Valganciclovir for suppression of human herpesvirus-8 replication: a randomized, double-blind, placebo-controlled, crossover trial.

BACKGROUND: Human herpesvirus-8 (HHV-8) replication is critical in the induction and maintenance of Kaposi sarcoma, primary effusion lymphoma, and some cases of Castleman disease. In vitro and observational studies suggest that ganciclovir inhibits HHV-8 replication, but no randomized clinical trials have been conducted. METHODS: A total of 26 men infected with HHV-8 were randomized to receive 8 weeks of valganciclovir administered orally (900 mg once per day) or 8 weeks of placebo administered orally. After a 2-week washout period, participants in each group received the study drug they had not yet taken (either valganciclovir or placebo), for 8 additional weeks. Oral swab samples were collected daily during the study, and HHV-8 and CMV DNA were quantified by real-time PCR. RESULTS: A total of 16 human immunodeficiency virus (HIV)-positive men and 10 HIV-negative men enrolled in and completed the study. Of the 3,439 swab samples that participants had been expected to provide, 3029 (88%) were available for analysis. HHV-8 was detected on 44% of swabs collected from participants who were receiving placebo, compared with 23% of swabs collected from participants who were receiving valganciclovir (relative risk [RR], 0.54 [95% confidence interval {CI}, 0.33-0.90]; P = .02). Valganciclovir reduced oropharyngeal shedding of cytomegalovirus by 80% (RR, 0.20 [95% CI, 0.08-0.48]; P < .001). Shedding of HHV-8 and shedding of cytomegalovirus were independent. Hematologic, renal, or hepatic toxicities were no more common among participants who received the active drug, compared with those who received placebo, though participants who received valganciclovir reported more days of diarrhea. CONCLUSIONS: Valganciclovir administered orally once per day is well tolerated and significantly reduces the frequency and quantity of HHV-8 replication

Variability in the Dynamics of Mortality and Immobility Responses of Freshwater Arthropods Exposed to Chlorpyrifos

The species sensitivity distribution (SSD) concept is an important probabilistic tool for environmental risk assessment (ERA) and accounts for differences in species sensitivity to different chemicals. The SSD model assumes that the sensitivity of the species included is randomly distributed. If this assumption is violated, indicator values, such as the 50% hazardous concentration, can potentially change dramatically. Fundamental research, however, has discovered and described specific mechanisms and factors influencing toxicity and sensitivity for several model species and chemical combinations. Further knowledge on how these mechanisms and factors relate to toxicologic standard end points would be beneficial for ERA. For instance, little is known about how the processes of toxicity relate to the dynamics of standard toxicity end points and how these may vary across species. In this article, we discuss the relevance of immobilization and mortality as end points for effects of the organophosphate insecticide chlorpyrifos on 14 freshwater arthropods in the context of ERA. For this, we compared the differences in response dynamics during 96 h of exposure with the two end points across species using dose response models and SSDs. The investigated freshwater arthropods vary less in their immobility than in their mortality response. However, differences in observed immobility and mortality were surprisingly large for some species even after 96 h of exposure. As expected immobility was consistently the more sensitive end point and less variable across the tested species and may therefore be considered as the relevant end point for population of SSDs and ERA, although an immobile animal may still potentially recover. This is even more relevant because an immobile animal is unlikely to survive for long periods under field conditions. This and other such considerations relevant to the decision-making process for a particular end point are discussed

Association between the 2008–09 Seasonal Influenza Vaccine and Pandemic H1N1 Illness during Spring–Summer 2009: Four Observational Studies from Canada

In three case-control studies and a household transmission cohort, Danuta Skowronski and colleagues find an association between prior seasonal flu vaccination and increased risk of 2009 pandemic H1N1 flu

Fate and effects of the insecticide chlorpyrifos in outdoor plankton-dominated microcosms in Thailand

The fate and effects of the insecticide chlorpyrifos were studied in plankton-dominated, freshwater microcosms in Thailand. Disappearance rates of chlorpyrifos from the water column in the present study were similar to those in temperate regions. Insecticide accumulation in the sediment was relatively small, with the major part in the top layer (depth, 1.5 cm). Application of chlorpyrifos led to significant changes in freshwater biological communities. Clam shrimps (Conchostraca) and the cladoceran Moina micrura were the most susceptible species (no-observed-effect concentration [NOEC], 0.1 mu g/L) and macroinvertebrates the most sensitive community (NOEC, 0.1 mu g/L). These results are in agreement with those from semifield experiments with chlorpyrifos in temperate regions. The results of an in situ bioassay were used to calculate a NOEC of 0.1 mu g/L and a 48-h median lethal concentration of 0.6 mu g/L for M. micrura, which are similar to toxicity values reported for Daphnia magna in studies in temperate regions. Overall, these findings support the use of toxicity data from temperate regions for the risk assessment of low-persistent insecticides like chlorpyrifos for aquatic communities in tropical regions

Who’s joining the club?:participation of socially vulnerable children and adolescents in club-organised sports

Sport is often considered as a promising instrument for reaching a wide array of policy objectives. Social inclusion is one of the goals frequently mentioned. Though one can argue about the feasibility of the many claims made, sport can only reasonably be expected to play a role if the targeted population is effectively taking part in sports. This is what is investigated in this study. The focus lies on the sports participation of children (primary school) and adolescents (secondary school), more particularly in a club-organised setting. The purpose of this study is to investigate whether family related factors associated with a higher risk for social exclusion can be considered as determinants of club sport participation among children and adolescents. Data are based on a large-scale cross-sectional survey (2009), collected in 39 schools in Flanders (Belgium), with a total of 3005 children and adolescents (aged 6–18) participating in the research. A multilevel logistic regression has been conducted, controlling also for differences between schools. Income poverty and parental education come forward as important determinants for club-organised sports participation. No evidence was found that living in a single parent-household affects the likelihood of club-organised sports participation. While sport is often considered as an important instrument for social inclusion, the study shows that children and adolescents who are likely to occupy a more vulnerable position in society as a whole, have higher odds to be left out with regard to sport club participation as well