxyclomiphene and (E)-4-hydroxy-N-desethylclomiphene as the active clomiphene metabolites, the formation of which strongly depends on the polymorphic CYP2D6 enzyme. Our data provide first evidence of a biological rationale for the variability in the response to clomiphene treatment.     

Late gadolinium enhanced cardiovascular magnetic resonance of lamin A/C gene mutation related dilated cardiomyopathy

Background

The purpose of this study was to identify early features of lamin A/C gene mutation related dilated cardiomyopathy (DCM) with cardiovascular magnetic resonance (CMR). We characterise myocardial and functional findings in carriers of lamin A/C mutation to facilitate the recognition of these patients using this method. We also investigated the connection between myocardial fibrosis and conduction abnormalities.

Methods

Seventeen lamin A/C mutation carriers underwent CMR. Late gadolinium enhancement (LGE) and cine images were performed to evaluate myocardial fibrosis, regional wall motion, longitudinal myocardial function, global function and volumetry of both ventricles. The location, pattern and extent of enhancement in the left ventricle (LV) myocardium were visually estimated.

Results

Patients had LV myocardial fibrosis in 88% of cases. Segmental wall motion abnormalities correlated strongly with the degree of enhancement. Myocardial enhancement was associated with conduction abnormalities. Sixty-nine percent of our asymptomatic or mildly symptomatic patients showed mild ventricular dilatation, systolic failure or both in global ventricular analysis. Decreased longitudinal systolic LV function was observed in 53% of patients.

Conclusions

Cardiac conduction abnormalities, mildly dilated LV and depressed systolic dysfunction are common in DCM caused by a lamin A/C gene mutation. However, other cardiac diseases may produce similar symptoms. CMR is an accurate tool to determine the typical cardiac involvement in lamin A/C cardiomyopathy and may help to initiate early treatment in this malignant familiar form of DCM.     

Identifying emerging trends in recreational drug use; outcomes from the Psychonaut Web Mapping Project

Background

This paper presents the outcomes of the 2-year European Union funded Psychonaut Web Mapping Project which aimed at developing and implementing an integrated web mapping system to promptly identify and learn about novel psychoactive substances (NPS; “legal highs”) through the regular monitoring of the Internet.

Methods

More than 200 discussion forums, social media, online shops, websites and other Internet resources (e.g. YouTube, eBay, Google, Google Insight) have been extensively and regularly monitored in 7 European countries (UK, Finland, Norway, Belgium, Germany, Italy and Spain) for emerging trends of NPS throughout the period of the study.

Results

Key online resources have been identified as “leading edge” which have provided accurate and timely information on novel emerging compounds. In total more than 400 substances/products have been recorded. NPS have been noted online before reaching wider audiences.

Discussion

Although a high number of novel psychoactive substances have been identified in the 2-year duration of the project, not all have become trends that needed public health response. Conversely, new recreational drug phenomena such as “spice drugs,” mephedrone and naphyrone were all identified as emerging trends in forums and websites. In addition, it has been possible for the first time to collate detailed information on these and several more compounds even though no or limited scientific publications were available. It is therefore recommended that these monitoring activities are to be continued, that more countries, researchers and health professionals are involved, and that the findings are widely shared with all the relevant agencies, health professionals and future research projects.Implications, advantages and limitations of using the Internet as primary source for identifying emerging trends are also discussed.