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The changing epidemiology of Staphylococcus aureus?
Strains of methicillin-resistant Staphylococcus aureus (MRSA), which had been largely confined to hospitals and long-term care facilities, are emerging in the community. The changing epidemiology of MRSA bears striking similarity to the emergence of penicillinase-mediated resistance in S. aureus decades ago. Even though the origin (hospital or the community) of the emerging MRSA strains is not known, the prevalence of these strains in the community seems likely to increase substantially
Understanding heterogeneity in the host response to Staphylococcus aureus infection for prognostic biomarker discovery
Single-Dose Oritavancin Treatment of Acute Bacterial Skin and Skin Structure Infections: SOLO Trial Efficacy by Eron Severity and Management Setting.
INTRODUCTION: Introduction of new antibiotics enabling single-dose administration, such as oritavancin may significantly impact site of care decisions for patients with acute bacterial skin and skin structure infections (ABSSSI). This analysis compared the efficacy of single-dose oritavancin with multiple-dose vancomycin in patients categorized according to disease severity via modified Eron classification and management setting. METHODS: SOLO I and II were phase 3 studies evaluating single-dose oritavancin versus 7-10 days of vancomycin for treatment of ABSSSI. Patient characteristics were collected at baseline and retrospectively analyzed. Study protocols were amended, allowing outpatient management at the discretion of investigators. In this post hoc analysis, patients were categorized according to a modified Eron severity classification and management setting (outpatient vs. inpatient) and the efficacy compared. RESULTS: Overall, 1910 patients in the SOLO trials were categorized into Class I (520, 26.5%), II (790, 40.3%), and III (600, 30.6%). Of the 767 patients (40%) in the SOLO trials who were managed entirely in the outpatient setting 40.3% were categorized as Class II and 30.6% were Class III. Clinical efficacy was similar between oritavancin and vancomycin treatment groups, regardless of severity classification and across inpatient and outpatient settings. Class III patients had lower response rates (oritavancin 73.3%, vancomycin 76.6%) at early clinical evaluation when compared to patients in Class I (82.6%) or II (86.1%); however, clinical cure rates at the post-therapy evaluation were similar for Class III patients (oritavancin 79.8%, vancomycin 79.9%) when compared to Class I and II patients (79.1-85.7%). CONCLUSION: Single-dose oritavancin therapy results in efficacy comparable to multiple-dose vancomycin in patients categorized according to modified Eron disease severity classification regardless of whether management occurred in the inpatient or outpatient setting. FUNDING: The Medicines Company, Parsippany, NJ, USA. TRIAL REGISTRATION: ClinicalTrials.gov identifiers, NCT01252719 (SOLO I) and NCT01252732 (SOLO II)
Synergistic Antibacterial Effects of Metallic Nanoparticle Combinations
© The Author(s) 2019.Metallic nanoparticles have unique antimicrobial properties that make them suitable for use within medical and pharmaceutical devices to prevent the spread of infection in healthcare. The use of nanoparticles in healthcare is on the increase with silver being used in many devices. However, not all metallic nanoparticles can target and kill all disease-causing bacteria. To overcome this, a combination of several different metallic nanoparticles were used in this study to compare effects of multiple metallic nanoparticles when in combination than when used singly, as single elemental nanoparticles (SENPs), against two common hospital acquired pathogens (Staphylococcus aureus and Pseudomonas. aeruginosa). Flow cytometry LIVE/DEAD assay was used to determine rates of cell death within a bacterial population when exposed to the nanoparticles. Results were analysed using linear models to compare effectiveness of three different metallic nanoparticles, tungsten carbide (WC), silver (Ag) and copper (Cu), in combination and separately. Results show that when the nanoparticles are placed in combination (NPCs), antimicrobial effects significantly increase than when compared with SENPs (P < 0.01). This study demonstrates that certain metallic nanoparticles can be used in combination to improve the antimicrobial efficiency in destroying morphologically distinct pathogens within the healthcare and pharmaceutical industry.Peer reviewe
Planetary Dynamics and Habitable Planet Formation In Binary Star Systems
Whether binaries can harbor potentially habitable planets depends on several
factors including the physical properties and the orbital characteristics of
the binary system. While the former determines the location of the habitable
zone (HZ), the latter affects the dynamics of the material from which
terrestrial planets are formed (i.e., planetesimals and planetary embryos), and
drives the final architecture of the planets assembly. In order for a habitable
planet to form in a binary star system, these two factors have to work in
harmony. That is, the orbital dynamics of the two stars and their interactions
with the planet-forming material have to allow terrestrial planet formation in
the habitable zone, and ensure that the orbit of a potentially habitable planet
will be stable for long times. We have organized this chapter with the same
order in mind. We begin by presenting a general discussion on the motion of
planets in binary stars and their stability. We then discuss the stability of
terrestrial planets, and the formation of potentially habitable planets in a
binary-planetary system.Comment: 56 pages, 29 figures, chapter to appear in the book: Planets in
Binary Star Systems (Ed. N. Haghighipour, Springer publishing company
The role of planetary formation and evolution in shaping the composition of exoplanetary atmospheres
Over the last twenty years, the search for extrasolar planets revealed us the
rich diversity of the outcomes of the formation and evolution of planetary
systems. In order to fully understand how these extrasolar planets came to be,
however, the orbital and physical data we possess are not enough, and they need
to be complemented with information on the composition of the exoplanets.
Ground-based and space-based observations provided the first data on the
atmospheric composition of a few extrasolar planets, but a larger and more
detailed sample is required before we can fully take advantage of it. The
primary goal of the Exoplanet Characterization Observatory (EChO) is to fill
this gap, expanding the limited data we possess by performing a systematic
survey of hundreds of extrasolar planets. The full exploitation of the data
that EChO and other space-based and ground-based facilities will provide in the
near future, however, requires the knowledge of what are the sources and sinks
of the chemical species and molecules that will be observed. Luckily, the study
of the past history of the Solar System provides several indications on the
effects of processes like migration, late accretion and secular impacts, and on
the time they occur in the life of planetary systems. In this work we will
review what is already known about the factors influencing the composition of
planetary atmospheres, focusing on the case of gaseous giant planets, and what
instead still need to be investigated.Comment: 26 pages, 9 figures, 1 table. Accepted for publication on
Experimental Astronomy, special issue on the M3 EChO mission candidat
Origin of the cataclysmic Late Heavy Bombardment period of the terrestrial planets
Nature, 435, pp. 466-469, http://dx.doi.org./10.1038/nature03676International audienc
High-level production of violacein by the newly isolated Duganella violaceinigra str. NI28 and its impact on Staphylococcus aureus
A violacein-producing bacterial strain was isolated and identified as a relative of Duganella violaceinigra YIM 31327 based upon phylogenetic analyses using the 16S rRNA, gyrB and vioA gene sequences and a fatty acid methyl ester (FAME) analysis. This new strain was designated D. violaceinigra str. NI28. Although these two strains appear related based upon these analyses, the new isolate was phenotypically different from the type strain as it grew 25% faster on nutrient media and produced 45-fold more violacein. When compared with several other violacein producing strains, including Janthinobacterium lividum, D. violaceinigra str. NI28 was the best violacein producer. For instance, the crude violacein yield with D. violaceinigra str. NI28 was 6.0 mg/OD at 24 hours, a value that was more than two-fold higher than all the other strains. Finally, the antibacterial activity of D. violaceinigra str. NI28 crude violacein was assayed using several multidrug resistant Staphylococcus aureus. Addition of 30 mu M crude violacein led to a 96% loss in the initial S. aureus population while the minimum inhibitory concentration was 1.8 mu M. Consequently, this novel isolate represents a phenotypic variant of D. violaceinigra capable of producing much greater quantities of crude violacein, an antibiotic effective against multidrug resistant S. aureusopen
Planetary population synthesis
In stellar astrophysics, the technique of population synthesis has been
successfully used for several decades. For planets, it is in contrast still a
young method which only became important in recent years because of the rapid
increase of the number of known extrasolar planets, and the associated growth
of statistical observational constraints. With planetary population synthesis,
the theory of planet formation and evolution can be put to the test against
these constraints. In this review of planetary population synthesis, we first
briefly list key observational constraints. Then, the work flow in the method
and its two main components are presented, namely global end-to-end models that
predict planetary system properties directly from protoplanetary disk
properties and probability distributions for these initial conditions. An
overview of various population synthesis models in the literature is given. The
sub-models for the physical processes considered in global models are
described: the evolution of the protoplanetary disk, the planets' accretion of
solids and gas, orbital migration, and N-body interactions among concurrently
growing protoplanets. Next, typical population synthesis results are
illustrated in the form of new syntheses obtained with the latest generation of
the Bern model. Planetary formation tracks, the distribution of planets in the
mass-distance and radius-distance plane, the planetary mass function, and the
distributions of planetary radii, semimajor axes, and luminosities are shown,
linked to underlying physical processes, and compared with their observational
counterparts. We finish by highlighting the most important predictions made by
population synthesis models and discuss the lessons learned from these
predictions - both those later observationally confirmed and those rejected.Comment: 47 pages, 12 figures. Invited review accepted for publication in the
'Handbook of Exoplanets', planet formation section, section editor: Ralph
Pudritz, Springer reference works, Juan Antonio Belmonte and Hans Deeg, Ed
Side Chain Hydrophobicity Modulates Therapeutic Activity and Membrane Selectivity of Antimicrobial Peptide Mastoparan-X
The discovery of new anti-infective compounds is stagnating and multi-resistant bacteria continue to emerge, threatening to end the "antibiotic era". Antimicrobial peptides (AMPs) and lipo-peptides such as daptomycin offer themselves as a new potential class of antibiotics; however, further optimization is needed if AMPs are to find broad use as antibiotics. In the present work, eight analogues of mastoparan-X (MPX) were investigated, having side chain modifications in position 1, 8 and 14 to modulate peptide hydrophobicity. The self-association properties of the peptides were characterized, and the peptide-membrane interactions in model membranes were compared with the bactericidal and haemolytic properties. Alanine substitution at position 1 and 14 resulted in higher target selectivity (red blood cells versus bacteria), but also decreased bactericidal potency. For these analogues, the gain in target selectivity correlated to biophysical parameters showing an increased effective charge and reduction in the partitioning coefficient for membrane insertion. Introduction of an unnatural amino acid, with an octyl side chain by amino acid substitution, at positions 1, 8 and 14 resulted in increased bactericidal potency at the expense of radically reduced membrane target selectivity. Overall, optimized membrane selectivity or bactericidal potency was achieved by changes in side chain hydrophobicity of MPX. However, enhanced potency was achieved at the expense of selectivity and vice versa in all cases
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