Agua Salud alphavirus infection, dissemination and transmission in Aedes aegypti mosquitoes

Mosquitoes are competent vectors for many important arthropod-borne viruses (arboviruses). In addition to arboviruses, insect-specific viruses (ISV) have also been discovered in mosquitoes. ISVs are viruses that replicate in insect hosts but are unable to infect and replicate in vertebrates. They have been shown to interfere with arbovirus replication in some cases. Despite the increase in studies on ISV–arbovirus interactions, ISV interactions with their hosts and how they are maintained in nature are still not well understood. In the present study, we investigated the infection and dissemination of the Agua Salud alphavirus (ASALV) in the important mosquito vector Aedes aegypti through different infection routes (per oral infection, intrathoracic injection) and its transmission. We show here that ASALV infects the female Ae. aegypti and replicates when mosquitoes are infected intrathoracically or orally. ASALV disseminated to different tissues, including the midgut, salivary glands and ovaries. However, we observed a higher virus load in the brain than in the salivary glands and carcasses, suggesting a tropism towards brain tissues. Our results show that ASALV is transmitted horizontally during adult and larval stages, although we did not observe vertical transmission. Understanding ISV infection and dissemination dynamics in Ae. aegypti and their transmission routes could help the use of ISVs as an arbovirus control strategy in the future

Developing a new national MDMA policy:Results of a multi-decision multi-criterion decision analysis

BACKGROUND: Ecstasy (3,4-methylenedioxymethamphetamine (MDMA)) has a relatively low harm and low dependence liability but is scheduled on List I of the Dutch Opium Act (‘hard drugs’). Concerns surrounding increasing MDMA-related criminality coupled with the possibly inappropriate scheduling of MDMA initiated a debate to revise the current Dutch ecstasy policy. METHODS: An interdisciplinary group of 18 experts on health, social harms and drug criminality and law enforcement reformulated the science-based Dutch MDMA policy using multi-decision multi-criterion decision analysis (MD-MCDA). The experts collectively formulated policy instruments and rated their effects on 25 outcome criteria, including health, criminality, law enforcement and financial issues, thematically grouped in six clusters. RESULTS: The experts scored the effect of 22 policy instruments, each with between two and seven different mutually exclusive options, on 25 outcome criteria. The optimal policy model was defined by the set of 22 policy instrument options which gave the highest overall score on the 25 outcome criteria. Implementation of the optimal policy model, including regulated MDMA sales, decreases health harms, MDMA-related organised crime and environmental damage, as well as increases state revenues and quality of MDMA products and user information. This model was slightly modified to increase its political feasibility. Sensitivity analyses showed that the outcomes of the current MD-MCDA are robust and independent of variability in weight values. CONCLUSION: The present results provide a feasible and realistic set of policy instrument options to revise the legislation towards a rational MDMA policy that is likely to reduce both adverse (public) health risks and MDMA-related criminal burden

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Is maternal smoking during pregnancy a risk factor for Hyperkinetic disorder? - Findings from a sibling design.

International audienceBackground Studies have consistently shown that pregnancy smoking is associated with twice the risk of hyperactivity/inattention problems in the offspring. An association of this magnitude may make behavioural difficulties one of the most important health effects related to smoking during pregnancy. However, social and genetic confounders may fully or partially account for these findings. Methods A cohort including all singletons born in Finland January 1, 1987 through December 31, 2001 was followed until January 1, 2006 based on linkage of national registers. Data were available for 97% (N=868 449) of the population. We followed singleton children of smoking and non-smoking mothers until they had an ICD-10 diagnosis of Hyperkinetic disorder (HKD) or to the end of the observation period. We used sibling-matched Cox regression analyses to control for social and genetic confounding. Results We found a much smaller association between exposure to maternal smoking during pregnancy and risk of HKD in children using the sibling-matched analysis (HR=1.20, 95% CI 0.97-1.49) than was observed in the entire cohort (HR 2.01, 95% CI: 1.90-2.12). Conclusions Our findings suggest that the strong association found in previous studies may be due to time stable familial factors, such as environmental and genetic factors. If smoking is a causal factor, the effect is small and less important than previous studies indicate

The development of a rational national MDMA policy and its relevance for psychiatry

Achtergrond: MDMA (ecstasy) is een relatief veilige drug en induceert weinig afhankelijkheid, maar staat desondanks samen met andere harddrugs op lijst I van de Nederlandse Opiumwet. Bezorgdheid over de aan MDMA gerelateerde criminaliteit, het aantal gezondheidsincidenten en de mogelijk onterechte plaatsing van MDMA op lijst I hebben geleid tot een voortdurend debat over het huidige Nederlandse ecstasybeleid.Doel: Ontwikkeling van een rationeel MDMA-beleid waarbij men rekening houdt met alle aspecten gerelateerd aan de productie, verkoop en gebruik van MDMA.Methode: Een interdisciplinaire groep van 18 experts formuleerde een wetenschappelijk onderbouwd MDMA-beleid door de verwachte effecten van 95 beleidsopties op 25 uitkomsten te beoordelen, waaronder gezondheid, criminaliteit, rechtshandhaving en financiën. Het optimale beleidsmodel werd gevormd door een combinatie van 22 beleidsopties met de hoogste totaalscore op alle 25 uitkomsten. Resultaat Het optimale beleidsmodel bestond uit een vorm van gereguleerde productie en verkoop van MDMA, beter kwaliteitsbeheer van ecstasypillen en intensievere bestrijding van de MDMA-gerelateerde georganiseerde criminaliteit. Een dergelijk beleid zou leiden tot een kleine toename in de prevalentie van ecstasygebruik, maar met minder gezondheidsschade, minder MDMA-gerelateerde misdaad en minder milieuschade. Om de praktische uitvoerbaarheid en de politieke haalbaarheid te vergroten werd het optimale model enigszins aangepast.Conclusie: Het ontwikkelde optimale model biedt een politiek en maatschappelijk haalbare set van beleidsinstrumentopties, waarmee men plaatsing van MDMA op lijst I kan herzien, wat de schade van MDMA voor gebruikers en de samenleving kan verminderen. Voor de psychiatrie betekent het bevordering van therapeutisch onderzoek en minder hinder door nodeloze stigmatisering bij de behandeling van patiënten.</div

Antibiotic Breakdown by Susceptible Bacteria Enhances the Establishment of beta-Lactam Resistant Mutants

For a better understanding of the evolution of antibiotic resistance, it is imperative to study the factors that determine the initial establishment of mutant resistance alleles. In addition to the antibiotic concentration, the establishment of resistance alleles may be affected by interactions with the surrounding susceptible cells from which they derive, for instance via the release of nutrients or removal of the antibiotic. Here, we investigate the effects of social interactions with surrounding susceptible cells on the establishment of Escherichia coli mutants with increasing beta-lactamase activity (i.e., the capacity to hydrolyze beta-lactam antibiotics) from single cells under the exposure of the antibiotic cefotaxime (CTX) on agar plates. We find that relatively susceptible cells, expressing a beta-lactamase with very low antibiotic-hydrolyzing activity, increase the probability of mutant cells to survive and outgrow into colonies due to the active breakdown of the antibiotic. However, the rate of breakdown by the susceptible strain is much higher than expected based on its low enzymatic activity. A detailed theoretical model suggests that this observation may be explained by cell filamentation causing delayed lysis. While susceptible cells may hamper the spread of higher-resistant beta-lactamase mutants at relatively high frequencies, our findings show that they promote their initial establishment.</p

The development of a rational national MDMA policy and its relevance for psychiatry

Achtergrond: MDMA (ecstasy) is een relatief veilige drug en induceert weinig afhankelijkheid, maar staat desondanks samen met andere harddrugs op lijst I van de Nederlandse Opiumwet. Bezorgdheid over de aan MDMA gerelateerde criminaliteit, het aantal gezondheidsincidenten en de mogelijk onterechte plaatsing van MDMA op lijst I hebben geleid tot een voortdurend debat over het huidige Nederlandse ecstasybeleid.Doel: Ontwikkeling van een rationeel MDMA-beleid waarbij men rekening houdt met alle aspecten gerelateerd aan de productie, verkoop en gebruik van MDMA.Methode: Een interdisciplinaire groep van 18 experts formuleerde een wetenschappelijk onderbouwd MDMA-beleid door de verwachte effecten van 95 beleidsopties op 25 uitkomsten te beoordelen, waaronder gezondheid, criminaliteit, rechtshandhaving en financiën. Het optimale beleidsmodel werd gevormd door een combinatie van 22 beleidsopties met de hoogste totaalscore op alle 25 uitkomsten. Resultaat Het optimale beleidsmodel bestond uit een vorm van gereguleerde productie en verkoop van MDMA, beter kwaliteitsbeheer van ecstasypillen en intensievere bestrijding van de MDMA-gerelateerde georganiseerde criminaliteit. Een dergelijk beleid zou leiden tot een kleine toename in de prevalentie van ecstasygebruik, maar met minder gezondheidsschade, minder MDMA-gerelateerde misdaad en minder milieuschade. Om de praktische uitvoerbaarheid en de politieke haalbaarheid te vergroten werd het optimale model enigszins aangepast.Conclusie: Het ontwikkelde optimale model biedt een politiek en maatschappelijk haalbare set van beleidsinstrumentopties, waarmee men plaatsing van MDMA op lijst I kan herzien, wat de schade van MDMA voor gebruikers en de samenleving kan verminderen. Voor de psychiatrie betekent het bevordering van therapeutisch onderzoek en minder hinder door nodeloze stigmatisering bij de behandeling van patiënten.</div

Ecological models in support of regulatory risk assessments of pesticides:Developing a strategy for the future

This brief communication reports on the main findings of the LEMTOX workshop, held from 9 to 12 September 2007, at the Helmholtz Centre for Environmental Research (UFZ) in Leipzig, Germany. The workshop brought together a diverse group of stakeholders from academia, regulatory authorities, contract research organizations, and industry, representing Europe, the United States, and Asia, to discuss the role of ecological modeling in risk assessments of pesticides, particularly under the European regulatory framework. The following questions were addressed: What are the potential benefits of using ecological models in pesticide registration and risk assessment? What obstacles prevent ecological modeling from being used routinely in regulatory submissions? What actions are needed to overcome the identified obstacles? What recommendations should be made to ensure good modeling practice in this context? The workshop focused exclusively on population models, and discussion was focused on those categories of population models that link effects on individuals (e.g., survival, growth, reproduction, behavior) to effects on population dynamics. The workshop participants concluded that the overall benefits of ecological modeling are that it could bring more ecology into ecological risk assessment, and it could provide an excellent tool for exploring the importance of, and interactions among, ecological complexities. However, there are a number of challenges that need to be overcome before such models will receive wide acceptance for pesticide risk assessment, despite having been used extensively in other contexts (e.g., conservation biology). The need for guidance on Good Modeling Practice (on model development, analysis, interpretation, evaluation, documentation, and communication), as well as the need for case studies that can be used to explore the added value of ecological models for risk assessment, were identified as top priorities. Assessing recovery potential of exposed nontarget species and clarifying the ecological relevance of standard laboratory test results are two areas for which ecological modeling may be able to provide considerable benefit