Differential Impact of Serial Measurement of Nonplatelet Thromboxane Generation on Long-Term Outcome After Cardiac Surgery.

BACKGROUND: Systemic thromboxane generation, not suppressible by standard aspirin therapy and likely arising from nonplatelet sources, increases the risk of atherothrombosis and death in patients with cardiovascular disease. In the RIGOR (Reduction in Graft Occlusion Rates) study, greater nonplatelet thromboxane generation occurred early compared with late after coronary artery bypass graft surgery, although only the latter correlated with graft failure. We hypothesize that a similar differential association exists between nonplatelet thromboxane generation and long-term clinical outcome. METHODS AND RESULTS: Five-year outcome data were analyzed for 290 RIGOR subjects taking aspirin with suppressed platelet thromboxane generation. Multivariable modeling was performed to define the relative predictive value of the urine thromboxane metabolite, 11-dehydrothromboxane B CONCLUSIONS: Long-term nonplatelet thromboxane generation after coronary artery bypass graft surgery is a novel risk factor for 5-year adverse outcome, including death. In contrast, nonplatelet thromboxane generation in the early postoperative period appears to be driven predominantly by inflammation and did not independently predict long-term clinical outcome

Antibacterial activity of blue light against nosocomial wound pathogens growing planktonically and as mature biofilms

The blue wavelengths within the visible light spectrum are intrinisically antimicrobial and can photodynamically inactivate the cells of a wide spectrum of bacteria (Gram positive and negative) and fungi. Furthermore, blue light is equally effective against both drug-sensitive and -resistant members of target species and is less detrimental to mammalian cells than is UV radiation. Blue light is currently used for treating acnes vulgaris and Helicobacter pylori infections; the utility for decontamination and treatment of wound infections is in its infancy. Furthermore, limited studies have been performed on bacterial biofilms, the key growth mode of bacteria involved in clinical infections. Here we report the findings of a multicenter in vitro study performed to assess the antimicrobial activity of 400-nm blue light against bacteria in both planktonic and biofilm growth modes. Blue light was tested against a panel of 34 bacterial isolates (clinical and type strains) comprising Acinetobacter baumannii, Enterobacter cloacae, Stenotrophomonas maltophilia, Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, Enterococcus faecium, Klebsiella pneumoniae, and Elizabethkingia meningoseptica. All planktonic-phase bacteria were susceptible to blue light treatment, with the majority (71%) demonstrating a ≥ 5-log10 decrease in viability after 15 to 30 min of exposure (54 J/cm2 to 108 J/cm2). Bacterial biofilms were also highly susceptible to blue light, with significant reduction in seeding observed for all isolates at all levels of exposure. These results warrant further investigation of blue light as a novel decontamination strategy for the nosocomial environment, as well as additional wider decontamination applications

Are Debris Disks and Massive Planets Correlated?

Using data from the Spitzer Space Telescope Legacy Science Program ``Formation and Evolution of Planetary Systems'' (FEPS), we have searched for debris disks around 9 FGK stars (2-10 Gyr), known from radial velocity (RV) studies to have one or more massive planets. Only one of the sources, HD 38529, has excess emission above the stellar photosphere; at 70 micron the signal-to-noise ratio in the excess is 4.7 while at wavelengths < 30 micron there is no evidence of excess. The remaining sources show no excesses at any Spitzer wavelengths. Applying survival tests to the FEPS sample and the results for the FGK survey published in Bryden et al. (2006), we do not find a significant correlation between the frequency and properties of debris disks and the presence of close-in planets. We discuss possible reasons for the lack of a correlation.Comment: 24 pages, 3 figures. Accepted to Astrophysical Journa

Cymantrene–Triazole "Click" Products: Structural Characterization and Electrochemical Properties

We report the first known examples of triazole-derivatized cymantrene complexes (η5-[4-substituted triazol-1-yl]cyclopentadienyl)tricarbonylmanganese(I), obtained via a “click” chemical synthesis, bearing a phenyl, 3-aminophenyl, or 4-aminophenyl moiety at the 4-position of the triazole ring. Structural characterization data using multinuclear NMR, UV–vis, ATR-IR, and mass spectrometric methods are provided, as well as crystallographic data for (η5-[4-phenyltriazol-1-yl]cyclopentadienyl)tricarbonylmanganese(I) and (η5-[4-(3-aminophenyl)triazol-1-yl]cyclopentadienyl)tricarbonylmanganese(I). Cyclic voltammetric characterization of the redox behavior of each of the three cymantrene–triazole complexes is presented together with digital simulations, in situ infrared spectroelectrochemistry, and DFT calculations to extract the associated kinetic and thermodynamic parameters. The trypanocidal activity of each cymantrene–triazole complex is also examined, and these complexes are found to be more active than cymantrene alone

Habitable Zones in the Universe

Habitability varies dramatically with location and time in the universe. This was recognized centuries ago, but it was only in the last few decades that astronomers began to systematize the study of habitability. The introduction of the concept of the habitable zone was key to progress in this area. The habitable zone concept was first applied to the space around a star, now called the Circumstellar Habitable Zone. Recently, other, vastly broader, habitable zones have been proposed. We review the historical development of the concept of habitable zones and the present state of the research. We also suggest ways to make progress on each of the habitable zones and to unify them into a single concept encompassing the entire universe.Comment: 71 pages, 3 figures, 1 table; to be published in Origins of Life and Evolution of Biospheres; table slightly revise

The Fluoroquinolone Finafloxacin Protects BALB/c Mice Against an Intranasal Infection With Francisella tularensis Strain SchuS4

The efficacy of the novel fluoroquinolone finafloxacin was evaluated as a potential therapeutic in vitro and in vivo, following an intranasal infection of Francisella tularensis strain SchuS4 in BALB/c mice. We demonstrated that short treatment courses of finafloxacin provide high levels of protection, with a single dose resulting in a significant increase in time to death when compared to ciprofloxacin. In addition, following investigation into the window of opportunity for treatment, we have shown that finafloxacin can provided protection when administered up to 96 h post-challenge. This is particularly encouraging since mice displayed severe signs of disease at this time point. In summary, finafloxacin may be a promising therapy for use in the event of exposure to F. tularensis, perhaps enabling the treatment regimen to be shortened or if therapy is delayed. The efficacy of finafloxacin against other biological threat agents also warrants investigation

The supportive care needs of parents caring for a child with a rare disease : a scoping review

Background: Parents caring for a child with a rare disease report unmet needs, the origins of which are varied and complex. Few studies have systematically attempted to identify the supportive care needs of parents with a child with a rare disease comprehensively. We have used the widely accepted Supportive Care Needs Framework (SCNF) as the structure for this review. Objective: The purpose of the current review was to identify the supportive care needs of parents with a child with a rare disease, irrespective of condition. Methods: We conducted a scoping study review comprising 29 studies (1990–2014) to identify and examine the research literature related to the supportive care needs of parents, and to compare these needs with the seven domains outlined in the SCNF. Results: Most common needs cited were social needs (72% of papers), followed by informational needs (65% of papers) and emotional needs (62% of papers), with the most common parental needs overall being information about their child's disease, emotional stress, guilt and uncertainty about their child's future health care needs, parents own caring responsibilities and the need for more general support. Conclusion: A paucity of studies exists that explore the supportive care needs of parents of a child with a rare disease. The SCNF only partially reflects the breadth and type of needs of these parents, and a preliminary revised framework has been suggested. Further research is required in this area, particularly empirical research to amend or confirm the suggested new framework

Deep Sequencing of RNA from Blood and Oral Swab Samples Reveals the Presence of Nucleic Acid from a Number of Pathogens in Patients with Acute Ebola Virus Disease and Is Consistent with Bacterial Translocation across the Gut.

In this study, samples from the 2013-2016 West African Ebola virus outbreak from patients in Guinea with Ebola virus disease (EVD) were analyzed to discover and classify what other pathogens were present. Throat swabs were taken from deceased EVD patients, and peripheral blood samples were analyzed that had been taken from patients when they presented at the treatment center with acute illness. High-throughput RNA sequencing (RNA-seq) and bioinformatics were used to identify the potential microorganisms. This approach confirmed Ebola virus (EBOV) in all samples from patients diagnosed as acute positive for the virus by quantitative reverse transcription-PCR in deployed field laboratories. Nucleic acid mapping to Plasmodium was also used on the patient samples, confirming results obtained with an antigen-based rapid diagnostic test (RDT) conducted in the field laboratories. The data suggested that a high Plasmodium load, as determined by sequence read depth, was associated with mortality and influenced the host response, whereas a lower parasite load did not appear to affect outcome. The identifications of selected bacteria from throat swabs via RNA-seq were confirmed by culture. The data indicated that the potential pathogens identified in the blood samples were associated with translocation from the gut, suggesting the presence of bacteremia, which transcriptome data suggested may induce or aggravate the acute-phase response observed during EVD. Transcripts mapping to different viruses were also identified, including those indicative of lytic infections. The development of high-resolution analysis of samples from patients with EVD will help inform care pathways and the most appropriate general antimicrobial therapy to be used in a resource-poor setting. IMPORTANCE Our results highlight the identification of an array of pathogens in the blood of patients with Ebola virus disease (EVD). This has not been done before, and the data have important implications for the treatment of patients with EVD, particularly considering antibiotic stewardship. We show that EVD patients who were also infected with Plasmodium, particularly at higher loads, had more adverse outcomes than patients with lower levels of Plasmodium. However, the presence of Plasmodium did not influence the innate immune response, and it is likely that the presence of EBOV dominated this response. Several viruses other than EBOV were identified, and bacteria associated with sepsis were also identified. These findings were indicative of bacterial translocation across the gut during the acute phase of EVD