gov was performed to identify randomized controlled trials. The primary outcomes were trough forced expiratory volume in 1 s (FEV1) (reported pre-bronchodilator values) and exacerbation rate. Secondary outcomes included other spirometric parameters, health-related quality of life, the overall mortality rate and adverse events. Weighted mean differences (WMDs), relative risks (RRs) and 95% confidence intervals (CIs) were calculated and pooled using a random effects model. Results: Eleven trials involving 9675 patients met the inclusion criteria. Roflumilast significantly reduced the mean exacerbation rate (mild, moderate or severe) (WMD = -0.23; 95% Cl = -0.33 to -0.13;

p smaller than 0.00001) and improved trough FEV1 (WMD = 53.52 ml; 95% CI = 42.49 to 64.55; p smaller than 0.00001), and other post-bronchodilator spirornetric parameters (e.g., forced vital capacity, etc.). Roflumilast did not improve St George’s Respiratory APR-246 supplier Questionnaire total score (WMD = -0.70 units; 95% CI = -2.65 to 1.26; p = 0.49) and decrease the overall mortality rate (RR = 0.90; 95% CI = 0.63 to 1.29; p = 0.56). Roflumilast increased some adverse events including diarrhea, headache, nausea, weight loss, and insomnia. Conclusions: Roflumilast significantly

reduces the mean exacerbation rate in COPD patients. Although there are insufficient clinical evidence on other clinical endpoints and high risk of some adverse events, roflumilast therapy may benefit COPD patients. Further studies are needed to pay more attention to the long-term Selleck Fludarabine GPCR Compound Library ic50 efficacy and safety of roflumilast. (C) 2013 Elsevier Ltd. All rights reserved.”
“Amoebae serve as hosts for various intracellular bacteria, including human pathogens. These microbes are able to overcome amoebal defense mechanisms and successfully establish a niche for replication, which is usually the cytoplasm. Here, we report on the discovery of a bacterial

symbiont that is located inside the nucleus of its Hartmannella sp. host. This symbiont, tentatively named ‘Candidatus Nucleicultrix amoebiphila’, is only moderately related to known bacteria (similar to 90% 16S and 23S rRNA sequence similarity) and member of a novel clade of protist symbionts affiliated with the Rickettsiales and Rhodospirillales. Screening of 16S rRNA amplicon data sets revealed a broad distribution of these bacteria in freshwater and soil habitats. ‘Candidatus Nucleicultrix amoebiphila’ traffics within 6 h post infection to the host nucleus. Maximum infection levels are reached after 96-120 h, at which time point the nucleus is pronouncedly enlarged and filled with bacteria. Transmission of the symbionts occurs vertically upon host cell division but may also occur horizontally through host cell lysis. Although we observed no impact on the fitness of the original Hartmannella sp. host, the bacteria are rather lytic for Acanthamoeba castellanii.