Intrapartum detection of Group B streptococci colonization by rapid PCR-test on labor ward

OBJECTIVE Group B streptococci (GBS) may lead to early onset neonatal sepsis with severe morbidity and mortality of newborns. Intrapartum detection of GBS is needed. The objective was to compare a PCR-based test performed in the laboratory versus labor ward. STUDY DESIGN 300 patients were included prospectively. In phase I, swabs were analyzed by selective culture and rapid PCR in the laboratory. In phase II, swabs were analyzed accordingly, but the PCR test was conducted in labor ward. Test performances were analyzed and compared. RESULTS In phase I the rapid PCR test had a sensitivity of 85.71% and a specificity of 95.9%. The GBS colonization rate was 18.67%. Overall 8.5% of the PCR results were invalid. In phase II the PCR test showed a sensitivity of 85.71% and a specificity of 95.65%. The GBS colonization rate was 23.3%. Overall 23.5% of swabs tested with PCR were invalid. Initiation of specific, short 2-hour training for operating personnel in the labor ward reduced the invalid test rate to 13.4%. CONCLUSION The rapid PCR-based test yields adequate results to identify GBS colonization when performed in labor ward. In order to reduce the number of invalid tests a short training period is needed.

Judaism defended against the attacks of T. J. C. of Oxford : a reply to 2 letters on the Damascus question, in "The Times" newspaper of the 20th and 27th oct., 1840

by Morris J. Raphall

Zionistisches A-B-C-Buch

hrsg. ... von der Zionistischen Vereinigung für Deutschland

2D and 3D crystallization of a bacterial homologue of human vitamin C membrane transport proteins

Most organisms are able to synthesize vitamin C whereas humans are not. In order to contribute to the elucidation of the molecular working mechanism of vitamin C transport through biological membranes, we cloned, overexpressed, purified, functionally characterized, and 2D- and 3D-crystallized a bacterial protein (UraDp) with 29% of amino acid sequence identity to the human sodium-dependent vitamin C transporter 1 (SVCT1). Ligand-binding experiments by scintillation proximity assay revealed that uracil is a substrate preferably bound to UraDp. For structural analysis, we report on the production of tubular 2D crystals and present a first projection structure of UraDp from negatively stained tubes. On the other hand the successful growth of UraDp 3D crystals and their crystallographic analysis is described. These 3D crystals, which diffract X-rays to 4.2Å resolution, pave the way towards the high-resolution crystal structure of a bacterial homologue with high amino acid sequence identity to human SVCT1.

Oxypurinol directly and immediately activates the drug-specific T cells via the preferential use of HLA-B*58:01

Allopurinol (ALP) hypersensitivity is a major cause of severe cutaneous adverse reactions and is strongly associated with the HLA-B*58:01 allele. However, it can occur in the absence of this allele with identical clinical manifestations. The immune mechanism of ALP-induced severe cutaneous adverse reactions is poorly understood, and the T cell-reactivity pattern in patients with or without the HLA-B*58:01 allele is not known. To understand the interactions among the drug, HLA, and TCR, we generated T cell lines that react to ALP or its metabolite oxypurinol (OXP) from HLA-B*58:01(+) and HLA-B*58:01(-) donors and assessed their reactivity. ALP/OXP-specific T cells reacted immediately to the addition of the drugs and bypassed intracellular Ag processing, which is consistent with the "pharmacological interaction with immune receptors" (p-i) concept. This direct activation occurred regardless of HLA-B*58:01 status. Although most OXP-specific T cells from HLA-B*58:01(+) donors were restricted by the HLA-B*58:01 molecule for drug recognition, ALP-specific T cells also were restricted to other MHC class I molecules. This can be explained by in silico docking data that suggest that OXP binds to the peptide-binding groove of HLA-B*58:01 with higher affinity. The ensuing T cell responses elicited by ALP or OXP were not limited to particular TCR Vβ repertoires. We conclude that the drug-specific T cells are activated by OXP bound to HLA-B*58:01 through the p-i mechanism.

Interferon-free treatment of chronic hepatitis C with faldaprevir, deleobuvir and ribavirin: SOUND-C3, a Phase 2b study.

BACKGROUND & AIMS The safety and efficacy of the interferon-free combination of faldaprevir (NS3/A4 protease inhibitor), deleobuvir (BI 207127, non-nucleoside polymerase inhibitor), and ribavirin in treatment-naïve patients chronically infected with HCV genotype-1 was explored. METHODS SOUND-C3 was a multicenter, open-label Phase 2b study. Treatment-naïve patients chronically infected with HCV genotype-1a (IL28B CC genotype only; n = 12) and genotype-1b (n = 20) were assigned to 16 weeks of treatment with faldaprevir 120 mg once daily, deleobuvir 600 mg twice daily, and weight-based ribavirin. Patients with compensated liver disease, including cirrhosis, were eligible for inclusion in this study. The primary endpoint was sustained virological response 12 weeks after completion of therapy. RESULTS Sustained virological response rates 12 weeks after completion of therapy were 17% and 95% in patients infected with HCV genotype-1a and genotype-1b respectively. All four patients with cirrhosis achieved sustained virological response 12 weeks after completion of therapy. The most frequently reported adverse events of at least moderate intensity were anaemia (16%), nausea, vomiting and fatigue (9% each). Three (9%) patients discontinued because of adverse events. CONCLUSIONS The interferon-free regimen of faldaprevir, deleobuvir and ribavirin was efficacious in patients infected with genotype-1b and generally well tolerated.

Stress-induced modulation of NF-κB activation, inflammation-associated gene expression, and cytokine levels in blood of healthy men

Acute psychosocial stress stimulates transient increases in circulating pro-inflammatory plasma cytokines, but little is known about stress effects on anti-inflammatory cytokines or underlying mechanisms. We investigated the stress kinetics and interrelations of pro- and anti-inflammatory measures on the transcriptional and protein level. Forty-five healthy men were randomly assigned to either a stress or control group. While the stress group underwent an acute psychosocial stress task, the second group participated in a non-stress control condition. We repeatedly measured before and up to 120min after stress DNA binding activity of the pro-inflammatory transcription factor NF-κB (NF-κB-BA) in peripheral blood mononuclear cells, whole-blood mRNA levels of NF-κB, its inhibitor IκBα, and of the pro-inflammatory cytokines interleukin (IL)-1ß and IL-6, and the anti-inflammatory cytokine IL-10. We also repeatedly measured plasma levels of IL-1ß, IL-6, and IL-10. Compared to non-stress, acute stress induced significant and rapid increases in NF-κB-BA and delayed increases in plasma IL-6 and mRNA of IL-1ß, IL-6, and IκBα (p's<.045). In the stress group, significant increases over time were also observed for NF-κB mRNA and plasma IL-1ß and IL-10 (p's<.055). NF-κB-BA correlated significantly with mRNA of IL-1β (r=.52, p=.002), NF-κB (r=.48, p=.004), and IκBα (r=.42, p=.013), and marginally with IL-6 mRNA (r=.31, p=.11). Plasma cytokines did not relate to NF-κB-BA or mRNA levels of the respective cytokines. Our data suggest that stress induces increases in NF-κB-BA that relate to subsequent mRNA expression of pro-inflammatory, but not anti-inflammatory cytokines, and of regulatory-cytoplasmic-proteins. The stress-induced increases in plasma cytokines do not seem to derive from de novo synthesis in circulating blood cells.

Observation of an Excited B±c Meson State with the ATLAS Detector

A search for excited states of the B ± c meson is performed using 4.9  fb −1 of 7 TeV and 19.2  fb −1 of 8 TeV pp collision data collected by the ATLAS experiment at the LHC. A new state is observed through its hadronic transition to the ground state, with the latter detected in the decay B ± c →J/ψπ ± . The state appears in the m(B ± c π + π − )−m(B ± c )−2m(π ± ) mass difference distribution with a significance of 5.2 standard deviations. The mass of the observed state is 6842±4±5  MeV , where the first error is statistical and the second is systematic. The mass and decay of this state are consistent with expectations for the second S -wave state of the B ± c meson, B ± c (2S) .

Stimulation of monocytes by placental microparticles involves toll-like receptors and nuclear factor kappa-light-chain-enhancer of activated B cells.

Human pregnancy is accompanied by a mild systemic inflammatory response, which includes the activation of monocytes circulating in maternal blood. This response is exaggerated in preeclampsia, a placental-dependent disorder specific to human pregnancies. We and others showed that placental syncytiotrophoblast membrane microparticles (STBM) generated in vitro from normal placentas stimulated peripheral blood monocytes, which suggest a contribution of STBM to the systemic maternal inflammation. Here, we analyzed the inflammatory potential of STBM prepared from preeclamptic placentas on primary monocytes and investigated the mode of action in vitro. STBM generated in vitro by placental villous explants of normal or preeclamptic placentas were co-incubated with human peripheral blood monocytes. In some cases, inhibitors of specific cellular functions or signaling pathways were used. The analysis of the monocytic response was performed by flow cytometry, enzyme-linked immunoassays, real-time PCR, and fluorescence microscopy. STBM derived from preeclamptic placentas up-regulated the cell surface expression of CD54, and stimulated the secretion of the pro-inflammatory interleukin (IL)-6 and IL-8 in a similar, dose-dependent manner as did STBM prepared from normal placentas. STBM bound to the cell surface of monocytes, but phagocytosis was not necessary for activation. STBM-induced cytokine secretion was impaired in the presence of inhibitors of toll-like receptor (TLR) signaling or when nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation was blocked. Our results suggest that the inflammatory reaction in monocytes may be initiated by the interaction of STBM with TLRs, which in turn signal through NF-κB to mediate the transcription of genes coding for pro-inflammatory factors.

Allerunterthänigst-gründliche Gegen-Information Und Exceptiones Sub- & Obreptionis : An Die Römis. Kayserl. ... Majestät ... Auff das am 12. May nup. und 19. currentis mensis erlassene Kayserl. Rescript, Juncta Petitione Humillima Pro Clementissima cassatione ejusdem ... ; In Sachen Judenschafft zu Franckfurth am Mayn Contrà Den Magistrat daselbsten ; Bey höchst-preyßlichen Reichs-Hof-Rath Den 23. Julii 1714 übergeben ; Mit Beylagen A, B, C & D ; Das Bau-Weesen betreffend

Burgerschafftl. Abgeordneter [Johann Dieterich Notebohm ; Joachim Hoppe] [[Elektronische Ressource]]

Das republikanische A B C

Boberach: Die Reichsverfassung soll die Menschenrechte garantieren und die Pflichten der Staatsbürger regeln. Republikanische Prinzipien sollen für die Gemeinden, die Kreise, die Staaten und das Reich gelten, das aus 19 Gliedstaaten bestehen soll. Als Organe sind vorgesehen: Reichstag (Oberhaus und Unterhaus), Reichsrat, Reichsobmann, der von den Landtagen gewählt wird, Reichsgericht mit Laienmehrheit, Heerwesen, Steuerangelegenheiten, Kirchen- und Schulwesen sind den Gemeinden zu überlassen. Eine allgemeine Einkommensteuer soll die Landesbedürfnisse, eine Luxussteuer soll Gemeinden und Kreise, Zölle auf Luxuswaren und ausländische Produkte die Ausgaben des Reiches finanzieren