Effects of radiation on respiratory disease mortality: analysis of the national registry for radiation workers in United Kingdom.

PURPOSE: While some evidence of an effect of radiation exposure on respiratory disease at low dose levels has now emerged, there is heterogeneity in the risks between different studies and countries. In this paper, we aim to show the effect of radiation on three different sub-types of respiratory disease mortality through the analysis of the NRRW cohort in UK. MATERIALS AND METHODS: The NRRW cohort consisted of 174,541 radiation workers. Doses to the surface of the body were monitored using individual film badges. Most of the doses are associated with X-rays and gamma rays and to a less extent of beta and neutron particles. The overall mean 10-year lagged lifetime external dose was 23.2 mSv. Some workers were potentially exposed to alpha particles. However, doses from internal emitters were not available for the NRRW cohort. 25% of male workers and 17% of female workers were identified as being monitored for internal exposure. The Poisson regression methods for grouped survival data with a stratified baseline hazard function were used to describe the dependence of the risk on cumulative external radiation dose. The disease was analyzed by the following subgroups: Pneumonia (1066 cases including 17 cases of influenza), COPD and allied disease (1517 cases) and other remaining respiratory diseases (479 cases). RESULTS: There was very little radiation effect on pneumonia mortality, but evidence of a reduction in mortality risk for COPD and allied disease (ERR/Sv= -0.56, 95%CI: -0.94, -0.06; p = .02) and an increase in risk for other respiratory disease mortality (ERR/Sv = 2.30, 95%CI: 0.67, 4.62; p = .01) with increasing cumulative external dose were observed. The effects of radiation were more prominent amongst workers monitored for internal exposure. The reduction in mortality risk of COPD and allied disease per cumulative external dose was statistically significant for the radiation workers monitored for internal exposure (ERR/Sv= -0.59, 95%CI: -0.99, -0.05; p = .017) but not significant among the workers who were not monitored (ERR/Sv= -0.43, 95%CI: -1.20, 0.74; p = .42). A statistically significant increased risk was observed for other respiratory diseases among monitored radiation workers (ERR/Sv = 2.46, 95%CI: 0.69, 5.08; p = .019), but not among unmonitored workers (ERR/Sv = 1.70, 95%CI: -0.82, 5.65; p = .25). CONCLUSION: The effects of radiation exposure can be different depending on the type of respiratory disease. No effect was seen in pneumonia; a reduction in mortality risk of COPD, and increased mortality risk of other respiratory diseases were observed with cumulative external radiation dose. More studies are needed to verify these findings.

Home Non-Invasive Ventilation in COPD: A Global Systematic Review.

Background: Uncertainty remains around the benefit of home non-invasive ventilation (NIV) for stable chronic obstructive pulmonary disease (COPD) patients and those with a recent exacerbation (post-hospital). The aim of this systematic review was to: (1) update the evidence base with studies published in any language, including Chinese language studies not indexed in standard medical databases, and (2) explore the impact of additional studies on the evidence base. Methods: Standard systematic review methodology was used for identifying and appraising studies. Randomized controlled trials (RCTs) and non-randomized studies reporting mortality, hospitalizations, exacerbations, quality of life, adverse events, or adherence were included. Random effects meta-analysis was undertaken for mortality and hospitalizations, with studies sub-grouped by population and study design. Sensitivity analysis was performed to explore the effect of including studies from Western and non-Western countries. Results: A total of 103 studies were included, substantially more than in previous reviews. There was no significant effect on mortality for the stable population. There was a benefit from NIV for the post-hospital population based on non-randomized studies, or RCTs from non-Western countries. There was a small but significant reduction in hospital admissions (1-2/year) with NIV across all sub-groups, and a variable reduction in duration of stay with greater reductions in studies from China. Conclusions: The evidence base on home NIV is considerably larger than previously presented. While NIV may reduce hospital admissions and improve quality of life, there is still little evidence of a reduction in mortality, regardless of country. Individual participant data analysis may clarify which patients would benefit most from NIV.

Pharmacological blockage of fibro/adipogenic progenitor expansion and suppression of regenerative fibrogenesis is associated with impaired skeletal muscle regeneration.

Acute skeletal muscle injury triggers an expansion of fibro/adipogenic progenitors (FAPs) and a transient stage of fibrogenesis characterized by extracellular matrix deposition. While the perpetuation of such phase can lead to permanent tissue scarring, the consequences of its suppression remain to be studied. Using a model of acute muscle damage we were able to determine that pharmacological inhibition of FAP expansion by Nilotinib, a tyrosine kinase inhibitor with potent antifibrotic activity, exerts a detrimental effect on myogenesis during regeneration. We found that Nilotinib inhibits the damage-induced expansion of satellite cells in vivo, but it does not affect in vitro proliferation, suggesting a non cell-autonomous effect. Nilotinib impairs regenerative fibrogenesis by preventing the injury-triggered expansion and differentiation of resident CD45(-):CD31(-):α7integrin(-):Sca1(+) mesenchymal FAPs. Our data support the notion that the expansion of FAPs and transient fibrogenesis observed during regeneration play an important trophic role toward tissue-specific stem cells.

The neonicotinoid imidacloprid impairs honey bee aversive learning of simulated predation.

Neonicotinoid insecticides can impair bee learning and memory--cognitive features that play a key role in colony fitness because they facilitate foraging. For example, the commonly used neonicotinoid imidacloprid reduces honey bee olfactory learning. However, no studies have previously determined whether imidacloprid can impair aversive associative learning, although such learning should enhance bee survival by allowing bees to avoid dangerous foraging sites. To mimic attempted predation of foragers, we developed an electro-mechanical predator that consistently attacked foragers with a pinching bite at a fixed force and elicited aversive olfactory learning in a sting extension response (SER) assay. We show that chronic exposure to a sublethal concentration of imidacloprid (25.6 µg l(-1)=20.8 ppb) over 4 days (mean of 1.5 ng per bee day(-1)), significantly impaired aversive short-term learning and memory retention. Imidacloprid treatment reduced short-term learning by 87% and memory retention by 85% in comparison with control bees. Imidacloprid therefore impairs the ability of honey bees to associate a naturalistic predation stimulus--biting--with floral odor compounds. Such learning should enhance bee survival, suggesting that xenobiotics could alter more complex ecological interactions such as predator-prey relationships.