Immune responses and protection induced by mucosal and systemic immunisation with recombinant measles nucleoprotein in a mouse model of measles virus-induced encephalitis.

In this study the immunogenicity of recombinant nucleoprotein (Np) administered intranasally or intraperitoneally, and its ability to support a systemic protective anti-virus antibody response was examined, in a mouse model of measles virus (MV)-induced encephalitis. Although both intranasal and intraperitoneal routes of immunisation resulted in priming Np- and MV-specific T-cell responses, the intraperitoneal route was shown to prime for a predominantly IgG2a serum anti-MV antibody response of high avidity, which confered complete protection following intracranial challenge with a neuroadapted strain of MV. On the other hand, intranasal priming resulted in a mixed IgG1, IgG2a serum anti-MV antibody response of low avidity, and only 43% of immunised mice survived following intracranial challenge with the neuroadapted strain of MV. These findings suggest that the route of immunisation in combination with an appropriate adjuvant could influence the induction of a quality antibody response with protective capacity

Susceptibility testing and reporting of new antibiotics with a focus on tedizolid: an international working group report

Inappropriate use and overuse of antibiotics are among the most important factors in resistance development, and effective antibiotic stewardship measures are needed to optimize outcomes. Selection of appropriate antimicrobials relies on accurate and timely antimicrobial susceptibility testing. However, the availability of clinical breakpoints and in vitro susceptibility testing often lags behind regulatory approval by several years for new antimicrobials. A Working Group of clinical/medical microbiologists from Brazil, Canada, Mexico, Saudi Arabia, Russia and the UK recently examined issues surrounding antimicrobial susceptibility testing for novel antibiotics. While commercially available tests are being developed, potential surrogate antibiotics may be used as marker of susceptibility. Using tedizolid as an example of a new antibiotic, this special report makes recommendations to optimize routine susceptibility reporting

Psychiatric Context of Acute/Early HIV Infection. The NIMH Multisite Acute HIV Infection Study: IV

Acute/early HIV infection is a period of high risk for HIV transmission. Better understanding of behavioral aspects during this period could improve interventions to limit further transmission. Thirty-four participants with acute/early HIV infection from six US cities were assessed with the Mini International Diagnostic Interview, Beck Depression Inventory II, State-Trait Anxiety Inventory, Brief COPE, and an in-depth interview. Most had a pre-HIV history of alcohol or substance use disorder (85%); a majority (53%) had a history of major depressive or bipolar disorder. However, post-diagnosis coping was predominantly adaptive, with only mild to moderate elevations of anxious or depressive mood. Respondents described challenges managing HIV in tandem with pre-existing substance abuse problems, depression, and anxiety. Integration into medical and community services was associated with adaptive coping. The psychiatric context of acute/early HIV infection may be a precursor to infection, but not necessarily a barrier to intervention to reduce forward transmission of HIV among persons newly infected

Detecting imipenem resistance in Acinetobacter baumannii by automated systems (BD Phoenix, Microscan WalkAway, Vitek 2); high error rates with Microscan WalkAway

<p>Abstract</p> <p>Background</p> <p>Increasing reports of carbapenem resistant <it>Acinetobacter baumannii </it>infections are of serious concern. Reliable susceptibility testing results remains a critical issue for the clinical outcome. Automated systems are increasingly used for species identification and susceptibility testing. This study was organized to evaluate the accuracies of three widely used automated susceptibility testing methods for testing the imipenem susceptibilities of <it>A. baumannii </it>isolates, by comparing to the validated test methods.</p> <p>Methods</p> <p>Selected 112 clinical isolates of <it>A. baumanii </it>collected between January 2003 and May 2006 were tested to confirm imipenem susceptibility results. Strains were tested against imipenem by the reference broth microdilution (BMD), disk diffusion (DD), Etest, BD Phoenix, MicroScan WalkAway and Vitek 2 automated systems. Data were analysed by comparing the results from each test method to those produced by the reference BMD test.</p> <p>Results</p> <p>MicroScan performed true identification of all <it>A. baumannii </it>strains while Vitek 2 unidentified one strain, Phoenix unidentified two strains and misidentified two strains. Eighty seven of the strains (78%) were resistant to imipenem by BMD. Etest, Vitek 2 and BD Phoenix produced acceptable error rates when tested against imipenem. Etest showed the best performance with only two minor errors (1.8%). Vitek 2 produced eight minor errors(7.2%). BD Phoenix produced three major errors (2.8%). DD produced two very major errors (1.8%) (slightly higher (0.3%) than the acceptable limit) and three major errors (2.7%). MicroScan showed the worst performance in susceptibility testing with unacceptable error rates; 28 very major (25%) and 50 minor errors (44.6%).</p> <p>Conclusion</p> <p>Reporting errors for <it>A. baumannii </it>against imipenem do exist in susceptibility testing systems. We suggest clinical laboratories using MicroScan system for routine use should consider using a second, independent antimicrobial susceptibility testing method to validate imipenem susceptibility. Etest, whereever available, may be used as an easy method to confirm imipenem susceptibility.</p

Feasibility of a cohort study on health risks caused by occupational exposure to radiofrequency electromagnetic fields

Breckenkamp J, Berg-Beckhoff G, Muenster E, et al. Feasibility of a cohort study on health risks caused by occupational exposure to radiofrequency electromagnetic fields. Environmental Health. 2009;8(1):23.Background: The aim of this study was to examine the feasibility of performing a cohort study on health risks from occupational exposure to radiofrequency electromagnetic fields (RF-EMF) in Germany. Methods: A set of criteria was developed to evaluate the feasibility of such a cohort study. The criteria aimed at conditions of exposure and exposure assessment (level, duration, preferably on an individual basis), the possibility to assemble a cohort and the feasibility of ascertaining various disease endpoints. Results: Twenty occupational settings with workers potentially exposed to RF-EMF and, in addition, a cohort of amateur radio operators were considered. Based on expert ratings, literature reviews and our set of predefined criteria, three of the cohorts were identified as promising for further evaluation: the personnel (technicians) of medium/short wave broadcasting stations, amateur radio operators, and workers on dielectric heat sealers. After further analyses, the cohort of workers on dielectric heat sealers seems not to be feasible due to the small number of exposed workers available and to the difficulty of assessing exposure (exposure depends heavily on the respective working process and mixture of exposures, e.g. plastic vapours), although exposure was highest in this occupational setting. The advantage of the cohort of amateur radio operators was the large number of persons it includes, while the advantage of the cohort of personnel working at broadcasting stations was the quality of retrospective exposure assessment. However, in the cohort of amateur radio operators the exposure assessment was limited, and the cohort of technicians was hampered by the small number of persons working in this profession. Conclusion: The majority of occupational groups exposed to RF-EMF are not practicable for setting up an occupational cohort study due to the small numbers of exposed subjects or due to exposure levels being only marginally higher than those of the general public

Conjunctive input processing drives feature selectivity in hippocampal CA1 neurons

Feature-selective firing allows networks to produce representations of the external and internal environments. Despite its importance, the mechanisms generating neuronal feature selectivity are incompletely understood. In many cortical microcircuits the integration of two functionally distinct inputs occurs nonlinearly through generation of active dendritic signals that drive burst firing and robust plasticity. To examine the role of this processing in feature selectivity, we recorded CA1 pyramidal neuron membrane potential and local field potential in mice running on a linear treadmill. We found that dendritic plateau potentials were produced by an interaction between properly timed input from entorhinal cortex and hippocampal CA3. These conjunctive signals positively modulated the firing of previously established place fields and rapidly induced new place field formation to produce feature selectivity in CA1 that is a function of both entorhinal cortex and CA3 input. Such selectivity could allow mixed network level representations that support context-dependent spatial maps.Howard Hughes Medical InstituteRikagaku Kenkyūjo (Japan

Loss of Arc renders the visual cortex impervious to the effects of sensory experience or deprivation

A myriad of mechanisms have been suggested to account for the full richness of visual cortical plasticity. We found that visual cortex lacking Arc is impervious to the effects of deprivation or experience. Using intrinsic signal imaging and chronic visually evoked potential recordings, we found that Arc−/− mice did not exhibit depression of deprived-eye responses or a shift in ocular dominance after brief monocular deprivation. Extended deprivation also failed to elicit a shift in ocular dominance or open-eye potentiation. Moreover, Arc−/− mice lacked stimulus-selective response potentiation. Although Arc−/− mice exhibited normal visual acuity, baseline ocular dominance was abnormal and resembled that observed after dark-rearing. These data suggest that Arc is required for the experience-dependent processes that normally establish and modify synaptic connections in visual cortex.Howard Hughes Medical InstituteNational Science Foundation (U.S.

A Unified Model of the GABA(A) Receptor Comprising Agonist and Benzodiazepine Binding Sites

We present a full-length α(1)β(2)γ(2) GABA receptor model optimized for agonists and benzodiazepine (BZD) allosteric modulators. We propose binding hypotheses for the agonists GABA, muscimol and THIP and for the allosteric modulator diazepam (DZP). The receptor model is primarily based on the glutamate-gated chloride channel (GluCl) from C. elegans and includes additional structural information from the prokaryotic ligand-gated ion channel ELIC in a few regions. Available mutational data of the binding sites are well explained by the model and the proposed ligand binding poses. We suggest a GABA binding mode similar to the binding mode of glutamate in the GluCl X-ray structure. Key interactions are predicted with residues α(1)R66, β(2)T202, α(1)T129, β(2)E155, β(2)Y205 and the backbone of β(2)S156. Muscimol is predicted to bind similarly, however, with minor differences rationalized with quantum mechanical energy calculations. Muscimol key interactions are predicted to be α(1)R66, β(2)T202, α(1)T129, β(2)E155, β(2)Y205 and β(2)F200. Furthermore, we argue that a water molecule could mediate further interactions between muscimol and the backbone of β(2)S156 and β(2)Y157. DZP is predicted to bind with interactions comparable to those of the agonists in the orthosteric site. The carbonyl group of DZP is predicted to interact with two threonines α(1)T206 and γ(2)T142, similar to the acidic moiety of GABA. The chlorine atom of DZP is placed near the important α(1)H101 and the N-methyl group near α(1)Y159, α(1)T206, and α(1)Y209. We present a binding mode of DZP in which the pending phenyl moiety of DZP is buried in the binding pocket and thus shielded from solvent exposure. Our full length GABA(A) receptor is made available as Model S1