Oxidative Stress and NF-κB signaling are involved in LPS induced pulmonary dysplasia in chick embryos

Inflammation or dysbacteriosis-derived lipopolysaccharides (LPS) adversely influence the embryonic development of respiratory system. However, the precise pathological mechanisms still remain to be elucidated. In this study, we demonstrated that LPS exposure caused lung maldevelopment in chick embryos, including higher embryo mortality, increased thickness of alveolar gas exchange zone, and accumulation of PAS+ immature pulmonary cells, accompanied with reduced expression of alveolar epithelial cell markers and lamellar body count. Upon LPS exposure, pulmonary cell proliferation was significantly altered and cell apoptosis was inhibited as well, indicating a delayed progress of pulmonary development. LPS treatment also resulted in reduced CAV-1 expression and up-regulation of Collagen I, suggesting increased lung fibrosis, which was verified by Masson staining. Moreover, LPS induced enhanced Nrf2 expression in E18 lungs, and the increased reactive oxygen species (ROS) production was confirmed in MLE-12 cells in vitro. Antioxidant vitamin C restored the LPS induced down-regulation of ABCA3, SP-C and GATA-6 in MLE-12 cells. Furthermore, LPS induced activation of NF-κB signaling in MLE-12 cells, and the LPS-induced decrease in SP-C expression was partially abrogated by blocking NF-κB signaling with Bay-11-7082. Bay-11-7082 also inhibited LPS-induced increases of ROS and Nrf2 expression. Taken together, we have demonstrated that oxidative stress and NF-κB signaling are involved in LPS induced disruption of pulmonary cell development in chick embryos

Prenatal exposures and exposomics of asthma

This review examines the causal investigation of preclinical development of childhood asthma using exposomic tools. We examine the current state of knowledge regarding early-life exposure to non-biogenic indoor air pollution and the developmental modulation of the immune system. We examine how metabolomics technologies could aid not only in the biomarker identification of a particular asthma phenotype, but also the mechanisms underlying the immunopathologic process. Within such a framework, we propose alternate components of exposomic investigation of asthma in which, the exposome represents a reiterative investigative process of targeted biomarker identification, validation through computational systems biology and physical sampling of environmental medi

Holographic Multiverse

We explore the idea that the dynamics of the inflationary multiverse is encoded in its future boundary, where it is described by a lower dimensional theory which is conformally invariant in the UV. We propose that a measure for the multiverse, which is needed in order to extract quantitative probabilistic predictions, can be derived in terms of the boundary theory by imposing a UV cutoff. In the inflationary bulk, this is closely related (though not identical) to the so-called scale factor cutoff measure.Comment: 23 pages, 4 figures. Replaced to match published versio

First-Principles Semiclassical Initial Value Representation Molecular Dynamics

A method for carrying out semiclassical initial value representation calculations using first-principles molecular dynamics (FP-SC-IVR) is presented. This method can extract the full vibrational power spectrum of carbon dioxide from a single trajectory providing numerical results that agree with experiment even for Fermi resonant states. The computational demands of the method are comparable to those of classical single-trajectory calculations, while describing uniquely quantum features such as the zero-point energy and Fermi resonances. By propagating the nuclear degrees of freedom using first-principles Born-Oppenheimer molecular dynamics, the stability of the method presented is improved considerably when compared to dynamics carried out using fitted potential energy surfaces and numerical derivatives.Comment: 5 pages, 2 figures, made stylistic and clarity change

Strong signature of natural selection within an FHIT intron implicated in prostate cancer risk

Previously, a candidate gene linkage approach on brother pairs affected with prostate cancer identified a locus of prostate cancer susceptibility at D3S1234 within the fragile histidine triad gene (FHIT), a tumor suppressor that induces apoptosis. Subsequent association tests on 16 SNPs spanning approximately 381 kb surrounding D3S1234 in Americans of European descent revealed significant evidence of association for a single SNP within intron 5 of FHIT. In the current study, resequencing and genotyping within a 28.5 kb region surrounding this SNP further delineated the association with prostate cancer risk to a 15 kb region. Multiple SNPs in sequences under evolutionary constraint within intron 5 of FHIT defined several related haplotypes with an increased risk of prostate cancer in European-Americans. Strong associations were detected for a risk haplotype defined by SNPs 138543, 142413, and 152494 in all cases (Pearson's χ2 = 12.34, df 1, P = 0.00045) and for the homozygous risk haplotype defined by SNPs 144716, 142413, and 148444 in cases that shared 2 alleles identical by descent with their affected brothers (Pearson's χ2 = 11.50, df 1, P = 0.00070). In addition to highly conserved sequences encompassing SNPs 148444 and 152413, population studies revealed strong signatures of natural selection for a 1 kb window covering the SNP 144716 in two human populations, the European American (π = 0.0072, Tajima's D= 3.31, 14 SNPs) and the Japanese (π = 0.0049, Fay & Wu's H = 8.05, 14 SNPs), as well as in chimpanzees (Fay & Wu's H = 8.62, 12 SNPs). These results strongly support the involvement of the FHIT intronic region in an increased risk of prostate cancer. © 2008 Ding et al

Economic evaluation of the treatment of Acute Bacterial Skin and Skin Structure Infections (ABSSSIs) from the national payer perspective : introduction of a new treatment to the patient journey. A simulation of three European countries

The aim of this study was to develop a spending predictor model to evaluate the direct costs associated with the management of ABSSSIs from the National health-care provider's perspective of Italy, Romania, and Spain. METHODOLOGY: A decision-analytic model was developed to evaluate the diagnostic and clinical pathways of hospitalized ABSSSI patients based on scientific guidelines and real-world data. A Standard of Care (SoC) scenario was compared with a dalbavancin scenario in which the patients could be discharged early. The epidemiological and cost parameters were extrapolated from national administrative databases (i.e., hospital information system). A probabilistic sensitivity analysis (PSA) and one-way sensitivity analysis (OWA) were performed. RESULTS: Overall, the model estimated an average annual number of patients with ABSSSIs of approximately 50,000 in Italy, Spain, and Romania. On average, the introduction of dalbavancin reduced the length of stay by 3.3 days per ABSSSI patient. From an economic perspective, dalbavancin did not incur any additional cost from the National Healthcare perspective, and the results were consistent among the countries. The PSA and OWA demonstrated the robustness of these results. CONCLUSION: This model represents a useful tool for policymakers by providing information regarding the economic and organizational consequences of an early discharge approach in ABSSSI management

Strange Quark Matter and Compact Stars

Astrophysicists distinguish between three different types of compact stars. These are white dwarfs, neutron stars, and black holes. The former contain matter in one of the densest forms found in the Universe which, together with the unprecedented progress in observational astronomy, make such stars superb astrophysical laboratories for a broad range of most striking physical phenomena. These range from nuclear processes on the stellar surface to processes in electron degenerate matter at subnuclear densities to boson condensates and the existence of new states of baryonic matter--like color superconducting quark matter--at supernuclear densities. More than that, according to the strange matter hypothesis strange quark matter could be more stable than nuclear matter, in which case neutron stars should be largely composed of pure quark matter possibly enveloped in thin nuclear crusts. Another remarkable implication of the hypothesis is the possible existence of a new class of white dwarfs. This article aims at giving an overview of all these striking physical possibilities, with an emphasis on the astrophysical phenomenology of strange quark matter. Possible observational signatures associated with the theoretically proposed states of matter inside compact stars are discussed as well. They will provide most valuable information about the phase diagram of superdense nuclear matter at high baryon number density but low temperature, which is not accessible to relativistic heavy ion collision experiments.Comment: 58 figures, to appear in "Progress in Particle and Nuclear Physics"; References added for sections 1,2,3,5; Equation (116) corrected; Figs. 1 and 58 update