ERP evidence suggests executive dysfunction in ecstasy polydrug users

Background: Deficits in executive functions such as access to semantic/long-term memory have been shown in ecstasy users in previous research. Equally, there have been many reports of equivocal findings in this area. The current study sought to further investigate behavioural and electro-physiological measures of this executive function in ecstasy users. Method: Twenty ecstasy–polydrug users, 20 non-ecstasy–polydrug users and 20 drug-naïve controls were recruited. Participants completed background questionnaires about their drug use, sleep quality, fluid intelligence and mood state. Each individual also completed a semantic retrieval task whilst 64 channel Electroencephalography (EEG) measures were recorded. Results: Analysis of Variance (ANOVA) revealed no between-group differences in behavioural performance on the task. Mixed ANOVA on event-related potential (ERP) components P2, N2 and P3 revealed significant between-group differences in the N2 component. Subsequent exploratory univariate ANOVAs on the N2 component revealed marginally significant between-group differences, generally showing greater negativity at occipito-parietal electrodes in ecstasy users compared to drug-naïve controls. Despite absence of behavioural differences, differences in N2 magnitude are evidence of abnormal executive functioning in ecstasy–polydrug users

Preconditioning of mesenchymal stromal cells with low-intensity ultrasound: influence on chondrogenesis and directed SOX9 signaling pathways

Background: Continuous low-intensity ultrasound (cLIUS) facilitates the chondrogenic differentiation of human mesenchymal stromal cells (MSCs) in the absence of exogenously added transforming growth factor-beta (TGFβ) by upregulating the expression of transcription factor SOX9, a master regulator of chondrogenesis. The present study evaluated the molecular events associated with the signaling pathways impacting SOX9 gene and protein expression under cLIUS. Methods: Human bone marrow-derived MSCs were exposed to cLIUS stimulation at 14 kPa (5 MHz, 2.5 Vpp) for 5 min. The gene and protein expression of SOX9 was evaluated. The specificity of SOX9 upregulation under cLIUS was determined by treating the MSCs with small molecule inhibitors of select signaling molecules, followed by cLIUS treatment. Signaling events regulating SOX9 expression under cLIUS were analyzed by gene expression, immunofluorescence staining, and western blotting. Results: cLIUS upregulated the gene expression of SOX9 and enhanced the nuclear localization of SOX9 protein when compared to non-cLIUS-stimulated control. cLIUS was noted to enhance the phosphorylation of the signaling molecule ERK1/2. Inhibition of MEK/ERK1/2 by PD98059 resulted in the effective abrogation of cLIUS-induced SOX9 expression, indicating that cLIUS-induced SOX9 upregulation was dependent on the phosphorylation of ERK1/2. Inhibition of integrin and TRPV4, the upstream cell-surface effectors of ERK1/2, did not inhibit the phosphorylation of ERK1/2 and therefore did not abrogate cLIUS-induced SOX9 expression, thereby suggesting the involvement of other mechanoreceptors. Consequently, the effect of cLIUS on the actin cytoskeleton, a mechanosensitive receptor regulating SOX9, was evaluated. Diffused and disrupted actin fibers observed in MSCs under cLIUS closely resembled actin disruption by treatment with cytoskeletal drug Y27632, which is known to increase the gene expression of SOX9. The upregulation of SOX9 under cLIUS was, therefore, related to cLIUS-induced actin reorganization. SOX9 upregulation induced by actin reorganization was also found to be dependent on the phosphorylation of ERK1/2. Conclusions: Collectively, preconditioning of MSCs by cLIUS resulted in the nuclear localization of SOX9, phosphorylation of ERK1/2 and disruption of actin filaments, and the expression of SOX9 was dependent on the phosphorylation of ERK1/2 under cLIUS

Envelope Determinants of Equine Lentiviral Vaccine Protection

Lentiviral envelope (Env) antigenic variation and associated immune evasion present major obstacles to vaccine development. The concept that Env is a critical determinant for vaccine efficacy is well accepted, however defined correlates of protection associated with Env variation have yet to be determined. We reported an attenuated equine infectious anemia virus (EIAV) vaccine study that directly examined the effect of lentiviral Env sequence variation on vaccine efficacy. The study identified a significant, inverse, linear correlation between vaccine efficacy and increasing divergence of the challenge virus Env gp90 protein compared to the vaccine virus gp90. The report demonstrated approximately 100% protection of immunized ponies from disease after challenge by virus with a homologous gp90 (EV0), and roughly 40% protection against challenge by virus (EV13) with a gp90 13% divergent from the vaccine strain. In the current study we examine whether the protection observed when challenging with the EV0 strain could be conferred to animals via chimeric challenge viruses between the EV0 and EV13 strains, allowing for mapping of protection to specific Env sequences. Viruses containing the EV13 proviral backbone and selected domains of the EV0 gp90 were constructed and in vitro and in vivo infectivity examined. Vaccine efficacy studies indicated that homology between the vaccine strain gp90 and the N-terminus of the challenge strain gp90 was capable of inducing immunity that resulted in significantly lower levels of post-challenge virus and significantly delayed the onset of disease. However, a homologous N-terminal region alone inserted in the EV13 backbone could not impart the 100% protection observed with the EV0 strain. Data presented here denote the complicated and potentially contradictory relationship between in vitro virulence and in vivo pathogenicity. The study highlights the importance of structural conformation for immunogens and emphasizes the need for antibody binding, not neutralizing, assays that correlate with vaccine protection. © 2013 Craigo et al

Intentional injury reported by young people in the Federated States of Micronesia, Kingdom of Tonga and Vanuatu

<p>Abstract</p> <p>Background</p> <p>Intentional injury presents a threat to the physical and psychological well being of young people, especially in developing countries, which carry the greatest part of the global injury burden. While the importance of this problem is recognized, there are limited population data in low and middle income countries that can guide public health action. The present study investigates the prevalence and distribution of intentional injury among young people in three Pacific Island societies, and examines behavioural and psychosocial factors related to risk of intentional injury.</p> <p>Methods</p> <p>Population surveys were conducted with <b>s</b>tudents aged 11–17 years in Pohnpei State in the Federated States of Micronesia (n = 1495), the Kingdom of Tonga (n = 2808) and Vanuatu (n = 4474). Surveys measured self-reported injury and intentional injury, sources of intentional injury, and the range of behavioural, psychological, educational and social variables that may be related to injury risk.</p> <p>Results</p> <p>Among boys and girls aged 14–17 years the respective period prevalence of intentional injury was 62% and 56% in Pohnpei, 58% and 41% in Tonga, and 33% and 24% in Vanuatu. The prevalence of intentional injury declined with age in Tonga and Vanuatu, but there was little evidence of an age-trend in Pohnpei. Across the three societies, the major sources of intentional injury among boys were 'other persons' followed by boyfriends/girlfriends and fathers. Mothers, boyfriends/girlfriends and other persons were primary sources of injury among girls. An intentional injury was reported more often by those who had been bullied (OR 1.40–1.66, P < 0.05), by regular smokers in Tonga and Vanuatu (OR 1.52–2.21, P < 0.05), and illicit drug users in Pohnpei and Vanuatu (OR 1.87–1.92, P < 0.05).</p> <p>Conclusion</p> <p>Intentional injury was reported extensively in these three populations. Interventions directed towards the school environment and which take into account the role of bullying and drug use need to be considered.</p

S. pneumoniae transmission according to inclusion in conjugate vaccines: Bayesian analysis of a longitudinal follow-up in schools

BACKGROUND: Recent trends of pneumococcal colonization in the United States, following the introduction of conjugate vaccination, indicate that non-vaccine serotypes tend to replace vaccine serotypes. The eventual extent of this replacement is however unknown and depends on serotype-specific carriage and transmission characteristics. METHODS: Here, some of these characteristics were estimated for vaccine and non-vaccine serotypes from the follow-up of 4,488 schoolchildren in France in 2000. A Bayesian approach using Markov chain Monte Carlo data augmentation techniques was used for estimation. RESULTS: Vaccine and non-vaccine serotypes were found to have similar characteristics: the mean duration of carriage was 23 days (95% credible interval (CI): 21, 25 days) for vaccine serotypes and 22 days (95% CI: 20, 24 days) for non-vaccine serotypes; within a school of size 100, the Secondary Attack Rate was 1.1% (95% CI: 1.0%, 1.2%) for both vaccine and non-vaccine serotypes. CONCLUSION: This study supports that, in 3–6 years old children, no competitive advantage exists for vaccine serotypes compared to non-vaccine serotypes. This is an argument in favour of important serotype replacement. It would be important to validate the result for infants, who are known to be the main reservoir in maintaining transmission. Overall reduction in pathogenicity should also be taken into account in forecasting the future burden of pneumococcal colonization in vaccinated populations

The context influences doctors' support of shared decision-making in cancer care

Most cancer patients in westernised countries now want all information about their situation, good or bad, and many wish to be involved in decision-making. The attitudes to and use of shared decision-making (SDM) by cancer doctors is not well known. Australian cancer clinicians treating breast, colorectal, gynaecological, haematological, or urological cancer were surveyed to identify their usual approach to decision-making and their comfort with different decision-making styles when discussing treatment with patients. A response rate of 59% resulted in 624 complete surveys, which explored usual practice in discussing participation in decision-making, providing information, and perception of the role patients want to play. Univariate and multivariate analyses were performed to identify predictors of use of SDM. Most cancer doctors (62.4%) reported using SDM and being most comfortable with this approach. Differences were apparent between reported high comfort with SDM and less frequent usual practice. Multivariate analysis showed that specialisation in breast or urological cancers compared to other cancers (AOR 3.02), high caseload of new patients per month (AOR 2.81) and female gender (AOR 1.87) were each independently associated with increased likelihood of use of SDM. Barriers exist to the application of SDM by doctors according to clinical situation and clinician characteristics

Restored Agricultural Wetlands in central Iowa: Habitat Quality and Amphibian Response

Amphibians are declining throughout the United States and worldwide due, partly, to habitat loss. Conservation practices on the landscape restore wetlands to denitrify tile drainage effluent and restore ecosystem services. Understanding how water quality, hydroperiod, predation, and disease affect amphibians in restored wetlands is central to maintaining healthy amphibian populations in the region. We examined the quality of amphibian habitat in restored wetlands relative to reference wetlands by comparing species richness, developmental stress, and adult leopard frog (Lithobates pipiens) survival probabilities to a suite of environmental metrics. Although measured habitat variables differed between restored and reference wetlands, differences appeared to have sub-lethal rather than lethal effects on resident amphibian populations. There were few differences in amphibian species richness and no difference in estimated survival probabilities between wetland types. Restored wetlands had more nitrate and alkaline pH, longer hydroperiods, and were deeper, whereas reference wetlands had more amphibian chytrid fungus zoospores in water samples and resident amphibians exhibited increased developmental stress. Restored and reference wetlands are both important components of the landscape in central Iowa and maintaining a complex of fish-free wetlands with a variety of hydroperiods will likely contribute to the persistence of amphibians in this landscape