Telavancin for hospital-acquired pneumonia: Clinical response and 28-day survival

U.S. Food and Drug Administration draft guidance for future antibiotic clinical trials of bacterial nosocomial pneumonia recommends the use of diagnostic criteria according to American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) guidelines and the use of a primary endpoint of 28-day all-cause mortality. The effect of applying these guidelines on outcomes of phase III nosocomial pneumonia studies of telavancin was evaluated in a post hoc analysis. ATS/IDSA criteria were applied in a blind fashion to the original all-treated (AT) group. Clinical cure rates at final follow-up were determined in the refined AT and clinically evaluable (CE) groups (ATS/IDSA-AT and ATS/IDSA-CE, respectively). The exploratory endpoint of 28-day survival was evaluated for the ATS/IDSA-AT group. Noninferiority of telavancin versus vancomycin was demonstrated, with similar cure rates in the ATS/IDSA-AT (59% versus 59%) and ATS/IDSA-CE (83% versus 80%) groups. Cure rates favored telavancin in ATS/IDSA-CE patients where Staphylococcus aureus was the sole pathogen (86% versus 75%). Overall, 28-day survival rates were similar in the telavancin (76%) and vancomycin (77%) groups but lower in telavancin-treated patients with preexisting moderate-to-severe renal impairment (creatinine clearance [CL(CR)] of <50 ml/min). Telavancin should be administered to patients with moderate-to-severe renal impairment only if treatment benefit outweighs the risk or if no suitable alternatives are available

Ascaroside Expression in Caenorhabditis elegans Is Strongly Dependent on Diet and Developmental Stage

Background: The ascarosides form a family of small molecules that have been isolated from cultures of the nematode Caenorhabditis elegans. They are often referred to as “dauer pheromones” because most of them induce formation of long-lived and highly stress resistant dauer larvae. More recent studies have shown that ascarosides serve additional functions as social signals and mating pheromones. Thus, ascarosides have multiple functions. Until now, it has been generally assumed that ascarosides are constitutively expressed during nematode development. Methodology/Principal Findings: Cultures of C. elegans were developmentally synchronized on controlled diets. Ascarosides released into the media, as well as stored internally, were quantified by LC/MS. We found that ascaroside biosynthesis and release were strongly dependent on developmental stage and diet. The male attracting pheromone was verified to be a blend of at least four ascarosides, and peak production of the two most potent mating pheromone components, ascr#3 and asc#8 immediately preceded or coincided with the temporal window for mating. The concentration of ascr#2 increased under starvation conditions and peaked during dauer formation, strongly supporting ascr#2 as the main population density signal (dauer pheromone). After dauer formation, ascaroside production largely ceased and dauer larvae did not release any ascarosides. These findings show that both total ascaroside production and the relative proportions of individual ascarosides strongly correlate with these compounds' stage-specific biological functions. Conclusions/Significance: Ascaroside expression changes with development and environmental conditions. This is consistent with multiple functions of these signaling molecules. Knowledge of such differential regulation will make it possible to associate ascaroside production to gene expression profiles (transcript, protein or enzyme activity) and help to determine genetic pathways that control ascaroside biosynthesis. In conjunction with findings from previous studies, our results show that the pheromone system of C. elegans mimics that of insects in many ways, suggesting that pheromone signaling in C. elegans may exhibit functional homology also at the sensory level. In addition, our results provide a strong foundation for future behavioral modeling studies

Antibody responses to the full-length VAR2CSA and its DBL domains in Cameroonian children and teenagers

Additional file 2. IgG levels to VAR2CSA domains in 10–15 year old Cameroonian girls living in Ngali II and Ntouessong villages. IgG levels to VAR2CSA DBL domains and full-length protein (FV2) were measured in 11–15 year old girls residing in Ngali II and Ntouessong villages. DBL1 domain was from 3D7 strain and all the other proteins from FCR3 parasite strain. Median MFI and Inter-Quartile Range (IQR) are plotted

Mycobacterium tuberculosis Responds to Chloride and pH as Synergistic Cues to the Immune Status of its Host Cell

PubMed ID: 23592993This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

NuSTAR Hard X-ray Survey of the Galactic Center Region I: Hard X-ray Morphology and Spectroscopy of the Diffuse Emission

We present the first sub-arcminute images of the Galactic Center above 10 keV, obtained with NuSTAR. NuSTAR resolves the hard X-ray source IGR J17456-2901 into non-thermal X-ray filaments, molecular clouds, point sources and a previously unknown central component of hard X-ray emission (CHXE). NuSTAR detects four non-thermal X-ray filaments, extending the detection of their power-law spectra with $\Gamma\sim1.3$-$2.3$ up to ~50 keV. A morphological and spectral study of the filaments suggests that their origin may be heterogeneous, where previous studies suggested a common origin in young pulsar wind nebulae (PWNe). NuSTAR detects non-thermal X-ray continuum emission spatially correlated with the 6.4 keV Fe K$\alpha$ fluorescence line emission associated with two Sgr A molecular clouds: MC1 and the Bridge. Broad-band X-ray spectral analysis with a Monte-Carlo based X-ray reflection model self-consistently determined their intrinsic column density ($\sim10^{23}$ cm$^{-2}$), primary X-ray spectra (power-laws with $\Gamma\sim2$) and set a lower limit of the X-ray luminosity of Sgr A* flare illuminating the Sgr A clouds to $L_X \stackrel{>}{\sim} 10^{38}$ erg s$^{-1}$. Above ~20 keV, hard X-ray emission in the central 10 pc region around Sgr A* consists of the candidate PWN G359.95-0.04 and the CHXE, possibly resulting from an unresolved population of massive CVs with white dwarf masses $M_{\rm WD} \sim 0.9 M_{\odot}$. Spectral energy distribution analysis suggests that G359.95-0.04 is likely the hard X-ray counterpart of the ultra-high gamma-ray source HESS J1745-290, strongly favoring a leptonic origin of the GC TeV emission.Comment: 27 pages. Accepted for publication in the Astrophysical Journa

MAX: Development of a Laue diffraction lens for nuclear astrophysics

The next generation of instrumentation for nuclear astrophysics will have to achieve an improvement in sensitivity by a factor of 10-100 over present technologies. With the focusing gamma-ray telescope MAX we take up this challenge and propose to combine the required sensitivity with high spectral and angular resolution, and the capability to measure the polarization of the photons. MAX is a space-borne crystal diffraction telescope, featuring a broad-band Laue lens optimized for the observation of compact sources in two wide energy bands of high astrophysical relevance. Gamma rays will be focused from the large collecting area of a crystal diffraction lens onto a very small detector volume. As a consequence, the signal to background ratio is greatly enhanced, leading to unprecedented sensitivities