Background Isoflurane may be protective in pre-clinical models of lung injury but its use in patients with lung injury remains controversial and the mechanism of its protective effects remains unclear. We hypothesized that this protection is mediated at the level of alveolar tight junctions and investigated the possibility in a two-hit model of lung injury that mirrors human acute respiratory distress syndrome. Methods Wild-type mice were treated with isoflurane one hour after exposure to nebulized endotoxin (n=8) or saline control (n=9) then allowed to recover for 24 hrs prior to mechanical ventilation (MV, tidal volume 15 mL/kg, 2 hrs) producing ventilator-induced lung injury. Mouse lung epithelial cells were similarly treated with isoflurane one hour after exposure to lipopolysaccharide. Cells were cyclically stretched the following day to mirror the MV protocol used in vivo. Results Mice treated with isoflurane following exposure to inhaled endotoxin and prior to MV exhibited significantly less physiologic lung dysfunction. These effects appeared to be mediated by decreased vascular leak, but not altered inflammatory indices. Mouse lung epithelial cells treated with lipopolysaccharide and cyclic stretch and lungs harvested from mice following treatment with lipopolysaccharide and MV had decreased levels of a key tight junction protein (i.e. zona occludens 1) that was rescued by isoflurane treatment. Conclusions Isoflurane rescued lung injury induced by a two-hit model of endotoxin exposure followed by MV by maintaining the integrity of the alveolar-capillary barrier possibly by modulating the expression of a key tight junction protein.

This study reports on the drug use outcomes in an efficacy trial of a culturally grounded, school-based, substance abuse prevention curriculum in rural Hawai‘i. The curriculum (Ho‘ouna Pono) was developed through a series of preprevention and pilot/feasibility studies funded by the National Institute on Drug Abuse, and focuses on culturally relevant drug resistance skills training. The present study used a dynamic wait-listed control group design (Brown, Wyman, Guo, & Peña, 2006), in which cohorts of middle/intermediate public schools on Hawai‘i Island were exposed to the curriculum at different time periods over a 2-year time frame. A total of 486 youth participated in the study. Approximately 90% of these youth were 11 or 12 years of age at the start of the trial. Growth curve modeling over 6 waves of data was conducted for alcohol, marijuana, cigarettes/e-cigarettes, crystal methamphetamine, and other hard drugs. The findings for alcohol use were contrary to the hypothesized effects of the intervention, but may have been a reflection of a lack equivalence among the cohorts in risk factors that were unaccounted for in the study. Despite this issue, the findings also indicated small, statistically significant changes in the intended direction for cigarette/e-cigarette and hard drug use. The present study complements prior pilot research on the curriculum, and has implications for addressing Native Hawaiian and Pacific Islander health disparities.

BackgroundResidents of disadvantaged neighbourhoods report higher levels of depressive symptoms; however, few studies have employed prospective designs during adolescence, when depression tends to emerge. We examined associations of neighbourhood social fragmentation, income inequality and median household income with depressive symptoms in a nationally representative survey of adolescents.MethodsThe NEXT Generation Health Study enrolled 10th-grade students from 81 US high schools in the 2009–2010 school year. Depressive symptoms were assessed with the Modified Depression Scale (wave 1) and the paediatric Patient-Reported Outcome Measurement Information System (waves 2–6). Neighbourhood characteristics at waves 1, 3, 4, and 5 were measured at the census tract level using geolinked data from the American Community Survey 5-year estimates. We used linear mixed models to relate neighbourhood disadvantage to depressive symptoms controlling for neighbourhood and individual sociodemographic factors.ResultsNone of the models demonstrated evidence for associations of social fragmentation, income inequality or median household income with depressive symptoms.ConclusionDespite the prospective design, repeated measures and nationally representative sample, we detected no association between neighbourhood disadvantage and depressive symptoms. This association may not exist or may be too small to detect in a geographically dispersed sample. Given the public health significance of neighbourhood effects, future research should examine the developmental timing of neighbourhood effects across a wider range of ages than in the current sample, consider both objective and subjective measures of neighbourhood conditions, and use spatially informative techniques that account for conditions of nearby neighbourhoods.

Background: Hepatitis E virus (HEV) is an important public health threat resulting in more than 3 million symptomatic cases and 70,000 deaths annually. HEV is classified into at least eight genotypes, and five are associated with human infection. Genotypes 1 and 2 primarily affect humans, whereas genotypes 3 and 4 circulate in both humans and swine and are considered zoonotic viruses. Previous studies in Central Thailand have reported human HEV isolates with high similarity to swine strains and high seroprevalence in pigs, suggesting the potential for pig-to-human transmission.Objectives: This study aimed to detect and analyse HEV in pork products and pig stools collected from local markets and pig farms in Nakhon Pathom Province in Central Thailand.Methods: A total of 177 pig stool and 214 pork product samples were detected for HEV by using RT-PCR amplification. Next, nucleotide sequencing and phylogenetic analysis were performed. Results:We found one sample of pork products (1/214, 0.5%), which was a pig liver sample (1/51, 2.0%), and 49 HEV-positive samples in pig stools (49/177, 27.7%). Phylogenetic analysis showed that all these HEV sequences belonged to genotype 3, with a high correlation between our samples and HEV from humans and swine was previously reported in Thailand. Conclusions:This study suggested that the consumption of poorly sanitized or uncooked animal meat or food and frequent exposure to pig stools may be risk factors for HEV infections in humans.