Repurposing of Meropenem and Nadifloxacin for Treatment of Burn Patients?

The escalating number of multidrug resistant pathogens has demanded the swift development of new and potent antibiotics (ref. 2). Metallo-[beta]-lactamases (MBLs) continue to evolve, rendering the latest generation of carbapenem antibiotics useless (ref. 8). SPM-1, a recently discovered MBL, was isolated from a juvenile leukemia patient residing in a hospital in San Palo, Brazil just prior to the patient succumbing to septicemia brought on by Pseudomonas aeruginosa expressing SPM-1 (ref. 8). Screening of the Johns Hopkins Compound library of 1,514 FDA or FAD approved drugs (ref. 1) identified a novel SPM-1 inhibitor that is synergistically compatible with meropenem. Using clinically achievable concentrations, meropenem coupled with nadifloxacin inhibits Pseudomonas aeruginosa expressing SPM-1. This shotgun approach to new drug discovery provided a prompt solution to the grave problem of antibiotic resistant pathogens that are thriving in hospitals today

Cardiac and Renal Delayed Effects of Acute Radiation Exposure: Organ Differences in Vasculopathy, Inflammation, Senescence and Oxidative Balance

We have previously shown significant pathology in the heart and kidney of murine hematopoietic-acute radiation syndrome (H-ARS) survivors of 8.7-9.0 Gy total-body irradiation (TBI). The goal of this study was to determine temporal relationships in the development of vasculopathy and the progression of renal and cardiovascular delayed effects of acute radiation exposure (DEARE) at TBI doses less than 9 Gy and to elucidate the potential roles of senescence, inflammation and oxidative stress. Our results show significant loss of endothelial cells in coronary arteries by 4 months post-TBI (8.53 or 8.72 Gy of gamma radiation). This loss precedes renal dysfunction and interstitial fibrosis and progresses to abnormalities in the arterial media and adventitia and loss of coronary arterioles. Major differences in radiation-induced pathobiology exist between the heart and kidney in terms of vasculopathy progression and also in indices of inflammation, senescence and oxidative imbalance. The results of this work suggest a need for different medical countermeasures for multiple targets in different organs and at various times after acute radiation injury to prevent the progression of DEARE

Microbial hitchhikers harbouring antimicrobial-resistance genes in the riverine plastisphere

Background: The widespread nature of plastic pollution has given rise to wide scientific and social concern regarding the capacity of these materials to serve as vectors for pathogenic bacteria and reservoirs for Antimicrobial Resistance Genes (ARG). In- and ex-situ incubations were used to characterise the riverine plastisphere taxonomically and functionally in order to determine whether antibiotics within the water influenced the ARG profiles in these microbiomes and how these compared to those on natural surfaces such as wood and their planktonic counterparts. Results: We show that plastics support a taxonomically distinct microbiome containing potential pathogens and ARGs. While the plastisphere was similar to those biofilms that grew on wood, they were distinct from the surrounding water microbiome. Hence, whilst potential opportunistic pathogens (i.e. Pseudomonas aeruginosa, Acinetobacter and Aeromonas) and ARG subtypes (i.e. those that confer resistance to macrolides/lincosamides, rifamycin, sulfonamides, disinfecting agents and glycopeptides) were predominant in all surface-related microbiomes, especially on weathered plastics, a completely different set of potential pathogens (i.e. Escherichia, Salmonella, Klebsiella and Streptococcus) and ARGs (i.e. aminoglycosides, tetracycline, aminocoumarin, fluoroquinolones, nitroimidazole, oxazolidinone and fosfomycin) dominated in the planktonic compartment. Our genome-centric analysis allowed the assembly of 215 Metagenome Assembled Genomes (MAGs), linking ARGs and other virulence-related genes to their host. Interestingly, a MAG belonging to Escherichia –that clearly predominated in water– harboured more ARGs and virulence factors than any other MAG, emphasising the potential virulent nature of these pathogenic-related groups. Finally, ex-situ incubations using environmentally-relevant concentrations of antibiotics increased the prevalence of their corresponding ARGs, but different riverine compartments –including plastispheres– were affected differently by each antibiotic. Conclusions: Our results provide insights into the capacity of the riverine plastisphere to harbour a distinct set of potentially pathogenic bacteria and function as a reservoir of ARGs. The environmental impact that plastics pose if they act as a reservoir for either pathogenic bacteria or ARGs is aggravated by the persistence of plastics in the environment due to their recalcitrance and buoyancy. Nevertheless, the high similarities with microbiomes growing on natural co-occurring materials and even more worrisome microbiome observed in the surrounding water highlights the urgent need to integrate the analysis of all environmental compartments when assessing risks and exposure to pathogens and ARGs in anthropogenically-impacted ecosystems. 1SQe33MjkWBo3cdx_C_SmDVideo Abstrac

Delayed Effects of Acute Radiation Exposure in a Murine Model of the H-ARS: Multiple-Organ Injury Consequent to <10 Gy Total Body Irradiation

The threat of radiation exposure from warfare or radiation accidents raises the need for appropriate animal models to study the acute and chronic effects of high dose rate radiation exposure. The goal of this study was to assess the late development of fibrosis in multiple organs (kidney, heart, and lung) in survivors of the C57BL/6 mouse model of the hematopoietic-acute radiation syndrome (H-ARS). Separate groups of mice for histological and functional studies were exposed to a single uniform total body dose between 8.53 and 8.72 Gy of gamma radiation from a Cs radiation source and studied 1-21 mo later. Blood urea nitrogen levels were elevated significantly in the irradiated mice at 9 and 21 mo (from ∼22 to 34 ± 3.8 and 69 ± 6.0 mg dL, p < 0.01 vs. non-irradiated controls) and correlated with glomerosclerosis (29 ± 1.8% vs. 64 ± 9.7% of total glomeruli, p < 0.01 vs. non-irradiated controls). Glomerular tubularization and hypertrophy and tubular atrophy were also observed at 21 mo post-total body irradiation (TBI). An increase in interstitial, perivascular, pericardial and peribronchial fibrosis/collagen deposition was observed from ∼9-21 mo post-TBI in kidney, heart, and lung of irradiated mice relative to age-matched controls. Echocardiography suggested decreased ventricular volumes with a compensatory increase in the left ventricular ejection fraction. The results indicate that significant delayed effects of acute radiation exposure occur in kidney, heart, and lung in survivors of the murine H-ARS TBI model, which mirrors pathology detected in larger species and humans at higher radiation doses focused on specific organs

Meta-analysis of genome-wide association studies from the CHARGE consortium identifies common variants associated with carotid intima media thickness and plaque

Carotid intima media thickness (cIMT) and plaque determined by ultrasonography are established measures of subclinical atherosclerosis that each predicts future cardiovascular disease events. We conducted a meta-analysis of genome-wide association data in 31,211 participants of European ancestry from nine large studies in the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. We then sought additional evidence to support our findings among 11,273 individuals using data from seven additional studies. In the combined meta-analysis, we identified three genomic regions associated with common carotid intima media thickness and two different regions associated with the presence of carotid plaque (P < 5 × 10 -8). The associated SNPs mapped in or near genes related to cellular signaling, lipid metabolism and blood pressure homeostasis, and two of the regions were associated with coronary artery disease (P < 0.006) in the Coronary Artery Disease Genome-Wide Replication and Meta-Analysis (CARDIoGRAM) consortium. Our findings may provide new insight into pathways leading to subclinical atherosclerosis and subsequent cardiovascular events

Measurements of Dihadron Correlations Relative to the Event Plane in Au+Au Collisions at sNN=200\sqrt{s_{NN}}=200 GeV

Dihadron azimuthal correlations containing a high transverse momentum (\pt) trigger particle are sensitive to the properties of the nuclear medium created at RHIC through the strong interactions occurring between the traversing parton and the medium, i.e. jet-quenching. Previous measurements revealed a strong modification to dihadron azimuthal correlations in Au+Au collisions with respect to \pp\ and \dAu\ collisions. The modification increases with the collision centrality, suggesting a path-length dependence to the jet-quenching effect. This paper reports STAR measurements of dihadron azimuthal correlations in mid-central (20-60\%) Au+Au collisions at \snn=200~GeV as a function of the trigger particle's azimuthal angle relative to the event plane, \phis=|\phit-\psiEP|. The azimuthal correlation is studied as a function of both the trigger and associated particle \pt. The subtractions of the combinatorial background and anisotropic flow, assuming Zero Yield At Minimum (\zyam), are described. The away-side correlation is strongly modified, and the modification varies with \phis, which is expected to be related to the path-length that the away-side parton traverses. The pseudo-rapidity (\deta) dependence of the near-side correlation, sensitive to long range \deta correlations (the ridge), is also investigated. The ridge and jet-like components of the near-side correlation are studied as a function of \phis. The ridge appears to drop with increasing \phis while the jet-like component remains approximately constant. ...Comment: 50 pages, 39 figures, 6 table

Studies of di-jet survival and surface emission bias in Au+Au collisions via angular correlations with respect to back-to-back leading hadrons

We report first results from an analysis based on a new multi-hadron correlation technique, exploring jet-medium interactions and di-jet surface emission bias at RHIC. Pairs of back-to-back high transverse momentum hadrons are used for triggers to study associated hadron distributions. In contrast with two- and three-particle correlations with a single trigger with similar kinematic selections, the associated hadron distribution of both trigger sides reveals no modification in either relative pseudo-rapidity or relative azimuthal angle from d+Au to central Au+Au collisions. We determine associated hadron yields and spectra as well as production rates for such correlated back-to-back triggers to gain additional insights on medium properties.Comment: By the STAR Collaboration. 6 pages, 2 figure

A mechanistic understanding of polyethylene biodegradation by the marine bacterium Alcanivorax

Polyethylene (PE) is one of the most recalcitrant carbon-based synthetic materials produced and, currently, the most ubiquitous plastic pollutant found in nature. Over time, combined abiotic and biotic processes are thought to eventually breakdown PE. Despite limited evidence of biological PE degradation and speculation that hydrocarbon-degrading bacteria found within the plastisphere is an indication of biodegradation, there is no clear mechanistic understanding of the process. Here, using high-throughput proteomics, we investigated the molecular processes that take place in the hydrocarbon-degrading marine bacterium Alcanivorax sp. 24 when grown in the presence of low density PE (LDPE). As well as efficiently utilising and assimilating the leachate of weathered LDPE, the bacterium was able to reduce the molecular weight distribution (M from 122 to 83 kg/mol) and overall mass of pristine LDPE films (0.9 % after 34 days of incubation). Most interestingly, Alcanivorax acquired the isotopic signature of the pristine plastic and induced an extensive array of metabolic pathways for aliphatic compound degradation. Presumably, the primary biodegradation of LDPE by Alcanivorax sp. 24 is possible via the production of extracellular reactive oxygen species as observed both by the material's surface oxidation and the measurement of superoxide in the culture with LDPE. Our findings confirm that hydrocarbon-biodegrading bacteria within the plastisphere may in fact have a role in degrading PE

Observation of the antimatter helium-4 nucleus

High-energy nuclear collisions create an energy density similar to that of the universe microseconds after the Big Bang, and in both cases, matter and antimatter are formed with comparable abundance. However, the relatively short-lived expansion in nuclear collisions allows antimatter to decouple quickly from matter, and avoid annihilation. Thus, a high energy accelerator of heavy nuclei is an efficient means of producing and studying antimatter. The antimatter helium-4 nucleus ($^4\bar{He}$), also known as the anti-{\alpha} ($\bar{\alpha}$), consists of two antiprotons and two antineutrons (baryon number B=-4). It has not been observed previously, although the {\alpha} particle was identified a century ago by Rutherford and is present in cosmic radiation at the 10% level. Antimatter nuclei with B < -1 have been observed only as rare products of interactions at particle accelerators, where the rate of antinucleus production in high-energy collisions decreases by about 1000 with each additional antinucleon. We present the observation of the antimatter helium-4 nucleus, the heaviest observed antinucleus. In total 18 $^4\bar{He}$ counts were detected at the STAR experiment at RHIC in 10$^9$ recorded Au+Au collisions at center-of-mass energies of 200 GeV and 62 GeV per nucleon-nucleon pair. The yield is consistent with expectations from thermodynamic and coalescent nucleosynthesis models, which has implications beyond nuclear physics.Comment: 19 pages, 4 figures. Submitted to Nature. Under media embarg

System size and energy dependence of near-side di-hadron correlations

Two-particle azimuthal ($\Delta\phi$) and pseudorapidity ($\Delta\eta$) correlations using a trigger particle with large transverse momentum ($p_T$) in $d$+Au, Cu+Cu and Au+Au collisions at $\sqrt{s_{{NN}}}$ =\xspace 62.4 GeV and 200~GeV from the STAR experiment at RHIC are presented. The \ns correlation is separated into a jet-like component, narrow in both $\Delta\phi$ and $\Delta\eta$, and the ridge, narrow in $\Delta\phi$ but broad in $\Delta\eta$. Both components are studied as a function of collision centrality, and the jet-like correlation is studied as a function of the trigger and associated $p_T$. The behavior of the jet-like component is remarkably consistent for different collision systems, suggesting it is produced by fragmentation. The width of the jet-like correlation is found to increase with the system size. The ridge, previously observed in Au+Au collisions at $\sqrt{s_{{NN}}}$ = 200 GeV, is also found in Cu+Cu collisions and in collisions at $\sqrt{s_{{NN}}}$ =\xspace 62.4 GeV, but is found to be substantially smaller at $\sqrt{s_{{NN}}}$ =\xspace 62.4 GeV than at $\sqrt{s_{{NN}}}$ = 200 GeV for the same average number of participants ($\langle N_{\mathrm{part}}\rangle$). Measurements of the ridge are compared to models.Comment: 17 pages, 14 figures, submitted to Phys. Rev.