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Oxycodone is an opioid analgesic that closely resembles morphine. Oxymorphone, the active metabolite of oxycodone, is formed in a reaction catalyzed by CYP2D6, which is under polymorphic genetic control. The role of oxymorphone in the analgesic effect of oxycodone is not yet clear. In this study, controlled-release (CR) oxycodone and morphine were examined in cancer pain. CR oxycodone and morphine were administered to 45 adult patients with stable pain for 3–6 days after open-label titration in a randomized, double-blind, cross-over trial. Twenty patients were evaluable. Both opioids provided adequate analgesia. The variation in plasma morphine concentrations was higher than that of oxycodone, consistent with the lower bioavailability of morphine. Liver dysfunction affected selectively either oxycodone or morphine metabolism. Three patients with markedly aberrant plasma opioid concentrations are presented. Significant individual variation in morphine and oxycodone metabolism may account for abnormal responses during treatment of chronic cancer pain. [ABSTRACT FROM AUTHOR]

Soft rot Pectobacteria are broad host range enterobacterial pathogens that cause disease on a variety of plant species including the major crop potato. Pectobacteria are aggressive necrotrophs that harbor a large arsenal of plant cell wall degrading enzymes as their primary virulence determinants. These enzymes together with additional virulence factors are employed to macerate the host tissue and promote host cell death to provide nutrients for the pathogens. In contrast to (hemi)biotrophs such as Pseudomonas, type three secretion systems (T3SS) and T3 effectors do not appear central to pathogenesis of Pectobacteria. Indeed, recent genomic analysis of several Pectobacterium species including the emerging pathogen Pectobacterium wasabiae has shown that many strains lack the entire T3SS as well as the T3 effectors. Instead, this analysis has indicated the presence of novel virulence determinants. Resistance to broad host range Pectobacteria is complex and does not appear to involve single resistance genes. Instead, activation of plant innate immunity systems including both SA and JA/ET mediated defenses appears to play a central role in attenuation of Pectobacterium virulence. These defenses are triggered by detection of pathogen-associated molecular patterns (PAMPs) or recognition of modified-self such as damage-associated molecular patterns (DAMPs) and result in enhancement of basal immunity (Pattern-triggered immunity, PTI). In particular plant cell-wall fragments released by the action of the degradative enzymes secreted by Pectobacteria are major players in enhanced immunity towards these pathogens. Most notably bacterial pectin degrading enzymes release oligogalacturonide (OG) fragments recognized as DAMPs activating innate immune responses. Recent progress in understanding OG recognition and signaling allows novel genetic screens for OG-insensitive mutants and will provide new insights into plant defense strategies against necrotrophs such as Pectobacteria.

Uskonnonopetus eroaa asemaltaan, muodoltaan ja toteutukseltaan Euroopan eri maissa. Espanjassa katolilainen uskonto on vaikuttanut voimakkaasti yhteiskuntaan, kulttuuriin ja koulukasvatukseen, myös uskonnonopetukseen. Poliittiset suhdanteet ovat niin ikään vaikuttaneet voimakkaasti uskonnonopetuksen kehitykseen maassa. Tarkastelen tähän kehitykseen vaikuttaneita tekijöitä sekä nykyistä espanjalaista uskonnonopetusta.

Background: Transcatheter valve-in-valve (VIV) implantation is an alternative option in inoperable or high-risk patients with prosthetic valve dysfunction. Aim of this retrospective multicenter study was to evaluate early and midterm clinical and hemodynamic outcomes of patients undergoing aortic (VIV-A) and mitral VIV (VIV-M)., Methods: We analyzed data of 66 procedures performed in 65 patients who underwent VIV procedures in the VIV-A and VIV-M position at 5 Italian institutions from January 2008 to May 2015. VIV-A and VIV-M were 44 (68%) and 22 (32%), respectively; 1 patient underwent combined mitroaortic VIV. Study devices were both balloon-expandable and self-expandable. Outcomes were defined according to the updated Valve Academic Research Consortium definitions., Results: Overall all-cause 30-day mortality was 6% (4 patients), and it was 4.5% and 9% in VIV-A and VIV-M, respectively (2 patients in each group). Mean follow-up was 14 ± 14 months. Kaplan-Meier survival of the entire cohort at 1, 2, 3, and 4 years was 84.4% ± 4.9%, 80.5% ± 6%, 74.3 ± 8.1%, and 62% ± 13.2%, respectively. Age (hazard ratio: 1.1; 95% confidence interval: 1.0 to 1.3; p = 0.035) and diabetes (hazard ratio: 7.2, 95% confidence interval: 2.1 to 23.7; p = 0.001) were identified as independent predictors of mortality. Degenerated surgical aortic prostheses with an internal diameter (ID) less than 20 mm had significantly higher gradients if compared to prostheses with ID 21 to 23 mm and greater than 23 mm. After VIV-A, a severe stenosis (mean gradient greater than 35 mm Hg) was detected in 3 (6.8%) cases, all with ID less than 20 mm., Conclusions: VIV provides good early and midterm results in high-risk or inoperable patients with mitral or aortic bioprosthesis dysfunction. Age and diabetes are independently associated with mortality. Size of bioprosthesis ID has a significant impact on postoperative gradients., (Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)