UV-degradation of IPBC in natural water sample

IPBC as a preservative compound for wood furniture has been used for more than thirty years. The degradation of IPBC caused of bacterial biotransformation and UV-light has been considered to be the main reason for IPBC degradation. In our experiments Hg UV-lamp has been used to expose the IPBC solution for UV-light and we found that it degrades immediately. By using GC-MS we found it gives two main products with molecular mass of 112 and 98. The 98m/z is the final product when the UV-light gives enough energy. In a natural water sample only little IPBC degradation product has been found, and it has a molecular mass of 112. This is caused by lower energy that is emitted from natural sunshine compared to the Hg UV-lamp. The little effect sunlight has on IPBC makes it a good outdoor preservative.

Solving the IRAK-4 enigma: application of kinase-dead knock-in mice.

Interleukin-1 receptor-associated kinase (IRAK-4) is an essential component of the signal transduction complex downstream of the interleukin (IL)-1- and Toll-like receptors. Though regarded as the first kinase in the signaling cascade, the role of IRAK-4 kinase activity versus its scaffold function has been controversial. In order to investigate the role of IRAK-4 kinase function in vivo, we generated "knock-in" mice where the wild-type IRAK-4 gene is replaced with a mutant gene encoding kinase-deficient IRAK-4 protein (IRAK-4 KD). IRAK-4 kinase is rendered inactive by mutating the conserved lysine residues in the ATP pocket essential for coordinating ATP. Analyses of embryonic fibroblasts and macrophages obtained from IRAK-4 KD mice demonstrated lack of cellular responsiveness to stimulation with IL-1beta or Toll-like receptor 4 (TLR4) and TLR7 agonists. IRAK-4 KD cells were severely impaired in NF-kappaB, JNK, and p38 activation in response to IL-1beta or TLR7 ligand. In addition, activation of JNK and p38 was affected in lipopolysaccharide (LPS)-stimulated IRAK-4 KD macrophages. As a consequence, IL-1 receptor/TLR4/TLR7-mediated production of cytokines and chemokines was largely absent in these cells. Additionally, microarray analysis identified IL-1beta response genes and revealed that the induction of IL-1beta-responsive mRNAs is largely ablated in IRAK-4 KD cells. In summary, our results suggest that IRAK-4 kinase activity plays a critical role in IL-1R-, TLR4-, and TLR7-mediated induction of inflammatory responses

Patient-Reported Outcomes in First-Line Antiretroviral Therapy: Results From NEAT001/ANRS143 Trial Comparing Darunavir/Ritonavir in Combination With Tenofovir/Emtricitabine or Raltegravir

Background: There are few data comparing patient-reported outcomes (PROs) in randomized trials of initial antiretroviral therapy. We present results from a substudy of the NEAT001/ ANRS143 trial. Methods: The randomized trial compared first-line DRV/r 800/100 mg once daily plus RAL 400 mg twice daily and DRV/r plus TDF/ FTC 245/200 mg once daily. Changes in PROs were assessed with 3 questionnaires: EuroQoL 5 domains (EQ-5D), Center for Epidemiologic Studies Depression (CES-D) scale, and HIV Treatment Satisfaction Questionnaire. Major depressive disorder (MDD) was defined as CES-D $16. General estimating equations were used to model change over 96 weeks in PROs from baseline. Results: Of the 805 participants, 797 (99substudy. Baseline PRO data were similar for the 2 randomized groups. Health status improved over time with a mean increase in EQ-5D visual analogue scale (VAS) of 8.0 by W96 [95to 9.4; P, 0.001], and no statistically significant differences between groups (difference of 0.3 on VAS score (95global P value$ 0.05 for all domains over follow-up). There was no significant difference between groups on CES-D [difference of 20.1 (95% CI: 21.3 to 1.1); P = 0.9], or MDD during follow-up, adjusted for baseline MDD (odds ratio = 0.98, 95% CI: 0.82 to 1.18; P = 0.9). RAL + DRV/r group had lower level of convenience (P = 0.03) and fitted less well into patients’ lifestyle (P = 0.007) than the TDF/FTC + DRV/r regimen, and was associated with lower treatment satisfaction [median score: 53 RAL + DRV/r vs 55 TDF/FTC + DRV/r (P = 0.001)]. Conclusion: PROs improved after starting antiretroviral therapy, with no statistically significant difference between groups. The lower satisfaction with RAL + DRV/r may be explained by twicedaily administration