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The Phase IV, 8-week, randomized, double-blind, placebo-controlled ACTIVATE study (NCT02424344) evaluated the effect of aclidinium/formoterol (AB/FF) 400/12 μg twice daily on lung hyperinflation, exercise capacity, and physical activity in patients with moderate-to-severe COPD. Patients received AB/FF (n=134) or placebo (n=133) (1:1) via the Genuair™/Pressair® dry powder inhaler for 8 weeks. From Weeks 5 to 8, all patients participated in behavioral intervention (BI; daily messages providing step goals). The primary end point was trough functional residual capacity (FRC) at Week 4. Exercise endurance time and physical activity were assessed at Week 4 (pharmacotherapy only) and at Week 8 (8 weeks of pharmacotherapy plus 4 weeks of BI). Other end points included post-dose FRC, residual volume, and inspiratory capacity (IC) at rest and during exercise. After 4 weeks, trough FRC improved with AB/FF versus placebo but did not reach significance (125 mL; P=0.0690). However, post-dose FRC, residual volume, and IC at rest improved significantly with AB/FF at Week 4 versus placebo (all P<0.0001). AB/FF significantly improved exercise endurance time and IC at isotime versus placebo at Week 4 (P<0.01 and P<0.0001, respectively) and Week 8 (P<0.05 and P<0.0001, respectively). AB/FF achieved higher step counts (P<0.01) with fewer inactive patients (P<0.0001) at Week 4 versus placebo. Following BI, AB/FF maintained improvements in physical activity at Week 8 and nonsignificant improvements were observed with placebo. AB/FF 400/12 μg demonstrated improvements in lung hyperinflation, exercise capacity, and physical activity versus placebo that were maintained following the addition of BI. A 4-week period of BI might be too short to augment the improvements of physical activity observed with AB/FF.

BackgroundPortomesenteric vein thrombosis (PMVT) is a rare but severe complication after laparoscopic bariatric surgery, with potentially serious consequences. We aimed to describe the incidence, clinical features, management, outcome, and midterm follow-up in patients with PMVT after laparoscopic sleeve gastrectomy (LSG).MethodsThis retrospective and descriptive study included patients who underwent LSG between November 2009 and July 2015 and developed PMVT. The following data were analyzed: age, gender, body mass index (BMI), thrombosis risk factors, surgical technique, thromboembolic prophylaxis, primary surgery outcomes, clinical features, treatment, thrombophilia testing results, and follow-up findings, including imaging and endoscopic findings.ResultsA total of 1236 patients underwent LSG, and 5 (0.4 %) developed PMVT. The mean age was 34.4 years, and 3 patients were women. The mean BMI was 38.5 kg/m2. Two patients had received hormonal contraceptive treatment. Four patients had a history of smoking. All of the patients received anticoagulant treatment, and none required surgery. The mean hospitalization duration was 7.6 days. Two patients showed complete recanalization. One patient showed portal cavernomatosis on delayed images. Two patients had a positive thrombophilia test. No portal hypertension endoscopic findings were observed.ConclusionsPMVT is a rare complication, for which smoking was identified as a predominant risk factor. Early diagnosis and prompt anticoagulant therapy could lead to a dramatic decrease in the incidence of intestinal infarction, mortality, and extrahepatic portal hypertension in the near future. However, careful follow-up is necessary to evaluate the impact of PMVT on long-term patient outcomes.

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BackgroundmicroRNAs (miRNAs) are non-coding short RNAs that regulate gene expression in eukaryotes by translational inhibition or cleavage of complementary mRNAs. In plants, miRNAs are known to target mostly transcription factors and are implicated in diverse aspects of plant growth and development. A role has been suggested for the miRNA pathway in antiviral defense in plants. In this work, a bioinformatics approach was taken to test whether plant miRNAs from six species could have antiviral activity by targeting the genomes of plant infecting viruses.ResultsAll plants showed a repertoire of miRNAs with potential for targeting viral genomes. The viruses were targeted by abundant and conserved miRNA families in regions coding for cylindrical inclusion proteins, capsid proteins, and nuclear inclusion body proteins. The parameters for our predicted miRNA:target pairings in the viral genomes were similar to those for validated targets in the plant genomes, indicating that our predicted pairings might behave in-vivo as natural miRNa-target pairings. Our screening was compared with negative controls comprising randomly generated miRNAs, animal miRNAs, and genomes of animal-infecting viruses. We found that plant miRNAs target plant viruses more efficiently than any other sequences, but also, miRNAs can either preferentially target plant-infecting viruses or target any virus without preference.ConclusionsOur results show a strong potential for antiviral activity of plant miRNAs and suggest that the miRNA pathway may be a support mechanism to the siRNA pathway in antiviral defense.

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The pilot-scale solar degradation of trimethoprim (TMP) in different water matrices (demineralized water: DW, simulated natural freshwater: SW; simulated wastewater: SWW; and real effluent: RE) was investigated in this study. DOC removal was lower in the case of SW compared to DW, which can be attributed to the presence of inorganic anions which may act as scavengers of the HO·. Furthermore, the presence of organic carbon and higher salt content in SWW and RE led to lower mineralization per dose of hydrogen peroxide compared to DW and SW. Toxicity assays in SWW and RE were also performed indicating that toxicity is attributed to the compounds present in RE and their by-products formed during solar Fenton treatment and not to the intermediates formed by the oxidation of TMP. A large number of compounds generated by the photocatalytic transformation of TMP were identified by UPLC-QToF/MS. The degradation pathway revealed differences among the four matrices; however hydroxylation, demethylation and cleavage reactions were observed in all matrices. To the best of our knowledge this is the first time that TMP degradation products have been identified by adopting a solar Fenton process at a pilot-scale set-up, using four different aqueous matrices.