Performance of cobas® 4800 and m2000 real-time™ assays for detection of Chlamydia trachomatis and Neisseria gonorrhoeae in rectal and self-collected vaginal specimen

A prospective, multicenter trial was designed to compare the performance characteristics of the cobas® 4800 (Roche Diagnostics, Indianapolis, IN, USA) and m2000 real-time™ (Abbott Molecular Inc., Des Plaines, IL, USA) assays for detection of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) in rectal and self-collected vaginal swabs. Rectal (n = 234) or self-collected vaginal swabs (n = 687) were obtained from consenting individuals visiting their general practitioners, dermatologists, gynecologists, sexually transmitted disease clinics, or family planning centers from May 2010 to February 2011. High concordance rates (≥96%) were observed between the cobas® 4800 and m2000 real-time™ assays for CT/NG detection in both rectal and self-collected vaginal swabs. The performance profiles confirm the usefulness of both kinds of swab types for CT and NG detection using described nucleic acid amplification tests assays. Based on this study, rectal and self-collected vaginal swabs offer a noninvasive alternative, which may improve screening for CT and NG infections.     

Lack of lithium-like behavioral and molecular effects in IMPA2 knockout mice.

Lithium is a potent mood-stabilizing medication in bipolar disorder. Despite 50 years of clinical use, the mechanism of action is unknown. Multiple effects have been attributed to lithium including the uncompetitive inhibition of inositol monophosphatase (IMPase). IMPA2, one of the genes that encode IMPase, is located in a region with linkage to bipolar disorder. Owing to the role of IMPase in cell signaling and the possibility that this enzyme is a target for mood-stabilizing drugs, we generated IMPA2(-/-) mice. Possible involvement of IMPase in complex behaviors related to affective disorders was assessed by monitoring the behavior of the IMPA2(-/-) mice in the forced swim test, the tail suspension test (TST), the elevated zero-maze and open field test. It has been described that chronically lithium-treated mice exhibit reduced immobility time in the forced swim test and decreased exploratory behavior. We found increased rearing of IMPA2(-/-) mice in the open field, suggesting an increased exploratory behavior. Although immobility time of IMPA2(-/-) female but not male mice in the forced swim test was reduced, no difference was found between male and female IMPA2(-/-) and IMPA2(+/+) mice in the TST and overall there was no clear effect of the deletion of IMPA2 on depression-like behavior. Frontal cortex IMPase activity and inositol levels in the IMPA2(-/-) mice did not differ from IMPA2(+/+) mice, but kidney inositol levels were reduced. In conclusion, phenotypic characterization of the IMPA2(-/-) mouse indicates that deleting IMPA2 does not mimic the effects of lithium treatment.     

Prioritization strategies for pandemic influenza vaccine in 27 countries of the European Union and the Global Health Security Action Group: a review

Background  

Although there is rapid progress in vaccine research regarding influenza pandemic vaccines it is expected that pandemic influenza vaccine production can only start once the pandemic virus has been recognized. Therefore, pandemic vaccine capacity will be limited at least during the first phase of an influenza pandemic, requiring vaccine prioritization strategies. WHO recommends developing preliminary priorities for pandemic vaccine use. The goal of this review is to provide a thorough overview of pandemic vaccine prioritization concepts in the 27 European Union (EU) member states and the four non-EU countries of the Global Health Security Action Group.     

Modeling anti-KLH ELISA data using two-stage and mixed effects models in support of immunotoxicological studies

During preclinical drug development, the immune system is specifically evaluated after prolonged treatment with drug candidates, because the immune system may be an important target system. The response of antibodies against a T-cell-dependent antigen is recommenced by the FDA and EMEA for the evaluation of immunosuppression/enhancement. For that reason, we developed a semiquantitative enzyme-linked immunosorbent assay to measure antibodies against keyhole limpet hemocyanin. To our knowledge, the analysis of this kind of data is at this moment not yet fully explored. In this article, we describe two approaches for modeling immunotoxic data using nonlinear models. The first is a two-stage model in which we fit an individual nonlinear model for each animal in the first stage, and the second stage consists of testing possible treatment effects using the individual maximum likelihood estimates obtained in the first stage. In the second approach, the inference about treatment effects is based on a nonlinear mixed model, which accounts for heterogeneity between animals. In both approaches, we use a three-parameter logistic model for the mean structure.     

Rapid genotyping of blood group antigens by multiplex polymerase chain reaction and DNA microarray hybridization

BACKGROUND: In the Netherlands, 500,000 blood donors are active. Blood of all donors is currently typed serologically for ABO, the Rh phenotype, and K. Only a subset of donors is typed twice for a larger set of red cell (RBC) and/or platelet (PLT) antigens. To increase the direct availability of typed RBCs and PLTs, a high-throughput technique is being developed to genotype the whole donor cohort for all clinically relevant RBC and PLT antigens. STUDY DESIGN AND METHODS: A multiplex polymerase chain reaction was developed to both amplify and fluorescently label 19 gene fragments of RBC and PLT antigens in one reaction. To test the setup of the genotyping method by microarray, a pilot study with human PLT antigen (HPA)-typed donor samples was performed. On each slide, 12 arrays are present containing 20 probes per PLT antigen system (28 for HPA-3). The allele-specific oligohybridization method was used to discriminate between two different alleles. RESULTS: Two blinded panels encompassing 94 donors were genotyped for HPA-1 through -5 and -15; no discrepancies were found compared to their serologic typing (HPA-1, -2, -3, -4, and -5) and genotyping (HPA-15; TaqMan, Applied Biosystems). CONCLUSION: This study shows that the HPA microarray provides a reliable and fast genotyping procedure. With further development an automated throughput for complete typing of large donor cohorts can be obtained.